124 research outputs found

    Not Rambo, Not Hero : The Principal as Designer, Teacher and Steward

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    If we are to create schools that are generative and proactive places designed to fulfill the dual purpose of enculturation and equal access to knowledge, we must attend to the leader behavior of school principals

    Development of a cDNA array for chicken gene expression analysis

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    BACKGROUND: The application of microarray technology to functional genomic analysis in the chicken has been limited by the lack of arrays containing large numbers of genes. RESULTS: We have produced cDNA arrays using chicken EST collections generated by BBSRC, University of Delaware and the Fred Hutchinson Cancer Research Center. From a total of 363,838 chicken ESTs representing 24 different adult or embryonic tissues, a set of 11,447 non-redundant ESTs were selected and added to an existing collection of clones (4,162) from immune tissues and a chicken bursal cell line (DT40). Quality control analysis indicates there are 13,007 useable features on the array, including 160 control spots. The array provides broad coverage of mRNAs expressed in many tissues; in addition, clones with expression unique to various tissues can be detected. CONCLUSIONS: A chicken multi-tissue cDNA microarray with 13,007 features is now available to academic researchers from [email protected]. Sequence information for all features on the array is in GenBank, and clones can be readily obtained. Targeted users include researchers in comparative and developmental biology, immunology, vaccine and agricultural technology. These arrays will be an important resource for the entire research community using the chicken as a model

    Conformational Change Induced by Putidaredoxin Binding to Ferrous CO-ligated Cytochrome P450cam Characterized by 2D IR Spectroscopy

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    The importance of conformational dynamics to protein function is now well-appreciated. An outstanding question is whether they are involved in the effector role played by putidaredoxin (Pdx) in its reduction of the O2 complex of cytochrome P450cam (P450cam), an archetypical member of the cytochrome P450 superfamily. Recent studies have reported that binding of Pdx induces a conformational change from a closed to an open state of ferric P450cam, but a similar conformational change does not appear to occur for the ferrous, CO-ligated enzyme. To better understand the effector role of Pdx when binding the ferrous, CO-ligated P450cam, we applied 2D IR spectroscopy to compare the conformations and dynamics of the wild-type (wt) enzyme in the absence and presence of Pdx, as well as of L358P P450cam (L358P), which has served as a putative model for the Pdx complex. The CO vibrations of the Pdx complex and L358P report population of two conformational states in which the CO experiences distinct environments. The dynamics among the CO frequencies indicate that the energy landscape of substates within one conformation are reflective of the closed state of P450cam, and for the other conformation, differ from the free wt enzyme, but are equivalent between the Pdx complex and L358P. The two states co-populated by the Pdx complex are postulated to reflect a loosely bound encounter complex and a more tightly bound state, as is commonly observed for the dynamic complexes of redox partners. Significantly, this study shows that the binding of Pdx to ferrous, CO-ligated P450cam does perturb the conformational ensemble in a way that might underlie the effector role of Pdx

    Telemedicine Facilitates CHF Home Health Care for Those with Systolic Dysfunction

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    An estimated 5 million Americans have congestive heart failure (CHF) and one in five over the age of 40 will develop CHF. There are numerous examples of CHF patients living beyond the years normally expected for people with the disease, usually attributed to taking an active role in disease management. A relatively new alternative for CHF outpatient care is telemedicine and e-health. We investigated the effects of a 6-week in-home telemedicine education and monitoring program for those with systolic dysfunction on the utilization of health care resources. We also measured the effects of the unit 4.5 months after its removal (a total of 6 months post introduction of the unit into the home). Concurrently, we assessed participants' perceptions of the value of having a telemedicine unit. Participants in the telemedicine group reported weighing more times a week with less variability than did the control group. Telemedicine led to a reduction in physician and emergency department visits and those in the experimental group reported the unit facilitating self-care, though this was not significantly different from the control group (possibly due to small sample size). These findings suggest a possibility for improvement in control of CHF when telemedicine is implemented. Our review of the literature also supports the role of telemedicine in facilitating home health care and self-management for CHF patients. There are many challenges still to be addressed before this potential can be reached and further research is needed to identify opportunities in telemedicine

    Neural G0:a quiescent-like state found in neuroepithelial-derived cells and glioma

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    Single‐cell RNA sequencing has emerged as a powerful tool for resolving cellular states associated with normal and maligned developmental processes. Here, we used scRNA‐seq to examine the cell cycle states of expanding human neural stem cells (hNSCs). From these data, we constructed a cell cycle classifier that identifies traditional cell cycle phases and a putative quiescent‐like state in neuroepithelial‐derived cell types during mammalian neurogenesis and in gliomas. The Neural G0 markers are enriched with quiescent NSC genes and other neurodevelopmental markers found in non‐dividing neural progenitors. Putative glioblastoma stem‐like cells were significantly enriched in the Neural G0 cell population. Neural G0 cell populations and gene expression are significantly associated with less aggressive tumors and extended patient survival for gliomas. Genetic screens to identify modulators of Neural G0 revealed that knockout of genes associated with the Hippo/Yap and p53 pathways diminished Neural G0 in vitro, resulting in faster G1 transit, down‐regulation of quiescence‐associated markers, and loss of Neural G0 gene expression. Thus, Neural G0 represents a dynamic quiescent‐like state found in neuroepithelial‐derived cells and gliomas

    Genome-wide RNAi screens in human brain tumor isolates reveal a novel viability requirement for PHF5A

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    To identify key regulators of human brain tumor maintenance and initiation, we performed multiple genome-wide RNAi screens in patient-derived glioblastoma multiforme (GBM) stem cells (GSCs). These screens identified the plant homeodomain (PHD)-finger domain protein PHF5A as differentially required for GSC expansion, as compared with untransformed neural stem cells (NSCs) and fibroblasts. Given PHF5A's known involvement in facilitating interactions between the U2 snRNP complex and ATP-dependent helicases, we examined cancer-specific roles in RNA splicing. We found that in GSCs, but not untransformed controls, PHF5A facilitates recognition of exons with unusual C-rich 3â€Č splice sites in thousands of essential genes. PHF5A knockdown in GSCs, but not untransformed NSCs, astrocytes, or fibroblasts, inhibited splicing of these genes, leading to cell cycle arrest and loss of viability. Notably, pharmacologic inhibition of U2 snRNP activity phenocopied PHF5A knockdown in GSCs and also in NSCs or fibroblasts overexpressing MYC. Furthermore, PHF5A inhibition compromised GSC tumor formation in vivo and inhibited growth of established GBM patient-derived xenograft tumors. Our results demonstrate a novel viability requirement for PHF5A to maintain proper exon recognition in brain tumor-initiating cells and may provide new inroads for novel anti-GBM therapeutic strategies

    Cancer-Specific requirement for BUB1B/BUBR1 in human brain tumor isolates and genetically transformed cells

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    To identify new candidate therapeutic targets for Glioblastoma multiforme (GBM), we combined functional genetics and GBM network modeling to identify kinases required for the growth of patient-derived brain tumor initiating cells (BTICs), but which are dispensable to proliferating human neural stem cells (NSCs). This approach yielded BUB1B/BUBR1, a critical mitotic spindle checkpoint player, as the top scoring GBM-lethal kinase. Knockdown of BUB1B inhibited expansion of BTIC isolates, both in vitro and in vivo, without affecting proliferation of NSCs or astrocytes. Mechanistic studies revealed that BUB1B’s GLEBs domain activity is required to suppress lethal kinetochore-microtubule (KT-MT) attachment defects in GBM isolates and genetically transformed cells with altered sister KT dynamics, which likely favor KT-MT instability. These results indicate that GBM tumors have added requirement for BUB1B to suppress lethal consequences of altered KT function. They further suggest that sister KT measurements may predict cancer-specific sensitivity to BUB1B inhibition and perhaps other mitotic targets that affect KT-MT stability

    Extracellular Connective Tissue Fibrils: A Single Line of Descent

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    Interview no. 816

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    Part of Health Care on the Border Project; biographical information; Woman\u27s Auxiliary of El Paso County Medical Society; El Paso hospital in existence in early 1940s; husband\u27s internship at El Paso City-County Hospitals; acquisition of S.T. Turner Home by Medical Society; husband\u27s involvement in pioneering El Paso Orthopedic Surgical Group; Frank Goodwin, M.D, El Paso\u27s first orthopedic surgeon; Medical Auxiliary collection of physician log books from 1869-1940s
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