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排序方式: 共有465条查询结果,搜索用时 609 毫秒
161.
Anat Achiron Joab Chapman David Magalashvili Mark Dolev Mor Lavie Eran Bercovich Michael Polliack Glen M. Doniger Yael Stern Olga Khilkevich Shay Menascu Gil Hararai Micharel Gurevich Yoram Barak 《PloS one》2013,8(8)
Background/Aims
Large-scale population studies measuring rates and dynamics of cognitive decline in multiple sclerosis (MS) are lacking. In the current cross-sectional study we evaluated the patterns of cognitive impairment in MS patients with disease duration of up to 30 years.Methods
1,500 patients with MS were assessed by a computerized cognitive battery measuring verbal and non-verbal memory, executive function, visual spatial perception, verbal function, attention, information processing speed and motor skills. Cognitive impairment was defined as below one standard deviation (SD) and severe cognitive impairment as below 2SD for age and education matched healthy population norms.Results
Cognitive performance in our cohort was poorer than healthy population norms. The most frequently impaired domains were information processing speed and executive function. MS patients with secondary-progressive disease course performed poorly compared with clinically isolated syndrome, relapsing-remitting and primary progressive MS patients. By the fifth year from disease onset, 20.9% of patients performed below the 1SD cutoff for impairment, p = 0.005, and 6.0% performed below the 2SD cutoff for severe cognitive impairment, p = 0.002. By 10 years from onset 29.3% and 9.0% of patients performed below the 1SD and 2SD cutoffs, respectively, p = 0.0001. Regression modeling suggested that cognitive impairment may precede MS onset by 1.2 years.Conclusions
The rates of cognitive impairment in this large sample of MS patients were lower than previously reported and severe cognitive impairment was evident only in a relatively small group of patients. Cognitive impairment differed significantly from expected normal distribution only at five years from onset, suggesting the existence of a therapeutic window during which patients may benefit from interventions to maintain cognitive health. 相似文献162.
Corti P Young S Chen CY Patrick MJ Rochon ER Pekkan K Roman BL 《Development (Cambridge, England)》2011,138(8):1573-1582
Arteriovenous malformations (AVMs) are fragile direct connections between arteries and veins that arise during times of active angiogenesis. To understand the etiology of AVMs and the role of blood flow in their development, we analyzed AVM development in zebrafish embryos harboring a mutation in activin receptor-like kinase I (alk1), which encodes a TGFβ family type I receptor implicated in the human vascular disorder hereditary hemorrhagic telangiectasia type 2 (HHT2). Our analyses demonstrate that increases in arterial caliber, which stem in part from increased cell number and in part from decreased cell density, precede AVM development, and that AVMs represent enlargement and stabilization of normally transient arteriovenous connections. Whereas initial increases in endothelial cell number are independent of blood flow, later increases, as well as AVMs, are dependent on flow. Furthermore, we demonstrate that alk1 expression requires blood flow, and despite normal levels of shear stress, some flow-responsive genes are dysregulated in alk1 mutant arterial endothelial cells. Taken together, our results suggest that Alk1 plays a role in transducing hemodynamic forces into a biochemical signal required to limit nascent vessel caliber, and support a novel two-step model for HHT-associated AVM development in which pathological arterial enlargement and consequent altered blood flow precipitate a flow-dependent adaptive response involving retention of normally transient arteriovenous connections, thereby generating AVMs. 相似文献
163.
Alon LT Pietrokovski S Barkan S Avrahami L Kaidanovich-Beilin O Woodgett JR Barnea A Eldar-Finkelman H 《FEBS letters》2011,585(8):1158-1162
Mammalian glycogen synthase kinase-3 (GSK-3), a critical regulator in neuronal signaling, cognition, and behavior, exists as two isozymes GSK-3α and GSK-3β. Their distinct biological functions remains largely unknown. Here, we examined the evolutionary significance of each of these isozymes. Surprisingly, we found that unlike other vertebrates that harbor both GSK-3 genes, the GSK-3α gene is missing in birds. GSK-3-mediated tau phosphorylation was significantly lower in adult bird brains than in mouse brains, a phenomenon that was reproduced in GSK-3α knockout mouse brains. Tau phosphorylation was detected in brains from bird embryos suggesting that GSK-3 isozymes play distinct roles in tau phosphorylation during development. Birds are natural GSK-3α knockout organisms and may serve as a novel model to study the distinct functions of GSK-3 isozymes. 相似文献
164.
