Does Dietary Mitigation of Enteric Methane Production Affect Rumen Function and Animal Productivity in Dairy Cows?

It has been suggested that the rumen microbiome and rumen function might be disrupted if methane production in the rumen is decreased. Furthermore concerns have been voiced that geography and management might influence the underlying microbial population and hence the response of the rumen to mitigation strategies. Here we report the effect of the dietary additives: linseed oil and nitrate on methane emissions, rumen fermentation, and the rumen microbiome in two experiments from New Zealand (Dairy 1) and the UK (Dairy 2). Dairy 1 was a randomized block design with 18 multiparous lactating cows. Dairy 2 was a complete replicated 3 x 3 Latin Square using 6 rumen cannulated, lactating dairy cows. Treatments consisted of a control total mixed ration (TMR), supplementation with linseed oil (4% of feed DM) and supplementation with nitrate (2% of feed DM) in both experiments. Methane emissions were measured in open circuit respiration chambers and rumen samples were analyzed for rumen fermentation parameters and microbial population structure using qPCR and next generation sequencing (NGS). Supplementation with nitrate, but not linseed oil, decreased methane yield (g/kg DMI; P<0.02) and increased hydrogen (P<0.03) emissions in both experiments. Furthermore, the effect of nitrate on gaseous emissions was accompanied by an increased rumen acetate to propionate ratio and consistent changes in the rumen microbial populations including a decreased abundance of the main genus Prevotella and a decrease in archaeal mcrA (log10 copies/g rumen DM content). These results demonstrate that methane emissions can be significantly decreased with nitrate supplementation with only minor, but consistent, effects on the rumen microbial population and its function, with no evidence that the response to dietary additives differed due to geography and different underlying microbial populations

The threats posed by the pet trade in alien terrestrial invertebrates in South Africa

The pet trade has been a major pathway for the introduction of vertebrate invaders, but little is known about its role in invertebrate invasions. Here we assess the trade in terrestrial invertebrates (excluding spiders) in South Africa and the potential of this trade to result in biological invasions and impacts. Pet stores, websites, and expositions were visited, and a list of the taxa traded was compiled. DNA barcoding was used to determine if the species were correctly identified in the trade. Information on invasion history and impact elsewhere was used to assess the potential for species to become invasive and have impact in South Africa. We found 53 alien terrestrial invertebrate taxa that were traded, although only 36 of these matched a valid species name. Of 11 species tested using DNA barcoding nine were correctly identified. Species accumulation curves were produced, but did not reach an asymptote, suggesting there are many species in the trade that were not recorded. The most common species were used as food for pets, rather than as pets themselves. None of the species were reported to be invasive elsewhere, and few had records of causing negative impacts (the exception being moderate impacts to human health caused by venomous scorpions). Therefore, there is little evidence that the invertebrates traded pose a significant threat to South Africa. However, given uncertainties in which taxa are traded and the lack of data on invasiveness and impact, there might be a significant invasion debt. We recommend continued monitoring and engagement with the industry.The South African Department of Forestry, Fisheries, and the Environment (DFFtE)http://www.elsevier.de/jnc2021-06-01hj2020Zoology and Entomolog

Unpacking the enabling factors for hand, cord and birth-surface hygiene in Zanzibar maternity units.

Recent national surveys in The United Republic of Tanzania have revealed poor standards of hygiene at birth in facilities. As more women opt for institutional delivery, improving basic hygiene becomes an essential part of preventative strategies for reducing puerperal and newborn sepsis. Our collaborative research in Zanzibar provides an in-depth picture of the state of hygiene on maternity wards to inform action. Hygiene was assessed in 2014 across all 37 facilities with a maternity unit in Zanzibar. We used a mixed methods approach, including structured and semi-structured interviews, and environmental microbiology. Data were analysed according to the WHO 'cleans' framework, focusing on the fundamental practices for prevention of newborn and maternal sepsis. For each 'clean' we explored the following enabling factors: knowledge, infrastructure (including equipment), staffing levels and policies. Composite indices were constructed for the enabling factors of the 'cleans' from the quantitative data: clean hands, cord cutting, and birth surface. Results from the qualitative tools were used to complement this information.Only 49% of facilities had the 'infrastructural' requirements to enable 'clean hands', with the availability of constant running water particularly lacking. Less than half (46%) of facilities met the 'knowledge' requirements for ensuring a 'clean delivery surface'; six out of seven facilities had birthing surfaces that tested positive for multiple potential pathogens. Almost two thirds of facilities met the 'infrastructure (equipment) requirement' for 'clean cord'; however, disposable cord clamps being frequently out of stock, often resulted in the use of non-sterile thread made of fabric. This mixed methods approach, and the analytical framework based on the WHO 'cleans' and the enabling factors, yielded practical information of direct relevance to action at local and ministerial levels. The same approach could be applied to collect and analyse data on infection prevention from maternity units in other contexts

Exosomal transport of hepatocyte-derived drug-modified proteins to the immune system.

