The use of biodiversity as source of new chemical entities against defined molecular targets for treatment of malaria, tuberculosis, and T-cell mediated diseases: a review

The modern approach to the development of new chemical entities against complex diseases, especially the neglected endemic diseases such as tuberculosis and malaria, is based on the use of defined molecular targets. Among the advantages, this approach allows (i) the search and identification of lead compounds with defined molecular mechanisms against a defined target (e.g. enzymes from defined pathways), (ii) the analysis of a great number of compounds with a favorable cost/benefit ratio, (iii) the development even in the initial stages of compounds with selective toxicity (the fundamental principle of chemotherapy), (iv) the evaluation of plant extracts as well as of pure substances. The current use of such technology, unfortunately, is concentrated in developed countries, especially in the big pharma. This fact contributes in a significant way to hamper the development of innovative new compounds to treat neglected diseases. The large biodiversity within the territory of Brazil puts the country in a strategic position to develop the rational and sustained exploration of new metabolites of therapeutic value. The extension of the country covers a wide range of climates, soil types, and altitudes, providing a unique set of selective pressures for the adaptation of plant life in these scenarios. Chemical diversity is also driven by these forces, in an attempt to best fit the plant communities to the particular abiotic stresses, fauna, and microbes that co-exist with them. Certain areas of vegetation (Amazonian Forest, Atlantic Forest, Araucaria Forest, Cerrado-Brazilian Savanna, and Caatinga) are rich in species and types of environments to be used to search for natural compounds active against tuberculosis, malaria, and chronic-degenerative diseases. The present review describes some strategies to search for natural compounds, whose choice can be based on ethnobotanical and chemotaxonomical studies, and screen for their ability to bind to immobilized drug targets and to inhibit their activities. Molecular cloning, gene knockout, protein expression and purification, N-terminal sequencing, and mass spectrometry are the methods of choice to provide homogeneous drug targets for immobilization by optimized chemical reactions. Plant extract preparations, fractionation of promising plant extracts, propagation protocols and definition of in planta studies to maximize product yield of plant species producing active compounds have to be performed to provide a continuing supply of bioactive materials. Chemical characterization of natural compounds, determination of mode of action by kinetics and other spectroscopic methods (MS, X-ray, NMR), as well as in vitro and in vivo biological assays, chemical derivatization, and structure-activity relationships have to be carried out to provide a thorough knowledge on which to base the search for natural compounds or their derivatives with biological activity.

A new species of Symbra (Hymenoptera, Eurytomidae, Heimbrinae) from dry forest in Brazil and new occurrence records for other Heimbrinae

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

PALEOCLIMATIC CONTROLS ON STABLE OXYGEN AND CARBON ISOTOPES IN CALICHE OF THE ABO FORMATION (PERMIAN), SOUTH-CENTRAL NEW-MEXICO, USA

The stable oxygen and carbon isotopic composition of caliche in fluvial and supratidal rocks of the Abo Formation (Permian), south-central New Mexico, is controlled by palecoclimate and depositional environment. Fluvial caliche consists of low-Mg calcite nodules and vertically oriented tubules that display stage II texture. Micrite matrix support, brecciation, ooids/pisoliths, aveolar-septal texture, and peloids are common in the fluvial caliche and, along with red color and slickensides in the host shale, indicate pedogenesis in a well-oxidized vadose zone. In contrast, periodic waterlogging of the supratidal paleosols, probably due to high water table, is indicated by drab colors, carbonaceous flecks, horizontal rhizoliths, and the paucity of vadose textures in the stage II caliche nodules.Stable oxygen isotopes are similar in the fluvial and supratidal caliches and range from 21.6 to 30.5 parts per thousand (SMOW). The data exhibit a crude bimodality and delta-O-18 enrichment with a decrease in age (higher in the section). Consideration of these data in the context of delta-temperature relations suggests that 1) surface waters responsible for caliche formation increased in delta-O-18 (from roughly -8 to + 1 parts per thousand) over the 18 m.y. time interval that separated the lowest stratigraphic nodule horizon from the highest, 2) the increasing delta-O-18 values also reflect a warming trend (approximately 15-degrees to nearly 30-degrees-C) in the mean monthly temperature over this same time period, with perhaps an associated increase in Permian ocean temperatures, and 3) the significant variation in delta-O-18 from oldest to youngest caliche was probably enhanced by the amount effect, such that as the temperature increased, the amount of precipitation decreased, resulting in high delta-O-18 values.Caliches in the Abo are enriched in heavy carbon (-7.2 to -1.5 part per thousand PDB) compared to that of soil carbonate derived exclusively from C3 plants (-12 part per thousand PDB), and the supratidal caliches contain somewhat heavier carbon compared to the fluvial caliche. The delta-C-13 values for both environments increase with a decrease in caliche age. These results indicate that as the temperature increased and rainfall decreased with time, the level of C3 plant productivity apparently declined, allowing a greater influx of atmospheric CO2 into the soil. This can only occur when soil respiration rates are quite low or at very shallow depths (less than 10 cm), or both. Atmospheric CO2 seems to have invaded the supratidal soils to a somewhat greater extent than the fluvial soils.

Alien fishes in lakes of the Doce river basin (Brazil): Range, new occurrences and conservation of native communities

The present study shows the distribution of alien fish species in tropical lakes in the middle Doce river basin, southeastern Brazil, obtained from a rapid assessment program. The causes for their introductions were sport-fishing improvement in some specific lakes and aquaculture in the studied basin. Presently, these species have a wide distribution occurring in 41 of the 54 lakes studied, representing an actual threat to regional native fish community. The natural connection among lakes and streams during the rainy season and the dispersal mediated by local people are the main invasion agents for alien fishes. The success of these invaders is probably due to absence of pre-existing effective competitors or top-predators in the invaded communities. We consider that the eradication of alien fishes by means of the available management tools may be very difficult due to the large number of lakes invaded and to the wide spectrum of lake conditions and resources exploited by these alien species. We recommend the use of environmental education as a tool to stop the human-mediated dispersion of aliens and to improve conservation of native fish community in lakes where these alien species are not present yet. © 2004 Instituto de Ciências Biológicas - UFMG.

New evidence for nucleolar dominance in hybrids of Drosophila arizonae and Drosophila mulleri

Drosophila mulleri (MU) and D. arizonae (AR) are cryptic species of the mulleri complex, mulleri subgroup, repleta group. Earlier cytogenetic studies revealed that these species have different regulatory mechanisms of nucleolar organizing activity. In these species, nucleolar organizing regions are found in both the X chromosome and the microchromosome. In the salivary glands of hybrids between MU females and AR males, there is an interspecific dominance of the regulatory system of the D. arizonae nucleolar organizer involving, in males, amplification and activation of the nucleolar organizer from the microchromosome. The authors who reported these findings obtained hybrids only in that cross-direction. More recently, hybrids in the opposite direction, i.e., between MU males and AR females, have been obtained. The purpose of the present study was to evaluate, in these hybrids, the association of the nucleoli with the chromosomes inherited from parental species in order to cytogenetically confirm the dominance patterns previously described. Our results support the proposed dominance of the AR nucleolar organizer activity over that of MU, regardless of cross-direction. ©FUNPEC-RP.

Molecular hybridization: A useful tool in the design of new drug prototypes

Molecular hybridization is a new concept in drug design and development based on the combination of pharmacophoric moieties of different bioactive substances to produce a new hyrid compound with improved affinity and efficacy, when compared to the parent drugs. Additionally, this strategy can results in compounds presenting modified selectivity profile, different and/or dual modes of action and reduced undesired side effects. So, in this described several example of different strategies for drug design, discovery and pharmacomodulation focused on new innovative hybrid compounds presenting analgesic, anti-inflammatory, platelet anti-aggregating, anti-infections, anticancer, cardio- and neuroactive properties.

Chile: in search of a new export drive

Includes bibliography

Macroeconomic policies in times of crisis: options and perspectives

Includes bibliography

Integrated X-ray crystallography, optical and computational methods in studies of structure and luminescence of new synthesized complexes of lanthanides with ligands derived from 2,6-diformylpyridine

The reaction of 2,6-diformylpyridine-bis(benzoylhydrazone) [dfpbbh] and 2,6-diformylpyridine-bis(4-phenylsemicarbazone) [dfpbpsc] with lanthanides salts yielded the new chelates complexes [Eu(dfpbpsc-H +) 2]NO 3 (1), [Dy(fbhmp) 2][Dy(dfpbbh-2H +) 2]·2EtOH·2H 2O (fbhmp = 2-formylbenzoylhydrazone-6-methoxide-pyridine; Ph = phenyl; Py = pyridine; Et = ethyl) and [Er 2(dfpbbh-2H +) 2(μ-NO 3)(H 2O) 2(OH)]·H 2O. X-ray diffraction analysis was employed for the structural characterization of the three chelate complexes. In the case of complex 1, optical, synthetic and computational methods were also exploited for ground state structure determinations and triplet energy level of the ligand and HOMO-LUMO calculations, as well as for a detailed study of its luminescence properties. © 2010 Elsevier Ltd. All rights reserved.

Integration of the feminine into Latin American culture: in search of a new social paradigm

Includes bibliography

The institutionality of gender in the State: new analytical perspectives

Includes bibliography

Modernization and new services of the Brazilian active control network

The Brazilian Network for Continuous Monitoring of GNSS - RBMC is a national network of continuously operating reference GNSS stations. Since its establishment in December of 1996, it has been playing an essential role for the maintenance and user access of the fundamental geodetic frame in the country. In order to provide better services for RBMC, the Brazilian Institute of Geography and Statistics - IBGE and the National Institute of Colonization and Land Reform - INCRA are both partners involved in the National Geospatial Framework Project - PIGN. This paper provides an overview of the recent modernization phases the RBMC network has undergone highlighting its future steps. These steps involve the installation of new equipment, provide real time data from a group of core stations and compute real-time DGPS corrections, based on CDGPS (The real-time Canada-Wide DGPS Service) (The Real-Time Canada-Wide DGPS Service. http://www.cdgps.com/ 2009a). In addition to this, a post-mission Precise Point Positioning (PPP) service has been established based on the current Geodetic Survey Division of NRCan (CSRS-PPP) service. This service is operational since April 2009 and is in large use in the country. All activities mentioned before are based on a cooperation signed at the end of 2004 with the University of New Brunswick, supported by the Canadian International Development Agency and the Brazilian Cooperation Agency. The Geodetic Survey Division of NRCan is also participating in this modernization effort under the same project. This infrastructure of 66 GNSS stations, the real time, post processing services and the potentiality of providing Wide Area DGPS corrections in the future show that the RBMC system is comparable to those available in USA and Europe. © Springer-Verlag Berlin Heidelberg 2012.