A5021017639- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Genetic diversity and population structure
- Fish Ecology and Management Studies
- Bioinformatics and Genomic Networks
- Physiological and biochemical adaptations
- Genomics and Phylogenetic Studies
- Suicide and Self-Harm Studies
- Mitochondrial Function and Pathology
- Long-Term Effects of COVID-19
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Atherosclerosis and Cardiovascular Diseases
- Adipose Tissue and Metabolism
- Genetic and phenotypic traits in livestock
- Environmental DNA in Biodiversity Studies
- Evolution and Genetic Dynamics
- Health disparities and outcomes
- Identification and Quantification in Food
- Bacteriophages and microbial interactions
- Cholesterol and Lipid Metabolism
- Autism Spectrum Disorder Research
- Insect-Plant Interactions and Control
- Plant Virus Research Studies
- Mental Health Research Topics
- Venous Thromboembolism Diagnosis and Management
Oak Ridge National Laboratory
2020-2024
Predictive Biology (United States)
2022-2024
University of Hawaiʻi at Mānoa
2024
University of Hawaii System
2024
Predictive Science (United States)
2023
University of North Carolina at Charlotte
2023
National Energy Technology Laboratory
2020-2022
AstraZeneca (United Kingdom)
2022
University of Washington
1994-2022
AstraZeneca (United States)
2020
The ABC1 transporter was identified as the defect in Tangier disease by a combined strategy of gene expression microarray analysis, genetic mapping, and biochemical studies. Patients with have cellular cholesterol removal, which results near zero plasma levels HDL massive tissue deposition cholesteryl esters. Blocking or activity reduces apolipoprotein-mediated lipid efflux from cultured cells, increasing enhances it. is induced loading cAMP treatment reduced upon subsequent removal...
Lipid-poor high density lipoprotein apolipoproteins remove cholesterol and phospholipids from cells by an active secretory pathway controlled ABC transporter called ABCA1. This is induced cAMP analogs in a cell-specific manner. Here we provide evidence that increased plasma membrane ABCA1 accounts for the enhanced apolipoprotein-mediated lipid secretion macrophages analogs. Treatment of RAW264 with 8-bromo-cAMP caused parallel increases apoA-I-mediated efflux, mRNA protein levels,...
Neither the disease mechanism nor treatments for COVID-19 are currently known. Here, we present a novel molecular that provides therapeutic intervention points can be addressed with existing FDA-approved pharmaceuticals. The entry point virus is ACE2, which component of counteracting hypotensive axis RAS. Bradykinin potent part vasopressor system induces hypotension and vasodilation degraded by ACE enhanced angiotensin1-9 produced ACE2. perform new analysis on gene expression data from cells...
How an atherosclerotic plaque evolves from minimal diffuse intimal hyperplasia to a critical lesion is not well understood. Cellular proliferation relatively infrequent and modest event in both primary restenotic coronary atherectomy specimens, leading us believe that other processes, such as the formation of extracellular matrix, cell migration, neovascularization, calcification might be more important for formation. The investigation proteins are overexpressed compared with normal vessel...
Extensive fibrin deposition in the lungs and altered levels of circulating blood coagulation proteins COVID-19 patients imply local derangement pathways that limit formation and/or promote its clearance. We examined transcriptional profiles bronchoalveolar lavage fluid (BALF) samples to identify molecular mechanisms underlying these coagulopathies. mRNA for regulators kallikrein–kinin (C1-inhibitor), (thrombomodulin, endothelial protein C receptor), fibrinolytic (urokinase urokinase...
Skin is composed of diverse cell populations that cooperatively maintain homeostasis. Up-regulation the nuclear factor κB (NF-κB) pathway may lead to development chronic inflammatory disorders skin, but its role during early events remains unclear. Through analysis single-cell RNA sequencing data via iterative random forest leave one out prediction, an explainable artificial intelligence method, we identified immunoregulatory for a unique paired related homeobox-1 (Prx1) + fibroblast...
The mechanism of oxidative phosphorylation is well understood, but evolution the proteins involved not. We combined phylogenetic, genomic, and structural biology analyses to examine twelve mitochondrial encoded closely related, yet phenotypically diverse, Pacific salmon. Two separate identified same seven positively selected sites in ND5. A strong signal was also detected at three ND2. An energetic coupling analysis revealed several structures ND5 protein that may have co-evolved with sites....
