989 research outputs found
Good practices for student learning: Mixed-method evidence from the Wabash National Study
Kathleen M. Goodman, Marcia Baxter Magolda, Tricia A. Seifert, and Patricia M. King review both quantitative and qualitative data to understand students' college experiences and provide powerful information to guide educators.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83756/1/20048_ftp.pd
Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes
Background & Aims: Hepatocyte-like cells (HLCs), differentiated from pluripotent stem cells by the use of soluble factors, can model human liver function and toxicity. However, at present HLC maturity and whether any deficit represents a true fetal state or aberrant differentiation is unclear and compounded by comparison to potentially deteriorated adult hepatocytes. Therefore, we generated HLCs from multiple lineages, using two different protocols,
for direct comparison with fresh fetal and adult hepatocytes.
Methods: Protocols were developed for robust differentiation. Multiple transcript, protein and functional analyses compared HLCs to fresh human fetal and adult hepatocytes.
Results: HLCs were comparable to those of other laboratories by multiple parameters. Transcriptional changes during differentiation mimicked human embryogenesis and showed more similarity to pericentral than periportal hepatocytes. Unbiased proteomics demonstrated greater proximity to liver than 30 other human organs or tissues. However, by comparison to fresh material,
HLC maturity was proven by transcript, protein and function to be fetal-like and short of the adult phenotype. The expression of 81% phase 1 enzymes in HLCs was significantly upregulated and half were statistically not different from fetal hepatocytes. HLCs secreted albumin and metabolized testosterone (CYP3A) and dextrorphan (CYP2D6) like fetal hepatocytes. In seven bespoke tests,
devised by principal components analysis to distinguish fetal from adult hepatocytes, HLCs from two different source laboratories consistently demonstrated fetal characteristics.
Conclusions: HLCs from different sources are broadly comparable with unbiased proteomic evidence for faithful differentiation down the liver lineage. This current phenotype mimics human fetal rather than adult hepatocytes
Pseudoprogression After Proton Therapy of Pediatric Spinal Pilocytic Astrocytoma and Myxopapillary Ependymoma
https://openworks.mdanderson.org/sumexp23/1025/thumbnail.jp
Lessons Learned From 10 Years of Preschool Intervention for Health Promotion: JACC State-of-the-Art Review.
Implementing a health promotion program for children is a complex endeavor. In this review, we outline the key lessons learned over 10 years of experience in implementing the SI! Program (Salud Integral-Comprehensive Health) for cardiovascular health promotion in preschool settings in 3 countries: Colombia (Bogotá), Spain (Madrid), and the United States (Harlem, New York). By matching rigorous efficacy studies with implementation science, we can help bridge the divide between science and educational practice. Achieving sustained lifestyle changes in preschool children through health promotion programs is likely to require the integration of several factors: 1) multidisciplinary teams; 2) multidimensional educational programs; 3) multilevel interventions; 4) local program coordination and community engagement; and 5) scientific evaluation through randomized controlled trials. Implementation of effective health promotion interventions early in life may induce long-lasting healthy behaviors that could help to curb the cardiovascular disease epidemic.This work is supported by the SHE Foundation and “la Caixa”
Foundation (LCF/CE16/10700001). The project in Colombia was
funded by Santo Domingo Foundation; the study in the United
States (FAMILIA) was funded by the American Heart Association
(grant no. 14SFRN20490315); and the study in Spain (SI! Program)
was funded by the SHE Foundation, the research grant FIS-PI11/
01885 (Fondo de Investigación Sanitaria del Instituto de Salud
Carlos III), and Fundació la Marató de TV3 (369/C/2016). Dr SantosBeneit is the recipient of grant LCF/PR/MS19/12220001 funded by
“la Caixa” Foundation (ID 100010434). Dr Fernández-Jiménez is