Sinem Yilmaz-Ozcan Asli Sade Baris Kucukkaraduman Yasemin Kaygusuz Kerem Mert Senses Sreeparna Banerjee Ali Osmay Gure 《PloS one》2014,9(9)
Cancer-testis (CT) genes are expressed in various cancers but not in normal tissues other than in cells of the germline. Although DNA demethylation of promoter-proximal CpGs of CT genes is linked to their expression in cancer, the mechanisms leading to demethylation are unknown. To elucidate such mechanisms we chose to study the Caco-2 colorectal cancer cell line during the course of its spontaneous differentiation in vitro, as we found CT genes, in particular PAGE2, -2B and SPANX-B, to be up-regulated during this process. Differentiation of these cells resulted in a mesenchymal-to-epithelial transition (MET) as evidenced by the gain of epithelial markers CDX2, Claudin-4 and E-cadherin, and a concomitant loss of mesenchymal markers Vimentin, Fibronectin-1 and Transgelin. PAGE2 and SPAN-X up-regulation was accompanied by an increase in Ten-eleven translocation-2 (TET2) expression and cytosine 5-hydroxymethylation as well as the disassociation of heterochromatin protein 1 and the polycomb repressive complex 2 protein EZH2 from promoter-proximal regions of these genes. Reversal of differentiation resulted in down-regulation of PAGE2, -2B and SPANX-B, and induction of epithelial-to-mesenchymal transition (EMT) markers, demonstrating the dynamic nature of CT gene regulation in this model. 相似文献
165.
Protein homeostasis (proteostasis) networks are dynamic throughout the lifespan of an organism. During Caenorhabditis elegans adulthood, the maintenance of metastable proteins and the activation of stress responses are inversely associated with germline stem cell proliferation. Here, we employed the thymidylate synthase inhibitor 5-fluoro-2′-deoxyuridine (FUdR) to chemically inhibit reproduction, thus allowing for examination of the interplay between reproduction and somatic proteostasis. We found that treatment with FUdR modulates proteostasis decline both before and after reproduction onset, such that effective induction of the heat shock response was maintained during adulthood and that metastable temperature-sensitive mutant phenotypes were rescued under restrictive conditions. However, FUdR treatment also improved the folding capacity of germline- and gonadogenesis-defective mutants, suggesting that proteostasis modulation by FUdR is independent of germline stem cell proliferation or inhibition of reproduction. Our data, therefore, indicate that FUdR converges on alternative regulatory signals that modulate C. elegans proteostasis capacity during development and adulthood. 相似文献
166.
167.
A possible relation between new neuronal recruitment and migratory behavior in Acrocephalus warblers
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Evidence suggests a possible correlation between learning abilities of adults and new neuronal recruitment into their brains. The hypothesis is that this brain plasticity enables animals to adapt to environmental changes. We examined whether there are differences in neuronal recruitment between resident and migrant birds. We predicted that migrants, which are more exposed to spatial changes than residents, will recruit more new neurons. To test this, we compared neuronal recruitment in two closely related bird species ‐ the migrant reed warbler (Acrocephalus scirpaceus), and the resident Clamorous warbler (A. Stentoreus) ‐ during spring, summer, and autumn. Wild birds were caught, treated with BrdU and sacrificed five weeks later. New neurons were recorded in the Hippocampus and Nidopallium caudolateral. The results support our hypothesis, as more new neurons were found in the migrant species, in both brain regions and all seasons. We suggest that this phenomenon enables enhanced navigational abilities, which are required for the migratory lifestyle. However, in contrast to our hypothesis, in spring we found less new neurons in adults of both species, as compared to other seasons. We suggest that in spring, when birds settle in breeding territories, they require less spatial skills, and this might enable to reduce the cost of neuronal recruitment, as reflected by less new neurons in their brains. We also found age differences, with overall higher neuronal recruitment in juveniles. Finally, we advocate the importance of studying wild populations, for a better understanding of the adaptive significance of neuronal replacement in the vertebrate brain. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 1194–1209, 2014 相似文献
168.
169.
170.
Dalit Modan-Moses Amit Yaroslavsky Brigitte Kochavi Anat Toledano Sharon Segev Fadel Balawi Edith Mitrany Daniel Stein 《PloS one》2012,7(9)