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Flavan-based phytoconstituents inhibit Mpro, a SARS-COV-2 molecular target, .

J Biomol Struct Dyn 2021 Aug 4:1-15. Epub 2021 Aug 4.

Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan.

A well-validated approach can provide promising drug candidates for the treatment of the ongoing CoVID19 pandemic. In this study, we have screened 32 phytochemical constituents (PCCs) with Mpro binding site (PDB:6W63) based on which we identified three possible candidates that are likely to be effective against CoVID19-viz., licoleafol (binding energy: -8. Read More

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Secondary organic aerosols produced from photochemical oxidation of secondarily evaporated biomass burning organic gases: Chemical composition, toxicity, optical properties, and climate effect.

Environ Int 2021 Jul 30;157:106801. Epub 2021 Jul 30.

Department of Earth and Planetary Sciences, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address:

Biomass burning (BB) is an important source of primary organic aerosols (POA). These POA contain a significant fraction of semivolatile organic compounds, and can release them into the gas phase during the dilution process in transport. Such evaporated compounds were termed "secondarily evaporated BB organic gases (SBB-OGs)" to distinguish them from the more studied primary emissions. Read More

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Mammalian acetate-dependent acetyl CoA synthetase 2 contains multiple protein destabilization and masking elements.

J Biol Chem 2021 Jul 31:101037. Epub 2021 Jul 31.

Department of Medicine, Columbia University Medical Center, New York, New York, United States of America; Department of Research, James J. Peters VA Medical Center, New York, New York, United States of America. Electronic address:

Besides contributing to anabolism, cellular metabolites serve as substrates or co-factors for enzymes and may also have signaling functions. Given these roles, multiple control mechanisms likely ensure fidelity of metabolite-generating enzymes. Acetate-dependent acetyl CoA synthetases (ACS) are de novo sources of acetyl CoA, a building block for fatty acids and a substrate for acetyltransferases. Read More

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Doublecortin-like expressing astrocytes of the suprachiasmatic nucleus are implicated in the biosynthesis of vasopressin and influences circadian rhythms.

Glia 2021 Aug 3. Epub 2021 Aug 3.

Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands.

We have recently identified a novel plasticity protein, doublecortin-like (DCL), that is specifically expressed in the shell of the mouse suprachiasmatic nucleus (SCN). DCL is implicated in neuroplastic events, such as neurogenesis, that require structural rearrangements of the microtubule cytoskeleton, enabling dynamic movements of cell bodies and dendrites. We have inspected DCL expression in the SCN by confocal microscopy and found that DCL is expressed in GABA transporter-3 (GAT3)-positive astrocytes that envelope arginine vasopressin (AVP)-expressing cells. Read More

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Impact of natural selection on global patterns of genetic variation, and association with clinical phenotypes, at genes involved in SARS-CoV-2 infection.

Res Sq 2021 Jul 27. Epub 2021 Jul 27.

We investigated global patterns of genetic variation and signatures of natural selection at host genes relevant to SARS-CoV-2 infection ( , and ). We analyzed novel data from 2,012 ethnically diverse Africans and 15,997 individuals of European and African ancestry with electronic health records, and integrated with global data from the 1000GP. At , we identified 41 non-synonymous variants that were rare in most populations, several of which impact protein function. Read More

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Tumor elastography and its association with cell-free tumor DNA in the plasma of breast tumor patients: a pilot study.

Quant Imaging Med Surg 2021 Aug;11(8):3518-3534

Shenzhen Key Laboratory of Viral Oncology, Center for Clinical Research and Innovation (CCRI), Shenzhen Hospital, Southern Medical University, Shenzhen, China.

Background: Breast tumor stiffness, which can be objectively and noninvasively evaluated by ultrasound elastography (UE), has been useful for the differentiation of benign and malignant breast lesions and the prediction of clinical outcomes. Liquid biopsy analyses, including cell-free tumor DNA (ctDNA), exhibit great potential for personalized treatment. This study aimed to investigate the correlations between the UE and ctDNA for early breast cancer diagnosis. Read More

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Pathway-Specific Defects in T, B, and NK Cells and Age-Dependent Development of High IgE in Mice Heterozygous for a CADINS-Associated Dominant Negative CARD11 Allele.

