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Evidence for a credit-card-swipe mechanism in the human PC floppase ABCB4.

Structure 2021 Jun 1. Epub 2021 Jun 1.

Institute of Biochemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. Electronic address:

ABCB4 is described as an ATP-binding cassette (ABC) transporter that primarily transports lipids of the phosphatidylcholine (PC) family but is also capable of translocating a subset of typical multidrug-resistance-associated drugs. The high degree of amino acid identity of 76% for ABCB4 and ABCB1, which is a prototype multidrug-resistance-mediating protein, results in ABCB4's second subset of substrates, which overlap with ABCB1's substrates. This often leads to incomplete annotations of ABCB4, in which it was described as exclusively PC-lipid specific. Read More

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Identification of the predominant human NK cell effector subset mediating ADCC against HIV-infected targets coated with BNAbs or plasma from PLWH.

Eur J Immunol 2021 Jun 4. Epub 2021 Jun 4.

The Wistar Institute, HIV Immunopathogenesis Laboratory, Philadelphia, PA, 19104, USA.

The potential of immunotherapy strategies utilizing BNAbs such as 3BNC117 and 10-1074 to limit viral replication while also facilitating clearance of HIV infected cells has heightened interest in identifying the predominant NK effector subset(s) capable of mediating Antibody Dependent Cellular Cytotoxicity (ADCC). Utilizing Advanced Poly-chromatic Flow Cytometry, we identified that CD57 positive NK cells from ART-suppressed PLWH expressed significantly higher levels of the CD16 FcγR Receptor, 2B4 ADCC co-receptor and HLA-DR activation marker while NKG2C positive NK cells expressed significantly higher levels of the CD2 ADCC co-receptor (p<0.001, n = 32). Read More

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Insights into Emergence of Antibiotic Resistance in Acid-Adapted Enterohaemorrhagic .

Antibiotics (Basel) 2021 May 2;10(5). Epub 2021 May 2.

School of Life Sciences, Anhui Agricultural University, Hefei 230036, China.

The emergence of multidrug-resistant pathogens presents a global challenge for treating and preventing disease spread through zoonotic transmission. The water and foodborne Enterohaemorrhagic (EHEC) are capable of causing intestinal and systemic diseases. The root cause of the emergence of these strains is their metabolic adaptation to environmental stressors, especially acidic pH. Read More

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RAD51AP1 mediates RAD51 activity through nucleosome interaction.

J Biol Chem 2021 May 28:100844. Epub 2021 May 28.

Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado 80523. Electronic address:

RAD51 Associated Protein 1 (RAD51AP1) is a key protein in the homologous recombination (HR) DNA repair pathway. Loss of RAD51AP1 leads to defective HR, genome instability, and telomere erosion. RAD51AP1 physically interacts with the RAD51 recombinase and promotes RAD51-mediated capture of donor DNA, synaptic complex assembly, and displacement-loop formation when tested with nucleosome-free DNA substrates. Read More

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ACE4, a novel transcriptional activator involved in the regulation of cellulase genes on cellulose in .

Appl Environ Microbiol 2021 May 28:AEM0059321. Epub 2021 May 28.

The State Key Laboratory of Bioreactor Engineering, New World Institute of Biotechnology, East China University of Science and Technology, Shanghai, China.

The filamentous fungus is a model strain for cellulase production. Cellulase gene expression in is controlled by multiple transcription factors. Here, we identified by comparative genomic screening a novel transcriptional activator ACE4 (ctivator of ellulase xpression 4) that positively regulates cellulase gene expression on cellulose in . Read More

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Plexin-A4 mediates amyloid-β-induced tau pathology in Alzheimer's disease animal model.

Prog Neurobiol 2021 May 15:102075. Epub 2021 May 15.

Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea; SNU Dementia Research Center, Seoul National University College of Medicine, Seoul 03080, South Korea. Electronic address:

Amyloid-β (Aβ) and tau are major pathological hallmarks of Alzheimer's disease (AD). Several studies have revealed that Aβ accelerates pathological tau transition and spreading during the disease progression, and that reducing tau can mitigate pathological features of AD. However, molecular links between Aβ and tau pathologies remain elusive. Read More

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Bullshit Ability as an Honest Signal of Intelligence.

