Effect Of Homogenate From Different Oyster Species On Perkinsus Marinus Proliferation And Subtilisin Gene Transcription

The modulation of Perkinsus marinus proliferation and subtilisin gene transcription by host (oyster) tissue was examined. Perkinsus rnarinus cells were cultured for 4 weeks in media supplemented with extract from either one of four different Crassostrea virginica stocks or with extract from one of two other Crassostrea species, C. ariakensis and C. gigas. After 4 weeks in culture, we determined cell counts and relative subtilisin gene transcription levels using quantitative real-time polymerise chain reaction (qRTPCR). Cell proliferation and subtilisin gene transcription were significantly lower when P. marinus\u27 cells were grown in the presence of homogenate from any of the three oyster species than in unsupplemented media. Perkinstrs marinas subtilisin gene transcription was also significantly lower in cells cultured in media supplemented with homogenate from either C. ariakensis or C. gigas, than in media containing extract from the native oyster host, C. virginica. Gene transcription levels among cells grown in media supplemented with homogenate from the different stocks of C. virginica were not significantly different from one another

Direct activation of NADPH oxidase 2 by 2-deoxyribose-1-phosphate triggers nuclear factor kappa B-dependent angiogenesis.

AbstractAims: Deoxyribose-1-phosphate (dRP) is a proangiogenic paracrine stimulus released by cancer cells, platelets, and macrophages and acting on endothelial cells. The objective of this study was to clarify how dRP stimulates angiogenic responses in human endothelial cells.Results: Live cell imaging, electron paramagnetic resonance, pull-down of dRP-interacting proteins, followed by immunoblotting, gene silencing of different NADPH oxidases (NOXs), and their regulatory cosubunits by small interfering RNA (siRNA) transfection, and experiments with inhibitors of the sugar transporter glucose transporter 1 (GLUT1) were utilized to demonstrate that dRP acts intracellularly by directly activating the endothelial NOX2 complex, but not NOX4. Increased reactive oxygen species generation in response to NOX2 activity leads to redox-dependent activation of the transcription factor nuclear factor kappa B (NF-κB), which, in turn, induces vascular endothelial growth factor receptor 2 (VEGFR2) upregulation. Using endothelial tube formation assays, gene silencing by siRNA, and antibody-based receptor inhibition, we demonstrate that the activation of NF-κB and VEGFR2 is necessary for the angiogenic responses elicited by dRP. The upregulation of VEGFR2 and NOX2-dependent stimulation of angiogenesis by dRP were confirmed in excisional wound and Matrigel plug vascularization assays in vivo using NOX2−/− mice.Innovation: For the first time, we demonstrate that dRP acts intracellularly and stimulates superoxide anion generation by direct binding and activation of the NOX2 enzymatic complex.Conclusions: This study describes a novel molecular mechanism underlying the proangiogenic activity of dRP, which involves the sequential activation of NOX2 and NF-κB and upregulation of VEGFR2. Antioxid. Redox Signal. 28, 110–130

Dexamethasone serum concentrations after intravenous administration in horses during race training

Dexamethasone (DXM) sodium phosphate is a widely used corticosteroid for inflammatory conditions in horses, regulated in racing jurisdictions in the USA by a 0.005 ng/ml serum/plasma threshold. This study seeks to describe serum concentrations of DXM at 48 and 72 h after intravenous administration of 20 mg DXM sodium phosphate over 1 to 5 days, and to identify a possible source of DXM overages. 74 horses (39 Thoroughbreds, 13 Standardbreds, 22 Quarter Horses) in active race training received 20 mg DXM sodium phosphate. Serum was collected before injection, at 48 and 72 h post last injection, and analysed by LC/MS-MS (limit of quantification (LOQ) = 2.5 pg/ml). No differences were identified by ANOVA (P≤0.05) for racing breeds, age, gender or the number of days of DXM sodium phosphate administration, so data were pooled for each time point. The DXM serum concentration at 48 h (mean ± standard deviation, range) was 2.18±1.56 pg/ml (&&2.5 to 40 pg/ml). Summary statistics could not be derived for 72 h DXM serum concentration data owing to censored data, but ranged from &2.5 to 95.8 pg/ml. There was one extreme outlier (Tukey) at 48 h, and two extreme outliers at 72 h. A separate study was conducted using sedentary experimental horses to determine the likelihood that positive DXM samples could result from environmental transfer. Urine was collected from a mare 2 to 3 h post administration of 20 mg DXM. Hay with 100 ml of the DXM (17 ng/ml) containing urine was offered to each of six experimental horses and blood was collected at 0, 4, 8, 12, 16, 20 and 24 h. All six horses had plasma DXM concentration above the limit of detection and five of six had plasma DXM concentrations above the LOQ for at least one sample time

Hot topics, urgent priorities, and ensuring success for racial/ethnic minority young investigators in academic pediatrics.

BackgroundThe number of racial/ethnic minority children will exceed the number of white children in the USA by 2018. Although 38% of Americans are minorities, only 12% of pediatricians, 5% of medical-school faculty, and 3% of medical-school professors are minorities. Furthermore, only 5% of all R01 applications for National Institutes of Health grants are from African-American, Latino, and American Indian investigators. Prompted by the persistent lack of diversity in the pediatric and biomedical research workforces, the Academic Pediatric Association Research in Academic Pediatrics Initiative on Diversity (RAPID) was initiated in 2012. RAPID targets applicants who are members of an underrepresented minority group (URM), disabled, or from a socially, culturally, economically, or educationally disadvantaged background. The program, which consists of both a research project and career and leadership development activities, includes an annual career-development and leadership conference which is open to any resident, fellow, or junior faculty member from an URM, disabled, or disadvantaged background who is interested in a career in academic general pediatrics.MethodsAs part of the annual RAPID conference, a Hot Topic Session is held in which the young investigators spend several hours developing a list of hot topics on the most useful faculty and career-development issues. These hot topics are then posed in the form of six "burning questions" to the RAPID National Advisory Committee (comprised of accomplished, nationally recognized senior investigators who are seasoned mentors), the RAPID Director and Co-Director, and the keynote speaker.Results/conclusionsThe six compelling questions posed by the 10 young investigators-along with the responses of the senior conference leadership-provide a unique resource and "survival guide" for ensuring the academic success and optimal career development of young investigators in academic pediatrics from diverse backgrounds. A rich conversation ensued on the topics addressed, consisting of negotiating for protected research time, career trajectories as academic institutions move away from an emphasis on tenure-track positions, how "non-academic" products fit into career development, racism and discrimination in academic medicine and how to address them, coping with isolation as a minority faculty member, and how best to mentor the next generation of academic physicians

KLF9 and JNK3 Interact to Suppress Axon Regeneration in the Adult CNS

Neurons in the adult mammalian CNS decrease in intrinsic axon growth capacity during development in concert with changes in Krüppel-like transcription factors (KLFs). KLFs regulate axon growth in CNS neurons including retinal ganglion cells (RGCs). Here, we found that knock-down of KLF9, an axon growth suppressor that is normally upregulated 250-fold in RGC development, promotes long-distance optic nerve regeneration in adult rats of both sexes. We identified a novel binding partner, MAPK10/JNK3 kinase, and found that JNK3 (c-Jun N-terminal kinase 3) is critical for KLF9\u27s axon-growth-suppressive activity. Interfering with a JNK3-binding domain or mutating two newly discovered serine phosphorylation acceptor sites, Ser106 and Ser110, effectively abolished KLF9\u27s neurite growth suppression in vitro and promoted axon regeneration in vivo. These findings demonstrate a novel, physiologic role for the interaction of KLF9 and JNK3 in regenerative failure in the optic nerve and suggest new therapeutic strategies to promote axon regeneration in the adult CNS

Efficacy and safety of simeprevir and sofosbuvir with and without ribavirin in subjects with recurrent genotype 1 hepatitis C postorthotopic liver transplant: the randomized GALAXY study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136282/1/tri12896.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136282/2/tri12896_am.pd

Crossâ Network Directory Service: Infrastructure to enable collaborations across distributed research networks

IntroductionExisting largeâ scale distributed health data networks are disconnected even as they address related questions of healthcare research and public policy. This paper describes the design and implementation of a fully functional prototype openâ source tool, the Crossâ Network Directory Service (CNDS), which addresses much of what keeps distributed networks disconnected from each other.MethodsThe set of services needed to implement a Crossâ Directory Service was identified through engagement with stakeholders and workgroup members. CNDS was implemented using PCORnet and Sentinel network instances and tested by participating data partners.ResultsWeb services that enable the four major functional features of the service (registration, discovery, communication, and governance) were developed and placed into an openâ source repository. The services include a robust metadata model that is extensible to accommodate a virtually unlimited inventory of metadata fields, without requiring any further software development. The user interfaces are programmatically generated based on the contents of the metadata model.ConclusionThe CNDS pilot project gathered functional requirements from stakeholders and collaborating partners to build a software application to enable crossâ network data and resource sharing. The two partnersâ one from Sentinel and one from PCORnetâ tested the software. They successfully entered metadata about their organizations and data sources and then used the Discovery and Communication functionality to find data sources of interest and send a crossâ network query. The CNDS software can help integrate disparate health data networks by providing a mechanism for data partners to participate in multiple networks, share resources, and seamlessly send queries across those networks.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149237/1/lrh210187.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149237/2/lrh210187_am.pd

Cross-Species Array Comparative Genomic Hybridization Identifies Novel Oncogenic Events in Zebrafish and Human Embryonal Rhabdomyosarcoma

Human cancer genomes are highly complex, making it challenging to identify specific drivers of cancer growth, progression, and tumor maintenance. To bypass this obstacle, we have applied array comparative genomic hybridization (array CGH) to zebrafish embryonal rhabdomyosaroma (ERMS) and utilized cross-species comparison to rapidly identify genomic copy number aberrations and novel candidate oncogenes in human disease. Zebrafish ERMS contain small, focal regions of low-copy amplification. These same regions were commonly amplified in human disease. For example, 16 of 19 chromosomal gains identified in zebrafish ERMS also exhibited focal, low-copy gains in human disease. Genes found in amplified genomic regions were assessed for functional roles in promoting continued tumor growth in human and zebrafish ERMS – identifying critical genes associated with tumor maintenance. Knockdown studies identified important roles for Cyclin D2 (CCND2), Homeobox Protein C6 (HOXC6) and PlexinA1 (PLXNA1) in human ERMS cell proliferation. PLXNA1 knockdown also enhanced differentiation, reduced migration, and altered anchorage-independent growth. By contrast, chemical inhibition of vascular endothelial growth factor (VEGF) signaling reduced angiogenesis and tumor size in ERMS-bearing zebrafish. Importantly, VEGFA expression correlated with poor clinical outcome in patients with ERMS, implicating inhibitors of the VEGF pathway as a promising therapy for improving patient survival. Our results demonstrate the utility of array CGH and cross-species comparisons to identify candidate oncogenes essential for the pathogenesis of human cancer

The Vehicle, Fall 1996

Vol. 38, No. 1 Table of Contents DarcyMichael Maypage 1 Time in TimeJoe Howardpage 2 Sestina for DyingAmy Haynespage 3 VioletsSandra Beauchamppage 5 Melody\u27s SongSandra Beauchamppage 7 A Spinning Top ContemplationThomas T. Brownpage 10 Lady of the NightShari Grierpage 13 The Difference Between a Hand and a Killing JarJason S. Loguepage 14 The Bat I KilledMichael Maypage 15 UntitledKimberly Mannypage 16 ReleaseKimberly Mannypage 17 Fountain in the RainEric Chisauskypage 18 War, the Old Fashioned WayCarmella Cosenzapage 19 AloneCarmella Cosenzapage 20 MotelMichael Maypage 21 UntitledAndrea Traxlerpage 22 UntitledMichael Maypage 23 From Across the CourtyardShannon Goodallpage 24 CommunionShannon Goodallpage 26 Please Come HomeKendall W. Baumannpage 27 UntitledMichael Maypage 29 Indefinite SacrificeAmanda Watsonpage 30 Recovery RoomAbby Kollerpage 31 Questioning FaithMichael Kawapage 31 MerulaMichael Maypage 32 Biographiespage 33https://thekeep.eiu.edu/vehicle/1066/thumbnail.jp