Publications

immediate-early gene induction by the stresses anisomycin and arsenite in human osteosarcoma cells involves mapk cascade signaling to elk-1, creb and srf.	cellular stress activates multiple mitogen-activated protein kinase (mapk) cascades and immediate-early gene (ieg) transcription. to address how these events are linked, we investigated the endogenous signaling/transcription factor network driving ieg activation by arsenite and anisomycin in the human osteosarcoma cell line hos/te-85. induction of ieg transcription by both stresses corresponded temporally with the phosphorylation of the regulatory factors elk-1 and camp response element-binding ...	2003	12660819
erk(mapk) activity as a determinant of tumor growth and dormancy; regulation by p38(sapk).	after dissemination from a primary tumor, cancer cells may resume growth, leading to overt metastasis, or enter a state of protracted dormancy. however, mechanisms that determine their fate, or markers that predict it, are mostly unavailable. we previously showed that in hep3 human head and neck carcinoma, the extracellular signal-regulated kinase (erk)(mapk)/p38(sapk) activity ratio predicts whether the cells will proliferate or enter a state of dormancy in vivo. the proliferative balance of hi ...	2003	12670923
early modifications in the expression of mitogen-activated protein kinase (mapk/erk), stress-activated kinases sapk/jnk and p38, and their phosphorylated substrates following focal cerebral ischemia.	focal ischemia induced by middle cerebral artery occlusion (mcao) to adult rats results in necrosis at the infarct core and activation of complex signal pathways for cell death and cell survival in the penumbra. upstream from the cell death promoters and executioners are several kinases that, once activated by phosphorylation, may activate several transcription factor substrates involved in cell death and cell survival. in the present study we examined, by immunohistochemistry, the expression of ...	2003	12677442
activation of cytosolic phospholipase a2 in human t-lymphocytes involves inhibitor-kappab and mitogen-activated protein kinases.	the group iv 85 kda cytosolic phospholipase a(2) regulates many aspects of innate immunity. however, the function of this enzyme in t-cells remains controversial. we show here that human peripheral blood lymphocytes and jurkat cells express cytosolic phospholipase a(2) and produce prostaglandin a(2) and leukotriene b(4). selective inhibitors of this enzyme suppressed ca(2+)-ionophore-, mitogen- and t-cell receptor-mediated expression of interleukin-2 at the level of transcription from the promot ...	2003	12679154
effects of mobile phone radiation on reproduction and development in drosophila melanogaster.	in this report we examined the effects of a discontinuous radio frequency (rf) signal produced by a gsm multiband mobile phone (900/1,900 mhz; sar approximately 1.4 w/kg) on drosophila melanogaster, during the 10-day developmental period from egg laying through pupation. as found earlier with low frequency exposures, the non-thermal radiation from the gsm mobile phone increased numbers of offspring, elevated hsp70 levels, increased serum response element (sre) dna-binding and induced the phospho ...	2003	12682907
circadian and photic regulation of phosphorylation of erk1/2 and elk-1 in the suprachiasmatic nuclei of the syrian hamster.	in this study we investigated the circadian and photic regulation of phosphorylation of the extracellular signal-related kinase (erk) 1/2, and the transcription factor elk-1 in the suprachiasmatic nuclei of the syrian hamster. we report that levels of phosphorylated erk (p-erk) are rhythmic, peaking during the mid subjective day, whereas phosphorylated elk-1 (p-elk-1) shows no distinct rhythm. light pulses during the subjective night rapidly, but transiently, induce p-erk, whereas p-elk-1 is als ...	2003	12684495
prevalence of chronic wasting disease and bovine tuberculosis in free-ranging deer and elk in south dakota.	heads of hunter-harvested deer and elk were collected throughout south dakota (usa) and within established chronic wasting disease (cwd) surveillance areas from 1997-2002 to determine infection with cwd and bovine tuberculosis (tb). we used immunohistochemistry to detect cwd-infected individuals among 1,672 deer and elk sampled via geographically targeted surveillance. a total of 537 elk (cervus elaphus nelsoni), 813 white-tailed deer (odocoileus virginianus), and 322 mule deer (o. hemionus) was ...	2003	12685066
enzootic ataxia in farmed red deer.		2003	12696718
molecular determinants of the cell-cycle regulated mcm1p-fkh2p transcription factor complex.	the mads-box transcription factor mcm1p and forkhead (fkh) transcription factor fkh2p act in a dna-bound complex to regulate cell-cycle dependent expression of the clb2 cluster in saccharomyces cerevisiae. binding of fkh2p requires prior binding by mcm1p. here we have investigated the molecular determinants governing the formation of the mcm1p- fkh2p complex. fkh2p exhibits cooperativity in complex formation with mcm1p and we have mapped a small region of fkh2p located immediately upstream of th ...	2003	12711672
the epithelial-specific ets transcription factor esx/ese-1/elf-3 modulates breast cancer-associated gene expression.	several members of the ets family of transcription factors contribute to tumorigenesis in many different tissues, including breast epithelium. the esx gene is an epithelial-specific ets member that is particularly relevant to breast cancer. esx is amplified in early breast cancers, it is overexpressed in human breast ductal carcinoma in situ, and there may be a positive feedback loop between the her2/neu proto-oncogene and esx. despite this progress in our understanding of esx, its ability to re ...	2003	12713734
lithium enhances long-term potentiation independently of hippocampal neurogenesis in the rat dentate gyrus.	we measured the temporal and spatial profiles of neural precursor cells, hippocampal long-term potentiation (ltp), and signaling molecules in neurogenesis-induced adult rats. chronic lithium treatment produced a significant 54% and 40% increase in the numbers of bromodeoxyuridine [brdu(+)] cells after 12 h and 28 days, respectively, after treatment completion in the dentate gyrus (dg). both ltp obtained from slices perfused with artificial cerebrospinal fluid (acsf-ltp) and ltp recorded in the p ...	2003	12716419
metabotropic glutamate receptor 5-regulated elk-1 phosphorylation and immediate early gene expression in striatal neurons.	the galphaq protein-coupled metabotropic glutamate receptor subtype-5 (mglur5) is densely expressed in medium spiny projection neurons of striatum. emerging evidence suggests a significant role of mglur5 in the addictive plasticity of striatal neurons that is likely derived from inducible cellular gene expression related to stimulation of mglur5 and associative signaling proteins. in this study, we found that activation of mglur5 with a selective agonist (rs)-2-chloro-5-hydroxy-phenylglycine (ch ...	2003	12716432
relationship between the characteristics of epididymal red deer spermatozoa and penetrability into zona-free hamster ova.	a heterologous (zona-free hamster oocytes) in vitro fertilization (ivf) system was used to evaluate the relationship between sperm factors and penetration capacity of epididymal red deer spermatozoa. the sperm parameters evaluated in 36 sperm samples obtained postmortem from stags selectively shot during the rutting season were sperm motility, functional integrity of plasma membrane by means of the hypo-osmotic swelling test (host), and, simultaneously, viability and acrosomal status via a tripl ...	2003	12721216
