Community transcriptomics reveals universal patterns of protein sequence conservation in natural microbial communities

Background Combined metagenomic and metatranscriptomic datasets make it possible to study the molecular evolution of diverse microbial species recovered from their native habitats. The link between gene expression level and sequence conservation was examined using shotgun pyrosequencing of microbial community DNA and RNA from diverse marine environments, and from forest soil. Results Across all samples, expressed genes with transcripts in the RNA sample were significantly more conserved than non-expressed gene sets relative to best matches in reference databases. This discrepancy, observed for many diverse individual genomes and across entire communities, coincided with a shift in amino acid usage between these gene fractions. Expressed genes trended toward GC-enriched amino acids, consistent with a hypothesis of higher levels of functional constraint in this gene pool. Highly expressed genes were significantly more likely to fall within an orthologous gene set shared between closely related taxa (core genes). However, non-core genes, when expressed above the level of detection, were, on average, significantly more highly expressed than core genes based on transcript abundance normalized to gene abundance. Finally, expressed genes showed broad similarities in function across samples, being relatively enriched in genes of energy metabolism and underrepresented by genes of cell growth. Conclusions These patterns support the hypothesis, predicated on studies of model organisms, that gene expression level is a primary correlate of evolutionary rate across diverse microbial taxa from natural environments. Despite their complexity, meta-omic datasets can reveal broad evolutionary patterns across taxonomically, functionally, and environmentally diverse communities.Gordon and Betty Moore FoundationAgouron InstituteNational Science Foundation (U.S.)Center for Microbial Oceanography: Research and Educatio

Climate Change and Biosphere Response: Unlocking the Collections Vault

Natural history collections (NHCs) are an important source of the long-term data needed to understand how biota respond to ongoing anthropogenic climate change. These include taxon occurrence data for ecological modeling, as well as information that can be used to reconstruct mechanisms through which biota respond to changing climates. The full potential of NHCs for climate change research cannot be fully realized until high-quality data sets are conveniently accessible for research, but this requires that higher priority be placed on digitizing the holdings most useful for climate change research (e.g., whole-biota studies, time series, records of intensively sampled common taxa). Natural history collections must not neglect the proliferation of new information from efforts to understand how present-day ecosystems are responding to environmental change. These new directions require a strategic realignment for many NHC holders to complement their existing focus on taxonomy and systematics. To set these new priorities, we need strong partnerships between NHC holders and global change biologists

Pharmacists detecting atrial fibrillation in general practice: a qualitative focus group study

Background: Atrial fibrillation (AF) affects up to 10% of people aged ≥65 years, yet a third of all cases remain undetected. Practice-based pharmacists are in an ideal position to facilitate opportunistic AF screening, while increasing general practice capacity at a time of workforce crisis. Aim: To explore the perspectives of three stakeholder groups involved in the ‘Pharmacists Detecting Atrial Fibrillation’ (PDAF) study to elucidate the facilitators and barriers to pharmacist-led AF screening in general practice. Design & setting: A qualitative study took place, comprising homogeneous focus groups with stakeholders in Kent, UK. Method: The stakeholder groups — patients, general practice staff (GPS), and clinical pharmacists (CPs) — were recruited using convenience sampling. Audio-recordings were transcribed verbatim and analysed using a deductive Theoretical Domains Framework (TDF) approach. Results: Twenty-five patients, four pharmacists, and nine practice staff participated in six focus groups. Three main themes were identified: knowledge and awareness; prioritisation of resources; and environmental considerations. The public’s lack of awareness of AF-related risks and pharmacist-led screening services was highlighted. Practice-based pharmacists were perceived as an underutilised educational resource which, together with novel electrocardiogram devices, enabled convenient access to screening while reducing GPs’ workload. Participants agreed that AF screening should be incorporated into personalised health checks and at-risk groups should be prioritised, such as care home residents. Patients favoured the general practice environment over the community pharmacy where concerns of privacy, staffing, and commercialisation were raised. Conclusion: The findings of this study support the introduction of pharmacist-led AF screening programmes in general practice surgeries. Commissioners should consider the added value of utilising CPs and focus on the delivery of AF screening within an integrated service

Modelling and prediction of the peak-radiated sound in subsonic axisymmetric air jets using acoustic analogy-based asymptotic analysis

This paper uses asymptotic analysis within the generalized acoustic analogy formulation (Goldstein 2003 JFM488, 315–333. (doi:10.1017/S0022112003004890)) to develop a noise prediction model for the peak sound of axisymmetric round jets at subsonic acoustic Mach numbers (Ma). The analogy shows that the exact formula for the acoustic pressure is given by a convolution product of a propagator tensor (determined by the vector Green's function of the adjoint linearized Euler equations for a given jet mean flow) and a generalized source term representing the jet turbulence field. Using a low-frequency/small spread rate asymptotic expansion of the propagator, mean flow non-parallelism enters the lowest order Green's function solution via the streamwise component of the mean flow advection vector in a hyperbolic partial differential equation. We then address the predictive capability of the solution to this partial differential equation when used in the analogy through first-of-its-kind numerical calculations when an experimentally verified model of the turbulence source structure is used together with Reynolds-averaged Navier–Stokes solutions for the jet mean flow. Our noise predictions show a reasonable level of accuracy in the peak noise direction at Ma = 0.9, for Strouhal numbers up to about 0.6, and at Ma = 0.5 using modified source coefficients. Possible reasons for this are discussed. Moreover, the prediction range can be extended beyond unity Strouhal number by using an approximate composite asymptotic formula for the vector Green's function that reduces to the locally parallel flow limit at high frequencies

Deep Eutectic Solvents Based on Natural Ascorbic Acid Analogues and Choline Chloride

Deep eutectic solvents (DES) are one of the most promising green technologies to emerge in recent years given their combination of environmentally friendly credentials and useful functionalities. Considering the continued search for new DES -- especially those that exemplify the aforementioned characteristics, we report the preparation of DES based on natural analogues of L-ascorbic acid for the first time. The onset of eutectic melting occurred at temperatures far below the melting point of the individual components and resulted in the generation of glass forming fluids with glass transition temperatures, viscosities and flow behavior that are comparable to similar systems. This work expands the current array of DES that can be produced using naturally occurring components, which given their potential to be bio-derived, interesting physicochemical properties (e.g. propensity to supercool and vitrify) and apparent antibacterial nature, may provide utility within a range of applications

Basal terraces on melting ice shelves

Ocean waters melt the margins of Antarctic and Greenland glaciers, and individual glaciers' responses and the integrity of their ice shelves are expected to depend on the spatial distribution of melt. The bases of the ice shelves associated with Pine Island Glacier (West Antarctica) and Petermann Glacier (Greenland) have similar geometries, including kilometer-wide, hundreds-of-meter high channels oriented along and across the direction of ice flow. The channels are enhanced by, and constrain, oceanic melt. New meter-scale observations of basal topography reveal peculiar glaciated landscapes. Channel flanks are not smooth, but are instead stepped, with hundreds-of-meters-wide flat terraces separated by 5–50 m high walls. Melting is shown to be modulated by the geometry: constant across each terrace, changing from one terrace to the next, and greatly enhanced on the ~45° inclined walls. Melting is therefore fundamentally heterogeneous and likely associated with stratification in the ice-ocean boundary layer, challenging current models of ice shelf-ocean interactions

High Frequency Asymptotics for the Spin-Weighted Spheroidal Equation

We fully determine a uniformly valid asymptotic behaviour for large $a \omega$ and fixed $m$ of the angular solutions and eigenvalues of the spin-weighted spheroidal differential equation. We fully complement the analytic work with a numerical study.Comment: The .tar.gz file should contain 1 tex file, 24 figures in .ps format and 1 bibliography file in .bbl format. All these files are located in the same director

Opportunistic screening for atrial fibrillation by clinical pharmacists in UK general practice during the influenza vaccination season: a cross-sectional feasibility study

