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This page shows you the most recent publications within this specialty of the MedWorm directory. This is page number 9.
Phase-amplitude coupling supports phase coding in human ECoG
Prior studies have shown that high-frequency activity (HFA) is modulated by the phase of low-frequency activity. This phenomenon of phase-amplitude coupling (PAC) is often interpreted as reflecting phase coding of neural representations, although evidence for this link is still lacking in humans. Here, we show that PAC indeed supports phase-dependent stimulus representations for categories. Six patients with medication-resistant epilepsy viewed images of faces, tools, houses, and scenes during simultaneous acquisition of intracranial recordings. Analyzing 167 electrodes, we observed PAC at 43% of electrodes. Further inspec...
Source: eLife - September 23, 2015 Category: Biomedical Science Authors: Watrous, A. J., Deuker, L., Fell, J., Axmacher, N. Tags: Neuroscience Source Type: research
Reverse evolution leads to genotypic incompatibility despite functional and active site convergence
Understanding the extent to which enzyme evolution is reversible can shed light on the fundamental relationship between protein sequence, structure, and function. Here, we perform an experimental test of evolutionary reversibility using directed evolution from a phosphotriesterase to an arylesterase, and back, and examine the underlying molecular basis. We find that wild-type phosphotriesterase function could be restored (>104-fold activity increase), but via an alternative set of mutations. The enzyme active site converged towards its original state, indicating evolutionary constraints imposed by catalytic requirements...
Source: eLife - September 23, 2015 Category: Biomedical Science Authors: Kaltenbach, M., Jackson, C. J., Campbell, E. C., Hollfelder, F., Tokuriki, N. Tags: Genomics and evolutionary biology Source Type: research
[Focus] Aging as a driver of leukemogenesis
Certain leukemia-initiating mutations drive expansion of hemopoietic clones specifically under the selection pressures that prevail in an aged microenvironment. (Source: Science Translational Medicine)
Source: Science Translational Medicine - September 23, 2015 Category: Biomedical Science Authors: McKerrell, T., Vassiliou, G. S. Tags: Focus Source Type: research
[Research Articles] A small-molecule antivirulence agent for treating Clostridium difficile infection
We describe pharmacological targeting of the cysteine protease domain (CPD) within the C. difficile major virulence factor toxin B (TcdB). Through a targeted screen with an activity-based probe for this protease domain, we identified a number of potent CPD inhibitors, including one bioactive compound, ebselen, which is currently in human clinical trials for a clinically unrelated indication. This drug showed activity against both major virulence factors, TcdA and TcdB, in biochemical and cell-based studies. Treatment in a mouse model of CDI that closely resembles the human infection confirmed a therapeutic benefit in the f...
Source: Science Translational Medicine - September 23, 2015 Category: Biomedical Science Authors: Bender, K. O., Garland, M., Ferreyra, J. A., Hryckowian, A. J., Child, M. A., Puri, A. W., Solow-Cordero, D. E., Higginbottom, S. K., Segal, E., Banaei, N., Shen, A., Sonnenburg, J. L., Bogyo, M. Tags: Research Articles Source Type: research
[Research Articles] A light-reflecting balloon catheter for atraumatic tissue defect repair
A congenital or iatrogenic tissue defect often requires closure by open surgery or metallic components that can erode tissue. Biodegradable, hydrophobic light-activated adhesives represent an attractive alternative to sutures, but lack a specifically designed minimally invasive delivery tool, which limits their clinical translation. We developed a multifunctional, catheter-based technology with no implantable rigid components that functions by unfolding an adhesive-loaded elastic patch and deploying a double-balloon design to stabilize and apply pressure to the patch against the tissue defect site. The device uses a fiber-...
Source: Science Translational Medicine - September 23, 2015 Category: Biomedical Science Authors: Roche, E. T., Fabozzo, A., Lee, Y., Polygerinos, P., Friehs, I., Schuster, L., Whyte, W., Casar Berazaluce, A. M., Bueno, A., Lang, N., Pereira, M. J. N., Feins, E., Wasserman, S., O'Cearbhaill, E. D., Vasilyev, N. V., Mooney, D. J., Karp, J. M., del Nido Tags: Research Articles Source Type: research
[Research Articles] Broadly neutralizing human monoclonal JC polyomavirus VP1-specific antibodies as candidate therapeutics for progressive multifocal leukoencephalopathy
We examined antibody responses against JCPyV major capsid protein VP1 (viral protein 1) variants in the serum and cerebrospinal fluid (CSF) of healthy donors (HDs), JCPyV-positive multiple sclerosis patients treated with the anti–VLA-4 monoclonal antibody natalizumab (NAT), and patients with NAT-associated PML. Before and during PML, CSF antibody responses against JCPyV VP1 variants show "recognition holes"; however, upon immune reconstitution, CSF antibody titers rise, then recognize PML-associated JCPyV VP1 variants, and may be involved in elimination of the virus. We therefore reasoned that the memory B cell reper...
