Diazhovgaard5253
Septins are conserved cytoskeletal proteins that regulate cell cortex mechanics. The mechanisms of their interactions with the plasma membrane remain poorly understood. Here, we show by cell-free reconstitution that binding to flat lipid membranes requires electrostatic interactions of septins with anionic lipids and promotes the ordered self-assembly of fly septins into filamentous meshworks. Transmission electron microscopy reveals that both fly and mammalian septin hexamers form arrays of single and paired filaments. Atomic force microscopy and quartz crystal microbalance demonstrate that the fly filaments form mechanically rigid, 12- to 18-nm thick, double layers of septins. By contrast, C-terminally truncated septin mutants form 4-nm thin monolayers, indicating that stacking requires the C-terminal coiled coils on DSep2 and Pnut subunits. Our work shows that membrane binding is required for fly septins to form ordered arrays of single and paired filaments and provides new insights into the mechanisms by which septins may regulate cell surface mechanics.A previous report found an association of topic choice with race-based funding disparities among R01 applications submitted to the National Institutes of Health ('NIH') between 2011 and 2015. Applications submitted by African American or Black ('AAB') Principal Investigators ('PIs') skewed toward a small number of topics that were less likely to be funded (or 'awarded'). It was suggested that lower award rates may be related to topic-related biases of peer reviewers. However, the report did not account for differential funding ecologies among NIH Institutes and Centers ('ICs'). In a re-analysis, we find that 10% of 148 topics account for 50% of applications submitted by AAB PIs. These applications on 'AAB Preferred' topics were funded at lower rates, but peer review outcomes were similar. The lower rate of funding for these topics was primarily due to their assignment to ICs with lower award rates, not to peer-reviewer preferences.Despite the high burden of pain experienced by hospitalised neonates, there are few analgesics with proven efficacy. Testing analgesics in neonates is experimentally and ethically challenging and minimising the number of neonates required to demonstrate efficacy is essential. EEG (electroencephalography)-derived measures of noxious-evoked brain activity can be used to assess analgesic efficacy; however, as variability exists in neonate's responses to painful procedures, large sample sizes are often required. Here, we present an experimental paradigm to account for individual differences in noxious-evoked baseline sensitivity which can be used to improve the design of analgesic trials in neonates. The paradigm is developed and tested across four observational studies using clinical, experimental, and simulated data (92 neonates). We provide evidence of the efficacy of gentle brushing and paracetamol, substantiating the need for randomised controlled trials of these interventions. This work provides an important step towards safe, cost-effective clinical trials of analgesics in neonates.Risk factors for cardiovascular diseases trigger molecular changes that harm the endothelial cells in the heart, but exercise can suppress these effects.Clamp loaders are AAA+ ATPases that load sliding clamps onto DNA. We mapped the mutational sensitivity of the T4 bacteriophage sliding clamp and clamp loader by deep mutagenesis, and found that residues not involved in catalysis or binding display remarkable tolerance to mutation. An exception is a glutamine residue in the AAA+ module (Gln 118) that is not located at a catalytic or interfacial site. Gln 118 forms a hydrogen-bonded junction in a helical unit that we term the central coupler, because it connects the catalytic centers to DNA and the sliding clamp. A suppressor mutation indicates that hydrogen bonding in the junction is important, and molecular dynamics simulations reveal that it maintains rigidity in the central coupler. The glutamine-mediated junction is preserved in diverse AAA+ ATPases, suggesting that a connected network of hydrogen bonds that links ATP molecules is an essential aspect of allosteric communication in these proteins.
Oral appliance (OA) therapy usage can be objectively measured through temperature-sensing data chips embedded in the appliance. Initial reports of group data for short-term treatment usage suggest good nightly hours of usage. However, individual variability in treatment usage patterns has not been assessed. We aimed to identify OA treatment usage subtypes in the first 60 days and the earliest predictors of these usage patterns.
OSA patients were recruited for a study of OA therapy with an embedded compliance chip (DentiTrac, Braebon, Canada). Fifty-eight participants with 60 days of downloadable treatment usage data (5-minute readings) were analyzed. A hierarchical cluster analysis was used to group participants with similar usage patterns. A random forest classification model was used to identify the minimum number of days to predict usage subtype.
Three user groups were identified and named "consistent users" (48.3%), "inconsistent users" (32.8%) and "non-users" (19.0%). The first twenty days provided optimal data to predict which treatment usage group a patient would belong to at 60-days (90% accuracy). The strongest predictors of user group were downloaded usage data; average wear time and number of days missed.
Granular analysis of OA usage data suggests the existence of treatment user subtypes (consistent, inconsistent and non-users). Our data suggest that 60-day usage patterns can be identified in the first twenty days of treatment using downloaded treatment usage data. Understanding initial treatment usage patterns provide an opportunity for early intervention to improve long-term usage and outcomes.
