Beyond osteogenesis: an in vitro comparison of the potentials of six bone morphogenetic proteins

Bone morphogenetic proteins (BMPs) other than the clinically available BMP-2 and BMP-7 may be useful for improving fracture healing through both increasing osteogenesis and creating a favorable healing environment by altering cytokine release by endogenous cells. Given the spectrum of potential applications for BMPs, the objective of this study was to evaluate various BMPs under a variety of conditions to provide further insight into their therapeutic capabilities. The alkaline phosphatase (ALP) activity of both C(2)C(12) and human adipose-derived stem cells (hASCs) was measured after exposure of increasing doses of recombinant human BMP-2, -4, -5, -6, -7, or -9 for 3 and 7 days. BMPs-2, -4, -5, -6, -7, and -9 were compared in terms of their ability to affect the release of stromal derived factor-1 (SDF-1), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (b-FGF) from human bone marrow stromal cells (hBMSCs). Gene expression of ALP, osteocalcin, SDF-1, VEGF, and b-FGF following shRNA-mediated knockdown of BMP-2 and BMP-6 in hBMSCs or human osteoblasts under osteogenic differentiation conditions was also evaluated. Collectively, BMPs-6 and -9 produced the greatest osteogenic differentiation of C(2)C(12) and hASCs as determined by ALP. The hBMSC secretion of SDF-1 was most affected by BMP-5, VEGF by BMP-4, and b-FGF by BMP-2. The knockdown of BMP-2 in BMSCs had no effect on any of the genes measured whereas BMP-6 knockdown in hBMSCs caused a significant increase in VEGF gene expression. BMP-2 and BMP-6 knockdown in human osteoblasts caused significant increases in VEGF gene expression and trends toward decreases in osteocalcin expression. These findings support efforts to study other BMPs as potential bone graft supplements, and to consider combined BMP delivery for promotion of multiple aspects of fracture healing

Improving Test Score Reporting: Perspectives From the ETS Score Reporting Conference

This volume includes 3 papers based on presentations at a workshop on communicating assessment information to particular audiences, held at Educational Testing Service (ETS) on November 4th, 2010, to explore some issues that influence score reports and new advances that contribute to the effectiveness of these reports. Jessica Hullman, Rebecca Rhodes, Fernando Rodriguez, and Priti Shah present the results of recent research on graph comprehension and data interpretation, especially the role of presentation format, the impact of prior quantitative literacy and domain knowledge, the trade‐off between reducing cognitive load and increasing active processing of data, and the affective influence of graphical displays. Rebecca Zwick and Jeffrey Sklar present the results of the Instructional Tools in Educational Measurement and Statistics for School Personnel (ITEMS) project, funded by the National Science Foundation and conducted at the University of California, Santa Barbara to develop and evaluate 3 web‐based instructional modules intended to help educators interpret test scores. Zwick and Sklar discuss the modules and the procedures used to evaluate their effectiveness. Diego Zapata‐Rivera presents a new framework for designing and evaluating score reports, based on work on designing and evaluating score reports for particular audiences in the context of the CBAL (Cognitively Based Assessment of, for, and as Learning) project (Bennett & Gitomer, 2009), which has been applied in the development and evaluation of reports for various audiences including teachers, administrators and students.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108325/1/ets202281.pd

Suppressing Aneuploidy-Associated Phenotypes Improves the Fitness of Trisomy 21 Cells

An abnormal number of chromosomes, or aneuploidy, accounts for most spontaneous abortions, causes developmental defects, and is associated with aging and cancer. The molecular mechanisms by which aneuploidy disrupts cellular function remain largely unknown. Here, we show that aneuploidy disrupts the morphology of the nucleus. Mutations that increase the levels of long-chain bases suppress nuclear abnormalities of aneuploid yeast independent of karyotype identity. Quantitative lipidomics indicates that long-chain bases are integral components of the nuclear membrane in yeast. Cells isolated from patients with Down syndrome also show that abnormal nuclear morphologies and increases in long-chain bases not only suppress these abnormalities but also improve their fitness. We obtained similar results with cells isolated from patients with Patau or Edward syndrome, indicating that increases in long-chain bases improve the fitness of aneuploid cells in yeast and humans. Targeting lipid biosynthesis pathways represents an important strategy to suppress nuclear abnormalities in aneuploidy-associated diseases