Source: Science Translational Medicine - September 23, 2015 Category: Biomedical Science Authors: Jelcic, I., Combaluzier, B., Jelcic, I., Faigle, W., Senn, L., Reinhart, B. J., Stroh, L., Nitsch, R. M., Stehle, T., Sospedra, M., Grimm, J., Martin, R. Tags: Research Articles Source Type: research
[Research Articles] JC polyomavirus mutants escape antibody-mediated neutralization
JC polyomavirus (JCV) persistently infects the urinary tract of most adults. Under conditions of immune impairment, JCV causes an opportunistic brain disease, progressive multifocal leukoencephalopathy (PML). JCV strains found in the cerebrospinal fluid of PML patients contain distinctive mutations in surface loops of the major capsid protein, VP1. We hypothesized that VP1 mutations might allow the virus to evade antibody-mediated neutralization. Consistent with this hypothesis, neutralization serology revealed that plasma samples from PML patients neutralized wild-type JCV strains but failed to neutralize patient-cognate ...
Source: Science Translational Medicine - September 23, 2015 Category: Biomedical Science Authors: Ray, U., Cinque, P., Gerevini, S., Longo, V., Lazzarin, A., Schippling, S., Martin, R., Buck, C. B., Pastrana, D. V. Tags: Research Articles Source Type: research
[Editors' Choice] NK cells set sights on cancer stem cells
(Source: Science Translational Medicine)
Source: Science Translational Medicine - September 23, 2015 Category: Biomedical Science Authors: Beswick, E. J. Tags: Editors ' Choice Source Type: research
[Editors' Choice] The importance of lipid for the Alzheimer's brain
(Source: Science Translational Medicine)
Source: Science Translational Medicine - September 23, 2015 Category: Biomedical Science Authors: Janson, C. G. Tags: Editors ' Choice Source Type: research
[Editors' Choice] A dose of exercise to kick-start your gastric bypass
(Source: Science Translational Medicine)
Source: Science Translational Medicine - September 23, 2015 Category: Biomedical Science Authors: Lanza, I. R. Tags: Editors ' Choice Source Type: research
[Editors' Choice] March to the beat of adaptive immunity
(Source: Science Translational Medicine)
Source: Science Translational Medicine - September 23, 2015 Category: Biomedical Science Authors: Singh, A. M. Tags: Editors ' Choice Source Type: research
[Editors' Choice] Precision cancer medicine: Hype or hope?
(Source: Science Translational Medicine)
Source: Science Translational Medicine - September 23, 2015 Category: Biomedical Science Authors: Wang, A. Z. Tags: Editors ' Choice Source Type: research
Modelling the Stoichiometric Regulation of C-Rich Toxins in Marine Dinoflagellates
by Adriano Pinna, Laura Pezzolesi, Rossella Pistocchi, Silvana Vanucci, Stefano Ciavatta, Luca Polimene Toxin production in marine microalgae was previously shown to be tightly coupled with cellular stoichiometry. The highest values of cellular toxin are in fact mainly associated with a high carbon to nutrient cellular ratio. In particular, the cellular accumulation of C-rich toxins (i.e., with C:N > 6.6) can be stimulated by both N and P deficiency. Dinoflagellates are the main producers of C-rich toxins and may represent a serious threat for human health and the marine ecosystem. As such, the development of a numerical ...
