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Translocation of short and long polymers through an interacting pore
F. Piguet and D. P. Foster We perform two-dimensional Langevin dynamics simulations of electric-field driven polymer translocation through an attractive nanopore. We investigate the effect of the location of the attractive region using different pore patterns. This is found to have an impact on both the translocation time as ... [J. Chem. Phys. 138, 084902 (2013)] published Thu Feb 28, 2013. (Source: Journal of Chemical Physics)
Source: Journal of Chemical Physics - March 1, 2013 Category: Physics Source Type: research

Reply
This is a reply in response to the correspondence from Uller regarding our recent publication by Lee et al entitled “Thymic stromal lymphopoietin is induced by respiratory syncytial virus-infected airway epithelial cells and promotes a type 2 response to infection” in the JACI. In that publication we demonstrate that infection of primary human airway epithelial cells by respiratory syncytial virus (RSV) or Sendai virus induces the cytokine thymic stromal lymphopoietin (TSLP) in a retinoic acid–induced gene I (RIG-I)- and nuclear factor-κB (NF-κB)-dependent manner. Uller and colleagues have shown that simvastatin...
Source: Journal of Allergy and Clinical Immunology - March 1, 2013 Category: Allergy & Immunology Authors: Steven F. Ziegler Tags: Correspondence Source Type: research

Signaling or binding: the role of the platelet activating factor receptor in invasive pneumococcal disease
Abstract Streptococcus pneumoniae (the pneumococcus) is an opportunistic human pathogen, which causes serious invasive disease such as pneumonia, bacteremia and meningitis. The interaction of the bacteria with host receptors precedes the development of invasive disease. One host receptor implicated in pneumococcal adhesion to, invasion of and ultimately translocation of cell layers is the platelet activating factor receptor (PAFR). PAFR is a G‐protein coupled receptor which binds PAF, a potent phospholipid activator involved in many leukocyte functions, platelet aggregation and inflammation. PAFR has been proposed to bin...
Source: Cellular Microbiology - February 28, 2013 Category: Microbiology Authors: Federico Iovino, Matthijs C. Brouwer, Diederik Beek, Grietje Molema, Jetta JE. Bijlsma Tags: Microreview Source Type: research

Follicular Lymphoma in Taiwan: A Low Frequency of t(14;18) with Grade 3A Tumours More Closely Related to Grade 3B Than to Low‐grade Tumours
ConclusionIn Taiwan, FL3A was more closely related to FL3B than to LG tumours and literature review showed that the frequency of t(14;18)/IGH‐BCL2 in FL in Taiwan is among the lowest in the world.© 2013 Blackwell Publishing Ltd (Source: Histopathology)
Source: Histopathology - February 27, 2013 Category: Pathology Authors: Yi‐Hsuan Lu, Sheng‐Tsung Chang, Chin‐Li Lu, Szu‐Yin Kuo, Hongxiang Liu, Shu‐Hui Lin, Khin Than Win, Yen‐Chuan Hsieh, Shih‐Sung Chuang Tags: Original Article Source Type: research

Impact of chromosomal translocation and genomic instability on personalized medicine
Personalized Medicine , March 2013, Vol. 10, No. 2, Pages 111-114. (Source: Future Medicine: Personalized Medicine)
Source: Future Medicine: Personalized Medicine - February 27, 2013 Category: Genetics & Stem Cells Tags: article Source Type: research

Transition of Organizational Category on Renal Cancer
The incidence of kidney cancer is gradually increasing, with a rate of 2–3% per decade. The kidney develops various kinds of neoplasms, some of which are associated with familial cancer syndromes. Such cases have provided clues to identify the cancer-responsible genes. In 2004, the World Health Organization published a new classification system of renal neoplasms, incorporating recent knowledge obtained in the cytogenetic and molecular biological fields, i.e. genes responsible for each histologic subtype (von Hippel-Lindau for clear cell renal cell carcinoma, c-met for papillary renal cell carcinoma type 1, etc.). Su...
Source: Japanese Journal of Clinical Oncology - February 27, 2013 Category: Cancer & Oncology Authors: Nagashima, Y., Kuroda, N., Yao, M. Tags: Review Articles Source Type: research

Attenuated antigen-specific T cell responses in cirrhosis are accompanied by elevated serum interleukin-10 levels and down-regulation of HLA-DR on monocytes
Conclusion: Our data suggest that bacterial translocation, endotoxaemia, inflammation and T cell activation in cirrhosis are accompanied by an increase in circulating anti-inflammatory cytokines, reduced monocytic MHC class II expression and attenuated cytokine production in T cells. These changes are likely to contribute to altered adaptive immune responses during infection or after vaccination. (Source: BMC Gastroenterology)
Source: BMC Gastroenterology - February 27, 2013 Category: Gastroenterology Authors: Jack PeterOliver FreyAndreas StallmachTony Bruns Source Type: research

