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Protonation kinetics in proteins at basic pH determined by pH-dependent NMR relaxation reveal the entire relationship between kinetics and pKa values
Ionizable amino acid side chains in proteins undergo constant protonation and deprotonation reactions. These proton exchange dynamics are a fundamental feature of proteins and their electrostatic character, as well as the basis for many biological processes, such as general acid–base enzyme catalysis. Such dynamics have been measured in a site-specific way for aspartates, glutamates, and histidines by pH-dependent NMR relaxation experiments. Linear free-energy relationships between kinetic and thermodynamic parameters have been established that allow the description of proton-mediated proton exchange at low to neutral pH. Here, we complement the picture by determining the proton exchange kinetics of lysine and tyrosine side chains at basic pH. They display matching linear free-energy relationships that enable the description of hydroxide-mediated proton exchange at high pH. The underlying maximal second-order rate constants are approximately a factor of 40 higher for hydronium association compared to hydroxide dissociation. These combined findings provide a general framework for describing protonation kinetics, allowing for the prediction of protonation and deprotonation rate constants for ionizable groups with all possible pKa values across the entire pH range.a in pka im Titel tiefgestell
Uptake, localization and dissolution of barium sulfate nanoparticles in human lung cells explored by the combination of ICP-MS, TEM and NanoSIMS
Background: Barium sulfate nanoparticles (BaSO4-NPs) are considered to be poorly soluble, chemically inert, and
therefore relatively non-toxic. For humans, inhalative exposure represents the most significant route of uptake.
Objective and methods: Cellular effects after exposure to BaSO4-NPs for 24 and 72 have been investigated in this
study on primary human lung cells. To track the fate of BaSO4-NPs in human lung cells, we used inductively
coupled plasma mass spectrometry (ICP-MS) to quantify cellular uptake of NPs, as well as transmission electron
microscopy (TEM) and nanoscale secondary ion mass spectrometry (NanoSIMS) to investigate subcellular distribution
of NPs through high-resolution elemental imaging.
Results and conclusions: We show that BaSO4 nanoparticles have been taken up by normal human bronchial
epithelial cells (NHBEC) in a dose-dependent manner. However, no clear time-dependent uptake could be
observed. The barium sulfate nanoparticles were visible in vesicles within the cytosol by TEM, which was
confirmed by high-resolution NanoSIMS images. Nevertheless, no uptake of the particles into the nucleus was
observed in this study. However, it was shown that BaSO4-NPs were partly dissolved, and barium ions were
distributed throughout the entire cell. Toxicity of the particles was indicated by a dose- and time-dependent loss
of viability in human lung cells
Privilegien der Halloren : Konzept für eine Ausstellung des Technischen Halloren- und Salinemuseums im Stadtmuseum Halle
Um den Nährboden für die Ausstellungsgestaltung in dieser Bachelorarbeit zu bereiten, wird in intensiver Grundlagenarbeit zu Salz, Siedemethoden und der halleschen Stadtgeschichte der Überblick erarbeitet, der aufzeigt in welchem wirtschaftlichen, sozialen und politischen Umfeld die Halloren agierten. Für
eine freie, kreative und inspirative Schöpfung von Inszenierungen bedarf es historischer und fachlicher Fundamente. Diese werden sowohl anhand von Primär-, als auch von Sekundärliteratur recherchiert, um eine fundierte und umfängliche Sicht auf das Thema der Ausstellung zu erlangen. Die Grundlagen der Ausstellungsgestaltung basieren auf Literatur zu Museologie und Ausstellungsgestaltung. Zielgruppe der Ausstellung sind alle nicht notwendigerweise fachlich vorgebildeten geschichtlich Interessierten und Menschen, die sich mit Privilegierung und (positiver) Diskriminierung auseinandersetzen möchten. Um auch Kindern und Jugendlichen einen informativen und anregenden Ausstellungsbesuch zu ermöglichen, soll die Ausstellung universell ansprechende ausstellungs- und museumspädagogische
Mittel bieten.Literaturverzeichnis: Seite 46-5
Kreativität in hybriden Arbeitswelten fördern: Die Rolle von individueller Autonomie
Der Beitrag untersucht, wie der Grad an individueller Autonomie bezüglich der Freiheit bei der Wahl von Arbeitsort und -zeit kreatives Arbeiten in hybriden Arbeitswelten fördern bzw. hemmen kann. Mittels einer systematischen Literaturrecherche werden jeweils die Chancen und Herausforderungen eines hohen und niedrigen Autonomiegrads für die Kreativität von Mitarbeitenden aufgezeigt. Aufbauend darauf werden fünf zentrale Handlungsempfehlungen für HR-Verantwortliche und Führungskräfte abgeleitet und anhand eines Interviews mit PwC Deutschland Einblicke in die gelebte Praxis gegeben. Es wird deutlich, dass eine gezielte Gestaltung von Autonomie, Struktur und Zusammenarbeit auf allen organisationalen Ebenen notwendig ist, um das kreative Potenzial, das hybride Arbeit ermöglicht, auszuschöpfen
Allostatic load and its determinants in a German sample : results from the Carla cohort
Background:
Allostatic load (AL) is a surrogate of the physiological response to stress and reflects the ‘wear and tear’ on the body. Previous studies indicated that socioeconomic and behavioral determinants influence AL, which in turn is associated with health outcomes. Therefore, AL is increasingly used to operationalize the relationship between social inequality, stress, and health outcomes. This study aimed to investigate associated factors and patterns of AL in the population over a 20-year period using data from the CARLA cohort.
