Isoprenoids determine Th1/Th2 fate in pathogenic T cells, providing a mechanism of modulation of autoimmunity by atorvastatin.

3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is a critical enzyme in the mevalonate pathway that regulates the biosynthesis of cholesterol as well as isoprenoids that mediate the membrane association of certain GTPases. Blockade of this enzyme by atorvastatin (AT) inhibits the destructive proinflammatory T helper cell (Th)1 response during experimental autoimmune encephalomyelitis and may be beneficial in the treatment of multiple sclerosis and other Th1-mediated autoimmune diseases. Here we present evidence linking specific isoprenoid intermediates of the mevalonate pathway to signaling pathways that regulate T cell autoimmunity. We demonstrate that the isoprenoid geranylgeranyl-pyrophosphate (GGPP) mediates proliferation, whereas both GGPP and its precursor, farnesyl-PP, regulate the Th1 differentiation of myelin-reactive T cells. Depletion of these isoprenoid intermediates in vivo via oral AT administration hindered these T cell responses by decreasing geranylgeranylated RhoA and farnesylated Ras at the plasma membrane. This was associated with reduced extracellular signal-regulated kinase (ERK) and p38 phosphorylation and DNA binding of their cotarget c-fos in response to T cell receptor activation. Inhibition of ERK and p38 mimicked the effects of AT and induced a Th2 cytokine shift. Thus, by connecting isoprenoid availability to regulation of Th1/Th2 fate, we have elucidated a mechanism by which AT may suppress Th1-mediated central nervous system autoimmune disease

Exploring Strategies for Retaining Information Technology Professionals: A Case Study

In the 21st century, retaining information technology (IT) professionals is critical to a company\u27s productivity and overall success. Senior IT leaders need effective strategies to retain skilled IT professionals. Guided by the general systems theory and the transformational leadership theory, the purpose of this qualitative exploratory case study was to explore the retention strategies used by 2 senior IT leaders in Atlanta, Georgia to retain IT professionals. Semistructured interviews were employed to elicit detailed narratives from these IT leaders on their experiences in retaining IT professionals. A review of company documents, as well as member-checking of initial interview transcripts, helped to bolster the trustworthiness of final interpretations. Those final interpretations included 4 main themes: (a) job-related benefits and compensation; (b) people-related approaches such as promotion, rewards, and recognition; (c) management, organizational, and leadership essentials that include recruiting, hiring, and retaining employees; and (d) barriers, critical factors, and ineffective strategies affecting the retention of IT professionals. By implementing supportive management practice and encouraging employees to embrace the organization culture, company leaders can succeed in retaining key IT staff. These findings may influence social change by uncovering strategies to retain IT professionals within the company and help IT professionals understand leaders\u27 retention strategies

Biosecurity for today's swine operation

Original authors: Johnna S. Seaman and Thomas J. Fangman, Department of Veterinary Medicinestats202303upload"Disease control is one of the most challenging areas for producers and veterinarians in swine production. Biosecurity is often perceived as keeping diseases out of a swine herd. However, excluding disease from a herd is nearly impossible because of the natural presence of pathogens — the endemic pathogen load — in all swine herds. Therefore, the goal of a biosecurity program is to keep out pathogens that the herd has not been exposed to and to minimize the impact of endemic pathogens. With a good biosecurity program, optimal growth can be reached by minimizing the negative effects of subclinical illnesses. High reproductive performance can be achieved with a decrease of costly factors such as embryonic loss or preweaning mortality due to disease. This publication introduces key elements of an effective biosecurity program. A final plan can be developed in cooperation with your herd veterinarian to best accommodate constraints for a given operation."--First page.Reviewed by Marcia Carlson Shannon (Department of Animal Sciences). Original authors: Johnna S. Seaman and Thomas J. Fangman (Department of Veterinary Medicine

Single Channel Testing for Characterization of the Direct Gas Cooled Reactor and the SAFE‐100 Heat Exchanger

Experiments have been designed to characterize the coolant gas flow in two space reactor concepts that are currently under investigation by NASA Marshall Space Flight Center and Los Alamos National Laboratory: the direct‐drive gas‐cooled reactor (DDG) and the SAFE‐100 heatpipe‐cooled reactor (HPR). For the DDG concept, initial tests have been completed to measure pressure drop versus flow rate for a prototypic core flow channel, with gas exiting to atmospheric pressure conditions. The experimental results of the completed DDG tests presented in this paper validate the predicted results to within a reasonable margin of error. These tests have resulted in a re‐design of the flow annulus to reduce the pressure drop. Subsequent tests will be conducted with the re‐designed flow channel and with the outlet pressure held at 150 psi (1 MPa). Design of a similar test for a nominal flow channel in the HPR heat exchanger (HPR‐HX) has been completed and hardware is currently being assembled for testing this channel at 150 psi. When completed, these test programs will provide the data necessary to validate calculated flow performance for these reactor concepts (pressure drop and film temperature rise). © 2004 American Institute of PhysicsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87574/2/741_1.pd

Management and outcomes of traumatic hemothorax in children

Background: Adult guidelines for the management of traumatic hemothorax are well established; however, there have been no similar studies conducted in the pediatric population. The purpose of our study was to assess the management and outcomes of children with traumatic hemothorax. Materials and Methods: Following Institutional Review Board approval, we conducted a retrospective cross-sectional study of all trauma patients diagnosed with a hemothorax at a Level-1 pediatric trauma center from 2007 to 2012. Results: Forty-six children with hemothorax were identified, 23 from blunt mechanism and 23 from penetrating mechanism. The majority of children injured by penetrating mechanisms were treated with tube thoracostomy while the majority of blunt injury patients were observed (91.3% vs. 30.4% tube thoracostomy, penetrating vs. blunt, P = 0.00002). Among patients suffering from blunt mechanism, children who were managed with chest tubes had a greater volume of hemothorax than those who were observed. All children who were observed underwent serial chest radiographs demonstrating no progression and required no delayed procedures. Children with a hemothorax identified only by computed tomography, after negative plain radiograph, did not require intervention. No child developed a delayed empyema or fibrothorax. Conclusion: The data suggest that a small-volume hemothorax resulting from blunt mechanism may be safely observed without mandatory tube thoracostomy and with overall low complication rates

The tangled nomenclatural history of Haplopelia forbesi Salvadori, 1904 : Were Forbes and Robinson right all along?

Acknowledgements: Alex Bond (NHMUK) and Rachel Petts (Manchester Museum) provided information about the only other specimen known to have been identified as Haplopelia forbesi. We are grateful to Martim Melo and Luís Lima Valente for access to Hugo José Eira Pereira's M.Sc. thesis and information about recent Lemon Dove samples collected in the Gulf of Guinea. We are indebted to Peter Jones for invaluable comments on the manuscript. Robert Prŷs-Jones, Alan Tye and an anonymous reviewer provided very helpful suggestions on the submitted draft.Peer reviewedPublisher PD

IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord. It is considered a severe variant of multiple sclerosis (MS), and frequently is misdiagnosed as MS, but prognosis and optimal treatments differ. A serum immunoglobulin G autoantibody (NMO-IgG) serves as a specific marker for NMO. Here we show that NMO-IgG binds selectively to the aquaporin-4 water channel, a component of the dystroglycan protein complex located in astrocytic foot processes at the blood-brain barrier. NMO may represent the first example of a novel class of autoimmune channelopathy