Cigarette smoke exposure severely reduces peripheral insulin sensitivity without changing GLUT4 expression in oxidative muscle of Wistar rats
CONCLUSION: These results suggest that passive smoking stimulates GLUT4 transcription without changing total protein content, but impairs the ability of GLUT4 translocation to the PM. On the other hand, training seems to reduce the deleterious effects, even under the influence of cigarette smoking.OBJETIVO: Avaliar o efeito da exposição à fumaça de cigarro e do treinamento de corrida em esteira rolante sobre a expressão do transportador de glicose GLUT4 no músculo oxidativo solear de ratos. MATERIAIS E MÉTODOS: Ratos Wistar foram divididos em: (C) controle, (E) exercitado, (SS) fumante sedentário e (ES) fumante exe...
Source: Arquivos Brasileiros de Endocrinologia e Metabologia - February 26, 2013 Category: Endocrinology Source Type: research

Structure, translocation in nuclear pore complex [Biophysics and Computational Biology]
The molecular structure of the yeast nuclear pore complex (NPC) and the translocation of model particles have been studied with a molecular theory that accounts for the geometry of the pore and the sequence and anchoring position of the unfolded domains of the nucleoporin proteins (the FG-Nups), which control selective... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - February 26, 2013 Category: Science Authors: Tagliazucchi, M., Peleg, O., Kroger, M., Rabin, Y., Szleifer, I. Tags: Biological Sciences Source Type: research

Molecular characteristics of horse phospholipase C zeta (PLCζ)
Abstract A sperm‐specific phospholipase C (PLC), PLCzeta (PLCζ), is thought to underlie the initiation of calcium ([Ca2+]i) oscillations that induce egg activation in mammals. In large domestic species, only bovine, porcine and recently equine PLCζ have been cloned, and the physiological functions of these molecules have not been fully characterized. Here, we evaluated the physiological functions of equine PLCζ (ePLCζ) in mouse oocytes. ePLCζ was cloned from testis using RT‐PCR. The expression of ePLCζ messenger RNA was confirmed in testis but not in other tissues. Microinjection of ePLCζ complementary RNA (cRNA...
Source: Animal Science Journal - February 26, 2013 Category: Zoology Authors: Kana Sato, Takuya Wakai, Yasunari Seita, Akiko Takizawa, Rafael A. Fissore, Junya Ito, Naomi Kashiwazaki Tags: Rapid Communication Source Type: research

Contamination of amniotic fluid with maternal balanced t(11;22) translocation cells
(Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - February 26, 2013 Category: Genetics & Stem Cells Authors: Siv Fokstuen, Franz Binkert, Analia Munoz, Niklaus Erb, Peter Dürig, Hans Jörg Altermatt, Jean‐Louis Blouin, Dieter Kotzot Tags: Clinical Report Source Type: research

Posttranslational modifications and secretion efficiency of immunogenic hepatitis B virus L protein deletion variants
Conclusions: The large deletion in 1-48preS/S in presence of the myristoylation site facilitated formation and secretion of protein particles with neutralizing preS1 epitopes at their surface and could be a useful feature for future hepatitis B vaccines. (Source: Virology Journal)
Source: Virology Journal - February 25, 2013 Category: Virology Authors: Baiba Niedre-OtomereAnce BogdanovaRuta BruvereVelta OseWolfram GerlichPaul PumpensDieter GlebeTatjana Kozlovska Source Type: research

Suppression of PU.1‐linked TLR4 expression by cilostazol with decrease of cytokine production in macrophages from patients with rheumatoid arthritis
Conclusions and ImplicationsCilostazol down‐regulated LPS‐stimulated PU.1‐linked TLR4 expression and TLR4/MyD88/NF‐κB signal pathways, and then suppressed inflammatory cytokine production in synovial macrophages from RA patients. Also cilostazol markedly inhibited the severity of CIA in mice. (Source: British Journal of Pharmacology)
Source: British Journal of Pharmacology - February 25, 2013 Category: Drugs & Pharmacology Authors: SY Park, SW Lee, SH Baek, CW Lee, WS Lee, BY Rhim, KW Hong, CD Kim Tags: Research Paper Source Type: research

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management
Disease overviewMultiple myeloma accounts for approximately 10% of hematologic malignancies. DiagnosisThe diagnosis requires 10% or more clonal plasma cells on bone marrow examination or a biopsy proven plasmacytoma plus evidence of associated end‐organ damage. In addition, the presence of 60% or more clonal plasma cells in the marrow is also considered as myeloma regardless of the presence or absence of end‐organ damage. Risk stratificationIn the absence of concurrent trisomies, patients with 17p deletion, t(14;16), and t(14;20) are considered to have high‐risk myeloma. Patients with t(4;14) translocation are consid...
Source: American Journal of Hematology - February 25, 2013 Category: Hematology Authors: S. Vincent Rajkumar Tags: A Continuing Medical Education Series Source Type: research

Oxidative stress regulates the ubiquitin-proteasome system and immunoproteasome functioning in a mouse model of X-adrenoleukodystrophy
Oxidative damage is a pivotal aetiopathogenic factor in X-linked adrenoleukodystrophy. This is a neurometabolic disease characterized by the accumulation of very-long-chain fatty acids owing to the loss of function of the peroxisomal transporter Abcd1. Here, we used the X-linked adrenoleukodystrophy mouse model and patient’s fibroblasts to detect malfunctioning of the ubiquitin–proteasome system resulting from the accumulation of oxidatively modified proteins, some involved in bioenergetic metabolism. Furthermore, the immunoproteasome machinery appears upregulated in response to oxidative stress, in the absence...
Source: Brain - February 24, 2013 Category: Neurology Authors: Launay, N., Ruiz, M., Fourcade, S., Schluter, A., Guilera, C., Ferrer, I., Knecht, E., Pujol, A. Tags: Original Articles Source Type: research

Dermatofibrosarcoma Protuberans in Childhood Treated with Slow Mohs Micrographic Surgery
Abstract Dermatofibrosarcoma protuberans (DFSP) in childhood is a rare tumor with high recurrence rates. Wide local excision can result in disfiguring mutilation, whereas Mohs micrographic surgery (MMS) reduces surgical margins. MMS in children is not performed routinely, as the required infrastructures such as a histopathology lab in close proximity to the operating room is often lacking. We retrospectively reviewed children diagnosed with DFSP treated at our hospital over 2 years. We recorded surgical treatment details, including margins, duration of inpatient stay, outcome, follow‐up, and molecular genetic tumor tiss...
Source: Pediatric Dermatology - February 22, 2013 Category: Dermatology Authors: Marjam J. Barysch, Lisa Weibel, Kathrin Neuhaus, Ulrike Subotic, Leo Schärer, Davide Donghi, Juerg Hafner, Ralph Braun, Severin Läuchli, Reinhard Dummer, Clemens Schiestl Tags: Clinical and Laboratory Investigation Source Type: research

Concentration Dependence of G{alpha}t on Rod Sensitivity [Signal Transduction]
In this study, we replaced cone transducin α (cTα) for rod transducin α (rTα) in rod photoreceptors of transgenic mice, which also express S opsin, to evaluate the role of Gα subtype on signal amplification from different GPCRs in the same cell; such analysis may explain functional differences between retinal rod and cone photoreceptors. We showed that ectopically expressed cTα 1) forms a heterotrimeric complex with rod Gβ1γ1, 2) substitutes equally for rTα in generating photoresponses initiated by either rhodopsin or S-cone opsin, and 3) exhibited similar light-activated translocation as endogenous rTα in rods a...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Mao, W., Miyagishima, K. J., Yao, Y., Soreghan, B., Sampath, A. P., Chen, J. Tags: Signal Transduction Source Type: research

Role of p21WAF1 in IL-20-induced Migration [Cell Biology]
The role of inflammatory cytokine interleukin-20 (IL-20) has not yet been studied in cancer biology. Here, we demonstrated up-regulation of both IL-20 and IL-20R1 in muscle-invasive bladder cancer patients. The expressions of IL-20 and IL-20R1 were observed in bladder cancer 5637 and T-24 cells. We found that IL-20 significantly increased the expression of matrix metalloproteinase (MMP)-9 via binding activity of NF-κB and AP-1 in bladder cancer cells and stimulated the activation of ERK1/2, JNK, p38 MAPK, and JAK-STAT signaling. Among the pathways examined, only ERK1/2 inhibitor U0126 significantly inhibited IL-20-induced...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Lee, S.-J., Cho, S.-C., Lee, E.-J., Kim, S., Lee, S.-B., Lim, J.-H., Choi, Y. H., Kim, W.-J., Moon, S.-K. Tags: Immunology Source Type: research

PIP5K{alpha} Facilitates LPS-induced Microglial Inflammation [Immunology]
Phosphatidylinositol (PI) 4,5-bisphosphate (PIP2), generated by PI 4-phosphate 5-kinase (PIP5K), regulates many critical cellular events. PIP2 is also known to mediate plasma membrane localization of the Toll/IL-1 receptor domain-containing adaptor protein (TIRAP), required for the MyD88-dependent Toll-like receptor (TLR) 4 signaling pathway. Microglia are the primary immune competent cells in brain tissue, and TLR4 is important for microglial activation. However, a functional role for PIP5K and PIP2 in TLR4-dependent microglial activation remains unclear. Here, we knocked down PIP5Kα, a PIP5K isoform, in a BV2 microglial...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Nguyen, T. T. N., Kim, Y. M., Kim, T. D., Le, O. T. T., Kim, J. J., Kang, H. C., Hasegawa, H., Kanaho, Y., Jou, I., Lee, S. Y. Tags: Signal Transduction Source Type: research

AMPK Activation by Emodin [Cell Biology]
AMP-activated protein kinase has been described as a key signaling protein that can regulate energy homeostasis. Here, we aimed to characterize novel AMP-activated kinase (AMPK)-activating compounds that have a much lower effective concentration than metformin. As a result, emodin, a natural anthraquinone derivative, was shown to stimulate AMPK activity in skeletal muscle and liver cells. Emodin enhanced GLUT4 translocation and [14C]glucose uptake into the myotube in an AMPK-dependent manner. Also, emodin inhibited glucose production by suppressing the expression of key gluconeogenic genes, such as phosphoenolpyruvate carb...
Source: Journal of Biological Chemistry - February 22, 2013 Category: Chemistry Authors: Song, P., Kim, J. H., Ghim, J., Yoon, J. H., Lee, A., Kwon, Y., Hyun, H., Moon, H.-Y., Choi, H.-S., Berggren, P.-O., Suh, P.-G., Ryu, S. H. Tags: Metabolism Source Type: research

