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排序方式: 共有432条查询结果,搜索用时 109 毫秒
71.
Enpeng Zhao Mark P. Keller Mary E. Rabaglia Angie T. Oler Donnie S. Stapleton Kathryn L. Schueler Elias Chaibub Neto Jee Young Moon Ping Wang I-Ming Wang Pek Yee Lum Irena Ivanovska Michele Cleary Danielle Greenawalt John Tsang Youn Jeong Choi Robert Kleinhanz Jin Shang Yun-Ping Zhou Andrew D. Howard Bei B. Zhang Christina Kendziorski Nancy A. Thornberry Brian S. Yandell Eric E. Schadt Alan D. Attie 《Mammalian genome》2009,20(8):476-485
Type 2 diabetes results from severe insulin resistance coupled with a failure of β cells to compensate by secreting sufficient insulin. Multiple genetic loci are involved in the development of diabetes, although the effect of each gene on diabetes susceptibility is thought to be small. MicroRNAs (miRNAs) are noncoding 19–22-nucleotide RNA molecules that potentially regulate the expression of thousands of genes. To understand the relationship between miRNA regulation and obesity-induced diabetes, we quantitatively profiled approximately 220 miRNAs in pancreatic islets, adipose tissue, and liver from diabetes-resistant (B6) and diabetes-susceptible (BTBR) mice. More than half of the miRNAs profiled were expressed in all three tissues, with many miRNAs in each tissue showing significant changes in response to genetic obesity. Furthermore, several miRNAs in each tissue were differentially responsive to obesity in B6 versus BTBR mice, suggesting that they may be involved in the pathogenesis of diabetes. In liver there were approximately 40 miRNAs that were downregulated in response to obesity in B6 but not BTBR mice, indicating that genetic differences between the mouse strains play a critical role in miRNA regulation. In order to elucidate the genetic architecture of hepatic miRNA expression, we measured the expression of miRNAs in genetically obese F2 mice. Approximately 10% of the miRNAs measured showed significant linkage (miR-eQTLs), identifying loci that control miRNA abundance. Understanding the influence that obesity and genetics exert on the regulation of miRNA expression will reveal the role miRNAs play in the context of obesity-induced type 2 diabetes. 相似文献
72.
Grainne P. Cleary Leigh A.L. Corner James OKeeffe Nicola M. Marples 《Mammalian Biology》2009,74(6):438-447
The diet of the Eurasian badger (Meles meles) in the Republic of Ireland was studied by examination of the stomach contents of 686 badgers, collected between March 2005 and September 2006. It was found that the relative importance of different food types, as indicated by their frequency of occurrence and ingested bulk in the diet, fluctuated seasonally. Tipulid larvae (Cl. Insecta, Ord. Tipulidae) dominated the diet in spring; Anura (Cl. Amphibia) and Aculeata (Ord. Hymenoptera) during the summer; and Noctuid larvae (Cl. Insecta, Ord. Noctuidae) in autumn and winter. Thus this type of foraging behaviour supports the contention that badgers are generalist foragers with seasonal food preferences. This feeding behaviour is more similar to that of badgers in Italy and Spain than to badgers in England. 相似文献
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We investigated the short‐term impact of disturbance on genetic diversity and structure of the tropical butterfly Drupadia theda Felder (Lepidoptera: Lycaenidae). Populations were sampled from five landscapes in East Kalimantan (Borneo, Indonesia) which were differentially disturbed by selective logging and the 1997/1998 El Niño Southern Oscillation (ENSO)‐induced drought and fires. Sampling occurred before (in 1997) and after the forest fires (in 1998, 1999, 2000, and 2004). Drupadia theda populations underwent serious population size reductions following the 1997/1998 ENSO event. For a total of 208 individuals, we sequenced a 509‐bp segment of mtDNA containing the control region plus the 5’ end of the 12S rDNA gene. Haplotype diversity in D. theda populations ranged from 0.468 to 0.953. Just after the 1997/1998 ENSO event, number of recorded individuals and genetic diversity were very low in D. theda populations sampled in the two severely burned areas and in a small pristine forest fragment that was surrounded by burned forest and thereby affected by drought. Interestingly, higher levels of genetic diversity were observed in logged forest compared to proximate pristine forest. After 1998, the genetic composition within the three ENSO‐disturbed areas diverged. In the twice‐burned forest, the genetic diversity in 1999 already approached pre‐fire levels, while it remained nearly unchanged in proximate once‐burned forest. Our data suggest that the 1997/1998 ENSO‐induced drought and fires caused massive reductions in the genetic diversity of D. theda and that population recoveries were linked to their geographical position relative to patches of unburned forest (and thus to source populations). 相似文献
76.
Ana R. M. Polónia Daniel F. R. Cleary Leticia N. Duarte Nicole J. de Voogd Newton C. M Gomes 《Microbial ecology》2014,67(3):553-567
Coral reefs are among the most diverse and productive ecosystems in the world. Most research has, however, focused on eukaryotes such as corals and fishes. Recently, there has been increasing interest in the composition of prokaryotes, particularly those inhabiting corals and sponges, but these have mainly focused on bacteria. There have been very few studies of coral reef Archaea, despite the fact that Archaea have been shown to play crucial roles in nutrient dynamics, including nitrification and methanogenesis, of oligotrophic environments such as coral reefs. Here, we present the first study to assess Archaea in four different coral reef biotopes (seawater, sediment, and two sponge species, Stylissa massa and Xestospongia testudinaria). The archaeal community of both sponge species and sediment was dominated by Crenarchaeota, while the seawater community was dominated by Euryarchaeota. The biotope explained more than 72 % of the variation in archaeal composition. The number of operational taxonomic units (OTUs) was highest in sediment and seawater biotopes and substantially lower in both sponge hosts. No “sponge-specific” archaeal OTUs were found, i.e., OTUs found in both sponge species but absent from nonhost biotopes. Despite both sponge species hosting phylogenetically distinct microbial assemblages, there were only minor differences in Kyoto Encyclopedia of Genes and Genomes (KEGG) functional pathways. In contrast, most functional pathways differed significantly between microbiomes from sponges and nonhost biotopes including all energy metabolic pathways. With the exception of the methane and nitrogen metabolic pathway, all energy metabolic pathways were enriched in sponges when compared to nonhost biotopes. 相似文献
77.
O'Nuallain B Klyubin I Mc Donald JM Foster JS Welzel A Barry A Dykoski RK Cleary JP Gebbink MF Rowan MJ Walsh DM 《Journal of neurochemistry》2011,119(1):189-201
Diverse lines of evidence indicate that pre-fibrillar, diffusible assemblies of the amyloid β-protein (Aβ) play an important role in Alzheimer's disease pathogenesis. Although the precise molecular identity of these soluble toxins remains unsettled, recent experiments suggest that sodium dodecyl sulfate (SDS)-stable Aβ dimers may be the basic building blocks of Alzheimer's disease-associated synaptotoxic assemblies and as such present an attractive target for therapeutic intervention. In the absence of sufficient amounts of highly pure cerebral Aβ dimers, we have used synthetic disulfide cross-linked dimers (free of Aβ monomer or fibrils) to generate conformation-specific monoclonal antibodies. These dimers aggregate to form kinetically trapped protofibrils, but do not readily form fibrils. We identified two antibodies, 3C6 and 4B5, which preferentially bind assemblies formed from covalent Aβ dimers, but do not bind to Aβ monomer, amyloid precursor protein, or aggregates formed by other amyloidogenic proteins. Monoclonal antibody 3C6, but not an IgM isotype-matched control antibody, ameliorated the plasticity-disrupting effects of Aβ extracted from the aqueous phase of Alzheimer's disease brain, thus suggesting that 3C6 targets pathogenically relevant Aβ assemblies. These data prove the usefulness of covalent dimers and their assemblies as immunogens and recommend further investigation of the therapeutic and diagnostic utility of monoclonal antibodies raised to such assemblies. 相似文献
78.
