Breeding programmes to improve male reproductive performance and efficiency of insemination dose production in paternal lines: feasibility and limitations

[EN] This paper aims at reviewing the current genetic knowledge of the issues related to the efficient use of bucks in artificial insemination (AI). Differences between lines have been found relevant in semen production and quality traits not necessarily related to their specialization as maternal or paternal lines. Accurate heritability estimates indicate that genetic selection for increasing semen production by improving male libido and reducing the number of rejected ejaculates may not be effective. However, total sperm produced per ejaculate appears to be as an interesting trait to select for, despite that genetic correlation between ejaculate volume and sperm concentration has not been yet accurately estimated. Semen pH has shown low to medium heritability estimates and a low coefficient of variation, therefore it is not advisable to attempt improvement by direct selection. In general, sperm motility traits have shown low heritabilities but, the rate of motile sperms per ejaculate has been considered as convenient to select for. Morphological characteristics of the spermatozoa have revealed as medium to highly heritable. There are evidences of high genetic correlations between sperm traits before and after freezing-thawing. There are few studies regarding the estimation of heterosis of seminal traits but results indicate important and favorable direct and maternal heterosis in crosses between maternal lines. However, this has not been confirmed in a cross between two paternal lines. Until now, attempts to find parametric or non-parametric functions to predict ejaculate fertility through seminal characteristics recorded in routinely evaluations have been very unsatisfactory. Hence, it may be necessary to find other semen quality markers, or to evaluate some of the currently used ones in a more precise manner or closer to the AI time in order to improve the ability to predict ejaculate fertility. Several seminal characteristics phenotypically correlated to male fertility, could be considered as potential traits to select for in order to genetically improving this trait. However, only the semen pH has been checked for this purpose, and a negative result has been obtained. Other traits can be studied in the future but bearing in mind that the required experiments will need large number of bucks for an accurate estimation of the genetic correlation of the trait with male fertility. This means that these experiments will be expensive and difficult to set up. The most common criterion to select paternal lines, average daily gain, seems not to be genetically correlated to male fertility and seminal traits. Thus, selection for average daily gain has no detrimental consequences on these traits, and a multi-trait selection, including growth rate and seminal traits directly related to an efficient AI semen dose production, is feasible in paternal lines. The male contribution to fertility after natural mating and after AI with semen doses with high concentration is negligible, but it has been found that, under more restrictive conditions of AI, male contributions to fertility and litter size are low but higher in magnitude than the ones obtained after natural mating. The genetic correlation between the female and male contributions to fertility has been found to be moderate to high and positive.This study was supported by the Generalitat Valenciana Research Programme (Prometeo 2009/125) and Spanish Research Projects (INIA RTA2005-00088-CO2; INIA RTA2008-00070-CO2; CICYT AGL2008-03274). Raquel Lavara was supported by a research grant from the Spanish Ministry of Education (MEC, FPU AP2007-03755) and Llibertat Tusell by a research grant from INIA.Piles, M.; Tusell, L.; Lavara García, R.; Baselga Izquierdo, M. (2013). Breeding programmes to improve male reproductive performance and efficiency of insemination dose production in paternal lines: feasibility and limitations. World Rabbit Science. 21(2):61-75. doi:10.4995/wrs.2013.1240SWORD617521

Observation of the gamma-ray binary HESS J0632+057 with the HESS, MAGIC, and VERITAS telescopes

The results of gamma-ray observations of the binary system HESS J0632 + 057 collected during 450 hr over 15 yr, between 2004 and 2019, are presented. Data taken with the atmospheric Cherenkov telescopes H.E.S.S., MAGIC, and VERITAS at energies above 350 GeV were used together with observations at X-ray energies obtained with Swift-XRT, Chandra, XMM-Newton, NuSTAR, and Suzaku. Some of these observations were accompanied by measurements of the Hα emission line. A significant detection of the modulation of the very high-energy gamma-ray fluxes with a period of 316.7 ± 4.4 days is reported, consistent with the period of 317.3 ± 0.7 days obtained with a refined analysis of X-ray data. The analysis of data from four orbital cycles with dense observational coverage reveals short-timescale variability, with flux-decay timescales of less than 20 days at very high energies. Flux variations observed over a timescale of several years indicate orbit-to-orbit variability. The analysis confirms the previously reported correlation of X-ray and gamma-ray emission from the system at very high significance, but cannot find any correlation of optical Hα parameters with fluxes at X-ray or gamma-ray energies in simultaneous observations. The key finding is that the emission of HESS J0632 + 057 in the X-ray and gamma-ray energy bands is highly variable on different timescales. The ratio of gamma-ray to X-ray flux shows the equality or even dominance of the gamma-ray energy range. This wealth of new data is interpreted taking into account the insufficient knowledge of the ephemeris of the system, and discussed in the context of results reported on other gamma-ray binary systems.C. B. Adams, W. Benbow, A. Brill, J. H. Buckley, M. Capasso, A. J. Chromey ... et al

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification. Funding: UK Research and Innovation and National Institute for Health Research

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Allowable misalignment of various elements of the TMX magnet set

A series of drift-surface and magnetic-field calculations has been carried out to try to estimate the accuracy with which the elements of the TMX magnet set must be magnetically aligned. The results of these calculations, for 500 G at the solenoidal center, are summarized

Determining plasma-fueling sources with an end-loss ion spectrometer. Revision 1

To help identify the major sources of fueling gas in Tandem Mirror Experiment-Upgrade (TMX-U), we mounted a mass-sensitive, E parallel B, end-loss ion spectrometer (ELIS) near the machine's centerline. We set the electric field in the ELIS to simultaneously measure the axial loss currents of both hydrogen and deuterium. We then initiated plasma discharges, where we injected either hydrogen or deuterium gas into the central cell. We also selected and deselected the central-cell neutral beams that were fueled with hydrogen gas. The end-cell neutral beams were always selected and fueled with deuterium. By taking the ratio of the hydrogen end-loss current to the deuterium end-loss current (with a known deuterium-gas feed rate), we were able to infer the effective fueling rates that were due to wall reflux, central-cell beams, and end-cell beams. The results were the following: wall reflux, 6 Torr x 1/s; central-cell beams, 15 Torr x 1/s; and end-cell beams 1 Torr x 1/s

Determining plasma-fueling sources with an end-loss ion spectrometer

To help identify the major sources of fueling gas in Tandem Mirror Experiment-Upgrade (TMX-U), we mounted a mass-sensitive, E parallel to B, end-loss ion spectrometer (ELIS) near the machine's centerline. We set the electric field in the ELIS to simultaneously measure the axial loss currents of both hydrogen and deuterium. We then initiated plasma discharges, where we injected either hydrogen or deuterium gas into the central cell. We also selected and deselected the central-cell neutral beams that were fueled with hydrogen gas. The end-cell neutral beams were always selected and fueled with deuterium. By taking the ratio of the hydrogen end-loss current to the deuterium end-loss current (with a known deuterium-gas feed rate), we were able to infer the effective fueling rates that were due to wall reflux, central-cell beams, and end-cell beams. The results were the following: wall reflux, 6 Torr.l/s; central-cell beams, 15 Torr.l/s; and end-cell beams 1 Torr.l/s. 3 refs., 3 figs., 1 tab