Granular analysis of OA usage data suggests the existence of treatment user subtypes (consistent, inconsistent and non-users). Our data suggest that 60-day usage patterns can be identified in the first twenty days of treatment using downloaded treatment usage data. Understanding initial treatment usage patterns provide an opportunity for early intervention to improve long-term usage and outcomes.A novel bacterial strain, EJ-4T, isolated from stream water collected at Seo-ho in Suwon, Republic of Korea, was characterized based on a polyphasic taxonomic approach. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain EJ-4T belonged to the genus Comamonas. The isolate is Gram-stain-negative, non-motile, aerobic, rod-shaped and forms pale yellow colonies on trypticase soy agar. The optimal growth of this strain was observed aerobically at 30 °C, pH 7 and 0.5 % NaCl. The major fatty acids were summed feature 3 (C16 1 ω7c and/or C16 1 ω6c; 39.7 %) and C16 0 (32.0 %). The G+C content of strain EJ-4T was 58.4mol %. The average nucleotide identity and digital DNA-DNA hybridization values between strain EJ-4T and Comamoas testosteroni were 91.8 and 31.2 %, respectively. The major polar lipids detected in the isolate were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The predominant isoprenoid quinone was ubiquinone-8. Based on the results of polyphasic taxonomic analysis of strain EJ-4T, we describe a novel species of the genus Comamonas, for which the name Comamonas suwonensis sp. nov. has been proposed, with EJ-4T (=KCTC 82074T=JCM 34179T=KEMB 1602-279T) as the type strain.A novel Gram-stain-negative, facultative aerobic and rod-shaped bacterium, designated as MKL-01T and isolated from the blood of immunocompromised patient, was genotypically and phenotypically characterized. The colonies were found to be creamy yellow and convex. Phylogenetic analysis based on 16S rRNA gene and whole-genome sequences revealed that strain MKL-01T was most closely related to Cupriavidus gilardii LMG 5886T, present within a large cluster in the genus Cupriavidus. The genome sequence of strain MKL-01T showed the highest average nucleotide identity value of 92.1 % and digital DNA-DNA hybridization value of 44.8 % with the closely related species C. gilardii LMG 5886T. The genome size of the isolate was 5 750 268 bp, with a G+C content of 67.87 mol%. The strain could grow at 10-45 °C (optimum, 37-40 °C), in the presence of 0-10 % (w/v) NaCl (optimum, 0.5%) and at pH 6.0-10.0 (optimum, pH 7.0). Strain MKL-01T was positive for catalase and negative for oxidase. The major fatty acids were C16 0, summed feature 3 (C16 1 ω7c/C16 1 ω6c and/or C16 1 ω6c/C16 1 ω7c) and summed feature 8 (C18 1 ω7c and/or C18 1 ω6c). The polar lipid profile consisted of phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids and one unidentified polar lipid. Moreover, strain MKL-01T contained ubiquinone Q-8 as the sole respiratory quinone. Based on its molecular, phenotypic and chemotaxonomic properties, strain MKL-01T represents a novel species of the genus Cupriavidus; the name Cupriavidus cauae sp. nov. is proposed for this strain. The type strain is MKL-01T.Group A rotaviruses (RVAs) infect a wide variety of mammalian and avian species. Animals act as a potential reservoir to RVA human infections by direct virion transmission or by contributing genes to reassortants. Here, we report the molecular characterization of a rare human RVA strain Ni17-46 with a genotype G15P[14], isolated in Japan in 2017 during rotavirus surveillance in a paediatric outpatient clinic. The genome constellation of this strain was G15-P[14]-I2-R2-C2-M2-A13-N2-T9-E2-H3. This is the first report of an RVA with G15 genotype in humans, and sequencing and phylogenetic analysis results suggest that human infection with this strain has zoonotic origin from the bovine species. Given the fact that this strain was isolated from a patient with gastroenteritis and dehydration symptoms, we must take into account the virulence of this strain in humans.A novel Gram-stain-negative, aerobic, gliding, rod-shaped and carotenoid-pigmented bacterium, designated A20-9T, was isolated from a microbial consortium of polyethylene terephthalate enriched from a deep-sea sediment sample from the Western Pacific. Growth was observed at salinities of 1-8 %, at pH 6.5-8 and at temperatures of 10-40 °C. The results of phylogenetic analyses based on the genome indicated that A20-9T formed a monophyletic branch affiliated to the family Schleiferiaceae, and the 16S rRNA gene sequences exhibited the maximum sequence similarity of 93.8 % with Owenweeksia hongkongensis DSM 17368T, followed by similarities of 90.4, 90.1 and 88.8 % with Phaeocystidibacter luteus MCCC 1F01079T, Vicingus serpentipes DSM 103558T and Salibacter halophilus MCCC 1K02288T, respectively. Its complete genome size was 4 035 598 bp, the genomic DNA G+C content was 43.2 mol%. Whole genome comparisons indicated that A20-9T and O. hongkongensis DSM 17368T shared 67.8 % average nucleotide identity, 62.7 % average amino acid identity value, 46.6% of conserved proteins and 17.8 % digital DNA-DNA hybridization identity. A20-9T contained MK-7 as the major respiratory quinone. Its major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and phospatidylcholine; and the major fatty acids were iso-C15 0 (37.5 %), iso-C16 0 3-OH (12.4 %), and summed feature 3 (C16 1ω7c /C16 1ω6c, 11.6 %). Combining the genotypic and phenotypic data, A20-9T could be distinguished from the members of other genera within the family Schleiferiaceae and represents a novel genus, for which the name Croceimicrobium hydrocarbonivorans gen. nov., sp. nov. A-366 in vivo is proposed. The type strain is A20-9T (=MCCC 1A17358T =KCTC 72878T).