Synthetic and natural polycations for gene therapy: State of the art and new perspectives

Currently, the major drawback of gene therapy is the gene transfection rate. The two main types of vectors that. are used in gene therapy are based on viral or non-viral gene delivery systems. There are several non-viral systems that can be used to transfer foreign genetic material into the human body. In order to do so, the DNA to be transferred must escape the processes that affect the disposition of macromolecules. These processes include the interaction with blood components, vascular endothelial cells and uptake by the reticuloendothelial system. Furthermore, the degradation of therapeutic DNA by serum nucleases is also a potential obstacle for functional delivery to the target cell. Cationic polymers have a great potential for DNA complexation and may be useful as non-viral vectors for gene therapy applications. The objective of this review was to address the state of the art in gene therapy using synthetic and natural polycations and the latest strategies to improve the efficiency of gene transfer into the cell.

Influence of the network former on the properties of magnesium spinels

Undoped and/or doped with 1 mol% of Co2+ Mg2TiO4 and Mg2SnO4 powders were synthesized by the polymeric precursor method. The influence of the network former (Sn4+ or Ti4+) on the thermal, structural and optical properties was investigated. The recorded mass losses are due to the escape of water and adsorbed gases and to the elimination of the organic matter. Mg2TiO4 crystallizes at lower temperatures and also presents more ordered structure with a smaller unit call and having more intense green color than Mg2SnO4 has.

Irregular Satellites of Jupiter: a study of the capture direction

The irregular satellites of Jupiter are believed to be captured asteroids or planetesimals. In the present work is studied the direction of capture of these objects as a function of their orbital inclination. We performed numerical simulations of the restricted three-body problem, Sun-Jupiter-particle, taking into account the growth of Jupiter. The integration was made backward in time. Initially, the particles have orbits as satellites of Jupiter, which has its present mass. Then, the system evolved with Jupiter losing mass and the satellites escaping from the planet. The reverse of the escape direction corresponds to the capture direction. The results show that the Lagrangian points L1 and L2 mainly guide the direction of capture. Prograde satellites are captured through these two gates with very narrow amplitude angles. In the case of retrograde satellites, these two gates are wider. The capture region increases as the orbital inclination increases. In the case of planar retrograde satellites the directions of capture cover the whole 360 degrees around Jupiter. We also verified that prograde satellites are captured earlier in actual time than retrograde ones.

Numerical study of low-cost alternative orbits around the Moon

In this paper, we have investigated a region of direct stable orbits around the Moon, whose stability is related to the H2 Family of periodic orbits and to the quasi-periodic orbits that oscillate around them. The stability criteria adopted was that the path did not escape from the Moon during an integration period of 1000 days (remaining with negative two-body Moon-probe orbital energy during this period). Considering the three-dimensional four-body Sun-Earth-Moon-probe problem, we investigated the evolution of the size of the stability region, taking into account the eccentricity of the Earth's orbit, the eccentricity and inclination of the Moon's orbit, and the solar radiation pressure on the probe. We also investigated the evolution of the region's size and its location by varying the inclination of the probe's initial osculating orbit relative to the Moon's orbital plane between 0 degrees and 180 degrees. The size of the stability region diminishes; nevertheless, it remains significant for 0 <= i <= 25 degrees and 35 degrees <= i <= 45 degrees. The orbits of this region could be useful for missions by space vehicles that must remain in orbit around the Moon for periods of up to 1000 days, requiring low maintenance costs. (c) 2005 COSPAR. Published by Elsevier Ltd. All rights reserved.

ARE CORPORAL ALLOMETRIC MEASUREMENTS GOOD PREDICTORS of PALATABILITY IN NEOTROPICAL BUTTERFLIES (LEPIDOPTERA)?

Since palatable butterflies are more dependent on evasive flight to escape from predators, they should be more restricted in their flight-related morphology than unpalatable ones. We compared: the ratios between the (1) length of head plus thorax and the length of abdomen (A/B), (2) length of the tip of the head to wing base and the length of the wing base to end of the abdomen (C/D), (3) the variances of A/B and C/D, (4) the proportion between the thoracic and the body weight, and (5) the flight speed between palatable and unpalatable butterflies. A/B and thoracic/body weight were higher for palatable species, indicating higher body symmetry and muscular mass. However, flight speed did not differ. Unexpectedly, the variance of A/B was higher for palatable species while that of C/D did not differ. Therefore, corporal allometric measurements of Neotropical butterflies are good predictors of palatability, though not of flight speed.