Variation in mitochondrial DNA is often assumed to be neutral and used construct the genealogical relationships among populations species. However, if extant variation result of episodes positive selection, these genealogies may incorrect, although this information itself provide biologically evolutionary meaningful information. In fact, Darwinian selection has been detected mitochondrial-encoded subunits that comprise complex I from diverse taxa with seemingly dissimilar bioenergetic life...
Abstract Background A mechanistic understanding of the spread SARS-CoV-2 and diligent tracking ongoing mutagenesis are key importance to plan robust strategies for confining its transmission. Large numbers available sequences their dates transmission provide an unprecedented opportunity analyze evolutionary adaptation in novel ways. Addition high-resolution structural information can reveal functional basis these processes at molecular level. Integrated systems biology-directed analyses data...
In addition to its essential role in viral polyprotein processing, the SARS-CoV-2 3C-like protease (3CLpro) can cleave human immune signaling proteins, like NF-κB Essential Modulator (NEMO) and deregulate host response. Here, vitro assays show that 3CLpro cleaves NEMO with fine-tuned efficiency. Analysis of 2.50 Å resolution crystal structure C145S bound
Identification of proteins dysregulated by COVID-19 infection is critically important for better understanding its pathophysiology, building prognostic models, and identifying new targets. Plasma proteomic profiling 4,301 was performed in two independent datasets tested the association three outcomes (infection, ventilation, death). We identified 1,449 consistently associated both with any these outcomes. subsequently created highly accurate models that distinctively predict infection,...
Abstract We present an ensemble transfer learning method to predict suicide from Veterans Affairs (VA) electronic medical records (EMR). A diverse set of base models was trained a binary outcome constructed reported suicide, attempt, and overdose diagnoses with varying choices study design prediction methodology. Each model used twenty cross-sectional 190 longitudinal variables observed in eight time intervals covering 7.5 years prior the prediction. Ensembles seven were created fine-tuned...
Abstract Transforming growth factor–β (TGF-β) plays an important role in vascular lesion formation and possibly the renarrowing process (“restenosis”) that occurs after balloon angioplasty. Secreted a latent form by most cells, TGF-β requires enzymatic conversion before it is biologically active. TGF-β–inducible gene h3 (βig-h3) novel molecule induced when cells are treated with TGF-β1. This study examined expression of βig-h3 normal diseased human tissue. To determine pattern arteries,...
Organisms can adapt to local environmental conditions as a plastic response or become adapted through natural selection on genetic variation. The ability increased water temperatures will be of paramount importance for many fish species the climate continues warm and resources limited. Because reduce dissolved oxygen available fish, we hypothesized that adaptation low environments would involve improved respiration oxidative phosphorylation (OXPHOS). To test this hypothesis, subjected...
Here we determine the sex-specific influence of mtDNA type (mitotype) and diet on mitochondrial functions physiology in two Drosophila melanogaster lines. In many species, males females differ aspects their energy production. These influences may be caused by differences evolutionary history physiological functions. We predicted mutations should stronger than as a result organelle's maternal mode inheritance majority metazoans. contrast, would greater due to higher metabolic flexibility....
Abstract Despite SARS-CoV and SARS-CoV-2 being equipped with highly similar protein arsenals, the corresponding zoonoses have spread among humans at extremely different rates. The specific characteristics of these viruses that led to such distinct outcomes remain unclear. Here, we apply proteome-wide comparative structural analysis aiming identify unique molecular elements in proteome may explain differing consequences. By combining modeling dynamics simulations, suggest nonconservative...
The heritability of autism spectrum disorder (ASD), based on 680,000 families and five countries, is estimated to be nearly 80%, yet reported from SNP-based studies are consistently lower, few significant loci have been identified with genome-wide association studies. This gap in genomic information may reside rare variants, interaction among variants (epistasis), or cryptic structural variation (SV) provide mechanisms that underlie ASD. Here we use a method identify potential SVs...
Abstract While it has been proposed in several taxa that the mitochondrial genome is associated with adaptive evolution to different climatic conditions, making links between haplotypes and organismal phenotypes remains a challenge. Mitonuclear discordance occurs small brown planthopper (SBPH), Laodelphax striatellus, one haplogroup (HGI) more common cold climate region of China relative another form (HGII) despite strong nuclear gene flow, providing promising model investigate adaptation...