Metabolomic and flux-balance analysis of age-related decline of hypoxia tolerance in Drosophila muscle tissue

The fruit fly D. melanogaster is increasingly used as a model organism for studying acute hypoxia tolerance and for studying aging, but the interactions between these two factors are not well known. Here we show that hypoxia tolerance degrades with age in post-hypoxic recovery of whole-body movement, heart rate and ATP content. We previously used 1H NMR metabolomics and a constraint-based model of ATP-generating metabolism to discover the end products of hypoxic metabolism in flies and generate hypotheses for the biological mechanisms. We expand the reactions in the model using tissue- and age-specific microarray data from the literature, and then examine metabolomic profiles of thoraxes after 4 hours at 0.5% O2 and after 5 minutes of recovery in 40- versus 3-day-old flies. Model simulations were constrained to fluxes calculated from these data. Simulations suggest that the decreased ATP production during reoxygenation seen in aging flies can be attributed to reduced recovery of mitochondrial respiration pathways and concomitant over-dependence on the acetate production pathway as an energy source.Comment: 30 page

Conditions for proton temperature anisotropy to drive instabilities in the solar wind

Using high-resolution data from Solar Orbiter, we investigate the plasma conditions necessary for the proton temperature anisotropy driven mirror-mode and oblique firehose instabilities to occur in the solar wind. We find that the unstable plasma exhibits dependencies on the angle between the direction of the magnetic field and the bulk solar wind velocity which cannot be explained by the double-adiabatic expansion of the solar wind alone. The angle dependencies suggest that perpendicular heating in Alfv\'enic wind may be responsible. We quantify the occurrence rate of the two instabilities as a function of the length of unstable intervals as they are convected over the spacecraft. This analysis indicates that mirror-mode and oblique firehose instabilities require a spatial interval of length greater than 2 to 3 unstable wavelengths in order to relax the plasma into a marginally stable state and thus closer to thermodynamic equilibrium in the solar wind. Our analysis suggests that the conditions for these instabilities to act effectively vary locally on scales much shorter than the correlation length of solar wind turbulence.Comment: 16 pages, 8 figures. Accepted for publication in Ap

Application of an equine composite pain scale and its association with plasma adrenocorticotropic hormone concentrations and serum cortisol concentrations in horses with colic

This study assessed the application of a modified equine composite pain scale (CPS) and identified the inter‐observer reliability. Associations between CPS scores and the measured concentrations of serum cortisol ([cortisol]) and plasma adrenocorticotrophic hormone ([ACTH]) in horses presenting with colic were determined. The study design was prospective, uni‐centred and observational. The inter‐observer reliability of the adapted CPS was determined for 59 horses hospitalised for a variety of conditions. The associations between CPS, ACTH and cortisol were assessed in a further 49 horses admitted for medical or surgical colic. During hospitalisation, blood samples were obtained each morning and analysed for serum [cortisol] and plasma [ACTH]. Horses were pain scored using the adapted CPS score. Data from the most painful time point (n = 48 horses; n = 48 [cortisol]; n = 44 [ACTH]) and all data time points (n = 49 horses and n = 133 time points) were used for analysis of association between [cortisol], [ACTH] and CPS score. The CPS score inter‐observer reliability was excellent (n = 59 horses; n = 102 pain scores; weighted kappa 0.863). CPS score and [cortisol] were positively associated at the most painful time point (P < 0.001) and at all data time points (P < 0.001). No significant association was found between CPS score and [ACTH]. [ACTH] was associated with [cortisol] (P = 0.034) when all time points were analysed but not when only the most painful point was analysed. The significant correlation identified between CPS score and [cortisol] in medical and surgical colic cases provides physiological validation of pain scores as a marker of underlying stress in horses with colic

Legume seed production for sustainable seed supply and crop productivity: case of groundnut in Tanzania and Uganda