Alternative Transfers to the NEOs 99942 Apophis, 1994 WR12, and 2007 UW1 via Derived Trajectories from Periodic Orbits of Family G

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Structural and geochronological studies of the Médio Coreaú domain, NE Brazil: Constraints on Brasiliano/Pan-African tectonic evolution in the NW part of the Borborema Province

Recent structural investigations and geochronological studies of rocks from the Médio Coreaú domain in the NW part of northeast Brazil's Borborema Province provide important constraints on the tectonic evolution of the region both preceeding and during the assembly of West Gondwana. Field observations of structural features and fabrics have revealed the presence of four distinct deformational phases in the MCD: D1, D2, D3 and D4. Only the early Paleoproterozoic gneisses record the D1 tectonic event and its preservation is cryptic owing to strong overprinting by the subsequent tectonic phases. The D2, D3 and D4 events affected younger supracrustal rocks and Neoproterzoic magmatic units, and U-Pb geochronological constraints show that all of these tectonic phases represent deformational events that occurred during Brasiliano collision between the West African craton and the NW part of the Borborema Province. The D2 phase, lasting between ca. 622 and 591 Ma, represents a frontal collision stage, which generated NW verging thrust-nappe systems, low-angle foliation, high-grade metamorphism and crustal anatexis. Transition to a strike-slip regime (D3) occurred at around 591 Ma when the region entered a phase of escape tectonics. During this time, the motion of crustal blocks towards NE and E was accommodated along numerous anastomosing shear zones. Syntectonic emplacement of granitoid plutons took place in transtensional domains of the shear zone system. The intrusion of late tectonic granitoids and rapid uplift and cooling of the orogen around 560 Ma as a result of D4 transpressional movements marked the end of the D3 transcurrent regime. These findings show that only the early Paleoproterozoic gneisses in the Médio Coreaú domain are polycyclic in nature. Rather than representing distinct orogenic events, the D2, D3 and D4 tectonic phases are a manifestation of progressive deformational events that developed in response to changes in the regional stress field during convergence and collision between the Borborema Province and its surrounding cratons.

Implantation failures: Success of assisted hatching with quarter-laser zona thinning

Implantation failure after IVF is one of the factors associated with a reduced chance of pregnancy for some patients. Assisted hatching methodologies are designed to facilitate the embryo's escape from the zona pellucida, and this strategy has been suggested as a means of improving pregnancy rates in patients with previous implantation failure. The aim of this prospective and randomized study was to evaluate the efficacy of quarter-laser zona thinning assisted hatching (qLZT-AH) in improving the implantation of embryos in patients with previous implantation failure. A total of 150 patients with a history of previous implantation failure were treated with intracytoplasmic sperm injection, and allocated into two groups: group 1, only one previous implantation failure, and group 2, repeated implantation failures. The patients in each group were randomized at the time of embryo transfer into a control group (no qLZT-AH) or experimental group where qLZT-AH was performed. For patients with repeated implantation failures, the implantation rate in those who received laser-thinned embryos was significantly higher (P=0.02) than in those whose embryos were not laser-thinned (10.9 and 2.6% respectively). However, this difference was not observed in patients who presented with only one previous implantation failure. The data demonstrate that qLZT-AH is an effective strategy for improving the implantation of embryos in patients with repeated implantation failures.

