The Plasmodium bottleneck: malaria parasite losses in the mosquito vector

Nearly one million people are killed every year by the malaria parasite Plasmodium. Although the disease-causing forms of the parasite exist only in the human blood, mosquitoes of the genus Anopheles are the obligate vector for transmission. Here, we review the parasite life cycle in the vector and highlight the human and mosquito contributions that limit malaria parasite development in the mosquito host. We address parasite killing in its mosquito host and bottlenecks in parasite numbers that might guide intervention strategies to prevent transmission.

Bernstein's problem on weighted polynomial approximation

We formulate a necessary and sufficient condition for polynomials to be dense in a space of continuous functions on the real line, with respect to Bernstein's weighted uniform norm. Equivalently, for a positive finite measure [lletra "mu" minúscula de l'alfabet grec] on the real line we give a criterion for density of polynomials in Lp[lletra "mu" minúscula de l'alfabet grec entre parèntesis].

Statistical discrimination of steroid profiles in doping control with support vector machines.

Due to their performance enhancing properties, use of anabolic steroids (e.g. testosterone, nandrolone, etc.) is banned in elite sports. Therefore, doping control laboratories accredited by the World Anti-Doping Agency (WADA) screen among others for these prohibited substances in urine. It is particularly challenging to detect misuse with naturally occurring anabolic steroids such as testosterone (T), which is a popular ergogenic agent in sports and society. To screen for misuse with these compounds, drug testing laboratories monitor the urinary concentrations of endogenous steroid metabolites and their ratios, which constitute the steroid profile and compare them with reference ranges to detect unnaturally high values. However, the interpretation of the steroid profile is difficult due to large inter-individual variances, various confounding factors and different endogenous steroids marketed that influence the steroid profile in various ways. A support vector machine (SVM) algorithm was developed to statistically evaluate urinary steroid profiles composed of an extended range of steroid profile metabolites. This model makes the interpretation of the analytical data in the quest for deviating steroid profiles feasible and shows its versatility towards different kinds of misused endogenous steroids. The SVM model outperforms the current biomarkers with respect to detection sensitivity and accuracy, particularly when it is coupled to individual data as stored in the Athlete Biological Passport.

Electroisomerització en compostos fotocròmics: formació reversible d'enllaços C-C i C-O

La present memòria descriu processos d'electroisomerització en compostos fotocròmics, [2.2]metaciclofans i naptopirans. Els estudis electroquímics i espectroelectroquímics mostren la formació d'enllaços C-C i C-O pels [2.2]metaciclofans i naptopirans, respectivament.

Intrusive versus domiciliated triatomines and the challenge of adapting vector control practices against Chagas disease

Chagas disease prevention remains mostly based on triatomine vector control to reduce or eliminate house infestation with these bugs. The level of adaptation of triatomines to human housing is a key part of vector competence and needs to be precisely evaluated to allow for the design of effective vector control strategies. In this review, we examine how the domiciliation/intrusion level of different triatomine species/populations has been defined and measured and discuss how these concepts may be improved for a better understanding of their ecology and evolution, as well as for the design of more effective control strategies against a large variety of triatomine species. We suggest that a major limitation of current criteria for classifying triatomines into sylvatic, intrusive, domiciliary and domestic species is that these are essentially qualitative and do not rely on quantitative variables measuring population sustainability and fitness in their different habitats. However, such assessments may be derived from further analysis and modelling of field data. Such approaches can shed new light on the domiciliation process of triatomines and may represent a key tool for decision-making and the design of vector control interventions.

Atlas of Mexican Triatominae (Reduviidae: Hemiptera) and vector transmission of Chagas disease

Chagas disease is one of the most important yet neglected parasitic diseases in Mexico and is transmitted by Triatominae. Nineteen of the 31 Mexican triatomine species have been consistently found to invade human houses and all have been found to be naturally infected with Trypanosoma cruzi. The present paper aims to produce a state-of-knowledge atlas of Mexican triatomines and analyse their geographic associations with T. cruzi, human demographics and landscape modification. Ecological niche models (ENMs) were constructed for the 19 species with more than 10 records in North America, as well as for T. cruzi. The 2010 Mexican national census and the 2007 National Forestry Inventory were used to analyse overlap patterns with ENMs. Niche breadth was greatest in species from the semiarid Nearctic Region, whereas species richness was associated with topographic heterogeneity in the Neotropical Region, particularly along the Pacific Coast. Three species,Triatoma longipennis, Triatoma mexicana and Triatoma barberi, overlapped with the greatest numbers of human communities, but these communities had the lowest rural/urban population ratios. Triatomine vectors have urbanised in most regions, demonstrating a high tolerance to human-modified habitats and broadened historical ranges, exposing more than 88% of the Mexican population and leaving few areas in Mexico without the potential for T. cruzitransmission.

Spatial distribution of triatomines in domiciles of an urban area of the Brazilian Southeast Region

Reports of triatomine infestation in urban areas have increased. We analysed the spatial distribution of infestation by triatomines in the urban area of Diamantina, in the state of Minas Gerais, Brazil. Triatomines were obtained by community-based entomological surveillance. Spatial patterns of infestation were analysed by Ripley’s K function and Kernel density estimator. Normalised difference vegetation index (NDVI) and land cover derived from satellite imagery were compared between infested and uninfested areas. A total of 140 adults of four species were captured (100 Triatoma vitticeps, 25Panstrongylus geniculatus, 8 Panstrongylus megistus, and 7 Triatoma arthurneivai specimens). In total, 87.9% were captured within domiciles. Infection by trypanosomes was observed in 19.6% of 107 examined insects. The spatial distributions ofT. vitticeps, P. geniculatus, T. arthurneivai, and trypanosome-positive triatomines were clustered, occurring mainly in peripheral areas. NDVI values were statistically higher in areas infested by T. vitticeps and P. geniculatus. Buildings infested by these species were located closer to open fields, whereas infestations of P. megistus andT. arthurneivai were closer to bare soil. Human occupation and modification of natural areas may be involved in triatomine invasion, exposing the population to these vectors.

Assessing the mitochondrial DNA diversity of the Chagas disease vector Triatoma sordida (Hemiptera: Reduviidae)

Triatoma sordida is a species that transmits Trypanosoma cruzi to humans. In Brazil, T. sordida currently deserves special attention because of its wide distribution, tendency to invade domestic environments and vectorial competence. For the planning and execution of control protocols to be effective against Triatominae, they must consider its population structure. In this context, this study aimed to characterise the genetic variability of T. sordida populations collected in areas with persistent infestations from Minas Gerais, Brazil. Levels of genetic variation and population structure were determined in peridomestic T. sordida by sequencing a polymorphic region of the mitochondrial cytochrome b gene. Low nucleotide and haplotype diversity were observed for all 14 sampled areas; π values ranged from 0.002-0.006. Most obtained haplotypes occurred at low frequencies, and some were exclusive to only one of the studied populations. Interpopulation genetic diversity analysis revealed strong genetic structuring. Furthermore, the genetic variability of Brazilian populations is small compared to that of Argentinean and Bolivian specimens. The possible factors related to the reduced genetic variability and strong genetic structuring obtained for studied populations are discussed in this paper.

Analysis of significant factors influencing visual acuity in ocular syphilis.

BACKGROUND: The aim of this study is to determine whether statistical associations can be demonstrated in ocular syphilis between baseline clinical and laboratory parameters with visual acuity at presentation and with any change in visual acuity after treatment. METHODS: Charts of 26 patients (42 eyes) with ocular syphilis presenting to the Uveitis clinic of the Jules-Gonin Eye Hospital were reviewed. A baseline cross-sectional analysis was performed in order to identify any association between visual acuity at presentation and demographic, clinical or laboratory parameters. After treatment, any analogy between these parameters and a change in visual acuity was subsequently assessed in a series of univariate comparisons. RESULTS: The following factors were associated with worse initial visual acuity: severity of visual field impairment at presentation (p=0.012), macular oedema (p=0.004) and optic neuropathy (p=0.031). There was a borderline association with the presence of vasculitis on fluroangiography (p=0.072). Improvement in best corrected visual acuity after treatment was significantly associated with the presence of vasculitis on fluroangiography (p=0.005), neurosyphilis, according to lumbar puncture findings (p=0.037) and marginally with anterior uveitis (p=0.070). Inflammation relapse was associated with the coexistence of pain as presenting sign (p<0.001) and with a longer duration of symptoms prior to the initial visit (p=0.023). CONCLUSIONS: Severe ocular inflammation associated with vasculitis, vitritis or anterior uveitis in ocular syphilis would appear to be a reversible phenomenon that responds well to appropriate antibiotic treatment, resulting in improvement in visual acuity. Prompt treatment enables a good visual prognosis, while any delay in therapy increases the risk of subsequent relapse.

Inducible gene and shRNA expression in resident hematopoietic stem cells in vivo.

