Genome-wide scan reveals genomic regions and candidate genes underlying direct and maternal effects of preweaning calf mortality in Nellore cattle.

We conducted analysis to estimate genetic parameters and to identify genomic regions and candidate genes affecting direct and maternal effects of preweaning calf mortality (PWM) in Nellore cattle. Phenotypic records of 67,196 animals, and 8443 genotypes for 410,936 SNPs were used. Analysis were performed through the weighted single-step GBLUP approach and considering a threshold animal model via Bayesian Inference. Direct and maternal heritability estimates were of 0.2143 ± 0.0348 and 0.0137 ± 0.0066, respectively. The top 10 genomic regions accounted for 13.61 and 14.23% of the direct and maternal additive genetic variances and harbored a total of 63 and 91 positional candidate genes, respectively. Two overlapping regions on BTA2 were identified for both direct and maternal effects. Candidate genes are involved in biological mechanisms i.e. embryogenesis, immune response, feto-maternal communication, circadian rhythm, hormone alterations, myometrium adaptation, and milk secretion, which are critical for the successful calf growth and survival during preweaning period.

Genomic reaction norm models exploiting genotype × environment interaction on sexual precocity indicator traits in Nellore cattle.

Brazilian beef cattle are raised predominantly on pasture in a wide range of environments. In this scenario, genotype by environment (G×E) interaction is an important source of phenotypic variation in the reproductive traits. Hence, the evaluation of G×E interactions for heifer's early pregnancy (HP) and scrotal circumference (SC) traits in Nellore cattle, belonging to three breeding programs, was carried out to determine the animal's sensitivity to the environmental conditions (EC). The dataset consisted of 85 874 records for HP and 151 553 records for SC, from which 1800 heifers and 3343 young bulls were genotyped with the BovineHD BeadChip. Genotypic information for 826 sires was also used in the analyses. EC levels were based on the contemporary group solutions for yearling body weight. Linear reaction norm models (RNM), using pedigree information (RNM_A) or pedigree and genomic information (RNM_H), were used to infer G×E interactions. Two validation schemes were used to assess the predictive ability, with the following training populations: (a) forward scheme-dataset was split based on year of birth from 2008 for HP and from 2011 for SC; and (b) environment-specific scheme-low EC (-3.0 and -1.5) and high EC (1.5 and 3.0). The inclusion of the H matrix in RNM increased the genetic variance of the intercept and slope by 18.55 and 23.00% on average respectively, and provided genetic parameter estimates that were more accurate than those considering pedigree only. The same trend was observed for heritability estimates, which were 0.28-0.56 for SC and 0.26-0.49 for HP, using RNM_H, and 0.26-0.52 for SC and 0.22-0.45 for HP, using RNM_A. The lowest correlation observed between unfavorable (-3.0) and favorable (3.0) EC levels were 0.30 for HP and -0.12 for SC, indicating the presence of G×E interaction. The G×E interaction effect implied differences in animals' genetic merit and re-ranking of animals on different environmental conditions. SNP marker-environment interaction was detected for Nellore sexual precocity indicator traits with changes in effect and variance across EC levels. The RNM_H captured G×E interaction effects better than RNM_A and improved the predictive ability by around 14.04% for SC and 21.31% for HP. Using the forward scheme increased the overall predictive ability for SC (20.55%) and HP (11.06%) compared with the environment-specific scheme. The results suggest that the inclusion of genomic information combined with the pedigree to assess the G×E interaction leads to more accurate variance components and genetic parameter estimates.

Genetic association of growth traits with carcass and meat traits in Nellore cattle.

The aim of this study was to estimate genetic and phenotypic associations of growth traits with carcass and meat traits in Nellore cattle. Data from male and female animals were used for weaning weight (WW; N = 241,416), yearling weight (YW, N = 126,596), weight gain from weaning to yearling (GWY, N = 78,687), and yearling hip height (YHH, N = 90,720), respectively; 877 male animals were used for hot carcass weight (HCW) and 884 for longissimus muscle area (LMA), backfat thickness (BT), marbling score (MS), and shear force (SF). The variance components were estimated by the restricted maximum likelihood method using three-trait animal models that included WW. The model for WW included direct and maternal additive genetic, maternal permanent environmental, and residual effects as random effects; contemporary group as fixed effects; and age of dam at calving and age of animal as covariates (linear and quadratic effects). For the other traits, maternal effects and the effect of age of dam at calving were excluded from the model. Heritability ranged from 0.10 ± 0.12 (LMA) to 0.44 ± 0.007 (YW). Genetic correlations ranged from -0.40 ± 0.38 (WW x LMA) to 0.55 ± 0.10 (HCW x YW). Growth, carcass, and meat traits have sufficient genetic variability to be included as selection criteria in animal breeding programs.

Genome-wide association study identified genomic regions and putative candidate genes affecting meat color traits in Nellore cattle.

Single and multiple-trait GWAS were conducted to detect genomic regions and candidate genes associated with meat color traits (L*, lightness; a*, redness; b*, yellowness) in Nellore cattle. Phenotypic records of 5000 animals, and 3794 genotypes for 614,274 SNPs were used. The BLUPF90 family programs were used through single step GWAS approach. The top 10 genomic regions from single-trait GWAS explained 13.64%, 15.12% and 13% of genetic variance of L*, a* and b*, which harbored 129, 70, and 84 candidate genes, respectively. Regarding multiple-trait GWAS, the top 10 SNP windows explained 17.46%, 18.98% and 13.74% of genetic variance of L*, a* and b*, and harbored 124, 86, and 82 candidate genes, respectively. Pleiotropic effects were evidenced by the overlapping regions detected on BTA 15 and 26 associated with L* and a* (genetic correlation of -0.53), and on BTA 18 associated with a* and b* (genetic correlation of 0.60). Similar genomic regions located on BTA 2, 5, 6, and 18 were detected through single and multi-trait GWAS. Overlapped regions harbored a total of 30 functional candidate genes involved in mitochondrial activity, structural integrity of muscles, lipid oxidation, anaerobic metabolism, and muscular pH.

Genetic parameter estimates for carcass traits and visual scores including or not genomic information.

The objective of this study was to determine whether visual scores used as selection criteria in Nellore breeding programs are effective indicators of carcass traits measured after slaughter. Additionally, this study evaluated the effect of different structures of the relationship matrix ( and ) on the estimation of genetic parameters and on the prediction accuracy of breeding values. There were 13,524 animals for visual scores of conformation (CS), finishing precocity (FP), and muscling (MS) and 1,753, 1,747, and 1,564 for LM area (LMA), backfat thickness (BF), and HCW, respectively. Of these, 1,566 animals were genotyped using a high-density panel containing 777,962 SNP. Six analyses were performed using multitrait animal models, each including the 3 visual scores and 1 carcass trait. For the visual scores, the model included direct additive genetic and residual random effects and the fixed effects of contemporary group (defined by year of birth, management group at yearling, and farm) and the linear effect of age of animal at yearling. The same model was used for the carcass traits, replacing the effect of age of animal at yearling with the linear effect of age of animal at slaughter. The variance and covariance components were estimated by the REML method in analyses using the numerator relationship matrix () or combining the genomic and the numerator relationship matrices (). The heritability estimates for the visual scores obtained with the 2 methods were similar and of moderate magnitude (0.23-0.34), indicating that these traits should response to direct selection. The heritabilities for LMA, BF, and HCW were 0.13, 0.07, and 0.17, respectively, using matrix and 0.29, 0.16, and 0.23, respectively, using matrix . The genetic correlations between the visual scores and carcass traits were positive, and higher correlations were generally obtained when matrix was used. Considering the difficulties and cost of measuring carcass traits postmortem, visual scores of CS, FP, and MS could be used as selection criteria to improve HCW, BF, and LMA. The use of genomic information permitted the detection of greater additive genetic variability for LMA and BF. For HCW, the high magnitude of the genetic correlations with visual scores was probably sufficient to recover genetic variability. The methods provided similar breeding value accuracies, especially for the visual scores.