Source: PLoS One - September 23, 2015 Category: Biomedical Science Authors: Adriano Pinna et al. Source Type: research
Neuroprotective Potential of Mesenchymal Stem Cell-Based Therapy in Acute Stages of TNBS-Induced Colitis in Guinea-Pigs
Conclusion MSC-based therapies applied at the acute stages of TNBS-induced colitis start exerting their neuroprotective effects towards enteric neurons by 24 hours post treatment. The neuroprotective efficacy of MSC-based therapies can be exerted independently to their anti-inflammatory effects. (Source: PLoS One)
Source: PLoS One - September 23, 2015 Category: Biomedical Science Authors: Ainsley M. Robinson et al. Source Type: research
Hypoxia in the St. Lawrence Estuary: How a Coding Error Led to the Belief that “Physics Controls Spatial Patterns”
by Daniel Bourgault, Frédéric Cyr Two fundamental sign errors were found in a computer code used for studying the oxygen minimum zone (OMZ) and hypoxia in the Estuary and Gulf of St. Lawrence. These errors invalidate the conclusions drawn from the model, and call into question a proposed mechanism for generating OMZ that challenges classical understanding. The study in question is being cited frequently, leading the discipline in the wrong direction. (Source: PLoS One)
Source: PLoS One - September 23, 2015 Category: Biomedical Science Authors: Daniel Bourgault et al. Source Type: research
Telocytes in the Spleen
by Yuqiao Chang, Cixia Li, Li Gan, He Li, Zhikun Guo Telocytes, a novel type of interstitial cells with very long and thin prolongations, have been identified in many organs in mammals. At present, the ultrastructural, immunocytochemical and electrophysiological properties of telocytes in multiple organs have been understood. However, telocytes in spleen, especially their roles in spleen have not been reported. The aim of this study was to investigate the ultrastructure, distribution and immunophenotypes of splenic telocytes. Rat spleen was harvested for the ultrastructure analysis by transmission electron microscopy (TEM...
Source: PLoS One - September 23, 2015 Category: Biomedical Science Authors: Yuqiao Chang et al. Source Type: research
Giant Panda (Ailuropoda melanoleuca) Buccal Mucosa Tissue as a Source of Multipotent Progenitor Cells
by Hilary M. A. Prescott, Craig Manning, Aaron Gardner, William A. Ritchie, Romain Pizzi, Simon Girling, Iain Valentine, Chengdong Wang, Colin A. B. Jahoda Since the first mammal was cloned, the idea of using this technique to help endangered species has aroused considerable interest. However, several issues limit this possibility, including the relatively low success rate at every stage of the cloning process, and the dearth of usable tissues from these rare animals. iPS cells have been produced from cells from a number of rare mammalian species and this is the method of choice for strategies to improve cloning efficienc...
Source: PLoS One - September 23, 2015 Category: Biomedical Science Authors: Hilary M. A. Prescott et al. Source Type: research
Drosophila americana Diapausing Females Show Features Typical of Young Flies
by Micael Reis, Felipe B. Valer, Cristina P. Vieira, Jorge Vieira (Source: PLoS One)
Source: PLoS One - September 23, 2015 Category: Biomedical Science Authors: Micael Reis et al. Source Type: research
Genome-Wide Association Study for Autism Spectrum Disorder in Taiwanese Han Population
Conclusions We reported Taiwanese Han specific susceptibility genes and variants for ASD. However, further replication in other Asian populations is warranted to validate our findings. Investigation in the biological functions of our reported genetic variants might also allow for better understanding on the underlying pathogenesis of autism. (Source: PLoS One)
Source: PLoS One - September 23, 2015 Category: Biomedical Science Authors: Po-Hsiu Kuo et al. Source Type: research
Serum Angiopoietin-Like Protein 2 Concentrations Are Independently Associated with Heart Failure
Conclusion Our results demonstrate a higher circulating ANGPTL2 level in patients with HF, and the upregulating ANGPTL2 levels might be associated with metabolic derangements and inflammation. (Source: PLoS One)
Source: PLoS One - September 23, 2015 Category: Biomedical Science Authors: Chi-Lun Huang et al. Source Type: research
Isolation of a Novel Phage with Activity against Streptococcus mutans Biofilms
by Marion Dalmasso, Eric de Haas, Horst Neve, Ronan Strain, Fabien J. Cousin, Stephen R. Stockdale, R. Paul Ross, Colin Hill Streptococcus mutans is one of the principal agents of caries formation mainly, because of its ability to form biofilms at the tooth surface. Bacteriophages (phages) are promising antimicrobial agents that could be used to prevent or treat caries formation by S. mutans. The aim of this study was to isolate new S. mutans phages and to characterize their antimicrobial properties. A new phage, ɸAPCM01, was isolated from a human saliva sample. Its genome was closely related to the only two other availa...
