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991.
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993.
NA-Seq: A Discovery Tool for the Analysis of Chromatin Structure and Dynamics during Differentiation
Gaetano Gargiulo Samuel Levy Gabriele Bucci Mauro Romanenghi Lorenzo Fornasari Karen Y. Beeson Susanne M. Goldberg Matteo Cesaroni Marco Ballarini Fabio Santoro Natalie Bezman Gianmaria Frigè Philip D. Gregory Michael C. Holmes Robert L. Strausberg Pier Giuseppe Pelicci Fyodor D. Urnov Saverio Minucci 《Developmental cell》2009,16(3):466-481
994.
Nicola Saino Diego Rubolini Esa Lehikoinen Leonid V. Sokolov Andrea Bonisoli-Alquati Roberto Ambrosini Giuseppe Boncoraglio Anders P. M?ller 《Biology letters》2009,5(4):539-541
Phenological responses to climate change vary among taxa and across trophic levels. This can lead to a mismatch between the life cycles of ecologically interrelated populations (e.g. predators and prey), with negative consequences for population dynamics of some of the interacting species. Here we provide, to our knowledge, the first evidence that climate change might disrupt the association between the life cycles of the common cuckoo (Cuculus canorus), a migratory brood parasitic bird, and its hosts. We investigated changes in timing of spring arrival of the cuckoo and its hosts throughout Europe over six decades, and found that short-distance, but not long-distance, migratory hosts have advanced their arrival more than the cuckoo. Hence, cuckoos may keep track of phenological changes of long-distance, but not short-distance migrant hosts, with potential consequences for breeding of both cuckoo and hosts. The mismatch to some of the important hosts may contribute to the decline of cuckoo populations and explain some of the observed local changes in parasitism rates of migratory hosts. 相似文献
995.
Allelic genes encoding water-borne signal proteins (pheromones) were amplified and sequenced from the somatic (macronuclear) sub-chromosomic genome of Antarctic and Arctic strains of the marine ciliate, Euplotes nobilii. Their open reading frames appeared to be specific for polypeptide sequences of 83 to 94 amino acids identifiable with cytoplasmic pheromone precursors (pre-pro-pheromones), requiring two proteolytic steps to remove the pre- and pro-segments and secrete the mature pheromones. Differently from most of the macronuclear genes that have so far been characterized from Euplotes and other hypotrich ciliates, the 5′ and 3′ non-coding regions of all the seven E. nobilii pheromone genes are much longer than the coding regions (621 to 700 versus 214 to 285 nucleotides), and the 5′ regions in particular show nearly identical sequences across the whole set of pheromone genes. These structural peculiarities of the non-coding regions are likely due to the presence of intron sequences and provide presumptive evidence that they are site of basic, conserved activities in the mechanism that regulates the expression of the E. nobilii pheromone genes. 相似文献
996.
The Influence of Clinical Information in the Histopathologic Diagnosis of Melanocytic Skin Neoplasms
Gerardo Ferrara Zsolt Argenyi Giuseppe Argenziano Rino Cerio Lorenzo Cerroni Arturo Di Blasi Elisa A. A. Feudale Caterina M. Giorgio Cesare Massone Oscar Nappi Carlo Tomasini Carmelo Urso Iris Zalaudek Harald Kittler H. Peter Soyer 《PloS one》2009,4(4)
Background
We tested the relevance of clinical information in the histopathologic evaluation of melanocytic skin neoplasm (MSN).Methods
Histopathologic specimens from 99 clinically atypical MSN were circulated among ten histopathologists; each case had clinical information available in a database with a five-step procedure (no information; age/sex/location; clinical diagnosis; clinical image; dermoscopic image); each step had a histopathologic diagnosis (D1 through D5); each diagnostic step had a level of diagnostic confidence (LDC) ranging from 1 (no diagnostic certainty) to 5 (absolute diagnostic certainty). The comparison of the LDC was employed with an analysis of variance (ANOVA) for repeated measures.Findings
In D1 (no information), 36/99 cases (36.3%) had unanimous diagnosis; in D5 (full information available), 51/99 cases (51.5%) had unanimous diagnosis (p for difference between proportions <0.001). The observer agreement expressed as kappa increased significantly from D1 to D5. The mean LDC linearly increased for each observer from D1 through D5 (p for linear trend <0.001). On average, each histopathologist changed his initial diagnosis in 7 cases (range: 2–23). Most diagnostic changes were in D2 (age/sex/location).Interpretation
The histopathologic criteria for the diagnosis of MSN can work as such, but the final histopathologic diagnosis is a clinically-aided interpretation. Clinical data sometimes reverse the initial histopathologic evaluation. 相似文献997.
Sina Ghaemmaghami Misol Ahn Pierre Lessard Kurt Giles Giuseppe Legname Stephen J. DeArmond Stanley B. Prusiner 《PLoS pathogens》2009,5(11)
Quinacrine is a potent antiprion compound in cell culture models of prion disease but has failed to show efficacy in animal bioassays and human clinical trials. Previous studies demonstrated that quinacrine inefficiently penetrates the blood-brain barrier (BBB), which could contribute to its lack of efficacy in vivo. As quinacrine is known to be a substrate for P-glycoprotein multi-drug resistance (MDR) transporters, we circumvented its poor BBB permeability by utilizing MDR0/0 mice that are deficient in mdr1a and mdr1b genes. Mice treated with 40 mg/kg/day of quinacrine accumulated up to 100 µM of quinacrine in their brains without acute toxicity. PrPSc levels in the brains of prion-inoculated MDR0/0 mice diminished upon the initiation of quinacrine treatment. However, this reduction was transient and PrPSc levels recovered despite the continuous administration of quinacrine. Treatment with quinacrine did not prolong the survival times of prion-inoculated, wild-type or MDR0/0 mice compared to untreated mice. A similar phenomenon was observed in cultured differentiated prion-infected neuroblastoma cells: PrPSc levels initially decreased after quinacrine treatment then rapidly recovered after 3 d of continuous treatment. Biochemical characterization of PrPSc that persisted in the brains of quinacrine-treated mice had a lower conformational stability and different immunoaffinities compared to that found in the brains of untreated controls. These physical properties were not maintained upon passage in MDR0/0 mice. From these data, we propose that quinacrine eliminates a specific subset of PrPSc conformers, resulting in the survival of drug-resistant prion conformations. Transient accumulation of this drug-resistant prion population provides a possible explanation for the lack of in vivo efficacy of quinacrine and other antiprion drugs. 相似文献
998.
Prion proteins are known to misfold into a range of different aggregated forms, showing different phenotypic and pathological states. Understanding strain specificities is an important problem in the field of prion disease. Little is known about which PrPSc structural properties and molecular mechanisms determine prion replication, disease progression and strain phenotype. The aim of this work is to investigate, through a mathematical model, how the structural stability of different aggregated forms can influence the kinetics of prion replication. The model-based results suggest that prion strains with different conformational stability undergoing in vivo replication are characterizable in primis by means of different rates of breakage. A further role seems to be played by the aggregation rate (i.e. the rate at which a prion fibril grows). The kinetic variability introduced in the model by these two parameters allows us to reproduce the different characteristic features of the various strains (e.g., fibrils' mean length) and is coherent with all experimental observations concerning strain-specific behavior. 相似文献
999.
Neasham D Gallo V Guarrera S Dunning A Overvad K Tjonneland A Clavel-Chapelon F Linseisen JP Malaveille C Ferrari P Boeing H Benetou V Trichopoulou A Palli D Crosignani P Tumino R Panico S Bueno-De-Mesquita HB Peeters PH van Gib CH Lund E Gonzalez CA Martinez C Dorronsoro M Barricarte A Navarro C Quiros JR Berglund G Jarvholm B Khaw KT Key TJ Bingham S Diaz TM Riboli E Matullo G Vineis P 《DNA Repair》2009,8(1):60-71
We followed-up for mortality and cancer incidence 1088 healthy non-smokers from a population-based study, who were characterized for 22 variants in 16 genes involved in DNA repair pathways. Follow-up was 100% complete. The association between polymorphism and mortality or cancer incidence was analyzed using Cox Proportional Hazard regression models. Ninety-five subjects had died in a median follow-up time of 78 months (inter-quartile range 59-93 months). None of the genotypes was clearly associated with total mortality, except variants for two Double-Strand Break DNA repair genes, XRCC3 18067 C>T (rs#861539) and XRCC2 31479 G>A (rs#3218536). Adjusted hazard ratios were 2.25 (1.32-3.83) for the XRCC3 C/T genotype and 2.04 (1.00-4.13) for the T/T genotype (reference C/C), and 2.12 (1.14-3.97) for the XRCC2 G/A genotype (reference G/G). For total cancer mortality, the adjusted hazard ratios were 3.29 (1.23-7.82) for XRCC3 C/T, 2.84 (0.81-9.90) for XRCC3 T/T and 3.17 (1.21-8.30) for XRCC2 G/A. With combinations of three or more adverse alleles, the adjusted hazard ratio for all cause mortality was 17.29 (95% C.I. 8.13-36.74), and for all incident cancers the HR was 5.28 (95% C.I. 2.17-12.85). Observations from this prospective study suggest that polymorphisms of genes involved in the repair of DNA double-strand breaks significantly influence the risk of cancer and non-cancer disease, and can influence mortality. 相似文献
1000.
Anti-predator behaviour often represents a trade-off between the benefits of reducing predation risk and the drawbacks of
limiting access to resources (e.g. food availability, mating and nesting sites). The effectiveness of avoidance behaviour
relies on the ability to detect predator cues, which may provide reliable information on predation risk. Using controlled
laboratory experiments, we studied the relative importance of visual and chemical cues in the triggering of anti-predator
responses in Galaxias maculatus, where Oncorhyncus mykiss was used as the predator. Metabolic cost was also estimated, measured as oxygen consumption. Exposure to different types
of predator cue induced diverse behavioural responses in G. maculatus. Detection of the exotic predator, using both visual and chemical stimuli, resulted in reduced G. maculatus swimming activity and changes in respiratory rate. 相似文献