Proton nuclear magnetic resonance spectroscopy based investigation on propylene glycol toxicosis in a Holstein cow

Background  

It is unknown which metabolites are responsible for propylene glycol (PG)-induced toxicosis, and a better understanding of the underlying mechanisms explaining incidences of abnormal behaviour of dairy cows fed PG is therefore needed.     

The efficiency of mapping of quantitative trait loci using cofactor analysis in half-sib design

This simulation study was designed to study the power and type I error rate in QTL mapping using cofactor analysis in half-sib designs. A number of scenarios were simulated with different power to identify QTL by varying family size, heritability, QTL effect and map density, and three threshold levels for cofactor were considered. Generally cofactor analysis did not increase the power of QTL mapping in a half-sib design, but increased the type I error rate. The exception was with small family size where the number of correctly identified QTL increased by 13% when heritability was high and 21% when heritability was low. However, in the same scenarios the number of false positives increased by 49% and 45% respectively. With a liberal threshold level of 10% for cofactor combined with a low heritability, the number of correctly identified QTL increased by 14% but there was a 41% increase in the number of false positives. Also, the power of QTL mapping did not increase with cofactor analysis in scenarios with unequal QTL effect, sparse marker density and large QTL effect (25% of the genetic variance), but the type I error rate tended to increase. A priori, cofactor analysis was expected to have higher power than individual chromosome analysis especially in experiments with lower power to detect QTL. Our study shows that cofactor analysis increased the number of false positives in all scenarios with low heritability and the increase was up to 50% in low power experiments and with lower thresholds for cofactors.     

Supplementary selenium influences the response to fatty acid-induced oxidative stress in humans

The mutual influences of wheat selenium (Se) andn-3 polyunsaturated fatty acids(n- 3 PUFA) on plasma Se and indicators of increased oxidative stress were investigated in a randomized, doubleblind study with 31 women (23.5 ±3.4 yr). Groups 1 and 2 ingested 5.4 g n-3 PUFA daily (as ethyl esters), whereas groups 3 and 4 received placebo capsules. Groups 2 and 3 received 3 slices of high Se bread daily, providing 115 Μg Se, in addition to the 77± 26 ug Se in the diet. Groups 1 and 4 received placebo slices. Blood samples were drawn at baseline and at 3 and 6 wk. Serum Se concentrations increased in both groups given Seenriched bread, but significantly less in subjects givenn-3 PUFA (group 2). There were no changes in the plasma ratio α-tocopherol:mg cholesterol or plasma ascorbic acid levels. In group1, plasmaconjugated dienes and thiobarbituric acid-reactive substances (TBARS) rose by 130% (p < 0.005) and 126% (p < 0.005), respectively. Two-way ANOVA showed significant interaction effects of Se andn-3 PUFA on changes in conjugated dienes (p = 0.03) and TBARS (p = 0.015), Se treatment apparently modifying the peroxidative effects ofn-3 PUFA. In subjects receivingn-3 PUFA, changes in conjugated dienes and TBARS were negatively correlated with changes in serum Se. In summary,n-3 PUFA modified the effect of Se supplementation, whereas Se seemed to modify the peroxidative effects ofn-3 PUFA.     

In vivo analysis of the regulatory genes in the nystatin biosynthetic gene cluster of Streptomyces noursei ATCC 11455 reveals their differential control over antibiotic biosynthesis

Six putative regulatory genes are located at the flank of the nystatin biosynthetic gene cluster in Streptomyces noursei ATCC 11455. Gene inactivation and complementation experiments revealed that nysRI, nysRII, nysRIII, and nysRIV are necessary for efficient nystatin production, whereas no significant roles could be demonstrated for the other two regulatory genes. To determine the in vivo targets for the NysR regulators, chromosomal integration vectors with the xylE reporter gene under the control of seven putative promoter regions upstream of the nystatin structural and regulatory genes were constructed. Expression analyses of the resulting vectors in the S. noursei wild-type strain and regulatory mutants revealed that the four regulators differentially affect certain promoters. According to these analyses, genes responsible for initiation of nystatin biosynthesis and antibiotic transport were the major targets for regulation. Data from cross-complementation experiments showed that nysR genes could in some cases substitute for each other, suggesting a functional hierarchy of the regulators and implying a cascade-like mechanism of regulation of nystatin biosynthesis.     

Circadian and Circannual Variations of Cell Cycle Distribution in the Mouse Bone Marrow

The cell cycle distribution of bone marrow cells from the femurs of female C3H mice has been investigated by flow cytometry according to the time of the day and month of the year. Both circadian and seasonal variations were found for the different cell cycle phases as well as the total cell numbers per femur. Both the mesor, the acrophase and the amplitude of the S, G₂ and (G₁ + G₀) phases varied significantly in some months, while in other months only insignificant rhythms were found. The relative cell cycle distribution only partly reflected variations in the total numbers of proliferating cells, since the total cell number per femur was also variable.

The total numbers of cells in DNA synthesis seem to be higher in the first part of the year, indicating increased cell proliferation during winter and spring. In this period the acrophases of DNA synthesis and G₂ were in the morning, while the second half of the year showed the peak later in the day.

In general, hemopoietic cell proliferation seems to constitute a labile equilibrium with rapidly changing activities.     

Optimal Sleep Duration in the Subarctic with Respect to Obesity Risk Is 8–9 Hours

Introduction

Sleep duration, chronotype and social jetlag have been associated with body mass index (BMI) and abdominal obesity. The optimal sleep duration regarding BMI has previously been found to be 7–8 hours, but these studies have not been carried out in the subarctic or have lacked some central variables. The aims of our study were to examine the associations between sleep variables and body composition for people living in the subarctic, taking a range of variables into consideration, including lifestyle variables, health variables and biological factors.

Methods

The cross sectional population Tromsø Study was conducted in northern Norway, above the Arctic Circle. 6413 persons aged 30–65 years completed questionnaires including self-reported sleep times, lifestyle and health. They also measured height, weight, waist and hip circumference, and biological factors (non-fasting serum level of cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and glucose). The study period was from 1 October 2007 to 19 December 2008.

Results

The optimal sleep length regarding BMI and waist circumference was found to be 8–9 hours. Short sleepers (<6 h) had about 80% increased risk of being in the BMI≥25 kg/m2 group and male short sleepers had doubled risk of having waist circumference ≥102 cm compared to 8–9 hours sleepers. We found no impact of chronotype or social jetlag on BMI or abdominal obesity after controlling for health, lifestyle, and biological parameters.

Conclusions

In our subarctic population, the optimal sleep duration time regarding risk of overweight and abdominal obesity was 8–9 hours, which is one hour longer compared to findings from other studies. Short sleepers had 80% increased risk of being overweight, and men had a doubled risk of having abdominal obesity. We found no associations between chronotype or social jetlag and BMI or abdominal obesity, when we took a range of life-style, health and biological variables into consideration.     

Azithromycin versus placebo for the treatment of HIV-associated chronic lung disease in children and adolescents (BREATHE trial): study protocol for a randomised controlled trial

Background

Human immunodeficiency virus (HIV)-related chronic lung disease (CLD) among children is associated with substantial morbidity, despite antiretroviral therapy. This may be a consequence of repeated respiratory tract infections and/or dysregulated immune activation that accompanies HIV infection. Macrolides have anti-inflammatory and antimicrobial properties, and we hypothesised that azithromycin would reduce decline in lung function and morbidity through preventing respiratory tract infections and controlling systemic inflammation.

Methods/design

We are conducting a multicentre (Malawi and Zimbabwe), double-blind, randomised controlled trial of a 12-month course of weekly azithromycin versus placebo. The primary outcome is the mean change in forced expiratory volume in 1 second (FEV₁) z-score at 12 months. Participants are followed up to 18 months to explore the durability of effect. Secondary outcomes are FEV₁ z-score at 18 months, time to death, time to first acute respiratory exacerbation, number of exacerbations, number of hospitalisations, weight for age z-score at 12 and 18 months, number of adverse events, number of malaria episodes, number of bloodstream Salmonella typhi infections and number of gastroenteritis episodes. Participants will be followed up 3-monthly, and lung function will be assessed every 6 months. Laboratory substudies will be done to investigate the impact of azithromycin on systemic inflammation and on development of antimicrobial resistance as well as impact on the nasopharyngeal, lung and gut microbiome.

Discussion

The results of this trial will be of clinical relevance because there are no established guidelines on the treatment and management of HIV-associated CLD in children in sub-Saharan Africa, where 80% of the world’s HIV-infected children live and where HIV-associated CLD is highly prevalent.

Trial registration

ClinicalTrials.gov, NCT02426112. Registered on 21 April 2015.