Cross-Species Analyses Identify the BNIP-2 and Cdc42GAP Homology (BCH) Domain as a Distinct Functional Subclass of the CRAL_TRIO/Sec14 Superfamily

The CRAL_TRIO protein domain, which is unique to the Sec14 protein superfamily, binds to a diverse set of small lipophilic ligands. Similar domains are found in a range of different proteins including neurofibromatosis type-1, a Ras GTPase-activating Protein (RasGAP) and Rho guanine nucleotide exchange factors (RhoGEFs). Proteins containing this structural protein domain exhibit a low sequence similarity and ligand specificity while maintaining an overall characteristic three-dimensional structure. We have previously demonstrated that the BNIP-2 and Cdc42GAP Homology (BCH) protein domain, which shares a low sequence homology with the CRAL_TRIO domain, can serve as a regulatory scaffold that binds to Rho, RhoGEFs and RhoGAPs to control various cell signalling processes. In this work, we investigate 175 BCH domain-containing proteins from a wide range of different organisms. A phylogenetic analysis with ∼100 CRAL_TRIO and similar domains from eight representative species indicates a clear distinction of BCH-containing proteins as a novel subclass within the CRAL_TRIO/Sec14 superfamily. BCH-containing proteins contain a hallmark sequence motif R(R/K)h(R/K)(R/K)NL(R/K)xhhhhHPs (‘h’ is large and hydrophobic residue and ‘s’ is small and weekly polar residue) and can be further subdivided into three unique subtypes associated with BNIP-2-N, macro- and RhoGAP-type protein domains. A previously unknown group of genes encoding ‘BCH-only’ domains is also identified in plants and arthropod species. Based on an analysis of their gene-structure and their protein domain context we hypothesize that BCH domain-containing genes evolved through gene duplication, intron insertions and domain swapping events. Furthermore, we explore the point of divergence between BCH and CRAL-TRIO proteins in relation to their ability to bind small GTPases, GAPs and GEFs and lipid ligands. Our study suggests a need for a more extensive analysis of previously uncharacterized BCH, ‘BCH-like’ and CRAL_TRIO-containing proteins and their significance in regulating signaling events involving small GTPases

A comparison of methods to harmonize cortical thickness measurements across scanners and sites

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants' demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LME INT), (2) LME that models both site-specific random intercepts and age-related random slopes (LME INT+ SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2-81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3-85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (X-2 (3) = 63.704, p < 0.001) as well as casecontrol differences in age-related cortical thinning (X-2 (3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (X-2 (3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects.Stress-related psychiatric disorders across the life spa

Choice of primary health care source in an urbanized low-income community in Singapore: A mixed-methods study

10.1093/fampra/cmt064Family Practice31181-91FAPR

Optimal Shell Thickness of Metal@Insulator Nanoparticles for Net Enhancement of Photogenerated Polarons in P3HT Films

Embedding metal nanoparticles in the active layer of organic solar cells has been explored as a route for improving charge carrier generation, with localized field enhancement as a proposed mechanism. However, embedded metal nanoparticles can also act as charge recombination sites. To suppress such recombination, the metal nanoparticles are commonly coated with a thin insulating shell. At the same time, this insulating shell limits the extent that the localized enhanced electric field influences charge generation in the organic medium. It is presumed that there is an optimal thickness which maximizes field enhancement effects while suppressing recombination. Atomic Layer Deposition (ALD) was used to deposit Al₂O₃ layers of different thicknesses onto silver nanoparticles (Ag NPs), in a thin film of P3HT. Photoinduced absorption (PIA) spectroscopy was used to study the dependence of the photogenerated P3HT⁺ polaron population on the Al₂O₃ thickness. The optimal thickness was found to be 3–5 nm. This knowledge can be further applied in the design of metal nanoparticle-enhanced solar cells

Report 38: SARS-CoV-2 setting-specific transmission rates: a systematic review and meta-analysis

Since the end of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly across the world. Understanding the drivers of SARS-CoV-2 transmission is crucial for disease control policies but evidence of transmission rates in different settings remains limited. We conducted a systematic review to estimate the secondary attack rate (SAR) and observed reproduction number (Robs) in different settings and to explore differences by age, symptom status, duration of exposure and household size. A total of 97 studies were identified, 45 of which met inclusion criteria for meta-analysis. Households showed the highest transmission rates, with pooled SAR and Robs estimates of 21.1% (95% CI: 17.4%-24.8%) and 0.96 (95% CI: 0.67-1.32), respectively. Household SAR estimates were significantly higher where the duration of household exposure exceeded 5 days compared with exposure of 5 days or less. Attack rates related to familiar and prolonged close contacts, such as social events with family and friends were higher than those related to low-risk casual contacts, such as strangers (SAR of 5.9%, 95% CI: 3.8%-8.1% vs. 1.2%, 95% CI: 0.3%-2.1%). Estimates of SAR for asymptomatic index cases were approximately two thirds of those for symptomatic index (3.5% vs. 12.8%, p<0.001). We find moderate evidence for less transmission both from and to individuals under 20 years of age in the household context, but this difference is less evident when examining all settings. Prolonged contact in households and in settings with familiar close contacts increases the potential for transmission of SARS-CoV-2. Additionally, the differences observed in transmissibility by symptom status of index cases and the potential for age-dependent effects has important implications for outbreak control strategies such as contact tracing, testing and rapid isolation of cases. There was limited data to allow exploration of transmission patterns in workplaces, schools, and care-homes, highlighting the need for further research in such settings