Africanized honeybees: Biological characteristics, urban nesting behavior and accidents caused in Brazilian cities (Hymenoptera: Apidae)

In 1956 African honeybee queens (Apis mellifera scutellata) were imported from South Africa and Tanzania to Brazil, as part of a government project to increase Brazilian honey production. The European honeybees existing in that country had not adapted well to the tropical conditions and consequently, had a low productivity. The newly introduced bee was known to produce substantially more honey than the other subspecies, but was also famous for its great aggressiveness and quicker attack of intruders with less disturbance. Hoping to create a new hybrid bee that would be both docile and productive, the scientist Warwick Estevam Kerr tried to cross the African and the European subspecies under controlled conditions. However, an accident resulted in the escape of 26 swarms into the Brazilian countryside, where their queens mated with drones of the European resident honeybees. The poly-hybrid bees resulting from these crossings expressed scutellata-like reproductive, foraging, and defensive behaviors and, for this reason, were called Africanized honeybees. They spread rapidly from the introduction area of the African honeybees (near Rio Claro, São Paulo state) to as far south as mid-Argentina and to the north of Texas, also settling in Arizona, New Mexico, California and Nevada, due to their high adaptability to variable ecological conditions. In spite of a few undesirable behaviors, these bees have been invoking larger economic interest because they produce much more honey, have good resistance to diseases and are excellent pollinators. In Brazil, because people frequently disturb the environment, the occupation of urban refuges by Africanized honeybees has been increasing in the last years. The concern with accidents is generally associated with the high swarming frequency recorded during the year and the variety of shelters available in urban areas. This paper deals with the biological characteristics of the Africanized honeybees, their nesting behavior in urban environments, and accidents caused by these bees in Brazilian cities.

Chitosan nanoparticles for non-viral gene therapy

The cationic polysaccharide chitosan has been widely used for non-viral transfection in vitro and in vivo and has many advantages over other polycations. Chitosan is biocompatible and biodegradable and protects DNA against DNase degradation. However following administration the ChitosanDNA polyplexes must overcome a series of barriers before DNA is delivered to the cell nucleus. This paper describes the most important parameters involved in the chitosan-DNA interaction and their effects of on the condensation, shape, size and protection of DNA. Strategies developed for chitosanDNA polyplexes to avoid non-specific interaction with blood components and to overcome intracellular obstacles as the crossing of die cell membrane, endosomal escape and nuclear import are presented. © 2006 American Chemical Society.

Interplanetary natural routes via Moon and Lagrangiam points L1 and L2

Swing-by techniques are extensively used in interplanetary missions to minimize fuel consumption and to raise payloads of spaceships. The effectiveness of this type of maneuver has been proven since the beginning of space exploration. According to this premise, we have explored the existence of a natural and direct links between low Earth orbits and the lunar sphere of influence, to obtain low-energy interplanetary trajectories through swing-bys with the Moon and the Earth. The existence of these links are related to a family of retrograde periodic orbits around the Lagrangian equilibrium point L1 predicted for the circular, planar, restricted three-body Earth-Moon-particle problem. The trajectories in these links are sensitive to small disturbances. This enables them to be conveniently diverted reducing so the cost of the swing-by maneuver. These maneuvers allow us a gain in energy sufficient for the trajectories to escape from the Earth-Moon system and to stabilize in heliocentric orbits between the Earth and Venus or Earth and Mars. On the other hand, still within the Earth sphere of influence, and taking advantage of the sensitivity of the trajectories, is possible to design other swing-bys with the Earth or Moon. This allows the trajectories to have larger reach, until they can reach the orbit of other planets as Venus and Mars.(3σ)Broucke, R.A., Periodic Orbits in the Restricted Three-Body Problem with Earth-Moon Masses, JPL Technical Report 32-1168, 1968.

Inhibition of human neutrophil apoptosis by Paracoccidioides brasiliensis: Role of interleukin-8

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by Paracoccidiodes brasiliensis that presents a wide spectrum of clinical manifestations. Because of the great number of neutrophils polymorphonuclear neutrophils (PMN) found in the P. brasiliensis granuloma, studies have been done to evaluate the role of these cells during the development of the infection. This fungus is found intracellularly in PMN and monocytes/macrophages, suggesting that it is capable of evading damage and surviving inside these cells. Thus, in the present study, we investigated whether P. brasiliensis can prolong the lifetime of PMN, and if this process would be related with IL-8 levels. PMN apoptosis and intracellular levels of IL-8 were analysed by flow cytometry and culture supernatants IL-8 levels were evaluated by enzyme-linked immunosorbent assay. We found that coincubation with P. brasiliensis yeast cells results in an inhibition of PMN apoptosis, which was associated with increase in IL-8 production by these cells. Cocultures treatment with monoclonal antibody anti-IL-8 reversed the inhibitory effect of P. brasiliensis on PMN apoptosis, besides to increase spontaneous apoptosis of these cells. These data show that, in contrast to other microbial pathogens that drive phagocytes into apoptosis to escape killing, P. brasiliensis can extend the lifetime of normal human PMN by inducing autocrine IL-8 production. © 2008 The Authors.

Metabolismo de carboidratos não-estruturais em ruminantes

The carbohydrates provide 50 to 80% of the dry matter of grain and roughage and can be divided into structural (cellulose, hemicellulose) and non-structural (starch, pectin and sugars). The non-structural carbohydrates are primarily digested in the rumen and its dynamic process is a sequence for the supply of nutrients to the intestine. The quality and quantity of products resulting from ruminal fermentation are dependent on the type and activity of microorganisms in the rumen influenced by the type of food processing and that are subject of cereal grains that make up the diet. The NSC escape of rumen fermentation to be digested into glucose in the small intestine by pancreatic enzymes of origin (α-amylase) and intestinal mucosa (maltase and isomaltase). Starch is the most important energy supplier of cereals, which are important components of diets for intensive production of milk and meat.

Genetic and modifying factors that determine the risk of brain tumors

Some modifying factors may determine the risk of brain tumors. Until now, it could not be attempted to identify people at risk and also to improve significantly disease progression. Current therapy consists of surgical resection, followed by radiation therapy and chemotherapy. Despite of these treatments, the prognosis for patients is poor. In this review, we highlight general aspects concerning genetic alterations in brain tumors, namely astrocytomas, glioblastomas, oligodendrogliomas, medulloblastomas and ependymomas. The influence of these genetic alterations in patients' prognosis is discussed. Mutagen sensivity is associated with cancer risk. The convincing studies that linked DNA damages and DNA repair alterations with brain tumors are also described. Another important modifying factor is immunity. General immune response against cancer, tumor microenvironment and immune response, mechanisms of tumor escape, CNS tumor immunology, immune defects that impair anti-tumor systemic immunity in brain tumor patients and local immunosuppressive factors within CNS are also reviewed. New hope to treatment perspectives, as dendritic-cell-based vaccines is summarized too. Concluding, it seems well established that there is association between brain tumor risk and mutagen sensivity, which is highly heritable. Primary brain tumors cause depression in systemic host immunity; local immunosuppressive factors and immunological characteristics of tumor cells may explain the poor prognosis and DNA damages responses can alert immune system. However, it is necessary to clarify if individuals with both constitutional defects in immune functions and genetic instability have higher risk of developing brain tumors. Cytogenetic prospective studies and gene copy number variations analysis also must be performed in peripheral lymphocytes from brain tumor patients. © 2011 Bentham Science Publishers Ltd.

A aprendizagem matemática em uma posição de fronteira: Foregrounds e intencionalidade de estudantes de uma favela brasileira

In a large metropolis, students from different neighbourhoods can experience very different life opportunities. This can influence their attitude towards schooling and learning, including the learning of mathematics. We interviewed a group of six students from a favela in a large city in the interior of the state of São Paulo in Brazil. We invited the students to look into their future and explore whether or not there could be learning motives that linked mathematics in school to possible out-of-school practices, either in terms of possible future jobs or further studies. We identified some themes in the students' descriptions of their experiences. The first theme is discrimination. The students feel discriminated against due to the fact that they come from a poor neighbourhood. They fear being trapped in some stereotypes. The second theme is escape. There is a strong motivation to begin a new life away from the favela. A third theme concerns the obscurity of mathematics. It seems clear to everybody that education is relevant to ensure a change in life. However, the mathematics lessons do not provide any clues regarding how mathematics might function is this respect. The fourth theme is uncertainty with respect to the future. The students could easily formulate almost unattainable aspirations, while reality might impose some very heavy limitations. In this article we introduce a theoretical framework for discussing the relation between favela students' life conditions in relation to their educational experiences and opportunities. Students' intentions for learning are related to their foregrounds, that is, how they perceive their future possibilities, as made evident to them by their social environment. Students in a favela could experience what we call a borderland position, a relational space where individuals meet their social environment and come to terms with the multiple choices that cultural and economic diversity make available to them.