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PubMed2000

Intergenic transcription and developmental remodeling of chromatin subdomains in the human beta-globin locus.

Gene activation requires chromatin remodeling complexes, which hyperacetylate histones and enable factor access; however, the targeting mechanisms leading to the establishment and maintenance of large, hyperacetylated DNase-sensitive chromatin domains are unknown. Recent work has shown that histone acetyltransferases are associated with RNA-pol II complexes, suggesting that transcription of chromatin plays a role in chromatin modification. Here we show the human beta-globin locus is divided into three differentially activated chromatin subdomains. Large transcripts precisely delineate the active domains at key cell cycle points associated with chromatin transitions and remodeling. We identify an element that initiates these transcripts, located in a region required for chromatin activation. The results suggest that intergenic transcription is required for chromatin remodeling of chromosomal domains.

Acetyltransferases↗
PubMed2002

Charged molecular alloys: synthesis and characterization of the binary anions Pd(7)As(16)(4-) and Pd(2)As(14)(4-).

Pd(PCy(3))(2) (Cy = cyclohexyl) reacts with As(7)(3-) in en/tol solvent mixtures to give Pd(2)As(14)(4-) (2) and Pd(7)As(16)(4-) (4) as the [K(2,2,2-crypt)](+) salts. The anions were characterized by EDX, ESI-MS, and single-crystal X-ray diffraction. Anion 2 formally contains two norbornadiene-like As(7)(5-) groups bound to square-planar Pd(III) centers linked by a Pd-Pd bond (d(Pd)(-)(Pd) = 2.7144(6) A). Anion 4 has a highly distorted capped trigonal prismatic Pd(7) core stabilized by 2 As(5)(1-), 2 As(2)(2-), and 2 As(3-) anions. The 6 Pd(I) ions are in distorted 5-coordinate environments whereas the lone Pd(II) ion is square planar. Complexes 2 and 4 are rare examples of organic-free, homoleptic transition metal anions containing group 15 elements, and they represent an emerging class of charged "molecular alloys".

Journal Article↗
PubMed2006

Irreducible representation and projection operator application to understanding nonlinear optical phenomena: hyper-Raman, sum frequency generation, and four-wave mixing spectroscopy.

Symmetry plays an essential role in understanding optical activities of a molecule in infrared and Raman vibrational spectroscopy as well as in nonlinear optical vibrational spectroscopy. Each vibrational mode belongs to an irreducible representation of the underlying symmetry group. In this paper, using the alpha-helical polypeptide symmetry as an example, we calculate all the third rank nonzero hyper-Raman tensors as well as the infrared and Raman tensors by applying the projection operators to each irreducible species. We demonstrate that the projection operator method provides selection rules for the infrared, Raman, and hyper-Raman vibrational transitions and also other nonlinear optical spectroscopy such as sum frequency generation and the four-, five-, and six-wave mixing coherent vibrational transitions. Specific expressions for all nonzero elements of the corresponding nonlinear susceptibility tensors in a laboratory-fixed coordinate frame are also deduced.

Optics and Photonics↗
PubMed2001

The home stretch, a first analysis of the nearly completed genome of Rhodobacter sphaeroides 2.4.1.

Rhodobacter sphaeroides 2.4.1 is an alpha-3 purple nonsulfur eubacterium with an extensive metabolic repertoire. Under anaerobic conditions, it is able to grow by photosynthesis, respiration and fermentation. Photosynthesis may be photoheterotrophic using organic compounds as both a carbon and a reducing source, or photoautotrophic using carbon dioxide as the sole carbon source and hydrogen as the source of reducing power. In addition, R. sphaeroides can grow both chemoheterotrophically and chemoautotrophically. The structural components of this metabolically diverse organism and their modes of integrated regulation are encoded by a genome of approximately 4.5 Mb in size. The genome comprises two chromosomes CI and CII (2.9 and 0.9 Mb, respectively) and five other replicons. Sequencing of the genome has been carried out by two groups, the Joint Genome Institute, which carried out shotgun-sequencing of the entire genome and The University of Texas-Houston Medical School, which carried out a targeted sequencing strategy of CII. Here we describe our current understanding of the genome when data from both of these groups are combined. Previous work had suggested that the two chromosomes are equal partners sharing responsibilities for fundamental cellular processes. This view has been reinforced by our preliminary analysis of the virtually completed genome sequence. We also have some evidence to suggest that two of the plasmids, pRS241a and pRS241b encode chromosomal type functions and their role may be more than that of accessory elements, perhaps representing replicons in a transition state.

