N-arylsulfonyl-2-vinyltryptamines as new 5-HT6 serotonin receptor ligands

Several new 2-vinyl-Nb,Nb-dimethyltryptamines were prepared using Fischer indole synthesis followed by simple functional group transformations and evaluated on 5-HT4, 5-HT5, 5-HT6 and 5-HT7 serotonin receptors. It was found that 2-vinyl substitution conferred a potent and selective 5-HT6 binding activity to these molecules which could be enhanced by Na-arylsulfonyl substituents.     

Vipp1: a very important protein in plastids?!

As a key feature in oxygenic photosynthesis, thylakoid membranes play an essential role in the physiology of plants, algae, and cyanobacteria. Despite their importance in the process of oxygenic photosynthesis, their biogenesis has remained a mystery to the present day. A decade ago, vesicle-inducing protein in plastids 1 (Vipp1) was described to be involved in thylakoid membrane formation in chloroplasts and cyanobacteria. Most follow-up studies clearly linked Vipp1 to membranes and Vipp1 interactions as well as the defects observed after Vipp1 depletion in chloroplasts and cyanobacteria indicate that Vipp1 directly binds to membranes, locally stabilizes bilayer structures, and thereby retains membrane integrity. Here current knowledge about the structure and function of Vipp1 is summarized with a special focus on its relationship to the bacterial phage shock protein A (PspA), as both proteins share a common origin and appear to have retained many similarities in structure and function.     

Learned Vocal Variation Is Associated with Abrupt Cryptic Genetic Change in a Parrot Species Complex

Contact zones between subspecies or closely related species offer valuable insights into speciation processes. A typical feature of such zones is the presence of clinal variation in multiple traits. The nature of these traits and the concordance among clines are expected to influence whether and how quickly speciation will proceed. Learned signals, such as vocalizations in species having vocal learning (e.g. humans, many birds, bats and cetaceans), can exhibit rapid change and may accelerate reproductive isolation between populations. Therefore, particularly strong concordance among clines in learned signals and population genetic structure may be expected, even among continuous populations in the early stages of speciation. However, empirical evidence for this pattern is often limited because differences in vocalisations between populations are driven by habitat differences or have evolved in allopatry. We tested for this pattern in a unique system where we may be able to separate effects of habitat and evolutionary history. We studied geographic variation in the vocalizations of the crimson rosella (Platycercus elegans) parrot species complex. Parrots are well known for their life-long vocal learning and cognitive abilities. We analysed contact calls across a ca 1300 km transect encompassing populations that differed in neutral genetic markers and plumage colour. We found steep clinal changes in two acoustic variables (fundamental frequency and peak frequency position). The positions of the two clines in vocal traits were concordant with a steep cline in microsatellite-based genetic variation, but were discordant with the steep clines in mtDNA, plumage and habitat. Our study provides new evidence that vocal variation, in a species with vocal learning, can coincide with areas of restricted gene flow across geographically continuous populations. Our results suggest that traits that evolve culturally can be strongly associated with reduced gene flow between populations, and therefore may promote speciation, even in the absence of other barriers.     

Barriers to HIV testing in Côte d'Ivoire: the role of individual characteristics and testing modalities

Background

Expanding HIV testing requires a better understanding of barriers to its uptake. We investigated barriers to HIV testing in Côte d''Ivoire, taking into account test circumstances (client vs. provider-initiated).

Methods

We used data from the 2005 nationally representative Demographic and Health Survey conducted in Côte d''Ivoire. Socio-demographic characteristics, sexual behaviour and knowledge and attitudes toward HIV/AIDS associated with recent (<2 years) HIV testing were identified using gender-specific univariate and multivariate logistic regressions. Among women, differential effects of barriers to testing according to test circumstance (whether they have been offered for a prenatal test or not) were assessed through interaction tests.

