A minority of 46,XX true hermaphrodites are positive for the Y-DNA sequence including SRY

Summary A total of 30 cases of 46,XX true hermaphroditism was analysed for Y-DNA sequences including the recently cloned gene for male testis-determination SRY. In 3 cases, a portion of the Y chromosome including SRY was present and, in 2 cases, was localised, to Xp22 by in situ hybridisation. Since previous studies have shown that the majority of XX males are generated by an X-Y chromosomal interchange, the Xp22 position of the Yp material suggests that certain cases of hermaphroditism can arise by the same meiotic event. The phenotype in the 3 SRY-positive cases may be caused by X-inactivation resulting in somatic mosaicism of testis-determining factor expression giving rise to both testicular and ovarian tissues. Autosomal or X-linked mutation(s) elsewhere in the sex-determining pathway may explain the phenotype observed in the remaining 27 SRY-negative cases.     

The PAI-1 swing: microenvironment and cancer cell migration

Cancer is a complex and dynamic process caused by a cellular dysfunction leading to a whole organ or even organism vital perturbation. To better understand this process, we need to study each one of the levels involved, which allows the scale change, and to integrate this knowledge. A matricellular protein, PAI-1, is able to induce in vitro cell behaviour modifications, morphological changes, and to promote cell migration. PAI-1 influences the mesenchymo-amaeboid transition. This matricellular protein should be considered as a potential 'launcher' of the metastatic process acting at the molecular, cellular, tissular levels and, as a consequence, at the organism's level.     

Modelling molecular interactions with game networks' theory

We present a method to model biological systems, the theory of games networks. It extends game theory by multiplying the number of games, and by allowing agents to play several games simultaneously. Some important notions of biological systems, such as locality of interactions and modularity, can then be modelled.     

Ecological and Control Techniques for Sand Flies (Diptera: Psychodidae) Associated with Rodent Reservoirs of Leishmaniasis

Background

Leishmaniasis remains a global health problem because of the substantial holes that remain in our understanding of sand fly ecology and the failure of traditional vector control methods. The specific larval food source is unknown for all but a few sand fly species, and this is particularly true for the vectors of Leishmania parasites. We provide methods and materials that could be used to understand, and ultimately break, the transmission cycle of zoonotic cutaneous leishmaniasis.

Methods and Findings

We demonstrated in laboratory studies that analysis of the stable carbon and nitrogen isotopes found naturally in plant and animal tissues was highly effective for linking adult sand flies with their larval diet, without having to locate or capture the sand fly larvae themselves. In a field trial, we also demonstrated using this technique that half of captured adult sand flies had fed as larvae on rodent feces. Through the identification of rodent feces as a sand fly larval habitat, we now know that rodent baits containing insecticides that have been shown in previous studies to pass into the rodents'' feces and kill sand fly larvae also could play a future role in sand fly control. In a second study we showed that rubidium incorporated into rodent baits could be used to demonstrate the level of bloodfeeding by sand flies on baited rodents, and that the elimination of sand flies that feed on rodents can be achieved using baits containing an insecticide that circulates in the blood of baited rodents.

Conclusions

Combined, the techniques described could help to identify larval food sources of other important vectors of the protozoa that cause visceral or dermal leishmaniasis. Unveiling aspects of the life cycles of sand flies that could be targeted with insecticides would guide future sand fly control programs for prevention of leishmaniasis.     

Etude entomologique de cinq foyers de leishmaniose cutanée dans la province de Sidi Kacem au nord du Maroc

Résumé. La leishmaniose cutanée est un important problème de santé publique dans la province de Sidi Kacem au nord-ouest du Maroc. L'incidence de cette affetion, due aussi bien à Leishmania tropica qu'à L. infantum est en augmentation progressive depuis 1997. La présente étude a été menée dans le but d'étudier l'écologie et la dynamique des populations des vecteurs de cette maladie dans les principaux foyers de cette province. Un total de 4504 spécimens appartenant à deux genres et six espèces a été capturé à l'aide de pièges adhésifs et lumineux, dans cinq foyers. Les espèces dominantes sont Phlebotomus sergenti représentant 42,6% du total des phlébotomes capturés et P. longicuspis avec 27,2% des captures. Ces deux espèces sont présentes de mai à novembre et évoluent en deux générations avec deux pics de densité, le premier en juin et le second en septembre. En considérant la grande spécificité vecteur-parasite connue en épidémiologie des leishmanioses ainsi que l'abondance des espèces capturées pendant la saison favorable à la transmission, P. sergenti et P. longicuspis seraient respectivement les vecteurs les plus probables des leishmanioses à L. tropica et à L. infantum dans la région étudiée. Le risque de transmission de la maladie serait plus grand durant le deuxième pic de densité en fin été- début automne.     

First synthesis of two deoxy Lewisx pentaosyl glycosphingolipids

The Lewis^x–Lewis^x interaction has been increasingly studied, using a variety of techniques including nuclear magnetic resonance spectroscopy, mass spectrometry, vesicle adhesion, atomic force microscopy, and surface plasmon resonance spectroscopy. However, the detailed molecular mechanism of these weak, divalent cation dependent interactions remains unclear, and new models are needed to probe the nature of this phenomenon in term of key roles of the different hydroxyl groups on Lewis^x trisaccharide determinant involved in the Lewis^x–Lewis^x interaction. An interesting solution is to synthesize a series of Lewis^x pentaosyl glycosphingolipid derivatives in which one of the eight hydroxyl groups of Lewis^x trisaccharide is replaced by a hydrogen atom, and to test the adhesion induced by interaction of these derivatives, in order to gain insight into the functions played by the hydroxyl groups of the Lewis^x trisaccharide. This article describes the synthesis of 3d-deoxy and 4d-deoxy Lewis^x pentaosyl glycosphingolipids, to be used for study of the Lewis^x–Lewis^x interaction. Botao Fan: Deceased October 22, 2006     

Evaluation of changes in serum protein profiles during neoadjuvant chemotherapy in HER2‐positive breast cancer using an LC‐MALDI‐TOF/MS procedure

Comparison of protein profiles of sera acquired before and after preoperative chemotherapy for breast cancer may reveal tumor markers that could be used to monitor tumor response. In this study, we analyzed pre‐ and post‐chemotherapy protein profiles of sera from 39 HER2‐postive breast cancer patients (n=78 samples) who received 6 months of preoperative chemotherapy using LC‐MALDI‐TOF/MS technology. We detected qualitative and quantitative differences in pair‐wise comparison of pre‐ and post chemotherapy samples that were different in patients who achieved pathological complete response (pCR, n=21) compared with those with residual disease (n=18). We identified 2329 and 3152 peaks as differentially expressed in the pre‐chemotherapy samples of the responders and non‐responders. Comparison of matching pre‐ and post‐chemotherapy samples identified 34 (32 decreased, two increased) and 304 peaks (157 decreased, 147 increased) that significantly changed (p<0.01, false discovery rate ≤20%) after treatment in responders and non‐responders, respectively. The top 11 most significantly altered peptide peaks with the greatest change in intensity were positively identified. These corresponded to eight proteins including α‐2‐macroglobulin, complement 3, hemopexin, and serum amyloid P in the responder group and chains C and A of apolipoprotein A‐I, hemopexin precursor, complement C, and amyloid P component in the non‐responding groups. All proteins decreased after therapy, except chain C apolipoprotein A and hemopexin precursor that increased. These results suggest that changes in serum protein levels occur in response to chemotherapy and these changes partly appear different in patients who are highly sensitive to chemotherapy compared with those with lesser response.     

A possible common origin of “Y-negative” human XX males and XX true hermaphrodites

Summary We have studied nine patients aged 1 month to 16 years with 46, XX karyotypes and testicular tissue. Some of these patients were followed through puberty. Phenotypically, two presented normal and seven abnormal external genitalia (AG). Among this latter group, four showed hypospadias and three true hermaphroditism (TH). The endocrine data were similar in all three groups: testosterone levels were within normal limits during puberty, decreasing in adulthood; gonadotrophin levels were above the control values at mid puberty. Histologies of the two sub groups of AG patients were identical up to 5 years of age and presented differences when compared with controls, regardless of the ovarian part of the ovotestis. However, in patients older than 8 years, germ cells disappeared and dysgenesis became obvious. In one patient, the ovarian zone of the gonad was detected only after complete serial sections of the removed gonad were examined. Southern blot analysis with Y-DNA probes displayed Y-specific material for the classic 46 XX males and a lack of such sequences for all patients with AG and TH. Based on these findings, we postulate that 46, XX males with AG and 46, XX TH may represent altenative manifestations of the same genetic defect. These data together with those concerning familial cases of 46, XX males with AG and 46, XX TH suggest an autosomally (or pseudoautosomally) determined mechanism.