J Immunol 2021 Aug 2. Epub 2021 Aug 2.

Department of Biological Chemistry and Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD

CARD11 is a multidomain scaffold protein required for normal activation of NF-κB, JNK, and mTOR during Ag receptor signaling. Germline CARD11 mutations cause at least three types of primary immunodeficiency including CARD11 deficiency, B cell expansion with NF-κB and T cell anergy (BENTA), and CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS). CADINS is uniquely caused by heterozygous loss-of-function CARD11 alleles that act as dominant negatives. Read More

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Footprint of greenhouse forcing in daily temperature variability.

Proc Natl Acad Sci U S A 2021 Aug;118(32)

Research Department of Complexity Science, Potsdam Institute for Climate Impact Research, 14473 Potsdam, Germany;

Changes in mean climatic conditions will affect natural and societal systems profoundly under continued anthropogenic global warming. Changes in the high-frequency variability of temperature exert additional pressures, yet the effect of greenhouse forcing thereon has not been fully assessed or identified in observational data. Here, we show that the intramonthly variability of daily surface temperature changes with distinct global patterns as greenhouse gas concentrations rise. Read More

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A systemic approach to explore the mechanisms of drug resistance and altered signaling cascades in extensively drug-resistant tuberculosis.

Adv Protein Chem Struct Biol 2021 24;127:343-364. Epub 2021 Mar 24.

School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India. Electronic address:

Background And Aim: The persistence of extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (MTB) continue to pose a significant challenge to the treatment and control of tuberculosis infections worldwide. XDR-MTB strains exhibit resistance against first-line anti-TB drugs, fluoroquinolones, and second-line injectable drugs. The mechanisms of drug resistance of MTB remains poorly understood. Read More

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Discovery of the Pseudomonas Polyyne Protegencin by a Phylogeny-Guided Study of Polyyne Biosynthetic Gene Cluster Diversity.

mBio 2021 Aug 3:e0071521. Epub 2021 Aug 3.

Microbiomes, Microbes and Informatics Group, Organisms and Environment Division, School of Biosciences, Cardiff Universitygrid.5600.3, Cardiff, United Kingdom.

Natural products that possess alkyne or polyyne moieties have been isolated from a variety of biological sources and possess a broad a range of bioactivities. In bacteria, the basic biosynthesis of polyynes is known, but their biosynthetic gene cluster (BGC) distribution and evolutionary relationship to alkyne biosynthesis have not been addressed. Through comprehensive genomic and phylogenetic analyses, the distribution of alkyne biosynthesis gene cassettes throughout bacteria was explored, revealing evidence of multiple horizontal gene transfer events. Read More

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Oxidative deamination of lysine residues by polyphenols generates an equilibrium of aldehyde and 2-piperidinol products.

J Biol Chem 2021 Jul 30:101035. Epub 2021 Jul 30.

Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan; Japan Agency for Medical Research and Development, CREST, Tokyo, Japan. Electronic address:

Polyphenols, especially catechol-type polyphenols, exhibit lysyl oxidase-like activity and mediate oxidative deamination of lysine residues in proteins. Previous studies have shown that polyphenol-mediated oxidative deamination of lysine residues can be associated with altered electrical properties of proteins and increased cross-reactivity with natural IgM antibodies. This interaction suggested that oxidized proteins could act as innate antigens and elicit an innate immune response. Read More

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The Autotransporter Adhesin Ata Recognizes Host Glycans as High-Affinity Receptors.

ACS Infect Dis 2021 Aug 2. Epub 2021 Aug 2.

