The Biology Instrument for the Viking Mars Mission

Two Viking spacecraft have successfully soft landed on the surface of Mars. Each carries, along with other scientific instruments, one biology laboratory with three different experiments designed to search for evidence of living microorganisms in material sampled from the Martian surface. This 15.5-kg biology instrument which occupies a volume of almost 28.3 dm3 is the first to carry out an in situ search for extraterrestrial life on a planet. The three experiments are called the pyrolytic release, labeled release, and gas exchange. The pyrolytic release experiment has the capability to measure the fixation of carbon dioxide or carbon monoxide into organic matter. The labeled release experiment detects metabolic processes by monitoring the production of volatile carbon compounds from a radioactively labeled nutrient mixture. The gas exchange experiment monitors the gas changes in the head space above a soil sample which is either incubated in a humid environment or supplied with a rich organic nutrient solution. Each experiment can analyze a soil sample as it is received from the surface or, as a control, analyze a soil which has been heated to above 160C. Each instrument has the capability to receive four different soils dug from the Martian surface and perform a number of analysis cycles depending on the particular experiment. This paper describes in detail the design and operation of the three experiments and the supporting subsystems

Common variants near MC4R are associated with fat mass, weight and risk of obesity.

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits

Quasielastic (e,e′p) reaction on 12C,56Fe, and 197Au

We report the results from a systematic study of the quasielastic (e,e′p) reaction on 12C, 56Fe, and 197Au performed at Jefferson Lab. We have measured nuclear transparency and extracted spectral functions (corrected for radiation) over a Q2 range of 0.64–3.25 (GeV∕c)2 for all three nuclei. In addition, we have extracted separated longitudinal and transverse spectral functions at Q2 of 0.64 and 1.8 (GeV∕c)2 for these three nuclei (except for 197Au at the higher Q2). The spectral functions are compared to a number of theoretical calculations. The measured spectral functions differ in detail but not in overall shape from most of the theoretical models. In all three targets the measured spectral functions show considerable excess transverse strength at Q2=0.64 (GeV∕c)2, which is much reduced at 1.8 (GeV∕c)2

Separated spectral functions for the quasifree 12C(e,e′p) reaction

A separation of the longitudinal and transverse 12C(e,e′p) cross sections in the quasifree region has been performed in parallel kinematics at Q2 of 0.64 and 1.8 GeV2 for initial proton momentum <80 MeV. The separated transverse and longitudinal spectral functions at Q2=0.64GeV2 show significant differences for missing energy between 25 and 60 MeV indicating a breakdown in the single nucleon knockout picture. The transverse spectral functions exhibit definite momentum transfer dependence

Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P&lt;10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P&lt;5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research