WWOX at the crossroads of cancer, metabolic syndrome related traits and CNS pathologies

WWOX was cloned as a putative tumor suppressor gene mapping to chromosomal fragile site FRA16D. Deletions affecting WWOX accompanied by loss of expression are frequent in various epithelial cancers. Translocations and deletions affecting WWOX are also common in multiple myeloma and are associated with worse prognosis. Metanalysis of gene expression datasets demonstrates that low WWOX expression is significantly associated with shorter relapse-free survival in ovarian and breast cancer patients. Although somatic mutations affecting WWOX are not frequent, analysis of TCGA tumor datasets led to identifying 44 novel mutations in various tumor types. The highest frequencies of mutations were found in head and neck cancers and uterine and gastric adenocarcinomas. Mouse models of gene ablation led us to conclude that Wwox does not behave as a highly penetrant, classical tumor suppressor gene since its deletion is not tumorigenic in most models and its role is more likely to be of relevance in tumor progression rather than in initiation. Analysis of signaling pathways associated with WWOX expression confirmed previous in vivo and in vitro observations linking WWOX function with the TGFβ/SMAD and WNT signaling pathways and with specific metabolic processes. Supporting these conclusions recently we demonstrated that indeed WWOX behaves as a modulator of TGFβ/SMAD signaling by binding and sequestering SMAD3 in the cytoplasmic compartment. As a consequence progressive loss of WWOX expression in advanced breast cancer would contribute to the pro-metastatic effects resulting from TGFβ/SMAD3 hyperactive signaling in breast cancer.Recently, GWAS and resequencing studies have linked the WWOX locus with familial dyslipidemias and metabolic syndrome related traits. Indeed, gene expression studies in liver conditional KO mice confirmed an association between WWOX expression and lipid metabolism.Finally, very recently the first human pedigrees with probands carrying homozygous germline loss of function WWOX mutations have been identified. These patients are characterized by severe CNS related pathology that includes epilepsy, ataxia and mental retardation. In summary, WWOX is a highly conserved and tightly regulated gene throughout evolution and when defective or deregulated the consequences are important and deleterious as demonstrated by its association not only with poor prognosis in cancer but also with other important human pathologies such as metabolic syndrome and CNS related pathologic conditions.Centro de Investigaciones Inmunológicas Básicas y Aplicada

WWOX at the crossroads of cancer, metabolic syndrome related traits and CNS pathologies

WWOX was cloned as a putative tumor suppressor gene mapping to chromosomal fragile site FRA16D. Deletions affecting WWOX accompanied by loss of expression are frequent in various epithelial cancers. Translocations and deletions affecting WWOX are also common in multiple myeloma and are associated with worse prognosis. Metanalysis of gene expression datasets demonstrates that low WWOX expression is significantly associated with shorter relapse-free survival in ovarian and breast cancer patients. Although somatic mutations affecting WWOX are not frequent, analysis of TCGA tumor datasets led to identifying 44 novel mutations in various tumor types. The highest frequencies of mutations were found in head and neck cancers and uterine and gastric adenocarcinomas. Mouse models of gene ablation led us to conclude that Wwox does not behave as a highly penetrant, classical tumor suppressor gene since its deletion is not tumorigenic in most models and its role is more likely to be of relevance in tumor progression rather than in initiation. Analysis of signaling pathways associated with WWOX expression confirmed previous in vivo and in vitro observations linking WWOX function with the TGFβ/SMAD and WNT signaling pathways and with specific metabolic processes. Supporting these conclusions recently we demonstrated that indeed WWOX behaves as a modulator of TGFβ/SMAD signaling by binding and sequestering SMAD3 in the cytoplasmic compartment. As a consequence progressive loss of WWOX expression in advanced breast cancer would contribute to the pro-metastatic effects resulting from TGFβ/SMAD3 hyperactive signaling in breast cancer.Recently, GWAS and resequencing studies have linked the WWOX locus with familial dyslipidemias and metabolic syndrome related traits. Indeed, gene expression studies in liver conditional KO mice confirmed an association between WWOX expression and lipid metabolism.Finally, very recently the first human pedigrees with probands carrying homozygous germline loss of function WWOX mutations have been identified. These patients are characterized by severe CNS related pathology that includes epilepsy, ataxia and mental retardation. In summary, WWOX is a highly conserved and tightly regulated gene throughout evolution and when defective or deregulated the consequences are important and deleterious as demonstrated by its association not only with poor prognosis in cancer but also with other important human pathologies such as metabolic syndrome and CNS related pathologic conditions.Centro de Investigaciones Inmunológicas Básicas y Aplicada

Habitable Zones of Host Stars During the Post-MS Phase

A star will become brighter and brighter with stellar evolution, and the distance of its habitable zone will become farther and farther. Some planets outside the habitable zone of a host star during the main sequence phase may enter the habitable zone of the host star during other evolutionary phases. A terrestrial planet within the habitable zone of its host star is generally thought to be suited to life existence. Furthermore, a rocky moon around a giant planet may be also suited to life survive, provided that the planet-moon system is within the habitable zone of its host star. Using Eggleton's code and the boundary flux of habitable zone, we calculate the habitable zone of our Solar after the main sequence phase. It is found that Mars' orbit and Jupiter's orbit will enter the habitable zone of Solar during the subgiant branch phase and the red giant branch phase, respectively. And the orbit of Saturn will enter the habitable zone of Solar during the He-burning phase for about 137 million years. Life is unlikely at any time on Saturn, as it is a giant gaseous planet. However, Titan, the rocky moon of Saturn, may be suitable for biological evolution and become another Earth during that time. For low-mass stars, there are similar habitable zones during the He-burning phase as our Solar, because there are similar core masses and luminosities for these stars during that phase.Comment: 6 pages, 7 figures. Accepted by Ap & S

Scaling of stochasticity in dengue hemorrhagic fever epidemics

In this paper we analyze the stochastic version of a minimalistic multi-strain model, which captures essential differences between primary and secondary infections in dengue fever epidemiology, and investigate the interplay between stochasticity, seasonality and import. The introduction of stochasticity is needed to explain the fluctuations observed in some of the available data sets, revealing a scenario where noise and complex deterministic skeleton strongly interact. For large enough population size, the stochastic system can be well described by the deterministic skeleton gaining insight on the relevant parameter values purely on topological information of the dynamics, rather than classical parameter estimation of which application is in general restricted to fairly simple dynamical scenarios

Habitable Zones and UV Habitable Zones around Host Stars

Ultraviolet radiation is a double-edged sword to life. If it is too strong, the terrestrial biological systems will be damaged. And if it is too weak, the synthesis of many biochemical compounds can not go along. We try to obtain the continuous ultraviolet habitable zones, and compare the ultraviolet habitable zones with the habitable zones of host stars. Using the boundary ultraviolet radiation of ultraviolet habitable zone, we calculate the ultraviolet habitable zones of host stars with masses from 0.08 to 4.00 \mo. For the host stars with effective temperatures lower than 4,600 K, the ultraviolet habitable zones are closer than the habitable zones. For the host stars with effective temperatures higher than 7,137 K, the ultraviolet habitable zones are farther than the habitable zones. For hot subdwarf as a host star, the distance of the ultraviolet habitable zone is about ten times more than that of the habitable zone, which is not suitable for life existence.Comment: 5 pages, 3 figure

Genetic diversity among farmer-preferred cassava landraces in Uganda

Understanding of genetic diversity among a breeding population is an important requirement for crop improvement as it allows for the selection of diverse parental combinations and formation of heterotic pools for genetic gain. This study was carried out to determine genetic diversity within and among 51 farmer-preferred cassava ( Manihot esculenta ) landraces and 15 elite accessions grown in Uganda. Twenty six simple sequence repeat (SSR) markers used for genetic diversity assessment in this study revealed a total of 154 alleles, of which 24% were unique alleles present only in landraces. The genetic diversity and observed herozygosity in landraces were slightly higher than in elite accessions. Elite accessions clustered with some of the landraces indicating that there were some alleles in common. However, 58.8% of the landraces fell into 3 different clusters independent of the elite accessions. Including these landraces with unique alleles in cassava breeding schemes will increase the chances of producing farmer preferred adapted elite cultivars. The study also revealed genetic differentiation among accessions from different regions providing an opportunity for establishment of heterotic pools within a breeding programme.La compr\ue9hension de la diversit\ue9 g\ue9n\ue9tique est une condition importante dans la s\ue9lection de diverses combinaisons parentales et la formation des groupes h\ue9terotiques d\u2019int\ue9r\ueat g\ue9n\ue9tique pour l\u2019am\ue9lioration des cultures. Cette \ue9tude \ue9tait conduite pour d\ue9terminer la diversit\ue9 g\ue9n\ue9tique parmi 51 vari\ue9t\ue9s locales de manioc ( Manihot esculenta ) pr\ue9f\ue9r\ue9es des fermiers et 15 accessions \ue9lites cultiv\ue9es en Ouganda. Vingt six marqueurs simples \ue0 sequence r\ue9p\ue9t\ue9e (SSR) utilis\ue9s pour l\u2019\ue9valuation de la diversit\ue9 g\ue9n\ue9tique ont r\ue9v\ue9l\ue9 un total de 154 all\ue8les, parmi lesquelles 24% \ue9taient des all\ue8les uniques pr\ue9sentes dans les races locales seulement. La diversit\ue9 g\ue9n\ue9tique et l\u2019h\ue9terozygosit\ue9 observ\ue9es dans les races locales \ue9taient l\ue9g\ue8rement sup\ue9rieures que dans les accessions \ue9lites. Celles-ci s\u2019\ue9taient regroup\ue9es avec quelques vari\ue9t\ue9s locales indiquant donc qu\u2019elles avaient quelques all\ue8les en commun. Par ailleurs, 58.8% des races locales ont form\ue9 trois diff\ue9rents groupes ind\ue9pendamment des accessions \ue9lites. Inclure ces races locales \ue0 all\ue8les uniques dans les syst\ue8mes d\u2019am\ue9lioration du manioc permettra d\u2019augmenter les chances de produire des cultivars \ue9lites pr\ue9f\ue9r\ue9s des fermiers. L\u2019\ue9tude montre aussi que la diff\ue9renciation g\ue9n\ue9tique trouv\ue9e parmi les accessions de diff\ue9rentes r\ue9gions est une opportunit\ue9 offerte pour l\u2019\ue9tablissement des groupes h\ue9terotiques dans le programme d\u2019am\ue9lioration

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters