Kinetics and Optimality of Influenza A Virus Locomotion.

Influenza A viruses (IAVs) must navigate through a dense extracellular mucus to infect airway epithelial cells. The mucous layer, composed of glycosylated biopolymers (mucins), presents sialic acid that binds to ligands on the viral envelope and can be irreversibly cleaved by viral enzymes. It was recently discovered that filamentous IAVs exhibit directed persistent motion along their long axis on sialic acid-coated surfaces.

Topology-based protein classification: A deep learning approach.

Utilizing Artificial Intelligence (AI) in computational biology techniques could offer significant advantages in alleviating the growing workloads faced by structural biologists, especially with the emergence of big data. In this study, we employed Delaunay tessellation as a promising method to obtain the overall structural topology of proteins. Subsequently, we developed multi-class deep neural network models to classify protein superfamilies based on their local topology.

nsP2 Protease Inhibitor Blocks the Replication of New World Alphaviruses and Offer Protection in Mice.

New World alphaviruses, including Venezuelan equine encephalitis virus (VEEV), eastern equine encephalitis virus (EEEV), and western equine encephalitis virus (WEEV), are mosquito-transmitted viruses that cause disease in humans. These viruses are endemic to the western hemisphere, and disease in humans may lead to encephalitis and long-term neurological sequelae. There are currently no FDA-approved vaccines or antiviral therapeutics available for the prevention or treatment of diseases caused by these viruses.

Phenome-wide investigation of bidirectional causal relationships between major depressive disorder and common human diseases.

The high comorbidity of major depressive disorder (MDD) with other diseases has been well-documented. However, the pairwise causal connections for MDD comorbid networks are poorly characterized. We performed Phenome-wide Mendelian randomization (MR) analyses to explore bidirectional causal associations between MDD (N = 807,553) and 877 common diseases from FinnGen datasets (N = 377,277).

Proteomics in Acute Heart Transplant Rejection, On Behalf of the GRAfT Investigators.

Background: Proteomic phenotyping can provide insights into rejection pathophysiology, novel biomarkers, and therapeutic targets.

Methods: Within the prospective, multicenter Genomic Research Alliance for Transplantation study, 181 proteins were evaluated from blood drawn at the time of endomyocardial biopsy; protein fold change, logistic regression, and pathway analyses were conducted, with protein discovery adjusted for a 5% false discovery rate.

Results: Among 104 adult heart transplant patients (31% female sex, 53% Black race, median age 52 y), 74 had no rejection, 18 developed acute cellular rejection (ACR), and 12 developed antibody-mediated rejection (AMR).

Gut microbiome's causal role in head and neck cancer: findings from mendelian randomization.

Introduction: The gut microbiome (GM) has been implicated in cancer pathogenesis and treatment, including head and neck cancers (HNC). However, the specific microbial compositions influencing HNC and the underlying mechanisms remain largely unknown.

Methods: This study utilized published genome-wide association studies (GWAS) summary data-based two-sample Mendelian randomization (MR) to uncover the GM compositions that exert significant causal effects on HNC.

Host-Driven Ubiquitination Events in Vector-Transmitted RNA Virus Infections as Options for Broad-Spectrum Therapeutic Intervention Strategies.

Many vector-borne viruses are re-emerging as public health threats, yet our understanding of the virus-host interactions critical for productive infection remains limited. The ubiquitination of proteins, including host- and pathogen-derived proteins is a highly prominent and consistent post-translational modification that regulates protein function through signaling and degradation. Viral proteins are documented to hijack the host ubiquitination machinery to modulate multiple host processes including antiviral defense mechanisms.

Using a Failing Human Ventricular Cardiomyocyte Model to Re-Evaluate Ca Cycling, Voltage Dependence, and Spark Characteristics.

Previous studies have observed alterations in excitation-contraction (EC) coupling during end-stage heart failure that include action potential and calcium (Ca) transient prolongation and a reduction of the Ca transient amplitude. Underlying these phenomena are the downregulation of potassium (K) currents, downregulation of the sarcoplasmic reticulum Ca ATPase (SERCA), increase Ca sensitivity of the ryanodine receptor, and the upregulation of the sodium-calcium (Na-Ca) exchanger. However, in human heart failure (HF), debate continues about the relative contributions of the changes in calcium handling vs.

Gain-of-Function and Loss-of-Function Mutations in the RyR2-Expressing Gene Are Responsible for the CPVT1-Related Arrhythmogenic Activities in the Heart.

Mutations in the ryanodine receptor (RyR2) gene have been linked to arrhythmia and possibly sudden cardiac death (SCD) during acute emotional stress, physical activities, or catecholamine perfusion. The most prevalent disorder is catecholaminergic polymorphic ventricular tachycardia (CPVT1). Four primary mechanisms have been proposed to describe CPVT1 with a RyR2 mutation: (a) gain-of-function, (b) destabilization of binding proteins, (c) store-overload-induced Ca release (SOICR), and (d) loss of function.

Novel Insights Into the Causal Effects and Shared Genetics Between Body Fat and Parkinson Disease.

Aims: Existing observational studies examining the effect of body fat on the risk of Parkinson disease (PD) have yielded inconsistent results. We aimed to investigate this causal relationship at the genetic level.

