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[Current trends in bioethics in Canada].

In Canada, interest in bioethics intensified during the 1980s when a number of public and private agencies published papers on the opportunities and consequences presented by biotechnology in the industrial, agricultural, and medical fields. Bioethics is now a common subject in the universities, especially in the philosophy and religion study programs. It is also growing in importance as part of the training of health professionals. Several important bioethics centers and the Canadian Bioethics Society constitute a dynamic focus for the promotion of research and academic studies in this field. As in other countries, debate has centered around research involving human subjects, reproductive technologies, abortion, the dying process, organ transplants, and AIDS. Various guidelines and legislative measures have been established to deal with these questions.

Acquired Immunodeficiency Syndrome↗

Prescribing exercise--walking and jogging.

The family doctor is the ideal person to lead his patients back to a form of existence which is more dynamic and health-promoting than their customary way of life. Many basic fears of doctors are unfounded, for it is not difficult to acquire a knowledge of the ergological principles involved in natural movement and sport. Patients should be guided into 'forgetting' about their ailments, but at the same time remembering their limitations. The prescription of sensible forms of exercise, e.g. walking and jogging, is advocated. Some tried and sensible programmes are given.

Exercise Therapy↗

Changes in breastfeeding initiation and duration in Peru, 1977-1986.

Both breastfeeding initiation and duration increased in Peru during 1977-86. Although one would have expected that the average incidence and duration of breastfeeding would have declined as a result of changes in population characteristics, the potential for an overall decline was more than overcome by changes in behavior. A net increase in initiation and duration is shown for all subgroups of interest. The largest absolute increases are documented for children who, in 1977, were the least likely to be breastfed and who were breastfed for the shortest durations.

Adolescent↗

Adhesion of sickle neutrophils and erythrocytes to fibronectin.

The pathophysiology of vaso-occlusive crisis in sickle cell disease involves interactions among blood cells, plasma proteins, and vessel wall components. The initial goal of this work was to quantify the adhesion of sickle red blood cells (RBCs) to fibronectin immobilized on glass under both static and dynamic shear stress conditions. High-power microscopic inspection of static assay plates showed striking numbers of adherent neutrophils as well as RBCs. Sickle neutrophils and RBCs were significantly more adherent to fibronectin than the corresponding normal cells in static adhesion assays. Adhesion of both sickle neutrophils and sickle RBCs in dynamic adhesion assays was promoted by a period of static incubation preceding initiation of shear stress conditions. Adherent neutrophils remained attached at shear stresses up to 51 dyne/cm2; most adherent RBCs were attached at shear stresses up to 13 dyne/cm2, but detached at a shear stress of 20 dyne/cm2. Sickle neutrophil adhesion was enhanced significantly by autologous plasma. Elevated levels of plasma interleukin-6 (IL-6; but not IL-1 or IL-8) were found in 6 of 9 sickle cell disease samples examined, and elevated levels of tumor necrosis factor were found in 2 of 9 samples. Plasma IL-6 levels correlated positively with both the number of sickle neutrophils adherent to fibronectin and the ability of sickle plasma to enhance adhesion of normal neutrophils to fibronectin. These data suggest possible roles for neutrophil activation and for fibronectin in mediating sickle neutrophil and RBC adhesion.

Adult↗

Influence of the geometry of the left main coronary artery bifurcation on the distribution of sudanophilia in the daughter vessels.

The proximal portions of the left anterior descending (LAD) and left circumflex (LCx) coronary arteries are among the sites most predisposed to atherosclerotic disease. This predisposition might be a consequence of their location immediately distal to the left main (LM) coronary artery bifurcation, which may increase the susceptibility of these segments by promoting an adverse fluid dynamic environment within them. The detailed geometry of the bifurcation influences this environment and would therefore affect the susceptibility of the proximal daughter vessels to disease. This hypothesis was tested by examination of the relationship between the geometry of the LM bifurcation and the distribution of sudanophilia in the proximal portions of the LAD and LCx. The geometric parameters at the LM bifurcation, including all three angles and LM length, were obtained from multiangle photographs of 17 vascular casts by use of objective computer-based algorithms. A robust index, the relative proximal involvement (RPI), was developed to measure the localization of disease to the proximal portions of the daughter vessels. The RPI of the LAD segment correlated best with an interaction term that included the planarity of the LM bifurcation and the LCx-LAD branch angle (P = .013). In addition to supporting the concept of geometric risk factors, these observations also suggest that interactions between the hemodynamic influences of multiple geometric variables may play a role in the mediation of tissue susceptibility by geometric factors.

