Investigating the Bromoform Membrane Interactions Using Atomistic Simulations and Machine Learning: Implications for Climate Change Mitigation.

Methane emissions from livestock contribute to global warming. Seaweeds used as food additive offer a promising emission mitigation strategy because seaweeds are enriched in bromoform─a methanogenesis inhibitor. Therefore, understanding bromoform storage and production in seaweeds and particularly in a cell-like environment is crucial.

Examining hydrogen peroxide-containing organelles in seaweeds.

Seaweeds, particularly the red seaweed , produce and sequester bromomethanes, which are known for mitigating methane emissions in ruminants when used as a feed supplement. Bromomethane synthesis requires hydrogen peroxide (H O ). We developed a staining assay utilizing 3,3'-diaminobenzidine (DAB) for identifying H O in three groups of seaweeds (red, brown, and green), including intensely pigmented species.

ML-enhanced peroxisome capacity enables compartmentalization of multienzyme pathway.

Repurposing an organelle for specialized metabolism provides an avenue for fermentable, unicellular organisms such as Saccharomyces cerevisiae to mimic compartmentalization of metabolic pathways within different plant tissues. Peroxisomes are attractive organelles for repurposing as they are not required for yeast viability when grown on glucose and can efficiently compartmentalize heterologous enzymes to enable physical separation of cytosolic native metabolism and peroxisomal engineered metabolism. However, when not required, peroxisomes are repressed, leading to low functional capacities for heterologous proteins.

A High-Throughput Method for Quantifying Fecundity.

The fruit fly, , is an experimentally tractable model system that has recently emerged as a powerful "new approach methodology" (NAM) for chemical safety testing. As oogenesis is well conserved at the molecular and cellular level, measurements of fecundity can be useful for identifying chemicals that affect reproductive health across species. However, standard fecundity assays have been difficult to perform in a high-throughput manner because experimental factors such as the physiological state of the flies and environmental cues must be carefully controlled to achieve consistent results.

A high-throughput method for quantifying fecundity.

Measurements of Drosophila fecundity are used in a wide variety of studies, such as investigations of stem cell biology, nutrition, behavior, and toxicology. In addition, because fecundity assays are performed on live flies, they are suitable for longitudinal studies such as investigations of aging or prolonged chemical exposure. However, standard Drosophila fecundity assays have been difficult to perform in a high-throughput manner because experimental factors such as the physiological state of the flies and environmental cues must be carefully controlled to achieve consistent results.

AI in cellular engineering and reprogramming.

During the last decade, artificial intelligence (AI) has increasingly been applied in biophysics and related fields, including cellular engineering and reprogramming, offering novel approaches to understand, manipulate, and control cellular function. The potential of AI lies in its ability to analyze complex datasets and generate predictive models. AI algorithms can process large amounts of data from single-cell genomics and multiomic technologies, allowing researchers to gain mechanistic insights into the control of cell identity and function.

A tradeoff between enterovirus A71 particle stability and cell entry.

A central role of viral capsids is to protect the viral genome from the harsh extracellular environment while facilitating initiation of infection when the virus encounters a target cell. Viruses are thought to have evolved an optimal equilibrium between particle stability and efficiency of cell entry. In this study, we genetically perturb this equilibrium in a non-enveloped virus, enterovirus A71 to determine its structural basis.

Harnessing the power of artificial intelligence to advance cell therapy.

Cell therapies are powerful technologies in which human cells are reprogrammed for therapeutic applications such as killing cancer cells or replacing defective cells. The technologies underlying cell therapies are increasing in effectiveness and complexity, making rational engineering of cell therapies more difficult. Creating the next generation of cell therapies will require improved experimental approaches and predictive models.

Decoding CAR T cell phenotype using combinatorial signaling motif libraries and machine learning.

Chimeric antigen receptor (CAR) costimulatory domains derived from native immune receptors steer the phenotypic output of therapeutic T cells. We constructed a library of CARs containing ~2300 synthetic costimulatory domains, built from combinations of 13 signaling motifs. These CARs promoted diverse human T cell fates, which were sensitive to motif combinations and configurations.

Predicting Epitope Candidates for SARS-CoV-2.

Epitopes are short amino acid sequences that define the antigen signature to which an antibody or T cell receptor binds. In light of the current pandemic, epitope analysis and prediction are paramount to improving serological testing and developing vaccines. In this paper, known epitope sequences from SARS-CoV, SARS-CoV-2, and other Coronaviridae were leveraged to identify additional antigen regions in 62K SARS-CoV-2 genomes.

A hydrophilic microenvironment in the substrate-translocating groove of the YidC membrane insertase is essential for enzyme function.

The YidC family of proteins are membrane insertases that catalyze the translocation of the periplasmic domain of membrane proteins via a hydrophilic groove located within the inner leaflet of the membrane. All homologs have a strictly conserved, positively charged residue in the center of this groove. In Bacillus subtilis, the positively charged residue has been proposed to be essential for interacting with negatively charged residues of the substrate, supporting a hypothesis that YidC catalyzes insertion via an early-step electrostatic attraction mechanism.

A defective viral genome strategy elicits broad protective immunity against respiratory viruses.

RNA viruses generate defective viral genomes (DVGs) that can interfere with replication of the parental wild-type virus. To examine their therapeutic potential, we created a DVG by deleting the capsid-coding region of poliovirus. Strikingly, intraperitoneal or intranasal administration of this genome, which we termed eTIP1, elicits an antiviral response, inhibits replication, and protects mice from several RNA viruses, including enteroviruses, influenza, and SARS-CoV-2.

Dissection of neuronal splicing and implications for neurodegeneration in X-linked dystonia-parkinsonism.

X-linked dystonia-parkinsonism (XDP) is a monogenic neurodegenerative disorder of the basal ganglia, which presents as a combination of hyperkinetic movements and parkinsonian features. The underlying genetic mechanism involves the insertion of a SINE-VNTR-Alu retrotransposon within the gene. Interestingly, alterations of have been involved in multiple neurological diseases.

AI-driven prediction of SARS-CoV-2 variant binding trends from atomistic simulations.

We present a novel technique to predict binding affinity trends between two molecules from atomistic molecular dynamics simulations. The technique uses a neural network algorithm applied to a series of images encoding the distance between two molecules in time. We demonstrate that our algorithm is capable of separating with high accuracy non-hydrophobic mutations with low binding affinity from those with high binding affinity.

Examining the interplay between face mask usage, asymptomatic transmission, and social distancing on the spread of COVID-19.

COVID-19's high virus transmission rates have caused a pandemic that is exacerbated by the high rates of asymptomatic and presymptomatic infections. These factors suggest that face masks and social distance could be paramount in containing the pandemic. We examined the efficacy of each measure and the combination of both measures using an agent-based model within a closed space that approximated real-life interactions.

Characterization of the Features of Water Inside the SecY Translocon.

Despite extended experimental and computational studies, the mechanism regulating membrane protein folding and stability in cell membranes is not fully understood. In this review, I will provide a personal and partial account of the scientific efforts undertaken by Dr. Stephen White to shed light on this topic.

Vaping Associated Pulmonary Nontuberculous Mycobacteria.

Introduction: E-cigarette or vaping product use associated lung injury (EVALI) has been an important health risk in both children and adults. The pathophysiology of EVALI is not well understood. However, it is speculated that certain substances such as Vitamin E Acetate (VEA), particularly in marijuana containing vape cartridges may result in lung injury and lead to respiratory dysfunction.

K channel C-type gating involves asymmetric selectivity filter order-disorder transitions.

K potassium channels regulate cellular excitability using their selectivity filter (C-type) gate. C-type gating mechanisms, best characterized in homotetrameric potassium channels, remain controversial and are attributed to selectivity filter pinching, dilation, or subtle structural changes. The extent to which such mechanisms control C-type gating of innately heterodimeric Ks is unknown.

Mapping Attenuation Determinants in Enterovirus-D68.

Enterovirus (EV)-D68 has been associated with epidemics in the United Sates in 2014, 2016 and 2018. This study aims to identify potential viral virulence determinants. We found that neonatal type I interferon receptor knockout mice are susceptible to EV-D68 infection via intraperitoneal inoculation and were able to recapitulate the paralysis process observed in human disease.

SU(3)_{1} Chiral Spin Liquid on the Square Lattice: A View from Symmetric Projected Entangled Pair States.

Quantum spin liquids can be faithfully represented and efficiently characterized within the framework of projected entangled pair states (PEPS). Guided by extensive exact diagonalization and density matrix renormalization group calculations, we construct an optimized symmetric PEPS for a SU(3)_{1} chiral spin liquid on the square lattice. Characteristic features are revealed by the entanglement spectrum (ES) on an infinitely long cylinder.

Comparison of Aortitis Versus Noninflammatory Aortic Aneurysms Among Patients Who Undergo Open Aortic Aneurysm Repair.

Objective: Distinguishing aortitis-induced aneurysms from noninflammatory aortic aneurysms is difficult and often incidentally diagnosed on histologic examination after surgical repair. This study was undertaken to examine surgically diagnosed aortitis and identify patient characteristics and imaging findings associated with the disease.

Methods: In this case-control study, cases had newly diagnosed, biopsy-proven noninfectious aortitis after open thoracic aortic aneurysm surgical repair.