Standardization of "exchange" techniques to measure estradiol receptors in extracts exposed to biospecific adsorbants]

The measurement of the binding of steroid hormone receptors to biospecific adsorbants requires the development of "exchange" techniques. Two types of techniques based on the principle of differential dissociation were standardized: solid phase exchange with hydroxylapatite and liquid phase exchange with adsorption of the ligand to charcoal dextran. In both cases, binding of oestradiol to its receptor was measured in calf uterine cytosol extracts. Results obtained by both techniques were comparable. The half-times of the oestradiol-receptor complex dissociation determined from exchange kinetics are on the same order as those obtained by direct methods used in previous studies.     

Germline KRAS mutations cause Noonan syndrome

Noonan syndrome (MIM 163950) is characterized by short stature, facial dysmorphism and cardiac defects. Heterozygous mutations in PTPN11, which encodes SHP-2, cause approximately 50% of cases of Noonan syndrome. The SHP-2 phosphatase relays signals from activated receptor complexes to downstream effectors, including Ras. We discovered de novo germline KRAS mutations that introduce V14I, T58I or D153V amino acid substitutions in five individuals with Noonan syndrome and a P34R alteration in a individual with cardio-facio-cutaneous syndrome (MIM 115150), which has overlapping features with Noonan syndrome. Recombinant V14I and T58I K-Ras proteins show defective intrinsic GTP hydrolysis and impaired responsiveness to GTPase activating proteins, render primary hematopoietic progenitors hypersensitive to growth factors and deregulate signal transduction in a cell lineage-specific manner. These studies establish germline KRAS mutations as a cause of human disease and infer that the constellation of developmental abnormalities seen in Noonan syndrome spectrum is, in large part, due to hyperactive Ras.     

Surface PEGylation of hollow mesoporous silica nanoparticles via aminated intermediate

A hybrid of organic/inorganic system, hollow mesoporous silica nanoparticles functionalized with poly(ethylene glycol), was synthesized in the presence of coupling agent and aminated ends. Doxorubicin (DOX) was used as a model drug to evaluate the effect of PEGylation on the loading capacity and release pattern of the system. Characterization with transmission electron microscopy (TEM) and scanning electron microscopy (SEM), X-ray diffraction (XRD), nitrogen adsorption-desorption, thermogravimetric analysis (TGA) and Fourier transformed infrared (FTIR) confirmed the PEG conjugation, as well as the amorphous mesoporous nature of the synthesized particles. Due to the capping effect of PEG molecules over the pores in the silica structure, the synthesized system was able to retain higher amount of cargo and establish a controlled manner when releasing.     

A new species of the genus Zhangixalus (Amphibia: Rhacophoridae) from Vietnam

ABSTRACT

A new rhacophorid species is described from Vietnam on the basis of nine specimens collected in Quan Ba District, Ha Giang Province, northeastern Vietnam. The new species is morphologically similar to Zhangixalus pinglongensis, Z. dorsoviridis, and Z. nigropunctatus, however, it differs from the latter by having the flank cream with large black blotches on axilla and groin. The genetic distance between the new species and Zhangixalus pinglongensis, Z. dorsoviridis and Z. nigropunctatus is >3.57% (16S mtDNA gene fragment). Zhangixalus jodiae sp. nov. can be distinguished from all other species of Zhangixalus and other small rhacophorid species from Southeast Asia by a combination of the following characters: size small (SVL 36.1–39.8 mm in males); head as long as wide; vomerine teeth present; dorsal surface of head and body green without spots; axilla cream with large black blotches, groin and front-rear parts of the thigh, ventral surface of tibia black with orange blotches; lower jaw region greyish, chest and belly cream.

http://www.zoobank.org/urn:lsid:zoobank.org:pub:89597718-024F-4FFC-B0AE-2005F12CF66C     

Intestinal vasoactive peptide receptors in enterocytes : specific binding and stimulation of cyclic AMP]

Receptors for the vasoactive intestinal peptide (VIP) were characterized on enterocytes isolated from Rat small intestine. Native VIP inhibited competitively the binding of 125I-VIP to enterocytes and strongly stimulated cyclic AMP production; both these effects were observed for concentrations of VIP as low as 0.5-1.0 ng/ml (0.15-0.30 nM) which are compatible with the VIP concentration in the gut.     

Physiogenomic resources for rat models of heart, lung and blood disorders

Cardiovascular disorders are influenced by genetic and environmental factors. The TIGR rodent expression web-based resource (TREX) contains over 2,200 microarray hybridizations, involving over 800 animals from 18 different rat strains. These strains comprise genetically diverse parental animals and a panel of chromosomal substitution strains derived by introgressing individual chromosomes from normotensive Brown Norway (BN/NHsdMcwi) rats into the background of Dahl salt sensitive (SS/JrHsdMcwi) rats. The profiles document gene-expression changes in both genders, four tissues (heart, lung, liver, kidney) and two environmental conditions (normoxia, hypoxia). This translates into almost 400 high-quality direct comparisons (not including replicates) and over 100,000 pairwise comparisons. As each individual chromosomal substitution strain represents on average less than a 5% change from the parental genome, consomic strains provide a useful mechanism to dissect complex traits and identify causative genes. We performed a variety of data-mining manipulations on the profiles and used complementary physiological data from the PhysGen resource to demonstrate how TREX can be used by the cardiovascular community for hypothesis generation.