Rifaximin resistance in Clostridioides difficile is associated with specific rpoB alleles and multilocus sequence typing (MLST) clades

Background and Objectives Rifaximin (RFX) has recently been suggested as an alternative treatment option for Clostridioides difficile infection. This study reports the survey on RFX susceptibility within a C. difficile test cohort that represents the five clinically relevant phylogenetic clades. Methods Agar dilution assays were conducted to determine the minimum inhibitory concentrations (MICs) of RFX for 129 clinical C. difficile isolates from Germany (86), Indonesia (29), and Ghana (14). Genome sequence data were obtained for 50 representative isolates, including all those with a minimum inhibitory concentration MIC[RFX] of ≥ 32.0 µg/mL, to identify the underlying rpoB gene resistance alleles, determine the multilocus sequence typing (MLST) sequence types (STs), and infer phylogenetic relatedness. Results 10.1% of the isolates were found to be resistant to RFX. The resistance rate varies by region, with 4.7% in Germany, 27.6% in Indonesia, and 7.1% in Ghana. Three distinct rpoB alleles were associated with RFX resistance. The presence of a specific rpoB allele correlates with the MLST-based ST of the isolate, indicating that the rifaximin-resistant isolates belong to phylogenetic clades 1, 2, and 4. These isolates are represented by six different ribotypes: 010, 017, 027, 046, 084, and 131. Furthermore, we identified seven amino acid substitutions resulting from SNPs in the rpoB gene through alignment analysis. These substitutions are found in both RFX-resistant and susceptible isolates, suggesting that they are neutral mutations in relation to RFX susceptibility. These observations also indicate that RFX resistance arose independently in different clades. Conclusions A substantial rate of RFX resistance, particularly among Indonesian isolates, was observed. This may be attributed to the prolonged use of rifampicin, especially in the treatment of tuberculosis. RFX resistance has been linked to specific amino acid substitutions in the β-subunit of RNA polymerase encoded by the rpoB gene. To the best of our knowledge, one of the identified RFX resistance-associated rpoB alleles (H502N, R505K, I750M) has not been previously described, whereupon, the amino acid substitutions I750M as well as I750V, E1037Q, A1205V, N1207A, A1208T, and D1232E were identified as neutral mutations that do not confer resistance to RFX

Constituent of extracellular polymeric substances (EPS) produced by a range of soil bacteria and fungi

Abstract Extracellular polymeric substances (EPS) produced by soil bacteria and fungi are crucial for microbial growth and provide many functions for the soil and its microbes. EPS composition may depend on microbial community composition and the soil physical and chemical environment, nevertheless, not much is known about the EPS constituents’ specific roles nor how they interact to alter biofilm’s functions. We hypothesized that EPS production would be enhanced with the presence of a surface and with a more labile carbon source. Also, that even though carbohydrates and proteins are the main constituents of EPS, we could still find quantifiable amounts of mannosamine and galactosamine (two amino sugars previously shown to be part of microbial biofilms). Ten soil bacterial and ten soil fungal species were cultured with glycerol or starch and with or without a quartz matrix. After a 4-day cultivation, EPS were extracted, and seven constituents were determined: carbohydrates, DNA, proteins, muramic acid, mannosamine, galactosamine, and glucosamine. We found EPS composition was strongly modified by microbial type, whereas differences in EPS production were driven mostly by environmental conditions. The EPS-carbohydrate/protein ratio was higher for cultures grown in starch media than in glycerol and increased in the presence of quartz. EPS-carbohydrate concentration reflected environmental changes of substrate quality and surface presence. Contrastingly, changes in the other EPS constituent composition are likely due to intrinsic microbial characteristics. Our findings open the pathway to study microbial biofilms in more complex environments (such as soils) and shed light to the importance of extracellular structures to microbial processes

Bridging the Gap: Introducing Joint Models for Longitudinal and Time-to-event Data in the Social Sciences

