2,907 results match your criteria biologically plausible

The Coronavirus Network Explorer: mining a large-scale knowledge graph for effects of SARS-CoV-2 on host cell function.

BMC Bioinformatics 2021 May 3;22(1):229. Epub 2021 May 3.

Digital Insights, QIAGEN, Redwood City, USA.

Background: Leveraging previously identified viral interactions with human host proteins, we apply a machine learning-based approach to connect SARS-CoV-2 viral proteins to relevant host biological functions, diseases, and pathways in a large-scale knowledge graph derived from the biomedical literature. Our goal is to explore how SARS-CoV-2 could interfere with various host cell functions, and to identify drug targets amongst the host genes that could potentially be modulated against COVID-19 by repurposing existing drugs. The machine learning model employed here involves gene embeddings that leverage causal gene expression signatures curated from literature. Read More

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A Computational Model for Pain Processing in the Dorsal Horn Following Axonal Damage to Receptor Fibers.

Brain Sci 2021 Apr 16;11(4). Epub 2021 Apr 16.

Department of Mathematics, University of Texas at Arlington, Arlington, TX 76019, USA.

Computational modeling of the neural activity in the human spinal cord may help elucidate the underlying mechanisms involved in the complex processing of painful stimuli. In this study, we use a biologically-plausible model of the dorsal horn circuitry as a platform to simulate pain processing under healthy and pathological conditions. Specifically, we distort signals in the receptor fibers akin to what is observed in axonal damage and monitor the corresponding changes in five quantitative markers associated with the pain response. Read More

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Direct Phenotyping and Principal Component Analysis of Type Traits Implicate Novel QTL in Bovine Mastitis through Genome-Wide Association.

Animals (Basel) 2021 Apr 17;11(4). Epub 2021 Apr 17.

Department of Animal Science, Cornell University, Ithaca, NY 14853, USA.

Our objectives were to robustly characterize a cohort of Holstein cows for udder and teat type traits and perform high-density genome-wide association studies for those traits within the same group of animals, thereby improving the accuracy of the phenotypic measurements and genomic association study. Additionally, we sought to identify a novel udder and teat trait composite risk index to determine loci with potential pleiotropic effects related to mastitis. This approach was aimed at improving the biological understanding of the genetic factors influencing mastitis. Read More

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EPISPOT: An epigenome-driven approach for detecting and interpreting hotspots in molecular QTL studies.

Am J Hum Genet 2021 Apr 21. Epub 2021 Apr 21.

MRC Biostatistics Unit, University of Cambridge, Cambridge CB2 0SR, UK; The Alan Turing Institute, London NW1 2DB, UK; Department of Medical Genetics, University of Cambridge, Cambridge CB2 0QQ, UK.

We present EPISPOT, a fully joint framework which exploits large panels of epigenetic annotations as variant-level information to enhance molecular quantitative trait locus (QTL) mapping. Thanks to a purpose-built Bayesian inferential algorithm, EPISPOT accommodates functional information for both cis and trans actions, including QTL hotspot effects. It effectively couples simultaneous QTL analysis of thousands of genetic variants and molecular traits with hypothesis-free selection of biologically interpretable annotations which directly contribute to the QTL effects. Read More

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Application of adverse outcome pathway networks to integrate mechanistic data informing the choice of a point of departure for hydrogen sulfide exposure limits.

Crit Rev Toxicol 2021 Apr 27:1-16. Epub 2021 Apr 27.

ExxonMobil Biomedical Sciences, Inc., Annandale, NJ, USA.

Acute exposure to hydrogen sulfide initiates a series of hallmark biological effects that occur progressively at increasing exposure levels: odor perception, conjunctivitis, olfactory paralysis, "knockdown," pulmonary edema, and apnea. Although effects of exposure to high concentrations of hydrogen sulfide are clear, effects associated with chronic, low-level exposure in humans is under debate, leading to uncertainty in the critical effect used in regulatory risk assessments addressing low dose exposures. This study integrates experimental animal, observational epidemiology, and occupational exposure evidence by applying a pathway-based approach. Read More

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Genome Wide Association Study Identifies Two Novel Loci Associated with Female Stress and Urgency Urinary Incontinence.

J Urol 2021 Apr 27:101097JU0000000000001822. Epub 2021 Apr 27.

Institute for Reproductive and Developmental Biology (IRDB), Imperial College London, UK.