Wolvekamp MC Cleary ML Cox SL Shaw JM Jenkin G Trounson AO 《Animal reproduction science》2001,65(1-2):135-147
The Northern Hairy-nosed Wombat (Lasiorhinus krefftii) is a highly endangered marsupial species and every possible option for sustaining the species needs to be explored. One important approach may be the development of assisted reproductive technologies in the non-endangered Common Wombat (Vombatus ursinus) and Southern Hairy-nosed Wombat (Lasiorhinus latifrons) for application in breeding the Northern Hairy-nosed Wombat.In this study, it was examined whether cryopreserved Wombat ovarian tissue would develop following xenografting to immunologically deficient rats. Ovarian tissue was collected from Common Wombats (n = 3) and cryopreserved as small cortical pieces. After thawing the cortical pieces were grafted underneath the kidney capsule of Nude rats (n = 16). The grafts were recovered at 2, 4, and 10 weeks after transplantation and their gross and histological appearance investigated. Two weeks after grafting (n = 2), the tissue was revascularized and healthy primordial follicles were present. At week 4 (n = 2), some follicular development was present. At week 10, six rats received human chorionic gonadotrophin (hCG) to trigger follicle and oocyte maturation while another six rats were not given any treatment. The administration of hCG did not induce preovulatory follicles and oocyte maturation although type 5 follicles were present in ovarian tissue collected 10 weeks posttransplantation in both treated and untreated groups. This study demonstrates for the first time that Wombat ovarian tissue can survive and function when grafted into immunocompromized rats and that Wombat ovarian follicles can be recruited to growth and development in an ovarian xenograft. This model system has the potential to produce mature oocytes from endangered species for use in assisted reproductive technologies such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and mature oocytes from non-endangered species for nuclear transfer which may be necessary for the preservation of critically endangered species. 相似文献
79.
Ruping Wang Rachel A. Cleary Tao Wang Jia Li Dale D. Tang 《The Journal of biological chemistry》2014,289(20):14157-14169
Profilin-1 (Pfn-1) is an actin-regulatory protein that has a role in modulating smooth muscle contraction. However, the mechanisms that regulate Pfn-1 in smooth muscle are not fully understood. Here, stimulation with acetylcholine induced an increase in the association of the adapter protein cortactin with Pfn-1 in smooth muscle cells/tissues. Furthermore, disruption of the protein/protein interaction by a cell-permeable peptide (CTTN-I peptide) attenuated actin polymerization and smooth muscle contraction without affecting myosin light chain phosphorylation at Ser-19. Knockdown of cortactin by lentivirus-mediated RNAi also diminished actin polymerization and smooth muscle force development. However, cortactin knockdown did not affect myosin activation. In addition, cortactin phosphorylation has been implicated in nonmuscle cell migration. In this study, acetylcholine stimulation induced cortactin phosphorylation at Tyr-421 in smooth muscle cells. Phenylalanine substitution at this position impaired cortactin/Pfn-1 interaction in response to contractile activation. c-Abl is a tyrosine kinase that is necessary for actin dynamics and contraction in smooth muscle. Here, c-Abl silencing inhibited the agonist-induced cortactin phosphorylation and the association of cortactin with Pfn-1. Finally, treatment with CTTN-I peptide reduced airway resistance and smooth muscle hyperreactivity in a murine model of asthma. These results suggest that the interaction of cortactin with Pfn-1 plays a pivotal role in regulating actin dynamics, smooth muscle contraction, and airway hyperresponsiveness in asthma. The association of cortactin with Pfn-1 is regulated by c-Abl-mediated cortactin phosphorylation. 相似文献
80.
The Bcl-2 oncogenic protein was synthesized in vitro and shown to post-translationally integrate asymmetrically into microsomal membranes with no requirement for an amino-terminal signal sequence. Instead, a carboxyl-terminal hydrophobic domain of Bcl-2 served as an insertion sequence essential for membrane assembly since a Bcl-2 mutant lacking this domain completely lost its ability to associate with microsomal membranes. The data demonstrate that Bcl-2 is tightly associated with the lipid bilayer with the nature of an integral membrane protein. The membrane orientation of Bcl-2 was determined using a protease protection assay, which showed that it is predominantly localized to the cytoplasmic face of membranes. A similar type of membrane processing has been shown for cytochrome b5 and also suggested for the viral oncogenic protein polyoma middle-T antigen. 相似文献