Extreme skewing of X-chromosome inactivation (XCI) is rare in the normal female population but is observed frequently in carriers of some X-linked mutations. Recently, it has been shown that various forms of X-linked mental retardation (XLMR) have a strong association with skewed XCI in female carriers, but the mechanisms underlying this skewing are unknown. ATR-X syndrome, caused by mutations in a ubiquitously expressed, chromatin-associated protein, provides a clear example of XLMR in which phenotypically normal female carriers virtually all have highly skewed XCI biased against the X chromosome that harbors the mutant allele. Here, we have used a mouse model to understand the processes causing skewed XCI. In female mice heterozygous for a null Atrx allele, we found that XCI is balanced early in embryogenesis but becomes skewed over the course of development, because of selection favoring cells expressing the wild-type Atrx allele. Unexpectedly, selection does not appear to be the result of general cellular-viability defects in Atrx-deficient cells, since it is restricted to specific stages of development and is not ongoing throughout the life of the animal. Instead, there is evidence that selection results from independent tissue-specific effects. This illustrates an important mechanism by which skewed XCI may occur in carriers of XLMR and provides insight into the normal role of ATRX in regulating cell fate. 相似文献
Diarrhoea is a common problem in dogs and can result in disturbance of the normal intestinal microbiota. However, little is known about the gastrointestinal microbiota of dogs with chronic diarrhoea and controlled canine studies of dietary management are scarce. The aims of this study were to investigate the predominant faecal microbiota of chronic diarrhoea dogs and to examine the effect(s) of a fibre blend on the canine faecal microbiota. A 3-week fibre supplementation feeding study was performed in nine chronic diarrhoea and eight control dogs. Atopobium cluster, Lactobacillus–Enterococcus group and Clostridium cluster XIV were the predominant bacterial groups in all dogs. Chronic diarrhoea dogs had significantly higher Bacteroides counts at baseline and significantly lower Atopobium cluster counts following fibre supplementation compared with control dogs. Atopobium cluster levels increased significantly in control dogs, while counts of sulphate-reducing bacteria decreased significantly and Clostridium clusters I and II counts increased significantly in chronic diarrhoea dogs during fibre supplementation. Microbial profiles (detected by denaturing gradient gel electrophoresis) demonstrated interindividual variation, with greater similarity seen between the chronic diarrhoea and control dogs' profiles after fibre supplementation compared with baseline. In conclusion, fibre supplementation induced changes in the canine faecal microbiota, with greater resemblance between the microbiota of chronic diarrhoea and control dogs after this dietary modulation. 相似文献
Ankistromeces Nolan & Cribb, 2004 and Phthinomita Nolan & Cribb, 2006 are sister genera of threadlike blood flukes (Trematoda: Aporocotylidae) infecting teleost fishes of the tropical Indo-west Pacific. Here, we report new collections of these genera from Australia, Indonesia, and Japan. A new species of Ankistromeces, Ankistromeces kawamurain. sp., is described from Siganus spinus (Linnaeus) off Okinawa, Japan, and a new species of Phthinomita, Phthinomita abdita n. sp., from Choerodon cephalotes (Castelnau), in Moreton Bay, Australia; the new species are morphologically cryptic within their respective genera and are delineated by molecular and ecological data. Ankistromeces olsoni Nolan & Cribb, 2006 is reported from Siganus fuscescens (Houttuyn) off Heron Island (southern Great Barrier Reef), Lizard Island (northern Great Barrier Reef), and Okinawa and Wakayama Prefectures, Japan and from Siganus spinus (Linnaeus) from off Bali, Indonesia. Ankistromeces mariae Nolan & Cribb, 2004 is re-reported from the type-host, Meuschenia freycineti (Quoy & Gaimard), from a new location, Gypsy Bay, Tasmania. Phthinomita poulini Nolan & Cribb, 2006 is re-reported from its type-locality, Lizard Island, from a range of mullids, including five new host species, and its range is extended to include Moreton Bay. Phthinomita symplocos Nolan & Cribb, 2006 is reported from Bali and P. hallae Nolan & Cribb, 2006, P. jonesi Nolan & Cribb, 2006, P. littlewoodi Nolan & Cribb, 2006, and P. munozae Nolan & Cribb, 2006 are each re-reported from their type-host and type-localities. New cox1 mtDNA data were generated for all known species of these two genera from new and archival material. Analyses of these data enabled an evaluation of all known Phthinomita species; P. robertsthomsoni Nolan & Cribb, 2006 is synonymised with P. adlardi Nolan & Cribb, 2006, and P. brooksi Nolan & Cribb, 2006 is synonymised with P. sasali Nolan & Cribb, 2006. We highlight the failure of ITS2 data to delineate closely related aporocotylid species. In contrast, cox1 sequence data are proving reliable and effective in this context and we recommend their incorporation in future studies of blood fluke taxonomy.
Necrotizing enterocolitis (NEC) is one of the most severe and unpredictable complications of prematurity. There are two possible mechanisms involved in the pathogenesis of NEC: individual inflammatory response and impaired blood flow in mesenteric vessels with secondary ischemia of the intestine. The aim of this study was to evaluate the possible relationship between polymorphisms: Il-1β 3953C>T, Il-6 ?174G>C and ?596G>A, TNFα ?308G>A, and 86 bp variable number tandem repeat polymorphism of interleukin-1 receptor antagonist (Il-1RN VNTR 86 bp) and three polymorphisms that may participate in arteries tension regulation and in consequence in intestine blood flow impairment: eNOS (894G>T and ?786T>C) and END-1 (5665G>T) and NEC in 100 infants born from singleton pregnancy, before 32 + 0 weeks of gestation, exposed to antenatal steroids therapy, and without congenital abnormalities. In study population, 22 (22%) newborns developed NEC. Surgery-requiring NEC was present in 7 children. Statistical analysis showed 20-fold higher prevalence of NEC in infants with the genotype TT [OR 20 (3.71–208.7); p = 0.0004] of eNOS 894G>T gene polymorphism. There was a higher prevalence of allele C carriers of eNOS 786T>C in patients with surgery-requiring NEC [OR 4.881 (1.33–21.99); p = 0.013]. Our investigation did not confirm any significant prevalence for NEC development in another studied genotypes/alleles. This study confirms the significant role of polymorphisms that play role in intestine blood flow. Identifying gene variants that increase the risk for NEC development may be useful in screening infants with inherent vulnerability and creating strategies for individualized care. 相似文献
Mahella australiensis Bonilla Salinas et al. 2004 is the type species of the genus Mahella, which belongs to the family Thermoanaerobacteraceae. The species is of interest because it differs from other known anaerobic spore-forming bacteria in its G+C content, and in certain phenotypic traits, such as carbon source utilization and relationship to temperature. Moreover, it has been discussed that this species might be an indigenous member of petroleum and oil reservoirs. This is the first completed genome sequence of a member of the genus Mahella and the ninth completed type strain genome sequence from the family Thermoanaerobacteraceae. The 3,135,972 bp long genome with its 2,974 protein-coding and 59 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献
Prevotella multisaccharivorax Sakamoto et al. 2005 is a species of the large genus Prevotella, which belongs to the family Prevotellaceae. The species is of medical interest because its members are able to cause diseases in the human oral cavity such as periodontitis, root caries and others. Although 77 Prevotella genomes have already been sequenced or are targeted for sequencing, this is only the second completed genome sequence of a type strain of a species within the genus Prevotella to be published. The 3,388,644 bp long genome is assembled in three non-contiguous contigs, harbors 2,876 protein-coding and 75 RNA genes and is a part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献
Random vascular patterned caudally based McFarlane-type skin flaps were elevated in groups of Fischer 344 rats. Groups of rats were then acutely exposed on an intermittent basis to smoke generated from well-characterized research filter cigarettes. Previously developed smoke inhalation exposure protocols were employed using a Maddox-ORNL inhalation exposure system. Rats that continued smoke exposure following surgery showed a significantly greater mean percent area of flap necrosis compared with sham-exposed groups or control groups not exposed. The possible pathogenesis of this observation as well as considerations and correlations with chronic human smokers are discussed. Increased risks of flap necrosis by smoking in the perioperative period are suggested by this study. 相似文献
Protein-glycan recognition is often mediated by multivalent binding. These multivalent bindings can be further complicated by cooperative interactions between glycans and individual glycan binding subunits. Here we have demonstrated a nanocube-based lipid bilayer array capable of quantitatively elucidating binding dissociation constants, maximum binding capacity, and binding cooperativity in a high-throughput format. Taking cholera toxin B subunit (CTB) as a model cooperativity system, we studied both GM1 and GM1-like gangliosides binding to CTB. We confirmed the previously observed CTB-GM1 positive cooperativity. Surprisingly, we demonstrated fucosyl-GM1 has approximately 7 times higher CTB binding capacity than GM1. In order to explain this phenomenon, we hypothesized that the reduced binding cooperativity of fucosyl-GM1 caused the increased binding capacity. This was unintuitive, as GM1 exhibited higher binding avidity (16 times lower dissociation constant). We confirmed the hypothesis using a theoretical stepwise binding model of CTB. Moreover, by taking a mixture of fucosyl-GM1 and GM2, we observed the mild binding avidity fucosyl-GM1 activated GM2 receptors enhancing the binding capacity of the lipid bilayer surface. This was unexpected as GM2 receptors have negligible binding avidity in pure GM2 bilayers. These unexpected discoveries demonstrate the importance of binding cooperativity in multivalent binding mechanisms. Thus, quantitative analysis of multivalent protein-glycan interactions in heterogeneous glycan systems is of critical importance. Our user-friendly, robust, and high-throughput nanocube-based lipid bilayer array offers an attractive method for dissecting these complex mechanisms. 相似文献