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This study aimed to reveal interactions of the stress response sigma subunits (factors) σD and σH of RNA polymerase and promoters in Gram-positive bacterium Corynebacterium glutamicum by combining wet-lab obtained data and in silico modeling. Computer modeling-guided point mutagenesis of C. glutamicum σH subunit led to the creation of a panel of σH variants. Their ability to initiate transcription from naturally occurring hybrid σD/σH-dependent promoter Pcg0441 and two control canonical promoters (σD-dependent PrsdA and σH-dependent PuvrD3) was measured and interpreted using molecular dynamics simulations of homology models of all complexes. The results led us to design the artificial hybrid promoter PD35H10 combining the −10 element of the PuvrD3 promoter and the −35 element of the PrsdA promoter. This artificial hybrid promoter PD35-rsdAH10-uvrD3 showed almost optimal properties needed for the bio-orthogonal transcription (not interfering with the native biological processes). [ABSTRACT FROM AUTHOR]

Abstract Background Exploring the dynamics of gut microbiome colonisation during early-life stages is important for understanding the potential impact of microbes on host development and fitness. Evidence from model organisms suggests a crucial early-life phase when shifts in gut microbiota can lead to immune dysregulation and reduced host condition. However, our understanding of gut microbiota colonisation in long-lived vertebrates, especially during early development, remains limited. We therefore used a wild population of common buzzard nestlings (Buteo buteo) to investigate connections between the early-life gut microbiota colonisation, environmental and host factors. Results We targeted both bacterial and eukaryotic microbiota using the 16S and 28S rRNA genes. We sampled the individuals during early developmental stages in a longitudinal design. Our data revealed that age significantly affected microbial diversity and composition. Nest environment was a notable predictor of microbiota composition, with particularly eukaryotic communities differing between habitats occupied by the hosts. Nestling condition and infection with the blood parasite Leucocytozoon predicted microbial community composition. Conclusion Our findings emphasise the importance of studying microbiome dynamics to capture changes occurring during ontogeny. They highlight the role of microbial communities in reflecting host health and the importance of the nest environment for the developing nestling microbiome. Overall, this study contributes to understanding the complex interplay between microbial communities, host factors, and environmental variables, and sheds light on the ecological processes governing gut microbial colonisation during early-life stages.

The objective of the current study was to compare changes of various aspects of quality of life according to the SF36 Health Survey after either inpatient rehabilitation (IPR) or outpatient rehabilitation (OPR) in patients with low back pain. To do this, a follow-up study (6 months) with a case-control design (n=150 matched pairs) of prospectively recruited patients suffering from low back pain and participating either in IPR or in OPR was carried out. To compare the effectiveness of IPR and OPR in terms of quality of life, the effect sizes (ES) of the changes in SF36 subscales 6 months after the rehabilitation programmes had ended were determined in those patients who had displayed abnormal values in the SF36 subscales before the intervention. The most important improvements in both IPR and OPR are found for 'bodily pain' and 'physical role'. The improvement in 'physical role' is higher after OPR (OPR 1.7; IPR 1.2), whereas the change in the subscale 'mental health index' is lower after OPR (OPR 0.5; IPR 1.0). After adjusting for differing baseline values, improvements of psychosocial aspects such as 'vitality' and 'social function' tend to be more pronounced after IPR ('vitality': IPR 1.3; OPR 0.8; 'social function': IPR 1.0; OPR 0.6). The outcome of IPR and OPR is similar in terms of several aspects of quality of life. However, the differences in psychosocial aspects result in the assumption that patients with impaired mental health, vitality or social abilities might receive a greater benefit from IPR whereas those with an impaired physical role might profit more from OPR. This needs to be studied in more detail in randomized controlled trials. [ABSTRACT FROM AUTHOR]

An abstract of the article "A Systems Biology-Motivated Approach to Improve Dual-Phase Production Processes with Corynebacterium glutamicum" by J. Lange and colleagues is presented.

Abstract Background The expression of genes in Corynebacterium glutamicum, a Gram-positive non-pathogenic bacterium used mainly for the industrial production of amino acids, is regulated by seven different sigma factors of RNA polymerase, including the stress-responsive ECF-sigma factor SigH. The sigH gene is located in a gene cluster together with the rshA gene, putatively encoding an anti-sigma factor. The aim of this study was to analyze the transcriptional regulation of the sigH and rshA gene cluster and the effects of RshA on the SigH regulon, in order to refine the model describing the role of SigH and RshA during stress response. Results Transcription analyses revealed that the sigH gene and rshA gene are cotranscribed from four sigH housekeeping promoters in C. glutamicum. In addition, a SigH-controlled rshA promoter was found to only drive the transcription of the rshA gene. To test the role of the putative anti-sigma factor gene rshA under normal growth conditions, a C. glutamicum rshA deletion strain was constructed and used for genome-wide transcription profiling with DNA microarrays. In total, 83 genes organized in 61 putative transcriptional units, including those previously detected using sigH mutant strains, exhibited increased transcript levels in the rshA deletion mutant compared to its parental strain. The genes encoding proteins related to disulphide stress response, heat stress proteins, components of the SOS-response to DNA damage and proteasome components were the most markedly upregulated gene groups. Altogether six SigH-dependent promoters upstream of the identified genes were determined by primer extension and a refined consensus promoter consisting of 45 original promoter sequences was constructed. Conclusions The rshA gene codes for an anti-sigma factor controlling the function of the stress-responsive sigma factor SigH in C. glutamicum. Transcription of rshA from a SigH-dependent promoter may serve to quickly shutdown the SigH-dependent stress response after the cells have overcome the stress condition. Here we propose a model of the regulation of oxidative and heat stress response including redox homeostasis by SigH, RshA and the thioredoxin system.

Introduction: The United Nations underlines the participation in all domains of daily living for people with intellectual and/or multiple disabilities in the Disability Rights Convention, which also includes medical services. In line with this, the German Federal Participation Act has further developed the relevant disability policy at the national level. This also implies access to comprehensive medical care. In 2015, Germany created a legal basis for the establishment of medical centres for adults with intellectual and/or multiple disabilities in order to ensure basic medical care for these patients. However, the medical centres cannot provide complex rehabilitation. Mobile rehabilitation can be another tool to address the underuse of medical rehabilitation for people with intellectual and/or multiple disabilities. Mobile rehabilitation refers to rehabilitation services provided in a patient's home or local community, rather than in a traditional inpatient or outpatient rehabilitation facility. The advantages of mobile rehabilitation are its accessibility for patients with mobility problems, the comfort of a familiar environment, which can reduce stress, and the fact that rehabilitation can be tailored to the patient's living conditions and daily routine. In Germany, mobile rehabilitation is currently only available in the field of geriatrics.Within the framework of the feasibility study 'Social space-oriented individualised medical rehabilitation for people with intellectual and/or multiple disabilities (SIMRE),' a social space-oriented rehabilitation concept was developed to close the rehabilitation gap for people with intellectual and/or multiple disabilities. It is funded by the German Federal Ministry of Health. This study protocol describes the procedure of this feasibility study., Methods: This study is a prospective mixed methods feasibility study. The rehabilitation concept combines outpatient and home-based rehabilitation, medical, and therapeutic care for people with intellectual and/or multiple disabilities., Analysis: The primary target criteria are the feasibility and acceptance of the concept by participants, relatives, carers and the rehabilitation staff. Guided interviews with participants and their relatives and/or carers will be analysed using the content-structuring analysis according to Kuckartz. Quantitative analysis will include a cost-benefit analysis to provide information on the economic feasibility of the rehabilitation concept. Changes in individual participation, quality of life and rehabilitation goals will be assessed using a before-and-after comparison with questionnaires. The frequency and type of rehabilitation procedures used will be evaluated quantitatively.The trial was prospectively registered in the German Clinical Trials Register on 17 August 2023. (https://www.drks.de/DRKS00032493)., Ethics and Dissemination: Ethical approval was granted by the Ethics Committee of Hannover Medical School (reference number: 10985_BO_S_2023).1. Publication: The results of the project will be made available to the public through open access publications. We plan to develop a treatment guideline for the treatment concept based on clinical experience.2. Widespread implementation: If the project is continued and adequately staffed, the rehabilitative care concept could be implemented nationwide, and the University Hospital could be available as a reference clinic., Trial Registration Number: German Clinical Trials Register (reference number: DRKS00032493)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)