Adolescent↗

Coverage dependent desorption dynamics of deuterium on Si(100) surfaces: interpretation with a diffusion-promoted desorption model.

We studied coverage dependence of time-of-flight (TOF) spectra of D2 molecules thermally desorbed from the D/Si(100) surface. The mean translational energies Et of desorbed D2 molecules were found to increase from 0.20+/-0.05 eV to 0.40+/-0.04 eV as the desorption coverage window was decreased from 1.0 ML> or =thetaD> or =0.9 ML to 0.2 ML> or =thetaD> or =0 ML, being consistent with the kinetics switch predicted in the interdimer mechanism. The measured TOF spectra were deconvoluted into 2H, 3H, and 4H components by a curve fitting method along the principle of detailed balance. As a result, it turned out that the desorption kinetics changes from the 4H to the 3H situation at high coverage above thetaD=0.9 ML, while the 2H desorption is dominant for a quite wide coverage region up to thetaD=0.8 ML. A dynamic desorption mechanism by which the desorption is promoted by D-atom diffusion to dangling bonds was proposed.

Journal Article↗

[Effects of returning maize straw into field on dynamic change of soil microbial biomass C, N and P under different promoted decay condition].

A 2-year field experiment of wheat-maize rotation was conducted on a cinnamon soil of east Hebei Province to study the effects of returning maize straw into field on the dynamics of soil microbial biomass C, N and P, and their relationships with soil nutrients and enzyme activities. The results showed that under the condition of returning maize straw combined with applying chemical fertilizer to adjust straw C/N, the application of effective microorganisms could increase soil microbial biomass C, N and P in each crop growth period, advance their peak time, and better regulate soil nutrient supply, compared with no application of effective microorganisms. Soil microbial biomass had a significantly positive correlation with soil enzyme activities, but its correlation with soil hydrolysable N and available P was strongly affected by crop growth and fertilization system.

Carbon↗

Dynamic aspects of DNA/protein interactions in the transcriptional initiation complex and the hormone-responsive domains of the phosphoenolpyruvate carboxykinase promoter in vivo.

Transcription initiation of the gene encoding phosphoenolpyruvate carboxykinase (PEPCK) is stimulated by glucocorticoids and glucagon, via cAMP, and dominantly inhibited by insulin in rat liver and H4IIE cells. Lysolecithin-permeabilized H4IIE cells recover completely and continue to multiply, yet are transiently penetrable by macromolecules. These cells, after various hormonal treatments, were utilized for in situ DNase I protection studies of the PEPCK promoter. Nearly all of the sites of protein interaction observed in vitro are protected in vivo as well as several additional sites. The DNase I protection pattern is the same in cells without or with any of the hormone treatments, suggesting that hormonal modulation of transcription does not involve addition or removal of factors from the hormone response elements of the promoter. We focused on the organization and stability of the transcription initiation complex as well as the dynamic nature of distal promoter factors in their interaction with DNA. The transcription initiation complex was detected, and it appears to be co-existent with a short region of naked single-stranded DNA over the TATA box on the template strand, as determined by potassium permanganate reactivity. This complex is quite stable, even under conditions of much reduced RNA synthesis, which suggests that the complex is not broken down and reformed with each round of initiation by RNA polymerase II. Other factors bind to the PEPCK promoter with half-lives ranging from a few minutes to more than 40 min. The cAMP response element apparently involves transcriptional modulation achieved through modification of a bound factor (presumably cAMP response element-binding protein), whereas the glucocorticoid/insulin-responsive region of the promoter functions through factors which are involved in a rapid exchange, suggesting quite different modes of transcriptional regulation.

