Article added to library!
x
Pubchase is a service of protocols.io - free, open access, crowdsourced protocols repository. Explore protocols.
Sign in
Reset password
or connect with
Facebook
By signing in you are agreeing to our
Terms Of Service and Privacy Policy
Systems Biology
Cell-wide analysis of protein thermal unfolding reveals determinants of thermostability
Feb 24, 2017   Science (New York, N.Y.)
Leuenberger P, Ganscha S, Kahraman A, Cappelletti V, Boersema PJ, von Mering C, Claassen M, Picotti P
Cell-wide analysis of protein thermal unfolding reveals determinants of thermostability
Feb 24, 2017
Science (New York, N.Y.)
Temperature-induced cell death is thought to be due to protein denaturation, but the determinants of thermal sensitivity of proteomes remain largely uncharacterized. We developed a structural proteomic strategy to measure protein thermostability on a proteome-wide scale and with domain-level resolution. We applied it to Copyright © 2017, American Association for the Advancement of Science.
Quantifying protein (dis)order
Feb 24, 2017   Science (New York, N.Y.)
Vogel C
Quantifying protein (dis)order
Feb 24, 2017
Science (New York, N.Y.)
Hepatic DsbA-L protects mice from diet-induced hepatosteatosis and insulin resistance
Feb 24, 2017   FASEB Journal : Official Publication Of The Federation Of American Societies For Experimental Biology
Chen H, Bai J, Dong F, Fang H, Zhang Y,   . . . . . .   , Wu J, Zeng R, Zhou Z, Dong LQ, Liu F
Hepatic DsbA-L protects mice from diet-induced hepatosteatosis and insulin resistance
Feb 24, 2017
FASEB Journal : Official Publication Of The Federation Of American Societies For Experimental Biology
Hepatic insulin resistance and hepatosteatosis in diet-induced obesity are associated with various metabolic diseases, yet the underlying mechanisms remain to be fully elucidated. Here we show that the expression levels of the disulfide-bond A oxidoreductase-like protein (DsbA-L) are significantly reduced in the liver of obese mice and humans. Liver-specific knockout or adenovirus-mediated overexpression of DsbA-L exacerbates or alleviates, respectively, high-fat diet-induced mitochondrial dysfunction, hepatosteatosis, and insulin resistance in mice. Mechanistically, we found that DsbA-L is localized in mitochondria and that its deficiency is associated with impairment of maximum respiratory capacity, elevated cellular oxidative stress, and increased JNK activity. Our results identify DsbA-L as a critical regulator of mitochondrial function, and its down-regulation in the liver may contribute to obesity-induced hepatosteatosis and whole body insulin resistance.-Chen, H., Bai, J., Dong, F., Fang, H., Zhang, Y., Meng, W., Liu, B., Luo, Y., Liu, M., Bai, Y., Abdul-Ghani, M. A., Li, R., Wu, J., Zeng, R., Zhou, Z., Dong, L. Q., Liu, F. Hepatic DsbA-L protects mice from diet-induced hepatosteatosis and insulin resistance.© FASEB.
Rapid protein alignment in the cloud: HAMOND combines fast DIAMOND alignments with Hadoop parallelism
Feb 24, 2017   Journal Of Biotechnology
Yu J, Blom J, Sczyrba A, Goesmann A
Rapid protein alignment in the cloud: HAMOND combines fast DIAMOND alignments with Hadoop parallelism
Feb 24, 2017
Journal Of Biotechnology
The introduction of next generation sequencing has caused a steady increase in the amounts of data that have to be processed in modern life science. Sequence alignment plays a key role in the analysis of sequencing data e.g. within whole genome sequencing or metagenome projects. BLAST is a commonly used alignment tool that was the standard approach for more than two decades, but in the last years faster alternatives have been proposed including RapSearch, GHOSTX, and DIAMOND. Here we introduce HAMOND, an application that uses Apache Hadoop to parallelize DIAMOND computation in order to scale-out the calculation of alignments. HAMOND is fault tolerant and scalable by utilizing large cloud computing infrastructures like Amazon Web Services. HAMOND has been tested in comparative genomics analyses and showed promising results both in efficiency and accuracy.Copyright © 2017. Published by Elsevier B.V.