Journal Article↗
PubMed2006

Retroviral invasion of the koala genome.

Endogenous retroviruses are a common ancestral feature of mammalian genomes with most having been inactivated over time through mutation and deletion. A group of more intact endogenous retroviruses are considered to have entered the genomes of some species more recently, through infection by exogenous viruses, but this event has never been directly proved. We have previously reported koala retrovirus (KoRV) to be a functional virus that is associated with neoplasia. Here we show that KoRV also shows features of a recently inserted endogenous retrovirus that is vertically transmitted. The finding that some isolated koala populations have not yet incorporated KoRV into their genomes, combined with its high level of activity and variability in individual koalas, suggests that KoRV is a virus in transition between an exogenous and endogenous element. This ongoing dynamic interaction with a wild species provides an exciting opportunity to study the process and consequences of retroviral endogenization in action, and is an attractive model for studying the evolutionary event in which a retrovirus invades a mammalian genome.

Animals↗
PubMed2005

Catechol-O-methyltransferase haplotypes are associated with psychosis in Alzheimer disease.

Psychotic symptoms in subjects with Alzheimer disease (AD with psychosis, AD+P) define a phenotype characterized by greater cognitive burden than in AD without psychosis. We have proposed that genes of small effect may contribute to the risk for expression of psychosis in multiple disorders, including AD. Recently, sex-differential association of a three-locus haplotype, including a G-->A transition at codon 108/158 of catechol-O-methyltransferase (COMT) resulting in a Val-->Met substitution, has been reported to confer an increased risk for schizophrenia. The main objective of the study was to determine if COMT genetic variation is associated with risk of psychosis in AD, and included a case-control study of 373 individuals diagnosed with AD with, or without, psychosis. All subjects were characterized for alleles at the three loci associated with schizophrenia, RS737865, COMT G-->A 108/158 (RS4680), and RS165599, and for a C/T transition adjacent to an estrogen response element (ERE6) in the COMT P2 promoter region. Both single locus and haplotype tests of association were conducted. Logit models were used to examine independent and interacting effects of alleles at the associated loci. All analyses were stratified by sex. In female subjects, RS4680 demonstrated a modest association with AD+P; RS737865 demonstrated a trend towards an association. There was a highly significant association of AD+P with the four-locus haplotype, which resulted from additive effects of alleles at RS4680 and ERE6 (or RS737865, as this locus was in almost absolute linkage disequilibrium (LD) with ERE6). In male subjects, no single locus test was significant, but there remained a strong association between AD+P and the four-locus haplotype. This association appeared to result from interaction of the ERE6/RS737865, RS4680, and RS165599 loci. Genetic variation in COMT is associated with AD+P, and thus appears to contribute to psychosis risk across disorders. Sex-differential associations of COMT with psychosis may result from variation at, or in LD with, ERE6. Examination of variation at ERE6 in subjects with schizophrenia, and further examination of the independent and additive effects of variations in COMT on gene expression, is warranted.

Aged↗
PubMed2004

Heteroscorpionate ligands based on bis(pyrazol-1-yl)methane: design and coordination chemistry.

Scorpionates represent one of the most versatile types of tridentate ligand that can coordinate to a wide variety of elements, e.g. from early to late transition metals, and the coordination chemistry of these systems has developed greatly in recent years. This Perspective gives an account of studies on the following aspects: (1) the preparative methods for a new class of heteroscorpionate [RR'C(pz)2] ligand derived from bis(pyrazol-1-yl)methane and (2) the description of metal complexes containing these ligands, examples of which incorporate a range of different metals from the Periodic Table.

