On the rise of the new B.1.1.529 variant: Five dimensions of access to a COVID-19 vaccine.

Mass COVID-19 vaccination, as the last resort to bring society to a new normal, has been rapidly rolled out in the US. However, because of the lifting of international travel restrictions, amid the many uncertainties induced by the emerging B.1.

Ecological Approach to Understanding Superinfection Inhibition in Bacteriophage.

In microbial communities, viruses compete with each other for host cells to infect. As a consequence of competition for hosts, viruses evolve inhibitory mechanisms to suppress their competitors. One such mechanism is superinfection exclusion, in which a preexisting viral infection prevents a secondary infection.

Deterministic and stochastic modeling for PDGF-driven gliomas reveals a classification of gliomas.

Motivated by our study of infiltrating dynamics of immune cells into tumors, we propose a stochastic model in terms of Ito stochastic differential equations to study how two parameters, the chemoattractant production rate and the chemotactic coefficient, influence immune cell migration and how these parameters distinguish two types of gliomas. We conduct a detailed analysis of the stochastic model and its deterministic counterpart. The deterministic model can differentiate two types of gliomas according to the range of the chemoattractant production rate as two equilibrium solutions, while the stochastic model also can differentiate two types of gliomas according to the ranges of the chemoattractant production rate and chemotactic coefficient with thresholds as one non-zero ergodic invariant measure and one weak persistent state when the noise intensities are small.

Health inequities in COVID-19 vaccination among the elderly: Case of Connecticut.

Background: In the United States, distribution plans for the COVID-19 vaccination were established at the state level. However, some states, such as Connecticut, followed an age-based strategy without considering occupations or co-morbid conditions due to its simplicity in implementation. This strategy raised concerns about exacerbating health inequities because it did not prioritize vulnerable communities, specifically, minorities and low-income groups.

Reopening International Borders without Quarantine: Contact Tracing Integrated Policy against COVID-19.

With the COVID-19 vaccination widely implemented in most countries, propelled by the need to revive the tourism economy, there is a growing prospect for relieving the social distancing regulation and reopening borders in tourism-oriented countries and regions. This need incentivizes stakeholders to develop border control strategies that fully evaluate health risks if mandatory quarantines are lifted. In this study, we have employed a computational approach to investigate the contact tracing integrated policy in different border-reopening scenarios in Hong Kong, China.

Rhinovirus Reduces the Severity of Subsequent Respiratory Viral Infections by Interferon-Dependent and -Independent Mechanisms.

Coinfection by heterologous viruses in the respiratory tract is common and can alter disease severity compared to infection by individual virus strains. We previously found that inoculation of mice with rhinovirus (RV) 2 days before inoculation with a lethal dose of influenza A virus [A/Puerto Rico/8/34 (H1N1) (PR8)] provides complete protection against mortality. Here, we extended that finding to a second lethal respiratory virus, pneumonia virus of mice (PVM), and analyzed potential mechanisms of RV-induced protection.

Proinflammatory responses in SARS-CoV-2 infected and soluble spike glycoprotein S1 subunit activated human macrophages.

Critically ill COVID-19 patients infected with SARS-CoV-2 display signs of generalized hyperinflammation. Macrophages trigger inflammation to eliminate pathogens and repair tissue, but this process can also lead to hyperinflammation and resulting exaggerated disease. The role of macrophages in dysregulated inflammation during SARS-CoV-2 infection is poorly understood.

EfgA is a conserved formaldehyde sensor that leads to bacterial growth arrest in response to elevated formaldehyde.

Normal cellular processes give rise to toxic metabolites that cells must mitigate. Formaldehyde is a universal stressor and potent metabolic toxin that is generated in organisms from bacteria to humans. Methylotrophic bacteria such as Methylorubrum extorquens face an acute challenge due to their production of formaldehyde as an obligate central intermediate of single-carbon metabolism.

Targeting SUMOylation dependency in human cancer stem cells through a unique SAE2 motif revealed by chemical genomics.

Natural products (NPs) encompass a rich source of bioactive chemical entities. Here, we used human cancer stem cells (CSCs) in a chemical genomics campaign with NP chemical space to interrogate extracts from diverse strains of actinomycete for anti-cancer properties. We identified a compound (McM25044) capable of selectively inhibiting human CSC function versus normal stem cell counterparts.

MRI-based quantification of ophthalmic changes in healthy volunteers during acute 15° head-down tilt as an analogue to microgravity.

Spaceflight is known to cause ophthalmic changes in a condition known as spaceflight-associated neuro-ocular syndrome (SANS). It is hypothesized that SANS is caused by cephalad fluid shifts and potentially mild elevation of intracranial pressure (ICP) in microgravity. Head-down tilt (HDT) studies are a ground-based spaceflight analogue to create cephalad fluid shifts.

Genetic Context Significantly Influences the Maintenance and Evolution of Degenerate Pathways.

