The ubiquitous transcription factor Yin Yang 1 (YY1) is known to have a fundamental role in normal biologic processes such as embryogenesis, differentiation, replication, and cellular proliferation. YY1 exerts its effects on genes involved in these processes via its ability to initiate, activate, or repress transcription depending upon the context in which it binds. Mechanisms of action include direct activation or repression, indirect activation or repression via cofactor recruitment, or activation or repression by disruption of binding sites or conformational DNA changes. YY1 activity is regulated by transcription factors and cytoplasmic proteins that have been shown to abrogate or completely inhibit YY1-mediated activation or repression; however, these mechanisms have not yet been fully elucidated. Since expression and function of YY1 are known to be intimately associated with progression through phases of the cell cycle, the physiologic significance of YY1 activity has recently been applied to models of tumor biology. The majority of the data are consistent with the hypothesis that YY1 overexpression and/or activation is associated with unchecked cellular proliferation, resistance to apoptotic stimuli, tumorigenesis and metastatic potential. Studies involving hematopoetic tumors, epithelial-based tumors, endocrine organ malignancies, hepatocellular carcinoma, and retinoblastoma support this hypothesis. Molecular mechanisms that have been investigated include YY1-mediated downregulation of p53 activity, interference with poly-ADP-ribose polymerase, alteration in c-myc and nuclear factor-kappa B (NF-kappaB) expression, regulation of death genes and gene products, and differential YY1 binding in the presence of inflammatory mediators. Further, recent findings implicate YY1 in the regulation of tumor cell resistance to chemotherapeutics and immune-mediated apoptotic stimuli. Taken together, these findings provide strong support of the hypothesis that YY1, in addition to its regulatory roles in normal biologic processes, may possess the potential to act as an initiator of tumorigenesis and may thus serve as both a diagnostic and prognostic tumor marker; furthermore, it may provide an effective target for antitumor chemotherapy and/or immunotherapy.

Background: Apathy is the most common noncognitive symptom inAlzheimer’s disease (AD). The structural correlates of apathy in AD have not yet been described. Methods: We analyzed magnetic resonance imaging data of 35 AD patients with and without apathy. Results: There was a significant linear association between apathy severity and cortical gray matter atrophy in the bilateral anterior cingulate [Brodmann area (BA) 24; r = 0.39–0.42, p = 0.01] and left medial frontal cortex (BA 8 and 9; r = 0.4, p < 0.02). Left mean cingulate cortical thinning predicted the presence/absence of apathy at the trend level of significance. Conclusion: Our study demonstrates a strong association between apathy and the integrity of medial frontal regions in AD.

The deleterious effects of tumor-promoting tobacco carcinogen, nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, nicotine-derived nitrosamine ketone) have undoubtedly been stipulated. Though many tobacco agents play a part in the development of lung tumors, the potent effects of NNK remain unmatched. It is therefore critical to distinguish the variety of cofactors involved in NNK-mediated pathogenesis, and the unique pathways necessary for successful cellular biotransformation. Current reviews have consistently identified the strengths of NNK and prospective tumor capabilities. Others have delineated specific cellular factors mediating NNK and lung tumors, and have identified metabolic and signaling pathways largely responsible for NNK activation and tumorigenic initiation. Unique to this review is that it summarizes the extensive network of cofactors and cellular mechanisms that promote NNK-specific lung tumorigenesis. As such, it displays a fuller, more comprehensive overview, bringing us one step closer to understanding the fatal consequences of NNK, thus, discovering new avenues that successfully break the cycle of NNK-mediated lung carcinogenesis. Contents 1. Introduction 2. Activation of NNK-mediated lung tumorigenesis 3. Effects of NNK on cellular factors 4. Repression of NNK-mediated lung tumorigenesis 5. Concluding remarks

Background: Alzheimer disease (AD) is the most common form of dementia worldwide. Mild cognitive impairment (MCI) is the recent terminology for patients with cognitive deficiencies in the absence of functional decline. Most patients with MCI harbor the pathologic changes of AD and demonstrate transition to dementia at a rate of 10% to 15% per year. Patients with AD and MCI experience progressive brain atrophy.Objective: To analyze the structural magnetic resonance imaging data for 24 patients with amnestic MCI and 25 patients with mild AD using an advanced 3-dimensional cortical mapping technique.Design: Cross-sectional cohort design.Patients/Methods: We analyzed the structural magnetic resonance imaging data of 24 amnestic MCI (mean MMSE, 28.1; SD, 1.7) and 25 mild AD patients (all MMSE scores, Ͼ18; mean MMSE, 23.7; SD, 2.9) using an advanced 3-dimensional cortical mapping technique. Results:We observed significantly greater cortical atrophy in patients with mild AD. The entorhinal cortex, right more than left lateral temporal cortex, right parietal cortex, and bilateral precuneus showed 15% more atrophy and the remainder of the cortex primarily exhibited 10% to 15% more atrophy in patients with mild AD than in patients with amnestic MCI. Conclusion:There are striking cortical differences between mild AD and the immediately preceding cognitive state of amnestic MCI. Cortical areas affected earlier in the disease process are more severely affected than those that are affected late. Our method may prove to be a reliable in vivo disease-tracking technique that can also be used for evaluating disease-modifying therapies in the future.

Minimally invasive catheter-based electrophysiological (EP) interventions are becoming a standard procedure in diagnosis and treatment of cardiac arrhythmias. As a result of technological advances that enable small feature sizes and a high level of integration, nonfluoroscopic intracardiac echocardiography (ICE) imaging catheters are attracting increasing attention. ICE catheters improve EP procedural guidance while reducing the undesirable use of fluoroscopy, which is currently the common catheter guidance method. Phased-array ICE catheters have been in use for several years now, although only for side-looking imaging. We are developing a forward-looking ICE catheter for improved visualization. In this effort, we fabricate a 24-element, fine-pitch 1-D array of capacitive micromachined ultrasonic transducers (CMUT), with a total footprint of 1.73 mm × 1.27 mm. We also design a custom integrated circuit (IC) composed of 24 identical blocks of transmit/receive circuitry, measuring 2.1 mm × 2.1 mm. The transmit circuitry is capable of delivering 25-V unipolar pulses, and the receive circuitry includes a transimpedance preamplifier followed by an output buffer. The CMUT array and the custom IC are designed to be mounted at the tip of a 10-Fr catheter for high-frame-rate forward-looking intracardiac imaging. Through-wafer vias incorporated in the CMUT array provide access to individual array elements from the back side of the array. We successfully flip-chip bond a CMUT array to the custom IC with 100% yield. We coat the device with a layer of polydimethylsiloxane (PDMS) to electrically isolate the device for imaging in water and tissue. The pulse-echo in water from a total plane reflector has a center frequency of 9.2 MHz with a 96% fractional bandwidth. Finally, we demonstrate the imaging capability of the integrated device on commercial phantoms and on a beating ex vivo rabbit heart (Langendorff model) using a commercial ultrasound imaging system.