Showing papers by "University of Leicester published in 2000"

A Posteriori Error Estimation in Finite Element Analysis

Abstract: This monograph presents a summary account of the subject of a posteriori error estimation for finite element approximations of problems in mechanics. The study primarily focuses on methods for linear elliptic boundary value problems. However, error estimation for unsymmetrical systems, nonlinear problems, including the Navier-Stokes equations, and indefinite problems, such as represented by the Stokes problem are included. The main thrust is to obtain error estimators for the error measured in the energy norm, but techniques for other norms are also discussed.

The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences

Abstract: Campylobacter jejuni, from the delta-epsilon group of proteobacteria, is a microaerophilic, Gram-negative, flagellate, spiral bacterium—properties it shares with the related gastric pathogen Helicobacter pylori. It is the leading cause of bacterial food-borne diarrhoeal disease throughout the world1. In addition, infection with C. jejuni is the most frequent antecedent to a form of neuromuscular paralysis known as Guillain–Barre syndrome2. Here we report the genome sequence of C. jejuni NCTC11168. C. jejuni has a circular chromosome of 1,641,481 base pairs (30.6% G+C) which is predicted to encode 1,654 proteins and 54 stable RNA species. The genome is unusual in that there are virtually no insertion sequences or phage-associated sequences and very few repeat sequences. One of the most striking findings in the genome was the presence of hypervariable sequences. These short homopolymeric runs of nucleotides were commonly found in genes encoding the biosynthesis or modification of surface structures, or in closely linked genes of unknown function. The apparently high rate of variation of these homopolymeric tracts may be important in the survival strategy of C. jejuni.

Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome.

Abstract: The cellular-stress response can mediate cellular protection through expression of heat-shock protein (Hsp) 70, which can interfere with the process of apoptotic cell death. Stress-induced apoptosis proceeds through a defined biochemical process that involves cytochrome c, Apaf-1 and caspase proteases. Here we show, using a cell-free system, that Hsp70 prevents cytochrome c/dATP-mediated caspase activation, but allows the formation of Apaf-1 oligomers. Hsp70 binds to Apaf-1 but not to procaspase-9, and prevents recruitment of caspases to the apoptosome complex. Hsp70 therefore suppresses apoptosis by directly associating with Apaf-1 and blocking the assembly of a functional apoptosome.

Phytochromes and light signal perception by plants—an emerging synthesis

Abstract: For plants, the sensing of light in the environment is as important as vision is for animals. Fluctuations in light can be crucial to competition and survival. One way plants sense light is through the phytochromes, a small family of diverse photochromic protein photoreceptors whose origins have been traced to the photosynthetic prokaryotes. During their evolution, the phytochromes have acquired sophisticated mechanisms to monitor light. Recent advances in understanding the molecular mechanisms of phytochromes and their significance to evolutionary biology make possible an interim synthesis of this rapidly advancing branch of photobiology.

Empirical assessment of effect of publication bias on meta-analyses.

Abstract: Objective: To assess the effect of publication bias on the results and conclusions of systematic reviews and meta-analyses. Design: Analysis of published meta-analyses by trim and fill method. Studies: 48 reviews in Cochrane Database of Systematic Reviews that considered a binary endpoint and contained 10 or more individual studies. Main outcome measures: Number of reviews with missing studies and effect on conclusions of meta-analyses. Results: The trim and fill fixed effects analysis method estimated that 26 (54%) of reviews had missing studies and in 10 the number missing was significant. The corresponding figures with a random effects model were 23 (48%) and eight. In four cases, statistical inferences regarding the effect of the intervention were changed after the overall estimate for publication bias was adjusted for. Conclusions: Publication or related biases were common within the sample of meta-analyses assessed. In most cases these biases did not affect the conclusions. Nevertheless, researchers should check routinely whether conclusions of systematic reviews are robust to possible non-random selection mechanisms.

An LDL-receptor-related protein mediates Wnt signalling in mice.