Evol Psychol 2021 Apr-Jun;19(2):14747049211000317

Department of Psychology, 8430University of Waterloo, Ontario, Canada.

Navigating social systems efficiently is critical to our species. Humans appear endowed with a cognitive system that has formed to meet the unique challenges that emerge for highly social species. Bullshitting, communication characterised by an intent to be convincing or impressive without concern for truth, is ubiquitous within human societies. Read More

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Trained Innate Immunity in Hematopoietic Stem Cell and Solid Organ Transplantation.

Transplantation 2021 Feb 8. Epub 2021 Feb 8.

1 Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland.

While significant progress has been made to improve short-term survival of transplant patients, long-term acceptance of allografts in solid organ and hematopoietic stem cell (HSC) transplantation is still a significant challenge. Current therapeutics for preventing or treating allograft rejection rely on potent immunosuppressive drugs that primarily target T cells of the adaptive immune response. Promising advances in transplant immunology have highlighted the importance of innate immune responses in allograft acceptance and rejection. Read More

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February 2021

Molecular cloning of duck CD40 and its immune function research.

Poult Sci 2021 Jun 11;100(6):101100. Epub 2021 Mar 11.

Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Wenjiang 611130, People's Republic of China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Wenjiang 611130, People's Republic of China.

Cosignal molecules are cell surface molecules that transduce signals to other cells to modulate immune response positively (costimulate) or negatively (cosuppress). Costimulatory signals are key factors in determining whether T/B cells are capable of responding to specific antigens and ultimately mediating an appropriate immune response. In this study, the cDNA sequence containing the complete coding frame of the costimulatory molecule duck CD40 gene was cloned and reported for the first time, and its mediated antiviral innate immune was verified in vitro. Read More

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Instantaneous movement-unrelated midbrain activity modifies ongoing eye movements.

Elife 2021 May 6;10. Epub 2021 May 6.

Werner Reichardt Centre for Integrative Neuroscience, Tübingen University, Tübingen, Germany.

At any moment in time, new information is sampled from the environment and interacts with ongoing brain state. Often, such interaction takes place within individual circuits that are capable of both mediating the internally ongoing plan as well as representing exogenous sensory events. Here, we investigated how sensory-driven neural activity can be integrated, very often in the same neuron types, into ongoing saccade motor commands. Read More

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Exploring the role of finance, natural resources, and governance on the environment and economic growth in South Asian countries.

Environ Sci Pollut Res Int 2021 May 6. Epub 2021 May 6.

Southwestern University of Finance and Economics, Chengdu, China.

We studied the influence of finance, natural resources, and governance on environmental degradation and economic growth for seven countries of the South Asian Association for Regional Cooperation (SAARC) using the latest panel data over 1996-2018. Panel cointegration tests and the long-run algorithms capable of addressing endogeneity and cross-sectional dependence have been applied to analyze the variables' linkages. To explore the short-run causalities, we further utilized a panel heterogeneous causality test. Read More

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Analysis of Binding Modes of Antigen-Antibody Complexes by Molecular Mechanics Calculation.

J Chem Inf Model 2021 May 3;61(5):2396-2406. Epub 2021 May 3.

Graduate School of Pharmaceutical Sciences, Chiba UniversityRINGGOLD, Inohana 1-8-1, Chuo-ku, Chiba 260-8675, Japan.

Antibodies are one of the most important protein molecules in biopharmaceutics. Due to the recent advance in technology for producing monoclonal antibodies, many structural data are available on the antigen-antibody complexes. To characterize the molecular interaction in antigen-antibody recognition, we computationally analyzed 500 complex structures by molecular mechanics calculations. Read More

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Molecular Mechanisms of Apoptosis Induction and Its Regulation by Fatty Acids in Pancreatic β-Cells.

