Identification of Novel sRNAs in Mycobacterial Species

Bacterial small RNAs (sRNAs) are short transcripts that typically do not encode proteins and often act as regulators of gene expression through a variety of mechanisms. Regulatory sRNAs have been identified in many species, including Mycobacterium tuberculosis, the causative agent of tuberculosis. Here, we use a computational algorithm to predict sRNA candidates in the mycobacterial species M. smegmatis and M. bovis BCG and confirmed the expression of many sRNAs using Northern blotting. Thus, we have identified 17 and 23 novel sRNAs in M. smegmatis and M. bovis BCG, respectively. We have also applied a high-throughput technique (Deep-RACE) to map the 5′ and 3′ ends of many of these sRNAs and identified potential regulators of sRNAs by analysis of existing ChIP-seq datasets. The sRNAs identified in this work likely contribute to the unique biology of mycobacteria

Scientific mindfulness: a foundation for future themes in international business

We conceptualize new ways to qualify what themes should dominate the future IB research agenda by examining three questions: Whom should we ask? What should we ask and which selection criteria should we apply? What are the contextual forces? We propose scientific mindfulness as the way forward for generating themes in IB research

A study protocol for a randomised controlled feasibility trial of an intervention to increase activity and reduce sedentary behaviour in people with severe mental illness: Walking fOR Health (WORtH) Study

Abstract Background People with severe mental illness (SMI) are less physically active and more sedentary than healthy controls, contributing to poorer physical health outcomes in this population. There is a need to understand the feasibility and acceptability, and explore the effective components, of health behaviour change interventions targeting physical activity and sedentary behaviour in this population in rural and semi-rural settings. Methods This 13-week randomised controlled feasibility trial compares the Walking fOR Health (WORtH) multi-component behaviour change intervention, which includes education, goal-setting and self-monitoring, with a one-off education session. It aims to recruit 60 inactive adults with SMI via three community mental health teams in Ireland and Northern Ireland. Primary outcomes are related to feasibility and acceptability, including recruitment, retention and adherence rates, adverse events and qualitative feedback from participants and clinicians. Secondary outcome measures include self-reported and accelerometer-measured physical activity and sedentary behaviour, anthropometry measures, physical function and mental wellbeing. A mixed-methods process evaluation will be undertaken. This study protocol outlines changes to the study in response to the COVID-19 pandemic. Discussion This study will address the challenges and implications of remote delivery of the WORtH intervention due to the COVID-19 pandemic and inform the design of a future definitive randomised controlled trial if it is shown to be feasible. Trial registration The trial was registered on clinicaltrials.gov ( NCT04134871 ) on 22 October 2019

Developing an inverted Barrovian sequence; insights from monazite petrochronology

In the Himalayan region of Sikkim, the well-developed inverted metamorphic sequence of the Main Central Thrust (MCT) zone is folded, thus exposing several transects through the structure that reached similar metamorphic grades at different times. In-situ LA-ICP-MS U–Th–Pb monazite ages, linked to pressure–temperature conditions via trace-element reaction fingerprints, allow key aspects of the evolution of the thrust zone to be understood for the first time. The ages show that peak metamorphic conditions were reached earliest in the structurally highest part of the inverted metamorphic sequence, in the Greater Himalayan Sequence (GHS) in the hanging wall of the MCT. Monazite in this unit grew over a prolonged period between ~37 and 16 Ma in the southerly leading-edge of the thrust zone and between ~37 and 14.5 Ma in the northern rear-edge of the thrust zone, at peak metamorphic conditions of ~790 ◦C and 10 kbar. Monazite ages in Lesser Himalayan Sequence (LHS) footwall rocks show that identical metamorphic conditions were reached ~4–6 Ma apart along the ~60 km separating samples along the MCT transport direction. Upper LHS footwall rocks reached peak metamorphic conditions of ~655 ◦C and 9 kbar between ~21 and 16 Ma in the more southerly-exposed transect and ~14.5–12 Ma in the northern transect. Similarly, lower LHS footwall rocks reached peak metamorphic conditions of ~580 ◦C and 8.5 kbar at ~16 Ma in the south, and 9–10 Ma in the north. In the southern transect, the timing of partial melting in the GHS hanging wall (~23–19.5 Ma) overlaps with the timing of prograde metamorphism (~21 Ma) in the LHS footwall, confirming that the hanging wall may have provided the heat necessary for the metamorphism of the footwall. Overall, the data provide robust evidence for progressively downwards-penetrating deformation and accretion of original LHS footwall material to the GHS hanging wall over a period of ~5 Ma. These processes appear to have occurred several times during the prolonged ductile evolution of the thrust. The preserved inverted metamorphic sequence therefore documents the formation of sequential ‘paleothrusts’ through time, cutting down from the original locus of MCT movement at the LHS–GHS protolith boundary and forming at successively lower pressure and temperature conditions. The petrochronologic methods applied here constrain a complex temporal and thermal deformation history, and demonstrate that inverted metamorphic sequences can preserve a rich record of the duration of progressive ductile thrusting