Animals↗

Potential impacts of multiple partners on mycorrhizal community dynamics.

The significance of arbuscular mycorrhizal (AM) fungi in terrestrial ecosystems is widely acknowledged, but the causes and consequences of diversity in these fungi are not well understood. A recent frequency-dependent model suggests that dynamics within mycorrhizal mutualisms could promote the coexistence of at least two competing plant species and two competing fungal species within a community. Models are developed here in which simultaneous association with multiple partners may result in elevated or depressed fitness relative to association with either partner alone. This increases the range of conditions under which negative feedback occurs and coexistence of all four species is possible. Differences between plants in the relative proportions of fungi at which maximum fitness occurs may facilitate coexistence, as may differences between fungi in their abilities to establish interplant connections. These models suggest additional mechanisms by which mutualistic interactions could promote local diversity of plants and AM fungi.

Ecosystem↗

SUMO-1 modification of human transcription factor (TF) IID complex subunits: inhibition of TFIID promoter-binding activity through SUMO-1 modification of hsTAF5.

The TFIID complex is composed of the TATA-binding protein (TBP) and TBP-associated factors (TAFs) and is the only component of the general RNA polymerase II (RNAP II) transcription machinery with intrinsic sequence-specific DNA-binding activity. Binding of transcription factor (TF) IID to the core promoter region of protein-coding genes is a key event in RNAP II transcription activation and is the first and rate-limiting step of transcription initiation complex assembly. Intense research efforts in the past have established that TFIID promoter-binding activity as well as the function of TFIID-promoter complexes is tightly regulated through dynamic TFIID interactions with positive- and negative-acting transcription regulatory proteins. However, very little is known about the role of post-translational modifications in the regulation of TFIID. Here we show that the human TFIID subunits hsTAF5 and hsTAF12 are modified by the small ubiquitin-related modifier SUMO-1 in vitro and in human cells. We identify Lys-14 in hsTAF5 and Lys-19 in hsTAF12 as the primary SUMO-1 acceptor sites and show that SUMO conjugation has no detectable effect on nuclear import or intranuclear distribution of hsTAF5 and hsTAF12. Finally, we demonstrate that purified human TFIID complex can be SUMO-1-modified in vitro at both hsTAF5 and hsTAF12. We find that SUMO-1 conjugation at hsTAF5 interferes with binding of TFIID to promoter DNA, whereas modification of hsTAF12 has no detectable effect on TFIID promoter-binding activity. Our observations suggest that reversible SUMO modification at hsTAF5 contributes to the dynamic regulation of TFIID promoter-binding activity in human cells.

Amino Acid Sequence↗

Dynamics of stimulus-expression coupling as revealed by monitoring of prolactin promoter-driven reporter activity in individual, living mammotropes.

Single-cell paradigms have greatly expanded our knowledge about stimulus-secretion coupling, but the understanding of stimulus-gene expression coupling has lagged behind for lack of a dynamic model sufficiently sensitive to provide single-cell resolution. In the present study, we made continuous indirect measurements within individual, living cells of expression dynamics both before and after treatment with a gene-activating secretagogue. This was accomplished by transfecting (via microinjection) individual, primary mammotropes with a PRL promoter-driven luciferase reporter plasmid, and then quantifying the rate of photonic emissions (reflective of endogenous gene activity). We found that individual cells exhibit spontaneous, random, short-term fluctuations of basal reporter activity and are extremely heterogeneous in terms of responses to a stimulatory agent (TRH). In addition, we found that responses are affected by several factors including the secretory status of the pituitary donor, the manner in which the stimulus is presented, and by the initial level of reporter activity. Moreover, the responsiveness of an individual cell can fluctuate dramatically over time. These results invite speculation that a given cell can "sense" its gene activation state and regulate its response accordingly to satisfy requirements for the corresponding secretory product.

Animals↗

Protein motions promote catalysis.

A relationship between molecular dynamics motions of noncatalytic residues and enzyme activity has recently been proposed. We present examples where mutations either near or distal from the active site residues modify internal enzyme motion with resulting modification of catalysis. A better understanding of internal protein motions correlated to catalysis will lead to a greater insight into enzyme function.

Animals↗

IQGAP1 promotes cell motility and invasion.

The dynamic processes of cell migration and invasion are largely coordinated by Rho family GTPases. The scaffolding protein IQGAP1 binds to Cdc42, increasing the amount of active Cdc42 both in vitro and in cells. Here we show that overexpression of IQGAP1 in mammalian cells enhances cell migration in a Cdc42- and Rac1-dependent manner. Importantly, cell motility was significantly decreased both by knock down of endogenous IQGAP1 using small interfering RNA and by transfection of a dominant negative IQGAP1 construct, IQGAP1DeltaGRD. Cell invasion was similarly altered by manipulating intracellular IQGAP1 concentrations. Moreover, invasion mediated by constitutively active Cdc42 was attenuated by IQGAP1DeltaGRD. Thus, IQGAP1 has a fundamental role in cell motility and invasion.

Animals↗

Estrogen regulation of trefoil factor 1 expression by estrogen receptor alpha and Sp proteins.

Estrogen-responsive genes in human breast cancer cells often have an estrogen response element (ERE) positioned next to an Sp1 binding site. In chromatin immunoprecipitation (ChIP) assays, we investigated the binding of estrogen receptor alpha (ER), Sp1, and Sp3 to the episomal and native estrogen-responsive trefoil factor 1 (TFF1; formerly pS2) promoter in MCF-7 breast cancer cells. Mutation of the Sp site upstream of the ERE reduced estrogen responsiveness and prevented binding of Sp1 and Sp3, but not ER to the episomal promoter. In the absence of estradiol (E2), Sp1, Sp3, histone deacetylase 1 (HDAC), and HDAC2, and low levels of acetylated H3 and H4 are associated with the native promoter, with the histones being engaged in dynamic reversible acetylation. Following E2 addition, levels of ER and acetylated H3 and H4 bound to the native promoter increases. There is clearance of Sp1, but not of Sp3, from the promoter while HDAC1 and HDAC2 remain bound. These data are consistent with a model in which Sp1 or Sp3 aid in recruitment of HDACs and histone acetyltransferases (HATs) to mediate dynamic acetylation of histones associated with the TFF1 promoter, which is in a state of readiness to respond to events occurring following the addition of estrogen.

Acetylation↗

Agonist-modulated palmitoylation of endothelial nitric oxide synthase.

The nitric oxide synthases (NOS) comprise a family of enzymes which differ in primary structure, biological roles, subcellular distribution, and post-translational modifications. The endothelial nitric oxide synthase (ec-NOS) is unique among the NOS isoforms in being modified by N-terminal myristoylation, which is necessary for its targeting to the endothelial cell membrane. The subcellular localization of the ecNOS, but not enzyme myristoylation, is dynamically regulated by agonists such as bradykinin, which promote ecNOS translocation from membrane to cytosol, as well as enhancing enzyme phosphorylation. Using transiently transfected endothelial cells, we now show that a myristoylation-deficient mutant ecNOS undergoes phosphorylation despite restriction to the cytosol, suggesting that phosphorylation may be a consequence rather than a cause of ecNOS translocation. We therefore explored whether other post-translational modifications might regulate ecNOS targeting and now report that ecNOS is reversibly palmitoylated. Biosynthetic labeling of endothelial cells with [3H]palmitic acid followed by immunoprecipitation of ecNOS revealed that the enzyme is palmitoylated; the label is released by hydroxylamine, consistent with formation of a fatty acyl thioester, and authentic palmitate can be recovered from labeled ecNOS following acid hydrolysis. Importantly, pulse-chase experiments in endothelial cells biosynthetically labeled with [3H]palmitate show that bradykinin treatment promotes ecNOS depalmitoylation. We conclude that ecNOS palmitoylation is dynamically regulated by bradykinin and propose that depalmitoylation of the enzyme may result in its cytosolic translocation and subsequent phosphorylation.

