Signs of a vector's adaptive choice: on the evasion of infectious hosts and parasite-induced mortality

Laboratory and field experiments have demonstrated in many cases that malaria vectors do not feed randomly, but show important preferences either for infected or non-infected hosts. These preferences are likely in part shaped by the costs imposed by the parasites on both their vertebrate and dipteran hosts. However, the effect of changes in vector behaviour on actual parasite transmission remains a debated issue. We used the natural associations between a malaria-like parasite Polychromophilus murinus, the bat fly Nycteribia kolenatii and a vertebrate host the Daubenton's bat Myotis daubentonii to test the vector's feeding preference based on the host's infection status using two different approaches: 1) controlled behavioural assays in the laboratory where bat flies could choose between a pair of hosts; 2) natural bat fly abundance data from wild-caught bats, serving as an approximation of realised feeding preference of the bat flies. Hosts with the fewest infectious stages of the parasite were most attractive to the bat flies that did switch in the behavioural assay. In line with the hypothesis of costs imposed by parasites on their vectors, bat flies carrying parasites had higher mortality. However, in wild populations, bat flies were found feeding more based on the bat's body condition, rather than its infection level. Though the absolute frequency of host switches performed by the bat flies during the assays was low, in the context of potential parasite transmission they were extremely high. The decreased survival of infected bat flies suggests that the preference for less infected hosts is an adaptive trait. Nonetheless, other ecological processes ultimately determine the vector's biting rate and thus transmission. Inherent vector preferences therefore play only a marginal role in parasite transmission in the field. The ecological processes rather than preferences per se need to be identified for successful epidemiological predictions.

Expression of the inducible NO synthase in human monocytic U937 cells allows high output nitric oxide production.

Nitric oxide (NO) produced by inducible NO synthase (iNOS, NOS-2) is an important component of the macrophage-mediated immune defense toward numerous pathogens. Murine macrophages produce NO after cytokine activation, whereas, under similar conditions, human macrophages produce low levels or no NO at all. Although human macrophages can express iNOS mRNA and protein on activation, whether they possess the complete machinery necessary for NO synthesis remains controversial. To define the conditions necessary for human monocytes/macrophages to synthesize NO when expressing a functional iNOS, the human monocytic U937 cell line was engineered to synthesize this enzyme, following infection with a retroviral expression vector containing human hepatic iNOS (DFGiNOS). Northern blot and Western blot analysis confirmed the expression of iNOS in transfected U937 cells both at the RNA and protein levels. NOS enzymatic activity was demonstrated in cell lysates by the conversion of L-[3H]arginine into L-[3H]citrulline and the production of NO by intact cells was measured by nitrite and nitrate accumulation in culture supernatants. When expressing functional iNOS, U937 cells were capable of releasing high levels of NO. NO production was strictly dependent on supplementation of the culture medium with tetrahydrobiopterin (BH4) and was not modified by stimulation of the cells with different cytokines. These observations suggest that (1) human monocytic U937 cells contain all the cofactors necessary for NO synthesis, except BH4 and (2) the failure to detect NO in cytokine-stimulated untransfected U937 cells is not due to the presence of a NO-scavenging molecule within these cells nor to the destabilization of iNOS protein. DFGiNOS U937 cells represent a valuable human model to study the role of NO in immunity toward tumors and pathogens.

Genomic insights into the Ixodes scapularis tick vector of Lyme disease.

Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing ∼57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick-host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host 'questing', prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent.

On the interplay between Q^2 and t dependence in exclusive diffractive production of real photons and vector mesons in ep collisions

We show how the familiar phenomenological way of combining the Q2 (photon virtuality) and t (squared momentum transfer) dependences of the scattering amplitude in Deeply Virtual Compton Scattering (DVCS) [1, 2] and Vector Meson Production (VMP) [2] processes can be understood in an off-mass-shell generalization of dual amplitudes with Mandelstam analyticity [3]. By comparing different approaches, we managed also to constrain the numerical values of the free parameters.

Full instability behavior of N-dimensional dynamical systems with a one-directional nonlinear vector field

We show how certain N-dimensional dynamical systems are able to exploit the full instability capabilities of their fixed points to do Hopf bifurcations and how such a behavior produces complex time evolutions based on the nonlinear combination of the oscillation modes that emerged from these bifurcations. For really different oscillation frequencies, the evolutions describe robust wave form structures, usually periodic, in which selfsimilarity with respect to both the time scale and system dimension is clearly appreciated. For closer frequencies, the evolution signals usually appear irregular but are still based on the repetition of complex wave form structures. The study is developed by considering vector fields with a scalar-valued nonlinear function of a single variable that is a linear combination of the N dynamical variables. In this case, the linear stability analysis can be used to design N-dimensional systems in which the fixed points of a saddle-node pair experience up to N21 Hopf bifurcations with preselected oscillation frequencies. The secondary processes occurring in the phase region where the variety of limit cycles appear may be rather complex and difficult to characterize, but they produce the nonlinear mixing of oscillation modes with relatively generic features

Rotenoids from Tephrosia toxicaria with larvicidal activity against Aedes aegypti, the main vector of dengue fever

In the search for new larvicides from plants, we have investigated the potential activity of the rotenoids deguelin (1), 12a-hydroxy-α-toxicarol (2) and tephrosin (3), isolated from the bioactive ethanol extract of roots of Tephrosia toxicaria Pers., against Aedes aegypti, the main vector of dengue. The absolute configuration of these compounds was determined by circular dichroism (CD) spectra. The LC50 values of the compounds evaluated justify the potential of T. toxicaria as a new natural larvicide.

PREDICTING THE BOILING POINT OF PCDD/Fs BY THE QSPR METHOD BASED ON THE MOLECULAR DISTANCE-EDGE VECTOR INDEX

The quantitative structure property relationship (QSPR) for the boiling point (Tb) of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) was investigated. The molecular distance-edge vector (MDEV) index was used as the structural descriptor. The quantitative relationship between the MDEV index and Tb was modeled by using multivariate linear regression (MLR) and artificial neural network (ANN), respectively. Leave-one-out cross validation and external validation were carried out to assess the prediction performance of the models developed. For the MLR method, the prediction root mean square relative error (RMSRE) of leave-one-out cross validation and external validation was 1.77 and 1.23, respectively. For the ANN method, the prediction RMSRE of leave-one-out cross validation and external validation was 1.65 and 1.16, respectively. A quantitative relationship between the MDEV index and Tb of PCDD/Fs was demonstrated. Both MLR and ANN are practicable for modeling this relationship. The MLR model and ANN model developed can be used to predict the Tb of PCDD/Fs. Thus, the Tb of each PCDD/F was predicted by the developed models.

Loss Modelling of Three-Level Inverters controlled with Space Vector Modulation Technique

The objective of this master’s thesis is to investigate the loss behavior of three-level ANPC inverter and compare it with conventional NPC inverter. The both inverters are controlled with mature space vector modulation strategy. In order to provide the comparison both accurate and detailed enough NPC and ANPC simulation models should be obtained. The similar control model of SVM is utilized for both NPC and ANPC inverter models. The principles of control algorithms, the structure and description of models are clarified. The power loss calculation model is based on practical calculation approaches with certain assumptions. The comparison between NPC and ANPC topologies is presented based on results obtained for each semiconductor device, their switching and conduction losses and efficiency of the inverters. Alternative switching states of ANPC topology allow distributing losses among the switches more evenly, than in NPC inverter. Obviously, the losses of a switching device depend on its position in the topology. Losses distribution among the components in ANPC topology allows reducing the stress on certain switches, thus losses are equally distributed among the semiconductors, however the efficiency of the inverters is the same. As a new contribution to earlier studies, the obtained models of SVM control, NPC and ANPC inverters have been built. Thus, this thesis can be used in further more complicated modelling of full-power converters for modern multi-megawatt wind energy conversion systems.

Estudo da Adesão à Quimioprofilaxia Anti-retroviral para a Infecção por HIV em Mulheres Sexualmente Vitimadas

Objetivos: embora não existam dados apropriados para estabelecer sua eficácia, alguns serviços tem utilizado, profilaticamente, a terapia anti-retroviral para o HIV nos casos de violência sexual. O objetivo deste estudo foi avaliar a aceitabilidade, tolerância e adesão a um esquema quimioprofilático para o HIV. Pacientes e método: foram avaliadas 62 mulheres vítimas de estupro e/ou atentado violento ao pudor com coito ectópico anal. Os agressores foram referidos como desconhecidos. A profilaxia foi iniciada dentro das primeiras 48 h da violência e mantida por 4 semanas, sendo administrados diariamente: zidovudina, 600 mg; indinavir, 2.400 mg e lamivudina, 300 mg. Resultados: a taxa de descontinuidade foi de 24,2%, sendo em 12 casos (80%) decorrente de intolerância gástrica. Os efeitos colaterais estiveram presentes em 43 casos (69,4%), sendo as náuseas e vômitos os mais freqüentes. A complexidade posológica e o tempo de uso foram fatores possivelmente associados ao uso inadequado das drogas, ocorrendo em 10,6% dos casos. Conclusão: a taxa de descontinuidade da quimioprofilaxia foi semelhante à observada em outras indicações.

