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Cell surface and secreted proteins provide essential functions for multicellular life. They enter the endoplasmic reticulum (ER) lumen co-translationally, where they mature and fold into their complex three-dimensional structures. The ER is populated with a host of molecular chaperones, associated co-factors, and enzymes that assist and stabilize folded states. Together, they ensure that nascent proteins mature properly or, if this process fails, target them for degradation. BiP, the ER HSP70 chaperone, interacts with unfolded client proteins in a nucleotide-dependent manner, which is tightly regulated by eight DnaJ-type proteins and two nucleotide exchange factors (NEFs), SIL1 and GRP170. Loss of SIL1′s function is the leading cause of Marinesco-Sjögren syndrome (MSS), an autosomal recessive, multisystem disorder. The development of animal models has provided insights into SIL1′s functions and MSS-associated pathologies. This review provides an in-depth update on the current understanding of the molecular mechanisms underlying SIL1′s NEF activity and its role in maintaining ER homeostasis and normal physiology. A precise understanding of the underlying molecular mechanisms associated with the loss of SIL1 may allow for the development of new pharmacological approaches to treat MSS. 相似文献
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A small handful of recent studies have addressed a phenomenon known as “phantom vibration syndrome”. This refers to when phone users perceive their device to vibrate, indicating that a call or text is incoming, when in fact the phone did not vibrate at all. Though these studies show that most users do not find phantom vibration hallucinations to be very bothersome, they also find that a large majority of users experience this phenomenon. This paper explores what the striking prevalence of phantom vibration syndrome means for our contemporary relationships with technology. I begin with a review of the theories purporting to explain these data, which largely rely on particular understandings of the brain. Next I develop an alternative theory of phantom vibration syndrome based on insights from the philosophical tradition of phenomenology. This account considers the ways users develop bodily and perceptual habits regarding how the phone is understood and used. By critically contrasting these different theories, we can refine our questions about what the high prevalence of phantom vibration syndrome implies about our contemporary technological situation. 相似文献
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Christian Veauthier Gunnar Gaede Helena Radbruch Klaus-Dieter Wernecke Friedemann Paul 《International journal of molecular sciences》2015,16(7):16514-16528
Quality of Life (QoL) is decreased in multiple sclerosis (MS), but studies about the impact of sleep disorders (SD) on health-related quality of Life (HRQoL) are lacking. From our original cohort, a cross-sectional polysomnographic (PSG) study in consecutive MS patients, we retrospectively analysed the previously unpublished data of the Nottingham Health Profile (NHP). Those MS patients suffering from sleep disorders (n = 49) showed significantly lower HRQoL compared to MS patients without sleep disorders (n = 17). Subsequently, we classified the patients into four subgroups: insomnia (n = 17), restless-legs syndrome, periodic limb movement disorder and SD due to leg pain (n = 24), obstructive sleep apnea (n = 8) and patients without sleep disorder (n = 17). OSA and insomnia patients showed significantly higher NHP values and decreased HRQoL not only for the sleep subscale but also for the “energy” and “emotional” area of the NHP. In addition, OSA patients also showed increased NHP values in the “physical abilities” area. Interestingly, we did not find a correlation between the objective PSG parameters and the subjective sleep items of the NHP. However, this study demonstrates that sleep disorders can reduce HRQoL in MS patients and should be considered as an important confounder in all studies investigating HRQoL in MS. 相似文献
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An increasing number of connectionist models have been proposed to explain behavioral deficits in developmental disorders. These simulations motivate serious consideration of the theoretical implications of the claim that a developmental disorder fits within the parameter space of a particular computational model of normal development. The authors examine these issues in depth with respect to a series of new simulations investigating past-tense formation in Williams syndrome. This syndrome and the past-tense domain are highly relevant because both have been used to make strong theoretical claims about the processes underlying normal language acquisition. The authors conclude that computational models have great potential to advance psychologists' understanding of developmental deficits because they focus on the developmental process itself as a pivotal causal factor in producing atypical phenotypic outcomes. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
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Cell suspensions of Escherichia coli as a model for bacterial populations in wastewaters were treated with ozone as a disinfectant in a continuously operated pilot plant with a plug flow reactor. Suspensions with an initial number of CFU (colony forming units) of 108 mL?1 were ozonized with ozone concentrations up to 12 mg/L. Metabolic activities and membrane functions break down with increasing ozone concentrations. The fluorochromization using 3′,6′-diacetylfluorescein (FDA) proved to be a suitable method for the detection of an alteration in permeability of the cell membranes and an inactivation of metabolic activity. By fluorescence microscopic and photometric investigations it could be clearly demonstrated that, in the case of disinfection with ozone, inactivation of the cells includes first of all a damage of the cell membranes. In contrast to the determination of the number of CFU, fluorochromization allows the detection of alteration in metabolic activities. 相似文献
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The authors explore the extent to which eating disorders, specifically anorexia nervosa (AN) and bulimia nervosa (BN), represent culture-bound syndromes and discuss implications for conceptualizing the role genes play in their etiology. The examination is divided into 3 sections: a quantitative meta-analysis of changes in incidence rates since the formal recognition of AN and BN, a qualitative summary of historical evidence of eating disorders before their formal recognition, and an evaluation of the presence of these disorders in non-Western cultures. Findings suggest that BN is a culture-bound syndrome and AN is not. Thus, heritability estimates for BN may show greater variability cross-culturally than heritability estimates for AN, and the genetic bases of these disorders may be associated with differential pathoplasticity. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
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Johan M. Thevelein 《Yeast (Chichester, England)》1994,10(13):1753-1790