A Suppressor/Enhancer Screen in Drosophila Reveals a Role for Wnt-Mediated Lipid Metabolism in Primordial Germ Cell Migration

Wnt proteins comprise a large family of secreted ligands implicated in a wide variety of biological roles. WntD has previously been shown to inhibit the nuclear accumulation of Dorsal/NF-κB protein during embryonic dorsal/ventral patterning and the adult innate immune response, independent of the well-studied Armadillo/β-catenin pathway. In this paper, we present a novel phenotype for WntD mutant embryos, suggesting that this gene is involved in migration of primordial germ cells (PGC) to the embryonic gonad. Additionally, we describe a genetic suppressor/enhancer screen aimed at identifying genes required for WntD signal transduction, based on the previous observation that maternal overexpression of WntD results in lethally dorsalized embryos. Using an algorithm to narrow down our hits from the screen, we found two novel WntD signaling components: Fz4, a member of the Frizzled family, and the Drosophila Ceramide Kinase homolog, Dcerk. We show here that Dcerk and Dmulk (Drosophila Multi-substrate lipid kinase) redundantly mediate PGC migration. Our data are consistent with a model in which the activity of lipid phosphate phosphatases shapes a concentration gradient of ceramide-1-phosphate (C1P), the product of Dcerk, allowing proper PGC migration

Prevalence of hepatic iron overload and association with hepatocellular cancer in end-stage liver disease: results from the National Hemochromatosis Transplant Registry

Background : It is unclear whether mild to moderate iron overload in liver diseases other than hereditary haemochromatosis (HH) contributes to hepatocellular carcinoma. This study examined the association between hepatic iron grade and hepatocellular carcinoma in patients with end-stage liver disease of diverse aetiologies. Methods : The prevalence of hepatic iron overload and hepatocellular carcinoma was examined in 5224 patients undergoing liver transplantation. Explant pathology reports were reviewed for the underlying pathological diagnosis, presence of hepatocellular carcinoma and degree of iron staining. The distribution of categorical variables was studied using Χ 2 tests. Results : Both iron overload and hepatocellular carcinoma were the least common with biliary cirrhosis (1.8 and 2.8% respectively). Hepatocellular carcinoma was the most common in patients with hepatitis B (16.7%), followed by those with hepatitis C (15.1%) and HH (14.9%). In the overall cohort, any iron overload was significantly associated with hepatocellular carcinoma ( P =0.001), even after adjustment for the underlying aetiology of liver disease. The association between hepatic iron content and hepatocellular carcinoma was the strongest in patients with biliary cirrhosis ( P <0.001) and hepatitis C ( P <0.001). Conclusions : Iron overload is associated with hepatocellular carcinoma in patients with end-stage liver disease, suggesting a possible carcinogenic or cocarcinogenic role for iron in chronic liver disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75573/1/j.1478-3231.2007.01596.x.pd

OPENMENDEL: A Cooperative Programming Project for Statistical Genetics

Statistical methods for genomewide association studies (GWAS) continue to improve. However, the increasing volume and variety of genetic and genomic data make computational speed and ease of data manipulation mandatory in future software. In our view, a collaborative effort of statistical geneticists is required to develop open source software targeted to genetic epidemiology. Our attempt to meet this need is called the OPENMENDELproject (https://openmendel.github.io). It aims to (1) enable interactive and reproducible analyses with informative intermediate results, (2) scale to big data analytics, (3) embrace parallel and distributed computing, (4) adapt to rapid hardware evolution, (5) allow cloud computing, (6) allow integration of varied genetic data types, and (7) foster easy communication between clinicians, geneticists, statisticians, and computer scientists. This article reviews and makes recommendations to the genetic epidemiology community in the context of the OPENMENDEL project.Comment: 16 pages, 2 figures, 2 table

How and When Socially Entrepreneurial Nonprofit Organizations Benefit From Adopting Social Alliance Management Routines to Manage Social Alliances?

