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https://www.readbyqxmd.com/read/29344887/phosphoproteomics-based-profiling-of-kinase-activities-in-cancer-cells
#1
Jakob Wirbel, Pedro Cutillas, Julio Saez-Rodriguez
Cellular signaling, predominantly mediated by phosphorylation through protein kinases, is found to be deregulated in most cancers. Accordingly, protein kinases have been subject to intense investigations in cancer research, to understand their role in oncogenesis and to discover new therapeutic targets. Despite great advances, an understanding of kinase dysfunction in cancer is far from complete.A powerful tool to investigate phosphorylation is mass-spectrometry (MS)-based phosphoproteomics, which enables the identification of thousands of phosphorylated peptides in a single experiment...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29344147/systematic-analysis-of-the-molecular-mechanism-of-microrna-124-in-hepatoblastoma-cells
#2
Guiming Wang, Hong Liu, Zhigang Wei, Hongyan Jia, Yu Liu, Jiansheng Liu
The present study aimed to identify the molecular mechanisms of microRNA-124 (miRNA-124/miR-124) in hepatoblastoma. The GSE6207 microarray dataset, obtained from the Gene Expression Omnibus database, included samples extracted from HepG2 cells transfected with miR-124 duplex (the experimental group) or negative control (the control group) at 4, 8, 16, 24, 32, 72 and 120 h after transfection. Differentially expressed genes (DEGs) were screened between the two groups. miR-124 activity was inferred based on the expression of its target genes...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343629/the-markov-blankets-of-life-autonomy-active-inference-and-the-free-energy-principle
#3
REVIEW
Michael Kirchhoff, Thomas Parr, Ensor Palacios, Karl Friston, Julian Kiverstein
This work addresses the autonomous organization of biological systems. It does so by considering the boundaries of biological systems, from individual cells to Home sapiens, in terms of the presence of Markov blankets under the active inference scheme-a corollary of the free energy principle. A Markov blanket defines the boundaries of a system in a statistical sense. Here we consider how a collective of Markov blankets can self-assemble into a global system that itself has a Markov blanket; thereby providing an illustration of how autonomous systems can be understood as having layers of nested and self-sustaining boundaries...
January 2018: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29343499/a-population-phylogenetic-view-of-mitochondrial-heteroplasmy
#4
Peter R Wilton, Arslan Zaidi, Kateryna Makova, Rasmus Nielsen
The mitochondrion has recently emerged as an active player in a myriad of cellular processes. Additionally, it was recently shown that more than 200 diseases are known to be linked to variants in mitochondrial DNA or in nuclear genes interacting with mitochondria. This has reinvigorated interest in its biology and population genetics. Mitochondrial heteroplasmy, or genotypic variation of mitochondria within an individual, is now understood to be common in humans and important in human health. However, it is still not possible to make quantitative predictions about the inheritance of heteroplasmy and its proliferation within the body, partly due to the lack of an appropriate model...
January 17, 2018: Genetics
https://www.readbyqxmd.com/read/29342276/a-predictive-quantitative-model-of-spiking-activity-and-stimulus-secretion-coupling-in-oxytocin-neurons
#5
Jorge Maícas-Royo, Gareth Leng, Duncan J MacGregor
Oxytocin neurons of the rat hypothalamus project to the posterior pituitary where they secrete their products into the bloodstream. The pattern and quantity of that release depends on the afferent inputs to the neurons, on their intrinsic membrane properties, and on non-linear interactions between spiking activity and exocytosis: a given number of spikes will trigger more secretion when they arrive close together. Here we present a quantitative computational model of oxytocin neurons that can replicate the results of a wide variety of published experiments...
January 12, 2018: Endocrinology
https://www.readbyqxmd.com/read/29341386/at-the-core-of-reasoning-dissociating-deductive-and-non-deductive-load
#6
John P Coetzee, Martin M Monti
In recent years, neuroimaging methods have been used to investigate how the human mind carries out deductive reasoning. According to some, the neural substrate of language is integral to deductive reasoning. According to others, deductive reasoning is supported by a language-independent distributed network including left frontopolar and frontomedial cortices. However, it has been suggested that activity in these frontal regions might instead reflect non-deductive factors such as working memory load and general cognitive difficulty...
