Allelic Diversity at the Merozoite Surface Protein-1 (MSP-1) Locus in Natural Plasmodium falciparum Populations: a Brief Overview

The merozoite surface protein-1 (MSP-1) locus of Plasmodium falciparum codes for a major asexual blood-stage antigen currently proposed as a major malaria vaccine candidate. The protein, however, shows extensive polymorphism, which may compromise its use in sub-unit vaccines. Here we compare the patterns of allelic diversity at the MSP-1 locus in wild isolates from three epidemiologically distinct malaria-endemic areas: the hypoendemic southwestern Brazilian Amazon (n = 54), the mesoendemic southern Vietnam (n = 238) and the holoendemic northern Tanzania (n = 79). Fragments of the variable blocks 2, 4a, 4b and 6 or 10 of this single-copy gene were amplified by the polymerase chain reaction, and 24 MSP-1 gene types were defined as unique combinations of allelic types in each variable block. Ten different MSP-1 types were identified in Brazil, 23 in Vietnam and 13 in Tanzania. The proportion of genetically mixed infections (isolates with parasites carrying more than one MSP-1 version) ranged from 39% in Brazil to 44% in Vietnam and 60% in Tanzania. The vast majority (90%) of the typed parasite populations from Brazil and Tanzania belonged to the same seven most frequent MSP-1 gene types. In contrast, these seven gene types corresponded to only 61% of the typed parasite populations from Vietnam. Non-random associations were found between allelic types in blocks 4a and 6 among Vietnamese isolates, the same pattern being observed in independent studies performed in 1994, 1995 and 1996. These results suggest that MSP-1 is under selective pressure in the local parasite population. Nevertheless, the finding that similar MSP-1 type frequencies were found in 1994 and 1996 argues against the prominence of short-term frequency-dependent immune selection of MSP-1 polymorphisms. Non-random associations between MSP-1 allelic types, however, were not detected among isolates from Brazil and Tanzania. A preliminary analysis of the distribution of MSP-1 gene types per host among isolates from Tanzania, but not among those from Brazil and Vietnam, shows significant deviation from that expected under the null hypothesis of independent distribution of parasites carrying different gene types in the human hosts. Some epidemiological consequences of these findings are discussed

Photoaffinity labeling of the T cell receptor on living cytotoxic T lymphocytes.

Using a direct binding assay based on photoaffinity labeling, we have studied the interaction of an antigenic peptide with MHC class I molecules and the TCR on living cells. Two photoreactive derivatives of the H-2Kd (Kd) restricted Plasmodium berghei circumsporozoite (PbCS) peptide 253-260 (YIPSAEKI) were used. The first derivative contained an N-terminal photoreactive iodo, 4-azido salicyloyl (IASA) group and biotin on the TCR contact residue Lys259 [IASA-YIPSAEK(biotin)I]. As previously described, this derivative selectively bound to and labeled the Kd molecule. The second photoreactive compound, the isomeric biotin-YIPSAEK(IASA)I, also efficiently bound to the Kd molecule, but failed to label this protein. A CTL clone derived from a mouse immunized with this derivative recognized this conjugate but not the parental P. berghei circumsporozoite peptide or the [IASA-YIPSAEK-(biotin)I] derivative in an Kd-restricted manner. Incubation of the cloned CTL cells with biotin-YIPSAEK(IASA)I, but not its isomer, followed by UV irradiation resulted in photoaffinity labeling of the TCR-alpha chain that was dependent on the conjugate binding to the Kd molecule. The TCR labeling was partially inhibited by anti-LFA 1 and anti-ICAM1 mAb, but was increased by addition of beta 2m or soluble KdQ10. The exquisite labeling selectivity of the two photoprobes opens a new, direct approach to the molecular analysis of antigen presentation and recognition by living CTL.

Molecular identification of similar species of the genus Biomphalaria (Mollusca: Planorbidae) determined by a polymerase chain reaction-restriction fragment length polymorphism

The freshwater snails Biomphalaria straminea, B. intermedia, B. kuhniana and B. peregrina, are morphologically similar; based on this similarity the first three species were therefore grouped in the complex B. straminea. The morphological identification of these species is based on characters such as vaginal wrinkling, relation between prepuce: penial sheath:deferens vas and number of muscle layers in the penis wall. In this study the polymerase chain reaction restriction fragment length polymorphism technique was used for molecular identification of these molluscs. This technique is based on the amplification of the internal transcribed spacer regions ITS1 e ITS2 of the ribosomal RNA gene and subsequent digestion of these fragments by restriction enzymes. Six enzymes were tested: Dde I, Mnl I, Hae III, Rsa I, Hpa II e Alu I. The restriction patterns obtained with DdeI presented the best profile for separation of the four species of Biomphalaria. The profiles obtained with all the enzymes were used to estimate the genetic distances among the species through analysis of common banding patterns.

Ocular distribution, spectrum of activity, and in vivo viral neutralization of a fully humanized anti-herpes simplex virus IgG Fab fragment following topical application.

Herpes simplex ocular infection is a major cause of corneal blindness. Local antiviral treatments exist but are associated with corneal toxicity, and resistance has become an issue. We evaluated the biodistribution and efficacy of a humanized anti-herpes simplex virus (anti-HSV) IgG FAb fragment (AC-8; 53 kDa) following repeated topical administration. AC-8 was found in the corneal epithelium, anterior stroma, subepithelial stromal cells, and retinal glial cells, with preferential entry through the ocular limbus. AC-8 was active against 13 different strains of HSV-1, with 50% and 90% mean effective concentrations (MEC(50) and MEC(90), respectively) ranging from 0.03 to 0.13 μg/ml, indicating broad-spectrum activity. The in vivo efficacy of AC-8 was evaluated in a mouse model of herpes-induced ocular disease. Treatment with low-dose AC-8 (1 mg/ml) slightly reduced the ocular disease scores. A greater reduction of the disease scores was observed in the 10-mg/ml AC-8-treated group, but not as much as with trifluridine (TFT). AC-8 treatment reduced viral titers but less than trifluridine. AC-8 did not display any toxicity to the cornea or other structures in the eye. In summary, topical instillation of an anti-HSV FAb can be used on both intact and ulcerated corneas. It is well tolerated and does not alter reepithelialization. Further studies to improve the antiviral effect are needed for AC-8 to be considered for therapeutic use.

Comparative Analysis by Polymerase Chain Reaction Amplified Minicircles of Kinetoplast DNA of a Stable Strain of Trypanosoma cruzi from S��o Felipe, Bahia, its Clones and Subclones: Possibility of Predominance of a Principal Clone in this Area

Molecular characterization of one stable strain of Trypanosoma cruzi, the 21 SF, representative of the pattern of strains isolated from the endemic area of S��o Felipe, State of Bahia, Brazil, maintained for 15 years in laboratory by serial passages in mice and classified as biodeme Type II and zymodeme 2 has been investigated. The kinetoplast DNA (kDNA) of parental strain, 5 clones and 14 subclones were analyzed. Schizodeme was established by comparative study of the fragments obtained from digestion of the 330-bp fragments amplified by polymerase chain reaction (PCR) from the variable regions of the minicicles, and digested by restriction endonucleases Rsa I and Hinf I. Our results show a high percentual of similarity between the restriction fragment lenght polymorphism (RFLP) for the parental strain and its clones and among these individual clones and their subclones at a level of 80 to 100%.This homology indicates a predominance of the same "principal clone" in the 21SF strain and confirms the homogeneity previously observed at biological and isozymic analysis. These results suggest the possibility that the T. cruzi strains with similar biological and isoenzymic patterns, circulating in this endemic area, are representative of one dominant clone. The presence of "principal clones" could be responsible for a predominant tropism of the parasites for specific organs and tissues and this could contribute to the pattern of clinico-pathological manifestations of Chagas's disease in one geographical area.

Tratamiento de la litiasis urinaria en pacientes pedi��tricos mediante litotricia extracorp��rea

La patologia liti��sica urinaria infantil afecta a un 5 ���10% d���aquesta poblaci��. El tractament de la litiasi en edat infantil inclou desde tractament m��nimament invasiu com la litotr��psia extracorp��ria per ones de xoc (LEOX) a tractament quir��rgic (endourol��gic o obert). Es va realitzar un estudi retrospectiu amb un total de 82 pacients en edat pedi��trica amb patologia liti��sica tractada mitjan��ant litotr��psia per ones de xoc. Es van analitzar de forma descriptiva els resultats sobre aquest grup de pacients. Dels 82 pacients estudiats, el 54% van ser nens i el 46% nenes, amb una edat mitjana de 8.6 anys. Es va analitzar la resposta a litotr��psia segons tamany i grups d���edat per estrats observant que no hi havia difer��ncies significatives respecte al n��mero de sessions necess��ries por grups d���edat per�� amb tend��ncia a la significaci�� en el grup de menor edat (de 0 a 3 anys). Tanmateix, aquest grup de pacients presentaven comparativamente litiasi de major tamany que el grup de m��s edat (de 16 a 20 anys). Les complicacions es van presentar en nom��s 10 pacients (8%) considerant com a tals la pres��ncia de fragments obstructius, dolor lumbar o carrer liti��sic. Despr��s d���analitzar els resultats es pot concloure que la litotr��cia per ones de xoc constitueix un tractament efica�� pel tractament de la litiasi independentment de la seva localitzaci��, no trobant difer��ncies per grups d���edat i aconseguint bones tases de ���stone free��� incl��s per litiasi coraliformes en pacients en edat infantil i amb escasses complicacions.

Fragment N2, a caspase-3-generated RasGAP fragment, inhibits breast cancer metastatic progression

The p120 RasGAP protein negatively regulates Ras via its GAP domain. RasGAP carries several other domains that modulate several signaling molecules such as Rho. RasGAP is also a caspase-3 substrate. One of the caspase-3-generated RasGAP fragments, corresponding to amino acids 158-455 and called fragment N2, was previously reported to specifically sensitize cancer cells to death induced by various anticancer agents. Here, we show that fragment N2 inhibits migration in vitro and that it impairs metastatic progression of breast cancer to the lung. Hence, stress-activated caspase-3 might contribute to the suppression of metastasis through the generation of fragment N2. These results indicate that the activity borne by fragment N2 has a potential therapeutic relevance to counteract the metastatic process.

Mitochondrial DNA variation of Triatoma infestans populations and its implication on the specific status of T. melanosoma

DNA sequence comparison of 412 base-pairs fragments of the mitochondrial cytochrome B gene was used to infer the genetic structure of nine geographical Triatoma infestans populations and their phylogenetic relationship with T. melanosoma and T. brasiliensis. T. infestans and T. melanosoma were compared by morphometry, allozyme and cytogenetic analyses, as well as subjected to reciprocal crosses, in order to clarify the taxonomic status of the latter. No differences were found to distinguish the two species and the crosses between them yielded progeny. T. infestans populations presented four haplotypes that could be separated in two clusters: one formed by the samples from Bolivia (Andes and Chaco) and the other formed by samples from Argentina and Brazil. Silvatic and domestic T. infestans populations from Bolivia (Andes) were genetically identical.

Amino acid sequences of proteins from Leptospira serovar pomona

This report describes a partial amino acid sequences from three putative outer envelope proteins from Leptospira serovar pomona. In order to obtain internal fragments for protein sequencing, enzymatic and chemical digestion was performed. The enzyme clostripain was used to digest the proteins 32 and 45 kDa. In situ digestion of 40 kDa molecular weight protein was accomplished using cyanogen bromide. The 32 kDa protein generated two fragments, one of 21 kDa and another of 10 kDa that yielded five residues. A fragment of 24 kDa that yielded nineteen residues of amino acids was obtained from 45 kDa protein. A fragment with a molecular weight of 20 kDa, yielding a twenty amino acids sequence from the 40 kDa protein.

Proteolytic processing of the Cyt1Ab1 toxin produced by Bacillus thuringiensis subsp. medellin

Bacillus thuringiensis produces d-endotoxins that require proteolytic processing to become active. The activation of the B. thuringiensis subsp. medellin 28 kDa (Cyt1Ab1) cytolytic toxin by trypsin, chymotrypsin and gut extract from Culex quinquefasciatus larvae was analyzed. The Cyt1Ab1 toxin of B. thuringiensis subsp. medellin was processed by all proteases tested to fragments between 23 and 25 kDa, while processing of the Cyt1Aa1 toxin produce fragments between 22.5 and 24.5 kDa. The Cyt1Ab1 toxin was preferentially processed at the alkaline pH of 12. The in vitro proteolytic processing of the Cyt1Ab1 toxin by C. quinquefasciatus larvae midgut extract showed a 25 kDa fragment; a similar result was observed when the activation was performed in the in vivo experiments. The solubilized Cyt1Ab1 toxin and the protease resistant cores generated by in vitro processing showed hemolytic activity but not mosquitocidal activity. Amino terminal sequence of the C. quinquefasciatus gut extract resistant fragment indicated that the cutting site was located between Lys31 and Asp32, with a sequence DDPNEKNNHNS; while for the trypsin-resistant fragment the cutting site was determined between Leu29 and Arg30, and for the chymotrypsin-resistant fragment between Arg30 and Lys31.

Role of BRCA2 in control of the RAD51 recombination and DNA repair protein.

Individuals carrying BRCA2 mutations are predisposed to breast and ovarian cancers. Here, we show that BRCA2 plays a dual role in regulating the actions of RAD51, a protein essential for homologous recombination and DNA repair. First, interactions between RAD51 and the BRC3 or BRC4 regions of BRCA2 block nucleoprotein filament formation by RAD51. Alterations to the BRC3 region that mimic cancer-associated BRCA2 mutations fail to exhibit this effect. Second, transport of RAD51 to the nucleus is defective in cells carrying a cancer-associated BRCA2 truncation. Thus, BRCA2 regulates both the intracellular localization and DNA binding ability of RAD51. Loss of these controls following BRCA2 inactivation may be a key event leading to genomic instability and tumorigenesis.

CD8 beta increases CD8 coreceptor function and participation in TCR-ligand binding.

To study the role of CD8 beta in T cell function, we derived a CD8 alpha/beta-(CD8-/-) T cell hybridoma of the H-2Kd-restricted N9 cytotoxic T lymphocyte clone specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS 252-260. This hybridoma was transfected either with CD8 alpha alone or together with CD8 beta. All three hybridomas released interleukin 2 upon incubation with L cells expressing Kd-peptide derivative complexes, though CD8 alpha/beta cells did so more efficiently than CD8 alpha/alpha and especially CD8-/- cells. More strikingly, only CD8 alpha/beta cells were able to recognize a weak agonist peptide derivative variant. This recognition was abolished by Fab' fragments of the anti-Kd alpha 3 monoclonal antibody SF1-1.1.1 or substitution of Kd D-227 with K, both conditions known to impair CD8 coreceptor function. T cell receptor (TCR) photoaffinity labeling indicated that TCR-ligand binding on CD8 alpha/beta cells was approximately 5- and 20-fold more avid than on CD8 alpha/a and CD8-/- cells, respectively. SF1-1.1.1 Fab' or Kd mutation D227K reduced the TCR photoaffinity labeling on CD8 alpha/beta cells to approximately the same low levels observed on CD8-/- cells. These results indicate that CD8 alpha/beta is a more efficient coreceptor than CD8alpha/alpha, because it more avidly strengthens TCR-ligand binding.

RasGAP-derived fragment N increases the resistance of beta cells towards apoptosis in NOD mice and delays the progression from mild to overt diabetes.

The caspase-3-generated RasGAP N-terminal fragment (fragment N) inhibits apoptosis in a Ras-PI3K-Akt-dependent manner. Fragment N protects various cell types, including insulin-secreting cells, against different types of stresses. Whether fragment N exerts a protective role during the development of type 1 diabetes is however not known. Non-obese diabetic (NOD) mice represent a well-known model for spontaneous development of type 1 diabetes that shares similarities with the diseases encountered in humans. To assess the role of fragment N in type 1 diabetes development, a transgene encoding fragment N under the control of the rat insulin promoter (RIP) was back-crossed into the NOD background creating the NOD-RIPN strain. Despite a mosaic expression of fragment N in the beta cell population of NOD-RIPN mice, islets isolated from these mice were more resistant to apoptosis than control NOD islets. Islet lymphocytic infiltration and occurrence of a mild increase in glycemia developed with the same kinetics in both strains. However, the period of time separating the mild increase in glycemia and overt diabetes was significantly longer in NOD-RIPN mice compared to the control NOD mice. There was also a significant decrease in the number of apoptotic beta cells in situ at 16 weeks of age in the NOD-RIPN mice. Fragment N exerts therefore a protective effect on beta cells within the pro-diabetogenic NOD background and this prevents a fast progression from mild to overt diabetes.

Immunological and protective properties of novel malaria blood stage peptide antigens

ABSTRACT Malaria is a major worldwide public health problem, with transmission occurring throughout Africa, Asia, Oceania and Latin America. Over two billion people live in malarious areas of the world and it is estimated that 300-500 million cases and 1.5-2.7 million deaths occur annually. The increase in multi-drug resistant parasites and insecticide-resistant vectors has made the development of malaria vaccine a public health priority. The published genome offers tremendous opportunity for the identification of new antigens that can befast-tracked for vaccine development. We identified potential protein antigens present on the surface of asexual malaria blood stages through bioinformatics and published transcriptome and proteorn�� analysis. Amongst the proteins identified, we selected those that contain predicted a-helical coiled-coil regions, which are generally short and structurally stable as isolated fragments. Peptides were synthesized and used to immunize mice. Most peptides tested were immunogenic as demonstrated in ELISA assays, and induced antibodies of varying titres. In immunofluorescence assays, anti-sera from immunized mice reacted with native proteins expressed at different intraerythrocytic developmental stages of the parasite's cycle. In parallel in vitro ADCI functional studies, human antibodies affinity purified on some of these peptides inhibited parasite growth in association with monocytes in magnitudes similar to that seen in semiimmune African adults. Siudies using human immune sera taken from different malaria endemic regions, demonstrated that majority of peptides were recognized at high prevalence. 73 peptides were next tested in longitudinal studies in two cohorts separated in space and time in coastal Kenya. In these longitudinal analyses, antibody responses to peptides were sequentially examined in two cohorts of children at risk of clinical malaria in order to characterize the level of peptide recognition by age, and the role of anti-peptide antibodies in protection from clinical malaria. Ten peptides were associated ?with a significantly reduced odds ratio for an episode of clinical malaria in the first cohort of children and two of these peptides (LR146 and ��S202.11) were associated with a significantly reduced odds ratio in both cohorts. This study has identified proteins PFB0145c and MAL6P1.37 among others as likely targets of protective antibodies. Our findings support further studies to systematically assess immunogenicity of peptides of interest in order to establish clear criteria for optimal design of potential vaccine constructs to be tested in clinical trials. RESUME La malaria est un probl��me de sant�� publique mondial principalement en Afrique, en Asie, en Oc��anie et en Am��rique latine. Plus de 2 milliards de personnes vivent dans des r��gions end��miques et le nombre de cas par ann��e est estim�� entre 300 et 500 millions. 1.5 �� 2.7 millions de d��c��s surviennent annuellement dans ces zones. L'augmentation de la r��sistance aux m��dicaments et aux insecticides fait du d��veloppement d'un vaccin une priorit��. Le s��quen��age complet du g��nome du parasite offre l'opportunit�� d'identifier de nouveaux antig��nes qui peuvent rapidement mener au d��veloppement d'un vaccin. Des prot��ines antig��niques potentielles pr��sentes �� la surface des globules rouges infect��s ont ��t�� identifi��es par bioinformatique et par l'analyse du prot��ome et du transcriptome. Nous avons s��lectionn��, parmi ces prot��ines, celles contenant des motifs dits "a helical coiled-coil" qui sont g��n��ralement courts et structurellement stables. Ces r��gions ont ��t�� obtenues par synth��se peptidique et utilis��es pour immuniser des souris. La plupart des peptides test��s sont immunog��niques et induisent un titre variable d'anticorps d��termin�� par ELISA. Les r��sultats de tests d'immunofluorescence indiquent que les sera produits chez la souris reconnaissent les prot��ines natives exprim��es aux diff��rents stades de d��veloppement du parasite. En parall��le, des ��tudes d'ADCI in vitro montrent qu�� des anticorps humains purifi��s �� partir de ces peptides associ��s �� des monocytes inhibent la croissance du parasite aussi bien que celle observ��e chez des adultes africains prot��g��s. Des ��tudes d'antig��nicit�� utilisant des sera de personnes prot��g��es de diff��rents ��ges vivant dans des r��gions end��miques montrent que la majorit�� des peptides sont reconnus avec une haute pr��valence. 73 peptides ont ��t�� test��s dans une ��tude longitudinale avec 2 cohortes de la c��te du Kenya. Ces 2 groupes viennent de zones bien distinctes et les pr��l��vements n'ont pas ��t�� effectu��s pendant la m��me p��riode. Dans cette ��tude, la r��ponse anticorps contre les peptides synth��tiques a ��t�� test��e dans les 2 cohortes d'enfants �� risque de d��velopper un ��pisode de malaria afin de caract��riser le niveau de reconnaissance des peptides en fonction de l'��ge et de d��terminer le r��le des anticorps anti-peptides dans la protection contre la malaria. Parmi ces peptides, 10 sont associ��s �� une r��duction significative des risques de d��velopper un ��pisode de malaria dans la premi��re cohorte alors qu'un seul (LR146 et AS202.11) l'est dans les 2 cohortes. Cette ��tude a identifi��, parmi d'autres, les prot��ines PFB0145c et MAL6P1.37 comme pouvant ��tre la cible d'anticorps. Ces r��sultats sont en faveur de futures ��tudes qui ��valueraient syst��matiquement l'immunog��nicit�� des peptides d'int��r��t dans le but d'��tablir des crit��res de s��lection clairs pour le d��veloppement d'un vaccin. R��sum�� pour un large public La malaria est un probl��me de sant�� publique mondial principalement en Afrique, en Asie, en Oc��anie et en Am��rique latine. Plus de 2 milliards de personnes vivent dans des r��gions end��miques et le nombre de cas par ann��e est estim�� entre 300 et 500 millions. 1.5 �� 2.7 millions de d��c��s surviennent annuellement dans ces zones. La r��sistance aux m��dicaments et aux insecticides augmente de plus en plus d'o�� la n��cessit�� de d��velopper un vaccin. Le s��quen��age complet du g��nome (ensemble des g��nes) de P. falciparum a conduit au d��veloppement de nouvelles .��tudes �� large ��chelle dans le domaine des prot��ines du parasite (prot��ome) ; dans l'utilisation d'algorithmes, de techniques informatiques et statistiques pour l'analyse de donn��es biologiques (bioinformatique) et dans les technologies de transcription et de profiles d'expression (transcriptome). Nous avons identifi��, en utilisant les outils ci-dessus, des nouvelles prot��ines antig��niques qui sont pr��sentes au stade sanguin de la malaria. Nous avons s��lectionn��, parmi ces prot��ines, celles contenant un motif dit "a-helical coiled-coil" qui sont des domaines impliqu��s dans un large ��ventail de fonctions biologiques. Des peptides repr��sentant ces r��gions structurellement stables ont ��t�� synth��tis��s et utilis��s pour immuniser des souris. La plupart des peptides test��s sont immunog��niques et induisent un titre variable d'anticorps d��termin�� par ELISA. Les r��sultats de tests d'immunofluorescence indiquent que plusieurs sera de souris immunis��es avec ces peptides reconnaissent les prot��ines natives exprim��es �� la surface des globules rouges infect��s. En parall��le, des ��tudes d'ADCI in vitro montrent que des anticorps humains purifi��s �� partir de ces peptides en pr��sence de monocytes inhibent la croissance du parasite de mani��re similaire �� celle observ��e chez des adultes africains prot��g��s. Des ��tudes d'antig��nicit�� utilisant des sera de personnes immunes de diff��rents ��ges (adultes et enfants) vivant dans des r��gions end��miques montrent que la majorit�� des peptides sont reconnus avec une haute pr��valence. 73 peptides ont ��t�� test��s dans des ��tudes ��pid��miologiques dans 2 villages c��tiers du Kenya Ces 2 groupes vivent dans des zones bien distinctes et les pr��l��vements n'ont pas ��t�� effectu��s pendant la m��me p��riode. Dans ces ��tudes, la r��ponse anticorps dirig��e contre les peptides synth��tiques a ��t�� test��e en utilisant 467 ��chantillons sanguins d'enfants �� risque de d��velopper un ��pisode de malaria afin de caract��riser le niveau de reconnaissance des peptides en fonction de l'��ge et de d��terminer le r��le des anticorps anti-peptides dans la protection contre la malaria c��r��brale. Parmi ces peptides, 10 sont associ��s �� une protection contre un ��pisode de malaria dans le premier village alors qu'un seul l'est dans les 2 villages. Ces r��sultats sont en faveur de futures ��tudes qui ��valueraient syst��matiquement l'immunog��nicit�� des peptides int��ressants dans le but d'��tablir des crit��res de s��lection clairs pour le d��veloppement d'un vaccin.

Courtship song genes and speciation in sand flies

Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae) is a vector of visceral leishmaniasis in the Americas and it might represent a complex of sibling species. Reproductive isolation between closely related species often involves differences in courtship behaviour. cacophony (cac) and period (per) are two Drosophila genes that control features of the "lovesong" males produce during courtship that has been implicated in the sexual isolation between closely related species. We are using gene fragments from L. longipalpis' homologues of these two genes to study the speciation process in this putative species complex.