Insights into gliomagenesis: systems biology unravels key pathways

Technological advances have enabled a better characterization of all the genetic alterations in tumors. A picture that emerges is that tumor cells are much more genetically heterogeneous than originally expected. Thus, a critical issue in cancer genomics is the identification of the genetic alterations that drive the genesis of a tumor. Recently, a systems biology approach has been used to characterize such alterations and find associations between them and the process of gliomagenesis. Here, we discuss some implications of this strategy for the development of new therapeutic and diagnostic protocols for cancer

The role of exon shuffling in shaping protein-protein interaction networks

<p>Abstract</p> <p>Background</p> <p>Physical protein-protein interaction (PPI) is a critical phenomenon for the function of most proteins in living organisms and a significant fraction of PPIs are the result of domain-domain interactions. Exon shuffling, intron-mediated recombination of exons from existing genes, is known to have been a major mechanism of domain shuffling in metazoans. Thus, we hypothesized that exon shuffling could have a significant influence in shaping the topology of PPI networks.</p> <p>Results</p> <p>We tested our hypothesis by compiling exon shuffling and PPI data from six eukaryotic species: <it>Homo sapiens</it>, <it>Mus musculus</it>, <it>Drosophila melanogaster</it>, <it>Caenorhabditis elegans</it>, <it>Cryptococcus neoformans</it> and <it>Arabidopsis thaliana</it>. For all four metazoan species, genes enriched in exon shuffling events presented on average higher vertex degree (number of interacting partners) in PPI networks. Furthermore, we verified that a set of protein domains that are simultaneously promiscuous (known to interact to multiple types of other domains), self-interacting (able to interact with another copy of themselves) and abundant in the genomes presents a stronger signal for exon shuffling.</p> <p>Conclusions</p> <p>Exon shuffling appears to have been a recurrent mechanism for the emergence of new PPIs along metazoan evolution. In metazoan genomes, exon shuffling also promoted the expansion of some protein domains. We speculate that their promiscuous and self-interacting properties may have been decisive for that expansion.</p

Sense-antisense pairs in mammals: functional and evolutionary considerations

Analysis of a catalog of S-AS pairs in the human and mouse genomes revealed several putative roles for natural antisense transcripts and showed that some are artifacts of cDNA library construction

Influencia del acondicionamiento de la dentina con ácido poliacrílico en la resistencia al cizallamiento de un cemento de ionómero de vidrio modificado con resina con tecnología de nano relleno.

Purpose: This in vitro study aimed to evaluate the influence of dentin conditioning with polyacrylic acid on the shear bond strength of the nano-filled resin-modified glass ionomer cement Ketac N100 (3MESPE). Material and methods: Eighteen bovine incisors were randomly divided into two groups (n=18): group 1, without dentin surface treatment, and group 2, with dentin surface treated with 10% polyacrylic acid for 15 seconds. In both groups the primer was applied before the application of the nano-filled resin-modified glass ionomer cement (Ketac N100) and light-cured for 20 seconds. After 24 hours, the specimens were submitted to thermocycling for 350 cycles, and the teeth were immersed in distilled water at room temperature. After 24 hours, specimens were tested for shear bond strength at 1mm/minute crosshead speed. The collected data were analyzed using the non-parametric test of Mann Whitney (p&lt;0.05). Results: There was a significant difference in shear bond strength values between the treatment and control groups, the group with dentin conditioning with 10% polyacrylic acid showed higher shear strength values than the group without dentin treatment. Conclusion: Application of 10% polyacrylic acid on dentin increases the shear bond strength values of nano-filled resin-modified glass ionomer cement.Objetivo: Este estudio in vitro tuvo como objetivo evaluar la influencia del acondicionamiento de la dentina con ácido poliacrílico sobre la resistencia al cizallamiento del cemento de ionómero de vidrio modificado con resina con tecnología de nano relleno Ketac N100 (3MESPE). Material y Métodos: Dieciocho incisivos bovinos se dividieron aleatoriamente en dos grupos (n = 18): el grupo 1, sin tratamiento de la superficie dentinaria, y el grupo 2, con la superficie dentinaria tratada con ácido poliacrílico al 10% durante 15 segundos. En ambos grupos, el Primer se aplicó antes de la aplicación del cemento de ionómero devidrio modificado con resina con tecnología de nano relleno (Ketac N100) y se fotopolimerizó durante 20 segundos. Después de 24 horas, las muestras se sometieron a 350 ciclos de termociclado y los dientes se sumergieron en agua destilada a temperatura ambiente.Después de 24 horas, las muestras se evaluaron para determinar la resistencia al cizallamiento a una velocidad constante de 1 mm / minuto. Los datos recolectados fueron analizados mediante la prueba no paramétrica de Mann Whitney (p&lt;0.05). Resultados: Hubo una diferencia significativa en los valores de resistencia al cizallamiento entre los grupos de tratamiento y control, el grupo con acondicionamiento de dentina con ácido poliacrílico al 10% mostró valores de resistencia al cizallamiento más altos que el grupo sin tratamiento de la dentina. Conclusión: La aplicación de ácido poliacrílico al 10% sobre la dentina aumenta los valores de resistencia al cizallamiento del cemento de ionómero de vidrio modificado con resina con tecnología de nano relleno

A genetic network that suppresses genome rearrangements in Saccharomyces cerevisiae and contains defects in cancers.

Gross chromosomal rearrangements (GCRs) play an important role in human diseases, including cancer. The identity of all Genome Instability Suppressing (GIS) genes is not currently known. Here multiple Saccharomyces cerevisiae GCR assays and query mutations were crossed into arrays of mutants to identify progeny with increased GCR rates. One hundred eighty two GIS genes were identified that suppressed GCR formation. Another 438 cooperatively acting GIS genes were identified that were not GIS genes, but suppressed the increased genome instability caused by individual query mutations. Analysis of TCGA data using the human genes predicted to act in GIS pathways revealed that a minimum of 93% of ovarian and 66% of colorectal cancer cases had defects affecting one or more predicted GIS gene. These defects included loss-of-function mutations, copy-number changes associated with reduced expression, and silencing. In contrast, acute myeloid leukaemia cases did not appear to have defects affecting the predicted GIS genes

Exact cosmological solutions of models with an interacting dark sector

In this work we extend the first order formalism for cosmological models that present an interaction between a fermionic and a scalar field. Cosmological exact solutions describing universes filled with interacting dark energy and dark matter have been obtained. Viable cosmological solutions with an early period of decelerated expansion followed by late acceleration have been found, notably one which presents a dark matter component dominating in the past and a dark energy component dominating in the future. In another one, the dark energy alone is the responsible for both periods, similar to a Chaplygin gas case. Exclusively accelerating solutions have also been obtained.Comment: 14 pages, 4 figures;v.4: published versio

Dipole-quadrupole interactions and the nature of phase III of compressed hydrogen

A new class of strongly infrared active structures is identified for phase III of compressed molecular H2 by constant-pressure ab initio molecular dynamics and density-functional perturbation calculations. These are planar quadrupolar structures obtained as a distortion of low-pressure quadrupolar phases, after they become unstable at about 150 GPa due to a zone-boundary soft phonon. The nature of the II-III transition and the origin of the IR activity are rationalized by means of simple electrostatics, as the onset of a stabilizing dipole-quadrupole interaction.Comment: 4 pages, 3 figures. To appear in Phys. Rev. Let

Definition of the Gene Content of the Human Genome: The Need for Deep Experimental Verification

Based on the analysis of the drafts of the human genome sequence, it is being speculated that our species may possess an unexpectedly low number of genes. The quality of the drafts, the impossibility of accurate gene prediction and the lack of sufficient transcript sequence data, however, render such speculations very premature. The complexity of human gene structure requires additional and extensive experimental verification of transcripts that may result in major revisions of these early estimates of the number of human genes

Systematic detection of putative tumor suppressor genes through the combined use of exome and transcriptome sequencing

Abstract Background To identify potential tumor suppressor genes, genome-wide data from exome and transcriptome sequencing were combined to search for genes with loss of heterozygosity and allele-specific expression. The analysis was conducted on the breast cancer cell line HCC1954, and a lymphoblast cell line from the same individual, HCC1954BL. Results By comparing exome sequences from the two cell lines, we identified loss of heterozygosity events at 403 genes in HCC1954 and at one gene in HCC1954BL. The combination of exome and transcriptome sequence data also revealed 86 and 50 genes with allele specific expression events in HCC1954 and HCC1954BL, which comprise 5.4% and 2.6% of genes surveyed, respectively. Many of these genes identified by loss of heterozygosity and allele-specific expression are known or putative tumor suppressor genes, such as BRCA1, MSH3 and SETX, which participate in DNA repair pathways. Conclusions Our results demonstrate that the combined application of high throughput sequencing to exome and allele-specific transcriptome analysis can reveal genes with known tumor suppressor characteristics, and a shortlist of novel candidates for the study of tumor suppressor activities