Institute for Glycomics, Griffith University, Gold Coast, Queensland 4215, Australia.

is a significant opportunistic pathogen responsible for infections of the lung, blood, skin, urinary tract, and soft tissues, with some strains exhibiting almost complete resistance to commonly used antibiotics. This multidrug resistance, together with a dearth of new antibiotic development, mean novel methods of treatment and prevention are urgently needed. Although many factors required to colonize the host have been identified, little is known about the specific host molecules recognized by these factors. Read More

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Transcript pattern analysis of Arf-family genes in the phytopathogen Fusarium oxysporum f. sp. lycopersici reveals the role of Arl3 in the virulence.

Antonie Van Leeuwenhoek 2021 Aug 2. Epub 2021 Aug 2.

Laboratorio de Diferenciación Celular, Instituto de Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Ciudad Universitaria, 58038, Morelia, Michoacán, Mexico.

Fusarium oxysporum f. sp. lycopersici is an important plant pathogen that has been used to understand the virulence mechanisms that soil inhabiting fungi exhibit during the infection process. Read More

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Exploring the Clinical Characteristics of COVID-19 Clusters Identified Using Factor Analysis of Mixed Data-Based Cluster Analysis.

Front Med (Lausanne) 2021 16;8:644724. Epub 2021 Jul 16.

Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.

The COVID-19 outbreak has brought great challenges to healthcare resources around the world. Patients with COVID-19 exhibit a broad spectrum of clinical characteristics. In this study, the Factor Analysis of Mixed Data (FAMD)-based cluster analysis was applied to demographic information, laboratory indicators at the time of admission, and symptoms presented before admission. Read More

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Transcriptome Responses of Ripe Cherry Tomato Fruit Exposed to Chilling and Rewarming Identify Reversible and Irreversible Gene Expression Changes.

Front Plant Sci 2021 16;12:685416. Epub 2021 Jul 16.

The New Zealand Institute for Plant & Food Research Limited, Food Industry Science Centre, Palmerston North, New Zealand.

Tomato fruit stored below 12°C lose quality and can develop chilling injury upon subsequent transfer to a shelf temperature of 20°C. The more severe symptoms of altered fruit softening, uneven ripening and susceptibility to rots can cause postharvest losses. We compared the effects of exposure to mild (10°C) and severe chilling (4°C) on the fruit quality and transcriptome of 'Angelle', a cherry-type tomato, harvested at the red ripe stage. Read More

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Association between Stroke Quality Assessments and Mortality within 30 Days among Patients Who Underwent Hemorrhagic Stroke Surgeries in South Korea.

Cerebrovasc Dis 2021 Jul 30:1-10. Epub 2021 Jul 30.

Institute of Health Services Research, Yonsei University, Seoul, Republic of Korea.

Introduction: In South Korea, to improve the quality of medical services provided to stroke patients, stroke quality assessments have been implemented since 2006. To further promote improvement of care, financial incentives were introduced since 2012. This study aims to examine the association between stroke quality assessments and mortality within 30 days among South Korean adults who underwent hemorrhagic stroke surgeries to provide evidence of the importance of such assessments. Read More

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Aurora kinase A (AURKA) promotes the progression and imatinib resistance of advanced gastrointestinal stromal tumors.

Cancer Cell Int 2021 Jul 31;21(1):407. Epub 2021 Jul 31.

Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jiefang Road, Hangzhou, Zhejiang, People's Republic of China.

Background: Gastrointestinal stromal tumor (GIST) is a common tumor that originates from the alimentary system mesenchyme. Compared to typical gastrointestinal carcinomas, GISTs exhibit unique malignant behaviors. Bioinformatic tools and subsequent experiments were applied to investigate novel targets involved in GIST progression and imatinib resistance. Read More

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Peripheral Levels of C-reactive protein, tumor necrosis factor-α, interleukin-6, and interleukin-1β across the mood spectrum in bipolar disorder: a meta-analysis of mean differences and variability.

Brain Behav Immun 2021 Jul 28. Epub 2021 Jul 28.

Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, 75 Pigdon's Road, Waurn Ponds, Geelong, VIC, 3216, Australia. Electronic address:

Importance: It is unclear whether differences exist in the magnitude and variability of pro-inflammatory mediators in the different phases of bipolar disorder (BD) and among subjects with BD, as compared to healthy controls.

Objective: To run a comparative meta-analysis of C-Reactive Protein (CRP), IL-1, IL-6, TNF-α in BD vs healthy controls, measuring mean and variability effects on all subjects. Sensitivity analyses include disease activity. Read More

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Modulators of Immunoregulatory Exonucleases PLD3 and PLD4 Identified by High-Throughput Screen.

Bioorg Med Chem Lett 2021 Jul 28:128293. Epub 2021 Jul 28.

Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, United States. Electronic address:

PLD3 and PLD4 have recently been revealed to be endosomal exonucleases that regulate the innate immune response by digesting the ligands of nucleic acid sensors. These enzymes can suppress RNA and DNA innate immune sensors like toll-like receptor 9, and PLD4-deficent mice exhibit inflammatory disease. Targeting these immunoregulatory enzymes presents an opportunity to indirectly regulate innate immune nucleic acid sensors that could yield immunotherapies, adjuvants, and nucleic acid drug stabilizers. Read More

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Micro-structural investigations on oppositely charged mixed surfactant gels with potential dermal applications.

Sci Rep 2021 Jul 30;11(1):15527. Epub 2021 Jul 30.

Department of Chemistry, Vidyasagar University, Midnapore, 721102, West Bengal, India.

Dicarboxylic amino acid-based surfactants (N-dodecyl derivatives of -aminomalonate, -aspartate, and -glutamate) in combination with hexadecyltrimethylammonium bromide (HTAB) form a variety of aggregates. Composition and concentration-dependent mixtures exhibit liquid crystal, gel, precipitate, and clear isotropic phases. Liquid crystalline patterns, formed by surfactant mixtures, were identified by polarizing optical microscopy. Read More

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Brain-dead and coma patients exhibit different serum metabolic profiles: preliminary investigation of a novel diagnostic approach in neurocritical care.

Sci Rep 2021 Jul 30;11(1):15519. Epub 2021 Jul 30.

Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, Wroclaw University of Science and Technology, Norwida 4/6, 50-373, Wroclaw, Poland.

There is a clear difference between severe brain damage and brain death. However, in clinical practice, the differentiation of these states can be challenging. Currently, there are no laboratory tools that facilitate brain death diagnosis. Read More

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Characterisation of seizure induction methods in .

eNeuro 2021 Jul 30. Epub 2021 Jul 30.

Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, M13 9PL, UK

Epilepsy is one of the most common neurological disorders. Around one third of patients do not respond to current medications. This lack of treatment indicates a need for better understanding of the underlying mechanisms and, importantly, the identification of novel targets for drug manipulation. Read More

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iTRAQ-based proteomic analysis of sperm reveals candidate proteins that affect the quality of spermatozoa from boars on plateaus.

Proteome Sci 2021 Jul 30;19(1). Epub 2021 Jul 30.

College of Animal Science, Tibet Agricultural and Animal Husbandry University, Linzhi, Tibet, 860000, P.R. China.

Background: Tibetan pigs (TP) exhibit heritable adaptations to their hypoxic environments as a result of natural selection. However, candidate proteins that affect the sperm quality of boars on plateaus have not yet been clearly investigated.

Methods: In this study, to reveal the candidate proteins that affect the quality of spermatozoa of boars on plateaus, we analyzed the sperm quality using computer-assisted semen analysis (CASA) system and reactive oxygen species (ROS) levels. Read More

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The secreted tyrosine kinase VLK is essential for normal platelet activation and thrombus formation.

Blood 2021 Jul 30. Epub 2021 Jul 30.

Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States.

Tyrosine phosphorylation of extracellular proteins is observed in cell cultures and in vivo, but little is known about the functional roles of tyrosine phosphorylation of extracellular proteins. Vertebrate Lonesome Kinase (VLK) is a broadly expressed secretory pathway tyrosine kinase present in platelet ɑ-granules. It is released from platelets upon activation and phosphorylates substrates extracellularly. Read More

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Hollow porous molecularly imprinted polymers as emerging adsorbents.

Environ Pollut 2021 Jul 10;288:117775. Epub 2021 Jul 10.

Department of Chemistry, Punjabi University, Patiala, Punjab, 147002, India.

Hollow porous molecularly imprinted polymers (HPMIPs) are identified as promising adsorbents with many advantageous properties (e.g., large number of imprinted cavities, highly accessible binding sites, controllable pore structure, and fast mass transfer). Read More

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Role of ATP in the RNA Translocation Mechanism of SARS-CoV-2 NSP13 Helicase.

J Phys Chem B 2021 Jul 30. Epub 2021 Jul 30.

Department of Chemistry, Oklahoma State University, Stillwater, Oklahoma 74074, United States.

The COVID-19 pandemic has demonstrated the need to develop potent and transferable therapeutics to treat coronavirus infections. Numerous antiviral targets are being investigated, but nonstructural protein 13 (nsp13) stands out as a highly conserved and yet understudied target. Nsp13 is a superfamily 1 (SF1) helicase that translocates along and unwinds viral RNA in an ATP-dependent manner. Read More

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Care transitions and social needs: a Geriatric Emergency care Applied Research (GEAR) Network scoping review and consensus statement.

Acad Emerg Med 2021 Jul 30. Epub 2021 Jul 30.

Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT), Durham VA Health Care System, Durham, NC, USA.

Objectives: Individual-level social needs have been shown to substantially impact emergency department (ED) care transitions of older adults. The Geriatric Emergency care Applied Research (GEAR) Network aimed to identify care transition interventions, particularly addressing social needs, and prioritize future research questions.

Methods: GEAR engaged 49 interdisciplinary stakeholders, derived clinical questions, and conducted searches of electronic databases to identify ED discharge care transition interventions in older adult populations. Read More

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Individual physiological and mitochondrial responses during 12 weeks of intensified exercise.

Physiol Rep 2021 Aug;9(15):e14962

Institute for Health and Sport (iHeS), Victoria University, Melbourne, Australia.

Aim: Observed effects of exercise are highly variable between individuals, and subject-by-training interaction (i.e., individual response variability) is often not estimated. Read More

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PSGL-1 Is a T Cell Intrinsic Inhibitor That Regulates Effector and Memory Differentiation and Responses During Viral Infection.

Front Immunol 2021 13;12:677824. Epub 2021 Jul 13.

Infectious and Inflammatory Disease Center, NCI Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States.

Effective T cell differentiation during acute virus infections leads to the generation of effector T cells that mediate viral clearance, as well as memory T cells that confer protection against subsequent reinfection. While inhibitory immune checkpoints have been shown to promote T cell dysfunction during chronic virus infections and in tumors, their roles in fine tuning the differentiation and responses of effector and memory T cells are only just beginning to be appreciated. We previously identified PSGL-1 as a fundamental regulator of T cell exhaustion that sustains expression of several inhibitory receptors, including PD-1. Read More

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Structural and functional basis for pan-CoV fusion inhibitors against SARS-CoV-2 and its variants with preclinical evaluation.

Signal Transduct Target Ther 2021 07 29;6(1):288. Epub 2021 Jul 29.

Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences and Biosafety Level 3 Laboratory, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China.

The COVID-19 pandemic poses a global threat to public health and economy. The continuously emerging SARS-CoV-2 variants present a major challenge to the development of antiviral agents and vaccines. In this study, we identified that EK1 and cholesterol-coupled derivative of EK1, EK1C4, as pan-CoV fusion inhibitors, exhibit potent antiviral activity against SARS-CoV-2 infection in both lung- and intestine-derived cell lines (Calu-3 and Caco2, respectively). Read More

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