Improvingagriculturalproductivityandproductionisaprerequisite to sustain rural livelihoods in developing countries of sub-Saharan Africa SSA).Thisrequiresincreaseduseofqualityseedofimproved and well-adapted crop varieties. Legumes are particularly critical in ensuring food and nutritional securities of the majority of farming households. However, their productivity has been constrained because of limited availability of quality seed, jeopardizing henceforth food security and rural livelihoods. The lack of interest in productionoflegumeseedsbypotentialseedproducers,especially the private sector, is attributable to limited information on the cost and profitability of producing these seeds. Using primary data collectedfromTanzaniaandUganda,weanalyzedthecoststructureof improved groundnut (Arachis hypogaea L.) seed production to assess viability. We adopted cost-benefit analysis framework to evaluate different seed production models. Results showed that groundnutseedpricevariedbetween1and2US$kg−1 forcertified andqualitydeclaredseedandbetween2and3.5US$kg−1 forearly generationseed.Overall,upto50%increaseintotalseedproduction costsresultedinreduceddropinthegrossmarginearned.However, when production costs increased by 75–100%, the gross margin droppedbyabout18%and50%inTanzaniaandinUganda,respectively. These findings indicated that groundnut seed could be providedtofarmersinremotecommunitiesatanaffordablepricewhile still keeping seed producers profitably in business. Availing these seeds to smallholder producers is a major step in achieving food securityandnutritionalhealthindevelopingcountries inSSA

South African Hypertension Guideline 2006

Outcomes. Extensive data from many randomised controlled trials have shown the benefit of treating hypertension. The target blood pressure (BP) for antihypertensive management should be systolic BP < 140 mmHg, diastolic BP < 90 mmHg, with minimal or no drug side-effects. However, a lesser reduction will elicit benefit although this is not optimal. The reduction of BP in the elderly should generally be achieved gradually over 6 months. Stricter BP control is required for patients with end-organ damage, co-existing risk factors and co-morbidity, e.g. diabetes mellitus. Co-existent risk factors should also be controlled. Benefits. Reduction in risk of stroke, cardiac failure, renal insufficiency and coronary artery disease. The major precautions and contraindications to each antihypertensive drug recommended are listed. Recommendations. Correct BP measurement procedure is described. Evaluation of cardiovascular risk factors and recommendations for antihypertensive therapy are stipulated. The total cardiovascular disease risk profile should be determined for all patients and this should inform management strategies. Lifestyle modification and patient education are cornerstones in the management of every patient. Drug therapy for the patient with uncomplicated hypertension should be as follows: first line – low-dose thiazide or thiazide-like diuretics; second line – add either an angiotensin-converting enzyme inhibitor (ACE-I) or a calcium channel blocker (CCB); third line – add another second-line drug not already used. In resistant hypertension where a fourth drug is needed, use either a centrally acting drug, vasodilator, alpha-blocker, or beta-blocker. The order of drug choice may change in those with compelling indications for a particular drug class. The guideline includes management of specific situations including hypertensive emergency and urgency, severe hypertension with target-organ damage and hypertension in diabetes mellitus, etc. Validity. The guideline was developed by a joint Southern African Hypertension Society and National Department of Health Directorate: Chronic Diseases, Disabilities and Geriatrics working group. Input was also obtained from representatives of the various related professional societies

Successful nesting by 2 endangered Hawaiian waterbird species in a restored Indigenous wetland agroecosystem

The Hawaiian Stilt (Himantopus mexicanus knudseni) and Hawaiian Gallinule (Gallinula galeata sandvicensis) are federally endangered waterbirds endemic to the Hawaiian Islands. Both species are conservation-reliant; their population persistence is dependent on invasive predator control and removal of invasive plants that degrade habitat. We present observations of successful nesting by one Hawaiian Stilt pair and one Hawaiian Gallinule pair at a site managed within an adaptive Indigenous agroecological framework on the island of O‘ahu, Hawai‘i. The Hawaiian Stilt nest, found in February 2019, contained 4 eggs and produced 3 hatchlings, 2 of which were banded and monitored after hatching. The Hawaiian Gallinule nest, found in February 2020, contained 6 eggs and produced 5 hatchlings. Although no individuals were banded from this nest, 2 adults and 2 hatchlings were continuously observed in the nesting area after the eggs hatched. Lo‘i kalo Hawaiian wetland agroecosystems centered around the cultivation of kalo (taro; Colocasia esculenta), have the potential to expand Hawaiian waterbird habitat beyond state and federal protected areas. We are aware of unpublished accounts of Hawaiian waterbirds nesting in commercially farmed lo‘i kalo, but until now, there have been no previously published accounts of native waterbirds breeding in lo‘i kalo managed as Indigenous agroecosystems

Safety and efficacy of antenatal milk expressing for women with diabetes in pregnancy: protocol for a randomised controlled trial

Many maternity providers recommend that women with diabetes in pregnancy express and store breast milk in late pregnancy so breast milk is available after birth, given (1) infants of these women are at increased risk of hypoglycaemia in the first 24 h of life; and (2) the delay in lactogenesis II compared with women without diabetes that increases their infant\u27s risk of receiving infant formula. The Diabetes and Antenatal Milk Expressing (DAME) trial will establish whether advising women with diabetes in pregnancy (pre-existing or gestational) to express breast milk from 36 weeks gestation increases the proportion of infants who require admission to special or neonatal intensive care units (SCN/NICU) compared with infants of women receiving standard care. Secondary outcomes include birth gestation, breastfeeding outcomes and economic impact

Key stakeholder perspectives on the development and real-world implementation of a home-based physical activity program for mothers at risk of postnatal depression: a qualitative study

Background: Physical activity (PA) is a modifiable risk factor for postnatal depression (PND) and programs are needed to enhance PA amongst women at risk of PND. Key stakeholder involvement in informing development and implementation of such programs is vital. However, little research demonstrates key stakeholder insights to inform the design and delivery of PA programs for improving PND. The aim of this study was to explore key stakeholder perspectives on the design and delivery of a home-based PA program for mothers with PND symptoms to inform future real-world implementation and scale-up. Methods: A descriptive qualitative study was undertaken whereby semi-structured interviews were conducted with representatives from various key stakeholder organisations involved in postnatal PA and/or mental health, public health and policy in Australia (n = 11). Interviews were conducted between September to November 2019 and explored stakeholder perceptions on the design and delivery of a home-based PA program for mothers with PND symptoms. The interview schedule was informed by both the Consolidated Framework for Implementation Research (CFIR) and the PRACTical planning for Implementation and Scale-up (PRACTIS) guide. Data were analysed thematically using both deductive and inductive coding. Results: The relative priority of PND and PA was high for most organisations involved, although none implemented PA programs supporting women at risk of PND. Most stakeholders perceived the program as appealing due to addressing barriers to postnatal PA, although identified some feasibility issues regarding funding and delivery mechanisms. Suggestions for program adaptations included an equity focus (e.g. providing socioeconomically disadvantaged women with a greater program dose; translating web-app based content into various languages). Planned components of the program were suggested to align (i.e. relative advantage) with existing initiatives (e.g. equipment hire for nurseries scheme) and screening systems for PND (timing of referral). Perceived barriers to scale-up included logistics/cost of equipment, organisational capacity demands and safety risks/liability. Perceived enablers to scale-up included linking the program with ‘adjunct’ programs and services. Conclusions: While the program was appealing and most organisations could see a role in endorsing and/or referring to the program, funding and delivery mechanisms still need to be identified

Participation in physical play and leisure : developing a theory- and evidence-based intervention for children with motor impairments

Peer reviewedPublisher PD

ERK1/2 signaling dominates over RhoA signaling in regulating early changes in RNA expression induced by endothelin-1 in neonatal rat cardiomyocytes

Cardiomyocyte hypertrophy is associated with changes in gene expression. Extracellular signal-regulated kinases 1/2 (ERK1/2) and RhoA [activated by hypertrophic agonists (e.g. endothelin-1)] regulate gene expression and are implicated in the response, but their relative significance in regulating the cardiomyocyte transcriptome is unknown. Our aim was to establish the significance of ERK1/2 and/or RhoA in the early cardiomyocyte transcriptomic response to endothelin-1.Cardiomyocytes were exposed to endothelin-1 (1 h) with/without PD184352 (to inhibit ERK1/2) or C3 transferase (C3T, to inhibit RhoA). RNA expression was analyzed using microarrays and qPCR. ERK1/2 signaling positively regulated approximately 65% of the early gene expression response to ET-1 with a small (approximately 2%) negative effect, whereas RhoA signaling positively regulated approximately 10% of the early gene expression response to ET-1 with a greater (approximately 14%) negative contribution. Of RNAs non-responsive to endothelin-1, 66 or 448 were regulated by PD184352 or C3T, respectively, indicating that RhoA had a more significant effect on baseline RNA expression. mRNAs upregulated by endothelin-1 encoded a number of receptor ligands (e.g. Ereg, Areg, Hbegf) and transcription factors (e.g. Abra/Srf) that potentially propagate the response.ERK1/2 dominates over RhoA in the early transcriptomic response to endothelin-1. RhoA plays a major role in maintaining baseline RNA expression but, with upregulation of Abra/Srf by endothelin-1, RhoA may regulate changes in RNA expression over longer times. Our data identify ERK1/2 as a more significant node than RhoA in regulating the early stages of cardiomyocyte hypertrophy