Untersuchungen über das gelenk in der taille der apocriten hymenopteren

Ohne ZusammenfassungVerzeichnis der Abkürzungen Ap. Apophyse (des Metasternits zwischen Propodeal- und Metacoxenöffnung) - d.P. dorsale Platte (der Propodealöffnung) - d.I. dorsaler Intersegmentalschlauchteil - G. Ö. Große (ventrale) Öffnung des Propodeums - Gr. Seitengruben, Einsenkungen in den Seiten des Kieles - H. G. Hilfsgelenk, die Richtung der Bewegung bestimmende gelenkartige Verbindung zwischen Tergitecken und Aushöhlungen ventral von den Propodealzapfen - I.M. Intersegmentalmembran zwischen 2. Abdominal- und Mittelsegment bzw. Metasternit - Ki. Kiel des 2. Tergites - K.L. Kiellamelle - K.O. Kleine (dorsale) Öffnung des Propodeums - M.C. Metacoxen - Mi.S. Mittelsegment (Propodeum) - M.St. Metasternit - P.Ö. Propodealöffnung - R.d. Retractor dorsalis intersternalis - R.l.st. Retractor lateralis intersternalis - R.l.t. Retractor lateralis intertergalis - R.m. Retractor medius intersternalis - r.K.L. rechte Kiellamelle - S. . . . s. Schnittebene dureb das 2. Abdominalsegment, die in die Propodealöffnung punktiert eingezeichnet ist - St. II, III ... 2., 3... Sternit - St.P. Sternitplatte - S.W. Seitenwulst (des II. Tergites) - T.E. Tergitecke - T.Ö. Öffnung hinter dem Kiel des II. Tergites - Te. II, III ... Tergit des 2., 3. Abdominalsegmentes - Z. Propodealzapfen - v.S. ventraler Intersegmentalschlauchteil - Ü. Übergangsstelle des dorsalen in den ventralen Teil des Intersegmental-membranschlaucbes     

Design and synthesis of 4,5,6,7‐tetrahydro‐1H‐1,2‐diazepin‐7‐one derivatives as a new series of Phosphodiesterase 4 (PDE4) inhibitors

Phosphodiesterase 4 (PDE4) inhibitors have attractive therapeutic potential in respiratory, inflammatory, metabolic and CNS disorders. The present work details the design, chemical exploration and biological profile of a novel PDE4 inhibitor chemotype. A diazepinone ring was identified as an under-represented heterocyclic system fulfilling a set of PDE4 structure-based design hypotheses. Rapid exploration of the structure activity relationships for the series was enabled by robust and scalable two/three-steps parallel chemistry protocols. The resulting compounds demonstrated PDE4 inhibitory activity in cell free and cell-based assays comparable to the Zardaverine control used, suggesting potential avenues for their further development.     

A variant of KCC2 from patients with febrile seizures impairs neuronal Cl− extrusion and dendritic spine formation

Genetic variation in SLC12A5 which encodes KCC2, the neuron-specific cation-chloride cotransporter that is essential for hyperpolarizing GABAergic signaling and formation of cortical dendritic spines, has not been reported in human disease. Screening of SLC12A5 revealed a co-segregating variant (KCC2-R952H) in an Australian family with febrile seizures. We show that KCC2-R952H reduces neuronal Cl⁻ extrusion and has a compromised ability to induce dendritic spines in vivo and in vitro. Biochemical analyses indicate a reduced surface expression of KCC2-R952H which likely contributes to the functional deficits. Our data suggest that KCC2-R952H is a bona fide susceptibility variant for febrile seizures.     

Differential Interaction Kinetics of a Bipolar Structure-Specific Endonuclease with DNA Flaps Revealed by Single-Molecule Imaging

As DNA repair enzymes are essential for preserving genome integrity, understanding their substrate interaction dynamics and the regulation of their catalytic mechanisms is crucial. Using single-molecule imaging, we investigated the association and dissociation kinetics of the bipolar endonuclease NucS from Pyrococcus abyssi (Pab) on 5′ and 3′-flap structures under various experimental conditions. We show that association of the PabNucS with ssDNA flaps is largely controlled by diffusion in the NucS-DNA energy landscape and does not require a free 5′ or 3′ extremity. On the other hand, NucS dissociation is independent of the flap length and thus independent of sliding on the single-stranded portion of the flapped DNA substrates. Our kinetic measurements have revealed previously unnoticed asymmetry in dissociation kinetics from these substrates that is markedly modulated by the replication clamp PCNA. We propose that the replication clamp PCNA enhances the cleavage specificity of NucS proteins by accelerating NucS loading at the ssDNA/dsDNA junctions and by minimizing the nuclease interaction time with its DNA substrate. Our data are also consistent with marked reorganization of ssDNA and nuclease domains occurring during NucS catalysis, and indicate that NucS binds its substrate directly at the ssDNA-dsDNA junction and then threads the ssDNA extremity into the catalytic site. The powerful techniques used here for probing the dynamics of DNA-enzyme binding at the single-molecule have provided new insight regarding substrate specificity of NucS nucleases.     

Distribution of Gd- alleles in some ethnic groups of the USSR

Summary A population study of Gd^- allele distribution was made in similar (age-sex) samples of schoolchildren and students from different ethnic groups: Russians, Ashkenazi Jews, and Azerbaijanians. Both the frequency and the spectrum of the Gd^- alleles were quite different. The Gd^- frequency in Russians (Kostroma region) was 0.36%; in Ashkenazim (Gomel region), 0.91%; in Azerbaijanians (Sheki region and Apsheron region), 3.6% and 10.5%, respectively. G6PD deficiency in Russians is represented by familial forms; in Ashkenazi Jews by class II alleles Kirovograd and Zhitomir; and in Azerbaijanians, by a wide spectrum of class II and III alleles. Genetic factors involved in the formation of Gd^- allele frequencies and the spectrum in these three ethnic groups are discussed.     

A functional Wood–Ljungdahl pathway devoid of a formate dehydrogenase in the gut acetogens Blautia wexlerae,Blautia luti and beyond

Species of the genus Blautia are typical inhabitants of the human gut and considered as beneficial gut microbes. However, their role in the gut microbiome and their metabolic features are poorly understood. Blautia schinkii was described as an acetogenic bacterium, characterized by a functional Wood–Ljungdahl pathway (WLP) of acetogenesis from H₂ + CO₂. Here we report that two relatives, Blautia luti and Blautia wexlerae do not grow on H₂ + CO₂. Inspection of the genome sequence revealed all genes of the WLP except genes encoding a formate dehydrogenase and an electron-bifurcating hydrogenase. Enzyme assays confirmed this prediction. Accordingly, resting cells neither converted H₂ + CO₂ nor H₂ + HCOOH + CO₂ to acetate. Carbon monoxide is an intermediate of the WLP and substrate for many acetogens. Blautia luti and B. wexlerae had an active CO dehydrogenase and resting cells performed acetogenesis from HCOOH + CO₂ + CO, demonstrating a functional WLP. Bioinformatic analyses revealed that many Blautia strains as well as other gut acetogens lack formate dehydrogenases and hydrogenases. Thus, the use of formate instead of H₂ + CO₂ as an interspecies hydrogen and electron carrier seems to be more common in the gut microbiome.