An arginyl in the N-terminus of the V1a vasopressin receptor is part of the conformational switch controlling activation by agonist.

Defining how the agonist-receptor interaction differs from that of the antagonist-receptor and understanding the mechanisms of receptor activation are fundamental issues in cell signalling. The V1a vasopressin receptor (V1aR) is a member of a family of related G-protein coupled receptors that are activated by neurohypophysial peptide hormones, including vasopressin (AVP). It has recently been reported that an arginyl in the distal N-terminus of the V1aR is critical for binding agonists but not antagonists. To determine specific features required at this locus to support high affinity agonist binding and second messenger generation, Arg46 was substituted by all other 19 encoded amino acids. Our data establish that there is an absolute requirement for arginyl, as none of the [R46X]V1aR mutant constructs supported high affinity agonist binding and all 19 had defective signalling. In contrast, all of the mutant receptors possessed wildtype binding for both peptide and nonpeptide antagonists. The ratio of Ki to EC50, an indicator of efficacy, was increased for all substitutions. Consequently, although [R46X]V1aR constructs have a lower affinity for agonist, once AVP has bound all 19 are more likely than the wildtype V1aR to become activated. Therefore, in the wildtype V1aR, Arg46 constrains the inactive conformation of the receptor. On binding AVP this constraint is alleviated, promoting the transition to active V1aR. Our findings explain why arginyl is conserved at this locus throughout the evolutionary lineage of the neurohypophysial peptide hormone receptor family of G-protein coupled receptors.     

Genital oedema in patients treated by continuous ambulatory peritoneal dialysis: an unusual presentation of inguinal hernia.

Four patients receiving continuous ambulatory peritoneal dialysis presented with scrotal or labial oedema but no detectable cough impulse. Two of the patients later developed clinical evidence of inguinal hernia, and in the other two inguinal hernias were found at operation. These cases suggest that genital oedema occurring in a patient receiving continuous ambulatory peritoneal dialysis is a sign of a small inguinal hernia which may not be detectable clinically.     

The shape of human gene family phylogenies

Background  

The shape of phylogenetic trees has been used to make inferences about the evolutionary process by comparing the shapes of actual phylogenies with those expected under simple models of the speciation process. Previous studies have focused on speciation events, but gene duplication is another lineage splitting event, analogous to speciation, and gene loss or deletion is analogous to extinction. Measures of the shape of gene family phylogenies can thus be used to investigate the processes of gene duplication and loss. We make the first systematic attempt to use tree shape to study gene duplication using human gene phylogenies.     

Structural gene for the alkaline extracellular protease of Saccharomycopsis lipolytica.

Mutants for Saccharomycopsis lipolytica temperature sensitive for alkaline extracellular protease production, but not for growth, were isolated. Thirty-three isolates were temperature sensitive for protease production, and one (xpr-32) produced a temperature-sensitive protease. Genetic analysis indicated that xpr-32 was located in gene XPR2, and allele xpr2-7 was found to also produce a temperature-sensitive protease. None of five independently isolated xpr2 mutations affects the production of extracellular ribonucleases and acid protease(s). Diploids with zero, one, or two active alleles of the XPR2 locus were constructed, and the XPR2 locus was shown to exhibit a gene dosage effect on alkaline extracellular protease synthesis (enzyme activity/cell protein). These results suggest that the XPR2 gene is the structural gene for the alkaline extracellular protease of S. lipolytica.     

DIALYSIS WITH STIRRING

Substances to be purified by dialysis are placed in collodion bags together with a toy "marble" or a bubble of air. The bags are stoppered and placed in glass tubes of a rocking machine. Distilled water of the desired temperature is circulated through the tubes (around the bags) at a rate of about 8 cc. per minute per bag while the machine is in motion. The rolling of the marbles or bubbles causes stirring which makes it possible to remove the salts from a protein solution in 24 to 48 hours.     

Patterns of evolution among lower Jurassic crinoids

The crinoid families Isocrinidae and Pentacrinitidae are well represented in the British Lower Jurassic, allowing a detailed investigation of their evolution at this time. The pseudopelagic pentacrinitids diverged from the benthic isocrinids during the Triassic. Seirocrinus arose from Pentacrinites through hyper‐morphosis prior to the start of the Jurassic but both genera subsequently show extreme evolutionary conservatism, perhaps attributable to constraints imposed by their unusual life‐style. From a single species in the Hettangian, the benthic isocrinids diversified in the Sinemurian and Carixian. A “central lineage”;, comprising three species of Chladocrinus, evolved along a peramorphocline by “intermittent anagenesis”;, prolonged periods of evolutionary stasis punctuated by short periods of gradualistic change. Two main offshoots, Balanocrinus and Hispidocrinus gen. nov., represent shifts into new habitats. Balanocrinus arose through progenesis, with subsequent evolution along a paedomorphocline, while Hispidocrinus may have arisen through extreme peramorphosis, although its spinose brachials are an evolutionary innovation. Both genera show an apparently punctuated mode of evolution. There is some correlation between morphology and faciès, and also between the emergence of new species and times of high sea level. Benthic isocrinids appear to have been greatly affected by the early Toarcian anoxic event but the pseudopelagic pentacrinitids were not.     

Divergent patrilineal signals in three Roma populations

Previous studies have revealed that the European Roma share close genetic, linguistic and cultural similarities with Indian populations despite their disparate geographical locations and divergent demographic histories. In this study, we report for the first time Y-chromosome distributions in three Roma collections residing in Belgrade, Vojvodina and Kosovo. Eighty-eight Y-chromosomes were typed for 14 SNPs and 17 STRs. The data were subsequently utilized for phylogenetic comparisons to pertinent reference collections available from the literature. Our results illustrate that the most notable difference among the three Roma populations is in their opposing distributions of haplogroups H and E. Although the Kosovo and Belgrade samples exhibit elevated levels of the Indian-specific haplogroup H-M69, the Vojvodina collection is characterized almost exclusively by haplogroup E-M35 derivatives, most likely the result of subsequent admixture events with surrounding European populations. Overall, the available data from Romani groups points to different levels of gene flow from local populations.