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At least 307 records · Page 17Linked to original sources
PubMed2004

Children's meal patterns have changed over a 21-year period: the Bogalusa Heart Study.

OBJECTIVE: The objective of this study was to analyze children's meal patterns over 2 decades. DESIGN: One 24-hour dietary recall was collected on each child who participated in one of seven cross-sectional surveys. SUBJECTS/SETTING: Dietary intake data were collected on 1,584 10-year-old children (65% white, 35% African American), in Bogalusa, LA, from 1973 to 1994. STATISTICAL ANALYSES: Descriptive statistics and one-way analysis of variance adjusting for gender and ethnicity. RESULTS: From 1973 to 1978, there was a marked increase (P<.0001) in the percentage of children who skipped breakfast, from 8.2% to 29.6%. When school breakfast was introduced in 1981, the proportion of children skipping breakfast declined to 12.5% (P<.01). From 1973-1974 to 1993-1994, the percentage of children eating a school lunch declined from 89.7% (1973-1974) to 78.2% (1993-1994) (P<.001); eating lunch brought from home increased from 5.9% to 11.1% (P<.01); consuming a home dinner decreased from 89.2% to 75.9% (P<.01); eating a dinner prepared outside the home increased from 5.4% to 19.0% (P<.01); consuming a meal at a restaurant increased from 0.3% to 5.4% (P<.0001); consuming snacks decreased (P<.0001); total eating episodes decreased from 6.6 to 5.2 (P<.0001); and eating time span significantly decreased from 12.4 hours to 11.5 hours (P<.0001). Despite these changes in meal patterns, no associations were found between meal patterns and overweight status. CONCLUSIONS: Striking alterations in the meal patterns of children occurred over the 2-decade period. These changes may have implications for the changes in the dietary intakes of children during the same time. However, data from this study do not support an association between meal patterns and children's overweight status. Further research with multiple days of assessment is needed to better understand the complexity of diet as it relates to childhood obesity.

Analysis of Variance↗
PubMed2002

Attenuating functions of the C terminus of lambda integrase.

The tyrosine family site-specific recombinases, in contrast to the related type I topoisomerases, which act as monomers on a single DNA molecule, rely on multi-protein complexes to synapse partner DNAs and coordinate two sequential strand exchanges involving four nicking-closing reactions. Here, we analyze three mutants of the catalytic domain of lambda integrase (Int), A241V, I353M and W350ter that are defective for normal recombination, but possess increased topoisomerase activity. The mutant enzymes can carry out individual DNA strand exchanges using truncated substrates or Holliday junctions, and they show more DNA-cleavage activity than wild-type Int on isolated att sites. Structural modeling predicts that the substituted residues may destabilize interactions between the C-terminal beta-strand (beta7) of Int and the core of the protein. The cleavage-competent state of Int requires the repositioning of the nucleophile (Y342) located on beta6 and the catalyst K235 located on the flexible beta2-beta3 loop, relative to their positions in a crystal structure of the inactive conformation. We propose that the anchoring of beta7 against the protein core restrains the movement of Tyr342 and/or Lys235, causing an attenuation of cleavage activity in most contexts. Within a bona fide recombination complex, the release of strand beta7 would allow Tyr342 and Lys235 to assume catalytically active conformations in coordination with other Int protomers in the complex. The loss of beta7 packing by misalignment or truncation in the mutant proteins described here causes a loss of regulated activity, thereby favoring DNA cleavage activity in monomeric complexes and forfeiting the coordination of strand-exchange necessary for efficient recombination.

Amino Acid Sequence↗
PubMed2003

An Xp; Yq translocation causing a novel contiguous gene syndrome in brothers with generalized epilepsy, ichthyosis, and attention deficits.