Synthetic Gene Circuits Learn to Classify
Feb 23, 2017   Cell Systems
Didovyk A, Tsimring LS
Synthetic Gene Circuits Learn to Classify
Feb 23, 2017
Cell Systems
An efficient computational algorithm is developed to design microRNA-based synthetic cell classifiers and to optimize their performance.Copyright © 2017 Elsevier Inc. All rights reserved.
Mutant Kras- and p16-regulated NOX4 activation overcomes metabolic checkpoints in development of pancreatic ductal adenocarcinoma
Feb 24, 2017   Nature Communications
Ju HQ, Ying H, Tian T, Ling J, Fu J,   . . . . . .   , Hung MC, DePinho RA, Huang P, Xu RH, Chiao PJ
Mutant Kras- and p16-regulated NOX4 activation overcomes metabolic checkpoints in development of pancreatic ductal adenocarcinoma
Feb 24, 2017
Nature Communications
Kras activation and p16 inactivation are required to develop pancreatic ductal adenocarcinoma (PDAC). However, the biochemical mechanisms underlying these double alterations remain unclear. Here we discover that NAD(P)H oxidase 4 (NOX4), an enzyme known to catalyse the oxidation of NAD(P)H, is upregulated when p16 is inactivated by looking at gene expression profiling studies. Activation of NOX4 requires catalytic subunit p22
Context-independent essential regulatory interactions for apoptosis and hypertrophy in the cardiac signaling network
Feb 24, 2017   Scientific Reports
Kang JH, Lee HS, Park D, Kang YW, Kim SM, Gong JR, Cho KH
Context-independent essential regulatory interactions for apoptosis and hypertrophy in the cardiac signaling network
Feb 24, 2017
Scientific Reports
Apoptosis and hypertrophy of cardiomyocytes are the primary causes of heart failure and are known to be regulated by complex interactions in the underlying intracellular signaling network. Previous experimental studies were successful in identifying some key signaling components, but most of the findings were confined to particular experimental conditions corresponding to specific cellular contexts. A question then arises as to whether there might be essential regulatory interactions that prevail across diverse cellular contexts. To address this question, we have constructed a large-scale cardiac signaling network by integrating previous experimental results and developed a mathematical model using normalized ordinary differential equations. Specific cellular contexts were reflected to different kinetic parameters sampled from random distributions. Through extensive computer simulations with various parameter distributions, we revealed the five most essential context-independent regulatory interactions (between: (1) αAR and Gαq, (2) IP3 and calcium, (3) epac and CaMK, (4) JNK and NFAT, and (5) p38 and NFAT) for hypertrophy and apoptosis that were consistently found over all our perturbation analyses. These essential interactions are expected to be the most promising therapeutic targets across a broad spectrum of individual conditions of heart failure patients.
Towards an optimized workflow for middle-down proteomics
Feb 24, 2017   Analytical Chemistry
Cristobal A, Marino F, Post H, van den Toorn HW, Mohammed S, Heck AJ
Towards an optimized workflow for middle-down proteomics
Feb 24, 2017
Analytical Chemistry
Mass spectrometry (MS)-based proteomics workflows can crudely be classified into two distinct regimes, either targeting relatively small peptides (i.e. 0.7 kDa < Mw < 3.0 kDa) or small to medium sized intact proteins (i.e. 10 kDa < Mw < 30 kDa), respectively termed bottom-up and top-down proteomics. Recently, a niche has started to be explored covering the analysis of middle-range peptides (i.e. 3.0 kDa < Mw < 10 kDa), aptly termed middle-down proteomics. Although middle-down proteomics can follow, in principle, a modular workflow similiar to that of bottom-up proteomics, we hypothesized that each of these modules would benefit from targeted optimization to improve its overall performance in the analysis of middle-range sized peptides. Hence, to generate middle-range sized peptides from cellular lysates we explored the use of the proteases Asp-N and Glu-C, and a non-enzymatic acid induced cleavage. To increase the depth of the proteome, an SCX separation, carefully tuned to improve the separation of longer peptides, combined with RP-LC using columns packed with material possessing a larger pore size were used. Finally, after evaluating the combination of potentially beneficial MS settings, we also assessed the peptide fragmentation techniques HCD, ETD and EThcD for characterization of middle-range sized peptides. These combined improvements clearly improve the detection and sequence coverage of middle-range peptides and should guide researchers to explore further how middle-down proteomics may lead to an improved proteome coverage, beneficial for, amongst other things, the enhanced analysis of (co-occurring) post-translational modifications.