January 16, 2018: Human Brain Mapping
https://www.readbyqxmd.com/read/29340065/integrating-gene-and-lncrna-expression-to-infer-subpathway-activity-for-tumor-analyses
#7
Chunlong Zhang, Yanjun Xu, Haixiu Yang, Yingqi Xu, Qun Dong, Siyao Liu, Tan Wu, Yunpeng Zhang
LncRNAs acting as miRNA sponges to indirectly regulate mRNAs is a novel layer of gene regulation, therefore, it is necessary to integrate lncRNA and gene levels for interpreting tumor biological mechanism. In this study, we developed a lncRNA-gene integrated strategy to infer functional activities for tumor analyses at the subpathway level. In this strategy, we reconstructed subpathway graphs by embedding lncRNA components and considered the expression levels of both genes and lncRNAs to infer subpathway activities for each tumor sample...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29338005/inferring-cell-state-by-quantitative-motility-analysis-reveals-a-dynamic-state-system-and-broken-detailed-balance
#8
Jacob C Kimmel, Amy Y Chang, Andrew S Brack, Wallace F Marshall
Cell populations display heterogeneous and dynamic phenotypic states at multiple scales. Similar to molecular features commonly used to explore cell heterogeneity, cell behavior is a rich phenotypic space that may allow for identification of relevant cell states. Inference of cell state from cell behavior across a time course may enable the investigation of dynamics of transitions between heterogeneous cell states, a task difficult to perform with destructive molecular observations. Cell motility is one such easily observed cell behavior with known biomedical relevance...
January 16, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29337692/generation-of-superoxide-and-hydrogen-peroxide-by-side-reactions-of-mitochondrial-2-oxoacid-dehydrogenase-complexes-in-isolation-and-in-cells
#9
Victoria I Bunik, Martin D Brand
Mitochondrial 2-oxoacid dehydrogenase complexes oxidize 2-oxoglutarate, pyruvate, branched-chain 2-oxoacids and 2-oxoadipate to the corresponding acyl-CoAs and reduce NAD+ to NADH. The isolated enzyme complexes generate superoxide anion radical or hydrogen peroxide in defined reactions by leaking electrons to oxygen. Studies using isolated mitochondria in media mimicking cytosol suggest that the 2-oxoacid dehydrogenase complexes contribute little to the production of superoxide or hydrogen peroxide relative to other mitochondrial sites at physiological steady-states...
June 27, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29337679/the-effects-of-physical-activity-on-chronic-subclinical-systemic-inflammation
#10
Alba Maria Dalbello Tir, Marina Labor, Davor Plavec
Chronic subclinical systemic inflammation (CSSI) is a pathogenic event and a common risk factor for many noncommunicable diseases like atherosclerosis, metabolic syndrome, cardiovascular disease, insulin resistance and type 2 diabetes, cancer, and obstructive lung disease. On the other hand, regular physical activity has been found to reduce this risk. Many studies of different design were conducted to assess the association between inflammatory mediators as markers of CSSI and regular physical activity. The aim of this review was to present the current level of evidence and understanding of potential mechanisms by which physical activity reduces inflammatory mediators involved in CSSI and the types of physical activity required for the expected effect...
December 20, 2017: Arhiv za Higijenu Rada i Toksikologiju
https://www.readbyqxmd.com/read/29335380/mitochondrial-activity-in-gametes-and-uniparental-inheritance-a-comment-on-what-can-we-infer-about-the-origin-of-sex-in-early-eukaryotes
#11
Fabrizio Ghiselli, Sophie Breton, Liliana Milani
No abstract text is available yet for this article.
March 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29333706/estimating-the-footprint-of-pollution-on-coral-reefs-with-models-of-species-turnover
#12
Christopher J Brown, Richard Hamilton
Ecological communities typically change along gradients of human impact, though it is difficult to estimate the footprint of impacts for diffuse threats like pollution. Here we develop a joint model of benthic habitats on lagoonal coral reefs and use it to infer change in benthic composition along a gradient of distance from logging operations. The model estimates both changes in abundances of benthic groups and their compositional turn-over, a type of beta-diversity. We detect compositional turnover across the gradient and use the model to predict the footprint of turbidity impacts from logging...
January 15, 2018: Conservation Biology: the Journal of the Society for Conservation Biology
https://www.readbyqxmd.com/read/29332992/experiment-design-for-early-molecular-events-in-hiv-infection
#13
Aditya Jagarapu, LaMont Cannon, Ryan Zurakowski
The recent introduction of integrase inhibitors to the HIV antiviral repertoire permits us to create in vitro experiments that reliably terminate HIV infection at the point of chromosomal integration. This allows us to isolate the dynamics of a single round of infection, without needing to account for the influence of multiple overlapping rounds of infection. By measuring the various nucleic acid concentrations in a population of infected target cells at multiple time points, we can infer the rates of these molecular events with great accuracy, which allows us to compare the rates between target cells with different functional phenotypes...
May 2017: Proceedings of the ... American Control Conference
https://www.readbyqxmd.com/read/29331218/knowing-when-to-stop-aberrant-precision-and-evidence-accumulation-in-schizophrenia
#14
Roberto Limongi, Bartosz Bohaterewicz, Magdalena Nowicka, Aleksandra Plewka, Karl J Friston
Predictive coding and active inference formulations of the dysconnection hypothesis suggest that subjects with schizophrenia (SZ) hold unduly precise prior beliefs to compensate for a failure of sensory attenuation. This implies that SZ subjects should both initiate responses prematurely during evidence-accumulation tasks and fail to inhibit their responses at long stop-signal delays. SZ and healthy control subjects were asked to report the timing of billiards-ball collisions and were occasionally required to withhold their responses...