Journal Article↗
PubMed2006

Relativistic quasidegenerate perturbation theory with four-component general multiconfiguration reference functions.

Relativistic quasidegenerate perturbation theory (QDPT) using general multiconfiguration (GMC) reference functions is developed and implemented. It is the relativistic counterpart of the nonrelativistic QDPT with GMC reference and thus retains all the advantages of the nonrelativistic GMC reference QDPT, such as applicability to any configuration space and small computational cost compared to the complete configuration-space case. The method is applied to the potential-energy curves of the ground states of I(2) and Sb(2) molecules, the excitation energies of CH(3)I, and the energies of the lowest terms of C, Si, and Ge atoms, and is shown to provide a balanced description of potential-energy curves and accurate transition energies for systems containing heavy elements and to provide much better results compared to the reference function (i.e., active space configuration interaction) level.

Journal Article↗
PubMed1986

Evolutionary progression at synaptic connections made by identified homologous neurones.

A comparative ultrastructural study of photoreceptor synapses formed upon homologous postsynaptic neurones in insects has been made by using serial-section electron microscopy in representative Diptera from a monophyletic series of 14 families. At all of the synaptic contacts there is a presynaptic dense bar, surmounted in phylogenetically more recent families by a presynaptic platform. Opposite the bar lies a pair of postsynaptic elements that invariably originate one each from two unique monopolar neurones L1 and L2. Both elements contain increasingly elaborate cisternae in more recent flies. Within the phylogenetic series, the postsynaptic ensemble itself changes from the original dyad to a tetradic configuration in more recent Muscomorpha by the addition of two new postsynaptic elements from an amacrine cell. This transition occurs once only in the series, which, gauged by the fossil record, covers divergences from the stem line extending back greater than 200 million years.

Animals↗
PubMed1998

Multiple G1 regulatory elements control the androgen-dependent proliferation of prostatic carcinoma cells.

Prostatic epithelial cells and most primary prostate tumors are dependent on androgen for growth, but how androgen regulates cellular proliferation remains unsolved. Using poorly understood mechanisms, recurrent tumor cells evade the androgen requirement. We utilized androgen-dependent prostatic tumor cells to demonstrate that androgen exerts its effect on the cell cycle by influencing specific aspects of G1-S progression. Androgen depletion of these cells results in early G1 arrest, characterized by reduced cyclin-dependent kinase activity, and underphosphorylated retinoblastoma tumor suppressor protein (RB). The reduction in kinase activity was partially attributed to reduction of specific G1 cyclins and alternate regulation of cyclin-dependent kinase inhibitors. Using this information, we developed a reliable assay to assess the ability of specific G1 regulatory proteins to circumvent these controls and promote androgen-independent growth. As expected, inactivation of RB was required for progression through the cell cycle. Surprisingly, overexpression of G1 cyclins, which drives RB phosphorylation, was insufficient to promote androgen-independent cell cycle progression. Introduction of viral oncoproteins did promote G1-S progression in the absence of androgen, dependent on their ability to sequester RB and related proteins. These results provide the first evidence that multiple elements governing the G1-S transition dictate androgen-dependent growth, and the formation of androgen-independent prostatic tumors may be because of misregulation of these processes.

Androgens↗
PubMedDate not supplied

Shaping the advanced practice psychiatric-mental health nursing role: a futuristic model.

As advanced practice psychiatric-mental health nursing has transitioned from earlier models of practice, elements of clinical specialist and psychiatric nurse practitioner roles are being blended to produce a new type of practitioner. The challenge of preserving mental health expertise while expanding advanced practice primary and primary mental health care competencies is addressed in several nursing education models. At New York University's Division of Nursing, faculty have designed a program around elements identified as essential to the autonomy demanded of the evolving role, knowledge, and skills basic to broad based health care and mental health care delivery with quality patient care outcomes and the competencies necessary for accountability as care providers in a changing health care delivery system. Essential elements, resources to identify them, and strategies to attain them are discussed. Approaches that promote student, clinician, and faculty development and maximize education affirm the specialty's capacity for innovation and the profession's capacity for new direction and futuristic change.