PURPOSE: We describe two brothers with generalized epilepsy, attention deficits, congenital ichthyosis, and Leri-Weill dyschondrosteosis who harbor an unusual Xp; Yq translocation chromosome, resulting in a novel contiguous gene syndrome because of deletion of genes from the distal short arm of the X chromosome. METHODS: Physical examination, neuropsychologic testing, EEG, and neuroimaging studies were performed. Because of their unusual phenotype, karyotyping, fluorescence in situ hybridization, and further molecular analyses were carried out to refine the break points of the underlying unbalanced sex chromosome rearrangement. RESULTS: The subjects had generalized epilepsy, X-linked ichthyosis, Madelung deformities, mesomelia, normal intelligence, and attention deficits. The brothers' karyotype was unbalanced; they inherited a maternal derivative X chromosome. Deleted distal Xp genes included short-stature homeobox on the X chromosome (SHOX), aryl sulfatase E (ARSE), variably charged X-chromosome mRNA gene A (VCX-A), and steroid sulfatase (STS). The final karyotype was 46,Y,der(X)t(X; Y)(p22.3; q11.2).ish der(X) (DXZ1+, KAL+, STS-, SHOX-) mat. CONCLUSIONS: Loss of distal contiguous Xp genes resulted in a syndrome comprising bony deformities, ichthyosis, attention problems, and generalized epilepsy. Candidate epilepsy genes within the deleted segment, such as ASMT, a gene involved in the final synthesis of melatonin, are discussed. Cytogenetic analyses should be included in the clinical evaluation of patients with generalized epilepsy and complex phenotypes.

Adolescent↗
PubMedDate not supplied

HCA Richmond Hospitals' new marketing strategy a winning plan.

HCA Richmond Hospitals, a five-hospital system in Richmond, Va., is positioning itself as a winner in a highly competitive, healthcare-saturated market since overhauling is marketing strategy a little over a year ago. The marketing strategy enables individual hospital to target their own unique constituencies. "Understanding the intricate marketing dynamics of hospital systems is today of critical importance and equal complexity," said Tony Bejamin, principal of Oxygen Advertising Inc., New York, the agency that remodeled HCA Richmond Hospitals' marketing strategy.

Catchment Area, Health↗
PubMed2002

Expression analyses and interaction with the anaphase promoting complex protein Apc2 suggest a role for inversin in primary cilia and involvement in the cell cycle.

Homozygous inv mice lack a functional inversin protein and exhibit situs inversus plus severe cystic changes in the kidney and pancreas. Although the inversin sequence has provided few clues to its function, we and others have previously identified calmodulin as a binding partner. We now provide evidence that inversin interacts with the anaphase promoting complex protein Apc2. As expected of an Apc2 target, inversin possesses D-boxes and site-directed mutagenesis of the well-conserved D-box residues abrogates inversin-Apc2 interaction. An inversin-specific antibody reveals a dynamic expression pattern throughout the cell cycle and strong expression in the primary cilia of renal epithelium. Our data support a role for inversin in primary cilia and involvement in the cell cycle. Mutations of the proteins polaris, cystin and polycystin-2 which are expressed in renal epithelium primary cilia, lead to renal cystic changes. Aberrant cell proliferation is also involved in cyst development. The data reported here suggest that inversin may provide a link between these two mechanisms.

Amino Acid Motifs↗
PubMed2006

Systems-level analyses identify extensive coupling among gene expression machines.

Here, we develop computational methods to assess and consolidate large, diverse protein interaction data sets, with the objective of identifying proteins involved in the coupling of multicomponent complexes within the yeast gene expression pathway. From among approximately 43 000 total interactions and 2100 proteins, our methods identify known structural complexes, such as the spliceosome and SAGA, and functional modules, such as the DEAD-box helicases, within the interaction network of proteins involved in gene expression. Our process identifies and ranks instances of three distinct, biologically motivated motifs, or patterns of coupling among distinct machineries involved in different subprocesses of gene expression. Our results confirm known coupling among transcription, RNA processing, and export, and predict further coupling with translation and nonsense-mediated decay. We systematically corroborate our analysis with two independent, comprehensive experimental data sets. The methods presented here may be generalized to other biological processes and organisms to generate principled, systems-level network models that provide experimentally testable hypotheses for coupling among biological machines.

Cluster Analysis↗
PubMed2004

Protein-protein interactions governing septin heteropentamer assembly and septin filament organization in Saccharomyces cerevisiae.

Mitotic yeast (Saccharomyces cerevisiae) cells express five related septins (Cdc3, Cdc10, Cdc11, Cdc12, and Shs1) that form a cortical filamentous collar at the mother-bud neck necessary for normal morphogenesis and cytokinesis. All five possess an N-terminal GTPase domain and, except for Cdc10, a C-terminal extension (CTE) containing a predicted coiled coil. Here, we show that the CTEs of Cdc3 and Cdc12 are essential for their association and for the function of both septins in vivo. Cdc10 interacts with a Cdc3-Cdc12 complex independently of the CTE of either protein. In contrast to Cdc3 and Cdc12, the Cdc11 CTE, which recruits the nonessential septin Shs1, is dispensable for its function in vivo. In addition, Cdc11 forms a stoichiometric complex with Cdc12, independent of its CTE. Reconstitution of various multiseptin complexes and electron microscopic analysis reveal that Cdc3, Cdc11, and Cdc12 are all necessary and sufficient for septin filament formation, and presence of Cdc10 causes filament pairing. These data provide novel insights about the connectivity among the five individual septins in functional septin heteropentamers and the organization of septin filaments.

Amino Acid Sequence↗
PubMed2006

Knowledge-based real-space explorations for low-resolution structure determination.

The accurate and effective interpretation of low-resolution data in X-ray crystallography is becoming increasingly important as structural initiatives turn toward large multiprotein complexes. Substantial challenges remain due to the poor information content and ambiguity in the interpretation of electron density maps at low resolution. Here, we describe a semiautomated procedure that employs a restraint-based conformational search algorithm, RAPPER, to produce a starting model for the structure determination of ligase interacting factor 1 in complex with a fragment of DNA ligase IV at low resolution. The combined use of experimental data and a priori knowledge of protein structure enabled us not only to generate an all-atom model but also to reaffirm the inferred sequence registry. This approach provides a means to extract quickly from experimental data useful information that would otherwise be discarded and to take into account the uncertainty in the interpretation--an overriding issue for low-resolution data.

Algorithms↗
PubMed2006

Distinct ubiquitin-ligase complexes define convergent pathways for the degradation of ER proteins.

Many misfolded endoplasmic reticulum (ER) proteins are eliminated by ERAD, a process in which substrates are polyubiquitylated and moved into the cytosol for proteasomal degradation. We have identified in S. cerevisiae distinct ubiquitin-ligase complexes that define different ERAD pathways. Proteins with misfolded ER-luminal domains use the ERAD-L pathway, in which the Hrd1p/Hrd3p ligase forms a near stoichiometric membrane core complex by binding to Der1p via the linker protein Usa1p. This core complex associates through Hrd3p with Yos9p, a substrate recognition protein in the ER lumen. Substrates with misfolded intramembrane domains define a pathway (ERAD-M) that differs from ERAD-L by being independent of Usa1p and Der1p. Membrane proteins with misfolded cytosolic domains use the ERAD-C pathway and are directly targeted to the Doa10p ubiquitin ligase. All three pathways converge at the Cdc48p ATPase complex. These results lead to a unifying concept for ERAD that may also apply to mammalian cells.

Adenosine Triphosphatases↗
PubMed2004

Ecological and evolutionary implications of immunological priming in invertebrates.

Invertebrates have an immune response that differs considerably from the acquired immune response found in vertebrates. However, new studies indicate that past experience with a pathogen can provide individual invertebrates, or their descendants, with enhanced immunity. This prophylactic effect, termed immunological priming, is functionally similar to the acquired immune response in vertebrates. This newfound complexity of invertebrate immunity begs investigation into the conditions under which immunological priming should evolve, and its consequences for population dynamics.

Journal Article↗
PubMed2005

Cooperative dimerization of fibroblast growth factor 1 (FGF1) upon a single heparin saccharide may drive the formation of 2:2:1 FGF1.FGFR2c.heparin ternary complexes.

