The sarcoplasmic reticulum luminal thiol oxidase ERO1 regulates cardiomyocyte excitation-coupled calcium release and response to hemodynamic load

: Two related ER oxidation 1 (ERO1) proteins, ERO1α and ERO1β, dynamically regulate the redox environment in the mammalian endoplasmic reticulum (ER). Redox changes in cysteine residues on intralumenal loops of calcium release and reuptake channels have been implicated in altered calcium release and reuptake. These findings led us to hypothesize that altered ERO1 activity may affect cardiac functions that are dependent on intracellular calcium flux. We established mouse lines with loss of function insertion mutations in Ero1l and Ero1lb encoding ERO1α and ERO1β. The peak amplitude of calcium transients in homozygous Ero1α mutant adult cardiomyocytes was reduced to 42.0 ± 2.2% (n=10, P ≤ 0.01) of values recorded in wild-type cardiomyocytes. Decreased ERO1 activity blunted cardiomyocyte inotropic response to adrenergic stimulation and sensitized mice to adrenergic blockade. Whereas all 12 wild-type mice survived challenge with 4 mg/kg esmolol, 6 of 8 compound Ero1l and Ero1lb mutant mice succumbed to this level of β adrenergic blockade (P ≤ 0.01). In addition, mice lacking ERO1α were partially protected against progressive heart failure in a transaortic constriction model [at 10 wk postprocedure, fractional shortening was 0.31 ± 0.02 in the mutant (n=20) vs. 0.23 ± 0.03 in the wild type (n=18); P ≤ 0.01]. These findings establish a role for ERO1 in calcium homeostasis and suggest that modifying the lumenal redox environment may affect the progression of heart failure

Universal sublinear resistivity in vanadium kagome materials hosting charge density waves

The recent discovery of a charge density (CDW) state in ScV$_6$Sn$_6$ at $T_{\textrm{CDW}}$ = 91 K offers new opportunities to understand the origins of electronic instabilities in topological kagome systems. By comparing to the isostructural non-CDW compound LuV$_6$Sn$_6$, we unravel interesting electrical transport properties in ScV$_6$Sn$_6$, above and below the charge ordering temperature. We observed that by applying a magnetic field along the $a$ axis, the temperature behavior of the longitudinal resistivity in ScV$_6$Sn$_6$ changes from metal-like to insulator-like above the CDW transition. We show that in the charge ordered state ScV$_6$Sn$_6$ follows the Fermi liquid behavior while above that, it transforms into a non-Fermi liquid phase in which the resistivity varies sublinearly over a broad temperature range. The sublinear resistivity, which scales by $T^{3/5}$ is a common feature among other vanadium-containing kagome compounds exhibiting CDW states such as KV$_3$Sb$_5$, RbV$_3$Sb$_5$, and CsV$_3$Sb$_5$. By contrast, the non-Fermi liquid behavior does not occur in LuV$_6$Sn$_6$. We explain the $T^{3/5}$ universal scaling behavior from the Coulomb scattering between Dirac electrons and Van Hove singularities; common features in the electronic structure of kagome materials. Finally, we show anomalous Hall-like behavior in ScV$_6$Sn$_6$ below $T_{\textrm{CDW}}$, which is absent in the Lu compound. Comparing the transport properties of ScV$_6$Sn$_6$ and LuV$_6$Sn$_6$ is valuable to highlight the impacts of the unusual CDW in the Sc compound.Comment: 12 pages, 6 figures. Power law behavior of resistivity as a function temperature is modified and theoretical explanation is added in the second versio

Benchmarking HTAP databases for performance isolation and real-time analytics

Hybrid Transactional/Analytical Processing (HTAP) databases are designed to execute real-time analytics and provide performance isolation for online transactions and analytical queries. Real-time analytics emphasize analyzing the fresh data generated by online transactions. And performance isolation depicts the performance interference between concurrently executing online transactions and analytical queries. However, HTAP databases are extreme lack micro-benchmarks to accurately measure data freshness. Despite the abundance of HTAP databases and benchmarks, there needs to be more thorough research on the performance isolation and real-time analytics capabilities of HTAP databases. This paper focuses on the critical designs of mainstream HTAP databases and the state-of-the-art and state-of-the-practice HTAP benchmarks. First, we systematically introduce the advanced technologies adopted by HTAP databases for real-time analytics and performance isolation capabilities. Then, we summarize the pros and cons of the state-of-the-art and state-of-the-practice HTAP benchmarks. Next, we design and implement a micro-benchmark for HTAP databases, which can precisely control the rate of fresh data generation and the granularity of fresh data access. Finally, we devise experiments to evaluate the performance isolation and real-time analytics capabilities of the state-of-the-art HTAP database. In our continued pursuit of transparency and community collaboration, we will soon make available our comprehensive specifications, meticulously crafted source code, and significant results for public access at https://www.benchcouncil.org/mOLxPBench

Hiring foreign domestic workers out of status, not necessity: reflections on some preliminary findings from Malaysia

Research on foreign domestic workers has been heavily featured in sociology, and to lesser extents, work and employment, economics and international relations. We take an alternative viewpoint seeing the hiring households as consumers in order to investigate their real intentions for hiring foreign domestic workers. This study reports some preliminary findings from a larger scale study which suggests that, surprisingly, hiring intentions have no significant relationship with either necessity or convenience. On the other hand, social status appears to be the most significant predictor of hiring intentions. This study provides some discussions and reflections on this alternative view of foreign domestic workers and calls for further research

An Inferential Metamorphic Testing Approach to Eliminating False Positives in SQLIV Penetration Test

SQL Injection Vulnerability (SQLIV) has been the top-ranked threat to the Web security consistently for many years. Penetration tests, which are a most widely adopted technique to detect SQLIV, are usually affected by testing inaccuracy. This problem is even worse in inference based, blind penetration tests for online Web sites, where Web page variations (such as those caused by inbuilt dynamic modules or user interactions) may lead to a large number of False Positives (FP)

Decreased Anterior Cingulate Cortex γ-Aminobutyric Acid in Youth With Tourette's Disorder

γ-Aminobutyric acid has been implicated in the pathophysiology of Tourette's disorder. The present study primarily sought to examine in vivo γ-aminobutyric acid levels in the anterior cingulate cortex in psychotropic medication-free adolescents and young adults. Secondarily, we sought to determine associations between γ-aminobutyric acid in the anterior cingulate cortex and measures of tic severity, tic-related impairment, and anxiety and depression symptoms. γ-Aminobutyric acid levels were measured using proton magnetic resonance spectroscopy. Analysis of covariance compared γ-aminobutyric acid levels in 15 youth with Tourette's disorder (mean age = 15.0, S.D. = 2.7) and 36 healthy comparison subjects (mean age = 15.9, S.D. = 2.1). Within the Tourette disorder group, we examined correlations between γ-aminobutyric acid levels and tic severity and tic-related impairment, as well as anxiety and depression severity. Anterior cingulate cortex γ-aminobutyric acid levels were lower in participants with Tourette's disorder compared with control subjects. Within the Tourette disorder group, γ-aminobutyric acid levels did not correlate with any clinical measures. Our findings support a role for γ-aminobutyric acid in Tourette's disorder. Larger prospective studies will further elucidate this role

LIN28B promotes colon cancer migration and recurrence.

LIN28B is involved in "stemness" and tumourigenesis by negatively regulating the maturation of let-7 microRNA family members. In this study, we showed that LIN28B expression promotes migration and recurrence of colon cancer. Immunohistochemistry and reverse-transcription polymerase chain reactions were performed to detect LIN28B expression in colon cancer tissue microarrays, paraffin-embedded surgical resected tissues and cancer cells. Loss-of-function, migration and proliferation analyses were performed to delineate the potential roles of LIN28B in colon cancer. LIN28B was upregulated in colon cancer tissue compared to normal mucosa, and its overexpression correlated with reduced patient survival and increased tumour recurrence. LIN28B suppression inhibited the migration of SW480 colon cancer cells and facilitated the cytotoxicity induced by oxaliplatin in SW480 and HCT116 colon cancer cells. In conclusion, LIN28B overexpression contributes to colon tumourigenesis, and LIN28B may serve as a diagnostic tool and therapeutic target for colon cancer