Cells of the adult human heart

Abstract: Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies

Cells of the adult human heart

Abstract: Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Dissolved organic matter quality and bioavailability changes across an urbanization gradient in headwater streams

Landscape urbanization broadly alters watersheds and stream ecosystems, yet the impact of nonpoint source urban inputs on the quantity, quality, and ultimate fate of dissolved organic matter (DOM) is poorly understood. We assessed DOM quality and microbial bioavailability in eight first-order Coastal Plain headwater streams along a gradient of urbanization (i.e., percent watershed impervious cover); none of the streams had point source discharges. DOM quality was measured using fluorescence excitation-emission matrices (EEMs) coupled with parallel factor analysis (PARAFAC). Bioavailability was assessed using biodegradable dissolved organic carbon (BDOC) incubations. Results showed that watershed impervious cover was significantly related to stream DOM composition: increasing impervious cover was associated with decreased amounts of natural humic-like DOM and enriched amounts of anthropogenic fulvic acid-like and protein-like DOM. Microbial bioavailability of DOM was greater in urbanized streams during spring and summer, and was related to decreasing proportions of humic-like DOM and increasing proportions of protein-like DOM. Increased bioavailability was associated with elevated extracellular enzyme activity of the initial microbial community supplied to samples during BDOC incubations. These findings indicate that changes in stream DOM quality due to watershed urbanization may impact stream ecosystem metabolism and ultimately the fate of organic carbon transported through fluvial systems. © 2014 American Chemical Society

“In My Mind, It Was Just Temporary”: A Qualitative Study of the Impacts of Cancer on Men and Their Strategies to Cope

Individuals who are diagnosed and treated for cancer use a variety of strategies to manage its impacts. However, there is currently a lack of research on men’s experience with managing cancer impacts, which is necessary to better support them throughout the cancer care continuum. This study explored the experience of men diagnosed with cancer, focusing on the impacts of the illness and its treatment and men’s strategies to cope. A qualitative descriptive design was used. Thirty-one men ( M age = 52.7 [26–82] years) diagnosed with various cancer types were recruited to take part in individual telephone interviews ( n = 14) or online focus groups ( n = 17) addressing the impacts of cancer and strategies they used to cope with these impacts. Directed content analysis was performed, using Fitch’s (2008) supportive care framework to guide the analysis. Cancer impacts and strategies used to cope were classified into six categories: physical, psychological, interpersonal, informational, practical, and spiritual. Results indicate that the cancer experience is diverse and multifaceted rather than homogeneous. Medical and supportive care services could be more effectively personalized to meet the diversity of men’s needs by adopting a comprehensive and holistic approach to supportive care. Working in partnership with patients, it appears promising to recognize and identify men’s needs and match them to appropriate resources to provide truly supportive care