AVPR2 variants and V2 vasopressin receptor function in nephrogenic diabetes insipidus

BACKGROUND: The AVPR2 gene encodes the type 2 vasopressin receptor, a member of the vasopressin/oxytocin receptor subfamily of G protein-coupled receptors. Disruption of AVPR2 causes X-linked congenital nephrogenic diabetes insipidus (NDI), yet the functional significance of most gene sequence variations found in association with NDI has not been proven. The large number of naturally occurring AVPR2 mutations constitutes a model system for studying the structure-function relationship of G protein-coupled receptors. This analysis can be aided by examining amino acid sequence variation and conservation among evolutionarily disparate members of the subfamily. METHODS: Twenty-five new NDI patients were evaluated by DNA sequencing for mutations in AVPR2. Receptors encoded by eighteen NDI alleles were tested for physiologic signaling activity in response to varying concentrations of arginine vasopressin (AVP) in a sensitive cell culture assay. Seventeen amino acid sequences from the vasopressin/oxytocin receptor subfamily were aligned and conserved residues were identified and correlated with the locations of NDI associated variations. RESULTS: Twenty-four variant alleles were found among the 25 new patients. Thirteen had no prior family history of expressed NDI. All 18 of the NDI-associated AVPR2 alleles tested for function demonstrated diminished response to stimulation with AVP. Twelve failed to respond at all, whereas six signaled only at high AVP concentrations. Evolutionarily conserved residues clustered in the transmembrane domains and in the first and second extracellular loops, and NDI-associated missense mutations appeared mostly in the conserved domains. CONCLUSIONS: Sporadic cases are frequent and they usually represent the X-linked rather than the autosomal form of NDI. Genetic and functional testing can confirm this in individual cases. Mutations in this study affecting ligand binding domains tend to retain partial signaling in vitro, whereas those that introduce a charged residue in a transmembrane domain are inactive. The minimal partial signaling observed in cultured cells is unlikely to correlate with clinically significant urine concentrating ability. Other AVPR2 mutations with milder effects on receptor function probably exist, but may not be expressed clinically as typical NDI.     

Chi recombination activity in phage lambda decays as a function of genetic distance

In Escherichia coli, chi is a recombination hotspot that stimulates RecBCD-dependent exchange at and to one side of itself. chi activity is highest at chi and decreases with distance from chi. The decrease in chi activity may be a simple property of the physical distance over which chi can stimulate recombination. Alternatively, the decay in chi activity with distance may reflect the high likelihood that chi-stimulated recombination occurs in a single chi-proximal act, to the exclusion of additional chi-stimulated exchanges more distal to chi. To test the models, we determined if chi activity decreases as a function of physical distance (i.e., DNA base pairs) or genetic distance (homologous DNA base pairs). Our results indicate that chi activity decays as a function of genetic distance. In addition, we found that the sbcB gene product (exonuclease I, a 3'-->5' ssDNA exonuclease) modulates the distance over which chi can act. In contrast, the recJ gene product (a 5'-->3' ssDNA exonuclease) does not alter the decay of chi activity.     

Comparison of the resistance of C57BL/6 and C3H/He mice to infection with Mycobacterium paratuberculosis

Susceptibility of C57BL/6 (Bcgs) and C3H/HeN (Bcgr) mice to an intraperitoneal infection with Mycobacterium paratuberculosis strain 19698 was compared (by histopathology and the number of mycobacteria isolated from the spleen). Mycobacterial counts from the spleen of Bcgr mice progressively decreased over the course of infection but remained unchanged in Bcgs mice. Granulomatous lesions and acid-fast bacteria were consistently present in the liver and lymph nodes of Bcgs mice, whereas lesions were transient or absent in Bcgr mice. These results indicate that Bcgr mice are inherently resistant to M. paratuberculosis, whereas Bcgs mice are inherently susceptible. These differences may prove useful in elucidating the mechanisms of resistance and susceptibility to paratuberculosis and other mycobacterial infections.     

