High-Risk Lineages of Hybrid Plasmids Carrying Virulence and Carbapenemase Genes.

Carbapenem-resistant (CRE) are a global health threat due to their high morbidity and mortality rates and limited treatment options. This study examines the plasmid-mediated transmission of virulence and antibiotic resistance determinants in carbapenem-resistant () and () isolated from Russian hospitals. : We performed short- and long-read whole-genome sequencing of 53 clinical isolates (48 and 5 ) attributed to 15 genetic lineages and collected from 21 hospitals across nine Russian cities between 2016 and 2022.

Facade-Based Bicelles as a New Tool for Production of Active Membrane Proteins in a Cell-Free System.

Integral membrane proteins are important components of a cell. Their structural and functional studies require production of milligram amounts of proteins, which nowadays is not a routine process. Cell-free protein synthesis is a prospective approach to resolve this task.

Sarcopenia in cirrhosis: Prospects for therapy targeted to gut microbiota.

Decreased muscle mass and function, also known as sarcopenia, is common in patients with cirrhosis and is associated with a poor prognosis. Although the pathogenesis of this disorder has not been fully elucidated, a disordered gut-muscle axis probably plays an important role. Decreased barrier function of the gut and liver, gut dysbiosis, and small intestinal bacterial overgrowth (SIBO) can lead to increased blood levels of ammonia, lipopolysaccharides, pro-inflammatory mediators, and myostatin.

Cingulin and paracingulin tether myosins-2 to junctions to mechanoregulate the plasma membrane.

The mechanisms that regulate the spatial sorting of nonmuscle myosins-2 (NM2) isoforms and couple them mechanically to the plasma membrane are unclear. Here we show that the cytoplasmic junctional proteins cingulin (CGN) and paracingulin (CGNL1) interact directly with NM2s through their C-terminal coiled-coil sequences. CGN binds strongly to NM2B, and CGNL1 to NM2A and NM2B.

Synthesis and evaluation of avermectin-imidazo[1,2-a]pyridine hybrids as potent GABA receptor modulators.

The γ-aminobutyric acid type A (GABA) receptors are pentameric transmembrane protein complexes. They have attracted extensive attention from the scientific community due to their significant pharmacological potential. Here we report the first synthesis of avermectin-imidazo[1,2-a]pyridine hybrids promising as GABA receptor positive allosteric modulators (PAMs).

Cingulin binds to the ZU5 domain of scaffolding protein ZO-1 to promote its extended conformation, stabilization, and tight junction accumulation.

Zonula occludens-1 (ZO-1), the major scaffolding protein of tight junctions (TJs), recruits the cytoskeleton-associated proteins cingulin (CGN) and paracingulin (CGNL1) to TJs by binding to their N-terminal ZO-1 interaction motif. The conformation of ZO-1 can be either folded or extended, depending on cytoskeletal tension and intramolecular and intermolecular interactions, and only ZO-1 in the extended conformation recruits the transcription factor DbpA to TJs. However, the sequences of ZO-1 that interact with CGN and CGNL1 and the role of TJ proteins in ZO-1 TJ assembly are not known.

The neuropeptide cycloprolylglycine produces antidepressant-like effect and enhances gene expression in the mice cortex.

Background: Cycloprolylglycine (CPG) is an endogenous dipeptide with a wide range of psychotropic activity and putative therapeutic potential for depression. A small but growing body of data suggests that antidepressant-like effect of CPG is associated with neuroplastic changes in the brain or 5-HT system modulation. However, the mechanisms of the dipeptide action remain elusive.

Screening and Behavioral Validation of a Novel Peptide, LCGA-17, With Anxiolytic-Like Properties.

The aim of the study was to develop better anxiolytics and antidepressants. We focused on GABA receptors and the α2δ auxiliary subunit of V-gated Ca channels as putative targets because they are established as mediators of efficacious anxiolytics, antidepressants, and anticonvulsants. We further focused on short peptides as candidate ligands because of their high safety and tolerability profiles.

ERK1/2 kinases and dopamine D2 receptors participate in the anticonvulsant effects of a new derivative of benzoylpyridine oxime and valproic acid.

Inhibition of the activity of extracellular signal-regulated kinases (ERK1/2) induced by the activation of the dopamine D2 receptor signalling cascade may be a promising pharmacological target. The aim of this work was to study the involvement of ERK1/2 and dopamine D2 receptor in the mechanism of the anticonvulsant action of valproic acid (VA) and a new benzoylpyridine oxime derivative (GIZH-298), which showed antiepileptic activity in different models of epilepsy. We showed that subchronic exposure to maximal electroshock seizures (MES) for 5 days reduced the density of dopamine D2 receptors in the striatum of mice.