Background: Genome-wide association studies (GWAS) have not identified replicable genetic risk loci for stress or urgency urinary incontinence.

Methods: We carried out a discovery stage case control GWAS in three independent discovery cohorts of European women (n=8,979) for stress incontinence, urgency incontinence, and any incontinence phenotypes. We conducted replication in six additional studies of European ancestry (n=4,069). Read More

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Temporal Coding in Spiking Neural Networks With Alpha Synaptic Function: Learning With Backpropagation.

IEEE Trans Neural Netw Learn Syst 2021 Apr 26;PP. Epub 2021 Apr 26.

The timing of individual neuronal spikes is essential for biological brains to make fast responses to sensory stimuli. However, conventional artificial neural networks lack the intrinsic temporal coding ability present in biological networks. We propose a spiking neural network model that encodes information in the relative timing of individual spikes. Read More

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Maternal smoking during pregnancy, offspring smoking, adverse childhood events, and risk of major depression: a sibling design study.

Psychol Med 2021 Apr 26:1-11. Epub 2021 Apr 26.

Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA.

Background: Evidence of a biologically plausible association between maternal smoking during pregnancy (MSP) and the risk of depression is discounted by null findings from two sibling studies. However, valid causal inference from sibling studies is subject to challenges inherent to human studies of MSP and biases particular to this design. We addressed these challenges in the first sibling study of MSP and depression conducted among adults past the peak age for the onset of depression, utilizing a prospectively collected and biologically validated measure of MSP and accounting for non-shared as well as mediating factors. Read More

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Vitamin D Resistance as a Possible Cause of Autoimmune Diseases: A Hypothesis Confirmed by a Therapeutic High-Dose Vitamin D Protocol.

Front Immunol 2021 7;12:655739. Epub 2021 Apr 7.

Akademie für menschliche Medizin und evolutionäre Gesundheit, Schlangenbad, Germany.

Vitamin D (cholecalciferol) is a secosteroid and prohormone which is metabolized in various tissues to the biologically most active vitamin D hormone 1,25(OH)D (calcitriol). 1,25(OH)D has multiple pleiotropic effects, particularly within the immune system, and is increasingly utilized not only within prophylaxis, but also within therapy of various diseases. In this context, the latest research has revealed clinical benefits of high dose vitamin D therapy in autoimmune diseases. Read More

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Systematic review and meta-analysis of genetic association studies of pelvic organ prolapse.

Int Urogynecol J 2021 Apr 24. Epub 2021 Apr 24.

Department of Epidemiology & Biostatistics, Imperial College London, Norfolk Place, London, UK.

Introduction And Hypothesis: Family and twin studies demonstrate that pelvic organ prolapse (POP) is heritable, but the genetic etiology is poorly understood. This review aimed to identify genetic loci and specific polymorphisms associated with POP, while assessing the strength, consistency, and risk of bias among reported associations.

Methods: Updating an earlier systematic review, PubMed and HuGE Navigator as well as relevant conference abstracts were searched using genetic and phenotype keywords from 2015 to 2020. Read More

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MicroRNA governs bistable cell differentiation and lineage segregation via a noncanonical feedback.

Mol Syst Biol 2021 04;17(4):e9945

Department of Biochemistry & Cellular and Molecular Biology, The University of Tennessee, Knoxville, TN, USA.

Positive feedback driven by transcriptional regulation has long been considered a key mechanism underlying cell lineage segregation during embryogenesis. Using the developing spinal cord as a paradigm, we found that canonical, transcription-driven feedback cannot explain robust lineage segregation of motor neuron subtypes marked by two cardinal factors, Hoxa5 and Hoxc8. We propose a feedback mechanism involving elementary microRNA-mRNA reaction circuits that differ from known feedback loop-like structures. Read More

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Comparison of Artificial and Spiking Neural Networks on Digital Hardware.

Front Neurosci 2021 6;15:651141. Epub 2021 Apr 6.

APT Group, Department of Computer Science, University of Manchester, Manchester, United Kingdom.

Despite the success of Deep Neural Networks-a type of Artificial Neural Network (ANN)-in problem domains such as image recognition and speech processing, the energy and processing demands during both training and deployment are growing at an unsustainable rate in the push for greater accuracy. There is a temptation to look for radical new approaches to these applications, and one such approach is the notion that replacing the abstract neuron used in most deep networks with a more biologically-plausible spiking neuron might lead to savings in both energy and resource cost. The most common spiking networks use neurons for which a simple translation from a pre-trained ANN to an equivalent spike-based network (SNN) is readily achievable. Read More

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Pulmonary toxicity associated with occupational and environmental exposure to pesticides and herbicides.

