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Structural insights into the mechanisms and pharmacology of K potassium channels.

J Mol Biol 2021 Apr 19:166995. Epub 2021 Apr 19.

Cardiovascular Research Institute; Departments of Biochemistry and Biophysics, and Cellular and Molecular Pharmacology; California Institute for Quantitative Biomedical Research; Kavli Institute for Fundamental Neuroscience University of California, San Francisco, California 93858-2330 USA; Molecular Biophysics and Integrated Bio-imaging Division Lawrence Berkeley National Laboratory, Berkeley, CA 94720 USA. Electronic address:

Leak currents, defined as voltage and time independent flows of ions across cell membranes, are central to cellular electrical excitability control. The K (KCNK) potassium channel class comprises an ion channel family that produces potassium leak currents that oppose excitation and stabilize the resting membrane potential in cells in the brain, cardiovascular system, immune system, and sensory organs. Due to their widespread tissue distribution, Ks contribute to many physiological and pathophysiological processes including anesthesia, pain, arrythmias, ischemia, hypertension, migraine, intraocular pressure regulation, and lung injury responses. Read More

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Potent Toxic Effects of Taroxaz-104 on the Replication of SARS-CoV-2 Particles.

Authors:
Amgad M Rabie

Chem Biol Interact 2021 Apr 19:109480. Epub 2021 Apr 19.

Dr. Amgad Rabie's Research Lab. for Drug Discovery (DARLD), Mansoura, Egypt; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt. Electronic address:

Polyphenolics and 1,3,4-oxadiazoles are two of the most potent bioactive classes of compounds in medicinal chemistry, since both are known for their diverse pharmacological activities in humans. One of their prominent activities is the antimicrobial/antiviral activities, which are much apparent when the key functional structural moieties of both of them meet into the same compounds. The current COVID-19 pandemic motivated us to computationally screen and evaluate our library of previously-synthesized 2-(3,4,5-trihydroxyphenyl)-1,3,4-oxadiazoles against the major SARS-CoV-2 protein targets. Read More

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Comparative analysis of Student's live online learning readiness during the coronavirus (COVID-19) pandemic in the higher education sector.

Comput Educ 2021 Jul 8;168:104211. Epub 2021 Apr 8.

Department of Supply Chain and Information Management, The Hang Seng University of Hong Kong, Siu Lek Yuen, N.T, Hong Kong.

Amid the coronavirus outbreak, many countries are facing a dramatic situation in terms of the global economy and human social activities, including education. The shutdown of schools is affecting many students around the world, with face-to-face classes suspended. Many countries facing the disastrous situation imposed class suspension at an early stage of the coronavirus outbreak, and Asia was one of the earliest regions to implement live online learning. Read More

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Gain and loss of antibiotic resistant genes in multidrug resistant bacteria: One Health perspective.

J Microbiol 2021 Apr 20. Epub 2021 Apr 20.

Laboratory of Molecular Environmental Microbiology, Department of Environmental Science and Ecological Engineering, Korea University, Seoul, 02841, Republic of Korea.

The emergence of multidrug resistance (MDR) has become a global health threat due to the increasing unnecessary use of antibiotics. Multidrug resistant bacteria occur mainly by accumulating resistance genes on mobile genetic elements (MGEs), made possible by horizontal gene transfer (HGT). Humans and animal guts along with natural and engineered environments such as wastewater treatment plants and manured soils have proven to be the major reservoirs and hot-spots of spreading antibiotic resistance genes (ARGs). Read More

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Lewis acidic zinc(II) salen-type Schiff-base complexes: sensing properties and responsive nanostructures.

Authors:
Santo Di Bella

Dalton Trans 2021 Apr 20. Epub 2021 Apr 20.

Dipartimento di Scienze Chimiche, Università di Catania, I-95125 Catania, Italy.

In this frontier article some peculiar characteristics of Zn(salen)-type Schiff-base complexes are reviewed. The paper is mainly focused on the most recent and relevant achievements on responsive supramolecular nanostructures and sensing properties, both of them related to the Lewis acidic character of the ZnII centre in these molecular species, providing an interpretation of these features. The sensing properties of Zn(salen)-type complexes mainly originate from optical spectroscopic changes associated with the formation of the adducts upon addition of a Lewis base (analyte), either by deaggregation of dimeric species or displacement of the solvent coordinated to the metal centre. Read More

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Secondary metabolites in plant defence mechanisms.

