Genetic associations between accumulated productivity, and reproductive and growth traits in Nelore cattle

The total meat yield in a beef cattle production cycle is economically very important and depends on the number of calves born per year or birth season, being directly related to reproductive potential. Accumulated Productivity (ACP) is an index that expresses a cow`s capacity to give birth regularly at a young age and to wean animals of greater body weight. Using data from cattle participating in the ""Program for Genetic Improvement of the Nelore Breed"" (PMGRN - Nelore Brasil), bi-trait analyses were performed using the Restricted Maximum Likelihood method based on an ACP animal model and the following traits: age at first calving (AFC), female body weight adjusted for 365 (BW365) and 450 (BW450) days of age, and male scrotal circumference adjusted for 365 (SC365), 450 (SC450), 550 (SC550) and 730 (SC730) days of age. Median estimated ACP heritability was 0.19 and the genetic correlations with AFC, BW365, BW450, SC365, SC450, SC550 and SC730 were 0.33, 0.70, 0.65, 0.08, 0.07, 0.12 and 0.16, respectively. ACP increased and AFC decreased over time, revealing that the selection criteria genetically improved these traits. Selection based on ACP appears to favor the heaviest females at 365 and 450 days of age who showed better reproductive performance as regards AFC. Scrotal circumference was not genetically associated with ACP. (C) 2007 Elsevier B.V. All rights reserved.

Deregulation of LOXL1 and HTRA1 Gene Expression in Endometriosis

Endometriosis is a gynecologic disease characterized by the presence of endometrial tissue outside the uterine cavity. Although 15% of the female population in reproductive age is affected by endometriosis, its pathogenesis remains unclear. According to the most accepted pathogenesis hypothesis, endometrial fragments from the menstrual phase are transported through the uterine tubes to the peritoneal cavity, where they undergo implantation and growth, invading adjacent tissues. However, the establishment of the disease requires that endometrial cells present molecular characteristics favoring the onset and progression of ectopic implantation. In this investigation, we analyzed the differential gene expression profiles of peritoneal and ovarian endometriotic lesions compared to the endometrial tissue of nonaffected women using rapid subtraction hybridization (RaSH). In our study, this method was applied to samples of endometriotic lesions from affected women and to biopsies of endometrium of healthy women without endometriosis, where we could identify 126 deregulated genes. To evaluate the expression of genes found by RaSH method, we measured LOXL1, HTRA1, and SPARC genes by real-time polymerase chain reaction. Significant different expression was obtained for HTRA1 and LOXL1, upregulated in the ectopic endometrium, suggesting that these genes are involved in the physiopathology of endometriosis and may favor the viability of endometrial cells at ectopic sites.

Preimplantation development and expression of Hsp-70 and Bax genes in bovine blastocysts derived from oocytes matured in alpha-MEM supplemented with growth factors and synthetic macromolecules

In vitro culture conditions affect both the maternal and embryonic expression of genes and is likely to alter both oocyte and embryo developmental competence. The search for better and less variable culture conditions simulating those in vivo has led to the development of defined culture media, with lower impact on the molecular reprogramming of oocytes and embryos. We evaluated embryo development and relative abundance (RA) of Hsp-70 and Bax transcripts in bovine blastocysts produced from oocytes matured in a chemically defined IVM system with synthetic polymers. Immature cumulus oocyte complexes (COCs) were matured for 22-24 h in alpha-MEM supplemented with IGF-1, insulin, 0.1% polyvinyl alcohol (PVA), or 0.1% polyvinylpyrrolidone (PVP), but without FSH or LH. The control group consisted of COCs matured it, TCM plus FSH and 10% estrous cow serum. After fertilization. presumptive zygotes were co-cultured with cumulus cells until 224 h post-insemination. Total RNA was isolated from embryo pools, reverse transcribed into cDNA, and subjected to transcript analysis by real-time PCR. Cleavage rate was higher (P < 0.05) for the control group (68.3%) than for the PVA (54.4%) and PVP-40 (58.3%) groups. Nevertheless. there was no difference among the PVA, PVP-40 and control groups in blastocyst or hatching rates. similarly, no difference in relative abundance of Hsp-70 and Bax transcripts was detected in comparison to the control group. We inferred that bovine oocytes can be matured in serum- and gonadotrophin-free medium supplemented with PVA or PVP, enriched with IGF-I and insulin, without altering post-cleavage development and relative abundance of some genes associated with stress and apoptosis. (C) 2009 Elsevier Inc. All rights reserved.

