Assessment of growth hormone gene polymorphism effects on reproductive traits in Holstein dairy cattle in Tunisia

Research to assess the effect of single genes on reproductive traits in bovine species is imperative to elucidate genes' functions and acquire a better perspective of quantitative traits. The present study was undertaken to characterize genetic diversity in the bovine growth hormone (GH) gene in a population of 410 Holstein dairy cows in Tunisia. The analyses were based on single nucleotide polymorphisms, and GH-AluI and GH-MspI detections and genotyping were carried out using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Data were analyzed using a mixed linear model with the MIXED procedure to reveal the possible effect of GH genotypes on reproductive traits. The frequency data of AluI(L//V) and MspI(+//−) alleles were 87.04//12.96 and 70.06//29.94, respectively. The distribution of the frequency of GH genotypes for LL/LV/VV and (−/−)//(+/−)//(+/+) were 77.75//18.59//3.66 and 15.37//29.13//55.50, respectively. The results of the statistical analyses proved that GH-AluI showed a substantial favorable effect on exanimate traits except for the age at first calving; however, only a suggestive effect of GH-MspI on the calving interval (CI) and the days open (DI) was found. The homozygous LL genotype seemed to be advantageous with respect to the CI and the DI compared with LV and VV genotypes. Heterozygous MspI(+/−) cows tended to have a longer CI and DI than MspI(+/+) and MspI(−/−) cows, but the difference was not statistically significant. A significant effect of different GH-AluI–MspI combined genotypes was found on the number of inseminations per conception, the CI and the DI, and the LL/– combined genotype seemed to be associated with better reproductive performance. Based on these results, the LL genotype of the GH locus can be considered to be a favorable genotype for reproductive traits in Holstein dairy cattle, although these findings need to be confirmed by further research before polymorphisms can be used in a marker-assisted selection program.</p

Practical issues and limitations of brain attenuation correction on a simultaneous PET-MR scanner

BACKGROUND: Despite the advent of clinical PET-MR imaging for routine use in 2011 and the development of several methods to address the problem of attenuation correction, some challenges remain. We have identified and investigated several issues that might affect the reliability and accuracy of current attenuation correction methods when these are implemented for clinical and research studies of the brain. These are (1) the accuracy of converting CT Hounsfield units, obtained from an independently acquired CT scan, to 511 keV linear attenuation coefficients; (2) the effect of padding used in the MR head coil; (3) the presence of close-packed hair; (4) the effect of headphones. For each of these, we have examined the effect on reconstructed PET images and evaluated practical mitigating measures. RESULTS: Our major findings were (1) for both Siemens and GE PET-MR systems, CT data from either a Siemens or a GE PET-CT scanner may be used, provided the conversion to 511 keV μ-map is performed by the PET-MR vendor’s own method, as implemented on their PET-CT scanner; (2) the effect of the head coil pads is minimal; (3) the effect of dense hair in the field of view is marked (> 10% error in reconstructed PET images); and (4) using headphones and not including them in the attenuation map causes significant errors in reconstructed PET images, but the risk of scanning without them may be acceptable following sound level measurements. CONCLUSIONS: It is important that the limitations of attenuation correction in PET-MR are considered when designing research and clinical PET-MR protocols in order to enable accurate quantification of brain PET scans. Whilst the effect of pads is not significant, dense hair, the use of headphones and the use of an independently acquired CT-scan can all lead to non-negligible effects on PET quantification. Although seemingly trivial, these effects add complications to setting up protocols for clinical and research PET-MR studies that do not occur with PET-CT. In the absence of more sophisticated PET-MR brain attenuation correction, the effect of all of the issues above can be minimised if the pragmatic approaches presented in this work are followed

Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages

Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.We thank S. Lecher, S. Li and J. Zallet for technical support. Calculations were performed at the sciCORE scientific computing core facility at the University of Basel. This work was supported by the Swiss National Science Foundation (grants 310030_166687 (S.G.) and 320030_153442 (M.E.) and Swiss HIV Cohort Study grant 740 to L.F.), the European Research Council (309540-EVODRTB to S.G.), TB-PAN-NET (FP7-223681 to S.N.), PathoNgenTrace projects (FP7-278864-2 to S.N.), SystemsX.ch (S.G.), the German Center for Infection Research (DZIF; S.N.), the Novartis Foundation (S.G.), the Natural Science Foundation of China (91631301 to Q.G.), and the National Institute of Allergy and Infectious Diseases (5U01-AI069924-05) of the US National Institutes of Health (M.E.)