New Phytol 1994 Aug;127(4):617-633

Biochemistry & Physiology Department, AFRC Institute of Arable Crops Research, Rothamsted Experimental Station, Harpenden, Herts AL5 2JQ, UK.

Many secondary metabolites found in plants have a role in defence against herbivores, pests and pathogens. In this review, a few examples are described and discussed, and some of the problems in determining the precise role(s) of such metabolites highlighted. The role of secondary metabolites in defence may involve deterrence/anti-feedant activity, toxicity or acting as precursors to physical defence systems. Read More

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Seasonal changes in the pigments of Norway spruce, Picea abies (L.) Karst, and the influence of summer ozone exposures.

New Phytol 1991 Oct;119(2):251-259

Institute of Environmental and Biological Sciences, Lancaster University, Lancaster LAI 4YQ, UK.

There are always significant pigment changes in Norway spruce [Picea abies (L.) Karst.] needles with time in different year classes, even through the winter, but no significant changes in current year needles occur either during summer exposure due to ozone (70 nl i ) or in the winter following. Read More

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October 1991

Factors deciding the assembly and thermostability of the DmrB cage.

Int J Biol Macromol 2021 Apr 16. Epub 2021 Apr 16.

Chemical Biology Unit, Institute of Nano Science and Technology, Habitat Centre, Sector-81, Knowledge City, Mohali (SAS Nagar), Punjab 140306, India. Electronic address:

Dihydromethanopterin reductase (DmrB), is a naturally occurring cage protein found in various archaeal and a few bacterial species. It exists as 24mer with cubic geometry where 8 trimeric subunits are present at the corners of each cube. Each trimer is made up of three monomeric units and six FMN, where two molecules of FMN are present at the interface of each monomer. Read More

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Systematic comparison and prediction of the effects of missense mutations on protein-DNA and protein-RNA interactions.

PLoS Comput Biol 2021 Apr 19;17(4):e1008951. Epub 2021 Apr 19.

Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan, P. R. China.

The binding affinities of protein-nucleic acid interactions could be altered due to missense mutations occurring in DNA- or RNA-binding proteins, therefore resulting in various diseases. Unfortunately, a systematic comparison and prediction of the effects of mutations on protein-DNA and protein-RNA interactions (these two mutation classes are termed MPDs and MPRs, respectively) is still lacking. Here, we demonstrated that these two classes of mutations could generate similar or different tendencies for binding free energy changes in terms of the properties of mutated residues. Read More

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Use of Chronic Prescription Medications and Prevalence of Polypharmacy in Survivors of Childhood Cancer.

Front Oncol 2021 1;11:642544. Epub 2021 Apr 1.

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.

Background: As survivors of childhood cancer age, development of cancer treatment-related chronic health conditions often occur. This study aimed to describe the pattern of chronic prescription medication use and identify factors associated with polypharmacy among survivors of childhood cancer.

Methods: This was a retrospective study conducted at the pediatric oncology long-term follow-up clinic in Hong Kong. Read More

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Drug interactions and risks associated with the use of triptans, ditans and monoclonal antibodies in migraine.

Curr Opin Neurol 2021 Apr 12. Epub 2021 Apr 12.

Department of Internal Medicine, Division of Pharmacology and Vascular Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

Purpose Of Review: The aim of this study was to review current evidence concerning potential risks and interactions associated with concomitant use of drugs indicated for the abortive treatment of migraine, namely triptans and ditans, and more recently developed drugs used for the preventive treatment. The latter drug class encompasses monoclonal antibodies (mAbs), which target either calcitonin gene-related peptide (CGRP) or its receptor.

Recent Findings: To date, no pharmacokinetic interactions between these drug classes have been reported. Read More

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Bridging the digital divide with data-free platforms: Online survey reaching families with young children during the COVID-19 pandemic.

JMIR Pediatr Parent 2021 Apr 12. Epub 2021 Apr 12.

DSI-NRF Centre for Excellence in Human Development, University of the Witwatersrand, Office 154, First Floor, East Wing, Wits School of Public Health Education Campus27 St Andrews Road, Parktown, Johannesburg, ZA.

Background: The COVID-19 pandemic and containment measures have severely affected families around the world. It is frequently assumed that digital technologies can supplement and perhaps even replace services for families. This is challenging in conditions of high device and data costs as well as poor internet provision and access, raising concerns about widening inequalities in availability of support and consequent effects on child and family outcomes. Read More

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Synaptic AP2 CCV life cycle regulation by the Eps15, ITSN1, Sgip1/AP2, synaptojanin1 interactome.

Sci Rep 2021 Apr 13;11(1):8007. Epub 2021 Apr 13.

Department of Cellular Biochemistry, University Medical Center, Georg-August University Göttingen, Humboldtallee 23, 37073, Göttingen, Germany.

The AP1/σ1B knockout causes impaired synaptic vesicle recycling and enhanced protein sorting into endosomes, leading to severe intellectual disability. These disturbances in synaptic protein sorting induce as a secondary phenotype the upregulation of AP2 CCV mediated endocytosis. Synapses contain canonical AP2 CCV and AP2 CCV with a more stable coat and thus extended life time. Read More

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Comparative analysis of C chemical shifts of β-sheet amyloid proteins and outer membrane proteins.

J Biomol NMR 2021 Apr 12. Epub 2021 Apr 12.

Department of Chemistry, Massachusetts Institute of Technology, 170 Albany Street, Cambridge, MA, 02139, USA.

Cross-β amyloid fibrils and membrane-bound β-barrels are two important classes of β-sheet proteins. To investigate whether there are systematic differences in the backbone and sidechain conformations of these two families of proteins, here we analyze the C chemical shifts of 17 amyloid proteins and 7 β-barrel membrane proteins whose high-resolution structures have been determined by NMR. These 24 proteins contain 373 β-sheet residues in amyloid fibrils and 521 β-sheet residues in β-barrel membrane proteins. Read More

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Spontaneous Reports of Serious Adverse Drug Reactions Resulting From Drug-Drug Interactions: An Analysis From the French Pharmacovigilance Database.

Front Pharmacol 2020 24;11:624562. Epub 2021 Mar 24.

Univ. Bordeaux, INSERM, BPH, U1219, Team Pharmacoepidemiology, Bordeaux, France.

Few data are available on the clinical impact of drug-drug interactions (DDIs). Most of the studies are limited to the analysis of exposure to potential DDI or the targeted impact of the combination of a few drugs or therapeutic classes. The analysis of adverse drug reaction (ADR) reports could be a mean to study generally the adverse effects identified due to a DDI. Read More

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Genetic suppression of lethal mutations in fatty acid biosynthesis mediated by a secondary lipid synthase.

Appl Environ Microbiol 2021 Apr 9. Epub 2021 Apr 9.

Marine Biology Research Division, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA USA

The biosynthesis and incorporation of polyunsaturated fatty acids into phospholipid membranes is a unique feature of certain marine Gammaproteobacteria inhabiting high-pressure and/or low temperature environments. In these bacteria, monounsaturated and saturated fatty acids are produced via the classical dissociated Type II fatty acid synthase mechanism, while omega-3 polyunsaturated fatty acids such as EPA (20:53) and DHA (22:63) are produced by a hybrid polyketide/fatty acid synthase - encoded by the genes - also referred to as the secondary lipid synthase mechanism. In this work, phenotypes associated with partial or complete loss of monounsaturated biosynthesis are shown to be compensated for by several-fold increased production of polyunsaturated fatty acids in the model marine bacterium SS9. Read More

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Simultaneous action of microbial phospholipase C and lipase on model bacterial membranes - Modeling the processes crucial for bioaugmentation.

Biochim Biophys Acta Biomembr 2021 Apr 6;1863(7):183620. Epub 2021 Apr 6.

Department of Environmental Chemistry, Faculty of Chemistry, Jagiellonian University in Krakow, Gronostajowa 2, 30-387 Kraków, Poland. Electronic address:

Bioaugmentation is a promising method of the remediation of soils polluted by persistent organic pollutants (POP). Unfortunately, it happens frequently that the microorganisms inoculated into the soil die out due to the presence of enzymes secreted by autochthonous microorganisms. Especially destructive are here phospholipases C (PLC) and lipases which destruct the microorganism's cellular membrane. Read More

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A targeted e-learning approach for keeping universities open during the COVID-19 pandemic while reducing student physical interactions.

PLoS One 2021 8;16(4):e0249839. Epub 2021 Apr 8.

Neuroscience and Behavioural Disorders Programme, Duke-NUS Medical School, Singapore, Singapore.

The COVID-19 pandemic led to widespread closure of universities. Many universities turned to e-learning to provide educational continuity, but they now face the challenge of how to reopen safely and resume in-class learning. This is difficult to achieve without methods for measuring the impact of school policies on student physical interactions. Read More

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Heat stress during late pregnancy and postpartum influences genetic parameter estimates for birth weight and weight gain in dual-purpose cattle offspring generations.

J Anim Sci 2021 Apr 2. Epub 2021 Apr 2.

Institute of Animal Breeding and Genetics, Justus-Liebig-University, Giessen, Germany.

Impact of direct heat stress (HS) on genetic parameter estimates, i.e., HS close to the trait recording date, was verified in several previous studies conducted in dairy and beef cattle populations. Read More

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Investigating the mediating role of online learning motivation in the COVID-19 pandemic situation in Bangladesh.

J Comput Assist Learn 2021 Mar 2. Epub 2021 Mar 2.

Department of Business Administration, Faculty of Business & Social Science (FBSS) Bangladesh University of Professionals (BUP) Dhaka Bangladesh.

The purpose of this paper is to investigate the mediating role of online learning motivation (OLM) in the COVID-19 pandemic situation in Bangladesh by observing and comparing direct lectures (DL), instructor-learner interaction (ILI), learner-learner interaction (LLI), and internet self-efficacy (ISE) as predictors of OLM and online learning satisfaction (OLS). Data were collected from 442 undergraduate and graduate students from more than 35 universities in Bangladesh. To test the hypotheses, the PLS-SEM approach was applied using SmartPLS 3. Read More

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Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds.

J Med Chem 2021 Apr 5;64(8):4623-4661. Epub 2021 Apr 5.

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.

Targeting the protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-molecule Keap1-Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket. Read More

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Differentiating Neuroblastoma: A Systematic Review of the Retinoic Acid, Its Derivatives, and Synergistic Interactions.

J Pers Med 2021 Mar 16;11(3). Epub 2021 Mar 16.

Cancer Bio-Engineering Group, Department of Anatomy and Regenerative Medicine, RCSI University of Medicine and Health Sciences, D02 YN77 Dublin, Ireland.

A neuroblastoma (NB) is a solid paediatric tumour arising from undifferentiated neuronal cells. Despite the recent advances in disease management and treatment, it remains one of the leading causes of childhood cancer deaths, thereby necessitating the development of new therapeutic agents and regimens. Retinoic acid (RA), a vitamin A derivative, is a promising agent that can induce differentiation in NB cells. Read More

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Chaperone Networks in Fungal Pathogens of Humans.

J Fungi (Basel) 2021 Mar 12;7(3). Epub 2021 Mar 12.

Michael Smith Laboratories, Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.

The heat shock proteins (HSPs) function as chaperones to facilitate proper folding and modification of proteins and are of particular importance when organisms are subjected to unfavourable conditions. The human fungal pathogens are subjected to such conditions within the context of infection as they are exposed to human body temperature as well as the host immune response. Herein, the roles of the major classes of HSPs are briefly reviewed and their known contributions in human fungal pathogens are described with a focus on and . Read More

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Transcriptomic Analysis Reveals Host miRNAs Correlated with Immune Gene Dysregulation during Fatal Disease Progression in the Ebola Virus Cynomolgus Macaque Disease Model.

Microorganisms 2021 Mar 23;9(3). Epub 2021 Mar 23.

Diagnostic Systems Division, U.S. Army Medical Research Institute of Infectious Diseases, Ft. Detrick, MD 21702, USA.

Ebola virus is a continuing threat to human populations, causing a virulent hemorrhagic fever disease characterized by dysregulation of both the innate and adaptive host immune responses. Severe cases are distinguished by an early, elevated pro-inflammatory response followed by a pronounced lymphopenia with B and T cells unable to mount an effective anti-viral response. The precise mechanisms underlying the dysregulation of the host immune system are poorly understood. Read More

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Untargeted In Silico Compound Classification-A Novel Metabolomics Method to Assess the Chemodiversity in Bryophytes.

