Análise multivariada do efeito de diferentes densidades de alojamento sobre lesões podais em frangos de corte.

Este trabalho objetivou avaliar a utilização de estatísticas multivariadas para análise de um conjunto de dados com diferentes densidades de alojamento em frangos de corte. Foi conduzido um experimento com duas densidades de alojamento (11,07 e 13,21 aves/m²), e mensuradas variáveis de desempenho, qualidade de cama e incidência de lesões podais. A análise de fatores gerou 3 autovalores que acumularam 80,4% variância total dos dados. O Fator 1 (41,6% da variância) foi o único estatisticamente significativo pela análise de variância, e agrupou todas as variáveis relacionadas com umidade de cama e graus de lesão podal, mostrando haver uma inter-relação entre as mesmas. Estes dois grupos de variáveis foram utilizados na análise de componentes principais. Os dois primeiros componentes principais gerados acumularam 86,5% da variância total dos dados, e sua epresentação gráfica agrupou variáveis de umidade de cama e os graus mais severos de lesão podal com a maior densidade de alojamento. A análise multivariada utilizada foi eficiente no desdobramento das inter-relações entre as variáveis e demonstrou que o aumento da densidade de alojamento foi determinante na maior incidência de lesões por pododermatite e sua relação com a maior umidade da cama. This study aimed to evaluate the use of multivariate statistics to analyze a data set of different animal densities in broiler chickens. Was conducted an experiment with two animal densities (11.07 and 13.21 birds/m²); the variables measured were performance, litter quality and incidence of foot pad dermatitis. Factor analysis generated three eigenvalues which accumulated 80.4% of the total variance. Factor 1 (41.6 % of variance) was the only statistically significant by analysis of variance, and grouped all variables related to litter moisture and degrees of foot pad dermatitis, showing that there is a relationship between them. These two groups of variables wereused in the principal components analysis. The first two principal components generated accumulated 86.5% of the total variance of the data and their graphical representation grouped variables related to litter moisture and the most severe degrees of foot pad dermatitis with the highest density of housing. The multivariate analysis used was efficient in the deployment of inter-relationships between variab les and showed that increased housing density was determinant in the increased incidence of pododermatitis injuries and its relation to higher litter moisture

Molecular interaction of connexin 30.3 and connexin 31 suggests a dominant-negative mechanism associated with erythrokeratodermia variabilis

Connexins are homologous four-transmembrane-domain proteins and major components of gap junctions. We recently identified mutations in either GJB3 or GJB4 genes, encoding respectively connexin 31 (Cx31) or 30.3 (Cx30.3), as causally involved in erythrokeratodermia variabilis (EKV), a mostly autosomal dominant disorder of keratinization. Despite slight differences, phenotypes of EKV Mendes Da Costa (Cx31) and EKV Cram-Mevorah (Cx30.3) show major clinical overlap and both Cx30.3 and Cx31 are expressed in the upper epidermal layers. These similarities suggested to us that Cx30.3 and Cx31 may interact at a molecular level. Indeed, expression of wild-type Cx30.3 in HeLa cell resulted only in minor amounts of protein addressed to the plasma membrane. Mutant Cx30.3 was hardly detectable and disturbed intercellular coupling. In sharp contrast, co-expression of both wild-type proteins led to a gigantic increase of stabilized heteromeric gap junctions. Furthermore, co-expressed wild-type Cx30.3 and Cx31 coprecipitate, which demonstrates a physical interaction. Inhibitor experiments revealed that this interaction begins in the endoplasmic reticulum. These results not only provide new insights into epidermal connexin synthesis and polymerization, but also allow a novel molecular explanation for the similarity of EKV phenotypes

Effect of feed deprivation during the post hatch holding birth time on the performance of broiler chicks from breeders of different age

The present research work hás been carried out in order to evaluate on the post born period of broilers from different broiler breeders age, the effect of feed deprivation between hatching and housing, on feed intake, weight gain, feed conversion and viability up to 42 days old, and weight lost. A total of 480 male chicks were distributed in a randomized factorial design of 3 X 3, with two broiler breeders age (30 and 60 weeks) and three feed deprivation times (0, 24, 48 h post hatching). The broiler breeder age did not affect the chicks lost of weight between hatching and housing, but the feed deprivation time affect this parameter. Chicks from 60-week-old broiler breeders showed greater feed intake 72 hours post hatching. Feed intake and weight gains were influenced by the breeder age 0f 7 and 21 days old, the chick from older breeder siplaying greater feed intake and weight gain. However, at 42 days of age, even if the birds had been subjected to periods of post hatching fasting, they did not display differences on their performance. Chicks from 30-week-old broiler breeders displayed a better feed conversion.Este estudo foi conduzido para avaliar o efeito do jejum entre o nascimento e o alojamento sobre o consumo de ração, ganho de peso, conversão alimentar e viabilidade criatória até 42 dias de idade; perda de peso e consumo de ração no período que suceder ao nascimento, em frangos de corte provenientes de matrizes de diferentes idades. Foram utilizados 480 pintainhos de corte, machos, em um delineamento inteiramente casualizado, em esquema fatorial 2 x 3 com os fatores idades de matriz (30 e 60 semanas) e períodos de jejum (0, 24 e 48 horas pós-eclosão). A idade da matriz não influenciou a perda de peso dos pintainhos entre o nascimento e o alojamento, variável esta afetada apenas pelo período de jejum a qual as aves foram submetidas. Pintainhos oriundos de matizes de 60 semanas de idade consumiram maior quantidade de ração nas 72 horas pós-eclosão. A idade da matriz influenciou também o consumo de ração e o ganho de peso aos 7 e 21dias de idade, sendo que pintainhos oriundos de matrizes mais velhas tiveram maior consumo e ganho de peso. No entanto, aos 42 dias, mesmo que as aves tenham sido submetidas a períodos de jejum pós-natal, não houve diferença no desempenho. Pintainhos oriundos de matrizes de 30 semanas tiveram melhor conversão alimentar nesta idade.