Results

Recent HIV testing was reported by 6.1% of men and 9.5% of women (including 4.6% as part of antenatal care). Among men, having a low socioeconomic status, having a low HIV-related knowledge level and being employed [compared to those inactive: adjusted Odds Ratio (aOR) 0.46; 95% confidence interval (CI) 0.25–0.87] were associated with lower proportions of recent HIV testing. Among women without a prenatal HIV testing offer, living outside the capital (aOR 0.38; CI 0.19–0.77) and reporting a unique lifetime sexual partner constituted additional barriers to HIV testing. By contrast, among women recently offered to be tested in prenatal care, none of these variables was found to be associated with recent HIV testing.

Conclusions

Various dimensions of individuals'' characteristics constituted significant barriers to HIV testing in Côte d''Ivoire in 2005, with gender specificities. Such barriers are substantially reduced when testing was proposed in the framework of antenatal care. This suggests that provider-initiated testing strategies may help overcome individual barriers to HIV testing.     

Bio-samtools: Ruby bindings for SAMtools, a library for accessing BAM files containing high-throughput sequence alignments

ABSTRACT: BACKGROUND: The SAMtools utilities comprise a very useful and widely used suite of software for manipulating files and alignments in the SAM and BAM format, used in a wide range of genetic analyses. The SAMtools utilities are implemented in C and provide an API for programmatic access, to help make this functionality available to programmers wishing to develop in the high level Ruby language we have developed bio-samtools, a Ruby binding to the SAMtools library. RESULTS: The utility of SAMtools is encapsulated in 3 main classes, Bio::DB::Sam, representing the alignment files and providing access to the data in them, Bio::DB::Alignment, representing the individual read alignments inside the files and Bio::DB::Pileup, representing the summarised nucleotides of reads over a single point in the nucleotide sequence to which the reads are aligned. CONCLUSIONS: bio-samtools is a flexible and easy to use interface that programmers of many levels of experience can use to access the information in the popular and common SAM/BAM format.     

Peters Plus syndrome is a new congenital disorder of glycosylation and involves defective Omicron-glycosylation of thrombospondin type 1 repeats

Peters Plus syndrome is an autosomal recessive disorder characterized by anterior eye chamber defects, disproportionate short stature, developmental delay, and cleft lip and/or palate. It is caused by splice site mutations in what was thought to be a beta1,3-galactosyltransferase-like gene (B3GALTL). Recently, we and others found this gene to encode a beta1,3-glucosyltransferase involved in the synthesis of the disaccharide Glc-beta1,3-Fuc-Omicron-that occurs on thrombospondin type 1 repeats of many biologically important proteins. No functional tests have been performed to date on the presumed glycosylation defect in Peters Plus syndrome. We have established a sensitive immunopurification-mass spectrometry method, using multiple reaction monitoring, to analyze Omicron-fucosyl glycans. It was used to compare the reporter protein properdin from Peters Plus patients with that from control heterozygous relatives. In properdin from patients, we could not detect the Glc-beta1,3-Fuc-Omicron-disaccharide, and we only found Fuc-Omicron-at all four Omicron-fucosylation sites. In contrast, properdin from heterozygous relatives and a healthy volunteer carried the Glc-beta1,3-Fuc-Omicron-disaccharide. These data firmly establish Peters Plus syndrome as a new congenital disorder of glycosylation.     

Cytochemistry of Phosphatases in Myxococcus xanthus

An Mg(2+)-dependent and a K(+)-stimulated adenosine triphosphatase were localized by cytochemistry at or near both surfaces of the cytoplasmic membrane of Myxococcus xanthus. An alkaline and an acid phosphatase resided at the external surface of the membrane or in the periplasm. All enzymes could be extracted from partially fixed cells with Mg(2+)-deficient buffers. Suboptimal external phosphate elicited dissociation of adenosine triphosphatase from the membrane but not that of the unspecific phosphatases. The dissociated enzymes migrated into the cytoplasm where they were associated mainly with cytoplasmic aggregates.