January 10, 2018: Schizophrenia Research
https://www.readbyqxmd.com/read/29329747/antibacterial-properties-of-latarcin-1-derived-cell-penetrating-peptides
#15
Deepthi Poornima Budagavi, Archana Chugh
Cell-penetrating peptides (CPPs) and antimicrobial peptides (AMPs) share certain physicochemical parameters such as amphipathicity, hydrophobicity, cationicity and pI, due to which these two groups of peptides also exhibit overlapping functional characteristics. In our current work, we have evaluated antimicrobial properties of cell-penetrating peptides derived from Latarcin1. Latarcin derived peptide (LDP) exhibited antimicrobial activity against representative microorganisms tested and bactericidal effect against methicillin resistant Staphylococcus aureus (MRSA), which was used as model organism of study in the present work...
January 9, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29328958/stdp-based-spiking-deep-convolutional-neural-networks-for-object-recognition
#16
Saeed Reza Kheradpisheh, Mohammad Ganjtabesh, Simon J Thorpe, Timothée Masquelier
Previous studies have shown that spike-timing-dependent plasticity (STDP) can be used in spiking neural networks (SNN) to extract visual features of low or intermediate complexity in an unsupervised manner. These studies, however, used relatively shallow architectures, and only one layer was trainable. Another line of research has demonstrated - using rate-based neural networks trained with back-propagation - that having many layers increases the recognition robustness, an approach known as deep learning. We thus designed a deep SNN, comprising several convolutional (trainable with STDP) and pooling layers...
December 23, 2017: Neural Networks: the Official Journal of the International Neural Network Society
https://www.readbyqxmd.com/read/29328877/designing-difference-in-difference-studies-best-practices-for-public-health-policy-research
#17
Coady Wing, Kosali Simon, Ricardo A Bello-Gomez
The difference in difference (DID) design is a quasi-experimental research design that researchers often use to study causal relationships in public health settings where randomized controlled trials (RCTs) are infeasible or unethical. However, causal inference poses many challenges in DID designs. In this article, we review key features of DID designs with an emphasis on public health policy research. Contemporary researchers should take an active approach to the design of DID studies, seeking to construct comparison groups, sensitivity analyses, and robustness checks that help validate the method's assumptions...
January 12, 2018: Annual Review of Public Health
https://www.readbyqxmd.com/read/29326172/diversity-and-connectivity-of-layer-5-somatostatin-expressing-interneurons-in-the-mouse-barrel-cortex
#18
Nigro Maximiliano José, Yoshiko Hashikawa, Bernardo Rudy
Inhibitory interneurons represent 10-15% of the neurons in the somatosensory cortex, and their activity powerfully shapes sensory processing. Three major groups of GABAergic interneurons have been defined according to developmental, molecular, morphological, electrophysiological, and synaptic features. Dendritic-targeting somatostatin-expressing interneurons (SST-INs) have been shown to display diverse morphological, electrophysiological and molecular properties and activity patterns in vivo. However, the correlation between these properties and SST-IN subtype is unclear...
January 11, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29325176/dynamic-motif-occupancy-dynamo-analysis-identifies-transcription-factors-and-their-binding-sites-driving-dynamic-biological-processes
#19
Zheng Kuang, Zhicheng Ji, Jef D Boeke, Hongkai Ji
Biological processes are usually associated with genome-wide remodeling of transcription driven by transcription factors (TFs). Identifying key TFs and their spatiotemporal binding patterns are indispensable to understanding how dynamic processes are programmed. However, most methods are designed to predict TF binding sites only. We present a computational method, dynamic motif occupancy analysis (DynaMO), to infer important TFs and their spatiotemporal binding activities in dynamic biological processes using chromatin profiling data from multiple biological conditions such as time-course histone modification ChIP-seq data...
January 9, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29325153/network-perturbation-analysis-of-gene-transcriptional-profiles-reveals-protein-targets-and-mechanism-of-action-of-drugs-and-influenza-a-viral-infection
#20
Heeju Noh, Jason E Shoemaker, Rudiyanto Gunawan
Genome-wide transcriptional profiling provides a global view of cellular state and how this state changes under different treatments (e.g. drugs) or conditions (e.g. healthy and diseased). Here, we present ProTINA (Protein Target Inference by Network Analysis), a network perturbation analysis method for inferring protein targets of compounds from gene transcriptional profiles. ProTINA uses a dynamic model of the cell-type specific protein-gene transcriptional regulation to infer network perturbations from steady state and time-series differential gene expression profiles...
January 9, 2018: Nucleic Acids Research
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