Introduced Drosophila subobscura populations perform better than native populations during an oviposition choice task due to increased fecundity but similar learning ability

The success of invasive species is tightly linked to their fitness in a putatively novel environment. While quantitative components of fitness have been studied extensively in the context of invasive species, fewer studies have looked at qualitative components of fitness, such as behavioral plasticity, and their interaction with quantitative components, despite intuitive benefits over the course of an invasion. In particular, learning is a form of behavioral plasticity that makes it possible to finely tune behavior according to environmental conditions. Learning can be crucial for survival and reproduction of introduced organisms in novel areas, for example, for detecting new predators, or finding mates or oviposition sites. Here we explored how oviposition performance evolved in relation to both fecundity and learning during an invasion, using native and introduced Drosophila subobscura populations performing an ecologically relevant task. Our results indicated that, under comparable conditions, invasive populations performed better during our oviposition task than did native populations. This was because invasive populations had higher fecundity, together with similar cognitive performance when compared to native populations, and that there was no interaction between learning and fecundity. Unexpectedly, our study did not reveal an allocation trade‐off (i.e., a negative relationship) between learning and fecundity. On the contrary, the pattern we observed was more consistent with an acquisition trade‐off, meaning that fecundity could be limited by availability of resources, unlike cognitive ability. This pattern might be the consequence of escaping natural enemies and/or competitors during the introduction. The apparent lack of evolution of learning may indicate that the introduced population did not face novel cognitive challenges in the new environment (i.e., cognitive “pre‐adaptation”). Alternatively, the evolution of learning may have been transient and therefore not detected.     

Design and synthesis of a peptide derived from positions 195–244 of human cdc25C phosphatase

We have designed, synthesized and purified a 51 amino acid peptide derived from an essential domain of human cdc25C phosphatase. In vivo, differential phosphorylation of this domain regulates either the induction of mitotic processes, or the checkpoint arrest of eukaryotic cells in response to DNA damage. Peptide synthesis was achieved using the stepwise Fmoc strategy and resulted in an important yield of highly pure peptide. The final peptide was identified by amino acid analysis, electrospray mass spectrometry and nuclear magnetic resonance, which revealed that one of the two methionines within the peptide was oxidized into its sulphoxide derivative We investigated whether this 51 amino acid peptide folded into secondary structures in solution by circular dichroism and observed the formation of alpha helices in TFE. Finally, we verified that this peptide could bind to its biologically relevant 14‐3‐3 partner in vitro by fluorescence spectroscopy. Copyright © 1999 European Peptide Society and John Wiley & Sons, Ltd.     

Combinatorial effect of blueberry extracts and oxaliplatin in human colon cancer cells

The use of natural compounds to potentiate the effect of drugs and lower their adverse effects is an active area of research. The objective is to determine the effect of combined blueberry extracts (BE) and oxaliplatin (OX) in colon cancer cells. The results demonstrated that treatments of BE/OX showed inhibitory effects on HCT-116 cell and nontoxic effect on CCD-18Co normal colon cells. Flow cytometry analysis indicated that treatment with the BE, OX or in combination could induce G0/G1 cell cycle arrest, apoptosis, increase of reactive oxygen species, and induce loss of mitochondrial membrane potential in HCT-116 cells. Furthermore, after treatments, the expression of inflammatory cytokines was decreased, cyclin D1 and CDK4 were decreased; caspases-3 and 9 were activated; the Akt/Bad/Bcl-2 pathway was modulated. Moreover, the combination treatment had a considerably higher growth inhibitory effect on human colon cancer HCT-116 cells than that of BE or oxaliplatin alone. Our results showed that BE increased the anticolon cancer effect of OX making it an attractive strategy as adjuvant therapy to potentially reduce the adverse side effects associated with chemotherapeutic drugs.     