Source: PLoS One - September 23, 2015 Category: Biomedical Science Authors: Marion Dalmasso et al. Source Type: research
High-Density Genetic Mapping with Interspecific Hybrids of Two Sea Urchins, Strongylocentrotus nudus and S. intermedius, by RAD Sequencing
This study showed the efficiency of RAD-Seq based high-density genetic map construction using F1 progenies for species with no prior genomic information. The genetic maps are essential for QTL mapping and are useful as framework to order and orientate contiguous scaffolds from sea urchin genome assembly. The integration of the genetic map with genome assembly would provide an unprecedented opportunity to conduct QTL analysis, comparative genomics, and population genetics studies. (Source: PLoS One)
Source: PLoS One - September 23, 2015 Category: Biomedical Science Authors: Zunchun Zhou et al. Source Type: research
Protective effect of pioglitazone on morphine-induced neuroinflammation in the rat lumbar spinal cord
Conclusions: It is concluded that oral administration of the pioglitazone attenuates morphine-induced tolerance and the neuroinflammation in the lumbar region of the rat spinal cord. This action of the pioglitazone may be, at least in part, due to an interaction with the spinal pro-inflammatory cytokine expression and the nuclear factor-kappa B activity. (Source: Journal of Biomedical Science)
Source: Journal of Biomedical Science - September 23, 2015 Category: Biomedical Science Authors: Mohammad CharkhpourHamed GhavimiSaeed GhanbarzadehBahman YousefiArash KhorramiMehran MesgariKambiz Hassanzadeh Source Type: research
GP supply, deprivation and emergency admission to hospital for COPD and diabetes complications in counties across Ireland: an exploratory analysis
Conclusion Geographical variation in rates of admission to hospital for chronic disease is associated with both population need and health system factors. These findings suggest that primary care resourcing must be a key consideration in any efforts to tackle acute hospital capacity problems. (Source: Irish Journal of Medical Science)
Source: Irish Journal of Medical Science - September 23, 2015 Category: Journals (General) Source Type: research
Determination of Cefalothin and Cefazolin in Human Plasma, Urine and Peritoneal Dialysate by UHPLC-MS/MS: application to a pilot pharmacokinetic study in humans.
This article is protected by copyright. All rights reserved. PMID: 26394804 [PubMed - as supplied by publisher] (Source: Biomedical Chromatography : BMC)
Source: Biomedical Chromatography : BMC - September 23, 2015 Category: Biomedical Science Authors: Parker SL, Guerra Valero YC, Roberts DM, Lipman J, Roberts JA, Wallis SC Tags: Biomed Chromatogr Source Type: research
The Impact of an Inverse Correlation between Plasma B-type Natriuretic Peptide Levels and Insulin Resistance on the Diabetic Condition in Patients with Heart Failure
This study was designed to precisely examine this relationship, taking into consideration the possible association between natriuretic peptide (NP) levels and insulin resistance. (Source: Metabolism - Clinical and Experimental)
Source: Metabolism - Clinical and Experimental - September 23, 2015 Category: Biomedical Science Authors: Yasunori Inoue, Makoto Kawai, Kosuke Minai, Kazuo Ogawa, Tomohisa Nagoshi, Takayuki Ogawa, Michihiro Yoshimura Source Type: research
Cord Blood Copeptin Concentrations In Fetal Macrosomia
Excessive fetal growth is associated with increased adiposity and reduced insulin sensitivity at birth. Copeptin, a surrogate marker of arginine vasopressin (AVP) secretion, is upregulated in states of hyperinsulinemia and is considered one of the mediators of insulin resistance. We aimed to investigate cord blood concentrations of copeptin (C-terminal fragment of AVP pro-hormone) in healthy large-for-gestational-age-(LGA) infants at term. (Source: Metabolism - Clinical and Experimental)
Source: Metabolism - Clinical and Experimental - September 23, 2015 Category: Biomedical Science Authors: Despina D. Briana, Stavroula Baka, Maria Boutsikou, Theodora Boutsikou, Marieta Xagorari, Dimitrios Gourgiotis, Ariadne Malamitsi-Puchner Source Type: research
Non-alcoholic fatty liver disease and risk of cardiovascular disease
Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver diseases worldwide, causing considerable liver-related mortality and morbidity. During the past decade, it has also become increasingly evident that NAFLD is a multisystem disease that affects many extra-hepatic organ systems, including the heart and the vascular system. In this updated clinical review, we discuss the rapidly expanding body of clinical and epidemiological evidence that supports a strong association of NAFLD with cardiovascular diseases (CVD) and other functional and structural myocardial abnormalities. (Source: Metaboli...
