Septin C-Terminal Domain Interactions: Implications for Filament Stability and Assembly

Septins form a conserved family of filament forming GTP binding proteins found in a wide range of eukaryotic cells. They share a common structural architecture consisting of an N-terminal domain, a central GTP binding domain and a C-terminal domain, which is often predicted to adopt a coiled-coil conformation, at least in part. The crystal structure of the human SEPT2/SEPT6/SEPT7 heterocomplex has revealed the importance of the GTP binding domain in filament formation, but surprisingly no electron density was observed for the C-terminal domains and their function remains obscure. The dearth of structural information concerning the C-terminal region has motivated the present study in which the putative C-terminal domains of human SEPT2, SEPT6 and SEPT7 were expressed in E. coli and purified to homogeneity. The thermal stability and secondary structure content of the domains were studied by circular dichroism spectroscopy, and homo- and hetero-interactions were investigated by size exclusion chromatography, chemical cross-linking, analytical ultracentrifugation and surface plasmon resonance. Our results show that SEPT6-C and SEPT7-C are able to form both homo- and heterodimers with a high alpha-helical content in solution. The heterodimer is elongated and considerably more stable than the homodimers, with a K (D) of 15.8 nM. On the other hand, the homodimer SEPT2-C has a much lower affinity, with a K (D) of 4 mu M, and a moderate alpha-helical content. Our findings present the first direct experimental evidence toward better understanding the biophysical properties and coiled-coil pairings of such domains and their potential role in filament assembly and stability.

Home blood pressure monitoring and control in a group of hypertensive patients

This qualitative study was performed with 71 hypertensive patients, with the objectives to compare outpatient and home blood pressure monitoring (HBPM), to assess blood pressure control, and characterize white-coat hypertension. A nurse performed the outpatient blood pressure measurement. The home blood pressure monitoring was carried out over seven days. White-coat hypertension was quantified as a difference between the outpatient measurement and home blood pressure monitoring in the ranges from 1 to 5, 6 to 10 and > 10 mmHg. The outpatient blood pressure measurement was significantly higher (p<0.05) than the home blood pressure measurement. Pressure control corresponded to 9.9% in the outpatient measurement and 23.9% in the home blood pressure measurement. The white-coat effect > 10 mmHg was 57.7% for systolic and 32.4% for diastolic pressure, in the range from 6 to 10 mmHg. Home blood pressure measurement provided a better assessment of hypertensive patients' control.

Microencapsulation of lycopene by spray drying: Characterization, stability and application of microcapsules

Microencapsulation can be an alternative to minimize lycopene instability. Thus, the aim of this study was to microencapsulate lycopene by spray drying, using a modified starch (Capsul (R)) as an encapsulating agent, and to assess the functionality of the capsules applying them in cake. The quantity of lycopene was varied at 5, 10 and 15% in a solution containing 30% of solids in order to obtain the microcapsules. These microcapsules were evaluated as to encapsulation efficiency and morphology and then submitted to a stability test and applied in cakes. Encapsulation efficiency values varied between 21 and 29%. The microcapsules had a rounded outer surface with the formation of concavities and they varied in size. The stability test revealed that microencapsulation offered greater protection to lycopene compared to its free form and it was observed that the microcapsules were able to release pigment and color the studied food system in a homogenous manner. (C) 2011 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.

DengueTools: innovative tools and strategies for the surveillance and control of dengue

Dengue fever is a mosquito-borne viral disease estimated to cause about 230 million infections worldwide every year, of which 25,000 are fatal. Global incidence has risen rapidly in recent decades with some 3.6 billion people, over half of the world's population, now at risk, mainly in urban centres of the tropics and subtropics. Demographic and societal changes, in particular urbanization, globalization, and increased international travel, are major contributors to the rise in incidence and geographic expansion of dengue infections. Major research gaps continue to hamper the control of dengue. The European Commission launched a call under the 7th Framework Programme with the title of 'Comprehensive control of Dengue fever under changing climatic conditions'. Fourteen partners from several countries in Europe, Asia, and South America formed a consortium named 'DengueTools' to respond to the call to achieve better diagnosis, surveillance, prevention, and predictive models and improve our understanding of the spread of dengue to previously uninfected regions (including Europe) in the context of globalization and climate change. The consortium comprises 12 work packages to address a set of research questions in three areas: Research area 1: Develop a comprehensive early warning and surveillance system that has predictive capability for epidemic dengue and benefits from novel tools for laboratory diagnosis and vector monitoring. Research area 2: Develop novel strategies to prevent dengue in children. Research area 3: Understand and predict the risk of global spread of dengue, in particular the risk of introduction and establishment in Europe, within the context of parameters of vectorial capacity, global mobility, and climate change. In this paper, we report on the rationale and specific study objectives of 'DengueTools'. DengueTools is funded under the Health theme of the Seventh Framework Programme of the European Community, Grant Agreement Number: 282589 Dengue Tools.

