Signal duration and the time scale dependence of signal integration in biochemical pathways

Signal duration (e.g. the time scales over which an active signaling intermediate persists) is a key regulator of biological decisions in myriad contexts such as cell growth, proliferation, and developmental lineage commitments. Accompanying differences in signal duration are numerous downstream biological processes that require multiple steps of biochemical regulation. Here, we present an analysis that investigates how simple biochemical motifs that involve multiple stages of regulation can be constructed to differentially process signals that persist at different time scales. We compute the dynamic gain within these networks and resulting power spectra to better understand how biochemical networks can integrate signals at different time scales. We identify topological features of these networks that allow for different frequency dependent signal processing properties. Our studies suggest design principles for why signal duration in connection with multiple steps of downstream regulation is a ubiquitous control motif in biochemical systems.Comment: 27 pages, 4 figure

Platform for Plasmodium vivax vaccine discovery and development

Plasmodium vivax is the most prevalent malaria parasite on the American continent. It generates a global burden of 80-100 million cases annually and represents a tremendous public health problem, particularly in the American and Asian continents. A malaria vaccine would be considered the most cost-effective measure against this vector-borne disease and it would contribute to a reduction in malaria cases and to eventual eradication. Although significant progress has been achieved in the search for Plasmodium falciparum antigens that could be used in a vaccine, limited progress has been made in the search for P. vivax components that might be eligible for vaccine development. This is primarily due to the lack of in vitro cultures to serve as an antigen source and to inadequate funding. While the most advanced P. falciparum vaccine candidate is currently being tested in Phase III trials in Africa, the most advanced P. vivax candidates have only advanced to Phase I trials. Herein, we describe the overall strategy and progress in P. vivax vaccine research, from antigen discovery to preclinical and clinical development and we discuss the regional potential of Latin America to develop a comprehensive platform for vaccine development

Persistent developmental stuttering as a cortical-subcortical dysfunction: evidence from muscle activation Gagueira persistente do desenvolvimento como disfunção córtico-subcortical: evidências pela ativação muscular

BACKGROUND: One contemporary view of stuttering posits that speech disfluencies arise from anomalous speech motor control. PURPOSE: To verify the rest muscle tension and speech reaction time of fluent and stuttering adults. METHOD: 22 adults, divided in two groups: G1 - 11 fluent individuals; G2 - 11 stutterers. Electromyography recordings (inferior orbicularis oris) were collected in two different situations: during rest and in a reaction time activity. RESULTS: The groups were significantly different considering rest muscle tension (G2 higher recordings) and did not differ when considering speech reaction time and muscle activity during speech. There was a strong positive correlation between speech reaction time and speech muscle activity for G2 - the longer the speech reaction time, the higher the muscle activity during speech. CONCLUSION: In addition to perceptible episodes of speech disfluency, stutterers exhibit anomalies in speech motor output during fluent speech. Correlations with a possible cortical-subcortical disorder are discussed.<br>INTRODUÇÃO: Atualmente considera-se que as disfluências da fala na gagueira sejam decorrentes de controle motor anormal. OBJETIVO: Verificar o repouso e tempo de reação para fala em adultos fluentes e gagos. MÉTODO: 22 adultos, divididos em dois grupos: G1 - 11 fluentes; G2 - 11 gagos. Os dados eletromiográficos (orbicular dos lábios inferior) foram obtidos em duas situações: repouso e atividade de tempo de reação. RESULTADOS: Os grupos apresentaram diferenças significantes para a tensão muscular de repouso (G2 valores maiores) e não se diferenciaram quanto ao tempo de reação e atividade muscular de fala. Houve correlação positiva entre o tempo de reação e a atividade muscular de fala para G2 - quanto maior o tempo de reação maior a atividade muscular de fala. CONCLUSÃO: Além dos episódios perceptíveis de disfluência, gagos apresentam alterações no output motor de fala durante a produção da fala fluente. Correlações com possível distúrbio cortico-subcortical são discutidas

Evaluation and Tuning of Model Trajectories and Spreading Rates in the Baltic Sea Using Surface Drifter Observations

Results from experiments with surface drifters in the Baltic Sea in 2010–2011 are presented and discussed. In a first experiment, 12 SVP-B (Surface Velocity Program, with Barometer) drifters with a drogue at 12–18 m depth were deployed in the Baltic Sea. In a second experiment, shallow drifters extending to a depth of 1.5 m were deployed in the Gulf of Finland. Results from the SVP-B drifter experiment are compared to results from a regional ocean model and a trajectory code. Differences between the observed SVP-B drifters and simulated drifters are found for absolute dispersion (i.e., squared displacement from initial position) and relative dispersion (i.e., squared distance between two initially paired drifters). The former is somewhat underestimated since the simulated currents are neither as fast nor as variable as those observed. The latter is underestimated both due to the above-mentioned reasons and due to the resolution of the ocean model. For the shallower drifters, spreading in the upper 1–2 m of the Gulf of Finland is investigated. The spreading rate is about 200 m/day for separations &lt;0.5 km, 500 m/day for separations below 1 km and in the range of 0.5–3 km/day for separations in the range of 1–4 km. The spreading rate does not follow Richardson’s law. The initial spreading, up to a distance of about d=100–150 m, is governed by the power law d∼t 0.27 whereas for larger separations the distance increases as d∼t2.5.BalticWa