Amino Acid Oxidoreductases↗

The Eukaryotic Promoter Database EPD.

The Eukaryotic Promoter Database (EPD) is an annotated non-redundant collection of experimentally characterised eukaryotic POL II promoters. The underlying definition of a promoter is that of a transcription initiation site. All information presented in EPD results from an independent evaluation of primary experimental data shown in the biological literature. Sequences flanking transcription initiation sites are indirectly given by pointers to EMBL sequences. The annotation part of a promoter entry includes description of the promoter-defining evidence, cross-references to other databases, and bibliographic references. Being designed as a resource for comparative sequence analysis, EPD is structured in a way that facilitates dynamic extraction of biologically meaningful promoter subsets. The database is available through the World Wide Web at URL http://cmpteam4.unil.ch

Animals↗

Factors influencing participation in worksite smoking cessation and weight loss programs: the Healthy Worker Project.

Worksite intervention for health behavior change has attracted much recent interest as a potentially cost-effective way to promote healthier behaviors in the general population. In evaluating the impact of health promotion activities, it is essential to consider the entire work force rather than just self-selected participants. Overall, recruitment results reported to date have varied widely. There are a large number of factors pertaining to both employee and worksite characteristics that could contribute to variability in how well worksite health promotion programs attract employees. A critical issue that has received little research attention is the dynamics of participation in employee health promotion programs as they are offered repeatedly over time. The present study examined participation rates and contributing factors in worksite health promotion programs for weight loss and smoking cessation in the Healthy Worker Project, a randomized trial of worksite intervention conducted among 16 intervention and 16 control worksites in the Minneapolis/St. Paul metropolitan area between 1987 and 1990. Data analyses focused on characterizing individuals enrolling in worksite health promotion programs in comparison to those in the worksite population as a whole who would be considered in need of such programs.

Adult↗

Pivotal role of anionic phospholipids in determining dynamic behavior of lung surfactant.

Phosphatidylglycerol (PG) and phosphatidylinositol (PI) are anionic phospholipids (APLs) present in lung surfactant of virtually all species studied, although their specific contribution to function is unknown. This study examines how APLs influence surfactant monolayer stability and adsorption under static and dynamic conditions. Interfacial properties of surfactants reconstituted with native phospholipids (PL), and phospholipids devoid of anionic species (DAPL), were characterized by pulsating bubble surfactometry. Measurements were made for PL and DAPL alone; with 3% surfactant proteins B and C (SP-B/C); with SP-B/C and 5% surfactant protein A (SP-A); and with SP-B/C, SP-A, and 8% neutral lipids (NL). Equilibrium and dynamic properties of PL and DAPL were similar. However, whereas (DAPL + SP-B/C) and (DAPL + SP-B/C + SP-A) mixtures were similar to corresponding PL mixtures with respect to gamma(equil), they displayed markedly different dynamic behavior. In particular, the degree of film compression required to reach gamma(min) was significantly increased in DAPL mixtures (80 to 90% area reduction) compared with PL, although both samples reached gamma(min) < 3.0 dynes/cm. The addition of NL to (DAPL + SP-B/C + SP-A) produced an increase in gamma(min) to 15 to 20 dynes/cm during dynamic compression, whereas NL had no significant impact on the behavior of (PL + SP-B/C + SP-A). Purified PG (5% wt/wt) restored nearly normal dynamic properties to (DAPL + SP-B/C + SP-A + NL), whereas phosphatidylcholine (PC) (5% wt/wt) had no beneficial effect. These results suggest that APLs play a critical role in promoting surface film stability during dynamic compression through interactions with nonlipid surfactant components, and prevent destabilization of the surface film by cholesterol and other NL.

Animals↗