First evaluation of antibody responses to Culex quinquefasciatus salivary antigens as a serological biomarker of human exposure to Culex bites: A pilot study in Côte d’Ivoire

BackgroundCulex mosquitoes are vectors for a variety of pathogens of public health concern. New indicators of exposure to Culex bites are needed to evaluate the risk of transmission of associated pathogens and to assess the efficacy of vector control strategies. An alternative to entomological indices is the serological measure of antibodies specific to mosquito salivary antigens. This study investigated whether the human IgG response to both the salivary gland extract and the 30 kDa salivary protein of Culex quinquefasciatus may represent a proxy of human exposure to Culex bites.Methodology/Principal findingsA multidisciplinary survey was conducted with children aged 1 to 14 years living in neighborhoods with varying exposure to Culex quinquefasciatus in the city of Bouaké, Côte d’Ivoire. Children living in sites with high exposure to Cx quinquefasciatus had a significantly higher IgG response to both salivary antigens compared with children living in the control site where only very few Culex were recorded. Moreover, children from any Culex-high exposed sites had significantly higher IgG responses only to the salivary gland extract compared with children from the control village, whereas no difference was noted in the anti-30 kDa IgG response. No significant differences were noted in the specific IgG responses between age and gender. Sites and the use of a bed net were associated with the level of IgG response to the salivary gland extract and to the 30 kDa antigen, respectively.Conclusions/SignificanceThese findings suggest that the IgG response to Culex salivary gland extracts is suitable as proxy of exposure; however, the specificity to the Culex genus needs further investigation. The lower antigenicity of the 30 kDa recombinant protein represents a limitation to its use. The high specificity of this protein to the Culex genus makes it an attractive candidate and other specific antibody responses might be more relevant as a biomarker of exposure. These epidemiological observations may form a starting point for additional work on developing serological biomarkers of Culex exposure.     

Anorectal Human Papillomavirus: Current Concepts

Increased anorectal human papillomavirus (HPV) infection is related to the recent trends in sexual behavior in both homosexual and heterosexual groups and prevalence of infection with human immunodeficiency virus (HIV). Clinical presentation and natural history depend on the serotype involved. HPV 6 and 11 are found in the benign wart. Local control can be achieved with a wide selection of surgical and topical techniques. HPV 16, 18, and 31 are found in dysplastic lesions and have the potential to progress to invasive anal squamous cell carcinoma. Recognition and early management of dysplastic lesions is crucial to prevent the morbidity and mortality associated with anal cancer. While low-grade lesions can be closely observed, high-grade lesions should be eradicated. Different strategies can be used to eradicate the disease while preserving anorectal function. Studies on the efficacy of vaccination on anorectal HPV showed promising results in select population groups and led to the recent expansion of current vaccination recommendations.     

Nuclear Ep-ICD Expression Is a Predictor of Poor Prognosis in “Low Risk” Prostate Adenocarcinomas

IntroductionMolecular markers for predicting prostate cancer (PCa) that would have poor prognosis are urgently needed for a more personalized treatment for patients. Regulated intramembrane proteolysis of Epithelial cell adhesion molecule results in shedding of the extracellular domain (EpEx) and release of its intracellular domain (Ep-ICD) which triggers oncogenic signaling and might correlate to tumor aggressiveness. This study aimed to explore the potential of Ep-ICD and EpEx to identify PCa that have poor prognosis.MethodsImmunohistochemical analysis of Ep-ICD and EpEx was carried out in normal prostate tissues (n = 100), benign prostate hyperplasia (BPH, n = 83), and prostate cancer (n = 249) using domain specific antibodies. The expression of Ep-ICD and EpEx was correlated with clinico- pathological parameters and disease free survival (DFS).ResultsReduced expression of nuclear Ep-ICD and membrane EpEx was observed in PCa in comparison with BPH and normal prostate tissues (p = 0.006, p < 0.001 respectively). For patients who had PCa with Gleason Score less than 7, preserved nuclear Ep-ICD emerged as the most significant marker in multivariate analysis for prolonged DFS, where these patients did not have recurrence during follow up of up to 12 years (p = 0.001).ConclusionReduced expression of nuclear Ep-ICD was associated with shorter disease free survival in patients with a Gleason Score less than 7 and may be useful in identifying patients likely to have aggressive tumors with poor prognosis. Furthermore, nuclear Ep-ICD can differentiate between normal and prostate cancer tissues for ambiguous cases.     

Determination of complex polysaccharides by HPAE-PAD in foods: validation using accuracy profile

The increasing supplementation of foods with carbohydrates substitutes and the growing regulatory requirements for controlling these products, turn into the necessary development and validation of accurate analytical control techniques. This paper presents the simultaneous validation of two close analytical procedures for the determination of sucralose and fructooligosaccharides (FOS) in fruit juices using high-performance anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD). This study consisted in applying the accuracy profile procedure with a three-level validation experimental design. Decision criteria, namely acceptability limits (+/-10%) and proportion of result contained in the calculated tolerance intervals (80%), were decided on a consensus basis with end-users, whereas no official references were available. In conclusion, the proposed analytical procedures were validated over the selected validation domains for fruit juices and came out on very capable techniques. Validation strategy was purposely oriented towards the ease of use in routine and the liability of the methods rather than extreme performances. This objective is consistent with this of contract laboratories which need to reach a known level of guarantee for the results which they produce. In that respect, accuracy profile represents a very convenient tool to ascertain such a goal.     

PCRPi: Presaging Critical Residues in Protein interfaces,a new computational tool to chart hot spots in protein interfaces

Protein–protein interactions (PPIs) are ubiquitous in Biology, and thus offer an enormous potential for the discovery of novel therapeutics. Although protein interfaces are large and lack defining physiochemical traits, is well established that only a small portion of interface residues, the so-called hot spot residues, contribute the most to the binding energy of the protein complex. Moreover, recent successes in development of novel drugs aimed at disrupting PPIs rely on targeting such residues. Experimental methods for describing critical residues are lengthy and costly; therefore, there is a need for computational tools that can complement experimental efforts. Here, we describe a new computational approach to predict hot spot residues in protein interfaces. The method, called Presaging Critical Residues in Protein interfaces (PCRPi), depends on the integration of diverse metrics into a unique probabilistic measure by using Bayesian Networks. We have benchmarked our method using a large set of experimentally verified hot spot residues and on a blind prediction on the protein complex formed by HRAS protein and a single domain antibody. Under both scenarios, PCRPi delivered consistent and accurate predictions. Finally, PCRPi is able to handle cases where some of the input data is either missing or not reliable (e.g. evolutionary information).     

Droserone from cell cultures of Triphyophyllum peltatum (Dioncophyllaceae) and its biosynthetic origin

The growth and droserone content of callus cultures of Triphyophyllum peltatum grown in liquid 1/5 Linsmaier and Skoog medium was studied. During a lag phase in growth, droserone concentrations in the medium reached a value of 2.1 mg g-1 fr. wt. After this maximum value the concentration decreased slightly to 1.8 mg g-1 fr. wt., while the growth of the calli was enhanced (25% increase in fr. wt. within 7 days). Plumbagin and isoshinanolone were likewise present in the medium. By feeding 13C2-labelled acetate to the cultures the biosynthesis of droserone was elucidated. The incorporation of whole C2-units unambiguously shows its acetogenic origin and fits well in the biosynthetic scheme suggested for the structurally--and biogenetically--related naphthylisoquinoline alkaloids.