High binding affinity of repressor IoIR avoids costs of untimely induction of myo-inositol utilization by Salmonella Typhimurium

Growth of Salmonella enterica serovar Typhimurium strain 14028 with myo-inositol (MI) is characterized by a bistable phenotype that manifests with an extraordinarily long (34 h) and variable lag phase. When cells were pre-grown in minimal medium with MI, however, the lag phase shortened drastically to eight hours, and to six hours in the absence of the regulator IoIR. To unravel the molecular mechanism behind this phenomenon, we investigated this repressor in more detail. Flow cytometry analysis of the iolR promoter at a single cell level demonstrated bistability of its transcriptional activation. Electrophoretic mobility shift assays were used to narrow the potential binding region of IoIR and identified at least two binding sites in most iol gene promoters. Surface plasmon resonance spectroscopy quantified IolR binding and indicated its putative oligomerization and high binding affinity towards specific iol gene promoters. In competitive assays, the ioIR deletion mutant, in which iol gene repression is abolished, showed a severe growth disadvantage of -15% relative to the parental strain in rich medium. We hypothesize that the strong repression of iol gene transcription is required to maintain a balance between metabolic flexibility and fitness costs, which follow the inopportune induction of an unusual metabolic pathway

Defining clinical trial quality from the perspective of resource-limited settings: a qualitative study based on interviews with investigators, sponsors, and monitors conducting clinical trials in sub-Saharan Africa

In recent decades, the quality management of clinical trials has been criticised for being inefficient and ineffective. This has led to a waste of clinical trial investment and has made it particularly difficult to conduct clinical trials in settings with limited resources. The lack of a universally accepted comprehensive definition of clinical trial quality was suggested as one of the possible causes of inadequate quality management. However, resource-limited countries were not considered in the attempt to create such a definition. In our study, we developed a quality concept based on qualitative interviews from the perspective of investigators, sponsors, and monitors with experience in conducting clinical trials in sub-Saharan Africa. The analysis of these stakeholders' definitions of clinical trial quality has produced a Clinical Trial Quality Concept that includes quality promoting factors (i.e., Context adaptation; Infrastructure; Partnership; Operational excellence; Quality system) in addition to conventional scientific and ethical factors. The results thus support the need for a multidimensional quality concept to reflect clinical trial quality more comprehensively. We recommend the term "Comprehensive Quality Management (CQM)" for this concept. CQM has the potential to serve as a basis for the current revision of quality management principles in international clinical trial guidelines. Furthermore, the sub-Saharan African perspective has highlighted additional considerations compared to the existing comprehensive INQUIRE clinical trial quality framework. Therefore, we propose including the following three points relevant to resource-limited settings in the framework: 1) Communicating potential infrastructural disadvantages to funders, sponsors, and auditors. 2) Preventing potential exploitation of research populations and workforce in low- and middle-income countries by following existing ethical frameworks. 3) Including "Context adaptation" as an additional framework category (i.e., promoting factor)

Defining clinical trial quality from the perspective of resource-limited settings: A qualitative study based on interviews with investigators, sponsors, and monitors conducting clinical trials in sub-Saharan Africa

Background Increasing clinical trial cost and complexity, as well as a high waste of clinical trial investment over the past decades, have changed the way clinical trial quality is managed. Recent evidence has highlighted that the lack of a clear clinical trial quality definition may have contributed to previous inefficiencies. This study aims to support the understanding of what clinical trial quality entails from the perspective of resource-limited settings. Methodology/Principal findings We conducted 46 semi-structured interviews involving investigators, sponsors, and monitors with experience in conducting clinical trials in 27 countries in sub-Saharan Africa. The questionnaire addressed the overall meaning of clinical trial quality and a conclusive clinical trial quality definition, as well as specific aspects of resource-limited settings across the clinical trial process. We held the interviews either in person, via Skype or by phone. They were recorded and transcribed verbatim, and we performed the analysis using The Framework Method. The analysis of clinical trial quality definitions resulted in 11 elements, which were summarised into a clinical trial quality concept consisting of two components: 1) clinical trial quality building factors (Scientific factors and Moral factors) and 2) promoting factors (Context adaptation; Infrastructure; Partnership; Operational excellence; Quality system). 12 resource-limited settings specific themes were identified. These themes were all categorised under the promoting factors "Context adaptation", "Infrastructure", and "Partnership". Conclusions/Significance We found that in order to enable comprehensive clinical trial quality management, clinical trial quality should be defined by a multidimensional concept that includes not only scientific and ethical, but also quality-promoting factors. Such a concept is of general relevance and not limited to clinical trials in resource-limited settings, where it naturally carries particular weight. In addition, from the perspective of sub-Saharan Africa, we identified specific categories that appear to be critical for the conduct of clinical trials in resource-limited settings, and we propose respective changes to a particular existing clinical trial quality framework (i.e., INQUIRE)