Curr Opin Pulm Med 2021 Apr 20. Epub 2021 Apr 20.

Maastricht University Campus Venlo, Venlo Department of Pharmacology and Toxicology, FHML, Maastricht University, Maastricht ILD Care Foundation Research Team, Ede Department of Pulmonology, ILD Center of Excellence, St. Antonius Hospital, Nieuwegein, The Netherlands.

Purpose Of The Review: Critical review on the notion that exposure to pesticides and herbicides lead to adverse effects in pulmonary health.

Recent Findings: The lung effects of several chemical classes of pesticides and herbicides is biologically plausible. However, the studies that describe the association between exposure and toxic lung effects have numerous limitations. Read More

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Topical Microbial Therapeutics against Respiratory Viral Infections.

Trends Mol Med 2021 Apr 17. Epub 2021 Apr 17.

Research Group Environmental Ecology and Applied Microbiology, Department of Bioscience Engineering, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium. Electronic address:

Emerging evidence suggests that microbial therapeutics can prevent and treat respiratory viral diseases, especially when applied directly to the airways. This review presents established beneficial effects of locally administered microbial therapeutics against respiratory viral diseases and the inferred related molecular mechanisms. Several mechanisms established in the intestinal probiotics field as well as novel, niche-specific insights are relevant in the airways. Read More

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Pesticide exposure and gender discrepancy in breast cancer.

Eur Rev Med Pharmacol Sci 2021 Apr;25(7):2898-2915

Occupational Medicine, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.

Objective: It is biologically plausible that occupational and environmental pesticide exposure may contribute to breast cancer risk. Persistent chemical compounds, such as pesticides, tend to be lipophilic and are detected in human breast milk and adipose tissue. Therefore, the present systematic review aims to clarify the gender difference in breast cancer concerning pesticide exposure. Read More

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Unveiling the urease like intrinsic catalytic activities of two dinuclear nickel complexes towards the in situ syntheses of aminocyanopyridines.

Dalton Trans 2021 Apr 19;50(14):4848-4858. Epub 2021 Mar 19.

Discipline of Chemistry, School of Basic Sciences, Indian Institute of Technology Indore, Simrol, Khandwa Road, Indore 453552, India.

Designing metal complexes as functional models for metalloenzymes remains one of the main targets in synthetic bioinorganic chemistry. Furthermore, the utilization of the product(s) derived from the catalytic reaction for subsequent organic transformation that occurs in biological systems is an even more difficult challenge for biochemists. Urease, the most efficient enzyme known, catalyzes the hydrolysis of urea and it contains an essential dinuclear Ni cluster in the active site. Read More

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Modeling Working Memory in a Spiking Neuron Network Accompanied by Astrocytes.

Front Cell Neurosci 2021 31;15:631485. Epub 2021 Mar 31.

Scientific and Educational Mathematical Center "Mathematics of Future Technology," Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia.

We propose a novel biologically plausible computational model of working memory (WM) implemented by a spiking neuron network (SNN) interacting with a network of astrocytes. The SNN is modeled by synaptically coupled Izhikevich neurons with a non-specific architecture connection topology. Astrocytes generating calcium signals are connected by local gap junction diffusive couplings and interact with neurons via chemicals diffused in the extracellular space. Read More

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Surveillance of Depleted Uranium-exposed Gulf War Veterans: More Evidence for Bone Effects.

Health Phys 2021 06;120(6):671-682

Department of Medicine, University of Maryland School of Medicine, Baltimore, MD.

Abstract: Gulf War I veterans who were victims of depleted uranium (DU) "friendly-fire" incidents have undergone longitudinal health surveillance since 1994. During the spring of 2019, 36 members of the cohort were evaluated with a monitoring protocol including exposure assessment for total and isotopic uranium concentrations in urine and a comprehensive review of health outcomes, including measures of bone metabolism and bone mineral density (BMD) determination. Elevated urine U concentrations were observed in cohort members with retained depleted uranium (DU) shrapnel fragments. Read More

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Cancer immune control dynamics: a clinical data driven model of systemic immunity in patients with metastatic melanoma.

