Exploring the limit of metazoan thermal tolerance via comparative proteomics: thermally induced changes in protein abundance by two hydrothermal vent polychaetes

Temperatures around hydrothermal vents are highly variable, ranging from near freezing up to 300°C. Nevertheless, animals thrive around vents, some of which live near the known limits of animal thermotolerance. Paralvinella sulfincola, an extremely thermotolerant vent polychaete, and Paralvinella palmiformis, a cooler-adapted congener, are found along the Juan de Fuca Ridge in the northwestern Pacific. We conducted shipboard high-pressure thermotolerance experiments on both species to characterize the physiological adaptations underlying P. sulfincola's pronounced thermotolerance. Quantitative proteomics, expressed sequence tag (EST) libraries and glutathione assays revealed that P. sulfincola (i) exhibited an upregulation in the synthesis and recycling of glutathione with increasing temperature, (ii) downregulated nicotinamide adenine dinucleotide (NADH) and succinate dehydrogenases (key enzymes in oxidative phosphorylation) with increasing temperature, and (iii) maintained elevated levels of heat shock proteins (HSPs) across all treatments. In contrast, P. palmiformis exhibited more typical responses to increasing temperatures (e.g. increasing HSPs at higher temperatures). These data reveal differences in how a mesotolerant and extremely thermotolerant eukaryote respond to thermal stress, and suggest that P. sulfincola's capacity to mitigate oxidative stress via increased synthesis of antioxidants and decreased flux through the mitochondrial electron transport chain enable pronounced thermotolerance. Ultimately, oxidative stress may be the key factor in limiting all metazoan thermotolerance.Organismic and Evolutionary Biolog

Coupled dynamics of voltage and calcium in paced cardiac cells

We investigate numerically and analytically the coupled dynamics of transmembrane voltage and intracellular calcium cycling in paced cardiac cells using a detailed physiological model and its reduction to a three-dimensional discrete map. The results provide a theoretical framework to interpret various experimentally observed modes of instability ranging from electromechanically concordant and discordant alternans to quasiperiodic oscillations of voltage and calcium

Complete genome sequence of Candidatus Ruthia magnifica

The hydrothermal vent clam Calyptogena magnifica (Bivalvia: Mollusca) is a member of the Vesicomyidae. Species within this family form symbioses with chemosynthetic Gammaproteobacteria. They exist in environments such as hydrothermal vents and cold seeps and have a rudimentary gut and feeding groove, indicating a large dependence on their endosymbionts for nutrition. The C. magnifica symbiont, Candidatus Ruthia magnifica, was the first intracellular sulfur-oxidizing endosymbiont to have its genome sequenced (Newton et al. 2007). Here we expand upon the original report and provide additional details complying with the emerging MIGS/MIMS standards. The complete genome exposed the genetic blueprint of the metabolic capabilities of the symbiont. Genes which were predicted to encode the proteins required for all the metabolic pathways typical of free-living chemoautotrophs were detected in the symbiont genome. These include major pathways including carbon fixation, sulfur oxidation, nitrogen assimilation, as well as amino acid and cofactor/vitamin biosynthesis. This genome sequence is invaluable in the study of these enigmatic associations and provides insights into the origin and evolution of autotrophic endosymbiosis

The effect of COVID-19 on maternal newborn and child health (MNCH) services in Bangladesh, Nigeria and South Africa: call for a contextualised pandemic response in LMICs

Global response to COVID-19 pandemic has inadvertently undermined the achievement of existing public health priorities and laregely overlooked local context. Recent evidence suggests that this will cause additional maternal and childhood mortality and morbidity especially in low- and middle-income countries (LMICs). Here we have explored the contextual factors influencing maternal, neonatal and children health (MNCH) care in Bangladesh, Nigeria and South Africa amidst the pandemic. Our findings suggest that between March and May 2020, there was a reduction in utilisation of basic essential MNCH services such as antenatal care, family planning and immunization due to: a) the implementation of lockdown which triggered fear of contracting the COVID-19 and deterred people from accessing basic MNCH care, and b) a shift of focus towards pandemic, causing the detriment to other health services, and c) resource constraints. Taken together these issues have resulted in compromised provision of basic general healthcare. Given the likelihood of recurrent waves of the pandemic globally, COVID-19 mitigation plans therefore should be integrated with standard care provision to enhance system resilience to cope with all health needs. This commentary suggests a four-point contextualised mitigation plan to safeguard MNCH care during the pandemic using the observed countries as exemplars for LMIC health system adaptations to maintain the trajectory of progress regarding sustainable development goals (SDGs)

Isotopic evidences for microbiologically mediated and direct C input to soil compounds from three different leaf litters during their decomposition

We show the potentiality of coupling together different compound-specific isotopic analyses in a laboratory experiment, where 13C-depleted leaf litter was incubated on a 13C-enriched soil. The aim of our study was to identify the soil compounds where the C derived from three different litter species is retained. Three 13C-depleted leaf litter (Liquidambar styraciflua L., Cercis canadensis L. and Pinus taeda L., δ13CvsPDB ≈ −43‰), differing in their degradability, were incubated on a C4 soil (δ13CvsPDB ≈ −18‰) under laboratory-controlled conditions for 8 months. At harvest, compound-specific isotope analyses were performed on different classes of soil compounds [i.e. phospholipids fatty acids (PLFAs), n-alkanes and soil pyrolysis products]. Linoleic acid (PLFA 18:2ω6,9) was found to be very depleted in 13C (δ13CvsPDB ≈ from −38 to −42‰) compared to all other PLFAs (δ13CvsPDB ≈ from −14 to −35‰). Because of this, fungi were identified as the first among microbes to use the litter as source of C. Among n-alkanes, long-chain (C27–C31) n-alkanes were the only to have a depleted δ13C. This is an indication that not all of the C derived from litter in the soil was transformed by microbes. The depletion in 13C was also found in different classes of pyrolysis products, suggesting that the litter-derived C is incorporated in less or more chemically stable compounds, even only after 8 months decomposition

