Showing papers by "Université de Montréal published in 1997"
TL;DR: A new and simple method to find indicator species and species assemblages characterizing groups of sites, and a new way to present species-site tables, accounting for the hierarchical relationships among species, is proposed.
Abstract: This paper presents a new and simple method to find indicator species and species assemblages characterizing groups of sites The novelty of our approach lies in the way we combine a species relative abundance with its relative frequency of occurrence in the various groups of sites This index is maximum when all individuals of a species are found in a single group of sites and when the species occurs in all sites of that group; it is a symmetric indicator The statistical significance of the species indicator values is evaluated using a randomization procedure Contrary to TWINSPAN, our indicator index for a given species is independent of the other species relative abundances, and there is no need to use pseudospecies The new method identifies indicator species for typologies of species releves obtained by any hierarchical or nonhierarchical classification procedure; its use is independent of the classification method Because indicator species give ecological meaning to groups of sites, this method provides criteria to compare typologies, to identify where to stop dividing clusters into subsets, and to point out the main levels in a hierarchical classification of sites Species can be grouped on the basis of their indicator values for each clustering level, the heterogeneous nature of species assemblages observed in any one site being well preserved Such assemblages are usually a mixture of eurytopic (higher level) and stenotopic species (characteristic of lower level clusters) The species assemblage approach demonstrates the importance of the ''sampled patch size,'' ie, the diversity of sampled ecological combinations, when we compare the frequencies of core and satellite species A new way to present species-site tables, accounting for the hierarchical relationships among species, is proposed A large data set of carabid beetle distributions in open habitats of Belgium is used as a case study to illustrate the new method
7,449 citations
TL;DR: Mgp, a mineral-binding ECM protein3 synthesized by vascular smooth-muscle cells and chondrocytes, is the first inhibitor of calcification of arteries and cartilage to be characterized in vivo.
Abstract: Calcification of the extracellular matrix (ECM) can be physiological or pathological. Physiological calcification occurs in bone when the soft ECM is converted into a rigid material capable of sustaining mechanical force; pathological calcification can occur in arteries and cartilage and other soft tissues. No molecular determinant regulating ECM calcification has yet been identified. A candidate molecule is matrix GLA protein (Mgp), a mineral-binding ECM protein synthesized by vascular smooth-muscle cells and chondrocytes, two cell types that produce an uncalcified ECM. Mice that lack Mgp develop to term but die within two months as a result of arterial calcification which leads to blood-vessel rupture. Chondrocytes that elaborate a typical cartilage matrix can be seen in the affected arteries. Mgp-deficient mice additionally exhibit inappropriate calcification of various cartilages, including the growth plate, which eventually leads to short stature, osteopenia and fractures. These results indicate that ECM calcification must be actively inhibited in soft tissues. To our knowledge, Mgp is the first inhibitor of calcification of arteries and cartilage to be characterized in vivo.
2,030 citations
TL;DR: In this paper, the authors reexamine the findings of Perron (1989) regarding the claim that most macroeconomic time series are best construed as stationary fluctuations around a deterministic trend function if allowance is made for the possibility of a shift in the intercept of the trend function in 1929 (a crash) and a shifting in slope in 1973 (a slowdown in growth).
1,860 citations
TL;DR: The outcomes of the 12 large randomized, controlled trials that were studied were not predicted accurately 35 percent of the time by the meta-analyses published previously on the same topics.
Abstract: Background Meta-analyses are now widely used to provide evidence to support clinical strategies. However, large randomized, controlled trials are considered the gold standard in evaluating the efficacy of clinical interventions. Methods We compared the results of large randomized, controlled trials (involving 1000 patients or more) that were published in four journals (the New England Journal of Medicine, the Lancet, the Annals of Internal Medicine, and the Journal of the American Medical Association) with the results of meta-analyses published earlier on the same topics. Regarding the principal and secondary outcomes, we judged whether the findings of the randomized trials agreed with those of the corresponding meta-analyses, and we determined whether the study results were positive (indicating that treatment improved the outcome) or negative (indicating that the outcome with treatment was the same or worse than without it) at the conventional level of statistical significance (P<0.05). Results We identi...
1,146 citations
TL;DR: A strong relationship was found between these complaints and polysomnographic findings; increasing sleep latency and number of awakenings and decreasing sleep efficiency were associated with worsening symptoms.