BMC Bioinformatics 2021 Apr 16;22(1):197. Epub 2021 Apr 16.

Department of Medical Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Background: Recent clinical advances in cancer immuno-therapeutics underscore the need for improved understanding of the complex relationship between cancer and the multiple, multi-functional, inter-dependent, cellular and humoral mediators/regulators of the human immune system. This interdisciplinary effort exploits engineering analysis methods utilized to investigate anomalous physical system behaviors to explore immune system behaviors. Cancer Immune Control Dynamics (CICD), a systems analysis approach, attempts to identify differences between systemic immune homeostasis of 27 healthy volunteers versus 14 patients with metastatic malignant melanoma based on daily serial measurements of conventional peripheral blood biomarkers (15 cell subsets, 35 cytokines). Read More

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Bioinspired Gain-Modulated Recurrent Neural Network for Controlling Musculoskeletal Robot.

IEEE Trans Neural Netw Learn Syst 2021 Apr 16;PP. Epub 2021 Apr 16.

The motor cortex can arouse abundant transient responses to generate complex movements with the regulation of neuromodulators, while its architecture remains unchanged. This characteristic endows humans with flexible and robust abilities in adapting to dynamic environments, which is exactly the bottleneck in the control of complex robots. In this article, inspired by the mechanisms of the motor cortex in encoding information and modulating motor commands, a biologically plausible gain-modulated recurrent neural network is proposed to control a highly redundant, coupled, and nonlinear musculoskeletal robot. Read More

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Systemic PFOS and PFOA exposure and disturbed lipid homeostasis in humans: what do we know and what not?

Crit Rev Toxicol 2021 Apr 15:1-24. Epub 2021 Apr 15.

Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

Associations between per- and polyfluoroalkyl substances (PFASs) and increased blood lipids have been repeatedly observed in humans, but a causal relation has been debated. Rodent studies show reverse effects, i.e. Read More

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Statistical analysis of comparative tumor growth repeated measures experiments in the ovarian cancer patient derived xenograft (PDX) setting.

Sci Rep 2021 Apr 13;11(1):8076. Epub 2021 Apr 13.

Division of Medical Oncology, Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Repeated measures studies are frequently performed in patient-derived xenograft (PDX) models to evaluate drug activity or compare effectiveness of cancer treatment regimens. Linear mixed effects regression models were used to perform statistical modeling of tumor growth data. Biologically plausible structures for the covariation between repeated tumor burden measurements are explained. Read More

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Inflexible Updating of the Self-Other Divide During a Social Context in Autism; Psychophysical, Electrophysiological, and Neural Network Modeling Evidence.

Biol Psychiatry Cogn Neurosci Neuroimaging 2021 Apr 9. Epub 2021 Apr 9.

Vanderbilt Brain Institute, Vanderbilt University, Nashville, USA; Hearing and Speech Sciences, Vanderbilt University Medical Center, Nashville, USA; Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, USA.

Background: Autism spectrum disorder (ASD) affects many aspects of life, from social interactions to (multi)sensory processing. Similarly, the condition expresses at the variety of levels of description, from genetics to neural circuits and interpersonal behavior. We attempt to bridge between domains and levels of description by detailing the behavioral, electrophysiological, and putative neural network basis of peri-personal space (PPS) updating in ASD during a social context, given that the encoding of this space relies on appropriate multisensory integration, is malleable by social context, and thought to delineate the boundary between self and other. Read More

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Bone fracture as a novel immune-related adverse event with immune checkpoint inhibitors: Case series and large-scale pharmacovigilance analysis.

Int J Cancer 2021 Apr 12. Epub 2021 Apr 12.

Head and Neck Medical Oncology Unit, Fondazione IRCCS-Istituto Nazionale dei Tumori, Milan, Italy.

Although immune checkpoint inhibitors (ICIs) are associated with different immune-related adverse events (irAEs), the potential effect on the skeleton is poorly defined albeit biologically plausible and assessable through pharmacovigilance. We described a case series of patients experiencing skeletal fractures while on ICIs at the National Cancer Institute of Milan. To better characterize the clinical features of skeletal irAEs reported with ICIs, we queried the FDA Adverse Event Reporting System (FAERS) and performed disproportionality analysis by means of reporting odds ratios (RORs), deemed significant by a lower limit of the 95% confidence interval (LL95% CI) > 1. Read More

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Dysfunctional mode switching between fixation and saccades: collaborative insights into two unusual clinical disorders.

J Comput Neurosci 2021 Apr 10. Epub 2021 Apr 10.

Laboratory of Sensorimotor Research, NEI, NIH, DHHS, Bethesda, MD, USA.

Voluntary rapid eye movements (saccades) redirect the fovea toward objects of visual interest. The saccadic system can be considered as a dual-mode system: in one mode the eye is fixating, in the other it is making a saccade. In this review, we consider two examples of dysfunctional saccades, interrupted saccades in late-onset Tay-Sachs disease and gaze-position dependent opsoclonus after concussion, which fail to properly shift between fixation and saccade modes. Read More

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Shear-driven rolling of DNA-adhesive microspheres.

Biophys J 2021 Apr 8. Epub 2021 Apr 8.

Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Many biologically important cell binding processes, such as the rolling of leukocytes in the vasculature, are multivalent, being mediated by large numbers of weak binding ligands. Quantitative agreement between experiments and models of rolling has been elusive and often limited by the poor understanding of the binding and unbinding kinetics of the ligands involved. Here, we present a cell-free experimental model for such rolling, consisting of polymer microspheres whose adhesion to a glass surface is mediated by ligands with well-understood force-dependent binding free energy-short complementary DNA strands. Read More

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A biomimetic neural encoder for spiking neural network.

Nat Commun 2021 04 9;12(1):2143. Epub 2021 Apr 9.

Department of Engineering Science and Mechanics, Pennsylvania State University, University Park, PA, USA.

Spiking neural networks (SNNs) promise to bridge the gap between artificial neural networks (ANNs) and biological neural networks (BNNs) by exploiting biologically plausible neurons that offer faster inference, lower energy expenditure, and event-driven information processing capabilities. However, implementation of SNNs in future neuromorphic hardware requires hardware encoders analogous to the sensory neurons, which convert external/internal stimulus into spike trains based on specific neural algorithm along with inherent stochasticity. Unfortunately, conventional solid-state transducers are inadequate for this purpose necessitating the development of neural encoders to serve the growing need of neuromorphic computing. Read More

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Tuned inhibition in perceptual decision-making circuits can explain seemingly suboptimal confidence behavior.

PLoS Comput Biol 2021 Mar 29;17(3):e1008779. Epub 2021 Mar 29.

Department of Cognitive Sciences, University of California Irvine, Irvine, California, United States of America.

Current dominant views hold that perceptual confidence reflects the probability that a decision is correct. Although these views have enjoyed some empirical support, recent behavioral results indicate that confidence and the probability of being correct can be dissociated. An alternative hypothesis suggests that confidence instead reflects the magnitude of evidence in favor of a decision while being relatively insensitive to the evidence opposing the decision. Read More

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Stylistic Composition of Melodies Based on a Brain-Inspired Spiking Neural Network.

Qian Liang Yi Zeng

Front Syst Neurosci 2021 11;15:639484. Epub 2021 Mar 11.

Research Center for Brain-Inspired Intelligence, Institute of Automation, Chinese Academy of Sciences, Beijing, China.

Current neural network based algorithmic composition methods are very different compared to human brain's composition process, while the biological plausibility of composition and generative models are essential for the future of Artificial Intelligence. To explore this problem, this paper presents a spiking neural network based on the inspiration from brain structures and musical information processing mechanisms at multiple scales. Unlike previous methods, our model has three novel characteristics: (1) Inspired by brain structures, multiple brain regions with different cognitive functions, including musical memory and knowledge learning, are simulated and cooperated to generate stylistic melodies. Read More

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Neuronal-Plasticity and Reward-Propagation Improved Recurrent Spiking Neural Networks.

Front Neurosci 2021 12;15:654786. Epub 2021 Mar 12.

Research Center for Brain-Inspired Intelligence, Institute of Automation, Chinese Academy of Sciences (CASIA), Beijing, China.

Different types of dynamics and plasticity principles found through natural neural networks have been well-applied on Spiking neural networks (SNNs) because of their biologically-plausible efficient and robust computations compared to their counterpart deep neural networks (DNNs). Here, we further propose a special Neuronal-plasticity and Reward-propagation improved Recurrent SNN (NRR-SNN). The historically-related adaptive threshold with two channels is highlighted as important neuronal plasticity for increasing the neuronal dynamics, and then global labels instead of errors are used as a reward for the paralleling gradient propagation. Read More

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