Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · May 2004
ReviewCardiac fiber orientation and the left-right asymmetry determining mechanism.
The invariant nature of body situs within and across vertebrate species implies that a highly conserved pathway controls the specification of the left-right (L/R) axis. Situs-specific morphogenesis begins at the end of this pathway and leads to normal organ arrangement, also known as situs solitus. Occasionally, individuals have a complete, mirror image reversal of this asymmetry, called situs inversus totalis (SIT). ⋯ However, the helical myofiber pattern within the left ventricle (LV) wall is only partially mirror imaged: apical and superficial basal fiber orientation are as in normal persons, whereas the deeper basal layers have an inverted fiber orientation. Because of this bivalent fiber orientation pattern, LV deformation in humans with SIT is mirror imaged only near the base, but near the apex it is as in normal subjects. Apparently, the embryonic L/R controlling genetic pathway does determine situs-specific gross anatomy morphogenesis, but it is not the only factor regulating fiber architecture within the LV wall.
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Recent years have witnessed a dramatic increase in publications implicating free radicals and oxidative stress in virtually every aspect of biology and medicine. Redox Neurology may be defined as the study of the roles of free radicals, transition metals, oxidative stress, and antioxidant defenses in diseases of the nervous system. ⋯ Opportunities for research and teaching careers in the redox neurosciences are outlined. The paper concludes with a forecast of several research themes likely to preoccupy this nascent discipline in the days ahead.
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Ann. N. Y. Acad. Sci. · Mar 2004
Comparative StudyMitochondrial localization of human PANK2 and hypotheses of secondary iron accumulation in pantothenate kinase-associated neurodegeneration.
Mutations in the pantothenate kinase 2 gene (PANK2) lead to pantothenate kinase-associated neurodegeneration (PKAN, formerly Hallervorden-Spatz syndrome). This neurodegenerative disorder is characterized by iron accumulation in the basal ganglia. Pantothenate kinase is the first enzyme in the biosynthesis of coenzyme A from pantothenate (vitamin B(5)). ⋯ Furthermore, PANK2 uses an unconventional translational start codon, CUG, which is polymorphic in the general population. The variant sequence, CAG (allele frequency: 0.05), leads to skipping of the mitochondrial targeting signal and cytosolic localization of PANK2. This common variant may cause mitochondrial dysfunction and impart susceptibility to late-onset neurodegenerative disorders with brain iron accumulation, including Parkinson's disease.
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Ann. N. Y. Acad. Sci. · Mar 2004
Comparative StudyIroning iron out in Parkinson's disease and other neurodegenerative diseases with iron chelators: a lesson from 6-hydroxydopamine and iron chelators, desferal and VK-28.
In Parkinson's disease (PD) and its neurotoxin-induced models, 6-hydroxydopamine (6-OHDA) and N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), significant accumulation of iron occurs in the substantia nigra pars compacta. The iron is thought to be in a labile pool, unbound to ferritin, and is thought to have a pivotal role to induce oxidative stress-dependent neurodegeneration of dopamine neurons via Fenton chemistry. The consequence of this is its interaction with H(2)O(2) to generate the most reactive radical oxygen species, the hydroxyl radical. ⋯ Desferal also protected against 6-OHDA-induced deficit in locomotor activity, rearing, and exploratory behavior (sniffing) in a novel environment. Since the lowest neuroprotective dose (1.3 micro g) of desferal was 200 times less than 6-OHDA, its neuroprotective activity may not be attributed to interference with the neurotoxin activity, but rather iron chelation. These studies led us to develop novel brain-permeable iron chelators, the VK-28 series, with iron chelating and neuroprotective activity similar to desferal for ironing iron out from PD and other neurodegenerative diseases, such as Alzheimer's disease, Friedreich's ataxia, and Huntington's disease.
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Ann. N. Y. Acad. Sci. · Dec 2003
Emotion in the infant's face: insights from the study of infants with facial anomalies.
Darwin viewed "experiments in nature" as an important strategy for elucidating the evolutionary bases of human emotional expressions. Infants with craniofacial anomalies are of special interest because morphological abnormalities and resulting distortions or deficits in their facial expressions could make it more difficult for caregivers to read and accurately interpret their signals. As part of a larger study on the effects of craniofacial anomalies on infant facial expression and parent-infant interaction, infants with different types of craniofacial conditions and comparison infants were videotaped interacting with their mothers at 3 and 6 months. ⋯ A 4 (infant group) x 4 (expression category) ANOVA showed a significant main effect for expression category, F(3) 5 71.9, P 5 0.000, but no significant effect for infant group or group 3 expression interaction. The observers' ratings were thus highly "accurate" in terms of a priori Baby FACS criteria, even in the case of infants with severely disfiguring facial conditions. These findings demonstrate that the signal value of infant facial expressions is remarkably robust, suggesting that the capacity to read emotional meaning in infants' facial expressions may have a biological basis.