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991.
992.
Huntington's disease (HD) is one of several neurodegenerative disorders caused by expansion of CAG repeats in a coding gene. Somatic CAG expansion rates in HD vary between organs, and the greatest instability is observed in the brain, correlating with neuropathology. The fundamental mechanisms of somatic CAG repeat instability are poorly understood, but locally formed secondary DNA structures generated during replication and/or repair are believed to underlie triplet repeat expansion. Recent studies in HD mice have demonstrated that mismatch repair (MMR) and base excision repair (BER) proteins are expansion inducing components in brain tissues. This study was designed to simultaneously investigate the rates and modes of expansion in different tissues of HD R6/1 mice in order to further understand the expansion mechanisms in vivo. We demonstrate continuous small expansions in most somatic tissues (exemplified by tail), which bear the signature of many short, probably single-repeat expansions and contractions occurring over time. In contrast, striatum and cortex display a dramatic--and apparently irreversible--periodic expansion. Expansion profiles displaying this kind of periodicity in the expansion process have not previously been reported. These in vivo findings imply that mechanistically distinct expansion processes occur in different tissues. 相似文献
993.
Claas Wodarczyk Gianfranco Distefano Isaline Rowe Massimiliano Gaetani Barbara Bricoli Mordi Muorah Andrea Spitaleri Valeria Mannella Piero Ricchiuto Monika Pema Maddalena Castelli Ariel E. Casanova Luca Mollica Manuela Banzi Manila Boca Corinne Antignac Sophie Saunier Giovanna Musco Alessandra Boletta 《PloS one》2010,5(9)
Mutations in PKD1, the gene encoding for the receptor Polycystin-1 (PC-1), cause autosomal dominant polycystic kidney disease (ADPKD). The cytoplasmic C-terminus of PC-1 contains a coiled-coil domain that mediates an interaction with the PKD2 gene product, Polycystin-2 (PC-2). Here we identify a novel domain in the PC-1 C-terminal tail, a polyproline motif mediating an interaction with Src homology domain 3 (SH3). A screen for interactions using the PC-1 C-terminal tail identified the SH3 domain of nephrocystin-1 (NPHP1) as a potential binding partner of PC-1. NPHP1 is the product of a gene that is mutated in a different form of renal cystic disease, nephronophthisis (NPHP). We show that in vitro pull-down assays and NMR structural studies confirmed the interaction between the PC-1 polyproline motif and the NPHP1 SH3 domain. Furthermore, the two full-length proteins interact through these domains; using a recently generated model system allowing us to track endogenous PC-1, we confirm the interaction between the endogenous proteins. Finally, we show that NPHP1 trafficking to cilia does not require PC-1 and that PC-1 may require NPHP1 to regulate resistance to apoptosis, but not to regulate cell cycle progression. In line with this, we find high levels of apoptosis in renal specimens of NPHP patients. Our data uncover a link between two different ciliopathies, ADPKD and NPHP, supporting the notion that common pathogenetic defects, possibly involving de-regulated apoptosis, underlie renal cyst formation. 相似文献
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996.
David H Shu Thomas PP Ransom Colleen M O'Connell Jafna L Cox Stephanie M Kaiser Shirl A Gee Richard C Rowe Ehud Ur Ali Syed Imran 《Cardiovascular diabetology》2006,5(1):1-9
Introduction
Anemia and diabetes are risk factors for short-term mortality following an acute myocardial infarction(AMI). Anemia is more prevalent in patients with diabetes. We performed a retrospective study to assess the impact of the combination of diabetes and anemia on post-myocardial infarction outcomes.Methods
Data relating to all consecutive patients hospitalized with AMI was obtained from a population-based disease-specific registry. Patients were divided into 4 groups: diabetes and anemia (group A, n = 716), diabetes and no anemia (group B, n = 1894), no diabetes and anemia (group C, n = 869), and no diabetes and no anemia (group D, n = 3987). Mortality at 30 days and 31 days to 36 months were the main outcome measures.Results
30-day mortality was 32.3% in group A, 16.1% in group B, 21.5% in group C, 6.6% in group D (all p < 0.001). 31-day to 36-month mortality was 47.6% in group A, 20.8% in group B, 34.3% in group C, and 10.4% in group D (all p < 0.001). Diabetes and anemia remained independent risk factors for mortality with odds ratios of 1.61 (1.41–1.85, p < 0.001) and 1.59 (1.38–1.85, p < 0.001) respectively at 36 months. Cardiovascular death from 31-days to 36-months was 43.7% of deaths in group A, 54.1% in group B, 47.0% in group C, 50.8% group D (A vs B, p < 0.05).Interpretation
Patients with both diabetes and anemia have a significantly higher mortality than those with either diabetes or anemia alone. Cardiovascular death remained the most likely cause of mortality in all groups. 相似文献997.
