Artificial Intelligence Enabled Histological Prediction of Remission or Activity and Clinical Outcomes in Ulcerative Colitis.

BACKGROUND & AIMS: Microscopic inflammation has significant prognostic value in ulcerative colitis (UC); however, its assessment is complex with high interobserver variability. We aimed to develop and validate an artificial intelligence (AI) computer-aided diagnosis system to evaluate UC biopsies and predict prognosis. METHODS: A total of 535 digitalized biopsies (273 patients) were graded according to the PICaSSO Histologic Remission Index (PHRI), Robarts, and Nancy Histological Index. A convolutional neural network classifier was trained to distinguish remission from activity on a subset of 118 biopsies, calibrated on 42 and tested on 375. The model was additionally tested to predict the corresponding endoscopic assessment and occurrence of flares at 12 months. The system output was compared with human assessment. Diagnostic performance was reported as sensitivity, specificity, prognostic prediction through Kaplan-Meier, and hazard ratios of flares between active and remission groups. We externally validated the model in 154 biopsies (58 patients) with similar characteristics but more histologically active patients. RESULTS: The system distinguished histological activity/remission with sensitivity and specificity of 89% and 85% (PHRI), 94% and 76% (Robarts Histological Index), and 89% and 79% (Nancy Histological Index). The model predicted the corresponding endoscopic remission/activity with 79% and 82% accuracy for UC endoscopic index of severity and Paddington International virtual ChromoendoScopy ScOre, respectively. The hazard ratio for disease flare-up between histological activity/remission groups according to pathologist-assessed PHRI was 3.56, and 4.64 for AI-assessed PHRI. Both histology and outcome prediction were confirmed in the external validation cohort. CONCLUSION: We developed and validated an AI model that distinguishes histologic remission/activity in biopsies of UC and predicts flare-ups. This can expedite, standardize, and enhance histologic assessment in practice and trials.

Genetic parameters for udder conformation traits derived from Cartesian coordinates generated by robotic milking systems in North American Holstein cattle.

Udder conformation is directly related to milk yield, cow health, workability, and welfare. Automatic milking systems (AMS, also known as milking robots) have become popular worldwide, and the number of dairy farms adopting these systems have increased considerably over the past years. In each milking visit, AMS record the location of the 4 teats as Cartesian coordinates in a xyz plan, which can then be used to derive udder conformation traits. AMS generate a large amount of per milking visit data for individual cows, which contribute to an accurate assessment of important traits such as udder conformation without the addition of human classifier errors (in subjective scoring systems). Therefore, the primary objectives of this study were to estimate genomic-based genetic parameters for udder conformation traits derived from AMS records in North American Holstein cattle and to assess the genetic correlation between the derived traits for evaluating the feasibility of multi-trait genomic selection for breeding cows that are more suitable for milking in AMS. The Cartesian teat coordinates measured during each milking visit were collected by 36 milking robots in 4,480 Holstein cows from 2017 to 2021, resulting in 5,317,488 records. A total of 4,118 of these Holstein cows were also genotyped for 57,600 single nucleotide polymorphisms. Five udder conformation traits were derived: udder balance (UB, mm), udder depth (UD, mm), front teat distance (FTD, mm), rear teat distance (RTD, mm), and distance front-rear (DFR, mm). In addition, 2 traits directly related to cow productivity in the system were added to the study: daily milk yield (DY) and milk electroconductivity (EC; as an indicator of mastitis). Variance components and genetic parameters for UB, UD, FTD, RTD, DFR, DY, and EC were estimated based on repeatability animal models. The estimates of heritability (±standard error, SE) for UB, UD, FTD, RTD, DFR, DY, and EC were 0.41 ± 0.02, 0.79 ± 0.01, 0.53 ± 0.02, 0.40 ± 0.02, 0.65 ± 0.02, 0.20 ± 0.02, and 0.46 ± 0.02, respectively. The repeatability estimates (±SE) for UB, UD, FTD, RTD, and DFR were 0.82 ± 0.01, 0.93 ± 0.01, 0.87 ± 0.01, 0.83 ± 0.01, and 0.88 ± 0.01, respectively. The strongest genetic correlations were observed between the FTD and RTD (0.54 ± 0.03), UD and DFR (-0.47 ± 0.03), DFR and FTD (0.32 ± 0.03), and UD and FTD (-0.31 ± 0.03). These results suggest that udder conformation traits derived from Cartesian coordinates from AMS are moderately to highly heritable. Furthermore, the moderate genetic correlations between these traits should be considered when developing selection sub-indexes. The most relevant genetic correlations between traits related to cow milk productivity and udder conformation traits were between UD and EC (-0.25 ± 0.03) and between DFR and DY (0.30 ± 0.04), in which both genetic correlations are favorable. These findings will contribute to the design of genomic selection schemes for improving udder conformation in North American Holstein cattle, especially in precision dairy farms.

Transgenerational effects of the maternal gestational environment on the post-natal performance of beef cattle: A reaction norm approach.

In tropical beef cattle production systems, animals are commonly raised on pastures, exposing them to potential stressors. The end of gestation typically overlaps with a dry period characterized by limited food availability. Late gestation is pivotal for fetal development, making it an ideal scenario for inter- and transgenerational effects of the maternal gestational environment. Intergenerational effects occur due to exposure during gestation, impacting the development of the embryo and its future germline. Transgenerational effects, however, extend beyond direct exposure to the subsequent generations. The objective of the present study was to verify these effects on the post-natal performance of zebu beef cattle. We extended the use of a reaction norm model to identify genetic variation in the animals' responses to transgenerational effects. The inter- and transgenerational effects were predominantly positive (-0.09% to 19.74%) for growth and reproductive traits, indicating improved animal performance on the phenotypic scale in more favourable maternal gestational environments. Additionally, these effects were more pronounced in the reproductive performance of females. On average, the ratio of direct additive genetic variances of the slope and intercept of the reaction norm ranged from 1.23% to 3.60% for direct and from 10.17% to 11.42% for maternal effects. Despite its relatively modest magnitude, this variation proved sufficient to prompt modifications in parameter estimates. The average percentage variation of direct heritability estimates ranged from 19.3% for scrotal circumference to 33.2% for yearling weight across the environmental descriptors evaluated. Genetic correlations between distant environments for the studied traits were generally high for direct effects and far from unity for maternal effects. Changes in EBV rankings of sires across different gestational environments were also observed. Due to the multifaceted nature of inter- and transgenerational effects of the maternal gestational environment on various traits of beef cattle raised under tropical pasture conditions, they should not be overlooked by producers and breeders. There were differences in the specific response of beef cattle to variations in the quality of the maternal gestational environment, which can be partially explained by transgenerational epigenetic inheritance. Adopting a reaction norm model to capture a portion of the additive variance induced by inter- or transgenerational effects could be an alternative for future research and animal genetic evaluations.

Genetic parameters for various semen production and quality traits and indicators of male and female reproductive performance in Nellore cattle.

BACKGROUND: Given the economic relevance of fertility and reproductive traits for the beef cattle industry, investigating their genetic background and developing effective breeding strategies are paramount. Considering their late and sex-dependent phenotypic expression, genomic information can contribute to speed up the rates of genetic progress per year. In this context, the main objectives of this study were to estimate variance components and genetic parameters, including heritability and genetic correlations, for fertility, female precocity, and semen production and quality (andrological attributes) traits in Nellore cattle incorporating genomic information. RESULTS: The heritability estimates of semen quality traits were low-to-moderate, while moderate-to-high estimates were observed for semen morphological traits. The heritability of semen defects ranged from low (0.04 for minor semen defects) to moderate (0.30 for total semen defects). For seminal aspect (SMN_ASPC) and bull reproductive fitness (BULL_FIT), low (0.19) and high (0.69) heritabilities were observed, respectively. The heritability estimates for female reproductive traits ranged from 0.16 to 0.39 for rebreeding of precocious females (REBA) and probability of pregnancy at 14 months (PP14), respectively. Semen quality traits were highly genetically correlated among themselves. Moderate-to-high genetic correlations were observed between the ability to remain productive in the herd until four years of age (stayability; STAY) and the other reproductive traits, indicating that selection for female reproductive performance will indirectly contribute to increasing fertility rates. High genetic correlations between BULL_FIT and female reproductive traits related to precocity (REBA and PP14) and STAY were observed. The genetic correlations between semen quality and spermatic morphology with female reproductive traits ranged from -0.22 (REBA and scrotal circumference) to 0.48 (REBA and sperm vigor). In addition, the genetic correlations between REBA with semen quality traits ranged from -0.23 to 0.48, and with the spermatic morphology traits it ranged from -0.22 to 0.19. CONCLUSIONS: All male and female fertility and reproduction traits evaluated are heritable and can be improved through direct genetic or genomic selection. Selection for better sperm quality will positively influence the fertility and precocity of Nellore females. The findings of this study will serve as background information for designing breeding programs for genetically improving semen production and quality and reproductive performance in Nellore cattle.