Abstract: Wnt genes comprise a large family of secreted polypeptides that are expressed in spatially and tissue-restricted patterns during vertebrate embryonic development1. Mutational analysis in mice has shown the importance of Wnts in controlling diverse developmental processes such as patterning of the body axis, central nervous system and limbs, and the regulation of inductive events during organogenesis2. Although many components of the Wnt signalling pathway have been identified, little is known about how Wnts and their cognate Frizzled receptors signal to downstream effector molecules. Here we present evidence that a new member of the low-density lipoprotein (LDL)-receptor-related protein family, LRP6 (ref. 3), is critical for Wnt signalling in mice. Embryos homozygous for an insertion mutation in the LRP6 gene exhibit developmental defects that are a striking composite of those caused by mutations in individual Wnt genes. Furthermore, we show a genetic enhancement of a Wnt mutant phenotype in mice lacking one functional copy of LRP6. Together, our results support a broad role for LRP6 in the transduction of several Wnt signals in mammals.

Genealogies of mouse inbred strains.

Abstract: The mouse is a prime organism of choice for modelling human disease. Over 450 inbred strains of mice have been described, providing a wealth of different genotypes and phenotypes for genetic and other studies. As new strains are generated and others become extinct, it is useful to review periodically what strains are available and how they are related to each other, particularly in the light of available DNA polymorphism data from microsatellite and other markers. We describe the origins and relationships of inbred mouse strains, 90 years after the generation of the first inbred strain. Given the large collection of inbred strains available, and that published information on these strains is incomplete, we propose that all genealogical and genetic data on inbred strains be submitted to a common electronic database to ensure this valuable information resource is preserved and used efficiently.

IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans

Abstract: The purpose of these guidelines is to provide concise guidance on the planning, performing and interpretation of studies to monitor groups or individuals exposed to genotoxic agents. Most human carcinogens are genotoxic but not all genotoxic agents have been shown to be carcinogenic in humans. Although the main interest in these studies is due to the association of genotoxicity with carcinogenicity, there is also an inherent interest in monitoring human genotoxicity independently of cancer as an endpoint. The most often studied genotoxicity endpoints have been selected for inclusion in this document and they are structural and numerical chromosomal aberrations assessed using cytogenetic methods (classical chromosomal aberration analysis (CA), fluorescence in situ hybridisation (FISH), micronuclei (MN)); DNA damage (adducts, strand breaks, crosslinking, alkali-labile sites) assessed using bio-chemical/electrophoretic assays or sister chromatid exchanges (SCE); protein adducts; and hypoxanthine-guanine phosphoribosyltransferase (HPRT) mutations. The document does not consider germ cells or gene mutation assays other than HPRT or markers of oxidative stress, which have been applied on a more limited scale.

Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-beta family.

Abstract: BACKGROUND Primary pulmonary hypertension (PPH), resulting from occlusion of small pulmonary arteries, is a devastating condition. Mutations of the bone morphogenetic protein receptor type II gene ( BMPR2), a component of the transforming growth factor beta (TGF-β) family which plays a key role in cell growth, have recently been identified as causing familial PPH. We have searched for BMPR2 gene mutations in sporadic PPH patients to determine whether the same genetic defect underlies the more common form of the disorder. METHODS We investigated 50 unrelated patients, with a clinical diagnosis of PPH and no identifiable family history of pulmonary hypertension, by direct sequencing of the entire coding region and intron/exon boundaries of the BMPR2 gene. DNA from available parent pairs (n=5) was used to assess the occurrence of spontaneous (de novo) mutations contributing to sporadic PPH. RESULTS We found a total of 11 different heterozygous germline mutations of the BMPR2 gene in 13 of the 50 PPH patients studied, including missense (n=3), nonsense (n=3), and frameshift (n=5) mutations each predicted to alter the cell signalling response to specific ligands. Parental analysis showed three occurrences of paternal transmission and two of de novo mutation of the BMPR2 gene in sporadic PPH. CONCLUSION The sporadic form of PPH is associated with germline mutations of the gene encoding the receptor protein BMPR-II in at least 26% of cases. A molecular classification of PPH, based upon the presence or absence of BMPR2 mutations, has important implications for patient management and screening of relatives.

LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.

Abstract: The lipodystrophies are a group of disorders characterized by the absence or reduction of subcutaneous adipose tissue. Partial lipodystrophy (PLD; MIM 151660) is an inherited condition in which a regional (trunk and limbs) loss of fat occurs during the peri-pubertal phase. Additionally, variable degrees of resistance to insulin action, together with a hyperlipidaemic state, may occur and simulate the metabolic features commonly associated with predisposition to atherosclerotic disease. The PLD locus has been mapped to chromosome 1q with no evidence of genetic heterogeneity. We, and others, have refined the location to a 5.3-cM interval between markers D1S305 and D1S1600 (refs 5, 6). Through a positional cloning approach we have identified five different missense mutations in LMNA among ten kindreds and three individuals with PLD. The protein product of LMNA is lamin A/C, which is a component of the nuclear envelope. Heterozygous mutations in LMNA have recently been identified in kindreds with the variant form of muscular dystrophy (MD) known as autosomal dominant Emery-Dreifuss MD (EDMD-AD; ref. 7) and dilated cardiomyopathy and conduction-system disease (CMD1A). As LMNA is ubiquitously expressed, the finding of site-specific amino acid substitutions in PLD, EDMD-AD and CMD1A reveals distinct functional domains of the lamin A/C protein required for the maintenance and integrity of different cell types.

The importance of music to adolescents

Abstract: Aims. The study aims to determine the importance of music to adolescents in England, and investigates why they listen to and perform music. Sample. A total of 2465 adolescents (1149 males; 1266 females; 50 participants did not state their sex) between 13 and 14 years of age who were attending Year 9 at one of 22 secondary schools in the North Staffordshire region of England. Method. A questionnaire asked participants (a) about their degree of involvement with musical activities; (b) to rate the importance of music relative to other activities; and (c) to rate the importance of several factors that might determine why they and other people of their age and sex might listen to/perform pop and classical music. Results. Responses indicated that i) over 50% of respondents either played an instrument currently or had played regularly before giving up, and the sample listened to music for an average of 2.45 hours per day; ii) listening to music was preferred to other indoor activities but not to outdoor activities; iii) listening to/playing pop music has different perceived benefits to listening to/ playing classical music; iv) responses to suggested reasons for listening to music could be grouped into three factors; and v) responses to suggested reasons for playing music could be grouped into four factors. Conclusions. These results indicate that music is important to adolescents, and that this is because it allows them to (a) portray an ‘ image’ to the outside world and (b) satisfy their emotional needs.

Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: Epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity.

Abstract: The immune system has evolved specialized cellular and molecular mechanisms for targeting and regulating immune responses at epithelial surfaces. Here we show that small intestinal intraepithelial lymphocytes and lamina propria lymphocytes migrate to thymus-expressed chemokine (TECK). This attraction is mediated by CC chemokine receptor (CCR)9, a chemoattractant receptor expressed at high levels by essentially all CD4+ and CD8+ T lymphocytes in the small intestine. Only a small subset of lymphocytes in the colon are CCR9+, and lymphocytes from other tissues including tonsils, lung, inflamed liver, normal or inflamed skin, inflamed synovium and synovial fluid, breast milk, and seminal fluid are universally CCR9−. TECK expression is also restricted to the small intestine: immunohistochemistry reveals that intense anti-TECK reactivity characterizes crypt epithelium in the jejunum and ileum, but not in other epithelia of the digestive tract (including stomach and colon), skin, lung, or salivary gland. These results imply a restricted role for lymphocyte CCR9 and its ligand TECK in the small intestine, and provide the first evidence for distinctive mechanisms of lymphocyte recruitment that may permit functional specialization of immune responses in different segments of the gastrointestinal tract. Selective expression of chemokines by differentiated epithelium may represent an important mechanism for targeting and specialization of immune responses.

Y-Chromosomal Diversity in Europe Is Clinal and Influenced Primarily by Geography, Rather than by Language

Abstract: Clinal patterns of autosomal genetic diversity within Europe have been interpreted in previous studies in terms of a Neolithic demic diffusion model for the spread of agriculture; in contrast, studies using mtDNA have traced many founding lineages to the Paleolithic and have not shown strongly clinal variation. We have used 11 human Y-chromosomal biallelic polymorphisms, defining 10 haplogroups, to analyze a sample of 3,616 Y chromosomes belonging to 47 European and circum-European populations. Patterns of geographic differentiation are highly nonrandom, and, when they are assessed using spatial autocorrelation analysis, they show significant clines for five of six haplogroups analyzed. Clines for two haplogroups, representing 45% of the chromosomes, are continentwide and consistent with the demic diffusion hypothesis. Clines for three other haplogroups each have different foci and are more regionally restricted and are likely to reflect distinct population movements, including one from north of the Black Sea. Principal-components analysis suggests that populations are related primarily on the basis of geography, rather than on the basis of linguistic affinity. This is confirmed in Mantel tests, which show a strong and highly significant partial correlation between genetics and geography but a low, nonsignificant partial correlation between genetics and language. Genetic-barrier analysis also indicates the primacy of geography in the shaping of patterns of variation. These patterns retain a strong signal of expansion from the Near East but also suggest that the demographic history of Europe has been complex and influenced by other major population movements, as well as by linguistic and geographic heterogeneities and the effects of drift.

Systematic review of water fluoridation.

Abstract: Objective: To review the safety and efficacy of fluoridation of drinking water. Design: Search of 25 electronic databases and world wide web. Relevant journals hand searched; further information requested from authors. Inclusion criteria were a predefined hierarchy of evidence and objectives. Study validity was assessed with checklists. Two reviewers independently screened sources, extracted data, and assessed validity. Main outcome measures: Decayed, missing, and filled primary/permanent teeth. Proportion of children without caries. Measure of effect was the difference in change in prevalence of caries from baseline to final examination in fluoridated compared with control areas. For potential adverse effects, all outcomes reported were used. Results: 214 studies were included. The quality of studies was low to moderate. Water fluoridation was associated with an increased proportion of children without caries and a reduction in the number of teeth affected by caries. The range (median) of mean differences in the proportion of children without caries was −5.0% to 64% (14.6%). The range (median) of mean change in decayed, missing, and filled primary/permanent teeth was 0.5 to 4.4 (2.25) teeth. A dose-dependent increase in dental fluorosis was found. At a fluoride level of 1 ppm an estimated 12.5% (95% confidence interval 7.0% to 21.5%) of exposed people would have fluorosis that they would find aesthetically concerning. Conclusions: The evidence of a beneficial reduction in caries should be considered together with the increased prevalence of dental fluorosis. There was no clear evidence of other potential adverse effects.

Colorectal cancer prevention in ulcerative colitis: a case-control study.

Abstract: Background: The risk of colorectal cancer (CRC) in ulcerative colitis (UC) increases with extent and duration of disease. Identifying other risk factors would allow targeting of sub-groups at greatest risk, enabling more cost-effective surveillance. Methods: We conducted a case-control study comparing 102 cases of CRC in UC with matched controls. Odds ratios (OR) for cancer risk were estimated by conditional logistic regression. A multivariate model assessed the contribution of individual variables. Results: Regular 5-aminosalicylic acid (5-ASA) therapy reduces cancer risk by 75% (OR 0.25, 95% CI: 0.13–0.48, P < 0.00001). Adjusting for other variables, taking mesalazine regularly reduces risk by 81% (OR 0.19, 95% CI: 0.06–0.61, P=0.006) and visiting a hospital doctor more than twice a year also reduces risk (OR 0.16, 95% CI: 0.04–0.60, P=0.007). Considering variables independently, having a family history of sporadic CRC in any relative increases risk fivefold (OR 5.0, 95% CI: 1.10–22.82, P < 0.04). Conclusions: CRC risk among UC patients can be reduced by regular therapy with 5-ASA medication. Colonoscopic surveillance may be best targeted on those unable to take 5-ASAs (e.g. due to allergy) and those with a positive family history of CRC.

Immunolocalisation of oestrogen receptor beta in human tissues

Abstract: Oestrogens exert their actions via specific nuclear protein receptors that are members of the steroid/thyroid receptor superfamily of transcription factors. Recently, a second oestrogen receptor (ERbeta) has been cloned, and using reverse transcription-PCR and immunohistochemistry it has been shown to have a wide tissue distribution in the rat that is distinct from the classical oestrogen receptor, ERalpha. Using commercial polyclonal antisera against peptides specific to human ERbeta, we have determined the sites of ERbeta expression in archival and formalin-fixed human tissue and compared its expression with that of ERalpha. ERbeta was localised to the cell nuclei of a wide range of normal adult human tissues including ovary, Fallopian tube, uterus, lung, kidney, brain, heart, prostate and testis. In the ovary, ERbeta was present in multiple cell types including granulosa cells in small, medium and large follicles, theca and corpora lutea, whereas ERalpha was weakly expressed in the nuclei of granulosa cells, but not in the theca nor in the copora lutea. In the endometrium, both ERalpha and ERbeta were observed in luminal epithelial cells and in the nuclei of stromal cells but, significantly, ERbeta was weak or absent from endometrial glandular epithelia. Epithelial cells in most male tissues including the prostate, the urothelium and muscle layers of the bladder, and Sertoli cells in the testis, were also immunopositive for ERbeta. Significant ERbeta immunoreactivity was detected in most areas of the brain, with the exception of the hippocampus - a tissue that stained positively for ERalpha. In conclusion, the almost ubiquitous immunohistochemical localisation of ERbeta indicates that ERbeta may play a major role in the mediation of oestrogen action. The differential expression of ERalpha and ERbeta in some of these tissues suggests a more complex control mechanism in oestrogenic potential than originally envisioned.

