Showing papers by "Stony Brook University published in 1999"

Cutaneous wound healing.

Abstract: The primary function of the skin is to serve as a protective barrier against the environment. Loss of the integrity of large portions of the skin as a result of injury or illness may lead to major disability or even death. Every year in the United States more than 1.25 million people have burns1 and 6.5 million have chronic skin ulcers caused by pressure, venous stasis, or diabetes mellitus.2 The primary goals of the treatment of wounds are rapid wound closure and a functional and aesthetically satisfactory scar. Recent advances in cellular and molecular biology have greatly expanded our understanding . . .

Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder.

Abstract: Background We examined relapse after response to a first episode of schizophrenia or schizoaffective disorder. Methods Patients with first-episode schizophrenia were assessed on measures of psychopathologic variables, cognition, social functioning, and biological variables and treated according to a standardized algorithm. The sample for the relapse analyses consisted of 104 patients who responded to treatment of their index episode and were at risk for relapse. Results Five years after initial recovery, the cumulative first relapse rate was 81.9% (95% confidence interval [CI], 70.6%-93.2%); the second relapse rate was 78.0% (95% CI, 46.5%-100.0%). By 4 years after recovery from a second relapse, the cumulative third relapse rate was 86.2% (95% CI, 61.5%-100.0%). Discontinuing antipsychotic drug therapy increased the risk of relapse by almost 5 times (hazard ratio for an initial relapse, 4.89 [99% CI, 2.49-9.60]; hazard ratio for a second relapse, 4.57 [99% CI, 1.49-14.02]). Subsequent analyses controlling for antipsychotic drug use showed that patients with poor premorbid adaptation to school and premorbid social withdrawal relapsed earlier. Sex, diagnosis, obstetric complications, duration of psychotic illness before treatment, baseline symptoms, neuroendocrine measures, methylphenidate hydrochloride challenge response, neuropsychologic and magnetic resonance imaging measures, time to response of the initial episode, adverse effects during treatment, and presence of residual symptoms after the initial episode were not significantly related to time to relapse. Conclusions There is a high rate of relapse within 5 years of recovery from a first episode of schizophrenia and schizoaffective disorder. This risk is diminished by maintenance antipsychotic drug treatment.

Nucleolar Arf sequesters Mdm2 and activates p53.

Abstract: The Ink4/Arf locus encodes two tumour-suppressor proteins, p16Ink4a and p19Arf, that govern the antiproliferative functions of the retinoblastoma and p53 proteins, respectively. Here we show that Arf binds to the product of the Mdm2 gene and sequesters it into the nucleolus, thereby preventing negative-feedback regulation of p53 by Mdm2 and leading to the activation of p53 in the nucleoplasm. Arf and Mdm2 co-localize in the nucleolus in response to activation of the oncoprotein Myc and as mouse fibroblasts undergo replicative senescence. These topological interactions of Arf and Mdm2 point towards a new mechanism for p53 activation.

Responses of tundra plants to experimental warming:meta‐analysis of the international tundra experiment

Abstract: The International Tundra Experiment (ITEX) is a collaborative, multisite experiment using a common temperature manipulation to examine variability in species response across climatic and geographic gradients of tundra ecosystems. ITEX was designed specifically to examine variability in arctic and alpine species response to increased temperature. We compiled from one to four years of experimental data from 13 different ITEX sites and used meta-analysis to analyze responses of plant phenology, growth, and reproduction to experimental warming. Results indicate that key phenological events such as leaf bud burst and flowering occurred earlier in warmed plots throughout the study period; however, there was little impact on growth cessation at the end of the season. Quantitative measures of vegetative growth were greatest in warmed plots in the early years of the experiment, whereas reproductive effort and success increased in later years. A shift away from vegetative growth and toward reproductive effort and success in the fourth treatment year suggests a shift from the initial response to a secondary response. The change in vegetative response may be due to depletion of stored plant reserves, whereas the lag in reproductive response may be due to the formation of flower buds one to several seasons prior to flowering. Both vegetative and reproductive responses varied among life-forms; herbaceous forms had stronger and more consistent vegetative growth responses than did woody forms. The greater responsiveness of the herbaceous forms may be attributed to their more flexible morphology and to their relatively greater proportion of stored plant reserves. Finally, warmer, low arctic sites produced the strongest growth responses, but colder sites produced a greater reproductive response. Greater resource investment in vegetative growth may be a conservative strategy in the Low Arctic, where there is more competition for light, nutrients, or water, and there may be little opportunity for successful germination or seedling development. In contrast, in the High Arctic, heavy investment in producing seed under a higher temperature scenario may provide an opportunity for species to colonize patches of unvegetated ground. The observed differential response to warming suggests that the primary forces driving the response vary across climatic zones, functional groups, and through time.

Geometry of the complex of curves I: Hyperbolicity

Abstract: The Complex of Curves on a Surface is a simplicial complex whose vertices are homotopy classes of simple closed curves, and whose simplices are sets of homotopy classes which can be realized disjointly. It is not hard to see that the complex is finite-dimensional, but locally infinite. It was introduced by Harvey as an analogy, in the context of Teichmuller space, for Tits buildings for symmetric spaces, and has been studied by Harer and Ivanov as a tool for understanding mapping class groups of surfaces. In this paper we prove that, endowed with a natural metric, the complex is hyperbolic in the sense of Gromov. In a certain sense this hyperbolicity is an explanation of why the Teichmuller space has some negative-curvature properties in spite of not being itself hyperbolic: Hyperbolicity in the Teichmuller space fails most obviously in the regions corresponding to surfaces where some curve is extremely short. The complex of curves exactly encodes the intersection patterns of this family of regions (it is the "nerve" of the family), and we show that its hyperbolicity means that the Teichmuller space is "relatively hyperbolic" with respect to this family. A similar relative hyperbolicity result is proved for the mapping class group of a surface. We also show that the action of pseudo-Anosov mapping classes on the complex is hyperbolic, with a uniform bound on translation distance.

A leucine-rich nuclear export signal in the p53 tetramerization domain: regulation of subcellular localization and p53 activity by NES masking.

Abstract: Appropriate subcellular localization is crucial for regulating p53 function. We show that p53 export is mediated by a highly conserved leucine-rich nuclear export signal (NES) located in its tetramerization domain. Mutation of NES residues prevented p53 export and hampered tetramer formation. Although the p53-binding protein MDM2 has an NES and has been proposed to mediate p53 export, we show that the intrinsic p53 NES is both necessary and sufficient for export. This report also demonstrates that the cytoplasmic localization of p53 in neuroblastoma cells is due to its hyperactive nuclear export: p53 in these cells can be trapped in the nucleus by the export-inhibiting drug leptomycin B or by binding a p53-tetramerization domain peptide that masks the NES. We propose a model in which regulated p53 tetramerization occludes its NES, thereby ensuring nuclear retention of the DNA-binding form. We suggest that attenuation of p53 function involves the conversion of tetramers into monomers or dimers, in which the NES is exposed to the proteins which mediate their export to the cytoplasm.

Identification of Cd36 ( Fat ) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats

Abstract: The human insulin-resistance syndromes, type 2 diabetes, obesity, combined hyperlipidaemia and essential hypertension, are complex disorders whose genetic basis is unknown. The spontaneously hypertensive rat (SHR) is insulin resistant and a model of these human syndromes. Quantitative trait loci (QTLs) for SHR defects in glucose and fatty acid metabolism, hypertriglyceridaemia and hypertension map to a single locus on rat chromosome 4. Here we combine use of cDNA microarrays, congenic mapping and radiation hybrid (RH) mapping to identify a defective SHR gene, Cd36 (also known as Fat, as it encodes fatty acid translocase), at the peak of linkage to these QTLs. SHR Cd36 cDNA contains multiple sequence variants, caused by unequal genomic recombination of a duplicated ancestral gene. The encoded protein product is undetectable in SHR adipocyte plasma membrane. Transgenic mice overexpressing Cd36 have reduced blood lipids. We conclude that Cd36 deficiency underlies insulin resistance, defective fatty acid metabolism and hypertriglyceridaemia in SHR and may be important in the pathogenesis of human insulin-resistance syndromes.

Effects of Writing About Stressful Experiences on Symptom Reduction in Patients With Asthma or Rheumatoid Arthritis: A Randomized Trial

Abstract: ContextNonpharmacological treatments with little patient cost or risk are useful supplements to pharmacotherapy in the treatment of patients with chronic illness. Research has demonstrated that writing about emotionally traumatic experiences has a surprisingly beneficial effect on symptom reports, well-being, and health care use in healthy individuals.ObjectiveTo determine if writing about stressful life experiences affects disease status in patients with asthma or rheumatoid arthritis using standardized quantitative outcome measures.DesignRandomized controlled trial conducted between October 1996 and December 1997.SettingOutpatient community residents drawn from private and institutional practice.PatientsVolunteer sample of 112 patients with asthma (n=61) or rheumatoid arthritis (n=51) received the intervention; 107 completed the study, 58 in the asthma group and 49 in the rheumatoid arthritis group.InterventionPatients were assigned to write either about the most stressful event of their lives (n=71; 39 asthma, 32 rheumatoid arthritis) or about emotionally neutral topics (n=41; 22 asthma, 19 rheumatoid arthritis) (the control intervention).Main Outcome MeasuresAsthma patients were evaluated with spirometry and rheumatoid arthritis patients were clinically examined by a rheumatologist. Assessments were conducted at baseline and at 2 weeks and 2 months and 4 months after writing and were done blind to experimental condition.ResultsOf evaluable patients 4 months after treatment, asthma patients in the experimental group showed improvements in lung function (the mean percentage of predicted forced expiratory volume in 1 second [FEV1] improved from 63.9% at baseline to 76.3% at the 4-month follow-up; P<.001), whereas control group patients showed no change. Rheumatoid arthritis patients in the experimental group showed improvements in overall disease activity (a mean reduction in disease severity from 1.65 to 1.19 [28%] on a scale of 0 [asymptomatic] to 4 [very severe] at the 4-month follow-up; P=.001), whereas control group patients did not change. Combining all completing patients, 33 (47.1%) of 70 experimental patients had clinically relevant improvement, whereas 9 (24.3%) of 37 control patients had improvement (P=.001).ConclusionPatients with mild to moderately severe asthma or rheumatoid arthritis who wrote about stressful life experiences had clinically relevant changes in health status at 4 months compared with those in the control group. These gains were beyond those attributable to the standard medical care that all participants were receiving. It remains unknown whether these health improvements will persist beyond 4 months or whether this exercise will prove effective with other diseases.

Measuring living standards with proxy variables

Abstract: Very few demographic surveys in developing countries have gathered information on household incomes or consumption expenditures. Researchers interested in living standards therefore have had little alternative but to rely on simple proxy indicators. The properties of these proxies have not been analyzed systematically. We ask what hypotheses can be tested using proxies, and compare these indicators with consumption expenditures per adult, our preferred measure of living standards. We find that the proxies employed in much demographic research are very weak predictors of consumption per adult. Nevertheless, hypothesis tests based on proxies are likely to be powerful enough to warrant consideration.

Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline.

Abstract: Development of the nematode Caenorhabditis elegans is highly reproducible and the fate of every somatic cell has been reported. We describe here a previously uncharacterized cell fate in C. elegans: we show that germ cells, which in hermaphrodites can differentiate into sperm and oocytes, also undergo apoptotic cell death. In adult hermaphrodites, over 300 germ cells die, using the same apoptotic execution machinery (ced-3, ced-4 and ced-9) as the previously described 131 somatic cell deaths. However, this machinery is activated by a distinct pathway, as loss of egl-1 function, which inhibits somatic cell death, does not affect germ cell apoptosis. Germ cell death requires ras/MAPK pathway activation and is used to maintain germline homeostasis. We suggest that apoptosis eliminates excess germ cells that acted as nurse cells to provide cytoplasmic components to maturing oocytes.

On the Varieties of National Attachment: Blind Versus Constructive Patriotism

Abstract: Two studies explored a theoretical distinction between “blind” and “constructive” patriotism. Blind patriotism is defined as an attachment to country characterized by unquestioning positive evaluation, staunch allegiance, and intolerance of criticism. Constructive patriotism is defined as an attachment to country characterized by support for questioning and criticism of current group practices that are intended to result in positive change. Items designed to investigate these dimensions of national attachment were administered to two groups of undergraduates in separate surveys. Measures of the two constructs derived from factor analysis of the responses proved to be reliable and valid. Blind patriotism was positively associated with political disengagement, nationalism, perceptions of foreign threat, perceived importance of symbolic behaviors, and selective exposure to pro-U.S. information. In contrast, constructive patriotism was positively associated with multiple indicators of political involvement, including political efficacy, interest, knowledge, and behavior. The implications of this distinction for theory and research on patriotism are discussed.

Psychological abuse: a variable deserving critical attention in domestic violence.

Abstract: Policy makers and researchers give psychological abuse considerably less attention than physical abuse in the partner abuse area. One reason for the relative neglect of psychological abuse is that there are difficulties in arriving at a common definition of psychological abuse that might be useful to both the mental health and legal professions. Another reason for the relative neglect of psychological abuse has been an implicit assumption that physical abuse exacts a greater psychological toll on victims than does psychological abuse. At the extreme level of physical abuse, this assumption seems defensible, but at levels of physical aggression that are most common in marriage and long-term relationships, psychological abuse appears to have as great an impact as physical abuse. Even direct ratings of psychological and physical abuse by women in physically abusive relationships indicate that psychological abuse has a greater adverse effect on them than physical abuse. Retrospective reports, longitudinal research, and treatment dropout research all provide evidence that psychological abuse can exact a negative effect on relationships that is as great as that of physical abuse. Finally, psychological abuse almost always precedes physical abuse, so that prevention and treatment efforts clearly need to address psychological abuse. Eight measures of various forms of psychological abuse that have reasonable psychometric properties and considerable construct validity are reviewed and a definition of psychological abuse in intimate relations is provided.

Lemur traits and Madagascar ecology: coping with an island environment.

Abstract: The last decade's lemur research includes successes in discovering new living and extinct species and learning about the distribution, biogeography, physiology, behavior, and ecology of previously little-studied species. In addition, in both the dry forest and rain forest, long-term studies of lemur demography, life history, and reproduction, have been completed in conjunction with data on tree productivity, phenology, and climate. Lemurs contrast with anthropoids in several behavioral features, including female dominance, targeted female-female aggression, lack of sexual dimorphism regardless of mating system, sperm competition coupled with male-male aggression, high infant mortality, cathemerality, and strict seasonal breeding. Hypotheses to explain these traits include the "energy conservation hypothesis" (ECH) suggesting that harsh and unpredictable climate factors on the island of Madagascar have affected the evolution of female dominance, and the "evolutionary disequilibrium hypotheses" (EVDH) suggesting that the recent megafauna extinctions have influenced lemurs to become diurnal. These hypotheses are compared and contrasted in light of recent empirical data on climate, subfossils, and lemur behavior. New data on life histories of the rain forest lemurs at Ranomafana National Park give further support to the ECH. Birth seasons are synchronized within each species, but there is a 6-month distribution of births among species. Gestation and lactation lengths vary among sympatric lemurs, but all lemur species in the rain forest wean in synchrony at the season most likely to have abundant resources. Across-species weaning synchrony seen in Ranomafana corroborates data from the dry forest that late lactation and weaning is the life history event that is the primary focus of the annual schedule. Lemur adaptations may assure maximum offspring survival in this environment with an unpredictable food supply and heavy predation. In conclusion, a more comprehensive energy frugality hypothesis (EFH) is proposed, which postulates that the majority of lemur traits are either adaptations to conserve energy (e.g., low basal metabolic rate (BMR), torpor, sperm competition, small group size, seasonal breeding) or to maximize use of scarce resources (e.g., cathemerality, territoriality, female dominance, fibrous diet, weaning synchrony). Among primates, the isolated adaptive radiation of lemurs on Madagascar may have been uniquely characterized by selection toward efficiency to cope with the harsh and unpredictable island environment.

CoREST: A functional corepressor required for regulation of neural-specific gene expression

Abstract: Several genes encoding proteins critical to the neuronal phenotype, such as the brain type II sodium channel gene, are expressed to high levels only in neurons. This cell specificity is due, in part, to long-term repression in nonneural cells mediated by the repressor protein REST/NRSF (RE1 silencing transcription factor/neural-restrictive silencing factor). We show here that CoREST, a newly identified human protein, functions as a corepressor for REST. A single zinc finger motif in REST is required for CoREST interaction. Mutations of the motif that disrupt binding also abrogate repression. When fused to a Gal4 DNA-binding domain, CoREST functions as a repressor. CoREST is present in cell lines that express REST, and the proteins are found in the same immunocomplex. CoREST contains two SANT (SW13/ADA2/NCoR/TFIIIB B) domains, a structural feature of the nuclear receptor and silencing mediator for retinoid and thyroid human receptors (SMRT)-extended corepressors that mediate inducible repression by steroid hormone receptors. Together, REST and CoREST mediate repression of the type II sodium channel promoter in nonneural cells, and the REST/CoREST complex may mediate long-term repression essential to maintenance of cell identity.

Carbon monoxide provides protection against hyperoxic lung injury.

Abstract: Findings in recent years strongly suggest that the stress-inducible gene heme oxygenase (HO)-1 plays an important role in protection against oxidative stress. Although the mechanism(s) by which this protection occurs is poorly understood, we hypothesized that the gaseous molecule carbon monoxide (CO), a major by-product of heme catalysis by HO-1, may provide protection against oxidative stress. We demonstrate here that animals exposed to a low concentration of CO exhibit a marked tolerance to lethal concentrations of hyperoxia in vivo. This increased survival was associated with highly significant attenuation of hyperoxia-induced lung injury as assessed by the volume of pleural effusion, protein accumulation in the airways, and histological analysis. The lungs were completely devoid of lung airway and parenchymal inflammation, fibrin deposition, and pulmonary edema in rats exposed to hyperoxia in the presence of a low concentration of CO. Furthermore, exogenous CO completely protected against hyperoxia-induced lung injury in rats in which endogenous HO enzyme activity was inhibited with tin protoporphyrin, a selective inhibitor of HO. Rats exposed to CO also exhibited a marked attenuation of hyperoxia-induced neutrophil infiltration into the airways and total lung apoptotic index. Taken together, our data demonstrate, for the first time, that CO can be therapeutic against oxidative stress such as hyperoxia and highlight possible mechanism(s) by which CO may mediate these protective effects.

Destruction of Myc by ubiquitin‐mediated proteolysis: cancer‐associated and transforming mutations stabilize Myc

Abstract: The human proto-oncogene c-myc encodes a highly unstable transcription factor that promotes cell proliferation. Although the extreme instability of Myc plays an important role in preventing its accumulation in normal cells, little is known about how Myc is targeted for rapid destruction. Here, we have investigated mechanisms regulating the stability of Myc. We show that Myc is destroyed by ubiquitin-mediated proteolysis, and define two elements in Myc that oppositely regulate its stability: a transcriptional activation domain that promotes Myc destruction, and a region required for association with the POZ domain protein Miz-1 that stabilizes Myc. We also show that Myc is stabilized by cancer-associated and transforming mutations within its transcriptional activation domain. Our data reveal a complex network of interactions regulating Myc destruction, and imply that enhanced protein stability contributes to oncogenic transformation by mutant Myc proteins.

Evolution of Proto-Neutron Stars

Abstract: We study the thermal and chemical evolution during the Kelvin-Helmholtz phase of the birth of a neutron star, employing neutrino opacities that are consistently calculated with the underlying equation of state (EOS). Expressions for the diffusion coefficients appropriate for general relativistic neutrino transport in the equilibrium diffusion approximation are derived. The diffusion coefficients are evaluated using a field-theoretical finite-temperature EOS that includes the possible presence of hyperons. The variation of the diffusion coefficients is studied as a function of EOS and compositional parameters. We present results from numerical simulations of proto-neutron star cooling for internal stellar properties as well as emitted neutrino energies and luminosities. We discuss the influence of the initial stellar model, the total mass, the underlying EOS, and the addition of hyperons on the evolution of the proto-neutron star and on the expected signal in terrestrial detectors. We find that the differences in predicted luminosities and emitted neutrino energies do not depend much upon the details of the initial models or the underlying high-density EOS for early times (t<10 s), provided that opacities are calculated consistently with the EOS. The same holds true for models that allow for the presence of hyperons, except when the initial mass is significantly larger than the maximum mass for cold, catalyzed matter. For times larger than about 10 s, and prior to the occurrence of neutrino transparency, the neutrino luminosities decay exponentially with a time constant that is sensitive to the high-density properties of matter. We also find the average emitted neutrino energy increases during the first 5 s of evolution and then decreases nearly linearly with time. In general, increasing the proto-neutron star mass increases the average energy and the luminosity of neutrinos, as well as the overall evolutionary timescale. The influence of hyperons or variations in the dense matter EOS is increasingly important at later times. Metastable stars, those with hyperons that are unstable to collapse upon deleptonization, have relatively long evolution times, which increase the nearer the mass is to the maximum mass supportable by a cold, deleptonized star.

Measurement of the Flux and Zenith-Angle Distribution of Upward Throughgoing Muons by Super-Kamiokande

Abstract: A total of 614 upward throughgoing muons of minimum energy 1.6thinspthinspGeV are observed by Super-Kamiokande during 537 detector live days. The measured muon flux is [1.74{plus_minus}0.07(stat){plus_minus} 0.02(sys)]{times}10{sup {minus}13} cm{sup {minus}2}thinsps{sup {minus}1}thinspsr{sup {minus}1} compared to an expected flux of [1.97{plus_minus}0.44(theor)]{times} 10{sup {minus}13} cm{sup {minus}2}thinsps{sup {minus}1}thinspsr{sup {minus}1} . The absolute measured flux is in agreement with the prediction within the errors. However, the zenith-angle dependence of the observed upward throughgoing muon flux does not agree with no-oscillation predictions. The observed distortion in shape is consistent with the {nu}{sub {mu}}{leftrightarrow}{nu}{sub {tau}} oscillation hypothesis with sin{sup 2}thinsp2{theta} {gt}0.4 and 1{times}10{sup {minus}3}{lt}{Delta}m{sup 2}{lt}1{times}1 0{sup {minus}1} eV{sup 2} at 90{percent} confidence level. {copyright} {ital 1999} {ital The American Physical Society}

Image thresholding by indicator kriging

Abstract: We consider the problem of segmenting a digitized image consisting of two univariate populations. Assume a priori knowledge allows incomplete assignment of voxels in the image, in the sense that a fraction of the voxels can be identified as belonging to population II/sub 0/, a second fraction to II/sub 1/, and the remaining fraction have no a priori identification. Based upon estimates of the short length scale spatial covariance of the image, we develop a method utilizing indicator kriging to complete the image segmentation.

A New Catalog of Photometric Redshifts in the Hubble Deep Field

Abstract: Using the newly available infrared images of the Hubble Deep Field in the J, H, and K bands and an optimal photometric method, we have refined a technique to estimate the redshifts of 1067 galaxies. A detailed comparison of our results with the spectroscopic redshifts in those cases where the latter are available shows that this technique gives very good results for bright enough objects [AB(8140)<26.0]. From a study of the distribution of residuals [Δzrms/(1+z)≈0.1 at all redshifts], we conclude that the observed errors are mainly due to cosmic variance. This very important result allows for the assessment of errors in quantities to be directly or indirectly measured from the catalog. We present some of the statistical properties of the ensemble of galaxies in the catalog, and we finish by presenting a list of bright high-redshift (z≈5) candidates extracted from our catalog together with recent spectroscopic redshift determinations confirming that two of them are at z=5.34 and z=5.60.

Impact of high velocity cold spray particles

Abstract: This article presents experimental data and a computational model of the cold spray solid particle impact process. Copper particles impacting onto a polished stainless steel substrate were examined in this study. The high velocity impact causes significant plastic deformation of both the particle and the substrate, but no melting was observed. The plastic deformation exposes clean surfaces that, under the high impact pressures, result in significant bond strengths between the particle and substrate. Experimental measurements of the splat and crater sizes compare well with the numerical calculations. It was shown that the crater depth is significant and increases with impact velocity. However, the splat diameter is much less sensitive to the impact velocity. It was also shown that the geometric lengths of the splat and crater scale linearly with the diameter of the impacting particle. The results presented will allow a better understanding of the bonding process during cold spray.

Inhibition of the Mitogen-Activated Protein Kinase Kinase Superfamily by a Yersinia Effector

Abstract: The bacterial pathogen Yersinia uses a type III secretion system to inject several virulence factors into target cells. One of the Yersinia virulence factors, YopJ, was shown to bind directly to the superfamily of MAPK (mitogen-activated protein kinase) kinases (MKKs) blocking both phosphorylation and subsequent activation of the MKKs. These results explain the diverse activities of YopJ in inhibiting the extracellular signal-regulated kinase, c-Jun amino-terminal kinase, p38, and nuclear factor kappa B signaling pathways, preventing cytokine synthesis and promoting apoptosis. YopJ-related proteins that are found in a number of bacterial pathogens of animals and plants may function to block MKKs so that host signaling responses can be modulated upon infection.