Knowledge Discovery in Biological Databases for Revealing Candidate Genes Linked to Complex Phenotypes

Genetics and “omics” studies designed to uncover genotype to phenotype relationships often identify large numbers of potential candidate genes, among which the causal genes are hidden. Scientists generally lack the time and technical expertise to review all relevant information available from the literature, from key model species and from a potentially wide range of related biological databases in a variety of data formats with variable quality and coverage. Computational tools are needed for the integration and evaluation of heterogeneous information in order to prioritise candidate genes and components of interaction networks that, if perturbed through potential interventions, have a positive impact on the biological outcome in the whole organism without producing negative side effects. Here we review several bioinformatics tools and databases that play an important role in biological knowledge discovery and candidate gene prioritization. We conclude with several key challenges that need to be addressed in order to facilitate biological knowledge discovery in the future.&nbsp

Impaired M3 and enhanced M2 muscarinic receptor contractile function in a streptozotocin model of mouse diabetic urinary bladder

We investigated the contractile roles of M2 and M3 muscarinic receptors in urinary bladder from streptozotocin-treated mice. Wild-type and M2 muscarinic receptor knockout (M2 KO) mice were given a single injection of vehicle or streptozotocin (125 mg kg−1) 2–24 weeks prior to bladder assays. The effect of forskolin on contractions elicited to the muscarinic agonist, oxotremorine-M, was measured in isolated urinary bladder (intact or denuded of urothelium). Denuded urinary bladder from vehicle-treated wild-type and M2 KO mice exhibited similar contractile responses to oxotremorine-M, when contraction was normalized relative to that elicited by KCl (50 mM). Eight to 9 weeks after streptozotocin treatment, the EC50 value of oxotremorine-M increased 3.1-fold in urinary bladder from the M2 KO mouse (N = 5) compared to wild type (N = 6; P < 0.001). Analogous changes were observed in intact bladder. In denuded urinary bladder from vehicle-treated mice, forskolin (5 µM) caused a much greater inhibition of contraction in M2 KO bladder compared to wild type. Following streptozotocin treatment, this forskolin effect increased 1.6-fold (P = 0.032). At the 20- to 24-week time point, the forskolin effect increased 1.7-fold for denuded as well as intact bladders (P = 0.036, 0.01, respectively). Although streptozotocin treatment inhibits M3 receptor-mediated contraction in denuded urinary bladder, muscarinic contractile function is maintained in wild-type bladder by enhanced M2 contractile function. M2 receptor activation opposes forskolin-induced relaxation of the urinary bladder, and this M2 function is enhanced following streptozotocin treatment

Azimuthal anisotropy: transition from hydrodynamic flow to jet suppression

Measured 2nd and 4th azimuthal anisotropy coefficients v_{2,4}(N_{part}), p_T) are scaled with the initial eccentricity \varepsilon_{2,4}(N_{part}) of the collision zone and studied as a function of the number of participants N_{part} and the transverse momenta p_T. Scaling violations are observed for p_T \alt 3 GeV/c, consistent with a $p_T^2$ dependence of viscous corrections and a linear increase of the relaxation time with $p_T$. These empirical viscous corrections to flow and the thermal distribution function at freeze-out constrain estimates of the specific viscosity and the freeze-out temperature for two different models for the initial collision geometry. The apparent viscous corrections exhibit a sharp maximum for p_T \agt 3 GeV/c, suggesting a breakdown of the hydrodynamic ansatz and the onset of a change from flow-driven to suppression-driven anisotropy.Comment: 5 pages, 4 figs; submitted for publicatio

Moisture increase in response to high-altitude warming evidenced by tree-rings on the southeastern Tibetan Plateau

Rapid warming has been observed in the high-altitude areas around the globe, but the implications on moisture change are not fully understood. Here we use tree-rings to reveal common moisture change on the southeastern Tibetan Plateau (TP) during the past five centuries, and show that regional moisture change in late spring to early summer (April–June) is closely related to large-scale temperature anomaly over the TP, with increased moisture coincident with periods of high temperature. The most recent pluvial during the 1990s–2000s is likely the wettest for the past five centuries, which coincides with the warmest period on the TP during the past millennium. Dynamic analysis reveals that vertical air convection is enhanced in response to anomalous TP surface warming, leading to an increase in lower-tropospheric humidity and effective precipitation over the southeastern TP. The coherent warm-wet relationship identified in both tree-rings and dynamic analysis implies a generally wetter condition on the southeastern TP under future warming.postprin

Unparticle physics in top pair signals at the LHC and ILC

We study the effects of unparticle physics in the pair productions of top quarks at the LHC and ILC. By considering vector, tensor and scalar unparticle operators, as appropriate, we compute the total cross sections for pair production processes depending on scale dimension d_{\U}. We find that the existence of unparticles would lead to measurable enhancements on the SM predictions at the LHC. In the case of ILC this may become two orders of magnitude larger than that of SM, for smaller values of d_\U, a very striking signal for unparticles.Comment: 19 pages, 9 figures, analysis for ILC has been adde

Hydrodynamic Description of Granular Convection

We present a hydrodynamic model that captures the essence of granular dynamics in a vibrating bed. We carry out the linear stability analysis and uncover the instability mechanism that leads to the appearance of the convective rolls via a supercritical bifurcation of a bouncing solution. We also explicitly determine the onset of convection as a function of control parameters and confirm our picture by numerical simulations of the continuum equations.Comment: 14 pages, RevTex 11pages + 3 pages figures (Type csh

Equation of state of asymmetric nuclear matter and collisions of neutron-rich nuclei

The ratio of pre-equilibrium neutrons to protons from collisions of neutron-rich nuclei is studied as a function of their kinetic energies. This ratio is found to be sensitive to the density dependence of the nuclear symmetry energy, but is independent of the compressibility of symmetric nuclear matter and the in-medium nucleon-nucleon cross sections. The experimental measurement of this ratio thus provides a novel means for determining the nuclear equation of state of asymmetric nuclear matter.Comment: 11 pages + 3 postscript figures, Phys. Rev. Lett. (1997) in pres