Background: Growing prevalence of atrial fibrillation (AF) in the ageing population, and its associated life-changing health and resource implications, have led to a need to improve its early detection. Primary care is an ideal place to screen for AF, however this is limited by shortages in general practitioner (GP) resources. Recent increases in the number of clinical pharmacists within primary care, makes them ideally placed to conduct AF screening. This study aimed to determine the feasibility of GP practice-based clinical pharmacists to screen the over 65s for AF, using digital technology and pulse palpation during the influenza vaccination season. Methods and Findings: Screening was conducted over two influenza vaccination seasons, 2017-2018 and 2018-2019 in four GP practices in Kent, UK. Pharmacists were trained by a cardiologist to pulse palpate, record and interpret a single-lead ECG (SLECG). Eligible persons aged ≥65 years, attending an influenza vaccination clinic were offered a free heart rhythm check. 604 participants were screened (median age 73 years, 42.7% male). Total prevalence of AF was 4.3%. All participants with AF qualified for anticoagulation and were more likely to be male (57.7%); older; have an increased BMI and have a CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥ 75, Diabetes, previous Stroke, Age 65-74 years, Sex category) score ≥ 3. The sensitivity and specificity of clinical pharmacists diagnosing AF using pulse palpation was 76.9% [95% CI: 56.4-91.0] and 92.2% [89.7-94.3], respectively. This rose to 88.5% (69.9-97.6) and 97.2% [95.5-98.4] with a SLECG. At follow-up, four participants (0.7%) were diagnosed with new AF and 3 (0.5%) were initiated on anticoagulation. Screening with SLECG also helped identify new non-AF cardiovascular diagnoses, such as left ventricular hypertrophy, in 28 participants (4.6%). The screening strategy was cost-effective in 71.8% and 64.3% of the estimates for SLECG or pulse palpation, respectively. Feedback from participants (422/604) was generally positive. Key limitations of the study were that the intervention did not reach individuals who did not attend the practice for an influenza vaccination and there was a limited representation of UK ethnic minority groups in the study cohort. Conclusions: This study demonstrates that AF screening performed by GP practice-based pharmacists was feasible, economically viable and positively endorsed by participants. Furthermore, diagnosis of AF by the clinical pharmacist using a SLECG was more sensitive and more specific than the use of pulse palpation alone. Future research should explore the key barriers preventing the adoption of national screening programmes

Fluoxetine for maintenance of remission and to improve quality of life in patients with Crohn's Disease: a pilot randomized placebo-controlled trial

Background and Aims: Previous studies have shown that antidepressants reduce inflammation in animal models of colitis. The present trial aimed to examine whether fluoxetine added to standard therapy for Crohn's disease [CD] maintained remission, improved quality of life [QoL] and/or mental health in people with CD as compared to placebo. Methods: A parallel randomized double-blind placebo controlled trial was conducted. Participants with clinically established CD, with quiescent or only mild disease, were randomly assigned to receive either fluoxetine 20 mg daily or placebo, and followed for 12 months. Participants provided blood and stool samples and completed mental health and QoL questionnaires. Immune functions were assessed by stimulated cytokine secretion [CD3/CD28 stimulation] and flow cytometry for cell type. Linear mixed-effects models were used to compare groups. Results: Of the 26 participants, 14 were randomized to receive fluoxetine and 12 to placebo. Overall, 14 [54%] participants were male. The mean age was 37.4 [SD=13.2] years. Fluoxetine had no effect on inflammatory bowel disease activity measured using either the Crohn's Disease Activity Index [F(3, 27.5)= 0.064, p=0.978] or faecal calprotectin [F(3, 32.5)=1.08, p=0.371], but did have modest effects on immune function. There was no effect of fluoxetine on physical, psychological, social or environmental QoL, anxiety or depressive symptoms as compared to placebo [all p>0.05]. Conclusions: In this small pilot clinical trial, fluoxetine was not superior to placebo in maintaining remission or improving QoL