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In addition to identifying the expected ATR-targeted S/T-Q motif, we identified enrichment of an S/T-P-X-K motif in the set of ATR-dependent events, suggesting that ATR promotes signaling via proline-directed kinase(s) during meiosis. Indeed, we found that ATR signaling is important for the proper localization of CDK2 in spermatocytes. Overall, our analysis establishes a map of ATR signaling in mouse testes and highlights potential meiotic-specific actions of ATR during prophase I progression.DNA damage response mechanisms have meiotic roles that ensure successful gamete formation. While completion of meiotic double-strand break (DSB) repair requires the canonical RAD9A-RAD1-HUS1 (9A-1-1) complex, mammalian meiocytes also express RAD9A and HUS1 paralogs, RAD9B and HUS1B, predicted to form alternative 9-1-1 complexes. The RAD1 subunit is shared by all predicted 9-1-1 complexes and localizes to meiotic chromosomes even in the absence of HUS1 and RAD9A. Here, we report that testis-specific disruption of RAD1 in mice resulted in impaired DSB repair, germ cell depletion, and infertility. Unlike Hus1 or Rad9a disruption, Rad1 loss in meiocytes also caused severe defects in homolog synapsis, impaired phosphorylation of ATR targets such as H2AX, CHK1, and HORMAD2, and compromised meiotic sex chromosome inactivation. Together, these results establish critical roles for both canonical and alternative 9-1-1 complexes in meiotic ATR activation and successful prophase I completion.<br /><br /> , derived from observational data published by the Robert Koch Institute, Berlin, Germany, is a commonly used parameter to illustrate the course of the COVID-19 pandemic in Germany. The parameter <br /><br /> , equivalent to the doubling-time of the virus described by our research group, has also been useful in this regard.<br /><br /> To identify and compare parameters suitable for monitoring the course of the pandemic and to evaluate the extent to which these reflect qualitatively and quantitatively the effects of interventional measures introduced to control the pandemic.<br /><br /> Parameters potentially useful for monitoring the course of the pandemic were obtained empirically or derived using the Bateman SIZ model and observational data for the daily increase in the number of new infections. The doubling-time in the number of infections, <br /><br /> was obtained by curve-fitting observational data for the previous 14-day interval and a fixed value for t<br /><br /> (half-life for rate of recovery = 6.24 days). The effects of the interventional measuparameter for making decisions in real-time, with minimum delay, whether lockdown measures should be implemented.<br /><br /> This clinical practice guideline is based on a systematic review to assess the use of multiparametric magnetic resonance imaging (mpMRI) in the diagnosis of clinically significant prostate cancer (csPCa) for biopsy-naive men and men with a prior negative transrectal ultrasound-guided systematic biopsy (TRUS-SB) at elevated risk.<br /><br /> The methods of the clinical practice guideline included searches to September of 2020 of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. Internal and external reviews were conducted.<br /><br /> The recommendations areRecommendation 1 For biopsy-naive patients at elevated risk of csPCa, mpMRI is recommended prior to biopsy in patients who are candidates for curative management with suspected clinically localized prostate cancer.- If the mpMRI is positive, mpMRI-targeted biopsy (TB) and TRUS-SB should be performed together to maximize detection of csPCa.- If the mpMRI is negative, consider forgoing any biopsy after discussion of the risks and benefits with the patiengeted biopsy (TB) and TRUS-SB should be performed together to maximize detection of csPCa.- If the mpMRI is negative, consider forgoing any biopsy after discussion of the risks and benefits with the patient as part of shared decision-making and ongoing followup.Recommendation 2 In patients who had a prior negative TRUS-SB and demonstrate a high risk of having csPCa in whom curative management is being considered- mpMRI should be performed.- If the mpMRI is positive, targeted biopsy should be performed. Concomitant TRUS-SB can be considered depending on the patient's risk profile and time since prior TRUS-SB biopsy.- If the mpMRI is negative, consider forgoing a TRUS-SB only after discussion of the risks and benefits with the patient as part of shared decision-making and ongoing followup.Recommendation 3 mpMRI should be performed and interpreted in compliance with the current Prostate Imaging Reporting &amp; Data System (PI-RADS) guidelines.Three Gram-negative, rod-shaped, oxidase-positive, non-spore-forming, non-motile strains (C130915_07T, C150915_16 and C150915_17) were isolated from lymph nodes of Algerian cows. On the basis of 16S rRNA gene and whole genome similarities, the isolates were almost identical and clearly grouped in the genus Pseudochrobactrum. This allocation was confirmed by the analysis of fatty acids (C19cyclo, C18  1, C18  0, C16  1 and C16  0) and of polar lipids (major components phosphatidylethanolamine, ornithine-lipids, phosphatidylglycerol, cardiolipin and phosphatidylcholine, plus moderate amounts of phosphatidylmonomethylethanolamine, phosphatidyldimethylethanolamine and other aminolipids). Genomic, physiological and biochemical data differentiated these isolates from previously described Pseudochrobactrum species in DNA relatedness, carbon assimilation pattern and growth temperature range. Thus, these organisms represent a novel species of the genus Pseudochrobactrum, for which the name Pseudochrobactrum