Heat stress and β-adrenergic agonists alter the adipose transcriptome and fatty acid mobilization in ruminant livestock

Growth and feed efficiency of cattle are improved by supplementation with the beta-adrenergic agonists (βAA), ractopamine hydrochloride (RH; β1AA) or zilpaterol hydrochloride (ZH; β2AA) (Elam et al., 2009). βAA supplementation alters adipose deposition by inhibiting fatty acid biosynthesis and promoting lipolysis of stored triacylglycerols into free fatty acids (FFAs) (Johnson et al., 2014). However, β2 adrenoceptors (βAR) desensitize with chronic activation (Re et al., 1997); supplementation is thus limited to the last 20 to 40 d of feeding. The annual economic impact of heat stress (HS) has been estimated to exceed $2.4 billion (St-Pierre et al., 2003). Heat-stressed livestock have reduced growth rates, dry matter intake, and average daily gain (Mitlöhner et al., 2001; St-Pierre et al., 2003). In response to acute stress, signaling pathways for lipolysis of circulating and stored triglycerides are activated, while chronic stress increases lipogenesis and adipogenesis (Campbell et al., 2009; Peckett et al., 2011). In cattle, HS also increases the responsiveness of adipocytes to lipolytic signals, increasing lipolysis (Faylon et al., 2015). The objective of this study was to understand how HS and βAA independently and interactively affect adipose tissue. Prior work identified minimal impact of RH on metabolic properties (Barnes et al., 2019) and on the transcriptome of skeletal muscle (Kubik et al., 2018). We therefore hypothesized that RH may be primarily affecting adipose; specifically, that lipolytic activity is increased due to heat and βAA in an additive fashion. We tested this hypothesis in RH-supplemented lambs and ZH-supplemented cattle exposed to HS for 30 and 21 d, respectively

Feasibility of offering nicotine replacement therapy as a relapse prevention treatment in routine smoking cessation services

Background: National Health Service stop smoking services (NHS SSS) in the UK offer cost- effective smoking cessation services. Despite high abstinence rates after acute cessation treatment, the majority of clients have relapsed by one year. Several interventions have been identified, from trial data, as effective in preventing relapse to smoking. This study investigated uptake, feasibility and acceptability of offering nicotine replacement therapy (NRT) as a relapse prevention intervention (RPI) in NHS SSS. Methods: Eligible smokers who had successfully completed acute cessation treatment using NRT at Nottingham City NHS SSS between April 2010 and January 2011 were offered the RPI and the rate of uptake was monitored. Consenting individuals completed a baseline questionnaire, providing demographic and smoking behaviour data. The RPI consisted of using NRT for a further 12 weeks after initial cessation-orientated treatment had ended. At a six-month review, self-reported smoking status was assessed via telephone. Anonymised demographic data on NHS SSS users who did not agree to participate in the study were retrieved from NHS SSS records and used to determine the presence of any socio-demographic differences between individuals who agreed to participate in the study and those who did not. Semi-structured telephone interviews were conducted with a selection of participants; these were audio-recorded, transcribed and analysed to identify participants’ views on the RPI. Results: Of 493 stop smoking service clients who were assessed, 260 were eligible for and offered the RPI and 115 (44%, CI 38%- 50%) accepted. Individuals who accepted NRT were significantly more likely to be older (p < 0.001) and to pay for their prescriptions (p < 0.001). Quitters who had never worked or were unemployed were significantly less likely to accept the offer of relapse prevention compared to those in routine and manual occupations (55% reduction in odds, p = 0.026). Interview findings revealed that clients who accepted extended NRT felt the longer duration of pharmacological and psychological support were both valuable in helping them to remain abstinent. Conclusion: In routine smoking cessation service care, it is feasible to offer clients extended courses of NRT as a RPI. The RPI was acceptable to them as almost half of the eligible clients offered this treatment accepted it. Keywords: Smoking relapse prevention, Nicotine replacement therapy, Feasibility study, Smoking cessation servic

The unusual M-dwarf Warm Jupiter TOI-1899~b: Refinement of orbital and planetary parameters