X‐ray spectra of a large sample of quasars with ASCA

Abstract: The results from an X-ray spectral analysis of a large sample of quasars, observed with ASCA, are presented. The sample was selected to include all ASCA observations of quasars, with z>0.05 and MV 99 per cent confidence, confirming the well-known trend between Γ and Hβ FWHM in Seyfert 1s, but at higher luminosities. Other spectral complexities are observed from this sample. A soft X-ray excess, with blackbody temperatures in the range 100–300 eV, is seen in many low-z radio-quiet quasars. In most cases the temperatures are probably too hot to originate directly from the disc and could imply that some reprocessing is involved. Iron K-line emission features are also found in the RQQs, but often from partially ionized material. Indeed, in the highest-luminosity RQQs there is neither evidence for iron line emission nor the reflection component expected from disc reflection models. These observations can be explained by an increase in the quasar accretion rate with luminosity, leading to an increase in the ionization state of the surface layers of the disc. The occurrence of ionized or ‘warm’ absorbers is rare in this sample, with only five detections in low-z objects. However, excess neutral X-ray absorption is found towards several of the high-z, predominantly radio-loud, quasars. Although found to increase with quasar redshift, this ‘intrinsic’ absorption may be associated with radio-loud active galactic nuclei.

World‐City Network: A New Metageography?

Abstract: (2000). World-City Network: A New Metageography? Annals of the Association of American Geographers: Vol. 90, No. 1, pp. 123-134.

Millennial-Scale Dynamics of Southern Amazonian Rain Forests

Abstract: Amazonian rain forest-savanna boundaries are highly sensitive to climatic change and may also play an important role in rain forest speciation. However, their dynamics over millennial time scales are poorly understood. Here, we present late Quaternary pollen records from the southern margin of Amazonia, which show that the humid evergreen rain forests of eastern Bolivia have been expanding southward over the past 3000 years and that their present-day limit represents the southernmost extent of Amazonian rain forest over at least the past 50,000 years. This rain forest expansion is attributed to increased seasonal latitudinal migration of the Intertropical Convergence Zone, which can in turn be explained by Milankovitch astronomic forcing.

Inverted Electron-Hole Alignment in InAs-GaAs Self-Assembled Quantum Dots

Abstract: New information on the electron-hole wave functions in InAs-GaAs self-assembled quantum dots is deduced from Stark effect spectroscopy. Most unexpectedly it is shown that the hole is localized towards the top of the dot, above the electron, an alignment that is inverted relative to the predictions of all recent calculations. We are able to obtain new information on the structure and composition of buried quantum dots from modeling of the data. We also demonstrate that the excited state transitions arise from lateral quantization and that tuning through the inhomogeneous distribution of dot energies can be achieved by variation of electric field.

Characterization of Potentially Chemopreventive Phenols in Extracts of Brown Rice That Inhibit the Growth of Human Breast and Colon Cancer Cells

Abstract: Rice is a staple diet in Asia, where the incidence of breast and colon cancer is markedly below that in the Western world. We investigated potential colon and breast tumor-suppressive properties of rice, testing the hypothesis that rice contains phenols that interfere with the proliferation or colony-forming ability of breast or colon cells. Brown rice, its white milled counterpart, and bran from brown rice were boiled and extracted with ethyl acetate. The extracts were analyzed by high pressure liquid chromatography-mass spectrometry. Eight phenols, protocatechuic acid, p-coumaric acid, caffeic acid, ferulic acid, sinapic acid, vanillic acid, methoxycinnamic acid, and tricin, were identified in the extracts of bran and intact brown rice. These extracts were separated into nine fractions by column chromatography. The effect of bran extract and its fractions at 100 microg/ml on cell viability and colony-forming ability of human-derived breast and colon cell lines was assessed. Bran extract decreased numbers of viable MDA MB 468 and HBL 100 breast cells and colon-derived SW 480 and human colonic epithelial cells as judged by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4 -sulfophenyl)-2H-tetrazolium assay. It also reduced colony formation of SW 480 colon and MDA MB 468 breast cells. Of the eight phenols identified in the brown rice bran, when applied at 50 microM, caffeic acid decreased numbers of all cell types except HBL 100. Tricin, ferulic acid, and methoxycinnamic acid interfered with cell viability in one or more cell lines. Tricin (50 microM) and the other phenols (200 microM) inhibited colony formation of SW 480 cells. Clonogenicity of MDA MB 468 cells was inhibited by caffeic acid, ferulic acid, and tricin (50 microM). Tricin was the most potent anticlonogenic of the compounds with IC50s of 16 microM in the SW 480 colon cells and 0.6 microM in the MDA MB 468 breast cells. The results suggest that: (a) brown rice and bran contain compounds with putative cancer chemopreventive properties; (b) certain phenols contained in brown rice bran, e.g., tricin, may be associated with this activity; and (c) these phenols are present at much lower levels in white than in brown rice. Thus, the consumption of rice bran or brown rice instead of milled white rice may be advantageous with respect to cancer prevention.

Reduced vas deferens contraction and male infertility in mice lacking P2X1 receptors.

Abstract: P2X1 receptors for ATP are ligand-gated cation channels, present on many excitable cells including vas deferens smooth muscle cells1,2,3,4,5. A substantial component of the contractile response of the vas deferens to sympathetic nerve stimulation, which propels sperm into the ejaculate, is mediated through P2X receptors1. Here we show that male fertility is reduced by ∼90% in mice with a targeted deletion of the P2X1 receptor gene. Male mice copulate normally—reduced fertility results from a reduction of sperm in the ejaculate and not from sperm dysfunction. Female mice and heterozygote mice are unaffected. In P2X1-receptor-deficient mice, contraction of the vas deferens to sympathetic nerve stimulation is reduced by up to 60% and responses to P2X receptor agonists are abolished. These results show that P2X1 receptors are essential for normal male reproductive function and suggest that the development of selective P2X1 receptor antagonists may provide an effective non-hormonal male contraceptive pill. Also, agents that potentiate the actions of ATP at P2X1 receptors may be useful in the treatment of male infertility.

A study of patients' expectations and satisfaction in Singapore hospitals.

Abstract: In today’s highly competitive healthcare environment, hospitals increasingly realise the need to focus on service quality as a means to improve their competitive position. Customer‐based determinants and perceptions of service quality therefore play an important role when choosing a hospital. This paper attempts to determine the expectations and perceptions of patients through the use of a generic, internationally used market research technique called SERVQUAL. An analysis covering 252 patients revealed that there was an overall service quality gap between patients’ expectations and perceptions. Thus, improvements are required across all the six dimensions, namely, tangibility, reliability, responsiveness, assurance, empathy and accessibility and affordability.

Active ERK/MAP kinase is targeted to newly forming cell-matrix adhesions by integrin engagement and v-Src.

Abstract: Integrin engagement generates cellular signals leading to the recruitment of structural and signalling molecules which, in concert with rearrangements of the actin cytoskeleton, leads to the formation of focal adhesion complexes. Using antisera reactive either with total ERK or with phosphorylated/activated forms of ERK, in rat embryo fibroblasts and embryonic avian cells that express v‐Src, we found that active ERK is targeted to newly forming focal adhesions after integrin engagement or activation of v‐Src. UO126, an inhibitor of MAP kinase kinase 1 (MEK1), suppressed focal adhesion targeting of active ERK and cell spreading. Also, integrin engagement and v‐Src induced myosin light chain kinase (MLCK)‐dependent phosphorylation of myosin light chain downstream of the MEK/ERK pathway, and MLCK and myosin activities are required for the focal adhesion targeting of ERK. The translocation of active ERK to newly forming focal adhesions may direct specificity towards appropriate downstream targets that influence adhesion assembly. These findings support a role for ERK in the regulation of the adhesion/cytoskeletal network and provide an explanation for the role of ERK in cell motility.