Understanding the evolution of novel physiological traits is highly relevant for expanding the characterization and manipulation of biological systems. Acquisition of new traits can be achieved through horizontal gene transfer (HGT). Here, we investigate drivers that promote or deter the maintenance of HGT-driven degeneracy, occurring when processes accomplish identical functions through nonidentical components.

Exploratory-Phase-Free Estimation of GP Hyperparameters in Sequential Design Methods-At the Example of Bayesian Inverse Problems.

Methods for sequential design of computer experiments typically consist of two phases. In the first phase, the exploratory phase, a space-filling initial design is used to estimate hyperparameters of a Gaussian process emulator (GPE) and to provide some initial global exploration of the model function. In the second phase, more design points are added one by one to improve the GPE and to solve the actual problem at hand (e.

Implementing and Assessing an Alchemical Method for Calculating Protein-Protein Binding Free Energy.

Protein-protein binding is fundamental to most biological processes. It is important to be able to use computation to accurately estimate the change in protein-protein binding free energy due to mutations in order to answer biological questions that would be experimentally challenging, laborious, or time-consuming. Although nonrigorous free-energy methods are faster, rigorous alchemical molecular dynamics-based methods are considerably more accurate and are becoming more feasible with the advancement of computer hardware and molecular simulation software.

Global Transcriptional Response of to Formaldehyde Stress Expands the Role of EfgA and Is Distinct from Antibiotic Translational Inhibition.

The potency and indiscriminate nature of formaldehyde reactivity upon biological molecules make it a universal stressor. However, some organisms such as possess means to rapidly and effectively mitigate formaldehyde-induced damage. EfgA is a recently identified formaldehyde sensor predicted to halt translation in response to elevated formaldehyde as a means to protect cells.

Cross-Feeding of a Toxic Metabolite in a Synthetic Lignocellulose-Degrading Microbial Community.

The recalcitrance of complex organic polymers such as lignocellulose is one of the major obstacles to sustainable energy production from plant biomass, and the generation of toxic intermediates can negatively impact the efficiency of microbial lignocellulose degradation. Here, we describe the development of a model microbial consortium for studying lignocellulose degradation, with the specific goal of mitigating the production of the toxin formaldehyde during the breakdown of methoxylated aromatic compounds. Included are , a lignin degrader; , a cellulose degrader; and sometimes , an oleaginous yeast.

Implementation of adaptive integration method for free energy calculations in molecular systems.

Estimating free energy differences by computer simulation is useful for a wide variety of applications such as virtual screening for drug design and for understanding how amino acid mutations modify protein interactions. However, calculating free energy differences remains challenging and often requires extensive trial and error and very long simulation times in order to achieve converged results. Here, we present an implementation of the adaptive integration method (AIM).

Assessment of software methods for estimating protein-protein relative binding affinities.

A growing number of computational tools have been developed to accurately and rapidly predict the impact of amino acid mutations on protein-protein relative binding affinities. Such tools have many applications, for example, designing new drugs and studying evolutionary mechanisms. In the search for accuracy, many of these methods employ expensive yet rigorous molecular dynamics simulations.

A Systematic Review and Meta-Analysis on the Longitudinal Effects of Unilateral Knee Extension Exercise on Muscle Strength.

The aim of the study was to investigate the time-dependent increase in the knee extensors' isometric strength as a response to voluntary, unilateral, isometric knee extension exercise (UIKEE). To do so, a systematic review was carried out to obtain data for a Bayesian longitudinal model-based meta-analysis (BLMBMA). For the systematic review, PubMed, Web of Science, SCOPUS, Chochrane Library were used as databases.

Quorum sensing provides a molecular mechanism for evolution to tune and maintain investment in cooperation.

As selection frequently favors noncooperating defectors in mixed populations with cooperators, mechanisms that promote cooperation stability clearly exist. One potential mechanism is bacterial cell-to-cell communication, quorum sensing (QS), which can allow cooperators to prevent invasion by defectors. However, the impact of QS on widespread maintenance of cooperation in well-mixed conditions has not been experimentally demonstrated over extended evolutionary timescales.

DHFR and DHPS Mutations Are Associated With HIV-1 Co-Infection and a Novel DHPS Mutation I504T Is Identified in Western Kenya.

Antifolate resistance is significant in Kenya and presumed to result from extensive use and cross-resistance between antifolate antimalarials and antibiotics, including cotrimoxazole/Bactrim used for HIV-1 chemotherapy. However, little is known about antifolate-resistant malaria in the context of newly diagnosed HIV-1 co-infection prior to administration of HIV-1 chemotherapy. Blood samples from a cross-sectional study of asymptomatic adult Kenyans enrolled during voluntary HIV testing were analyzed by PCR for spp.

On the quantum origin of few response properties.

In modern physics, the entanglement between quantum states is a well-established phenomenon. Going one step forward, one can conjecture the likely existence of an entanglement between excitations of one-particle quantum states. Working with a density matrix that is well defined within the polarization propagator formalism, together with information theory, we found that the quantum origin of, at least, few molecular response properties can be described by the entanglement between two pairs of virtual excitations of molecular orbitals (MOs).