Hemodynamic and Genetic Associations with the Risk of Idiopathic Pulmonary Arterial Hypertension Development in an Ethnic Cohort of Kazakhs.

Introduction: Idiopathic pulmonary arterial hypertension (IPAH) is a progressive and fatal disease. The aim of this study was to evaluate the association of polymorphism of the type 2 bone morphogenetic protein receptor gene (BMPR2) with the risk of IPAH development in an ethnic group of Kazakhs. We also describe the clinical and hemodynamic characteristics and outcomes of patients with and without carriers of BMPR2 gene mutations in IPAH.

Complete genome sequence of a human influenza a virus (H1N1) detected in Kazakhstan in the fall of 2022.

An virus strain, ), was isolated in Karaganda, Central Kazakhstan during a study of acute respiratory infections among hospital inpatients in 2022. Here, we present the complete genome sequence of this strain.

The Structural Permissiveness of Triosephosphate Isomerase (TpiA) of Escherichia coli.

Triosephosphate isomerase (TpiA) is widely regarded as an example of an optimally evolved enzyme due to its essential role in biological systems, its structural conservation, and its near-perfect kinetic parameters. In this study, we investigated the structural robustness of the archetypal TpiA variant from Escherichia coli using an in vitro 5-amino acid linker scanning method. The resulting library was introduced into a tpiA mutant strain for functional complementation.

Defense and senescence interplay in legume nodules.

Immunity and senescence play a crucial role in the functioning of the legume symbiotic nodules. The miss-regulation of one of these processes compromises the symbiosis leading to death of the endosymbiont and the arrest of the nodule functioning. The relationship between immunity and senescence has been extensively studied in plant organs where a synergistic response can be observed.

Scipion3: A workflow engine for cryo-electron microscopy image processing and structural biology.

Image-processing pipelines require the design of complex workflows combining many different steps that bring the raw acquired data to a final result with biological meaning. In the image-processing domain of cryo-electron microscopy single-particle analysis (cryo-EM SPA), hundreds of steps must be performed to obtain the three-dimensional structure of a biological macromolecule by integrating data spread over thousands of micrographs containing millions of copies of allegedly the same macromolecule. The execution of such complicated workflows demands a specific tool to keep track of all these steps performed.

EAM highlights in FEMS 2023: from the Petri dish to planet Earth.

On 9-13 July 2023, the 10th FEMS Congress took place in Hamburg, Germany. As part of this major event in European microbiology, the European Academy of Microbiology (EAM) organized two full sessions. One of these sessions aimed to highlight the research of four recently elected EAM fellows and saw presentations on bacterial group behaviours and development of resistance to antibiotics, as well as on new RNA viruses including bacteriophages and giant viruses of amoebae.

Scipion-Chem: An Open Platform for Virtual Drug Screening.

Virtual drug screening (VDS) tackles the problem of drug discovery by computationally reducing the number of potential pharmacological molecules that need to be tested experimentally to find a new drug. To do so, several approaches have been developed through the years, typically focusing on either the physicochemical characteristics of the receptor structure (structure-based virtual screening) or those of the potential ligands (ligand-based virtual screening). Scipion is a workflow engine well suited for structural studies of biological macromolecules.

Inflammatory macrophages reprogram to immunosuppression by reducing mitochondrial translation.

Acute inflammation can either resolve through immunosuppression or persist, leading to chronic inflammation. These transitions are driven by distinct molecular and metabolic reprogramming of immune cells. The anti-diabetic drug Metformin inhibits acute and chronic inflammation through mechanisms still not fully understood.

The adaptive antioxidant response during fasting-induced muscle atrophy is oppositely regulated by ZEB1 and ZEB2.

Reactive oxygen species (ROS) serve important homeostatic functions but must be constantly neutralized by an adaptive antioxidant response to prevent supraphysiological levels of ROS from causing oxidative damage to cellular components. Here, we report that the cellular plasticity transcription factors ZEB1 and ZEB2 modulate in opposing directions the adaptive antioxidant response to fasting in skeletal muscle. Using transgenic mice in which or were specifically deleted in skeletal myofibers, we show that in fasted mice, the deletion of , but not , increased ROS production and that the adaptive antioxidant response to fasting essentially requires ZEB1 and is inhibited by ZEB2.

Cell type dependent stability and virulence of a recombinant SARS-CoV-2, and engineering of a propagation deficient RNA replicon to analyze virus RNA synthesis.

Engineering of reverse genetics systems for newly emerged viruses allows viral genome manipulation, being an essential tool for the study of virus life cycle, virus-host interactions and pathogenesis, as well as for the development of effective antiviral strategies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent human coronavirus that has caused the coronavirus disease (COVID-19) pandemic. The engineering of a full-length infectious cDNA clone and a fluorescent replicon of SARS-CoV-2 Wuhan-Hu-1, using a bacterial artificial chromosome, is reported.

A new isoflavonoid derivative, evaluation of the antioxidant capacity and phenolic content of DC.