Abstract: One hundred thirty-three cases of restless legs syndrome (RLS), diagnosed with criteria recently formulated by an international study group, were studied by questionnaire and with all-night polysomnographic recordings. Results show that RLS starts at a mean age of 27.2 years and before age 20 in 38.3% of patients. Symptoms often appear in one leg only and also involve upper limbs in about half of all cases. Most patients (94%) report sleep-onset insomnia or numerous nocturnal awakenings due to RLS symptoms. A strong relationship was found between these complaints and polysomnographic findings; increasing sleep latency and number of awakenings and decreasing sleep efficiency were associated with worsening symptoms. Periodic leg movements in sleep (index > 5 movements/h sleep) were found in 80.2% of patients. This study shows that this percentage is increased when 2 recording nights are considered (most severe score). Eighty patients of 127 (63%) reported the presence of RLS in at least one of their first-degree relatives. In these families, 221 of 568 first-degree relatives (39%) were reported by the patients to be affected with RLS.
900 citations
TL;DR: In this article, a tabu search heuristic was proposed for solving three well-known routing problems: the periodic vehicle routing problem, the periodic traveling salesman problem, and the multi-depot vehicle routing problems.
Abstract: We propose a tabu search heuristic capable of solving three well-known routing problems: the periodic vehicle routing problem, the periodic traveling salesman problem, and the multi-depot vehicle routing problem. Computational experiments carried out on instances taken from the literature indicate that the proposed method outperforms existing heuristics for all three problems. © 1997 John Wiley & Sons, Inc. Networks 30: 105–119, 1997
826 citations
TL;DR: It is shown that the claim that quantum cryptography can provide protocols that are unconditionally secure, that is, for which the security does not depend on any restriction on the time, space, or technology available to the cheaters, does not hold for any quantum bit commitment protocol.
Abstract: The claim of quantum cryptography has always been that it can provide protocols that are unconditionally secure, that is, for which the security does not depend on any restriction on the time, space, or technology available to the cheaters. We show that this claim does not hold for any quantum bit commitment protocol. Since many cryptographic tasks use bit commitment as a basic primitive, this result implies a severe setback for quantum cryptography. The model used encompasses all reasonable implementations of quantum bit commitment protocols in which the participants have not met before, including those that make use of the theory of special relativity.
812 citations
TL;DR: The data suggest that a reduction in frataxin results in oxidative damage, given the shared clinical features between Friedreich ataxia, vitamin E deficiency and some mitochondriopathies.
Abstract: Friedreich ataxia is a progressive neurodegenerative disorder caused by loss of function mutations in the frataxin gene. In order to unravel frataxin function we developed monoclonal antibodies raised against different regions of the protein. These antibodies detect a processed 18 kDa protein in various human and mouse tissues and cell lines that is severely reduced in Friedreich ataxia patients. By immunocytofluorescence and immunocytoelectron microscopy we show that frataxin is located in mitochondria, associated with the mitochondrial membranes and crests. Analysis of cellular localization of various truncated forms of frataxin expressed in cultured cells and evidence of removal of an N-terminal epitope during protein maturation demonstrated that the mitochondrial targetting sequence is encoded by the first 20 amino acids. Given the shared clinical features between Friedreich ataxia, vitamin E deficiency and some mitochondriopathies, our data suggest that a reduction in frataxin results in oxidative damage.
693 citations
TL;DR: The tissue‐restricted GATA‐4 transcription factor and Nkx2‐5 homeodomain protein are two early markers of precardiac cells and the GATA/Nkx partnership may represent a paradigm for transcription factor interaction during organogenesis.
Abstract: The tissue-restricted GATA-4 transcription factor and Nkx2-5 homeodomain protein are two early markers of precardiac cells. Both are essential for heart formation, but neither can initiate cardiogenesis. Overexpression of GATA-4 or Nkx2-5 enhances cardiac development in committed precursors, suggesting each interacts with a cardiac cofactor. We tested whether GATA-4 and Nkx2-5 are cofactors for each other by using transcription and binding assays with the cardiac atrial natriuretic factor (ANF) promoter_the only known target for Nkx2-5. Co-expression of GATA-4 and Nkx2-5 resulted in synergistic activation of the ANF promoter in heterologous cells. The synergy involves physical Nkx2-5-GATA-4 interaction, seen in vitro and in vivo, which maps to the C-terminal zinc finger of GATA-4 and a C-terminus extension; similarly, a C-terminally extended homeodomain of Nkx2-5 is required for GATA-4 binding. Structure/function studies suggest that binding of GATA-4 to the C-terminus autorepressive domain of Nkx2-5 may induce a conformational change that unmasks Nkx2-5 activation domains. GATA-6 cannot substitute for GATA-4 for interaction with Nkx2-5. This interaction may impart functional specificity to GATA factors and provide cooperative crosstalk between two pathways critical for early cardiogenesis. Given the co-expression of GATA proteins and NK2 class members in other tissues, the GATA/Nkx partnership may represent a paradigm for transcription factor interaction during organogenesis.
681 citations
TL;DR: Feature of gene content together with eubacterial characteristics of genome organization and expression not found before in mitochondrial genomes indicate that R. americana mtDNA more closely resembles the ancestral proto-mitochondrial genome than any other mtDNA investigated to date.
Abstract: Mitochondria, organelles specialized in energy conservation reactions in eukaryotic cells, have evolved from eubacteria-like endo-symbionts 1–3 whose closest known relatives are the rickettsial group of α-proteobacteria 4,5. Because characterized mitochondrial genomes vary markedly in structure3, it has been impossible to infer from them the initial form of the proto-mitochondrial genome. This would require the identification of minimally derived mitochondrial DNAs that better reflect the ancestral state. Here we describe such a primitive mitochondrial genome, in the freshwater protozoon Reclinomonas americana6. This protist displays ultrastructural characteristics that ally it with the retortamonads7,8, a protozoan group that lacks mitochondria8,9. R. americana mtDNA (69,034 base pairs) contains the largest collection of genes (97) so far identified in any mtDNA, including genes for 5S ribosomal RNA, the RNA component of RNase P, and at least 18 proteins not previously known to be encoded in mitochondria. Most surprising are four genes specifying a multisubunit, eubacterial-type RNA polymerase. Features of gene content together with eubacterial characteristics of genome organization and expression not found before in mitochondrial genomes indicate that R. americana mtDNA more closely resembles the ancestral proto-mitochondrial genome than any other mtDNA investigated to date.
618 citations
TL;DR: In this paper, the authors identify some of the main issues in freight transportation planning and operations, and present appropriate Operations Research models and methods, as well as computer-based planning tools.
TL;DR: In this article, palladium-catalyzed couplings between various 9,9-disubstituted poly(2,7-dibromofluorenes) have been used to obtain process-able polyfluorenes in good yields.
Abstract: Well-defined poly(2,7-fluorene) derivatives have been prepared through palladium-catalyzed couplings between various 9,9-disubstituted or 9-monosubstituted 2,7-dibromofluorenes and 2,7-bis(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-9,9-dioctylfluorene. Using this versatile synthetic method, process- able polyfluorenes have been obtained in good yields. In solution, all these neutral yellow polymers exhibit blue emission (maximum of emission around 410 nm) with high quantum yields (up to 0.87). Moreover, novel acidic polyfluorene derivatives have been synthesized (i.e., poly(2,7'-(alkyl 9,9-dioctyl-7,2'-bifluorene- 9'-carboxylate))s) which show, upon base doping, electrical conductivities of 10-6-10-5 S/cm. This new doping method for conjugated polymers could open the way to the preparation of air-stable electron- injecting electrodes. Both photophysical and electrical properties of these polymers are quite promising for the fabrication of efficient blue-light-emitting devices.
TL;DR: In this article, it was shown that a confidence set which does not satisfy this characterization has zero coverage probability (level) in the neighborhood of non-identification subsets and will have a nonzero probability of being unbounded under any distribution compatible with the model.
