Orientation of the Calcium Channel β Relative to the α12.2 Subunit Is Critical for Its Regulation of Channel Activity

BACKGROUND: The Ca(v)beta subunits of high voltage-activated Ca(2+) channels control the trafficking and biophysical properties of the alpha(1) subunit. The Ca(v)beta-alpha(1) interaction site has been mapped by crystallographic studies. Nevertheless, how this interaction leads to channel regulation has not been determined. One hypothesis is that betas regulate channel gating by modulating movements of IS6. A key requirement for this direct-coupling model is that the linker connecting IS6 to the alpha-interaction domain (AID) be a rigid structure. METHODOLOGY/PRINCIPAL FINDINGS: The present study tests this hypothesis by altering the flexibility and orientation of this region in alpha(1)2.2, then testing for Ca(v)beta regulation using whole cell patch clamp electrophysiology. Flexibility was induced by replacement of the middle six amino acids of the IS6-AID linker with glycine (PG6). This mutation abolished beta2a and beta3 subunits ability to shift the voltage dependence of activation and inactivation, and the ability of beta2a to produce non-inactivating currents. Orientation of Ca(v)beta with respect to alpha(1)2.2 was altered by deletion of 1, 2, or 3 amino acids from the IS6-AID linker (Bdel1, Bdel2, Bdel3, respectively). Again, the ability of Ca(v)beta subunits to regulate these biophysical properties were totally abolished in the Bdel1 and Bdel3 mutants. Functional regulation by Ca(v)beta subunits was rescued in the Bdel2 mutant, indicating that this part of the linker forms beta-sheet. The orientation of beta with respect to alpha was confirmed by the bimolecular fluorescence complementation assay. CONCLUSIONS/SIGNIFICANCE: These results show that the orientation of the Ca(v)beta subunit relative to the alpha(1)2.2 subunit is critical, and suggests additional points of contact between these subunits are required for Ca(v)beta to regulate channel activity

Topology of molecular machines of the endoplasmic reticulum: a compilation of proteomics and cytological data

The endoplasmic reticulum (ER) is a key organelle of the secretion pathway involved in the synthesis of both proteins and lipids destined for multiple sites within and without the cell. The ER functions to both co- and post-translationally modify newly synthesized proteins and lipids and sort them for housekeeping within the ER and for transport to their sites of function away from the ER. In addition, the ER is involved in the metabolism and degradation of specific xenobiotics and endogenous biosynthetic products. A variety of proteomics studies have been reported on different subcompartments of the ER providing an ER protein dictionary with new data being made available on many protein complexes of relevance to the biology of the ER including the ribosome, the translocon, coatomer proteins, cytoskeletal proteins, folding proteins, the antigen-processing machinery, signaling proteins and proteins involved in membrane traffic. This review examines proteomics and cytological data in support of the presence of specific molecular machines at specific sites or subcompartments of the ER

Geospatial Semantics

Geospatial semantics is a broad field that involves a variety of research areas. The term semantics refers to the meaning of things, and is in contrast with the term syntactics. Accordingly, studies on geospatial semantics usually focus on understanding the meaning of geographic entities as well as their counterparts in the cognitive and digital world, such as cognitive geographic concepts and digital gazetteers. Geospatial semantics can also facilitate the design of geographic information systems (GIS) by enhancing the interoperability of distributed systems and developing more intelligent interfaces for user interactions. During the past years, a lot of research has been conducted, approaching geospatial semantics from different perspectives, using a variety of methods, and targeting different problems. Meanwhile, the arrival of big geo data, especially the large amount of unstructured text data on the Web, and the fast development of natural language processing methods enable new research directions in geospatial semantics. This chapter, therefore, provides a systematic review on the existing geospatial semantic research. Six major research areas are identified and discussed, including semantic interoperability, digital gazetteers, geographic information retrieval, geospatial Semantic Web, place semantics, and cognitive geographic concepts.Comment: Yingjie Hu (2017). Geospatial Semantics. In Bo Huang, Thomas J. Cova, and Ming-Hsiang Tsou et al. (Eds): Comprehensive Geographic Information Systems, Elsevier. Oxford, U

Influential Factors for and Outcomes of Hospitalized Patients with Suicide-Related Behaviors: A National Record Study in Taiwan from 1997-2010.

BACKGROUND:Investigating the factors related to suicide is crucial for suicide prevention. Psychiatric disorders, gender, socioeconomic status, and catastrophic illnesses are associated with increased risk of suicide. Most studies have typically focused on the separate influences of physiological or psychological factors on suicide-related behaviors, and have rarely used national data records to examine and compare the effects of major physical illnesses, psychiatric disorders, and socioeconomic status on the risk of suicide-related behaviors. OBJECTIVES:To identify the characteristics of people who exhibited suicide-related behaviors and the multiple factors associated with repeated suicide-related behaviors and deaths by suicide by examining national data records. DESIGN:This is a cohort study of Taiwan's national data records of hospitalized patients with suicide-related behaviors from January 1, 1997, to December 31, 2010. PARTICIPANTS:The study population included all people in Taiwan who were hospitalized with a code indicating suicide or self-inflicted injury (E950-E959) according to the International Classification of Disease, Ninth Revision, Clinical Modification. RESULTS:Self-poisoning was the most common method of self-inflicted injury among hospitalized patients with suicide-related behaviors who used a single method. Those who were female, had been hospitalized for suicide-related behaviors at a younger age, had a low income, had a psychiatric disorder (i.e., personality disorder, major depressive disorder, bipolar disorder, schizophrenia, alcohol-related disorder, or adjustment disorder), had a catastrophic illness, or had been hospitalized for suicide-related behaviors that involved two methods of self-inflicted injury had a higher risk of hospitalization for repeated suicide-related behaviors. Those who were male, had been hospitalized for suicide-related behaviors at an older age, had low income, had schizophrenia, showed repeated suicide-related behaviors, had a catastrophic illness, or had adopted a single lethal method had an increased risk of death by suicide. CONCLUSIONS:High-risk factors should be considered when devising suicide-prevention strategies

Detection of matrix metalloproteinase (MMP)-2 and MMP-9 in canine seminal plasma

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that play a central role in degradation of protein components of the extracellular matrix and basement membrane. Previous studies have shown that MMP-2 and MMP-9 are present in human seminal plasma, but there is little information available on the presence of MMPs in canine seminal plasma. This study aims to investigate the presence of MMPs in canine seminal plasma and their clinical manifestation at the level of various semen parameters in canine species. Latent and active forms of MMP-2 and MMP-9 were evaluated using gelatin zymography and their association with semen parameters was examined. Results demonstrate that both latent and active forms of MMP-2 and MMP-9 are present in canine seminal plasma and the latent forms are predominant. The latent and active MMP-9 activities were elevated in the semen with unsatisfactory quality traits and proMMP-2 was inversely correlated with semen quality whereas, MMP-2 was positively correlated with semen quality traits. These findings suggest that proMMP-9 and MMP-9 activation contributes to the variation in semen, while the activation of MMP-2 improves the sperm functionality. (C) 2011 Elsevier B.V. All rights reserved

Comparison of arthroplasty vs. osteosynthesis for displaced femoral neck fractures: a meta-analysis

Abstract Background This meta-analysis compared clinical outcomes of arthroplasty vs. osteosynthesis for displaced femoral neck fractures. Methods Meta-analysis was performed on the difference in revision rate and overall mortality between participants undergoing osteosynthesis vs. total hip arthroplasty (THA), osteosynthesis vs. hemiarthroplasty (HA), or THA vs. HA. Results Pooled direct and indirect results indicated no significant difference in mortality between THA and HA (pooled OR = 0.87, 95% CI 0.55 to 1.38; P = 0.556), between THA and osteosynthesis (pooled OR = 1.17, 95% CI 0.69 to 1.99; P = 0.553), and between HA and osteosynthesis (pooled OR = 1.21, 95% CI 0.84 to 1.74; P = 0.304). Pooled direct and indirect results indicated no significant difference in revision rates between THA and HA (pooled OR = 0.90, 95% CI 0.26 to 3.19; P = 0.874). But, fewer revisions (OR = 0.19, 95% CI 0.10 to 0.34; P = 0.000) were seen in patients treated with THA than osteosynthesis and also in those treated with HA than osteosynthesis (OR = 0.12, 95% CI 0.07 to 0.20; P = 0.000). After excluding studies without showing normal cognition in inclusion criteria, pooled direct and indirect results also indicated no significant difference in mortality between THA, HA, and osteosynthesis. Similarly, there was no significant difference in revision rates between THA and HA, but HA and THA had significantly lower revision rates compared with osteosynthesis. Conclusions There was no significant difference in overall mortality among osteosynthesis, HA, and THA. However, HA and THA had significantly lower revision rates compared with osteosynthesis. Results of the present study provide support for the use of hip arthroplasty to treat displaced fractures of the femoral neck