Proceedings of the Schistosome Genome Project

"The host-parasite relationship" is a vast and diverse research field which, despite huge human and financial input over many years, remains largely shrouded in mystery. Clearly, the adaptation of parasites to their different host species, and to the different environmental stresses that they represent, depends on interactions with, and responses to, various molecules of host and/or parasite origin. The schistosome genome project is a primary strategy to reach the goal; this systematic research project has successfully developed novel technologies for qualitative and quantitative characterization of schistosome genes and genome organization by extensive international collaboration between top quality laboratories. Schistosomes are a family of parasitic blood flukes (Phylum Platyhelminthes), which have seven pairs of autosomal chromosomes and one pair of sex chromosomes (ZZ for a male worm and ZW for a female), of a haploid genome size of 2.7x108 base pairs (Simpson et al. 1982). Schistosomes are ideal model organisms for the development of genome mapping strategies since they have a small genome size comparable to that of well-characterized model organisms such as Caenorhabditis elegans (100 Mb) and Drosophila (165 Mb), and contain functional genes with a high level of homology to the host mammalian genes. Here we summarize the current progress in the schistosome genome project, the information of 3,047 transcribed genes (Expressed Sequence Tags; EST), complete sets of cDNA and genomic DNA libraries (including YAC and cosmid libraries) with a mapping technique to the well defined schistosome chromosomes. The schistosome genome project will further identify and characterize the key molecules that are responsible for host-parasite adaptation, i.e., successful growth, development, maturation and reproduction of the parasite within its host in the near future

Towards the Physical Map of the Trypanosoma cruzi Nuclear Genome: Construction of YAC and BAC Libraries of the Reference Clone T. cruzi CL-Brener

Strategies to construct the physical map of the Trypanosoma cruzi nuclear genome have to capitalize on three main advantages of the parasite genome, namely (a) its small size, (b) the fact that all chromosomes can be defined, and many of them can be isolated by pulse field gel electrophoresis, and (c) the fact that simple Southern blots of electrophoretic karyotypes can be used to map sequence tagged sites and expressed sequence tags to chromosomal bands. A major drawback to cope with is the complexity of T. cruzi genetics, that hinders the construction of a comprehensive genetic map. As a first step towards physical mapping, we report the construction and partial characterization of a T. cruzi CL-Brener genomic library in yeast artificial chromosomes (YACs) that consists of 2,770 individual YACs with a mean insert size of 365 kb encompassing around 10 genomic equivalents. Two libraries in bacterial artificial chromosomes (BACs) have been constructed, BACI and BACII. Both libraries represent about three genome equivalents. A third BAC library (BAC III) is being constructed. YACs and BACs are invaluable tools for physical mapping. More generally, they have to be considered as a common resource for research in Chagas disease

Anàlisi i disseny d'un reflector per banda W

Les ones passives mil·limètriques (30 a 300GHz) tenen la peculiaritat de propagar-se en medis com la boira o la roba, a diferència del rang visible o l’infraroig. D’aquesta peculiaritat, surt l’interès de reproduir imatges per diverses aplicacions (seguretat, vigilància, etc...). És per aquest motiu que es treballa en el disseny d’un reflector per aquest tipus d’aplicació, treballant a una de les finestres de propagació d’aquest rang, la de la banda W. Es dissenyen i analitzen tres tipus de reflector: parabòlic simètric, offset i Cassegrain. D’aquests, s’estudien les seves figures de mèrit i directivitats buscant que aquestes siguin el més elevades possibles per obtenir una bona resolució, així com l’escaneig de l’escena de la qual es vol obtenir una imatge, veient aquí els efectes de les aberracions més comunes.

arrayMap 2014: an updated cancer genome resource.

Somatic copy number aberrations (CNA) represent a mutation type encountered in the majority of cancer genomes. Here, we present the 2014 edition of arrayMap (http://www.arraymap.org), a publicly accessible collection of pre-processed oncogenomic array data sets and CNA profiles, representing a vast range of human malignancies. Since the initial release, we have enhanced this resource both in content and especially with regard to data mining support. The 2014 release of arrayMap contains more than 64,000 genomic array data sets, representing about 250 tumor diagnoses. Data sets included in arrayMap have been assembled from public repositories as well as additional resources, and integrated by applying custom processing pipelines. Online tools have been upgraded for a more flexible array data visualization, including options for processing user provided, non-public data sets. Data integration has been improved by mapping to multiple editions of the human reference genome, with the majority of the data now being available for the UCSC hg18 as well as GRCh37 versions. The large amount of tumor CNA data in arrayMap can be freely downloaded by users to promote data mining projects, and to explore special events such as chromothripsis-like genome patterns.

Relocalization of telomeric Ku and SIR proteins in response to DNA strand breaks in yeast.

Telomeric TG-rich repeats and their associated proteins protect the termini of eukaryotic chromosomes from end-to-end fusions. Associated with the cap structure at yeast telomeres is a subtelomeric domain of heterochromatin, containing the silent information regulator (SIR) complex. The Ku70/80 heterodimer (yKu) is associated both with the chromosome end and with subtelomeric chromatin. Surprisingly, both yKu and the chromatin-associated Rap1 and SIR proteins are released from telomeres in a RAD9-dependent response to DNA damage. yKu is recruited rapidly to double-strand cuts, while low levels of SIR proteins are detected near cleavage sites at later time points. Consistently, yKu- or SIR-deficient strains are hypersensitive to DNA-damaging agents. The release of yKu from telomeric chromatin may allow efficient scanning of the genome for DNA strand breaks.

Mycoplasma hominis in mid-trimester amniotic fluid : relation to pregnangy outcome

RESUME Introduction : Les naissances prématurées compliquent 6-10 % des grossesses dans les pays industrialisés et contribuent de façon notable aux taux de mortalité périnatale et de morbidité néonatale. Il a été démontré que la colonisation bactérienne du liquide amniotique joue un rôle dans l'étiologie des accouchements prématurés spontanés et des ruptures prématurées des membranes. Le but de ce travail était d'évaluer la présence de Mycoplasma hominis dans le liquide amniotique prélevé au 2eme trimestre de grossesse chez des patientes asymptomatiques et de déterminer son association avec une issue défavorable de la grossesse. Matériels et méthodes : Les échantillons de liquide amniotique de 456 patientes ayant subi une amniocentèse trans-abdominale entre les 15eme et I7eme semaines de grossesse pour diverses indications ont été testés par PCR (Polymerase Chain Reaction) afin d'identifier Mycoplasma hominis. Les produits ainsi amplifiés étaient ensuite détectés par ELISA (Enzyme-Linked Immunosorbent Assay). Les données cliniques étaient obtenues après l'accouchement. Résultats : Mycoplasma hominis a été identifié dans 29 (6,4%) des échantillons de liquide amniotique. Le taux de menace d'accouchement prématuré chez les patientes positives pour Mycoplasma hominis (14,3%) était plus élevé que chez les patientes négatives (3,3 %) (p=0,01). De même, les naissances prématurées spontanées avec membranes intactes étaient plus fréquentes chez les patientes positives (10,7%) que chez les patientes négatives (1,9 %) (p=0,02). Le taux de menace d'accouchement prématuré lors d'une grossesse antérieure était plus de trois fois plus élevé chez les patientes positives, cependant ce résultat n'était pas statistiquement significatif. Finalement, la présence du mycoplasme n'était pas corrélée à la gestose, au retard de croissance intra-utérin ou aux anomalies chromosomiques foetales. Conclusions : Les résultats montrent que la présence de Mycoplasma hominis dans le liquide amniotique prélevé entre les 15eme et I7eme semaines d' aménorrhée chez des patientes asymptomatiques est associée à un taux plus élevé de menace d'accouchement prématuré et de naissances prématurées spontanées. La détection de ce microorganisme au 2eme trimestre de la grossesse peut donc identifier les patientes à risque de menace d'accouchement et de naissance prématurées. Abstract Objective: The relationship between detection of Mycoplasma hominis in mid-trimester amniotic fluid and subsequent pregnancy outcome was investigated. Study design: Amniotic fluids from 456 women of European background who underwent a transabdominal amniocentesis at weeks 15-17 of pregnancy were tested for M. hominis by polymerase chain reaction (PCR). The amplicons were hybridized to an internal probe and detected by ELISA. Pregnancy outcomes and clinical data were subsequently obtained. Results: M. hominis were identified in 29 (6.4%) of the amniotic fluids. The rate of preterm labor in women positive for M. hominis (14.3%) was higher than in the negative women (3.3%) (p = 0.01). Similarly, a spontaneous preterm birth with intact membranes occurred in 10.7% of the M. hominis-posltive women as opposed to only 1.9% of the negative women (p = 0.02). The presence of this mycoplasma was not correlated with fetal chromosomal aberrations, intrauterine growth restriction or preeclampsia. Conclusions: Detection of M. hominis in second-trimester amniotic fluids can identify women at increased risk for subsequent preterm labor and delivery.

Comparative Meiotic Studies in Triatoma sordida (Stål) and T. guasayana Wygodzinsky & Abalos (Reduviidae, Heteroptera)

Triatoma sordida and T. guasayana are competent Trypanosoma cruzi vectors, with overlapping distribution areas in Argentina. Both species are morphologically similar, and their immature stages are hard to discriminate. Cytogenetic studies in the genus Triatoma reveal scarce karyotypic variations, being 2n= 20 + XY the most frequent diploid number in males. In the present work the meiotic behaviour of different Argentinian populations of T. sordida and T. guasayana has been analyzed; the meiotic karyotype of both species has also been compared. The species differ in total chromosome area and in the relative area of the sex chromosomes. These meiotic karyotypic differences constitute an additional tool for the taxonomic characterization of T. sordida and T. guasayana. The analysis of an interpopulation hybrid of T. sordida (Brazil x Argentina) reveals a regular meiotic behaviour, despite the presence of heteromorphic bivalents. Our observations support the hypothesis that karyotype variations through the gain or loss of heterochromatin can not be considered as a primary mechanism of reproductive isolation in Triatoma.

Clonal heterogeneity and chromosomal instability at disease presentation in high hyperdiploid acute lymphoblastic leukemia.

Although aneuploidy has many possible causes, it often results from underlying chromosomal instability (CIN) leading to an unstable karyotype with cell-to-cell variation and multiple subclones. To test for the presence of CIN in high hyperdiploid acute lymphoblastic leukemia (HeH ALL) at diagnosis, we investigated 20 patients (10 HeH ALL and 10 non-HeH ALL), using automated four-color interphase fluorescence in situ hybridization (I-FISH) with centromeric probes for chromosomes 4, 6, 10, and 17. In HeH ALL, the proportion of abnormal cells ranged from 36.3% to 92.4%, and a variety of aneuploid populations were identified. Compared with conventional cytogenetics, I-FISH revealed numerous additional clones, some of them very small. To investigate the nature and origin of this clonal heterogeneity, we determined average numerical CIN values for all four chromosomes together and for each chromosome and patient group. The CIN values in HeH ALL were relatively high (range, 22.2-44.7%), compared with those in non-HeH ALL (3.2-6.4%), thus accounting for the presence of numerical CIN in HeH ALL at diagnosis. We conclude that numerical CIN may be at the origin of the high level of clonal heterogeneity revealed by I-FISH in HeH ALL at presentation, which would corroborate the potential role of CIN in tumor pathogenesis.

Early expression of the type III secretion system of Parachlamydia acanthamoebae during a replicative cycle within its natural host cell Acanthamoeba castellanii.

The type three secretion system (T3SS) operons of Chlamydiales bacteria are distributed in different clusters along their chromosomes and are conserved at both the level of sequence and genetic organization. A complete characterization of the temporal expression of multiple T3SS components at the transcriptional and protein levels has been performed in Parachlamydia acanthamoebae, replicating in its natural host cell Acanthamoeba castellanii. The T3SS components were classified in four different temporal clusters depending on their pattern of expression during the early, mid- and late phases of the infectious cycle. The putative T3SS transcription units predicted in Parachlamydia are similar to those described in Chlamydia trachomatis, suggesting that T3SS units of transcriptional expression are highly conserved among Chlamydiales bacteria. The maximal expression and activation of the T3SS of Parachlamydia occurred during the early to mid-phase of the infectious cycle corresponding to a critical phase during which the intracellular bacterium has (1) to evade and/or block the lytic pathway of the amoeba, (2) to differentiate from elementary bodies (EBs) to reticulate bodies (RBs), and (3) to modulate the maturation of its vacuole to create a replicative niche able to sustain efficient bacterial growth.

Als Marie Bonaparte sich taub stellte ...

Between 1927 and 1931 Marie Bonaparte had herself operated upon her clitoris three times. She did so against Freud's advice with whom she was in analysis. Among psychoanalysts these operations are still often regarded as "errors" or aberrations. But for Marie Bonaparte, who was in various ways familiar with physics and a somatic approach, surgery was the first choice, psychoanalysis only a possible alternative. She was not impressed by the skepticism of her colleagues, and adhered even more emphatically to her own strategy

Sex determination: why so many ways of doing it?

Sexual reproduction is an ancient feature of life on earth, and the familiar X and Y chromosomes in humans and other model species have led to the impression that sex determination mechanisms are old and conserved. In fact, males and females are determined by diverse mechanisms that evolve rapidly in many taxa. Yet this diversity in primary sex-determining signals is coupled with conserved molecular pathways that trigger male or female development. Conflicting selection on different parts of the genome and on the two sexes may drive many of these transitions, but few systems with rapid turnover of sex determination mechanisms have been rigorously studied. Here we survey our current understanding of how and why sex determination evolves in animals and plants and identify important gaps in our knowledge that present exciting research opportunities to characterize the evolutionary forces and molecular pathways underlying the evolution of sex determination.

Study of gene flow through a hybrid zone in the common shrew (Sorex araneus) using microsatellites

The common shrew (Sorer araneus) is subdivided into several chromosomal races. As hybrid zones between them have been characterized, this organism is of particular interest in studying the role of chromosomes in speciation. Six microsatellite loci were used to evaluate the level of gene how in the S. araneus hybrid zone between the Cordon and Valais races. Most of these loci were very polymorphic, the total number of alleles detected per locus ranging from 3 to 20. Using Mantel tests, we showed that the effect of rivers as barriers to gene flow is less important at this sampling scale. The effect of the chromosomal race is of particular importantance in diminishing gene flow.

Effects of physiological self-crowding of DNA on shape and biological properties of DNA molecules with various levels of supercoiling.

DNA in bacterial chromosomes and bacterial plasmids is supercoiled. DNA supercoiling is essential for DNA replication and gene regulation. However, the density of supercoiling in vivo is circa twice smaller than in deproteinized DNA molecules isolated from bacteria. What are then the specific advantages of reduced supercoiling density that is maintained in vivo? Using Brownian dynamics simulations and atomic force microscopy we show here that thanks to physiological DNA-DNA crowding DNA molecules with reduced supercoiling density are still sufficiently supercoiled to stimulate interaction between cis-regulatory elements. On the other hand, weak supercoiling permits DNA molecules to modulate their overall shape in response to physiological changes in DNA crowding. This plasticity of DNA shapes may have regulatory role and be important for the postreplicative spontaneous segregation of bacterial chromosomes.

A 35.7 kb DNA fragment from the Bacillus subtilis chromosome containing a putative 12.3 kb operon involved in hexuronate catabolism and a perfectly symmetrical hypothetical catabolite-responsive element.

The Bacillus subtilis strain 168 chromosomal region extending from 109 degrees to 112 degrees has been sequenced. Among the 35 ORFs identified, cotT and rapA were the only genes that had been previously mapped and sequenced. Out of ten ORFs belonging to a single putative transcription unit, seven are probably involved in hexuronate catabolism. Their sequences are homologous to Escherichia coli genes exuT, uidB, uxaA, uxaB, uxaC, uxuA and uxuB, which are all required for the uptake of free D-glucuronate, D-galacturonate and beta-glucuronide, and their transformation into glyceraldehyde 3-phosphate and pyruvate via 2-keto-3-deoxygluconate. The remaining three ORFs encode two dehydrogenases and a transcriptional regulator. The operon is preceded by a putative catabolite-responsive element (CRE), located between a hypothetical promoter and the RBS of the first gene. This element, the longest and the only so far described that is fully symmetrical, consists of a 26 bp palindrome matching the theoretical B. subtilis CRE sequence. The remaining predicted amino acid sequences that share homologies with other proteins comprise: a cytochrome P-450, a glycosyltransferase, an ATP-binding cassette transporter, a protein similar to the formate dehydrogenase alpha-subunit (FdhA), protein similar to NADH dehydrogenases, and three homologues of polypeptides that have undefined functions.

Sorafenib for the treatment of metastatic thyroid cancer patients.

Segons resultats de fases II amb inhibidors tirosina quinasa i el coneixement de les alteracions moleculars de la carcinogènesis tiroïdal, es va dissenyar un estudi retrospectiu de pacients amb càncer de tiroide metastàtic tractats amb sorafenib. S’analitzaren la taxa de respostes, toxicitat, supervivència i la correlació amb els marcadors tumorals de 34 pacients. Segons subtipus histològic, la taxa de respostes va ser 47% en medul•lars, 19% en diferenciats i 33% en anaplàsics. La mitjana de supervivència-lliure-de-progressió va ser 13.5, 10.5 i 4.4 mesos, respectivament. Es va observar correlació significativa entre la reducció dels nivells de marcador tumoral i la resposta. El perfil de toxicitat va ser favorable.