New thermodynamic activity-based approach allows predicting the feasibility of glycolysis

Thermodynamic feasibility analyses help evaluating the feasibility of metabolic pathways. This is an important information used to develop new biotechnological processes and to understand metabolic processes in cells. However, literature standard data are uncertain for most biochemical reactions yielding wrong statements concerning their feasibility. In this article we present activity-based equilibrium constants for all the ten glycolytic reactions, accompanied by the standard reaction data (standard Gibbs energy of reaction and standard enthalpy of reaction). We further developed a thermodynamic activity-based approach that allows to correctly determine the feasibility of glycolysis under different chosen conditions. The results show for the first time that the feasibility of glycolysis can be explained by thermodynamics only if (1) correct standard data are used and if (2) the conditions in the cell at non-equilibrium states are accounted for in the analyses. The results here will help to determine the feasibility of other metabolisms and to understand metabolic processes in cells in the future

Effects of collaboration scripts and heuristic worked examples on the acquisition of mathematical argumentation skills of teacher students with different levels of prior achievement

A challenging demand for mathematics teacher students is to produce acceptable scientific mathematical argumentations. We investigated to what extent mathematics teacher students with different levels of prior achievement who collaborated in dyads can be supported in their development of mathematical argumentation skills by two different instructional approaches that were systematically varied in a 2 × 2-factorial design: collaboration scripts (with vs. without) and heuristic worked examples vs. problem solving. An experimental study was run in the context of a two-weeks preparatory course for beginning mathematics teacher students (N = 101). Mathematical argumentation skills were conceptualized as consisting of an individual-mathematical and a social-discursive component. Results indicated positive effects of both scaffolds on the social-discursive component. Moreover, the effects of both scaffolds on both components were dependent on learners' prior achievement (high-school GPA). Heuristic worked examples and collaboration scripts were particularly effective in the facilitation of mathematical argumentation skills for teacher students with higher general learning prerequisites. Possible process-based explanations for this pattern of results as well as ways to more specifically address the needs of teacher students with lower prior achievement are discussed

Effekte heuristischer Lösungsbeispiele in kooperativen Settings auf mathematische Argumentationskompetenz bei Lehramtsstudierenden

Mathematisches Argumentieren zählt zu den professionellen Anforderungen an angehende Mathematiklehrkräfte. Zur Förderung derartiger komplexer Kompetenzen haben sich heuristische Lösungsbeispiele als geeignet erwiesen. Offen ist, wie dieser Ansatz in kooperativen Settings auf unterschiedliche Kompetenzkomponenten bei Lernenden mit heterogenen Lernvoraussetzungen wirkt. Vorgestellt werden Fragestellungen, Design und Ergebnisse der Interventionsstudien aus dem DFG-Projekt ELK-Math

Amyloid-precursor-protein-lowering small molecules for disease modifying therapy of Alzheimer's disease

Alzheimer's disease (AD) is the most common form of dementia in the elderly with progressive cognitive decline and memory loss. According to the amyloid-hypothesis, AD is caused by generation and subsequent cerebral deposition of β-amyloid (Aβ). Aβ is generated through sequential cleavage of the transmembrane Amyloid-Precursor-Protein (APP) by two endoproteinases termed beta- and gamma-secretase. Increased APP-expression caused by APP gene dosage effects is a risk factor for the development of AD. Here we carried out a large scale screen for novel compounds aimed at decreasing APP-expression. For this we developed a screening system employing a cell culture model of AD. A total of 10,000 substances selected for their ability of drug-likeness and chemical diversity were tested for their potential to decrease APP-expression resulting in reduced Aβ-levels. Positive compounds were further evaluated for their effect at lower concentrations, absence of cytotoxicity and specificity. The six most promising compounds were characterized and structure function relationships were established. The novel compounds presented here provide valuable information for the development of causal therapies for AD

Multi-walled carbon nanotube-physicochemical properties predict the systemic acute phase response following pulmonary exposure in mice

Pulmonary exposure to multi-walled carbon nanotubes (MWCNTs) has been linked to an increased risk of developing cardiovascular disease in addition to the well-documented physicochemical-dependent adverse lung effects. A proposed mechanism is through a strong and sustained pulmonary secretion of acute phase proteins to the blood. We identified physicochemical determinants of MWCNT-induced systemic acute phase response by analyzing effects of pulmonary exposure to 14 commercial, well-characterized MWCNTs in female C57BL/6J mice pulmonary exposed to 0, 6, 18 or 54 μg MWCNT/mouse. Plasma levels of acute phase response proteins serum amyloid A1/2 (SAA1/2) and SAA3 were determined on day 1, 28 or 92. Expression levels of hepatic Saa1 and pulmonary Saa3 mRNA levels were assessed to determine the origin of the acute phase response proteins. Pulmonary Saa3 mRNA expression levels were greater and lasted longer than hepatic Saa1 mRNA expression. Plasma SAA1/2 and SAA3 protein levels were related to time and physicochemical properties using adjusted, multiple regression analyses. SAA3 and SAA1/2 plasma protein levels were increased after exposure to almost all of the MWCNTs on day 1, whereas limited changes were observed on day 28 and 92. SAA1/2 and SAA3 protein levels did not correlate and only SAA3 protein levels correlated with neutrophil influx. The multiple regression analyses revealed a protective effect of MWCNT length on SAA1/2 protein level on day 1, such that a longer length resulted in lowered SAA1/2 plasma levels. Increased SAA3 protein levels were positively related to dose and content of Mn, Mg and Co on day 1, whereas oxidation and diameter of the MWCNTs were protective on day 28 and 92, respectively. The results of this study reveal very differently controlled pulmonary and hepatic acute phase responses after MWCNT exposure. As the responses were influenced by the physicochemical properties of the MWCNTs, this study provides the first step towards designing MWCNT that induce less SAA