The related glycosaminoglycans heparin and heparan sulfate are essential for the activity of the fibroblast growth factor (FGF) family as they form an integral part of the signaling complex at the cell surface. Using size-exclusion chromatography we have studied the capacities of a variety of heparin oligosaccharides to bind FGF1 and FGFR2c both separately and together in ternary complexes. In the absence of heparin, FGF1 had no detectable affinity for FGFR2c. However, 2:2:1 complexes formed spontaneously in solution between FGF1, FGFR2c, and heparin octasaccharide (dp8). The dp8 sample was the shortest chain length that bound FGFR2c, that dimerized FGF1, and that promoted a strong mitogenic response to FGF1 through FGFR2c. Heparin hexasaccharide and various selectively desulfated heparin dp12s failed to bind FGFR2c and could only interact with FGF1 monomerically. These saccharides formed 1:1:1 complexes with FGF1 and FGFR2c, which had no tendency to self-associate, suggesting that binding of two FGF1 molecules to the same saccharide chain is a prerequisite for subsequent FGFR2c dimerization. We found that FGF1 dimerization upon heparin was favored over monomeric interactions even when a large excess of saccharide was present. A cooperative mechanism of FGF1 dimerization could explain how 2:2:1 signaling complexes form at the cell surface, an environment rich in heparan sulfate.

Chromatography, Gel↗
PubMed2002

A cyclophilin functions in pre-mRNA splicing.

We report that the cyclophilin USA-CyP is part of distinct complexes with two spliceosomal proteins and is involved in both steps of pre-mRNA splicing. The splicing factors hPrp18 and hPrp4 have a short region of homology that defines a high affinity binding site for USA-CyP in each protein. USA-CyP forms separate, stable complexes with hPrp18 and hPrp4 in which the active site of the cyclophilin is exposed. The cyclophilin inhibitor cyclosporin A slows pre-mRNA splicing in vitro, and we show that its inhibition of the second step of splicing is caused by blocking the action of USA-CyP within its complex with hPrp18. Cyclosporin A also slows splicing in vivo, and we show that this slowing results specifically from inhibition of USA-CyP. Our results lead to a model in which USA-CyP is carried into the spliceosome in complexes with hPrp4 and hPrp18, and USA-CyP acts during splicing within these complexes. These results provide an example of the function of a cyclophilin in a complex process and provide insight into the mechanisms of action of cyclophilins.

Amino Acid Sequence↗
PubMed2006

Daily consumption for six weeks of a lignan complex isolated from flaxseed does not affect endothelial function in healthy postmenopausal women.

The occurrence of menopause is associated with an increased risk of cardiovascular events, and this has partly been attributed to the decline in circulating levels of estrogen. A lignan complex rich in the plant lignan secoisolariciresinol diglucoside (SDG) was isolated from flaxseed. SDG is metabolized by the colonic microflora to the mammalian lignans enterodiol and enterolactone and is hypothesized to be cardioprotective due to their structural similarity to estrogen. The aim of this study was to investigate the effect of a lignan complex, providing 500 mg/d of SDG, on markers of endothelial function. Healthy postmenopausal women (n = 22) completed a randomized, double-blind, placebo-controlled, crossover study. Women consumed daily a low-fat muffin, with or without a lignan complex, for 6 wk, separated by a 6-wk washout period. Flow-mediated, endothelium-dependent vasodilatation (FMD) and nitroglycerine-mediated, endothelium-independent vasodilatation were measured at the end of each intervention period. The sum of Plasma nitrite and nitrate (NOx), endothelin-1 (ET-1), and asymmetric dimethylarginine (ADMA) were measured at the beginning and end of each intervention period. FMD was 3.6 +/- 0.9% (mean +/- SEM) after the lignan complex intervention period compared with 3.9 +/- 0.7% after the placebo period (P = 0.72). Plasma concentrations of NOx, ET-1, and ADMA were not affected. We conclude that daily consumption for 6 wk of a low-fat muffin enriched with a lignan complex had no effect on endothelial function in healthy postmenopausal women.

4-Butyrolactone↗
PubMed2004

High factor VIII levels in venous thromboembolism show linkage to imprinted loci on chromosomes 5 and 11.

High factor VIII (FVIII) levels are known to be a risk factor for deep venous thrombosis, but the mechanisms responsible for high FVIII levels remain unclear. Here, a new phenotype "FVIII level residuum" (FVIII-R) was defined in order to eliminate the impact of common determinants on FVIII levels. We studied 13 families of patients with thrombosis and reproducibly high FVIII levels of unknown origin. Since familial clustering was evident, we looked for a possible genetic basis. A genome scan was performed with 402 evenly spaced microsatellite markers. A quantitative linkage analysis using variance component methods showed suggestive evidence for linkage of FVIII-R with a locus on chromosome 8 (logarithm of odds [LOD] = 2.1). In addition, we performed parametric exploratory linkage analysis of dichotomized FVIII-R, taking a parent-of-origin effect into account. Single-trait-locus MOD-score analysis showed suggestive evidence for linkage under an imprinting model at chromosomes 5 and 11. Furthermore, a 2-trait-locus analysis under a multiplicative model for the loci of chromosomes 5 and 11 yielded a remarkable LOD of 4.44. It confirmed the finding of paternal imprinting, obtained by single-trait-locus analysis, at both loci. Our results suggest that high FVIII levels in venous thromboembolism represent a complex trait caused by several genetic factors.

