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Freedom and Subjection in Islam through the Prism of Salafism in Tunisia
Keywords: Tunisia, Salafism, freedom, Islam, subject, subjectionSchlagworte: Tunesien, Salafismus, Freiheit, Islam, Untertan, Unterwerfun
Evaluation of Cas13d as a tool for genetic interaction mapping
Mapping genetic interactions (GIs) is crucial for understanding genetic network complexity. In this study, we investigate the utility of Cas13d, a CRISPR system targeting RNA, for GI mapping and compare it to Cas9 and Cas12a, two DNA nucleases commonly used for GI mapping. We find that Cas13d induces faster target gene perturbation and generates more uniform cell populations with double perturbations than Cas9 or Cas12a. We then encounter Cas13d gRNA-gRNA interference when concatenating gRNAs targeting different genes into one gRNA array, which we overcome by a dual promoter gRNA expression strategy. Moreover, by concatenating three gRNAs targeting the same gene into one array, we are able to maximize the Cas13d-mediated knockdown effects. Combining these strategies enhances proliferation phenotypes while reducing library size and facilitates reproducible quantification of GIs in oncogenic signaling pathways. Our study highlights the potential of Cas13d for GI mapping, promising advancements in understanding therapeutically relevant drug response pathways
How FocA facilitates fermentation and respiration of formate by Escherichia coli
Formic acid is an important source of reductant and energy for many microorganisms. Formate is also produced as a fermentation product, e.g., by enterobacteria like Escherichia coli. As such, formic acid shares many features in common with dihydrogen, explaining perhaps why their metabolism and physiology show considerable overlap. At physiological pH, formic acid is mainly present as the dissociated formate anion and therefore cannot diffuse freely across the cytoplasmic membrane. Specific and bidirectional translocation of formate across the cytoplasmic membrane is, however, achieved in E. coli by the homopentameric membrane protein, FocA. Formic acid translocation from the cytoplasm into the periplasm (efflux) serves to maintain a near-neutral cytosolic pH and to deliver formate to the periplasmically-oriented respiratory formate dehydrogenases, Fdh-N and Fdh-O. These enzymes oxidize formate, with the electrons being used to reduce nitrate, oxygen, or other acceptors. In the absence of exogenous electron acceptors, formate is re-imported into the cytoplasm by FocA, where it is sensed by the transcriptional regulator FhlA, resulting in induction of the formate regulon. The genes and operons of the formate regulon encode enzymes necessary to assemble the formate hydrogenlyase complex, which disproportionates formic acid into H2 and CO2. Combined, these mechanisms of dealing with formate help to maintain cellular pH homeostasis and are suggested to maintain the proton gradient during growth and in stationary phase cells. This review highlights our current understanding of how formate metabolism helps balance cellular pH, how it responds to the redox status, and how it helps conserve energy
al-Muhāǧirūn min Ifrīqiyā ǧanūb aṣ-Ṣaḥrāʾ fī Tūnis : hal hīya zaubaʿa fī finǧān?
الكلمات المفتاحية: مهاجرو إفريقيا جنوب الصحراء، سوق العمل التونسي، الإدماج متعدد الأبعاد، الاختلاف المزدوجKeywords: sub-Saharan immigrants, Tunisian labour market, multidimensional integration, difference-in-differencesSchlagworte: Einwanderer aus Ländern südlich der Sahara, tunesischer Arbeitsmarkt, multidimensionale Integration, Differenz-in-Differenze
Protected areas do not outperform urban wastelands in supporting insect pollinators and pollination in central Germany
The Natura 2000 network is central to Europe's conservation efforts to address biodiversity decline, with ongoing plans to expand protected areas and restore habitats across the European Union. However, due to the relative scarcity of biodiversity assessments within Natura 2000 sites, our understanding of how effective these areas are at protecting biodiversity and how they can be improved remains limited. At the same time, urban green spaces and associated disturbed, unmanaged vacant areas, also known as urban wastelands, have gained attention as potential conservation targets due to their high insect species richness. Here, we assess and compare the biodiversity of pollinators within Natura 2000 reserves and urban wastelands to evaluate their relative value for biodiversity protection and pollination services. To achieve this, we compared pollinator communities, their flower-visitation patterns and pollination services using potted experimental plants in flower-rich Natura 2000 sites and paired non-protected, unmanaged, yet similarly flower-rich urban wastelands. While the total biomass and overall abundance of insects did not differ between the two habitat types, wild bee abundance and richness were higher in urban wastelands, whereas pollinator communities were more heterogeneous among Natura 2000 sites. Though insect flower-visitation network metrics were similar across both habitats, seed set of experimental plants was higher in urban wastelands compared to Natura 2000 sites, indicating lower pollination services in the nature reserves. Our findings suggest that while Natura 2000 areas contained unique biodiversity compared to urban wastelands, the current status of protected areas in Germany is inadequate to conserve biodiversity hotspots for bees, including endangered species and the pollination services they provide. We highlight the potential for urban areas to support biodiversity conservation as well as the need to develop targeted strategies for bee conservation in Natura 2000 areas
Crystallization of n-alkanes under anisotropic nanoconfinement in lipid bilayers
Understanding crystallization behavior is integral to the design of pharmaceutical compounds for which the pharmacological properties depend on the crystal forms achieved. Very often, these crystals are based on hydrophobic molecules. One method for delivering crystal-forming hydrophobic drugs is by means of lipid nanoparticle carriers. However, so far, a characterization of the potential crystallization of fully hydrophobic molecules in a lipid environment has never been reported. In this work we investigate the crystallization behavior of two model hydrophobic chains, n-eicosane (C20) and n-triacontane (C30), in phospholipid bilayers. We combine static 2H nuclear magnetic resonance (NMR) spectroscopy and differential scanning calorimetry (DSC) and show that C30 molecules can indeed crystallize inside DMPC and POPC bilayers. The phase transition temperatures of C30 are slightly reduced inside DMPC, and rotator phase formation becomes a two-step process: Preorganized n-alkane chains assemble in rotator-phase crystallites just as fast as bulk C30, but further addition of molecules is notably slower. Under the same isothermal conditions, different crystal forms can be obtained by crystallization in the membrane and in bulk. In excess water conditions, homogeneous nucleation of C30 is observed. The initial anisotropic molecular arrangement of C30 molecules in the membrane is readily recovered upon reheating, showing reversibility. The shorter C20 molecules on the other hand become trapped in the DMPC membrane gel-phase upon cooling and do not crystallize. This work marks the first observation of the crystallization of hydrophobic chains inside a lipid bilayer environment. As such, it defines a fundamental starting point for studying the crystallization characteristics of various hydrophobic molecules in lipid membranes
TRIM2 : a double-edged sword preventing apoptosis
TRIM2 belongs to the TRIM-NHL class of ubiquitin E3-ligases and inhibits apoptosis by a dual function. Liao et al. reported in the recent issue that under glutamine deprivation, TRIM2 transcription is activated by ATF4 to increase the uptake of long fatty acids into mitochondria. Here, TRIM2 acts as a direct activator of CPT1 independent of its E3 ubiquitin ligase activity and prevents apoptosis otherwise triggered by starvation. On the contrary, TRIM E3-ubiquitin ligase has been described to ubiquitinate and thus target proapoptotic BIM for its degradation in the proteasome. Thus, TRIM2 inhibits apoptosis classically via its ligase activity but also independent of this stimulating energy metabolism
German evidence- and consensus-based guideline on the management of penile urethritis
Urethritis is a common condition predominantly caused by sexually transmitted pathogens such as Chlamydia trachomatis, Neisseria gonorrhoeae, and Mycoplasma genitalium. It is not possible to differentiate with certainty between pathogens on the basis of clinical characteristics alone. However, empirical antibiotic therapy is often initiated in clinical practice. The aim of this clinical practice guideline is to promote an evidence-based syndrome-orientated approach to the management of male adolescents and adults with symptoms of urethritis.
Besides recommendations for the diagnosis, classification and choice of treatment, this guideline provides recommendations for the indication to empirically treat patients with penile urethritis. A novel feature compared to existing, pathogen-specific guidelines is the inclusion of a flowchart for the syndrome-orientated practical management. For suspected gonococcal urethritis requiring empirical treatment, ceftriaxone is recommended. Due to the risk of Chlamydia trachomatis co-infection, doxycycline should also be prescribed, unless follow-up for the treatment of possible co-infections is assured. For suspected non-gonococcal urethritis, doxycycline is the recommended empirical treatment. In the empiric treatment of both gonococcal and non-gonococcal penile urethritis, azithromycin is reserved for cases where doxycycline is contraindicated. This guideline also includes detailed recommendations on differential diagnosis, pathogen-specific treatments and specific situations, as well as patient counselling and follow-up
Comparison of recognition of symptom burden in MPN between patient- and physician-reported assessment : an intraindividual analysis by the German Study Group for MPN (GSG-MPN)
Myeloproliferative neoplasms (MPN) are associated with a variety of symptoms that severely impact patients’ quality of life and ability to perform daily activities. Recent studies showed differences in the perception of physician- versus patient-reported symptom burden. However, studies directly comparing patient- and physician-reported ratings are lacking. Here, a retrospective analysis on symptom burden of 3979 MPN patients of the Bioregistry of the German Study Group for MPN was conducted to intra-individually compare physician and patient reports collected at the same time. Cohen’s kappa was calculated to assess the degree of agreement between patient and physician reports. Factors influencing baseline symptom severity were identified using linear regression and adjusted Cox models were calculated to investigate the effect of symptom burden on survival. MPN patients had a high symptom burden, which neither decreased over time nor upon cytoreductive therapy. All symptoms were more frequently reported by patients compared to physicians. Agreement remained low and only slightly improved when considering a higher threshold for patient symptom severity. Patients with severe symptom burden had inferior survival compared to patients with less severe symptoms. Assessment of symptom burden in MPN is therefore insufficient and patient-reported outcome tools need to be implemented into clinical routine
A new fibrin-heparine coated self-expanding stent for the rescue treatment of intracranial stenosis : a multicentric study
Introduction: Rescue intracranial stenting is necessary to provide sufficient recanalization after mechanical thrombectomy (MT) in patients with acute large vessel occlusions (LVO) due to an underlying intracranial atherosclerotic disease (ICAD). The CREDO heal is a novel stent that provides a potentially lower thrombogenicity due to surface modification. We present the first multicentric experience with the CREDO heal for acute rescue stenting. Methods: Data of 81 patients who underwent rescue stenting after MT at 12 centers in Germany and Spain were prospectively collected and retrospectively evaluated. Results: Final mTICI 2b‑3 was reached in 95.1% after median two MT maneuvers and stenting. Four periprocedural complications resulted in clinical deterioration (4.9%). Intraparenchymal hemorrhage occurred in one patient (1.2%) and functional independence at FU was reached by 42% of the patients. Most interventions were performed under Gp IIb/IIIa inhibitors. Conclusion: CREDO heal was effective and safe in our case series. However, more data is needed to define the optimal antithrombotic regime. The use under single antiplatelet medication is not supported by our study