Signals from inner space

Advances in knowledge of mammalian physiology have been achieved through endocrine studies of sheep and deer. Such advances include the role of the pineal gland as the mediator between changes in daily photoperiod and melatonin secretion, plus the role of thyroid hormones, for controlling reproduction in seasonally breeding livestock. Antlers provide an example of post-maturity bone formation in a mammal and we have shown that additional hardening (mineralisation) of the antlers results from activation of nearby oestradiol receptors. Based on studies of sheep, C-type natriuretic peptide has emerged in spite of its name as an important adaptive signal for fetal well-being and may be an important regulator of brain function

E-MSD: an integrated data resource for bioinformatics

The Macromolecular Structure Database (MSD) group (http://www.ebi.ac.uk/msd/) continues to enhance the quality and consistency of macromolecular structure data in the worldwide Protein Data Bank (wwPDB) and to work towards the integration of various bioinformatics data resources. One of the major obstacles to the improved integration of structural databases such as MSD and sequence databases like UniProt is the absence of up to date and well-maintained mapping between corresponding entries. We have worked closely with the UniProt group at the EBI to clean up the taxonomy and sequence cross-reference information in the MSD and UniProt databases. This information is vital for the reliable integration of the sequence family databases such as Pfam and Interpro with the structure-oriented databases of SCOP and CATH. This information has been made available to the eFamily group (http://www.efamily.org.uk/) and now forms the basis of the regular interchange of information between the member databases (MSD, UniProt, Pfam, Interpro, SCOP and CATH). This exchange of annotation information has enriched the structural information in the MSD database with annotation from wider sequence-oriented resources. This work was carried out under the ‘Structure Integration with Function, Taxonomy and Sequences (SIFTS)’ initiative (http://www.ebi.ac.uk/msd-srv/docs/sifts) in the MSD group

Meningococcal genetic variation mechanisms viewed through comparative analysis of Serogroup C strain FAM18

Copyright @ 2007 Public Library of ScienceThe bacterium Neisseria meningitidis is commonly found harmlessly colonising the mucosal surfaces of the human nasopharynx. Occasionally strains can invade host tissues causing septicaemia and meningitis, making the bacterium a major cause of morbidity and mortality in both the developed and developing world. The species is known to be diverse in many ways, as a product of its natural transformability and of a range of recombination and mutation-based systems. Previous work on pathogenic Neisseria has identified several mechanisms for the generation of diversity of surface structures, including phase variation based on slippage-like mechanisms and sequence conversion of expressed genes using information from silent loci. Comparison of the genome sequences of two N. meningitidis strains, serogroup B MC58 and serogroup A Z2491, suggested further mechanisms of variation, including C-terminal exchange in specific genes and enhanced localised recombination and variation related to repeat arrays. We have sequenced the genome of N. meningitidis strain FAM18, a representative of the ST-11/ET-37 complex, providing the first genome sequence for the disease-causing serogroup C meningococci; it has 1,976 predicted genes, of which 60 do not have orthologues in the previously sequenced serogroup A or B strains. Through genome comparison with Z2491 and MC58 we have further characterised specific mechanisms of genetic variation in N. meningitidis, describing specialised loci for generation of cell surface protein variants and measuring the association between noncoding repeat arrays and sequence variation in flanking genes. Here we provide a detailed view of novel genetic diversification mechanisms in N. meningitidis. Our analysis provides evidence for the hypothesis that the noncoding repeat arrays in neisserial genomes (neisserial intergenic mosaic elements) provide a crucial mechanism for the generation of surface antigen variants. Such variation will have an impact on the interaction with the host tissues, and understanding these mechanisms is important to aid our understanding of the intimate and complex relationship between the human nasopharynx and the meningococcus.This work was supported by the Wellcome Trust through the Beowulf Genomics Initiative

Talent identification and relative age effects in English male rugby union pathways: From entry to expertise

A common practice in youth rugby union is to group players based on (bi)annual age with fixed cut-off dates. The overrepresentation of players born at the start of the cut-off date and the underrepresentation of players born toward the end of the cut-off date are termed relative age effects (RAEs). The aim of this study was to examine RAEs during entry into professional and international rugby union pathways in England, as well as comparing them to their respective senior cohort: U15 Regional Academy Player (n = 1,114) vs. Senior Professional Player (n = 281) and U16–23 England Academy Player (n = 849) vs. Senior International Player (n = 48). Chi-square (χ2) analysis compared birth quarter (BQ) distributions against expected distributions. Odds ratios and 95% confidence intervals compared the likelihood of a BQ being selected. Findings revealed a significant overrepresentation of relatively older players compared with their relatively younger peers within both youth cohorts (P < 0.001; BQ1 = 42.5% vs. BQ4 = 9.6%; BQ1 = 36.5% vs. BQ4 = 15.2%). In comparison, there was no significant difference in the BQ distributions within both senior cohorts. Further, BQ4s were 3.86 and 3.9 times more likely to achieve senior professional and international levels than BQ1s and BQ2s, respectively. It is suggested that relatively younger players may have a greater likelihood of achieving expertise following entry into a rugby union talent pathway due to benefitting from more competitive play against relatively older counterparts during their development (e.g., reversal effects; the underdog hypothesis). Moreover, possible solutions (e.g., age and anthropometric banding; playing-up and playing-down) are discussed to encourage practitioners and policy makers to create the most appropriate learning environment for every player

Angular sensitivity of blowfly photoreceptors: intracellular measurements and wave-optical predictions

The angular sensitivity of blowfly photoreceptors was measured in detail at wavelengths λ = 355, 494 and 588 nm. The measured curves often showed numerous sidebands, indicating the importance of diffraction by the facet lens. The shape of the angular sensitivity profile is dependent on wavelength. The main peak of the angular sensitivities at the shorter wavelengths was flattened. This phenomenon as well as the overall shape of the main peak can be quantitatively described by a wave-optical theory using realistic values for the optical parameters of the lens-photoreceptor system. At a constant response level of 6 mV (almost dark adapted), the visual acuity of the peripheral cells R1-6 is at longer wavelengths mainly diffraction limited, while at shorter wavelengths the visual acuity is limited by the waveguide properties of the rhabdomere. Closure of the pupil narrows the angular sensitivity profile at the shorter wavelengths. This effect can be fully described by assuming that the intracellular pupil progressively absorbs light from the higher order modes. In light-adapted cells R1-6 the visual acuity is mainly diffraction limited at all wavelengths.

Nitrogen balance of dairy cows divergent for milk urea nitrogen breeding values consuming either plantain or perennial ryegrass

Inefficient nitrogen (N) use from pastoral dairy production systems has resulted in environmental degradation, as a result of excessive concentrations of urinary N excretion leaching into waterways and N₂O emissions from urination events into the atmosphere. The objectives of this study were to measure and evaluate the total N balance of lactating dairy cows selected for milk urea N concentration breeding values (MUNBVs) consuming either a 100% perennial ryegrass (Lolium perenne L.) or 100% plantain (Plantago lanceolata L.) diet. Sixteen multiparous lactating HolsteinFriesian × Jersey cows divergent for MUNBV were housed in metabolism crates for 72 h, where intake and excretions were collected and measured. No effect of MUNBV was detected for total N excretion; however, different excretion characteristics were detected, per urination event. Low MUNBV cows had a 28% reduction in the concentration of urinary urea nitrogen (g/event) compared to high MUNBV cows when consuming a ryegrass diet. Cows consuming plantain regardless of their MUNBV value had a 62% and 48% reduction in urinary urea nitrogen (g/event) compared to high and low MUNBV cows consuming ryegrass, respectively. Cows consuming plantain also partitioned more N into faeces. These results suggest that breeding for low MUNBV cows on ryegrass diets and the use of a plantain diet will reduce urinary urea nitrogen loading rates and therefore estimated nitrate leaching values, thus reducing the environmental impact of pastoral dairy production systems

Effects of ATX-MS-1467 immunotherapy over 16 weeks in relapsing multiple sclerosis

Objective: To assess safety, tolerability and efficacy of the antigen-specific immunotherapy ATX-MS-1467 in participants with relapsing multiple sclerosis (RMS) using different treatment protocols to induce tolerance. Methods: Two open-label trials in adult participants with RMS. Study 1 was a multicentre Phase 1b safety evaluation comparing intradermal (i.d., Cohort 1) with subcutaneous (Cohort 2) administration in 43 participants. Both cohorts received ATX-MS-1467 dosed at 25, 50, 100, 400, and 800 μg at 14-day intervals over 8 weeks, followed by 8 weeks with 4 additional 800 μg doses at 14-day intervals and 32 weeks off study medication. Study 2 was a Phase 2a, multicentre, single-arm, trial enrolling 37 participants. ATX-MS-1467 was titrated from 50 µg i.d. on Day 1 to 200 µg on Day 15 and 800 µg on Day 29 followed by biweekly administration of 800 μg for 16 weeks and 16 weeks off study medication. Efficacy was evaluated on MRI parameters and clinical variables. Safety end points included treatment-emergent adverse events and injection-site reactions. Results: In Study 1 there was a significant decrease in new/persisting T1 GdE lesions in Cohort 1 from baseline to Week 16, returning to baseline values at week 48. In Study 2, the number of T1 GdE lesions were significantly reduced on treatment and remained reduced at study completion. Safety results were unremarkable in both studies. Conclusion: Relatively slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions and a sustained effect post-treatment. Further trials of ATX-MS-1467 are warranted. Classification of Evidence: This work provides Class IV evidence that for patients with relapsing multiple sclerosis, slow ATX-MS-1467 titration and a longer full-dose i.d. treatment period is associated with reduction in GdE lesions

An evaluation of surface meteorology and fluxes over the Iceland and Greenland Seas in ERA5 reanalysis: the impact of sea ice distribution

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Renfrew, I. A., Barrell, C., Elvidge, A. D., Brooke, J. K., Duscha, C., King, J. C., Kristiansen, J., Cope, T. L., Moore, G. W. K., Pickart, R. S., Reuder, J., Sandu, I., Sergeev, D., Terpstra, A., Vage, K., & Weiss, A. An evaluation of surface meteorology and fluxes over the Iceland and Greenland Seas in ERA5 reanalysis: the impact of sea ice distribution. Quarterly Journal of the Royal Meteorological Society, (2020): 1-22, doi:10.1002/qj.3941.The Iceland and Greenland Seas are a crucial region for the climate system, being the headwaters of the lower limb of the Atlantic Meridional Overturning Circulation. Investigating the atmosphere–ocean–ice processes in this region often necessitates the use of meteorological reanalyses—a representation of the atmospheric state based on the assimilation of observations into a numerical weather prediction system. Knowing the quality of reanalysis products is vital for their proper use. Here we evaluate the surface‐layer meteorology and surface turbulent fluxes in winter and spring for the latest reanalysis from the European Centre for Medium‐Range Weather Forecasts, i.e., ERA5. In situ observations from a meteorological buoy, a research vessel, and a research aircraft during the Iceland–Greenland Seas Project provide unparalleled coverage of this climatically important region. The observations are independent of ERA5. They allow a comprehensive evaluation of the surface meteorology and fluxes of these subpolar seas and, for the first time, a specific focus on the marginal ice zone. Over the ice‐free ocean, ERA5 generally compares well to the observations of surface‐layer meteorology and turbulent fluxes. However, over the marginal ice zone, the correspondence is noticeably less accurate: for example, the root‐mean‐square errors are significantly higher for surface temperature, wind speed, and surface sensible heat flux. The primary reason for the difference in reanalysis quality is an overly smooth sea‐ice distribution in the surface boundary conditions used in ERA5. Particularly over the marginal ice zone, unrepresented variability and uncertainties in how to parameterize surface exchange compromise the quality of the reanalyses. A parallel evaluation of higher‐resolution forecast fields from the Met Office's Unified Model corroborates these findings.This study was part of the Iceland Greenland Seas Project. Funding was from the NERC AFIS grant (NE/N009754/1), the ALERTNESS (Advanced models and weather prediction in the Arctic: enhanced capacity from observations and polar process representations) project (Research Council of Norway project number 280573), the Trond Mohn Foundation (BFS2016REK01), and the National Science Foundation grant OCE‐1558742. The Leosphere WindCube v2 and the Wavescan buoy are part of the OBLO (Offshore Boundary Layer Observatory) infrastructure funded by the Research Council of Norway (project number 227777)

Dairy cows with different milk urea nitrogen breeding values display different grazing behaviours

The objective of this study was to describe the diurnal pattern of grazing behaviour of multi-parous dairy cows divergent for milk urea N breeding values (MUNBV) and the consistency of these differences across different sward compositions (perennial ryegrass [RG; Lolium perenne L.] or ryegrass with plantain [Plantago lanceolata L.; RGPL]) and stages of lactation (early and late lactation). Jaw movement recorders were fitted to 24 animals in early lactation and 16 cows in late lactation, in early lactation 12 cows were assigned to the ryegrass diet and 12 cows assigned to the plantain diet, in late lactation 8 cows were assigned to ryegrass with the remaining 8 cows assigned to the plantain diet. For each diet half of the animals during both stages of lactation were classified as high for MUNBV and the other half as low for MUNBV. Low MUNBV animals had more mastications per bite over the day (P < 0.01) with a one-unit decrease in MUNBV resulting in 0.07 more bites per mastication during the first two grazing bouts, as well as differences in the temporal distribution of grazing bouts compared with high MUNBV cows. A one-unit decrease in MUNBV resulted in a 0.11 ± 0.02 increase in mastications per bite during the first grazing bout across both stages of lactation and sward composition. Ingestive behaviour has a large impact on the physical features of ingesta and thereby rumen function. The results of this study indicate that dairy cows divergent for MUNBV grazing the same forage apply different grazing strategies in terms of oral processing of ingesta and diurnal meal pattern. These results present potential explanatory variables for phenotypical differences observed in dairy cows divergent for MUNBV

A Re-Annotation of the Saccharomyces Cerevisiae Genome

Discrepancies in gene and orphan number indicated by previous analyses suggest that S. cerevisiae would benefit from a consistent re-annotation. In this analysis three new genes are identified and 46 alterations to gene coordinates are described. 370 ORFs are defined as totally spurious ORFs which should be disregarded. At least a further 193 genes could be described as very hypothetical, based on a number of criteria. It was found that disparate genes with sequence overlaps over ten amino acids (especially at the N-terminus) are rare in both S. cerevisiae and Sz. pombe. A new S. cerevisiae gene number estimate with an upper limit of 5804 is proposed, but after the removal of very hypothetical genes and pseudogenes this is reduced to 5570. Although this is likely to be closer to the true upper limit, it is still predicted to be an overestimate of gene number. A complete list of revised gene coordinates is available from the Sanger Centre (S. cerevisiae reannotation: ftp://ftp/pub/yeast/SCreannotation)