Chromosomes, Human, Pair 11↗
PubMed2006

Magneto-optic spectroscopy of a protein tetramer binding two exciton-coupled chlorophylls.

In vitro chlorophyll (Chl) aggregates have often served as models for in vivo forms of long-wavelength Chl. However, the interaction of protein-bound Chl molecules is typically different than that occurring in solvent-based self-aggregates. We have chosen a water-soluble Chl-binding protein (WSCP) from cauliflower in order to help characterize the spectroscopic properties of Chl in a single well-defined native environment and also to study the pigment-pigment (exciton) interactions present in assemblies of this protein. WSCP forms tetrameric units upon binding two Chl molecules. We present the absorption, circular dichroism (CD), magnetic circular dichroism (MCD), and emission spectra at 1.7 K of recombinant WSCP tetramers containing either Chl a or Chl d. The spectroscopic characteristics provide evidence for significant exciton interaction between equivalent Chl molecules. Our simple exciton analysis allows an estimate of the molecular geometry of the dimer, which is predicted to have an "open sandwich"-type structure. We find that the ratio of the magnetic circular dichroism to absorption, deltaA/A, is substantially increased (approximately 60%) for Chl a in this system compared to its value in solution. This increase is in marked contrast to substantial reductions (>50%) of deltaA/A seen in solvent-based Chl aggregates and in photosynthetic reaction centers. Current theoretical models are unable to account for such large variations in the MCD to absorption ratio for Chl. We propose that spectroscopic studies of WSCP mutants will enable a fundamental understanding of Chl-Chl and Chl-protein interactions.

Absorption↗
PubMed2003

(18)O isotope exchange measurements reveal that calcium is involved in the binding of one substrate-water molecule to the oxygen-evolving complex in photosystem II.

Direct evidence is presented to show that calcium is inherently involved in the binding of one of the two substrate-water molecules to the oxygen-evolving complex in photosystem II. Previous rapid (millisecond range) (18)O isotope exchange measurements between added H(2)(18)O and the photogenerated O(2) have shown that the two substrate-water molecules bind to separate sites throughout the S-state cycle, as revealed by their kinetically distinct rates of (18)O exchange [Hillier, W., and Wydrzynski, T. (2000) Biochemistry 39, 4399-4405]. Upon extraction of the functionally bound calcium using a either a low-pH/citrate treatment or a NaCl/A23187/EGTA treatment and subsequent reconstitution of activity with strontium, we show for the first time a specific increase in the slow rate of (18)O exchange by a factor of 3-4. This increase in the slow rate of exchange is consistently observed across the S(1), S(2), and S(3) states. In contrast, the fast phase of (18)O exchange in the S(3) state appears to be affected little upon strontium reconstitution, while the fast phases of exchange in the S(1) and S(2) states remain largely unresolvable, at the detectable limits of the current techniques. The results are discussed in terms of a possible substrate bridging structure between the functional calcium and a catalytic manganese ion that gives rise to the slowly exchanging component.

Binding Sites↗
PubMed1999

The Tom channel in the mitochondrial outer membrane: alive and kicking.

The targeting of newly-made polypeptides to specific membranes, and the subsequent ability of a membrane to allow only certain polypeptides into its compartment, are essential to maintain the ultrastructure of Eukaryotic cells. Distinct oligomeric protein complexes in each cellular membrane catalyse these translocation processes. A recent report [Hill K et al. Nature 1998;395:516-521 (Ref. 1)] of the reconstitution of the translocation channel from the mitochondrial outer membrane, after producing the major structural component of the channel by recombinant means, promises a system to dissect in molecular detail the exact working of one of these protein translocation machines.

Bacteria↗