A naturally occuring insertion of a single amino acid rewires transcriptional regulation by glucocorticoid receptor isoforms

In addition to guiding proteins to defined genomic loci, DNA can act as an allosteric ligand that influences protein structure and activity. Here we compared genome-wide binding, transcriptional regulation, and, using NMR, the conformation of two glucocorticoid receptor (GR) isoforms that differ by a single amino acid insertion in the lever arm, a domain that adopts DNA sequence-specific conformations. We show that these isoforms differentially regulate gene expression levels through two mechanisms: differential DNA binding and altered communication between GR domains. Our studies suggest a versatile role for DNA in both modulating GR activity and also in directing the use of GR isoforms. We propose that the lever arm is a "fulcrum" for bidirectional allosteric signaling, conferring conformational changes in the DNA reading head that influence DNA sequence selectivity, as well as conferring changes in the dimerization domain that connect functionally with remote regulatory surfaces, thereby influencing which genes are regulated and the magnitude of their regulation

Glycosylation of mucins present in gastric juice: the effect of helicobacter pylori eradication treatment

It is suggested that gastric mucins, and in particular some specific glycan structures that can act as carbohydrate receptors, are involved in the interactions with Helicobacter pylori adhesins. The main aim of our study was to evaluate glycosylation pattern of glycoproteins of gastric juice before and at the end of eradication therapy. Gastric juices were taken from 13 clinical patients and subjected to analysis. Pooled fractions of the void volume obtained after gel filtration were subjected to ELISA tests. To assess the relative amounts of carbohydrate structures, lectins and monoclonal antibodies were used. Changes in the level of MUC 1 and MUC 5AC mucins and of carbohydrate structures, which are suggested to be receptors for Helicobacter pylori adhesins, were observed by the end of the eradication treatment. Our results support the idea about the involvement of MUC 5AC and MUC 1 with some specific sugar structures in the mechanism of Helicobacter pylori infection

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Upgrading of wastewater treatment plants in Poland. Phase I

In order to identify operation problems and to improve treatment efficiency, diagnostic studies have been carried out at selected treatment plants. Recommendations are made how to improve the situation. Chemical precipitation is one of the solutions considered

Role of hexosaminidase in the pathogenesis of cholesteatoma

Introduction: Cholesteatoma is a destructive lesion that leads to the destruction of adjacent structures. The aim of our study was to demonstrate the activity of N-acetylo-beta-D-hexosaminidase (HEX) in cholesteatoma and normal retroauricular skin and the possible correlation between HEX activity and bone resorption in cholesteatoma. Material and Methods: After removal, cholesteatomas and normal adult retroauricular skin were immediately frozen in - 80degrees C. To assess the enzymes activities Chatterjee et al. method in the modification of Zwierz et al. was used. Results: In 20 of 21 specimens we observed significantly higher activity of investigated enzyme in cholesteatoma tissue compared with that in normal skin. Release of HEX from the activated cells ranged from 1.08 to 5.57 fold as compared to controls. In one cholesteatoma specimen, the activity of HEX was 5.57 and in four cholesteatoma specimens, was 3.02 to 3.34 fold higher than in the skin. In these five cases the history of chronic otitis media ranged from 4 to 6 years, the granulation tissue and purulent otorrhea were present and more intense than in the other cases. The destruction of malleus and long process of incus were observed. Conclusions: Hex may play an important role in bone resorption in the area adjacent to cholesteatoma. It may be considered as a new pathogenetic factor in that destructive lesion. Further studies will be conducted on the correlation between the HEX activities and the local inflammatory infiltrate

Apoptose in der Pathogenese des Cholesteatoms bei Erwachsenen

Einleitung: Apoptose, also vorprogrammiertes Zellenabsterben, findet in jedem Organismus statt. Das Ziel der Arbeit war es, die Verteilung und apoptische Fähigkeit in einzelnen Epithelschichten von Cholesteatom im Vergleich zur gesunden Haut zu bestimmen.Material und Methode: Die Apoptose wurde mit dem hochspezifischen Antikörper gegen Antigene APO 2.7. markiert. Die Anzahl der apoptosischen Zellen wurde in drei unterschiedlichen Bereichen von Plattenepithel der Cholesteatommatrix und der gesunden Oberhaut berechnet, wobei der ±SD Durchschnitt berücksichtigt wurde. Bei diesen Messungen wurde das automatisches Analyse-System eingesetzt.Ergebnisse: Es wurden statistisch signifikante Unterschiede (p< 0,05) für APO2.7 Zellen im Plattenepithel der Cholesteatommatrix im Vergleich zur Haut festgestellt.Schlussfolgerungen: Die apoptosische Aktivität ist bei Plattenepithel der Cholesteatommatrix viel höher im Vergleich zur Haut. Die Apoptose-Zellen werden vor allem in der Verhornungsschicht beobachtet. Sie treten nicht in der Basalschicht von Plattenepithel der Cholesteatommatrix auf. Apoptose spielt eine wichtige Rolle bei der Pathogenese von Cholesteatom. Es scheint, dass sie an der Differenzierung und Akkumulation von Keratin-Resten im Mittelohr teilnimmt und zur Expansion von Cholesteatom beiträgt