the recipient of grant PI19/01704 funded by the Fondo de Investigación Sanitaria–Instituto de Salud Carlos III and co-funded by
the European Regional Development Fund/European Social Fund
“A way to make Europe”/“Investing in your future.” The Centro
Nacional de Investigaciones Cardiovasculares is supported by the
Instituto de Salud Carlos III, the Ministerio de Ciencia e Innovación, and the Pro CNIC Foundation, and is a Severo Ochoa Center
of Excellence (CEX2020-001041-S). All other authors have reported
that they have no relationships relevant to the contents of this
paper to disclose.S
Silencing BMI1 eliminates tumor formation of pediatric glioma CD133+ cells not by affecting known targets but by down-regulating a novel set of core genes
Abstract
Clinical outcome of children with malignant glioma remains dismal. Here, we examined the role of over-expressed BMI1, a regulator of stem cell self-renewal, in sustaining tumor formation in pediatric glioma stem cells. Our investigation revealed BMI1 over-expression in 29 of 54 (53.7%) pediatric gliomas, 8 of 8 (100%) patient derived orthotopic xenograft (PDOX) mouse models, and in both CD133+ and CD133− glioma cells. We demonstrated that lentiviral-shRNA mediated silencing of suppressed cell proliferation in vitro in cells derived from 3 independent PDOX models and eliminated tumor-forming capacity of CD133+ and CD133− cells derived from 2 PDOX models in mouse brains. Gene expression profiling showed that most of the molecular targets of BMI1 ablation in CD133+ cells were different from that in CD133- cells. Importantly, we found that silencing BMI1 in CD133+ cells derived from 3 PDOX models did not affect most of the known genes previously associated with the activated BMI1, but modulated a novel set of core genes, including RPS6KA2, ALDH3A2, FMFB, DTL, API5, EIF4G2, KIF5c, LOC650152, C20ORF121, LOC203547, LOC653308, and LOC642489, to mediate the elimination of tumor formation. In summary, we identified the over-expressed BMI1 as a promising therapeutic target for glioma stem cells, and suggest that the signaling pathways associated with activated BMI1 in promoting tumor growth may be different from those induced by silencing BMI1 in blocking tumor formation. These findings highlighted the importance of careful re-analysis of the affected genes following the inhibition of abnormally activated oncogenic pathways to identify determinants that can potentially predict therapeutic efficacy.http://deepblue.lib.umich.edu/bitstream/2027.42/110124/1/40478_2014_Article_160.pd
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Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.
Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer
Explorations, Vol. 5, No. 1
Articles include:
Cover: What Have We Done with Tomorrow? by Leslie C. Hyde, UMCES Extension Agent for Knox-Lincoln Counties.
Editorial Reflections, Carole J. Bombard
UMCES: an overview
Conversation with the Director: Assistant Vice-President Judith Bailey
Reaching Out for Teen Awareness, by Theresa M. Ferrari
Profile of a Harbormaster, by Carole J. Bombard
Minding Maine’s Business, by Mary S. Bowie
Family Resource Management: Learning to ease the burden, by Olive Dubord and Doris Cushman
Breaking Free and Taking Control: Helen Sawyer’s Story, by Doris Manley
Partnership in Conservation: The Josephine Newman Sanctuary, by Nancy Coverstone
The Mount Desert Island Health Promotion Project, by Ron Beard
Dynamics of Weed Control in Agriculture, by Leigh Morrow
From Generation to Generation: An Extension Homemaker Family, by Nadine B. Reimer
ICLAD: The Institute for Community Leadership and Development, by Jim Killacky and Deb Burwell
Exploding the Cinderella Syndrome: Strengthening Stepfamilies, by Wendy Pollock
Integrated Pest Management: Bringing it all together, by Glen Koehler and Jim Dill
Addressing the Issues, by Patricia M. Pierson
Anti-Bruise: What’s It All About? Maine Potato Harvest Anti-Bruise Program, by Neal D. Hallee
H.O.P.E. Addresses Teenage Pregnancy, by Jane M. Kelly
Saving Money and the Environment, by Vaughn H. Holyoke
Reservoir Tillage in Nonirrigated Potato Production, by Leigh Morrow
Managing Pesticide Drift, by James D. Dwyer, Leigh S. Morrow and James F. Dill
The St. George River Project — what have we done with tomorrow?
Putting Research to Work, by Stephen Belyea
The Best Maine Blue: Fresh Pack Blueberries, by Tom DeGomez
Maine’s Green Sea Urchin, by Benjamin A. Baxter
Interfaces and Cooperation: Wildlife and Fisheries Sampler, by Catherine A. Elliott
Extension Responds to the Salmonella Scare, by Nellie Hedstrom and Mahmoud El-Begearm
Influence of dental metallic artifact from multislice CT in the assessment of simulated mandibular lesions
OBJECTIVE: This study evaluated the influence of metallic dental artifacts on the accuracy of simulated mandibular lesion detection by using multislice technology. MATERIAL AND METHODS: Fifteen macerated mandibles were used. Perforations were done simulating bone lesions and the mandibles were subjected to axial 16 rows multislice CT images using 0.5 mm of slice thickness with 0.3 mm interval of reconstruction. Metallic dental restorations were done and the mandibles were subjected again to CT in the same protocol. The images were analyzed to detect simulated lesions in the mandibles, verifying the loci number and if there was any cortical perforation exposing medullar bone. The analysis was performed by two independent examiners using e-film software. RESULTS: The samples without artifacts presented better results compared to the gold standard (dried mandible with perforations). In the samples without artifacts, all cortical perforation were identified and 46 loci were detected (of 51) in loci number analysis. Among the samples with artifacts, 12 lesions out of 14 were recognized regarding medullar invasion, and 40 out of 51 concerning loci number. The sensitivity in samples without artifacts was 90% and 100% regarding loci number and medullar invasion, respectively. In samples with artifacts, these values dropped to 78% and 86%, respectively. The presence of metallic restorations affected the sensitivity values of the method, but the difference was not significant (p>0.05). CONCLUSIONS: Although there were differences in the results of samples with and without artifacts, the presence of metallic restoration did not lead to misinterpretation of the final diagnosis. However, the validity of multislice CT imaging in this study was established for detection of simulated mandibular bone lesions.CNPqFAPESPCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES
Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants
BACKGROUND:
Preterm infants with respiratory distress syndrome (RDS) given inositol had reduced bronchopulmonary dysplasia (BPD), death and severe retinopathy of prematurity (ROP). We assessed the safety and pharmacokinetics of daily inositol to select a dose providing serum levels previously associated with benefit, and to learn if accumulation occurred when administered throughout the normal period of retinal vascularization.
METHODS:
Infants ≤ 29 wk GA (n = 122, 14 centers) were randomized and treated with placebo or inositol at 10, 40, or 80 mg/kg/d. Intravenous administration converted to enteral when feedings were established, and continued to the first of 10 wk, 34 wk postmenstrual age (PMA) or discharge. Serum collection employed a sparse sampling population pharmacokinetics design. Inositol urine losses and feeding intakes were measured. Safety was prospectively monitored.
RESULTS:
At 80 mg/kg/d mean serum levels reached 140 mg/l, similar to Hallman's findings. Levels declined after 2 wk, converging in all groups by 6 wk. Analyses showed a mean volume of distribution 0.657 l/kg, clearance 0.058 l/kg/h, and half-life 7.90 h. Adverse events and comorbidities were fewer in the inositol groups, but not significantly so.
CONCLUSION:
Multiple dose inositol at 80 mg/kg/d was not associated with increased adverse events, achieves previously effective serum levels, and is appropriate for investigation in a phase III trial
Leptonic and Semileptonic Decays of Charm and Bottom Hadrons
We review the experimental measurements and theoretical descriptions of
leptonic and semileptonic decays of particles containing a single heavy quark,
either charm or bottom. Measurements of bottom semileptonic decays are used to
determine the magnitudes of two fundamental parameters of the standard model,
the Cabibbo-Kobayashi-Maskawa matrix elements and . These
parameters are connected with the physics of quark flavor and mass, and they
have important implications for the breakdown of CP symmetry. To extract
precise values of and from measurements, however,
requires a good understanding of the decay dynamics. Measurements of both charm
and bottom decay distributions provide information on the interactions
governing these processes. The underlying weak transition in each case is
relatively simple, but the strong interactions that bind the quarks into
hadrons introduce complications. We also discuss new theoretical approaches,
especially heavy-quark effective theory and lattice QCD, which are providing
insights and predictions now being tested by experiment. An international
effort at many laboratories will rapidly advance knowledge of this physics
during the next decade.Comment: This review article will be published in Reviews of Modern Physics in
the fall, 1995. This file contains only the abstract and the table of
contents. The full 168-page document including 47 figures is available at
http://charm.physics.ucsb.edu/papers/slrevtex.p
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