Xanthomonas hortorum – beyond gardens: Current taxonomy,genomics, and virulence repertoires

TaxonomyBacteria; Phylum Proteobacteria; Class Gammaproteobacteria; Order Lysobacterales (earlier synonym of Xanthomonadales); Family Lysobacteraceae (earlier synonym of Xanthomonadaceae); Genus Xanthomonas; Species X. hortorum; Pathovars: pv. carotae, pv. vitians, pv. hederae, pv. pelargonii, pv. taraxaci, pv. cynarae, and pv. gardneri.Host range Xanthomonas hortorum affects agricultural crops, and horticultural and wild plants. Tomato, carrot, artichoke, lettuce, pelargonium, ivy, and dandelion were originally described as the main natural hosts of the seven separate pathovars. Artificial inoculation experiments also revealed other hosts. The natural and experimental host ranges are expected to be broader than initially assumed. Additionally, several strains, yet to be assigned to a pathovar within X. hortorum, cause diseases on several other plant species such as peony, sweet wormwood, lavender, and oak‐leaf hydrangea.Epidemiology and control X. hortorum pathovars are mainly disseminated by infected seeds (e.g., X. hortorum pvs carotae and vitians) or cuttings (e.g., X. hortorum pv. pelargonii) and can be further dispersed by wind and rain, or mechanically transferred during planting and cultivation. Global trade of plants, seeds, and other propagating material constitutes a major pathway for their introduction and spread into new geographical areas. The propagules of some pathovars (e.g., X. horturum pv. pelargonii) are spread by insect vectors, while those of others can survive in crop residues and soils, and overwinter until the following growing season (e.g., X. hortorum pvs vitians and carotae). Control measures against X. hortorum pathovars are varied and include exclusion strategies (i.e., by using certification programmes and quarantine regulations) to multiple agricultural practices such as the application of phytosanitary products. Copper‐based compounds against X. hortorum are used, but the emergence of copper‐tolerant strains represents a major threat for their effective management. With the current lack of efficient chemical or biological disease management strategies, host resistance appears promising, but is not without challenges. The intrastrain genetic variability within the same pathovar poses a challenge for breeding cultivars with durable resistance.Useful websites https://gd.eppo.int/taxon/XANTGA, https://gd.eppo.int/taxon/XANTCR, https://gd.eppo.int/taxon/XANTPE, https://www.euroxanth.eu, http://www.xanthomonas.org, http://www.xanthomonas.org/dokuwiki     

Sensitivity of IFN-γ Release Assay to Detect Latent Tuberculosis Infection Is Retained in HIV-Infected Patients but Dependent on HIV/AIDS Progression

Background

Detection and treatment of latent TB infection (LTBI) in HIV infected individuals is strongly recommended to decrease morbidity and mortality in countries with high levels of HIV.

Objective

To assess the validity of a newly developed in-house ELISPOT interferon-γ release assay (IGRA) for the detection of LTBI amongst HIV infected individuals, in comparison with the Tuberculin Skin Test (TST).

Methodology/Principal Findings

ESAT6/CFP10 (EC) ELISPOT assays were performed, together with a TST, in 285 HIV infected individuals recruited in HIV clinics in Dakar, Senegal, who had no signs of active TB at time of enrolment. Thirty eight of the subjects (13.3%) failed to respond to PHA stimulation and were excluded from the analysis. In the 247 remaining patients, response to PHA did not vary according to CD4 cell count categories (p = 0.51). EC ELISPOT was positive in 125 (50.6%) subjects, while 53 (21.5%) had a positive TST. Concordance between EC ELISPOT and TST was observed in 151 patients (61.1%) (kappa = 0.23). The proportion of subjects with a positive response to the EC ELISPOT assay decreased with declining CD4 counts (p trend = 0.001), but were consistently higher than the proportion of TST responders. In multivariate analysis, the risk of being EC-ELISPOT positive in HIV infected individuals was associated with age, CD4 count and HIV-1 strain.

Conclusion

Our study indicates that IGRAs using M. tuberculosis specific antigens are likely to retain their validity for the diagnosis of LTBI among HIV positive individuals, but may be impaired by T-cell anergy in severely immuno-suppressed individuals.     

HIV-2 Integrase Variation in Integrase Inhibitor-Na?ve Adults in Senegal,West Africa

Background

Antiretroviral therapy for HIV-2 infection is hampered by intrinsic resistance to many of the drugs used to treat HIV-1. Limited studies suggest that the integrase inhibitors (INIs) raltegravir and elvitegravir have potent activity against HIV-2 in culture and in infected patients. There is a paucity of data on genotypic variation in HIV-2 integrase that might confer intrinsic or transmitted INI resistance.