Intrathecal opioids provide satisfactory conditions in labor analgesia and spinal anesthesia for cesarean section

Metastases is an uncommon cause of tumors in the sinonasal region. We report a patient with hepatocellular carcinoma which metastasized to the nasal cavity.     

Targeting Intercellular Communication in the Bone Microenvironment to Prevent Disseminated Tumor Cell Escape from Dormancy and Bone Metastatic Tumor Growth

Metastasis to the bone is a common feature of many cancers including those of the breast, prostate, lung, thyroid and kidney. Once tumors metastasize to the bone, they are essentially incurable. Bone metastasis is a complex process involving not only intravasation of tumor cells from the primary tumor into circulation, but extravasation from circulation into the bone where they meet an environment that is generally suppressive of their growth. The bone microenvironment can inhibit the growth of disseminated tumor cells (DTC) by inducing dormancy of the DTC directly and later on following formation of a micrometastatic tumour mass by inhibiting metastatic processes including angiogenesis, bone remodeling and immunosuppressive cell functions. In this review we will highlight some of the mechanisms mediating DTC dormancy and the complex relationships which occur between tumor cells and bone resident cells in the bone metastatic microenvironment. These inter-cellular interactions may be important targets to consider for development of novel effective therapies for the prevention or treatment of bone metastases.     

Effect of nutrient seed coating on the emergence of wheat and oats

A series of experiments was conducted under controlled soil moisture and temperature conditions in a growth chamber to examine the effect of a range of nutrient seed coatings on the emergence to wheat (Triticum aestivum L. cv. Kite) and oats (Avena sativa L. cv. Blackbutt) sown in a coarse sandy loam soil. Final emergence of oats was not reduced by a coating containing 10 kg P ha^–1 (as monocalcium phosphate [MCP]) whereas the same coating reduced wheat emergence by 15%. The emergence of both wheat and oats was severely reduced by urea coatings (supplying 10 kg N ha^–1) to 33 and 13% respectively; this injury was lessened markedly by the inclusion of phenyl phosphorodiamidate (PPD) in the urea coatings at 1% (w/w) (emergence increased to 66 and 56% respectively).Low soil moisture (67% of field capacity [FC]) resulted in almost no emergence of wheat coated with urea (± bentonites of different pH). In soil at FC, the addition of bentonite of pH 5 (B5) to urea coatings permitted greater emergence (54%) than when bentonite of pH 9 (B9) was added (32%) which, in turn, permitted greater emergence than urea coating alone (10%). When PPD and bentonite (B5 or B9) were combined either singly or together with urea in seed coatings, PPD was more effective than either of the bentonites in reducing injury and masked the slight positive effect of B5.Coatings containing various combinations of N and P sources (at 3.6 and at 8 kg ha^–1 respectively) all reduced the emergence of wheat compared to raw seed (91% emergence). When applied alone, MCP was least damaging (74%); the combination of MCP with ammonium sulfate (AS) caused somewhat more injury (68%) whilst combination with calcium nitrate (CN) caused most injury (29%). In contrast, CN alone caused relatively little damage (73%) whilst AS alone was more damaging (50%). There was no significant regression found between percentage emergence and either the calculated partial salt index or the pH of the nutrient coatings. Further work is needed to examine the mechanisms of injury due to nutrient seed coatings so that safe but effective formulations can be developed.     

Public Key Cryptography in Action

This article discusses data security and controls, primarily in the context of data base management systems (DBMSs), with an emphasis on basic principles and mechanisms that have been successfully used by practitioners in actual products and systems. The general discussion does not focus on particular products, although a later section does review several products to illustrate previously discussed concepts. The discussion of data bases is limited specifically to relational DBMSs, which store data in relations that have specific mathematical properties. All examples given are in SQL. It is assumed that readers are familiar with rudimentary concepts of relational data bases and SQL.

This article begins with a review of basic security objectives, followed by a discussion of access controls in the current generation of commercially available DBMSs. The problem of multilevel security is then introduced, including a review of techniques developed specifically for multilevel security.