Methods: We employed two-sample Mendelian randomization (TSMR) to investigate the causal effects of body fat on PD, with multiple sex-specific body fat measures being involved.

Mendelian randomization analysis of causal and druggable circulating inflammatory proteins in schizophrenia.

Background: Schizophrenia (SZ) is a severe mental disorder with complex origins. Observational studies suggested that inflammatory factors may play a role in the pathophysiology of SZ and we aim to investigate the potential genetic connection between them by examining the causal impact of circulating inflammatory proteins on SZ.

Methods: We utilized Mendelian randomization (MR) analysis to assess the causal relationship between circulating inflammatory proteins and SZ and the GWAS summary datasets were sourced from public databases.

Construction and validation of a mouse model for studying severe human adenovirus infections.

Human adenoviruses (HAdVs) are highly contagious pathogens with various genotypes implicated in acute respiratory disease (ARD) and linked to fatality, especially in immunosuppressed patients, young children, and military recruits. Currently, no vaccines or specific drugs are approved for clinical use. The hosts of adenoviruses are strictly species-specific, which strongly limits the development of vaccines and drugs against HAdVs.

Charting the neuroscience of interpersonal trust: A bibliographic literature review.

Interpersonal trust is essential for societal well-being, underpinning relationships from individuals to institutions. Neuroscience research on trust has advanced swiftly since 2001. While quantitative reviews, meta-analyses, and theoretical frameworks have effectively synthesized trust neuroscience research, bibliometric analysis remains underutilized.

The causal relationship between immune cell traits and schizophrenia: a Mendelian randomization analysis.

Introduction: The complex and unresolved pathogenesis of schizophrenia has posed significant challenges to its diagnosis and treatment. While recent research has established a clear association between immune function and schizophrenia, the causal relationship between the two remains elusive.

Methods: We employed a bidirectional two-sample Mendelian randomization approach to investigate the causal relationship between schizophrenia and 731 immune cell traits by utilizing public GWAS data.

Antidepressants account for the causal effect of major depressive disorder on type 2 diabetes.

Background: Patients with major depressive disorder (MDD) face an elevated risk of type 2 diabetes (T2D). However, the contribution of the disease itself versus the side effects of antidepressants to this increased risk remains unclear.

Objective: This study aimed to investigate the overall and independent effects of MDD and exposure to antidepressants on T2D risk.

Binding of Inhibitors to Nuclear Localization Signal Peptide from Venezuelan Equine Encephalitis Virus Capsid Protein Explored with All-Atom Replica Exchange Molecular Dynamics.

Several small molecule inhibitors have been designed to block binding of the Venezuelan equine encephalitis virus (VEEV) nuclear localization signal (NLS) sequence to the importin-α nuclear transport protein. To probe the inhibition mechanism on a molecular level, we used all-atom explicit water replica exchange molecular dynamics to study the binding of two inhibitors, I1 and I2, to the coreNLS peptide, representing the core fragment of the VEEV NLS sequence. Our objective was to evaluate the possibility of masking wherein binding of these inhibitors to the coreNLS occurs prior to its binding to importin-α.

A Benzimidazole-Based N-Heterocyclic Carbene Derivative Exhibits Potent Antiproliferative and Apoptotic Effects against Colorectal Cancer.

: Colorectal cancer (CRC) remains a major global health issue. Although chemotherapy is the first-line treatment, its effectiveness is limited due to drug resistance developed in CRC. To overcome resistance and improve the prognosis of CRC patients, investigating new therapeutic approaches is necessary.

Investigating the impact of clinical and genetic factors on the post-surgery prognosis of sinonasal squamous cell carcinoma.

Sinonasal squamous cell carcinoma (SNSCC) is an aggressive cancer affecting the nasal and sinus regions, with its progression factors, particularly genetic ones, not yet fully understood. Here, we first conducted a retrospective study with 219 SNSCC patients to identify clinical factors affecting SNSCC prognosis. Additionally, we mined a vast literature dataset to uncover genetic factors associated with SNSCC progression.

Proteomic analysis of dorsal root ganglia in a mouse model of paclitaxel-induced neuropathic pain.

Paclitaxel is a chemotherapy drug widely used for the treatment of various cancers based on its ability to potently stabilize cellular microtubules and block division in cancer cells. Paclitaxel-based treatment, however, accumulates in peripheral system sensory neurons and leads to a high incidence rate (over 50%) of chemotherapy induced peripheral neuropathy in patients. Using an established preclinical model of paclitaxel-induced peripheral neuropathy (PIPN), we examined proteomic changes in dorsal root ganglia (DRG) of adult male mice that were treated with paclitaxel (8 mg/kg, at 4 injections every other day) relative to vehicle-treated mice.

Boolean Modeling of Biological Network Applied to Protein-Protein Interaction Network of Autism Patients.

Cellular molecules interact with one another in a structured manner, defining a regulatory network topology that describes cellular mechanisms. Genetic mutations alter these networks' pathways, generating complex disorders such as autism spectrum disorder (ASD). Boolean models have assisted in understanding biological system dynamics since Kauffman's 1969 discovery, and various analytical tools for regulatory networks have been developed.