Carcass conformation and fat cover scores in beef cattle: A comparison of threshold linear models vs grouped data models

Background: Beef carcass conformation and fat cover scores are measured by subjective grading performed by trained technicians. The discrete nature of these scores is taken into account in genetic evaluations using a threshold model, which assumes an underlying continuous distribution called liability that can be modelled by different methods. Methods: Five threshold models were compared in this study: three threshold linear models, one including slaughterhouse and sex effects, along with other systematic effects, with homogeneous thresholds and two extensions with heterogeneous thresholds that vary across slaughterhouses and across slaughterhouse and sex and a generalised linear model with reverse extreme value errors. For this last model, the underlying variable followed a Weibull distribution and was both a log-linear model and a grouped data model. The fifth model was an extension of grouped data models with score-dependent effects in order to allow for heterogeneous thresholds that vary across slaughterhouse and sex. Goodness-of-fit of these models was tested using the bootstrap methodology. Field data included 2,539 carcasses of the Bruna dels Pirineus beef cattle breed. Results: Differences in carcass conformation and fat cover scores among slaughterhouses could not be totally captured by a systematic slaughterhouse effect, as fitted in the threshold linear model with homogeneous thresholds, and different thresholds per slaughterhouse were estimated using a slaughterhouse-specific threshold model. This model fixed most of the deficiencies when stratification by slaughterhouse was done, but it still failed to correctly fit frequencies stratified by sex, especially for fat cover, as 5 of the 8 current percentages were not included within the bootstrap interval. This indicates that scoring varied with sex and a specific sex per slaughterhouse threshold linear model should be used in order to guarantee the goodness-of-fit of the genetic evaluation model. This was also observed in grouped data models that avoided fitting deficiencies when slaughterhouse and sex effects were score-dependent. Conclusions: Both threshold linear models and grouped data models can guarantee the goodness-of-fit of the genetic evaluation for carcass conformation and fat cover, but our results highlight the need for specific thresholds by sex and slaughterhouse in order to avoid fitting deficiencies

Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation

Somatic hypermutation (SHM) introduces point mutations into immunoglobulin (Ig) genes but also causes mutations in other parts of the genome. We have used lentiviral SHM reporter vectors to identify regions of the genome that are susceptible ("hot") and resistant ("cold") to SHM, revealing that SHM susceptibility and resistance are often properties of entire topologically associated domains (TADs). Comparison of hot and cold TADs reveals that while levels of transcription are equivalent, hot TADs are enriched for the cohesin loader NIPBL, super-enhancers, markers of paused/stalled RNA polymerase 2, and multiple important B cell transcription factors. We demonstrate that at least some hot TADs contain enhancers that possess SHM targeting activity and that insertion of a strong Ig SHM-targeting element into a cold TAD renders it hot. Our findings lead to a model for SHM susceptibility involving the cooperative action of cis-acting SHM targeting elements and the dynamic and architectural properties of TADs

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability

Polymorphisms of the prion protein gene and their effects on litter size and risk evaluation for scrapie in Chinese Hu sheep

It is well known that scrapie is a fatal, neurodegenerative disease in sheep and goat, which belongs to the group of transmissible spongiform encephalopathies (TSEs) or prion diseases. It has been confirmed that the polymorphisms of prion protein gene (PRNP) at codons 136, 154, and 171 have strong relationship with scrapie in sheep. In the present study, nine polymorphisms of PRNP at codons 136, 154, and 171 and other six loci (at codons 101, 112, 127, 137, 138, and 152) were detected in 180 Chinese Hu sheep. All the alleles at codons 136, 154, and 171 have been identified and resulted in three new genotypes. The frequencies of predominant alleles were 85% (A136), 99.40% (R154), and 37.78% (Q171), respectively. The predominant haplotype ARQ has a relatively high frequency of 57.77%. The frequencies of dominant genotypes of ARR/ARQ and ARQ/ARQ were 30 and 26.67%, respectively. Three new found genotypes named ARQ/TRK, ARQ/TRR, and TRR/TRQ had the same lower frequencies (0.56%). The relationship of PRNP genotype with scrapie risk and litter size showed that the predominant genotypes are corresponded to the risk score of R1 (1.67%), R2 (32.22%), and R3 (42.22%). Just at the first parity, the individuals with ARH/ARH genotype had significantly larger litter size than the mean value and those with ARQ/ARQ and ARR/ARQ genotypes. In short, this study provided preliminary information about alleles and genotypes of PRNP in Chinese Hu sheep. It could be concluded that Hu sheep has a low susceptibility to natural scrapie, and the predominant PRNP genotype at least has no significant effect on litter size

Systemic and local antibiotic prophylaxis in the prevention of Staphylococcus epidermidis graft infection

BACKGROUND: The aim of the study was to investigate the in vivo efficacy of local and systemic antibiotic prophylaxis in the prevention of Staphylococcus (S.) epidermidis graft infection in a rat model and to evaluate the bacterial adherence to frequently used prosthetic graft materials. METHODS: Graft infections were established in the subcutaneous tissue of 120 male Wistar rats by implantation of Dacron/ePTFE grafts followed by topical inoculation with 2 × 10(7 )CFUs of clinical isolate of methicillin-resistant S. epidermidis. Each of the graft series included a control group, one contaminated group that did not receive any antibiotic prophylaxis, two contaminated groups that received systemic prophylaxis with teicoplanin or levofloxacin and two contaminated groups that received teicoplanin-soaked or levofloxacin-soaked grafts. The grafts were removed 7 days after implantation and evaluated by quantitative culture. RESULTS: There was significant bacterial growth inhibition in the groups given systemic or local prophylaxis (P < 0.05). Methicillin-resistant S. epidermidis had greater affinity to Dacron graft when compared with ePTFE graft in the untreated contaminated groups (P < 0.05). CONCLUSION: The study demonstrated that the usage of systemic or local prophylaxis and preference of ePTFE graft can be useful in reducing the risk of vascular graft infections caused by staphylococcal strains with high levels of resistance

Transcriptional correlates of the pathological phenotype in a Huntington’s disease mouse model

Huntington disease (HD) is a fatal neurodegenerative disorder without a cure that is caused by an aberrant expansion of CAG repeats in exon 1 of the huntingtin (HTT) gene. Although a negative correlation between the number of CAG repeats and the age of disease onset is established, additional factors may contribute to the high heterogeneity of the complex manifestation of symptoms among patients. This variability is also observed in mouse models, even under controlled genetic and environmental conditions. To better understand this phenomenon, we analysed the R6/1 strain in search of potential correlates between pathological motor/cognitive phenotypical traits and transcriptional alterations. HD-related genes (e.g., Penk, Plk5, Itpka), despite being downregulated across the examined brain areas (the prefrontal cortex, striatum, hippocampus and cerebellum), exhibited tissue-specific correlations with particular phenotypical traits that were attributable to the contribution of the brain region to that trait (e.g., striatum and rotarod performance, cerebellum and feet clasping). Focusing on the striatum, we determined that the transcriptional dysregulation associated with HD was partially exacerbated in mice that showed poor overall phenotypical scores, especially in genes with relevant roles in striatal functioning (e.g., Pde10a, Drd1, Drd2, Ppp1r1b). However, we also observed transcripts associated with relatively better outcomes, such as Nfya (CCAAT-binding transcription factor NF-Y subunit A) plus others related to neuronal development, apoptosis and differentiation. In this study, we demonstrated that altered brain transcription can be related to the manifestation of HD-like symptoms in mouse models and that this can be extrapolated to the highly heterogeneous population of HD patients

Genetic Background and Sex: Impact on Generalizability of Research Findings in Pharmacology Studies

Animal models consisting of inbred laboratory rodent strains have been a powerful tool for decades, helping to unravel the underpinnings of biological problems and employed to evaluate potential therapeutic treatments in drug discovery. While inbred strains demonstrate relatively reliable and predictable responses, using a single inbred strain alone or as a background to a mutation is analogous to running a clinical trial in a single individual and their identical twins. Indeed, complex etiologies drive the most common human diseases, and a single inbred strain that is a surrogate of a single genome, or data generated from a single sex, is not representative of the genetically diverse patient populations. Further, pharmacological and toxicology data generated in otherwise healthy animals may not translate to disease states where physiology, metabolism, and general health are compromised. The purpose of this chapter is to provide guidance for improving generalizability of preclinical studies by providing insight into necessary considerations for introducing systematic variation within the study design, such as genetic diversity, the use of both sexes, and selection of appropriate age and disease model. The outcome of implementing these considerations should be that reproducibility and generalizability of significant results are significantly enhanced leading to improved clinical translation

Variations in the prevalence of strains expressing an extended-spectrum beta-lactamase phenotype and characterization of isolates from Europe, the Americas and the Western Pacific region

To evaluate the prevalence of extended-spectrum beta -lactamase (ESBL)-producing strains among species of Enterobacteriaceae, a microdilution susceptibility test was performed with strains of Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, and Salmonella species that were isolated as part of the SENTRY project. The highest percentage of ESBL phenotype (defined as a minimum inhibitory concentration [MIC] greater than or equal to2 mug/mL for ceftazidime, ceftriaxone, or aztreonam) was detected among K. pneumoniae strains from Latin America (45%), followed by those from the Western Pacific region (25%), Europe (23%), the United States (8%), and Canada (5%). P. mirabilis and E. coli strains for which MICs of extended-spectrum cephalosporins or monobactams were elevated also were more prominent in Latin America. Testing with ceftazidime revealed more isolates with elevated MICs than did testing with ceftriaxone or aztreonam. ESBL strains showed high levels of co-resistance to aminoglycosides, tetracycline, trimethoprim-sulfamethoxazole, and ciprofloxacin. Imipenem remains highly effective against ESBL strains. Organisms expressing an ESBL are widely distributed worldwide, although prevalence rates are significantly higher in certain geographic regions