Accuracies of genomic prediction of feed efficiency traits using different prediction and validation methods in an experimental Nelore cattle population.

Animal feeding is the most important economic component of beef production systems. Selection for feed efficiency has not been effective mainly due to difficult and high costs to obtain the phenotypes. The application of genomic selection using SNP can decrease the cost of animal evaluation as well as the generation interval. The objective of this study was to compare methods for genomic evaluation of feed efficiency traits using different cross-validation layouts in an experimental beef cattle population genotyped for a high-density SNP panel (BovineHD BeadChip assay 700k, Illumina Inc., San Diego, CA). After quality control, a total of 437,197 SNP genotypes were available for 761 Nelore animals from the Institute of Animal Science, Sertãozinho, São Paulo, Brazil. The studied traits were residual feed intake, feed conversion ratio, ADG, and DMI. Methods of analysis were traditional BLUP, single-step genomic BLUP (ssGBLUP), genomic BLUP (GBLUP), and a Bayesian regression method (BayesCπ). Direct genomic values (DGV) from the last 2 methods were compared directly or in an index that combines DGV with parent average. Three cross-validation approaches were used to validate the models: 1) YOUNG, in which the partition into training and testing sets was based on year of birth and testing animals were born after 2010; 2) UNREL, in which the data set was split into 3 less related subsets and the validation was done in each subset a time; and 3) RANDOM, in which the data set was randomly divided into 4 subsets (considering the contemporary groups) and the validation was done in each subset at a time. On average, the RANDOM design provided the most accurate predictions. Average accuracies ranged from 0.10 to 0.58 using BLUP, from 0.09 to 0.48 using GBLUP, from 0.06 to 0.49 using BayesCπ, and from 0.22 to 0.49 using ssGBLUP. The most accurate and consistent predictions were obtained using ssGBLUP for all analyzed traits. The ssGBLUP seems to be more suitable to obtain genomic predictions for feed efficiency traits on an experimental population of genotyped animals.

Genome scan for postmortem carcass traits in Nellore cattle.

Carcass traits measured after slaughter are economically relevant traits in beef cattle. In general, the slaughter house payment system is based on HCW. Ribeye area (REA) is associated with the amount of the meat in the carcass, and a minimum of backfat thickness (BFT) is necessary to protect the carcass during cooling. The aim of this study was to identify potential genomic regions harboring candidate genes affecting those traits in Nellore cattle. The data set used in the present study consisted of 1,756 Nellore males with phenotype records. A subset of 1,604 animals had both genotypic and phenotypic information. Genotypes were generated based on a panel with 777,962 SNPs from the Illumina Bovine HD chip. The SNP effects were calculated based on the genomic breeding values obtained by using the single-step GBLUP approach and a genomic matrix re-weighting procedure. The proportion of the variance explained by moving windows of 100 consecutive SNPs was used to assess potential genomic regions harboring genes with major effects on each trait. The top 10 non-overlapping SNP-windows explained 8.72%, 11.38%, and 9.31% of the genetic variance for REA, BFT, and HCW, respectively. These windows are located on chromosomes 5, 7, 8, 10, 12, 20, and 29 for REA; chromosomes 6, 8, 10, 13, 16, 17, 18, and 24 for BFT; and chromosomes 4, 6, 7, 8, 14, 16, 17, and 21 for HCW. For REA, there were identified genes ( and ) involved in the cell cycle biological process which affects many aspects of animal growth and development. The and genes, both from AA transporter family, was also associated with REA. The AA transporters are essential for cell growth and proliferation, acting as carriers of tissue nutrient supplies. Various genes identified for BFT (, , , , , and ) have been associated with lipid metabolism in different mammal species. One of the most promising genes identified for HCW was the . There is evidence, in the literature, that this gene is located in putative QTL affecting carcass weight in beef cattle. Our results showed several genomic regions containing plausible candidate genes that may be associated with carcass traits in Nellore cattle. Besides contributing to a better understanding of the genetic control of carcass traits, the identified genes can also be helpful for further functional genomic studies.