Effects of eccentric and concentric training on capillarization and myosin heavy chain contents in rat skeletal muscles after hindlimb suspension

We studied the effects of different protocols of post-disuse rehabilitation on angiogenesis and myosin heavy chain (MHC) content in rat hindlimb muscles after caudal suspension. Thirty female Wistar rats were divided into five groups: (1) Control I, (2) Control II, (3) Suspended, (4) Suspended trained on declined treadmill, and (5) Suspended trained on flat treadmill. Fragments of the soleus and tibialis anterior (TA) muscles were frozen and processed by electrophoresis and immunohistochemistry (CD31 antibody). Hindlimb suspension caused reduction of capillary/fiber (C/F) ratios and contents of MHC type I (MHCI) in the soleus in parallel to increased capillary density. Flat treadmill protocols increased the content of the MHCI isoform. The C/F ratio was increased by concentric training after hypokinesis, but was not modified by eccentric training, which caused a greater reduction of capillary density compared to the other protocols. In the TA muscle, hindlimb suspension caused a non-significant increase in capillary density and C/F ratio with limited changes in MHC. The present data demonstrate that the different training protocols adopted and the functional performance of the muscles analyzed caused specific changes in capillarization and in the content of the various MHC types. (C) 2010 Published by Elsevier GmbH.

Organizational Learning in the Context of an Agri-Food Chain

This paper reports on the outcomes of the first stage of a longitudinal study that focused on the transformational change process being undertaken within the Supply Chain and Operations Area of a major Australian food manufacturing company. Organizational learning is an essential prerequisite for any successful change process and an organization's ability to learn is dependent on the existence of an environment within the organization that nurtures learning and the presence of key enablers that facilitate the learning process. An organization's capacity to learn can be enhanced through its ability to form and sustain collaborative relationships with its chain partners. The results show that an environment that supports organizational learning is being developed through consultative leadership and the empowerment of individuals within a culture that supports innovation and cross-functional teamwork but demands responsibility and accountability. The impact of these changes within the Supply Chain and Operations Area is evident in the significant improvement in the Area's productivity and efficiency levels over the past twelve months. The company's endeavours to engage its major supply chain partners in the learning process have been limited by the turmoil within the company. However the company has involved its supply chain partners in a series of mutually beneficial projects that have improved communication and built trust thereby laying the foundations for more collaborative chain relationships.

Mast cells and transforming growth factor-beta expression: a possible relationship in the development of porphyria cutanea tarda skin lesions

Background Porphyria cutanea tarda (PCT) is a metabolic disease characterized by vesicles and blisters in sun-exposed areas and scleroderma-like lesions in sun-exposed and non-sun-exposed areas. Mast cells participate in the pathogenesis of bullous diseases and diseases that show sclerosis, including PCT. Moreover, transforming growth factor-beta (TGF-beta) is the main cytokine in the development of tissue sclerosis. The correlation of mast cells and TGF-beta with the lesions of PCT has not been examined, however. The possible role of mast cells and TGF-beta (and the relationship between them) in the development of PCT lesions is discussed. Methods To quantify mast cells and cells expressing TGF-beta in skin samples from patients with PCT and controls, immunohistochemical studies were performed in tissue sections allied to morphometric analyses. Results The numbers of mast cells and cells expressing TGF-beta per square millimiter were increased in the PCT group relative to controls, and there was a direct and significant correlation between the mast cell number and cells expressing TGF-beta in PCT. Conclusions The results suggest that the increased number of mast cells and of cells expressing TGF-beta, as well as their direct correlation, may contribute to the pathogenesis of the skin lesions in PCT.

Obesity due to Melanocortin 4 Receptor (MC4R) Deficiency Is Associated with Increased Linear Growth and Final Height, Fasting Hyperinsulinemia, and Incompletely Suppressed Growth Hormone Secretion