algeriensis sp. nov. [https://www.selleckchem.com/products/azd2014.html Vistusertib price] is proposed (type strain C130915_07T=CECT30232T=LMG 32378T).Three novel strains of Gram-stain-negative, obligately anaerobic, spore-forming straight or slightly curved rods with pointed ends occurring singly or in pairs were isolated from the faeces of healthy human children. The strains were characterized by mesophilic fermentative metabolism and production of acetate, ethanol and H2 as the end metabolic products. Strains ASD3451 and ASD5720T were motile, fermented lactose and raffinose, and weakly fermented maltose. Strain ASD4241T was non-motile and did not ferment the carbohydrates listed above but fermented starch. Strains ASD3451 and ASD5720T shared average nucleotide identity higher than 98.5 % with each other, while ASD4241T had only 88.5-89 % identity to them. Based on phylogenetic and chemotaxonomic analyses, we propose Diplocloster agilis gen. nov., sp. nov. (ASD5720T=JCM 34353T=VKM B-3497T) and Diplocloster modestus sp. nov. (ASD4241T=JCM 34351T=VKM B-3498T) within the family Lachnospiraceae.Bacteria isolated from onion bulbs suffering from bacterial decay in the United States and Norway were previously shown to belong to the genus Rahnella based on partial housekeeping gene sequences and/or fatty acid analysis. However, many strains could not be assigned to any existing Rahnella species. Additionally, strains isolated from creek water and oak as well as a strain with bioremediation properties were assigned to Rahnella based on partial housekeeping gene sequences. The taxonomic status of these 21 strains was investigated using multilocus sequence analysis, whole genome analyses, phenotypic assays and fatty acid analysis. Phylogenetic and phylogenomic analyses separated the strains into five clusters, one of which corresponded to Rahnella aceris. The remaining four clusters could be differentiated both genotypically and phenotypically from each other and existing Rahnella species. Based on these results, we propose the description of four novel species Rahnella perminowiae sp. nov. (type strain SL6T=LMG 32257T=DSM 112609T), Rahnella bonaserana sp. nov. (H11bT=LMG 32256T=DSM 112610T), Rahnella rivi sp. nov. (FC061912-KT=LMG 32259T=DSM 112611T) and Rahnella ecdela sp. nov. (FRB 231T=LMG 32255T=DSM 112612T).A moderately halophilic bacterium, designated strain KX20305T, was isolated from sediment collected from a cold seep field in the South China Sea. Cells of strain KX20305T were Gram-stain-negative, rod-shaped, non-motile, facultatively anaerobic, oxidase- and catalase-positive, and grew optimally at 25-30 °C, pH 6.0-8.0 and with 3-6 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain KX20305T grouped with members of the genus Aequorivita, including Aequorivita aquimaris D-24T (98.3 % sequence similarity), Aequorivita vladivostokensis KMM 3516T (98.1 %) and Aequorivita echinoideorum CC-CZW007T (97.5 %). Genome sequencing of strain KX20305T revealed a genome size of 3.35 Mb and a DNA G+C content of 38.71 mol%. Genomic average nucleotide identity (orthoANI) values of strain KX20305T with A. aquimaris D-24T, A. vladivostokensis KMM 3516T and A. echinoideorum JCM 30378T were 83.8, 81.7 and 75.4 %, respectively, while in silico DNA-DNA hybridization (GGDC) values for strain KX20305T with these strains were 27.2, 25.0 and 19.6 %, respectively. The major fatty acids of strain KX20305T were iso-C15  0, iso-C17  0 3-OH and 10-methyl C16  0/iso-C17  1  ω9c. The predominant respiratory quinone was menaquinone-6 (MK-6). The polar lipids mainly comprised phosphatidylethanolamine, two unidentified aminolipids and two unidentified lipids. Based on comparative analysis of phylogenetic, phylogenomic, phenotypic and chemotaxonomic characteristics, strain KX20305T represents a novel species of the genus Aequorivita, for which the name Aequorivita iocasae sp. nov. is proposed. The type strain is KX20305T (=KCTC 82699T=MCCC 1K06238T=JCM 34635T).<br /><br /> To explore communication and engagement in everyday situations between persons with young-onset dementia (YOD) living in a nursing home (NH) and the caregivers.<br /><br /> The study draws on ethnographic methods aligned with participatory design. Three residents with YOD living in a NH and eight staff members were recruited. A narrative approach was used for data collection and analysis.<br /><br /> Three narrative vignettes were developed representing everyday situations in which communication and engagement was enacted among residents and caregiver staff (a) waiting for something to happen, (b) tensions about everyday communication, and (c) negotiating a combined living + working environment. The findings stress a paradoxical tension rooted in the NH as residence and workplace as well as place of calm and place of boredom. The everyday situations are interpreted differently from the perspective of the residents and staff.<br /><br /> The identified paradox of planned and spontaneous situations influences communication and engagement in everyday life, and the potentiality for active engagement embedded in contexts of units for residents with YOD. The degree to which everyday activities and encounters are redefined and renegotiated is an important part of caregiving practices in NH settings for residents with YOD.<br /><br />The identified paradox of planned and spontaneous situations influences communication and engagement in everyday life, and the potentiality for active engagement embedded in contexts of units for residents with YOD. The degree to which everyday activities and encounters are redefined and renegotiated is an important part of caregiving practices in NH settings for residents with YOD.