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Obesity leads to insulin resistance (IR) and type 2 diabetes. In humans, low levels of the hormone prolactin (PRL) correlate with IR, adipose tissue (AT) dysfunction, and increased prevalence of T2D. In obese rats, PRL treatment promotes insulin sensitivity and reduces visceral AT adipocyte hypertrophy. Here, we tested whether elevating PRL levels with the prokinetic and antipsychotic drug sulpiride, an antagonist of dopamine D2 receptors, improves metabolism in high fat diet (HFD)-induced obese male mice. Sulpiride treatment (30 days) reduced hyperglycemia, IR, and the serum and pancreatic levels of triglycerides in obese mice, reduced visceral and subcutaneous AT adipocyte hypertrophy, normalized markers of visceral AT function (PRL receptor, Glut4, insulin receptor and Hif-1α), and increased glycogen stores in skeletal muscle. However, the effects of sulpiride reducing hyperglycemia were also observed in obese prolactin receptor null mice. We conclude that sulpiride reduces obesity-induced hyperglycemia by mechanisms that are independent of prolactin/prolactin receptor activity. These findings support the therapeutic potential of sulpiride against metabolic dysfunction in obesity.

Introduction: Diagnosing extra-pulmonary tuberculosis (EPTB) is a challenge for physicians. It has been suggested that cancer antigen 125 (CA-125), which is produced by mesothelial cells, may be an EPTB diagnostic biomarker. Objective: To describe serum CA-125 levels behavior in patients with TB treated in a referral university hospital located in Cali, Colombia. Materials and methods: A cross-sectional study was conducted in 99 TB patients treated at Fundación Valle del Lili between 2007 and 2016 with CA-125 measurements (U/mL) made before TB treatment was started. Cases were classified as pulmonary TB (PTB) (n=33) or EPTB (n=66). A bivariate analysis was performed to compare the variables of interest (sociodemographic, clinical, and laboratory findings data) between EPTB and PTB groups, and to determine differences between patients with CA-125 positive results and those with negative results in relation to mortality. Results: Elevated CA-125 levels were reported in 55 patients (55.56%), and positive CA-125 results (>35 U/mL) were more frequent in the EPTB group (59.09% vs. 48.48%). In the EPTB group, results were positive in tuberculous serositis cases (100% pericardial TB, 68.42% peritoneal TB, and 66.66% pleural TB), and in 66.66% of miliary TB and spinal TB cases, respectively. Also, 15 TB infection-related deaths were reported in the follow-up period (n=66), of which 13 had a CA-125 positive result, finding a significant difference with those with negative results (p=0.021); however, 47.05% of the surviving patients also had a positive result. Conclusions: Most of tuberculous serositis, miliary TB, and spinal TB cases showed elevated CA-125 levels before starting TB treatment. Therefore, CA-125 may be useful for prognostic purposes in these patients.

Zebu cattle (Bos taurus indicus) are highly adapted to tropical regions. However, females reach puberty after taurine heifers, which affects the economic efficiency of beef cattle breeding in the tropical regions. The aims of this study were to establish associations between the haplotype alleles of the bovine genome and age at first calving (AFC) in the Nelore cattle, and to identify the genes and quantitative trait loci (QTL) related to this phenotype. A total of 2,273 Nelore cattle (995 males and 1,278 females) genotyped using the Illumina BovineHD BeadChip were used in the current study. The association analysis included females with valid first calving records as well as open heifers. Linkage disequilibrium (LD) analysis among the markers was performed using blocks of 5, 10, and 15 markers, which were determined by sliding windows shifting one marker at a time. Then, the haplotype block size to be used in the association study was chosen based on the highest r2 average among the SNPs in the block. The five HapAlleles most strongly associated with the trait (top five) were considered as significant associations. The results of the analysis revealed four genomic regions related to AFC, which overlapped with 20 QTL of the reproductive traits reported previously. Furthermore, there were 19 genes related to reproduction in those regions. In conclusion, the use of haplotypes allowed the detection of chromosomal regions associated with AFC in Nelore cattle, and provided the basis for elucidating the mechanisms underlying this trait.

