Al-2 quorum-sensing inhibitors affect the starvation response and reduce virulence in several <i>Vibrio</i> species, most likely by interfering with LuxPQ

The increase of disease outbreaks caused by Vibrio species in aquatic organisms as well as in humans, together with the emergence of antibiotic resistance in Vibrio species, has led to a growing interest in alternative disease control measures. Quorum sensing (QS) is a mechanism for regulating microbial gene expression in a cell density-dependent way. While there is good evidence for the involvement of auto-inducer 2 (AI-2)-based interspecies QS in the control of virulence in multiple Vibrio species, only few inhibitors of this system are known. From the screening of a small panel of nucleoside analogues for their ability to disturb AI-2-based QS, an adenosine derivative with a p-methoxyphenylpropionamide moiety at C-3′ emerged as a promising hit. Its mechanism of inhibition was elucidated by measuring the effect on bioluminescence in a series of Vibrio harveyi AI-2 QS mutants. Our results indicate that this compound, as well as a truncated analogue lacking the adenine base, block AI-2-based QS without interfering with bacterial growth. The active compounds affected neither the bioluminescence system as such nor the production of AI-2, but most likely interfered with the signal transduction pathway at the level of LuxPQ in V. harveyi. The most active nucleoside analogue (designated LMC-21) was found to reduce the Vibrio species starvation response, to affect biofilm formation in Vibrio anguillarum, Vibrio vulnificus and Vibrio cholerae, to reduce pigment and protease production in V. anguillarum, and to protect gnotobiotic Artemia from V. harveyi-induced mortality

Exploración vocacional en adolescentes: evaluación de una intervención en clase

Analisa-se o impacto de uma intervenção psicológica na exploração e tomada de decisão vocacional em adolescentes portugueses. Em contexto curricular e de classe, desenvolveram-se actividades de exploração do meio e do Eu com 39 alunos e 43 alunas do 9o ano, entre 13 e 17 anos (M=14,4, DP=0,95). Em um design pré/pós-teste, aplicaram-se o Career Exploration Survey (CES) e o Career Decision Difficulties Questionnaire (CDDQ). Os resultados do teste do sinal evidenciaram ganhos significativos (p<0,01) nas dimensões de exploração e diminuição significativa da falta de informação profissional (p<0,01) e do total das dificuldades de decisão (p<0,05). Observou-se um padrão de correlações negativas (ró de Spearman) entre as duas medidas vocacionais, evidenciando uma relação entre a informação explorada na intervenção e a diminuição das dificuldades de decisão por falta de motivação. Em geral, os resultados suportam a importância do papel da exploração da carreira na diminuição das dificuldades de tomada de decisão.This study analyses the impact of a psychological intervention to promote vocational exploration and decisionmaking in Portuguese adolescents. Activities to foster exploration of self and environment were developed in a classroom program with 39 boys and 43 girls, all 9th grade students, between 13 and 17 years of age (M=14,4, SD=0.95). Following a pre/post-test design, the Career Exploration Survey (CES), and the Career Decision Difficulties Questionnaire (CDDQ) were administered. Results of sign-test showed significant increments (p<0.01) in all of the exploration dimensions, significant reduction of lack of occupational information (p<0.01) and of the total of career decision-making difficulties (p<0.05). Negative correlations (Spearman’s rho) between the two career measures was observed, evidencing a relationship between information explored during intervention and decreased difficulty with decision-making due to lack of motivation. In general, results support the importance of career exploration on diminishing decision-making difficulties.Evalúa-se el impacto de una intervención psicológica que fomenta la exploración y la decisión vocacional en adolescentes portugueses. Fueran efectuadas actividades de exploración del medio ambiente y del yo en contexto curricular de clase con 39 alumnos y 43 alumnas del curso 3º ESO, 13 hasta 17 años (M=14,4, DP=0,95). Utilizó-se un diseño pre/posteste, con aplicación del Career Exploration Survey (CES) y Career Decision Difficulties Questionnaire (CDDQ). Resultados del test del señal evidencian beneficios significativos (p<0,01) en las dimensiones de la exploración, reducción significativa de ausencia de información ocupacional (p<0,01) y total de dificultades de decisión (p<0,05). Ha sido observado un patrón de correlaciones negativas (ró de Spearman) entre las dos medidas vocacionales, mostrando relación entre la información explorada e la disminución de las dificultades de decisión por falta de motivación. En general, resultados sostienen la importancia de la exploración de carrera en la disminución de las dificultades de decisió

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls.

PURPOSE: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate. METHODS: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants. RESULTS: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 × 10-18) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 × 10-13). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency. CONCLUSION: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing

Mathematical principle of cellular accommodation: A Schmitt trigger approach

WOS: 000374694400001Hysteresis usage was occupied to many physical problems. Up to today, there is a limited contributions to describe 3D bone remodeling algorithm. Many theories were developed to light mechanotranduction of bone tissue. Unfortunately current models are very far from explaining the situation of bone remodeling at loadless condition such as neutral axis of long bones and skull. They are supposed to resorp due to disuse atrophy according to background algorithms. At this point, Schmitt trigger-bistable circuit approach can be considered as a novel concept. It may establish a conceptual backbone as a process memory. It assumes the density retains its value until the input changes sufficiently to switch a change. In the load-carrying configuration, when the strain is higher than a certain threshold according to bone's strain history factor (SHF), the density is supposed to be high. However, in the loadless condition, the density rate is supposed to be low due to moderate strain history factor values, the density will retain its value. This system is very appropriate to solve bone remodeling. The purpose of this manuscript is to folds: first to consolidate a novel mathematical model for cellular accomodation, second to develop graphical representation for novel hysteresis functions

Active Free Surface Density Maps

International Conference on Quantum Science and Applications (ICQSA) -- MAY 25-27, 2016 -- Eskisehir Osmangazi University, Eskisehir, TURKEYWOS: 000440515300024Percolation problems were occupied to many physical problems after their establishment in 1957 by Broadbent and Hammersley. They can be used to solve complex systems such as bone remodeling. Volume fraction method was adopted to set some algorithms in the literature. However, different rate of osteoporosis could be observed for different microstructures which have the same mass density, mechanical stimuli, hormonal stimuli and nutrition. Thus it was emphasized that the bone might have identical porosity with different specific surfaces. Active free surface density of bone refers the used total area for its effective free surface. The purpose of this manuscript is to consolidate a mathematical approach which can be called as "active free surface density maps" for different surface patterns and derive their formulations. Active free surface density ratios were calculated for different Archimedean lattice models according to Helmholtz free energy and they were compared with their site and bond percolation thresholds from the background studies to derive their potential probability for bone remodeling.Eskisehir Osmangazi Univ, Ctr Quantum Res & Applications, Eskisehir Osmangazi Univ (ESOGU