In time-to-event analyses in social sciences, there often exist endogenous time-varying variables, where the event status is correlated with the trajectory of the covariate itself. Ignoring this endogeneity will result in biased estimates. In the field of biostatistics this issue is tackled by estimating a joint model for longitudinal and time-to-event data as it handles endogenous covariates properly. This method is underused in the social sciences even though it is very useful to model longitudinal and time-to-event processes appropriately. Therefore, this paper provides a gentle introduction to the method of joint models and highlights its advantages for social science research questions. We demonstrate its usage on an example on marital satisfaction and marriage dissolution and compare the results with classical approaches such as a time-to-event model with a time-varying covariate. In addition to demonstrating the method, our results contribute to the understanding of the relationship between marriage satisfaction, marriage dissolution and other covariates

Reservoir characterization by push–pull tests employing kinetic interface sensitive tracers – Quantification of residual trapping in geological storage of carbon dioxide

http://dx.doi.org/10.13039/501100002347 Federal Ministry of Education and Research Bonn Officehttp://dx.doi.org/10.13039/501100001659 German Research Foundatio

Belastungen und Beanspruchungen von Lehrkräften in Berlin

Lehrkräfte in Berlin bewerten ihre Arbeitsbedingungen deutlich schlechter als der nationale Durchschnitt aller Beruf, obwohl akademische Berufe normalerweise bessere Bedingungen bieten. Im Vergleich mit früheren Studien zeigen sich ein gleichbleibendes Muster. In Berlin wurden nun neue Tiefstwerte erreicht – während Ressourcen durchschnittlich bewertet werden, sind die Belastungen konstant extrem hoch. Besonders belastend sind die hohe Arbeitsintensität, ungünstige Arbeitszeiten, respektloses Verhalten und Lärm. Gleichzeitig fehlt es an Gestaltungsspielraum und Ressourcen, um diese Belastungen auszugleichen. Hinzu kommen schulspezifische Belastungen, wie hohe emotionale Anforderungen und ein hoher Druck durch viele außerunterrichtliche Aufgaben, die nicht zu den pädagogischen Kernaufgaben gehören. Dies wirft Frage auf, wie attraktiv der Lehrberuf derzeit noch ist

Speech-based digital cognitive assessments for detection of mild cognitive impairment: Validation against paper-based neurocognitive assessment scores

Background Cognitive decline in Alzheimer's disease (AD) often includes speech impairments, where subtle changes may precede clinical dementia onset. As clinical trials focus on early identification of patients for disease-modifying treatments, digital speech-based assessments for scalable screening have become crucial. Objective This study aimed to validate a remote, speech-based digital cognitive assessment for mild cognitive impairment (MCI) detection through the comparison with gold-standard paper-based neurocognitive assessments. Methods Within the PROSPECT-AD project, speech and clinical data were obtained from the German DELCODE and DESCRIBE cohorts, including 21 healthy controls (HC), 110 participants with subjective cognitive decline (SCD), and 59 with MCI. Spearman rank and partial correlations were computed between speech-based scores and clinical measures. Kruskal-Wallis tests assessed group differences. We trained machine learning models to classify diagnostic groups comparing classification accuracies between gold-standard assessment scores and a speech-based digital cognitive assessment composite score (SB-C). Results Global cognition, as measured by SB-C, significantly differed between diagnostic groups ( H (2) = 30.93, p  < 0.001). Speech-based scores were significantly correlated with global anchor scores (MMSE, CDR, PACC5). Speech-based composites for memory, executive function and processing speed were also correlated with respective domain-specific paper-based assessments. In logistic regression classification, the model combining SB-C and neuropsychological tests at baseline achieved a high discriminatory power in differentiating HC/SCD from MCI patients (Area Under the Curve = 0.86). Conclusions Our findings support speech-based cognitive assessments as a promising avenue towards remote MCI screening, with implications for scalable screening in clinical trials and healthcare.HORIZON EUROPE Marie Sklodowska-Curie Actions https://doi.org/10.13039/100018694Alzheimer's Drug Discovery Foundation https://doi.org/10.13039/100002565Alzheimer's Drug Discovery Foundation https://doi.org/10.13039/10000256

Titin-dependent biomechanical feedback tailors sarcomeres to specialized muscle functions in insects