Source: Metabolism - Clinical and Experimental - September 23, 2015 Category: Biomedical Science Authors: Amedeo Lonardo, Silvia Sookoian, Carlos J. Pirola, Giovanni Targher Source Type: research
A selective peroxisome proliferator-activated receptor δ agonist PYPEP suppresses atherosclerosis in association with improvement of the serum lipoprotein profiles in human apolipoprotein B100 and cholesteryl ester transfer protein double transgenic mice
Although peroxisome proliferator-activated receptor (PPAR) δ agonists have been shown to improve the serum lipoprotein profiles in humans, the impact of the changes in these lipoprotein profiles on atherosclerosis remains to be elucidated. The aim of this study was to investigate the relationship between the selective PPARδ agonist-induced alterations of serum lipoprotein profiles and the development of atherosclerosis in human apolipoprotein B100 and cholesterol ester transfer protein double transgenic (hApoB100/hCETP-dTg) mice with human-like hypercholesterolemic dyslipidemia. (Source: Metabolism - Clinical and Experimental)
Source: Metabolism - Clinical and Experimental - September 23, 2015 Category: Biomedical Science Authors: Noriyuki Naya, Keita Fukao, Akemi Nakamura, Tadateru Hamada, Masayuki Sugimoto, Midori Kojima, Norito Yoshimura, Ken-Ichiro Uwabe, Keiichi Imagawa, Kohji Nomura, Seijiro Hara, Toru Nakano, Takanori Iwasaki, Toshihiro Shinosaki, Kohji Hanasaki Source Type: research
The effects of abdominal lipectomy in metabolic syndrome components and insulin sensitivity in females: a systematic review and meta-analysis
Adipose tissue is an endocrine organ, which is implicated in the pathogenesis of obesity, metabolic syndrome and diabetes. Lipectomy offers a unique opportunity to permanently reduce the absolute number of fat cells, though its functional role remains unclear. This systematic review and meta-analysis review aims to assess the effect of abdominal lipectomy on metabolic syndrome components and insulin sensitivity in women. (Source: Metabolism - Clinical and Experimental)
Source: Metabolism - Clinical and Experimental - September 23, 2015 Category: Biomedical Science Authors: Konstantinos Seretis, Dimitrios G. Goulis, Georgios Koliakos, Efterpi Demiri Source Type: research
The effect of exercise on skeletal muscle glucose uptake in type 2 diabetes: an epigenetic perspective
Changes in eating habits and sedentary lifestyle are main contributors to type 2 diabetes (T2D) development, and studies suggest that epigenetic modifications are involved with the growing incidence of this disease. Regular exercise modulates many intracellular pathways improving insulin resistance and glucose uptake in skeletal muscle, both early abnormalities of T2D. Mitochondria dysfunction and decreased expression of glucose transporter (GLUT4) were identified as main factors of insulin resistance. (Source: Metabolism - Clinical and Experimental)
Source: Metabolism - Clinical and Experimental - September 23, 2015 Category: Biomedical Science Authors: Júlia Matzenbacher dos Santos, Marcos Lazaro Moreli, Shikha Tewari, Sandra Aparecida Benite-Ribeiro Source Type: research
Autocrine Effect of Vascular Endothelial Growth Factor-A is Essential for Mitochondrial Function in Brown Adipocytes
The obesity epidemic in the United States, and the accompanying condition of type 2 diabetes, puts a majority of the population at an increased risk of developing cardiovascular diseases including coronary artery disease, stroke, and myocardial infarction. In contrast to white adipose tissue (WAT), brown adipose tissue (BAT), is well vascularized, rich in mitochondria, and highly oxidative. While it is known that the angiogenic factor VEGF-A is required for brown adipocyte development, the functional consequences and exact mechanism remain to be elucidated. (Source: Metabolism - Clinical and Experimental)
Source: Metabolism - Clinical and Experimental - September 23, 2015 Category: Biomedical Science Authors: Kiana Mahdaviani, David Chess, Yuanyuan Wu, Orian Shirihai, Tamar Aprahamian Source Type: research
Anisotropic properties of human cortical bone with osteogenesis imperfecta.
Abstract The heterogeneity of bone shape and size variation is modulated by genetic, mechanical, nutritional, and hormonal patterning throughout its lifetime. Microstructural changes across cross sections are a result of mechanistic optimization that results over the years of evolution while being based on universal, time-invariant ingredients and patterns. Here we report changes across anatomical sections of bone with osteogenesis imperfecta (OI) that undermines the work of evolution through genetic mutation. This work examines the microstructure and molecular composition of different anatomical positions (anterio...
Source: Biomechanics and Modeling in Mechanobiology - September 23, 2015 Category: Biomedical Science Authors: Katti KS, Gu C, Katti DR Tags: Biomech Model Mechanobiol Source Type: research
Characterization of paliperidone photodegradation products by LC-Q-TOF multi-stage mass spectrometry.
This article is protected by copyright. All rights reserved. PMID: 26400838 [PubMed - as supplied by publisher] (Source: Biomedical Chromatography : BMC)
Source: Biomedical Chromatography : BMC - September 23, 2015 Category: Biomedical Science Authors: Skibiński R, Komsta Ł, Inglot T Tags: Biomed Chromatogr Source Type: research
Deletion of caspase-8 in mouse myeloid cells blocks microglia pro-inflammatory activation and confers protection in MPTP neurodegeneration model.
Abstract Increasing evidence involves sustained pro-inflammatory microglia activation in the pathogenesis of different neurodegenerative diseases, particularly Parkinson's disease (PD). We recently uncovered a completely novel and unexpected role for caspase-8 and its downstream substrates caspase-3/7 in the control of microglia activation and associated neurotoxicity to dopaminergic cells. To demonstrate the genetic evidence, mice bearing a floxed allele ofCASP8 were crossed onto a transgenic line expressing Cre under the control of Lysozyme 2 gene. Analysis of caspase-8 gene deletion in brain microglia demonstrat...
Source: Aging - September 23, 2015 Category: Biomedical Science Authors: Kavanagh E, Burguillos MA, Carrillo-Jimenez A, Oliva-Martin MJ, Santiago M, Rodhe J, Joseph B, Venero JL Tags: Aging (Albany NY) Source Type: research
Isolation of neoantigen-specific T cells from tumor and peripheral lymphocytes
Adoptively transferred tumor-infiltrating T lymphocytes (TILs) that mediate complete regression of metastatic melanoma have been shown to recognize mutated epitopes expressed by autologous tumors. Here, in an attempt to develop a strategy for facilitating the isolation, expansion, and study of mutated antigen–specific T cells, we performed whole-exome sequencing on matched tumor and normal DNA isolated from 8 patients with metastatic melanoma. Candidate mutated epitopes were identified using a peptide-MHC–binding algorithm, and these epitopes were synthesized and used to generate panels of MHC tetramers that were evalu...
Source: Journal of Clinical Investigation - September 22, 2015 Category: Biomedical Science Authors: Cyrille J. Cohen, Jared J. Gartner, Miryam Horovitz-Fried, Katerina Shamalov, Kasia Trebska-McGowan, Valery V. Bliskovsky, Maria R. Parkhurst, Chen Ankri, Todd. D. Prickett, Jessica S. Crystal, Yong F. Li, Mona El-Gamil, Steven A. Rosenberg, Paul F. Robbi Source Type: research
IL-34 is a Treg-specific cytokine and mediates transplant tolerance
In conclusion, we reveal that IL-34 serves as a suppressive Treg–specific cytokine and as a tolerogenic cytokine that efficiently inhibits alloreactive immune responses and mediates transplant tolerance. (Source: Journal of Clinical Investigation)
Source: Journal of Clinical Investigation - September 22, 2015 Category: Biomedical Science Authors: Séverine Bézie, Elodie Picarda, Jason Ossart, Laurent Tesson, Claire Usal, Karine Renaudin, Ignacio Anegon, Carole Guillonneau Source Type: research
Transplant tolerance: a new role for IL-34
Immune-suppressive cell populations, including Tregs and suppressor monocytes, have been implicated in long-term survival of allografts in both human transplant recipients and animal models. The factors that drive differentiation and function of these cell populations are not completely understood. In this issue, Bézie and colleagues identify IL-34 as an important mediator of allograft tolerance in a rat model of heart transplantation. Their data support a model in which IL-34 production by Tregs promotes a population of suppressive macrophages that in turn promote Treg differentiation. The results of this study support f...
Source: Journal of Clinical Investigation - September 22, 2015 Category: Biomedical Science Authors: James I. Kim, Laurence A. Turka Source Type: research
Insulin demand regulates β cell number via the unfolded protein response
Although stem cell populations mediate regeneration of rapid turnover tissues, such as skin, blood, and gut, a stem cell reservoir has not been identified for some slower turnover tissues, such as the pancreatic islet. Despite lacking identifiable stem cells, murine pancreatic β cell number expands in response to an increase in insulin demand. Lineage tracing shows that new β cells are generated from proliferation of mature, differentiated β cells; however, the mechanism by which these mature cells sense systemic insulin demand and initiate a proliferative response remains unknown. Here, we identified the β cell unfold...
Source: Journal of Clinical Investigation - September 22, 2015 Category: Biomedical Science Authors: Rohit B. Sharma, Amy C. O’Donnell, Rachel E. Stamateris, Binh Ha, Karen M. McCloskey, Paul R. Reynolds, Peter Arvan, Laura C. Alonso Source Type: research
How do reducing equivalents increase insulin secretion?
Glucose stimulation of insulin secretion in pancreatic β cells involves cell depolarization and subsequent opening of voltage-dependent Ca2+ channels to elicit insulin granule exocytosis. This pathway alone does not account for the entire magnitude of the secretory response in β cells. In this issue, Ferdaoussi, Dai, and colleagues reveal that insulin secretion is amplified by cytosolic isocitrate dehydrogenase–dependent transfer of reducing equivalents, which generates NADPH and reduced glutathione, which in turn activates sentrin/SUMO-specific protease-1 (SENP1). β Cell–specific deletion of Senp1 in murine models ...
Source: Journal of Clinical Investigation - September 22, 2015 Category: Biomedical Science Authors: Alan D. Attie Source Type: research
Isocitrate-to-SENP1 signaling amplifies insulin secretion and rescues dysfunctional β cells
Insulin secretion from β cells of the pancreatic islets of Langerhans controls metabolic homeostasis and is impaired in individuals with type 2 diabetes (T2D). Increases in blood glucose trigger insulin release by closing ATP-sensitive K+ channels, depolarizing β cells, and opening voltage-dependent Ca2+ channels to elicit insulin exocytosis. However, one or more additional pathway(s) amplify the secretory response, likely at the distal exocytotic site. The mitochondrial export of isocitrate and engagement with cytosolic isocitrate dehydrogenase (ICDc) may be one key pathway, but the mechanism linking this to insulin sec...
Source: Journal of Clinical Investigation - September 22, 2015 Category: Biomedical Science Authors: Mourad Ferdaoussi, Xiaoqing Dai, Mette V. Jensen, Runsheng Wang, Brett S. Peterson, Chao Huang, Olga Ilkayeva, Nancy Smith, Nathanael Miller, Catherine Hajmrle, Aliya F. Spigelman, Robert C. Wright, Gregory Plummer, Kunimasa Suzuki, James P. Mackay, Marti Source Type: research
FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature
Biomechanical forces, such as fluid shear stress, govern multiple aspects of endothelial cell biology. In blood vessels, disturbed flow is associated with vascular diseases, such as atherosclerosis, and promotes endothelial cell proliferation and apoptosis. Here, we identified an important role for disturbed flow in lymphatic vessels, in which it cooperates with the transcription factor FOXC2 to ensure lifelong stability of the lymphatic vasculature. In cultured lymphatic endothelial cells, FOXC2 inactivation conferred abnormal shear stress sensing, promoting junction disassembly and entry into the cell cycle. Loss of FOXC...
Source: Journal of Clinical Investigation - September 22, 2015 Category: Biomedical Science Authors: Amélie Sabine, Esther Bovay, Cansaran Saygili Demir, Wataru Kimura, Muriel Jaquet, Yan Agalarov, Nadine Zangger, Joshua P. Scallan, Werner Graber, Elgin Gulpinar, Brenda R. Kwak, Taija Mäkinen, Inés Martinez-Corral, Sagrario Ortega, Mauro Delorenzi, Fr Source Type: research
Stress-associated erythropoiesis initiation is regulated by type 1 conventional dendritic cells
Erythropoiesis is an important response to certain types of stress, including hypoxia, hemorrhage, bone marrow suppression, and anemia, that result in inadequate tissue oxygenation. This stress-induced erythropoiesis is distinct from basal red blood cell generation; however, neither the cellular nor the molecular factors that regulate this process are fully understood. Here, we report that type 1 conventional dendritic cells (cDC1s), which are defined by expression of CD8α in the mouse and XCR1 and CLEC9 in humans, are critical for induction of erythropoiesis in response to stress. Specifically, using murine models, we de...
Source: Journal of Clinical Investigation - September 22, 2015 Category: Biomedical Science Authors: Taeg S. Kim, Mark Hanak, Paul C. Trampont, Thomas J. Braciale Source Type: research
Complementary versus companion diagnostics: apples and oranges?
Authors: Milne CP, Bryan C, Garafalo S, McKiernan M Abstract There have been several major problems that have plagued biopharmaceutical development since the end of the 1990s, but two in particular have reached the point where they are impacting the economic viability of the industry: the lack of efficacy of new drugs and increasing competition among therapeutics that broadly attack certain common diseases and disease areas. The US FDA has noted that the era of one-size-fits-all treatment may well be reaching its end days as companies increasingly adopt approaches that involve biomarkers (there are now commercial d...
Source: Future Medicine: Biomarkers in Medicine - September 22, 2015 Category: Internal Medicine Tags: Biomark Med Source Type: research
Analytical solution of Luedeking–Piret equation for a batch fermentation obeying Monod growth kinetics
ABSTRACT Not so many fermentation mathematical models allow analytical solutions of batch process dynamics. The most widely used is the combination of the logistic microbial growth kinetics with Luedeking–Piret bioproduct synthesis relation. However, the logistic equation is principally based on formalistic similarities and only fits a limited range of fermentation types. In this article, we have developed an analytical solution for the combination of Monod growth kinetics with Luedeking–Piret relation, which can be identified by linear regression and used to simulate batch fermentation evolution. Two classical example...
Source: Biotechnology and Bioengineering - September 22, 2015 Category: Biomedical Science Authors: Alain Garnier, Bruno Gaillet Tags: Article Source Type: research
PDON: Parkinson’s disease ontology for representation and modeling of the Parkinson’s disease knowledge domain
Conclusions: Parkinson’s disease ontology delivers the knowledge domain of Parkinson’s disease in a compact, computer-readable form, which can be further edited and enriched by the scientific community and also to be used to construct, represent and automatically extend Parkinson’s-related computable models. A practical version of the Parkinson’s disease ontology for browsing and editing can be publicly accessed at http://bioportal.bioontology.org/ontologies/PDON. (Source: Theoretical Biology and Medical Modelling)
Source: Theoretical Biology and Medical Modelling - September 22, 2015 Category: Biomedical Science Authors: Erfan YounesiAshutosh MalhotraMichaela GündelPhil ScordisAlpha KodamullilMatt PageBernd MüllerStephan SpringstubbeUllrich WüllnerDieter SchellerMartin Hofmann-Apitius Source Type: research
Molecular Cytogenetic Analysis of Deschampsia antarctica Desv. (Poaceae), Maritime Antarctic
by Alexandra V. Amosova, Nadezhda L. Bolsheva, Tatiana E. Samatadze, Maryana O. Twardovska, Svyatoslav A. Zoshchuk, Igor O. Andreev, Ekaterina D. Badaeva, Viktor A. Kunakh, Olga V. Muravenko Deschampsia antarctica Desv. (Poaceae) (2n = 26) is one of the two vascular plants adapted to the harshest environment of the Antarctic. Although the species is a valuable model for study of environmental stress tolerance in plants, its karyotype is still poorly investigated. We firstly conducted a comprehensive molecular cytogenetic analysis of D. antarctica collected on four islands of the Maritime Antarctic. D. antarctica karyotype...
Source: PLoS One - September 22, 2015 Category: Biomedical Science Authors: Alexandra V. Amosova et al. Source Type: research
The Validation of Nematode-Specific Acetylcholine-Gated Chloride Channels as Potential Anthelmintic Drug Targets
We present here a novel strategy for target validation that employs the free-living nematode Caenorhabditis elegans to demonstrate the value of new ligand-gated ion channels as targets for anthelmintic discovery. Many successful anthelmintics, including ivermectin, levamisole and monepantel, are agonists of pentameric ligand-gated ion channels, suggesting that the unexploited pentameric ion channels encoded in parasite genomes may be suitable drug targets. We validated five members of the nematode-specific family of acetylcholine-gated chloride channels as targets of agonists with anthelmintic properties by ectopically exp...
Source: PLoS One - September 22, 2015 Category: Biomedical Science Authors: Claudia M. Wever et al. Source Type: research
Association between Hypertension and the Prevalence of Low Back Pain and Osteoarthritis in Koreans: A Cross-Sectional Study
The objective of this study was to investigate the association between hypertension and prevalence of low back pain (LBP) and osteoarthritis in Koreans. Methods A total 17,128 participants (age ≥20 years) who answered low back pain and osteoarthritis items in the 4th Korean National Health and Nutrition Examination Survey (2007–2009) were analyzed. Odds ratios were calculated using logistic regression and were adjusted for age, sex, income level, education, occupation, BMI, smoking status, alcohol consumption, and physical activity. Results Lifetime prevalence of LBP in hypertensive subjects was 34.4%, and that of oste...
Source: PLoS One - September 22, 2015 Category: Biomedical Science Authors: Young-Hyeon Bae et al. Source Type: research