Investigation of the mechanisms by which the molecular chaperone HSPA2 regulates the expression of sperm surface receptors involved in human sperm-oocyte recognition
In this study, we have extended our findings through the characterization of one such complex containing arylsulfatase A (ARSA), sperm adhesion molecule 1 (SPAM1) and the molecular chaperone, heat shock 70kDa protein 2 (HSPA2). Through the application of flow cytometry we revealed that this complex undergoes a capacitation-associated translocation to facilitate the repositioning of ARSA to the apical region of the human sperm head, a location compatible with a role in the mediation of sperm–zona pellucida (ZP) interactions. Conversely, SPAM1 appears to reorient away from the sperm surface, possibly reflecting its pri...
Source: Molecular Human Reproduction - February 22, 2013 Category: Molecular Biology Authors: Redgrove, K. A., Anderson, A. L., McLaughlin, E. A., O'Bryan, M. K., Aitken, R. J., Nixon, B. Tags: Editorial Source Type: research

Selective activation of protein kinase Cϵ in mitochondria is neuroprotective in vitro and reduces focal ischemic brain injury in mice
Abstract Activation of protein kinase Cϵ (PKCϵ) confers protection against neuronal ischemia/reperfusion. Activation of PKCϵ leads to its translocation to multiple intracellular sites, so a mitochondria‐selective PKCϵ activator was used to test the importance of mitochondrial activation to the neuroprotective effect of PKCϵ. PKCϵ can regulate key cytoprotective mitochondrial functions, including electron transport chain activity, reactive oxygen species (ROS) generation, mitochondrial permeability transition, and detoxification of reactive aldehydes. We tested the ability of mitochondria‐selective activation of P...
Source: Journal of Neuroscience Research - February 21, 2013 Category: Neuroscience Authors: Xiaoyun Sun, Grant R. Budas, Lijun Xu, George E. Barreto, Daria Mochly‐Rosen, Rona G. Giffard Tags: Research Article Source Type: research

Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins
Hemolysis occurs in many hematologic and nonhematologic diseases. Extracellular hemoglobin (Hb) has been found to trigger specific pathophysiologies that are associated with adverse clinical outcomes in patients with hemolysis, such as acute and chronic vascular disease, inflammation, thrombosis, and renal impairment. Among the molecular characteristics of extracellular Hb, translocation of the molecule into the extravascular space, oxidative and nitric oxide reactions, hemin release, and molecular signaling effects of hemin appear to be the most critical. Limited clinical experience with a plasma-derived haptoglobin (Hp) ...
Source: Blood - February 21, 2013 Category: Hematology Authors: Schaer, D. J., Buehler, P. W., Alayash, A. I., Belcher, J. D., Vercellotti, G. M. Tags: Perspectives, Red Cells, Iron, and Erythropoiesis Source Type: research

Nucleoplasmic calcium signaling and cell proliferation: calcium signaling in the nucleus
Calcium (Ca2+) is an essential signal transduction element involved in the regulation of several cellular activities and it is required at various key stages of the cell cycle. Intracellular Ca2+ is crucial for the orderly cell cycle progression and plays a vital role in the regulation of cell proliferation. Recently, it was demonstrated by in vitro and in vivo studies that nucleoplasmic Ca2+ regulates cell growth. Even though the mechanism by which nuclear Ca2+ regulates cell proliferation is not completely understood, there are reports demonstrating that activation of tyrosine kinase receptors (RTKs) leads to translocati...
Source: Cell Communication and Signaling - February 21, 2013 Category: Molecular Biology Authors: Rodrigo ResendeLidia AndradeAndre OliveiraErika GuimarãesSilvia GuatimosimM Leite Source Type: research

Sulforaphane prevents human platelet aggregation through inhibiting the phosphatidylinositol 3-kinase/Akt pathway.
In conclusion, we have demonstrated that sulforaphane prevented platelet aggregation and reduced thrombus formation in flow conditions; our data also support that the inhibition of the PI3K/Akt pathway by sulforaphane contributes it antiplatelet effects. PMID: 23426129 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - February 21, 2013 Category: Hematology Authors: Chuang WY, Kung PH, Kuo CY, Wu CC Tags: Thromb Haemost Source Type: research

Disruption of EXOC6B in a patient with developmental delay, epilepsy, and a de novo balanced t(2;8) translocation
s Zschocke & Dieter Kotzot (Source: European Journal of Human Genetics)
Source: European Journal of Human Genetics - February 20, 2013 Category: Genetics & Stem Cells Authors: Anne FrühmesserJonathon BlakeEdda HaberlandtBianka BayingBenjamin RaederHeiko RunzAna SpreizChristine FauthVladimir BenesGerd UtermannJohannes ZschockeDieter Kotzot Tags: balanced translocation gene disruption next-generation sequencing Source Type: research