Adaptable scaffolding of mathematical argumentation skills: The role of self-regulation when scaffolded with CSCL scripts and heuristic worked examples

Collaboration scripts and heuristic worked examples have been described as powerful scaffolds to support skill acquisition in CSCL. While CSCL scripts particularly facilitate argumentative discourse within groups, heuristic worked examples provide heuristics and worked out pathways to solve domain-specific tasks. Yet, both scripts and heuristic worked examples are often designed in a one-size-fits-all fashion. Granting learners the opportunity to adapt these scaffolds to their self-perceived needs might be a way to further enhance their effects. We tested this assumption in two experiments. In experiment 1, we compared the effects of learning with adaptable and non-adaptable CSCL scripts. In experiment 2, we compared the effects of learning with adaptable and non-adaptable heuristic worked examples. University students (N = 167) learned repeatedly in pairs with either adaptable or non-adaptable scaffolding in the context of mathematical conjecture problems. Results show that adaptable CSCL scripts were partly helpful for students with higher levels of self-regulation skills. Non-adaptable maximal scaffolding supported learning of distinctive skill components. Social-discursive components were best facilitated by maximal heuristic worked examples through content knowledge scaffolds. In contrast, CSCL scripts best facilitated domain-specific skill components by scaffolding learners’ engagement in social discourse about domain knowledge. The study provides recommendations for designing adaptable scaffolding by taking into account the relation between the targeted skill component and the activities scaffolded in the learning process. We suggest conducting future studies on adaptable scaffolding with a focus on supporting learning regulation and group awareness to improve learners’ success in CSCL environments

Fostering university freshmen’s mathematical argumentation skills with collaboration scripts

Students often have problems formulating und using arguments in mathematical contexts. Therefore, we investigated to what extent a collaboration script helps students overcome their problems and acquire mathematical argumentation skills. In two previous studies, we showed that collaboration scripts can have positive effects on learning cross-domain argumentation skills in the mathematical context. Yet, the effectiveness of the script depended on individual prerequisites such as final high school grade (GPA) and self-regulation skills. In this study, N = 96 participants learned in one of three script conditions. We found that a high-structured domain-general collaboration script for argumentation was more effective for acquiring domain-specific mathematical argumentation skills than a low-structured or an adaptable one. Furthermore, only in the condition with the low-structured script, learners’ self-regulated learning skills played an important role for the learning outcomes

Implementation of a National Reference Laboratory for Buruli Ulcer Disease in Togo

Background: In a previous study PCR analysis of clinical samples from suspected cases of Buruli ulcer disease (BUD) from Togo and external quality assurance (EQA) for local microscopy were conducted at an external reference laboratory in Germany. The relatively poor performance of local microscopy as well as effort and time associated with shipment of PCR samples necessitated the implementation of stringent EQA measures and availability of local laboratory capacity. This study describes the approach to implementation of a national BUD reference laboratory in Togo. Methodology: Large scale outreach activities accompanied by regular training programs for health care professionals were conducted in the regions "Maritime'' and "Central,'' standard operating procedures defined all processes in participating laboratories (regional, national and external reference laboratories) as well as the interaction between laboratories and partners in the field. Microscopy was conducted at regional level and slides were subjected to EQA at national and external reference laboratories. For PCR analysis, sample pairs were collected and subjected to a dry-reagent-based IS2404-PCR (DRB-PCR) at national level and standard IS2404 PCR followed by IS2404 qPCR analysis of negative samples at the external reference laboratory. Principal Findings: The inter-laboratory concordance rates for microscopy ranged from 89% to 94%; overall, microscopy confirmed 50% of all suspected BUD cases. The inter-laboratory concordance rate for PCR was 96% with an overall PCR case confirmation rate of 78%. Compared to a previous study, the rate of BUD patients with non-ulcerative lesions increased from 37% to 50%, the mean duration of disease before clinical diagnosis decreased significantly from 182.6 to 82.1 days among patients with ulcerative lesions, and the percentage of category III lesions decreased from 30.3% to 19.2%. Conclusions: High inter-laboratory concordance rates as well as case confirmation rates of 50% (microscopy), 71% (PCR at national level), and 78% (including qPCR confirmation at external reference laboratory) suggest high standards of BUD diagnostics. The increase of non-ulcerative lesions, as well as the decrease in diagnostic delay and category III lesions, prove the effect of comprehensive EQA and training measures involving also procedures outside the laboratory

Fostering argumentation skills in mathematics with adaptable collaboration scripts: only viable for good self-segulators?

Argumentation scripts have been proposed as an effective means to structure students’ argumentation and to support their acquisition of argumentation skills. Yet, argumentation scripts run the danger of overscripting students’ argumentation. A possible solution might be to offer adaptable argumentation scripts that allow students to adjust the script to their own needs. This study compares the effects of three argumentation scripts (high structured vs. low structured vs. adaptable) on students’ argumentation skills. Furthermore, we investigate to what extent students’ self-regulation skills influence the acquisition of argumentation skills in the three conditions. N = 109 math students were randomized to the three treatment conditions and worked in dyads on mathematical proof tasks in a CSCL environment. Students’ argumentation skills increased between pre- and post-tests with comparable gains in all three conditions. Only for students learning with the adaptable argumentation script, self-regulation skills were a significant positive predictor for argumentation skills