Six-year changes in body mass index and cardiorespiratory fitness of English schoolchildren from an affluent area

We compared values of body mass index (BMI) and cardiorespiratory fitness (20 m shuttle-run test) of n=157 boys and n=150 girls aged 10-11 measured in 2014 with measures from 2008 and 1998. Boys' fitness was lower (d=0.68) in 2014 than 2008, despite a small (d=0.37) decline in BMI. Girl's BMI changed trivially (d=0.08) but cardiorespiratory fitness was lower (d=0.47) in 2014 than 2008. This study suggests fitness is declining at 0.95% per year, which exceeds the 0.8% rate of decline we reported between 1998 and 2008 and is double the global average of 0.43%. Declines in fitness were independent of changes in BMI suggesting continued reductions in English children's habitual physical activity levels

Silicate weathering and carbon cycle controls on the Oligocene-Miocene transition glaciation

Changes in both silicate weathering rates and organic carbon burial have been proposed as drivers of the transient “Mi-1” glaciation event at the Oligocene-Miocene transition (OMT; ~23 Ma). However detailed geochemical proxy data are required to test these hypotheses. Here we present records of Li/Ca, Mg/Ca, Cd/Ca, U/Ca, δ18O, δ13C, and shell weight in planktonic foraminifera from marine sediments spanning the OMT in the equatorial Atlantic Ocean. Li/Ca values increase by 1 μmol/mol across this interval. We interpret this to indicate a ~20% increase in silicate weathering rates, which would have lowered atmospheric CO2, potentially forcing the Antarctic glaciation circa 23 Ma. δ13C of thermocline dwelling planktonic foraminifera track the global increase in seawater δ13C across the OMT and during the Mi-1 event, hence supporting a hypothesized global increase in organic carbon burial rates. High δ13C previously measured in epipelagic planktonic foraminifera and high Cd/Ca ratios during Mi-1 are interpreted to represent locally enhanced primary productivity, stimulated by increased nutrients supply to surface waters. The fingerprint of high export production and associated organic carbon burial at this site is found in reduced bottom water oxygenation (inferred from high foraminiferal U/Ca), and enhanced respiratory dissolution of carbonates, characterised by reduced foraminiferal shell weight. Replication of our results elsewhere would strengthen the case that weathering-induced CO2 sequestration preconditioned climate for Antarctic ice sheet growth across the OMT and increased burial of organic carbon acted as a feedback that intensified cooling at this time

Precise magnesium isotope measurements in core top planktic and benthic foraminifera

This study presents a new methodology to obtain highly precise measurements (±0.1‰) of magnesium isotope ratios in very small samples of foraminiferal carbonate (40–50 μg). Here this technique is used to examine Mg isotopic variation among different species of core top foraminifera over a range of different ambient conditions. Despite the high degree of temperature control on the abundance of elemental Mg incorporated into foraminiferal tests, analyses of surface dwelling Globigerinoides ruber and G. sacculifer from five cores, with associated sea surface temperatures ranging from 20 to 31°C, show no significant temperature-dependent variations in their Mg isotope ratios. Analyses of different size fractions of G. sacculifer show an increase in Mg/Ca with test size but no variation of Mg isotope ratio. In all, nine planktic and benthic species were analyzed; all show identical Mg isotope ratios with a mean of δ26Mg = −4.72‰, apart from small differences in three species, namely O. universa, G. sacculifer (which are both ∼0.4‰ lighter than the average), and P. obliquiloculata (which is ∼0.4‰ heavier). These results highlight the constancy of foraminiferal Mg isotope ratios, despite changing environmental conditions which dominate Mg/Ca variation and arguably affect Ca isotope fractionation. This is an important observation which needs to be included in any model of foraminiferal calcification. The insusceptibility of δ26Mg values to external parameters makes Mg isotopes ideally suited to constraining past variations in the Mg isotope budget of the oceans and the information this carries about the history of oceanic dolomitization, continental weathering, and hydrothermal behavior

Management of high-risk corneal grafts

MACMILLAN BUILDING,4 CRINAN ST, LONDON, ENGLAND, N1 9X

Glutathione Provides a Source of Cysteine Essential for Intracellular Multiplication of Francisella tularensis

Francisella tularensis is a highly infectious bacterium causing the zoonotic disease tularemia. Its ability to multiply and survive in macrophages is critical for its virulence. By screening a bank of HimarFT transposon mutants of the F. tularensis live vaccine strain (LVS) to isolate intracellular growth-deficient mutants, we selected one mutant in a gene encoding a putative γ-glutamyl transpeptidase (GGT). This gene (FTL_0766) was hence designated ggt. The mutant strain showed impaired intracellular multiplication and was strongly attenuated for virulence in mice. Here we present evidence that the GGT activity of F. tularensis allows utilization of glutathione (GSH, γ-glutamyl-cysteinyl-glycine) and γ-glutamyl-cysteine dipeptide as cysteine sources to ensure intracellular growth. This is the first demonstration of the essential role of a nutrient acquisition system in the intracellular multiplication of F. tularensis. GSH is the most abundant source of cysteine in the host cytosol. Thus, the capacity this intracellular bacterial pathogen has evolved to utilize the available GSH, as a source of cysteine in the host cytosol, constitutes a paradigm of bacteria–host adaptation

High major histocompatibility complex class I polymorphism despite bottlenecks in wild and domesticated populations of the zebra finch ()

