Guidelines for human gene nomenclature.

Standardized gene naming is crucial for effective communication about genes, and as genomics becomes increasingly important in healthcare, the need for a consistent language for human genes becomes ever more vital. Here we present the current HUGO Gene Nomenclature Committee (HGNC) guidelines for naming not only protein-coding but also RNA genes and pseudogenes, and outline the changes in approach and ethos that have resulted from the discoveries of the last few decades.National Human Genome Research Institute (NHGRI) grant U24HG003345 (1.5.2018-30.4.-2023) Wellcome Trust grant 208349/Z/17/Z (1.9.2017-31.8.2022

Herd-level animal management factors associated with the occurrence of bovine neonatal pancytopenia in calves in a multicountry study

Since 2007, mortality associated with a previously unreported haemorrhagic disease has been observed in young calves in several European countries. The syndrome, which has been named ‘bovine neonatal pancytopenia’ (BNP), is characterised by thrombocytopenia, leukocytopenia and a panmyelophthisis. A herd-level case-control study was conducted in four BNP affected countries (Belgium, France, Germany and the Netherlands) to identify herd management risk factors for BNP occurrence. Data were collected using structured face-to-face and telephone interviews of farm managers and their local veterinarians. In total, 363 case farms and 887 control farms were included in a matched multivariable conditional logistic regression analysis. Case-control status was strongly associated with the odds of herd level use of the vaccine PregSure® BVD (PregSure, Pfizer Animal Health) (matched adjusted odds ratio (OR) 107.2; 95% CI: 41.0–280.1). This was also the case for the practices of feeding calves colostrum from the calf’s own dam (OR 2.0; 95% CI: 1.1–3.4) or feeding pooled colostrum (OR 4.1; 95% CI: 1.9–8.8). Given that the study had relatively high statistical power and represented a variety of cattle production and husbandry systems, it can be concluded with some confidence that no other herd level management factors are competent causes for a sufficient cause of BNP occurrence on herd level. It is suggested that genetic characteristics of the dams and BNP calves should be the focus of further investigations aimed at identifying the currently missing component causes that together with PregSure vaccination and colostrum feeding represent a sufficient cause for occurrence of BNP in calves

Dietary Supplementation with Soluble Plantain Non-Starch Polysaccharides Inhibits Intestinal Invasion of Salmonella Typhimurium in the Chicken

Soluble fibres (non-starch polysaccharides, NSP) from edible plants but particularly plantain banana (Musa spp.), have been shown in vitro and ex vivo to prevent various enteric pathogens from adhering to, or translocating across, the human intestinal epithelium, a property that we have termed contrabiotic. Here we report that dietary plantain fibre prevents invasion of the chicken intestinal mucosa by Salmonella. In vivo experiments were performed with chicks fed from hatch on a pellet diet containing soluble plantain NSP (0 to 200 mg/d) and orally infected with S.Typhimurium 4/74 at 8 d of age. Birds were sacrificed 3, 6 and 10 d post-infection. Bacteria were enumerated from liver, spleen and caecal contents. In vitro studies were performed using chicken caecal crypts and porcine intestinal epithelial cells infected with Salmonella enterica serovars following pre-treatment separately with soluble plantain NSP and acidic or neutral polysaccharide fractions of plantain NSP, each compared with saline vehicle. Bacterial adherence and invasion were assessed by gentamicin protection assay. In vivo dietary supplementation with plantain NSP 50 mg/d reduced invasion by S.Typhimurium, as reflected by viable bacterial counts from splenic tissue, by 98.9% (95% CI, 98.1–99.7; P<0.0001). In vitro studies confirmed that plantain NSP (5–10 mg/ml) inhibited adhesion of S.Typhimurium 4/74 to a porcine epithelial cell-line (73% mean inhibition (95% CI, 64–81); P<0.001) and to primary chick caecal crypts (82% mean inhibition (95% CI, 75–90); P<0.001). Adherence inhibition was shown to be mediated via an effect on the epithelial cells and Ussing chamber experiments with ex-vivo human ileal mucosa showed that this effect was associated with increased short circuit current but no change in electrical resistance. The inhibitory activity of plantain NSP lay mainly within the acidic/pectic (homogalacturonan-rich) component. Supplementation of chick feed with plantain NSP was well tolerated and shows promise as a simple approach for reducing invasive salmonellosis

World-wide distributions of lactase persistence alleles and the complex effects of recombination and selection

The genetic trait of lactase persistence (LP) is associated with at least five independent functional single nucleotide variants in a regulatory region about 14 kb upstream of the lactase gene [-13910*T (rs4988235), -13907*G (rs41525747), -13915*G (rs41380347), -14009*G (rs869051967) and -14010*C (rs145946881)]. These alleles have been inferred to have spread recently and present-day frequencies have been attributed to positive selection for the ability of adult humans to digest lactose without risk of symptoms of lactose intolerance. One of the inferential approaches used to estimate the level of past selection has been to determine the extent of haplotype homozygosity (EHH) of the sequence surrounding the SNP of interest. We report here new data on the frequencies of the known LP alleles in the 'Old World' and their haplotype lineages. We examine and confirm EHH of each of the LP alleles in relation to their distinct lineages, but also show marked EHH for one of the older haplotypes that does not carry any of the five LP alleles. The region of EHH of this (B) haplotype exactly coincides with a region of suppressed recombination that is detectable in families as well as in population data, and the results show how such suppression may have exaggerated haplotype-based measures of past selection

Harmful algal blooms and climate change: exploring future distribution changes

Harmful algae can cause death in fish, shellfish, marine mammals, and humans, via their toxins or from effects associated with their sheer quantity. There are many species, which cause a variety of problems around north-west Europe, and the frequency and distribution of algal blooms have altered in the recent past. Species distribution modelling was used to understand how harmful algal species may respond in the future to climate change, by considering environmental preferences and how these may shift. Most distribution studies to date use low resolution global model outputs. In this study, high resolution, downscaled shelf seas climate projections for the north-west European shelf were nested within lower resolution global projections, to understand how the distribution of harmful algae may change by the mid to end of century. Projections suggest that the habitat of most species (defined by temperature, salinity, depth, and stratification) will shift north this century, with suitability increasing in the central and northern North Sea. An increase in occurrence here might lead to more frequent detrimental blooms if wind, irradiance and nutrient levels are also suitable. Prioritizing monitoring of species in these susceptible areas could help in establishing early-warning systems for aquaculture and health protection schemes

The Economic Impact of Eradicating Peste des Petits Ruminants:A Benefit-Cost Analysis

Peste des petits ruminants (PPR) is an important cause of mortality and production loss among sheep and goats in the developing world. Despite control efforts in a number of countries, it has continued to spread across Africa and Asia, placing an increasing burden on the livelihoods of livestock keepers and on veterinary resources in affected countries. Given the similarities between PPR and rinderpest, and the lessons learned from the successful global eradication of rinderpest, the eradication of PPR seems appealing, both eliminating an important disease and improving the livelihoods of the poor in developing countries. We conducted a benefit-cost analysis to examine the conomic returns from a proposed programme for the global eradication of PPR. Based on our knowledge and experience, we developed the eradication strategy and estimated its costs. The benefits of the programme were determined from (i) the averted mortality costs, based on an analysis of the literature, (ii) the downstream impact of reduced mortality using a social accounting matrix, and (iii) the avoided control costs based on current levels of vaccination. The results of the benefit-cost analysis suggest strong economic returns from PPR eradication. Based on a 15-year programme with total discounted costs of US$2.26 billion, we estimate discounted benefits of US$76.5 billion, yielding a net benefit of US$74.2 billion. This suggests a benefit cost ratio of 33.8, and an internal rate of return (IRR) of 199%. As PPR mortality rates are highly variable in different populations, we conducted a sensitivity analysis based on lower and higher mortality scenarios. All the scenarios examined indicate that investment in PPR eradication would be highly beneficial economically. Furthermore, removing one of the major constraints to small ruminant production would be of considerable benefit to many of the most vulnerable communities in Africa and Asia

Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma (FiTNEss (UK-MRA Myeloma XIV Trial)): a study protocol for a randomised phase III trial

INTRODUCTION: Multiple myeloma is a bone marrow cancer, which predominantly affects older people. The incidence is increasing in an ageing population.Over the last 10 years, patient outcomes have improved. However, this is less apparent in older, less fit patients, who are ineligible for stem cell transplant. Research is required in this patient group, taking into account frailty and aiming to improve: treatment tolerability, clinical outcomes and quality of life. METHODS AND ANALYSIS: Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma is a national, phase III, multicentre, randomised controlled trial comparing standard (reactive) and frailty-adjusted (adaptive) induction therapy delivery with ixazomib, lenalidomide and dexamethasone (IRD), and to compare maintenance lenalidomide to lenalidomide+ixazomib, in patients with newly diagnosed multiple myeloma not suitable for stem cell transplant. Overall, 740 participants will be registered into the trial to allow 720 and 478 to be randomised at induction and maintenance, respectively.All participants will receive IRD induction with the dosing strategy randomised (1:1) at trial entry. Patients randomised to the standard, reactive arm will commence at the full dose followed by toxicity dependent reactive modifications. Patients randomised to the adaptive arm will commence at a dose level determined by their International Myeloma Working Group frailty score. Following 12 cycles of induction treatment, participants alive and progression free will undergo a second (double-blind) randomisation on a 1:1 basis to maintenance treatment with lenalidomide+placebo versus lenalidomide+ixazomib until disease progression or intolerance. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the North East-Tyne & Wear South Research Ethics Committee (19/NE/0125) and capacity and capability confirmed by local research and development departments for each participating centre prior to opening to recruitment. Participants are required to provide written informed consent prior to trial registration. Trial results will be disseminated by conference presentations and peer-reviewed publications

The Mid-infrared Instrument for JWST and Its In-flight Performance

The Mid-Infrared Instrument (MIRI) extends the reach of the James Webb Space Telescope (JWST) to 28.5 μm. It provides subarcsecond-resolution imaging, high sensitivity coronagraphy, and spectroscopy at resolutions of λ/Δλ ∼ 100-3500, with the high-resolution mode employing an integral field unit to provide spatial data cubes. The resulting broad suite of capabilities will enable huge advances in studies over this wavelength range. This overview describes the history of acquiring this capability for JWST. It discusses the basic attributes of the instrument optics, the detector arrays, and the cryocooler that keeps everything at approximately 7 K. It gives a short description of the data pipeline and of the instrument performance demonstrated during JWST commissioning. The bottom line is that the telescope and MIRI are both operating to the standards set by pre-launch predictions, and all of the MIRI capabilities are operating at, or even a bit better than, the level that had been expected. The paper is also designed to act as a roadmap to more detailed papers on different aspects of MIRI