Methods:
The analysis included 473 participants from the CARLA study (Cardiovascular Disease, Living and Ageing in Halle), aged 45–80 years at baseline. From recruitment in 2002 in Halle (Saale), three follow-up examinations took place until 2022. We calculated AL scores as the sum of standardized z-scores for metabolic, immune, cardiovascular, and anthropometric components. Descriptive statistics of AL scores were stratified by sex and age categories. Multiple regression analyses were conducted for the first and third follow-up to assess if there were changes in associations between sociodemographic factors and AL.
Results:
Average AL scores of men decreased, while women’s AL scores returned to baseline levels after an initial decrease observed at the first follow−up. Stratified analyses of AL scores revealed that women in the younger age cohorts had lower mean AL scores at baseline than men (women: −3.47, 95% CI [−4.24; −2.71] vs. men: −1.13, 95% CI [−1.84; −0.42] at age <55). At the same time, women showed higher mean AL scores than men in older age cohorts (women: −0.32, 95% CI [−1.58; 0.95] vs. men: −0.93, 95% CI [−1.99; 0.14] at age 65−<70).
Results of multiple regression models indicated lower AL scores for women (β: −1.21, 95% CI [−1.93, −0.49]). Professional status was associated with lower AL scores for men but not for women (β: −1.06, 95% CI [−2.02, −0.11] for men). Further, physical activity was negatively associated with AL scores for the total study sample and for women (β: −0.54, 95% CI [−0.82, −0.26]) for total sample and β: −0.74, 95% CI [−1.17, −0.32] for women).
Conclusion:
Our results highlight the importance of health awareness and physical activity for overall health, assessed by AL. Distinct AL score changes and sex-specific socioeconomic influences offer insights into sex-related patterns of aging. Further research is needed to understand the underlying mechanisms of socioeconomic influences on stress-related aging processes between sexes
A key residue of the extracellular gate provides quality control contributing to ABCG substrate specificity
For G-type ATP-binding cassette (ABC) transporters, a hydrophobic “di-leucine motif” as part of a hydrophobic extracellular gate has been described to separate a large substrate-binding cavity from a smaller upper cavity and proposed to act as a valve controlling drug extrusion. Here, we show that an L704F mutation in the hydrophobic extracellular gate of Arabidopsis ABCG36/PDR8/PEN3 uncouples the export of the auxin precursor indole-3-butyric acid (IBA) from that of the defense compound camalexin (CLX). Molecular dynamics simulations reveal increased free energy for CLX translocation in ABCG36L704F and reduced CLX contacts within the binding pocket proximal to the extracellular gate region. Mutation L704Y enables export of structurally related non-ABCG36 substrates, IAA, and indole, indicating allosteric communication between the extracellular gate and distant transport pathway regions. An evolutionary analysis identifies L704 as a Brassicaceae family-specific key residue of the extracellular gate that controls the identity of chemically similar substrates. In summary, our work supports the conclusion that L704 is a key residue of the extracellular gate that provides a final quality control contributing to ABCG substrate specificity, allowing for balance of growth-defense trade-offs
Synthesis of rhodamine TEMPO conjugates via isonitrile-based multicomponent-reactions for mitochondria-targeted ROS-detection in cancer cells
A novel series of profluorescent rhodamine nitroxide conjugates are synthesized utilizing well-known isonitrile-based multicomponent reactions (IMCRs). The synthesized conjugates are rationally designed as mitochondria-targeting probes for the detection of reactive oxygen species in living cells. Herein, the synthesized probes demonstrate high selectivity to target the mitochondria of both of PC3- and NIH3T3-cells which represent cancer and normal cell lines. Attaching TEMPO nitroxide to rhodamine leads to fluorescence quenching, allowing for ROS detection and quantification. The prepared sensors provide a reliable method for distinguishing between different oxidative environments in living organisms through different levels of fluorescence to be measured. The use of the Ugi multicomponent reaction enables an efficient and versatile synthetic approach, offering significant advantages over previously reported methods for constructing ROS-detecting probes. The simplicity of the reaction setup and the ability to generate a diverse library of products by varying Ugi components make this protocol highly adaptable for further chemical modification and potential applications in biological systems
Selecting relevant features for random forest-based crop type classifications by spatial assessments of backward feature reduction
