Inhibition of Plant-Pathogenic Bacteria by Short Synthetic Cecropin A-Melittin Hybrid Peptides

Short peptides of 11 residues were synthesized and tested against the economically important plant pathogenic bacteria Erwinia amylovora, Pseudomonas syringae, and Xanthomonas vesicatoria and compared to the previously described peptide Pep3 (WKLFKKILKVL-NH₂). The antimicrobial activity of Pep3 and 22 analogues was evaluated in terms of the MIC and the 50% effective dose (ED₅₀) for growth. Peptide cytotoxicity against human red blood cells and peptide stability toward protease degradation were also determined. Pep3 and several analogues inhibited growth of the three pathogens and had a bactericidal effect at low micromolar concentrations (ED₅₀ of 1.3 to 7.3 μM). One of the analogues consisting of a replacement of both Trp and Val with Lys and Phe, respectively, resulted in a peptide with improved bactericidal activity and minimized cytotoxicity and susceptibility to protease degradation compared to Pep3. The best analogues can be considered as potential lead compounds for the development of new antimicrobial agents for use in plant protection either as components of pesticides or expressed in transgenic plants.     

A phototaxis signalling complex in Dictyostelium discoideum

Phototaxis has been studied in a variety of organisms belonging to all three major taxonomic domains – the bacteria, the archaea and the eukarya. Dictyostelium discoideum is one of a small number of eukaryotic organisms which are amenable to studying the signalling pathways involved in phototaxis. In this study we provide evidence based on protein coimmunoprecipitation for a phototaxis signalling complex in Dictyostelium that includes the proteins RasD, filamin, ErkB, GRP125 and PKB.     

Neuroprotection of medical IOP-lowering therapy

Intraocular pressure (IOP)-lowering therapy has been shown to arrest or retard the progression of optic neuropathy typical for glaucoma and can, thus, be described as neuroprotective. At present, six classes of medical therapy are employed, namely parasympathomimetics, alpha/beta-sympathomimetics, β-blockers, carbonic anhydrase inhibitors, α₂-adrenergic receptor agonists and prostaglandin analogues. For several of these substances, some experimental evidence exists of a possible neuroprotective mechanism, beyond their IOP-lowering activity. β-Blockers are involved in the up-regulation of brain-derived neurotrophic factor (BDNF) and can decrease glutamate-mediated NMDA receptor activation. Not only systemic but also topical carbonic anhydrase inhibitors are able to increase retinal blood flow. α₂-Adrenergic receptor agonists can up-regulate the formation of BDNF and anti-apoptotic factors. Prostaglandin analogues increase blood flow to the eye, possibly including the retina. To date, evidence for a neuroprotective effect independent of IOP regulation in human glaucoma is scarce and has only been shown to be likely for the α₂-adrenergic receptor agonist, brimonidine.     

Genetic variants associated with breast cancer risk for Ashkenazi Jewish women with strong family histories but no identifiable BRCA1/2 mutation

The ability to establish genetic risk models is critical for early identification and optimal treatment of breast cancer. For such a model to gain clinical utility, more variants must be identified beyond those discovered in previous genome-wide association studies (GWAS). This is especially true for women at high risk because of family history, but without BRCA1/2 mutations. This study incorporates three datasets in a GWAS analysis of women with Ashkenazi Jewish (AJ) homogeneous ancestry. Two independent discovery cohorts comprised 239 and 238 AJ women with invasive breast cancer or preinvasive ductal carcinoma in situ and strong family histories of breast cancer, but lacking the three BRCA1/2 founder mutations, along with 294 and 230 AJ controls, respectively. An independent, third cohort of 203 AJ cases with familial breast cancer history and 263 healthy controls of AJ women was used for validation. A total of 19 SNPs were identified as associated with familial breast cancer risk in AJ women. Among these SNPs, 13 were identified from a panel of 109 discovery SNPs, including an FGFR2 haplotype. In addition, six previously identified breast cancer GWAS SNPs were confirmed in this population. Seven of the 19 markers were significant in a multivariate predictive model of familial breast cancer in AJ women, three novel SNPs [rs17663555(5q13.2), rs566164(6q21), and rs11075884(16q22.2)], the FGFR2 haplotype, and three previously published SNPs [rs13387042(2q35), rs2046210(ESR1), and rs3112612(TOX3)], yielding moderate predictive power with an area under the curve (AUC) of the ROC (receiver-operator characteristic curve) of 0.74. Population-specific genetic variants in addition to variants shared with populations of European ancestry may improve breast cancer risk prediction among AJ women from high-risk families without founder BRCA1/2 mutations.     