Int J Mol Sci 2021 Apr 20;22(8). Epub 2021 Apr 20.

Department of Biochemistry, Cell and Molecular Biology & Center for Research of Diabetes, Metabolism and Nutrition, Third Faculty of Medicine, Charles University, Ruská 87, 100 00 Prague, Czech Republic.

Pancreatic β-cell failure and death contribute significantly to the pathogenesis of type 2 diabetes. One of the main factors responsible for β-cell dysfunction and subsequent cell death is chronic exposure to increased concentrations of FAs (fatty acids). The effect of FAs seems to depend particularly on the degree of their saturation. Read More

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Brockarchaeota, a novel archaeal phylum with unique and versatile carbon cycling pathways.

Nat Commun 2021 04 23;12(1):2404. Epub 2021 Apr 23.

Department of Marine Science, University of Texas Austin, Port Aransas, TX, 78373, USA.

Geothermal environments, such as hot springs and hydrothermal vents, are hotspots for carbon cycling and contain many poorly described microbial taxa. Here, we reconstructed 15 archaeal metagenome-assembled genomes (MAGs) from terrestrial hot spring sediments in China and deep-sea hydrothermal vent sediments in Guaymas Basin, Gulf of California. Phylogenetic analyses of these MAGs indicate that they form a distinct group within the TACK superphylum, and thus we propose their classification as a new phylum, 'Brockarchaeota', named after Thomas Brock for his seminal research in hot springs. Read More

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Markers of Polyfunctional SARS-CoV-2 Antibodies in Convalescent Plasma.

mBio 2021 04 20;12(2). Epub 2021 Apr 20.

Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, New Hampshire, USA

Convalescent plasma is a promising therapy for coronavirus disease 2019 (COVID-19), but the antibody characteristics that contribute to efficacy remain poorly understood. This study analyzed plasma samples from 126 eligible convalescent blood donors in addition to 15 naive individuals, as well as an additional 20 convalescent individuals as a validation cohort. Multiplexed Fc Array binding assays and functional antibody response assays were utilized to evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody composition and activity. Read More

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Extracellular vesicles for tissue repair and regeneration: evidence, challenges and opportunities.

Adv Drug Deliv Rev 2021 Apr 16. Epub 2021 Apr 16.

Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Department of Materials, Imperial College London, London, UK; Department of Bioengineering, Imperial College London, London, UK; Institute of Biomedical Engineering, Imperial College London, London, UK. Electronic address:

Extracellular vesicles (EVs) are biological nanoparticles naturally secreted by cells, acting as delivery vehicles for molecular messages. During the last decade, EVs have been assigned multiple functions that have established their potential as therapeutic mediators for a variety of diseases and conditions. In this review paper, we report on the potential of EVs in tissue repair and regeneration. Read More

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Hybrid Amyloid-Based Redox Hydrogel for Bioelectrocatalytic H Oxidation.

Angew Chem Int Ed Engl 2021 Apr 19. Epub 2021 Apr 19.

Univ. Grenoble Alpes, CNRS, CEA, IRIG, Laboratoire de Chimie et Biologie des Métaux, 38000, Grenoble, France.

An artificial amyloid-based redox hydrogel was designed for mediating electron transfer between a [NiFeSe] hydrogenase and an electrode. Starting from a mutated prion-forming domain of fungal protein HET-s, a hybrid redox protein containing a single benzyl methyl viologen moiety was synthesized. This protein was able to self-assemble into structurally homogenous nanofibrils. Read More

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Advancing peptide siRNA-carrier designs through L/D-amino acid stereochemical modifications to enhance gene silencing.

Mol Ther Nucleic Acids 2021 Jun 19;24:462-476. Epub 2021 Mar 19.

Department of Oral Health Sciences, James B. Edwards College of Dental Medicine, Medical University of South Carolina (MUSC), Charleston, SC 29425, USA.

