Comparing methodologies to estimate fixed genetic effects and to predict genetic values for an Angus × Nellore cattle population.

The study assesses the need for and effectiveness of using ridge regression when estimating regression coefficients of covariates representing genetic effects due to breed proportion in a crossbreed genetic evaluation. It also compares 2 ways of selecting the ridge parameters. A large crossbred Angus × Nellore population with 294,045 records for weaning gain and 148,443 records for postweaning gain was used. Phenotypic visual scores varying from 1 to 5 for weaning and postweaning conformation, weaning and postweaning precocity, weaning and postweaning muscling, and scrotal circumference were analyzed. Three models were used to assess the need for ridge regression, having 4, 6, and 8 genetic covariates. All 3 models included the fixed contemporary group effect and random animal, maternal, and permanent environment effects. Model AH included fixed direct and maternal breed additive and the direct and maternal heterosis covariates, model AHE also included direct and maternal epistatic loss covariates, and model AHEC further included direct and maternal complementarity effects. The normal approach is to include these covariates as fixed effects in the model. However, being all derived from breed proportions, they are highly collinear and, consequently, may be poorly estimated. Ridge regression has been proposed as a method of reducing the collinearity. We found that collinearity was not a problem for models AH and AHE. We found a high variance inflation factor, >20, associated with some maternal covariates in the AHEC model reflecting instability of the regression coefficients and that this instability was well addressed by using ridge regression using a ridge parameter calculated from the variance inflation factor.

Origins and genetic diversity of British cattle breeds in Brazil assessed by pedigree analyses.

Pedigree information available for Angus (ANG), Devon (DEV), Hereford (HER), and Shorthorn (SHO) cattle in Brazil was analyzed to appraise the genetic diversity and population structure of these breeds. Pedigree records collected from the beginning of the 20th century until 2010 were used in the analyses. Over time, the number of herdbook registrations declined in HER after a peak in the 1970s, remained low in DEV and SHO, and increased steadily in ANG since the 1990s, such that it the latter is now the leading British cattle breed in Brazil. The average number of offspring registered per sire ranged from about 12 (SHO) to 20 (DEV) and the mean generation interval ranged from about 6.0 (HER and SHO) to 6.4 (ANG) years. In the reference population (calves born in 2009 and 2010, plus those born in 2008 for SHO) the mean equivalent number of generations known ranged from about 7 (SHO) to 9 (HER). In the 4 breeds studied, nearly all animals born over the last few years are inbred, even though the mean level of inbreeding in the reference population is below 4% in all breeds. The rate of inbreeding per generation, computed from the individual increase in inbreeding, ranged from about 0.2 (ANG) to 0.5% (DEV), with a corresponding effective population size of 245 and 92, respectively, which is above the recommended minimum critical threshold. The number of founders/ancestors contributing with 50% of the reference population gene pool was 211/26 for ANG, 41/14 for DEV, 164/25 for HER, and 79/10 for SHO, with effective number of founders/ancestors/founder genomes of 470/68/36, 89/33/16, 289/59/30, and 200/28/18 for ANG, DEV, HER, and SHO, respectively. The genetic contribution of different countries to the gene pool of each breed indicated that, throughout the period studied, DEV genes originated predominantly from the United Kingdom, while for the other breeds there was a changing pattern over time. Until the 1970s Argentina was the major supplier of ANG, while HER and SHO genes were mostly from Uruguay, but since then the United States took the leading role as supplier of ANG, HER, and SHO genes to Brazil. Our results reveal a mild increase in inbreeding in all breeds studied, with effective population size estimates indicating that reasonable levels of genetic diversity have been maintained in all 4 breeds. Continuous monitoring of inbreeding trends and of parameters derived from probability of gene origin should be ensured to warrant the long-term maintenance of genetic diversity.

Bioeconomic model and selection indices in Aberdeen Angus cattle.

A bioeconomic model was developed to calculate economic values for biological traits in full-cycle production systems and propose selection indices based on selection criteria used in the Brazilian Aberdeen Angus genetic breeding programme (PROMEBO). To assess the impact of changes in the performance of the traits on the profit of the production system, the initial values ​​of the traits were increased by 1%. The economic values for number of calves weaned (NCW) and slaughter weight (SW) were, respectively, R$ 6.65 and R$ 1.43/cow/year. The selection index at weaning showed a 44.77% emphasis on body weight, 14.24% for conformation, 30.36% for early maturing and 10.63% for muscle development. The eighteen-month index showed emphasis of 77.61% for body weight, 4.99% for conformation, 11.09% for early maturing, 6.10% for muscle development and 0.22% for scrotal circumference. NCW showed highest economic impact, and SW had important positive effect on the economics of the production system. The selection index proposed can be used by breeders and should contribute to greater profitability.

