Antifouling activity of the sponge metabolite agelasine D and synthesised analogs on Balanus improvisus

This study reports a screening study for antifouling (AF) activity of the natural compound agelasine D isolated from marine sponges of the genus Agelas and 20 synthesised analogs of agelasines and agelasimines. Agelasine D, together with two of the analogs, ie AV1003A and AKB695, displayed a strong inhibitory effect on settlement of Balanus improvisus cypris larvae. Agelasine D had an EC50 value of 0.11 microM while the two analogs AV1033A and AKB695 had EC50 values of 0.23 and 0.3 microM, respectively. None of these three compounds affected larval mortality as was the case with several of the analogs tested. Moreover, the effect of AV1033A and AKB695 was reversible. When cyprids after 24 h exposure to the compounds were transferred to fresh seawater, the settlement frequency compared with the controls was completely recovered. The properties of the agelasine D analogs AV1003A and AKB695 make them highly attractive candidates as AF agents in future marine coatings.     

End joining at Caenorhabditis elegans telomeres

Critically shortened telomeres can be subjected to DNA repair events that generate end-to-end chromosome fusions. The resulting dicentric chromosomes can enter breakage–fusion–bridge cycles, thereby impeding elucidation of the structures of the initial fusion events and a mechanistic understanding of their genesis. Current models for the molecular basis of fusion of critically shortened, uncapped telomeres rely on PCR assays that typically capture fusion breakpoints created by direct ligation of chromosome ends. Here we use independent approaches that rely on distinctive features of Caenorhabditis elegans to study the frequency of direct end-to-end chromosome fusion in telomerase mutants: (1) holocentric chromosomes that allow for genetic isolation of stable end-to-end fusions and (2) unique subtelomeric sequences that allow for thorough PCR analysis of samples of genomic DNA harboring multiple end-to-end fusions. Surprisingly, only a minority of end-to-end fusion events resulted from direct end joining with no additional genome rearrangements. We also demonstrate that deficiency for the C. elegans Ku DNA repair heterodimer does not affect telomere length or cause synthetic effects in the absence of telomerase.     

Genomic analysis of adaptive differentiation in Drosophila melanogaster

Drosophila melanogaster shows clinal variation along latitudinal transects on multiple continents for several phenotypes, allozyme variants, sequence variants, and chromosome inversions. Previous investigation suggests that many such clines are due to spatially varying selection rather than demographic history, but the genomic extent of such selection is unknown. To map differentiation throughout the genome, we hybridized DNA from temperate and subtropical populations to Affymetrix tiling arrays. The dense genomic sampling of variants and low level of linkage disequilibrium in D. melanogaster enabled identification of many small, differentiated regions. Many regions are differentiated in parallel in the United States and Australia, strongly supporting the idea that they are influenced by spatially varying selection. Genomic differentiation is distributed nonrandomly with respect to gene function, even in regions differentiated on only one continent, providing further evidence for the role of selection. These data provide candidate genes for phenotypes known to vary clinally and implicate interesting new processes in genotype-by-environment interactions, including chorion proteins, proteins regulating meiotic recombination and segregation, gustatory and olfactory receptors, and proteins affecting synaptic function and behavior. This portrait of differentiation provides a genomic perspective on adaptation and the maintenance of variation through spatially varying selection.     

PARC6, a novel chloroplast division factor, influences FtsZ assembly and is required for recruitment of PDV1 during chloroplast division in Arabidopsis

Chloroplast division in plant cells is accomplished through the coordinated action of the tubulin-like FtsZ ring inside the organelle and the dynamin-like ARC5 ring outside the organelle. This coordination is facilitated by ARC6, an inner envelope protein required for both assembly of FtsZ and recruitment of ARC5. Recently, we showed that ARC6 specifies the mid-plastid positioning of the outer envelope proteins PDV1 and PDV2, which have parallel functions in dynamin recruitment. PDV2 positioning involves direct ARC6–PDV2 interaction, but PDV1 and ARC6 do not interact indicating that an additional factor functions downstream of ARC6 to position PDV1. Here, we show that PARC6 (paralog of ARC6), an ARC6-like protein unique to vascular plants, fulfills this role. Like ARC6, PARC6 is an inner envelope protein with its N-terminus exposed to the stroma and Arabidopsis parc6 mutants exhibit defects of chloroplast and FtsZ filament morphology. However, whereas ARC6 promotes FtsZ assembly, PARC6 appears to inhibit FtsZ assembly, suggesting that ARC6 and PARC6 function as antagonistic regulators of FtsZ dynamics. The FtsZ inhibitory activity of PARC6 may involve its interaction with the FtsZ-positioning factor ARC3. A PARC6–GFP fusion protein localizes both to the mid-plastid and to a single spot at one pole, reminiscent of the localization of ARC3, PDV1 and ARC5. Although PARC6 localizes PDV1, it is not required for PDV2 localization or ARC5 recruitment. Our findings indicate that PARC6, like ARC6, plays a role in coordinating the internal and external components of the chloroplast division complex, but that PARC6 has evolved distinct functions in the division process.     

The HECT Domain of the Ubiquitin Ligase Rsp5 Contributes to Substrate Recognition

Ubiquitin modification of endosomal membrane proteins is a signal for active inclusion into the Multivesicular Body (MVB) pathway, resulting in lysosomal degradation. However, the endosome represents a dynamic site of protein sorting with a majority of proteins destined for recycling, rather than MVB targeting. Substrate recognition by ubiquitin ligases is therefore highly regulated. We have investigated substrate recognition by the Nedd4 ortholog Rsp5 as a model for understanding ligase-substrate interactions. Rsp5 interacts directly with its substrate Cps1 via a novel interaction mode. Perturbation of this mode of interaction revealed a compensatory role for the Rsp5 adaptor Bsd2. These results highlight the ability of Rsp5 to interact with substrates via multiple modalities, suggesting additional mechanisms of regulating this interaction and relevant outcomes.     

Development of microsatellite markers in the Australasian snake-necked turtle Chelodina rugusa and cross-species amplification

Seventeen microsatellite loci were developed for the snake-necked turtle, Chelodina rugosa (Ogilby, 1890). Sixteen of the loci were polymorphic but three of these loci had null alleles. One locus displayed linkage disequilibrium. These 17 markers were tested for amplification in eight congeneric species with varying success; 98% amplification in Chelodina burrungandjii, 72% in C. canni, 38% in C. expansa, 58% in C. longicollis, 67% in C. mccordi, 73% in C. oblonga, 81% in C. parkeri, and 68% in C. pritchardi. These microsatellite markers will be useful for population assignment, gene flow, mating systems and hybridization studies in the genus Chelodina.     

The Sedating Antidepressant Trazodone Impairs Sleep-Dependent Cortical Plasticity

Background

Recent findings indicate that certain classes of hypnotics that target GABA_A receptors impair sleep-dependent brain plasticity. However, the effects of hypnotics acting at monoamine receptors (e.g., the antidepressant trazodone) on this process are unknown. We therefore assessed the effects of commonly-prescribed medications for the treatment of insomnia (trazodone and the non-benzodiazepine GABA_A receptor agonists zaleplon and eszopiclone) in a canonical model of sleep-dependent, in vivo synaptic plasticity in the primary visual cortex (V1) known as ocular dominance plasticity.

Methodology/Principal Findings

After a 6-h baseline period of sleep/wake polysomnographic recording, cats underwent 6 h of continuous waking combined with monocular deprivation (MD) to trigger synaptic remodeling. Cats subsequently received an i.p. injection of either vehicle, trazodone (10 mg/kg), zaleplon (10 mg/kg), or eszopiclone (1–10 mg/kg), and were allowed an 8-h period of post-MD sleep before ocular dominance plasticity was assessed. We found that while zaleplon and eszopiclone had profound effects on sleeping cortical electroencephalographic (EEG) activity, only trazodone (which did not alter EEG activity) significantly impaired sleep-dependent consolidation of ocular dominance plasticity. This was associated with deficits in both the normal depression of V1 neuronal responses to deprived-eye stimulation, and potentiation of responses to non-deprived eye stimulation, which accompany ocular dominance plasticity.

Conclusions/Significance

Taken together, our data suggest that the monoamine receptors targeted by trazodone play an important role in sleep-dependent consolidation of synaptic plasticity. They also demonstrate that changes in sleep architecture are not necessarily reliable predictors of how hypnotics affect sleep-dependent neural functions.     

Long-term adherence to antiretroviral treatment and program drop-out in a high-risk urban setting in sub-Saharan Africa: a prospective cohort study

Background

Seventy percent of urban populations in sub-Saharan Africa live in slums. Sustaining HIV patients in these high-risk and highly mobile settings is a major future challenge. This study seeks to assess program retention and to find determinants for low adherence to antiretroviral treatment (ART) and drop-out from an established HIV/ART program in Kibera, Nairobi, one of Africa''s largest informal urban settlements.

Methods and Findings

A prospective open cohort study of 800 patients was performed at the African Medical Research Foundation (AMREF) clinic in the Kibera slum. Adherence to ART and drop-out from the ART program were independent outcomes. Two different adherence measures were used: (1) “dose adherence” (the proportion of a prescribed dose taken over the past 4 days) and (2) “adherence index” (based on three adherence questions covering dosing, timing and special instructions). Drop-out from the program was calculated based on clinic appointment dates and number of prescribed doses, and a patient was defined as being lost to follow-up if over 90 days had expired since the last prescribed dose. More than one third of patients were non-adherent when all three aspects of adherence – dosing, timing and special instructions – were taken into account. Multivariate logistic regression revealed that not disclosing HIV status, having a low level of education, living below the poverty limit (US$ 2/day) and not having a treatment buddy were significant predictors for non-adherence. Additionally, one quarter of patients dropped out for more than 90 days after the last prescribed ART dose. Not having a treatment buddy was associated with increased risk for drop-out (hazard ratio 1.4, 95% CI = 1.0–1.9).

Conclusion

These findings point to the dilemma of trying to sustain a growing number of people on life-long ART in conditions where prevailing stigma, poverty and food shortages threatens the long-term success of HIV treatment.     

Metabolic scaling in modular animals

Metabolic scaling is the relationship between organismal metabolic rate and body mass. Understanding the patterns and causes of metabolic scaling provides a powerful foundation for predicting biological processes at the level of individuals, populations, communities, and ecosystems. Despite intense interest in, and debate on, the mechanistic basis of metabolic scaling, relatively little attention has been paid to metabolic scaling in clonal animals with modular construction, such as colonial cnidarians, bryozoans, and colonial ascidians. Unlike unitary animals, modular animals are structural individuals subdivided into repeated morphological units, or modules, each able to acquire, process, and share resources. A modular design allows flexibility in organism size and shape with consequences for metabolic scaling. Furthermore, with careful consideration of the biology of modular animals, the size and shape of individual colonies can be experimentally manipulated to test competing theories pertaining to metabolic scaling. Here, we review metabolic scaling in modular animals and find that a wide range of scaling exponents, rather than a single value, has been reported for a variety of modular animals. We identify factors influencing variation in intraspecific scaling in this group that relate to the general observation that not all modules within a colony are identical. We highlight current gaps in our understanding of metabolic scaling in modular animals, and suggest future research directions, such as manipulating metabolic states and comparisons among species that differ in extent of module integration.