Biomarker-driven phenotyping in Parkinson's disease: A translational missing link in disease-modifying clinical trials
Feb 24, 2017   Movement Disorders : Official Journal Of The Movement Disorder Society
Espay AJ, Schwarzschild MA, Tanner CM, Fernandez HH, Simon DK,   . . . . . .   , Kieburtz K, Woo D, Macklin EA, Standaert DG, Lang AE
Biomarker-driven phenotyping in Parkinson's disease: A translational missing link in disease-modifying clinical trials
Feb 24, 2017
Movement Disorders : Official Journal Of The Movement Disorder Society
Past clinical trials of putative neuroprotective therapies have targeted PD as a single pathogenic disease entity. From an Oslerian clinicopathological perspective, the wide complexity of PD converges into Lewy bodies and justifies a reductionist approach to PD: A single-mechanism therapy can affect most of those sharing the classic pathological hallmark. From a systems-biology perspective, PD is a group of disorders that, while related by sharing the feature of nigral dopamine-neuron degeneration, exhibit unique genetic, biological, and molecular abnormalities, which probably respond differentially to a given therapeutic approach, particularly for strategies aimed at neuroprotection. Under this model, only biomarker-defined, homogenous subtypes of PD are likely to respond optimally to therapies proven to affect the biological processes within each subtype. Therefore, we suggest that precision medicine applied to PD requires a reevaluation of the biomarker-discovery effort. This effort is currently centered on correlating biological measures to clinical features of PD and on identifying factors that predict whether various prodromal states will convert into the classical movement disorder. We suggest, instead, that subtyping of PD requires the reverse view, where abnormal biological signals (i.e., biomarkers), rather than clinical definitions, are used to define disease phenotypes. Successful development of disease-modifying strategies will depend on how relevant the specific biological processes addressed by an intervention are to the pathogenetic mechanisms in the subgroup of targeted patients. This precision-medicine approach will likely yield smaller, but well-defined, subsets of PD amenable to successful neuroprotection. © 2017 International Parkinson and Movement Disorder Society.© 2017 International Parkinson and Movement Disorder Society.
Comprehensive analysis of long non-coding RNAs highlights their spatio-temporal expression patterns and evolutional conservation in Sus scrofa
Feb 24, 2017   Scientific Reports
Tang Z, Wu Y, Yang Y, Yang YT, Wang Z, Yuan J, Yang Y, Hua C, Fan X, Niu G, Zhang Y, Lu ZJ, Li K
Comprehensive analysis of long non-coding RNAs highlights their spatio-temporal expression patterns and evolutional conservation in Sus scrofa
Feb 24, 2017
Scientific Reports
Despite modest sequence conservation and rapid evolution, long non-coding RNAs (lncRNAs) appear to be conserved in expression pattern and function. However, analysis of lncRNAs across tissues and developmental stages remains largely uncharacterized in mammals. Here, we systematically investigated the lncRNAs of the Guizhou miniature pig (Sus scrofa), which was widely used as biomedical model. We performed RNA sequencing across 9 organs and 3 developmental skeletal muscle, and developed a filtering pipeline to identify 10,813 lncRNAs (9,075 novel). Conservation patterns analysis revealed that 57% of pig lncRNAs showed homology to humans and mice based on genome alignment. 5,455 lncRNAs exhibited typical hallmarks of regulatory molecules, such as high spatio-temporal specificity. Notably, conserved lncRNAs exhibited higher tissue specificity than pig-specific lncRNAs and were significantly enriched in testis and ovary. Weighted co-expression network analysis revealed a set of conserved lncRNAs that are likely involved in postnatal muscle development. Based on the high degree of similarity in the structure, organization, and dynamic expression of pig lncRNAs compared with human and mouse lncRNAs, we propose that these lncRNAs play an important role in organ physiology and development in mammals. Our results provide a resource for studying animal evolution, morphological complexity, breeding, and biomedical research.
Molecular dynamics simulations reveal ligand-controlled positioning of a peripheral protein complex in membranes
Feb 24, 2017   Nature Communications
Ryckbosch SM, Wender PA, Pande VS
Molecular dynamics simulations reveal ligand-controlled positioning of a peripheral protein complex in membranes
Feb 24, 2017
Nature Communications
Bryostatin is in clinical trials for Alzheimer's disease, cancer, and HIV/AIDS eradication. It binds to protein kinase C competitively with diacylglycerol, the endogenous protein kinase C regulator, and plant-derived phorbol esters, but each ligand induces different activities. Determination of the structural origin for these differing activities by X-ray analysis has not succeeded due to difficulties in co-crystallizing protein kinase C with relevant ligands. More importantly, static, crystal-lattice bound complexes do not address the influence of the membrane on the structure and dynamics of membrane-associated proteins. To address this general problem, we performed long-timescale (400-500 µs aggregate) all-atom molecular dynamics simulations of protein kinase C-ligand-membrane complexes and observed that different protein kinase C activators differentially position the complex in the membrane due in part to their differing interactions with waters at the membrane inner leaf. These new findings enable new strategies for the design of simpler, more effective protein kinase C analogs and could also prove relevant to other peripheral protein complexes.Natural supplies of bryostatin, a compound in clinical trials for Alzheimer's disease, cancer, and HIV, are scarce. Here, the authors perform molecular dynamics simulations to understand how bryostatin interacts with membrane-bound protein kinase C, offering insights for the design of bryostatin analogs.
Lysine acetyltransferase NuA4 and acetyl-CoA regulate glucose-deprived stress granule formation in Saccharomyces cerevisiae
Feb 23, 2017   PLoS Genetics
Rollins M, Huard S, Morettin A, Takuski J, Pham TT, Fullerton MD, Côté J, Baetz K
Lysine acetyltransferase NuA4 and acetyl-CoA regulate glucose-deprived stress granule formation in Saccharomyces cerevisiae
Feb 23, 2017
PLoS Genetics
Eukaryotic cells form stress granules under a variety of stresses, however the signaling pathways regulating their formation remain largely unknown. We have determined that the Saccharomyces cerevisiae lysine acetyltransferase complex NuA4 is required for stress granule formation upon glucose deprivation but not heat stress. Further, the Tip60 complex, the human homolog of the NuA4 complex, is required for stress granule formation in cancer cell lines. Surprisingly, the impact of NuA4 on glucose-deprived stress granule formation is partially mediated through regulation of acetyl-CoA levels, which are elevated in NuA4 mutants. While elevated acetyl-CoA levels suppress the formation of glucose-deprived stress granules, decreased acetyl-CoA levels enhance stress granule formation upon glucose deprivation. Further our work suggests that NuA4 regulates acetyl-CoA levels through the Acetyl-CoA carboxylase Acc1. Altogether this work establishes both NuA4 and the metabolite acetyl-CoA as critical signaling pathways regulating the formation of glucose-deprived stress granules.
Depletion of abundant human serum proteins by per se imprinted cryogels based on sample heterogeneity
Feb 23, 2017   Proteomics
Yang C, Liu YR, Zhang Y, Wang J, Tian LL, Yan YN, Cao WQ, Wang YY
Depletion of abundant human serum proteins by per se imprinted cryogels based on sample heterogeneity
Feb 23, 2017
Proteomics
Macroporous cryogels were prepared and used to deplete abundant proteins. It was accomplished based on the sample heterogeneity rather than any exogenous assistance. Human serum was added in monomer solutions to synthesize molecularly imprinted polymers (MIPs); therein some abundant proteins were imprinted in the polyacrylamide cryogels. Meanwhile the rare components remained aqueous. Chromatography and electrophoresis showed that albumin, serotransferrin and most globulins were depleted by columns packed with the MIPs. After the depletion lower abundance proteins were revealed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), peptide fingerprint analysis and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). This is an example that a "per se imprint" protocol enables to gradually dimidiate proteomes, simplify sample complexities and facilitate further proteome profiling or biomarker discovery. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.