Calpain small-1 modulates Akt/FoxO3A signaling and apoptosis through PP2A.

Here, we show that FoxO3A transcription factor is upregulated upon calpain small-1 (CAPNS1) depletion both in mouse embryonic fibroblasts (MEFs) and in the human mammary carcinoma cell line MCF-7. On starvation, CAPNS1 depletion is associated with a higher rate of FoxO3A dephosphorylation and translocation to the nucleus and to a sharper increase in the levels of p27Kip1 and Bim, the products of two FoxO target genes. Notably, FoxO3A depletion in CAPNS1-/- MEFs reduces both the induction of Bim and apoptosis. Both okadaic acid treatment and silencing of the protein phosphatase 2A (PP2A) catalytic subunit can partially reduce starvation-induced FoxO3A activation and apoptosis in CAPNS1-/- fibroblasts. PP2A associates more tightly with Akt in CAPNS1 knockout cells, indicating that PP2A is involved in calpain-mediated FoxO regulation. Finally, we show that PP2A regulatory subunits B56 alpha and gamma are in vitro substrates of calpain, and calpain regulates B56 alpha stability in vivo, suggesting a direct role of calpain in the regulation of PP2A function. In conclusion, for the first time we report that CAPNS1 interferes with PP2A-Akt interaction consequently affecting FoxO3A-dependent cell death. Calpain inhibition might therefore be exploited as a tool to induce apoptosis in tumors sensitive to FoxO activation.

Ceramide triggers an NF-kappaB-dependent survival pathway through calpain.

We have shown that C2 ceramide, a cell-permeable analog of this lipid second messenger, triggers an NF-kappaB dependent survival pathway that counteracts cell death. Activation of NF-kappaB and subsequent induction of prosurvival genes relies on calpain activity and is prevented on silencing of the calpain small subunit (Capn4) that is required for the function of ubiquitous calpains. We have demonstrated that p105 (NF-kappaB1) and its proteolytic product p50 can be targets of micro- and milli-calpain in vitro and that a p50 deletion mutant, lacking both the N- and the C-terminal ends, is resistant to calpain-mediated degradation. Capn4 silencing results in stabilization of endogenous p105 and p50 in diverse human cell lines. Furthermore, p105 processing and activation of NF-kappaB survival genes in response to C2 ceramide is impaired in Capn4-/- mouse embryonic fibroblasts defective in calpain activity. Altogether, these data argue for the existence of a ceramide-calpain-NF-kappaB axis with prosurvival functions.

Dentin bond strengths as a function of solvent and glutaraldehyde content.

PURPOSE: To evaluate the effect of the inclusion of glutaraldehyde on the shear bond strength of new ethanol-based adhesives (Gluma Comfort Bond & Desensitizer, GCBD and Gluma Comfort Bond, GCB) versus acetone-based Gluma One Bond (GOB) and a conventional three-step adhesive as a control. MATERIALS AND METHODS: Forty bovine incisors were mounted in acrylic, polished to 600-grit, and randomly assigned to four groups (n=10). Dentin was etched for 15 s using 35% phosphoric acid, rinsed, and lightly dried. After adhesive application and curing, Charisma composite was applied in a #5 gelatin capsule and light-cured. Specimens were loaded in shear using an Instron at 5 mm/min. Shear bond strengths were calculated by dividing failure load by bonded surface area. ANOVA showed a significant difference in means at P< 0.01, so Tukey's test was used for pairwise comparisons. RESULTS: Mean SBS (+/- SD, MPa) were: GOB: 8 (4.4)ab; GCB: 10 (4.4)ab; GCBD: 14 (6)bc; SBMP: 17.7 (6.4)c. Superscript letters indicate Tukey's homogeneous subsets (P< 0.05).

Interaction between the HPV-16 E2 transcriptional activator and p53.

The HPV-16 E2 protein is a major regulator of viral DNA replication and gene expression. Through interactions with the viral origin binding protein, E1, it localizes E1 to the origin of replication and stimulates the initiation of viral DNA replication. However, several recent reports have described a number of diverse activities of E2 relating to the induction of apoptosis through both p53 dependent and independent mechanisms, and to induction of growth arrest in both the G1 and G2M phases of the cell cycle. Recent studies have also shown that p53 can specifically inhibit HPV DNA replication, albeit through an unknown mechanism. Since p53 has been described in the replication centres of Herpes Viruses, Adenovirus and SV40 we decided to investigate whether any of the above activities of E2 may be related to an association with p53. We show, in a series of in vitro assays, specific interaction between p53 and HPV-16 E2 via residues in the carboxy terminal half of the E2 protein. Mutational analysis of p53 indicates that sequences in both the DNA binding and oligomerization domains are essential for the interaction, and a mutant of p53 which is unable to bind E2 is also unable to inhibit HPV DNA replication. Finally, using an inducible system of p53 expression we also show that E2 will complex with p53 in vivo. These results raise the intriguing possibility that p53 may also be involved in HPV DNA replication centres, and also provides explanations for some of the diverse activities reported for the HPV E2 proteins.

