Regulation of CLC-1 chloride channel biosynthesis by FKBP8 and Hsp90β.

Mutations in human CLC-1 chloride channel are associated with the skeletal muscle disorder myotonia congenita. The disease-causing mutant A531V manifests enhanced proteasomal degradation of CLC-1. We recently found that CLC-1 degradation is mediated by cullin 4 ubiquitin ligase complex. It is currently unclear how quality control and protein degradation systems coordinate with each other to process the biosynthesis of CLC-1. Herein we aim to ascertain the molecular nature of the protein quality control system for CLC-1. We identified three CLC-1-interacting proteins that are well-known heat shock protein 90 (Hsp90)-associated co-chaperones: FK506-binding protein 8 (FKBP8), activator of Hsp90 ATPase homolog 1 (Aha1), and Hsp70/Hsp90 organizing protein (HOP). These co-chaperones promote both the protein level and the functional expression of CLC-1 wild-type and A531V mutant. CLC-1 biosynthesis is also facilitated by the molecular chaperones Hsc70 and Hsp90β. The protein stability of CLC-1 is notably increased by FKBP8 and the Hsp90β inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) that substantially suppresses cullin 4 expression. We further confirmed that cullin 4 may interact with Hsp90β and FKBP8. Our data are consistent with the idea that FKBP8 and Hsp90β play an essential role in the late phase of CLC-1 quality control by dynamically coordinating protein folding and degradation

The ACR11 encodes a novel type of chloroplastic ACT domain repeat protein that is coordinately expressed with GLN2 in Arabidopsis

<p>Abstract</p> <p>Background</p> <p>The ACT domain, named after bacterial aspartate kinase, chorismate mutase and TyrA (prephenate dehydrogenase), is a regulatory domain that serves as an amino acid-binding site in feedback-regulated amino acid metabolic enzymes. We have previously identified a novel type of ACT domain-containing protein family, the ACT domain repeat (ACR) protein family, in <it>Arabidopsis</it>. Members of the ACR family, ACR1 to ACR8, contain four copies of the ACT domain that extend throughout the entire polypeptide. Here, we describe the identification of four novel ACT domain-containing proteins, namely ACR9 to ACR12, in <it>Arabidopsis</it>. The ACR9 and ACR10 proteins contain three copies of the ACT domain, whereas the ACR11 and ACR12 proteins have a putative transit peptide followed by two copies of the ACT domain. The functions of these plant ACR proteins are largely unknown.</p> <p>Results</p> <p>The ACR11 and ACR12 proteins are predicted to target to chloroplasts. We used protoplast transient expression assay to demonstrate that the <it>Arabidopsis </it>ACR11- and ACR12-green fluorescent fusion proteins are localized to the chloroplast. Analysis of an <it>ACR11 </it>promoter-β-glucuronidase (GUS) fusion in transgenic <it>Arabidopsis </it>revealed that the GUS activity was mainly detected in mature leaves and sepals. Interestingly, coexpression analysis revealed that the <it>GLN2</it>, which encodes a chloroplastic glutamine synthetase, has the highest mutual rank in the coexpressed gene network connected to <it>ACR11</it>. We used RNA gel blot analysis to confirm that the expression pattern of <it>ACR11 </it>is similar to that of <it>GLN2 </it>in various organs from 6-week-old <it>Arabidopsis</it>. Moreover, the expression of <it>ACR11 </it>and <it>GLN2 </it>is highly co-regulated by sucrose and light/dark treatments in 2-week-old <it>Arabidopsis </it>seedlings.</p> <p>Conclusions</p> <p>This study reports the identification of four novel ACT domain repeat proteins, ACR9 to ACR12, in <it>Arabidopsis</it>. The ACR11 and ACR12 proteins are localized to the chloroplast, and the expression of <it>ACR11 </it>and <it>GLN2 </it>is highly coordinated. These results suggest that the <it>ACR11 </it>and <it>GLN2 </it>genes may belong to the same functional module. The <it>Arabidopsis </it>ACR11 protein may function as a regulatory protein that is related to glutamine metabolism or signaling in the chloroplast.</p

Psychological Pathway from Obesity-Related Stigma to Anxiety via Internalized Stigma and Self-Esteem among Adolescents in Taiwan

The objective of this research was to examine the pathway from public stigma, to perceived stigma, to depression in adolescents via internalized stigma. Adolescents in grade 7 through 9 from a junior high school in Changhua County in Taiwan completed self-administered surveys from March to July in 2018. Adolescents were asked questions regarding depressive symptoms, obesity-related perceived stigma, and internalized stigma. Structural equation modeling was used to fit the pathway model. The pathway was first analyzed with the full sample and then stratified by actual and perceived weight status. Our final analytic sample consisted of 464 adolescents. The pathway model suggested an acceptable model fit. Perceived weight stigma (PWS) was significantly associated with internalized stigma regardless of actual or self-perceived weight status. Internalized stigma was significantly associated with anxiety for both actual (β = 0.186) and self-perceived nonoverweight (non-OW) participants (β = 0.170) but not for overweight (OW) participants (neither actual nor self-perceived). For OW adolescents, perceived weight stigma was associated with anxiety. However, the internalization process did not exist. It may be that the influence of perceived weight stigma is larger than internalized stigma on anxiety. It may also be that the level of internalization was not yet high enough to result in anxiet

Review of Recently Progress on Neural Electronics and Memcomputing Applications in Intrinsic SiOx-Based Resistive Switching Memory

In this chapter, we focus on the recent process on memcomputing (memristor + computing) in intrinsic SiOx-based resistive switching memory (ReRAM or called memristor). In the first section of the chapter, we investigate neuromorphic computing by mimicking the synaptic behaviors in integrating one-diode and one-resistive switching element (1D-1R) architecture. The power consumption can be minimized further in synaptic functions because sneak-path current has been suppressed and the capability for spike-induced synaptic behaviors has been demonstrated, representing critical milestones and achievements for the application of conventional SiOx-based materials in future advanced neuromorphic computing. In the next section of chapter, we will discuss an implementation technique of implication operations for logic-in-memory computation by using a SiOx-based memristor. The implication function and its truth table have been implemented with the unipolar or nonpolar operation scheme. Furthermore, a circuit with 1D-1R architecture with a 4 × 4 crossbar array has been demonstrated, which realizes the functionality of a one-bit full adder as same as CMOS logic circuits with lower design area requirement. This chapter suggests that a simple, robust approach to realize memcomputing chips is quite compatible with large-scale CMOS manufacturing technology by using an intrinsic SiOx-based memristor

Delayed Suspicion, Treatment and Isolation of Tuberculosis Patients in Pulmonology/Infectious Diseases and Non-Pulmonology/Infectious Diseases Wards

Background/PurposeDelayed diagnosis and isolation increases the risk of nosocomial transmission of tuberculosis (TB). To assess the risk of delayed management of TB, we analyzed the risk factors of prolonged delay in isolation of smear-positive TB patients in pulmonology/infectious diseases and other wards in a tertiary teaching hospital.MethodsWe enrolled smear-positive TB patients aged > 16 years with delayed respiratory isolation following hospitalization. Medical records were reviewed retrospectively. Time intervals between admission, order of sputum acid-fast staining, initiation of anti-tuberculous treatment and isolation were compared between pulmonology/infectious diseases wards (PIWs) and other wards. Risk factors were analyzed in patients with prolonged isolation delay of > 7 days in individual groups.ResultsIsolation was delayed in 191 (73.7%) of 259 hospitalized smear-positive TB patients. Median suspicion, treatment and isolation delays were 0, 3 and 4 days in PIWs and 1, 5 and 7 days in other wards. For patients admitted to non-PIWs, atypical chest radiographs, symptoms without dyspnea or not being admitted from the emergency department (ED) were risk factors for prolonged isolation delay exceeding 7 days. The only risk factor for delayed isolation in patients admitted to PIWs was age ≥ 70 years.ConclusionDelays in suspicion, treatment and isolation of TB patients were longer in non-PIWs. Clinicians should be alert to those admitted to non-PIWs with atypical chest radiographs, atypical symptoms, or not admitted from the ED

EFFECT OF ORAL ADMINISTRATION OF PHERETIMA ASPERGILLUM (EARTHWORM) IN RATS WITH CEREBRAL INFARCTION INDUCED BY MIDDLE-CEREBRAL ARTERY OCCLUSION.

We investigated the curative effect of Pheretima aspergillum (earthworm, PA) on rats with middle cerebral artery occlusion (MCAo). The MCAo-induced cerebral infarction was established and its underlying mechanisms by counting the infarction areas and evaluating the rats’ neurological status. Immunostaining was used to test the expression of NeuN, and glial fibrillary acidic (GFAP), S100B, and brain-derived neurotrophic factor (BDNF) proteins. Our results showed that oral administration of PA for two weeks to rats with MCAo successfully reduced cerebral infarction areas in the cortex and striatum, and also reduced scores of neurological deficit. The PA-treated MCAo rats showed greatly decreased neuronal death, glial proliferation, and S100B proteins in the penumbra area of the cortex and in the ischemic core area of the cortex, but BDNF did not changed. These results demonstrated novel and detailed cellular mechanisms underlying the neuroprotective effects of PA in MCAo rats

Influences of Stacking Architectures of TiO 2

We investigated the influences of stacking architectures of the TiO2 nanoparticle layers on characteristics and performances of DSSCs. TiO2 nanoparticles of different sizes and compositions were characterized for their morphological and optical/scattering properties in thin films. They were used to construct different stacking architectures of the TiO2 nanoparticle layers for use as working electrodes of DSSCs. Characteristics and performances of DSSCs were examined to establish correlation of the stacking architectures of TiO2 nanoparticle layers with characteristics of DSSCs. The results suggest that the three-layer DSSC architecture, with sandwiching a 20 nm TiO2 nanoparticle layer between a 37 nm TiO2 nanoparticle layer and a hundred nm sized TiO2 back scattering/reflection layer, is effective in enhancing DSSC efficiencies. The high-total-transmittance 37 nm TiO2 nanoparticle layer with a larger haze can serve as an effective front scattering layer to scatter a portion of the incident light into larger oblique angles and therefore increase optical paths and absorption