Context: Melanocortin receptor 4 (MC4R) deficiency is characterized by increased linear growth greater than expected for the degree of obesity. Objective: The objective of the investigation was to study the somatotroph axis in obese MC4R-deficient patients and equally obese controls. Patients and Methods: We obtained anthropometric measurements and insulin concentrations in 153 MC4R-deficient subjects and 1392 controls matched for age and severity of obesity. We measured fasting IGF-I, IGF-II, IGF binding protein (IGFBP)-1, IGFBP-3, and acid-labile subunit levels in a subset of 33 MC4R-deficient patients and 36 control subjects. We examined pulsatile GH secretion in six adult MC4R-deficient subjects and six obese controls. Results: Height so score was significantly greater in MC4R-deficient children under 5 yr of age compared with controls (mean +/- SEM: 2.3 +/- 0.06 vs. 1.8 +/- 0.04, P < 0.001), an effect that persisted throughout childhood. Final height (cm) was greater in MC4R-deficient men (mean +/- SEM 173 +/- 2.5 vs. 168 +/- 2.1, P < 0.001) and women (mean 165 +/- 2.1 vs. 158 +/- 1.9, P < 0.001). Fasting IGF-I, IGF-II, acid-labile subunit, and IGFBP-3 concentrations were similar in the two groups. GH levels were markedly suppressed in obese controls, but pulsatile GH secretion was retained in MC4R deficiency. The mean maximal GH secretion rate per burst (P < 0.05) and mass per burst (P < 0.05) were increased in MC4R deficiency, consistent with increased pulsatile and total GH secretion. Fasting insulin levels were markedly elevated in MC4R-deficient children. Conclusions: In MC4R deficiency, increased linear growth in childhood leads to increased adult final height, greater than predicted by obesity alone. GH pulsatility is maintained in MC4R deficiency, a finding consistent with animal studies, suggesting a role for MC4R in controlling hypothalamic somatostatinergic tone. Fasting insulin levels are significantly higher in children carrying MC4R mutations. Both of these factors may contribute to the accelerated growth phenotype characteristic of MC4R deficiency. (J Clin Endocrinol Metab 96: E181-E188, 2011)

Postnatal growth and cardiometabolic profile in young adults born large for gestational age

Context The association between large for gestational age (LGA) phenotype, postnatal growth and cardiometabolic risk (CMR) in adult life remains unclear. The role of IGF1 genotype on LGA-related outcomes in adult life is unknown. Aim To assess the postnatal growth, IGF-I levels, CMR and the influence of the 737.738 IGF1 in adults born LGA. Subjects Case-control study (n = 515) nested in a population-based prospective cohort (n = 2063); 117 LGA and 398 gender-matched controls appropriate for gestational age (AGA) subjects. Methods Anthropometry was evaluated at birth, at 9-10 and at 23-25 years old. At the age of 23-25 years, blood pressure (BP), glycaemia, insulinaemia, homeostasis model assessment - insulin resistance, lipids, fibrinogen, and plasma IGF-I and 737.738 IGF1 polymorphism were assessed. Results Large for gestational age subjects remained heavier and taller than AGA at 9-10 and 23-25 years (P < 0.05); at 23-25 years, LGA had greater waist circumference (WC; P < 0.05) and higher BP (P < 0.05) than controls. Body proportionality at birth did not predict metabolic outcome. LGA subjects presenting catch-down of weight in childhood had lower body mass index (BMI; P = 0.001), lower WC (P < 0.05) and lower BP (P < 0.05) at 2325 years. 737.738 IGF-I genotype differed between groups (P < 0.001). Homozygosis for polymorphic alleles was associated with increased odds of LGA (OR: 3.2; 95% CI: 1.5-6.9), higher IGF-I (56.9 +/- 16.4 vs 37.7 +/- 16.0 nm; P < 0.01) and lower BP (114/68 vs 121/73 mmHg; P < 0.05). Conclusions Young adults born LGA presented higher BMI, WC and BP and appear to be at higher CMR risk than AGA subjects. The 737.738 IGF1 polymorphism appears to play a role on birth size and LGA-related metabolic outcomes.

Growth after ventricular septal defect repair: does defect size matter? A 10-year experience

Aim: To evaluate whether the ventricular septal defect (VSD) size, along with the degree of preoperative growth impairment and age at repair, may influence postoperative growth, and if VSD size can be useful to identify children at risk for preoperative failure to thrive. Methods: Sixty-eight children submitted to VSD repair in a Brazilian tertiary-care institution were evaluated. Weight and height measurements were converted to Z-scores. Ventricular septal defect size was normalized by dividing it by the aortic root diameter (VSD/Ao ratio). Results: Twenty-six patients (38%) had significantly low weight-for-height, 10 patients (15%) had significantly low height-for-age and 13 patients (19%) had both conditions at repair. Catch-up growth occurred in 82% of patients for weight-for-age, in 75% of patients for height-for-age and in 89% of patients for weight-for-height. Weight-for-height Z-scores at surgery were significantly lower in patients who underwent repair before 9 months of age. The VSD/Ao ratio did not associate with any other data. On multivariate analysis, weight-for-age Z-scores and age at surgery were independent predictors of long-term weight and height respectively. Conclusion: The VSD/Ao ratio was not a good predictor of preoperative failure to thrive. Most patients had preoperative growth impairment and presented catch-up growth after repair. Preoperative growth status and age at surgery influenced long-term growth.

Can the Insulin Sensitivity Index (ISI) in Association with Insulin-like Growth Factor Binding Protein-1 Identify Insulin Resistance Early in Overweight Children?

Association between insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) has been reported. This prompted us to evaluate the power of the insulin sensitivity index (ISI) in association with IGFBP-1 to identify IR early in obese children/adolescents. OGTT was performed in 34 obese/overweight children/adolescents. Glucose, insulin and IGFBP-1 were measured in serum samples and ISI was calculated. Considering the presence of three or more risk factors for IR as a criterion for IR, ISI <4.6 showed 87.5% sensitivity and 94.5% specificity in diagnosing IR. IGFBP-1 was lower in the group with ISI <4.6 (p <0.01). In this group, three patients had higher than expected IGFBP-1, suggesting hepatic IR, while three patients with ISI >4.6 showed very low IGFBP-1 levels. Conclusion: ISI <4.6 is a good indicator of early peripheral IR and, associated with IGFBP-1, can identify increased risk of hepatic IR. Low IGFBP-1 levels among non-IR children may indicate increased portal insulin levels.

The-202 A Allele of Insulin-Like Growth Factor Binding Protein-3 (IGFBP3) Promoter Polymorphism Is Associated with Higher IGFBP-3 Serum Levels and Better Growth Response to Growth Hormone Treatment in Patients with Severe Growth Hormone Deficiency

Context: Genetic factors that influence the response to recombinant human GH (rhGH) therapy remain mostly unknown. To date, only the GH receptor gene has been investigated. Objective: The aim of the study was to assess the influence of a polymorphism in the IGF-binding protein-3 (IGFBP-3) promoter region (-202 A/C) on circulating IGFBP-3 levels and growth response to rhGH therapy in children with GH deficiency (GHD). Design and Patients: -202 A/C IGFBP3 genotyping (rs2854744) was correlated with data of 71 children with severe GHD who remained prepubertal during the first year of rhGH treatment. Main Outcome Measures: We measured IGFBP-3 levels and first year growth velocity (GV) during rhGH treatment. Results: Clinical and laboratory data at the start of treatment were indistinguishable among patients with different -202 A/C IGFBP3 genotypes. Despite similar rhGH doses, patients homozygous for the A allele presented higher IGFBP-3 SD score levels and higher mean GV in the first year of rhGH treatment than patients with AC or CC genotypes (first year GV, AA = 13.0 +/- 2.1 cm/yr, AC = 11.4 +/- 2.5 cm/yr, and CC = 10.8 +/- 1.9 cm/yr; P = 0.016). Multiple linear regression analyses demonstrated that the influence of -202 A/C IGFBP3 genotype on IGFBP-3 levels and GV during the first year of rhGH treatment was independent of other variables. Conclusion: The -202 A allele of IGFBP3 promoter region is associated with increased IGFBP-3 levels and GV during rhGH treatment in prepubertal GHD children. (J Clin Endocrinol Metab 94: 588-595, 2009)

Exposure to maternal smoking during fetal life affects food preferences in adulthood independent of the effects of intrauterine growth restriction

Experimental animal studies have shown that nicotine exposure during gestation alters the expression of fetal hypothalamic neuropeptides involved in the control of appetite. We aimed to determine whether the exposure to maternal smoking during gestation in humans is associated with an altered feeding behavior of the adult offspring. A longitudinal prospective cohort study was conducted including all births from Ribeirao Preto (Sao Paulo, Brazil) between 1978 and 1979. At 24 years of age, a representative random sample was re-evaluated and divided into groups exposed (n = 424) or not (n = 1586) to maternal smoking during gestation. Feeding behavior was analyzed using a food frequency questionnaire. Covariance analysis was used for continuous data and the chi(2) test for categorical data. Results were adjusted for birth weight ratio, body mass index, gender, physical activity and smoking, as well as maternal and subjects` schooling. Individuals exposed to maternal smoking during gestation ate more carbohydrates than proteins (as per the carbohydrate-to-protein ratio) than non-exposed individuals. There were no differences in the consumption of the macronutrients themselves. We propose that this adverse fetal life event programs the individual`s physiology and metabolism persistently, leading to an altered feeding behavior that could contribute to the development of chronic diseases in the long term.

Genetic associations between carcass traits measured by real-time ultrasound and scrotal circumference and growth traits in Nelore cattle

The aim of the present study was to evaluate the genetic correlations among real-time ultrasound carcass, BW, and scrotal circumference (SC) traits in Nelore cattle. Carcass traits, measured by real-time ultrasound of the live animal, were recorded from 2002 to 2004 on 10 farms across 6 Brazilian states on 2,590 males and females ranging in age from 450 to 599 d. Ultrasound records of LM area (LMA) and backfat thickness (BF) were obtained from cross-sectional images between the 12th and 13th ribs, and rump fat thickness (RF) was measured between the hook and pin bones over the junction between gluteus medius and biceps femoris muscles. Also, BW (n = 22,778) and SC ( n = 5,695) were recorded on animals born between 1998 and 2003. The BW traits were 120, 210, 365, 450, and 550-d standardized BW (W120, W210, W365, W450, and W550), plus BW (WS) and hip height (HH) on the ultrasound scanning date. The SC traits were 365-, 450-, and 550-d standardized SC (SC365, SC450, and SC550). For the BW and SC traits, the database used was from the Nelore Breeding Program-Nelore Brazil. The genetic parameters were estimated with multivariate animal models and REML. Estimated genetic correlations between LMA and other traits were 0.06 (BF), -0.04 ( RF), 0.05 (HH), 0.58 (WS), 0.53 (W120), 0.62 (W210), 0.67 (W365), 0.64 ( W450 and W550), 0.28 (SC365), 0.24 (SC450), and 0.00 ( SC550). Estimated genetic correlations between BF and with other traits were 0.74 ( RF), -0.32 (HH), 0.19 (WS), -0.03 (W120), -0.10 (W210), 0.04 (W365), 0.01 (W450), 0.06 ( W550), 0.17 (SC365 and SC450), and -0.19 (SC550). Estimated genetic correlations between RF and other traits were -0.41 (HH), -0.09 (WS), -0.13 ( W120), -0.09 ( W210), -0.01 ( W365), 0.02 (W450), 0.03 (W550), 0.05 ( SC365), 0.11 ( SC450), and -0.18 (SC550). These estimates indicate that selection for carcass traits measured by real-time ultrasound should not cause antagonism in the genetic improvement of SC and BW traits. Also, selection to increase HH might decrease subcutaneous fat as correlated response. Therefore, to obtain animals suited to specific tropical production systems, carcass, BW, and SC traits should be considered in selection programs.

Advantages and Pitfalls of the Polymerase Chain Reaction in the Diagnosis of Esophageal Ulcers in AIDS Patients

HIV-1-infected patients frequently have opportunistic esophageal infections which, when associated with severe immunodeficiency, can be attributed to unusual pathogens. The clinical presentation of several esophageal diseases is similar and the best method for a specific diagnosis of these patients has not been well defined. To evaluate the role of the polymerase chain reaction (PCR) in the etiologic definition of esophageal ulcers in HIV-1-infected patients, 96 esophageal biopsies from 79 HIV-1-infected patients were processed by PCR using specific primers for cytomegalovirus (CMV), herpes virus (HSV), human papilloma virus (HPV), HIV-1, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Treponema pallidum, and Haemophilus ducreyi. The PCR results were compared to the histopathologic results. Seventy-nine patients were studied (mean age: 34 years; 62% men; median CD4 + T cell = 103.59 cells/mu l (range 1-795.2 cells/mu l). The most common endoscopic findings were as follows: esophageal candidiasis (37.1%), esophageal ulcers (24.7%), esophagitis (11.2%), and lugol-negative areas (10.1%). The histopathologic findings in the esophageal ulcers (22 biopsies) were non-specific inflammation (31.8%), HSV (36.4%), Candida (13.6%), CMV (13.6%), or HPV disease (4.5%). In the esophageal ulcer biopsies, the PCR results were negative in 27.6% of cases, and positive for HIV (65.5%), CMV (31%), HPV (20.7%), HSV (10.3%), and H. ducreyi (6.9%). The histopathologic examination did not identify a pathogen or identified only Candida in 15 biopsies of esophageal ulcers. PCR was positive in ten (66.7%) and negative in five (33.3%) of these biopsies (idiopathic ulcers). PCR detected: HIV (53.3%), CMV (20%), HPV (13.3%), and H. ducreyi (6,7%). PCR detected more etiologic agents in esophageal ulcers than histopathology and was able to detect unusual pathogens. On the other hand, sometimes more than one pathogen was detected in the esophageal ulcers, making it difficult to reach an accurate diagnosis. This finding indicates the need for more studies to evaluate the benefit of this method in the routine evaluation of esophageal ulcer biopsies in HIV-1-infected patients.