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71.
Marquis-Nicholson R Aftimos S Ashton F Love JM Stone P McFarlane J George AM Love DR 《Gene》2011,486(1-2):37-40
Pseudotrisomy 13 syndrome is characterised by holoprosencephaly with or without polydactyly, but with a normal karyotype. The genetic cause of this syndrome remains unclear, but it is thought to be autosomal recessive. In order to identify possible candidate genes, we identified regions of homozygosity in the DNA of an affected foetus, which was the seventh pregnancy of a healthy non-consanguineous Cook Island Maori couple; this ethnic group derives from a small founder population. Several large regions of homozygosity were identified using a high density array. We excluded two candidate genes that lay within these regions, and suggest that Pseudotrisomy 13 syndrome might not be monogenic and that a larger cohort of patients should be analysed using high density dosage/SNP arrays as well as whole exome sequencing in order to clarify the genetic underpinning of this rare syndrome. 相似文献
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Matthew R. McFarlane Guosheng Liang Luke J. Engelking 《The Journal of biological chemistry》2014,289(4):2148-2156
Enterocytes are the only cell type that must balance the de novo synthesis and absorption of cholesterol, although the coordinate regulation of these processes is not well understood. Our previous studies demonstrated that enterocytes respond to the pharmacological blockade of cholesterol absorption by ramping up de novo sterol synthesis through activation of sterol regulatory element-binding protein-2 (SREBP-2). Here, we genetically disrupt both Insig1 and Insig2 in the intestine, two closely related proteins that are required for the feedback inhibition of SREBP and HMG-CoA reductase (HMGR). This double knock-out was achieved by generating mice with an intestine-specific deletion of Insig1 using Villin-Cre in combination with a germ line deletion of Insig2. Deficiency of both Insigs in enterocytes resulted in constitutive activation of SREBP and HMGR, leading to an 11-fold increase in sterol synthesis in the small intestine and producing lipidosis of the intestinal crypts. The intestine-derived cholesterol accumulated in plasma and liver, leading to secondary feedback inhibition of hepatic SREBP2 activity. Pharmacological blockade of cholesterol absorption was unable to further induce the already elevated activities of SREBP-2 or HMGR in Insig-deficient enterocytes. These studies confirm the essential role of Insig proteins in the sterol homeostasis of enterocytes. 相似文献
75.
Phenological shifts in North American red squirrels: disentangling the roles of phenotypic plasticity and microevolution 下载免费PDF全文
Jeffrey E. Lane Andrew G. McAdam S. Eryn McFarlane Cory T. Williams Murray M. Humphries David W. Coltman Jamieson C. Gorrell Stan Boutin 《Journal of evolutionary biology》2018,31(6):810-821
Phenological shifts are the most widely reported ecological responses to climate change, but the requirements to distinguish their causes (i.e. phenotypic plasticity vs. microevolution) are rarely met. To do so, we analysed almost two decades of parturition data from a wild population of North American red squirrels (Tamiasciurus hudsonicus). Although an observed advance in parturition date during the first decade provided putative support for climate change‐driven microevolution, a closer look revealed a more complex pattern. Parturition date was heritable [h2 = 0.14 (0.07–0.21 (HPD interval)] and under phenotypic selection [β = ?0.14 ± 0.06 (SE)] across the full study duration. However, the early advance reversed in the second decade. Further, selection did not act on the genetic contribution to variation in parturition date, and observed changes in predicted breeding values did not exceed those expected due to genetic drift. Instead, individuals responded plastically to environmental variation, and high food [white spruce (Picea glauca) seed] production in the first decade appears to have produced a plastic advance. In addition, there was little evidence of climate change affecting the advance, as there was neither a significant influence of spring temperature on parturition date or evidence of a change in spring temperatures across the study duration. Heritable traits not responding to selection in accordance with quantitative genetic predictions have long presented a puzzle to evolutionary ecologists. Our results on red squirrels provide empirical support for one potential solution: phenotypic selection arising from an environmental, as opposed to genetic, covariance between the phenotypic trait and annual fitness. 相似文献
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Humans create ecologically simplified landscapes that favour some wildlife species, but not others. Here, we explore the possibility that those species that tolerate or do well in human-modified environments, or 'synanthropic' species, are predominantly the hosts of zoonotic emerging and re-emerging infectious diseases (EIDs). We do this using global wildlife conservation data and wildlife host information extracted from systematically reviewed emerging infectious disease literature. The evidence for this relationship is examined with special emphasis on the Australasian, South East Asian and East Asian regions. We find that synanthropic wildlife hosts are approximately 15 times more likely than other wildlife in this region to be the source of emerging infectious diseases, and this association is essentially independent of the taxonomy of the species. A significant positive association with EIDs is also evident for those wildlife species of low conservation risk. Since the increase and spread of native and introduced species able to adapt to human-induced landscape change is at the expense of those species most vulnerable to habitat loss, our findings suggest a mechanism linking land conversion, global decline in biodiversity and a rise in EIDs of wildlife origin. 相似文献
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Synopsis A total of 3068 female spiny dogfish were examined to determine the age and length at maturity. The median age at maturity for females was 35.5 years with 95% confidence limits between 35.0 and 35.9 years. It was found that slower growing dogfish tended to mature at a smaller size. A deterministic model incorporating fecundity, growth and reproduction was used to examine the reproductive style of spiny dogfish. The age at maturity reported corresponds to the level that theoretically maximizes lifetime reproductive output for a cohort. 相似文献
80.
Mutation of the essential Schizosaccharomyces pombe rad4/cut5 gene causes sensitivity to UV and ionising radiation at the permissive temperature whilst at the restrictive temperature
cells fail to undergo DNA replication but still attempt mitosis owing to a defective S-phase checkpoint response. Many mutations
in genes encoding DNA replication proteins also abolish checkpoint responses, possibly because the replication machinery is
a pre-requisite for the generation of the signal. We demonstrate here that rad4/cut5 cells fail to arrest cell division when treated with the replication inhibitor hydroxyurea at the semi-permissive temperature
32° C, but retain essentially normal replicative capacity. This demonstrates that the replication and checkpoint function
of the rad4/cut5 gene product can be separated and that the Rad4 protein differs from other replication proteins in being directly involved
in generating the S-phase checkpoint signal. Furthermore, we have investigated the checkpoint response or rad4/cut5-deficient cells to γ-irradiation and UV-mimetic drugs. We find that, at the restrictive temperature, the rad4
−
/cut5
−
cells fail to delay mitosis in response to γ-irradiation whilst retaining a normal checkpoint response to the UV-mimetic drug
4-nitroquinoline-1-oxide. The lack of the γ-irradiation checkpoint is reminiscent of the deficiency associated with mutation
of the human ATM locus, the causative deficiency of the heritable disorder ataxia telangiectasia. The implications of our results for the
organisation of distinct checkpoint-response pathways in both fission yeast and mammalian cells are discussed. Moreover the
data are consistent with a model in which the generation of the S-Phase checkpoint signal is DNA polymerase ɛ dependent.
Received: 29 October 1996 / Accepted: 14 January 1997 相似文献