109 research outputs found

    The Relationship Between Education and Police Stress : Associate Degree Versus Bachelor Degree

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    Research was conducted to further investigate whether police officers with Bachelor degrees experience less stress than officers with Associate degrees. Sixty police officers from the Charleston Police Department were the respondents in the study. The officers were measured regarding levels of stress experienced from inter-departmental issues, rule, and regulations. The respondents were also evaluated using the Fear of Negative Evaluation Scale, Job Satisfaction Index, and Stress Quiz. While there were no significant differences between the two groups, police officers with Bachelor degrees reported less stress than officers with Associate degrees

    Dominant Negative Effects by Inactive Spa47 Mutants Inhibit T3SS Function and Shigella Virulence

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    Type three secretion systems (T3SS) are complex nano-machines that evolved to inject bacterial effector proteins directly into the cytoplasm of eukaryotic cells. Many high-priority human pathogens rely on one or more T3SSs to cause disease and evade host immune responses, underscoring the need to better understand the mechanisms through which T3SSs function and their role(s) in supporting pathogen virulence. We recently identified the Shigella protein Spa47 as an oligomerization-activated T3SS ATPase that fuels the T3SS and supports overall Shigella virulence. Here, we provide both in vitro and in vivo characterization of Spa47 oligomerization and activation in the presence and absence of engineered ATPase-inactive Spa47 mutants. The findings describe mechanistic details of Spa47-catalyzed ATP hydrolysis and uncover critical distinctions between oligomerization mechanisms capable of supporting ATP hydrolysis in vitro and those that support T3SS function in vivo. Concentration-dependent ATPase kinetics and experiments combining wild-type and engineered ATPase inactive Spa47 mutants found that monomeric Spa47 species isolated from recombinant preparations exhibit low-level ATPase activity by forming short-lived oligomers with active site contributions from at least two protomers. In contrast, isolated Spa47 oligomers exhibit enhanced ATP hydrolysis rates that likely result from multiple preformed active sites within the oligomeric complex, as is predicted to occur within the context of the type three secretion system injectisome. High-resolution fluorescence microscopy, T3SS activity, and virulence phenotype analyses of Shigella strains co-expressing wild-type Spa47 and the ATPase inactive Spa47 mutants demonstrate that the N-terminus of Spa47, not ATPase activity, is responsible for incorporation into the injectisome where the mutant strains exhibit a dominant negative effect on T3SS function and Shigella virulence. Together, the findings presented here help to close a significant gap in our understanding of how T3SS ATPases are activated and define restraints with respect to how ATP hydrolysis is ultimately coupled to T3SS function in vivo

    Weight loss achieved using an energy restriction diet with normal or higher dietary protein decreased the number of CD14++CD16+ proinflammatory monocytes and plasma lipids and lipoproteins in middle-aged, overweight, and obese adults

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    Monocytes are involved in immune responses, and specific monocyte subpopulations (MS) that express intermediate to high levels of CD16 are associated with obesity and cardiovascular events. Consuming high protein (HP) when dieting improves body composition and cardiometabolic health outcomes, but whether HP affects MS during weight loss remains unknown. We assessed the effect of HP on energy restriction (ER)–induced changes in MS in overweight and obese adults. The relations between MS and plasma lipids and lipoproteins were also examined. We hypothesized that, independent of protein intake, ER-induced weight loss would decrease the numbers of MS and that MS and plasma lipids and lipoproteins would be related. Thirty-two adults (age 52 ± 1 years, body mass index 31.3 ± 0.5 kg/m2, means ± S.E.) consumed either a normal protein (n=18) or HP (n=14) (0.8 vs 1.5 g•kg−1•d−1 protein) ER diet (750-kcal/d [3138-kJ/d] deficit) for 16 weeks. The HP diet included 0.7 g•kg−1•d−1 of milk protein isolate. Fasting plasma lipids, lipoproteins, and the numbers of MS were analyzed. Over time, independent of protein intake, CD14++CD16+ cell number decreased, whereas CD14dimCD16++, CD14+CD16+, and CD14+CD16− cell numbers remained unchanged. CD14dimCD16++ cell number was negatively associated with total cholesterol (TC) and triglyceride, while CD14++CD16+ cell number was positively associated with TC, low-density lipoprotein cholesterol (LDL), TC to high-density lipoprotein cholesterol (HDL) ratio, and LDL to HDL ratio. Weight loss achieved while consuming an ER diet with either normal or high protein may improve immunity by partially decreasing proinflammatory monocytes. Associations between MS and plasma lipids and lipoproteins are confirmed in overweight and obese adults

    Does the worsening galactic cosmic radiation environment observed by CRaTER preclude future manned deep space exploration?

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    Abstract The Sun and its solar wind are currently exhibiting extremely low densities and magnetic field strengths, representing states that have never been observed during the space age. The highly abnormal solar activity between cycles 23 and 24 has caused the longest solar minimum in over 80 years and continues into the unusually small solar maximum of cycle 24. As a result of the remarkably weak solar activity, we have also observed the highest fluxes of galactic cosmic rays in the space age and relatively small solar energetic particle events. We use observations from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) on the Lunar Reconnaissance Orbiter to examine the implications of these highly unusual solar conditions for human space exploration. We show that while these conditions are not a show stopper for long-duration missions (e.g., to the Moon, an asteroid, or Mars), galactic cosmic ray radiation remains a significant and worsening factor that limits mission durations. While solar energetic particle events in cycle 24 present some hazard, the accumulated doses for astronauts behind 10 g/cm2 shielding are well below current dose limits. Galactic cosmic radiation presents a more significant challenge: the time to 3% risk of exposure-induced death (REID) in interplanetary space was less than 400 days for a 30 year old male and less than 300 days for a 30 year old female in the last cycle 23–24 minimum. The time to 3% REID is estimated to be ∼20% lower in the coming cycle 24–25 minimum. If the heliospheric magnetic field continues to weaken over time, as is likely, then allowable mission durations will decrease correspondingly. Thus, we estimate exposures in extreme solar minimum conditions and the corresponding effects on allowable durations

    TGF-β1 enhances cardiomyogenic differentiation of skeletal muscle-derived adult primitive cells

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    The optimal medium for cardiac differentiation of adult primitive cells remains to be established. We quantitatively compared the efficacy of IGF-1, dynorphin B, insulin, oxytocin, bFGF, and TGF-beta1 in inducing cardiomyogenic differentiation. Adult mouse skeletal muscle-derived Sca1+/CD45-/c-kit-/Thy-1+ (SM+) and Sca1-/CD45-/c-kit-/Thy-1+ (SM-) cells were cultured in basic medium (BM; DMEM, FBS, IGF-1, dynorphin B) alone and BM supplemented with insulin, oxytocin, bFGF, or TGF-beta1. Cardiac differentiation was evaluated by the expression of cardiac-specific markers at the mRNA (qRT-PCR) and protein (immunocytochemistry) levels. BM+TGF-beta1 upregulated mRNA expression of Nkx2.5 and GATA-4 after 4 days and Myl2 after 9 days. After 30 days, BM+TGF-beta1 induced the greatest extent of cardiac differentiation (by morphology and expression of cardiac markers) in SM- cells. We conclude that TGF-beta1 enhances cardiomyogenic differentiation in skeletal muscle-derived adult primitive cells. This strategy may be utilized to induce cardiac differentiation as well as to examine the cardiomyogenic potential of adult tissue-derived stem/progenitor cells

    Radiation environment at the Moon: Comparisons of transport code modeling and measurements from the CRaTER instrument

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    The Cosmic Ray Telescope for the Effects of Radiation (CRaTER), an instrument carried on the Lunar Reconnaissance Orbiter spacecraft, directly measures the energy depositions by solar and galactic cosmic radiations in its silicon wafer detectors. These energy depositions are converted to linear energy transfer (LET) spectra. High LET particles, which are mainly high‐energy heavy ions found in the incident cosmic ray spectrum, or target fragments and recoils produced by protons and heavier ions, are of particular importance because of their potential to cause significant damage to human tissue and electronic components. Aside from providing LET data useful for space radiation risk analyses for lunar missions, the observed LET spectra can also be used to help validate space radiation transport codes, used for shielding design and risk assessment applications, which is a major thrust of this work. In this work the Monte Carlo transport code HETC‐HEDS (High‐Energy Transport Code‐Human Exploration and Development in Space) is used to estimate LET contributions from the incident primary ions and their charged secondaries produced by nuclear collisions as they pass through the three pairs of silicon detectors. Also in this work, the contributions to the LET of the primary ions and their charged secondaries are analyzed and compared with estimates obtained using the deterministic space radiation code HZETRN 2010, developed at NASA Langley Research Center. LET estimates obtained from the two transport codes are compared with measurements of LET from the CRaTER instrument during the mission. Overall, a comparison of the LET predictions of the HETC‐HEDS code to the predictions of the HZETRN code displays good agreement. The code predictions are also in good agreement with the CRaTER LET measurements above 15 keV/µm but differ from the measurements for smaller values of LET. A possible reason for this disagreement between measured and calculated spectra below 15 keV/µm is an inadequate representation of the light ion spectra in HETC‐HEDS and HZETRN code calculations. It is also clear from the results of this work that Vavilov distributions need to be incorporated into the HETC‐HJEDS code before it will be able to recreate the observed LET spectra measured by the CRaTER instrument. Key Points Vavilov corrections should be incorporated into simulated results The predictions of the transport codes reasonably agree with the CRaTER LET The observed LET can be used to help validate space radiation transport codesPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108081/1/swe20145.pd

    A Pilot Study of Circulating Endothelial and Hematopoietic Progenitor Cells in Children With Sarcomas

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    Utilizing a multiparametric flow cytometry protocol, we assessed various cell types implicated in tumor angiogenesis that were found circulating in the peripheral blood of children with sarcomas (cases) based on their cell surface antigen expression. Circulating endothelial cells (CECs), endothelial colony-forming cells (ECFCs), and the ratio of 2 distinct populations of circulating hematopoietic stem and progenitor cells (CHSPCs), the proangiogenic CHSPCs (pCHSPCs) and nonangiogenic CHSPCs (nCHSPCs) were enumerated. Multiparametric flow cytometry was analyzed in cases at baseline and at 4 additional timepoints until the end of treatment and levels compared with each other and with healthy controls. At all timepoints, cases had significantly lower levels of CECs, but elevated ECFCs and a pCHSPC:nCHSPC ratio compared with controls (all P-values <0.05). There was no significant difference in any of the cell types analyzed based on tumor histology, stage (localized vs. metastatic), or tumor size. After treatment, only the CECs among the complete responders were significantly lower at end of therapy (P<0.01) compared with nonresponders, whereas the ECFCs among all cases significantly increased (P<0.05) compared with baseline. No decline in the pCHSPC:nCHSPC ratio was observed despite tumor response. On the basis of these results, a validation of CECs as prognostic biomarker is now warranted

    Neurofibromin is a novel regulator of Ras-induced reactive oxygen species production in mice and humans

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    Neurofibromatosis type 1 (NF1) predisposes individuals to early and debilitating cardiovascular disease. Loss of function mutations in the NF1 tumor suppressor gene, which encodes the protein neurofibromin, leads to accelerated p21(Ras) activity and phosphorylation of multiple downstream kinases, including Erk and Akt. Nf1 heterozygous (Nf1(+/-)) mice develop a robust neointima that mimics human disease. Monocytes/macrophages play a central role in NF1 arterial stenosis as Nf1 mutations in myeloid cells alone are sufficient to reproduce the enhanced neointima observed in Nf1(+/-) mice. Though the molecular mechanisms underlying NF1 arterial stenosis remain elusive, macrophages are important producers of reactive oxygen species (ROS) and Ras activity directly regulates ROS production. Here, we use compound mutant and lineage-restricted mice to demonstrate that Nf1(+/-) macrophages produce excessive ROS, which enhance Nf1(+/-) smooth muscle cell proliferation in vitro and in vivo. Further, use of a specific NADPH oxidase-2 inhibitor to limit ROS production prevents neointima formation in Nf1(+/-) mice. Finally, mononuclear cells from asymptomatic NF1 patients have increased oxidative DNA damage, an indicator of chronic exposure to oxidative stress. These data provide genetic and pharmacologic evidence that excessive exposure to oxidant species underlie NF1 arterial stenosis and provide a platform for designing novels therapies and interventions
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