TOI-1899~b is a rare exoplanet, a temperate Warm Jupiter orbiting an M-dwarf, first discovered by \citet{Canas2020_toi1899} from a TESS single-transit event. Using new radial velocities (RVs) from the precision RV spectrographs HPF and NEID, along with additional TESS photometry and ground-based transit follow-up, we are able to derive a much more precise orbital period of $P = 29.090312_{-0.000035}^{+0.000036}$~d, along with a radius of $R_p = 0.99\pm0.03$~\unit{R_{J}}. We have also improved the constraints on planet mass, $M_p = 0.67\pm{0.04}$~\unit{M_{J}}, and eccentricity, which is consistent with a circular orbit at 2$\sigma$ ($e = 0.044_{-0.027}^{+0.029}$). TOI-1899~b occupies a unique region of parameter space as the coolest known ($T_{eq} \approx$ 380~K) Jovian-sized transiting planet around an M-dwarf; we show that it has great potential to provide clues regarding the formation and migration mechanisms of these rare gas giants through transmission spectroscopy with JWST as well as studies of tidal evolution.Comment: 19 pages, 7 figures, 3 tables, submitted to AJ (comments welcome

Daily injection of the β2 adrenergic agonist clenbuterol improved poor muscle growth and body composition in lambs following heat stress-induced intrauterine growth restriction

Background: Intrauterine growth restriction (IUGR) is associated with reduced β2 adrenergic sensitivity, which contributes to poor postnatal muscle growth. The objective of this study was to determine if stimulating β2 adrenergic activity postnatal would rescue deficits in muscle growth, body composition, and indicators of metabolic homeostasis in IUGR offspring.Methods: Time-mated ewes were housed at 40°C from day 40 to 95 of gestation to produce IUGR lambs. From birth, IUGR lambs received daily IM injections of 0.8 μg/kg clenbuterol HCl (IUGR+CLEN; n = 11) or saline placebo (IUGR; n = 12). Placebo-injected controls (n = 13) were born to pair-fed thermoneutral ewes. Biometrics were assessed weekly and body composition was estimated by ultrasound and bioelectrical impedance analysis (BIA). Lambs were necropsied at 60 days of age.Results: Bodyweights were lighter (p ≤ 0.05) for IUGR and IUGR+CLEN lambs than for controls at birth, day 30, and day 60. Average daily gain was less (p ≤ 0.05) for IUGR lambs than controls and was intermediate for IUGR+CLEN lambs. At day 58, BIA-estimated whole-body fat-free mass and ultrasound-estimated loin eye area were less (p ≤ 0.05) for IUGR but not IUGR+CLEN lambs than for controls. At necropsy, loin eye area and flexor digitorum superficialis muscles were smaller (p ≤ 0.05) for IUGR but not IUGR+CLEN lambs than for controls. Longissimus dorsi protein content was less (p ≤ 0.05) and fat-to-protein ratio was greater (p ≤ 0.05) for IUGR but not IUGR+CLEN lambs than for controls. Semitendinosus from IUGR lambs had less (p ≤ 0.05) β2 adrenoreceptor content, fewer (p ≤ 0.05) proliferating myoblasts, tended to have fewer (p = 0.08) differentiated myoblasts, and had smaller (p ≤ 0.05) muscle fibers than controls. Proliferating myoblasts and fiber size were recovered (p ≤ 0.05) in IUGR+CLEN lambs compared to IUGR lambs, but β2 adrenoreceptor content and differentiated myoblasts were not recovered. Semitendinosus lipid droplets were smaller (p ≤ 0.05) in size for IUGR lambs than for controls and were further reduced (p ≤ 0.05) in size for IUGR+CLEN lambs.Conclusion: These findings show that clenbuterol improved IUGR deficits in muscle growth and some metabolic parameters even without recovering the deficit in β2 adrenoreceptor content. We conclude that IUGR muscle remained responsive to β2 adrenergic stimulation postnatal, which may be a strategic target for improving muscle growth and body composition in IUGR-born offspring

TOI-2015b: A Warm Neptune with Transit Timing Variations Orbiting an Active mid M Dwarf