Social alliance is defined as the collaboration between for-profit and nonprofit organizations. Building on the insights derived from the resource-based theory, we develop a conceptual framework to explain how socially entrepreneurial nonprofit organizations (SENPOs) can improve their social alliance performance by adopting strategic alliance management routines. We test our framework using the data collected from 203 UK-based SENPOs in the context of cause-related marketing campaign-derived social alliances. Our results confirm a positive relationship between social alliance management routines and social alliance performance. We also find that relational mechanisms, such as mutual trust, relational embeddedness, and relational commitment, mediate the relationship between social alliance management routines and social alliance performance. Moreover, our findings suggest that different types of social alliance motivation can influence the impact of social alliance management routines on different types of the relational mechanisms. In general, we demonstrate that SENPOs can benefit from adopting social alliance management routines and, in addition, highlight how and when the social alliance management routines–social alliance performance relationship might be shaped. Our study offers important academic and managerial implications, and points out future research directions

Search for Squarks and Gluinos in Events Containing Jets and a Large Imbalance in Transverse Energy

Using data corresponding to an integrated luminosity of 79 pb-1, D0 has searched for events containing multiple jets and large missing transverse energy in pbar-p collisions at sqrt(s)=1.8 TeV at the Fermilab Tevatron collider. Observing no significant excess beyond what is expected from the standard model, we set limits on the masses of squarks and gluinos and on the model parameters m_0 and m_1/2, in the framework of the minimal low-energy supergravity models of supersymmetry. For tan(beta) = 2 and A_0 = 0, with mu < 0, we exclude all models with m_squark < 250 GeV/c^2. For models with equal squark and gluino masses, we exclude m < 260 GeV/c^2.Comment: 10 pages, 3 figures, Submitted to PRL, Fixed typo on page bottom of p. 6 (QCD multijet background is 35.4 events

A measurement of the W boson mass using large rapidity electrons

We present a measurement of the W boson mass using data collected by the D0 experiment at the Fermilab Tevatron during 1994--1995. We identify W bosons by their decays to e-nu final states where the electron is detected in a forward calorimeter. We extract the W boson mass, Mw, by fitting the transverse mass and transverse electron and neutrino momentum spectra from a sample of 11,089 W -> e nu decay candidates. We use a sample of 1,687 dielectron events, mostly due to Z -> ee decays, to constrain our model of the detector response. Using the forward calorimeter data, we measure Mw = 80.691 +- 0.227 GeV. Combining the forward calorimeter measurements with our previously published central calorimeter results, we obtain Mw = 80.482 +- 0.091 GeV

Probing BFKL Dynamics in the Dijet Cross Section at Large Rapidity Intervals in ppbar Collisions at sqrt{s}=1800 and 630 GeV

Inclusive dijet production at large pseudorapidity intervals (delta_eta) between the two jets has been suggested as a regime for observing BFKL dynamics. We have measured the dijet cross section for large delta_eta in ppbar collisions at sqrt{s}=1800 and 630 GeV using the DO detector. The partonic cross section increases strongly with the size of delta_eta. The observed growth is even stronger than expected on the basis of BFKL resummation in the leading logarithmic approximation. The growth of the partonic cross section can be accommodated with an effective BFKL intercept of a_{BFKL}(20GeV)=1.65+/-0.07.Comment: Published in Physical Review Letter

Search for bottom squarks in pbarp collisions at sqrt(s)=1.8 TeV

We report on a search for bottom squarks produced in pbarp collisions at sqrt(s) = 1.8 TeV using the D0 detector at Fermilab. Bottom squarks are assumed to be produced in pairs and to decay to the lightest supersymmetric particle (LSP) and a b quark with branching fraction of 100%. The LSP is assumed to be the lightest neutralino and stable. We set limits on the production cross section as a function of bottom squark mass and LSP mass.Comment: 5 pages, Latex. submitted 3-12-1999 to PRD - Rapid Communicatio

Search for Charged Higgs Bosons in Decays of Top Quark Pairs

We present a search for charged Higgs bosons in decays of pair-produced top quarks using 109.2 +- 5.8 pb^-1 of data recorded from ppbar collisions at sqrt{s} = 1.8 TeV by the D0 detector during 1992-96 at the Fermilab Tevatron. No evidence is found for charged Higgs production, and most parts of the [m(H+),tan(beta)] parameter space where the decay t -> bH+ has a branching fraction close to or larger than that for t -> bW+ are excluded at 95% confidence level. Assuming m(t) = 175 GeV and sigma(ppbar -> ttbar) = 5.5 pb, for m(H+) = 60 GeV, we exclude tan(beta) 40.9.Comment: 11 pages, 3 figures, submitted to PR