MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Trends in Molecular Medicine' source. Thu, 09 Feb 2012 16:56:55 +0100 http://www.medworm.com/index.php?rid=5598958&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245020%26dopt%3DAbstract Authors: Gill HS, Grammatopoulos G, Adshead S, Tsialogiannis E, Tsiridis E Abstract Theoretical, desirable features of second-generation metal-on-metal (MoM) hip prostheses have led to their widespread use. However, the bearing surfaces, consisting of complex cobalt-chromium alloys, are subject to wear and the release of cobalt and chromium (CoCr) nanoparticles. These nanoparticles can reduce cellular viability, induce DNA damage, lead to chromosomal aberrations, and possibly stimulate increased metal hypersensitivity. Clinically, the effects can be both local (soft-tissue reactions) and systemic (arthroprosthetic cobaltism). This review assesses the literature concerning the in vitro and in vivo cytotoxic, genotoxic, and immunotoxic effects of CoCr wear particles, which is increas... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5598958 Thu, 12 Jan 2012 05:00:00 +0100 5598958 http://www.medworm.com/index.php?rid=5598959&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22240486%26dopt%3DAbstract Authors: Hemelaar J Abstract This review examines the enormous progress that has been made in the past decade in understanding the origin of HIV, HIV genetic variability, and the impact of global HIV diversity on the pandemic. Multiple zoonotic transmissions of simian immunodeficiency virus (SIV) have resulted in different HIV lineages in humans. In addition, the high mutation and recombination rates during viral replication result in a great genetic variability of HIV within individuals, as well as within populations, upon which evolutionary selection pressures act. The global HIV pandemic is examined in the context of HIV evolution, and the global diversity of HIV subtypes and recombinants is discussed in detail. Finally, the impact of HIV diversity on pathogenesis, transmission,... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5598959 Wed, 11 Jan 2012 05:00:00 +0100 5598959 http://www.medworm.com/index.php?rid=5598960&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22230382%26dopt%3DAbstract Authors: Russo V, Bondanza A, Ciceri F, Bregni M, Bordignon C, Traversari C, Bonini C Abstract T cells as the ultimate effectors of adaptive immune responses are currently used to treat patients affected by infectious diseases and certain tumors. Recently, T cells have been manipulated ex vivo with viral vectors coding for chimeric antigen receptors, exogenous T cell receptors, or 'suicide' genes to potentiate their efficacy and minimize possible side effects. However, the introduction of exogenous genes into T lymphocytes, particularly bacterial or viral transgene products, has occasionally produced immune-mediated elimination of transduced lymphocytes. This immune effect has recently been exploited in a trial of active immunotherapy in melanoma patients. In this opinion article, ... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5598960 Sat, 07 Jan 2012 05:00:00 +0100 5598960 http://www.medworm.com/index.php?rid=5533472&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178468%26dopt%3DAbstract Authors: Goldring MB, Marcu KB Abstract Osteoarthritis (OA) is a multifactorial disease subject to the effects of many genes and environmental factors. Alterations in the normal pattern of chondrocyte gene control in cartilage facilitate the onset and progression of OA. Stable changes in patterns of gene expression, not associated with alterations in DNA sequences, occur through epigenetic changes, including DNA methylation, histone modifications, and alterations in chromatin structure, as well as by microRNA (miRNA)-mediated mechanisms. Moreover, the ability of the host to repair damaged cartilage is reflected in alterations in gene control circuits, suggestive of an epigenetic and miRNA-dependent tug-of-war between tissue homeostasis and OA disease pathogenesis. Herein, we summar... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533472 Sat, 17 Dec 2011 05:00:00 +0100 5533472 http://www.medworm.com/index.php?rid=5533473&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178229%26dopt%3DAbstract Authors: Li X, Kumar A, Zhang F, Lee C, Tang Z Abstract No other member of the VEGF (vascular endothelial growth factor) family has been as mysterious as VEGF-B. Notwithstanding its name, VEGF-B can hardly be regarded as a growth factor because growth occurs fairly normally in Vegf-b deficient mice. Moreover, VEGF-B is barely angiogenic under most conditions, although it was expected to be an angiogenic factor for a long time. Under certain conditions, VEGF-B has been shown to be involved in blood vessel growth. Under other conditions, however, VEGF-B can act to inhibit tumor growth and angiogenesis. Given these contradictory findings, the biological function of VEGF-B appears enigmatic. In this review, we summarize recent advances in VEGF-B biology and discuss its multifaceted rol... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533473 Thu, 15 Dec 2011 05:00:00 +0100 5533473 http://www.medworm.com/index.php?rid=5533475&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177734%26dopt%3DAbstract Authors: Alexander S, Friedl P Abstract Cancer progression and outcome depend upon two key functions executed by tumor cells: the growth and survival capability leading to resistance to therapy and the invasion into host tissues resulting in local and metastatic dissemination. Although both processes are widely studied separately, the underlying cell-intrinsic and microenvironmentally controlled signaling pathways reveal substantial overlap in mechanism. Candidate signaling hubs that serve both tumor invasion and resistance include growth factor and chemokine signaling, integrin engagement, and components of the Ras/MAPKs, PI3K, and mTOR signaling pathways. In this review, we summarize these and other mechanisms controlled by the microenvironment that jointly support cancer cell su... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533475 Wed, 14 Dec 2011 05:00:00 +0100 5533475 http://www.medworm.com/index.php?rid=5533474&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22177735%26dopt%3DAbstract Authors: Grammatikos AP, Tsokos GC Abstract Recent evidence suggests that systemic autoimmunity and immunodeficiency are not separate entities, but rather are interconnected processes. Immunodeficiency results from distinct defects of the immune response and primarily presents as infections but also frequently with autoimmune features. Systemic autoimmunity is the combined effect of multiple genetic variations and infectious and immunoregulatory factors that result in dominant autoimmune manifestations, in addition to frequent and opportunistic infections. The overlap in disease manifestations and symptoms suggests that immunodeficiency should be considered in the presence of autoimmunity, and vice versa. In this review, we present the shared or similar aspects of immunodeficiency ... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533474 Wed, 14 Dec 2011 05:00:00 +0100 5533474 http://www.medworm.com/index.php?rid=5512557&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172275%26dopt%3DAbstract Authors: Wang ZY, Fu LY, Zhang HY Abstract New strategies for target identification are urgently needed to tackle the current productivity challenges in drug discovery. By examining successful human drug targets, it can be seen that approximately 50% are associated with genetic disorders. Further analysis shows that these successfully targeted genes share some common evolutionary features, which strongly suggests that evolutionary information can help identify drug targets with the greatest potential for therapeutic development. PMID: 22172275 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine) Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5512557 Tue, 13 Dec 2011 05:00:00 +0100 5512557 http://www.medworm.com/index.php?rid=5512556&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22172276%26dopt%3DAbstract Authors: Metcalfe SM, Fahmy TM Abstract Nanotechnology permits the design of therapeutic devices with defined structure and molecular composition. Modular designs employing surface-bound ligands provide specific homing devices for loaded cargo, and biocompatible and biodegradable constructs provide surrogate temporary microenvironments. We first present a case for developing 'smart' modular constructs as immunogenic vaccines to prime immune memory against specific pathogens where current vaccines fail. Second, we argue that nanotherapeutic intervention can harness pivotal molecular pathways recently discovered to regulate lineage development between pathogenic TH17 cells associated with autoimmune disease, versus tolerogenic regulatory T cells (Treg). Underpinned by molecular mecha... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5512556 Tue, 13 Dec 2011 05:00:00 +0100 5512556 http://www.medworm.com/index.php?rid=5512560&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22154696%26dopt%3DAbstract Authors: Stasyk T, Huber LA Abstract Abnormal protein phosphorylation is implicated in a variety of diseases, but until recently the complexity of tissue material, technical limitations, and the substantial volume of required data processing did not allow large-scale phosphoproteomic analysis of patient material, despite tremendous progress in developing mass spectrometry technologies. Phosphoproteomic approaches were primarily developed using model systems such as transformed cell lines, but technological advances in proteomics now make it feasible to analyze thousands of phosphorylation sites in a quantitative manner in patient materials or complex animal and cellular model systems to identify signaling abnormalities. This review summarizes very recent phosphoproteomic studies on... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5512560 Thu, 08 Dec 2011 05:00:00 +0100 5512560 http://www.medworm.com/index.php?rid=5512561&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22138491%26dopt%3DAbstract Authors: Lukacs GL, Verkman AS Abstract Cystic fibrosis (CF), the most common lethal genetic disease in the Caucasian population, is caused by loss-of-function mutations of the CF transmembrane conductance regulator (CFTR), a cyclic AMP-regulated plasma membrane chloride channel. The most common mutation, deletion of phenylalanine 508 (ΔF508), impairs CFTR folding and, consequently, its biosynthetic and endocytic processing as well as chloride channel function. Pharmacological treatments may target the ΔF508 CFTR structural defect directly by binding to the mutant protein and/or indirectly by altering cellular protein homeostasis (proteostasis) to promote ΔF508 CFTR plasma membrane targeting and stability. This review discusses recent basic research aimed at elucidating the stru... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5512561 Fri, 02 Dec 2011 05:00:00 +0100 5512561 http://www.medworm.com/index.php?rid=5474439&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22118960%26dopt%3DAbstract Authors: Gebler A, Zabel O, Seliger B Abstract Mesenchymal stem cells (MSCs) are currently being tested in clinical trials for the treatment of various diseases owing to the ease of generating and expanding these cells, the ability to differentiate them into various specialized mesenchymal tissue types and their immunosuppressive properties. However, their immunomodulatory potential remains controversial. This review describes the constitutive and regulated expression of molecules of the major histocompatibility complex (MHC) class I antigen processing machinery (APM), co-stimulatory B7 molecules and HLA-G. Furthermore, this review focuses on the secretion of factors, such as cytokines, in mesenchymal stem cells, their functional role in mounting and controlling immune responses me... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5474439 Fri, 25 Nov 2011 05:00:00 +0100 5474439 http://www.medworm.com/index.php?rid=5419031&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22078487%26dopt%3DAbstract Authors: Cavone L, Chiarugi A Abstract Despite significant advancement in developing therapies for multiple sclerosis (MS), drugs that cure this devastating disorder are an unmet need. Among the remedies showing efficacy in preclinical MS models, inhibitors of poly(ADP-ribose) polymerase (PARP)-1 have gained great momentum. Emerging evidence demonstrates that PARP-1 inhibitors epigenetically regulate gene expression and finely tune transcriptional activation in immune and neural cells. In this review, we present an appraisal of the effects of PARP-1 and its inhibitors on immune activation, with particular emphasis on the processes taking place during the autoimmune attack directed against the central nervous system. One explanation is that drugs inhibiting PARP-1 activity protect f... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5419031 Wed, 09 Nov 2011 05:00:00 +0100 5419031 http://www.medworm.com/index.php?rid=5419032&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22056243%26dopt%3DAbstract Authors: Lallemand-Breitenbach V, Zhu J, Chen Z, de Thé H Abstract Acute promyelocytic leukemia (APL) is a hematological malignancy driven by the PML/RARA oncogene. The prognosis for patients with APL was revolutionized by two treatments: retinoic acid (RA) and As(2)O(3) (arsenic trioxide). These were both shown a posteriori to target PML/RARA, explaining their exquisite specificity for APL. Arsenic, as a single agent, cures up to 70% of patients, whereas APL patients treated with the combination of RA and As(2)O(3) reach a stunning 90% cure rate. Recent physiopathological models highlight the key role of RA- and As(2)O(3)-triggered PML/RARA degradation, and the molecular mechanisms underlying As(2)O(3)-induced PML/RARA degradation have been recently clarified. As discussed below,... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5419032 Thu, 03 Nov 2011 04:00:00 +0100 5419032 http://www.medworm.com/index.php?rid=5379354&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018672%26dopt%3DAbstract Authors: Wild EJ, Carroll JB Abstract Research and patient communities are firmly interdependent. Engaged patient communities provide biological samples and data that drive discoveries which, in turn, fuel the development of novel therapies. Historically, Huntington's disease (HD) has benefited from trusting interactions between scientists and patients. However, even for HD, communication between the research and patient communities is suboptimal. The web platform HDBuzz was created to rectify this situation by providing accurate, accessible information on the latest HD research to patients and their supporters. PMID: 22018672 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine) Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5379354 Thu, 20 Oct 2011 04:00:00 +0100 5379354 http://www.medworm.com/index.php?rid=5379355&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22015021%26dopt%3DAbstract Authors: Porteous DJ, Millar JK, Brandon NJ, Sawa A Abstract Psychiatric genetics research, as exemplified by the DISC1 gene, aspires to inform on mental health etiology and to suggest improved strategies for intervention. DISC1 was discovered in 2000 through the molecular cloning of a chromosomal translocation that segregated with a spectrum of major mental illnesses in a single large Scottish family. Through in vitro experiments and mouse models, DISC1 has been firmly established as a genetic risk factor for a spectrum of psychiatric illness. As a consequence of its protein scaffold function, the DISC1 protein impacts on many aspects of brain function, including neurosignaling and neurodevelopment. DISC1 is a pathfinder for understanding psychopathology, brain development, signal... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5379355 Tue, 18 Oct 2011 04:00:00 +0100 5379355 http://www.medworm.com/index.php?rid=5379356&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22001540%26dopt%3DAbstract Authors: Fais S, Fauvarque MO Abstract Phagocytosis is used not only for immune defense but may also be used to obtain nutrients, as observed when tumor cells feed upon neighboring cells during "tumor cell cannibalism". The TM9 protein TM9SF4, important in canonical phagocytosis, is involved in this cannibalism by metastatic cells and may represent a novel therapeutic target. PMID: 22001540 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine) Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5379356 Fri, 14 Oct 2011 04:00:00 +0100 5379356 http://www.medworm.com/index.php?rid=5379357&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21996344%26dopt%3DAbstract Authors: Gendelman HE, Appel SH PMID: 21996344 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine) Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5379357 Tue, 11 Oct 2011 04:00:00 +0100 5379357 http://www.medworm.com/index.php?rid=5296270&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21962474%26dopt%3DAbstract Authors: Ji Z, Flaherty KT, Tsao H Abstract Metastatic melanoma is a highly lethal type of skin cancer and is often refractory to all traditional chemotherapeutic agents. Key insights into the genetic makeup of melanoma tumors have led to the development of promising targeted agents. An activated RAS pathway, anchored by oncogenic BRAF, appears to be the central motor driving melanoma proliferation. Although recent clinical trials have brought enormous hope to patients with melanoma, adverse effects and novel escape mechanisms of these inhibitors have already emerged. Definition of the limits of the first successful targeted therapies will provide the basis for further advances in management of disseminated melanoma. In this review, the current state of targeted therapy for melanom... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5296270 Thu, 29 Sep 2011 04:00:00 +0100 5296270 http://www.medworm.com/index.php?rid=5277273&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21955406%26dopt%3DAbstract Authors: Field JR, Walker AG, Conn PJ Abstract Although early clinical observations implicated dopamine dysfunction in the neuropathology of schizophrenia, accumulating evidence suggests that multiple neurotransmitter pathways are dysregulated. The psychotomimetic actions of NMDA receptor antagonists point to an imbalance of glutamatergic signaling. Encouragingly, numerous preclinical and clinical studies have elucidated several potential targets for increasing NMDA receptor function and equilibrating glutamatergic tone, including the metabotropic glutamate receptors 2, 3 and 5, the muscarinic acetylcholine receptors M(1) and M(4), and the glycine transporter GlyT1. Highly specific allosteric and orthosteric ligands have been developed that modify the activity of these novel target... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5277273 Mon, 26 Sep 2011 04:00:00 +0100 5277273 http://www.medworm.com/index.php?rid=5229079&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21917523%26dopt%3DAbstract Authors: Diano S, Horvath TL Abstract Nutrient availability is critical for the physiological functions of all tissues. By contrast, an excess of nutrients such as carbohydrate and fats impair health and shorten life due by stimulating chronic diseases, including diabetes, cancer and neurodegeneration. The control of circulating glucose and lipid levels involve mitochondria in both central and peripheral mechanisms of metabolism regulation. Mitochondrial uncoupling protein 2 (UCP2) has been implicated in physiological and pathological processes related to glucose and lipid metabolism, and in this review we discuss the latest data on the relationships between UCP2 and glucose and lipid sensing from the perspective of specific hypothalamic neuronal circuits and peripheral tissue func... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5229079 Mon, 12 Sep 2011 04:00:00 +0100 5229079 http://www.medworm.com/index.php?rid=5218546&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907001%26dopt%3DAbstract Authors: Bonizzi G, Cicalese A, Insinga A, Pelicci PG Abstract Among the hundreds of oncogenes and tumor suppressors that have been identified in the past 50 years, p53 is probably the best characterized; nevertheless, new functions are constantly being discovered. As a tumor suppressor, p53 regulates cellular responses to different stress stimuli by inducing reversible cell cycle arrest and DNA repair, or triggering senescence or apoptosis. Recent findings on the regulation of stem cell (SC) division and reprogramming suggest the intriguing possibility that p53 also carries out its tumor suppression function by regulating SC homeostasis. Specifically, p53 activation may counteract SC expansion by several emerging mechanisms including restriction of self-renewing divisions, inhibit... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5218546 Wed, 07 Sep 2011 04:00:00 +0100 5218546 http://www.medworm.com/index.php?rid=5218549&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21890410%26dopt%3DAbstract Authors: Crino PB Abstract The mTOR signaling network functions as a pivotal regulatory cascade during the development of the cerebral cortex. Aberrant hyperactivation of mTOR as a consequence of loss-of-function gene mutations encoding mTOR inhibitor proteins such as TSC1, TSC2, PTEN and STRADα has been recently linked to developmental cortical malformations associated with epilepsy and neurobehavioral disabilities. Investigation of mTOR signaling in these disorders provides for the first time exciting future avenues for assessment of biomarkers, patient stratification and prognostic measures as well as the opportunity for targeted therapy to regulate mTOR activity across all age groups. As we learn more about mTOR and its activity in the developing brain, many challenges will ar... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5218549 Fri, 02 Sep 2011 04:00:00 +0100 5218549 http://www.medworm.com/index.php?rid=5218548&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21890411%26dopt%3DAbstract Authors: Stefater JA, Ren S, Lang RA, Duffield JS Abstract Over the past decade, modern genetic tools have permitted scientists to study the function of myeloid lineage cells, including macrophages, as never before. Macrophages were first detected more than a century ago as cells that ingested bacteria and other microbes, but it is now known that their functional roles are far more numerous. In this review, we focus on the prevailing functions of macrophages beyond their role in innate immunity. We highlight examples of macrophages acting as regulators of development, tissue homoeostasis, remodeling (the reorganization or renovation of existing tissues) and repair. We also detail how modern genetic tools have facilitated new insights into these mysterious cells. PMID: 21890411 ... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5218548 Fri, 02 Sep 2011 04:00:00 +0100 5218548 http://www.medworm.com/index.php?rid=5218547&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21890412%26dopt%3DAbstract Authors: Konkel JE, Chen W Abstract The gastrointestinal mucosal immune system faces unique challenges in dealing not only with fed antigens but also both commensal and pathogenic bacteria. It is tasked with digesting, transporting and using nutritional antigens while protecting the host from pathogenic organisms. As such, mechanisms that mediate effective immunity and immune tolerance are active within the gut environment. To accomplish this, the mucosal immune system has evolved sophisticated mechanisms that safeguard the integrity of the mucosal barrier. Transforming growth factor-β (TGF-β) emerges as a key mediator, balancing the tolerogenic and immunogenic forces at play in the gut. In this review, we discuss the role of TGF-β in the generation and functioning of gut lympho... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5218547 Fri, 02 Sep 2011 04:00:00 +0100 5218547 http://www.medworm.com/index.php?rid=5218550&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21889406%26dopt%3DAbstract Authors: Cnop M, Foufelle F, Velloso LA Abstract The endoplasmic reticulum (ER) stress response, also commonly known as the unfolded protein response (UPR), is an adaptive response used to align ER functional capacity with demand. It is activated in various tissues under conditions related to obesity and type 2 diabetes. Hypothalamic ER stress contributes to inflammation and leptin/insulin resistance. Hepatic ER stress contributes to the development of steatosis and insulin resistance, and components of the UPR regulate liver lipid metabolism. ER stress in enlarged fat tissues induces inflammation and modifies adipokine secretion, and saturated fats cause ER stress in muscle. Finally, prolonged ER stress impairs insulin synthesis and causes pancreatic β cell apoptosis. In this rev... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5218550 Wed, 31 Aug 2011 04:00:00 +0100 5218550 http://www.medworm.com/index.php?rid=5218552&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21885341%26dopt%3DAbstract Authors: Mangold E, Ludwig KU, Nöthen MM Abstract Nonsyndromic orofacial clefts have a multifactorial etiology, involving both genetic and environmental factors. Although linkage and candidate gene studies have attempted to elucidate the underlying genetic architecture, only the interferon regulatory factor 6 (IRF6) gene has been identified as causative. The recent introduction of high-throughput genotyping technologies has enabled researchers to perform genome-wide association studies (GWAS). Four GWAS of nonsyndromic cleft lip with or without cleft palate have been conducted, and these have identified five new chromosomal loci. One locus, located in an intergenic region of chromosome 8q24, has been implicated in all GWAS and constitutes a major susceptibility locus. This review ... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5218552 Tue, 30 Aug 2011 04:00:00 +0100 5218552 http://www.medworm.com/index.php?rid=5218551&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21885342%26dopt%3DAbstract Authors: Hedrich CM, Tsokos GC Abstract The pathogenic origin of autoimmune diseases can be traced to both genetic susceptibility and epigenetic modifications arising from exposure to the environment. Epigenetic modifications influence gene expression and alter cellular functions without modifying the genomic sequence. CpG-DNA methylation, histone tail modifications and microRNAs (miRNAs) are the main epigenetic mechanisms of gene regulation. Understanding the molecular mechanisms that are involved in the pathophysiology of autoimmune diseases is essential for the introduction of effective, target-directed and tolerated therapies. In this review, we summarize recent findings that signify the importance of epigenetic modifications in autoimmune disorders while focusing on systemic l... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5218551 Tue, 30 Aug 2011 04:00:00 +0100 5218551 http://www.medworm.com/index.php?rid=5175029&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862410%26dopt%3DAbstract Authors: Aranke M, Bryan NS, Mian AI PMID: 21862410 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine) Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5175029 Fri, 19 Aug 2011 23:00:00 +0100 5175029 http://www.medworm.com/index.php?rid=5175028&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862411%26dopt%3DAbstract Authors: Brissot P, Bardou-Jacquet E, Jouanolle AM, Loréal O Abstract Iron disorders of genetic origin are mainly composed of iron overload diseases, the most frequent being HFE-related hemochromatosis. Hepcidin deficiency underlies iron overload in HFE-hemochromatosis as well as in several other genetic iron excess disorders, such as hemojuvelin or hepcidin-related hemochromatosis and transferrin receptor 2-related hemochromatosis. Deficiency of ferroportin, the only known cellular protein iron exporter, produces iron overload in the typical form of ferroportin disease. By contrast, genetically enhanced hepcidin production, as observed in matriptase-2 deficiency, generates iron-refractory iron deficiency anemia. Diagnosis of these iron storage disorders is usually established non... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5175028 Thu, 18 Aug 2011 23:00:00 +0100 5175028 http://www.medworm.com/index.php?rid=5175030&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21852192%26dopt%3DAbstract Authors: Babić M, Krmpotić A, Jonjić S Abstract The infection of mice with mouse cytomegalovirus (MCMV) as a model of human cytomegalovirus (HCMV) infection has been particularly informative in elucidating the role of innate and adaptive immune response mechanisms during infection. Millions of years of co-evolution between cytomegaloviruses (CMV) and their hosts has resulted in numerous attempts to overwhelm each other. CMVs devote many genes to modulating the host natural killer (NK) cell response and NK cells employ many strategies to cope with CMV infection. While focusing on these attack-counterattack measures, this review will discuss several novel mechanisms of immune evasion by MCMV, the role of Ly49 receptors in mediating resistance to MCMV, and the impact of the initial... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5175030 Mon, 15 Aug 2011 23:00:00 +0100 5175030 http://www.medworm.com/index.php?rid=5097673&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21816674%26dopt%3DAbstract Authors: Kodiha M, Stochaj U PMID: 21816674 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine) Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5097673 Mon, 01 Aug 2011 23:00:00 +0100 5097673 http://www.medworm.com/index.php?rid=5097672&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21816675%26dopt%3DAbstract Authors: Quarta C, Mazza R, Obici S, Pasquali R, Pagotto U Dysregulation of the endocannabinoid system (ECS) is a universal and, perhaps, causative feature of obesity. Central nervous system (CNS) circuits that regulate food intake were initially believed to be the targets for dysregulation. However, it is increasingly evident that endocannabinoids affect food intake, energy expenditure and substrate metabolism by acting on peripheral sites. Cannabinoid type 1 receptor (CB1r) antagonists can effectively treat obesity and associated metabolic alterations but, unfortunately, cause and exacerbate mood disorders. Drugs restricted to act on peripheral CB1rs might be safer and more effective, retaining the anti-obesity effects but lacking the adverse neurodepressive reactions. This review su... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5097672 Mon, 01 Aug 2011 23:00:00 +0100 5097672 http://www.medworm.com/index.php?rid=5097674&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21813326%26dopt%3DAbstract Authors: Soreq H, Wolf Y Recent reports of microRNA (miR) modulators of both neuronal and immune processes (here termed NeurimmiRs) predict therapeutic potential for manipulating NeurimmiR levels in diseases affecting both the immune system and higher brain functions, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS) and anxiety-related disorders. In our opinion, NeurimmiRs that function within both the nervous and the immune systems, such as miR-132 and miR-124, may act as 'negotiators' between these two interacting compartments. We suggest that NeurimmiRs primarily target transcriptional or other regulatory genes, which enables modulation of both immune and cognitive processes through direct or indirect alterations of neuron-glia and/or brain-to-body... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5097674 Sun, 31 Jul 2011 23:00:00 +0100 5097674 http://www.medworm.com/index.php?rid=5097675&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21802991%26dopt%3DAbstract Authors: Chang SH, Hla T Once mRNAs are transcribed, spliced and transported to the cytoplasm, their fate is determined by the complex interplay of RNA binding proteins (RBPs) and microRNAs (miRNAs) that act on regulatory elements within the transcripts. The importance of post-transcriptional regulatory mechanisms in angiogenesis is underscored by the observation that perturbations in miRNAs and/or RBPs lead to profound phenotypic alterations in vascular development, homeostasis and disease, with current data suggesting that mRNAs for key angiogenic regulators (secreted factors and intracellular signaling intermediates) are subject to stringent post-transcriptional regulation by both RBPs and miRNAs. In addition, an intricate network of miRNAs and RBPs allow robust gene regulation in v... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5097675 Thu, 28 Jul 2011 23:00:00 +0100 5097675 http://www.medworm.com/index.php?rid=5097676&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21802362%26dopt%3DAbstract Authors: Bayry J PMID: 21802362 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine) Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5097676 Wed, 27 Jul 2011 23:00:00 +0100 5097676 http://www.medworm.com/index.php?rid=5097677&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21795114%26dopt%3DAbstract Authors: Ho A, Shen J The presenilin genes harbor approximately 90% of mutations linked to early-onset familial Alzheimer's disease (FAD), but how these mutations cause the disease is still being debated. Genetic analysis in Drosophila and mice demonstrate that presenilin plays essential roles in synaptic function, learning and memory, as well as neuronal survival in the adult brain, and the FAD-linked mutations alter the normal function of presenilin in these processes. Presenilin has also been reported to regulate the calcium homeostasis of intracellular stores, and presynaptic presenilin controls neurotransmitter release and long-term potentiation through modulation of calcium release from intracellular stores. In this review, we highlight recent advances in deciphering the role of ... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5097677 Sun, 24 Jul 2011 23:00:00 +0100 5097677 http://www.medworm.com/index.php?rid=5097679&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21783421%26dopt%3DAbstract Authors: Kissler S Autoimmunity cannot yet be prevented or cured, in large part due to our poor understanding of disease etiology. Remarkable advances in genomic technology have recently enabled the discovery of a large number of disease-associated gene variations by genome-wide association studies. The next step towards understanding autoimmune disorders entails the functional study of susceptibility genes within experimental disease models. RNA interference (RNAi) is a promising tool for such investigations. Several features of RNAi, including its specificity, versatility and reversible nature, allow experimental systems to be tailored to relevant gene variations. This review discusses how the experimental use of RNAi is invaluable in bridging the gap between the identification of su... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5097679 Wed, 20 Jul 2011 23:00:00 +0100 5097679 http://www.medworm.com/index.php?rid=5097678&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21783422%26dopt%3DAbstract Authors: Cohen TJ, Lee VM, Trojanowski JQ Given the critical role for TDP-43 in diverse neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP), there has been a recent surge in efforts to understand the normal functions of TDP-43 and the molecular basis of dysregulation that occurs in TDP-43 proteinopathies. Here, we highlight recent findings examining TDP-43 molecular functions with particular emphasis on stress-mediated regulation of TDP-43 localization, putative downstream TDP-43 target genes and RNAs, as well as TDP-43 interacting proteins, all of which represent viable points of therapeutic intervention for ALS, FTLD-TDP and related proteinopathies. Finally, we review current mouse models of TDP-43 and discuss thei... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5097678 Wed, 20 Jul 2011 23:00:00 +0100 5097678 http://www.medworm.com/index.php?rid=5051666&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21775207%26dopt%3DAbstract Authors: Ibraghimov-Beskrovnaya O, Natoli TA Polycystic kidney diseases (PKDs) comprise a large group of genetic disorders characterized by formation of cysts in the kidneys and other organs, ultimately leading to end-stage renal disease. Although PKDs can be caused by mutations in different genes, they converge on a set of common molecular mechanisms involved in cystogenesis and ciliary dysfunction, and can be qualified as ciliopathies. Recent advances in understanding the mechanisms regulating disease progression have led to the development of new therapies that are being tested in both preclinical and clinical trials. In this article, we briefly review a network of molecular pathways of cystogenesis that are regulated by ciliary functions. We discuss the mTOR pathway in depth, highl... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5051666 Sun, 17 Jul 2011 23:00:00 +0100 5051666 http://www.medworm.com/index.php?rid=5051665&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21775208%26dopt%3DAbstract Authors: Grivas PD, Kiaris H, Papavassiliou AG PMID: 21775208 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine) Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5051665 Sun, 17 Jul 2011 23:00:00 +0100 5051665 http://www.medworm.com/index.php?rid=5051667&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21764377%26dopt%3DAbstract Authors: Raimundo N, Baysal BE, Shadel GS A role for mitochondria in tumor formation is suggested by mutations in enzymes of the TCA cycle: isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH) and fumarate hydratase (FH). Although they are all components of the TCA cycle, the resulting clinical presentations do not overlap. Activation of the hypoxia pathway can explain SDH phenotypes, but recent data suggest that FH and IDH mutations lead to tumor formation by repressing cellular differentiation. In this review, we discuss recent findings in the context of both mitochondrial and cytoplasmic components of the TCA cycle, and we propose that extrametabolic roles of TCA cycle metabolites result in reduced cellular differentiation. Furthermore, activation of the pseudohypoxia pathw... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5051667 Thu, 14 Jul 2011 23:00:00 +0100 5051667 http://www.medworm.com/index.php?rid=5051669&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763201%26dopt%3DAbstract Authors: Friedrichs K, Klinke A, Baldus S The pathophysiology of atrial fibrillation (AF) remains incompletely understood, despite its prevalence and contributing role in stroke and heart failure. Whereas previous studies have focused on the electrophysiological characteristics of AF, recent reports shed light on structural remodeling of the atria as a prerequisite for AF. Recent evidence suggests that atrial fibrosis is linked not only to stimulation of myocytes and fibroblasts, but also to the activation state of leukocytes. Recruitment of leukocytes with the release of reactive oxygen species, cytokines and growth factors is followed by increased matrix deposition, which leads to adverse atrial remodeling and suggests that inflammatory pathways are a prerequisite for AF. Here we rev... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5051669 Tue, 12 Jul 2011 23:00:00 +0100 5051669 http://www.medworm.com/index.php?rid=5051668&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763202%26dopt%3DAbstract Authors: Renvoisé A, Merhej V, Georgiades K, Raoult D The order Rickettsiales comprises obligate intracellular bacteria that are the ancestors of modern eukaryotes. These bacteria infect various vectors and hosts, with some species being pathogenic to man. Rickettsiales have small, degraded genomes and provide a paradigm for increased pathogenicity despite gene loss; significant levels of genetic exchange occur between bacteria that infect the same host and with the eukaryotic hosts themselves. Crosstalk between host and bacteria appears to be mediated by a Type IV secretion system and proteins containing eukaryotic-like repeat motifs. Rickettsiales also manipulate host reproduction and induce host resistance to viruses. Manipulation of its host by Rickettsiales has long been misunder... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5051668 Tue, 12 Jul 2011 23:00:00 +0100 5051668 http://www.medworm.com/index.php?rid=5051673&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21737347%26dopt%3DAbstract Authors: Borrmann S, Matuschewski K The worldwide burden of malaria can be substantially reduced using existing public health interventions. However, elimination of Plasmodium will require fundamentally different approaches. Novel experimental attenuation strategies for active immunization using knockout strains have recently stimulated renewed interest in whole-parasite vaccine approaches. Preventive drug administration during transmission of wild-type sporozoites is a complementary strategy for eliciting protective immune responses. These whole-cell immunization strategies are based on one fundamental principle: inducing protection by blocking parasite conversion from the clinically silent liver phase to the pathogenic intra-erythrocytic replication cycle. Here, we review the basis, ... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5051673 Wed, 06 Jul 2011 23:00:00 +0100 5051673 http://www.medworm.com/index.php?rid=5051671&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21741880%26dopt%3DAbstract Authors: Jacquet A House dust mite (HDM) allergy is a frequent inflammatory disease found worldwide. Although allergen-specific CD4(+) Th2 cells orchestrate the HDM allergic response, notably through induction of IgE directed towards mite allergens, recent studies have demonstrated that innate immunity activation also plays a critical role in HDM-induced allergy pathogenesis. HDM allergens can not only be considered proteins that induce adaptive Th2-biased responses in susceptible subjects but also as strong activators of innate immune cells, including skin keratinocytes and airway epithelial cells. The contribution of microbial adjuvant factors, derived from HDM carriers or the environment, is also essential in such cell stimulation. This review highlights how HDM allergens, together ... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5051671 Wed, 06 Jul 2011 23:00:00 +0100 5051671 http://www.medworm.com/index.php?rid=5051670&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21741881%26dopt%3DAbstract Authors: Walsh JT, Kipnis J Regulatory CD4(+)CD25(+)Foxp3(+) T cells (Tregs) have been the focus of significant attention for their role in controlling immune responses. Although knowledge of Treg biology has burgeoned, wide gaps remain in our understanding of Treg function under both normal and pathological conditions. Pioneering studies demonstrated roles for Tregs in cancer and autoimmune diseases, including experimental autoimmune encephalitis, and this knowledge is often applied to other pathologies including neurodegenerative conditions. However, differences between immunity in neurodegeneration and in malignancy or autoimmunity are often neglected. Thus, Treg manipulations in central nervous system (CNS) neurodegenerative conditions often yield unexpected outcomes. In this piece... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5051670 Wed, 06 Jul 2011 23:00:00 +0100 5051670 http://www.medworm.com/index.php?rid=5051672&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21741311%26dopt%3DAbstract Authors: Vereecke L, Beyaert R, van Loo G The intestinal epithelium is the largest surface area of the body in contact with the external environment. This specialized single cell layer is constantly renewed and is a physical barrier that separates intestinal microbiota from underlying tissues, preventing bacterial infiltration and subsequent inflammation. Specialized secretory epithelial cell types such as Paneth cells and goblet cells limit bacterial adhesion and infiltration by secreting antibacterial peptides and mucins, respectively. Rapid cell renewal coincides with apical exfoliation of 'old' enterocytes without compromising epithelial barrier integrity. When the intestinal epithelium is inflamed barrier integrity can be compromised, due to uncontrolled death of enterocytes allow... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5051672 Tue, 05 Jul 2011 23:00:00 +0100 5051672 http://www.medworm.com/index.php?rid=5001977&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21724465%26dopt%3DAbstract Authors: Lobito AA, Gabriel TL, Medema JP, Kimberley FC The tumor necrosis factor (TNF) and TNF receptor (TNFR) superfamilies comprise multidomain proteins with diverse roles in cell activation, proliferation and cell death. These proteins play pivotal roles in the initiation, maintenance and termination of immune responses and have vital roles outside the immune system. The discovery and analysis of diseases associated with mutations in these families has revealed crucial mechanistic details of their normal functions. This review focuses on mutations causing four different diseases, which represent distinct pathological mechanisms that can exist within these superfamilies: autoimmune lymphoproliferative syndrome (ALPS; FAS mutations), common variable immunodeficiency (CVID; TACI mutat... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5001977 Fri, 01 Jul 2011 23:00:00 +0100 5001977 http://www.medworm.com/index.php?rid=5001976&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21724466%26dopt%3DAbstract Authors: Degirolamo C, Modica S, Palasciano G, Moschetta A Colorectal cancer is the third most common malignancy worldwide and is often linked to obesity, a sedentary lifestyle, carbohydrate- and fat-rich diets and elevated fecal excretion of secondary bile acids. Accumulation of toxic bile acids triggers oxidative damage, mitochondrial dysfunction and tumor progression. Nuclear receptors are transcription factors crucially involved in the regulation of bile acid metabolism and detoxification, and their activation may confer protection from bile acid tumor-promoting activity. In this review, we explore the tangled relationships among bile acids, nuclear receptors and the intestinal epithelium, with particular emphasis on the role of the farnesoid X receptor in colorectal cancer prevent... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5001976 Fri, 01 Jul 2011 23:00:00 +0100 5001976 http://www.medworm.com/index.php?rid=5001975&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21724467%26dopt%3DAbstract Authors: Gomes-Pereira M, Cooper TA, Gourdon G DNA repeat expansions can result in the production of toxic RNA. RNA toxicity has been best characterised in the context of myotonic dystrophy. Nearly 20 mouse models have contributed significant and complementary insights into specific aspects of this novel disease mechanism. These models provide a unique resource to test pharmacological, anti-sense, and gene-therapy therapeutic strategies that target specific events of the pathobiological cascade. Further proof-of-principle concept studies and preclinical experiments require critical and thorough analysis of the multiple myotonic dystrophy transgenic lines available. This review provides in-depth assessment of the molecular and phenotypic features of these models and their contribution t... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5001975 Fri, 01 Jul 2011 23:00:00 +0100 5001975 http://www.medworm.com/index.php?rid=5001978&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723784%26dopt%3DAbstract Authors: Westbroek W, Gustafson AM, Sidransky E Clinical, genetic and pathological studies demonstrate that mutations in glucocerebrosidase (GBA), which encodes the lysosomal enzyme deficient in Gaucher disease (GD), are risk factors for Parkinson disease (PD) and related disorders. Some patients with GD and Gaucher carriers develop parkinsonism. Furthermore, subjects with PD have an increased frequency of GBA mutations. GBA-mutation carriers exhibit diverse parkinsonian phenotypes and have glucocerebrosidase-positive Lewy bodies. Although the mechanism for this association is unknown, we present several theories, including protein aggregation, prion transmission, lipid accumulation and impaired autophagy, mitophagy or trafficking. Each model has inherent limitations, and a second-hit ... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5001978 Wed, 29 Jun 2011 23:00:00 +0100 5001978 http://www.medworm.com/index.php?rid=5001979&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21703926%26dopt%3DAbstract Authors: Davis RP, van den Berg CW, Casini S, Braam SR, Mummery CL Recent advances in pluripotent stem cell biology now make it possible to generate human cardiomyocytes in vitro from both healthy individuals and from patients with cardiac abnormalities. This offers unprecedented opportunities to study cardiac disease development 'in a dish' and establish novel platforms for drug discovery, either to prevent disease progression or to reverse it. In this review paper, we discuss some of the genetic diseases that affect the heart and illustrate how these new paradigms could assist our understanding of cardiac pathogenesis and aid in drug discovery. In particular, we highlight the limitations of other commonly used model systems in predicting the consequences of drug exposure on the human... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5001979 Tue, 21 Jun 2011 23:00:00 +0100 5001979 http://www.medworm.com/index.php?rid=5001980&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21700497%26dopt%3DAbstract Authors: Bortoluzzi S, Biasiolo M, Bisognin A PMID: 21700497 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine) Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5001980 Mon, 20 Jun 2011 23:00:00 +0100 5001980 http://www.medworm.com/index.php?rid=4958352&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21652264%26dopt%3DAbstract Authors: Rukov JL, Shomron N The field of pharmacogenomics aims to predict which drugs will be most effective and safe for a particular individual based on their genome sequence or expression profile, thereby allowing personalized treatment. The bulk of pharmacogenomic research has focused on the role of single nucleotide polymorphisms, copy number variations or differences in gene expression levels of drug metabolizing or transporting genes and drug targets. In this review paper, we focus instead on microRNAs (miRNAs): small noncoding RNAs, prevalent in metazoans, that negatively regulate gene expression in many cellular processes. We discuss how miRNAs, by regulating the expression of pharmacogenomic-related genes, can play a pivotal role in drug efficacy and toxicity and have potent... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4958352 Sun, 05 Jun 2011 23:00:00 +0100 4958352 http://www.medworm.com/index.php?rid=4909433&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21620769%26dopt%3DAbstract Authors: Griciuc A, Aron L, Ueffing M Mutations that cause rhodopsin misfolding and retention within the endoplasmic reticulum (ER) are a prominent cause of retinitis pigmentosa. Here, we discuss the hypothesis that the failure of photoreceptor neurons to adapt to the stress caused by rhodopsin accumulation in the ER leads to a global collapse of homeostasis and to retinal degeneration. We review the molecular mechanisms underlying the activity of local ER conformational sensors and stress-relaying modules and consider how ER-derived stress signals are amplified and implemented to impact on downstream processes, including rhodopsin clearance and cell fate control. The emerging view is that alterations to the systems responsible for the detection, transduction and implementation of ER s... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4909433 Tue, 24 May 2011 23:00:00 +0100 4909433 http://www.medworm.com/index.php?rid=4857538&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21602104%26dopt%3DAbstract Authors: Whittle AJ, López M, Vidal-Puig A Current therapeutic strategies are proving inadequate to deal with growing obesity rates because of the inherent resistance of the human body to weight loss. The activation of human brown adipose tissue (BAT) represents an opportunity to increase energy expenditure and weight loss alongside improved lipid and glucose homeostasis. Research into the regulation of BAT has made increasing the thermogenic capacity of an individual to treat metabolic disease a plausible strategy, despite thermogenesis being under tight central nervous system control. Previous therapies targeted at the sympathetic nervous system have had deleterious effects because of a lack of organ specificity, but advances in our understanding of central BAT regulatory systems mi... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4857538 Thu, 19 May 2011 23:00:00 +0100 4857538 http://www.medworm.com/index.php?rid=4804489&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21514224%26dopt%3DAbstract Authors: Song JJ, Ott HC End-organ failure is one of the major healthcare challenges in the Western world. Yet, donor organ shortage and the need for immunosuppression limit the impact of transplantation. The regeneration of whole organs could theoretically overcome these hurdles. Early milestones have been met by combining stem and progenitor cells with increasingly complex scaffold materials and culture conditions. Because the native extracellular matrix (ECM) guides organ development, repair and physiologic regeneration, it provides a promising alternative to synthetic scaffolds and a foundation for regenerative efforts. Perfusion decellularization is a novel technology that generates native ECM scaffolds with intact 3D anatomical architecture and vasculature. This review summarizes... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804489 Tue, 19 Apr 2011 23:00:00 +0100 4804489 http://www.medworm.com/index.php?rid=4804488&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21514225%26dopt%3DAbstract Authors: Ramamoorthi K, Lin Y GABA (γ-aminobutyric acid) is the major inhibitory neurotransmitter in the brain. The GABAergic system is indispensable for maintaining the balance between excitation and inhibition (E/I balance) required for normal neural circuit function. E/I imbalances that result from perturbations in the development of this system, ranging from the generation of inhibitory neurons to the formation of their synaptic connections, have been implicated in several neurodevelopmental disorders. In this review, we discuss how impairments at different stages in GABAergic development can lead to disease states. We also highlight recent studies which show that modulation of the GABAergic system can successfully reverse cognitive deficits in disease models and suggest that ther... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804488 Tue, 19 Apr 2011 23:00:00 +0100 4804488 http://www.medworm.com/index.php?rid=4804487&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21514226%26dopt%3DAbstract Authors: Pyne S, Pyne NJ Sphingosine 1-phosphate (S1P) is a bioactive lipid that has both physiological and pathophysiological roles. It regulates cellular processes such as proliferation, migration, survival and differentiation and affects all organ systems. S1P not only activates S1P-specific receptors to initiate cellular signalling pathways but also directly regulates specific intracellular target proteins. The therapeutic opportunities surrounding S1P signalling are numerous and exemplified by the recent approval of FTY720 (a sphingosine analogue, Gilenya™) for the treatment of relapsing multiple sclerosis. A major focus of research is to develop small-molecule antagonists/agonists/inhibitors that are specific to the different S1P receptor subtypes and the enzymes that regulate ... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804487 Tue, 19 Apr 2011 23:00:00 +0100 4804487 http://www.medworm.com/index.php?rid=4804490&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21507717%26dopt%3DAbstract Authors: Ogbomo H, Cinatl J, Mody CH, Forsyth PA Malignant gliomas (MGs) are deadly brain tumors with a median survival after resection, radiotherapy and chemotherapy of only 12 months. The natural immunosuppressive state of MG patients and the locally restricted growth of MGs render this neoplasm an excellent target for immunotherapy. Consequently, several failed attempts were made to treat MGs with immune cells. Recent preclinical experimental studies, however, demonstrate that natural killer (NK) cells can kill MGs and therefore hold promise in immunotherapy of MGs. This review describes the experimental and clinical evidence that support the potential of NK cells in therapy of MGs as well as the limitations to NK therapy. Finally, we propose strategies that could circumvent mitigat... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804490 Mon, 18 Apr 2011 23:00:00 +0100 4804490 http://www.medworm.com/index.php?rid=4804493&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21481637%26dopt%3DAbstract Authors: Saharinen P, Eklund L, Pulkki K, Bono P, Alitalo K Solid tumors require blood vessels for growth and dissemination, and lymphatic vessels as additional conduits for metastatic spread. The identification of growth factor receptor pathways regulating angiogenesis has led to the clinical approval of the first antiangiogenic molecules targeted against the vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR)-2 pathway. However, in many cases resistance to anti-VEGF-VEGFR therapy occurs, and thus far the clinical benefit has been limited to only modest improvements in overall survival. Therefore, novel treatment modalities are required. Here, we discuss the members of the VEGF-VEGFR family as well as the angiopoietin growth factors and their Tie receptors as potential nov... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804493 Thu, 07 Apr 2011 23:00:00 +0100 4804493 http://www.medworm.com/index.php?rid=4804492&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21482187%26dopt%3DAbstract Authors: Patterson PH Recent studies have highlighted a connection between infection during pregnancy and the increased risk of autism in the offspring. Parallel studies of cerebral spinal fluid, blood and postmortem brains reveal an ongoing, hyper-responsive inflammatory-like state in many young as well as adult autism subjects. There are also indications of gastrointestinal problems in at least a subset of autistic children. Work on the maternal infection risk factor using animal models indicates that aspects of brain and peripheral immune dysregulation can begin during fetal development and continue through adulthood. The offspring of infected or immune-activated dams also display cardinal behavioral features of autism, as well as neuropathology consistent with that seen in human au... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804492 Wed, 06 Apr 2011 23:00:00 +0100 4804492 http://www.medworm.com/index.php?rid=4804491&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21482188%26dopt%3DAbstract Authors: Polajnar M, Zerovnik E In recent years, research into the molecular bases of neurodegenerative diseases has progressed, and therapies have been developed to combat the causative agents. Based on the observation that progressive myoclonus epilepsies (PMEs) and neurodegenerative diseases share common features of neurodegeneration, we propose that the two pathologies share common underlying molecular characteristics. It is well documented that autophagy is overloaded or impaired in neurodegenerative conditions, and it is also impaired in some PMEs, the clearest example being EPM2 (Lafora disease). Although more research into this connection is warranted, we propose that existing therapies for PMEs could be augmented with similar drugs as those used for neurodegenerative diseases.... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804491 Wed, 06 Apr 2011 23:00:00 +0100 4804491 http://www.medworm.com/index.php?rid=4697572&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21459041%26dopt%3DAbstract Authors: Boutten A, Goven D, Artaud-Macari E, Boczkowski J, Bonay M Several convergent destructive mechanisms such as oxidative stress, alveolar cell apoptosis, extracellular matrix proteolysis and chronic inflammation contribute to chronic obstructive pulmonary disease (COPD) development. Evidence suggests that oxidative stress contributes to the pathophysiology of COPD, particularly during exacerbations. Nuclear factor erythroid-2-related factor 2 (NRF2), a transcription factor expressed predominantly in epithelium and alveolar macrophages, has an essential protective role in the lungs through the activation of antioxidant response element-regulated antioxidant and cytoprotective genes. Animal models and human studies have identified NRF2 and several NRF2 target genes as a protective... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4697572 Thu, 31 Mar 2011 23:00:00 +0100 4697572 http://www.medworm.com/index.php?rid=4697573&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21439907%26dopt%3DAbstract Authors: Rowell JL, McCarthy DO, Alvarez CE Studies using dogs provide an ideal solution to the gap in animal models for natural disease and translational medicine. This is evidenced by approximately 400 inherited disorders being characterized in domesticated dogs, most of which are relevant to humans. There are several hundred isolated populations of dogs (breeds) and each has a vastly reduced genetic variation compared with humans; this simplifies disease mapping and pharmacogenomics. Dogs age five- to eight-fold faster than do humans, share environments with their owners, are usually kept until old age and receive a high level of health care. Farseeing investigators recognized this potential and, over the past decade, have developed the necessary tools and infrastructure to utilize... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4697573 Wed, 23 Mar 2011 00:00:00 +0100 4697573 http://www.medworm.com/index.php?rid=4639471&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21429800%26dopt%3DAbstract Authors: Peter CJ, Akbarian S Alterations in histone lysine methylation and other epigenetic regulators of gene expression contribute to changes in brain transcriptomes in mood and psychosis spectrum disorders, including depression and schizophrenia. Genetic association studies and animal models implicate multiple lysine methyltransferases and demethylases in the neurobiology of emotion and cognition. Here, we review the role of histone lysine methylation and transcriptional regulation in normal and diseased neurodevelopment and discuss various methyltransferases and demethylases as potential therapeutic targets in the treatment of neuropsychiatric disease. PMID: 21429800 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine) Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4639471 Mon, 21 Mar 2011 00:00:00 +0100 4639471 http://www.medworm.com/index.php?rid=4639474&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21411369%26dopt%3DAbstract Authors: Qureshi IA, Mehler MF Non-coding RNAs (ncRNAs) and their associated regulatory networks are increasingly being implicated in mediating a complex repertoire of neurobiological functions. Cognitive and behavioral processes are proving to be no exception. In this review, we discuss the emergence of many novel, diverse and rapidly expanding classes and subclasses of short and long ncRNAs. We briefly review the life cycles and molecular functions of these ncRNAs. We also examine how ncRNA circuitry mediates brain development, plasticity, stress responses and aging, and highlight its potential roles in the pathophysiology of cognitive disorders, including neural developmental and age-associated neurodegenerative diseases, as well as those that manifest throughout the lifespan. P... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4639474 Mon, 14 Mar 2011 00:00:00 +0100 4639474 http://www.medworm.com/index.php?rid=4639473&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21411370%26dopt%3DAbstract Authors: Bai RY, Staedtke V, Riggins GJ Despite advances in treatment for glioblastoma multiforme (GBM), patient prognosis remains poor. Although there is growing evidence that molecular targeting could translate into better survival for GBM, current clinical data show limited impact on survival. Recent progress in GBM genomics implicate several activated pathways and numerous mutated genes. This molecular diversity can partially explain therapeutic resistance and several approaches have been postulated to target molecular changes. Furthermore, most drugs are unable to reach effective concentrations within the tumor owing to elevated intratumoral pressure, restrictive vasculature and other limiting factors. Here, we describe the preclinical and clinical developments in treatment strate... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4639473 Mon, 14 Mar 2011 00:00:00 +0100 4639473 http://www.medworm.com/index.php?rid=4639472&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21411371%26dopt%3DAbstract Authors: Makhlouf M, Rougeulle C Silencing one X chromosome is essential for the development of female mammals, but the regulation of this process appears to vary between species. In the mouse, which has thus far been the leading model system in the field, X chromosome inactivation (XCI) is tightly coupled to pluripotency and the underlying mechanisms have just begun to be deciphered. However, mechanistic aspects of XCI regulation in other species have yet to be thoroughly investigated. Here we review current knowledge of the developmental regulation of XCI in mice and humans and discuss the extent to which the intimate link between XCI and pluripotency extends beyond rodents. PMID: 21411371 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine) Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4639472 Mon, 14 Mar 2011 00:00:00 +0100 4639472 http://www.medworm.com/index.php?rid=4580321&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21388883%26dopt%3DAbstract Authors: He Y, Hoskins JM, McLeod HL Variation in drug efficacy and toxicity remains an important clinical concern. Presently, single nucleotide polymorphisms (SNPs) only explain a portion of this problem, even in situations where the pharmacological trait is clearly heritable. The Human CNV Project identified copy number variations (CNVs) across approximately 12% of the human genome, and these CNVs were considered causes of diseases. Although the contribution of CNVs to the pathogenesis of many common diseases is questionable, CNVs play a clear role in drug-related genes by altering drug metabolizing and drug response. In this review, we provide a comprehensive evaluation of the clinical relevance of CNVs to drug efficacy, toxicity, and disease prevalence in world populations, and dis... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4580321 Mon, 07 Mar 2011 00:00:00 +0100 4580321 http://www.medworm.com/index.php?rid=4580320&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21388884%26dopt%3DAbstract Authors: Mesko B, Poliska S, Nagy L Gene expression profiling in clinical genomics has yet to deliver robust and reliable approaches for developing diagnostics and contributing to personalized medicine. Owing to technological developments and the recent accumulation of expression profiles, it is a timely and relevant question whether peripheral blood gene expression profiling can be used routinely in clinical decision making. Here, we review the available gene expression profiling data of peripheral blood in autoimmune and chronic inflammatory diseases and suggest that peripheral blood mononuclear cells are suitable for descriptive and comparative gene expression analyses. A gene-disease interaction network in chronic inflammatory diseases, a general protocol for future studies and a d... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4580320 Mon, 07 Mar 2011 00:00:00 +0100 4580320 http://www.medworm.com/index.php?rid=4580325&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21376665%26dopt%3DAbstract Authors: Perl A, Hanczko R, Telarico T, Oaks Z, Landas S Metabolism of glucose through the pentose phosphate pathway (PPP) influences the development of diverse pathologies. Hemolytic anemia due to deficiency of PPP enzyme glucose 6-phosphate dehydrogenase is the most common genetic disease in humans. Recently, inactivation of another PPP enzyme, transaldolase (TAL), has been implicated in male infertility and fatty liver progressing to steatohepatitis and cancer. Hepatocarcinogenesis was associated with activation of aldose reductase and redox-sensitive transcription factors and prevented by N-acetylcysteine. In this paper, we discuss how alternative formulations of the PPP with and without TAL reflect cell type-specific metabolic control of oxidative stress, a crucial source of infla... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4580325 Wed, 02 Mar 2011 00:00:00 +0100 4580325 http://www.medworm.com/index.php?rid=4580324&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21376666%26dopt%3DAbstract Authors: Kong HH Recent advances in DNA sequencing methodology have facilitated studies of human skin microbes that circumvent difficulties in isolating and characterizing fastidious microbes. Sequence-based approaches have identified a greater diversity of cutaneous bacteria than studies using traditional cultivation techniques. However, improved sequencing technologies and analytical methods are needed to study all skin microbes, including bacteria, archaea, fungi, viruses and mites, and how they interact with each other and their human hosts. This review discusses current skin microbiome research, with a primary focus on bacteria, and the challenges facing investigators striving to understand how skin microorganisms contribute to health and disease. PMID: 21376666 [PubMed - as s... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4580324 Wed, 02 Mar 2011 00:00:00 +0100 4580324 http://www.medworm.com/index.php?rid=4580323&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21376667%26dopt%3DAbstract Authors: Masters SL, O'Neill LA The pathogenesis of type 2 diabetes, Alzheimer's disease and amyotrophic lateral sclerosis continues to be debated. Recently, the inflammasome protein complex has been shown to be a key regulator of IL-1β, a cytokine implicated in each of these diseases. In all three cases, it is now apparent that unique protein aggregates caused by inappropriate oligomerization or misfolding are sensed by the inflammasome, providing a unifying mechanism for this IL-1β production. What evolved as an innate defense against infection-related particles, therefore, now seems to be a driving force for inflammation in these diseases. This review discusses the basic research behind these findings and the potential for new therapeutic interventions this affords. PMID: 2137... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4580323 Wed, 02 Mar 2011 00:00:00 +0100 4580323 http://www.medworm.com/index.php?rid=4580322&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21376668%26dopt%3DAbstract Authors: Andorfer CA, Necela BM, Thompson EA, Perez EA Recognition that breast cancer is a heterogeneous disease in which each patient's tumor has specific characteristics has led to a search for biomarkers and combinations of markers (signatures) to improve the diagnosis, prognostic classification and prediction of therapeutic benefit versus toxicity for individual tumors and patients. Many microRNAs (miRNAs) are aberrantly expressed in cancer and seem to influence tumor behavior and progression. miRNAs have great potential to evolve into effective biomarkers in the clinic because of their extreme stability and ease of detection. However, there are several major technical challenges as well as numerous discrepancies among currently reported miRNA signatures. In this review, we discuss... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4580322 Wed, 02 Mar 2011 00:00:00 +0100 4580322 http://www.medworm.com/index.php?rid=4580326&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21367659%26dopt%3DAbstract Authors: Greulich H, Pollock PM Fibroblast growth factor receptors (FGFRs) play diverse roles in the control of cell proliferation, cell differentiation, angiogenesis and development. Activating the mutations of FGFRs in the germline has long been known to cause a variety of skeletal developmental disorders, but it is only recently that a similar spectrum of somatic FGFR mutations has been associated with human cancers. Many of these somatic mutations are gain-of-function and oncogenic and create dependencies in tumor cell lines harboring such mutations. A combination of knockdown studies and pharmaceutical inhibition in preclinical models has further substantiated genomically altered FGFR as a therapeutic target in cancer, and the oncology community is responding with clinical trials ... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4580326 Mon, 28 Feb 2011 00:00:00 +0100 4580326 http://www.medworm.com/index.php?rid=4580327&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21354374%26dopt%3DAbstract Authors: Chan E, Prado DE, Weidhaas JB MicroRNAs (miRNAs) are key regulators of gene expression that regulate important oncogenes and tumor suppressors. Many miRNAs can also act as oncogenes or tumor suppressors, and thus the altered expression of miRNAs is a hallmark of many cancer types. Dysregulated miRNAs provide a potentially powerful new tool that could be used to enable the characterization of tumor environments and identify novel and important oncogenic pathways. More recently, there has been growing interest in the field of miRNAs as biomarkers of cancer risk, diagnosis and response to therapy. Understanding the associations between miRNA expression and cancer phenotypes, and the potential of miRNA profiling in clinical applications, promises to be highly rewarding in the fiel... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4580327 Thu, 24 Feb 2011 00:00:00 +0100 4580327 http://www.medworm.com/index.php?rid=4580328&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21353638%26dopt%3DAbstract We describe the current panel of optogenetic probes, methods of targeting these probes to specific cell types in the nervous system, and strategies of photostimulating cells in awake, behaving animals. Finally, we survey the application of optogenetic tools to studying functional neuroanatomy, behavior and the etiology and treatment of various neurological disorders. PMID: 21353638 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine) Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4580328 Wed, 23 Feb 2011 00:00:00 +0100 4580328 http://www.medworm.com/index.php?rid=4525692&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21345730%26dopt%3DAbstract Authors: Bangalore S PMID: 21345730 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine) Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4525692 Mon, 21 Feb 2011 00:00:00 +0100 4525692 http://www.medworm.com/index.php?rid=4525691&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21345731%26dopt%3DAbstract Authors: Banerjee Y, Taranikanti V, Alriyami M PMID: 21345731 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine) Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4525691 Mon, 21 Feb 2011 00:00:00 +0100 4525691 http://www.medworm.com/index.php?rid=4525693&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21334976%26dopt%3DAbstract Authors: Passini MA, Cheng SH Spinal muscular atrophy (SMA) is a neuromuscular disease caused by a deficiency of functional SMN protein because of mutations in SMN1. A decrease in SMN activity results in motor neuron cell loss in the spinal cord, leading to a weakness of the proximal muscles responsible for crawling, walking, head/neck control and swallowing as well as the involuntary muscles that control breathing and coughing. Thus, patients present with pulmonary manifestations, paralysis and a shortened lifespan. Gene therapy is emerging as a promising therapeutic strategy for SMA given that the molecular basis for this monogenic disorder is well established. Recent advances and findings from preclinical studies in animal models provide optimism that gene therapy might be an effect... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4525693 Fri, 18 Feb 2011 00:00:00 +0100 4525693 http://www.medworm.com/index.php?rid=4471121&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21310659%26dopt%3DAbstract Authors: Lai TW, Shyu WC, Wang YT Despite abundant evidence from basic/preclinical research that excessive NMDAR (N-methyl-d-aspartate receptor) stimulation is a crucial step required for brain damage following a stroke, clinical trials for NMDAR blockers have all ended with disappointments. The past decade of stroke research has revealed distinct NMDAR subpopulations and many specific effectors downstream of these receptors that are differentially responsible for neuronal survival and death. These new advancements provide promising targets for the development of novel NMDAR-based neuroprotective stroke therapies that could have greater therapeutic windows and reduced side effects. In this review, we discuss these advancements with a particular emphasis on the identification of novel s... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4471121 Tue, 08 Feb 2011 00:00:00 +0100 4471121 http://www.medworm.com/index.php?rid=4471124&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21277256%26dopt%3DAbstract Authors: Doroudgar S, Glembotski CC Intercellular communication depends on many factors, including proteins released via the classical or non-classical secretory pathways, many of which must be properly folded to be functional. Owing to their adverse effects on the secretion machinery, stresses such as ischemia can impair the folding of secreted proteins. Paradoxically, cells rely on secreted proteins to mount a response designed to resist stress-induced damage. This review examines this paradox using proteins secreted from the heart, cardiokines, as examples, and focuses on how the ischemic heart maintains or even increases the release of select cardiokines that regulate important cellular processes in the heart, including excitation-contraction coupling, hypertrophic growth, myocardi... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4471124 Tue, 01 Feb 2011 00:00:00 +0100 4471124 http://www.medworm.com/index.php?rid=4471123&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21288771%26dopt%3DAbstract Authors: Speidel D PMID: 21288771 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine) Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4471123 Mon, 31 Jan 2011 00:00:00 +0100 4471123 http://www.medworm.com/index.php?rid=4471122&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21288772%26dopt%3DAbstract Authors: van der Maarel SM, Tawil R, Tapscott SJ Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) has an unusual pathogenic mechanism. FSHD is caused by deletion of a subset of D4Z4 macrosatellite repeat units in the subtelomere of chromosome 4q. Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues. In FSHD, the combination of inefficient chromatin silencing of the D4Z4 repeat and polymorphisms on the FSHD-permissive alleles that stabilize the DUX4 mRNAs emanating from the repeat result in inappropriate DUX4 protein expression in muscle cells. FSHD is thereby the first example of a human disease caused by the inefficient repression of a retr... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4471122 Mon, 31 Jan 2011 00:00:00 +0100 4471122 http://www.medworm.com/index.php?rid=4402071&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21251877%26dopt%3DAbstract Authors: Hart BA, Gran B, Weissert R The high failure rate of immunotherapies in multiple sclerosis (MS) clinical trials demonstrates problems in translating new treatment concepts from animal models to the patient. One main reason for this 'immunotherapy gap' is the usage of immunologically immature, microbiologically clean and genetically homogeneous rodent strains. Another reason is the artificial nature of the experimental autoimmune encephalomyelitis model, which favors CD4+ T cell driven autoimmune mechanisms, whereas CD8+ T cells are prevalent in MS lesions. In this paper, we discuss preclinical models in humanized rodents and non-human primates that are genetically closer to MS. We also discuss models that best reproduce specific aspects of MS pathology and how these can potent... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4402071 Tue, 18 Jan 2011 00:00:00 +0100 4402071 http://www.medworm.com/index.php?rid=4402070&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21251878%26dopt%3DAbstract Authors: Morandi A, Plaza-Menacho I, Isacke CM Recent studies demonstrate that the receptor tyrosine kinase RET is overexpressed in a subset of ER-positive breast cancers and that crosstalk between RET and ER is important in responses to endocrine therapy. The development of small molecular inhibitors that target RET allows the opportunity to consider combination therapies as a strategy to improve response to treatment and to prevent and combat endocrine resistance. This review discusses: (i) the current knowledge about RET, its co-receptors and ligands in breast cancer; (ii) the breast cancer clinical trials involving agents that target RET; and (iii) the challenges that remain in terms of specificity of available inhibitors and in understanding the complex molecular mechanisms that u... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4402070 Tue, 18 Jan 2011 00:00:00 +0100 4402070 http://www.medworm.com/index.php?rid=4402072&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21237710%26dopt%3DAbstract Authors: Pritchett J, Athwal V, Roberts N, Hanley NA, Hanley KP The transcription factor SOX9 is crucial for multiple aspects of development. Mutations in SOX9 cause campomelic dysplasia, a haploinsufficiency disorder concordant with the expression profile of SOX9 during embryogenesis. The mechanistic understanding of development has revealed roles for SOX9 in regulating cartilage extracellular matrix (ECM) production and cell proliferation, among others. More recently, it transpires that SOX9 becomes expressed and induces destructive ECM components in organ fibrosis and related disorders. Although commonly absent from the parent cell type, SOX9 is expressed in a wide range of cancers, where it regulates cell proliferation. These data have potential diagnostic, prognostic and therapeut... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4402072 Thu, 13 Jan 2011 00:00:00 +0100 4402072 http://www.medworm.com/index.php?rid=4402073&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21236731%26dopt%3DAbstract Authors: Zylka MJ Adenosine receptor agonists have potent antinociceptive effects in diverse preclinical models of chronic pain. By contrast, the efficacy of adenosine and adenosine receptor agonists in treating pain in humans is unclear. Two ectonucleotidases that generate adenosine in nociceptive neurons were recently identified. When injected spinally, these enzymes have long-lasting adenosine A(1) receptor-dependent antinociceptive effects in inflammatory and neuropathic pain models. Furthermore, recent findings indicate that spinal adenosine A(2A) receptor activation can enduringly inhibit neuropathic pain symptoms. Collectively, these studies suggest the possibility of treating chronic pain in humans by targeting specific adenosine receptor subtypes in anatomically defined region... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4402073 Wed, 12 Jan 2011 00:00:00 +0100 4402073 http://www.medworm.com/index.php?rid=4338319&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21195665%26dopt%3DAbstract Authors: Kiefel H, Pfeifer M, Bondong S, Hazin J, Altevogt P The cell adhesion molecule L1 (L1CAM) was originally identified as a neural adhesion molecule essential for neurite outgrowth and axon guidance. Many studies have now shown that L1CAM is overexpressed in human carcinomas and associated with poor prognosis. So far, L1CAM-mediated cellular signaling has been largely attributed to an association with growth factor receptors, referred to as L1CAM-'assisted' signaling. New data demonstrate that L1CAM can signal via two additional mechanisms: 'forward' signaling via regulated intramembrane proteolysis and 'reverse' signaling via the activation of the transcription factor nuclear factor (NF)-κB. Taken together, these findings lead to a new understanding of L1CAM downstream signalin... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4338319 Thu, 30 Dec 2010 00:00:00 +0100 4338319 http://www.medworm.com/index.php?rid=4338318&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21195666%26dopt%3DAbstract Authors: Pneumaticos SG, Triantafyllopoulos GK, Chatziioannou S, Basdra EK, Papavassiliou AG Autologous bone grafts and allografts are the most accepted procedures for achieving spinal fusion. Recently, breakthroughs in understanding bone biology have led to the development of novel approaches to address the clinical problem of bone regeneration in an unfavorable environment, while bypassing the drawbacks of traditional treatments, including limited availability, donor site morbidity, risk of disease transmission and reduced osteogenicity. These approaches have also been studied for their effectiveness in reaching successful spinal fusion. This review focuses on the cellular and molecular mechanisms explaining the rationale behind these methods, including bone marrow aspirate and mesen... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4338318 Thu, 30 Dec 2010 00:00:00 +0100 4338318 http://www.medworm.com/index.php?rid=4338320&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21195026%26dopt%3DAbstract Authors: Lai-Cheong JE, McGrath JA, Uitto J Revertant mosaicism is a naturally occurring phenomenon involving spontaneous correction of a pathogenic mutation in a somatic cell. Recent studies suggest that it is not a rare event and that it could be clinically relevant to phenotypic expression and patient treatment. Indeed, revertant cell therapy represents a potential 'natural gene therapy' because in vivo reversion obviates the need for further genetic correction. Revertant mosaicism has been observed in several inherited conditions, including epidermolysis bullosa, a heterogeneous group of blistering skin disorders. These diseases provide a useful model for studying revertant mosaicism because of the visual and accessible nature of skin. This overview highlights the latest developmen... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4338320 Wed, 29 Dec 2010 00:00:00 +0100 4338320 http://www.medworm.com/index.php?rid=4338321&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21185230%26dopt%3DAbstract Authors: Correll CU, Lencz T, Malhotra AK Mechanisms underlying antipsychotic cardiometabolic adverse effects are incompletely understood. This hampers the identification of high-risk patients, low-risk antipsychotics and preventive/ameliorative treatments. Recent clinical, molecular and genetic data suggest that: (i) antipsychotic-naïve samples provide the greatest power for mechanistic studies; (ii) weight and metabolic effects can be discordant, pointing to overlapping and distinct mechanisms; (iii) antipsychotics affect satiety and energy homeostasis signaling; (iv) the specific peptides mediating these effects are unknown but probably overlap with those involved in idiopathic obesity; and (v) single nucleotide polymorphisms in genes encoding known neurotransmitter receptors and m... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4338321 Wed, 22 Dec 2010 00:00:00 +0100 4338321 http://www.medworm.com/index.php?rid=4338322&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21183406%26dopt%3DAbstract Authors: Whalen EJ, Rajagopal S, Lefkowitz RJ Members of the seven-transmembrane receptor (7TMR), or G protein-coupled receptor (GPCR), superfamily represent some of the most successful targets of modern drug therapy, with proven efficacy in the treatment of a broad range of human conditions and disease processes. It is now appreciated that β-arrestins, once viewed simply as negative regulators of traditional 7TMR-stimulated G protein signaling, act as multifunctional adapter proteins that regulate 7TMR desensitization and trafficking and promote distinct intracellular signals in their own right. Moreover, several 7TMR biased agonists, which selectively activate these divergent signaling pathways, have been identified. Here we highlight the diversity of G protein- and β-arrestin-medi... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4338322 Tue, 21 Dec 2010 00:00:00 +0100 4338322 http://www.medworm.com/index.php?rid=4276677&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21163704%26dopt%3DAbstract Authors: Shaw PJ, McDermott MF, Kanneganti TD The NOD-like receptor (NLR) family members are cytosolic sensors of microbial components and danger signals. A subset of NLRs control inflammasome assembly that results in caspase-1 activation and, in turn, IL-1β and IL-18 production. Excessive inflammasome activation can cause autoinflammatory disorders, including the hereditary periodic fevers. Autoinflammatory and autoimmune diseases form a disease spectrum of aberrant, immune-mediated inflammation against self, through innate and adaptive immunity. However, the role of inflammasomes in autoimmune disease is less clear than in autoinflammation, despite the numerous effects IL-1β and IL-18 can have on shaping adaptive immunity. We summarize the role of inflammasomes in autoimmune disord... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4276677 Tue, 14 Dec 2010 00:00:00 +0100 4276677 http://www.medworm.com/index.php?rid=4276678&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21146459%26dopt%3DAbstract Authors: Vives-Bauza C, Przedborski S Parkinson's disease (PD) is a common neurodegenerative disorder of unknown cause. Some familial forms of PD are provoked by mutations in the genes encoding for the PTEN (phosphatase and tensin homolog)-induced putative kinase-1 (PINK1) and Parkin. Mounting evidence indicates that PINK1 and Parkin might function in concert to modulate mitochondrial degradation, termed mitophagy. However, the molecular mechanisms by which PINK1/Parkin affect mitophagy are just beginning to be elucidated. Herein, we review the main advances in our understanding of the PINK1/Parkin pathway. Because of the phenotypic similarities among the different forms of PD, a better understanding of PINK1/Parkin biology might have far-reaching pathogenic and therapeutic implication... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4276678 Thu, 09 Dec 2010 00:00:00 +0100 4276678 http://www.medworm.com/index.php?rid=4218321&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21112250%26dopt%3DAbstract Authors: Haynes BF, Moody MA, Liao HX, Verkoczy L, Tomaras GD The B cell arm of the immune response becomes activated soon after HIV-1 transmission, yet the initial antibody response does not control HIV-1 replication, and it takes months for neutralizing antibodies to develop against the autologous virus. Antibodies that can be broadly protective are made only in a minority of subjects and take years to develop-too late to affect the course of disease. New studies of the earliest stages of HIV-1 infection, new techniques to probe the human B cell repertoire, the modest degree of efficacy in a vaccine trial and new studies of human monoclonal antibodies that represent the types of immune responses an HIV-1 vaccine should induce are collectively illuminating paths that a successful HIV-... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4218321 Thu, 25 Nov 2010 00:00:00 +0100 4218321 http://www.medworm.com/index.php?rid=4218322&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21106440%26dopt%3DAbstract Authors: Gelman MA, Glenn JS Therapy for hepatitis C virus (HCV) infection is on the cusp of a new era. Until now, standard-of-care therapy has involved interferon (IFN) and ribavirin. With the first successful Phase III trials of specific targeted antiviral therapy for HCV (STAT-C) compounds, as well as three trials in progress giving the first glimpse of IFN-free combinations of STAT-C agents, this review looks ahead to the new classes of anti-HCV agents currently in clinical development. Successful pharmacologic control of HIV and TB frames the discussion, as well as consideration of the mutation frequency of HCV replication. Maximizing synergy between agents and minimizing cumulative toxicity will be critical to the design of future IFN-free STAT-C regimens. PMID: 21106440 [Pub... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4218322 Mon, 22 Nov 2010 00:00:00 +0100 4218322 http://www.medworm.com/index.php?rid=4201183&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21087899%26dopt%3DAbstract Authors: Ma CX, Janetka JW, Piwnica-Worms H Defects in p53 function, which occur frequently in human cancers due to mutations in TP53 or disruptions in the p53 regulatory pathway, render cells dependent on CHK1 (Checkpoint Kinase 1) to activate cell cycle checkpoints. In the presence of DNA damage or replication stress, inhibition of CHK1 leads to "mitotic catastrophe" and cell death in p53-deficient tumors while sparing p53-proficient cells. CHK1 inhibitors sensitize tumors to a variety of DNA-damaging agents or antimetabolites in preclinical models and are being evaluated in early phase clinical trials. In this review, we summarize recent advances and controversies in the development and application of CHK1 inhibitors as cancer therapeutics. PMID: 21087899 [PubMed - as supplied b... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4201183 Wed, 17 Nov 2010 00:00:00 +0100 4201183 http://www.medworm.com/index.php?rid=4201182&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21087900%26dopt%3DAbstract Authors: van den Heuvel MJ, Garg N, Van Kaer L, Haeryfar SM Invariant natural killer T (iNKT) cells are innate lymphocytes with unique specificity for glycolipid antigens and remarkable immunomodulatory properties. The role of costimulatory interactions in iNKT cell responses has recently come under scrutiny. Although iNKT cells and their prototype glycolipid agonist α-galactosylceramide (α-GalCer) have shown promise in several clinical trials conducted in patients with cancer or viral diseases, current iNKT cell-based therapies are far from effective. The concomitant targeting of T cell receptors (TCRs) and costimulatory molecules on iNKT cells represents an exciting new opportunity to optimize such therapeutic approaches. Here, we review recent advances in our understanding of iNKT... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4201182 Wed, 17 Nov 2010 00:00:00 +0100 4201182 http://www.medworm.com/index.php?rid=4201181&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21087901%26dopt%3DAbstract This article highlights the most common strategies for treating atherosclerosis using HDL. We further detail potential treatment opportunities that utilize nanotechnology to increase the amount of HDL in circulation. The synthesis of biomimetic HDL nanostructures that replicate the chemical and physical properties of natural HDL provides novel materials for investigating the structure-function relationships of HDL and for potential new therapeutics to combat CHD. PMID: 21087901 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine) Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4201181 Wed, 17 Nov 2010 00:00:00 +0100 4201181 http://www.medworm.com/index.php?rid=4201184&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21075055%26dopt%3DAbstract Authors: Pellegrini G, Rama P, De Luca M Cultures of limbal cells are a safe and effective treatment for the destruction of the human cornea owing to chemical burns. The essential feature of the graft is the presence of an adequate number of stem cells, which can be determined by the expression of the p63 transcription factor. Here, we will discuss the general principles defining the rigorous criteria for graftable limbal cultures in light of their clinical performances. Such criteria might prove relevant to the future therapeutic use of any cultured cell type. PMID: 21075055 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine) Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4201184 Thu, 11 Nov 2010 00:00:00 +0100 4201184 http://www.medworm.com/index.php?rid=4201185&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21074494%26dopt%3DAbstract Authors: Cho EC, Glaus C, Chen J, Welch MJ, Xia Y Inorganic nanoparticles (NPs) including semiconductor quantum dots (QDs), iron oxide NPs and gold NPs have been developed as contrast agents for diagnostics by molecular imaging. Compared with traditional contrast agents, NPs offer several advantages: their optical and magnetic properties can be tailored by engineering the composition, structure, size and shape; their surfaces can be modified with ligands to target specific biomarkers of disease; the contrast enhancement provided can be equivalent to millions of molecular counterparts; and they can be integrated with a combination of different functions for multimodal imaging. Here, we review recent advances in the development of contrast agents based on inorganic NPs for molecular imag... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4201185 Wed, 10 Nov 2010 00:00:00 +0100 4201185 http://www.medworm.com/index.php?rid=4166333&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21071272%26dopt%3DAbstract Authors: Lamichhane G The recent past has experienced a renaissance in tuberculosis (TB) research. New molecular biology reagents and genetic tools have been developed and whole genome sequences of Mycobacterium tuberculosis strains are now widely available. An increase in the prevalence of drug-resistant strains of M. tuberculosis has renewed focus on the development of new drugs against this millennia old disease. The identification of new targets in M. tuberculosis that might be inhibited to effectively kill the existing strains is now a global pursuit. This review summarizes recently identified targets in M. tuberculosis that have been validated beyond initial genetic identification. Advancing these defined targets for the development of inhibitors has the potential to produce new ... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4166333 Tue, 09 Nov 2010 00:00:00 +0100 4166333 http://www.medworm.com/index.php?rid=4123554&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20980198%26dopt%3DAbstract Authors: Donner A PMID: 20980198 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine) Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4123554 Mon, 25 Oct 2010 00:00:00 +0100 4123554 http://www.medworm.com/index.php?rid=4107940&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20971038%26dopt%3DAbstract Authors: Gillum MP, Erion DM, Shulman GI Sirtuin-1 (SirT1) is a nutrient-sensing deacetylase whose levels and activity increase with caloric restriction to preserve euglycemia and promote efficient energy utilization. Focusing on data obtained in vivo, we review how SirT1 orchestrates the adaptive response to fasting by stimulating hepatic gluconeogenesis and fatty acid oxidation, increasing circulating adiponectin levels and limiting immune activation. Finally, we consider its viability as a therapeutic target for the treatment of type 2 diabetes. PMID: 20971038 [PubMed - as supplied by publisher] (Source: Trends in Molecular Medicine) Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4107940 Wed, 20 Oct 2010 23:00:00 +0100 4107940 http://www.medworm.com/index.php?rid=4107939&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20971039%26dopt%3DAbstract Authors: Barach YS, Lee JS, Zang X T cell-mediated adaptive immune response is controlled by both positive costimulation and negative coinhibition, generated mainly by the interaction between the B7 family and their receptor CD28 family. Coinhibition is exploited by prostate cancer as an immune evasion pathway. Overexpression of coinhibitory B7x and B7-H3 in prostate cancer correlates with poor disease outcome, whereas tumor-infiltrating immune cells have enhanced expression of PD-L1 and its receptor PD-1. New insights into the complex mechanisms governing B7 expression in the tumor microenvironment have been reported and therapies aimed at overcoming T cell coinhibition with antagonistic monoclonal antibodies are emerging as effective tumor immunotherapies. Therapies that block B7x an... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4107939 Wed, 20 Oct 2010 23:00:00 +0100 4107939 http://www.medworm.com/index.php?rid=4077659&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20947431%26dopt%3DAbstract Authors: Trynka G, Wijmenga C, van Heel DA Coeliac disease is an inflammatory disorder of the small intestine with an autoimmune component and strong heritability. Genetic studies have confirmed strong association to HLA and identified 39 nonHLA risk genes, mostly immune-related. Over 50% of the disease-associated single nucleotide polymorphisms are correlated with gene expression. Most of the coeliac disease-associated regions are shared with other immune-related diseases, as well as with metabolic, haematological or neurological traits, or cancer. We review recent progress in the genetics of coeliac disease and describe the pathways these genes are in, the functional consequences of the associated markers on gene expression and the genes shared between coeliac disease and other trait... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4077659 Mon, 11 Oct 2010 23:00:00 +0100 4077659 http://www.medworm.com/index.php?rid=4062687&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20932800%26dopt%3DAbstract Authors: Dai C, Gu W The p53 tumor suppressor protein has well-established roles in monitoring various types of stress signals by activating specific transcriptional targets that control cell cycle arrest and apoptosis, although some activities are also mediated in a transcription-independent manner. Here, we review the recent advances in our understanding of the wide spectrum of post-translational modifications that act as epigenetic-like codes for modulating specific functions of p53 in vivo and how deregulation of these modifications might contribute to tumorigenesis. We also discuss future research priorities to further understand p53 post-translational modifications and the interpretation of genetic data in appreciation of the increasing evidence that p53 regulates cellular metabo... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4062687 Mon, 04 Oct 2010 23:00:00 +0100 4062687 http://www.medworm.com/index.php?rid=4043200&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20889378%26dopt%3DAbstract Authors: Soto C, Satani N Prion diseases are a group of infectious neurodegenerative diseases with an entirely novel mechanism of transmission, involving a protein-only infectious agent that propagates the disease by transmitting protein conformational changes. The disease results from extensive and progressive brain degeneration. The molecular mechanisms involved in neurodegeneration are not entirely known but involve multiple processes operating simultaneously and synergistically in the brain, including spongiform degeneration, synaptic alterations, brain inflammation, neuronal death and the accumulation of protein aggregates. Here, we review the pathways implicated in prion-induced brain damage and put the pieces together into a possible model of neurodegeneration in prion disorders... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4043200 Fri, 01 Oct 2010 23:00:00 +0100 4043200 http://www.medworm.com/index.php?rid=4003883&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20870460%26dopt%3DAbstract Authors: He X, Gao J, Gambhir SS, Cheng Z Near-infrared fluorescence (NIRF) imaging promises to improve cancer imaging and management; advances in nanomaterials allow scientists to combine new nanoparticles with NIRF imaging techniques, thereby fulfilling this promise. Here, we present a synopsis of current developments in NIRF nanoprobes, their use in imaging small living subjects, their pharmacokinetics and toxicity, and finally their integration into multimodal imaging strategies. We also discuss challenges impeding the clinical translation of NIRF nanoprobes for molecular imaging of cancer. Whereas utilization of most NIRF nanoprobes remains at a proof-of-principle stage, optimizing the impact of nanomedicine in cancer patient diagnosis and management will probably be realized thro... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4003883 Thu, 23 Sep 2010 23:00:00 +0100 4003883 http://www.medworm.com/index.php?rid=4003800&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20870461%26dopt%3DAbstract Authors: Slaets H, Hendriks JJ, Stinissen P, Kilpatrick TJ, Hellings N Therapies for multiple sclerosis (MS) reduce the relapse rate but are unable to stop neurological decline. Here, we evaluate the potential of leukemia inhibitory factor (LIF) as a novel therapeutic in diseases with a neurodegenerative and inflammatory component, such as MS. LIF, which can be a proinflammatory cytokine, can also modulate the immune response in a beneficial way. Recent evidence demonstrates a crucial role of LIF in neuroprotection and axonal regeneration as well as the prevention of demyelination. Finally, LIF is an important survival factor for stem cells and neuronal precursors. Therefore, we propose that LIF is a potential therapeutic candidate for MS. PMID: 20870461 [PubMed - as supplied by pu... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4003800 Thu, 23 Sep 2010 23:00:00 +0100 4003800 http://www.medworm.com/index.php?rid=4003593&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20870462%26dopt%3DAbstract Authors: Westermark GT, Westermark P According to the 'protein only hypothesis', Creutzfeldt-Jakob disease and other prion disorders are transmissible by misfolded and aggregated prion proteins that act as templates for the misfolding of the same protein in the recipient. The misfolding and aggregation of the prion protein are akin to the genesis of amyloid fibrils formed by several human and animal proteins associated with more common diseases. Two murine forms of amyloidosis, including a model of human AA amyloidosis, are transmissible. Here, we explore the possibility that human prion diseases and more common maladies associated with amyloid deposits might be transmissible by seeding or perhaps even by crossing species barriers. PMID: 20870462 [PubMed - as supplied by publisher]... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4003593 Thu, 23 Sep 2010 23:00:00 +0100 4003593 http://www.medworm.com/index.php?rid=4003942&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20869318%26dopt%3DAbstract Authors: Cash KJ, Clark HA Worldwide, diabetes is a rapidly growing problem that is managed at the individual level by monitoring and controlling blood glucose levels to minimize the negative effects of the disease. Because of limitations in diagnostic methods, significant research efforts are focused on developing improved methods to measure glucose. Nanotechnology has impacted these efforts by increasing the surface area of sensors, improving the catalytic properties of electrodes and providing nanoscale sensors. Here, we discuss developments in the past several years on both nanosensors that directly measure glucose and nanomaterials that improve glucose sensor function. Finally, we discuss challenges that must be overcome to apply these developments in the clinic. PMID: 2086931... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4003942 Tue, 21 Sep 2010 23:00:00 +0100 4003942 http://www.medworm.com/index.php?rid=4003998&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20864408%26dopt%3DAbstract Authors: Levenga J, de Vrij FM, Oostra BA, Willemsen R Fragile X syndrome (FXS) is caused by a lack of the fragile X mental retardation protein (FMRP); FMRP deficiency in neurons of patients with FXS causes intellectual disability (IQ<70) and several behavioural problems, including hyperactivity and autistic-like features. In the brain, no gross morphological malformations have been found, although subtle spine abnormalities have been reported. FXS has been linked to altered group I metabotropic glutamate receptor (mGluR)-dependent and independent forms of synaptic plasticity. Here, we discuss potential targeted therapeutic strategies developed to specifically correct disturbances in the excitatory mGluR and the inhibitory gamma-aminobutyric (GABA) receptor pathways that have been t... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4003998 Mon, 20 Sep 2010 23:00:00 +0100 4003998 http://www.medworm.com/index.php?rid=3987996&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20851684%26dopt%3DAbstract Authors: Sauter AW, Wehrl HF, Kolb A, Judenhofer MS, Pichler BJ Given the need for sophisticated in vivo detection techniques to better characterize the cellular and subcellular processes in animals and humans, molecular imaging has become an important discipline. Techniques in molecular imaging have developed from stand alone modalities to multimodality methods. Among these, the combination of positron emission tomography (PET) and computed tomography (CT) is a successful imaging method and has become an important tool in clinical practice. Technological approaches that combine magnetic resonance imaging (MRI) with diffuse optical tomography (DOT), fluorescence tomography (FT) and PET have now been introduced. PET/MRI and the resulting combination of molecular, morphological and funct... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3987996 Thu, 16 Sep 2010 23:00:00 +0100 3987996 http://www.medworm.com/index.php?rid=3987997&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20846905%26dopt%3DAbstract Authors: Chen ZG Using nanoparticles for the delivery of small molecules in anticancer therapy is a rapidly growing area of research. The advantages of using nanoparticles for drug delivery include enhanced water solubility, tumor-specific accumulation and improved antitumor efficacy, while reducing nonspecific toxicity. Current research in this field focuses on understanding precisely how small molecules are released from nanoparticles and delivered to the targeted tumor tissues or cells, and how the unique biodistribution of the drug-carrying nanoparticles limits toxicity in major organs. Here, we discuss existing nanoparticles for the delivery of small-molecule anticancer agents and recent advances in this field. PMID: 20846905 [PubMed - as supplied by publisher] (Source: Trends... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3987997 Mon, 13 Sep 2010 23:00:00 +0100 3987997 http://www.medworm.com/index.php?rid=3955101&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20817608%26dopt%3DAbstract Authors: Leduc V, Jasmin-Bélanger S, Poirier J Converging evidence from clinical and pathological studies indicate the presence of important relationships between the ongoing deterioration of brain lipid homeostasis, vascular changes and the pathophysiology of sporadic Alzheimer's disease (AD). These associations include the recognition of cholesterol transporters apolipoprotein E (APOE), APOC1 and APOJ as major genetic risk factors for common AD and observations associating risk factors for cardiovascular disease such as high midlife plasma cholesterol, diabetes, stroke, obesity and hypertension to dementia. Moreover, recent clinical findings lend support to the notion that progressive deterioration of cholesterol homeostasis in AD is a central player in the disease pathophysiology... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3955101 Tue, 31 Aug 2010 23:00:00 +0100 3955101 http://www.medworm.com/index.php?rid=3955102&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20810319%26dopt%3DAbstract Authors: Hatori M, Panda S The adaptation of behavior and physiology to changes in the ambient light level is of crucial importance to life. These adaptations include the light modulation of neuroendocrine function and temporal alignment of physiology and behavior to the day:night cycle by the circadian clock. These non-image-forming (NIF) responses can function independent of rod and cone photoreceptors but depend on ocular light reception, suggesting the participation of novel photoreceptors in the eye. The discovery of melanopsin in intrinsically photosensitive retinal ganglion cells (ipRGCs) and genetic proof for its important role in major NIF responses have offered an exciting entry point to comprehend how mammals adapt to the light environment. Here, we review the recent advance... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3955102 Sun, 29 Aug 2010 23:00:00 +0100 3955102 http://www.medworm.com/index.php?rid=3915746&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20739220%26dopt%3DAbstract Authors: Ahlers JD, Belyakov IM CD4(+) T cells occupy a central role in the induction and regulation of adaptive immune responses. Activated CD4(+) T helper (Th) cells exert immediate effector functions by producing cytokines and chemokines, providing help for the induction of CD8(+) cytotoxic T lymphocyte responses and memory, and providing help for immunoglobulin class switching, affinity maturation of antibody and B cell memory. Inherent in naïve CD4(+) T cells is the flexibility to adopt alternate lineage potentials, which depend upon regulatory mechanisms that change with tissue microenvironment and upon infection. Here, we discuss lineage instructive programs that regulate CD4(+) T cell differentiation and memory and how to translate this knowledge into vaccines and immunother... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3915746 Mon, 23 Aug 2010 23:00:00 +0100 3915746 http://www.medworm.com/index.php?rid=3915745&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20739221%26dopt%3DAbstract Authors: Neumann E, Lefèvre S, Zimmermann B, Gay S, Müller-Ladner U Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia and progressive joint destruction. Rheumatoid arthritis synovial fibroblasts (RASFs) are leading cells in joint erosion and contribute actively to inflammation. RASFs show an activated phenotype that is independent of the inflammatory environment and requires the combination of several factors. Although new aspects regarding RASF activation via matrix degradation products, epigenetic modifications, inflammatory factors, Toll-like receptor (TLR) activation and others have recently been uncovered, the primary pathophysiological processes in early arthritis leading to permanent activation are mostly unknown. Here, we re... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3915745 Mon, 23 Aug 2010 23:00:00 +0100 3915745 http://www.medworm.com/index.php?rid=3900189&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20728409%26dopt%3DAbstract Authors: Bonnefond A, Froguel P, Vaxillaire M The elucidation of several genetic etiologies of both monogenic and polygenic type 2 diabetes (T2D) has revealed several key regulators of glucose homeostasis and insulin secretion in humans. Genome-wide association studies (GWAS) have been instrumental in most of these recent discoveries. The T2D susceptibility genes identified so far are mainly involved in pancreatic beta-cell maturation or function. However, common DNA variants in those genes only explain approximately 10% of T2D heritability. The resequencing of whole exomes and whole genomes with next-generation technologies should identify additional genetic changes that contribute to the monogenic forms of diabetes and possibly provide novel clues to the genetic architecture of commo... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3900189 Wed, 18 Aug 2010 23:00:00 +0100 3900189 http://www.medworm.com/index.php?rid=3882286&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20708968%26dopt%3DAbstract Authors: Buehler PW, D'Agnillo F, Schaer DJ Hemoglobin-based oxygen carriers (HBOCs) have been developed to support blood oxygen transport capacity during hemorrhagic shock, hemolysis and ischemic insult. Existing product candidates have demonstrated considerable efficacy in experimental animal models and in clinical trial subjects; however, severe adverse safety signals that appeared in recent phase II and phase III clinical trials involving certain HBOCs have in part hindered further development and licensing. Emerging insights into hemoglobin (Hb) toxicity as well as physiologic Hb scavengers such as haptoglobin and CD163 that are capable of detoxifying extracellular Hb in vivo suggest that alternative product candidates could be designed. Together with novel animal models and bioma... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3882286 Wed, 11 Aug 2010 23:00:00 +0100 3882286 http://www.medworm.com/index.php?rid=3871579&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20692206%26dopt%3DAbstract Authors: Dang L, Jin S, Su SM The systematic sequencing of glioblastoma multiforme (GBM) genomes has identified the recurrent mutation of IDH1, a gene encoding NADP(+)-dependent isocitrate dehydrogenase 1 (IDH1) that catalyzes the oxidative decarboxylation of isocitrate yielding alpha-ketoglutarate (alpha-KG). Subsequent studies have confirmed recurrent IDH1 and IDH2 mutations in up to 70% of low-grade glioma and secondary GBM, as well as in 10% of acute myeloid leukemia (AML) cases. The heterozygous somatic mutations at arginine R132 (IDH1) and at R140 or R172 (IDH2) in the enzyme active site confer a gain of function to the enzymes, which can both produce the metabolite 2-hydroxyglutarate. This review surveys the prevalence of IDH mutations in cancer and explores current mechanistic ... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3871579 Wed, 04 Aug 2010 23:00:00 +0100 3871579 http://www.medworm.com/index.php?rid=3833682&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20688566%26dopt%3DAbstract Authors: Ye X, Wang Y, Nathans J Disorders of retinal vascular growth and function are responsible for vision loss in a variety of diseases, including diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity and retinal artery or vein occlusion. Over the past decade, a new signaling pathway that controls retinal vascular development has emerged from the study of inherited disorders - in both humans and mice - that are characterized by retinal hypovascularization. This pathway utilizes a glial-derived extracellular ligand, Norrin, that acts on a transmembrane receptor, Frizzled4, a coreceptor, Lrp5, and an auxiliary membrane protein, Tspan12, on the surface of developing endothelial cells. The resulting signal controls a transcriptional program that regulates e... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3833682 Mon, 02 Aug 2010 23:00:00 +0100 3833682 http://www.medworm.com/index.php?rid=3803473&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20667782%26dopt%3DAbstract Authors: Mayadas TN, Rosetti F, Ernandez T, Sethi S Glomerulonephritides represent a diverse array of diseases that have in common immune cell-mediated effector mechanisms that cause organ damage. The contribution of neutrophils to the pathogenesis of proliferative glomerulonephritis (GN) is not well recognized. Most equate neutrophils with killing pathogens and causing collateral tissue damage during acute inflammation. However, these phagocytes are endowed with additional characteristics that have been traditionally reserved for cells of the adaptive immune system. They communicate with other cells, exhibit plasticity in their responses and have the potential to coordinate and inform the subsequent immune response, thus countering the notion that they arrive, destroy and then disappe... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3803473 Sun, 25 Jul 2010 23:00:00 +0100 3803473 http://www.medworm.com/index.php?rid=3803472&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20667783%26dopt%3DAbstract Authors: Pantel K, Alix-Panabières C Ultrasensitive methods have been recently developed to detect circulating tumour cells (CTCs) in the peripheral blood and disseminated tumour cells (DTCs) in the bone marrow (BM) of cancer patients. Studies with these new methods indicate that BM is a common homing organ and a reservoir for DTCs derived from various organ sites including breast, prostate, lung and colon. Peripheral blood analyses, however, are more convenient for patients than invasive BM sampling and many research groups are currently assessing the clinical utility of CTCs for prognosis and monitoring response to systemic therapies. Moreover, molecular analyses of CTCs/DTCs have provided new insights into the biology of metastasis with important implications for the clinical man... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3803472 Sun, 25 Jul 2010 23:00:00 +0100 3803472 http://www.medworm.com/index.php?rid=3759186&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20605525%26dopt%3DAbstract Authors: Mieulet V, Lamb RF The TSC1/TSC2 tumor-suppressor complex regulates cell growth via controlling the mTOR (mammalian target of rapamycin) signaling pathway, which contributes to several disease processes, including cancer and diabetes. Abnormal activation of mTOR uncouples anabolic cell growth processes such as protein and lipid synthesis from external growth factor or nutrient cues. However, abnormal activation of mTOR upon loss of TSC1/TSC2 complex function is now known to lead to compensatory mechanisms that restrict the development of malignant tumors. The rare occurrence of complete loss of TSC1/TSC2 function in human tumors suggests that retaining growth suppressor activity might be beneficial during tumour evolution, perhaps by promoting survival when cells grow in a nut... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3759186 Wed, 30 Jun 2010 23:00:00 +0100 3759186 http://www.medworm.com/index.php?rid=3759185&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20605742%26dopt%3DAbstract Authors: Thomas WR, Hales BJ, Smith WA IgE antibodies in house dust mite (HDM) allergy follow a predictable pattern. Half are directed against two dominant allergens and the remainder largely against four midpotency allergens. This hierarchical pattern is not changed by the titre of the IgE response or severity of disease. The structures of these allergens are known and they can be produced as authentic recombinant allergens. There is also evidence that the allergenicity is augmented by the biological activity of the key allergens, validating them as targets for vaccination. Collectively, these developments should facilitate the development of new diagnostics, improve immunotherapy and allow vaccination with defined reagents. Highly purified recombinant polypeptides representing the im... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3759185 Wed, 30 Jun 2010 23:00:00 +0100 3759185 http://www.medworm.com/index.php?rid=3759187&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20591737%26dopt%3DAbstract Authors: Prinz M, Kalinke U Type I interferons (IFN-alpha and IFN-beta) were discovered more than five decades ago and are widely used for the treatment of human autoimmune diseases such as multiple sclerosis (MS). Despite their highly beneficial features, the precise mechanism of action remains speculative. Given the frequent side effects of IFN-alpha/beta therapy, understanding its action in an in vivo setting is vital to further improve this therapeutic approach. Major advances in our understanding of the IFN biology have recently been made and are particularly based on the combination of powerful genome-wide expression analysis in humans with gene-targeting techniques available for basic research. The recent discovery of a novel T-cell subset, Th17 cells, sheds new light on type I ... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3759187 Sun, 27 Jun 2010 23:00:00 +0100 3759187 http://www.medworm.com/index.php?rid=3710666&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20580607%26dopt%3DAbstract Authors: Dzierzak E, Robin C The placenta is a large, highly vascularised hematopoietic tissue that functions during the embryonic and foetal development of eutherian mammals. Although recognised as the interface tissue important in the exchange of oxygen, nutrients and waste products between the foetus and mother, the placenta has increasingly become a focus of research concerning the ontogeny of the blood system. Here, we describe recent data showing the intrinsic hematopoietic potential and appearance of hematopoietic cells in the mouse and human placenta and probe the biological rationale behind its hematopoietic function. As a rest tissue that contains potent hematopoietic stem cells (HSCs), the human placenta could represent (in addition to umbilical cord blood cells) an accessib... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3710666 Thu, 24 Jun 2010 23:00:00 +0100 3710666 http://www.medworm.com/index.php?rid=3701997&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20576469%26dopt%3DAbstract Authors: Lancaster MA, Gleeson JG Wnt signaling encompasses a variety of signaling cascades that can be activated by secreted Wnt ligands. Two such pathways, the canonical or beta-catenin pathway and the planar cell polarity (PCP) pathway, have recently received attention for their roles in multiple cellular processes within the kidney. Both of these pathways are important for kidney development as well as homeostasis and injury repair. The disruption of either pathway can lead to cystic kidney disease, a class of genetic diseases that includes the most common hereditary life-threatening syndrome polycystic kidney disease (PKD). Recent evidence implicates canonical and noncanonical Wnt pathways in cyst formation and points to a remarkable role for developmental processes in the adult k... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3701997 Mon, 21 Jun 2010 23:00:00 +0100 3701997 http://www.medworm.com/index.php?rid=3691613&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20570562%26dopt%3DAbstract Authors: Krammer F, Grabherr R The recent outbreak of swine-origin H1N1 influenza virus demonstrated the potential threat of new emerging human pathogenic influenza strains. Additionally, seasonal influenza virus strains cause substantial morbidity and mortality every year. Egg-derived influenza vaccines have served well to combat influenza infections since the 1940s. Still, faster and safer high-yielding production methods have to be established to meet the current needs for influenza vaccines. Insect cell-derived influenza vaccines are a new alternative to egg-derived vaccines. Three different approaches to insect cell-derived influenza vaccines have been established that could contribute to future influenza vaccine supply and development. PMID: 20570562 [PubMed - as supplied by ... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3691613 Thu, 03 Jun 2010 23:00:00 +0100 3691613 http://www.medworm.com/index.php?rid=3680512&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20556877%26dopt%3DAbstract Authors: Schon EA, DiMauro S, Hirano M, Gilkerson RW Until even only a few years ago, the idea that effective therapies for human mitochondrial disorders resulting from the dysfunction of the respiratory chain/oxidative phosphorylation system (OxPhos) could be developed was unimaginable. The obstacles to treating diseases caused by mutations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA), and which had the potential to affect nearly every organ system, seemed overwhelming. However, although clinically applicable therapies remain largely in the future, the landscape has changed dramatically and we can now envision the possibility of treating some of these disorders. Among these are techniques to upregulate mitochondrial biogenesis, enhance organellar fusion and fission, "shif... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3680512 Mon, 31 May 2010 23:00:00 +0100 3680512 http://www.medworm.com/index.php?rid=3680513&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20554248%26dopt%3DAbstract Authors: Tournier JN, Mohamadzadeh M Lung immune responses control pathogens while avoiding detrimental inflammation. The dynamics of lung homeostasis are not fully understood. Primary antimicrobial defenses are orchestrated by epithelial cells (ECs), interacting in close association with dendritic cells (DCs) and other innate immune cells. However, microbes, such as Bacillus anthracis use host cellular machinery, including DC-migratory capacity to reach the draining lymph nodes where they germinate and produce toxins that disrupt protective immunity leading to death. Here, we describe the immunobiology of major lung cell subsets and their cellular synapses, to reveal the dynamics of B. anthracis infection and its effects on lung immune mechanisms. Vaccines strategies that mobilize pro... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3680513 Wed, 26 May 2010 23:00:00 +0100 3680513 http://www.medworm.com/index.php?rid=3655232&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20537952%26dopt%3DAbstract Authors: Huang Y Human apolipoprotein (APO) E has three common isoforms that differentially affect lipid and neuronal homeostasis. APOE4, the major known genetic risk factor for Alzheimer's disease (AD), increases the occurrence and lowers the age of onset of AD. APOE4 carriers account for 65-80% of all AD cases, highlighting the importance of APOE4 in AD pathogenesis. Emerging data suggest that APOE4 contributes to AD through various pathways, some of which are dependent on amyloid-beta (Abeta). Although these Abeta-dependent roles of APOE4 have been widely studied, APOE4 has detrimental effects on neurons independent of Abeta: aberrant proteolysis of APOE4 generates neurotoxic fragments, stimulates Tau phosphorylation, which disrupts the cytoskeleton, and impairs mitochondrial functi... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3655232 Mon, 24 May 2010 23:00:00 +0100 3655232 http://www.medworm.com/index.php?rid=3655231&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20537953%26dopt%3DAbstract Authors: Georgel P, Schuster C, Zeisel MB, Stoll-Keller F, Berg T, Bahram S, Baumert TF With a global burden of 170 million chronically infected patients and a major cause of liver cirrhosis and hepatocellular carcinoma, hepatitis C virus (HCV) is a major public health challenge. Recent discoveries of viral and cellular factors mediating virus-host interactions have allowed scientists to uncover the key molecular mechanisms of viral infection and escape from innate and adaptive immune responses. These include the discovery of tight junction proteins as entry factors and microRNA-122, cyclophilins and lipoproteins as host factors for virus translation, replication and production. Furthermore, global genetic analyses have identified IL-28B as a genetic factor associated with the outcome ... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3655231 Mon, 24 May 2010 23:00:00 +0100 3655231 http://www.medworm.com/index.php?rid=3599840&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20493774%26dopt%3DAbstract Authors: Matarese G, Procaccini C, De Rosa V, Horvath TL, La Cava A Studies to understand the pathogenesis of obesity have revealed mediators that are responsible for the control of food intake and metabolism at the hypothalamic level. However, molecular insight explaining the link between obesity and low-degree chronic inflammation remains elusive. The adipocyte-derived hormone leptin, and thereby the nutritional status, could control immune self-tolerance by affecting regulatory T (Treg) cell responsiveness and function. Furthermore, resident Treg cells, which are capable of modulating metabolism and glucose homeostasis, are abundant in adipose tissue. Here, we provide an update on recent findings relating Treg cells to obesity and discuss how the intricate network of interactions am... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3599840 Tue, 18 May 2010 23:00:00 +0100 3599840 http://www.medworm.com/index.php?rid=3599839&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20493775%26dopt%3DAbstract Authors: Di Leva G, Croce CM MicroRNAs (miRNAs) are small noncoding RNAs that act as post-transcriptional repressors of gene expression in organisms ranging from plants to humans. A widespread role for miRNAs in diverse molecular processes driving the initiation and progression of various tumor types has recently been described. Here, we discuss the etiology of the aberrant expression of miRNAs in human cancers and their role in tumor metastasis, which might define miRNAs as oncogenes or tumor suppressors. Moreover, we highlight the genomic/epigenetic alterations and transcriptional/post-transcriptional mechanisms associated with the misexpression of miRNAs in cancer. A better understanding of miRNA biology might ultimately yield further insight into the molecular mechanisms of tumorig... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3599839 Tue, 18 May 2010 23:00:00 +0100 3599839 http://www.medworm.com/index.php?rid=3590639&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20488750%26dopt%3DAbstract Authors: Høyer-Hansen M, Nordbrandt SP, Jäättelä M Autophagy is an evolutionarily conserved lysosomal self-digestion process essential for cellular homeostasis, differentiation and survival. As an adaptive response, it protects organisms against a wide range of pathologies, including cancer, infection, neurodegeneration, heart disease and ageing. Thus, compounds activating autophagy could have great potential in the prevention of common diseases. Interestingly, recent data link autophagy to two functions of the active form of vitamin D (VD): the induction of cancer cell death and the clearance of Mycobacterium tuberculosis in macrophages. Because VD deficiency is associated with many pathologies resembling those induced by defective autophagy, it is tempting to speculate th... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3590639 Mon, 17 May 2010 23:00:00 +0100 3590639 http://www.medworm.com/index.php?rid=3545892&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20444648%26dopt%3DAbstract Authors: Freund A, Orjalo AV, Desprez PY, Campisi J Chronic inflammation is associated with aging and plays a causative role in several age-related diseases such as cancer, atherosclerosis and osteoarthritis. The source of this chronic inflammation is often attributed to the progressive activation of immune cells over time. However, recent studies have shown that the process of cellular senescence, a tumor suppressive stress response that is also associated with aging, entails a striking increase in the secretion of proinflammatory proteins and might be an important additional contributor to chronic inflammation. Here, we list the secreted factors that make up the proinflammatory phenotype of senescent cells and describe the impact of these factors on tissue homeostasis. We also summar... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3545892 Sun, 02 May 2010 23:00:00 +0100 3545892 http://www.medworm.com/index.php?rid=3530783&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20434954%26dopt%3DAbstract Authors: Huang X, Le QT, Giaccia AJ Hypoxia inducible factors (HIFs) regulate a variety of genes to prepare cells to adapt and survive under a hypoxic environment. Recently, microRNAs (miRNAs) have emerged as a new class of genes regulated by HIFs in response to hypoxia, of which miR-210 is the most consistently and predominantly upregulated miRNA. Functional studies have demonstrated that miR-210 is a versatile gene that regulates many aspects of hypoxia pathways, both in physiological and malignant conditions. Here, we summarize recent findings on the mechanism of hypoxia regulation of miR-210 expression and its multifaceted biological functions in normal physiological and malignant conditions, and discuss the challenges we face in elucidating the biological functions of miR-210 and ... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3530783 Wed, 28 Apr 2010 23:00:00 +0100 3530783 http://www.medworm.com/index.php?rid=3420798&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20347391%26dopt%3DAbstract Authors: Meents JE, Neeb L, Reuter U Migraine is among the most prevalent headache disorders and results from dysfunctions within the trigeminovascular system (TVS). The inflammatory processes that have been suggested to occur in the cascade of events resulting in migraine sensitise trigeminal nociceptors, possibly causing hyperalgesia and allodynia. Trigeminal nociceptors express the heat- and capsaicin-gated channel TRPV1, which seems to play a significant role in the development of peripheral and central sensitisation and of hyperalgesia and allodynia. Here, we review the molecular mechanisms leading to the sensitisation of TRPV1 and attempt to link them to migraine-relevant pathophysiological processes. We argue that antagonising TRPV1 sensitisation is a promising approach and shou... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3420798 Thu, 25 Mar 2010 00:00:00 +0100 3420798 http://www.medworm.com/index.php?rid=3408901&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20335067%26dopt%3DAbstract Authors: Ankrum J, Karp JM Mesenchymal stem cell (MSC) therapy is poised to establish a new clinical paradigm; however, recent trials have produced mixed results. Although MSC were originally considered to treat connective tissue defects, preclinical studies revealed potent immunomodulatory properties that prompted the use of MSC to treat numerous inflammatory conditions. Unfortunately, although clinical trials have met safety endpoints, efficacy has not been demonstrated. We believe the challenge to demonstrate efficacy can be attributed in part to an incomplete understanding of the fate of MSC following infusion. Here, we highlight the clinical status of MSC therapy and discuss the importance of cell-tracking techniques, which have advanced our understanding of the fate and function ... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3408901 Mon, 22 Mar 2010 00:00:00 +0100 3408901 http://www.medworm.com/index.php?rid=3399747&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20304704%26dopt%3DAbstract Authors: Cowan ML, Rahman TM, Krishna S Chronic liver diseases (CLDs) can cause progressive hepatic fibrosis culminating in cirrhosis. Fibrosis staging requires liver biopsy, which is invasive, expensive and frequently poorly tolerated by patients. Serum-based panels of fibrosis biomarkers have been developed as alternatives to biopsy. Recent advances in high-throughput proteomic methods have the potential to optimise combinations of biomarkers for the diagnosis of liver fibrosis. Here, we review the key recent developments in the field of proteomics and their application to this important clinical question. We critically discuss the challenges and priorities for future research that are of critical importance to clinical hepatology. PMID: 20304704 [PubMed - as supplied by publishe... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3399747 Fri, 19 Mar 2010 00:00:00 +0100 3399747 http://www.medworm.com/index.php?rid=3399746&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20304705%26dopt%3DAbstract Authors: Seliger B, Massa C, Rini B, Ko J, Finke J The immunologic approach to tumour therapy is hampered by the development of direct immune escape mechanisms and the induction of an immunosuppressive tumour microenvironment characterised by the expansion of myeloid-derived suppressor cells (MDSCs) and tumour-specific regulatory T cells (Tregs). The implementation of inhibitors targeting protein tyrosine kinases, which are involved in the process of tumour development and angiogenesis, has produced robust clinical responses. The consequences of these compounds on the functionality of immune effector cells have been investigated. This review summarises recent reports on the direct and indirect effects of protein tyrosine kinase inhibitors (TKIs) on the immune system and discusses the a... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3399746 Fri, 19 Mar 2010 00:00:00 +0100 3399746 http://www.medworm.com/index.php?rid=3399748&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20303826%26dopt%3DAbstract Authors: Karl MO, Reh TA The retina is subject to degenerative diseases that often lead to significant visual impairment. Non-mammalian vertebrates have the remarkable ability to replace neurons lost through damage. Fish, and to a limited extent birds, replace lost neurons by the dedifferentiation of Müller glia to a progenitor state followed by the replication of these neuronal progenitor cells. Over the past five years, studies have investigated whether regeneration can be stimulated in the mouse and rat retina. Several groups have reported that at least some types of neurons can be regenerated in the mammalian retina in vivo or in vitro, and that the regeneration of neurons can be stimulated using growth factors, transcription factors or subtoxic levels of excitatory amino acid... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3399748 Thu, 18 Mar 2010 00:00:00 +0100 3399748 http://www.medworm.com/index.php?rid=3319938&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20189876%26dopt%3DAbstract Authors: Bagri A, Kouros-Mehr H, Leong KG, Plowman GD Several ongoing clinical studies are designed to test the efficacy of antiangiogenic therapies in the adjuvant setting, where the goal is to increase the cure rate in patients who have just undergone surgical resection of all visible disease. Tumors depend on angiogenesis to support their growth and progression and blockade of this process has proven to be a valid strategy for treating multiple types of advanced metastatic cancer. However, results from the first of these clinical adjuvant studies were disappointing, stimulating extensive debate as to the potential of this approach. It will require additional clinical studies before we realize whether the effects of angiogenic blockade are durable, and if they are able to cure a subs... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3319938 Fri, 26 Feb 2010 00:00:00 +0100 3319938 http://www.medworm.com/index.php?rid=3291379&cid=s_36144_67_f&fid=36144&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20167536%26dopt%3DAbstract Authors: Prevarskaya N, Skryma R, Shuba Y Plasma membrane (PM) ion channels contribute to virtually all basic cellular processes and are also involved in the malignant phenotype of cancer cells. Here, we review the role of ion channels in cancer in the context of their involvement in the defined hallmarks of cancer: 1) self-sufficiency in growth signals, 2) insensitivity to antigrowth signals, 3) evasion of programmed cell death (apoptosis), 4) limitless replicative potential, 5) sustained angiogenesis and 6) tissue invasion and metastasis. Recent studies have indicated that the contribution of specific ion channels to these hallmarks varies for different types of cancer. Therefore, to determine the importance of ion channels as targets for cancer diagnosis and treatment their expressi... Trends in Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3291379 Tue, 16 Feb 2010 00:00:00 +0100 3291379