Bioprospecting the American Alligator Peptidome for antiviral peptides against Venezuelan equine encephalitis virus.

The innate immune protection provided by cationic antimicrobial peptides (CAMPs) has been shown to extend to antiviral activity, with putative mechanisms of action including direct interaction with host cells or pathogen membranes. The lack of therapeutics available for the treatment of viruses such as Venezuelan equine encephalitis virus (VEEV) underscores the urgency of novel strategies for antiviral discovery. American alligator plasma has been shown to exhibit strong in vitro antibacterial activity, and functionalized hydrogel particles have been successfully employed for the identification of specific CAMPs from alligator plasma.

Transmembrane Aggregation of Aβ10-40 Peptides in an Anionic Lipid Bilayer.

Using the all-atom model and 10 μs serial replica-exchange molecular dynamics (SREMD), we investigated the binding of Alzheimer's Aβ10-40 peptides to the anionic dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DMPC/DMPG) lipid bilayer. Our objective was to probe transmembrane Aβ10-40 aggregation and to test the utility of SREMD. Our results are threefold.

GOProFormer: A Multi-Modal Transformer Method for Gene Ontology Protein Function Prediction.

Protein Language Models (PLMs) are shown to be capable of learning sequence representations useful for various prediction tasks, from subcellular localization, evolutionary relationships, family membership, and more. They have yet to be demonstrated useful for protein function prediction. In particular, the problem of automatic annotation of proteins under the Gene Ontology (GO) framework remains open.

Genetic variations affecting ACE2 protein stability in minority populations.

While worldwide efforts for improving COVID-19 vaccines are currently considered a top priority, the role of the genetic variants responsible for virus receptor protein stability is less studied. Angiotensin-converting enzyme-2 is the primary target of the SARS-CoV-1/SARS-CoV-2 spike (S) glycoprotein, enabling entry into the human body. Here, we applied computational saturation mutagenesis approaches to determine the folding energy caused by all possible mutations in ACE2 proteins within ACE2 - SARS-CoV-1-S/ACE2 - SARS-CoV-2-S complexes.

Molecular Dynamics Simulations to Decipher the Role of Phosphorylation of SARS-CoV-2 Nonstructural Proteins (nsps) in Viral Replication.

Protein phosphorylation is a post-translational modification that enables various cellular activities and plays essential roles in protein interactions. Phosphorylation is an important process for the replication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To shed more light on the effects of phosphorylation, we used an ensemble of neural networks to predict potential kinases that might phosphorylate SARS-CoV-2 nonstructural proteins (nsps) and molecular dynamics (MD) simulations to investigate the effects of phosphorylation on nsps structure, which could be a potential inhibitory target to attenuate viral replication.

The Role of Ca Sparks in Force Frequency Relationships in Guinea Pig Ventricular Myocytes.

Calcium sparks are the elementary Ca release events in excitation-contraction coupling that underlie the Ca transient. The frequency-dependent contractile force generated by cardiac myocytes depends upon the characteristics of the Ca transients. A stochastic computational local control model of a guinea pig ventricular cardiomyocyte was developed, to gain insight into mechanisms of force-frequency relationship (FFR).

Evaluating anticancer properties of Withaferin A-a potent phytochemical.

Withaferin A is a C28 steroidal lactone derived from the plant , commonly known as Ashwagandha. Withaferin A has received great attention for its anticancer properties noted in cancer cells of various origins. Extracts of have been used in traditional Ayurvedic and Unani Indian medicine for their various pharmacological benefits.

A phenome-wide investigation of risk factors for severe COVID-19.

With the continued spread of COVID-19 globally, it is crucial to identify the potential risk or protective factors associated with COVID-19. Here, we performed genetic correlation analysis and Mendelian randomization analysis to examine genetic relationships between COVID-19 hospitalization and 405 health conditions and lifestyle factors in 456 422 participants from the UK Biobank. The genetic correlation analysis revealed 134 positive and 65 negative correlations, including those with intakes of a variety of dietary components.

Causal Associations Between Basal Metabolic Rate and COVID-19.

Many coronavirus disease 2019 (COVID-19) risk factors, including obesity and diabetes, are associated with an abnormal basal metabolic rate (BMR). We aimed to evaluate whether BMR could impact the susceptibility to or severity of COVID-19. We performed genetic correlation and Mendelian randomization (MR) analyses to assess genetic correlations and potential causal associations between BMR (n = 448,348) and three COVID-19 outcomes: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19 hospitalization, and critical COVID-19 (n = 1,086,211-2,597,856).

In-silico investigation of systematic missense mutations of middle east respiratory coronavirus spike protein.