We report the discovery of a close-in ($P_{\mathrm{orb}} = 3.349\:\mathrm{days}$) warm Neptune with clear transit timing variations (TTVs) orbiting the nearby ($d=47.3\:\mathrm{pc}$) active M4 star, TOI-2015. We characterize the planet's properties using TESS photometry, precise near-infrared radial velocities (RV) with the Habitable-zone Planet Finder (HP) Spectrograph, ground-based photometry, and high-contrast imaging. A joint photometry and RV fit yields a radius $R_p~=~3.37_{-0.20}^{+0.15} \:\mathrm{R_\oplus}$, mass $m_p~=~16.4_{-4.1}^{+4.1}\:\mathrm{M_\oplus}$, and density $\rho_p~=~2.32_{-0.37}^{+0.38} \:\mathrm{g cm^{-3}}$ for TOI-2015b, suggesting a likely volatile-rich planet. The young, active host star has a rotation period of $P_{\mathrm{rot}}~=~8.7 \pm~0.9~\mathrm{days}$ and associated rotation-based age estimate of $1.1~\pm~0.1\:\mathrm{Gyr}$. Though no other transiting planets are seen in the TESS data, the system shows clear TTVs of super period $P_{\mathrm{sup}}~\approx~430\:\mathrm{days}$ and amplitude $\sim$$100\:\mathrm{minutes}$. After considering multiple likely period ratio models, we show an outer planet candidate near a 2:1 resonance can explain the observed TTVs while offering a dynamically stable solution. However, other possible two-planet solutions -- including 3:2 and 4:3 resonance -- cannot be conclusively excluded without further observations. Assuming a 2:1 resonance in the joint TTV-RV modeling suggests a mass of $m_b~=~13.3_{-4.5}^{+4.7}\:\mathrm{M_\oplus}$ for TOI-2015b and $m_c~=~6.8_{-2.3}^{+3.5}\:\mathrm{M_\oplus}$ for the outer candidate. Additional transit and RV observations will be beneficial to explicitly identify the resonance and further characterize the properties of the system.Comment: 28 pages, 15 figures, 6 tables. As submitted to AAS Journal

Attention bias to emotional faces varies by IQ and anxiety in Williams syndrome

Individuals with Williams syndrome (WS) often experience significant anxiety. A promising approach to anxiety intervention has emerged from cognitive studies of attention bias to threat. To investigate the utility of this intervention in WS, this study examined attention bias to happy and angry faces in individuals with WS (N=46). Results showed a significant difference in attention bias patterns as a function of IQ and anxiety. Individuals with higher IQ or higher anxiety showed a significant bias toward angry, but not happy faces, whereas individuals with lower IQ or lower anxiety showed the opposite pattern. These results suggest that attention bias interventions to modify a threat bias may be most effectively targeted to anxious individuals with WS with relatively high IQ

Higher quality of life and lower depression for people on art in Uganda as compared to a community control group

Provision of antiretroviral treatment (ART) to people living with HIV (PLWH) has increased globally. Research measuring whether ART restores subjective well-being to "normal" levels is lacking, particularly in resource limited settings. The study objectives are to compare quality of life and depression symptoms for PLWH on ART to a general community population and to explore factors to explain these differences, including socio-economic status and the impact of urban or rural residence. PLWH on ART (n = 263) were recruited from ART delivery sites and participants not on ART (n = 160) were recruited from communities in Wakiso District, Uganda. Participants were interviewed using the translated World Health Organisation Quality of Life brief measure, the Hopkins Symptom Checklist depression section, and questions about socioeconomic status, residence as urban or rural and, for PLWH on ART, self-reported adherence and use of HIV counselling. Compared to the community sample and controlling for location of residence, PLWH on ART had significantly higher quality of life (QOL) for physical, psychological and environment domains, but not the social domain. These differences were not due to socio-economic status alone. Depression scores were significantly lower for PLWH on ART. Both comparisons controlled for the effect of location of residence. People on ART self-reported high adherence and the majority had used HIV counselling services. Our findings show better QOL amongst PLWH on ART compared to a general community sample, which cannot be explained solely by differences in socio-economic status nor location of residence. The general community sample results point towards the challenges of life in this setting. Access to health services may underpin this difference and further research should explore this finding, in addition to identification of psychological mechanisms that relate to better QOL. ART provision infrastructure has clear benefits. Further work should consider sustainability and replication for other health conditions. © 2014 Martin et al

Cortical brain abnormalities in 4474 individuals with schizophrenia and 5098 control subjects via the enhancing neuro Imaging genetics through meta analysis (ENIGMA) Consortium

BACKGROUND: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. METHODS: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide. RESULTS: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery