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Biomedical subjects

V Rodrigues

Publications and source records attributed to V Rodrigues.

At least 37 records · Page 2Linked to original sources

Sense organ identity in the Drosophila antenna is specified by the expression of the proneural gene atonal.

We have shown that the basic helix-loop-helix transcription factor Atonal is sufficient for specification of one of the three subsets of olfactory sense organs on the Drosophila antenna. Misexpression of Atonal in all sensory precursors in the antennal disc results in their conversion to coeloconic sensilla. The mechanism by which specific sense organ fate is triggered remains unclear. We have shown that the homeodomain transcription factor Cut which acts in the chordotonal-external sense organ choice does not play a role in olfactory sense organ development. The expression of atonal in specific domains of the antennal disc is regulated by an interplay of the patterning genes, Hedgehog and Wingless, and Drosophila epidermal growth factor receptor pathway.

Animals↗

Interleukin-5 and interleukin-10 are major cytokines in cerebrospinal fluid from patients with active neurocysticercosis.

Neurocysticercosis (NCC) is a common neurological disorder especially in developing countries, caused by infection of the brain with encysted larvae of the tapeworm Taenia solium. Seizures are a common finding associated with this disease. The objective of the present study was to evaluate the correlation between the levels of various cytokines present in the cerebrospinal fluid (CSF) of patients with NCC and the severity of the disease. The levels of the cytokines IL-1ss, TNF-alpha, IL-5, IL-10 and IFN-gamma were determined in the CSF of 22 patients with active NCC, 13 patients with inactive NCC and 15 control subjects. CSF from patients with active NCC presented significantly higher IL-5 levels compared to control subjects. IL-5 and IL-10 levels in CSF from NCC patients with inflammatory CSF were significantly higher than those detected in non-inflammatory CSF. These results show a predominant Th2 lymphocyte activation in human NCC and also indicate the possible use of cytokines in the CSF as a marker for the differential diagnosis between inactive disease and the active form of NCC.

Animals↗

Irregular chiasm-C-roughest, a member of the immunoglobulin superfamily, affects sense organ spacing on the Drosophila antenna by influencing the positioning of founder cells on the disc ectoderm.

We describe a role for Irregular chiasmC-roughest (IrreC-rst), an immunoglobulin (Ig) superfamily member, in patterning sense organs on the Drosophila antenna. IrreC-rst protein is initially expressed homogeneously on apical profiles of ectodermal cells in regions of the antennal disc. During specification of founder cells (FCs), the intracellular protein distribution changes and becomes concentrated in regions where specific intercellular contacts presumably occur. Loss of function mutations as well as misexpression of irreC-rst results in an altered arrangement of FCs within the disc compared to wildtype. Sense organ development occurs normally, although spacing is affected. Unlike its role in interommatidial spacing, irreC-rst does not affect apoptosis during antennal development. We propose that IrreC-rst affects the spatial relationship between sensory and ectodermal cells during FC delamination.

Animals↗

Genetic control of schistosome infections by the SM1 locus of the 5q31-q33 region is linked to differentiation of type 2 helper T lymphocytes.

Human susceptibility to Schistosoma mansoni infections is controlled by the SM1 locus on chromosome 5 in q31-q33. This genetic region encodes cytokines which regulate the development of helper T lymphocytes. In the present work, a clonal analysis of CD4(+) T lymphocytes of homozygous resistant and homozygous susceptible subjects was undertaken to evaluate whether SM1 controls helper T-cell differentiation. Of 121 CD4(+) T-cell clones (TCC) from three susceptible (S) and three resistant (R) subjects, 68 proliferated when stimulated by parasite antigens. Parasite-specific TCC derived from susceptible subjects (33 STCC) produced 10- to 1,000-fold less interleukin-4 and -5 than TCC from resistant subjects (25 RTCC). Clones from both patient groups produced, however, the same amount of gamma interferon. Parasite-specific STCC were type 1 helper (Th1) or Th0/1, whereas RTCC were either Th2 or Th0/2. These results, together with the localization of SM1 in 5q31-q33, indicate that the SM1 locus controls the differentiation of Th2 lymphocytes.

Adolescent↗

Sibling cell fate in the Drosophila adult external sense organ lineage is specified by prospero function, which is regulated by Numb and Notch.

Specification of cell fate in the adult sensory organs is known to be dependent on intrinsic and extrinsic signals. We show that the homeodomain transcription factor Prospero (Pros) acts as an intrinsic signal for the specification of cell fates within the mechanosensory lineage. The sensory organ precursors divide to give rise to two secondary progenitors - PIIa and PIIb. Pros is expressed in PIIb, which gives rise to the neuron and thecogen cells. Loss of Pros function affects the identity of PIIb and neurons fail to differentiate. Pros misexpression is sufficient for the transformation of PIIa to PIIb fate. The expression of Pros in the normal PIIb cell appears to be regulated by Notch signaling.

Animals↗

A glial cell arises from an additional division within the mechanosensory lineage during development of the microchaete on the Drosophila notum.

We have used different cell markers to trace the development of the sensory cells of the thoracic microchaete. Our results dictate a revision in the currently accepted model for cell lineage within the mechanosensory bristle. The sensory organ progenitor divides to form two secondary progenitors: PIIa and PIIb. PIIb divides first to give rise to a tertiary progenitor-PIII and a glial cell. This is followed by division of PIIa to form the shaft and socket cells as described before. PIII expresses high levels of Elav and low levels of Prospero and divides to produce neuron and sheath. Its sibling cell expresses low Elav and high Prospero and is recognized by the glial marker, Repo. This cell migrates away from the other cells of the lineage following differentiation. The proposed modification in lineage has important implications for previous studies on sibling cell fate choice and cell fate specification in sensory systems.

Animals↗

Functional complementation of the malvolio mutation in the taste pathway of Drosophila melanogaster by the human natural resistance-associated macrophage protein 1 (Nramp-1).

The malvolio (mvl) gene of Drosophila melanogaster encodes a protein with a high degree of homology to natural resistance-associated macrophage proteins (Nramps). This family of integral membrane proteins, many of which appear to function as cation transporters, is remarkably conserved in several phylogenetically distinct species. In Drosophila melanogaster, the protein Mvl is expressed in macrophages and in differentiated neurons; loss-of-function mutations lead to defects in gustatory behaviour. The human Nramp-1 protein was expressed in Drosophila melanogaster using the hsp70 promoter. Overexpression in normal animals does not lead to any alterations in their behaviour or physiology. In mutants, however, ubiquitous expression of human Nramp-1 can totally rescue the taste defect. This finding that Nramp-1 can complement the taste defect in mvl mutants provides a potent means of exploiting behavioural genetics to dissect the function of Nramp-1 and to identify other molecules involved with this transport system.

Animals↗

Patterning an epidermal field: Drosophila lozenge, a member of the AML-1/Runt family of transcription factors, specifies olfactory sense organ type in a dose-dependent manner.

Sense organ development in the Drosophila antenna is initiated by the selection of a founder cell from an epidermal field. This cell is believed to recruit neighbours to form a cluster of cells which then divides to form a mature sense organ. In most systems so far studied, sense organ type appears to be specified by the identity of proneural genes involved in the selection of precursors. The regulation of proneural gene expression is, in turn, controlled by the prepatterning genes. In the antenna, the only known proneural function is that of atonal, a gene that is involved in founder cell choice in the sensilla coeloconica, and no prepatterning gene function has yet been demonstrated. In this study, we show that Lozenge, a protein which possesses a DNA binding domain similar to that of the Acute myeloid leukemia-1/Runt transcription factors, functions in a dose-dependent manner to specify the fate of the other two types of sense organs in the antenna: the sensilla trichoidea and the sensilla basiconica. Our results suggest that Lozenge may act on the epidermal field, resulting in founder cells acquiring specific cell fates that lead to the development of an appropriate type of sense organ.

Animals↗

High prevalence of GB-C/hepatitis G virus in a Brazilian population with helminth infection.

A study of GB-C virus/Hepatitis G virus (GBV-C/ HGV) infection was carried out in a rural population of Northeastern Brazil, in which the prevalence of schistosomiasis is 80-90%. Despite the absence of parenteral risk exposure, the prevalence of GBV-C/HGV markers of infection was found to be unusually increased: viremia, 16.4%; specific antibody, 18.3%. It is therefore suspected that helminth infection influenced the immune response to GBV-C/HGV infection by shifting the balance of cytokine responses from Th1 to Th2, resulting in a delayed viral clearance. Phylogenetic analysis of viral isolates did not provide evidence for high rates of sexual or mother-to-infant viral transmission. The study revealed that viral strains belonged to types 1 and 2 only (predominant in Africa and Europe, respectively), suggesting that GBV-C/HGV was introduced into the New World by white conquerors and black slaves since the 16th century.

5' Untranslated Regions↗

Transforming growth factor beta and immunosuppression in experimental visceral leishmaniasis.

Hamsters infected with Leishmania donovani develop a disease similar to human kala-azar. They present hypergammaglobulinemia, and their T cells do not respond to parasite antigens. This unresponsiveness has been primarily ascribed to defects in antigen-presenting cells (APCs), because these cells are unable to stimulate proliferation of parasite-specific T cells from immunized animals. In this study, we show that APCs (adherent spleen cells) from L. donovani-infected hamsters produce high levels of the inhibitory cytokine transforming growth factor beta (TGF-beta). Immunohistochemical studies with an anti-TGF-beta monoclonal antibody (MAb) showed that this cytokine is abundantly produced in vivo by the spleen cells of infected animals. In addition, high levels of TGF-beta are produced in vitro by infected hamster cells, either spontaneously or after stimulation with parasite antigen or lipopolysaccharide. Furthermore, in vivo-infected adherent cells obtained from spleens of L. donovani-infected hamsters caused profound inhibition of the in vitro antigen-induced proliferative response of lymph node cells from hamsters immunized with leishmanial antigens. Moreover, this inhibition was totally abrogated by the anti-TGF-beta MAb. These results suggest that the immunosuppression observed in visceral leishmaniasis is, at least in part, due to the abundant production of TGF-beta during the course of the infection.

Animals↗

The human transcription enhancer factor-1, TEF-1, can substitute for Drosophila scalloped during wingblade development.

The human transcription enhancer factor-1 (TEF-1) belongs to a family of evolutionarily conserved proteins that have a DNA binding TEA domain. TEF-1 shares a 98% homology with Drosophila scalloped (sd) in the DNA binding domain and a 50% similarity in the activation domain. We have expressed human TEF-1 in Drosophila under the hsp-70 promoter and find that it can substitute for Sd function. The transformants rescue the wingblade defects as well as the lethality of loss-of-function alleles. Observation of reporter activity in the imaginal wing discs of the enhancer-trap alleles suggests that TEF-1 is capable of promoting sd gene regulation. The functional capability of the TEF-1 product was assessed by comparing the extent of rescue by heat shock (hs)-TEF-1 with that of hs-sd. The finding that TEF-1 can function in vivo during wingblade development offers a potent genetic system for the analysis of its function and in the identification of the molecular partners of TEF-1.

Amino Acid Sequence↗

Atonal is a proneural gene for a subset of olfactory sense organs in Drosophila.

BACKGROUND: The antenna of the adult fruit fly, Drosophila melanogaster, is covered with three morphologically distinct types of olfactory sense organs. In addition, mechano- and hygro-sensitive receptors are also present on its surface. While much has been learnt about the development of peripheral nervous system in Drosophila, the mechanisms underlying the development of olfactory sensilla are just beginning to be unraveled. The antennal sense organs have several properties that make them distinct from other sense organs. While each sensillum type is arranged in a well-defined region of the antenna, the position of an individual sensillum is not fixed. The development of these sense organs appears to combine an initial step of cell recruitment, as in photoreceptors, followed by cell lineage mechanisms, as in the development of other external sense organs. The earliest step in development, the selection of a sensory organ precursor, involves the interaction of proneural and neurogenic genes. The proneural gene for the antennal sense organs has been elusive so far. RESULTS: We show that the basic helix-loop-helix (bHLH) transcription factor encoded by atonal (ato) is a proneural gene for one morphological type of olfactory sensilla on the antenna and for all the olfactory sensilla on the maxillary palp. Loss of function and overexpression experiments together reveal that ato is both necessary and sufficient to specify these sensilla. Immunohistochemical experiments show that Ato expresses in a dynamic pattern in the developing antennal disc. CONCLUSIONS: Our results demonstrate that ato acts solely in the specification of antennal sensilla coeloconica. This along with our previous observation that the AS-C genes do not function in antenna allows us to suggest that other proneural genes must operate in the specification of sensilla basiconica and trichoidea. Our experiment involving overexpression of extramacrochaetae, a negative regulator of bHLH encoding genes, results in a significant reduction in the number of all three types of antennal sensilla. This suggests that the unidentified proneural gene(s) possibly encode bHLH factors.

Animals↗

Development of the Drosophila olfactory sense organs utilizes cell-cell interactions as well as lineage.

We have examined the mechanisms underlying the development of the olfactory sense organs on the third segment of the antenna of Drosophila. Our studies suggest that a novel developmental strategy is employed. Specification of the founder or precursor cell is not governed by the genes of the achaete-scute complex. Another basic helix-loop-helix encoding gene, atonal, is essential for determination of only a subset of the sensilla types--the sensilla coeloconica. Therefore, we predict the existence of additional proneural genes for the selection of sensilla trichoidea and sensilla basiconica. The choice of a founder cell from the presumed proneural domain is regulated by Notch activity. Soon after delamination of the founder cell, two to three additional neighboring cells also take on a sensory fate and these cells together form a presensillum cluster. The selection of neighbors does not occur when endocytosis is blocked using a temperature sensitive allele of shibire, thus suggesting that cell-cell communication is required for this step. The cells of the cluster divide once before terminal differentiation which is influenced by Notch activity. The final cell number within each sensillum is controlled by programmed cell death.

Animals↗

Mutations in masquerade, a novel serine-protease-like molecule, affect axonal guidance and taste behavior in Drosophila.

The masquerade (mas) locus encodes an extracellular molecule with a striking similarity to serine proteases. The serine residue, which is essential for enzymatic activity, has been substituted by glycine, suggesting that MAS could serve to antagonize serine protease activity [Murugasu-Oei et al. (1995), Genes Dev. 9, 139-154]. We describe the expression pattern of mas mRNA and protein in the developing embryonic, larval and pupal nervous system and in the epidermis. Total loss of mas function is lethal and results in aberrations in the embryonic central and peripheral nervous systems, consistent with a role in axonal guidance. The possibility that the observed deficits in taste behavior, exhibited by animals with partial loss of mas function, are a result of defects in the adult brain are discussed.

Animals↗

Segregation analysis indicates a major gene in the control of interleukine-5 production in humans infected with Schistosoma mansoni.

The interleukine-5 (IL-5) is a hormone of the immune system that is the main regulator of eosinopoiesis, eosinophil maturation and activation, and immunoglobulin A production. Thus, IL-5 contributes in several ways to human immune defenses against various pathogens, including helminths and infectious agents of the digestive and respiratory tracts. On the other hand, the increase in eosinophil number and the activation of these cells, which both have been related to elevated IL-5 production, are the cause of severe pathological disorders, as in asthma or hypereosinophilic syndromes. Although the immunological pathways leading to IL-5 synthesis have been identified, the reasons for the large variability observed in IL-5 production among subjects exposed to comparable antigenic stimulation are unknown. To investigate the role of genetic factors in this variability, we conducted a segregation analysis in a Brazilian population infected by the helminth parasite Schistosoma mansoni. The analysis was performed on IL-5 levels produced by blood mononuclear cells of these subjects after in vitro restimulation with either parasite extracts (IL-5/schistosomula sonicates [SS] phenotype) or a T-lymphocyte mitogen (IL-5/phytohemagglutin [PHA]). The results provide clear evidence for the segregation of a codominant major gene controlling IL-5/SS and IL-5/PHA production and accounting for 70% and 73% of the phenotypic variance, respectively; the frequency of the allele predisposing to low IL-5 production was approximately .22 for both phenotypes. No significant relationship was found between these genes and the gene controlling infection intensities by S. mansoni detected in a previous study. Linkage studies are ongoing to locate those genes that would help to characterize the genetic factors involved in pathological conditions such as severe helminth infections and allergic diseases.

Adolescent↗

Nramp defines a family of membrane proteins.

Nramp (natural resistance-associated macrophage protein) is a newly identified family of integral membrane proteins whose biochemical function is unknown. We report on the identification of Nramp homologs from the fly Drosophila melanogaster, the plant Oryza sativa, and the yeast Saccharomyces cerevisiae. Optimal alignment of protein sequences required insertion of very few gaps and revealed remarkable sequence identity of 28% (yeast), 40% (plant), and 55% (fly) with the mammalian proteins (46%, 58%, and 73% similarity), as well as a common predicted transmembrane topology. This family is defined by a highly conserved hydrophobic core encoding 10 transmembrane segments. Other features of this hydrophobic core include several invariant charged residues, helical periodicity of sequence conservation suggesting conserved and nonconserved faces for several transmembrane helices, a consensus transport signature on the intracytoplasmic face of the membrane, and structural determinants previously described in ion channels. These characteristics suggest that the Nramp polypeptides form part of a group of transporters or channels that act on as yet unidentified substrates.

Amino Acid Sequence↗