Validation of a new optical diagnosis training module to improve dysplasia characterization in inflammatory bowel disease: a multicenter international study.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) increases risk of dysplasia and colorectal cancer. Advanced endoscopic techniques allow for the detection and characterization of IBD dysplastic lesions, but specialized training is not widely available. We aimed to develop and validate an online training platform to improve the detection and characterization of colonic lesions in IBD: OPtical diagnosis Training to Improve dysplasia Characterization in Inflammatory Bowel Disease (OPTIC-IBD). METHODS: We designed a web-based learning module that includes surveillance principles, optical diagnostic methods, approach to characterization, and classifications of colonic lesions using still images and videos. We invited gastroenterologists from Canada, Italy, and the United Kingdom with a wide range of experience. Participants reviewed 24 educational videos of IBD colonic lesions, predicted histology, and rated their confidence. The primary endpoint was to improve accuracy in detecting dysplastic lesions after training on the platform. Furthermore, participants were randomized 1:1 to get additional training or not, with a final assessment occurring after 60 days. Diagnostic performance for dysplasia and rater confidence were measured. RESULTS: A total of 117 participants completed the study and were assessed for the primary endpoint. Diagnostic accuracy improved from 70.8% to 75.0% (P = .002) after training, with the greatest improvements seen in less experienced endoscopists. Improvements in both accuracy and confidence were sustained after 2 months of assessment, although the group randomized to receive additional training did not improve further. Similarly, participants' confidence in characterizing lesions significantly improved between before and after the course (P < .001), and it was sustained after 2 months of assessment. CONCLUSIONS: The OPTIC-IBD training module demonstrated that an online platform could improve participants' accuracy and confidence in the optical diagnosis of dysplasia in patients with IBD. The training platform can be widely available and improve endoscopic care for people with IBD. (Clinical trial registration number: NCT04924543.).

Weighted genomic prediction for growth and carcass-related traits in Nelore cattle.

This study aimed to assess the impact of differential weighting in genomic regions harboring candidate causal loci on the genomic prediction accuracy and dispersion for growth and carcass-related traits in Nelore cattle. The dataset contained 168 793 phenotypic records for adjusted weight at 450 days of age (W450), 83 624 for rib eye area (REA), 24 480 for marbling (MAR) and 82 981 for subcutaneous backfat thickness (BFT) and rump fat thickness (RFT). The pedigree harbored information from 244 254 animals born between 1977 and 2016, including 6283 sires and 50 742 dams. Animals (n = 7769) were genotyped with the low-density panel (Clarifide® Nelore 3.0), and the genotypes were imputed to a panel containing 735 044 markers. A linear animal model was applied to estimate the genetic parameters and to perform the weighted single-step genome-wide association study (WssGWAS). A total of seven models for genomic prediction were evaluated combining the SNP weights obtained in the iterations of the WssGWAS and the candidate QTL. The heritability estimated for W450 (0.35) was moderate, and for carcass-related traits, the estimates were moderate for REA (0.27), MAR (0.28) and RFT (0.28), and low for BFT (0.18). The prediction accuracy for W450 incorporating reported QTL previously described in the literature along with different SNPs weights was like those described for the default ssGBLUP model. The use of the ssGWAS to weight the SNP effects displayed limited advantages for the REA prediction accuracy. Comparing the ssGBLUP with the BLUP model, a meaningful improvement in the prediction accuracy from 0.09 to 0.63 (700%) was observed for MAR. The highest prediction accuracy was obtained for BFT and RFT in all evaluated models. The application of information obtained from the WssGWAS is an alternative to reduce the genomic prediction dispersion for growth and carcass-related traits, except for MAR. Furthermore, the results obtained herein pointed out that is possible to improve the prediction accuracy and reduce the genomic prediction dispersion for growth and carcass-related traits in young animals.

Genome-wide association study in thoroughbred horses naturally infected with cyathostomins.