Background Two subspecies of zebra finch, Taeniopygia guttata castanotis and T. g. guttata are native to Australia and the Lesser Sunda Islands, respectively. The Australian subspecies has been domesticated and is now an important model system for research. Both the Lesser Sundan subspecies and domesticated Australian zebra finches have undergone population bottlenecks in their history, and previous analyses using neutral markers have reported reduced neutral genetic diversity in these populations. Here we characterize patterns of variation in the third exon of the highly variable major histocompatibility complex (MHC) class I α chain. As a benchmark for neutral divergence, we also report the first mitochondrial NADH dehydrogenase 2 (ND2) sequences in this important model system. Results Despite natural and human-mediated population bottlenecks, we find that high MHC class I polymorphism persists across all populations. As expected, we find higher levels of nucleotide diversity in the MHC locus relative to neutral loci, and strong evidence of positive selection acting on important residues forming the peptide-binding region (PBR). Clear population differentiation of MHC allele frequencies is also evident, and this may be due to adaptation to new habitats and associated pathogens and/or genetic drift. Whereas the MHC Class I locus shows broad haplotype sharing across populations, ND2 is the first locus surveyed to date to show reciprocal monophyly of the two subspecies. Conclusions Despite genetic bottlenecks and genetic drift, all surveyed zebra finch populations have maintained high MHC Class I diversity. The diversity at the MHC Class I locus in the Lesser Sundan subspecies contrasts sharply with the lack of diversity in previously examined neutral loci, and may thus be a result of selection acting to maintain polymorphism. Given uncertainty in historical population demography, however, it is difficult to rule out neutral processes in maintaining the observed diversity. The surveyed populations also differ in MHC Class I allele frequencies, and future studies are needed to assess whether these changes result in functional immune differences

High and low levels of an NTRK2-driven genetic profile affect motor- and cognition-associated frontal gray matter in prodromal Huntington’s disease

This study assessed how BDNF (brain-derived neurotrophic factor) and other genes involved in its signaling influence brain structure and clinical functioning in pre-diagnosis Huntington’s disease (HD). Parallel independent component analysis (pICA), a multivariate method for identifying correlated patterns in multimodal datasets, was applied to gray matter concentration (GMC) and genomic data from a sizeable PREDICT-HD prodromal cohort (N = 715). pICA identified a genetic component highlighting NTRK2, which encodes BDNF’s TrkB receptor, that correlated with a GMC component including supplementary motor, precentral/premotor cortex, and other frontal areas (p < 0.001); this association appeared to be driven by participants with high or low levels of the genetic profile. The frontal GMC profile correlated with cognitive and motor variables (Trail Making Test A (p = 0.03); Stroop Color (p = 0.017); Stroop Interference (p = 0.04); Symbol Digit Modalities Test (p = 0.031); Total Motor Score (p = 0.01)). A top-weighted NTRK2 variant (rs2277193) was protectively associated with Trail Making Test B (p = 0.007); greater minor allele numbers were linked to a better performance. These results support the idea of a protective role of NTRK2 in prodromal HD, particularly in individuals with certain genotypes, and suggest that this gene may influence the preservation of frontal gray matter that is important for clinical functioning.This project was supported by 1U01NS082074 (V.C. and J.T., co-principal investigators) from the National Institutes of Health, National Institute of Neurological Disorders and Stroke. The PREDICT-HD study was supported by NIH/NINDS grant 5R01NS040068 awarded to J.P.; CHDI Foundation, Inc., A3917 and 6266 awarded to J.P.; Cognitive and Functional Brain Changes in Preclinical Huntington’s Disease (HD) 5R01NS054893 awarded to J.P.; 4D Shape Analysis for Modeling Spatiotemporal Change Trajectories in Huntington’s 1U01NS082086; Functional Connectivity in Premanifest Huntington’s Disease 1U01NS082083; and Basal Ganglia Shape Analysis and Circuitry in Huntington’s Disease 1U01NS082085 awarded to Christopher A. Ross

Food supplements increase adult tarsus length, but not growth rate, in an island population of house sparrows (Passer domesticus)

<p>Abstract</p> <p>Background</p> <p>Variation in food supply during early development can influence growth rate and body size in many species. However, whilst the detrimental effects of food restriction have often been studied in natural populations, how young individuals respond to an artificial increase in food supply is rarely investigated. Here, we investigated both the short-term and long-term effects of providing house sparrow chicks with food supplements during a key period of growth and development and assessed whether providing food supplements had any persistent effect upon adult size (measured here as tarsus length).</p> <p>Results</p> <p>Male nestlings tended to reach higher mass asymptotes than females. Furthermore, brood size was negatively associated with a chick's asymptotic mass. However, providing food supplements had no influence upon the growth rate or the asymptotic mass of chicks. Adults that received food supplements as chicks were larger, in terms of their tarsus length, than adults that did not receive extra food as chicks. In addition, the variation in tarsus length amongst adult males that were given food supplements as chicks was significantly less than the variance observed amongst males that did not receive food supplements.</p> <p>Conclusions</p> <p>Our results demonstrate that the food supply chicks experience during a critical developmental period can have a permanent effect upon their adult phenotype. Furthermore, providing extra food to chicks resulted in sex-biased variance in a size-related trait amongst adults, which shows that the degree of sexual size dimorphism can be affected by the environment experienced during growth.</p