Insulin-degrading enzyme Is a non proteasomal target of carfilzomib and affects the 20S proteasome inhibition by the drug

Carfilzomib is a last generation proteasome inhibitor (PI) with proven clinical efficacy in the treatment of relapsed/refractory multiple myeloma. This drug is considered to be extremely specific in inhibiting the chymotrypsin-like activity of the 20S proteasome, encoded by the β5 subunit, overcoming some bortezomib limitations, the first PI approved for multiple myeloma therapy which is however burdened by a significant toxicity profile, due also to its off-target effects. Here, molecular approaches coupled with molecular docking studies have been used to unveil that the Insulin-Degrading Enzyme, a ubiquitous and highly conserved Zn2+ peptidase, often found to associate with proteasome in cell-based models, is targeted by carfilzomib in vitro. The drug behaves as a modulator of IDE activity, displaying an inhibitory effect over 10-fold lower than for the 20S. Notably, the interaction of IDE with the 20S enhances in vitro the inhibitory power of carfilzomib on proteasome, so that the IDE-20S complex is an even better target of carfilzomib than the 20S alone. Furthermore, IDE gene silencing after delivery of antisense oligonucleotides (siRNA) significantly reduced carfilzomib cytotoxicity in rMC1 cells, a validated model of Muller glia, suggesting that, in cells, the inhibitory activity of this drug on cell proliferation is somewhat linked to IDE and, possibly, also to its interaction with proteasome

Drug discovery for Diamond-Blackfan anemia using reprogrammed hematopoietic progenitors

Diamond-Blackfan anemia (DBA) is a congenital disorder characterized by the failure of erythroid progenitor differentiation, severely curtailing red blood cell production. Because many DBA patients fail to respond to corticosteroid therapy, there is considerable need for therapeutics for this disorder. Identifying therapeutics for DBA requires circumventing the paucity of primary patient blood stem and progenitor cells. To this end, we adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells (iPSCs) from DBA patients. Reprogrammed DBA progenitors recapitulate defects in erythroid differentiation, which were rescued by gene complementation. Unbiased chemical screens identified SMER28, a small-molecule inducer of autophagy, which enhanced erythropoiesis in a range of in vitro and in vivo models of DBA. SMER28 acted through autophagy factor ATG5 to stimulate erythropoiesis and up-regulate expression of globin genes. These findings present an unbiased drug screen for hematological disease using iPSCs and identify autophagy as a therapeutic pathway in DBA.National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant R24-DK092760)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant R24-DK49216)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (Grant U54DK110805)National Heart, Lung, and Blood Institute (Grant UO1-HL100001)National Heart, Lung, and Blood Institute (Grant U01HL134812)National Heart, Lung, and Blood Institute (Grant R01HL04880)National Institutes of Health (U.S.) (Grant R24OD017870-01

Clinical significance of pneumatosis intestinalis - correlation of MDCT-findings with treatment and outcome.

To evaluate the clinical significance of pneumatosis intestinalis (PI) including the influence on treatment and outcome. Two radiologists jointly reviewed MDCT-examinations of 149 consecutive emergency patients (53 women, mean age 64, range 21-95) with PI of the stomach (n = 4), small (n = 68) and/or large bowel (n = 96). PI extension, distribution and possibly associated porto-mesenteric venous gas (PMVG) were correlated with other MDCT-findings, risk factors, clinical management, laboratory, histopathology, final diagnosis and outcome. The most frequent cause of PI was intestinal ischemia (n = 80,53.7 %), followed by infection (n = 18,12.1 %), obstructive (n = 12,8.1 %) and non-obstructive (n = 10,6.7 %) bowel dilatation, unknown aetiologies (n = 8,5.4 %), drugs (n = 8,5.4 %), inflammation (n = 7,4.7 %), and others (n = 6,4 %). Neither PI distribution nor extension significantly correlated with underlying ischemia. Overall mortality was 41.6 % (n = 62), mostly related to intestinal ischemia (p = 0.003). Associated PMVG significantly correlated with underlying ischemia (p = 0.009), as did the anatomical distribution of PMVG (p = 0.015). Decreased mural contrast-enhancement was the only other MDCT-feature significantly associated with ischemia (p p < 0.001). Elevated white blood count significantly correlated with ischemia (p = 0.03). In emergency patients, ischemia remains the most common aetiology of PI, showing the highest mortality. PI with associated PMVG is an alerting sign. PI together with decreased mural contrast-enhancement indicates underlying ischemia. • In emergency patients, PI may be caused by various disorders. • Intestinal ischemia remains the most common cause of PI in acute situations. • PI associated with decreased mural contrast-enhancement indicates acute intestinal ischemia. • PI associated with PMVG should alert the radiologist to possible underlying ischemia