RepoMed (Medizinische Hochschule Hannover)
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THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate
Get PDFTHOC5, a member of the THO complex, is essential for the 3'processing of some inducible genes, the export of a subset of mRNAs and stem cell survival. Here we show that THOC5 depletion results in altered 3'cleavage of >50% of mRNAs and changes in RNA polymerase II binding across genes. THOC5 is recruited close to high-density polymerase II sites, suggesting that THOC5 is involved in transcriptional elongation. Indeed, measurement of elongation rates in vivo demonstrated decreased rates in THOC5-depleted cells. Furthermore, THOC5 is preferentially recruited to its target genes in slow polymerase II cells compared with fast polymerase II cells. Importantly chromatin-associated THOC5 interacts with CDK12 (a modulator of transcription elongation) and RNA helicases DDX5, DDX17, and THOC6 only in slow polymerase II cells. The CDK12/THOC5 interaction promotes CDK12 recruitment to R-loops in a THOC6-dependent manner. These data demonstrate a novel function of THOC5 in transcription elongation
Auswertung der Zweijahresdaten zur intravitrealen Therapie mittels Anti-VEGF (Vascular Endothelial Growth Factor) bei Makulaödem nach retinalen Venenverschlüssen
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Efficacy of antiseptics and chemomechanical methods for dentin caries lesions: A systematic review with GRADE approach.
No full textObjectives Selective caries removal aims to remove carious tissue in deep dentin lesions. However, a discussion stands on the value of antiseptics and chemomechanical adjuvant methods to reduce the bacterial load on residual caries lesions. This systematic review has addressed two main clinical questions to compare the antimicrobial efficacy of available methods using (1) antiseptic or (2) chemomechanical agents before restoring dentin carious lesions. Methods We included randomized and non-randomized controlled trials (RCTs/ NRCTs). We searched eight databases from inception to October 2021. Paired reviewers independently screened studies, extracted data, and assessed the risk of bias. The primary outcome was the reduction in the number of total bacterial in dentin, whereas secondary outcomes were reduction in the number of Lactobacillus and Streptococcus. We used the ratio of ratio of post-treatment to baseline means between two interventions in the logarithmic scale as a proper effect measure. Certainty of evidence was assessed with the Grading of Recommendations, Assessment, Development and Evaluation approach. Results We included 14 RCTs and 9 NRCTs, with nine interventions. Regardless the method, the number of bacteria at baseline was similar or exceeded that after the intervention, particularly in NRCTs. The evidence was inconclusive for most comparisons. Among antiseptic agents, chlorhexidine (CHX) resulted in an average of 1.14 times [95% confidence interval (CI): 1.08-1.21] more total bacterial than photodynamic therapy in RCTs. Among NRCTS, the natural agents resulted in five times more total bacterial than CHX (95% CI: 2-11). For chemomechanical methods, the control resulted in eight times (95% CI: 4-17) more total bacterial than Carisolv (SHAA). Conclusions The certainty of the evidence was very low for all comparisons showing uncertainty whether one treatment could be more effective than another for dentin disinfection. So far, exclusively removing soft carious dentin would be enough to reduce the bacterial count
Generation of Chimeric Antigen Receptor (CAR)-T cells for the treatment of pediatric Germ Cell Tumors (pGCTs)
No full textOptimization of pharmacological interventions in the guinea pig animal model—a new approach to calculate the perilymph volume of the scala tympani
No full textThe guinea pig serves as a well-established animal model for inner ear research, offering valuable insights into the anatomy, physiology, and therapeutic interventions of the auditory system. However, the heterogeneity of results observed in both in-vivo experiments and clinical studies poses challenges in understanding and optimizing pharmacotherapy outcomes. This heterogeneity may be due to individual differences in the size of the guinea pig cochlea and thus in the volume of the scala tympani (ST), which can lead to different drug concentrations in the ST, a fact that has been largely overlooked thus far. To address this issue, we aimed to develop an approach for calculating the individual volume of perilymph within the ST before and after cochlear implant insertion. Method: In this study, high-resolution μCT images of a total of n = 42 guinea pig temporal bones were used to determine the volume of the ST. We compared fresh, frozen, and fixed tissues from both colored and albino strains to evaluate the potential influence of tissue condition and strain on the results. Results: Our findings demonstrate a variability in mean ST volume with a relative standard deviation (RSD) of 14.7%, comparable to studies conducted with humans (range RSD: 5 to 20%). This indicates that the guinea pig cochlea exhibits similar variability to that of the human cochlea. Consequently, it is crucial to consider this variability when designing and conducting studies utilizing the guinea pig as an animal model. Furthermore, we successfully developed a tool capable of estimating ST volume without the need for manual segmentation, employing two geometric parameters, basal diameter (A) and width (B) of the cochlea, corresponding to the cochlear footprint. The tool is available for free download and use on our website. Conclusion: This novel approach provides researchers with a valuable tool to calculate individual ST volume in guinea pigs, enabling more precise dosing strategies and optimization of drug concentrations for pharmacotherapy studies. Moreover, our study underscores the importance of acknowledging and accounting for inter-individual variability in animal models to enhance the translational relevance and applicability of research outcomes in the field of inner ear investigation