decelerating and sex-dependent tooth wear in norwegian red deer.	in ungulates, tooth wear is often suggested as a proximate cause of senescence. tooth wear is expected to be sex-dependent since energetic requirements and food selection varies largely between sexes in sexually dimorphic ungulates. furthermore, tooth wear may lower mastication efficiency, and we predict a negative correlation between tooth wear and body weight or condition. we tested these predictions on data on tooth wear (estimated as height of first molar) of 1,311 male and 1,348 female red ...	2003	12721823
induction of neurite outgrowth in pc12 cells by the bacterial nucleoside n6-methyldeoxyadenosine is mediated through adenosine a2a receptors and via camp and mapk signaling pathways.	we have previously shown that n(6)-methyldeoxyadenosine (mda) is an inducer of differentiation in several tumor cells. here we show that in addition to its ability to induce neurite-outgrowth in pc12 cells, mda also significantly enhances the nerve-growth factor-mediated neurite outgrowth of these cells. thus, mda acts synergistically with ngf to repress cdc2 and cdk2 synthesis and to enhance tyrosine hydroxylase synthesis. to further elucidate the mechanisms of action of mda, we investigated th ...	2003	12727227
insulin induces expression of adenosine kinase gene in rat lymphocytes by signaling through the mitogen-activated protein kinase pathway.	the activity of adenosine kinase (ak) was significantly impaired in splenocytes isolated from diabetic rats. administration of insulin to diabetic animals restored ak activity, protein, and mrna levels in diabetic splenocytes. experiments performed on cultured rat lymphocytes demonstrated that insulin did not change the stability of ak mrna. insulin induced ak gene expression in a dose- and time-dependent manner. maximal increases in ak mrna (3.9-fold) and activity level (3.7-fold) were observed ...	2003	12729803
senescent phenotype can be reversed by reduction of caveolin status.	hyporesponsiveness to growth factors is one of the fundamental characteristics of senescent cells. we previously reported that the up-regulation of caveolin attenuates the growth factor response and the subsequent downstream signal cascades in senescent human diploid fibroblasts. therefore, in the present experiment, we investigated the modulation of caveolin status in senescent cells to determine the effect of caveolin on mitogenic signaling efficiency and cell cycling. we reduced the level of ...	2003	12730243
nodular onchocercosis of red deer in central spain.	the presence of nodular onchocercosis was investigated post-mortem in 142 red deer (11 calves, 35 yearlings and 96 adults) shot from february 1998 to january 1999, and july-november 1999 in "quintos de mora" (toledo, central spain), a game property belonging to the national wildlife reserves. between 6 and 13 animals were analysed monthly by inspection for subcutaneous nodules of onchocerca spp. subcutaneous nodules of onchocerca sp. were detected in 24% of the animals. anatomical locations for ...	2003	12732468
survey of permanent wound tracts in the carcases of culled wild red deer in scotland.	the number and sites of permanent wound tracts in the carcases of 943 wild culled red deer (cervus elaphus) were recorded. during the peak period of the red deer rut there was a significant increase in the number of these tracts in the carcases, which was associated with a decrease from 89 per cent to 71 per cent in the probability of the first permanent wound tract also being the last (the terminal probability). there were significantly more permanent wound tracts in the carcases of one group ( ...	2003	12733558
src-crkii-c3g-dependent activation of rap1 switches growth hormone-stimulated p44/42 map kinase and jnk/sapk activities.	we demonstrate here that growth hormone (gh) stimulates the activation of rap1 and rap2 in nih-3t3 cells. full activation of rap1 and rap2 by gh necessitated the combined activity of both jak2 and c-src kinases, although c-src was predominantly required. gh-stimulated rap1 and rap2 activity was also demonstrated to be crkii-c3g-dependent. gh stimulated the tyrosine phosphorylation of c3g, which again required the combined activity of jak2 and c-src. c3g tyrosine residue 504 was required for gh-s ...	2003	12734187
interaction of filamin a with the insulin receptor alters insulin-dependent activation of the mitogen-activated protein kinase pathway.	the biological actions of insulin are associated with a rapid reorganization of the actin cytoskeleton within cells in culture. even though this event requires the participation of actin-binding proteins, the effect of filamin a (flna) on insulin-mediated signaling events is still unknown. we report here that human melanoma m2 cells lacking flna expression exhibited normal insulin receptor (ir) signaling, whereas flna-expressing a7 cells were unable to elicit insulin-dependent shc tyrosine phosp ...	2003	12734206
amyloid peptide-induced cytokine and chemokine expression in thp-1 monocytes is blocked by small inhibitory rna duplexes for early growth response-1 messenger rna.	in alzheimer's disease (ad) one finds increased deposition of a beta and also an increased presence of monocytes/macrophages in the vessel wall and activated microglial cells in the brain. ad patients show increased levels of proinflammatory cytokines by activated microglia. here we used a human monocytic thp-1 cell line as a model for microglia to delineate the cellular signaling mechanism involved in amyloid peptides (a beta(1-40) and a beta(1-42))-induced expression of inflammatory cytokines ...	2003	12734378
protein g binding to enriched serum immunoglobulin from nondomestic hoofstock species.	quick and cost-effective serologic assays, such as those based on enzyme-linked immunosorbent assay (elisa) technology, are useful for screening animal populations for infectious diseases. recombinant protein g is described as an almost universal elisa conjugate for the detection of antibodies from a wide range of animal species. however, there is limited data documenting the ability of protein g to bind immunoglobulin (ig) from many captive and free-ranging nondomestic hoofstock (order artiodac ...	2003	12735347
cloning and nucleotide sequence of the equine and elk pituitary pre-prolactin cdna.	we report the equine (equs equs) and elk (cervus elaphus) pituitary pre-prolactin (prl) cdna cloning, and their nucleotide and deduced amino acid sequences. pre-prl cdna was obtained by rna ligation mediated-rapid amplification of cdna ends (rlm-race) and polymerase chain reaction (pcr). the elk pre-prl cdna exhibits two polymorphisms at positions 96 and 672, which are silent since they encode for the same amino acids, proline and isoleucine, respectively. we found no polymorphisms in the equine ...	2003	12742553
the role of a conserved region of the second intracellular loop in at1 angiotensin receptor activation and signaling.	the pleiotropic actions of angiotensin ii are mediated by the primarily g(q) protein-coupled type 1 angiotensin (at(1)) receptor. in this study a mutational analysis of the function of the conserved dryxxv/ixxpl domain in the second intracellular loop of the rat at(1a) receptor was performed in cos7 cells. alanine substitution studies showed that single replacement of the highly conserved asp(125) and arg(126), but not tyr(127), moderately impaired angiotensin ii-induced inositol phosphate signa ...	2003	12746278
ets transcription factors er81 and elk1 regulate the transcription of the human presenilin 1 gene promoter.	we have previously defined a crucial dna element controlling 90% of the expression of the presenilin 1 gene at (-35 to +6). this region contains an ets transcription factor binding motif, and a 2-base pair alteration within the core sequence (ggaa to ttaa) of the ets consensus also reduced transcription by over 90%. we have shown that ets1/2 transcription factors bind specifically to the -10 ets element and activate ps1 transcription. the identification of other transcription factors recognizing ...	2003	12750007
a bipartite mechanism for erk2 recognition by its cognate regulators and substrates.	mitogen-activated protein (map) kinases control gene expression in response to extracellular stimuli and exhibit exquisite specificity for their cognate regulators and substrates. we performed a structure-based mutational analysis of erk2 to identify surface areas that are important for recognition of its interacting proteins. we show that binding and activation of mkp3 by erk2 involve two distinct protein-protein interaction sites in erk2. thus, the common docking (cd) site composed of glu-79, ...	2003	12754209
ternary complex factors: prime nuclear targets for mitogen-activated protein kinases.	ternary complex factors (tcfs), a subgroup of the ets protein family, were first described in the context of c-fos gene regulation. subsequently, their early identification as nuclear targets for mitogen-activated protein kinases served to exemplify the fundamental links in eukaryotic cells between growth factor-mediated signalling pathways and gene control. this article provides an overview of recent work on ternary complex factors, addressing their expression and molecular structure, as well a ...	2003	12757758
effect of thawing procedure on cryosurvival of deer spermatozoa: work in progress.	the objective of this study was to evaluate the effect of the thawing procedure on deer semen freezability. frozen semen from the genetic resource bank (grb) of the zoological park of buenos aires (argentina) was used. seven mature stags (two red deer, two père david's deer and three fallow deer) were used as semen donors. semen was diluted with a tris-egg yolk medium, packed in 0.25 ml straws and frozen in nitrogen vapour. for thawing, the frozen straws were subjected to the following procedure ...	2003	12763164
tyrosine phosphorylation of vhr phosphatase by zap-70.	the zap-70 tyrosine kinase is a key component of the signaling machinery for the t cell antigen receptor (tcr). whereas recruitment and activation of zap-70 are relatively well understood, the proteins phosphorylated by zap-70 are incompletely known. we report here that vhr, a vaccinia virus vh1-related dual-specific protein phosphatase that inactivates the mitogen-activated kinases erk2 and jnk, is phosphorylated at y138 by zap-70. tyr138 phosphorylation was required for vhr to inhibit the erk2 ...	2003	12447358
docking sites on mitogen-activated protein kinase (mapk) kinases, mapk phosphatases and the elk-1 transcription factor compete for mapk binding and are crucial for enzymic activity.	mitogen-activated protein kinase (mapk) cascades control gene expression patterns in response to extracellular stimuli. mapk/erk (extracellular-signal-regulated kinase) kinases (meks) activate mapks by phosphorylating them; activated mapks, in turn, phosphorylate target transcription factors, and are deactivated by phosphatases. one mechanism for maintaining signal specificity and efficiency is the interaction of mapks with their substrates and regulators through high-affinity docking sites. in ...	2003	12529172
echinococcus granulosus in finland.	echinococcus granulosus is shown to occur in eastern finland in a sylvatic cycle involving wolves (canis lupus) as the definitive host and reindeer (rangifer tarandus tarandus) and probably also elk (alces alces) and the wild forest reindeer (rangifer tarandus fennicus) as intermediate hosts. even though the prevalence of e. granulosus in reindeer has increased in recent years, it is still very low (<0.013%). the results suggest, however, that the reindeer is a good sentinel animal to show the c ...	2003	12531293
translocation of yope and yopn into eukaryotic cells by yersinia pestis yopn, tyea, sycn, yscb and lcrg deletion mutants measured using a phosphorylatable peptide tag and phosphospecific antibodies.	yersinia pestis, the causative agent of plague, exports a set of virulence proteins called yops upon contact with eukaryotic cells. a subset of these yops is translocated directly into the cytosol of host cells. in this study, a novel protein tag-based reporter system is used to measure the translocation of yops into cultured eukaryotic cells. the reporter system uses a small bipartite phosphorylatable peptide tag, termed the elk tag. translocation of an elk-tagged protein into eukaryotic cells ...	2003	12535078
effects of season, sex, and sample collection on concentrations of fecal cortisol metabolites in red deer (cervus elaphus).	seasonal variation, sex differences, and invasive sample collection may confound glucocorticoid measures as indices of stress. we investigated the effects of sex and season on glucocorticoid production on a non-invasive basis by measuring concentrations of cortisol metabolites in feces of undisturbed red deer (cervus elaphus). although feces can be collected easily, assignment to individuals is difficult. anonymous fecal samples may cause overrepresentation of particular individuals thus introdu ...	2003	12535624
storage of red deer epididymides for four days at 5 degrees c: effects on sperm motility, viability, and morphological integrity.	the purpose of this study was to assess the sperm motility, the plasma membrane integrity and the morphology of red deer spermatozoa when maintained within epididymides stored for 4 days at 5 degrees c, and to evaluate whether such stored spermatozoa are able to withstand a refrigeration process. thirty pairs of testes, with attached epididymides, were collected from 30 hunter-killed mature stags (cervus elaphus hispanicus), and spermatozoa from each one of the pairs were immediately collected i ...	2003	12541303
mapping of synergistic components of weakly interacting protein-protein motifs using arrays of paired peptides.	protein-protein recognition usually involves multiple interactions among different motifs that are scattered over protein surfaces. to identify such weak interactions, we have developed a novel double peptide synthesis (ds) method. this method allows us to map protein-protein interactions that involve two linear dis- continuous components from a polypeptide by the use of spatially addressable synergistic pairs of synthetic peptides. the ds procedure is based on the "spot" membrane-bound peptide ...	2003	12551909
case-control study of early-term abortions (early fetal losses) associated with mare reproductive loss syndrome in central kentucky.	to identify factors associated with abortions during early gestation classified as mare reproductive loss syndrome (mrls).	2003	12555985
beneficial effects of antioxidants and l-arginine on oxidation-sensitive gene expression and endothelial no synthase activity at sites of disturbed shear stress.	atherogenesis is enhanced in arterial segments exposed to disturbed blood flow, indicating the active participation of the hemodynamic environment in lesion formation. turbulent shear stress selectively regulates responsive genes in the endothelium and increases the damage induced by free radicals. the purpose of the present study was to evaluate the effects of intervention with antioxidants and l-arginine on endothelial no synthase (enos) and oxidation-sensitive gene perturbation induced by dis ...	2003	12525696
activation of mitogen-activated protein kinase pathway by keratinocyte growth factor or fibroblast growth factor-10 promotes cell proliferation in human endometrial carcinoma cells.	fibroblast growth factors (fgfs) exert diverse effects resulting from their interaction with cognate receptors on target cells. our current study was designed to examine the local production and action of two specific stromal-epithelial cell mediatory factors, keratinocyte growth factor (kgf) and fgf-10, in human endometrial carcinoma cells. the rt-pcr method was used to determine gene expression of kgf, fgf-10, and kgf receptor in human endometrial carcinoma cells (hec-1) and human endometrial ...	2003	12574212
widespread prpsc accumulation in muscles of hamsters orally infected with scrapie.	scrapie, bovine spongiform encephalopathy and chronic wasting disease are orally communicable, transmissible spongiform encephalopathies (tses). as zoonotic transmissions of tse agents may pose a risk to human health, the identification of reservoirs for infectivity in animal tissues and their exclusion from human consumption has become a matter of great importance for consumer protection. in this study, a variety of muscles from hamsters that were orally challenged with scrapie was screened for ...	2003	12776740
kinase-mediated regulation of common transcription factors accounts for the bone-protective effects of sex steroids.	it has been found that 4-estren-3alpha,17beta-diol, a synthetic ligand for the estrogen receptor (er) or androgen receptor (ar), which does not affect classical transcription, reverses bone loss in ovariectomized females or orchidectomized males without affecting the uterus or seminal vesicles, demonstrating that the classical genotropic actions of sex steroid receptors are dispensable for their bone-protective effects, but indispensable for their effects on reproductive organs. we have now inve ...	2003	12782668
transcriptional regulation of the cytosolic chaperonin theta subunit gene, cctq, by ets domain transcription factors elk-1, sap-1a, and net in the absence of serum response factor.	the chaperonin-containing t-complex polypeptide 1 (cct) is a molecular chaperone that facilitates protein folding in eukaryotic cytosol, and the expression of cct is highly dependent on cell growth. we show here that transcription of the gene encoding the theta subunit of mouse cct, cctq, is regulated by the ternary complex factors (tcfs), elk-1, sap-1a, and net (sap-2). reporter gene assay using hela cells indicated that the cctq gene promoter contains a cis-acting element of the ccggaagt seque ...	2003	12788937
sumo and transcriptional repression: dynamic interactions between the map kinase and sumo pathways.	sumo modification of proteins is being increasingly linked with transcriptional repression. we recently demonstrated that sumo modification also downregulates the transcriptional activity of the ets-domain transcription factor elk-1. however, as elk-1 becomes activated through map kinase-mediated phosphorylation, the sumo modification is lost, providing an elegant molecular switch that promotes the loss of repressive activities at the same time as permitting the recruitment of coactivator protei ...	2003	14504467
ribosomal rna analysis of babesia odocoilei isolates from farmed reindeer (rangifer tarandus tarandus) and elk (cervus elaphus canadensis) in wisconsin.	piroplasms isolated from a farmed reindeer and elk in wisconsin were determined to be babesia odocoilei, based on morphology and ribosomal rna (rrna) analysis. different clinical manifestations were observed in the two host species. the reindeer was parasitemic and exhibited acute babesiosis resulting in death, while the elk showed no parasites in blood smears and no overt clinical signs of babesiosis. b. odocoilei was, however, readily cultured from elk erythrocytes. small subunit rrna gene seq ...	2003	14505046
activation domain-mediator interactions promote transcription preinitiation complex assembly on promoter dna.	the interaction of activators with mediator has been proposed to stimulate the assembly of rna polymerase ii (pol ii) preinitiation complexes, but there have been few tests of this model. the finding that the major adenovirus e1a and mitogen-activated protein kinase-phosphorylated elk1 activation domains bind to sur2 uniquely among the metazoan mediator subunits and the development of transcriptionally active nuclear extracts from wt and sur2-/- embryonic stem cells, reported here, allowed a dir ...	2003	14506297
fractions of the semen of red deer (cervus elaphus)--their occurrence and characteristics in different periods of season.	during a complete season 145 ejaculates were collected from 4 red deer stags (cervus elaphus) using a modified artificial vagina. differences found in characteristics of ejaculates allowed to identify four different types of ejaculates: pre-mating, mating, transitory, and post-mating ejaculate. these types of ejaculates occurred exclusively during corresponding periods of the season in the sequence mentioned above. three fractions of ejaculates were identified: grey, white, and yellow. pre- and ...	2003	14510054
sublytic terminal complement attack induces c-fos transcriptional activation in myotubes.	sublytic c5b-9 alters the molecular phenotype of myotubes by inhibiting muscle-specific gene expression. here, we showed that c5b-9 induced c-fos mrna and transcription. using c-fos promoter-cat constructs and electrophoretic mobility shift assay (emsa), the minimal c-fos promoter activity was shown to increase within 30-min exposure to serum c5b-9, which also induced the binding of serum response factor (srf), along with ternary complex factor (tcf) elk1 and sap1a to the serum response element. ...	2003	14512164
other animal prion diseases.	in addition to bovine spongiform encephalopathy (bse) of cattle and scrapie of sheep and goats, a few other animal prion diseases have been reported. these include feline spongiform encephalopathy of zoological and domestic cats (fse) and transmissible spongiform encephalopathy (tse) of zoological ruminants and non-human primates, as well as chronic wasting disease of deer and elk (cwd) and transmissible mink encephalopathy of farmed mink (tme). the origins of tse in cats, zoo bovids, and non-hu ...	2003	14522860
the concerted signaling of erk1/2 and jnks is essential for pc12 cell neuritogenesis and converges at the level of target proteins.	mitogen-activated protein kinase (mapk) pathways are central signaling elements, which translate and integrate stimuli from cell surface receptors into cytoplasmic and transcriptional responses. here, we systematically compare the role of mapks in the nerve growth factor-induced long-term differentiation of pc12 cells and show the persistent nuclear and dose-dependent cytoplasmic activation of extracellular signal-regulated kinases 1 and 2 (erk1/2) and the increasing nuclear and cytoplasmic acti ...	2003	14550783
the chemopreventive bioflavonoid apigenin modulates signal transduction pathways in keratinocyte and colon carcinoma cell lines.	apigenin is a nonmutagenic chemopreventive agent found in fruits and green vegetables. in this study, we used two different epithelial cell lines (308 mouse keratinocytes and hct116 colon carcinoma cells) to determine the effect of apigenin on the mitogen-activated protein kinase (mapk) cascade. apigenin induced a dose-dependent phosphorylation of both extracellular signal-regulated protein kinase (erk) and p38 kinase but had little effect on the phosphorylation of c-jun amino terminal kinase (j ...	2003	14608117
meningeal worm in a reintroduced elk population in kentucky.	meningeal worm (parelaphostrongylus tenuis) has been implicated in the failure of several elk (cervus elaphus) restoration attempts in the eastern united states. however, limited post-release monitoring and a paucity of published literature prevents a clear understanding of this parasite's role in past failures. during winters of 1997-2001, the kentucky department of fish and wildlife resources translocated 1,044 elk from western states to eastern kentucky (usa) in an effort to restore a free-ra ...	2003	14567220
inter-species comparisons of hepatic cytochrome p450 enzyme levels in male ruminants.	our current knowledge about the biotransformation enzymes in wild ruminants is limited. the present study aimed to compare basic levels and specific activities of cytochrome p450 isoforms (cyp1a, 2a, 2b, 2c, 2d, 2e, 3a, 4a) in males of red deer ( cervus elaphus), fallow deer ( dama dama), roe deer ( capreolus capreolus) and mouflon ( ovis musimon). the proteins from the major cytochrome p450 (cyp) subfamilies were detected in all ruminant species by western blotting, using polyclonal antibodies ...	2003	14574442
transient expression of e1a and ras oncogenes causes downregulation of c-fos gene transcription in nontransformed ref52 cells.	stable transformation of rat embryo fibroblast (ref) cells with e1a and cha-ras oncogenes leads to downmodulation of c-fos gene transcription. this repression is provided in part by the association of elk-1 transcription factor with histone deacetylases mediated through effects of ras on map-kinase cascades. here, we focus on the primary effects of e1a and ras displayed in transient transfection assay on the transactivating capability of elk-1, which is a key transcription factor of c-fos gene r ...	2003	14576829
cellular effects of small molecule ptp1b inhibitors on insulin signaling.	protein tyrosine phosphatase 1b (ptp1b) is implicated as a negative regulator of insulin receptor (ir) signaling and a potential drug target for the treatment of type 2 diabetes and other associated metabolic syndromes. to further define the role of ptp1b in insulin signaling and to test the hypothesis that blocking the activity of ptp1b would augment the action of insulin, we prepared several cell permeable, potent and selective, small molecule ptp1b inhibitors, and evaluated their biological e ...	2003	14596593
efficacy trial of an irradiated cattle lungworm vaccine in red deer (cervus elaphus).	lungworm (dictyocaulus sp.) is the parasite of most concern to the new zealand deer industry. although lungworm can be controlled by anthelmintics there is an increasing concern over excessive drenching programmes and reliance on chemicals for parasite control. a live irradiated larval vaccine developed for cattle has been available in europe for the past 40 years but has never been evaluated in red deer in new zealand. four groups of red deer and two of cattle were hand reared from birth in par ...	2003	14597286
bovine tuberculosis in elk (cervus elaphus manitobensis) near riding mountain national park, manitoba, from 1992 to 2002.		2003	14601681
intersectin activates ras but stimulates transcription through an independent pathway involving jnk.	intersectin (itsn) is a molecular scaffold involved in regulating endocytosis and mitogenic signaling. we previously demonstrated that itsn transformed rodent fibroblasts, accelerated hormone-induced maturation of xenopus oocytes, and activated the elk-1 transcription factor through an mek- and erk-independent mechanism. we now demonstrate that itsn complexes with the ras guanine nucleotide exchange factor sos1 leading to increased rasgtp levels. using fluorescence resonant energy transfer analy ...	2003	12970366
high mobility group 1 b-box mediates activation of human endothelium.	severe sepsis and septic shock is a consequence of a generalized inflammatory systemic response because of an invasive infection that may result in acute organ dysfunction. mortality is high despite access to modern intensive care units. the nuclear dna binding protein high mobility group 1 (hmgb1) protein has recently been suggested to act as a late mediator of septic shock via its function as a macrophage-derived pro-inflammatory cytokine (j exp med 2000; 192: 565, science1999; 285: 248). we i ...	2003	12974876
subspecies and body size allometry affect milk production and composition, and calf growth in red deer: comparison of cervus elaphus hispanicus and cervus elaphus scoticus.	studies comparing lactation in wild mammals have shown that maternal weight scales with offspring weight, milk production, or its energy. however, no study appears to have scaled milk composition with maternal or offspring weight. although diet affects milk composition and production, their effects in biological studies have almost never seemed to be controlled. in this study, we compare two subspecies of red deer, scottish deer, cervus elaphus scoticus (10 lactations), and iberian deer, cervus ...	2003	13130438
babesia odocoilei infection in elk.	two male north american elk from a commercial herd were evaluated because of a sudden onset of lethargy, anorexia, and voiding of red urine. these 2 elk were kept in the same pen as 4 other male elk that had died during the preceding 2 months. laboratory analyses revealed anemia and intraerythrocytic parasites, later confirmed as babesia odocoilei (a protozoal hemoparasite of cervids). of the 240 elk remaining in the herd, 59 were screened for b odocoilei by microscopic evaluation of blood smear ...	2003	14552494
genetic diversity in european red deer (cervus elaphus l.): anthropogenic influences on natural populations.	allozyme, microsatellite and mtdna (rflp and sequence) data of european red deer populations were examined as to their capability of indicating anthropogenic influences such as the keeping of animals in enclosures, selective hunting for trophies translocation of specimens to improve trophy quality and habitat fragmentation. deer in enclosures revealed considerable deviations of allele frequencies from isolation-by-distance expectations but no remarkable loss of genetic diversity. particular allo ...	2003	14558447
the plasminogen activator inhibitor-1 gene is induced by cell adhesion through the mek/erk pathway.	the type-i plasminogen activator inhibitor (pai-1), the primary inhibitor of both tissue-type and urokinase-type plasminogen activators (t-pa, u-pa), is the primary regulator of plasminogen activation and possibly of extracellular proteolysis. in anchorage-dependent cells, the pai-1 gene is regulated by cell adhesion. pai-1 gene expression is induced more evidently in cells that adhered to the culture plate than in those that did not adhere. in this study, we further demonstrate that the pai-1 g ...	2003	14631113
fluctuating asymmetry in a secondary sexual trait: no associations with individual fitness, environmental stress or inbreeding, and no heritability.	it has been suggested that fluctuating asymmetry (fa) in secondary sexual traits may be a useful indicator of either individual quality or environmental stress. we tested this concept using a series of analyses of fa in male antler size in a wild red deer (cervus elaphus) population, using four measures of size repeated across successive years on the same individuals. we found no consistent evidence of correlations between traits in levels of fa, nor of any associations between known environment ...	2003	14635885
activated peripheral blood mononuclear cells induce p44/42 mitogen-activated protein kinase phosphorylation in trophoblast-like jar cells.	mammalian pregnancy bears many similarities to transplantation, since the fetus is semi-allogenic to mother. thus, mammals have developed numerous mechanisms to protect the developing fetus from maternal immunologic recognition and attack. we have previously shown that human choriocarcinoma jar cells, which resemble first trimester trophoblasts, regulate several important mrnas in activated peripheral blood mononuclear cells (pbmc). we now provide further evidence that communication between mate ...	2003	14638439
estimate and production of milk energy in two subspecies of red deer: cervus elaphus hispanicus and c. e. scoticus.	this study estimates the caloric value of red deer milk as assessed relating bomb calorimetry data with the main milk nutrients. the study also examines milk energy estimates and lactation variables to compare iberian red deer hinds (cervus elaphus hispanicus) and the most studied scottish red deer (c. e. scoticus). the final model predicted energy value (ecal) in kcal/g of fresh milk from fat (f) and protein (p) content of milk, but not lactose: ecal = 0.345 + 8.332 f + 5.403 p. energy content ...	2003	14648675
[dib (veterinarians in business) visits colleague niels van elk in dolfinarium hardewijk, the netherlands].		2003	14650727
model-based assessment of aspen responses to elk herbivory in rocky mountain national park, usa.	in rocky mountain national park (rmnp), aspen (populus tremuloides michx.) has been observed to be declining on elk (cervus elaphus nelsoni) winter range for many decades. to support elk management decisions, the savanna ecosystem model was adapted to explore interactions between elk herbivory and aspen dynamics. the simulated probability of successful vegetative regeneration for senescent aspen stands declines sharply when elk densities reach levels of 3-5 elk/km2, depending on model assumption ...	2003	14703920
immunohistochemical investigations of the autonomous innervation of the cervine testis.	the innervation of the cervine testis was studied in 6 roe deers, 7 red deers and 14 fallow deers. the results for the three species are rather similar. with anti-sera to neurofilament (nf) and neuron specific enolase (nse), all small and large nerve fascicles can be demonstrated, but single fibers are incompletely stained. immunoreactions against protein gene product-9.5 (pgp-9.5) and gap-43 (growth-associated protein-43) are better suited to depict the complete innervation pattern. bundles of ...	2003	14703994
characterization of chaotic dynamics in the vocalization of cervus elaphus corsicanus.		2003	14714785
cystic echinococcosis in the arctic and sub-arctic.	the northern biotype of echinococcus granulosus occurs throughout the holarctic zones of tundra and taiga, from eastern fennoscandia to the bering strait in eurasia and in north america from arctic alaska approximately to the northern border of the united states. the cycle of the cestode is complex in taiga at lower latitudes, because of the greater diversity of potential hosts. in the arctic and subarctic, however, four patterns of predator/prey relationships may be discerned. two natural cycle ...	2003	15027606
antibodies to ruminant alpha-herpesviruses and pestiviruses in norwegian cervids.	a serologic survey revealed that norwegian populations of free-ranging reindeer (rangifer tarandus tarandus), roe deer (capreolus capreolus), red deer (cervus elaphus), and moose (alces alces) have been exposed to alpha-herpesviruses and pestiviruses. a total of 3,796 serum samples collected during the period 1993-2000 were tested in a neutralization test for antibodies against bovine herpesvirus 1 (bhv-1) or cervid herpesvirus 2 (cerhv-2), and 3,897 samples were tested by a neutralization test ...	2003	14733272
estimating selection on neonatal traits in red deer using elasticity path analysis.	van tienderen recently published a method that links selection gradients between a phenotypic trait and multiple fitness components with the effects of these fitness components on the population growth rate (mean absolute fitness). the method allows selection to be simultaneously estimated across multiple fitness components in a population dynamic framework. in this paper we apply the method to a population of red deer living in the north block of the isle of rum, scotland. we show that (1) sele ...	2003	14761065
research on the influence of red deer (cervus elaphus l.) grazing on grassland production in the south-eastern part of slovenia.	almost 60% of slovenian territory is covered by forests and only finland and sweden are known as the more forest abundant countries in europe. among game that intensifies difficulties in the field of agricultural production, especially in north-eastern and south-eastern parts of the country, roe deer (capreolus capreolus l.), wild boar (sus scrofa l.) and red deer (cervus elaphus l.) prevail. negative impact of game on agricultural production in the above mentioned parts of slovenia has risen si ...	2003	15149125
the influence of environment, mode of nutrition and animal species on level of nitrosamine contamination in venison.	the work aimed to research occurrence of nitrosamines in raw venison from different game species and mode of nutrition effect on their meat concentrations. samples of venison from male and female elks, male and female red deer, male and female roe deer, male and female fallow deer, male and female wild boars, male and female brown hares and males and females of wild rabbits shot in poland during the permissible hunting seasons were used for the experiments after their jointing and cutting. in th ...	2003	22063687
conservation of cervus elaphus meat in modified atmospheres.	this study examines the effect of three types of modified atmospheres, each with a different gas composition (a:40% co(2)+60% n(2); b:80% co(2)+20% o(2); c:80% co(2)+20% n(2)), on the development of meat quality of cervus elaphus in order to suggest a gas composition that best preserves this type of meat. meat quality was assessed by examining ph, colour as l()a()b(*) values, drip loss (dl), cooking loss (cl) and shear force (sf). in samples of group a, ph values tended to be higher in all sto ...	2003	22063440
a new clue for the pathogenesis of hepatitis c virus infection: activation of the mapk/erk signaling initiated by envelope protein 2.	since cell signal transduction plays an important role in disclosing the nature of human diseases, the pathogenesis of viruses may result from the disturbance of intracellular signal cascades caused by viral proteins. hepatitis c virus (hcv) is a main causative agent of severe human liver disorders worldwide. so far, the mechanisms of hcv pathogenicity remain unclear. envelope protein 2 (e2) of hcv is thought to be responsible for initiating virus attachment to host cells, which is a prerequisit ...	2003	19448994
evolution and phylogeny of old world deer.	the phylogenetic pattern and timing of the radiation of old world deer was determined based on the complete mitochondrial cytochrome b gene from 33 cervinae taxa. using rooted and unrooted phylogenies derived from distinct theoretical approaches, strong support was achieved for monophyly of the old world deer with muntjacs as sister group as well as for the divergence of at least three distinct genera: rucervus, dama, and cervus. the latter clade comprises what have previously been regarded as t ...	2004	15522810
aboriginal overkill in the intermountain west of north america : zooarchaeological tests and implications.	zooarchaeological evidence has often been called on to help researchers determine prehistoric relative abundances of elk (cervus elaphus) in the greater yellowstone ecosystem. some interpret that evidence as indicating elk were abundant; others interpret it as indicating elk were rare. wildlife biologist charles kay argues that prehistoric faunal remains recovered from archaeological sites support his contention that aboriginal hunters depleted elk populations throughout the intermountain west, ...	2004	26190412
red deer stocks in the highlands of scotland.	grazing by hill sheep and red deer prevents the regeneration of woodland in many parts of the scottish highlands and has also led to extensive loss of heather cover. conservation bodies claim that there has been a rapid rise in highland deer numbers caused by inadequate management and that these need to be drastically reduced. here we show that the recent increase in red deer stocks has probably been overestimated and suggest that the gradual rise in numbers since 1970 may be a consequence of a ...	2004	15152241
molecular aspects of disease pathogenesis in the transmissible spongiform encephalopathies.	the transmissible spongiform encephalopathy (tse) diseases are a group of rare, fatal, and transmissible neurodegenerative diseases that include kuru and creutzfeldt-jakob disease (cjd) in humans, scrapie in sheep, transmissible mink encephalopathy (tme), and chronic wasting disease (cwd) in mule deer and elk. over the last 20 yr, they have gone from a fascinating but relatively obscure group of diseases to one that is a major agricultural and economic problem as well as a threat to human health ...	2004	15156065
tradeable hunting obligations--a new approach to regulating red deer numbers in the scottish highlands?	the population of red deer (cervus elaphus) in scotland has doubled over the last 30 years and there is increasing concern among conservationists about the long-term impact of increased grazing on native woodlands and other sensitive nature conservation sites. currently, the government relies on a voluntary approach to deer control, but landowners seem unable or unwilling to shoot sufficient numbers to meet cull targets. the aim of this paper is to examine alternatives to the 'voluntary approach ...	2004	15158288
activation of extracellular-signal regulated kinase is required for phagocytosis by lymnaea stagnalis haemocytes.	haemocytes are the primary defence cells of molluscs. in the present study, extracellular-signal regulated kinase (erk) 1/2-like proteins were identified within lymnaea stagnalis haemocytes, with apparent molecular weights of 44 and 43 kda, respectively. mitogen-activated protein kinase (mapk) activity assays have confirmed that the l. stagnalis erk possesses kinase activity towards elk-1. challenge of haemocytes with bacterial lipopolysaccharide (lps) resulted in a transient activation of erk, ...	2004	15158361
establishment of adult parelaphostrongylus tenuis, patent infections, and acquired immunity after experimental infection of white-tailed deer (odocoileus virginianus) and red deer (cervus elaphus elaphus).	experimental parelaphostrongylus tenuis infections were established in white-tailed deer (odocoileus virginianus) and an atypical host, red deer (cervus elaphus elaphus). groups of deer were fed 10, 25, or 100 third-stage larvae (l3) of p. tenuis and received a single equivalent challenge exposure at varying intervals. infections were monitored up to 6 yr in white-tailed deer and up to 2.8 yr in red deer. the prepatent period in white-tailed deer varied from 91 to 1,072 days (381 +/- 374) and in ...	2004	15165045
a novel role for mixed-lineage kinase-like mitogen-activated protein triple kinase alpha in neoplastic cell transformation and tumor development.	previously, no member of the mixed-lineage kinase (mlk) protein family was known to function as an oncogene. here, we demonstrate that mlk-like mitogen-activated protein triple kinase (mltk)-alpha, a member of the mlk family, induced neoplastic cell transformation and tumorigenesis in athymic nude mice. introduction of small interference rna (sirna)-mltk-alpha into mltk-alpha-overexpressing cells dramatically suppressed cell transformation. nuclear accumulation of the phisg-mltk-alpha fusion pro ...	2004	15172994
the p34g mutation reduces the transforming activity of k-ras and n-ras in nih 3t3 cells but not of h-ras.	ras proteins (h-, n-, and k-ras) operate as molecular switches in signal transduction cascades controlling cell proliferation, differentiation, or apoptosis. the interaction of ras with its effectors is mediated by the effector-binding loop, but different data about ras location to plasma membrane subdomains and new roles for some docking/scaffold proteins point to signaling specificities of the different ras proteins. to investigate the molecular mechanisms for these specificities, we compared ...	2004	15181015
progesterone determination in iberian red deer by time-resolved fluorometry: an alternative method to ria.	the validation for iberian red deer of a commercially available time-resolved fluoroimmunoassay (tr-fia) designed for analysis of progesterone in human beings was carried out. intra-assay coefficients of variation ranged from 3.6% to 7.4%, while inter-assay coefficients of variation varied from 5.2% to 15.5%. accuracy, evaluated by comparing results yielded by tr-fia with those obtained from a validated radioimmunoassay (ria) in the measurement of 14 samples, provided a high regression coefficie ...	2004	15181641
bovine tuberculosis (mycobacterium bovis) in wildlife in spain.	mycobacterium bovis infection in wildlife and feral species is a potential source of infection for livestock and a threat to protected and endangered species. the aim of this study was to identify spanish wild animal species infected with m. bovis through bacteriological culture and spacer oligonucleotide typing (spoligotyping) of isolates for epidemiological purposes. this study included samples from red deer (cervus elaphus), fallow deer (dama dama), wild boar (sus scrofa), iberian lynx (lynx ...	2004	15184440
differential regulation of the phosphoinositide 3-kinase and map kinase pathways by hepatocyte growth factor vs. insulin-like growth factor-i in myogenic cells.	hepatocyte growth factor (hgf) promotes the proliferation of adult myoblasts and inhibits their differentiation, whereas insulin-like growth factor i (igf-i) enhances both processes. recent studies indicate that activation of the phosphoinositide 3'-kinase (pi3k) pathway promotes myoblast differentiation, whereas activation of the mitogen-activated protein kinase/extracellular signal-regulated protein kinase (mapk/erk) promotes proliferation and inhibits their differentiation. this simple model ...	2004	15194438
morphometric and immunohistochemical study of the rumen of red deer during prenatal development.	abstract a detailed study of the ontogenesis of deer stomach has not been undertaken to date, and our aim was to sequence several histological phenomena that occur during the ontogenesis of one of the gastric compartments, the rumen. histomorphometric and immunohistochemical analyses were carried out on 50 embryos and fetuses of deer from the initial stages of prenatal life until birth. for the purposes of testing, the animals were divided into five experimental groups: group i, 1.4-3.6 cm crown ...	2004	15198691
chronic wasting disease in canada: part 1.	the purpose of part 1 is to provide an overview of published literature (1980-2002) on chronic wasting disease (cwd) to inform canadian readers about the disease and to explain canadian regulatory approaches to the surveillance and control of cwd. much of the scientific information is drawn from american publications obtained from internet searches in pubmed and medline databases. the following keywords were used: chronic wasting disease, prion, diagnosis, transmissible spongiform encephalopathi ...	2004	15206588
chronic wasting disease and potential transmission to humans.	chronic wasting disease (cwd) of deer and elk is endemic in a tri-corner area of colorado, wyoming, and nebraska, and new foci of cwd have been detected in other parts of the united states. although detection in some areas may be related to increased surveillance, introduction of cwd due to translocation or natural migration of animals may account for some new foci of infection. increasing spread of cwd has raised concerns about the potential for increasing human exposure to the cwd agent. the f ...	2004	15207045
diagnostic strategies and outcomes on three new zealand deer farms with severe outbreaks of bovine tuberculosis.	three commercial deer herds, each containing more than 500 deer, experienced outbreaks of tuberculosis (tb) ranging from a 6% prevalence to disease levels >50%. intensive diagnostic testing was carried out over short time intervals after the initial diagnosis of tb.	2004	15207804
transformation potential of ras isoforms correlates with activation of phosphatidylinositol 3-kinase but not erk.	the ras oncoproteins activate the raf-mek-erk kinase pathway, which plays an important role in cellular transformation. we observed that h-rasv12 exhibited a higher transforming potential than either k-rasv12 or n-rasv12 in both nih3t3 fibroblasts and rie-1 rat epithelial cell cultures. surprisingly n-ras and k-ras were more potent than h-ras in activation of mitogen-activated protein (map) kinase activity and ternary complex factor-dependent transcription. in contrast, h-ras was more effective ...	2004	15210703
sumoylation regulates nucleo-cytoplasmic shuttling of elk-1.	the transcription factor elk-1 is a nuclear target of mitogen-activated protein kinases and regulates immediate early gene activation by extracellular signals. we show that elk-1 is also conjugated to sumo on either lysines 230, 249, or 254. mutation of all three sites is necessary to fully block sumoylation in vitro and in vivo. this elk-1 mutant, elk-1(3r), shuttles more rapidly to nuclei of balb/c cells fused to transfected hela cells. coexpression of sumo-1 or -2 strongly reduces shuttling b ...	2004	15210726
ectopic expression of murine diphosphoinositol polyphosphate phosphohydrolase 1 attenuates signaling through the erk1/2 pathway.	signals from several receptor tyrosine kinases are transduced by activation of the ras family of gtp-binding proteins. activation of ras initiates a kinase cascade that culminates in activation of the mitogen-activated protein kinases (mapks). the mapks include the c-jun nh(2)-terminal protein kinases (jnks) and extracellular signal-regulated kinases (erks), both of which phosphorylate elk-1/tcf, a factor that activates transcription of the c-fos gene. in this report, we identify a novel 19 kda ...	2004	15212765
bcl10 mediates lipopolysaccharide/toll-like receptor-4 signaling through interaction with pellino2.	toll-like receptor (tlr) pathways signal through microbial components stimulation to induce innate immune responses. herein, we demonstrate that bcl10, a critical molecule that signals between the t cell receptor and ikappab kinase complexes, is involved in the innate immune system and is required for appropriate tlr4 pathway and nuclear factor-kappab (nf-kappab) activation. in response to lipopolysaccharide (lps) stimulation, bcl10 was recruited to tlr4 signaling complexes and associated with p ...	2004	15213237
androgen inhibition of map kinase pathway and elk-1 activation in proliferating osteoblasts.	non-aromatizable androgens have significant beneficial effects on skeletal homeostasis independently of conversion to estradiol, but the effects of androgens on bone cell metabolism and cell proliferation are still poorly understood. using an osteoblastic model with enhanced androgen responsiveness, mc3t3-e1 cells stably transfected with androgen receptor (ar) under the control of the type i collagen promoter (colar-mc3t3), the effects of androgens on mitogenic signaling were characterized. cult ...	2004	14766003
ternary complex factor sap-1 is required for erk-mediated thymocyte positive selection.	thymocyte selection and differentiation requires extracellular signal-regulated kinase (erk) signaling, but transcription factor substrates of erk in thymocytes are unknown. we have characterized the function of sap-1 (elk4), an erk-regulated transcription factor, in thymocyte development. early thymocyte development was normal, but single-positive thymocyte and peripheral t cell numbers were reduced, reflecting a t cell-autonomous defect. t cell receptor-induced activation of sap-1 target genes ...	2004	14770179
adaptive hypersensitivity to estrogen: mechanism for sequential responses to hormonal therapy in breast cancer.	clinical observations demonstrate that women with breast cancer often respond to subsequent endocrine manipulation after resistance to initial hormonal therapy develops. as a mechanistic explanation for these findings, we hypothesized that human breast tumors can adapt in response to the pressure exerted by endocrine therapy with development of hypersensitivity to estradiol. to understand the signaling pathways responsible, we examined estrogenic stimulation of cell proliferation in a model syst ...	2004	14734489
the role of hippocampal signaling cascades in consolidation of fear memory.	we investigated the involvement of hippocampal protein kinase a (pka), protein kinase c (pkc), calcium/calmodulin-dependent protein kinases (camk ii), and mitogen-activated extracellular signal-regulated kinases 1 and 2 (mek-1/2) in the phosphorylation of their downstream targets extracellular signal-regulated kinases 1 and 2 (erk-1/2), camp-response element-binding protein (creb), elk-1, and p90 ribosomal s6 kinase 1 (p90rsk-1). the role of these processes in memory consolidation of conditioned ...	2004	14739006