Genomics of severe and treatment‐resistant obsessive–compulsive disorder treated with deep brain stimulation: A preliminary investigation

Individuals with severe and treatment-resistant obsessive-compulsive disorder (trOCD) represent a small but severely disabled group of patients. Since trOCD cases eligible for deep brain stimulation (DBS) probably comprise the most severe end of the OCD spectrum, we hypothesize that they may be more likely to have a strong genetic contribution to their disorder. Therefore, while the worldwide population of DBS-treated cases may be small (~300), screening these individuals with modern genomic methods may accelerate gene discovery in OCD. As such, we have begun to collect DNA from trOCD cases who qualify for DBS, and here we report results from whole exome sequencing and microarray genotyping of our first five cases. All participants had previously received DBS in the bed nucleus of stria terminalis (BNST), with two patients responding to the surgery and one showing a partial response. Our analyses focused on gene-disruptive rare variants (GDRVs; rare, predicted-deleterious single-nucleotide variants or copy number variants overlapping protein-coding genes). Three of the five cases carried a GDRV, including a missense variant in the ion transporter domain of KCNB1, a deletion at 15q11.2, and a duplication at 15q26.1. The KCNB1 variant (hg19 chr20-47991077-C-T, NM_004975.3:c.1020G>A, p.Met340Ile) causes substitution of methionine for isoleucine in the trans-membrane region of neuronal potassium voltage-gated ion channel KV2.1. This KCNB1 substitution (Met340Ile) is located in a highly constrained region of the protein where other rare missense variants have previously been associated with neurodevelopmental disorders. The patient carrying the Met340Ile variant responded to DBS, which suggests that genetic factors could potentially be predictors of treatment response in DBS for OCD. In sum, we have established a protocol for recruiting and genomically characterizing trOCD cases. Preliminary results suggest that this will be an informative strategy for finding risk genes in OCD

Silver Linings at the Dawn of a ‘Golden Age'

ACKNOWLEDGMENTS We would like to thank the editors at Frontiers for their support and patience, and the careful consideration two reviewers gave to this manuscript. MJW would like to acknowledge that, at Fairbanks, he is working on the ancestral land of Troth Yeddha’, home of the Lower Tanana people. He would also like to acknowledge that the lands on which he does his work are the ancestral lands of the Dené people who stewarded those lands for thousands of years and continue to steward those lands, further he would like to thank them and respect their enduring relationship to their homelands.Peer reviewedPublisher PD

Editorial: A Golden Age for Strontium Isotope Research? Current Advances in Paleoecological and Archaeological Research

Peer reviewedPublisher PD

The temporal evolution of subduction initiation in the Samail ophiolite: high-precision U–Pb zircon petrochronology of the metamorphic sole