Cytochrome P4502E1 inhibitor, chlormethiazole, decreases lipopolysaccharide‐induced inflammation in rat Kupffer cells with ethanol treatment
ConclusionIn cultured Kupffer cell, using CMZ as inhibitor, ethanol‐induced CYP2E1 overexpression was proved to contribute to the sensitization of Kupffer cells to LPS stimuli, with amplification of ROS production and activation of NF‐κB, resulting in increased TNF‐α production. (Source: Hepatology Research)
Source: Hepatology Research - February 20, 2013 Category: Internal Medicine Authors: Qinyuan Ye, Xiangdong Wang, Qing Wang, Min Xia, Yanna Zhu, Fuzhi Lian, Wenhua Ling Tags: Original Article Source Type: research

Apoptosis induced by Trimethyltin chloride in human neuroblastoma cells SY5Y is regulated by a balance and cross-talk between NF-κB and MAPKs signaling pathways.
Abstract Trimethyltin chloride (TMT) has been known as a classic neurotoxicant which can cause serious neuronal degeneration diseases. Nuclear factor κB (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways play pivotal role in the central nerves system. In the present study, the intracellular pathways involved in TMT-induced apoptosis on human neuroblastoma cells SY5Y (SH-SY5Y) were investigated. We observed high level of nuclear NF-κB p65 submit, activated JNK, ERK, and p38 by TMT exposure. In contrast, low level of Bcl-2 and XIAP (two known NF-κB-regulated endogenous anti-apoptotic molecul...
Source: Archives of Toxicology - February 20, 2013 Category: Toxicology Authors: Qing Y, Liang Y, Du Q, Fan P, Xu H, Xu Y, Shi N Tags: Arch Toxicol Source Type: research

In vivo analysis of human nucleoporin repeat domain interactions.
Abstract The nuclear pore complex (NPC), assembled from ∼30 proteins termed nucleoporins (Nups), mediates selective nucleocytoplasmic trafficking. A subset of nucleoporins bear a domain with multiple FG motifs. As binding sites for transport receptors, FG Nups are critical in translocation through the NPC. Certain FG Nups are thought to associate via low affinity, cohesive interactions to form the permeability barrier of the pore, although the form and composition of this functional barrier are debated. We used GFP-Nup98/HoxA9 constructs with varying numbers of repeats, and also substituted FG domains from other ...
Source: Mol Biol Cell - February 20, 2013 Category: Molecular Biology Authors: Xu S, Powers MA Tags: Mol Biol Cell Source Type: research

The effect of surface topography on cell shape and early ERK1/2 signaling in macrophages; linkage with FAK and Src.
This study investigated the activation of FAK, Src, and ERK1/2 signaling intermediates of the proinflammatory ERK1/2 pathway in RAW 264.7 macrophages in response to polished (P), coarse-grit-blasted (B), acid etched (E), and grit-blasted and etched (SLA) surface topographies. In addition, the effects of these topographies on cell spreading, vinculin organization, and viability were determined. Macrophages on the SLA surface changed from predominantly well-spread cells to ones with a more spherical morphology over time. In contrast, macrophages on the P surface changed from being predominantly spherical cells to well spread...
Source: Cell Research - February 20, 2013 Category: Cytology Authors: Ghrebi S, Hamilton DW, Douglas Waterfield J, Brunette DM Tags: J Biomed Mater Res A Source Type: research

A Novel Point Mutation in the DNA-Binding Domain (DBD) of the Human Glucocorticoid Receptor Causes Primary Generalized Glucocorticoid Resistance by Disrupting the Hydrophobic Structure of its DBD.
Conclusions:The natural mutant receptor hGRαV423A causes primary generalized glucocorticoid resistance by affecting multiple steps in the cascade of glucocorticoid receptor action, which primarily involve decreased ability to bind to target glucocorticoid response elements and delayed translocation into the nucleus. PMID: 23426617 [PubMed - as supplied by publisher] (Source: The Journal of Clinical Endocrinology and Metabolism)
Source: The Journal of Clinical Endocrinology and Metabolism - February 20, 2013 Category: Endocrinology Authors: Roberts ML, Kino T, Nicolaides NC, Hurt DE, Katsantoni E, Sertedaki A, Komianou F, Kassiou K, Chrousos GP, Charmandari E Tags: J Clin Endocrinol Metab Source Type: research

Type-IVB effectors secretion signal [Microbiology]
Legionella and Coxiella are intracellular pathogens that use the virulence-related Icm/Dot type-IVB secretion system to translocate effector proteins into host cells during infection. These effectors were previously shown to contain a C-terminal secretion signal required for their translocation. In this research, we implemented a hidden semi-Markov model to characterize the... (Source: Proceedings of the National Academy of Sciences)
Source: Proceedings of the National Academy of Sciences - February 19, 2013 Category: Science Authors: Lifshitz, Z., Burstein, D., Peeri, M., Zusman, T., Schwartz, K., Shuman, H. A., Pupko, T., Segal, G. Tags: PNAS Plus Source Type: research

Functional insights into the Shigella type III needle tip IpaD in secretion control and cell contact
Summary Type III secretion apparatus (T3SA) are complex nanomachines that insert a translocation pore into the host cell membrane through which effector proteins are injected into the cytosol. In Shigella, the pore is inserted by a needle tip complex that also controls secretion. IpaD is the key protein that rules the composition of the tip complex before and upon cell contact or Congo red (CR) induction. However, how IpaD is involved in secretion control and translocon insertion remains not fully understood. Here, we report the phenotypic analysis of twenty ten amino acids deletion variants all along the coiled‐coil and...
Source: Molecular Microbiology - February 19, 2013 Category: Microbiology Authors: Lionel Schiavolin, Alaeddine Meghraoui, Youness Cherradi, Latéfa Biskri, Anne Botteaux, Abdelmounaaïm Allaoui Tags: Research Article Source Type: research

Histone Deacetylase Inhibition Attenuates Transcriptional Activity of Mineralocorticoid Receptor Through its Acetylation and Prevents Development of Hypertension.
Conclusions: These results indicate that HDACi attenuates transcriptional activity of MR through its acetylation and prevents development of hypertension in DOCA-induced hypertensive rats. PMID: 23421989 [PubMed - as supplied by publisher] (Source: Circulation Research)
Source: Circulation Research - February 19, 2013 Category: Cardiology Authors: Lee HA, Lee DY, Cho HM, Kim SY, Iwasaki Y, Kim I Tags: Circ Res Source Type: research

Betulinic acid alleviates non-alcoholic fatty liver by inhibiting SREBP1 activity via the AMPK-mTOR-SREBP signaling pathway.
Abstract Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialized countries. The discovery of food components that can ameliorate NAFLD is therefore of interest. Betulinic acid (BA) is a triterpenoid with many pharmacological activities, but the effect of BA on fatty liver is as yet unknown. To explore the possible anti-fatty liver effects and their underlying mechanisms, we used insulin-resistant HepG2 cells, primary rat hepatocytes and liver tissue from ICR mice fed a high-fat diet (HFD). Oil Red O staining revealed that BA significantly suppressed excessive triglyc...
Source: Biochemical Pharmacology - February 19, 2013 Category: Drugs & Pharmacology Authors: Quan HY, Kim DY, Kim SJ, Jo HK, Kim GW, Chung SH Tags: Biochem Pharmacol Source Type: research

Rac1 signaling is required for insulin-stimulated glucose uptake and is dysregulated in insulin resistant murine and human skeletal muscle.
Abstract The actin-cytoskeleton-regulating GTPase Rac1 is required for insulin-stimulated GLUT4 translocation in cultured muscle cells. However, involvement of Rac1 and its downstream signaling in glucose transport in insulin sensitive and insulin resistant mature skeletal muscle has not previously been investigated. We hypothesized that Rac1 and its downstream target, p21-activated kinase (PAK), are regulators of insulin-stimulated glucose uptake in mouse and human skeletal muscle, and are dysregulated in insulin resistant states.Muscle specific inducible Rac1 knockout (KO) mice and pharmacological inhibition of R...
Source: Diabetes - February 19, 2013 Category: Endocrinology Authors: Sylow L, Jensen TE, Kleinert M, Højlund K, Kiens B, Wojtaszewski J, Prats C, Schjerling P, Richter EA Tags: Diabetes Source Type: research

Novel transcriptional regulation of VEGF in inflammatory processes
This study builds upon our previous results in testing the role of mouse LITAF and STAT6B in the regulation of VEGF‐mediated processes. Cells cotransfected with a series of VEGF promoter deletions along with truncated forms of mLITAF and/or mSTAT6B identified a DNA binding site (between −338 and −305 upstream of the transcription site) important in LITAF and/or STAT6B‐mediated transcriptional regulation of VEGF. LITAF and STAT6B corresponding protein sites were identified. In addition, siRNA‐mediated knockdown of mLITAF and/or mSTAT6B leads to significant reduction in VEGF mRNA levels and inhibits LPS‐induced V...
Source: Journal of Cellular and Molecular Medicine - February 18, 2013 Category: Molecular Biology Authors: Xiaoren Tang, Yu Yang, Huaiping Yuan, Jian You, Marina Burkatovskaya, Salomon Amar Tags: Original Article Source Type: research

Identification and Molecular Cytogenetic Characterization of a novel complex Y chromosome rearrangement in a boy with disorder of sexual development.
Abstract Ambiguous genitalia or Disorders of the sexual development is a birth defect where the external genitals do not have the typical appearance of either a male or female. Here we report a boy with Ambiguous Genitalia and Short stature. The cytogenetic analysis by G-banding revealed a small Y chromosome and an additional material on the 15 p arm. Further, Molecular cytogenetic analysis by Fluorescence in situ hybridization (FISH) using whole chromosome paint probes showed the presence of Y sequences on 15p arm, confirming that it is a Y;15 translocation. Subsequent, FISH with centromere probe Y showed two sign...
Source: Gene - February 18, 2013 Category: Genetics & Stem Cells Authors: Dutta UR, Pidugu VK, Goud CV, Hoefers C, Hagemann M, Dalal A Tags: Gene Source Type: research

Novel transcriptional regulation of VEGF in inflammatory processes.
This study builds upon our previous results in testing the role of mouse LITAF and STAT6B in the regulation of VEGF-mediated processes. Cells cotransfected with a series of VEGF promoter deletions along with truncated forms of mLITAF and/or mSTAT6B identified a DNA binding site (between -338 and -305 upstream of the transcription site) important in LITAF and/or STAT6B-mediated transcriptional regulation of VEGF. LITAF and STAT6B corresponding protein sites were identified. In addition, siRNA-mediated knockdown of mLITAF and/or mSTAT6B leads to significant reduction in VEGF mRNA levels and inhibits LPS-induced VEGF secretio...
Source: J Cell Mol Med - February 18, 2013 Category: Molecular Biology Authors: Tang X, Yang Y, Yuan H, You J, Burkatovskaya M, Amar S Tags: J Cell Mol Med Source Type: research

Implications of purinergic receptor-mediated intracellular calcium transients in neural differentiation
Purinergic receptors participate, in almost every cell type, in controlling metabolic activities and many physiological functions including signal transmission, proliferation and differentiation. While most of P2Y receptors induce transient elevations of intracellular calcium concentration by activation of intracellular calcium pools and forward these signals as waves which can also be transmitted into neighboring cells, P2X receptors produce calcium spikes which also include activation of voltage-operating calcium channels. P2Y and P2X receptors induce calcium transients that activate transcription factors responsible for...
Source: BioMed Central - February 17, 2013 Category: Journals (General) Authors: Talita GlaserRodrigo R ResendeHenning Ulrich Source Type: research

Klebsiella pneumoniae targets an EGF receptor‐dependent pathway to subvert inflammation
Summary The NF‐κB transcriptional factor plays a key role governing the activation of immune responses. Klebsiella pneumoniae is an important cause of community‐acquired and nosocomial pneumonia. Evidence indicates that K. pneumoniae infections are characterized by lacking an early inflammatory response. Recently, we have demonstrated that Klebsiella antagonizes the activation of NF‐κB via the deubiquitinase CYLD. In this work, by applying a high‐throughput siRNA gain‐of‐function screen interrogating the human kinome, we identified 17 kinases that when targeted by siRNA restored IL‐1β‐dependent NF‐κ...
Source: Cellular Microbiology - February 17, 2013 Category: Microbiology Authors: Christian G. Frank, Verónica Reguerio, Marion Rother, David Moranta, André P. Maeurer, Junkal Garmendia, Thomas F. Meyer, José A. Bengoechea Tags: Research Article Source Type: research

Caffeoylserotonin Protects Human Keratinocyte HaCaT Cells against H2O2‐Induced Oxidative Stress and Apoptosis through Upregulation of HO‐1 Expression via Activation of the PI3K/Akt/Nrf2 Pathway
Caffeoylserotonin (CaS) has strong radical scavenging activity as well as antioxidant activities, protecting cells from lipid peroxidation, intracellular reactive oxygen species generation, DNA damage, and cell death. The molecular mechanism by which CaS protects against oxidative stress is not well understood. Here, we analyzed the cytoprotective activity of CaS in hydrogen peroxide (H2O2)‐treated keratinocyte HaCaT cells. H2O2 induced apoptosis in the cells through activation of pro‐apoptotic p21, Bax, and caspase‐3. Pretreatment with CaS inhibited apoptotic gene expression and activated the anti‐apoptotic gene, ...
Source: Phytotherapy Research - February 17, 2013 Category: Biochemistry Authors: Cam Ngoc Nguyen, Hye‐Eun Kim, Seong‐Gene Lee Tags: Research Article Source Type: research

Crystal structure of the entire respiratory complex I
A. Sazanov Complex I is the first and largest enzyme of the respiratory chain and has a central role in cellular energy production through the coupling of NADH:ubiquinone electron transfer to proton translocation. It is also implicated in many common human neurodegenerative diseases. Here, we report the (Source: Nature)
Source: Nature - February 17, 2013 Category: Research Authors: Rozbeh BaradaranJohn M. BerrisfordGurdeep S. MinhasLeonid A. Sazanov Tags: Article Source Type: research

Chain deformation in translocation phenomena
Soft Matter, 2013, 9,2750-2759DOI: 10.1039/C2SM27416G, PaperFarnoush Farahpour, Azadeh Maleknejad, Fathollah Varnik, Mohammad Reza EjtehadiDNA as a charged flexible macromolecule can deform in an electric field gradient. In translocation experiments with an applied external electric voltage, in the vicinity of a pore there is a region with such a gradient which extends the chain and facilitates the process of finding the pore entrance for the end monomers.The content of this RSS Feed (c) The Royal Society of Chemistry (Source: RSC - Soft Matter latest articles)
Source: RSC - Soft Matter latest articles - February 16, 2013 Category: Chemistry Authors: Farnoush Farahpour Source Type: research

