Expression profiling of rectal tumors defines response to neoadjuvant treatment related genes.

To date, no effective method exists that predicts the response to preoperative chemoradiation (CRT) in locally advanced rectal cancer (LARC). Nevertheless, identification of patients who have a higher likelihood of responding to preoperative CRT could be crucial in decreasing treatment morbidity and avoiding expensive and time-consuming treatments. The aim of this study was to identify signatures or molecular markers related to response to pre-operative CRT in LARC. We analyzed the gene expression profiles of 26 pre-treatment biopsies of LARC (10 responders and 16 non-responders) without metastasis using Human WG CodeLink microarray platform. Two hundred and fifty seven genes were differentially over-expressed in the responder patient subgroup. Ingenuity Pathway Analysis revealed a significant ratio of differentially expressed genes related to cancer, cellular growth and proliferation pathways, and c-Myc network. We demonstrated that high Gng4, c-Myc, Pola1, and Rrm1 mRNA expression levels was a significant prognostic factor for response to treatment in LARC patients (p<0.05). Using this gene set, we were able to establish a new model for predicting the response to CRT in rectal cancer with a sensitivity of 60% and 100% specificity. Our results reflect the value of gene expression profiling to gain insight about the molecular pathways involved in the response to treatment of LARC patients. These findings could be clinically relevant and support the use of mRNA levels when aiming to identify patients who respond to CRT therapy.

Iowa 100% E News, February 2001, Vol.1, no.1

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Iowa 100% E News, March 2001, Vol.1, no.2

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Iowa 100% E News, April 2001, Vol.1, no.3

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Iowa 100% E News, May/June 2001, Vol.1, no.4

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Iowa 100% E News, July/August 2001, Vol.1, no.5

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Iowa 100% E News, August/September 2001, Vol.1, no.6

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Iowa 100% E News, December 2001, Vol.1 no.8

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Administració pública electronica i immigracio: una nova oportunitat per una societat xarxa catalana inclusiva

Aquest projecte explora dues dinàmiques socials interrelacionades: a) L'increment de la diversitat cultural al territori català i la necessitat d'implementar polítiques públiques per millorar la convivència i la cohesió social. b) El desenvolupament de la societat xarxa catalana mitjançant la disseminació de les noves tecnologies de la informació i la comunicació en I'espai de I'administració pública. Mes en concret, el projecte aborda la qüestió de la participació de les persones immigrades en la societat xarxa catalana mitjançant una metodologia que combina la investigació online i offline. Es posa un especial èmfasi en I'estudi de I ‘accés i ús dels serveis oferts per I'administració pública electrònica de les persones immigrades a Catalunya. Els nous usuaris i usuàries dels serveis públics presenten condicionants i necessitats particulars que depenen del seu origen cultural i de la seva situació administrativa. Aquest projecte estudia el grau d'adequació de la e-Administració a les demandes i necessitats especifiques d'aquest grup de població. En aquest sentit, I'estudi explora les possibilitats per a poder promoure la cohesió social mitjançant el desenvolupament d'una administració pública electronica mes inclusiva i interactiva a Catalunya. L’anàlisi de I'adaptació i adopció de I'administració electrònica catalana en el context de la població immigrada s'ha fet des d'un doble camí metodològic. D' una banda, s'ha realitzat una incursió en com I'administració pública catalana, tant local com autonòmica, s'ha adaptat a la diversitat dels seus usuaris mitjançant I'observació de webs i entrevistes a responsables tècnics i polítics. D'altra banda, s'han fet entrevistes amb persones immigrades amb perfils socio-culturals diversos. podem apuntar que I'administració pública electrònica a Catalunya es una realitat per a moltes persones immigrades que ja han provat de fer-la servir per a usos socialment importants. Existeixen, però, impediments tant des de la pròpia dinàmica de I'administració, que no ha posat aquesta qüestió en un lloc prioritari, com des de les persones que desconfien dels seus propis coneixements i no sempre troben allò que busquen. Amb tot, ens trobem amb un espai que obre expectatives de futur molt amplies. Un espai molt idoni per a repensar les formes que exigeixen els reptes de la nova ciutadania

The genomic impact of 100 million years of social evolution in seven ant species.

Ants (Hymenoptera, Formicidae) represent one of the most successful eusocial taxa in terms of both their geographic distribution and species number. The publication of seven ant genomes within the past year was a quantum leap for socio- and ant genomics. The diversity of social organization in ants makes them excellent model organisms to study the evolution of social systems. Comparing the ant genomes with those of the honeybee, a lineage that evolved eusociality independently from ants, and solitary insects suggests that there are significant differences in key aspects of genome organization between social and solitary insects, as well as among ant species. Altogether, these seven ant genomes open exciting new research avenues and opportunities for understanding the genetic basis and regulation of social species, and adaptive complex systems in general.

Identification of potential small molecule binding pockets on Rho family GTPases

Rho GTPases are conformational switches that control a wide variety of signaling pathways critical for eukaryotic cell development and proliferation. They represent attractive targets for drug design as their aberrant function and deregulated activity is associated with many human diseases including cancer. Extensive high-resolution structures (.100) and recent mutagenesis studies have laid the foundation for the design of new structure-based chemotherapeutic strategies. Although the inhibition of Rho signaling with drug-like compounds is an active area of current research, very little attention has been devoted to directly inhibiting Rho by targeting potential allosteric non-nucleotide binding sites. By avoiding the nucleotide binding site, compounds may minimize the potential for undesirable off-target interactions with other ubiquitous GTP and ATP binding proteins. Here we describe the application of molecular dynamics simulations, principal component analysis, sequence conservation analysis, and ensemble small-molecule fragment mapping to provide an extensive mapping of potential small-molecule binding pockets on Rho family members. Characterized sites include novel pockets in the vicinity of the conformationaly responsive switch regions as well as distal sites that appear to be related to the conformations of the nucleotide binding region. Furthermore the use of accelerated molecular dynamics simulation, an advanced sampling method that extends the accessible time-scale of conventional simulations, is found to enhance the characterization of novel binding sites when conformational changes are important for the protein mechanism.

Iowa 100% E News, March 2002, Vol.2, no.3

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Iowa 100% E News, October/November 2001, Vol.1, no.7

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Iowa 100% E News, January 2002, Vol.2, no.1

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