M-CAT elements mediate cardiac- and embryonic skeletal muscle-specific expression of the cardiac troponin T gene and a number of other cardiac-specific genes. M-CAT binding factor was shown to be related to cloned human TEF-1, a transcriptional regulator of the SV40 viral enhancer. Here we describe the cloning of TEF-1 from chick heart and the identification of several novel isoforms. We show that TEF-1 mRNA is considerably enriched in cardiac and skeletal muscle, consistent with a proposed role in muscle gene transcription. The predominant TEF-1 isoforms, TEF-1A and a novel isoform TEF-1B, bind M-CAT elements with high affinity and in a sequence-specific manner. We further demonstrate that the C-terminal portion of TEF-1B, which contains the 13-amino acid exon that distinguishes this isoform, can activate transcription when linked to a heterologous DNA binding domain, while the same domain of TEF-1A cannot. Therefore, isoforms of TEF-1 may play different roles in the regulation of M-CAT-dependent promoters in striated muscle cells.
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The survival, differentiation, and maintenance of responsive neurons are regulated by nerve growth factor (NGF), which is secreted by the target and interacts with receptors on the axon tip. It is uncertain how the NGF signal is communicated retrogradely from distal axons to neuron cell bodies. Retrograde transport of activated receptors in endocytic vesicles could convey the signal. However, little is known about endocytosis of NGF receptors, and there is no evidence that NGF receptors continue to signal after endocytosis. We have examined early events in the membrane traffic of NGF and its receptor, gp140 TrkA (TrkA), in PC12 cells. NGF induced rapid and extensive endocytosis of TrkA in these cells, and the receptor subsequently moved into small organelles located near the plasma membrane. Some of these organelles contained clathrin and α-adaptin, which implies that TrkA is internalized by clathrin-mediated endocytosis. Using mechanical permeabilization and fractionation, intracellular organelles derived from endocytosis were separated from the plasma membrane. After NGF treatment, NGF was bound to TrkA in endocytic organelles, and TrkA was tyrosine-phosphorylated and bound to PLC-γ1, suggesting that these receptors were competent to initiate signal transduction. These studies raise the possibility that NGF induces formation of signaling endosomes containing activated TrkA. They are an important first step in elucidating the molecular mechanism of NGF retrograde signaling.
Technology has placed a new set of expectations and possibilities within our educational systems and many are struggling to adapt to the rapid rate of change it drives. At the same time, it has generated a new set of instructional forces within our classrooms and a new set of leadership requirements for educational leaders.
In this seminar, Don Hall will describe the journey of change and evolution in leading a school district to become known nationally for its excellence in use of technology to improve instruction. The journey has as its ultimate goal to transform the educational culture of schools in the District. The seminar will highlight how the strategic planning for the effective integration of educational technology requires organizations to take a holistic view of variables to positively impact the instructional experience for students.
Introduction: Conventional liver transplantation (CLTx) without venovenous bypass (VVB) remains controversial in the setting of impaired cardiac and renal function. The purpose of this study is to identify the incidence, potential risk factors, and outcomes of intraoperative cardiac arrest (ICA) in adults undergoing CLTx without VVB. Methods: Single-center, retrospective review of 862 consecutive conventional bicaval adult deceased CLTx without VVB between April 1, 2006 and June 30, 2013. Cardiac and renal impairment were identified from preoperative evaluations. ICA was defined as loss of vital signs requiring pharmacologic intervention, closed chest compressions, or open cardiac massage. Univariate analysis was performed to determine risk of ICA death among the identified patients. Results: ICA occurred in 28 of 862 (3.25%) CLTx. The patient demographics of this subset are shown in table 1. Two patients suffered ICA during the anhepatic phase, 25 patients arrested within 5 minutes of reperfusion, and 1 patient arrested 20 minutes after reperfusion. Twenty-five patients (89%) required cardiac massage or closed compressions with a median time of 3 minutes (range 1-60 minutes). There were 5 (18%) intraoperative deaths and 5 (18%) in-hospital deaths among the 28 patients. Eighteen patients (64.3%) with ICA survived to discharge. Univariate analysis did not identify any variable to predict risk for ICA death. Conclusions: Our single institution experience demonstrates that CLTx without VVB can be performed with a low incidence of ICA and mortality.Table: No Caption available.
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