Comparison of two non-invasive arterial blood pressure monitoring techniques in brown bears (Ursus arctos)

Monitoring arterial blood pressure (BP), represents a more accurate evaluation of hemodynamics than heart rate alone and is essential for preventing and treating infra- and post-operative complications in wildlife chemical immobilization.The objectives of the study were to test the correlation between standard oscillometry and Korotkoffs technique in anesthetized free-ranging brown bears in Croatia and Scandinavia and to assess the blood pressure in both locations.Five bears were snared and darted with xylazine and ketamine in Croatia, and 20 bears were darted from a helicopter with medetomidine and tiletamine-zolazepam in Scandinavia. Blood pressure was simultaneously measured with both techniques every 5 minutes. Correlation between techniques, trends of BP variation, and the factors of the capture which likely influenced BP were assessed.Successful measurements of BP were achieved in 93% of all attempts with the Korotkoffs technique but in only 29% of all attempts with oscillometry. The latter method mostly provided lower values of BP compared to Korotkoffs technique in yearlings. Most bears showed a decreasing trend in systolic and mean BP over time, consistent between the two techniques. All bears were hypertensive: the auscultatory technique detected moderate to severe systolic hypertension in 25% and 84% of bears in Croatia and in Scandinavia, respectively, with significantly higher BP in subadults and adults compared to yearlings. Only Korotkoffs method resulted in a reliable and effective tool for BP assessment in brown bears. The anesthetic protocols used in the present study in association with the capture methods produced hypertension in all animals

Personality traits and social entrepreneurship dimensions in Peru and Argentina

Esta investigación busca ampliar la comprensión de la influencia de los 5 Grandes Rasgos de Personalidad en las dimensiones del emprendimiento social (visión social, sostenibilidad, redes sociales, innovación y retorno financiero) para el caso de los emprendedores sociales argentinos y peruanos. Estudios previos han empleado muestras de estudiantes y, mayormente se han enfocado en contextos ajenos al Latinoamericano. Este estudio es original en la medida que analiza una muestra única de empresarios sociales que operan en países donde el emprendimiento social, si bien considerado valioso, no ha sido investigado en profundidad.  Se recopilaron datos de 109 empresarios sociales peruanos y argentinos a través de cuestionarios en línea. Se realizó un análisis factorial exploratorio separado para las variables dependientes y las independientes. Los hallazgos indican que el rasgo Afabilidad es el más influyente en las dimensiones del emprendedor social. El rasgo Apertura influye positiva y significativamente en las dimensiones Creación de redes sociales e Innovación. El rasgo Extraversión influye positivamente en las dimensiones Creación de redes sociales y Retorno financiero. Finalmente, el rasgo Neuroticismo influye significativa y negativamente en la dimensión redes sociales. Además, se encontraron diferencias entre las muestras peruanas y argentinas, que podrían derivarse del contexto cultural y económico.This research aims to increase the comprehension of the influence of the Big 5 Personality Traits on social entrepreneurship dimensions (social vision, sustainability, social network, innovation and financial returns) in the context of Argentinian and Peruvian social enterprises. Previous research was often based on student samples and most of them do not integrate the Latin American landscape. This paper presents a unique sample of entrepreneurs operating in countries where social entrepreneurship has not been deeply investigated, but considered as potentially relevant to bridge the division between the State and the free market in providing sustainable resources for the social sector growth. Data from 109 Peruvian and Argentinian social entrepreneurs was collected via online questionnaires, and analyzed using a separate exploratory factor analysis for the dependent and independent constructs. Findings indicate Conscientiousness as the most influential personality trait in social entrepreneur’s dimensions, affecting all except for financial returns. Openness has significantly positive influence to social network and innovation, as Extroversion to social network and financial returns, with a significantly negative influence to sustainability. Finally, Neuroticism has significantly negative influence to social networks. Additionally, differences between Peruvian and Argentinian samples were found and could stem from cultural-economic context

