Dobsonbek0370

BRCA2 controls RAD51 recombinase during homologous DNA recombination (HDR) through eight evolutionarily conserved BRC repeats, which individually engage RAD51 via the motif Phe-x-x-Ala. Using structure-guided molecular design, templated on a monomeric thermostable chimera between human RAD51 and archaeal RadA, we identify CAM833, a 529 Da orthosteric inhibitor of RAD51BRC with a Kd of 366 nM. The quinoline of CAM833 occupies a hotspot, the Phe-binding pocket on RAD51 and the methyl of the substituted α-methylbenzyl group occupies the Ala-binding pocket. In cells, CAM833 diminishes formation of damage-induced RAD51 nuclear foci; inhibits RAD51 molecular clustering, suppressing extended RAD51 filament assembly; potentiates cytotoxicity by ionizing radiation, augmenting 4N cell-cycle arrest and apoptotic cell death and works with poly-ADP ribose polymerase (PARP)1 inhibitors to suppress growth in BRCA2-wildtype cells. Thus, chemical inhibition of the protein-protein interaction between BRCA2 and RAD51 disrupts HDR and potentiates DNA damage-induced cell death, with implications for cancer therapy.Passive transfer of convalescent plasma or serum is a time-honored strategy for treating infectious diseases. Human convalescent plasma containing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently being used to treat patients with coronavirus disease 2019 where clinical efficacy trials are ongoing. Here, we assess therapeutic passive transfer in groups of SARS-CoV-2-infected African green monkeys with convalescent sera containing either high or low anti-SARS-CoV-2 neutralizing antibody titers. Differences in viral load and pathology are minimal between monkeys that receive the lower titer convalescent sera and untreated controls. However, lower levels of SARS-CoV-2 in respiratory compartments, reduced severity of virus-associated lung pathology, and reductions in coagulopathy and inflammatory processes are observed in monkeys that receive high titer sera versus untreated controls. Our data indicate that convalescent plasma therapy in humans may be an effective strategy provided that donor sera contain high anti-SARS-CoV-2 neutralizing titers given in early stages of the disease.Urethral catheterisation after medetomidine administration is the method of choice for semen collection in cats, but it yields variable results. This study tested whether scrotal manual stimulation can improve urethral sperm collection in domestic cats. The study was performed on 20 male cats, from which two urethral semen samples were collected, one before and one after 2min of transscrotal finger massage of the testes and epididymides. Both sperm samples were assessed for total sperm count and motility using computer-aided sperm analysis, viability and morphology (eosin-nigrosin staining). The transscrotal manual stimulation allowed a significantly higher number of spermatozoa to be obtained (P=0.0015). Viability was similar before and after the stimulation (median 92% and 90.5%), whereas the number of motile (median 60% and 70%) and morphologically normal (median 17% and 30.5%) spermatozoa was higher in the second sample (P=0.03 and P=0.002 respectively), which confirms that transscrotal massage induced the expulsion of a fresh pool of spermatozoa into the urethra. Transscrotal stimulation of the testes and epididymides significantly improves urethral semen collection in domestic cats and can be easily introduced into clinical practice.Purpose To systematically evaluate the horizontal transmission of Streptococcus mutans in children and analyze its relationship with dental caries. Methods Seven databases were searched for observational studies that have determined the transmission of S. mutans among children younger than seven years. Selection of included studies, data extraction, and quality assessment using Downs and Black's (1998) scoring system were performed. The inverse variance random-effect approach was used to pool the results, and statistical heterogeneity was evaluated using I-squared statistics. Results Fifteen studies were included for qualitative synthesis, five of which were pooled for quantitative analysis. The risk ratio (RR) of sharing only one genotype in caries-free children versus children with caries was found to be 0.60 (95 percent confidence interval [95% CI] equals 0.45 to 0.80; P ≤ 0.001). The RR of sharing more than one genotype was 1.46 (95% CI equals 1.13 to 1.89; P=0.004) in children with caries versus caries-free children. These findings imply that children sharing only one genotype have a 40 percent lesser risk, and children sharing more than one genotype have a 46 percent higher risk of having dental caries. Conclusions The systematic review provides evidence of the horizontal transmission of S. mutans and its association with dental caries.Purpose The purpose of this study was to assess the effect of potassium iodide (KI) after applying silver diamine fluoride (SDF) on the staining of demineralized dentin covered or not by a composite resin layer. Methods Dentin blocks from 30 bovine incisors were demineralized and randomly allocated in three groups (N equals 10) (1) control (no treatment); (2) treated with SDF; and (3) treated with SDF and KI. Half of the specimens of each group received a composite resin restoration immediately after treatment. A colorimetric evaluation, according to the CIE L*a*b* system, was performed at baseline and after seven, 14, 30, and 60 days. P22077 The ΔE data were analyzed using the generalized linear model (Δ equals 0.05). Results The use of KI immediately after applying SDF decreased the dentin staining at all assessment times. SDF treatment only stained the dentin under composite resin after 60 days. The application of KI reduced the dentin under composite resin staining as ΔE values were similar to the control group even after 60 days. Conclusions The use of potassium iodide minimizes the darkening of dentin and prevents the staining of the dentin under composite resin restorations in the long-term.Purpose Since pediatric zirconia crowns (ZRCs) are prefabricated, they may be sterilized following try-in for re-use. Possible changes in color stability, gloss, and translucency were evaluated for four brands of prefabricated zirconia crowns following autoclave and cold sterilization. Methods Sixteen maxillary right central incisor prefabricated ZRCs were obtained from NuSmile ®, Sprig, Cheng Crowns, and Kinder Krowns ® manufacturers and either autoclaved or cold sterilized. Gloss unit measurements were obtained with a small object Novo-Curve glossmeter. CIE-L*a*b* system values were measured with a CM-700d spectrophotometer under three different illuminants to calculate DE (quantitative representation of the perceived color). ΔE equals one was used for perceptibility threshold (PT) and ΔE equals 2.7 for acceptability threshold (AT). Results All groups' baseline was ΔE less than one for all illuminants except Cheng Crowns to be autoclaved, indicating crowns are not identical in color from the manufacturer. For autoclaving, Cheng Crowns reached ΔE PT greater than one following the 10th sterilization cycle for all illuminants (D65 1.