Transient receptor potential melastatin 7 cation channel kinase new player in angiotensin II–induced hypertension

Transient receptor potential melastatin 7 (TRPM7) is a bifunctional protein comprising a magnesium (Mg2+)/cation channel and a kinase domain. We previously demonstrated that vasoactive agents regulate vascular TRPM7. Whether TRPM7 plays a role in the pathophysiology of hypertension and associated cardiovascular dysfunction is unknown. We studied TRPM7 kinase–deficient mice (TRPM7Δkinase; heterozygous for TRPM7 kinase) and wild-type (WT) mice infused with angiotensin II (Ang II; 400 ng/kg per minute, 4 weeks). TRPM7 kinase expression was lower in heart and aorta from TRPM7Δkinase versus WT mice, effects that were further reduced by Ang II infusion. Plasma Mg2+ was lower in TRPM7Δkinase versus WT mice in basal and stimulated conditions. Ang II increased blood pressure in both strains with exaggerated responses in TRPM7Δkinase versus WT groups (P<0.05). Acetylcholine-induced vasorelaxation was reduced in Ang II–infused TRPM7Δkinase mice, an effect associated with Akt and endothelial nitric oxide synthase downregulation. Vascular cell adhesion molecule–1 expression was increased in Ang II–infused TRPM7 kinase–deficient mice. TRPM7 kinase targets, calpain, and annexin-1, were activated by Ang II in WT but not in TRPM7Δkinase mice. Echocardiographic and histopathologic analysis demonstrated cardiac hypertrophy and left ventricular dysfunction in Ang II–treated groups. In TRPM7 kinase–deficient mice, Ang II–induced cardiac functional and structural effects were amplified compared with WT counterparts. Our data demonstrate that in TRPM7Δkinase mice, Ang II–induced hypertension is exaggerated, cardiac remodeling and left ventricular dysfunction are amplified, and endothelial function is impaired. These processes are associated with hypomagnesemia, blunted TRPM7 kinase expression/signaling, endothelial nitric oxide synthase downregulation, and proinflammatory vascular responses. Our findings identify TRPM7 kinase as a novel player in Ang II–induced hypertension and associated vascular and target organ damage

The fabrication of small molecule organic light-emitting diode pixels by laser-induced forward transfer

Laser-induced forward transfer (LIFT) is a versatile organic light-emitting diode (OLED) pixel deposition process, but has hitherto been applied exclusively to polymeric materials. Here, a modified LIFT process has been used to fabricate small molecule Alq(3) organic light-emitting diodes (SMOLEDs). Small molecule thin films are considerably more mechanically brittle than polymeric thin films, which posed significant challenges for LIFT of these materials. The LIFT process presented here uses a polymeric dynamic release layer, a reduced environmental pressure, and a well-defined receiver-donor gap. The Alq(3) pixels demonstrate good morphology and functionality, even when compared to conventionally fabricated OLEDs. The Alq(3) SMOLED pixel performances show a significant amount of fluence dependence, not observed with polymerical OLED pixels made in previous studies. A layer of tetrabutyl ammonium hydroxide has been deposited on top of the aluminium cathode, as part of the donor substrate, to improve electron injection to the Alq(3), by over 600%. These results demonstrate that this variant of LIFT is applicable for the deposition of functional small molecule OLEDs as well as polymeric OLEDs. (C) 2013 American Institute of Physics. [http://dx.doi.org/10.1063/1.4788710

Assessment of genetic structure among Australian east coast populations of snapper Chrysophrys auratus (Sparidae)

Snapper Chrysophrys auratus is a high-value food fish in Australia targeted by both commercial and recreational fisheries. Along the east coast of Australia, fisheries are managed under four state jurisdictions (Queensland, Qld; New South Wales, NSW; Victoria, Vic.; and Tasmania, Tas.), each applying different regulations, although it is thought that the fisheries target the same biological stock. An allozyme-based study in the mid-1990s identified a weak genetic disjunction north of Sydney (NSW) questioning the single-stock hypothesis. This study, focused on east-coast C. auratus, used nine microsatellite markers to assess the validity of the allozyme break and investigated whether genetic structure exists further south. Nine locations were sampled spanning four states and over 2000 km, including sites north and south of the proposed allozyme disjunction. Analyses confirmed the presence of two distinct biological stocks along the east coast, with a region of genetic overlap around Eden in southern NSW, ~400 km south of the allozyme disjunction. The findings indicate that C. auratus off Vic. and Tas. are distinct from those in Qld and NSW. For the purpose of stock assessment and management, the results indicate that Qld and NSW fisheries are targeting a single biological stock.

sciCSR infers B cell state transition and predicts class-switch recombination dynamics using single-cell transcriptomic data

Class-switch recombination (CSR) is an integral part of B cell maturation. Here we present sciCSR (pronounced 'scissor', single-cell inference of class-switch recombination), a computational pipeline that analyzes CSR events and dynamics of B cells from single-cell RNA sequencing (scRNA-seq) experiments. Validated on both simulated and real data, sciCSR re-analyzes scRNA-seq alignments to differentiate productive heavy-chain immunoglobulin transcripts from germline 'sterile' transcripts. From a snapshot of B cell scRNA-seq data, a Markov state model is built to infer the dynamics and direction of CSR. Applying sciCSR on severe acute respiratory syndrome coronavirus 2 vaccination time-course scRNA-seq data, we observe that sciCSR predicts, using data from an earlier time point in the collected time-course, the isotype distribution of B cell receptor repertoires of subsequent time points with high accuracy (cosine similarity ~0.9). Using processes specific to B cells, sciCSR identifies transitions that are often missed by conventional RNA velocity analyses and can reveal insights into the dynamics of B cell CSR during immune response

Can greater muscularity in larger individuals resolve the 3/4 power-law controversy when modelling maximum oxygen uptake?

