Cas13-containing type VI CRISPR-Cas systems specifically target RNA; however, the mechanism of spacer acquisition remains unclear. We have previously reported the association of reverse transcriptase-Cas1 (RT-Cas1) fusion proteins with certain types of VI-A systems. Here, we show that RT-Cas1 fusion proteins are also recruited by type VI-B systems in bacteria from gut microbiomes, constituting a VI-B1 variant system that includes a CorA-encoding locus in addition to the CRISPR array and the RT-Cas1/Cas2 adaptation module.
View Article and Find Full Text PDFLight-driven sodium pumps (NaRs) are unique ion-transporting microbial rhodopsins. The major group of NaRs is characterized by an NDQ motif and has two aspartic acid residues in the central region essential for sodium transport. Here we identify a subgroup of the NDQ rhodopsins bearing an additional glutamic acid residue in the close vicinity to the retinal Schiff base.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2023
The temporal difference learning (TDL) algorithm has been essential to conceptualizing the role of dopamine in reinforcement learning (RL). Despite its theoretical importance, it remains unknown whether a neuronal implementation of this algorithm exists in the brain. Here, we provide an interpretation of the recently described signaling properties of ventral tegmental area (VTA) GABAergic neurons and show that a circuitry of these neurons implements the TDL algorithm.
View Article and Find Full Text PDFComput Struct Biotechnol J
September 2021
The ASCT1 transporter of the SLC1 family is largely involved in equilibration of neutral amino acids' pools across the plasma membrane and plays a prominent role in the transport of both L- and D-isomers of serine, essential for the normal functioning of the central nervous system in mammals. A number of mutations in ASCT1 (E256K, G381R, R457W) have been linked to severe neurodevelopmental disorders, however in the absence of ASCT1 structure it is hard to understand their impact on substrate transport. To ameliorate that we have determined a cryo-EM structure of human ASCT1 at 4.
View Article and Find Full Text PDFThe 2-TM-GxN family of membrane proteins is widespread in prokaryotes and plays an important role in transport of divalent cations. The canonical signature motif, which is also a selectivity filter, has a composition of Gly-Met-Asn. Some members though deviate from this composition, however no data are available as to whether this has any functional implications.
View Article and Find Full Text PDFNadR is a bifunctional enzyme that converts nicotinamide riboside (NR) into nicotinamide mononucleotide (NMN), which is then converted into nicotinamide adenine dinucleotide (NAD). Although a crystal structure of the enzyme from the Gram-negative bacterium is known, structural understanding of its catalytic mechanism remains unclear. Here, we purified the NadR enzyme from and established an assay to determine the combined activity of this bifunctional enzyme.
View Article and Find Full Text PDFCorA proteins belong to 2-TM-GxN family of membrane proteins, and play a major role in Mg transport in prokaryotes and eukaryotic mitochondria. The selection of substrate is believed to occur via the signature motif GxN, however there is no consensus how strict this selection within the family. To answer this question, we employed fluorescence-based transport assays on three different family members, namely CorA from bacterium Thermotoga maritima, CorA from the archeon Methanocaldococcus jannaschii and ZntB from bacterium Escherichia coli, reconstituted into proteoliposomes.
View Article and Find Full Text PDFZinc is an essential microelement to sustain all forms of life. However, excess of zinc is toxic, therefore dedicated import, export and storage proteins for tight regulation of the zinc concentration have evolved. In Enterobacteriaceae, several membrane transporters are involved in zinc homeostasis and linked to virulence.
View Article and Find Full Text PDFThe histological fibro genesis abilities in the area of implantation of allotransplantates applying intraabdominal and preperitoneal plastic surgery were examined during experimental research. The experiment involved 12 Russian chinchilla rabbits. The animals were spitted into two groups: I group--operated using IPOM methodology (intraperitonealonlaymesh, n = 6) with the installation "Proceed" mesh made by "Ethicon", group II--modeling preperitoneal plastics with the installation of "Ethicon's Ultrapro" mesh (n = 6).
View Article and Find Full Text PDFSingle crystalline Bi nanowires were grown by extrusion from Bi/Co thin films. The films were obtained by thermal evaporation in high vacuum. The average diameter, length and density of obtained nanowires were 100 nm, 30 microm and 6.
View Article and Find Full Text PDFJ Nanosci Nanotechnol
April 2012
Crystalline C60 and amorphous graphite-like films of nanocolumn arrays fabricated by glancing angle deposition of C60 fullerene at substrate temperatures of -425 K were studied by transmission electron microscopy (TEM) and atomic-force microscopy (AFM). Characteristic dimension of columns is 200-400 nm. We used co-deposition of C60 molecules and accelerated C60 ions to modify the structure and properties of nanocolumn arrays.
View Article and Find Full Text PDFThe experience of surgical treatment of 10 patients with external intestinal fistulae was analyzed. The plot of the operation was to exlude the duodenum from the digestion by performing the retrocolic gastroenteroanastomosis after Roux or on the ultrashort loop. Early operation prevent septic complications and electrolyte disbalance.
View Article and Find Full Text PDFOral and oro-pharyngeal squamous cell carcinomas (OSCC) exhibit surface breach, and recent studies have demonstrated bacterial contamination of primary and metastatic OSCC. Increasing concentrations of inflammatory products, such as interleukin (IL)-6 and vascular endothelial growth factor (VEGF), correlate with, and contribute to, cancer progression, but their regulation in OSCC is poorly understood. We hypothesized that monocyte-lineage cells and bacterial contamination may contribute important inflammatory products that can support OSCC progression.
View Article and Find Full Text PDFRetinol dehydrogenase 13 (RDH13) is a recently identified short-chain dehydrogenase/reductase related to microsomal retinoid oxidoreductase RDH11. In this study, we examined the distribution of RDH13 in human tissues, determined its subcellular localization and characterized the substrate and cofactor specificity of purified RDH13 in order to better understand its properties. The results of this study demonstrate that RDH13 exhibits a wide tissue distribution and, by contrast with other members of the RDH11-like group of short-chain dehydrogenases/reductases, is a mitochondrial rather than a microsomal protein.
View Article and Find Full Text PDFJ Nanosci Nanotechnol
July 2007
Carbon films 250 division by 500 nm in thickness deposited on Si wafers from mass-selected flow of accelerated C60 ions with energies of 5.0 +/- 0.1 keV at temperatures of 300 K and 673 K are characterized by TEM and nanoindentation.
View Article and Find Full Text PDFRetinoic acid biosynthesis in vertebrates occurs in two consecutive steps: the oxidation of retinol to retinaldehyde followed by the oxidation of retinaldehyde to retinoic acid. Enzymes of the MDR (medium-chain dehydrogenase/reductase), SDR (short-chain dehydrogenase/reductase) and AKR (aldo-keto reductase) superfamilies have been reported to catalyse the conversion between retinol and retinaldehyde. Estimation of the relative contribution of enzymes of each type was difficult since kinetics were performed with different methodologies, but SDRs would supposedly play a major role because of their low K(m) values, and because they were found to be active with retinol bound to CRBPI (cellular retinol binding protein type I).
View Article and Find Full Text PDFRetinol dehydrogenase 12 (RDH12) is a novel member of the short-chain dehydrogenase/reductase superfamily of proteins that was recently linked to Leber's congenital amaurosis 3 (LCA). We report the first biochemical characterization of purified human RDH12 and analysis of its expression in human tissues. RDH12 exhibits approximately 2000-fold lower K(m) values for NADP(+) and NADPH than for NAD(+) and NADH and recognizes both retinoids and lipid peroxidation products (C(9) aldehydes) as substrates.
View Article and Find Full Text PDFBlind randomized placebo-control research included 39 women. The following criteria were: menopause period for more then 1 year long; diabetes mellitus; arterial hypertension; hypercholesterolemia. The patients were divided into two groups.
View Article and Find Full Text PDFRecently, we reported the first biochemical characterization of a novel member of the short-chain dehydrogenase/reductase superfamily, retinal reductase 1 (RalR1) (Kedishvili et al. (2002) J. Biol.
View Article and Find Full Text PDFThe first experience of extramucosal laparoscopic esophagocardiomyotomy performance in 12 patients for achalasia of cardia was summarized. There were presented main technical stages of the operation, indications, early and immediate results of its application as well.
View Article and Find Full Text PDFExperience of surgical treatment of 8 patients with morbid obesity, using regulated cuff Lap Band, was adduced. Body mass of patients have constituted from 105 to 185, (14.5 +/- 2.
View Article and Find Full Text PDFAnalysis of 636 surgical interventions for malignant tumors in 576 chronic coronary patients showed that beta-blockers decreased the relative risk of ischemia and myocardial infarction during the postoperative period. Calcium antagonists verapamil and dihydropyridines also essentially decreased the probability of myocardial infarction and less so of myocardial ischemia. Antiischemic effect of nitrates was insignificant, and they increased the risk of myocardial infarction.
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