Curriculum↗
PubMed2003

Oxidative stress and neuronal adaptation in Alzheimer disease: the role of SAPK pathways.

Recent evidence indicates that oxidative stress occurs early in the progression of Alzheimer disease, significantly before the development of the hallmark pathologies, namely neurofibrillary tangles and senile plaques. The interaction of abnormal mitochondria, redox transition metals, and oxidative stress response elements contributes to the generation of reactive oxygen species in diseased neurons. Oxidative damage to major cellular molecules is seen in a number of disease states that are either acute or chronic and it is apparent that without eliciting compensations that restore redox balance, cells will rapidly succumb to death. Indeed, although oxidative stress is a prominent feature in Alzheimer disease, few vulnerable neurons show clear signs of apoptosis, suggesting that the level of oxidative stress does not significantly exceed neuronal oxidative defenses. In light of this observation, we propose that neurons in Alzheimer disease are exposed to low, but chronic, levels of oxidative stress that lead neurons to elicit adaptive responses such as the activation of stress-activated protein kinase pathways.

Alzheimer Disease↗
PubMed2000

Hormone activation induces nucleosome positioning in vivo.

The mouse mammary tumor virus (MMTV) promoter is induced by glucocorticoid hormone. A robust hormone- and receptor-dependent activation could be reproduced in Xenopus laevis oocytes. The homogeneous response in this system allowed a detailed analysis of the transition in chromatin structure following hormone activation. This revealed two novel findings: hormone activation led to the establishment of specific translational positioning of nucleosomes despite the lack of significant positioning in the inactive state; and, in the active promoter, a subnucleosomal particle encompassing the glucocorticoid receptor (GR)-binding region was detected. The presence of only a single GR-binding site was sufficient for the structural transition to occur. Both basal promoter elements and ongoing transcription were dispensable. These data reveal a stepwise process in the transcriptional activation by glucocorticoid hormone.

Animals↗
PubMed2004

The central role of the green alga Chlamydomonas reinhardtii in revealing the mechanism of state transitions.

This review focuses on the essential role played by the green alga Chlamydomonas reinhardtii in revealing both the mechanism and the physiological consequences of state transitions. Two aspects are considered. The first is the role of the cytochrome b6f complex in regulating state transitions, in light of the recently obtained 3D structure. The second is the switch between linear and cyclic electron flow that follows state transitions in Chlamydomonas. Structural and dynamic elements that might be involved in such a switch, as well as its consequences on the energetic metabolism, are discussed.

Animals↗
PubMed2001

Extreme damping in composite materials with a negative stiffness phase.

Composites with negative stiffness inclusions in a viscoelastic matrix are shown to have higher stiffness and mechanical damping tandelta than that of either constituent and exceeding conventional bounds. The causal mechanism is a greater deformation in and near the inclusions than the composite as a whole. Though a block of negative stiffness is unstable, negative stiffness inclusions in a composite can be stabilized by the surrounding matrix. Such inclusions may be made from single domains of ferroelastic material below its phase transition temperature or from prebuckled lumped elements.

Journal Article↗
PubMed2005

Band-selective measurements of electron dynamics in VO2 using femtosecond near-edge x-ray absorption.

We report on the first demonstration of femtosecond x-ray absorption spectroscopy, made uniquely possible by the use of broadly tunable bending-magnet radiation from "laser-sliced" electron bunches within a synchrotron storage ring. We measure the femtosecond electronic rearrangements that occur during the photoinduced insulator-metal phase transition in VO2. Symmetry- and element-specific x-ray absorption from V2p and O1s core levels (near 500 eV) separately measures the filling dynamics of differently hybridized V3d-O2p electronic bands near the Fermi level.

Journal Article↗