On the Corbeled Arch in the Maya Architecture

Estudio exploratorio pretende identificar, a través de una revisión documental, las prácticas de gestión de los recursos humanos que se consideran parte de la actuación socialmente responsable de las empresas peruanas que realizan reportes de sostenibilidad. De esa forma se busca determinar si existe un vínculo entre esas prácticas y la gestión de recursos humanos sostenible. En el proceso de selección de las prácticas se ha tomado el enfoque de los sistemas de trabajo sostenibles como una aproximación general que permite acercarnos a la comprensión de la gestión de recursos humanos sostenible

Stimmungsbild zu den Auswirkungen von Covid-19 auf die österreichische Versicherungswirtschaft : eine ad-hoc-Studie, durchgeführt von der ZHAW School of Management and Law und Mazars im Juni 2020

Das Institut für Risk & Insurance der ZHAW School of Management and Law und Mazars haben 11 Versicherer zu den Herausforderungen und Auswirkungen von Covid-19 auf die Österreichische Versicherungswirtschaft befragt. Die Gespräche zeigen, dass die Unternehmen vor unterschiedlichen Herausforderungen stehen, wie die Umstellung auf Home-Office Betrieb. Die größte Sorge bereitet die Unsicherheit bezüglich Pandemieverlauf, Finanzmarkt und Konjunktur. Gefragt nach den Auswirkungen auf das Geschäftsmodell ist klar, die Krise wirkt als Katalysator in Sachen Digitalisierung

Development and evaluation of a test to measure pedagogical content knowledge of biology teachers

In der Diskussion um professionelle Kompetenzen von Lehrkräften ist das Verhältnis von Wissen und unterrichtlichem Können bis heute unzureichend geklärt. Der vorliegende Artikel bietet eine Einführung in zentrale theoretische Modelle, die sich mit dem Zusammenwirken von Wissen und Können bei Lehrern beschäftigen. In aktuellen Modellen spielt das Reflexionswissen beziehungsweise die Reflexionsfähigkeit der Lehrkräfte eine zentrale Rolle, um das professionelle Wissen und Können miteinander in Bezug setzen zu können. Damit fällt dem Reflexionswissen eine bedeutende Schlüsselposition in der Ausbildung professioneller Kompetenz von Lehrkräften zu. In der hier vorliegenden Studie wurde ein videoclipgestützter Papier- und Bleistifttest zur Erfassung des fachdidaktischen Reflexionswissens von Biologielehrkräften entwickelt und hinsichtlich klassischer Testgütekriterien evaluiert. In der Diskussion werden die Einsatzmöglichkeiten des entwickelten Instruments in der Grundlagenforschung und der Lehrerbildung herausgearbeitet. (DIPF/Orig.)To date the unsolved problem of the relation of declarative knowledge and teaching skills forms a central component of the discourses about teachers\u27 professional competence. The present article offers an introduction to the most important models regarding to the relation of teachers\u27 declarative knowledge and teaching skills. It is shown that current models ascribe teacher reflection as an important aspect for integrating declarative knowledge and teaching skills. With this significant key position, reflection is a central part of teachers\u27 professional competence. The study at hand was designed as a video clip-supported paper and pencil test for measuring teachers\u27 pedagogical content knowledge and related reflections. Within the scope of the results the measuring instruments as well as psychometrical quality criteria are introduced. Finally, the various applications for usage of the developed instruments in the field of basic research and teacher education are discussed. (DIPF/Orig.

