The Kinetics of Sodium Transport in the Toad Bladder : I. Determination of the transport pool

A compartmental model of toad bladder sodium content has been developed, whereby it is possible to measure the four unidirectional fluxes across the opposite faces of the transport compartment, as well as the amount of sodium in the compartment. ²⁴Na is added to the mucosal medium of a short-circuited bladder mounted between halves of a chamber in which the fluid is stirred by rotating impellers. After a steady state is reached, nonradioactive medium is flushed through both sides of the chamber, collected, and counted. The data from each chamber are fitted to sums of exponentials and interpreted in terms of conventional compartmental analysis. Three exponentials are required, with half-times of 0.2, 2.2, and 14.0 min. It is shown that the first of these represents chamber washout, the second the transport pool, and the third a tissue compartment which is not involved in active sodium transport and which does not communicate with the transport pool. The second compartment contains 10.5 µEq of sodium per 100 mg dry weight, an amount equal to approximately 30% of total tissue sodium. The results also indicate, as expected from electrophysiological data, that the mucosal-facing side of the transport compartment is over 10 times as permeable to sodium as the serosal, or pump, side.     

Distribution of monoamine oxidase in the hippocampal region of the guinea pig

Summary 1. The distribution of monoamine oxidase (MAO) within the dentate area, a part of the hippocampal region, has been described for the adult guinea pig.2. The histochemical demonstration of the enzyme was done essentially according to the tryptamine-tetrazolium method of Glenner et al., and the staining reactivity was controlled by complete inhibition with iproniazide.3. Most of the MAO in the dentate area was present in a stratified pattern. Within the molecular layer, a supragranular third reacted heavily, while a more weakly staining superficial layer could be distinguished from an intermediate, still paler lamina. The granular cell bodies were unstained. In the hilus, five layers showing alternating stronger and weaker activity were observed. The distribution of the MAO staining was compared with conventional anatomical subdivision of the dentate region.4. The guinea pig dentate area appears to have a greater amount and more stratified distribution of MAO than the comparable region previously described in the rat.I am indebted to Mrs. E. Kjær Hansen, Mrs. L. Knudsen, Mr. A. Meier, Mr. Th. Nielsen, Mrs. K. Sørensen, and Miss M. Sørensen for skillful technical assistance. This study was supported in part by U.S.P.H.S. Grant NS 07998.     

The effect of bombesin on basal, alpha-methyl-p-tyrosine, haloperidol, morphine, bremazocine and stress-induced prolactin secretion

Intravenously administered bombesin lowered basal PRL levels in conscious male rats and prevented the morphine, bremazocine and stress-induced PRL secretion. The same dose of bombesin had no effect on PRL levels in alpha-methyl-p-tyrosine pretreated rats and did not affect haloperidol-stimulated PRL release. These results show that bombesin given intravenously acts as an inhibitor of PRL secretion and suggests that it does not act on the lactotrope itself but rather by an increase of the inhibitory dopaminergic tone.     

Key challenges for the creation and maintenance of specialist protein resources

As the volume of data relating to proteins increases, researchers rely more and more on the analysis of published data, thus increasing the importance of good access to these data that vary from the supplemental material of individual articles, all the way to major reference databases with professional staff and long‐term funding. Specialist protein resources fill an important middle ground, providing interactive web interfaces to their databases for a focused topic or family of proteins, using specialized approaches that are not feasible in the major reference databases. Many are labors of love, run by a single lab with little or no dedicated funding and there are many challenges to building and maintaining them. This perspective arose from a meeting of several specialist protein resources and major reference databases held at the Wellcome Trust Genome Campus (Cambridge, UK) on August 11 and 12, 2014. During this meeting some common key challenges involved in creating and maintaining such resources were discussed, along with various approaches to address them. In laying out these challenges, we aim to inform users about how these issues impact our resources and illustrate ways in which our working together could enhance their accuracy, currency, and overall value. Proteins 2015; 83:1005–1013. © 2015 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.     