Methods

We PCR amplified and analyzed 122 HIV-2 integrase consensus sequences from 39 HIV-2–infected, INI-naive adults in Senegal, West Africa. We assessed genetic variation and canonical mutations known to confer INI-resistance in HIV-1.

Results

No amino acid-altering mutations were detected at sites known to be pivotal for INI resistance in HIV-1 (integrase positions 143, 148 and 155). Polymorphisms at several other HIV-1 INI resistance-associated sites were detected at positions 72, 95, 125, 154, 165, 201, 203, and 263 of the HIV-2 integrase protein.

Conclusion

Emerging genotypic and phenotypic data suggest that HIV-2 is susceptible to the new class of HIV integrase inhibitors. We hypothesize that intrinsic HIV-2 integrase variation at “secondary” HIV-1 INI-resistance sites may affect the genetic barrier to HIV-2 INI resistance. Further studies will be needed to assess INI efficacy as part of combination antiretroviral therapy in HIV-2–infected patients.     

TRPC3 mediates T-cell receptor-dependent calcium entry in human T-lymphocytes

Stimulation of the T-cell receptor (TCR) activates Ca2+ entry across the plasma membrane, which is a key triggering event for the T-cell-associated immune response. We show that TRPC3 channels are important for the TCR-dependent Ca2+ entry pathway. The TRPC3 gene was found to be damaged in human T-cell mutants defective in Ca2+ influx. Mutations of the TRPC3 gene were accompanied by changes of TRPC3 gene expression. Introduction of the complete human TRPC3 cDNA into those mutants rescued Ca2+ currents as well as TCR-dependent Ca2+ signals. Our data provide the initial step toward understanding the molecular nature of endogenous Ca2+ channels participating in T-cell activation and put forward TRPC3 as a new target for modulating the immune response.     

Epidemiology and Genetic Characterization of Measles Strains in Senegal, 2004-2013

BackgroundIn Senegal, with the variable routine vaccination coverage, the risk for illness and death from measles still exists as evidenced by the measles epidemic episode in 2009. Since 2002 a laboratory-based surveillance system of measles was established by the Ministry of Health and the Institut Pasteur de Dakar. The present study analysed the data collected over the 10 years inclusive between 2004-2013 in order to define a measles epidemiological profile in Senegal, and we carried out a phylogenetic analysis of measles virus circulating in Senegal over the period 2009-2012.ConclusionImprovements in the measles surveillance in Senegal are required and the introduction of oral fluid and FTA cards as an alternative to transportation of sera should be investigated to improve surveillance. The introduction of a national vaccine database including number of doses of measles-containing vaccine will greatly improve efforts to interrupt and ultimately eliminate measles virus transmission in Senegal.     

A peptide carrier for the delivery of biologically active proteins into mammalian cells.

The development of peptide drugs and therapeutic proteins is limited by the poor permeability and the selectivity of the cell membrane. There is a growing effort to circumvent these problems by designing strategies to deliver full-length proteins into a large number of cells. A series of small protein domains, termed protein transduction domains (PTDs), have been shown to cross biological membranes efficiently and independently of transporters or specific receptors, and to promote the delivery of peptides and proteins into cells. TAT protein from human immunodeficiency virus (HIV-1) is able to deliver biologically active proteins in vivo and has been shown to be of considerable interest for protein therapeutics. Similarly, the third alpha-helix of Antennapedia homeodomain, and VP22 protein from herpes simplex virus promote the delivery of covalently linked peptides or proteins into cells. However, these PTD vectors display a certain number of limitations in that they all require crosslinking to the target peptide or protein. Moreover, protein transduction using PTD-TAT fusion protein systems may require denaturation of the protein before delivery to increase the accessibility of the TAT-PTD domain. This requirement introduces an additional delay between the time of delivery and intracellular activation of the protein. In this report, we propose a new strategy for protein delivery based on a short amphipathic peptide carrier, Pep-1. This peptide carrier is able to efficiently deliver a variety of peptides and proteins into several cell lines in a fully biologically active form, without the need for prior chemical covalent coupling or denaturation steps. In addition, this peptide carrier presents several advantages for protein therapy, including stability in physiological buffer, lack of toxicity, and lack of sensitivity to serum. Pep-1 technology should be extremely useful for targeting specific protein-protein interactions in living cells and for screening novel therapeutic proteins.