The 46359CT polymorphism of DNMT3B is associated with the risk of cervical cancer

Abnormal methylation is related to cancer development. Since DNMT3B is an enzyme that modulates genomic methylation, we hypothesized that genetic variants of the promoter DNMT3B may be associated with an increased risk of developing cervical cancer. Our aim was to investigate the association between ?579GT and 46359CT polymorphisms of DNMT3B and cervical cancer, high-grade squamous intraepithelial lesions (HSIL), and low-grade squamous intraepithelial lesions (LSIL). Samples from 200 healthy women and 130 women with squamous intraepithelial lesions (70 with cervical cancer, 30 with HSIL, and 30 with LSIL) were analyzed. Polymorphism genotyping was performed using PCR and restriction fragment length polymorphism. The ?579GT polymorphism was not associated with cervical cancer, HSIL, or LSIL. The CT genotype of 46359CT polymorphism was significantly associated with cervical cancer risk (OR 8.75, CI 1.27–374.1), whereas the TT genotype was associated with a significantly decreased risk of HSIL (OR 0.66, CI 0.01–0.32) and LSIL (OR 0.11, CI 0.026–0.45). Our results suggest that genotyping the 46359CT polymorphism in DNMT3B may help identify women who are genetically susceptible to cervical cancer development. Additional studies with larger sample sizes are necessary to confirm our findings.     

A comparison of the strength of biodiversity effects across multiple functions

In order to predict which ecosystem functions are most at risk from biodiversity loss, meta-analyses have generalised results from biodiversity experiments over different sites and ecosystem types. In contrast, comparing the strength of biodiversity effects across a large number of ecosystem processes measured in a single experiment permits more direct comparisons. Here, we present an analysis of 418 separate measures of 38 ecosystem processes. Overall, 45 % of processes were significantly affected by plant species richness, suggesting that, while diversity affects a large number of processes not all respond to biodiversity. We therefore compared the strength of plant diversity effects between different categories of ecosystem processes, grouping processes according to the year of measurement, their biogeochemical cycle, trophic level and compartment (above- or belowground) and according to whether they were measures of biodiversity or other ecosystem processes, biotic or abiotic and static or dynamic. Overall, and for several individual processes, we found that biodiversity effects became stronger over time. Measures of the carbon cycle were also affected more strongly by plant species richness than were the measures associated with the nitrogen cycle. Further, we found greater plant species richness effects on measures of biodiversity than on other processes. The differential effects of plant diversity on the various types of ecosystem processes indicate that future research and political effort should shift from a general debate about whether biodiversity loss impairs ecosystem functions to focussing on the specific functions of interest and ways to preserve them individually or in combination.     

Mapping Dominican transnationalism: narrow and broad transnational practices

This article maps the structure for understanding the Dominican transnational field. By transnational field we refer to a web of linkages that affects the lives of Dominicans in their places of residence in every social field. We find that social boundaries of the nation do not coincide with political ones and the degree of participation in transnational exchanges varies. We suggest that the structure of the transnational social field is better understood by establishing and defining broad and narrow transnational social practices.     

Protein domain definition should allow for conditional disorder

Abstract: Proteins are often classified in a binary fashion as either structured or disordered. However this approach has several deficits. Firstly, protein folding is always conditional on the physiochemical environment. A protein which is structured in some circumstances will be disordered in others. Secondly, it hides a fundamental asymmetry in behavior. While all structured proteins can be unfolded through a change in environment, not all disordered proteins have the capacity for folding. Failure to accommodate these complexities confuses the definition of both protein structural domains and intrinsically disordered regions. We illustrate these points with an experimental study of a family of small binding domains, drawn from the RNA polymerase of mumps virus and its closest relatives. Assessed at face value the domains fall on a structural continuum, with folded, partially folded, and near unstructured members. Yet the disorder present in the family is conditional, and these closely related polypeptides can access the same folded state under appropriate conditions. Any heuristic definition of the protein domain emphasizing conformational stability divides this domain family in two, in a way that makes no biological sense. Structural domains would be better defined by their ability to adopt a specific tertiary structure: a structure that may or may not be realized, dependent on the circumstances. This explicitly allows for the conditional nature of protein folding, and more clearly demarcates structural domains from intrinsically disordered regions that may function without folding.     

Liprin-α2 promotes the presynaptic recruitment and turnover of RIM1/CASK to facilitate synaptic transmission

The presynaptic active zone mediates synaptic vesicle exocytosis, and modulation of its molecular composition is important for many types of synaptic plasticity. Here, we identify synaptic scaffold protein liprin-α2 as a key organizer in this process. We show that liprin-α2 levels were regulated by synaptic activity and the ubiquitin–proteasome system. Furthermore, liprin-α2 organized presynaptic ultrastructure and controlled synaptic output by regulating synaptic vesicle pool size. The presence of liprin-α2 at presynaptic sites did not depend on other active zone scaffolding proteins but was critical for recruitment of several components of the release machinery, including RIM1 and CASK. Fluorescence recovery after photobleaching showed that depletion of liprin-α2 resulted in reduced turnover of RIM1 and CASK at presynaptic terminals, suggesting that liprin-α2 promotes dynamic scaffolding for molecular complexes that facilitate synaptic vesicle release. Therefore, liprin-α2 plays an important role in maintaining active zone dynamics to modulate synaptic efficacy in response to changes in network activity.