Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Jun 2007
The cdx-hox pathway in hematopoietic stem cell formation from embryonic stem cells.
Embryonic stem cells (ESCs) differentiated in vitro will yield a multitude of hematopoietic derivatives, yet progenitors displaying true stem cell activity remain difficult to obtain. Possible causes are a biased differentiation to primitive yolk sac-type hematopoiesis, and a variety of developmental or functional deficiencies. ⋯ We show here that brief pulses of ectopic Cdx4 or HoxB4 expression are sufficient to enhance hematopoiesis during ESC differentiation, presumably by acting as developmental switches to activate posterior Hox genes. Insights into the role of the Cdx-Hox gene pathway during embryonic hematopoietic development in the zebrafish have allowed us to improve the derivation of repopulating HSCs from murine ESCs.
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Ann. N. Y. Acad. Sci. · Mar 2007
ReviewPhosphorylation and other conundrums of Na/Ca exchanger, NCX1.
The Na+/Ca2+ exchanger (NCX) is an important Ca2+ transport mechanism in virtually all cells in the body. There are three genes that control the expression of NCX in mammals. ⋯ Here we briefly discuss three remarkable regulatory issues or "conundrums" that involve the most prevalently expressed gene, NCX1. (1) How is NCX1 regulated by phosphorylation? We suggest that the macromolecular complex of NCX1 plays a critical role in the regulation of NCX. The role of the macromolecular complex and evidence supporting its existence and functional importance is presented. (2) Can there be transport block of a single "mode" of NCX1 transport by drugs or therapeutic agents? The simple answer is "no." A brief explanation is provided. (3) How can NCX1 knockout mice live? The answer is "by other compensatory regulatory mechanisms." These conundrums highlight important features in NCX1 and lay the foundation for new experiments to elucidate function and regulation of NCX1 and provide a context for investigations that seek to understand novel therapeutic agents.
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Ann. N. Y. Acad. Sci. · Mar 2007
Comparative StudyGender-specific differences in salivary biomarker responses to acute psychological stress.
The stress response is regulated by two primary neuroendocrine systems, the hypothalamus-pituitary-adrenocortical (HPA) and sympathetic adrenomedullary (SAM) systems. This study investigated gender differences in the activities of these two systems in response to acute psychological stress. Subjects were categorized according to their score in Spielberger's Trait Anxiety Inventory (STAI), which assesses the predisposition to personal anxiety. ⋯ There were no gender differences in amylase levels in either the high- or low-anxiety groups. However, cortisol levels in highly anxious females were significantly lower than those in highly anxious males. Our findings show that highly anxious females exhibited lower cortisol release than highly anxious males, suggesting that high trait anxiety in females may be associated with an inability to respond with sufficient activation of HPA under acute psychological stress.
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Ann. N. Y. Acad. Sci. · Feb 2007
ReviewShifting paradigms in dementia: toward stratification of diagnosis and treatment using MRI.
Atrophy and cerebrovascular disease are the two most important magnetic resonance imaging (MRI) characteristics in the evaluation of dementia. On MRI, atrophy is the primary hallmark of neurodegenerative dementias including Alzheimer's disease (AD), while vascular dementia is characterized by the presence of ischemic vascular damage, such as territorial infarcts, lacunes, and white matter hyperintensities. Evidence is accumulating that vascular factors play an important role in the development of cognitive decline at old age and clinical AD. ⋯ The strict distinction between AD and vascular dementia is often artificial, as most patients suffer from both disorders to some extent. For the future, we see an important role for MRI in identifying those different compartments, regardless of clinical classification. Treatment could be directed by (and evaluated through) MRI patterns, rather than a diagnostic label.
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Ann. N. Y. Acad. Sci. · Feb 2007
Quantitative EEG and electromagnetic brain imaging in aging and in the evolution of dementia.
Electroencephalographic (EEG) changes with normal aging have long been reported. Departures from age-expected changes have been observed in mild cognitive impairment and dementia, the magnitude of which correlates with the degree of cognitive impairment. Such abnormalities include increased delta and theta activity, decreased mean frequency, and changes in coherence. ⋯ We have recently reported results from initial quantitative electroencephalography (QEEG) evaluations of normal elderly subjects (with only subjective reports of memory loss), predicting future cognitive decline or conversion to dementia, with high prediction accuracy (approximately 95%). In this report, source localization algorithms were used to identify the mathematically most probable underlying generators of abnormal features of the scalp-recorded EEG from these patients with differential outcomes. Using this QEEG method, abnormalities in brain regions identified in studies of AD using MEG, MRI, and positron emission tomography (PET) imaging were found in the premorbid recordings of those subjects who go on to decline or convert to dementia.