Cyathostomins are considered one of the most important parasites of horses. A group of horses within a herd can be responsible for eliminating the majority of parasite eggs. This phenotype might be explained by genetic factors. This study aimed to identify genomic regions associated with fecal egg count (FEC) and hematological parameters by performing a genomic-wide association study (GWAS) in Thoroughbred horses naturally infected with cyathostomins. Packed cell volume (PCV), differential leukocyte, and FEC were determined from 90 horses. All animals were genotyped using the Illumina Equine 70 K BeadChip panel containing 65,157 SNP markers. The five genomic windows that have explained the highest percentage of the additive genetic variance of a specific trait (top 5) were further explored to identify candidate genes. A total of 33, 21, 30, 21, and 19 genes were identified for FEC, PCV, eosinophils, neutrophils, and lymphocyte count, respectively. The top 5 marker regions explained 2.86, 2.56, 2.73, 2.33, and 2.37% of the additive genetic variation of FEC, PCV, eosinophils, neutrophils, and lymphocytes count, respectively. This is the first study correlating phenotypic horse health traits to GWAS analysis, which may be used for animal breeding activities, reducing losses due to parasite infections.

PICaSSO Histologic Remission Index (PHRI) in ulcerative colitis: development of a novel simplified histological score for monitoring mucosal healing and predicting clinical outcomes and its applicability in an artificial intelligence system.

Histological remission is evolving as an important treatment target in UC. We aimed to develop a simple histological index, aligned to endoscopy, correlated with clinical outcomes, and suited to apply to an artificial intelligence (AI) system to evaluate inflammatory activity. METHODS: Using a set of 614 biopsies from 307 patients with UC enrolled into a prospective multicentre study, we developed the Paddington International virtual ChromoendoScopy ScOre (PICaSSO) Histologic Remission Index (PHRI). Agreement with multiple other histological indices and validation for inter-reader reproducibility were assessed. Finally, to implement PHRI into a computer-aided diagnosis system, we trained and tested a novel deep learning strategy based on a CNN architecture to detect neutrophils, calculate PHRI and identify active from quiescent UC using a subset of 138 biopsies. RESULTS: PHRI is strongly correlated with endoscopic scores (Mayo Endoscopic Score and UC Endoscopic Index of Severity and PICaSSO) and with clinical outcomes (hospitalisation, colectomy and initiation or changes in medical therapy due to UC flare-up). A PHRI score of 1 could accurately stratify patients' risk of adverse outcomes (hospitalisation, colectomy and treatment optimisation due to flare-up) within 12 months. Our inter-reader agreement was high (intraclass correlation 0.84). Our preliminary AI algorithm differentiated active from quiescent UC with 78% sensitivity, 91.7% specificity and 86% accuracy. CONCLUSIONS: PHRI is a simple histological index in UC, and it exhibits the highest correlation with endoscopic activity and clinical outcomes. A PHRI-based AI system was accurate in predicting histological remission.

Characterization of runs of homozygosity, heterozygosity-enriched regions, and population structure in cattle populations selected for different breeding goals.

BACKGROUND: A decline in the level of genetic diversity in livestock can result in reduced response to selection, greater incidence of genetic defects, and inbreeding depression. In this context, various metrics have been proposed to assess the level of genetic diversity in selected populations. Therefore, the main goals of this study were to: 1) investigate the population structure of 16 cattle populations from 15 different pure breeds or composite populations, which have been selected for different breeds goals; and, 2) identify and compare runs of homozygosity (ROH) and heterozygosity-enriched regions (HER) based on different single nucleotide polymorphism (SNP) panels and whole-genome sequence data (WGS), followed by functional genomic analyses. RESULTS: A total of 24,187 ROH were found across all cattle populations, with 55% classified in the 2-4 Mb size group. Fourteen homozygosity islands were found in five populations, where four ROH islands located on BTA1, BTA5, BTA16, and BTA19 overlapped between the Brahman (BRM) and Gyr (GIR) breeds. A functional analysis of the genes found in these islands revealed candidate genes known to play a role in the melanogenesis, prolactin signaling, and calcium signaling pathways. The correlations between inbreeding metrics ranged from 0.02 to 0.95, where the methods based on homozygous genotypes (FHOM), uniting of gametes (FUNI), and genotype additive variance (FGRM) showed strong correlations among them. All methods yielded low to moderate correlations with the inbreeding coefficients based on runs of homozygosity (FROH). For the HER, 3576 runs and 26 islands, distributed across all autosomal chromosomes, were found in regions containing genes mainly related to the immune system, indicating potential balancing selection. Although the analyses with WGS did not enable detection of the same island patterns, it unraveled novel regions not captured when using SNP panel data. CONCLUSIONS: The cattle populations that showed the largest amount of ROH and HER were Senepol (SEN) and Montana (MON), respectively. Overlapping ROH islands were identified between GIR and BRM breeds, indicating a possible historical connection between the populations. The distribution and pattern of ROH and HER are population specific, indicating that different breeds have experienced divergent selection processes or different genetic processes.