CagA status and Helicobacter pylori eradication among dyspeptic patients.

AIM: Triple therapy seems more effective in curing Helicobacter pylori infection in patients with peptic ulcer than in those with non-ulcer dyspepsia. It has been suggested that this difference depends on the expression of CagA protein that is more frequent in the former. The objective of this study was to investigate a potential association between serum CagA positivity, severity of gastric mucosal inflammation and eradication success among peptic ulcer and non-ulcer dyspepsia patients. MATERIAL AND METHOD: Patients undergoing upper gastrointestinal endoscopy for investigation of dyspepsia at the Department of Gastroenterology, Hospital Vera Cruz, between March, 2000 and March 2001 were screened. H. pylori positive patients, as diagnosed by rapid urease test and histology were included. Severity of gastric mucosal inflammation was determined and serum CagA positivity was assessed using a commercially available ELISA assay prior to H. pylori 7-day eradication therapy with lansoprazole, clarithromycin and amoxicillin (30 mg, 500 mg and 1 g b.i.d., respectively). Eradication success was determined 8-24 weeks following completion of therapy. RESULTS: Seventy-four patients were included in the study (mean age 40.8, range 18-67, female = 28). CagA positivity was observed in 48% of patients. Gastroduodenal peptic ulceration was found in 54% of patients. Serum CagA positivity was significantly higher among peptic ulcer patients (62.5%), while CagA negativity was significantly higher among non-ulcer dyspepsia patients (67.7%). Lymphocyte and eosinophil infiltration was significantly higher among CagA + patients, despite being comparable when distributed among peptic ulcer and non-ulcer dyspepsia patients. Eradication was successful in 93.2% of patients, regardless of CagA status on a per protocol analysis. Based on a per protocol analysis, eradication success was comparable among peptic ulcer and non-ulcer dyspepsia patients, regardless of CagA status. CONCLUSION: Our results support the concept that CagA positivity is associated to peptic ulcer disease and to a higher severity of lymphocyte and eosinophil infiltration. Efficacy of treatment eradication of H. pylori may not be affected by serum CagA status.

Flavonoids from Lonchocarpus latifolius roots.

From the petrol extract of Lonchocarpus latifolius roots, 10 flavonoids were isolated. These included: 3,5-dimethoxy-2'',2''-dimethylpyrano-(5'',6'':8,7)-flavone, 3-methoxy-(2'',3'':7,8)-furanoflavanone, 3',4'-methylenedioxy-(2'',3'':7,8)-furanoflavanone, and (2,3-trans-3,4-trans)-3,4-dimethoxy-(2'',3'':7,8)-furanoflavan, as well as the previously known karanjachromene, karanjin, lanceolatin B, pongachromene, pongaglabrone and ponganpin. Only nine flavonoids could be quantified through HPLC analysis.

Prenylated flavonoids from Deguelia hatschbachii and their systematic significance in Deguelia.

Chemical investigation of dichloromethane and petrol extracts from the roots of D. hatshbachii A. M. G. Azevedo furnished thirteen compounds from which five are described for the first time and their structures were determined to be 3-(4'-hydroxyphenyl)-5-methoxy-6-( 3,3-dimethylallyl)-2"2"-dimethylchromene-(5",6":8,7)-3-(propyl-2-one)-4H-1-benzo-2,3-dihydropyran-2,4-dione; 6,4'-dihydroxy-3-(3,3-dimethylallyl)-2",2"-dimethylchromene (5",6":5,4)-2-methoxy deoxybenzoin; 6.4'-dihydroxy-3-(3,3-dimethylallyl)-2",2"-dimethylchromene (5",6":5,4)-2-methoxy-8-(propyl-2-one) deoxybenzon; 6-(3,3-dimethylallyl)-2",2"-dimethylchromene (5",6":4.5)-4'-hydroxy-3-methoxy stilbene and 3,5-dimethoxy-4'-hydroxy-4-(3,3-dimethylallyl) stilbene by spectral analysis (UV, IR, MS and ID- and 2D- NMR experiments). The root extracts and some isolated compounds were bioactive, as revealed by bioautography and brine shrimp lethality assays.

Regression of childhood Barrett's esophageal mucosa by antireflux surgery and bipolar electrocoagulation.

The authors report a case of a 13-year-old girl with Barrett's esophagus who underwent antireflux surgery and was subsequently treated with endoscopic thermal coagulation using bipolar electrocoagulation. Follow-up endoscopy 15 months after completion of the endoscopic therapy showed normal esophageal mucosa without intestinal metaplasia. Longer follow-up is needed to assess the long-term effects of endoscopic treatment of the Barrett's mucosa with thermal coagulation, and this procedure should still be considered under investigation.

Acid suppression with ranitidine plus oral triple therapy improves ulcer healing but not Helicobacter pylori eradication.

BACKGROUND/AIMS: To evaluate whether the addition of 2 weeks of ranitidine to a 1-week oral triple therapy (OTT) regimen improved ulcer healing and H. pylori eradication. METHODOLOGY: Two hundred and eleven consecutive patients with an endoscopic diagnosis of active duodenal ulcer (DU) and a positive antrum biopsy for H. pylori were enrolled. Those attending the Hospital Vera Cruz (Group A, n=142) received a 14-day course of ranitidine (150 mg after breakfast and dinner) plus a 1-week OTT, consisting of bismuth subcitrate, (240 mg after the 3 meals), tetracycline (500 mg, 10 min before the three meals and at bedtime), and furazolidone (200 mg after breakfast and dinner). Patients from the Hospital das Clinicas (Group B, n=69) received the same OTT as Group A but without ranitidine. Patients underwent endoscopy again on average 40 days (range: 30-60 days) after completing therapy in order to assess ulcer healing and H. pylori status. RESULTS: Both schedules were equally efficient in eradicating H. pylori with 90% (128/142) eradication in group A, and 84% (58/69) in group B (p=0.2). In contrast, the addition of ranitidine to OTT improved ulcer healing when compared with OTT alone (96%, 137/142, vs. 70%, 48/69; p<0.001). CONCLUSIONS: Our results demonstrate that the association of acid suppression, obtained with 2 week ranitidine administration with OTT improved ulcer healing but did not enhance H. pylori eradication.

[Centipede stings notified by the "Centro de Informações Toxicológicas de Belém", over a 2-year period]. / Acidentes por centopéia notificados pelo "Centro de Informações Toxicológicas de Belém", num período de dois anos.

Centipedes are arthropods of the class Chilopoda. The objective of this work was to study the incidence of accidents involving centipedes at "Centro de Informações Toxicológicas de Belém" (CIT-Belém) over a two-year period. Seventy-six patients were studied from March 30, 1998 until March 30, 2000. Centipede accidents occurred in 16.8% of all accidents by venomous animals at Centro de Informações Toxicológicas de Belém; compared to snake accidents, 44.4 % and scorpion accidents, 20.5%. The majority of cases occurred in the residence (86.8%). The most important age group was 20-49 years old (64.4%). The part of human body mostly affected was the superior members (47.4 %). Local pain and edema were found in 95.8% and 52.1% of the patients, respectively. Treatment was symptomatic. Healing occurred in 94.7%, although the outcome of 5.3% of cases was unknown. Centipede accidents are a benign accident, occurring within the residence and treatment consists of measures to decrease the pain.

Diagnostic value of fecal leukocytes in chronic bowel diseases.