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe pneumonia-like symptoms and is still pose a significant threat to global public health. A key component in the virulence of MERS-CoV is the Spike (S) protein, which binds with the host membrane receptor dipeptidyl peptidase 4 (DPP4). The goal of the present investigation is to examine the effects of missense mutations in the MERS-CoV S protein on protein stability and binding affinity with DPP4 to provide insight that is useful in developing vaccines to prevent coronavirus infection.

Persistent EGFR/K-RAS/SIAH pathway activation drives chemo-resistance and early tumor relapse in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. It disproportionately affects BRCA mutation carriers and young women, especially African American (AA) women. Chemoresistant TNBC is a heterogeneous and molecularly unstable disease that challenges our ability to apply personalized therapies.

Altered asymmetries of resting-state MRI in the left thalamus of first-episode schizophrenia.

Background: Schizophrenia (SCZ) is a complex psychiatric disorder associated with widespread alterations in the subcortical brain structure. Hemispheric asymmetries are a fundamental organizational principle of the human brain and relate to human psychological and behavioral characteristics. We aimed to explore the state of thalamic lateralization of SCZ.

Inflammation and immunity connect hypertension with adverse COVID-19 outcomes.

To explore the connection of hypertension and severe COVID-19 outcomes. A total of 68 observational studies recording mortality and/or general severity of COVID-19 were pooled for meta-analyses of the relationship of severe COVID-19 outcomes with hypertension as well as systolic and diastolic blood pressure. Genome-wide cross-trait meta-analysis (GWCTM) was performed to explore the genes linking between hypertension and COVID-19 severity.

A high-resolution flux-matrix model describes the spread of diseases in a spatial network and the effect of mitigation strategies.

Propagation of an epidemic across a spatial network of communities is described by a variant of the SIR model accompanied by an intercommunity infectivity matrix. This matrix is estimated from fluxes between communities, obtained from cell-phone tracking data recorded in the USA between March 2020 and February 2021. We apply this model to the SARS-CoV-2 pandemic by fitting just one global parameter representing the frequency of interaction between individuals.

Genetically manipulating endogenous Kras levels and oncogenic mutations in vivo influences tissue patterning of murine tumorigenesis.

Despite multiple possible oncogenic mutations in the proto-oncogene , unique subsets of these mutations are detected in different cancer types. As mutations occur early, if not being the initiating event, these mutational biases are ostensibly a product of how normal cells respond to the encoded oncoprotein. Oncogenic mutations can impact not only the level of active oncoprotein, but also engagement with proteins.

Analysis of neuroendocrine clones in NSCLCs using an immuno-guided laser-capture microdissection-based approach.

Clonal evolution and lineage plasticity are key contributors to tumor heterogeneity and response to treatment in cancer. However, capturing signal transduction events in coexisting clones remains challenging from a technical perspective. In this study, we developed and tested a signal-transduction-based workflow to isolate and profile coexisting clones within a complex cellular system like non-small cell lung cancers (NSCLCs).

Causal effect of COVID-19 on Alzheimer's disease: A Mendelian randomization study.

It was reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may cause brain size reduction and cognitive decline. Whether COVID-19 may contribute to the development of Alzheimer's disease (AD) is not known. We conducted genetic correlation and Mendelian randomization (MR) analyses to assess genetic relationships and potential causal associations between AD and three COVID-19 outcomes (SARS-CoV-2 infection, COVID-19 hospitalization, and critical COVID-19) by utilizing genome-wide association study datasets on these traits.

Severe COVID-19 increases the risk of schizophrenia.

The coronavirus SARS-CoV-2 invades the central nervous system, impacting the mental health of COVID-19 patients. We performed a two-sample Mendelian randomization analysis to assess the potential causal effects of COVID-19 on schizophrenia. Our analysis indicated that genetic liability to hospitalized COVID-19 was associated with an increased risk for schizophrenia (OR: 1.

Bidirectional causal associations between type 2 diabetes and COVID-19.

Observational studies have reported high comorbidity between type 2 diabetes (T2D) and severe COVID-19. However, the causality between T2D and COVID-19 has yet to be validated. We performed genetic correlation and Mendelian randomization (MR) analyses to assess genetic relationships and potential causal associations between T2D and three COVID-19 outcomes (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection, COVID-19 hospitalization, and critical COVID-19).

Data Size and Quality Matter: Generating Physically-Realistic Distance Maps of Protein Tertiary Structures.

With the debut of AlphaFold2, we now can get a highly-accurate view of a reasonable equilibrium tertiary structure of a protein molecule. Yet, a single-structure view is insufficient and does not account for the high structural plasticity of protein molecules. Obtaining a multi-structure view of a protein molecule continues to be an outstanding challenge in computational structural biology.