The 599 peptide has been previously shown to effectively deliver small interfering RNAs (siRNAs) to cancer cells, inducing targeted-oncogene silencing, with a consequent inhibition of tumor growth. Although effective, this study was undertaken to advance the 599 peptide siRNA-carrier design through L/D-amino acid stereochemical modifications. Consequently, 599 was modified to generate eight different peptide variants, incorporating either different stereochemical patterns of L/D-amino acids or a specific D-amino acid substitution. Read More

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β2 Integrin Regulation of Neutrophil Functional Plasticity and Fate in the Resolution of Inflammation.

Front Immunol 2021 30;12:660760. Epub 2021 Mar 30.

Department of Pathology and Cell Biology, University of Montreal, Montreal, QC, Canada.

Neutrophils act as the first line of cellular defense against invading pathogens or tissue injury. Their rapid recruitment into inflamed tissues is critical for the elimination of invading microorganisms and tissue repair, but is also capable of inflicting damage to neighboring tissues. The β integrins and Mac-1 (CD11b/CD18, αβ or complement receptor 3) in particular, are best known for mediating neutrophil adhesion and transmigration across the endothelium and phagocytosis of microbes. Read More

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State-Dependent Regulation of Cortical Processing Speed via Gain Modulation.

J Neurosci 2021 May 15;41(18):3988-4005. Epub 2021 Apr 15.

Department of Biology and Institute of Neuroscience

To thrive in dynamic environments, animals must be capable of rapidly and flexibly adapting behavioral responses to a changing context and internal state. Examples of behavioral flexibility include faster stimulus responses when attentive and slower responses when distracted. Contextual or state-dependent modulations may occur early in the cortical hierarchy and may be implemented via top-down projections from corticocortical or neuromodulatory pathways. Read More

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Discovery of novel pyrimidine molecules containing boronic acid as VCP/p97 Inhibitors.

Bioorg Med Chem 2021 May 23;38:116114. Epub 2021 Mar 23.

College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Nanjing 210037, PR China. Electronic address:

Valine-containing protein (VCP) is a member of the adenosine triphosphate family involved in a variety of cellular activities. VCP/p97 is capable of maintaining protein homeostasis and mediating the degradation of misfolded polypeptides by the ubiquitin-proteasome system (UPS). In this manuscript, a series of novel p97 inhibitors with pyrimidine as core structure were designed, synthesized and biologically evaluated. Read More

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ApoA1 Neutralizes Proinflammatory Effects of Dengue Virus NS1 Protein and Modulates Viral Immune Evasion.

J Virol 2021 Jun 10;95(13):e0197420. Epub 2021 Jun 10.

Laboratório de Biotecnologia e Bioengenharia Estrutural, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.

Dengue is a mosquito-borne infectious disease that is highly endemic in tropical and subtropical countries. Symptomatic patients can rapidly progress to severe conditions of hemorrhage, plasma extravasation, and hypovolemic shock, which leads to death. The blood tests of patients with severe dengue typically reveal low levels of high-density lipoprotein (HDL), which is responsible for reverse cholesterol transport (RCT) and regulation of the lipid composition in peripheral tissues. Read More

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Emergence of aac(6')-Ie-aph(2'')-Ia-positive enterococci with non-high-level gentamicin resistance mediated by IS1216V: adaptation to decreased aminoglycoside usage in Taiwan.

J Antimicrob Chemother 2021 Apr 2. Epub 2021 Apr 2.

Department of Microbiology and Immunology, College of Medicine, Kaohsiung Medical University, Taiwan.

Objectives: To explore the mechanisms mediating the different levels of gentamicin resistance in enterococci.

Methods: Susceptibility testing with gentamicin and PCR of resistance determinants were performed in 149 enterococcal isolates. Genetic relatedness was characterized by MLST and PFGE analysis. Read More

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Genetic Neuropathy Due to Impairments in Mitochondrial Dynamics.

Biology (Basel) 2021 Mar 26;10(4). Epub 2021 Mar 26.

Departments of Medical Genetics and Biochemistry & Molecular Biology, Cumming School of Medicine, Alberta Children's Hospital Research Institute, Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.