Sarcomeres are the universal contractile units of muscles that enable animals to move. Insect muscles display a remarkable functional diversity: they operate at extremely different contraction frequencies (ranging from ~1 to 1000 hertz) and amplitudes during flying, walking, and crawling. This is puzzling because sarcomeres are built from essentially the same actin-myosin components. Here, we address how functionally different sarcomeres are made. We show that the giant protein titin and the regulation of developmental contractility are key for the sarcomere specializations. I-band titin spans and determines the length of the sarcomeric I-band in a muscle type–specific manner. Unexpectedly, I-band titin also rules the length of the force-generating myosin filament using a feedback mechanism that is modulated by myosin contractility. We propose a model of how sarcomere specializations in insects are tuned, provide evidence for this model, and discuss its validity beyond insects.A mechanical mechanism instructs sarcomeres to fulfill the specific needs of different muscle types.Sarcomeres are the universal contractile units of muscles that enable animals to move. Insect muscles display a remarkable functional diversity: they operate at extremely different contraction frequencies (ranging from ~1 to 1000 hertz) and amplitudes during flying, walking, and crawling. This is puzzling because sarcomeres are built from essentially the same actin-myosin components. Here, we address how functionally different sarcomeres are made. We show that the giant protein titin and the regulation of developmental contractility are key for the sarcomere specializations. I-band titin spans and determines the length of the sarcomeric I-band in a muscle type–specific manner. Unexpectedly, I-band titin also rules the length of the force-generating myosin filament using a feedback mechanism that is modulated by myosin contractility. We propose a model of how sarcomere specializations in insects are tuned, provide evidence for this model, and discuss its validity beyond insects.A mechanical mechanism instructs sarcomeres to fulfill the specific needs of different muscle types

Overexpression of jojoba wax ester synthase in poplar increases foliar lipid accumulation, alters stomatal conductance, and increases water use efficiency

Abstract Poplars are important fast‐growing, water‐spending biomass tree crops. Here, we targeted the wax biosynthesis pathway of Populus × canescens by overexpressing jojoba ( Simmondsia chinensis ) wax ester synthase ( Sc WS) for the production of lipids. We found that ScWS overexpression caused accumulation of lipid droplets in leaf cells but did not increase wax load on the leaf surface. However, the stomata had a high fraction of closed or semi‐closed guard cells with aberrant lipid accumulation. This phenotype was accompanied by suppression of OCCLUDED STOMATAL PORE 1 ( OSP1 ) and decreased stomatal conductance in the ScWS ‐expressing poplars. During short‐ and long‐term drought scenarios under greenhouse and outdoor conditions, the Sc WS lines had increased water use efficiencies, leading to a water‐saving phenotype and delays in drought stress. In the Sc WS poplars, photosynthesis was reduced under high, but not under low light intensities. Biomass production of Sc WS lines was unaffected in short‐term experiments but dropped below that of wild‐type poplars at the end of two field seasons, indicating a long‐term growth trade‐off. Our results open new opportunities for the production of lipids in more water‐efficient poplars.Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659Niedersächsisches Ministerium für Wissenschaft und Kultur https://doi.org/10.13039/50110001057

Wild and zoo-housed orangutans differ in how they explore objects

Abstract In human infants, exploratory object manipulations (henceforth called “EOM”) stimulate cognitive development and affect cognitive performance in later life. Zoo-housed great apes are frequently used to study the evolution of human cognition, however, it is unknown how the zoo environment affects their daily expression of EOM. We investigated how wild and zoo-housed Sumatran orangutans differ in their daily EOM throughout life. We collected ~ 12′000 EOM events by 51 wild and zoo-housed individuals of all ages. Zoo-housed orangutans showed significantly higher EOM rates than wild orangutans. Exploratory actions were more diverse in zoos than in the wild, even with objects available in both settings. Zoo-housed orangutans also showed a larger repertoire of exploratory actions and a higher probability of multi-object exploration, including tool use. There was no difference between settings at which age individuals first showed specific exploratory actions. Our results show that the zoo environment significantly affects EOM in orangutans and that the species’ exploratory potential exceeds its natural expression. This may have important implications for cognitive performance, as zoo-housed individuals are likely to have a broader range of affordances to draw from when confronted with novel problems. These results highlight the potential of captive-wild comparisons to study cognitive development and evolution