Abstract: General characterizations of valid confidence sets and tests in problems which involve locally almost unidentified (LAU) parameters are provided and applied to several econo- metric models. Two types of inference problems are studied: (i) inference about parame- ters which are not identifiable on certain subsets of the parameter space, and (ii) inference about parameter transformations with discontinuities. When a LAU parameter or parametric function has an unbounded range, it is shown under general regularity conditions that any valid confidence set with level 1 - a for this parameter must be unbounded with probability close to 1 - a in the neighborhood of nonidentification subsets and will have a nonzero probability of being unbounded under any distribution compatible with the model: no valid confidence set which is almost surely bounded does exist. These properties hold even if "identifying restrictions" are imposed. Similar results also obtain for parameters with bounded ranges. Consequently, a confidence set which does not satisfy this characterization has zero coverage probability (level). This will be the case in particular for Wald-type confidence intervals based on asymptotic standard errors. Furthermore, Wald-type statistics for testing given values of a LAU parameter cannot be pivotal functions (i.e., they have distributions which depend on unknown nuisance param- eters) and even cannot be usefully bounded over the space of the nuisance parameters. These results are applied to several econometric problems: inference in simultaneous equations (instrumental variables (IV) regressions), linear regressions with autoregressive errors, inference about long-run multipliers and cointegrating vectors. For example, it is shown that standard "asymptotically justified" confidence intervals based on IV estimators (such as two-stage least squares) and the associated "standard errors" have zero coverage probability, and the corresponding t statistics have distributions which cannot be bounded by any finite set of distribution functions, a result of interest for interpreting IV regressions with "weak instruments." Furthermore, expansion methods (e.g., Edgeworth expansions) and bootstrap techniques cannot solve these difficulties. Finally, in a number of cases where Wald-type methods are fundamentally flawed (e.g., IV regressions with poor instruments), it is observed that likelihood-based methods (e.g., likelihood-ratio tests and confidence sets) combined with projection techniques can easily yield valid tests and confidence sets.
TL;DR: In this paper, the authors developed and implemented a statistical mechanical integral equation theory to describe the hydration structure of complex molecules, which is an extension of the reference interaction site model (RISM) in three dimensions, yields the average density from the solvent interactions sites at all points around a molecular solute of arbitrary shape.
Abstract: We developed and implemented a statistical mechanical integral equation theory to describe the hydration structure of complex molecules. The theory, which is an extension of the reference interaction site model (RISM) in three dimensions, yields the average density from the solvent interactions sites at all points r around a molecular solute of arbitrary shape. Both solute−solvent electrostatic and van der Waals interactions are fully included, and solvent packing is taken into account. The approach is illustrated by calculating the average oxygen and hydrogen density of liquid water around two molecular solutes: water and N-methylacetamide. Molecular dynamics simulations are performed to test the results obtained from the integral equation. It is observed that important microscopic structural features of the average water density due to hydrogen bonding are reproduced by the integral equation. The integral equation has a simple formal structure and is easy to implement numerically. It offers a powerful ...
TL;DR: The results do not warrant the routine implementation of programmes that involve psychological-distress screening and home nursing intervention for patients recovering from MI, and the poorer overall outcome for women, underline the need for further research and the inclusion of adequate numbers of women in future post-MI trials.
TL;DR: The fourth-corner method offers a way of analyzing the relationships between the supplementary variables associated with the rows and columns of a binary data table, and is shown to be applicable to a wide class of ecological problems.
Abstract: This paper addresses the following question: how does one relate the biological and behavioral characteristics of animals to habitat characteristics of the locations at which they are found? Ecologists often assemble data on species composition at different localities, habitat descriptions of these localities, and biological or behavioral traits of the species. These data tables are usually analyzed two by two: species composition against habitat characteristics, or against behavioral data, using such methods as canonical analysis. We propose a solution to the problem of estimating the parameters describing the relationship between habitat characteristics and biology or behavior, and of testing the statistical significance of these parameters; this problem is referred to as the fourth-corner problem, from its matrix formulation. In other words, the fourth-corner method offers a way of analyzing the relationships between the supplementary variables associated with the rows and columns of a binary (presence or absence) data table. The test case that motivated this study concerns a coral reef fish assemblage (280 species). Biological and behavioral characteristics of the species were used as supplementary variables for the rows, and characteristics of the environment for the columns. Parameters of the association between habitat characteristics (distance from beach, water depth, and substrate variables) and biological and behavioral traits of the species (feeding habits, ecological niche categories, size classes, egg types, activity rhythms) were estimated and tested for significance using permutations. Permutations can be performed in different ways, corresponding to different ecological hypotheses. Results were compared to predictions made independently by reef fish ecologists, in order to assess the method as well as the pertinence of the variables subjected to the analysis. The new method is shown to be applicable to a wide class of ecological problems.
Journal Article•
TL;DR: The expression of OX40L on DC suggests a physiologic role of this molecule during T cell priming by virtue of its ability to costimulate both T cell and DC activation and differentiation.
Abstract: OX40 ligand (OX40L), a member of the TNF family, was shown to be capable of signaling both the cells on which it is expressed and those expressing OX40, its cognate receptor. Here we show that OX40L is expressed on dendritic cells (DC), the most efficient APC to prime naive T cells. The expression and the functional activity of OX40L were examined by means of mAbs used to stain or cross-link OX40L on 1) freshly isolated human blood DC (bDC) and 2) monocyte-derived DC at different stages of differentiation. These were derived from monocytes cultured either with IL-4 and granulocyte-macrophage CSF (IL-4-Mo-DC) or with IL-4 and granulocyte-macrophage CSF plus TNF-alpha. Both types of Mo-DC expressed OX40L after stimulation through CD40; ligation of OX40L on activated IL-4-Mo-DC enhanced by 4- to 35-fold their cytokine production (TNF-alpha, IL-12 p40, IL-1 beta, and IL-6) and increased CD80, CD86, CD54, and CD40 expression. Stimulation of activated IL-4-Mo-DC through OX40L strikingly enhanced their maturation as evidenced by CD83 up-regulation, CD115 (CSF-1R) down-regulation, and typical morphologic changes. OX40L was constitutively expressed on a subset of bDC, and its ligation slightly enhanced CD40L-stimulated IL-12 production. OX40L was down-regulated after overnight culture and spontaneously reexpressed on a subset of mature bDC (CD83high, CD33high, CD11chigh, CD5+). Thus, the expression of OX40L on DC suggests a physiologic role of this molecule during T cell priming by virtue of its ability to costimulate both T cell and DC activation and differentiation.
TL;DR: The notions of diffuse transmission and of an ambient level of ACh in the CNS could also be of clinical relevance, in accounting for the production and nature of certain cholinergic deficits and the efficacy of substitution therapies.
TL;DR: A mathematical model that represented movements in terms of movement direction centered on the hand could not account for any of the arm-orientation-related response changes seen in this task, whereas models in intrinsic parameter spaces of joint kinematics and joint torques predicted many of the effects.
Abstract: Scott, Stephen H. and John F. Kalaska. Reaching movements with similar hand paths but different arm orientations. I. Activity of individual cells in motor cortex. J. Neurophysiol. 77: 826–852, 1997...
TL;DR: Recent studies provide further support for the hypothesis that spatial representations of limb position, target locations, and potential motor actions are expressed in the neuronal activity in parietal cortex.
TL;DR: In this article, the electrostatic contribution to the solvation free energy of 20 naturally occurring amino acids was examined using atomic models using free energy perturbation techniques with explicit water molecules.
Abstract: The electrostatic contribution to the solvation free energy of the 20 naturally occurring amino acids is examined using atomic models. The amino acids are modeled by N-acetyl-X-N‘-methylamide. Free energy perturbation techniques with explicit water molecules are used to evaluate the contribution of solute−solvent electrostatic interactions to the solvation free energies. An analysis based on the radial solvent charge distribution yields a basic rule to determine a set of atomic Born radii defining the dielectric boundary between the solute and the solvent in continuum electrostatic models. Minor adjustments are made to refine the atomic Born radii in order to reproduce quantitatively the electrostatic contribution to the solvation free energy calculated by free energy perturbation techniques. The good agreement of continuum electrostatic and molecular dynamics free energy perturbations suggests that the new set of atomic Born radii may be used as a computationally inexpensive alternative to the microscopi...
TL;DR: Since macrophages constitute the major site of liposome localization after parenteral administration and play an important role in the control of the immune system, cationic liposomes should be used with caution to deliver gene or antisense oligonucleotide to mammalian cells.
TL;DR: The results show that the cortisol response to anticipation of stress and to stress in the elderly specifically affects those memory functions that are dependent on hippocampal activity, and suggest that an altered cortisol responsivity to acute and/or chronic stress, with its detrimental effects on memory, could be an important factor explaining the genesis of memory deficits in aged populations.
Abstract: A group of 14 healthy elderly subjects was submitted to a nonstressful (attentional task) and a stressful (public speaking task) condition. Declarative (conscious recollection of learned information) and nondeclarative (retrieved information without conscious or explicit access) memory as well as salivary cortisol levels were measured before and after each condition. The results showed that the stressful condition significantly decreased declarative memory performance, whereas the nonstressful condition did not. Nondeclarative memory performance was not affected by either condition. Further analyses separating the subjects into responders and nonresponders in terms of stress-induced cortisol change revealed a very different pattern of cortisol secretion and declarative memory performance in both populations. We showed that the responders presented increased cortisol levels 60 min before the actual stressor, whereas the nonresponders presented increased cortisol levels 25 min before the actual stressor. Al...
TL;DR: A model is proposed and a tabu search heuristic is developed for its solution and results using both randomly generated data and real data confirm the efficiency of the proposed approach.
TL;DR: It is shown that a local increase in IL-1Ra production in OA knee joints by intraarticular injection of transduced synovial cells can reduce the progression of experimentally induced lesions.
Abstract: OBJECTIVE This study explored the therapeutic effect of interleukin-1 receptor antagonist (IL-1Ra), administered by gene transfer, on the progression of osteoarthritic (OA) lesions in an experimental dog model. METHODS Seventeen mature mongrel dogs were divided into 3 groups. Group 1 (n = 7) had an anterior cruciate ligament (ACL) section of the right knee through a stab wound incision. Groups 2 and 3 (n = 5 per group), had an ACL section of the right knee and partial synovectomy of the left knee. Each dog's synovium was subjected to enzymatic digestion, and the synovial fibroblasts were propagated in monolayer culture. Synovial cells from each dog were transduced in vitro using the retrovirus MFG with either the Escherichia coli beta-galactosidase (lac Z) gene (group 2) or the human IL-1Ra gene (group 3). Two days after surgery, the dogs received intraarticular injections as follows: group 1 phosphate buffered saline (PBS) (2 ml); group 2 autologous cells (60 x 10(6) cells/2 ml of PBS) transduced with the lac Z gene; group 3 autologous cells transduced with the IL-1Ra gene. Synovial fluid was aspirated at 2 weeks and 4 weeks. All dogs were euthanized at 4 weeks postsurgery. The right knees were dissected, and lesions were scored for macroscopic and microscopic changes. Synovial explants were dissected and representative specimens were used for histology or were cultured for 48 hours. The levels of IL-1Ra in synovial fluid and synovial explant conditioned medium were measured by specific enzyme-linked immunosorbent assay. RESULTS The level of IL-1Ra in synovial fluid of group 3 was 202.8 +/- 131.5 ng/ml (mean +/- SEM) at 2 weeks and 2.8 +/- 2.2 ng/ml at 4 weeks after surgery. Membrane explants isolated from dogs that received synovial cells transduced with the IL-1Ra gene (group 3) actively produced IL-1Ra (4.0 +/- 2.0 ng/gm of tissue wet weight). The severity of OA cartilage lesions was similar in groups 1 and 2. In contrast, group 3 dogs had a marked reduction in macroscopic lesion severity on the tibial plateaus (P < 0.01 for grade; P < 0.04 for size) and femoral condyles. Moreover, the histologic lesion severity was decreased on both plateaus (P < 0.06) and condyles. CONCLUSION This study showed that a local increase in IL-1Ra production in OA knee joints by intraarticular injection of transduced synovial cells can reduce the progression of experimentally induced lesions.
TL;DR: An optical method for the visualization of boundaries of cylindrical bovine humeral head articular cartilage disks, immersed in physiological solution, and compressed in unconfined geometry revealed that the lateral expansion, especially during the initial phase of relaxation, was inhomogeneous through the tissue depth.
TL;DR: The results suggest that CO may activate both a cyclicGMP signalling pathway and KCa channels in the same vascular tissues, and that the endogenously generated CO may significantly affect the vascular contractile responses.
Abstract: 1. Carbon monoxide (CO) induced a concentration-dependent relaxation of isolated rat tail artery tissues which were precontracted with phenylephrine or U-46619. This vasorelaxing effect of CO was independent of the presence of the intact endothelium. 2. The CO-induced vasorelaxation was partially inhibited by the blockade of either the cyclicGMP pathway or big-conductance calcium-activated K (KCa) channels. When both the cyclicGMP pathway and KCa channels were blocked, the CO-induced vasorelaxation was completely abolished. 3. Incubation of vascular tissues with hemin, in order to enhance the endogenous production of CO, suppressed the phenylephrine-induced vasocontraction in a time- and concentration-dependent manner. The hemin-induced suppression of the vascular contractile response to phenylephrine was abolished after the vascular tissues were co-incubated with either oxyhaemoglobin or zinc protoporphyrin-IX, suggesting an induced endogenous generation of CO from vascular tissues. 4. The effect of hemin incubation on vascular contractility did not involve the endogenous generation of nitric oxide. 5. Our results suggest that CO may activate both a cyclicGMP signalling pathway and KCa channels in the same vascular tissues, and that the endogenously generated CO may significantly affect the vascular contractile responses.