Mutations in the Non-Helical Linker Segment L1-2 of Keratin 5 in Patients with Weber-Cockayne Epidermolysis Bullosa Simplex

Keratins are the major structural proteins of the epidermis. Analyzing keratin gene sequences, appreciating the switch in keratin gene expression that takes place as epidermal cells commit to terminally differentiate, and elucidating how keratins assemble into 10 nm filaments, have provided the foundation that has led to the discoveries of the genetic bases of two major classes of human skin diseases, epidermolysis bullosa simplex (EBS) and epidermolytic hyperkeratosis (EH). These diseases involve point mutations in either the basal epidermal keratin pair, K5 and K14 (EBS), or the suprabasal pair, K1 and K10 (EH). In severe cases of EBS and EH, mutations are found in the highly conserved ends of the α-helical rod domain, regions that, by random mutagenesis, had already been found to be important for 10 nm filament assembly. In order to identify regions of the keratin polypeptides that might be more subtly involved in 10 nm filament assembly and to explore the diversity in mutations within milder cases of these diseases, we have focused on Weber-Cockayne EBS, where mild blistering occurs primarily on the hands and feet in response to mechanical stress. In this report, we show that affected members of two different W-C EBS families have point mutations within 1 residue of each other in the non-helical linker segment of the K5 polypeptide. Genetic linkage analyses, the absence of this mutation in \u3e150 wild-type alleles and filament assembly studies suggest that these mutations are responsible for the W-C EBS phenotype. These findings provide the best evidence to date that the non-helical linker region in the middle of the keratin polypeptides plays a subtle but significant role in intermediate filament structure and/or intermediate filament cytoskeletal architecture

Germinação de sementes de maracujá-amarelo em extrato aquoso de tiririca e ácido giberélico

Allelopathy refers to the ability of certain plant has to interfere with the metabolism of other compounds by chemicals released into the environment. Cyperus rotundus is a typical example of such a plant, having a high IBA concentration and being able to influence and act on germination and rooting of the other plants. The aim of this study was to evaluate the effect of bulbs and leaves extracts of Cyperus rotundus and gibberellic acid on the yellow passion fruit germination cycle. To obtain the aqueous extract bulbs and leaves were used along with a concentration of 1 g 10 mL-1 (p/v) (1 g of material plant to 10 mL of distilled water), forming stock solutions. Extracts were diluted in five concentrations (20, 40, 60, 80 and 100%) and five concentrations of gibberellic acid (200, 400, 600, 800 and 1000 mg L-1 GA3) were used. As a control treatment we used distilled water. The experimental design was completely randomized, with 16 treatments, five replicates, totaling 80 sampling units, each unit containing ten seeds. Daily counts were performed on the number of germinated seeds for subsequent calculation of germination percentage and germination speed index. Seeds of yellow passion fruit treated with concentrations of gibberellic acid had their germination inhibited and it is not recommended in the germination of the species. Concentrations of aqueous extract of leaves and sedge did not affect the germination of yellow passion fruit.Alelopatia se refere à capacidade que determinada planta possui de interferir no metabolismo de outra, por meio de compostos químicos liberados no meio. A tiririca é um exemplo típico deste tipo de planta, possuindo elevada concentração de ácido indolbutírico, podendo agir na germinação e enraizamento de outras plantas. Diante do exposto, objetivou-se com o presente trabalho avaliar o efeito de extratos de bulbos e folhas de tiririca e ácido giberélico na germinação de sementes de maracujá-amarelo. Para a obtenção dos extratos aquosos de tiririca utilizaram-se bulbos e folhas na concentração de 1 g 10 mL-1 (p/v) (1 g de matéria vegetal para 10 mL de água destilada), constituindo as soluções estoque. Foram utilizados extratos diluídos em cinco concentrações (20, 40, 60, 80 e 100%) e cinco concentrações de ácido giberélico (200, 400, 600, 800 e 1000 mg L-1 GA3). Como tratamento controle utilizou-se água destilada. O delineamento experimental foi inteiramente casualizado, apresentando 16 tratamentos, contendo cinco repetições, totalizando 80 unidades amostrais, contendo cada unidade dez sementes. Diariamente realizaram-se contagens do número de sementes germinadas para posterior cálculo de percentagem de germinação e Índice de Velocidade de Germinação. Sementes de maracujá-amarelo submetidas às concentrações de ácido giberélico tiveram sua germinação inibida, não sendo recomendado na germinação da espécie. Concentrações de extrato aquoso de folhas e bulbos de tiririca não influenciaram a germinação de sementes de maracujá-amarelo