Modifier effects between regulatory and protein-coding variation

Genome-wide associations have shown a lot of promise in dissecting the genetics of complex traits in humans with single variants, yet a large fraction of the genetic effects is still unaccounted for. Analyzing genetic interactions between variants (epistasis) is one of the potential ways forward. We investigated the abundance and functional impact of a specific type of epistasis, namely the interaction between regulatory and protein-coding variants. Using genotype and gene expression data from the 210 unrelated individuals of the original four HapMap populations, we have explored the combined effects of regulatory and protein-coding single nucleotide polymorphisms (SNPs). We predict that about 18% (1,502 out of 8,233 nsSNPs) of protein-coding variants are differentially expressed among individuals and demonstrate that regulatory variants can modify the functional effect of a coding variant in cis. Furthermore, we show that such interactions in cis can affect the expression of downstream targets of the gene containing the protein-coding SNP. In this way, a cis interaction between regulatory and protein-coding variants has a trans impact on gene expression. Given the abundance of both types of variants in human populations, we propose that joint consideration of regulatory and protein-coding variants may reveal additional genetic effects underlying complex traits and disease and may shed light on causes of differential penetrance of known disease variants.     

Axon-bearing and axon-less horizontal cell subtypes are generated consecutively during chick retinal development from progenitors that are sensitive to follistatin

Background  

Horizontal cells are retinal interneurons that modulate the output from photoreceptors. A rich literature on the morphological classification and functional properties of HCs in different animals exists, however, the understanding of the events underlying their development is still limited. In most vertebrates including chicken, two main horizontal cell (HC) subtypes are identified based on the presence or absence of an axon.     

A series of spirocyclic analogues as potent inhibitors of bacterial phenylalanyl-tRNA synthetases

We have identified a series of spirocyclic furan and pyrrolidine inhibitors of Enterococcus faecalis and Staphylococcus aureus phenylalanyl-tRNA synthetases. The most potent analogue 1b showed IC50=5 nM (E. faecalis PheRS) and IC50=2 nM (S. aureus PheRS) with high selectivity over the human enzyme. The crystal X-ray structure of analogue 1b was determined.     

Genetic and environmental contributions to weight, height, and BMI from birth to 19 years of age: an international study of over 12,000 twin pairs

Objective

To examine the genetic and environmental influences on variances in weight, height, and BMI, from birth through 19 years of age, in boys and girls from three continents.

Design and Settings

Cross-sectional twin study. Data obtained from a total of 23 twin birth-cohorts from four countries: Canada, Sweden, Denmark, and Australia. Participants were Monozygotic (MZ) and dizygotic (DZ) (same- and opposite-sex) twin pairs with data available for both height and weight at a given age, from birth through 19 years of age. Approximately 24,036 children were included in the analyses.

Results

Heritability for body weight, height, and BMI was low at birth (between 6.4 and 8.7% for boys, and between 4.8 and 7.9% for girls) but increased over time, accounting for close to half or more of the variance in body weight and BMI after 5 months of age in both sexes. Common environmental influences on all body measures were high at birth (between 74.1–85.9% in all measures for boys, and between 74.2 and 87.3% in all measures for girls) and markedly reduced over time. For body height, the effect of the common environment remained significant for a longer period during early childhood (up through 12 years of age). Sex-limitation of genetic and shared environmental effects was observed.

Conclusion

Genetics appear to play an increasingly important role in explaining the variation in weight, height, and BMI from early childhood to late adolescence, particularly in boys. Common environmental factors exert their strongest and most independent influence specifically in pre-adolescent years and more significantly in girls. These findings emphasize the need to target family and social environmental interventions in early childhood years, especially for females. As gene-environment correlation and interaction is likely, it is also necessary to identify the genetic variants that may predispose individuals to obesity.     

Association of the DTNBP1 locus with schizophrenia in a U.S. population

Linkage and association studies have recently implicated dystrobrevin-binding protein 1 (DTNBP1) in the etiology of schizophrenia. We analyzed seven previously tested DTNBP1 single-nucleotide polymorphisms (SNPs) in a cohort of 524 individuals with schizophrenia or schizoaffective disorder and 573 control subjects. The minor alleles of three SNPs (P1578, P1763, and P1765) were positively associated with the diagnosis of schizophrenia or schizoaffective disorder in the white subset of the study cohort (258 cases, 467 controls), with P1578 showing the most significant association (odds ratio 1.76, P =.0026). The same three SNPs were also associated in a smaller Hispanic subset (51 cases, 32 controls). No association was observed in the African American subset (215 cases, 74 controls). A stratified analysis of the white and Hispanic subsets showed association with the minor alleles of four SNPs (P1578, P1763, P1320, and P1765). Again, the most significant association was observed for P1578 (P =.0006). Haplotype analysis supported these findings, with a single risk haplotype significantly overrepresented in the white sample (P =.005). Our study provides further evidence for a role of the DTNBP1 gene in the genetic etiology of schizophrenia.