Detección de anticuerpos contra el virus de lengua azul en ovinos de dos localidades de Junín, Perú

The aim of this study was to detect antibodies against bluetongue virus (VLA) in a population of Junín breed sheep bred at 3800 m above the see level in the province of Jauja, Junín and in Blackbelly breed sheep raised at 600 m in the province of Chanchamayo, Junín, Peru. Blood samples (n=306) were collected from Junín sheep, older than 4 months of age, both sexes and from Blackbelly sheep (n=82) older than 4 months, both sexes, from small breeders from four districts (Perene, San Luis de Shauro, San Ramón and Pichanaki) from the province of Chanchamayo, Junín. Antibody detection against the VLA was done by competition ELISA test. All samples (306/306) of the Junín sheep were negative for antibodies against the VLA, while 56.1% (46/82) of the Blackbelly sheep samples had antibodies against the virus. The absence of antibodies against the VLA in sheep raised at 3800 m of altitude indicates that they were not exposed to the VLA, suggesting that high altitude and low temperatures constitute a barrier to the biology of the virus-transmitting vectors, whereas sheep raised at 600 m of altitude were exposed, indicating the presence of the vector or vectors competent for the transmission of bluetongue virus.El objetivo del presente estudio fue detectar anticuerpos contra el virus de lengua azul (VLA) en una población de ovinos de raza Junín criados a 3800 msnm en la provincia de Jauja, Junín, y en ovinos de raza Blackbelly criados a 600 msnm en la provincia de Chanchamayo, Junín, Perú. Se colectaron 306 muestras de sangre de ovinos Junín, mayores a 4 meses de edad, ambos sexos y 82 muestras de ovinos Blackbelly, mayores a 4 meses, ambos sexos, de pequeños criadores de cuatro distritos (Perene, San Luis de Shauro, San Ramón y Pichanaki) de la provincia de Chanchamayo, Junín. La detección de anticuerpos contra el VLA se hizo mediante la prueba de ELISA de competición. El 100% (306/306) de las muestras de los ovinos Junín resultaron negativos a anticuerpos contra el VLA, mientras que 56.1% (46/82) de las muestras de ovinos Blackbelly tuvieron anticuerpos contra el virus. La ausencia de anticuerpos contra el VLA en ovinos criados a 3800 msnm indica que no fueron expuestos al VLA, sugiriendo que la altitud y bajas temperaturas constituyen una barrea para la biología del vector transmisor del virus, en tanto que los ovinos criados a 600 msnm estuvieron expuestos, indicando la presencia del vector o vectores competentes para la transmisión del virus de lengua azul

Chapter 5: Food Security

The current food system (production, transport, processing, packaging, storage, retail, consumption, loss and waste) feeds the great majority of world population and supports the livelihoods of over 1 billion people. Since 1961, food supply per capita has increased more than 30%, accompanied by greater use of nitrogen fertilisers (increase of about 800%) and water resources for irrigation (increase of more than 100%). However, an estimated 821 million people are currently undernourished, 151 million children under five are stunted, 613 million women and girls aged 15 to 49 suffer from iron deficiency, and 2 billion adults are overweight or obese. The food system is under pressure from non-climate stressors (e.g., population and income growth, demand for animal-sourced products), and from climate change. These climate and non-climate stresses are impacting the four pillars of food security (availability, access, utilisation, and stability)

Relationship between area mortgage foreclosures, homeownership, and cardiovascular disease risk factors: The Hispanic Community Health Study/Study of Latinos

Abstract Background The risk of mortgage foreclosure disproportionately burdens Hispanic/Latino populations perpetuating racial disparities in health. In this study, we examined the relationship between area-level mortgage foreclosure risk, homeownership, and the prevalence of cardiovascular disease risk factors among participants of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods HCHS/SOL participants were age 18–74 years when recruited from four U.S. metropolitan areas. Mortgage foreclosure risk was obtained from the U.S. Department of Housing and Urban Development. Homeownership, sociodemographic factors, and cardiovascular disease risk factors were measured at baseline interview between 2008 and 2011. There were 13,856 individuals contributing to the analysis (median age 39 years old, 53% female). Results Renters in high foreclosure risk areas had a higher prevalence of hypertension and hypercholesterolemia but no association with smoking status compared to renters in low foreclosure risk areas. Renters were more likely to smoke cigarettes than homeowners. Conclusion Among US Hispanic/Latinos in urban cities, area foreclosure and homeownership have implications for risk of cardiovascular disease

Notch1 is required for maintenance of the reservoir of adult hippocampal stem cells

Notch1 regulates neural stem cell (NSC) number during development, but its role in adult neurogenesis is unclear. We generated nestin-CreER(T2)/R26R-YFP/Notch1(loxP/loxP) [Notch1inducible knock-out (iKO)] mice to allow tamoxifen (TAM)-inducible elimination of Notch1 and concomitant expression of yellow fluorescent protein (YFP) in nestin-expressing Type-1 NSCs and their progeny in the adult hippocampal subgranular zone (SGZ). Consistent with previous research, YFP+ cells in all stages of neurogenesis were evident in the subgranular zone (SGZ) of wild-type (WT) mice (nestin-CreER(T2)/R26R-YFP/Notch1(w/w)) after tamoxifen (post-TAM), producing adult-generated YFP+ dentate gyrus neurons. Compared with WT littermates, Notch1 iKO mice had similar numbers of total SGZ YFP+ cells 13 and 30 d post-TAM but had significantly fewer SGZ YFP+ cells 60 and 90 d post-TAM. Significantly fewer YFP+ Type-1 NSCs and transiently amplifying progenitors (TAPs) resulted in generation of fewer YFP+ granule neurons in Notch1 iKO mice. Strikingly, 30 d of running rescued this deficit, as the total YFP+ cell number in Notch iKO mice was equivalent to WT levels. This was even more notable given the persistent deficits in the Type-1 NSC and TAP reservoirs. Our data show that Notch1 signaling is required to maintain a reservoir of undifferentiated cells and ensure continuity of adult hippocampal neurogenesis, but that alternative Notch- and Type-1 NSC-independent pathways compensate in response to physical activity. These data shed light on the complex relationship between Type-1 NSCs, adult neurogenesis, the neurogenic niche, and environmental stimuli

Resilient Pedagogy: Practical Teaching Strategies to Overcome Distance, Disruption, and Distraction

Resilient Pedagogy offers a comprehensive collection on the topics and issues surrounding resilient pedagogy framed in the context of the COVID-19 pandemic and the social justice movements that have swept the globe. As a collection, Resilient Pedagogy is a multi-disciplinary and multi-perspective response to actions taken in different classrooms, across different institution types, and from individuals in different institutional roles with the purpose of allowing readers to explore the topics to improve their own teaching practice and support their own students through distance, disruption, and distraction

Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer

BH3 mimetics such as ABT-263 induce apoptosis in a subset of cancer models. However, these drugs have shown limited clinical efficacy as single agents in small-cell lung cancer (SCLC) and other solid tumor malignancies, and rational combination strategies remain underexplored. To develop a novel therapeutic approach, we examined the efficacy of ABT-263 across >500 cancer cell lines, including 311 for which we had matched expression data for select genes. We found that high expression of the proapoptotic gene Bcl2-interacting mediator of cell death (BIM) predicts sensitivity to ABT-263. In particular, SCLC cell lines possessed greater BIM transcript levels than most other solid tumors and are among the most sensitive to ABT-263. However, a subset of relatively resistant SCLC cell lines has concomitant high expression of the antiapoptotic myeloid cell leukemia 1 (MCL-1). Whereas ABT-263 released BIM from complexes with BCL-2 and BCL-XL, high expression of MCL-1 sequestered BIM released from BCL-2 and BCL-XL, thereby abrogating apoptosis. We found that SCLCs were sensitized to ABT-263 via TORC1/2 inhibition, which led to reduced MCL-1 protein levels, thereby facilitating BIM-mediated apoptosis. AZD8055 and ABT-263 together induced marked apoptosis in vitro, as well as tumor regressions in multiple SCLC xenograft models. In a Tp53; Rb1 deletion genetically engineered mouse model of SCLC, the combination of ABT-263 and AZD8055 significantly repressed tumor growth and induced tumor regressions compared with either drug alone. Furthermore, in a SCLC patient-derived xenograft model that was resistant to ABT-263 alone, the addition of AZD8055 induced potent tumor regression. Therefore, addition of a TORC1/2 inhibitor offers a therapeutic strategy to markedly improve ABT-263 activity in SCLC.United States. Dept. of Defense (Grant W81-XWH-13-1-0323)National Cancer Institute (U.S.) (Cancer Center Support Grant P30-CA14051