Role of the HSP70 Co-Chaperone SIL1 in Health and Disease

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.     

An experiential account of phantom vibration syndrome

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.     

Sleep Disorders Reduce Health-Related Quality of Life in Multiple Sclerosis (Nottingham Health Profile Data in Patients with Multiple Sclerosis)

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.     

Modeling language acquisition in atypical phenotypes.

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)     

Are eating disorders culture-bound syndromes? Implications for conceptualizing their etiology.

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)     

低强度激光血管内照射对海洛因戒断综合征的疗效观察

对于毒瘾戒断综合症的治疗一般采用强行戒断或逐步撤药等方法 ,但患者非常痛苦 ,且复吸率较高。为了观察低强度He -Ne激光对戒断症状的抑制作用 ,本文用低强度激光血管内照射疗法对 3 0例吸毒戒断综合征患者进行了治疗 ,并与对照组比较。结果证明 :实验组疗效明显优于对照组 (P <0 .0 1) ,为进一步的临床应用提供了临床依据。     

Health and Indoor Climate Complaints of 7043 office Workers in 61 Buildings in the Netherlands

During the winter of 1988/1989, the relationships between the prevalence of work-related health and indoor climate complaints and a number of building, management, workplace and personal characteristics have been investigated in a study in more than 60 office buildings located throughout the Netherlands. To collect the information, a questionnaire was prepared on health and indoor climate complaints and personal and workplace characteristics. A checklist was used to obtain information on building characteristics More than 7000 questionnaires were completed by the regular users of the buildings investigated. The results showed that the prevalence of symptoms was higher in air-conditioned buildings than in naturally or mechanically ventilated buildings. some other variables were also related with most work-related complaints after adjustment for selected management, personal, workplace and job characteristics. These included gender, work satisfaction in general, presence of allergies and/or respiratory symptoms, and personal control over temperature at the workplace. No differences were found in symptom prevalences between buildings with spray and steam humidification. The combination of air-conditioning and humidification did not lead to further increases in the prevalence of complaints as compared to buildings with only airconditioning or only humidification.     

Diagnostic Data Compression Techniques for Embedded Memories with Built-In Self-Test

A system-on-chip (SOC) usually consists of many memory cores with different sizes and functionality, and they typically represent a significant portion of the SOC and therefore dominate its yield. Diagnostics for yield enhancement of the memory cores thus is a very important issue. In this paper we present two data compression techniques that can be used to speed up the transmission of diagnostic data from the embedded RAM built-in self-test (BIST) circuit that has diagnostic support to the external tester. The proposed syndrome-accumulation approach compresses the faulty-cell address and March syndrome to about 28% of the original size on average under the March-17N diagnostic test algorithm. The key component of the compressor is a novel syndrome-accumulation circuit, which can be realized by a content-addressable memory. Experimental results show that the area overhead is about 0.9% for a 1Mb SRAM with 164 faults. A tree-based compression technique for word-oriented memories is also presented. By using a simplified Huffman coding scheme and partitioning each 256-bit Hamming syndrome into fixed-size symbols, the average compression ratio (size of original data to that of compressed data) is about 10, assuming 16-bit symbols. Also, the additional hardware to implement the tree-based compressor is very small. The proposed compression techniques effectively reduce the memory diagnosis time as well as the tester storage requirement.