High-precision dating of the metamorphic sole of ophiolites can provide insight into the tectonic evolution of ophiolites and subduction zone processes. To understand subduction initiation beneath a young, well-preserved and well-characterized ophiolite, we performed coupled zircon laser-ablation inductively coupled mass spectrometry trace element analyses and high-precision isotope dilution-thermal ionization mass spectrometry U–Pb dating on 25 samples from the metamorphic sole of the Samail ophiolite (Oman-United Arab Emirates). Zircon grains from amphibolite- to granulite-facies (0.8–1.3 GPa, ~700–900°C), garnet- and clinopyroxene-bearing amphibolite samples (n = 18) show systematic trends of decreasing heavy rare earth element slope (HREE; Yb/Dy) with decreasing Yb concentration, reflecting progressive depletion of the HREE during prograde garnet growth. For half of the garnet-clinopyroxene amphibolite samples, Ti-in-zircon temperatures increase, and U–Pb dates young with decreasing HREE slope, consistent with coupled zircon and garnet growth during prograde metamorphism. In the remaining samples, there is no apparent variation in Ti-in-zircon temperature with decreasing HREE slope, and the combined U–Pb and geochemical data suggest zircon crystallization along either the prograde to peak or prograde to initial retrograde portions of the metamorphic P–T–t path. The new data bracket the timing of prograde garnet and zircon growth in the highest grade rocks of the metamorphic sole between 96.698 ± 0.094 and 95.161 ± 0.064 Ma, in contrast with previously published geochronology suggesting prograde metamorphism at ~104 Ma. Garnet-free amphibolites and leucocratic pods from lower grade (but still upper amphibolite facies) portions of the sole are uniformly HREE enriched (Yb/Dy > 5) and are ~0.5–1.3 Myr younger than the higher grade rocks from the same localities, constraining the temporal offset between the metamorphism and juxtaposition of the higher and lower grade units. Positive zircon εHf (+6.5 to +14.6) for all but one of the dated amphibolites are consistent with an oceanic basalt protolith for the sole. Our new data indicate that prograde sole metamorphism (96.7–95.2 Ma) immediately predated and overlapped growth of the overlying ophiolite crust (96.1–95.2 Ma). The ~600 ky offset between the onset of sole metamorphism in the northern portion of the ophiolite versus the start of ophiolite magmatism is an order of magnitude shorter than previously proposed (~8 Ma) and is consistent with either spontaneous subduction initiation or an abbreviated period of initial thrusting during induced subduction initiation. Taken together, the sole and ophiolite crust preserve a record of the first ~1.5 Myr of subduction. A gradient in the initiation of high-grade metamorphism from the northwest (96.7 Ma) to southeast (96.0–95.7 Ma) may record propagation of the nascent subduction zone and/or variations in subduction rate along the length of the ophiolite

Escherichia coli biofilms have an organized and complex extracellular matrix structure

Bacterial biofilms are ubiquitous in nature, and their resilience is derived in part from a complex extracellular matrix that can be tailored to meet environmental demands. Although common developmental stages leading to biofilm formation have been described, how the extracellular components are organized to allow three-dimensional biofilm development is not well understood. Here we show that uropathogenic Escherichia coli (UPEC) strains produce a biofilm with a highly ordered and complex extracellular matrix (ECM). We used electron microscopy (EM) techniques to image floating biofilms (pellicles) formed by UPEC. EM revealed intricately constructed substructures within the ECM that encase individual, spatially segregated bacteria with a distinctive morphology. Mutational and biochemical analyses of these biofilms confirmed curli as a major matrix component and revealed important roles for cellulose, flagella, and type 1 pili in pellicle integrity and ECM infrastructure. Collectively, the findings of this study elucidated that UPEC pellicles have a highly organized ultrastructure that varies spatially across the multicellular community

Oil fate and mass balance for the Deepwater Horizon oil spill

Based on oil fate modeling of the Deepwater Horizon spill through August 2010, during June and July 2010, ~89% of the oil surfaced, ~5% entered (by dissolving or as microdroplets) the deep plume (\u3e900 m), and ~6% dissolved and biodegraded between 900 m and 40 m. Subsea dispersant application reduced surfacing oil by ~7% and evaporation of volatiles by ~26%. By July 2011, of the total oil, ~41% evaporated, ~15% was ashore and in nearshore (\u3c10 m) sediments, ~3% was removed by responders, ~38.4% was in the water column (partially degraded; 29% shallower and 9.4% deeper than 40 m), and ~2.6% sedimented in waters \u3e10 m (including 1.5% after August 2010). Volatile and soluble fractions that did not evaporate biodegraded by the end of August 2010, leaving residual oil to disperse and potentially settle. Model estimates were validated by comparison to field observations of floating oil and atmospheric emissions

Suicide rates amongst individuals from ethnic minority backgrounds: A systematic review and meta-analysis.

From Europe PMC via Jisc Publications RouterHistory: epub 2022-04-28, ppub 2022-05-01Publication status: PublishedBackgroundExisting evidence suggests that some individuals from ethnic minority backgrounds are at increased risk of suicide compared to their majority ethnic counterparts, whereas others are at decreased risk. We aimed to estimate the absolute and relative risk of suicide in individuals from ethnic minority backgrounds globally.MethodsDatabases (Medline, Embase, and PsycInfo) were searched for epidemiological studies between 01/01/2000 and 3/07/2020, which provided data on absolute and relative rates of suicide amongst ethnic minority groups. Studies reporting on clinical or specific populations were excluded. Pairs of reviewers independently screened titles, abstracts, and full texts. We used random effects meta-analysis to estimate overall, sex, location, migrant status, and ancestral origin, stratified pooled estimates for absolute and rate ratios. PROSPERO registration: CRD42020197940.FindingsA total of 128 studies were included with 6,026,103 suicide deaths in individuals from an ethnic minority background across 31 countries. Using data from 42 moderate-high quality studies, we estimated a pooled suicide rate of 12·1 per 100,000 (95% CIs 8·4-17·6) in people from ethnic minority backgrounds with a broad range of estimates (1·2-139·7 per 100,000). There was weak statistical evidence from 51 moderate-high quality studies that individuals from ethnic minority groups were more likely to die by suicide (RR 1·3 95% CIs 0·9-1·7) with again a broad range amongst studies (RR 0·2-18·5). In our sub-group analysis we only found evidence of elevated risk for indigenous populations (RR: 2·8 95% CIs 1·9-4·0; pooled rate: 23·2 per 100,000 95% CIs 14·7-36·6). There was very substantial heterogeneity (I2  > 98%) between studies for all pooled estimates.InterpretationThe homogeneous grouping of individuals from ethnic minority backgrounds is inappropriate. To support suicide prevention in marginalised groups, further exploration of important contextual differences in risk is required. It is possible that some ethnic minority groups (for example those from indigenous backgrounds) have higher rates of suicide than majority populations.FundingNo specific funding was provided to conduct this research. DK is funded by Wellcome Trust and Elizabeth Blackwell Institute Bristol. Matthew Spittal is a recipient of an Australian Research Council Future Fellowship (project number FT180100075) funded by the Australian Government. Rebecca Musgrove is funded by the NIHR Greater Manchester Patient Safety Translational Research Centre (PSTRC-2016-003)

Long-Term Changes in Physical Activity Following a One-Year Home-Based Physical Activity Counseling Program in Older Adults with Multiple Morbidities

This study assessed the sustained effect of a physical activity (PA) counseling intervention on PA one year after intervention, predictors of sustained PA participation, and three classes of post-intervention PA trajectories (improvers, maintainers, and decliners) in 238 older Veterans. Declines in minutes of PA from 12 to 24 months were observed for both the treatment and control arms of the study. PA at 12 months was the strongest predictor of post-intervention changes in PA. To our surprise, those who took up the intervention and increased PA levels the most, had significant declines in post-intervention PA. Analysis of the three post-intervention PA trajectories demonstrated that the maintenance group actually reflected a group of nonresponders to the intervention who had more comorbidities, lower self-efficacy, and worse physical function than the improvers or decliners. Results suggest that behavioral counseling/support must be ongoing to promote maintenance. Strategies to promote PA appropriately to subgroups of individuals are needed

Taxonomic patterns in the zoonotic potential of mammalian viruses

Predicting and simplifying which pathogens may spill over from animals to humans is a major priority in infectious disease biology. Many efforts to determine which viruses are at risk of spillover use a subset of viral traits to find trait-based associations with spillover. We adapt a new method—phylofactorization—to identify not traits but lineages of viruses at risk of spilling over. Phylofactorization is used to partition the International Committee on Taxonomy of Viruses viral taxonomy based on non-human host range of viruses and whether there exists evidence the viruses have infected humans. We identify clades on a range of taxonomic levels with high or low propensities to spillover, thereby simplifying the classification of zoonotic potential of mammalian viruses. Phylofactorization by whether a virus is zoonotic yields many disjoint clades of viruses containing few to no representatives that have spilled over to humans. Phylofactorization by non-human host breadth yields several clades with significantly higher host breadth. We connect the phylogenetic factors above with life-histories of clades, revisit trait-based analyses, and illustrate how cladistic coarse-graining of zoonotic potential can refine trait-based analyses by illuminating clade-specific determinants of spillover risk