The phytochemical investigation of both chloroform and ethyl acetate extracts of DC from an Algerian endemic plant led to the isolation of a new isoflavonoid Aspalathoidin compound () and nine known compounds (laburnetin, isokaempferide, retamasin B, ephedrodin, sakuretin, isoprunetin, genistein -7--β-glucoside, derrone-4'--methyl ether and eriodictyol-7,3'-dimethylether). Twelve phenolic compounds were identified in ethyl acetate and -butanol extracts through a qualitative investigation of phenolic compounds using HPLC. Finally, both extracts were estimated for their phenolic and flavonoid contents as well as the evaluation of their antioxidant activity using five different assays DPPH, CUPRAC, ABTS, GOR and the sun protection factor SPF was determined as an index of the photoprotective capacity of the DC extracts.

Structural mobility tunes signalling of the GluA1 AMPA glutamate receptor.

AMPA glutamate receptors (AMPARs), the primary mediators of excitatory neurotransmission in the brain, are either GluA2 subunit-containing and thus Ca-impermeable, or GluA2-lacking and Ca-permeable. Despite their prominent expression throughout interneurons and glia, their role in long-term potentiation and their involvement in a range of neuropathologies, structural information for GluA2-lacking receptors is currently absent. Here we determine and characterize cryo-electron microscopy structures of the GluA1 homotetramer, fully occupied with TARPγ3 auxiliary subunits (GluA1/γ3).

Morphological and Molecular Characterization of Bacterial Pathogens Associated with Leaf Mottle of Sunflower in Northern Kazakhstan.

Leaf mottle is a serious disease in the common sunflower ( L.), which affects plant growth and development and seed quality and yield. Over the past few years, the North Kazakhstan region, a sunflower-producing area in Kazakhstan, has been seriously affected by leaf mottle.

SARS-CoV-2 Mac1 is required for IFN antagonism and efficient virus replication in cell culture and in mice.

Several coronavirus (CoV) encoded proteins are being evaluated as targets for antiviral therapies for COVID-19. Included in these drug targets is the conserved macrodomain, or Mac1, an ADP-ribosylhydrolase and ADP-ribose binding protein encoded as a small domain at the N terminus of nonstructural protein 3. Utilizing point mutant recombinant viruses, Mac1 was shown to be critical for both murine hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV virulence.

Interplay between septins and ubiquitin-mediated xenophagy during entrapment.

Septins are cytoskeletal proteins implicated in numerous cellular processes including cytokinesis and morphogenesis. In the case of infection by , septins assemble into cage-like structures that entrap cytosolic bacteria targeted by autophagy. The interplay between septin cage entrapment and bacterial autophagy is poorly understood.

Contribution to pathogenesis of accessory proteins of deadly human coronaviruses.

Coronaviruses (CoVs) are enveloped and positive-stranded RNA viruses with a large genome (∼ 30kb). CoVs include essential genes, such as the replicase and four genes coding for structural proteins (S, M, N and E), and genes encoding accessory proteins, which are variable in number, sequence and function among different CoVs. Accessory proteins are non-essential for virus replication, but are frequently involved in virus-host interactions associated with virulence.

The Virulence and Infectivity of Listeria monocytogenes Are Not Substantially Altered by Elevated SigB Activity.

Listeria monocytogenes is a bacterial pathogen capable of causing severe infections but also thriving outside the host. To respond to different stress conditions, L. monocytogenes mainly utilizes the general stress response regulon, which largely is controlled by the alternative sigma factor Sigma B (SigB).

SARS-CoV-2 Mac1 is required for IFN antagonism and efficient virus replication in mice.

Unlabelled: Several coronavirus (CoV) encoded proteins are being evaluated as targets for antiviral therapies for COVID-19. Included in this set of proteins is the conserved macrodomain, or Mac1, an ADP-ribosylhydrolase and ADP-ribose binding protein. Utilizing point mutant recombinant viruses, Mac1 was shown to be critical for both murine hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV virulence.

Efficient CRISPR-Cas13d-Based Antiviral Strategy to Combat SARS-CoV-2.

The current SARS-CoV-2 pandemic forms a major global health burden. Although protective vaccines are available, concerns remain as new virus variants continue to appear. CRISPR-based gene-editing approaches offer an attractive therapeutic strategy as the CRISPR-RNA (crRNA) can be adjusted rapidly to accommodate a new viral genome sequence.

Structural basis and dynamics of Chikungunya alphavirus RNA capping by nsP1 capping pores.

Alphaviruses are emerging positive-stranded RNA viruses which replicate and transcribe their genomes in membranous organelles formed in the cell cytoplasm. The nonstructural protein 1 (nsP1) is responsible for viral RNA capping and gates the replication organelles by assembling into monotopic membrane-associated dodecameric pores. The capping pathway is unique to Alphaviruses; beginning with the N methylation of a guanosine triphosphate (GTP) molecule, followed by the covalent linkage of an mGMP group to a conserved histidine in nsP1 and the transfer of this cap structure to a diphosphate RNA.

Engineering potent live attenuated coronavirus vaccines by targeted inactivation of the immune evasive viral deubiquitinase.

Coronaviruses express a papain-like protease (PLpro) that is required for replicase polyprotein maturation and also serves as a deubiquitinating enzyme (DUB). In this study, using a Middle East respiratory syndrome virus (MERS-CoV) PLpro modified virus in which the DUB is selectively inactivated, we show that the PLpro DUB is an important MERS-CoV interferon antagonist and virulence factor. Although the DUB-negative rMERS-CoV replicates robustly in the lungs of human dipeptidyl peptidase 4 knock-in (hDPP4 KI) mice, it does not cause clinical symptoms.