HSP70 inhibition synergistically enhances the effects of magnetic fluid hyperthermia in ovarian cancer
Feb 22, 2017   Molecular Cancer Therapeutics
Court KA, Hatakeyama H, Wu SY, Lingegowda MS, Rodriguez-Aguayo C, Lopez-Berestein G, Ju-Seog L, Rinaldi C, Juan EJ, Sood AK, Torres-Lugo M
HSP70 inhibition synergistically enhances the effects of magnetic fluid hyperthermia in ovarian cancer
Feb 22, 2017
Molecular Cancer Therapeutics
UNASSIGNED: Hyperthermia has been investigated as a potential treatment for cancer. However, specificity in hyperthermia application remains a significant challenge. Magnetic fluid hyperthermia (MFH) may be an alternative to surpass such a challenge, but implications of MFH at the cellular level are not well understood. Therefore, the present work focused on the examination of gene expression after MFH treatment and using such information to identify target genes that when inhibited could produce an enhanced therapeutic outcome after MFH. Genomic analyzes were performed using ovarian cancer cells exposed to MFH for 30 min at 43°C, which revealed that heat shock protein genes, including HSPA6, were upregulated. HSPA6 encodes the heat shock protein Hsp70, and its expression was confirmed by PCR in HeyA8 and A2780cp20 ovarian cancer cells. Two strategies were investigated to inhibit Hsp70 related genes, siRNA and Hsp70 protein function inhibition by 2-phenylethyenesulfonamide (PES). Both strategies resulted in decreased cell viability following exposure to MFH. Combination index was calculated for PES treatment reporting a synergistic effect. In vivo efficacy experiments with HSPA6 siRNA and MFH were performed using the A2780cp20 and HeyA8 ovarian cancer mouse models. A significantly reduction in tumor growth rate was observed with combination therapy. PES and MFH efficacy were also evaluated in the HeyA8 intraperitoneal tumor model, and resulted in robust antitumor effects. This work demonstrated that HSP70 inhibition combination with MFH generate a synergistic effect and could be a promising target to enhance MFH therapeutic outcomes in ovarian cancer. Copyright ©2017, American Association for Cancer Research.
RNA-seq Analysis of Cold and Drought Responsive Transcriptomes of
Feb 22, 2017   Frontiers In Plant Science
Lu X, Zhou X, Cao Y, Zhou M, McNeil D, Liang S, Yang C
IL-1β induced and p38
Feb 22, 2017   The Journal Of Biological Chemistry
Kulawik A, Engesser R, Ehlting C, Raue A, Albrecht U, Hahn B, Lehmann WD, Gaestel M, Klingmüller U, Häussinger D, Timmer J, Bode JG
IL-1β induced and p38
Feb 22, 2017
The Journal Of Biological Chemistry
UNASSIGNED: The Interleukin (IL)-1β induced activation of the p38 Copyright © 2017, The American Society for Biochemistry and Molecular Biology.
Feb 22, 2017   Molecular & Cellular Proteomics : MCP
Nemeth J, Vongrad V, Metzner KJ, Strouvelle V, Weber R, Pedrioli P, Aebersold R, Guenthard H, Collins BC
Feb 22, 2017
Molecular & Cellular Proteomics : MCP
UNASSIGNED: Host directed therapies against HIV-1 are thought to be critical for long term containment of the HIV-1 pandemic but remain elusive. Since HIV-1 infects and manipulates important effectors of both the innate and adaptive immune system, identifying modulations of the host cell systems in humans during HIV-1 infection may be crucial for the development of immune based therapies. Here, we quantified the changes of the proteome in human CD4+ T cells upon HIV-1 infection, both in vitro and in vivo. A SWATH-MS approach was used to measure the proteome of human primary CD4+ T cells infected with HIV-1 in vitro as well as CD4+ T cells from HIV-1 infected patients with paired samples on and off antiretroviral treatment. In the in vitro experiment, the proteome of CD4+ T cells was quantified over a time course following HIV-1 infection. 1,725 host cell proteins and 4 HIV-1 proteins were quantified, with 145 proteins changing significantly during the time course. Changes in the proteome peaked 24 hours after infection, concomitantly with significant HIV-1 protein production. In the in vivo branch of the study, CD4+ T cells from viremic patients and those with no detectable viral load after treatment were sorted and the proteomes quantified. We consistently detected 895 proteins, 172 of which were considered to be significantly different between viraemic patients and patients undergoing successful treatment. The proteome of in vitro infected CD4+ T cells was modulated on multiple functional levels, including TLR-4 signalling and the type 1 interferon signalling pathway. Perturbations in the type 1 interferon signalling pathway were recapitulated in CD4+ T cells from patients. The study shows that proteome maps generated by SWATH-MS indicate a range of functionally significant changes in the proteome of HIV infected human CD4+ T cells. Exploring these perturbations in more detail may help identify new targets for immune based interventions. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.
