Mapping the Cellular Response to Small Molecules Using Chemogenomic Fitness Signatures

Genome-wide characterization of the in vivo cellular response to perturbation is fundamental to understanding how cells survive stress. Identifying the proteins and pathways perturbed by small molecules affects biology and medicine by revealing the mechanisms of drug action. We used a yeast chemogenomics platform that quantifies the requirement for each gene for resistance to a compound in vivo to profile 3250 small molecules in a systematic and unbiased manner. We identified 317 compounds that specifically perturb the function of 121 genes and characterized the mechanism of specific compounds. Global analysis revealed that the cellular response to small molecules is limited and described by a network of 45 major chemogenomic signatures. Our results provide a resource for the discovery of functional interactions among genes, chemicals, and biological processes

The Relationship between Work Related Injury and Participation in Exercise and Recreational Activities

Background/Purpose: The cost of health care is on the rise for both employers and employees. Research has shown that exercise in any capacity will improve overall health and fitness levels. Limited research has shown that proper exercise can lead to a decrease in musculoskeletal injuries. With the number of musculoskeletal injuries occurring in the workplace at high levels, establishing a connection between injury reduction and exercise is imperative. The purpose of this study was to determine if there is a relationship between participation in exercise and recreational activities and injury in the workplace. Methods: A random stratified sample of 396 persons was provided by the University of North Dakota payroll department, representing 20% of the university population. Surveys were sent out and 177 surveys were returned, which represented a 45% return rate. The survey included demographic data, work injury information, and exercise history information. Information of the 177 surveys was analyzed using the Statistical Package for the Social Sciences (SPSS) 11.0 program. Results: No significant difference was found between work injury and exercise {)(-1{1, n = 177) = .135, p\u3e .05). A significant relationship was found when comparing injury to cardiovascular RPE {)(-1{8, n = 137) = 16.188, P = .04). Discussion/Conclusion: Given the documented benefits of exercise and its relation to overall wellness, the assumption could be made that exercise and recreational activities would reduce the incidence of work injury. However, the results of this study did not meet that assumption. Future research needs to be done to expand on this area. The information collected from this research may be beneficial to the UNO Well ness Center, UNO Department of Physical Therapy, and the UNO Safety and Environmental Health Office

Development of polymorphic microsatellite markers of the Seychelles endemic tree Glionnetia sericea (Rubiaceae)

Glionnetia sericea (Rubiaceae) is an endemic and rare tree species of the Seychelles, restricted to altitudes between 500 and 900m with less than 1,000 remaining individuals. It survives in mist forests but also in smaller populations on granitic outcrops (inselbergs) and is pollinated by hawk moths which might ensure long-distance pollen flow. Understanding the reproductive ecology of this species will allow a better understanding on how such species survive in naturally fragmented habitats and will provide scientifically informed management recommendations. Here we report on ten species specific polymorphic microsatellite loci developed for a study of historic and contemporary gene flow. Based upon a sample of 81 adults, the number of alleles per locus ranged from 3 to 12 (mean of 6.1 per locus) with an average polymorphic information content of 0.52 across loci. Expected heterozygosity ranged from 0.27 to 0.82 with two of ten primers showing some deviation from Hardy-Weinberg expectatio

LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway

LST8, a Saccharomyces cerevisiae gene encoding a 34-kD WD-repeat protein, was identified by mutations that caused defects in sorting Gap1p to the plasma membrane. Here, we report that the Gap1p sorting defect in the lst8-1 mutant results from derepression of Rtg1/3p activity and the subsequent accumulation of high levels of intracellular amino acids, which signal Gap1p sorting to the vacuole. To identify the essential function of Lst8p, we isolated lst8 mutants that are temperature-sensitive for growth. These mutants show hypersensitivity to rapamycin and derepressed Gln3p activity like cells with compromised TOR pathway activity. Like tor2 mutants, lst8 mutants also have cell wall integrity defects. Confirming a role for Lst8p in the TOR pathway, we find that Lst8p associates with both Tor1p and Tor2p and is a peripheral membrane protein that localizes to endosomal or Golgi membranes and cofractionates with Tor1p. Further, we show that a sublethal concentration of rapamycin mimics the Gap1p sorting defect of an lst8 mutant. Finally, the different effects of lst8 alleles on the activation of either the Rtg1/3p or Gln3p transcription factors reveal that these two pathways constitute distinct, genetically separable outputs of the Tor–Lst8 regulatory complex

The Impact of Boko Haram Insurgency on the People of Borno State

Although researchers have examined the causes and impacts of terrorism in Nigeria, there is no known research on the impact of Boko Haram’s insurgency on the people of Borno State based on their lived experiences. The purpose of this qualitative study was to examine the social, political, and economic consequences of the Boko Haram insurgency on the people of Borno State. The study’s theoretical framework was based on the relative deprivation theory; the theory was used to diagnose the problem of the Boko Haram insurgency and articulate possible alternative solutions. The central research question concerned the adverse effects of the Boko Haram insurgency on the people of Borno State. Data for this study were primarily collected through face-to-face interviews with a purposeful sample of 10 participants who were exposed to the Boko Haram insurgency in Nigeria. A focus group discussion and document review were also conducted. Content analysis of collected data yielded 3 themes: (a) collapse of Borno State’s social, economic, and political structures and processes; (b) undesirable/negative implications of insurgency on Borno State’s corporate well-being; and (c) adapting to reality: coping with available relief services and programs. Implications for positive social change include giving voice to voiceless Nigerians and providing the Nigerian populace, multilateral and bilateral organizations, and the Nigerian government with information necessary to understand the effects of terrorism on the people of Borno State and promote resilience in the people who have experienced terrorism

The Flux Auto- and Cross-Correlation of the Lyman-alpha Forest. II. Modelling Anisotropies with Cosmological Hydrodynamic Simulations

The isotropy of the Lyman-alpha forest in real-space uniquely provides a measurement of cosmic geometry at z > 2. The angular diameter distance for which the correlation function along the line of sight and in the transverse direction agree corresponds to the correct cosmological model. However, the Lyman-alpha forest is observed in redshift-space where distortions due to Hubble expansion, bulk flows, and thermal broadening introduce anisotropy. Similarly, a spectrograph's line spread function affects the autocorrelation and cross-correlation differently. In this the second paper of a series on using the Lyman-alpha forest observed in pairs of QSOs for a new application of the Alcock-Paczynski (AP) test, these anisotropies and related sources of potential systematic error are investigated with cosmological hydrodynamic simulations. Three prescriptions for galactic outflow were compared and found to have only a marginal effect on the Lyman-alpha flux correlation (which changed by at most 7% with use of the currently favored variable-momentum wind model vs. no winds at all). An approximate solution for obtaining the zero-lag cross-correlation corresponding to arbitrary spectral resolution directly from the zero-lag cross-correlation computed at full-resolution (good to within 2% at the scales of interest) is presented. Uncertainty in the observationally determined mean flux decrement of the Lyman-alpha forest was found to be the dominant source of systematic error; however, this is reduced significantly when considering correlation ratios. We describe a simple scheme for implementing our results, while mitigating systematic errors, in the context of a future application of the AP test.Comment: 20 page

Strategic Operations Research and the Edelman Prize Finalist Applications 1989-1998

In an earlier study we examined the available evidence on the Edelman Prize finalist applications 1989-1998. This study concluded that 13 of the 42 private sector applications provide examples of strategic operations research (SOR) when SOR is defined as operations research that creates a sustainable competitive advantage. In a follow-up study we tested our classifications, gathering longitudinal information on the continued success of the Edelman applications. We contacted people who were familiar with all the private sector applications that were Edelman finalists 1989-1996 and had at least five years of history since the competition. We describe the post-Edelman history of these applications and use this data to reassess their strategic role. We found that the longitudinal data provides evidence to support our original classification, but also suggests that several additional applications were more strategic than was originally apparent. We conclude that almost 60% (20 of 34) of these applications created a sustainable competitive advantage for their firms and provide examples of SOR

Redox signaling via the molecular chaperone BiP protects cells against endoplasmic reticulum-derived oxidative stress

Oxidative protein folding in the endoplasmic reticulum (ER) has emerged as a potentially significant source of cellular reactive oxygen species (ROS). Recent studies suggest that levels of ROS generated as a byproduct of oxidative folding rival those produced by mitochondrial respiration. Mechanisms that protect cells against oxidant accumulation within the ER have begun to be elucidated yet many questions still remain regarding how cells prevent oxidant-induced damage from ER folding events. Here we report a new role for a central well-characterized player in ER homeostasis as a direct sensor of ER redox imbalance. Specifically we show that a conserved cysteine in the lumenal chaperone BiP is susceptible to oxidation by peroxide, and we demonstrate that oxidation of this conserved cysteine disrupts BiP's ATPase cycle. We propose that alteration of BiP activity upon oxidation helps cells cope with disruption to oxidative folding within the ER during oxidative stress.Cornell UniversityNational Institutes of Health (U.S.) (Grant GM46941

Development of thirteen polymorphic microsatellite markers for the Seychelles endangered and endemic jellyfish tree Medusagyne oppositifolia (Medusagynaceae)

The jellyfish tree Medusagyne oppositifolia is a flagship species of the Seychelles, being not only extremely rare and critically endangered, but also representing a monospecific endemic family, Medusagynaceae. The species survives in four populations on the Island of Mahé, where the total number of reproductive adults is 89. Natural regeneration is only known for the largest of these populations. Understanding the mechanisms driving the lack of natural regeneration in this species has great conservation relevance. We developed thirteen polymorphic microsatellite loci for this species to enable studies of historic and contemporary gene flow. The number of alleles per locus ranged from 2 to 15 (mean of 6.62 per locus) with an average polymorphic information content of 0.54 across loci. Expected heterozygosity ranged from 0.12 to 0.66 with only two of the 13 loci showing deviation from Hardy-Weinberg expectation. The markers will help to provide a better understanding of the significance of historic distributions, gene flow and recent anthropogenic habitat degradation for the in situ and ex-situ conservation of this flagship tree specie