Detection of potential functional variants based on systems-biology: the case of feed efficiency in beef cattle.

BACKGROUND: Potential functional variants (PFVs) can be defined as genetic variants responsible for a given phenotype. Ultimately, these are the best DNA markers for animal breeding and selection, especially for polygenic and complex phenotypes. Herein, we described the identification of PFVs for complex phenotypes (in this case, Feed Efficiency in beef cattle) using a systems-biology driven approach based on RNA-seq data from physiologically relevant organs. RESULTS: The systems-biology coupled with deep molecular phenotyping by RNA-seq of liver, muscle, hypothalamus, pituitary, and adrenal glands of animals with high and low feed efficiency (FE) measured by residual feed intake (RFI) identified 2,000,936 uniquely variants. Among them, 9986 variants were significantly associated with FE and only 78 had a high impact on protein expression and were considered as PFVs. A set of 169 significant uniquely variants were expressed in all five organs, however, only 27 variants had a moderate impact and none of them a had high impact on protein expression. These results provide evidence of tissue-specific effects of high-impact PFVs. The PFVs were enriched (FDR < 0.05) for processing and presentation of MHC Class I and II mediated antigens, which are an important part of the adaptive immune response. The experimental validation of these PFVs was demonstrated by the increased prediction accuracy for RFI using the weighted G matrix (ssGBLUP+wG; Acc = 0.10 and b = 0.48) obtained in the ssGWAS in comparison to the unweighted G matrix (ssGBLUP; Acc = 0.29 and b = 1.10). CONCLUSION: Here we identified PFVs for FE in beef cattle using a strategy based on systems-biology and deep molecular phenotyping. This approach has great potential to be used in genetic prediction programs, especially for polygenic phenotypes.

An International Multicenter Real-Life Prospective Study of Electronic Chromoendoscopy Score PICaSSO in Ulcerative Colitis.

BACKGROUND & AIMS: Endoscopic and histologic remission are important goals in the treatment of ulcerative colitis (UC). We investigated the correlation of the recently developed Paddington International Virtual ChromoendoScopy ScOre (PICaSSO) and other established endoscopic scores against multiple histological indices and prospectively assessed outcomes. METHODS: In this prospective multicenter international study, inflammatory activity was assessed with high-definition and virtual chromoendoscopy in the rectum and sigmoid using the Mayo Endoscopic Score (MES), UC Endoscopic Index of Severity (UCEIS), and PICaSSO. Targeted biopsies were taken for assessment using Robarts Histological Index (RHI), Nancy Histological index (NHI), ECAP (Extent, Chronicity, Activity, Plus score), Geboes, and Villanacci. Follow-up data were obtained at 6 and 12 months after colonoscopy. RESULTS: A total of 307 patients were recruited. There was strong correlation between PICaSSO and histology scores, significantly superior to correlation coefficients of MES and UCEIS with histology scores. A PICaSSO score of ≤3 detected histologic remission by RHI (≤3 + absence of neutrophils) with area under the receiver operating characteristic curve (AUROC) 0.90 (95% confidence interval [CI] 0.86-0.94) and NHI (≤1) AUROC 0.82 (95% CI 0.77-0.87). The interobserver agreement for PICaSSO was 0.88 (95% CI 0.83-0.92). At 6- and 12-months follow-up, PICaSSO score ≤3 predicted better outcomes than PICaSSO >3 (hazard ratio [HR] 0.19 [0.11-0.33] and 0.22 [0.13-0.34], respectively),} as well as PICaSSO 4-8 (HR 0.25 [0.12-0.53] and 0.22 (0.12-0.39), respectively) and similar to histologic remission. CONCLUSION: In this first real-life multicenter study, the PICaSSO score correlated strongly with multiple histological indices. Furthermore, PICaSSO score predicted specified clinical outcomes at 6 and 12 months, similar to histology. Thus, PICaSSO can be a useful endoscopic tool in the therapeutic management of UC.

Obesity activates immunomodulating properties of mesenchymal stem cells in adipose tissue with differences between localizations.

Mesenchymal stem cells from healthy adipose tissue are adipocytes progenitors with immunosuppressive potential that are used for years in cell therapy. Whether adipose stem cells (ASC) may prevent inflammation in early obesity is not known. To address this question, we performed a kinetic study of high-fat (HF) diet induced obesity in mice to follow the immune regulating functions of adipose stem cells (ASC) isolated from the subcutaneous (SAT) and the visceral adipose tissue (VAT). Our results show that, early in obesity and before inflammation was detected, HF diet durably and differently activated ASC from SAT and VAT. Subcutaneous ASC from HF-fed mice strongly inhibited the proliferation of activated T lymphocytes, whereas visceral ASC selectively inhibited TNFα expression by macrophages and simultaneously released higher concentrations of IL6. These depot specific differences may contribute to the low-grade inflammation that develops with obesity in VAT while inflammation in SAT is delayed. The mechanisms involved differ from those already described for naïve cells activation with inflammatory cytokines and probably engaged metabolic activation. These results evidence that adipose stem cells are metabolic sensors acquiring an obesity-primed immunocompetent state in answer to depot-specific intrinsic features with overnutrition, placing these cells ahead of inflammation in the local dialog with immune cells.

Genomic integration to identify molecular biomarkers associated with indicator traits of gastrointestinal nematode resistance in sheep.

This study aimed to integrate GWAS and structural variants to propose possible molecular biomarkers related to gastrointestinal nematode resistance traits in Santa Inês sheep. The phenotypic records FAMACHA, haematocrit, white blood cell count, red blood cell count, haemoglobin, platelets and egg counts per gram of faeces were collected from 700 naturally infected animals, belonging to four Brazilian flocks. A total of 576 animals were genotyped using the Ovine SNP12k BeadChip and were imputed using a reference population with Ovine SNP50 BeadChip. The GWAS approaches were based on SNPs, haplotypes, CNVs and ROH. The overlapping between the significant genomic regions detected from all approaches was investigated, and the results were integrated using a network analysis. Genes related to the immune system were found, such as ABCB1, IL6, WNT5A and IRF5. Genomic regions containing candidate genes and metabolic pathways involved in immune responses, inflammatory processes and immune cells affecting parasite resistance traits were identified. The genomic regions, biological processes and candidate genes uncovered could lead to biomarkers for selecting more resilient sheep and improving herd welfare and productivity. The results obtained are the start point to identify molecular biomarkers related to indicator traits of gastrointestinal nematode resistance in Santa Inês sheep.

Searching for causal relationships among latent variables concerning performance, carcass, and meat quality traits in broilers.

In causal relationship studies, the latent variables may summarize the phenotypes in theoretical traits according to their phenotypic correlations, improving the understanding of causal relationships between broilers phenotypes. In this study, we aimed to investigate potential causal relationships among latent variables in broilers using a structural equation model in the context of genetic analysis. The data used in this study comprised 14 traits in broilers with 2,017 records each, and 104,154 animals in pedigree. Four latent variables (WEIGHT, LOSSES, COLOUR, and VISCERA) were defined and validated using Bayesian Confirmatory Factor Analysis. Subsequently, a search for causal linkage structures was performed, obtaining a single causal link structure between the latent variables. Then, this information was used to fit the structural equation model (SEM). The results from the SEM indicated positive causal effects of the variables WEIGHT and LOSSES on the variables VISCERA and COLOUR, respectively, with structural coefficient estimates of 1.006 and 0.040, respectively. On the other hand, an antagonist causal effect of the variable WEIGHT on the variable LOSSES was verified, with a structural coefficient estimate of -4.333. These results highlight the causal relationship between performance and meat quality traits, which may be associated with the natural processes involved in the conversion of muscle into meat and the structural changes in muscle tissues due to intense selection for high growth rates in broilers.

Reduced rank analysis of morphometric and functional traits in Campolina horses.

Multitrait models can increase the accuracy of breeding value prediction and reduce bias due to selection by using traits measured before and after it has occurred. However, as the number of traits grows, a similar trend is expected for the number of parameters to be estimated, which directly affects the computing power and the amount of data required. The aim of the present study was to apply reduced rank (principal components model-PCM) and factor analytical models (FAM), to estimate (co)variance components for nineteen traits, jointly evaluated in a single analysis in Campolina horses. A total of 18 morphometric traits (MT) and one gait visual score (GtS), along with genealogical records of 48,806 horses, were analysed under a restricted maximum likelihood framework. Nine PCM, nine FAM and one standard multitrait model (MTM) were fitted to the data and compared to find the best suitable model. Based on Bayesian information criterion, the best model was the FAM option, considering five common factors (FAM5). After performing an intraclass analysis, none of MT were genetically negatively correlated, whereas GtS was negatively related to all MT, except for the genetic correlations among GtS and BLL, and between GtS and BLLBL (0.01 and 0.10 respectively). From all MT, two traits were derived computing ratios involving other traits, those had negative correlations with others MT, but all favourable for selection. Similar patterns were observed between the genetic parameters obtained from MTM and FAM5 respectively. The heritability estimates ranged from 0.09 (head width) to 0.47 (height at withers). Our results indicated that FAM was efficient to reduce the multitrait analysis dimensionality, and therefore, traits can be combined based on the first three eigenvectors from the additive genetic (co)variance matrix. In addition, there was sufficient genetic variation for selection, benefiting its potential implementation in a breeding program.

Variability of the ß-casein gene polymorphism in Curraleiro Pé-Duro cattle: a geographical genetics approach.

This study purposes to examine the distribution of A2A2 alleles in herds of Curraleiro Pé-Duro (CPD) cattle and test association patterns with geographical and municipal development data. Eight CPD herds were selected from the municipalities of Tocantins State, Brazil. The frequency of the A1 and A2 allele was 40.0 and 60.0%, and the frequencies of genotypes A1A1, A1A2, and A2A2 were 20.0, 39.0, and 41.0%, respectively. Correlation estimates supported that the preferred genotype (A2A2) was mostly present in the relatively higher developed mesoregion (West) (P < 0.05). However, genotypic frequencies varied at random according to human population of municipalities and human development index (P > 0.05). The evaluation of the variability of the ß-casein gene polymorphism, coupled with spatially explicit methods (spatial autocorrelation, mantel test, and interpolation procedures), revealed some level of spatial dependency. The results suggest that the production of A2A2 milk in indigenous CPD cattle is feasible. This will depend on the adoption of selection schemes.

Factors affecting secondary sex characteristics in the yellowtail tetra, Astyanax altiparanae.

This study interrogated factors which affect the appearance of secondary sexual characteristics, namely, fin spinelets (rigid dimorphic structure empirically associated with male sexual maturity in characids), in Astyanax altiparanae. Many variables such as the season of the year and several biotic components, including organism length, sex, phase of maturation, and the presence of gonads, were investigated. These factors were then associated with the physiological development of fin spinelets. The development of this trait is related to reproductive strategies but demonstrates considerable population variability as it is found throughout the year in some species but only during specific periods in others. Seventy-five specimens obtained from spontaneous spawn of farmed fish were arbitrarily grouped into small-, medium-, and large-sized groups in both summer and winter. Gonadal histology was performed to confirm each animal's sex and phase of maturation. Diaphanization of the fish was performed to visualize, count, and measure the fin spinelets. Finally, gonadectomization of some males was utilized to investigate the gonadal effect on the presence of fin spinelets. The present results show that the presence of fin spinelets is a secondary sexual characteristic of males which occurs independently of the season and is always present in males longer than 48 mm. However, in the summer, male specimens presented more rays with fin spinelets than during the winter. Furthermore, since fin spinelets were observed on immature males as well as spawning capable males, their presence cannot be directly associated with sexual maturity in male A. altiparanae, as previously supposed. Finally, gonadectomization resulted in an initial reduction in the length of fin spinelets. However, this trend was eventually normalized with time.

Random-effect meta-analysis of genetic parameter estimates for carcass and meat quality traits in beef cattle.

Considerable variability of genetic parameter estimates is observed among different studies for the same trait, which is associated with the distinct effects included in the statistical model, population breed, and sample sizes. The random-effect meta-analysis summarizes genetic parameters considering the heterogeneity among studies. Therefore, the aim of this study was to perform a random-effect meta-analysis of heritability and genetic correlation estimates for carcass and meat quality traits in beef cattle. A total of 152 estimates of heritability and 83 genetic correlations for longissimus muscle area (LMA), back fat thickness (BFT), and marbling score (MRB) were used. High heterogeneity among published studies was observed for all traits, indicating the need of a random-effects model to perform the analysis. Estimates of heritability through the meta-analysis using the random-effects model were high (0.30 to 0.34), indicating that fast genetic progress can be obtained for these traits. However, genetic correlations had low magnitude (lower than 0.25), which suggested that all three traits should be included in the selection scheme.

Progression of Inflammatory Bowel Diseases Throughout Latin America and the Caribbean: A Systematic Review.

BACKGROUND & AIMS: The incidence of inflammatory bowel diseases (IBD) is increasing in Latin America. We performed a systematic review to identify clinical and epidemiologic features of IBD in Latin America (including Mexico, Central America, and South America) and the Caribbean. METHODS: We searched MEDLINE, EMBASE, and SciELO databases for clinical or epidemiologic studies of Crohn's disease (CD) or ulcerative colitis (UC) from Latin American and Caribbean countries and territories that reported incidence, prevalence, ratio of UC:CD, IBD phenotype, and treatment, through September 12, 2018. Data were extracted from 61 articles for analysis. RESULTS: The incidence and prevalence of IBD have been steadily increasing in Latin America and the Caribbean. The incidence of CD in Brazil increased from 0.08 per 100,000 person-years in 1988 to 0.68 per 100,000 person-years in 1991-1995 to 5.5 per 100,000 person-years in 2015. The highest reported prevalence of IBD was in Argentina, in 2007, at 15 and 82 per 100,000 person-years for CD and UC, respectively. The ratio of UC:CD exceeded 1 in all regions throughout Latin America and the Caribbean with the exception of Brazil. Treatment with tumor necrosis factor antagonists increased steadily for patients with CD (43.4% of all patients in Brazil were treated in 2014) but less so for patients with UC (4.5% of all patients were treated in 2014). Surgery for IBD decreased with time. In Chile, surgeries were performed on 57.0% of patients with CD and 18.0% of patients with UC during the period of 1990-2002; these values decreased to 38.0% and 5.0%, respectively, during the period of 2012-2015. In Peru, 6.9% of patients with UC received colectomies in the period of 2001-2003 and 6.2% in 2004-2014. CONCLUSIONS: In a systematic review, we found the incidence of IBD to be increasing throughout Latin America and the Caribbean. Population-based epidemiology studies are needed to evaluate the increase in IBD in these regions, which differ from other global regions in climate, culture, demographics, diet, healthcare delivery and infrastructure, and socioeconomic status.

Mice born to females with oocyte-specific deletion of mitofusin 2 have increased weight gain and impaired glucose homeostasis.

Offspring born to obese and diabetic mothers are prone to metabolic diseases, a phenotype that has been linked to mitochondrial dysfunction and endoplasmic reticulum (ER) stress in oocytes. In addition, metabolic diseases impact the architecture and function of mitochondria-ER contact sites (MERCs), changes which associate with mitofusin 2 (MFN2) repression in muscle, liver and hypothalamic neurons. MFN2 is a potent modulator of mitochondrial metabolism and insulin signaling, with a key role in mitochondrial dynamics and tethering with the ER. Here, we investigated whether offspring born to mice with MFN2-deficient oocytes are prone to obesity and diabetes. Deletion of Mfn2 in oocytes resulted in a profound transcriptomic change, with evidence of impaired mitochondrial and ER function. Moreover, offspring born to females with oocyte-specific deletion of Mfn2 presented increased weight gain and glucose intolerance. This abnormal phenotype was linked to decreased insulinemia and defective insulin signaling, but not mitochondrial and ER defects in offspring liver and skeletal muscle. In conclusion, this study suggests a link between disrupted mitochondrial/ER function in oocytes and increased risk of metabolic diseases in the progeny. Future studies should determine whether MERC architecture and function are altered in oocytes from obese females, which might contribute toward transgenerational transmission of metabolic diseases.