Erratum: Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome (J. Exp. Med. (2020) 217:6 Doi:10.1084/jem.20191804)

The authors regret that in the original version of Table S1, the column for patient 12 was mistakenly duplicated in the column for patient 8. The online Table S1 PDF has been corrected. The error appears only in PDFs downloaded before June 4, 2020

Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome

Autosomal dominant hyper-IgE syndrome (AD-HIES) is typically caused by dominant-negative (DN) STAT3 mutations. Patients suffer from cold staphylococcal lesions and mucocutaneous candidiasis, severe allergy, and skeletal abnormalities. We report 12 patients from 8 unrelated kindreds with AD-HIES due to DN IL6ST mutations. We identified seven different truncating mutations, one of which was recurrent. The mutant alleles encode GP130 receptors bearing the transmembrane domain but lacking both the recycling motif and all four STAT3-recruiting tyrosine residues. Upon overexpression, the mutant proteins accumulate at the cell surface and are loss of function and DN for cellular responses to IL-6, IL-11, LIF, and OSM. Moreover, the patients’ heterozygous leukocytes and fibroblasts respond poorly to IL-6 and IL-11. Consistently, patients with STAT3 and IL6ST mutations display infectious and allergic manifestations of IL-6R deficiency, and some of the skeletal abnormalities of IL-11R deficiency. DN STAT3 and IL6ST mutations thus appear to underlie clinical phenocopies through impairment of the IL-6 and IL-11 response pathways

donor selection for adults and pediatrics

It is known that multiple factors impact on transplantation outcome; the heaviest ones are disease-related (disease refractoriness, phase, clonal abnormalities, etc. in malignancies and disease type and associated rejection risk in non-malignant diseases) and patient-related (age, comorbidities, infectious diseases/colonization, etc.). Moreover, donor-related issues and stem cell source may influence the extent of disease control and transplant-related mortality

Macrophage immune memory controls endometriosis in mice and humans

This folder contains original data for the accepted manuscript CELL-REPORTS-D-20-00069R1 according to the journal guidelines

Macrophage immune memory controls endometriosis in mice and humans

This folder contains original data for the accepted manuscript CELL-REPORTS-D-20-00069R1 according to the journal guidelines

ALUMINIUM OXIDE NANOPARTICLES COMPROMISE SPATIAL LEARNING AND MEMORY PERFORMANCE IN RATS

International audienceRecently, the biosafety and potential influences of nanoparticles on central nervous system have received more attention. In the present study, we assessed the effect of aluminium oxide nanoparticles (Al 2 O 3-NPs) on spatial cognition. Male Wistar rats were intravenously administered Al 2 O 3-NP suspension (20 mg/kg body weight/day) for four consecutive days, after which they were assessed. The results indicated that Al 2 O 3-NPs impaired spatial learning and memory ability. An increment in malondialdehyde levels with a concomitant decrease in superoxide dismutase activity confirmed the induction of oxidative stress in the hippocampus. Additionally, our findings showed that exposure to Al 2 O 3-NPs resulted in decreased acetylcholinesterase activity in the hippocampus. Furthermore , Al 2 O 3-NPs enhanced aluminium (Al) accumulation and disrupted mineral element homoeostasis in the hippocampus. However, they did not change the morphology of the hippocampus. Our results show a connection among oxidative stress, disruption of mineral element homoeostasis, and Al accumulation in the hippocampus, which leads to spatial memory deficit in rats treated with Al 2 O 3-NPs