Chains of Infinite Order, Chains with Memory of Variable Length, and Maps of the Interval

We show how to construct a topological Markov map of the interval whose invariant probability measure is the stationary law of a given stochastic chain of infinite order. In particular we characterize the maps corresponding to stochastic chains with memory of variable length. The problem treated here is the converse of the classical construction of the Gibbs formalism for Markov expanding maps of the interval.

A new approach for modeling and control of nonlinear systems via norm-bounded linear differential inclusions

A systematic approach to model nonlinear systems using norm-bounded linear differential inclusions (NLDIs) is proposed in this paper. The resulting NLDI model is suitable for the application of linear control design techniques and, therefore, it is possible to fulfill certain specifications for the underlying nonlinear system, within an operating region of interest in the state-space, using a linear controller designed for this NLDI model. Hence, a procedure to design a dynamic output feedback controller for the NLDI model is also proposed in this paper. One of the main contributions of the proposed modeling and control approach is the use of the mean-value theorem to represent the nonlinear system by a linear parameter-varying model, which is then mapped into a polytopic linear differential inclusion (PLDI) within the region of interest. To avoid the combinatorial problem that is inherent of polytopic models for medium- and large-sized systems, the PLDI is transformed into an NLDI, and the whole process is carried out ensuring that all trajectories of the underlying nonlinear system are also trajectories of the resulting NLDI within the operating region of interest. Furthermore, it is also possible to choose a particular structure for the NLDI parameters to reduce the conservatism in the representation of the nonlinear system by the NLDI model, and this feature is also one important contribution of this paper. Once the NLDI representation of the nonlinear system is obtained, the paper proposes the application of a linear control design method to this representation. The design is based on quadratic Lyapunov functions and formulated as search problem over a set of bilinear matrix inequalities (BMIs), which is solved using a two-step separation procedure that maps the BMIs into a set of corresponding linear matrix inequalities. Two numerical examples are given to demonstrate the effectiveness of the proposed approach.

Stability and dynamics of terrestrial planets in binary star systems: application on Alpha Centauri

Binary stars are frequent in the universe, with about 50% of the known main sequence stars being located at a multiple star system (Abt, 1979). Even though, they are universally thought as second rate sites for the location of exo-planets and the habitable zone, due to the difficulties of detection and high perturbation that could prevent planet formation and long term stability. In this work we show that planets in binary star systems can have regular orbits and remain on the habitable zone. We introduce a stability criterium based on the solution of the restricted three body problem and apply it to describe the short period planar and three-dimentional stability zones of S-type orbits around each star of the Alpha Centauri system. We develop as well a semi-analytical secular model to study the long term dynamics of fictional planets in the habitable zone of those stars and we verify that planets on the habitable zone would be in regular orbits with any eccentricity and with inclination to the binary orbital plane up until 35 degrees. We show as well that the short period oscillations on the semi-major axis is 100 times greater than the Earth's, but at all the time the planet would still be found inside the Habitable zone.

Survey of Bancroftian filariasis infection in humans and Culex mosquitoes in the western Brazilian Amazon region: implications for transmission and control

Introduction: The aim of this work was to identify possible lymphatic filariasis foci in the western Brazilian Amazonian that could be established from the reports of Rachou in the 1950s. The study was conducted in three cities of the western Brazilian Amazon region - Porto Velho and Guajará-Mirim (State of Rondônia) and Humaitá (State of Amazonas). Methods: For human infection evaluation thick blood smear stained with Giemsa was used to analyze samples collected from 10pm to 1am. Polymerase chain reaction (PCR) was used to examine mosquito vectors for the presence of Wuchereria bancrofti DNA. Humans were randomly sampled from night schools students and from inhabitants in neighborhoods lacking sanitation. Mosquitoes were collected from residences only. Results: A total 2,709 night students enrolled in the Program for Education of Young Adults (EJA), and 935 people registered in the residences near the schools were examined, being 641 from Porto Velho, 214 from Guajará-Mirim and 80 from Humaitá. No individual examined was positive for the presence of microfilariae in the blood stream. A total of 7,860 female Culex quinquefasciatus specimens examined were negative by PCR. Conclusions: This survey including human and mosquito examinations indicates that the western Amazon region of Brazil is not a focus of Bancroftian filariasis infection or transmission. Therefore, there is no need to be included in the Brazilian lymphatic filariasis control program.

