North American Approaches to Regulatory Coordination

Industrial Organization,

Self-renewal of single mouse hematopoietic stem cells is reduced by JAK2V617F without compromising progenitor cell expansion

Recent descriptions of significant heterogeneity in normal stem cells and cancers have altered our understanding of tumorigenesis, emphasizing the need to understand how single stem cells are subverted to cause tumors. Human myeloproliferative neoplasms (MPNs) are thought to reflect transformation of a hematopoietic stem cell (HSC) and the majority harbor an acquired V617F mutation in the JAK2 tyrosine kinase, making them a paradigm for studying the early stages of tumor establishment and progression. The consequences of activating tyrosine kinase mutations for stem and progenitor cell behavior are unclear. In this article, we identify a distinct cellular mechanism operative in stem cells. By using conditional knock-in mice, we show that the HSC defect resulting from expression of heterozygous human JAK2V617F is both quantitative (reduced HSC numbers) and qualitative (lineage biases and reduced self-renewal per HSC). The defect is intrinsic to individual HSCs and their progeny are skewed toward proliferation and differentiation as evidenced by single cell and transplantation assays. Aged JAK2V617F show a more pronounced defect as assessed by transplantation, but mice that transform reacquire competitive self-renewal ability. Quantitative analysis of HSC-derived clones was used to model the fate choices of normal and JAK2-mutant HSCs and indicates that JAK2V617F reduces self-renewal of individual HSCs but leaves progenitor expansion intact. This conclusion is supported by paired daughter cell analyses, which indicate that JAK2-mutant HSCs more often give rise to two differentiated daughter cells. Together these data suggest that acquisition of JAK2V617F alone is insufficient for clonal expansion and disease progression and causes eventual HSC exhaustion. Moreover, our results show that clonal expansion of progenitor cells provides a window in which collaborating mutations can accumulate to drive disease progression. Characterizing the mechanism(s) of JAK2V617F subclinical clonal expansions and the transition to overt MPNs will illuminate the earliest stages of tumor establishment and subclone competition, fundamentally shifting the way we treat and manage cancers

Efficient Activation of Reconstructed Rat Embryos by Cyclin-Dependent Kinase Inhibitors

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Autoimmunization of Ewes Against Pregnancy-associated Glycoproteins Does Not Interfere with the Establishment and Maintenance of Pregnancy

doi:10.1017/S1751731109004145Pregnancy-associated glycoproteins (PAGs) are a large grouping of placental proteins that belong to the aspartic peptidase gene family. Although useful to detect pregnancy in ruminant species, the function of these molecules is unclear. Several PAGs expressed by trophoblast binucleate cells can enter the maternal circulation, suggesting that they could have a systemic role in altering maternal physiology. The objective of this work was to examine whether these circulating placental antigens were important in pregnancy by actively immunizing ewes against them. PAGs were purified by pepstatin-affinity chromatography and conjugated to the immunogenic protein, keyhole limpet hemocyanin (KLH). Ewes were immunized with PAG-KLH conjugate (n522) or with KLH alone (n59), and bred to intact rams. Blood samples, collected on Day 0 (day of estrus), Day 10, Days 15 to 25 and weekly throughout pregnancy, were analyzed for PAG by an ELISA. On Day 30, pregnancy was confirmed by ultrasound. Ewes immunized against PAG-KLH produced a range of reactive anti-PAG titers, whereas all immunized ewes had high anti-KLH immunoreactivity. PAGs became detectable in the anti-KLH (control) ewes at Day 21.662.2 of pregnancy. Those ewes immunized against PAGs (n57), that had very low immunoreactivity toward PAGs, had measurable PAG by Day 22.961.3, and their PAG serum profiles throughout pregnancy did not differ from the controls. Those exhibiting moderate to high anti-PAG immunoreactivity (n515), had significantly lower PAG concentrations than controls, with antigen not becoming detectable until Day 48.1615.6. The decrease in circulating PAG in the immunized animals did not correlate with changes in pregnancy rates, lamb number or lamb birth weight. These results suggest that while PAGs may play a role in maintaining pregnancy, their major contribution is likely to be at the fetal-maternal interface. Their actions at extra-placental sites are presumably of more secondary importance.This work was supported by NIH Grant HD21896 and the Animal Reproductive Biology Group of the University of Missouri Food for the 21st Century Program

Effect of learning resources on Mendeley user adoption and productivity

Poster PresentationThis study was done to understand the user adoption pattern of a reference management tool such as Mendeley. Libraries can improve usage of reference management tools if they adopt a mix of learning support services. The study also found that structured support is more effective than ‘just-in-time’ support. Finally, support for early career researchers is more effective than for seasoned researchers. The results obtained from different Schools across North America were presented as a poster at the Special Libraries Association's Annual Library Conference in Boston in 2015.Special Libraries Association Annual Conference 201

Scholars@TAMU, an Integrated Research Information Management System, as Sociotechnical System: Contextualized Use Cases for Different Disciplinary Communities

Scholars@TAMU is a new research information management system (RIM) at Texas A&M that compiles scholarly expertise profiles for faculty and other research investigators to improve the discoverability of scholarly expertise, enhance the scholarly identity of researchers and facilitating new research collaborations. Scholars@TAMU serves as system of record for academic reputation at Texas A&M by harvesting publicly available research data (e.g., grants and publications), and restricted/proprietary data from disparate sources into compiled expertise profiles for faculty, investigators, scholars, clinicians, community partners, and facilities. We have used the concept of sociotechnical systems to guide the development of library services that use Scholars@TAMU for different disciplinary communities. Describing Scholars@TAMU as a socio-technical system highlights the interaction between people and the RIM, especially in the context of Texas A&M organizations and work places. The Office of Scholarly Communications is collaborating with subject liaisons librarians serving the College of Medicine, the Performance Studies Department, and the School of Public Health. While all three departments are broadly interested in scholarly impact and reputations, the varied norms of the disciplines as well as the specific goals of the faculty and organizations required us to develop different services as well as adapt Scholars@TAMU and the data contained in the faculty profiles for each organization. This presentation will describe the use cases identified in three disciplinary communities at Texas A&M broadly focused on scholarly and societal impact, as well as the contextualize programs that were developed to meet these needs

Nutritional skewing of conceptus sex in sheep: effects of a maternal diet enriched in rumen-protected polyunsaturated fatty acids (PUFA)

<p>Abstract</p> <p>Background</p> <p>Evolutionary theory suggests that in polygynous mammalian species females in better body condition should produce more sons than daughters. Few controlled studies have however tested this hypothesis and controversy exists as to whether body condition score or maternal diet is in fact the determining factor of offspring sex. Here, we examined whether maternal diet, specifically increased n-6 polyunsaturated fatty acid (PUFA) intake, of ewes with a constant body condition score around the time of conception influenced sex ratio.</p> <p>Methods</p> <p>Ewes (n = 44) maintained in similar body condition throughout the study were assigned either a control (C) diet or one (F) enriched in rumen-protected PUFA, but otherwise essentially equivalent, from four weeks prior to breeding until d13 post-estrus. On d13, conceptuses were recovered, measured, cultured to assess their capacity for interferon-tau (IFNT) production and their sex determined. The experiment was repeated with all ewes being fed the F diet to remove any effects of parity order on sex ratio. Maternal body condition score (BCS), plasma hormone and metabolite concentrations were also assessed throughout the study and related to diet.</p> <p>Results</p> <p>In total 129 conceptuses were recovered. Ewes on the F diet produced significantly more male than female conceptuses (proportion male = 0.69; deviation from expected ratio of 0.5, P < 0.001). Conceptus IFNT production was unaffected by diet (P > 0.1), but positively correlated with maternal body condition score (P < 0.05), and was higher (P < 0.05) in female than male conceptuses after 4 h culture. Maternal plasma hormone and metabolite concentrations, especially progesterone and fatty acid, were also modulated by diet.</p> <p>Conclusion</p> <p>These results provide evidence that maternal diet, in the form of increased amounts of rumen-protected PUFA fed around conception, rather than maternal body condition, can skew the sex ratio towards males. These observations may have implications to the livestock industry and animal management policies when offspring of one sex may be preferred over the other.</p

Nutritional Skewing of Conceptus Sex in Sheep: Effects of a Maternal Diet Enriched in Rumen-Protected Polyunsaturated Fatty acids (PUFA)

doi:10.1186/1477-7827-6-21Evolutionary theory suggests that in polygynous mammalian species females in better body condition should produce more sons than daughters. Few controlled studies have however tested this hypothesis and controversy exists as to whether body condition score or maternal diet is in fact the determining factor of offspring sex. Here, we examined whether maternal diet, specifically increased n-6 polyunsaturated fatty acid(PUFA) intake, of ewes with a constant body condition score around the time of conception influenced sex ratio.The research was supported by USDA/CSREES/NRI Grant 2001-35203- 10693 (to RMR) and a Life Sciences Molecular Biology Fellowship, University of Missouri (partial salary support for MPG)

FOXP2-positive diffuse large B-cell lymphomas exhibit a poor response to R-CHOP therapy and distinct biological signatures.

FOXP2 shares partially overlapping normal tissue expression and functionality with FOXP1; an established diffuse large B-cell lymphoma (DLBCL) oncogene and marker of poor prognosis. FOXP2 is expressed in the plasma cell malignancy multiple myeloma but has not been studied in DLBCL, where a poor prognosis activated B-cell (ABC)-like subtype display partially blocked plasma cell differentiation. FOXP2 protein expression was detected in ABC-DLBCL cell lines, and in primary DLBCL samples tumoral FOXP2 protein expression was detected in both germinal center B-cell-like (GCB) and non-GCB DLBCL. In biopsies from DLBCL patients treated with immunochemotherapy (R-CHOP), ≥ 20% nuclear tumoral FOXP2-positivity (n = 24/158) correlated with significantly inferior overall survival (OS: P = 0.0017) and progression-free survival (PFS: P = 0.0096). This remained significant in multivariate analysis against either the international prognostic index score or the non-GCB DLBCL phenotype (P < 0.05 for both OS and PFS). Expression of BLIMP1, a marker of plasmacytic differentiation that is commonly inactivated in ABC-DLBCL, did not correlate with patient outcome or FOXP2 expression in this series. Increased frequency of FOXP2 expression significantly correlated with FOXP1-positivity (P = 0.0187), and FOXP1 co-immunoprecipitated FOXP2 from ABC-DLBCL cells indicating that these proteins can co-localize in a multi-protein complex. FOXP2-positive DLBCL had reduced expression of HIP1R (P = 0.0348), which is directly repressed by FOXP1, and exhibited distinct patterns of gene expression. Specifically in ABC-DLBCL these were associated with lower expression of immune response and T-cell receptor signaling pathways. Further studies are warranted to investigate the potential functional cooperativity between FOXP1 and FOXP2 in repressing immune responses during the pathogenesis of high-risk DLBCL

Convergence Insufficiency, Accommodative Insufficiency, Visual Symptoms, and Astigmatism in Tohono O’odham Students

Purpose. To determine rate of convergence insufficiency (CI) and accommodative insufficiency (AI) and assess the relation between CI, AI, visual symptoms, and astigmatism in school-age children. Methods. 3rd–8th-grade students completed the Convergence Insufficiency Symptom Survey (CISS) and binocular vision testing with correction if prescribed. Students were categorized by astigmatism magnitude (no/low: <1.00 D, moderate: 1.00 D to <3.00 D, and high: ≥3.00 D), presence/absence of clinical signs of CI and AI, and presence of symptoms. Analyses determine rate of clinical CI and AI and symptomatic CI and AI and assessed the relation between CI, AI, visual symptoms, and astigmatism. Results. In the sample of 484 students (11.67 ± 1.81 years of age), rate of symptomatic CI was 6.2% and symptomatic AI 18.2%. AI was more common in students with CI than without CI. Students with AI only (p=0.02) and with CI and AI (p=0.001) had higher symptom scores than students with neither CI nor AI. Moderate and high astigmats were not at increased risk for CI or AI. Conclusions. With-the-rule astigmats are not at increased risk for CI or AI. High comorbidity rates of CI and AI and higher symptoms scores with AI suggest that research is needed to determine symptomatology specific to CI