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PubMed2002

[Prevention and health promotion].

Health as well as illness is not a state but a dynamic process. It depends among others on internal and external resources and possibilities which are given or not. Health behavior means the contribution of the individual to foster and develop their health. This includes all measures and behavior which contribute to early prevention or detection of illness. Traditional medicine engages in the investigation of causes and processes of disease and has not yet investigated prevention or health promoting behavior in the same way. This can also be seen in the concept of primary, secondary and tertiary prevention, which is disease oriented. Health promotion however--as stated in the Ottawa Charta in 1986 is the process of enabling people to increase control over and to improve their health.

Attitude to Health↗

PubMed2000

Suppression of microtubule dynamic instability and treadmilling by deuterium oxide.

Deuterium oxide (D(2)O) is known to promote the assembly of tubulin into microtubules in vitro, to increase the volume of mitotic spindles and the number and length of spindle microtubules, and to inhibit mitosis. Reasoning that its actions on cellular microtubules could be due to modulation of microtubule dynamics, we examined the effects of replacing H(2)O with D(2)O on microtubule dynamic instability, treadmilling, and steady-state GTPase activity. We found that replacing 50% or more of the H(2)O with D(2)O promoted microtubule polymerization and stabilized microtubules against dilution-induced disassembly. Using steady-state axoneme-seeded microtubules composed of pure tubulin and video microscopy, we found that 84% D(2)O decreased the catastrophe frequency by 89%, the shortening rate by 80%, the growing rate by 50%, and the dynamicity by 93%. Sixty percent D(2)O decreased the treadmilling rate of microtubules composed of tubulin and microtubule-associated proteins by 42%, and 89% D(2)O decreased the steady-state GTP hydrolysis rate by 90%. The mechanism responsible for the ability of D(2)O to stabilize microtubule dynamics may involve enhancement of hydrophobic interactions in the microtubule lattice and/or the substitution of deuterium bonds for hydrogen bonds.

Animals↗

PubMed1992

Birth kits for safe motherhood in Bangladesh.

Tetanus infection remains the leading cause of high neonatal mortality in Bangladesh. Birth kits which instruct and assist in a clean, safe birth are seen as a key measure in reducing the high incidence of neonatal deaths. A multisectoral programme has developed a simple kit and tested its potential for distribution to pregnant women. Initial results are positive and development is continuing.

Adult↗

PubMed2006

[Effect and mechanism of shenshuai mixture (SM) in promoting repair of kidney in acute renal failure rats].

OBJECTIVE: To dynamically observe the effect of Shenshuai Mixture (SM) on repair of kidney in acute renal failure (ARF) rats. METHODS: Male SD rats were divided into 4 groups randomly, the normal group, the SM group, the verapamil group and the model control group. Except those in the normal group were treated with normal saline without modeling, all remaining rats, after being made into ARF model by intra-muscular injection of glycerin, were treated with SM, verapamil and normal saline respectively via gastrogavage. Renal function, renal pathology, mRNA expression of epidermal growth factor (EGF) and protein expression of proliferating cell nuclear antigen (PCNA) were detected once every day from the 1st day to the 5th day. Results (1) BUN and Scr levels increased markedly 24 hrs after modeling, but the Scr level in the two treated groups was significantly lower than that in the model group (P < 0.05). Compared with that in the model group and the verapamil group, renal function was better in the SM group on the 3rd day (P < 0.01), and approach to normal level on the 5th day. (2) Renal pathological changes alleviated in every phase of ARF in the SM group than that in the model group, especially part of tubule regeneration could be seen on the 3rd day (metaphase), and renal structure was rehabilitated on the 5th day (convalescence), prior to those in the model group. (3) At the 3rd day expression of EGF mRNA and PCNA in tubule epithelial cell (TEC) increased remarkably in the SM group, higher than those in the model and verapamil group (P < 0.05). CONCLUSION: SM could promote renal tissue regeneration and rehabilitation, and shorten the course of ARF through up-regulating mRNA expression of EGF in TEC.

Acute Kidney Injury↗

PubMed2005

From peptide-bond formation to cotranslational folding: dynamic, regulatory and evolutionary aspects.

