196,157 research outputs found
Signaling pathways in the specification of arteries and veins
No full textThe establishment of arterial and venous identity of endothelial cells is critical for the proper anatomic configuration and function of the vascular tree. Arterial and venous specification of endothelial cells is determined by genetic factors, although surrounding cells and hemodynamic forces may also contribute to vascular remodeling. This review provides an overview of the signaling pathways and related transcription factors implicated in differentiation of endothelial cells. We will discuss, in particular, the role of upstream and downstream effectors of Wnt, Sox, and Notch pathways. The understanding of the molecular mechanisms that orchestrate endothelial differentiation may have therapeutic relevance for diseases such as atherosclerosis, arteriovenous malformations, aneurysms, and others
The molecular basis of the blood brain barrier differentiation and maintenance. Is it still a mystery?
No full textEndothelial cells (ECs) differ in morphology and functional responses in the different regions of the vascular tree. During embryo development they acquire organ specific characteristics to respond to the needs of the perfused organs. The brain microvasculature is a striking example of this process. This particular vasculature develops unique properties to assure a tight control of permeability between blood and the underlying nervous system. To this end, these cells present well developed cell to cell junctions, tight basement membrane and express a series of transporters which support the passage of nutrients and toxic agents inside or outside the brain, respectively. This highly differentiated EC phenotype is induced and maintained by the cross-talk with the surrounding cells such as pericytes and astrocytes. Recent evidence highlights the molecular basis of this cross-talk (constituting the neurovascular unit) and opens new perspectives in the development of drugs which modulate blood-brain-barrier (BBB) permeability properties. In this review we describe the specific features of the BBB and we discuss recent data on the role of Wnt as a mediator of brain angiogenesis and BBB differentiatio
Wnt/beta-catenin signaling controls development of the blood–brain barrier
No full textThe blood–brain barrier (BBB) is confined to the endothelium of brain capillaries and is indispensable for fluid homeostasis and neuronal function. In this study, we show that endothelial Wnt/beta-catenin (beta-cat) signaling regulates induction and maintenance of BBB characteristics during embryonic and postnatal development. Endothelial specific stabilization of beta-cat in vivo enhances barrier maturation, whereas inactivation of beta-cat causes significant down-regulation of claudin3 (Cldn3), up-regulation of plamalemma vesicle-associated protein, and BBB breakdown. Stabilization of beta-cat in primary brain endothelial cells (ECs) in vitro by N-terminal truncation or Wnt3a treatment increases Cldn3 expression, BBB-type tight junction formation, and a BBB characteristic gene signature. Loss of beta-cat or inhibition of its signaling abrogates this effect. Furthermore, stabilization of beta-cat also increased Cldn3 and barrier properties in nonbrain-derived ECs. These findings may open new therapeutic avenues to modulate endothelial barrier function and to limit the devastating effects of BBB breakdown
Wnt activation of immortalized brain endothelial cells as a tool for generating a standardized model of the blood brain barrier in vitro
No full textReproducing the characteristics and the functional responses of the blood–brain barrier (BBB) in vitro represents an important task for the research community, and would be a critical biotechnological breakthrough. Pharmaceutical and biotechnology industries provide strong demand for inexpensive and easy-to-handle in vitro BBB models to screen novel drug candidates. Recently, it was shown that canonical Wnt signaling is responsible for the induction of the BBB properties in the neonatal brain microvasculature in vivo. In the present study, following on from earlier observations, we have developed a novel model of the BBB in vitro that may be suitable for large scale screening assays. This model is based on immortalized endothelial cell lines derived from murine and human brain, with no need for co-culture with astrocytes. To maintain the BBB endothelial cell properties, the cell lines are cultured in the presence of Wnt3a or drugs that stabilize β-catenin, or they are infected with a transcriptionally active form of β-catenin. Upon these treatments, the cell lines maintain expression of BBB-specific markers, which results in elevated transendothelial electrical resistance and reduced cell permeability. Importantly, these properties are retained for several passages in culture, and they can be reproduced and maintained in different laboratories over time. We conclude that the brain-derived endothelial cell lines that we have investigated gain their specialized characteristics upon activation of the canonical Wnt pathway. This model may be thus suitable to test the BBB permeability to chemicals or large molecular weight proteins, transmigration of inflammatory cells, treatments with cytokines, and genetic manipulation
Dr. Duane M. Jackson, Morehouse College, July 2011
No full textThis video is a conversation with Dr. Duane M. Jackson. Dr. Jackson talks about his paper, "Recall and the Serial Position Effect: The Role of Primacy and Recency on Accounting Students' Performance." Jackie Daniel, AUC Woodruff Library, is the interviewer
"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States" By M. Carey.
No full text"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States: containing bried sketches of the moral and political character of those states.
By M. Carey, member of the American philosophical, and of the American Antiquarian Society, and author of The Olive Branch, Cindiciae Hibernicae, essays on banking, on political economy, and on internal improvement.
To which are now added the English editor's comments on the subject; together with Important Advice to Emigrants, and Cautions Against Impositions Practiced in the Outports
Timing and Strategy for Weaning From Venoarterial ECMO are Complex Issues
No full textOBJECTIVE:Weaning from venoarterial extracorporeal membrane oxygenation (VA ECMO) usually is performed without clear guidelines; yet, patients still die after removal of extracorporeal circulation because of inadequate heart or end-organ recovery. The aim of the study was to address the weaning procedure, analyzing the hemodynamic and echocardiographic picture of patients weaned and to identify predictors of poor outcome among this population.DESIGN:Observational study.SETTING:University hospital.PARTICIPANTS:One hundred twenty-nine VA ECMO cases.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:Forty-nine patients (38%) were weaned, 7 (5.4%) were bridged to a ventricular assist device, and 6 (5.2%) were listed for heart transplantation. Weaned patients showed a significant increase of pulse pressure (35 [0-50] mmHg before ECMO, 59 [53-67] mmHg at weaning, 61 [51-76] mmHg after ECMO (p<0.001]) and reduction of dose of inotropes (inotropic score [as defined in the text] 20 [14-40] before ECMO, 10 [3-15] at weaning, and 10 [5-15] after ECMO, p<0.001). Left ventricular ejection fraction (LVEF) increased from 19 (0-22.5)% before ECMO to 35 (22-55)% after ECMO (p<0.001). A significant improvement of right ventricular (RV) function was observed in weaned patients (RV dysfunction from 52% to 21%, p<0.001). Among weaned patients, 15 (31%) died. Patients who died after weaning had longer ECMO duration compared to discharged patients (8 [5-11] v 4 [2-6] days, p = 0.01) and more transfusions (22 [10-37] v 7 [0.5-15] units, p = 0.02); survival was lower in patients with central ECMO (postcardiotomy) compared to peripheral ECMO (p = 0.045). Mortality was higher in those with persistence of RV failure, continuous venovenous hemofiltration, higher inotropic score, lower systolic pressure, or higher leucocyte count at weaning.CONCLUSIONS:Successful weaning from ECMO is a multifaceted process, which encompasses consistent recovery of myocardial and end-organ function; LVEF, though improved, is still low at weaning. Hospital survival is correlated significantly to the duration of ECMO support and to bleeding complications
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Dr. Glendon Swarthout
No full textHosted by Roger M. Busfield, MSU Assistant Professor of Speech and Theater, Meet the Author is designed to introduce a general audience to a contemporary author and their work through in-depth interviews. This episode features a conversation between Dr. Glendon Swarthout, prolific author and English professor at MSU, and assistant professors Sam S. Baskett and Theodore B. Strandness
Simulation of thermal plant optimization and hydraulic aspects of thermal distribution loops for large campuses
No full textFollowing an introduction, the author describes Texas A&M University and its utilities system. After that, the author presents how to construct simulation models for chilled water and heating hot water distribution systems. The simulation model was used in a $2.3 million Ross Street chilled water pipe replacement project at Texas A&M University. A second project conducted at the University of Texas at San Antonio was used as an example to demonstrate how to identify and design an optimal distribution system by using a simulation model. The author found that the minor losses of these closed loop thermal distribution systems are significantly higher than potable water distribution systems. In the second part of the report, the author presents the latest development of software called the Plant Optimization Program, which can simulate cogeneration plant operation, estimate its operation cost and provide optimized operation suggestions. The author also developed detailed simulation models for a gas turbine and heat recovery steam generator and identified significant potential savings. Finally, the author also used a steam turbine as an example to present a multi-regression method on constructing simulation models by using basic statistics and optimization algorithms. This report presents a survey of the author??s working experience at the Energy Systems Laboratory (ESL) at Texas A&M University during the period of January 2002 through March 2004. The purpose of the above work was to allow the author to become familiar with the practice of engineering. The result is that the author knows how to complete a project from start to finish and understands how both technical and nontechnical aspects of a project need to be considered in order to ensure a quality deliverable and bring a project to successful completion. This report concludes that the objectives of the internship were successfully accomplished and that the requirements for the degree of Degree of Engineering have been satisfied
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