Idiosyncratic drug-induced liver injury (DILI) is a rare, often difficult to predict adverse reaction with complex pathomechanisms. However, it is now evident that certain forms of DILI are immune-mediated and may involve the activation of drug-specific T-cells. Exosomes are cell-derived vesicles that carry RNA, lipids and protein cargo from their cell of origin to distant cells, and may play a role in immune activation. Herein, primary human hepatocytes were treated with drugs associated with a high incidence of DILI (flucloxacillin, amoxicillin, isoniazid and nitroso-sulfamethoxazole) to characterize the proteins packaged within exosomes that are subsequently transported to dendritic cells for processing. Exosomes measured between 50-100 nm and expressed enriched CD63. LC-MS/MS identified 2109 proteins, with 608 proteins being quantified across all exosome samples. Data are available via ProteomeXchange with identifier PXD010760. Analysis of gene ontologies revealed that exosomes mirrored whole human liver tissue in terms of the families of proteins present, regardless of drug treatment. However, exosomes from nitroso-sulfamethoxazole-treated hepatocytes selectively packaged a specific subset of proteins. LC-MS also revealed the presence of hepatocyte-derived exosomal proteins covalently modified with amoxicillin, flucloxacillin and nitroso-sulfamethoxazole. Uptake of exosomes by monocyte-derived dendritic cells occurred silently, mainly via phagocytosis, and was inhibited by latrunculin A. An, amoxicillin-modified 9-mer peptide derived from the exosomal transcription factor protein SOX30 activated naïve T-cells from HLA-A*02:01 positive human donors. Conclusion. This study shows that exosomes have the potential to transmit drug-specific hepatocyte-derived signals to the immune system and provides a pathway for the induction of drug hapten-specific T-cell responses. This article is protected by copyright. All rights reserved

Maltreated children use more grammatical negations

Many studies reveal a strong impact of childhood maltreatment on language development, mainly resulting in shorter utterances, less rich vocabulary, or a delay in grammatical complexity. However, different theories suggest the possibility for resilience – a positive adaptation to an otherwise adverse environment – in children who experienced childhood maltreatment. Here, we investigated different measures for language development in spontaneous speech, examining whether childhood maltreatment leads to a language deficit only or whether it can also result in differences in language use due to a possible adaptation to a toxic environment. We compared spontaneous speech during therapeutic peer-play sessions of 32 maltreated and 32 non-maltreated children from the same preschool and equivalent in gender, age (2 to 5 years), home neighborhood, ethnicity, and family income. Maltreatment status was reported by formal child protection reports, and corroborated by independent social service reports. We investigated general language sophistication (i.e., vocabulary, talkativeness, mean length of utterance), as well as grammatical development (i.e., use of plurals, tense, grammatical negations). We found that maltreated and non-maltreated children showed similar sophistication across all linguistic measures, except for the use of grammatical negations. Maltreated children used twice as many grammatical negations as non-maltreated children. The use of this highly complex grammatical structure shows an advanced linguistic skill, which shows that childhood maltreatment does not necessarily lead to a language deficit. The result might indicate the development of a negativity bias in the structure of spontaneous language due to an adaptation to their experiences

The Effectiveness of Pharmacological and Non-Pharmacological Interventions for Improving Glycaemic Control in Adults with Severe Mental Illness: A Systematic Review and Meta-Analysis

People with severe mental illness (SMI) have reduced life expectancy compared with the general population, which can be explained partly by their increased risk of diabetes. We conducted a meta-analysis to determine the clinical effectiveness of pharmacological and non-pharmacological interventions for improving glycaemic control in people with SMI (PROSPERO registration: CRD42015015558). A systematic literature search was performed on 30/10/2015 to identify randomised controlled trials (RCTs) in adults with SMI, with or without a diagnosis of diabetes that measured fasting blood glucose or glycated haemoglobin (HbA1c). Screening and data extraction were carried out independently by two reviewers. We used random effects meta-analysis to estimate effectiveness, and subgroup analysis and univariate meta-regression to explore heterogeneity. The Cochrane Collaboration’s tool was used to assess risk of bias. We found 54 eligible RCTs in 4,392 adults (40 pharmacological, 13 behavioural, one mixed intervention). Data for meta-analysis were available from 48 RCTs (n = 4052). Both pharmacological (mean difference (MD), -0.11mmol/L; 95% confidence interval (CI), [-0.19, -0.02], p = 0.02, n = 2536) and behavioural interventions (MD, -0.28mmol//L; 95% CI, [-0.43, -0.12], p<0.001, n = 956) were effective in lowering fasting glucose, but not HbA1c (pharmacological MD, -0.03%; 95% CI, [-0.12, 0.06], p = 0.52, n = 1515; behavioural MD, 0.18%; 95% CI, [-0.07, 0.42], p = 0.16, n = 140) compared with usual care or placebo. In subgroup analysis of pharmacological interventions, metformin and antipsychotic switching strategies improved HbA1c. Behavioural interventions of longer duration and those including repeated physical activity had greater effects on fasting glucose than those without these characteristics. Baseline levels of fasting glucose explained some of the heterogeneity in behavioural interventions but not in pharmacological interventions. Although the strength of the evidence is limited by inadequate trial design and reporting and significant heterogeneity, there is some evidence that behavioural interventions, antipsychotic switching, and metformin can lead to clinically important improvements in glycaemic measurements in adults with SMI

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis