A century of research: what have we learned about the interaction of Trypanosoma cruzi with host cells?

Since the discovery of Trypanosoma cruzi and the brilliant description of the then-referred to "new tripanosomiasis" by Carlos Chagas 100 years ago, a great deal of scientific effort and curiosity has been devoted to understanding how this parasite invades and colonises mammalian host cells. This is a key step in the survival of the parasite within the vertebrate host, and although much has been learned over this century, differences in strains or isolates used by different laboratories may have led to conclusions that are not as universal as originally interpreted. Molecular genotyping of the CL-Brener clone confirmed a genetic heterogeneity in the parasite that had been detected previously by other techniques, including zymodeme or schizodeme (kDNA) analysis. T. cruzi can be grouped into at least two major phylogenetic lineages: T. cruzi I, mostly associated with the sylvatic cycle and T. cruzi II, linked to human disease; however, a third lineage, T. cruziIII, has also been proposed. Hybrid isolates, such as the CL-Brener clone, which was chosen for sequencing the genome of the parasite (Elias et al. 2005, El Sayed et al. 2005a), have also been identified. The parasite must be able to invade cells in the mammalian host, and many studies have implicated the flagellated trypomastigotes as the main actor in this process. Several surface components of parasites and some of the host cell receptors with which they interact have been described. Herein, we have attempted to identify milestones in the history of understanding T. cruzi- host cell interactions. Different infective forms of T. cruzi have displayed unexpected requirements for the parasite to attach to the host cell, enter it, and translocate between the parasitophorous vacuole to its final cytoplasmic destination. It is noteworthy that some of the mechanisms originally proposed to be broad in function turned out not to be universal, and multiple interactions involving different repertoires of molecules seem to act in concert to give rise to a rather complex interplay of signalling cascades involving both parasite and cellular components.

Experimental chemotherapy for Chagas disease: 15 years of research contributions from in vivo and in vitro studies

Chagas disease, which is caused by the intracellular parasite Trypanosoma cruzi, is a neglected illness with 12-14 million reported cases in endemic geographic regions of Latin America. While the disease still represents an important public health problem in these affected areas, the available therapy, which was introduced more than four decades ago, is far from ideal due to its substantial toxicity, its limited effects on different parasite stocks, and its poor activity during the chronic phase of the disease. For the past 15 years, our group, in collaboration with research groups focused on medicinal chemistry, has been working on experimental chemotherapies for Chagas disease, investigating the biological activity, toxicity, selectivity and cellular targets of different classes of compounds on T. cruzi. In this report, we present an overview of these in vitro and in vivo studies, focusing on the most promising classes of compounds with the aim of contributing to the current knowledge of the treatment of Chagas disease and aiding in the development of a new arsenal of candidates with anti-T. cruzi efficacy.

Off-label uses of anti-TNF therapy in three frequent disorders: Behçet's disease, sarcoidosis, and noninfectious uveitis.

Tumoral necrosis factor α plays a central role in both the inflammatory response and that of the immune system. Thus, its blockade with the so-called anti-TNF agents (infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab) has turned into the most important tool in the management of a variety of disorders, such as rheumatoid arthritis, spondyloarthropatties, inflammatory bowel disease, and psoriasis. Nonetheless, theoretically, some other autoimmune disorders may benefit from these agents. Our aim is to review these off-label uses of anti-TNF blockers in three common conditions: Behçet's disease, sarcoidosis, and noninfectious uveitis. Due to the insufficient number of adequate clinical trials and consequently to their lower prevalence compared to other immune disorders, this review is mainly based on case reports and case series.

Body composition: overview of methods and future directions of research.

A short overview is given on the most important analytical body composition methods. Principles of the methods and advantages and limitations of the methods are discussed also in relation to other fields of research such as energy metabolism. Attention is given to some new developments in body composition research such as chemical multiple-compartment models, computerized tomography or nuclear magnetic resonance imaging (tissue level), and multifrequency bioelectrical impedance. Possible future directions of body composition research in the light of these new developments are discussed.

Immunosuppresseurs: usages systémiques et neurologiques [Systemic and neurological uses of immunosuppressive agents].

Involvement of the central or peripheral nervous system, frequently present in systemic inflammatory immune disorders, has to be considered a severe threat and requires aggressive immunosuppressive treatment to achieve rapid remission. This is usually obtained with high-dose systemic corticosteroids combined with cyclophosphamide. Once remission is obtained, immunosuppressive agents with a more favorable safety profile are needed to exert a corticosteroid-sparing effect and minimize adverse events. New therapeutic approaches are currently developed to treat autoimmune diseases, mostly linked to the definition of new indications for biological agents such as TNF-alpha antagonists and rituximab.

The dynamics of research networks in Brite-Euram

Network formation within the BRITE--EURAM program is investigated.Wedescribe the role of the hub of the network, which is defined as the setofmain contractors that account for most of the participations. We studytheeffects that the conflict of objectives within European research fundingbetween pre-competitive research vs. European cohesion has on theformationof networks and on the relationship between different partnersof the network. \\A panel data set is constructed including the second and third frameworkof theBrite--Euram program. A model of joint production of research results isusedto test for changes in the behavior of partners within the twoframeworks. \\The main findings are that participations are very concentrated, that isasmall group of institutions account for most of the participations, butgoingfrom the second to the third framework the presence of subcontractorsand singleparticipants increases substantially. This result is reinforced by the factthat main contractors receive smaller spill-ins within networks, butspill-insincrease from the second to the third framework.

Influence activity and the organization of research and development

The organizational design of research and development conditions theincentives of the researchers of the research project. In particular,the organizational form determines the allocation of effort of theresearcher between time spent on research and time spent lobbying management. Researchers prefer to spend their time on research. However,the researchers only get utility from performing research if theproject is approved for its full duration. Spending time lobbyingmanagement for the continuation of the researcher s project increasesthe probability that the management observes a favorable signal aboutthe project. Organizing a research joint venture increases theflexibility of the organizational form with respect to the continuationdecision. For low correlation between the signals of the partners aboutthe expected profitability of the project, we find that the organizationof a research joint venture reduces influence activity by the researchersand increases expected profits of the partners. For high correlationbetween the signals, internal research projects lower influence activityby the researchers. We try to relate the correlation of the partnerssignals to the characteristics of basic research versus more appliedresearch projects, and find that the model is consistent with theobservation that research joint ventures seem involved in more basicresearch projects compared to internal R&D departments, whichconcentrate on more applied research.

Updated list of ant species (Hymenoptera, Formicidae) recorded in Santa Catarina State, southern Brazil, with a discussion of research advances and priorities

Updated list of ant species (Hymenoptera, Formicidae) recorded in Santa Catarina State, southern Brazil, with a discussion of research advances and priorities. A first working list of ant species registered in Santa Catarina State, southern Brazil was published recently. Since then, many studies with ants have been conducted in the state. With data compiled from published studies and collections in various regions of the state, we present here an updated list of 366 species (and 17 subspecies) in 70 ant genera in Santa Catarina, along with their geographical distribution in the seven state mesoregions. Two hundred and seven species are recorded in the Oeste mesoregion, followed by Vale do Itajaí (175), Grande Florianópolis (150), Norte (60), Sul (41), Meio Oeste (23) and Planalto Serrano (12). The increase in the number of records since 1999 results from the use of recently adopted sampling methods and techniques in regions and ecosystems poorly known before, and from the availability of new tools for the identification of ants. Our study highlights the Meio Oeste, Planalto Serrano, Sul and Norte mesoregions, as well as the deciduous forest, mangrove, grassland and coastal sand dune ecosystems as priority study areas in order to attain a more complete knowledge of the ant fauna in Santa Catarina State.

Uses of also in oral semi-informal German

In recent grammars and dictionaries also (`therefore, so, well¿) continues to be preferably presented as an adverb with a conclusive-consecutive connective function that essentially corresponds to its use in formal written German. Its function as a modal particle is documented, however, since the beginnings of what is known as Partikelforschung, though not all its uses have been systematically investigated contrasting oral and written German, either in mode or concept. In this article we analyse the uses of also in semi-informal oral interactions on the basis of empirical data (from a subsample of the VARCOM corpus). Specifically, we will analyse the presence and frequency of also at the beginning of a sentence or sequence, the functions it serves as a logical-semantic connector or discourse and interaction marker and the interrelations between these functions, in order to contrast these results with the description of also provided by current reference works.