Avaliação crítica dos efeitos adversos do tratamento anti-retroviral no feto, recém-nascido e lactente

A introdução da profilaxia da transmissão vertical do HIV com o uso de drogas anti-retrovirais aliadas a outras medidas resultou na redução de crianças infectadas pelo HIV em nosso meio. Esses medicamentos são de uso recente e não há dados conclusivos para definir a sua segurança durante a gravidez. Esse artigo analisa, através de revisão bibliográfica, os possíveis efeitos dessas drogas sobre o feto, o recém-nascido e durante a infância, incluindo o potencial de teratogenicidade, carcinogênese e sua toxicidade. As descrições incluem a identificação de risco aumentado na criança para toxicidade mitocondrial, alterações neurológicas, hematológicas, hepáticas em crianças expostas ao HIV. Baseados nos conhecimentos atuais, considera-se que o benefício na acentuada redução da transmissão vertical do HIV com o uso de drogas anti-retrovirais ultrapassa os riscos eventuais dos efeitos adversos. Entretanto, até que experiência de longo prazo se acumule, é necessário acompanhamento clínico especializado das crianças expostas. Nessa revisão sugere-se uma rotina de acompanhamento clínico-laboratorial ao longo do primeiro ano de vida e depois anualmente até o final da adolescência.

Avaliação ultra-sonográfica, ecocardiográfica fetal e resultados perinatais em gestantes portadoras do HIV em uso de terapia anti-retroviral

OBJETIVO: descrever as alterações estruturais e/ou funcionais fetais à ultra-sonografia e à ecocardiografia fetais e os resultados perinatais em gestantes soropositivas para o vírus da imunodeficiência humana (HIV) em relação a um grupo controle de pacientes atendidas pelo pré-natal de baixo risco. MÉTODOS: foram avaliadas, prospectivamente, 109 gestantes soropositivas para o HIV em uso de anti-retrovirais (Grupo de Estudo, GE) e 200 gestantes controles (GC), sendo realizado acompanhamento ultra-sonográfico obstétrico mensal e ecocardiografia fetal e pós-natal com a avaliação do volume de líquido amniótico, da adequação do peso fetal, da presença de alterações estruturais fetais e dos resultados perinatais. RESULTADOS: foram observados oito casos de alterações estruturais fetais (7,3%) contra dois (1%) no GC (p=0,61). Observamos quatro casos de cardiopatia congênita e quatro de hidronefrose no GE, com diferença estatística para as cardiopatias (p=0,015). Foram diagnosticados, no GE, oito (7,3%) casos de oligoidrâmnio e 11 (10%) casos de polidrâmnio contra dois casos (1%) de oligoidrâminio e nenhum de polidrâmnio (p de 0,004 e p<0,001, respectivamente). Onze recém-nascidos (10%) foram pequenos para a idade gestacional no GE contra três (2,7%) no GC (p=0,002). A incidência de prematuridade foi de 8,7 e 2,5% nos grupos de estudo e controle, respectivamente (p=0,041). A taxa de óbito fetal foi de 5,5% (seis casos) no GE, contra nenhum no GC (p=0,002). CONCLUSÕES: observamos maior prevalência de cardiopatia fetal e de alterações da quantidade de líquido amniótico no grupo estudado em relação ao GC. A taxa de óbito fetal no GE provavelmente está vinculada à presença de malformações fetais; já a incidência de neonatos pequenos para a idade gestacional e de prematuridade, está associada à terapia anti-retroviral e ao uso do tabaco e de drogas ilícitas.

Support vector machines in spectral data classification

Työssä käydään läpi tukivektorikoneiden teoreettista pohjaa sekä tutkitaan eri parametrien vaikutusta spektridatan luokitteluun.

The yellow fever 17D vaccine virus: molecular basis of viral attenuation and its use as an expression vector

The yellow fever (YF) virus is the prototype flavivirus. The use of molecular techniques has unraveled the basic mechanisms of viral genome structure and expression. Recent trends in flavivirus research include the use of infectious clone technology with which it is possible to recover virus from cloned cDNA. Using this technique, mutations can be introduced at any point of the viral genome and their resulting effect on virus phenotype can be assessed. This approach has opened new possibilities to study several biological viral features with special emphasis on the issue of virulence/attenuation of the YF virus. The feasibility of using YF virus 17D vaccine strain, for which infectious cDNA is available, as a vector for the expression of heterologous antigens is reviewed

The challenge of vector development in gene therapy

Gene therapy is the treatment of diseases based on the transfer of genetic information. Agents that carry or deliver DNA to target cells are called vectors (Latin vector: carrier, deliverer). Ideally, a vector should accommodate an unlimited amount of inserted DNA, lack the ability of autonomous replication of its own DNA, be easily manufactured, and be available in concentrated form. Secondly, it should have the ability to target specific cell types or to limit its gene expression to specific cell types, and to achieve sustained gene expression in the long term or in a controlled fashion. Finally, it should not be toxic or immunogenic. Such a vector does not exist and none of the DNA delivery systems so far available for in vivo gene transfer is perfect with respect to any of these points. Gene therapy and the means to promote it depend heavily on the development and improvement of new gene vector systems.