Mitochondria are dynamic organelles capable of fusing, dividing, and moving about the cell. These properties are especially important in neurons, which in addition to high energy demand, have unique morphological properties with long axons. Notably, mitochondrial dysfunction causes a variety of neurological disorders including peripheral neuropathy, which is linked to impaired mitochondrial dynamics. Read More

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The Psychological Responses of Nurses Caring for COVID-19 Patients: A Q Methodological Approach.

Int J Environ Res Public Health 2021 03 31;18(7). Epub 2021 Mar 31.

Institute of Health Science, College of Nursing, Gyeongsang National University, Jinju 52727, Korea.

Anxiety among nurses attending patients at the forefront of the global coronavirus disease-19 (COVID-19) pandemic is on the rise. Accordingly, examining the psychological response of nurses who have attended COVID-19 patients is necessary. This study aimed to categorize and characterize the psychological responses of nurses who have experienced COVID-19 patient care based on the Q methodology. Read More

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Subunits of the PBAP Chromatin Remodeler Are Capable of Mediating Enhancer-Driven Transcription in .

Int J Mol Sci 2021 Mar 11;22(6). Epub 2021 Mar 11.

Department of Biology, Università di Napoli Federico II, 80138 Naples, Italy.

The chromatin remodeler SWI/SNF is an important participant in gene activation, functioning predominantly by opening the chromatin structure on promoters and enhancers. Here, we describe its novel mode of action in which SWI/SNF factors mediate the targeted action of an enhancer. We studied the functions of two signature subunits of PBAP subfamily, BAP170 and SAYP, in . Read More

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Blockade of tumor necrosis factor superfamily members CD30 and OX40 abrogates disease activity in murine immune-mediated glomerulonephritis.

Kidney Int 2021 Mar 27. Epub 2021 Mar 27.

Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. Electronic address:

Co-stimulation is a prerequisite for pathogenic activity in T cell-mediated diseases and has been demonstrated to achieve tolerance in organ-specific autoimmunity as a therapeutic target. Here, we evaluated the involvement of the tumor necrosis factor family members CD30 and OX40 in immune-complex mediated kidney disease. In vitro stimulation and proliferation studies were performed with CD4 cells from wild type and CD30/OX40 double knock-out (CD30OX40) mice. Read More

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Reactive oxygen species formation in thiols solution mediated by pyrogenic carbon under aerobic conditions.

J Hazard Mater 2021 08 22;415:125726. Epub 2021 Mar 22.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, PR China. Electronic address:

Previous studies have demonstrated that pyrogenic carbon can mediate the reductive degradation of pollutants in solutions containing reducing reagents under anaerobic conditions. However, few studies have investigated oxidative species formation and pollutants transformation directly mediated by pyrogenic carbon under aerobic conditions. In this study, we found that activated carbon (AC) can not only mediate reductive hexachloroethane degradation in the absence of O but also mediate the oxidation of As(III) and sulfanilamide in L-Cysteine (Cys, a naturally abundant thiol compound) solution under aerobic conditions. Read More

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Long non-coding RNAs in the doxorubicin resistance of cancer cells.

Cancer Lett 2021 Jun 22;508:104-114. Epub 2021 Mar 22.

Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea; KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address:

Chemotherapy is the main treatment used for cancer patients failing surgery. Doxorubicin (DOX) is a well-known chemotherapeutic agent capable of suppressing proliferation in cancer cells and triggering apoptosis via inhibiting topoisomerase II activity and producing DNA breaks. This activity of DOX restrains mitosis and cell cycle progression. Read More

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Cross-kingdom inhibition of bacterial virulence and communication by probiotic yeast metabolites.

Microbiome 2021 03 24;9(1):70. Epub 2021 Mar 24.

Department of Chemistry, Ben-Gurion University of the Negev, 84105, Be'er Sheva, Israel.

Background: Probiotic milk-fermented microorganism mixtures (e.g., yogurt, kefir) are perceived as contributing to human health, and possibly capable of protecting against bacterial infections. Read More

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