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131.
Pyruvate dehydrogenase complex (PDC) deficiency is an inborn metabolic disorder that causes neurological abnormalities. In
this report, a murine model of PDC deficiency was analyzed using histology, magnetic resonance (MR) imaging and MR spectroscopy
(MRS) and the results compared to PDC-deficient female patients. Histological analysis of brains from PDC-deficient mice revealed
defects in neuronal cytoarchitecture in grey matter and reduced size of white matter structures. MR results were comparable
to previously published clinical MR findings obtained from PDC-deficient female patients. Specifically, a 15.4% increase in
relative lactate concentration, 64.4% loss of N-acetylaspartate concentration and a near complete loss of discernable glutamine plus glutamate concentration were observed
in a PDC deficient mouse compared to wild-type control. Lower apparent diffusion coefficients (ADCs) were observed within
the brain consistent with atrophy. These results demonstrate the usefulness of this murine model to systematically evaluate
the beneficial effects of dietary and pharmacological interventions.
Special issue dedicated to John P. Blass.
Lioudmila Pliss and Richard Mazurchuk are two investigators who contributed equally. 相似文献
132.
This article discusses a culturally specific response to traumatic events: orthostatic panic attacks among Vietnamese refugees. We compared the rate and severity of orthostatic panic as well as the rates and severity of associated flashbacks a month before and a month after September 11, 2001. After that date, the rate and severity of orthostatic panic greatly increased, as did the rate and severity of associated flashbacks. The central role of orthostatic panic as a response to traumatic events is illustrated through a patient's vignette. An explanation of why September 11 so profoundly influenced this population is adduced, including an explanation of why it resulted in considerable worsening of orthostatic panic. 相似文献
133.
Hubs in the protein-protein interaction network have been classified as "party" hubs, which are highly correlated in their mRNA expression with their partners while "date" hubs show lesser correlation. In this study, we explored the role of intrinsic disorder in date and party hub interactions. The data reveals that intrinsic disorder is significantly enriched in date hub proteins when compared with party hub proteins. Intrinsic disorder has been largely implicated in transient binding interactions. The disorder to order transition, which occurs during binding interactions in disordered regions, renders the interaction highly reversible while maintaining the high specificity. The enrichment of intrinsic disorder in date hubs may facilitate transient interactions, which might be required for date hubs to interact with different partners at different times. 相似文献
134.
Lutz B 《Molecular neurobiology》2007,36(1):92-101
The endocannabinoid system has emerged as a versatile neuromodulatory system, implicated in a plethora of physiological and
pathophysiological processes. Cannabinoid receptor type 1 (CB1 receptor) and endocannabinoids are widely distributed in the
brain. Their roles in learning and memory have been well documented, using rodents in various memory tests. Depending on the
test, the endocannabinoid system is required in the acquisition and/or extinction of memory. In particular, the activation
of CB1 receptor-mediated signaling is centrally involved in the facilitation of behavioral adaptation after the acquisition
of aversive memories. As several human psychiatric disorders, such as phobia, generalized anxiety disorders, and posttraumatic
stress disorder (PTSD) appear to involve aberrant memory processing and impaired adaptation to changed environmental conditions,
the hope has been fuelled that the endocannabinoid system might be a valuable therapeutic target for the treatment of these
disorders. This review summarizes the current data on the role of the endocannabinoid system in the modulation of extinction
learning. 相似文献
135.
Sahún I Gallego X Gratacòs M Murtra P Trullás R Maldonado R Estivill X Dierssen M 《Amino acids》2007,33(4):677-688
Summary. Sensitivity to pharmacological challenges has been reported in patients with panic disorder. We have previously validated
transgenic mice overexpressing the neurotrophin-3 (NT-3) receptor, TrkC (TgNTRK3), as an engineered murine model of panic
disorder. We could determine that TgNTRK3 mice presented increased cellularity in brain regions, such as the locus ceruleus,
that are important neural substrates for the expression of anxiety in severe anxiety states. Here, we investigated the sensitivity
to induce anxiety and panic-related symptoms by sodium lactate and the effects of various drugs (the α2-adrenoceptor antagonist,
yohimbine and the adenosine antagonist, caffeine), in TgNTRK3 mice. We found enhanced panicogenic sensitivity to sodium lactate
and an increased intensity and a differential pattern of Fos expression after the administration of yohimbine or caffeine
in TgNTRK3. Our findings validate the relevance of the NT-3/TrkC system to pathological anxiety and raise the possibility
that a specific set of fear-related pathways involved in the processing of anxiety-related information may be differentially
activated in panic disorder. 相似文献
136.
Karthikeyan Ardhanareeswaran Gianfilippo Coppola Flora Vaccarino 《The Yale journal of biology and medicine》2015,88(1):5-16
Autism spectrum disorder (ASD) affects as many as 1 in 68 children and is said to be the fastest-growing serious developmental disability in the United States. There is currently no medical cure or diagnostic test for ASD. Furthermore, the U.S. Food and Drug Administration has yet to approve a single drug for the treatment of autism’s core symptoms. Despite numerous genome studies and the identification of hundreds of genes that may cause or predispose children to ASD, the pathways underlying the pathogenesis of idiopathic ASD still remain elusive. Post-mortem brain samples, apart from being difficult to obtain, offer little insight into a disorder that arises through the course of development. Furthermore, ASD is a disorder of highly complex, human-specific behaviors, making it difficult to model in animals. Stem cell models of ASD can be generated by performing skin biopsies of ASD patients and then dedifferentiating these fibroblasts into human-induced pluripotent stem cells (hiPSCs). iPSCs closely resemble embryonic stem cells and retain the unique genetic signature of the ASD patient from whom they were originally derived. Differentiation of these iPSCs into neurons essentially recapitulates the ASD patient’s neuronal development in a dish, allowing for a patient-specific model of ASD. Here we review our current understanding of the underlying neurobiology of ASD and how the use of stem cells can advance this understanding, possibly leading to new therapeutic avenues. 相似文献
137.
TFG clusters COPII‐coated transport carriers and promotes early secretory pathway organization 下载免费PDF全文
Adam Johnson Nilakshee Bhattacharya Michael Hanna Janice G Pennington Amber L Schuh Lei Wang Marisa S Otegui Scott M Stagg Anjon Audhya 《The EMBO journal》2015,34(6):811-827
In mammalian cells, cargo‐laden secretory vesicles leave the endoplasmic reticulum (ER) en route to ER‐Golgi intermediate compartments (ERGIC) in a manner dependent on the COPII coat complex. We report here that COPII‐coated transport carriers traverse a submicron, TFG (Trk‐fused gene)‐enriched zone at the ER/ERGIC interface. The architecture of TFG complexes as determined by three‐dimensional electron microscopy reveals the formation of flexible, octameric cup‐like structures, which are able to self‐associate to generate larger polymers in vitro. In cells, loss of TFG function dramatically slows protein export from the ER and results in the accumulation of COPII‐coated carriers throughout the cytoplasm. Additionally, the tight association between ER and ERGIC membranes is lost in the absence of TFG. We propose that TFG functions at the ER/ERGIC interface to locally concentrate COPII‐coated transport carriers and link exit sites on the ER to ERGIC membranes. Our findings provide a new mechanism by which COPII‐coated carriers are retained near their site of formation to facilitate rapid fusion with neighboring ERGIC membranes upon uncoating, thereby promoting interorganellar cargo transport. 相似文献
138.
快速眼动(REM)睡眠期行为障碍(RBD)是REM睡眠期出现肌张力缺失并伴有与噩梦相关的复杂运动为特征的发作性疾病,RBD与帕金森病(PD)密切相关,在PD患者中的发生率高。伴RBD的PD患者临床上多表现为强直型,病程更长,运动症状、非运动症状更重,生活能力及生活质量的损害更突出。RBD的病理生理机制可能主要涉及脑桥被盖部、蓝斑/蓝斑下区复合体及其投射通路功能的紊乱。诊断RBD主要依据特征性临床表现及视频多导睡眠图(v-PSG)的监测结果。治疗上除了积极干预PD外,应对患者及其床伴采取保护措施;当患者的异常睡眠行为对其造成严重的困扰并具有危险性时,需给予药物治疗。 相似文献
139.
There is increasing awareness of the interplay among sleep, circadian rhythms, and psychopathology. Recent findings show that obsessive–compulsive disorder (OCD) is associated with late bedtimes. Sleep disruption may exacerbate impairments in executive functioning in individuals with OCD, making these individuals vulnerable to experiencing intrusive thoughts that come from “out of the blue” (autogenous obsessions; AO) and to having difficulty dismissing them. The current study investigated types of intrusive thoughts experienced by individuals with (DB) and without (NDB) delayed bedtimes. Bedtime, and AO (uncued, affectively negative) vs. reactive obsessions (RO; triggered by environment, affectively neutral) were examined in 212 adults. As hypothesized, individuals with DB reported more frequent intrusive thoughts, as well as more AO, than NDB individuals. Additionally, DB participants reported a greater urge to neutralize intrusive thoughts than NDB participants. Future work should test the replicability of these findings and explore circadian disruptions in OCD using biological markers. 相似文献
140.
Xavier Roda Gilabert Rafael Mora Jorge Martínez-Moreno 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2015,370(1682)
Despite recent advances in the identification of bipolar knapping, its role in many sites is not well known. We propose to assess the significance of this technique in the context of changes that occur in the Mesolithic. A lithic assemblage was recovered from unit SG at Font del Ros (Catalunya, Spain) in which pitted stones, cores and products arising from bipolar reduction (flakes, fragments and splintered pieces) were identified. This study indicates that the bipolar technique is fundamental in the settlement. These results are key to defining the organization of Holocene hunter-gatherer subsistence in northeast Iberia. 相似文献