BACKGROUND: The power function relationship, MR = a.m(b), between metabolic rate (MR) and body mass m has been the source of much controversy amongst biologists for many years. Various studies have reported mass exponents (b) greater than the anticipated 'surface-area' exponent 0.67, often closer to 0.75 originally identified by Kleiber. AIM: The study aimed to provide a biological explanation for these 'inflated' exponents when modelling maximum oxygen uptake (max), based on the observations from this and previous studies that larger individuals develop disproportionately more muscle mass in the arms and legs. RESEARCH DESIGN AND SUBJECTS: A cross-sectional study of 119 professional soccer players from Croatia aged 18-34 was carried out. RESULTS: Here we confirm that the power function relationship between max and body mass of the professional soccer players results in an 'inflated' mass exponent of 0.75 (95% confidence interval from 0.56 to 0.93), but also the larger soccer players have disproportionately greater leg muscle girths. When the analysis was repeated incorporating the calf and thigh muscle girths rather than body mass as predictor variables, the analysis not only explained significantly more of the variance in max, but the sum of the exponents confirmed a surface-area law. CONCLUSIONS: These findings confirm the pitfalls of fitting body-mass power laws and suggest using muscle-girth methodology as a more appropriate way to scale or normalize metabolic variables such as max for individuals of different body sizes

Profession Based Hierarchies as Barriers for Genuine Learning Processes

Under embargo until: 2021-06-26This chapter describes how profession based hierarchies (stratified social orders between professions) may appear in a teaching context of interprofessionality involving a variety of health professions presenting challenges to learning and offers suggestions on how these challenges can be overcome.acceptedVersio

Curvature force and dark energy

A curvature self-interaction of the cosmic gas is shown to mimic a cosmological constant or other forms of dark energy, such as a rolling tachyon condensate or a Chaplygin gas. Any given Hubble rate and deceleration parameter can be traced back to the action of an effective curvature force on the gas particles. This force self-consistently reacts back on the cosmological dynamics. The links between an imperfect fluid description, a kinetic description with effective antifriction forces, and curvature forces, which represent a non-minimal coupling of gravity to matter, are established.Comment: 14 pages; references added, to appear in New Journal of Physics (v3

A comparison of course-related stressors in undergraduate problem-based learning (PBL) versus non-PBL medical programmes

Background: Medical students report high levels of stress related to their medical training as well as to other personal and financial factors. The aim of this study is to investigate whether there are differences in course-related stressors reported by medical students on undergraduate problem-based learning (PBL) and non-PBL programmes in the UK. Method: A cross-sectional study of second-year medical students in two UK medical schools (one PBL and one non-PBL programme) was conducted. A 16-question self-report questionnaire, derived from the Perceived Medical Student Stress Scale and the Higher Education Stress Inventory, was used to measure course-related stressors. Following univariate analysis of each stressor between groups, multivariate logistic regression was used to determine which stressors were the best predictors of each course type, while controlling for socio-demographic differences between the groups. Results: A total of 280 students responded. Compared to the non-PBL students (N = 197), the PBL students (N = 83) were significantly more likely to agree that: they did not know what the faculty expected of them (Odds Ratio (OR) = 0.38, p = 0.03); there were too many small group sessions facilitated only by students resulting in an unclear curriculum (OR = 0.04, p < 0.0001); and that there was a lack of opportunity to explore academic subjects of interest (OR = 0.40, p = 0.02). They were significantly more likely to disagree that: there was a lack of encouragement from teachers (OR = 3.11, p = 0.02); and that the medical course fostered a sense of anonymity and feelings of isolation amongst students (OR = 3.42, p = 0.008). Conclusion: There are significant differences in the perceived course-related stressors affecting medical students on PBL and non-PBL programmes. Course designers and student support services should therefore tailor their work to minimise, or help students cope with, the specific stressors on each course type to ensure optimum learning and wellbeing among our future doctors

The LOFAR Transients Pipeline

Current and future astronomical survey facilities provide a remarkably rich opportunity for transient astronomy, combining unprecedented fields of view with high sensitivity and the ability to access previously unexplored wavelength regimes. This is particularly true of LOFAR, a recently-commissioned, low-frequency radio interferometer, based in the Netherlands and with stations across Europe. The identification of and response to transients is one of LOFAR's key science goals. However, the large data volumes which LOFAR produces, combined with the scientific requirement for rapid response, make automation essential. To support this, we have developed the LOFAR Transients Pipeline, or TraP. The TraP ingests multi-frequency image data from LOFAR or other instruments and searches it for transients and variables, providing automatic alerts of significant detections and populating a lightcurve database for further analysis by astronomers. Here, we discuss the scientific goals of the TraP and how it has been designed to meet them. We describe its implementation, including both the algorithms adopted to maximize performance as well as the development methodology used to ensure it is robust and reliable, particularly in the presence of artefacts typical of radio astronomy imaging. Finally, we report on a series of tests of the pipeline carried out using simulated LOFAR observations with a known population of transients.Comment: 30 pages, 11 figures; Accepted for publication in Astronomy & Computing; Code at https://github.com/transientskp/tk