Random Forest (RF) is a widely used machine learning algorithm for crop type mapping. RF’s variable importance aids in dimension reduction and identifying relevant multisource hyperspectral data. In this study, we examined spatial effects in a sequential backward feature elimination setting using RF variable importance in the example of a large-scale irrigation system in Punjab, Pakistan. We generated a reference classification with RF applied to 122 SAR and optical features from time series data of Sentinel‑1 and Sentinel‑2, respectively. We ranked features based on variable importance and iteratively repeated the classification by excluding the least important feature, assessing its agreement with the reference classification. McNemar’s test identified the critical point where feature reduction significantly affected the RF model’s predictions. Additionally, spatial assessment metrics were monitored at the pixel level, including spatial confidence (number of classifications agreeing with the reference map) and spatial instability (number of classes occurring during feature reduction). This process was repeated 10 times with ten distinct stratified random sampling splits, which showed similar variable rankings and critical points. In particular, VH SAR data was selected when cloud-free optical observations were unavailable. Omitting 80% of the features resulted in an insignificant loss of only 2% overall accuracy, while spatial confidence decreased by 5%. Moreover, the crop map at the critical point exhibited an increase in spatial instability from a single crop to 1.28. McNemar’s test and the spatial assessment metrics are recommended for optimized feature reduction benchmarks and identifying areas requiring additional ground data to improve the results
Optimizing non-communicable disease screening in Ethiopia : development and evaluation of service integration, and behavioral change communication at primary healthcare level
The aim of this dissertation is to discuss how to optimize non-communicable disease (NCD) screening in Ethiopia via service integration and behavioral change communication (BCC) at primary healthcare facilities (PHF). Cross-sectional studies among PHF attendees revealed low intention for clinical breast examination (CBE), cervical cancer screening (CCS), and blood pressure checks. Factors like spouse's education, gender, and prior screening experience influenced intention. We then developed BCC materials with high user satisfaction. Finally, a quasi-experimental study evaluated NCD screening service integration (CCS, CBE, blood pressure check, blood glucose check) with/without BCC. Integrating screening services and usage of BCC significantly increased uptake of all four screenings. Service integration without BCC increased CBE and blood glucose check service uptakes only. We recommend integrating NCD screening services and promoting its uptake via BCC at primary healthcare level
Alles auf einmal und nicht nur so halb?! Überlegungen zur Konzeption eines PCK-Modells für den Sachunterricht
Empirische Befunde unterstreichen die Bedeutsamkeit des fachdidaktischen Wissens (PCK) für die Unterrichtsqualität (Baumert et al. 2010; Carpenter & Fennema 1992; Hill, Rowan & Ball 2005; Park et al. 2011). Nach Shulman (1986, S. 9) verbindet und umfasst PCK das Fachwissen (CK) und das pädagogische Wissen (GPK) einer Lehrperson. Es war daher Ziel vieler Studien in unterschiedlichen Schulfächern und Schularten, das PCK von Lehrpersonen zu den jeweiligen Unterrichtsgegenständen zu erheben (Hartmann 2019; Jüttner et al. 2013; Lange et al. 2012; Park et al. 2011; Sorge et al. 2019). Die Forschungslage hierzu im Sachunterricht beschränkt sich auf einige wenige Studien (etwa Lange et al. 2012). Der Sachunterricht nimmt als Fach durch seine vielfältigen Bezüge eine besondere Stellung ein und bildet damit eine Gattung „sui generis“. In diesem Zusammenhang untersucht der Beitrag folgende Fragestellung: Welche Sachunterrichts-PCK Modelle könnten den komplexen Anforderungen an Generalist*innen und den spezifischen Erfordernissen des Fachs gerecht werden? Nach einer Einführung in die theoretische und empirische Rezeption der Trias GPK–PCK–CK werden drei verschiedene PCK-Modelle vorgeschlagen. Letztlich offenbart sich die Forderung bzw. Frage an die fachdidaktische Community hinsichtlich des PCK von Lehrpersonen im Sachunterricht: „Alles auf einmal und nicht nur so halb?!“. Der Beitrag zielt darauf ab, neue Betrachtungsmöglichkeiten und weitere Überlegungen für einen fruchtbaren fachdidaktischen Diskurs zu schaffen sowie Anstöße für mögliche sachunterrichtsdidaktische Forschungsarbeiten zu geben.„Wer wie wir heute in der fatalen Situation steht, infolge des bedingten Zweifel[s] bereits an der Möglichkeit der Wahrheit, die auch wieder geradezu die Voraussetzung unseres gewohnten verständigen/ verstandesgemäßen Gebrauchs der Wörter und Begriffe ist, nach Mitteln zu fahnden, um die Grenzen des Verstandes Überschreiten zu können, greift nach jedem Strohhalm. Und das Wort 'Widerstreit' schien mir für die Sachlage passend zu sein, da es genau in diesem Sinn als ein 'Kind' dieser Sprachnot verstanden werden kann.” (Ansgar Häußling in einem Brief an Gerold Scholz vom 1.2.2002