Advantages of spinal anesthesia in abdominal gynecologic surgery.

The advantages obtained in vaginal surgery and caesarean section using spinal anesthesia led us to test this anesthesia to verify feasibility, problems and advantages in abdominal surgery. Spinal anesthesia was performed in 60 patients between 21 and 87 years of age. Thirty-seven total abdominal hysterectomies with or without adnexectomy, 5 laparotomic miomectomies, 3 adnexectomies, 5 colposacropexies, 2 hysterectomies with lymphadenectomy, 7 Burch colposuspension with or without hysterectomy and 1 laparoscopy for sterilization were performed. No significant problems during surgery and the postoperative period were observed. Resumption of the different physiologic functions were more rapid, hospital stay shorter and compliance greater than with general anesthesia.

The effect of fuel composition on the mutagenicity of diesel engine exhaust.

The effect of fuel composition on the mutagenicity of diesel engine emission was investigated. To this end, a fuel matrix comprising fuels with different contents of aromatic and naphthenic compounds was used. Extracts of the organic phase of raw exhausts obtained with different fuels were tested for mutagenicity in bacterial reversion assays. The results obtained demonstrate that the mutagenicity of diesel exhaust is largely dependent on the aromatic content of the fuel. In fact, mutagenicity was greatly reduced when the aromatic content of the fuel was lowered by hydrogen treatment. Conversely, mutagenicity was enhanced when the fuel was enriched with fractions of di- or triaromatic compounds. The addition of di- and trinaphthenic compounds only produced borderline mutagenicity. No clear relationship was observed between sulfur content of the fuel and mutagenicity of the exhaust. Assays in bacterial strains with different sensitivity to nitroaromatic compounds suggest a low contribution of the highly mutagenic dinitropyrenes to the responses observed, and a relatively greater contribution of 1-nitropyrene or other nitroaromatics processed by the same bacterial nitroreductase.

[Pulmonary lymph node in acute juvenile paracoccidioidomycosis (a case report)]. / Linfonodo pulmonar na paracoccidioidomicose aguda infantil (relato de um caso).

The primary complex like Ghon was observed in a child's clinical roentgenographic study. C.S., white, male, 6 years old, was born in Curitiba (PR), Brazil and living in Guaratingueta (SP), Brazil, developed "common cold", bimodal diary fever, chills, shake and sweats. Dyspnea, cough with general lymphadenopathy. Foot and right shoulder arthralgias. Six months ago visited a cave, equitation practice, dog and cat contacts and no transfusion, frontal sweats, fever (38.4 degrees C). T.A. was 8/6, tachycardia in generalized lymphadenopathy. Cardiopulmonary system was normal, mesogastric tumoral mass, hepatosplenomegaly and no ascites. Bone marrow with eosinophilia; nodule demonstrated presence of P. brasiliensis, hypoalbuminemia; hyperglobulinemia; anemia; leukocytosis with eosinophilia. Immunodiffusion with exoantigen 43 kd of P. brasiliensis was 1/32. Primary complex like Ghon was observed in interstitial pneumonia followed by mediastinal and mesogastric mass (35 to 40 days). Clavicular osteolytic lesions (45 to 60 days) appeared during paracoccidioidomycosis therapy. Recovery was observed 2 months after treatment of acute infantile paracoccidioidomycosis.

Giant parathyroid adenoma demonstrated by dual tracer parathyroid imaging.

Noninvasive diagnostic imaging modalities have played an increasingly important role in preoperative localization of parathyroid lesions. The radionuclide method using TI-201 and Tc-99m subtraction imaging is quite successful in detecting such lesions, with a reported sensitivity of 92%. A case of surgically proven primary hyperparathyroidism, caused by an unusually large parathyroid adenoma and detected by the dual tracer method, is presented.

Ainhum--an unusual presentation involving the second toe in a white male.

Ainhum (dactolysis spontanea) is most frequently seen involving the fifth toes of black men. An atypical case involving the second toes bilaterally in a white male is presented. The differential diagnosis, radiological findings and pathological appearance of this rare entity are discussed.