Néstor-Guillermo Progeria Syndrome: a biochemical insight into Barrier-to-Autointegration Factor 1, alanine 12 threonine mutation

Background Premature aging syndromes recapitulate many aspects of natural aging and provide an insight into this phenomenon at a molecular and cellular level. The progeria syndromes appear to cause rapid aging through disruption of normal nuclear structure. Recently, a coding mutation (c.34G > A [p.A12T]) in the Barrier to Autointegration Factor 1 (BANF1) gene was identified as the genetic basis of Néstor-Guillermo Progeria syndrome (NGPS). This mutation was described to cause instability in the BANF1 protein, causing a disruption of the nuclear envelope structure. Results Here we demonstrate that the BANF1 A12T protein is indeed correctly folded, stable and that the observed phenotype, is likely due to the disruption of the DNA binding surface of the A12T mutant. We demonstrate, using biochemical assays, that the BANF1 A12T protein is impaired in its ability to bind DNA while its interaction with nuclear envelope proteins is unperturbed. Consistent with this, we demonstrate that ectopic expression of the mutant protein induces the NGPS cellular phenotype, while the protein localizes normally to the nuclear envelope. Conclusions Our study clarifies the role of the A12T mutation in NGPS patients, which will be of importance for understanding the development of the disease.

Structural Basis of Drug Resistance by Genetic Variants of HIV Type 1 Clade C Protease from India

Using computer modeling of three-dimensional structures and structural information available on the crystal structures of HIV-1 protease, we investigated the structural effects of mutations, in treatment-naive and treatment-exposed individuals from India and postulated mechanisms of resistance in clade C variants. A large number of models (14) have been generated by computational mutation of the available crystal structures of drug bound proteases. Localized energy minimization was carried out in and around the sites of mutation in order to optimize the geometry of interactions present. Most of the mutations result in structural differences at the flap that favors the semiopen state of the enzyme. Some of the mutations were also found to confer resistance by affecting the geometry of the active site. The E35D mutation affects the flap structure in clade B strains and E35N and E35K mutation, seen in our modeled strains, have a more profound effect. Common polymorphisms at positions 36 and 63 in clade C also affected flap structure. Apart from a few other residues Gln-58, Asn-83, Asn-88, and Gln-92 and their interactions are important for the transition from the closed to the open state. Development of protease inhibitors by structure-based design requires investigation of mechanisms operative for clade C to improve the efficacy of therapy.

Odour emissions from anaerobic piggery ponds. 1. Results of a three season, 14-month survey

Odour emission rates were measured for seven different anaerobic ponds treating piggery wastes at six to nine discrete locations across the surface of each pond on each sampling occasion over a 14-month period. Emission rate values varied between ponds, between seasons for the same pond and even for the same pond on different days of a sampling week. Average seasonal emission rates ranged from 7.9 to 46.5 OU/m2 s, while average emission rates ranged from 16.0 to 29.0 OU/m2 s. Factors potentially responsible for the variability in emission rates were investigated, including air and pond liquor temperatures, time of day of sample collection, season and the impact of a prolonged drought.

Studio portrait of Josef Molling with unidentified man; Heidelberg, Germany.

right: Joseph Molling sitting; left: unknown man standing

Studio portrait of Josef Molling with unidentified man; Heidelberg, Germany.

right: Joseph Molling sitting; left: unknown man standing

Joseph Molling with wife Margarete "Gretchen" nee Benjamin and son Peter on a walk.

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Portrait of Hedwig and Ludwig Heinemann and Margarete nee Benjamin and Joseph Molling.

Elderly couple Hedwig and Ludwig Heinemann envolved with Adolph Molling Business. Younger couple is Margarete "Gretchen" Molling geb. Benjamin and Joseph Molling.

Portrait of Joseph and his sister Elly Schoenbeck; Cologne, Germany. Portraits family

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Portrait of Joseph Rothschild and his wife Rosalie nee Stern; Bad Ems, Germany. Portraits Couples

Handwritten on verso of original photograph: Joseph u Rosalie Rothschild

Tombstone of Joseph Benjamin; Strangriede Cemetery, R83.8; Hannover Cemeteries Tombs

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Tombstone of Marianne Benjamin nee Sussmann; Strangriede Cemetery (R 83.9); Hannover Cemeteries Tombs

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Tombstones of Joseph Benjamin and Marianne Benjamin nee Sussmann; Strangriede Cemetery (R 83.8 and R 83.9); Hannover Cemeteries Tombs

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Portrait of Dr. Joseph Wallerstein holding his infant grandson Hans Stern.

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Tombstone of Joseph Benjamin; Strangriede Cemetery (R 83.8); Hannover Cemeteries Tombs

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Joseph Ritter von Wertheimer, Moritz Lazarus and Abraham Geiger; Officers of the first Jewish Council of Leipzig Portraits; Groups; Men

"Praesidium der ersten israelitischen Synode zu Leipzig. II Vicepraesident Ritter V. Wertheimer aus Wien. Praesident Prof. Dr. M. Lazarus aus Berlin. I Vicepraesident Dr. A. Geiger aus Frankfurt a/M."