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51.
Levy D Ronemus M Yamrom B Lee YH Leotta A Kendall J Marks S Lakshmi B Pai D Ye K Buja A Krieger A Yoon S Troge J Rodgers L Iossifov I Wigler M 《Neuron》2011,70(5):886-897
To explore the genetic contribution to autistic spectrum disorders (ASDs), we have studied genomic copy-number variation in a large cohort of families with a single affected child and at least one unaffected sibling. We confirm a major contribution from de novo deletions and duplications but also find evidence of a role for inherited "ultrarare" duplications. Our results show that, relative to males, females have greater resistance to autism from genetic causes, which raises the question of the fate of female carriers. By analysis of the proportion and number of recurrent loci, we set a lower bound for distinct target loci at several hundred. We find many new candidate regions, adding substantially to the list of potential gene targets, and confirm several loci previously observed. The functions of the genes in the regions of de novo variation point to a great diversity of genetic causes but also suggest functional convergence. 相似文献
52.
Aïssata Moussa Abba Maria De Koninck Anne-Marie Hamelin 《International breastfeeding journal》2010,5(1):1-7
Infant feeding by HIV-infected mothers has been a major global public health dilemma and a highly controversial matter. The controversy is reflected in the different sets of WHO infant feeding guidelines that have been issued over the last two decades. This thematic series, 'Infant feeding and HIV: lessons learnt and ways ahead' highlights the multiple challenges that HIV-infected women, infant feeding counsellors and health systems have encountered trying to translate and implement the shifting infant feeding recommendations in different local contexts in sub-Saharan Africa. As a background for the papers making up the series, this editorial reviews the changes in the guidelines in view of the roll out of prevention of mother to child transmission (PMTCT) programmes in sub-Saharan Africa between 2001 and 2010. 相似文献
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54.
Administration of several doses of MIF-I or alpha-MSH did not modify colonic temperature or the level of motor activity of rats in ambient temperatures of 4 degree or 20 degrees C. However, the thermoregulatory but not motor effects of the interaction between MIF-I or alpha-MSH with d-amphetamine were dependent upon ambient temperature. At 4 degree C, 1.0 mg/kg of both peptides enhanced the d-amphetamine-induced hypothermia, but at 20 degrees C both peptides blocked the hyperthermic effects of d-amphetamine. The hypothermic effect of chlorpromazine (CPZ) at 4 degree C and 20 degrees C was blocked by 1.0 mg/kg MIF-I but not by 1.0 mg/kg alpha-MSH. No linear dose response relationships between various doses of MIF-I or alpha-MSH and thermal responses were found. Administration of melanin or the use of hypophysectomized rats did not alter the significant interactions observed after peripheral injections. 相似文献
55.
Regina Cencic Hisashi Miura Abba Malina Francis Robert Sylvain Ethier T. Martin Schmeing Josée Dostie Jerry Pelletier 《PloS one》2014,9(10)
The clustered regularly interspaced short palindromic repeat (CRISPR)-associated enzyme Cas9 is an RNA-guided nuclease that has been widely adapted for genome editing in eukaryotic cells. However, the in vivo target specificity of Cas9 is poorly understood and most studies rely on in silico predictions to define the potential off-target editing spectrum. Using chromatin immunoprecipitation followed by sequencing (ChIP-seq), we delineate the genome-wide binding panorama of catalytically inactive Cas9 directed by two different single guide (sg) RNAs targeting the Trp53 locus. Cas9:sgRNA complexes are able to load onto multiple sites with short seed regions adjacent to 5′NGG3′ protospacer adjacent motifs (PAM). Yet among 43 ChIP-seq sites harboring seed regions analyzed for mutational status, we find editing only at the intended on-target locus and one off-target site. In vitro analysis of target site recognition revealed that interactions between the 5′ end of the guide and PAM-distal target sequences are necessary to efficiently engage Cas9 nucleolytic activity, providing an explanation for why off-target editing is significantly lower than expected from ChIP-seq data. 相似文献
56.
WWOX was cloned as a putative tumor suppressor gene mapping to chromosomal fragile site FRA16D. Deletions affecting WWOX accompanied by loss of expression are frequent in various epithelial cancers. Translocations and deletions affecting WWOX are also common in multiple myeloma and are associated with worse prognosis. Metanalysis of gene expression datasets demonstrates that low WWOX expression is significantly associated with shorter relapse-free survival in ovarian and breast cancer patients. Although somatic mutations affecting WWOX are not frequent, analysis of TCGA tumor datasets led to identifying 44 novel mutations in various tumor types. The highest frequencies of mutations were found in head and neck cancers and uterine and gastric adenocarcinomas. 相似文献
57.
Weihong Pan Chuanhui Yu Hung Hsuchou Reas S. Khan Abba J. Kastin 《Journal of neurochemistry》2009,111(3):819-827
The blood-brain barrier is a gatekeeper and modulatory interface for the CNS. Cerebral endothelial cells are the major component of the blood-brain barrier, and they modify inflammatory signals from the circulation to the CNS by production and secretion of secondary substances. The inflammatory mediators induced by tumor necrosis factor α (TNF) were determined by microarray analysis of RBE4 cerebral endothelial cells, at 0, 6, 12, or 24 h after TNF treatment. Interleukin (IL)-15 and its receptors were among the most robustly up-regulated genes. This was confirmed by real-time RT-PCR and western blotting. The three subunits of the IL15 receptor complex (IL15Rα, IL2Rβ, and IL2Rγ) showed differential regulation by TNF in their time course and amplitude of increased expression. Consistent with increased expression of the specific high affinity receptor IL15Rα, TNF increased cellular uptake of 125 I-IL15 and enhanced the fluorescent intensity of Alexa568-IL15 in RBE4 cells. TNF treatment in mice also increased the level of expression of IL15 receptors in enriched cerebral microvessels. We conclude that the cerebral microvascular IL15 system is a novel inflammatory mediator that transduces the actions of TNF. 相似文献
58.
We propose a dynamic allocation procedure that increases power and efficiency when measuring an average treatment effect in sequential randomized trials exploiting some subjects' previous assessed responses. Subjects arrive sequentially and are either randomized or paired to a previously randomized subject and administered the alternate treatment. The pairing is made via a dynamic matching criterion that iteratively learns which specific covariates are important to the response. We develop estimators for the average treatment effect as well as an exact test. We illustrate our method's increase in efficiency and power over other allocation procedures in both simulated scenarios and a clinical trial dataset. An R package “SeqExpMatch ” for use by practitioners is available on CRAN . 相似文献
59.
International trade in endangered species: the challenges and successes of the 17th conference of parties to the convention on international trade in endangered species of wild fauna and flora (CITES) 下载免费PDF全文
60.
Morpho-physiological specialization related to foraging can act as constraints on behaviour and ecological patterns of abundance
and distribution. We tested this prediction in two species (weeping or screaming hairy armadillos Chaetophractus vellerosus Gray, 1865 and mulitas Dasypus hybridus Desmarest, 1804) that represent the two subfamilies of armadillos (Dasypodidae, Xenarthra): Euphractinae and Dasypodinae.
The first subfamily possesses a well-developed masticatory apparatus that is considered primitive within the Xenarthra, while
Dasypodinae show reductions in various aspects of cranial morphology. We sampled signs (burrows and foraging holes) and captured
both species on 34 farms randomly selected in the north-eastern Pampas region of Argentina. We analyzed several niche dimensions.
The two species showed significant differences in habitat use, seasonal patterns and diet. Weeping armadillos were generalists
in their diet and active throughout the year. They were associated with calcareous-sand soil, as expected for a burrowing
animal of the deserts. They tolerated a wide range of environmental conditions. We found that mulitas are myrmecophagous,
and that they demonstrated a reduction in body temperature and activity during the cold season. As expected from their geographical
distribution, mulitas used mainly vegetation with high cover and were associated with humic soils. Niche segregation between
the two species of armadillos appeared to originate from different degrees of dietary specialization. 相似文献