Endocranial surfaces, volumes, and interconnectivities of extant and fossil odontocetes potentially offer information on the
general architecture of the brain and on the structure of the specialized cetacean circulatory system. Although conventional
methods for acquiring such data have generally involved invasive preparation of the specimen, particularly in the case of
fossils, new tomographic technologies afford nondestructive access to these internal morphologies. In this study we used high-resolution
X-ray computed tomography (HRXCT) to scan a skull of the extant Tursiops truncatus (Cetacea: Odontoceti). We processed the data to reveal the cranial endocast and details of internal skeletal architecture
(data at www.digimorph.org). Major features that can be discerned include aspects of the specimen's hypertrophied retia mirabilia,
the major canals and openings of the cranial cavity, and the relationship of the brain and endocranial circulatory structures
to the surrounding skeleton. CT data also provide information on the shape of the brain that may be lost in conventional anatomical
preparations, and readily provide volumetric and linear measurements of the endocast and its individual segments. These results
demonstrate the utility of HRXCT for interpreting the internal cranial anatomy of both extant and fossil cetaceans. 相似文献
998.
Histological analysis of GFP expression in murine bone. 总被引:7,自引:0,他引:7
Xi Jiang Zana Kalajzic Peter Maye Alen Braut Justin Bellizzi Mina Mina David W Rowe 《The journal of histochemistry and cytochemistry》2005,53(5):593-602
The power for appreciating complex cellular interactions during embryonic development using green fluorescent protein (GFP) as a visual histological marker has not been applied to adult tissues due to loss of GFP signal during paraffin embedding and a high autofluorescent background, particularly in section of bone and bone marrow. Here we demonstrate that the GFP signal is well preserved in frozen sections of adult decalcified bone. Using a tape-transfer system that preserves histological relationships, GFP expression can be related to standard histological stains used in bone biology research. The choice of a dual-filter cube and a strong GFP signal makes it possible to readily distinguish at least four different GFP colors that are distinctly different from the autofluorescent background. An additional advantage of the frozen sections is better preservation of immunological epitopes that allow colocalization of an immunostained section with an endogenous GFP and a strong lacZ signal emanating from a beta-gal marker gene. We present an approach for recording multiple images from the same histological section that allows colocalization of a GFP signal with subsequent stains and procedures that destroy GFP. Examples that illustrate the flexibility for dual imaging of various fluorescent signals are described in this study. The same imaging approach can serve as a vehicle for archiving, retrieving, and sharing histological images among research groups. 相似文献
999.
Elevational gradient analyses and the use of historical museum specimens: a cautionary tale 总被引:2,自引:0,他引:2
Rebecca J. Rowe 《Journal of Biogeography》2005,32(11):1883-1897
Aim The value of biodiversity informatics rests upon the capacity to assess data quality. Yet as these methods have developed, investigating the quality of the underlying specimen data has largely been neglected. Using an exceptionally large, densely sampled specimen data set for non‐flying small mammals of Utah, I evaluate measures of uncertainty associated with georeferenced localities and illustrate the implications of uncritical incorporation of data in the analysis of patterns of species richness and species range overlap along elevational gradients. Location Utah, USA, with emphasis on the Uinta Mountains. Methods Employing georeferenced specimen data from the Mammal Networked Information System (MaNIS), I converted estimates of areal uncertainty into elevational uncertainty using a geographic information system (GIS). Examining patterns in both areal and elevational uncertainty measures, I develop criteria for including localities in analyses along elevational gradients. Using the Uinta Mountains as a test case, I then examine patterns in species richness and species range overlap along an elevational gradient, with and without accounting for data quality. Results Using a GIS, I provide a framework for post‐hoc 3‐dimensional georeferencing and demonstrate collector‐recorded elevations as a valuable technique for detecting potential errors in georeferencing. The criteria established for evaluating data quality when analysing patterns of species richness and species range overlap in the Uinta Mountains test case reduced the number of localities by 44% and the number of associated specimens by 22%. Decreasing the sample size in this manner resulted in the subsequent removal of one species from the analysis. With and without accounting for data quality, the pattern of species richness along the elevational gradient was hump‐shaped with a peak in richness at about mid‐elevation, between 2300 and 2600 m. In contrast, the frequencies of different pair‐wise patterns of elevational range overlap among species differed significantly when data quality was and was not accounted for. Main conclusions These results indicate that failing to assess spatial error in data quality did not alter the shape of the observed pattern in species richness along the elevational gradient nor the pattern of species’ first and last elevational occurrences. However, it did yield misleading estimates of species richness and community composition within a given elevational interval, as well as patterns of elevational range overlap among species. Patterns of range overlap among species are often used to infer processes underlying species distributions, suggesting that failure to account for data quality may alter interpretations of process as well as perceived patterns of distribution. These results illustrate that evaluating the quality of the underlying specimen data is a necessary component of analyses incorporating biodiversity informatics. 相似文献
1000.
Avian predators learn to avoid defended insects on the basis of their conspicuous warning coloration. In many aposematic species, the level of chemical defence varies, with some individuals being more defended than others. Sequestration and production of defence chemicals is often costly and therefore less defended individuals enjoy the benefits of the warning signal without paying the full costs of chemical production. This is a fundamental theoretical problem for the evolutionary stability of aposematism, since less defended individuals appear to be at a selective advantage. However, if predators sample aposematic prey and selectively reject individuals on the basis of their chemical investment, aposematism could become evolutionarily stable. Previous research aimed at testing whether birds can use taste to discriminate between palatable and unpalatable prey has been confounded by other experimental factors. Here, we show that birds can taste and reject prey entirely on the basis of an individual's level of chemical defence and more importantly, they can make decisions on whether or not to consume a defended individual based upon their level of chemical investment. We discuss these results in relation to the evolution of aposematism, mimicry and defence chemistry. 相似文献