GH1-family 6-P-β-glucosidases from human microbiome lactic acid bacteria
In lactic acid bacteria and other bacteria, carbohydrate uptake is mostly governed by phosphoenolpyruvate-dependent phosphotransferase systems (PTSs). PTS-dependent translocation through the cell membrane is coupled with phosphorylation of the incoming sugar. After translocation through the bacterial membrane, the β-glycosidic bond in 6′-P-β-glucoside is cleaved, releasing 6-P-β-glucose and the respective aglycon. This reaction is catalyzed by 6-P-β-glucosidases, which belong to two glycoside hydrolase (GH) families: GH1 and GH4. Here, the high-resolution crystal structures of GH1 6-P-β-glucosidases from Lactobacill...
Source: Acta Crystallographica Section D - February 16, 2013 Category: Biochemistry Authors: Michalska, K.Tan, K.Li, H.Hatzos-Skintges, C.Bearden, J.Babnigg, G.Joachimiak, A. Tags: 6-P- β -glucosidases glycoside hydrolases GH1 cellobiose gentiobiose salicin research papers Source Type: research

Translocation t(X;11)(q22;q25) in a Woman with Premature Ovarian Failure.
This report describes an X;11 translocation, t(X;11)(q22;q25), in a woman diagnosed with POF. The FSH level was found to be elevated. Menstrual cycle was regular initially, and she had a spontaneous abortion at the 5th month of gestation at 16 years of age. Her mother was karyotypically normal while her father was not investigated. Male carriers of X;autosome translocations are mostly infertile, and hence the translocation is presumed to be of de novo origin. Fluorescence in situ hybridization using whole chromosome paint probes confirmed the rearrangement. PMID: 23429171 [PubMed - as supplied by publisher] (Source: Se...
Source: Sexual Development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation - February 16, 2013 Category: Genetics & Stem Cells Authors: Saranya B, Kavitha Devi D, Chandra RS, Jayashankar M, Santhiya ST Tags: Sex Dev Source Type: research

Comparative study of alleviating effects of GSH, Se and Zn under combined contamination of cadmium and chromium in rice (Oryza sativa).
Abstract A hydroponic experiment was conducted to study the ameliorative effects of separate or combined application of exogenous glutathione (GSH), selenium (Se) and zinc (Zn) upon 20 μM cadmium (Cd) plus 20 μM chromium (Cr) heavy metal stress (HM) in rice seedlings. The results showed that HM caused a marked reduction in seedling height, chlorophyll content (SPAD) and biomass, and activities of catalase (CAT) and ascorbate peroxidase (APX) in leaves and H(+)-ATPase in roots/leaves, but elevated superoxide dismutase (SOD) and guaiacol peroxidase (POD) activities in leaves with elevated malondialdehyde (MDA) ac...
Source: Biometals - February 16, 2013 Category: Biochemistry Authors: Cao F, Wang N, Zhang M, Dai H, Dawood M, Zhang G, Wu F Tags: Biometals Source Type: research

Guiding lights: recent developments in optogenetic control of biochemical signals.
Abstract Optogenetics arises from the innovative application of microbial opsins in mammalian neurons and has since been a powerful technology that fuels the advance of our knowledge in neuroscience. In recent years, there has been growing interest in designing optogenetic tools extendable to broader cell types and biochemical signals. To date, a variety of photoactivatable proteins (refers to induction of protein activity in contrast to fluorescence) have been developed based on the understanding of plant and microbial photoreceptors including phototropins, blue light sensors using flavin adenine dinucleotide prot...
Source: Pflugers Archiv : European Journal of Physiology - February 16, 2013 Category: Physiology Authors: Yin T, Wu YI Tags: Pflugers Arch Source Type: research

Synergistic effect of a biosurfactant and protamine on gene transfection efficiency.
Abstract Several barriers need to be overcome to ensure successful gene transfection, including passing of the foreign gene through the plasma membrane, escape of this material from lysosomal degradation, and its translocation into the nucleus. We previously showed that the biosurfactant mannosylerythritol lipid-A (MEL-A) enhanced the efficiency of gene transfection mediated by cationic liposomes by facilitating rapid delivery of foreign genes into target cells through membrane fusion between liposomes and the plasma membrane. Moreover, using MEL-A-containing cationic liposomes, the foreign gene was efficiently del...
Source: European Journal of Pharmaceutical Sciences - February 16, 2013 Category: Drugs & Pharmacology Authors: Inoh Y, Furuno T, Hirashima N, Kitamoto D, Nakanishi M Tags: Eur J Pharm Sci Source Type: research

Phospholipid Flippase-mediated Control of Cell Migration [Membrane Biology]
Type IV P-type ATPases (P4-ATPases) and CDC50 family proteins form a putative phospholipid flippase complex that mediates the translocation of aminophospholipids such as phosphatidylserine (PS) and phosphatidylethanolamine (PE) from the outer to inner leaflets of the plasma membrane. In Chinese hamster ovary (CHO) cells, at least eight members of P4-ATPases were identified, but only a single CDC50 family protein, CDC50A, was expressed. We demonstrated that CDC50A associated with and recruited P4-ATPase ATP8A1 to the plasma membrane. Overexpression of CDC50A induced extensive cell spreading and greatly enhanced cell migrati...
Source: Journal of Biological Chemistry - February 15, 2013 Category: Chemistry Authors: Kato, U., Inadome, H., Yamamoto, M., Emoto, K., Kobayashi, T., Umeda, M. Tags: Lipids Source Type: research