Seizure prediction and control in epilepsy

The first part of my thesis presents an overview of the different approaches used in the past two decades in the attempt to forecast epileptic seizure on the basis of intracranial and scalp EEG. Past research could reveal some value of linear and nonlinear algorithms to detect EEG features changing over different phases of the epileptic cycle. However, their exact value for seizure prediction, in terms of sensitivity and specificity, is still discussed and has to be evaluated. In particular, the monitored EEG features may fluctuate with the vigilance state and lead to false alarms. Recently, such a dependency on vigilance states has been reported for some seizure prediction methods, suggesting a reduced reliability. An additional factor limiting application and validation of most seizure-prediction techniques is their computational load. For the first time, the reliability of permutation entropy [PE] was verified in seizure prediction on scalp EEG data, contemporarily controlling for its dependency on different vigilance states. PE was recently introduced as an extremely fast and robust complexity measure for chaotic time series and thus suitable for online application even in portable systems. The capability of PE to distinguish between preictal and interictal state has been demonstrated using Receiver Operating Characteristics (ROC) analysis. Correlation analysis was used to assess dependency of PE on vigilance states. Scalp EEG-Data from two right temporal epileptic lobe (RTLE) patients and from one patient with right frontal lobe epilepsy were analysed. The last patient was included only in the correlation analysis, since no datasets including seizures have been available for him. The ROC analysis showed a good separability of interictal and preictal phases for both RTLE patients, suggesting that PE could be sensitive to EEG modifications, not visible on visual inspection, that might occur well in advance respect to the EEG and clinical onset of seizures. However, the simultaneous assessment of the changes in vigilance showed that: a) all seizures occurred in association with the transition of vigilance states; b) PE was sensitive in detecting different vigilance states, independently of seizure occurrences. Due to the limitations of the datasets, these results cannot rule out the capability of PE to detect preictal states. However, the good separability between pre- and interictal phases might depend exclusively on the coincidence of epileptic seizure onset with a transition from a state of low vigilance to a state of increased vigilance. The finding of a dependency of PE on vigilance state is an original finding, not reported in literature, and suggesting the possibility to classify vigilance states by means of PE in an authomatic and objectic way. The second part of my thesis provides the description of a novel behavioral task based on motor imagery skills, firstly introduced (Bruzzo et al. 2007), in order to study mental simulation of biological and non-biological movement in paranoid schizophrenics (PS). Immediately after the presentation of a real movement, participants had to imagine or re-enact the very same movement. By key release and key press respectively, participants had to indicate when they started and ended the mental simulation or the re-enactment, making it feasible to measure the duration of the simulated or re-enacted movements. The proportional error between duration of the re-enacted/simulated movement and the template movement were compared between different conditions, as well as between PS and healthy subjects. Results revealed a double dissociation between the mechanisms of mental simulation involved in biological and non-biologial movement simulation. While for PS were found large errors for simulation of biological movements, while being more acurate than healthy subjects during simulation of non-biological movements. Healthy subjects showed the opposite relationship, making errors during simulation of non-biological movements, but being most accurate during simulation of non-biological movements. However, the good timing precision during re-enactment of the movements in all conditions and in both groups of participants suggests that perception, memory and attention, as well as motor control processes were not affected. Based upon a long history of literature reporting the existence of psychotic episodes in epileptic patients, a longitudinal study, using a slightly modified behavioral paradigm, was carried out with two RTLE patients, one patient with idiopathic generalized epilepsy and one patient with extratemporal lobe epilepsy. Results provide strong evidence for a possibility to predict upcoming seizures in RTLE patients behaviorally. In the last part of the thesis it has been validated a behavioural strategy based on neurobiofeedback training, to voluntarily control seizures and to reduce there frequency. Three epileptic patients were included in this study. The biofeedback was based on monitoring of slow cortical potentials (SCPs) extracted online from scalp EEG. Patients were trained to produce positive shifts of SCPs. After a training phase patients were monitored for 6 months in order to validate the ability of the learned strategy to reduce seizure frequency. Two of the three refractory epileptic patients recruited for this study showed improvements in self-management and reduction of ictal episodes, even six months after the last training session.