To evaluate the importance of fecal leukocytes, 42 patients who showed signs of fecal leukocytes (++ or +++) were studied. Their endoscopic examinations with biopsy and/or radiology of the colon showed the following diagnoses: 33 had ulcerative colitis, four had colonic adenocarcinoma, two had Crohn's disease, two had amebic colitis and one had eosinophilic colitis. The presence of fecal leukocytes allowed for the diagnosis of colon disease in all the patients, and it might indicate exudative bowel disease. These results suggest that whenever fecal leukocytes are found in the feces, an examination for colon disease should be made.

[Electron microscopy of the liver in Gilbert's syndrome]. / Microscopia electrônica do fígado na síndrome de Gilbert.

Hepatic biopsy of five patients with Gilbert's syndrome was examined at the electron microscopy and only one disclosed incharacteristic alterations. The others were considered normal.

[Gilbert's syndrome in patients with splenomegaly]. / Síndrome de Gilbert em pacientes com esplenomegalia.

Three patients are reported with hyperbilirubinemia and splenomegaly. The diagnosis of Gilbert's syndrome was made by the caloric restriction test and enzymatic induction test. The splenomegaly was attributed to spherocytosis in two patients, while the third case had a probable diagnosis of spherocytosis.

[Absorption of medium chain triglycerides in patients with blind loop syndrome]. / Absorção de triglicérides de cadeia média em pacientes com síndrome de alça estagnada.

Absorption of medium chain triglycerides (MCT) was estimated in 10 patients with stagnant loop syndrome (SLS). Six patients had steatorrhea due to gastrojejunal anastomosis and 4 due to diabetic neuropathy. The diagnosis of SLS was confirmed by antibiotic therapeutic test after exclusion of other causes of malabsorption syndrome. Each patient was submitted to 2 types of diet during one week each, differing only in the type of added lipid. In the diet with long chain triglycerides (LCT), soy oil and butter were added. In the diet, with medium chain triglycerides, only MCT oil from babaçu was added. The excretion of lipid was determined in the feces in the last 3 days of each diet. The results showed that the medium fecal lipid excretion was 48.6 (sd = 19.8) g/d in the LCT diet and 26.6 (sd = 13.8) g/d in the MCT [d = 22.0; s(d) = 3.10; t = 7.10; p less than 0.001], which indicates that in patients with SLS, MCT diet was better absorbed than LCT diet. It is suggested that MCT oil may be used as a caloric source during nutritional recovery in SLS.

[Qualitative microscopic evaluation of fecal fats. Comparative study]. / Avaliação microscópica qualitativa da gordura fecal. Estudo comparativo.

Microscopical examination of stool fat is an easy laboratory procedure a long ago used as screening for steatorrhea. Quantitative analysis of stool fat is accepted as the best method to diagnose fat malabsorption, but stool collection and the laboratory technique are more difficult and time-consuming. The main objective of this work was performed to compare the accuracy of microscopical qualitative examination in the same fecal sample collected in 500 patients, 299 adults and 201 children, for the three days quantitative method. The diagnosis of steatorrhea was confirmed by chemical determination in 237 adults (stool fat values greater than 5 g) and 131 children (stool fat values greater than 2 g). From these 62 patients adults and 70 children were admitted as controls. The study showed that microscopical qualitative fat evaluation is highly comparable with findings obtained by chemical dosage. However, it is important to consider the use of two microscopic examination for each fecal sample, that must be carefully homogenized.

[Isoniazid acetylation in Gilbert's syndrome]. / A acetilação da isoniazida na síndrome de Gilbert.

Phenotyping of isoniazid acetylators in 19 Caucasoid patients with Gilbert's syndrome was achieved by evaluating the percentual of acetylisoniazid in the urine. The proportion of slow acetylators among the patients with Gilbert's syndrome was similar to those found among Caucasoids of control group. The conclusion was that Gilbert's syndrome doesn't interfere in the hepatic capacity of isoniazid acetylation.

Intestinal lymphangiectasia in systemic lupus erythematosus.

The case of a woman with SLE and protein-losing enteropathy secondary to intestinal lymphangiectasia is described. Corticosteroid therapy improved all clinical symptoms, laboratorial findings and intestinal histological alterations.