Study of association of TGF-ß1 polymorphism with breast density in a tertiary medical center of Malaysia

Early detection of breast cancer risk by screening tools such as mammography can reduces the cost of treatment management and the prognosis of the disease. The level of breast density of in mammogram is one of the potential cofounder factor for breast cancer risk. The development of mammary epithelial cells is determined by the genetic factor. Transforming growth factor-beta (TGF-ß) gene involves in the regulation of cell proliferation and cell division. This study aimed to assess the association of TGF-ß1 polymorphisms with breast density among women who underwent breast screening using mammogram. The detection of genotypes for three polymorphisms of TGF-ß1 assigned as rs1800469, rs1800470 and rs4803455 were performed using PCR-RFLP technique. The allele and genotype frequencies were calculated for control group that consists of BIRADS 1 and BIRADS 2 class whilst case group consisted of BIRADS 3 and BIRADS 4 class. Two polymorphisms (rs1800469 and rs1800470) yielded a significant association with breast density with p value of 0.004 and 0.003, respectively. However, the third polymorphism, rs4803455 did not yield a significant association (p value=0.090). Haplotype association analysis might suggest the haplotype GAA conferred susceptibility (p value= 0.02, OR=2.21[1.07-4.55]) rather than haplotype AAC predispose a protective effect (p value=0.004, OR=0.40[0.21-0.77]) to breast density development. This preliminary data on single and haplotype association might reveal the association of polymorphisms of TGF-ß1 with breast density and give an insight on the role of polymorphism in predisposing to breast density development

Multiple ITS Copies Reveal Extensive Hybridization within Rheum (Polygonaceae), a Genus That Has Undergone Rapid Radiation

During adaptive radiation events, characters can arise multiple times due to parallel evolution, but transfer of traits through hybridization provides an alternative explanation for the same character appearing in apparently non-sister lineages. The signature of hybridization can be detected in incongruence between phylogenies derived from different markers, or from the presence of two divergent versions of a nuclear marker such as ITS within one individual.In this study, we cloned and sequenced ITS regions for 30 species of the genus Rheum, and compared them with a cpDNA phylogeny. Seven species contained two divergent copies of ITS that resolved in different clades from one another in each case, indicating hybridization events too recent for concerted evolution to have homogenised the ITS sequences. Hybridization was also indicated in at least two further species via incongruence in their position between ITS and cpDNA phylogenies. None of the ITS sequences present in these nine species matched those detected in any other species, which provides tentative evidence against recent introgression as an explanation. Rheum globulosum, previously indicated by cpDNA to represent an independent origin of decumbent habit, is indicated by ITS to be part of clade of decumbent species, which acquired cpDNA of another clade via hybridization. However decumbent and glasshouse morphology are confirmed to have arisen three and two times, respectively.These findings suggested that hybridization among QTP species of Rheum has been extensive, and that a role of hybridization in diversification of Rheum requires investigation

Conscious monitoring and control (reinvestment) in surgical performance under pressure.

Research on intraoperative stressors has focused on external factors without considering individual differences in the ability to cope with stress. One individual difference that is implicated in adverse effects of stress on performance is "reinvestment," the propensity for conscious monitoring and control of movements. The aim of this study was to examine the impact of reinvestment on laparoscopic performance under time pressure

Evolution of Highly Pathogenic H5N1 Avian Influenza Viruses in Vietnam between 2001 and 2007

Highly pathogenic avian influenza (HPAI) H5N1 viruses have caused dramatic economic losses to the poultry industry of Vietnam and continue to pose a serious threat to public health. As of June 2008, Vietnam had reported nearly one third of worldwide laboratory confirmed human H5N1 infections. To better understand the emergence, spread and evolution of H5N1 in Vietnam we studied over 300 H5N1 avian influenza viruses isolated from Vietnam since their first detection in 2001. Our phylogenetic analyses indicated that six genetically distinct H5N1 viruses were introduced into Vietnam during the past seven years. The H5N1 lineage that evolved following the introduction in 2003 of the A/duck/Hong Kong/821/2002-like viruses, with clade 1 hemagglutinin (HA), continued to predominate in southern Vietnam as of May 2007. A virus with a clade 2.3.4 HA newly introduced into northern Vietnam in 2007, reassorted with pre-existing clade 1 viruses, resulting in the emergence of novel genotypes with neuraminidase (NA) and/or internal gene segments from clade 1 viruses. A total of nine distinct genotypes have been present in Vietnam since 2001, including five that were circulating in 2007. At least four of these genotypes appear to have originated in Vietnam and represent novel H5N1 viruses not reported elsewhere. Geographic and temporal analyses of H5N1 infection dynamics in poultry suggest that the majority of viruses containing new genes were first detected in northern Vietnam and subsequently spread to southern Vietnam after reassorting with pre-existing local viruses in northern Vietnam. Although the routes of entry and spread of H5N1 in Vietnam remain speculative, enhanced poultry import controls and virologic surveillance efforts may help curb the entry and spread of new HPAI viral genes

Histopathology of Growth Anomaly Affecting the Coral, Montipora capitata: Implications on Biological Functions and Population Viability

Growth anomalies (GAs) affect the coral, Montipora capitata, at Wai'ōpae, southeast Hawai'i Island. Our histopathological analysis of this disease revealed that the GA tissue undergoes changes which compromise anatomical machinery for biological functions such as defense, feeding, digestion, and reproduction. GA tissue exhibited significant reductions in density of ova (66.1–93.7%), symbiotic dinoflagellates (38.8–67.5%), mesenterial filaments (11.2–29.0%), and nematocytes (28.8–46.0%). Hyperplasia of the basal body wall but no abnormal levels of necrosis and algal or fungal invasion was found in GA tissue. Skeletal density along the basal body wall was significantly reduced in GAs compared to healthy or unaffected sections. The reductions in density of the above histological features in GA tissue were collated with disease severity data to quantify the impact of this disease at the colony and population level. Resulting calculations showed this disease reduces the fecundity of M. capitata colonies at Wai'ōpae by 0.7–49.6%, depending on GA severity, and the overall population fecundity by 2.41±0.29%. In sum, GA in this M. capitata population reduces the coral's critical biological functions and increases susceptibility to erosion, clearly defining itself as a disease and an ecological threat

Deriving a mutation index of carcinogenicity using protein structure and protein interfaces

With the advent of Next Generation Sequencing the identification of mutations in the genomes of healthy and diseased tissues has become commonplace. While much progress has been made to elucidate the aetiology of disease processes in cancer, the contributions to disease that many individual mutations make remain to be characterised and their downstream consequences on cancer phenotypes remain to be understood. Missense mutations commonly occur in cancers and their consequences remain challenging to predict. However, this knowledge is becoming more vital, for both assessing disease progression and for stratifying drug treatment regimes. Coupled with structural data, comprehensive genomic databases of mutations such as the 1000 Genomes project and COSMIC give an opportunity to investigate general principles of how cancer mutations disrupt proteins and their interactions at the molecular and network level. We describe a comprehensive comparison of cancer and neutral missense mutations; by combining features derived from structural and interface properties we have developed a carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with other methods, we observe that InCa can predict mutations that might not be detected by other methods. We also discuss general limitations shared by all predictors that attempt to predict driver mutations and discuss how this could impact high-throughput predictions. A web interface to a server implementation is publicly available at http://inca.icr.ac.uk/

Branch Mode Selection during Early Lung Development

Many organs of higher organisms, such as the vascular system, lung, kidney, pancreas, liver and glands, are heavily branched structures. The branching process during lung development has been studied in great detail and is remarkably stereotyped. The branched tree is generated by the sequential, non-random use of three geometrically simple modes of branching (domain branching, planar and orthogonal bifurcation). While many regulatory components and local interactions have been defined an integrated understanding of the regulatory network that controls the branching process is lacking. We have developed a deterministic, spatio-temporal differential-equation based model of the core signaling network that governs lung branching morphogenesis. The model focuses on the two key signaling factors that have been identified in experiments, fibroblast growth factor (FGF10) and sonic hedgehog (SHH) as well as the SHH receptor patched (Ptc). We show that the reported biochemical interactions give rise to a Schnakenberg-type Turing patterning mechanisms that allows us to reproduce experimental observations in wildtype and mutant mice. The kinetic parameters as well as the domain shape are based on experimental data where available. The developed model is robust to small absolute and large relative changes in the parameter values. At the same time there is a strong regulatory potential in that the switching between branching modes can be achieved by targeted changes in the parameter values. We note that the sequence of different branching events may also be the result of different growth speeds: fast growth triggers lateral branching while slow growth favours bifurcations in our model. We conclude that the FGF10-SHH-Ptc1 module is sufficient to generate pattern that correspond to the observed branching modesComment: Initially published at PLoS Comput Bio

Determinants of Glycan Receptor Specificity of H2N2 Influenza A Virus Hemagglutinin

The H2N2 subtype of influenza A virus was responsible for the Asian pandemic of 1957-58. However, unlike other subtypes that have caused pandemics such as H1N1 and H3N2, which continue to circulate among humans, H2N2 stopped circulating in the human population in 1968. Strains of H2 subtype still continue to circulate in birds and occasionally pigs and could be reintroduced into the human population through antigenic drift or shift. Such an event is a potential global health concern because of the waning population immunity to H2 hemagglutinin (HA). The first step in such a cross-species transmission and human adaptation of influenza A virus is the ability for its surface glycoprotein HA to bind to glycan receptors expressed in the human upper respiratory epithelia. Recent structural and biochemical studies have focused on understanding the glycan receptor binding specificity of the 1957-58 pandemic H2N2 HA. However, there has been considerable HA sequence divergence in the recent avian-adapted H2 strains from the pandemic H2N2 strain. Using a combination of structural modeling, quantitative glycan binding and human respiratory tissue binding methods, we systematically identify mutations in the HA from a recent avian-adapted H2N2 strain (A/Chicken/PA/2004) that make its quantitative glycan receptor binding affinity (defined using an apparent binding constant) comparable to that of a prototypic pandemic H2N2 (A/Albany/6/58) HA.National Institute of General Medical Sciences (U.S.) (GM57073)National Institute of General Medical Sciences (U.S.) (U54 GM62116)Singapore. Agency for Science, Technology and ResearchSingapore-MIT Alliance for Research and Technolog

Combined Analysis of all Three Phases of Solar Neutrino Data from the Sudbury Neutrino Observatory

We report results from a combined analysis of solar neutrino data from all phases of the Sudbury Neutrino Observatory. By exploiting particle identification information obtained from the proportional counters installed during the third phase, this analysis improved background rejection in that phase of the experiment. The combined analysis resulted in a total flux of active neutrino flavors from 8B decays in the Sun of (5.25 \pm 0.16(stat.)+0.11-0.13(syst.))\times10^6 cm^{-2}s^{-1}. A two-flavor neutrino oscillation analysis yielded \Deltam^2_{21} = (5.6^{+1.9}_{-1.4})\times10^{-5} eV^2 and tan^2{\theta}_{12}= 0.427^{+0.033}_{-0.029}. A three-flavor neutrino oscillation analysis combining this result with results of all other solar neutrino experiments and the KamLAND experiment yielded \Deltam^2_{21} = (7.41^{+0.21}_{-0.19})\times10^{-5} eV^2, tan^2{\theta}_{12} = 0.446^{+0.030}_{-0.029}, and sin^2{\theta}_{13} = (2.5^{+1.8}_{-1.5})\times10^{-2}. This implied an upper bound of sin^2{\theta}_{13} < 0.053 at the 95% confidence level (C.L.)

Tumor Blood Flow Differs between Mouse Strains: Consequences for Vasoresponse to Photodynamic Therapy

Fluctuations in tumor blood flow are common and attributed to factors such as vasomotion or local vascular structure, yet, because vessel structure and physiology are host-derived, animal strain of tumor propagation may further determine blood flow characteristics. In the present report, baseline and stress-altered tumor hemodynamics as a function of murine strain were studied using radiation-induced fibrosacomas (RIF) grown in C3H or nude mice. Fluctuations in tumor blood flow during one hour of baseline monitoring or during vascular stress induced by photodynamic therapy (PDT) were measured by diffuse correlation spectroscopy. Baseline monitoring revealed fluctuating tumor blood flow highly correlated with heart rate and with similar median periods (i.e., ∼9 and 14 min in C3H and nudes, respectively). However, tumor blood flow in C3H animals was more sensitive to physiologic or stress-induced perturbations. Specifically, PDT-induced vascular insults produced greater decreases in blood flow in the tumors of C3H versus nude mice; similarly, during baseline monitoring, fluctuations in blood flow were more regular and more prevalent within the tumors of C3H mice versus nude mice; finally, the vasoconstrictor L-NNA reduced tumor blood flow in C3H mice but did not affect tumor blood flow in nudes. Underlying differences in vascular structure, such as smaller tumor blood vessels in C3H versus nude animals, may contribute to strain-dependent variation in vascular function. These data thus identify clear effects of mouse strain on tumor hemodynamics with consequences to PDT and potentially other vascular-mediated therapies