Ribosomes are ribozymes exerting substrate positioning and promoting substrate-mediated catalysis. Peptide-bonds are formed within a symmetrical region, thus suggesting that ribosomes evolved by gene-fusion. Remote interactions dominate substrate positioning at stereochemistry suitable for peptide-bond formation and elaborate architectural-design guides the processivity of the reaction by rotatory motion. Nascent proteins are directed into the exit tunnel at extended conformation, complying with the tunnel's narrow entrance. Tunnel dynamics facilitate its interactive participation in elongation, discrimination, cellular signaling and nascent-protein trafficking into the chaperon-aided folding site. Conformational alterations, induced by ribosomal-recycling factor, facilitate subunit dissociation. Remarkably, although antibiotics discrimination is determined by the identity of a single nucleotide, involved also in resistance, additional nucleotides dictate antibiotics effectiveness.

Evolution, Molecular↗

PubMed2002

Dynamic chromatin alterations triggered by natural and synthetic activation domains.

The activation domains (ADs) of transcription activators recruit a multiplicity of enzymatic activities to gene promoters. The mechanisms by which such recruitment takes place are not well understood. Using chromatin immunoprecipitation, we demonstrate dynamic alterations in the abundance of histones H2A, H3, and H4 at promoters of genes regulated by the HSF and Gal4 activators of Saccharomyces cerevisiae. Transcriptional activation of these genes, particularly those regulated by HSF, is accompanied by a significant reduction in both acetylated and unacetylated histones at promoters and may involve the transient displacement of histone octamers. To gain insight into the function of ADs, we conducted a genetic screen to identify polypeptides that could substitute for the 340-residue C-terminal activator of HSF and rescue the temperature sensitivity caused by its deletion. We found that the ts(-) phenotype of HSF(1-493) could be complemented by peptides as short as 11 amino acids. Such peptides are enriched in acidic and hydrophobic residues, and exhibit both trans-activating and chromatin-modifying activities when fused to the Gal4 DNA-binding domain. We also demonstrate that a previously identified 14-amino acid histone H3-binding module of human CTF1/NF1, which is similar to synthetic ADs, can substitute for the HSF C-terminal activator in conferring temperature resistance and can mediate the modification of promoter chromatin structure. Possible mechanisms of AD function, including one involving direct interactions with histones, are discussed.

Amino Acid Sequence↗

PubMed1982

Bottle feeding and ideology in colonial Malaya: the production of change.

Considerable attention has been paid to the correlation between high infant morbidity and mortality rates and the increased incidence of bottle feeding. The shift from prolonged breast feeding to a mixed regime or the exclusive use of sweetened condensed milk or infant formula has been related to the promotional activities of milk companies, and typically has been presented as a relatively recent development in Third World countries. However, the marketing of tinned and powdered milk only partially explains the increased use of these products. In colonial Malaya, condensed milk was marketed from the late 19th century. Infant formula was available from the turn of the century and was widely advertised, first in the English-language press and later also in the vernacular presses. At the same time, other social and cultural factors served to discourage breast feeding. There were changes in ideas regarding ideal body weight for both women and infants, and regarding infant care and diet; these ideas were presented in the mass media. In addition, maternal and child health clinics, established in the 1920s to reduce the high infant mortality rate, both propagated popular beliefs about infant weight and supplied milk and educated women to artificially feed their infants. Industry, the media, and health services all promoted, if not always intentionally, bottle feeding rather than breast feeding. Bottle feeding as an ideal, if not a reality, was thus well established before the intensive promotion of milk products by multinational corporations that followed the political independence of the colony.

Advertising↗

PubMed1985

Nuclear magnetic resonance study of the proton exchange rate in the operator-promoter DNA sequence of the trp operon of Escherichia coli.

The dynamic behavior of a palindromic oligonucleotide (C-G-T-A-C-T-A-G-T-T-A-A-C-T-A-G-T-A-C-G) representative of the operator sequence and containing the Pribnow box of the trp operon of Escherichia coli was investigated. The resonances of the imino protons and of the H2 protons of the adenosine residues were all assigned. The opening rate constants of the base-pairs were calculated by monitoring the exchange rate of the observable imino protons (nine out of ten), using selective temperature (T1) measurements, which avoid the complication of cross-relaxation and spin diffusion. These measurements have to be performed in conditions where the exchange process is much faster than the opening and closing of the base-pairs, so that the observed exchange rate is equal to the opening rate. It is shown that the catalysis of the exchange process by phosphate dianions is not very efficient (kB approximately equal to 7 X 10(4) M-1 S-1). Hence, in phosphate buffer, the necessary opening-rate limiting condition is met only at high pH values (approximately equal to 9.5) where efficient catalysis by OH- takes place, or at very high buffer concentration. While G X C base-pairs show very little exchange, acting in the sequence as molecular "staples", the A X T base-pairs that are protected from the fraying have very different opening and closing rates, depending on the sequence. Although it seems possible that the opening process could occur at the base-pair level, it is localized at most to two base-pairs in that particular sequence. The activation energies for the opening process of all non-fraying base-pairs are very similar (19 +/- 1 kcal mol-1; 1 cal = 4.184 J), and the differences in the opening rates are essentially due to differences in the activation entropies. With regard to the role of this sequence in the promoter, it is observed that the end of the Pribnow box exchanges relatively easily, and that the activation parameters for the "breathing" process and for the isomerization step of the promoter--RNA polymerase are not very different.

Base Sequence↗

PubMed2006

Endocytic internalization in budding yeast requires coordinated actin nucleation and myosin motor activity.

Actin polymerization essential for endocytic internalization in budding yeast is controlled by four nucleation promoting factors (NPFs) that each exhibits a unique dynamic behavior at endocytic sites. How each NPF functions and is regulated to restrict actin assembly to late stages of endocytic internalization is not known. Quantitative analysis of NPF biochemical activities, and genetic analysis of recruitment and regulatory mechanisms, defined a linear pathway in which protein composition changes at endocytic sites control actin assembly and function. We show that yeast WASP initiates actin assembly at endocytic sites and that this assembly and the recruitment of a yeast WIP-like protein by WASP recruit a type I myosin with both NPF and motor activities. Importantly, type I myosin motor and NPF activities are separable, and both contribute to endocytic coat inward movement, which likely represents membrane invagination. These results reveal a mechanism in which actin nucleation and myosin motor activity cooperate to promote endocytic internalization.

Actins↗

PubMed1997

Temporal and spatial control of murine GATA-3 transcription by promoter-proximal regulatory elements.

GATA-3 is expressed in a temporally dynamic manner and fulfills vital functions during vertebrate fetal development. Homozygous mGATA-3 mutant embryos die at midgestation, thus complicating the analysis of its contribution to the development of specific cell fates in the many tissues where it is expressed during embryogenesis. We show here that the elements controlling GATA-3 regulation can be precisely refined, using transgenic mice, to discrete cis-acting domains: within 6 kb surrounding the transcriptional initiation site, separate sequences were found to control the expression of mGATA-3 in early muscle masses, in a subset of PNS neurons, in the genital tubercle, and in the branchial arches. The branchial arch regulatory element is particularly robust and was refined to a discrete enhancer sequence lying between nt -2832 and -2462 from the transcription initiation site. The enhancer contains potential binding sites for many well-characterized transcription factors, suggesting that mGATA-3 transcriptional activity may be regulated by these proteins (or related family members) in the mesenchyme of the arches that contribute to formation of the jaw. These studies show that discrete regulatory elements required for the elaboration of complex developmental programs can be individually localized, suggesting that the developmentally transient expression of individual transcription factors collaboratively contributes to the temporal and spatial pattern of cellular differentiation leading to the formation of adult anatomy.

Animals↗

PubMed2006

Partial shotgun sequencing of the Boechera stricta genome reveals extensive microsynteny and promoter conservation with Arabidopsis.

Comparative genomics provides insight into the evolutionary dynamics that shape discrete sequences as well as whole genomes. To advance comparative genomics within the Brassicaceae, we have end sequenced 23,136 medium-sized insert clones from Boechera stricta, a wild relative of Arabidopsis (Arabidopsis thaliana). A significant proportion of these sequences, 18,797, are nonredundant and display highly significant similarity (BLASTn e-value < or = 10(-30)) to low copy number Arabidopsis genomic regions, including more than 9,000 annotated coding sequences. We have used this dataset to identify orthologous gene pairs in the two species and to perform a global comparison of DNA regions 5' to annotated coding regions. On average, the 500 nucleotides upstream to coding sequences display 71.4% identity between the two species. In a similar analysis, 61.4% identity was observed between 5' noncoding sequences of Brassica oleracea and Arabidopsis, indicating that regulatory regions are not as diverged among these lineages as previously anticipated. By mapping the B. stricta end sequences onto the Arabidopsis genome, we have identified nearly 2,000 conserved blocks of microsynteny (bracketing 26% of the Arabidopsis genome). A comparison of fully sequenced B. stricta inserts to their homologous Arabidopsis genomic regions indicates that indel polymorphisms >5 kb contribute substantially to the genome size difference observed between the two species. Further, we demonstrate that microsynteny inferred from end-sequence data can be applied to the rapid identification and cloning of genomic regions of interest from nonmodel species. These results suggest that among diploid relatives of Arabidopsis, small- to medium-scale shotgun sequencing approaches can provide rapid and cost-effective benefits to evolutionary and/or functional comparative genomic frameworks.

Arabidopsis↗

PubMed2004

The Abl-related gene (Arg) requires its F-actin-microtubule cross-linking activity to regulate lamellipodial dynamics during fibroblast adhesion.

Microtubules (MTs) help establish and maintain cell polarity by promoting actin-dependent membrane protrusion at the leading edge of the cell, but the molecular mechanisms that mediate cross-talk between actin and MTs during this process are unclear. We demonstrate that the Abl-related gene (Arg) nonreceptor tyrosine kinase is required for dynamic lamellipodial protrusions after adhesion to fibronectin. arg-/- fibroblasts exhibit reduced lamellipodial dynamics as compared with wild-type fibroblasts, and this defect can be rescued by reexpression of an Arg-yellow fluorescent protein fusion. We show that Arg can bind MTs with high affinity and cross-link filamentous actin (F-actin) bundles and MTs in vitro. MTs concentrate and insert into Arg-induced F-actin-rich cell protrusions. Arg requires both its F-actin-binding domains and its MT-binding domain to rescue the defects in lamellipodial dynamics of arg-/- fibroblasts. These findings demonstrate that Arg can mediate physical contact between F-actin and MTs at the cell periphery and that this cross-linking activity is required for Arg to regulate lamellipodial dynamics in fibroblasts.

Actin Cytoskeleton↗

PubMed2005

Identification of developmentally specific enhancers for Tsix in the regulation of X chromosome inactivation.

X chromosome inactivation silences one of two X chromosomes in the mammalian female cell and is controlled by a binary switch that involves interactions between Xist and Tsix, a sense-antisense pair of noncoding genes. On the future active X chromosome, Tsix expression suppresses Xist upregulation, while on the future inactive X chromosome, Tsix repression is required for Xist-mediated chromosome silencing. Thus, understanding the binary switch mechanism depends on ascertaining how Tsix expression is regulated. Here we have taken an unbiased approach toward identifying Tsix regulatory elements within the X chromosome inactivation center. First, we defined the major Tsix promoter and found that it cannot fully recapitulate the developmental dynamics of Tsix expression, indicating a requirement for additional regulatory elements. We then delineated two enhancers, one classical enhancer mapping upstream of Tsix and a bipartite enhancer that flanks the major Tsix promoter. These experiments revealed the intergenic transcription element Xite as an enhancer of Tsix and the repeat element DXPas34 as a component of the bipartite enhancer. Each enhancer contains DNase I-hypersensitive sites and appears to confer developmental specificity to Tsix expression. Characterization of these enhancers will facilitate the identification of trans-acting regulatory factors for X chromosome counting and choice.

Animals↗

PubMed2006

Influences of the breathing route on upper airway dynamics properties in normal awake subjects with constant mouth opening.

MB (mouth breathing) promotes the occurrence of sleep-disordered breathing even in non-apnoeic subjects. Considering that MO (mouth opening) contributes to an increase in UA (upper airway) collapsibility independently of MB, the aim of the present study was to assess the influence of breathing route on UA dynamics in the presence of MO. Bilateral anterior magnetic phrenic nerve stimulation was performed 2 s after expiratory onset in 12 healthy male subjects during wakefulness (age, 50+/-5 years; body mass index, 27.8+/-2.4 kg/m(2)) during MB through a mouthpiece and during exclusive NB (nasal breathing) with the same mouthpiece in place. Twitch-induced V(I) (instantaneous flow), P(ph) and P(es) (pharyngeal and oesophageal pressures respectively) were recorded and the corresponding resistances were measured. A polynomial regression model, V(I)=k(1)P(d)+k(2)P(d)(2), was used to characterize flow-pressure relationship and to determine the P(d) value at which UA collapses. There was no difference in UA dynamic properties between NB and MB when UA collapse occurred above the pharyngeal catheter. For twitches where UA collapse occurred lower in the UA, pharyngeal resistance decreased from NB to MB (2.0+/-0.3 and 1.5+/-0.2 cmH(2)Oxl(-1)xs respectively; P=0.02; values are means+/-S.D.), whereas closing pressure increased (-25.7+/-10.1 and -18.0+/-3.0 cmH(2)O respectively; P=0.04). We conclude that (i) in the presence of MO the dynamic properties of the proximal UA free of phasic activity do not differ between NB and MB, and (ii) MB decreases the upstream resistance and increases collapsibility of the distal UA.

Adult↗

PubMed2006

Switching of NR5A proteins associated with the inhibin alpha-subunit gene promoter after activation of the gene in granulosa cells.

The inhibin alpha-subunit gene is transcriptionally activated by FSH in ovarian granulosa cells during follicular growth. We have investigated the roles of the NR5A family nuclear receptors steroidogenic factor 1 (SF-1) and liver receptor homolog 1 (LRH-1) in transcriptional activation of the inhibin alpha-subunit gene. Transfection assays using an inhibin alpha-subunit promoter reporter in GRMO2 granulosa cells show that LRH-1 and SF-1 act similarly to increase promoter activity, and that the activity of both transcription factors is augmented by the coactivators cAMP response element-binding protein-binding protein and steroid receptor coactivator 1. However, chromatin immunoprecipitation experiments illustrate differential dynamic association of LRH-1 and SF-1 with the alpha-subunit inhibin promoter in both primary cells and the GRMO2 granulosa cell line such that hormonal stimulation of transcription results in an apparent replacement of SF-1 with LRH-1. Transcriptional stimulation of the inhibin alpha-subunit gene is dependent on MAPK kinase activity, as is the dynamic association/disassociation of SF-1 and LRH-1 with the promoter. Inhibition of the phosphatidylinositol 3-kinase signaling pathway influences promoter occupancy and transcriptional activation by SF-1 but not LRH-1, suggesting a possible mechanistic basis for the distinct functions of these NR5A proteins in inhibin alpha-subunit gene regulation.

Animals↗

PubMed1999

[Age-related change in the alpha-tocopherolquinone/alpha-tocopherol ratio in the rat erythrocyte membrane].

alpha-Tocopherol (alpha-Toc), a lipophilic phenolic antioxidant that is localized mainly in the biomembrane, protects cells against oxidation-associated cytotoxicity by prevention of membrane lipid peroxidation, maintenance of the redox balance intracellular thiols and stabilization of the membrane structure. We investigated the age-related changes in redox dynamics of alpha-Toc in plasma and erythrocyte membrane of an elderly (66 weeks old) and young group (10 weeks old). Total, alpha-, beta + gamma-, delta-Toc and alpha-tocopherolquinone (alpha-TocQ) in plasma and erythrocyte membrane were determined by high-performance liquid chromatography (HPLC) with a series of multiple coulometric working electrodes (CWE). Rat venous blood sample was divided into plasma and erythrocyte layers by centrifugation, and then erythrocyte membrane sample was prepared according to the method of Dodge et al. under a stream of nitrogen. In plasma, total and alpha-Toc concentrations were increased, and beta + gamma-, delta-Toc and alpha-TocQ concentrations were decreased age-dependently. In the erythrocyte membrane, total, alpha-TocQ concentrations and three fractions of tocopherols decreased age-dependently. Also, a decrease in the alpha-TocQ/alpha-Toc ratio in erythrocyte membrane was observed in the elderly group. These findings suggest that the alpha-Toc uptake in erythrocyte membrane and utilization rate of alpha-Toc in erythrocyte membrane decline age-dependently. This decline may promote membrane lipid peroxidation. alpha-Toc redox dynamics in erythrocyte membrane were useful to investigate the pathophysiology of aging mechanisms related to oxidative stress.

Aging↗

PubMed1996

Delayed tyrosine phosphorylation and nuclear expression of STAT1 following antigen receptor stimulation of B lymphocytes.

The regulation of the STAT1 alpha transcription factor was assessed during B cell activation induced by cross-linking the surface IgM Ag receptor. Surface Ig ligation or pharmacologic stimulation with PMA and ionomycin resulted in the delayed (2-3 h after stimulation) nuclear appearance of tyrosine-phosphorylated STAT1 alpha, in contrast to the rapid induction that follows cytokine treatment. Nuclear expression of phosphorylated STAT1 alpha was abrogated by co-incubation of anti-Ig-treated B cells with the protein synthesis inhibitor cycloheximide (CHX), with the protein kinase inhibitor H-7, or with the immunosuppressive drug rapamycin. Tyrosine-phosphorylated STAT1 alpha was found to be recruited to the STAT binding site of the IFN regulatory factor-1 (IRF-1) gene promoter only after 2 to 3 h, and this association was also inhibitable by CHX and rapamycin. The arrival of STAT1 alpha coincided with attenuation of anti-Ig-induced STAT-binding activity specific for the IRF-1 promoter site, and both rapamycin and CHX treatment counteracted the loss of this activity. Furthermore, basal transcription of the endogenous IRF-1 gene was decreased as a result of anti-Ig treatment, and this effect of anti-Ig was blocked by co-incubation with rapamycin. Thus, STAT1 alpha plays a dynamic role in the composition of IRF-1 promoter-specific DNA binding complexes stimulated by B cell Ag receptor ligation, and nuclear expression of phosphorylated STAT1 alpha is regulated in a unique fashion by Ag receptor engagement. In addition, surface Ig cross-linking imparts negative regulatory control of IRF-1 gene expression, possibly through activation of STAT1 alpha.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2005

The herb community of a tropical forest in central Panamá: dynamics and impact of mammalian herbivores.

Mammals are hypothesized to either promote plant diversity by preventing competitive exclusion or limit diversity by reducing the abundance of sensitive plant species through their activities as browsers or disturbance agents. Previous studies of herbivore impacts in plant communities have focused on tree species and ignored the herbaceous community. In an experiment in mature-phase, tropical moist forest sites in central Panamá, we studied the impact of excluding ground-dwelling mammals on the richness and abundance of herbs in 16, 30x45-m plots. Within each plot, we censused the herbaceous community in 28, 2x2-m subplots (1,792 m2 total area sampled). We identified over 54 species of herbs averaging 1.21 ramets m-2 and covering approximately 4.25% of the forest floor. Excluding mammals for 5 years had no impact on overall species richness. Within exclosures, however, there was a significant two-fold increase in the density of rare species. Overall herbaceous density and percent cover did not differ between exclosures and adjacent control plots, although cover did increase over time. Mammalian exclusion significantly increased the total cover of three-dominant herb species, Pharus latifolius, Calathea inocephala, and Adiantum lucidum, but did not affect their density. This study represents one of the most extensive herbaceous community censuses conducted in tropical forests and is among a few that quantify herbaceous distribution and abundance in terms of both density and cover. Additionally, this work represents the first community level test of mammalian impacts on the herbaceous community in a tropical forest to date. Our results suggest that ground dwelling mammals do not play a key role in altering the relative abundance patterns of tropical herbs in the short term. Furthermore, our results contrast sharply with prior studies on similar temporal and spatial scales that demonstrate mammals strongly alter tree seedling composition and reduce seedling density. Thus, we question the pervasiveness of top-down control on tropical plant communities and the paradigm that defaunation will inexorably lead to widespread, catastrophic shifts in plant communities.

Adiantum↗