Robust detection of prostatic cancer is a challenge due to the multitude of variants and their representation in MR images. We propose a pattern recognition system with an incremental learning ensemble algorithm using support vector machines (SVM) tackling this problem employing multimodal MR images and a texture-based information strategy. The proposed system integrates anatomic, texture, and functional features. The data set was preprocessed using B-Spline interpolation, bias field correction and intensity standardization. First- and second-order angular independent statistical approaches and rotation invariant local phase quantization (RI-LPQ) were utilized to quantify texture information. An incremental learning ensemble SVM was implemented to suit working conditions in medical applications and to improve effectiveness and robustness of the system. The probability estimation of cancer structures was calculated using SVM and the corresponding optimization was carried out with a heuristic method together with a 3-fold cross-validation methodology. We achieved an average sensitivity of 0.844 ± 0.068 and a specificity of 0.780 ± 0.038, which yielded superior or similar performance to current state of the art using a total database of only 41 slices from twelve patients with histological confirmed information, including cancerous, unhealthy non-cancerous and healthy prostate tissue. Our results show the feasibility of an ensemble SVM being able to learn additional information from new data while preserving previously acquired knowledge and preventing unlearning. The use of texture descriptors provides more salient discriminative patterns than the functional information used. Furthermore, the system improves selection of information, efficiency and robustness of the classification. The generated probability map enables radiologists to have a lower variability in diagnosis, decrease false negative rates and reduce the time to recognize and delineate structures in the prostate.

The reproductive performance of bulls has a high impact on the beef cattle industry. Scrotal circumference (SC) is the most recorded reproductive trait in beef herds, and is used as a major selection criterion to improve precocity and fertility. The characterization of genomic regions affecting SC can contribute to the identification of diagnostic markers for reproductive performance and uncover molecular mechanisms underlying complex aspects of bovine reproductive biology. In this paper, we report a genome-wide scan for chromosome segments explaining differences in SC, using data of 861 Nellore bulls (Bos indicus) genotyped for over 777,000 single nucleotide polymorphisms. Loci that excel from the genome background were identified on chromosomes 4, 6, 7, 10, 14, 18 and 21. The majority of these regions were previously found to be associated with reproductive and body size traits in cattle. The signal on chromosome 14 replicates the pleiotropic quantitative trait locus encompassing PLAG1 that affects male fertility in cattle and stature in several species. Based on intensive literature mining, SP4, MAGEL2, SH3RF2, PDE5A and SNAI2 are proposed as novel candidate genes for SC, as they affect growth and testicular size in other animal models. These findings contribute to linking reproductive phenotypes to gene functions, and may offer new insights on the molecular biology of male fertility.

Adaptation of global food systems to climate change is essential to feed the world. Tropical cattle production, a mainstay of profitability for farmers in the developing world, is dominated by heat, lack of water, poor quality feedstuffs, parasites, and tropical diseases. In these systems European cattle suffer significant stock loss, and the cross breeding of taurine x indicine cattle is unpredictable due to the dilution of adaptation to heat and tropical diseases. We explored the genetic architecture of ten traits of tropical cattle production using genome wide association studies of 4,662 animals varying from 0% to 100% indicine. We show that nine of the ten have genetic architectures that include genes of major effect, and in one case, a single location that accounted for more than 71% of the genetic variation. One genetic region in particular had effects on parasite resistance, yearling weight, body condition score, coat colour and penile sheath score. This region, extending 20 Mb on BTA5, appeared to be under genetic selection possibly through maintenance of haplotypes by breeders. We found that the amount of genetic variation and the genetic correlations between traits did not depend upon the degree of indicine content in the animals. Climate change is expected to expand some conditions of the tropics to more temperate environments, which may impact negatively on global livestock health and production. Our results point to several important genes that have large effects on adaptation that could be introduced into more temperate cattle without detrimental effects on productivity.

As the methodologies available for the detection of positive selection from genomic data vary in terms of assumptions and execution, weak correlations are expected among them. However, if there is any given signal that is consistently supported across different methodologies, it is strong evidence that the locus has been under past selection. In this paper, a straightforward frequentist approach based on the Stouffer Method to combine P-values across different tests for evidence of recent positive selection in common variations, as well as strategies for extracting biological information from the detected signals, were described and applied to high density single nucleotide polymorphism (SNP) data generated from dairy and beef cattle (taurine and indicine). The ancestral Bovinae allele state of over 440,000 SNP is also reported. Using this combination of methods, highly significant (P