Int J Mol Sci 2021 Mar 23;22(6). Epub 2021 Mar 23.

Bioinformatics & Scientific Data, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120 Halle (Saale), Germany.

In plant ecology, biochemical analyses of bryophytes and vascular plants are often conducted on dried herbarium specimen as species typically grow in distant and inaccessible locations. Here, we present an automated in silico compound classification framework to annotate metabolites using an untargeted data independent acquisition (DIA)-LC/MS-QToF-sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH) ecometabolomics analytical method. We perform a comparative investigation of the chemical diversity at the global level and the composition of metabolite families in ten different species of bryophytes using fresh samples collected on-site and dried specimen stored in a herbarium for half a year. Read More

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Biological and Physico-Chemical Characteristics of Arginine-Rich Peptide Gemini Surfactants with Lysine and Cystine Spacers.

Int J Mol Sci 2021 Mar 24;22(7). Epub 2021 Mar 24.

Department of Inorganic Chemistry, Faculty of Pharmacy, Medical University of Gdańsk, 80-416 Gdańsk, Poland.

Ultrashort cationic lipopeptides (USCLs) and gemini cationic surfactants are classes of potent antimicrobials. Our recent study has shown that the branching and shortening of the fatty acids chains with the simultaneous addition of a hydrophobic -terminal amino acid in USCLs result in compounds with enhanced selectivity. Here, this approach was introduced into arginine-rich gemini cationic surfactants. Read More

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Structure-Based Virtual Screening and De Novo Design of PIM1 Inhibitors with Anticancer Activity from Natural Products.

Pharmaceuticals (Basel) 2021 Mar 18;14(3). Epub 2021 Mar 18.

Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon 34141, Korea.

Background: the proviral insertion site of Moloney murine leukemia (PIM) 1 kinase has served as a therapeutic target for various human cancers due to the enhancement of cell proliferation and the inhibition of apoptosis.

Methods: to identify effective PIM1 kinase inhibitors, structure-based virtual screening of natural products of plant origin and de novo design were carried out using the protein-ligand binding free energy function improved by introducing an adequate dehydration energy term.

Results: as a consequence of subsequent enzyme inhibition assays, four classes of PIM1 kinase inhibitors were discovered, with the biochemical potency ranging from low-micromolar to sub-micromolar levels. Read More

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Synthesis, Molecular Docking Studies and In Silico ADMET Screening of New Heterocycles Linked Thiazole Conjugates as Potent Anti-Hepatic Cancer Agents.

Molecules 2021 Mar 18;26(6). Epub 2021 Mar 18.

Chemistry Department, Faculty of Science, South Valley University, Qena 83523, Egypt.

Thiazoles are important scaffolds in organic chemistry. Biosynthesis of thiazoles is considered to be an excellent target for the design of novel classes of therapeutic agents. In this study, a new series of 2-ethylidenehydrazono-5-arylazothiazoles - and 2-ethylidenehydrazono-5-arylazo- thiazolones - were synthesized via the cyclocondensation reaction of the appropriate hydrazonyl halides - and - with ethylidene thiosemicarbazide , respectively. Read More

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Selective Styrene Oxidation to Benzaldehyde over Recently Developed Heterogeneous Catalysts.

Molecules 2021 Mar 17;26(6). Epub 2021 Mar 17.

Centro de Química Estrutural and Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisbn, Portugal.

The selective oxidation of styrene under heterogeneous catalyzed conditions delivers environmentally friendly paths for the production of benzaldehyde, an important intermediate for the synthesis of several products. The present review explores heterogeneous catalysts for styrene oxidation using a variety of metal catalysts over the last decade. The use of several classes of supports is discussed, including metal-organic frameworks, zeolites, carbon materials and silicas, among others. Read More

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Inhibitor Development against p7 Channel in Hepatitis C Virus.

Molecules 2021 Mar 3;26(5). Epub 2021 Mar 3.

State Key Laboratory of Molecular Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 333 Haike Road, Shanghai 201203, China.

Hepatitis C Virus (HCV) is the key cause of chronic and severe liver diseases. The recent direct-acting antiviral agents have shown the clinical success on HCV-related diseases, but the rapid HCV mutations of the virus highlight the sustaining necessity to develop new drugs. p7, the viroporin protein from HCV, has been sought after as a potential anti-HCV drug target. Read More

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