Seleção genômica ampla e novos métodos de melhoramento do milho.

Os objetivos deste trabalho foram verificar a acurácia do método da Seleção Genômica Ampla (GWS) no melhoramento de milho nas condições de estresse nutricional e propor novos métodos de melhoramento baseados em GWS. Foram estimados os dois componentes da eficiência no uso de nitrogênio e de fósforo (eficiência de absorção e de utilização) em 41 combinações híbridas, em dois experimentos, sob baixa e alta disponibilidades de N e P. Para a genotipagem da população de estimação, foram utilizados 80 marcadores microssatélites. As estimativas dos parâmetros genéticos foram obtidas via REML/BLUP, e a predição dos valores genéticos genômicos, via regressão aleatória (Random Regression - RR) aplicada à seleção genômica ampla (RR-BLUP/GWS). Para os caracteres em que a GWS apresentou altos valores de acurácia, essa foi comparada com os métodos de Seleção Recorrente Intra e Interpopulacional. Com o uso da GWS houve aumento significativo na acurácia seletiva e nos ganhos genéticos por unidade de tempo

Acromegaly, Mr Punch and caricature.

The origin of Mr Punch from the Italian Pulcinella of the Commedia dell'arte is well known but his feature, large hooked nose, protruding chin, kyphosis and sternal protrusion all in an exaggerated form also suggest the caricature of an acromegalic. This paper looks at the physical characteristics of acromegaly, the origin of Mr Punch and the development of caricature linking them together in the acromegalic caricature that now has a life of its own

Development and validation of the ACE tool: Assessing medical trainees' competency in evidence based medicine

BACKGROUND: While a variety of instruments have been developed to assess knowledge and skills in evidence based medicine (EBM), few assess all aspects of EBM - including knowledge, skills attitudes and behaviour - or have been psychometrically evaluated. The aim of this study was to develop and validate an instrument that evaluates medical trainees’ competency in EBM across knowledge, skills and attitude. METHODS: The ‘Assessing Competency in EBM’ (ACE) tool was developed by the authors, with content and face validity assessed by expert opinion. A cross-sectional sample of 342 medical trainees representing ‘novice’, ‘intermediate’ and ‘advanced’ EBM trainees were recruited to complete the ACE tool. Construct validity, item difficulty, internal reliability and item discrimination were analysed. RESULTS: We recruited 98 EBM-novice, 108 EBM-intermediate and 136 EBM-advanced participants. A statistically significant difference in the total ACE score was observed and corresponded to the level of training: on a 0-15-point test, the mean ACE scores were 8.6 for EBM-novice; 9.5 for EBM-intermediate; and 10.4 for EBM-advanced (p < 0.0001). Individual item discrimination was excellent (Item Discrimination Index ranging from 0.37 to 0.84), with internal reliability consistent across all but three items (Item Total Correlations were all positive ranging from 0.14 to 0.20). CONCLUSION: The 15-item ACE tool is a reliable and valid instrument to assess medical trainees’ competency in EBM. The ACE tool provides a novel assessment that measures user performance across the four main steps of EBM. To provide a complete suite of instruments to assess EBM competency across various patient scenarios, future refinement of the ACE instrument should include further scenarios across harm, diagnosis and prognosis

Acute phase reaction to LPS induced mastitis in early lactation dairy cows fed nitrogenic, glucogenic or lipogenic diets.

The availability of certain macronutrients is likely to influence the capacity of the immune system. Therefore, we investigated the acute phase response to intramammary (i.mam.) LPS in dairy cows fed either a nitrogenic diet (n = 10) high in crude protein, a glucogenic diet (n = 11) high in carbohydrates and glucogenic precursors, or a lipogenic diet (n = 11) high in lipids. Thirty-two dairy cows were fed one of the dietary concentrates directly after calving until the end of trial at 27 ± 3 DIM (mean ± SD). In wk 3 of lactation, 20 µg of LPS was i.mam. injected in one quarter, and sterile NaCl (0.9%) in the contralateral quarter. Milk samples of the LPS challenged and control quarter were taken hourly from before (0 h) until 9 h after LPS challenge, and analyzed for milk amyloid A (MAA), haptoglobin (Hp), and IL-8. In addition, blood samples were taken in the morning, and composite milk samples at morning and evening milkings from 1 d before until 3 d after LPS challenge, and again on d 9 to determine serum amyloid A (SAA) and Hp in blood, and MAA and Hp in milk. The mRNA abundance of various immunological and metabolic factors in blood leukocytes was quantified by RT-qPCR from samples taken at -18 h, -1 h, 6 h, 9 h and 23 h relative to LPS application. The dietary concentrates did not affect any of the parameters in blood, milk, and leukocytes. The IL-8 was increased from 2 h, Hp from 2 to 3 h, and MAA from 6 h relative to the LPS administration in the milk of the challenged quarter and remained elevated until 9 h. The MAA and Hp were also increased at 9 h after LPS challenge in whole udder composite milk, whereas Hp and SAA in blood were increased only after 23 h. All 4 parameters were decreased again on d 9. Similar for all groups, the mRNA abundance of Hp and the heat shock protein family A (HSP70) increased after the LPS challenge, while the mRNA expression of the tumor necrosis factor α (TNF) and the leukocyte integrin β 2 subunit (CD18) were decreased at 6 h after LPS challenge. The glucose transporter (GLUT)1 mRNA abundance decreased after LPS, whereas that of the GLUT3 increased, and that of the GLUT4 was not detectable. The mRNA abundance of GAPDH was increased at 9 h after LPS and remained elevated. The APP response was detected earlier in milk compared with blood indicating mammary production. However, immunological responses to LPS were not affected by the availability of specific macronutrients provided by the different diets

Effect of different dietary regimens at dry-off on performance, metabolism, and immune system in dairy cows.

Concentrate withdrawal and feed restriction are commonly used to reduce milk production and to facilitate dry-off, but may impair immune function in dairy cows. We investigated the effect of feed rations providing different amounts of nutrients in combination with feed restriction on performance, endocrine, and metabolic responses, as well as on leukocyte function before and after abrupt dry-off. Forty-three cows were studied from d 12 before until d 6 after dry-off (56 d before scheduled calving). Cows were fed experimental concentrates rich in crude protein (nitrogenic, n = 14), glucogenic precursors (glucogenic, n = 14), or lipids (lipogenic, n = 15). On d 3 before dry-off, total feed allowance was restricted to 50% in half of the animals of each dietary group, whereas feed allowance remained unchanged in the other animals. Performance parameters (milk yield, milk composition, and dry matter intake) were recorded, and daily blood and milk samples were taken and analyzed for various metabolic and endocrine parameters. Additionally, activity and mRNA abundance of several genes in leukocytes were measured at selected time points before and after feed restriction and dry-off, respectively. Feed restriction immediately resulted in a negative energy balance and decreased milk production. Concomitantly, concentrations of nonesterified fatty acids increased, whereas insulin, insulin-like growth factor-1, and glucagon decreased. After dry-off, energy balance turned positive and plasma nonesterified fatty acids decreased. Plasma glucose, insulin, and insulin-like growth factor-1 concentrations increased in all groups after dry-off. Glucose, insulin, and glucagon concentrations in plasma were higher in nonrestricted compared with restricted animals after dry-off. The experimental concentrate types marginally affected the investigated metabolic and endocrine factors, with the exception of elevated milk and plasma urea concentrations in cows fed the nitrogenic concentrate. Chemotactic and phagocytic activity of leukocytes were not affected by diets, feed restriction, or dry-off. Likewise, blood leukocyte mRNA abundance encoding for tumor necrosis factor α (TNF), heat shock protein family A (HSP70), and the glucose transporters (GLUT) 1 and 3 remained unchanged throughout the study period. Overall, the short-term negative energy balance induced by feed restriction was temporarily accompanied by metabolic adaptations, but did not alter the studied factors related to the immune system. Metabolic and endocrine adaptations supporting milk synthesis were continued during the first days after dry-off despite cessation of milking. Thus, the abrupt dry-off resulted in a short-term increase of glucose and triglyceride concentrations, with a delayed endocrine response to re-establish nutrient homeostasis in blood

No association between variation in the NR4A1 gene locus and metabolic traits in white subjects at increased risk for type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>The nuclear receptor NR4A1 is implicated in metabolic regulation in insulin-sensitive tissues, such as liver, adipose tissue, and skeletal muscle. Functional loss of NR4A1 results in insulin resistance and enhanced intramuscular and hepatic lipid content. Therefore, we investigated in a cohort of white European subjects at increased risk for type 2 diabetes whether genetic variation within the <it>NR4A1 </it>gene locus contributes to prediabetic phenotypes, such as insulin resistance, ectopic fat distribution, or β-cell dysfunction.</p> <p>Methods</p> <p>We genotyped 1495 subjects (989 women, 506 men) for five single nucleotide polymorphisms (SNPs) tagging 100% of common variants (MAF = 0.05) within the <it>NR4A1 </it>gene locus with an r²= 0.8. All subjects underwent an oral glucose tolerance test (OGTT), a subset additionally had a hyperinsulinemic-euglycemic clamp (n = 506). Ectopic hepatic (n = 296) and intramyocellular (n = 264) lipids were determined by magnetic resonance spectroscopy. Peak aerobic capacity, a surrogate parameter for oxidative capacity of skeletal muscle, was measured by an incremental exercise test on a motorized treadmill (n = 270).</p> <p>Results</p> <p>After appropriate adjustment and Bonferroni correction for multiple comparisons, none of the five SNPs was reliably associated with insulin sensitivity, ectopic fat distribution, peak aerobic capacity, or indices of insulin secretion (all p ≥ 0.05).</p> <p>Conclusions</p> <p>Our data suggest that common genetic variation within the <it>NR4A1 </it>gene locus may not play a major role in the development of prediabetic phenotypes in our white European population.</p