Hematopoietic stem cells (HSC) are probably the best understood somatic stem cells and often serve as a paradigm for other stem cells. Nevertheless, most current techniques to genetically manipulate them in vivo are either constitutive and/or induced in settings of hematopoietic stress such as after irradiation. Here, we present a conditional expression system that allows for externally controllable transgenesis and knockdown in resident HSCs, based on a lentiviral vector containing a tet-O sequence and a transgenic mouse line expressing a doxycyclin-regulated tTR-KRAB repressor protein. HSCs harvested from tTR-KRAB mice are transduced with the lentiviral vector containing a cDNA (i.e., Green Fluorescent Protein (GFP)) and/or shRNA (i.e., p53) of interest and then transplanted into lethally irradiated recipients. While the vector is effectively repressed by tTR-KRAB during homing and engraftment, robust GFP/shp53 expression is induced on doxycyclin treatment in HSCs and their progeny. Doxycylin-controllable transcription is maintained on serial transplantation, indicating that repopulating HSCs are stably modified by this approach. In summary, this easy to implement conditional system provides inducible and reversible overexpression or knock down of genes in resident HSCs in vivo using a drug devoid of toxic or activating effects.

Impact of Pre-Existing Immunity on the Selection of Rare Adenovirus Vector Candidates: Implications for HIV Vaccine Development

Background: Adenovirus serotype 5 (Ad5) phase IIb vaccine trial (STEP) was prematurely stopped due to a lack of efficacy and two-fold higher incidence of HIV infection among Ad5 seropositive vaccine recipients. We have recently demonstrated that Ad5 immune complexes (Ad5 ICs)-mediated activation of the dendritic cell (DC)-T cell axis was associated with the enhancement of HIV infection in vitro. Although the direct role of Ad5 neutralizing antibodies (NAbs) in the increase of HIV susceptibility during the STEP trial is still under debate, vector-specific NAbs remain a major hurdle for vector-based gene therapies or vaccine strategies. To surmount this obstacle, vectors based on ''rare'' Ad serotypes including Ad6, Ad26, Ad36 and Ad41 were engineered.Methods: The present study aimed to determine whether Ad ICmediated DC maturation could be circumvented using these Advector candidates.Results: We found that all Ad vectors tested forming ICs with plasma containing serotype-specific NAbs had the capacity to 1) mature human DCs as monitored by the up-regulation of costimulatory molecules and the release of pro-inflammatory cytokines (TNF-a), via the stabilization of Ad capsid at endosomal but not lysosomal pH rendering Ad DNA/TLR9 interactions possible and 2) potentiate Ad-specific CD4 and CD8 T cell responses.Conclusion: In conclusion, despite a conserved DC maturation potential, the low prevalence of serotype-specific NAbs renders rare Ad vectors attractive for vaccine strategies.

A comparison between joint coordinate system and attitude vector for multi-segment foot kinematics.

The joint angles of multi-segment foot models have been primarily described using two mathematical methods: the joint coordinate system and the attitude vector. This study aimed to determine whether the angles obtained through these two descriptors are comparable, and whether these descriptors have similar sensitivity to experimental errors. Six subjects walked eight times on an instrumented walkway while the joint angles among shank, hindfoot, medial forefoot, and lateral forefoot were measured. The angles obtained using both descriptors and their sensitivity to experimental errors were compared. There was no overall significant difference between the ranges of motion obtained using both descriptors. However, median differences of more than 6° were noticed for the medial-lateral forefoot joint. For all joints and rotation planes, both descriptors provided highly similar angle patterns (median correlation coefficient: R>0.90), except for the medial-lateral forefoot angle in the transverse plane (median R=0.77). The joint coordinate system was significantly more sensitive to anatomical landmarks misplacement errors. However, the absolute differences of sensitivity were small relative to the joints ranges of motion. In conclusion, the angles obtained using these two descriptors were not identical, but were similar for at least the shank-hindfoot and hindfoot-medial forefoot joints. Therefore, the angle comparison across descriptors is possible for these two joints. Comparison should be done more carefully for the medial-lateral forefoot joint. Moreover, despite different sensitivities to experimental errors, the effects of the experimental errors on the angles were small for both descriptors suggesting that both descriptors can be considered for multi-segment foot models.

Priors about observables in vector autoregressions

Standard practice in Bayesian VARs is to formulate priors on the autoregressive parameters, but economists and policy makers actually have priors about the behavior of observable variables. We show how this kind of prior can be used in a VAR under strict probability theory principles. We state the inverse problem to be solved and we propose a numerical algorithm that works well in practical situations with a very large number of parameters. We prove various convergence theorems for the algorithm. As an application, we first show that the results in Christiano et al. (1999) are very sensitive to the introduction of various priors that are widely used. These priors turn out to be associated with undesirable priors on observables. But an empirical prior on observables helps clarify the relevance of these estimates: we find much higher persistence of output responses to monetary policy shocks than the one reported in Christiano et al. (1999) and a significantly larger total effect.