Scaffolding proteins of vertebrate apical junctions: structure, functions and biophysics.

Tight and adherens junctions are specialized sites of cell-cell interaction in epithelia and endothelia, and are involved in barrier, adhesion, and signaling functions. These functions are orchestrated by a highly organized meshwork of macromolecules in the membrane and cytoplasmic compartments. In this review, we discuss the structural organization and functions of the major cytoplasmic scaffolding and adaptor proteins of vertebrate apical junctions (ZO proteins, afadin, PLEKHA7, cingulin, paracingulin, polarity complex proteins, and a few others), focusing on their interactions with cytoskeletal and signaling proteins.

Transcriptomic Insights into Mechanisms of Early Seed Maturation in the Garden Pea ( L.).

The garden pea ( L.) is a legume crop of immense economic value. Extensive breeding has led to the emergence of numerous pea varieties, of which some are distinguished by accelerated development in various stages of ontogenesis.

New sources of allele in the pea ( L.) carry the unique variant of candidate LysM-RLK gene .

At the onset of legume-rhizobial symbiosis, the mutual recognition of partners occurs based on a complicated interaction between signal molecules and receptors. Bacterial signal molecules named Nod factors ("nodulation factors") are perceived by the plant LysM-containing receptor-like kinases (LysM-RLKs) that recognize details of its structure (i.e.

Two Novel Amyloid Proteins, RopA and RopB, from the Root Nodule Bacterium .

Amyloids represent protein fibrils with a highly ordered spatial structure, which not only cause dozens of incurable human and animal diseases but also play vital biological roles in Archaea, Bacteria, and Eukarya. Despite the fact that association of bacterial amyloids with microbial pathogenesis and infectious diseases is well known, there is a lack of information concerning the amyloids of symbiotic bacteria. In this study, using the previously developed proteomic method for screening and identification of amyloids (PSIA), we identified amyloidogenic proteins in the proteome of the root nodule bacterium Among 54 proteins identified, we selected two proteins, RopA and RopB, which are predicted to have β-barrel structure and are likely to be involved in the control of plant-microbial symbiosis.

R40.76 binds to the α domain of ZO-1: role of ZO-1 (α+) in epithelial differentiation and mechano-sensing.

The barrier function of epithelia and endothelia depends on tight junctions, which are formed by the polymerization of claudins on a scaffold of ZO proteins. Two differentially spliced isoforms of ZO-1 have been described, depending on the presence of the α domain, but the function of this domain is unclear. ZO-1 also contains a C-terminal ZU5 domain, which is involved in a mechano-sensitive intramolecular interaction with the central (ZPSG) region of ZO-1.

A Dock-and-Lock Mechanism Clusters ADAM10 at Cell-Cell Junctions to Promote α-Toxin Cytotoxicity.

We previously identified PLEKHA7 and other junctional proteins as host factors mediating death by S. aureus α-toxin, but the mechanism through which junctions promote toxicity was unclear. Using cell biological and biochemical methods, we now show that ADAM10 is docked to junctions by its transmembrane partner Tspan33, whose cytoplasmic C terminus binds to the WW domain of PLEKHA7 in the presence of PDZD11.

The role of microtubules in the regulation of epithelial junctions.

The cytoskeleton is crucially important for the assembly of cell-cell junctions and the homeostatic regulation of their functions. Junctional proteins act, in turn, as anchors for cytoskeletal filaments, and as regulators of cytoskeletal dynamics and signalling proteins. The cross-talk between junctions and the cytoskeleton is critical for the morphogenesis and physiology of epithelial and other tissues, but is not completely understood.

Cell-specific diversity in the expression and organization of cytoplasmic plaque proteins of apical junctions.

Tight and adherens junctions play critical roles in the barrier, adhesion, and signaling functions of epithelial and endothelial cells. How the molecular organization of these junctions is tuned to the widely diverse physiological requirements of each tissue type is not well understood. Here, we address this question by examining the expression, localization, and interactions of major cytoplasmic plaque proteins of tight and adherens junctions in different cultured epithelial and endothelial cell lines.

The role of apical cell-cell junctions and associated cytoskeleton in mechanotransduction.

Tissues of multicellular organisms are characterised by several types of specialised cell-cell junctions. In vertebrate epithelia and endothelia, tight and adherens junctions (AJ) play critical roles in barrier and adhesion functions, and are connected to the actin and microtubule cytoskeletons. The interaction between junctions and the cytoskeleton is crucial for tissue development and physiology, and is involved in the molecular mechanisms governing cell shape, motility, growth and signalling.

, a new species of spined loach from South Korea, and redescription of (Teleostei: Cobitidae).

Cobitis nalbanti, new species, is described from the South Korean Han and Geum Rivers, draining to the Yellow Sea. It differs from its congeners by having a wide, ovoid lamina circularis; rounded scales with a large, slightly-displaced focal zone; a relatively long, protruded snout; the suborbital spine not reaching the center of the eye; the mandibular barbel not reaching the anterior edge of the eye; usually 12-14 dark brown blotches in the fourth Gambetta's zone; a single elongated black spot on the upper part of the caudal-fin base; the only streak on the head running from the tip of the snout to the nape, across the eye; 2n=48-51 and NF=66. Cobitis nalbanti was previously identified as C.

Anxiolytic activity of the neuroprotective peptide HLDF-6 and its effects on brain neurotransmitter systems in BALB/c and C57BL/6 mice.

This study is focused on a new amide derivative of the peptide HLDF-6 (Thr-Gly-Glu-Asn-His-Arg). This hexapeptide is a fragment of Human Leukaemia Differentiation Factor (HLDF). It displays a broad range of nootropic and neuroprotective activities.

PLEKHA7: Cytoskeletal adaptor protein at center stage in junctional organization and signaling.

PLEKHA7 is a recently characterized component of the cytoplasmic region of epithelial adherens junctions (AJ). It comprises two WW domains, a pleckstrin-homology domain, and proline-rich and coiled-coil domains. PLEKHA7 interacts with cytoplasmic components of the AJ (p120-catenin, paracingulin, afadin), stabilizes the E-cadherin complex by linking it to the minus ends of noncentrosomal microtubules, and stabilizes junctional nectins through the newly identified interactor PDZD11.

PLEKHA7 Recruits PDZD11 to Adherens Junctions to Stabilize Nectins.

PLEKHA7 is a junctional protein implicated in stabilization of the cadherin protein complex, hypertension, cardiac contractility, glaucoma, microRNA processing, and susceptibility to bacterial toxins. To gain insight into the molecular basis for the functions of PLEKHA7, we looked for new PLEKHA7 interactors. Here, we report the identification of PDZ domain-containing protein 11 (PDZD11) as a new interactor of PLEKHA7 by yeast two-hybrid screening and by mass spectrometry analysis of PLEKHA7 immunoprecipitates.

A multilocus assessment of nuclear and mitochondrial sequence data elucidates phylogenetic relationships among European spirlins (Alburnoides, Cyprinidae).

The phylogenetic relationships and taxonomy of the spirlins in the genus Alburnoides are examined by comparative sequencing analysis of mitochondrial and nuclear markers. Molecular analyses revealed 17 Eurasian lineages divided into two main clades, termed the Ponto-Caspian and European in accordance with the lineage distribution. The indel diagnostics of β-actin and S7 markers and translation of cyt b to the amino acid chain were evaluated as a reliable identifying tool for most of the recognised lineages.

Molecular phylogeny of the genus Gobio Cuvier, 1816 (Teleostei: Cyprinidae) and its contribution to taxonomy.

The phylogenetic relationships among gudgeons that represent most nominal taxa within Gobio gobio sensu lato were examined by mitochondrial and nuclear genome sequencing. The molecular analyses confirmed the separate generic status of Gobio as a monophyletic group and revealed 15 Eurasian lineages divided into two main clades, the Northern European and the Ponto-Caspian. The validity of eleven nominal taxa as distinct species was confirmed, gudgeons from the Volga River basin were described as a new species G.

Protein and lipid oxidative damage and complex I content are lower in the brain of budgerigar and canaries than in mice. Relation to aging rate.

What are the mechanisms determining the rate of animal aging? Of the two major classes of endothermic animals, bird species are strikingly long-lived compared to mammals of similar body size and metabolic rate. Thus, they are ideal models to identify longevity-related characteristics not linked to body size or low metabolic rates. Since oxidative stress seems to be related to the basic aging process, we measured specific markers of different kinds of oxidative damage to proteins, like glutamic and aminoadipic semialdehydes (GSA and AASA, specific protein carbonyls), Nɛ-(carboxyethyl)lysine (CEL), Nɛ-(carboxymethyl)lysine (CML), and Nɛ-(malondialdehyde)lysine (MDAL), as well as mitochondrial Complex I content and amino acid and membrane fatty acyl composition, in the brain of short-lived mice (maximum life span [MLSP] 3.