Chromosomal localization of the large subunit of mouse replication factor C in the mouse and human

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47015/1/335_2004_Article_BF00350900.pd

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Delayed Hair Follicle Morphogenesis and Hair Follicle Dystrophy in a Lipoatrophy Mouse Model of Pparg Total Deletion.

PPARγ regulates multiple aspects of skin physiology, including sebocyte differentiation, keratinocyte proliferation, epithelial stem cell survival, adipocyte biology, and inflammatory skin responses. However, the effects of its global deletion, namely of nonredundant key functions of PPARγ signaling in mammalian skin, are yet unknown because of embryonic lethality. Here, we describe the skin and hair phenotype of a whole-body PPARγ-null mouse (Pparg &lt;sup&gt;Δ/Δ&lt;/sup&gt; ), obtained by preserving PPARγ expression in the placenta. Pparg &lt;sup&gt;Δ/Δ&lt;/sup&gt; mice exhibited total lipoatrophy and complete absence of sebaceous glands. Right after birth, hair follicle (HF) morphogenesis was transiently delayed, along with reduced expression of HF differentiation markers and of transcriptional regulators necessary for HF development. Later, adult Pparg &lt;sup&gt;Δ/Δ&lt;/sup&gt; mice developed scarring alopecia and severe perifollicular inflammation. Skin analyses in other models of lipodystrophy, AZIP &lt;sup&gt;tg/+&lt;/sup&gt; and Adipoq-Cre &lt;sup&gt;tg/+&lt;/sup&gt; Pparg &lt;sup&gt;fl/fl&lt;/sup&gt; mice, coupled with skin graft experiments, showed that the early defects observed in hair morphogenesis were caused by the absence of adipose tissue. In contrast, the late alteration of HF cycle and appearance of inflammation were observed only in Pparg &lt;sup&gt;Δ/Δ&lt;/sup&gt; mice and likely were due to the lack sebaceous glands. Our findings underscore the increasing appreciation for the importance of adipose tissue-mediated signals in HF development and function

Efeitos da Heterogeneidade de Variância Residual entre Grupos de Contemporâneos na Avaliação Genética de Bovinos de Corte Effects of Heterogeneity of Residual Variance among Contemporary Groups on Genetic Evaluation of Beef Cattle

O objetivo deste estudo foi investigar, por meio de dados simulados, o efeito da heterogeneidade de variância residual entre grupos de contemporâneos (GC) sobre as avaliações genéticas de bovinos de corte, e comparar o uso de uma avaliação genética ponderada (R<FONT FACE=Symbol>&sup1;</FONT>Isigmae²) em relação à avaliação que pressupõe homogeneidade de variância (R=Isigmae²). A característica estudada foi ganho de peso pós-desmame corrigido para 345 dias, sendo esta simulada com variância fenotípica de 300 kg² e herdabilidade igual a 0,4. A estrutura de um conjunto real de dados foi utilizada para fornecer os GC e os pais referentes às observações de cada animal. Cinco níveis de heterogeneidade de variância residual foram considerados de forma que os componentes de variância fossem, na média, iguais aos da situação de homogeneidade de variância. Na medida em que níveis mais acentuados de heterogeneidade de variância residual foram considerados, os animais foram selecionados dos GC com maior variabilidade, especialmente com pressão de seleção intensa. Em relação à consistência de predição, os produtos e as vacas tiveram seus valores genéticos preditos mais afetados pela heterogeneidade de variância residual do que os touros. O fator de ponderação utilizado reduziu, mas não eliminou o efeito da heterogeneidade de variância. As avaliações genéticas ponderadas apresentaram resultados iguais ou superiores àqueles obtidos pelas avaliações que assumiram homogeneidade de variância. Mesmo quando não necessário, o uso de avaliações ponderadas produziu resultados não inferiores às avaliações que assumiram homogeneidade de variância.<br>The objective of this study was to investigate, via simulated data, the effect of heterogeneity of residual variance among contemporary groups (CG) on genetic evaluation of beef cattle, and to compare a weighted genetic evaluation procedure (R<FONT FACE=Symbol>&sup1;</FONT>Isigmae²) with one that assumes homogeneity of variances (R = Isigmae²). Different data sets of postweaning weight gain, adjusted to 345 days, were simulated with and without heterogeneity of residual variance, using a phenotypic variance of 300 kg² and a true heritability of 0.4. A real data set was used to provide the CG and parents related to each animal observation. Results showed that, when high levels of heterogeneity of residual variance were considered, animals were selected from CG with higher variability, especially with intense selection. With respect to prediction consistency, non parent animals and cows had their predicted breeding values more affected by heterogeneity of residual variance than sires. The weighed factor used reduced, but did not eliminate, the effect of heterogeneity of residual variance. The results of weighted genetic evaluations were similar or superior to those from evaluations that assumed homogeneity of variances. Even when the variances were homogeneous, the weighed genetic evaluations yielded results that were not inferior than those from the usual evaluations, which assumed homogeneity of variances

Ajustamento para heterogeneidade de variâncias para produção de leite e gordura entre rebanhos da raça Pardo-Suíça no Brasil Adjustment for heterogeneity of variance for milk and fat yield among herds of Brown Swiss in Brazil

Para verificar o efeito da inclusão das interações reprodutor x rebanho e reprodutor x rebanho-ano como fator de ajustamento da heterogeneidade de variância, registros de produção de leite e gordura foram estratificados, com base no desvio-padrão fenotípico da produção de leite ajustada, em duas classes: baixo (<1.280kg) e alto (>1.280kg) desvio-padrão. Três modelos foram utilizados, sem e com interação reprodutor x rebanho e reprodutor x rebanho-ano, em análises de característica única, geral e em cada classe de desvio-padrão. Médias e componentes de variâncias foram maiores na classe de alto desvio-padrão. Na classe de baixo desvio-padrão, a herdabilidade não se alterou com a inclusão dos efeitos de interação no modelo, sendo de 0,34 para produção de leite e de 0,32 para produção de gordura. Na classe de alto desvio-padrão, as herdabilidades foram: 0,37, 0,35 e 0,36, e de 0,35, 0,32 e 0,35, para produção de leite e gordura, nos modelos sem, com interação reprodutor x rebanho e com interação reprodutor x rebanho-ano, respectivamente. A inclusão do efeito de interação reprodutor x rebanho nos modelos foi significativa (P<0,01) para produção de gordura, em análise geral e na classe de alto desvio-padrão, pelo teste da razão de verossimilhança.<br>In order to verify the effect of including the interactions of sire x herd and the sire x herd-year, as a adjust factor of the variance heterogeneity, registers of milk and fat yields were classified into two classes of standard deviation: low (<1.280kg) and high (>1.280kg), based on phenotypic standard deviation of the milk production adjusted. Three models, without and with interaction of sire x herd and sire x herd-year, were used in the general univariate analyses and in each standard deviation class. Averages and variance components were higher in the high standard deviation. In the class of low standard deviation, heritability didn't alter with the inclusion of the interaction effects in the model, being of 0.34 for milk yield and 0.32 for fat yield. In the class of high standard deviation, heritabilities were: 0.37, 0.35 and 0.36, and of 0.35, 0.32 and 0.35, for milk and fat yield, in the models without and with interaction of sire x herd and with interaction of sire x herd-year, respectively. The inclusion of the interaction of sire x herd was significant (P<0.01) for fat yield, in general analyses and in the high standard deviation class, in the likelihood ratio test