An Open Label, Adaptive, Phase 1 Trial of High-Dose Oral Nitazoxanide in Healthy Volunteers: An Antiviral Candidate for SARS-CoV-2.

Funder: UnitaidRepurposing approved drugs may rapidly establish effective interventions during a public health crisis. This has yielded immunomodulatory treatments for severe coronavirus disease 2019 (COVID-19), but repurposed antivirals have not been successful to date because of redundancy of the target in vivo or suboptimal exposures at studied doses. Nitazoxanide is a US Food and Drug Administration (FDA) approved antiparasitic medicine, that physiologically-based pharmacokinetic (PBPK) modeling has indicated may provide antiviral concentrations across the dosing interval, when repurposed at higher than approved doses. Within the AGILE trial platform (NCT04746183) an open label, adaptive, phase I trial in healthy adult participants was undertaken with high-dose nitazoxanide. Participants received 1,500 mg nitazoxanide orally twice-daily with food for 7 days. Primary outcomes were safety, tolerability, optimum dose, and schedule. Intensive pharmacokinetic (PK) sampling was undertaken day 1 and 5 with minimum concentration (Cmin ) sampling on days 3 and 7. Fourteen healthy participants were enrolled between February 18 and May 11, 2021. All 14 doses were completed by 10 of 14 participants. Nitazoxanide was safe and with no significant adverse events. Moderate gastrointestinal disturbance (loose stools or diarrhea) occurred in 8 participants (57.1%), with urine and sclera discoloration in 12 (85.7%) and 9 (64.3%) participants, respectively, without clinically significant bilirubin elevation. This was self-limiting and resolved upon drug discontinuation. PBPK predictions were confirmed on day 1 but with underprediction at day 5. Median Cmin was above the in vitro target concentration on the first dose and maintained throughout. Nitazoxanide administered at 1,500 mg b.i.d. with food was safe with acceptable tolerability a phase Ib/IIa study is now being initiated in patients with COVID-19

Routine Antenatal Anti-D Prophylaxis in Women Who Are Rh(D) Negative: Meta-Analyses Adjusted for Differences in Study Design and Quality

Background: To estimate the effectiveness of routine antenatal anti-D prophylaxis for preventing sensitisation in pregnant Rhesus negative women, and to explore whether this depends on the treatment regimen adopted. Methods: Ten studies identified in a previous systematic literature search were included. Potential sources of bias were systematically identified using bias checklists, and their impact and uncertainty were quantified using expert opinion. Study results were adjusted for biases and combined, first in a random-effects meta-analysis and then in a random-effects metaregression analysis. Results: In a conventional meta-analysis, the pooled odds ratio for sensitisation was estimated as 0.25 (95 % CI 0.18, 0.36), comparing routine antenatal anti-D prophylaxis to control, with some heterogeneity (I 2 = 19%). However, this naïve analysis ignores substantial differences in study quality and design. After adjusting for these, the pooled odds ratio for sensitisation was estimated as 0.31 (95 % CI 0.17, 0.56), with no evidence of heterogeneity (I 2 = 0%). A meta-regression analysis wa

Comparison of diurnal variations, gestational age and gender related differences in fetal heart rate (FHR) parameters between appropriate-for-gestational-age (AGA) and small-for-gestational-age (SGA) fetuses in the home environment

Objective To assess the influence of gender, time of the day and gestational age on fetal heart rate (FHR) parameters between appropriate-for-gestational-age (AGA) and small-for-gestational age (SGA) fetuses using a portable fetal ECG monitor employed in the home setting. Methods We analysed and compared the antenatal FHR data collected in the home setting on 61 healthy pregnant women with singleton pregnancies from 24 weeks gestation. Of the 61 women, 31 had SGA fetuses (estimated fetal weight below the tenth gestational centile) and 30 were pregnant with AGA fetuses. FHR recordings were collected for up to 20 h. Two 90 min intervals were deliberately chosen retrospectively with respect to signal recording quality, one during day-time and one at night-time for comparison. Results Overall, success rate of the fetal abdominal ECG in the AGA fetuses was 75.7% compared to 48.6% in the SGA group. Based on randomly selected episodes of heart rate traces where recording quality exceeded 80% we were able to show a marginal difference between day and night-time recordings in AGA vs. SGA fetuses beyond 32 weeks of gestation. A selection bias in terms of covering different representation periods of fetal behavioural states cannot be excluded. In contrast to previous studies, we neither controlled maternal diet and activity nor measured maternal blood hormone and heart rate as all mothers were monitored in the home environment. Conclusion Based on clinically unremarkable, but statistically significant differences in the FHR parameters between the AGA and SGA group we suggest that further studies with large sample size are required to assess the clinical value of antenatal fetal ECG monitoring