Identification of antibody targets for tuberculosis serology using high-density nucleic acid programmable protein arrays
Feb 22, 2017   Molecular & Cellular Proteomics : MCP
Song L, Wallstrom G, Yu X, Hopper M, Van Duine J,   . . . . . .   , Jenny-Avital ER, Qiu J, LaBaer J, Magee DM, Achkar JM
Identification of antibody targets for tuberculosis serology using high-density nucleic acid programmable protein arrays
Feb 22, 2017
Molecular & Cellular Proteomics : MCP
UNASSIGNED: Better and more diverse biomarkers for the development of simple point-of-care tests for active tuberculosis (TB), a clinically heterogeneous disease, are urgently needed. We generated a proteomic Mycobacterium tuberculosis (Mtb) High-Density Nucleic Acid Programmable Protein Array (HD-NAPPA) that used a novel multiplexed strategy for expedited high-throughput screening for antibody responses to the Mtb proteome. We screened sera from HIV uninfected and co-infected TB patients and controls (n = 120) from the US and South Africa (SA) using the multiplex HD-NAPPA for discovery, followed by deconvolution and validation through single protein HD-NAPPA with biologically independent samples (n=124). We verified the top proteins with enzyme-linked immunosorbent assays (ELISA) using the original screening and validation samples (n=244) and heretofore untested samples (n= 41). We identified 8 proteins with TB biomarker value; four (Rv0054, Rv0831c, Rv2031c and Rv0222) of these were previously identified in serology studies, and four (Rv0948c, Rv2853, Rv3405c, Rv3544c) were not known to elicit antibody responses. Using ELISA data, we created classifiers that could discriminate patients' TB status according to geography (US or SA) and HIV (HIV- or HIV+) status. With ROC curve analysis under cross validation, the classifiers performed with an AUC for US/HIV- at 0.807; US/HIV+ at 0.782; SA/HIV- at 0.868; and SA/HIV+ at 0.723. With this study we demonstrate a new platform for biomarker/antibody screening and delineate its utility to identify previously unknown immunoreactive proteins. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.
Variant profiling of evolving prokaryotic populations
Feb 22, 2017   PeerJ
Zojer M, Schuster LN, Schulz F, Pfundner A, Horn M, Rattei T
Variant profiling of evolving prokaryotic populations
Feb 22, 2017
PeerJ
UNASSIGNED: Genomic heterogeneity of bacterial species is observed and studied in experimental evolution experiments and clinical diagnostics, and occurs as micro-diversity of natural habitats. The challenge for genome research is to accurately capture this heterogeneity with the currently used short sequencing reads. Recent advances in NGS technologies improved the speed and coverage and thus allowed for deep sequencing of bacterial populations. This facilitates the quantitative assessment of genomic heterogeneity, including low frequency alleles or haplotypes. However, false positive variant predictions due to sequencing errors and mapping artifacts of short reads need to be prevented. We therefore created VarCap, a workflow for the reliable prediction of different types of variants even at low frequencies. In order to predict SNPs, InDels and structural variations, we evaluated the sensitivity and accuracy of different software tools using synthetic read data. The results suggested that the best sensitivity could be reached by a union of different tools, however at the price of increased false positives. We identified possible reasons for false predictions and used this knowledge to improve the accuracy by post-filtering the predicted variants according to properties such as frequency, coverage, genomic environment/localization and co-localization with other variants. We observed that best precision was achieved by using an intersection of at least two tools per variant. This resulted in the reliable prediction of variants above a minimum relative abundance of 2%. VarCap is designed for being routinely used within experimental evolution experiments or for clinical diagnostics. The detected variants are reported as frequencies within a VCF file and as a graphical overview of the distribution of the different variant/allele/haplotype frequencies. The source code of VarCap is available at https://github.com/ma2o/VarCap. In order to provide this workflow to a broad community, we implemeted VarCap on a Galaxy webserver, which is accessible at http://galaxy.csb.univie.ac.at.
Bottom-up and top-down computations in word- and face-selective cortex
Feb 22, 2017   ELife
Kay KN, Yeatman JD
Bottom-up and top-down computations in word- and face-selective cortex
Feb 22, 2017
ELife
UNASSIGNED: The ability to read a page of text or recognize a person's face depends on category-selective visual regions in ventral temporal cortex (VTC). To understand how these regions mediate word and face recognition, it is necessary to characterize how stimuli are represented and how this representation is used in the execution of a cognitive task. Here, we show that the response of a category-selective region in VTC can be computed as the degree to which the low-level properties of the stimulus match a category template. Moreover, we show that during execution of a task, the bottom-up representation is scaled by the intraparietal sulcus (IPS), and that the level of IPS engagement reflects the cognitive demands of the task. These results provide an account of neural processing in VTC in the form of a model that addresses both bottom-up and top-down effects and quantitatively predicts VTC responses.
A novel physiological role for cardiac myoglobin in lipid metabolism
Feb 23, 2017   Scientific Reports
Hendgen-Cotta UB, Esfeld S, Coman C, Ahrends R, Klein-Hitpass L, Flögel U, Rassaf T, Totzeck M
A novel physiological role for cardiac myoglobin in lipid metabolism
Feb 23, 2017
Scientific Reports
Continuous contractile activity of the heart is essential and the required energy is mostly provided by fatty acid (FA) oxidation. Myocardial lipid accumulation can lead to pathological responses, however the underlying mechanisms remain elusive. The role of myoglobin in dioxygen binding in cardiomyocytes and oxidative skeletal muscle has widely been appreciated. Our recent work established myoglobin as a protector of cardiac function in hypoxia and disease states. We here unravel a novel role of cardiac myoglobin in governing FA metabolism to ensure the physiological energy production through β-oxidation, preventing myocardial lipid accumulation and preserving cardiac functions. In vivo
Proofreading of Peptide-MHC Complexes through Dynamic Multivalent Interactions
Feb 23, 2017   Frontiers In Immunology
Thomas C, Tampé R
Proofreading of Peptide-MHC Complexes through Dynamic Multivalent Interactions
Feb 23, 2017
Frontiers In Immunology
The adaptive immune system is able to detect and destroy cells that are malignantly transformed or infected by intracellular pathogens. Specific immune responses against these cells are elicited by antigenic peptides that are presented on major histocompatibility complex class I (MHC I) molecules and recognized by cytotoxic T lymphocytes at the cell surface. Since these MHC I-presented peptides are generated in the cytosol by proteasomal protein degradation, they can be metaphorically described as a window providing immune cells with insights into the state of the cellular proteome. A crucial element of MHC I antigen presentation is the peptide-loading complex (PLC), a multisubunit machinery, which contains as key constituents the transporter associated with antigen processing (TAP) and the MHC I-specific chaperone tapasin (Tsn). While TAP recognizes and shuttles the cytosolic antigenic peptides into the endoplasmic reticulum (ER), Tsn samples peptides in the ER for their ability to form stable complexes with MHC I, a process called peptide proofreading or peptide editing. Through its selection of peptides that improve MHC I stability, Tsn contributes to the hierarchy of immunodominant peptide epitopes. Despite the fact that it concerns a key event in adaptive immunity, insights into the catalytic mechanism of peptide proofreading carried out by Tsn have only lately been gained
Relationship between salivary/pancreatic amylase and body mass index: a systems biology approach
Feb 23, 2017   BMC Medicine
Bonnefond A, Yengo L, Dechaume A, Canouil M, Castelain M,   . . . . . .   , Balkau B, Marre M, Pattou F, Brousseau T, Froguel P
Relationship between salivary/pancreatic amylase and body mass index: a systems biology approach
Feb 23, 2017
BMC Medicine
BACKGROUND: Salivary (AMY1) and pancreatic (AMY2) amylases hydrolyze starch. Copy number of AMY1A (encoding AMY1) was reported to be higher in populations with a high-starch diet and reduced in obese people. These results based on quantitative PCR have been challenged recently. We aimed to re-assess the relationship between amylase and adiposity using a systems biology approach. METHODS: We assessed the association between plasma enzymatic activity of AMY1 or AMY2, and several metabolic traits in almost 4000 French individuals from D.E.S.I.R. longitudinal study. The effect of the number of copies of AMY1A (encoding AMY1) or AMY2A (encoding AMY2) measured through droplet digital PCR was then analyzed on the same parameters in the same study. A Mendelian randomization analysis was also performed. We subsequently assessed the association between AMY1A copy number and obesity risk in two case-control studies (5000 samples in total). Finally, we assessed the association between body mass index (BMI)-related plasma metabolites and AMY1 or AMY2 activity. RESULTS: We evidenced strong associations between AMY1 or AMY2 activity and lower BMI. However, we found a modest contribution of AMY1A copy number to lower BMI. Mendelian randomization identified a causal negative effect of BMI on AMY1 and AMY2 activities. Yet, we also found a significant negative contribution of AMY1 activity at baseline to the change in BMI during the 9-year follow-up, and a significant contribution of AMY1A copy number to lower obesity risk in children, suggesting a bidirectional relationship between AMY1 activity and adiposity. Metabonomics identified a BMI-independent association between AMY1 activity and lactate, a product of complex carbohydrate fermentation. CONCLUSIONS: These findings provide new insights into the involvement of amylase in adiposity and starch metabolism.
Epigenetic characteristics of the mitotic chromosome in 1D and 3D
Feb 23, 2017   Critical Reviews In Biochemistry And Molecular Biology
Oomen ME, Dekker J
Epigenetic characteristics of the mitotic chromosome in 1D and 3D
Feb 23, 2017
Critical Reviews In Biochemistry And Molecular Biology
While chromatin characteristics in interphase are widely studied, characteristics of mitotic chromatin and their inheritance through mitosis are still poorly understood. During mitosis, chromatin undergoes dramatic changes: transcription stalls, chromatin-binding factors leave the chromatin, histone modifications change and chromatin becomes highly condensed. Many key insights into mitotic chromosome state and conformation have come from extensive microscopy studies over the last century. Over the last decade, the development of 3C-based techniques has enabled the study of higher order chromosome organization during mitosis in a genome-wide manner. During mitosis, chromosomes lose their cell type-specific and locus-dependent chromatin organization that characterizes interphase chromatin and fold into randomly positioned loop arrays. Upon exit of mitosis, cells are capable of quickly rearranging the chromosome conformation to form the cell type-specific interphase organization again. The information that enables this rearrangement after mitotic exit is thought to be encoded at least in part in mitotic bookmarks, e.g. histone modifications and variants, histone remodelers, chromatin factors, and non-coding RNA. Here we give an overview of the chromosomal organization and epigenetic characteristics of interphase and mitotic chromatin in vertebrates. Second, we describe different ways in which mitotic bookmarking enables epigenetic memory of the features of interphase chromatin through mitosis. And third, we explore the role of epigenetic modifications and mitotic bookmarking in cell differentiation.
Diagnosis of major depressive disorder by combining multimodal information from heart rate dynamics and serum proteomics using machine-learning algorithm
Feb 22, 2017   Progress In Neuro-psychopharmacology & Biological Psychiatry
Kim EY, Lee MY, Kim SH, Ha K, Kim KP, Ahn YM
Diagnosis of major depressive disorder by combining multimodal information from heart rate dynamics and serum proteomics using machine-learning algorithm
Feb 22, 2017
Progress In Neuro-psychopharmacology & Biological Psychiatry
OBJECTIVE: Major depressive disorder (MDD) is a systemic and multifactorial disorder that involves abnormalities in multiple biochemical pathways and the autonomic nervous system. This study applied a machine-learning method to classify MDD and control groups by incorporating data from serum proteomic analysis and heart rate variability (HRV) analysis for the identification of novel peripheral biomarkers. METHODS: The study subjects consisted of 25 drug-free female MDD patients and 25 age- and sex-matched healthy controls. First, quantitative serum proteome profiles were analyzed by liquid chromatography-tandem mass spectrometry using pooled serum samples from 10 patients and 10 controls. Next, candidate proteins were quantified with multiple reaction monitoring (MRM) in 50 subjects. We also analyzed 22 linear and nonlinear HRV parameters in 50 subjects. Finally, we identified a combined biomarker panel consisting of proteins and HRV indexes using a support vector machine with recursive feature elimination. RESULTS: A separation between MDD and control groups was achieved using five parameters (apolipoprotein B, group-specific component, ceruloplasmin, RMSSD, and SampEn) at 80.1% classification accuracy. A combination of HRV and proteomic data achieved better classification accuracy. CONCLUSIONS: A high classification accuracy can be achieved by combining multimodal information from heart rate dynamics and serum proteomics in MDD. Our approach can be helpful for accurate clinical diagnosis of MDD. Further studies using larger, independent cohorts are needed to verify the role of these candidate biomarkers for MDD diagnosis. Copyright © 2017. Published by Elsevier Inc.

The link you entered does not seem to be valid

Please make sure the link points to nature.com contains a valid shared_access_token

Downloading PDF to your library...

Uploading PDF...

PDF uploading

Delete tag: