gebhart/patrepeval huggingface dataset:
The anti-hyperalgesic actions of the cannabinoid anandamide and the putative CB2 receptor agonist palmitoylethanolamide in visceral and somatic inflammatory pain (1998)

This study assessed the effects of two N-acylethanolamides in established rat models of visceral and somatic inflammatory pain. (1) The therapeutic effects of the cannabinoid anandamide and the putative CB2 agonist palmitoylethanolamide were tested in a model of persistent visceral pain (turpentine inflammation of the urinary bladder). Both anandamide (at a dose of 25 mg/kg) and palmitoylethanolamide (at doses of 10-30 mg/kg) were able to attenuate the viscero-visceral hyper-reflexia (VVH) induced by inflammation of the urinary bladder. (2) The effects of the same compounds on the behavioural response to subcutaneous formalin injection were assessed. The characteristic biphasic response was observed in control animals. Anandamide (dose range 5-25 mg/kg) and palmitoylethanolamide (dose range 5-10 mg/kg) both reduced the second phase of the response. The results confirm the analgesic potential of endogenous ligands at cannabinoid receptor sites. The anti-nociceptive effect of the putative CB2 receptor agonist, palmitoylethanolamide, is particularly interesting since it is believed to be a peripherally mediated effect. This observation might be exploited to separate central psychotropic effects from peripheral analgesic actions of the cannabinoids, under inflammatory conditions.
Increased Gene Dosage of Ube3a Results in Autism Traits and Decreased Glutamate Synaptic Transmission in Mice (2011)

People with autism spectrum disorder are characterized by impaired social interaction, reduced communication, and increased repetitive behaviors. The disorder has a substantial genetic component, and recent studies have revealed frequent genome copy number variations (CNVs) in some individuals. A common CNV that occurs in 1 to 3% of those with autism--maternal 15q11-13 duplication (dup15) and triplication (isodicentric extranumerary chromosome, idic15)--affects several genes that have been suggested to underlie autism behavioral traits. To test this, we tripled the dosage of one of these genes, the ubiquitin protein ligase Ube3a, which is expressed solely from the maternal allele in mature neurons, and reconstituted the three core autism traits in mice: defective social interaction, impaired communication, and increased repetitive stereotypic behavior. The penetrance of these autism traits depended on Ube3a gene copy number. In animals with increased Ube3a gene dosage, glutamatergic, but not GABAergic, synaptic transmission was suppressed as a result of reduced presynaptic release probability, synaptic glutamate concentration, and postsynaptic action potential coupling. These results suggest that Ube3a gene dosage may contribute to the autism traits of individuals with maternal 15q11-13 duplication and support the idea that increased E3A ubiquitin ligase gene dosage results in reduced excitatory synaptic transmission.
The Diagnosis and Initial Management of Head Injury (1992)

SINCE ancient times,1 head injuries have had an almost mysterious quality. Although trauma to the head may cause severe tissue disruption of the scalp, skull, and facial and subcranial structures, the ultimate determinant of survival and functional outcome is the degree and extent of brain damage, alone or in association with other major traumatic injuries.In the United States, a head injury occurs every seven seconds, with a death every five minutes. Head injury is the leading cause of death among people under the age of 24 years.2 Although statistics vary from year to year, approximately 200,000 people die or . . .
Myogenin expression, cell cycle withdrawal, and phenotypic differentiation are temporally separable events that precede cell fusion upon myogenesis. (1996)

During terminal differentiation of skeletal myoblasts, cells fuse to form postmitotic multinucleated myotubes that cannot reinitiate DNA synthesis. Here we investigated the temporal relationships among these events during in vitro differentiation of C2C12 myoblasts. Cells expressing myogenin, a marker for the entry of myoblasts into the differentiation pathway, were detected first during myogenesis, followed by the appearance of mononucleated cells expressing both myogenin and the cell cycle inhibitor p21. Although expression of both proteins was sustained in mitogen-restimulated myocytes, 5-bromodeoxyuridine incorporation experiments in serum-starved cultures revealed that myogenin-positive cells remained capable of replicating DNA. In contrast, subsequent expression of p21 in differentiating myoblasts correlated with the establishment of the postmitotic state. Later during myogenesis, postmitotic (p21-positive) mononucleated myoblasts activated the expression of the muscle structural protein myosin heavy chain, and then fused to form multinucleated myotubes. Thus, despite the asynchrony in the commitment to differentiation, skeletal myogenesis is a highly ordered process of temporally separable events that begins with myogenin expression, followed by p21 induction and cell cycle arrest, then phenotypic differentiation, and finally, cell fusion.
Prothrombinase Assembly and S1 Site Occupation Restore the Catalytic Activity of FXa Impaired by Mutation at the Sodium-binding Site (2002)

Two loop segments (183-189 and 221-225) in the protease domain of factor Xa contribute to the formation of a Na(+)-binding site. Studies with factor Xa indicate that binding of a single Na(+) ion to this site influences its activity by altering the S1 specificity site, and substitution of Tyr(225) with Pro diminishes sensitivity to Na(+). Using full-length factor Xa(Y225P), the allosteric relationship between the Na(+) site and other structural determinants in factor Xa and prothrombinase was investigated. Direct binding and kinetic measurements with probes that target the S1 specificity pocket indicate that assembly of the mutant in prothrombinase corrected the impaired binding of these probes observed with free factor Xa(Y225P). This appears to result from the apparent allosteric linkage between the factor Va, S1, and Na(+)-binding sites, since binding of the cofactor to membrane-bound factor Xa(Y225P) enhances binding at the S1 site and vice versa. Additional studies revealed that the internal salt bridge (Ile(16)-Asp(194)) of factor Xa(Y225P) is partially destabilized, a process that is reversible upon occupation of the S1 site. The data establish that alterations at the factor Xa Na(+)-binding site shift the zymogen-protease equilibrium to a more zymogen-like state, and as a consequence binding of S1-directed probes and factor Va are adversely affected. Therefore, the zymogen-like characteristics of factor Xa(Y225P) have allowed for the apparent allosteric linkage between the S1, factor Va, and Na(+) sites to become evident and has provided insight into the structural transitions which accompany the conversion of factor X to factor Xa.
Integrin and Growth Factor Receptor Crosstalk (2001)

Crosstalk between integrins and growth factor receptors are an important signaling mechanism to provide specificity during normal development and pathological processes in vascular biology. Evidence from several model systems demonstrates the physiological importance of the coordination of signals from growth factors and the extracellular matrix to support cell proliferation, migration, and invasion in vivo. Several examples of crosstalk between these two important classes of receptors indicate that integrin ligation is required for growth factor-induced biological processes. Furthermore, integrins can directly associate with growth factor receptors, thereby regulating the capacity of integrin/growth factor receptor complexes to propagate downstream signaling. Recent data suggest that antagonists of alpha(v) integrins can provide a therapeutic benefit in human cancer patients, whereas knockout mice lacking specific integrins can provide an interesting insight into the role of integrins during development. This review will focus on the biological importance of integrin and growth factor receptor crosstalk that occurs during cell growth, migration, and invasion as well as in endothelial cells during angiogenesis.
Characterization of a novel cGMP binding protein from rat lung. (1980)

A specific cGMP binding protein from rat lung has been partially purified and characterized. The binding protein is clearly distinct from the cGMP-dependent protein kinase as determined by several of its characteristics such as chromatographic behavior and spatial requirements for cGMP binding. The protein has a sedimentation coefficient of 7.8 S, a Stokes radius of 5.5 nm, and an estimated M, = 177,000. A cGMP phosphodiesterase activity co-purifies with the binding protein through several steps (ion exchange chromatography, gel filtration, and sucrose density gradient centrifugation) and the possibility exists that these two activities may be functions of the same protein. Several lines of evidence indicate that the cGMP binding site is distinct from the phosphodiesterase catalytic site. First, 1-methyl-3-isobutylxanthine is a competitive inhibitor of cGMP for phosphodiesterase activity, while under similar conditions this compound increases cGMP binding. Other phosphodiesterase inhibitors also increase cGMP binding and these effects are not due to substrate protection. Second, the cGMP analogue 2’-0monobutyryl cGMP is an effective inhibitor of cGMP phosphodiesterase activity, but at the same concentration this compound has no effect on cGMP binding. Third, heat or trypsin treatment of the protein causes loss of cGMP phosphodiesterase activity, while both treatments increase cGMP binding. The characteristics of the cGMP binding protein-phosphodiesterase and its presence in several cell types, ie. sea urchin sperm and rat platelets, which appear to contain very low levels of cGMP-dependent protein kinase, suggest that this protein may have a physiological role in mediating cGMP action.
Molecularchaperones as HSF1-specific transcriptional repressors (1998)

The rapid yet transient transcriptional activation of heat shock genes is mediated by the reversible conversion of HSF1 from an inert negatively regulated monomer to a transcriptionally active DNA-binding trimer. During attenuation of the heat shock response, transcription of heat shock genes returns to basal levels and HSF1 reverts to an inert monomer. These events coincide with elevated levels of Hsp70 and other heat shock proteins (molecular chaperones). Here, we show that the molecular chaperone Hsp70 and the cochaperone Hdj1 interact directly with the transactivation domain of HSF1 and repress heat shock gene transcription. Overexpression of either chaperone represses the transcriptional activity of a transfected GAL4-HSF1 activation domain fusion protein and endogenous HSF1. As neither the activation of HSF1 DNA binding nor inducible phosphorylation of HSF1 was affected, the primary autoregulatory role of Hsp70 is to negatively regulate HSF1 transcriptional activity. These results reveal that the repression of heat shock gene transcription, which occurs during attenuation, is due to the association of Hsp70 with the HSF1 transactivation domain, thus providing a plausible explanation for the role of molecular chaperones in at least one key step in the autoregulation of the heat shock response.
Electrical wiring of redox enzymes (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrical wiring of redox enzymesAdam HellerCite this: Acc. Chem. Res. 1990, 23, 5, 128–134Publication Date (Print):May 1, 1990Publication History Published online1 May 2002Published inissue 1 May 1990https://pubs.acs.org/doi/10.1021/ar00173a002https://doi.org/10.1021/ar00173a002research-articleACS PublicationsRequest reuse permissionsArticle Views2494Altmetric-Citations749LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Interleukin-10 (1993)

In the three years since its discovery, the pleiotropic cytokine interleukin-10 (IL-10) has been implicated as an important regulator of the functions of lymphoid and myeloid cells. IL-10's ability to block activation of cytokine synthesis and several accessory cell functions of macrophage renders this cytokine a potent suppressor of the effector functions of macrophages, T cells, and NK cells. In addition, IL-10 likely contributes to regulating proliferation and differentiation of B cells, mast cells, and thymocytes. The Epstein-Barr virus genome encodes a homolog of IL-10 (BCFR1, viral IL-10, vIL-10) which shares many of the cellular cytokine's biological activities and may therefore play a role in the host-virus interaction. This article reviews current studies of IL-10's biological activities and discusses its possible roles in regulation of immune responses.
Molecular cloning and characterization of a KCS gene from Cardamine graeca and its heterologous expression in Brassica oilseeds to engineer high nervonic acid oils for potential medical and industrial use (2009)

Nervonic acid 24:1 Delta15 (cis-tetracos-15-enoic acid) is a very long-chain monounsaturated fatty acid and exists in nature as an elongation product of oleic acid. There is an increasing interest in production of high nervonic acid oils for pharmaceutical, nutraceutical and industrial applications. Using a polymerase chain reaction approach, we have isolated a gene from Cardamine graeca L., which encodes a 3-ketoacyl-CoA synthase (KCS), the first component of the elongation complex involved in synthesis of nervonic acid. Expression of the Cardamine KCS in yeast resulted in biosynthesis of nervonic acid, which is not normally present in yeast cells. We transformed Arabidopsis and Brassica carinata with the Cardamine KCS under the control of the seed-specific promoter, napin. The T(3) generations of transgenic Arabidopsis and B. carinata plants expressing the Cardamine KCS showed that seed-specific expression resulted in relatively large comparative increases in nervonic acid proportions in Arabidopsis seed oil, and 15-fold increase in nervonic acid proportions in B. carinata seed oil. The highest nervonic acid level in transgenic B. carinata lines reached 44%, with only 6% of residual erucic acid. In contrast, similar transgenic expression of the Cardamine KCS in high erucic B. napus resulted in 30% nervonic acid but with 20% residual erucic acid. Experiments using the Lunaria KCS gene gave results similar to the latter. In both cases, the erucic acid content is too high for human or animal consumption. Thus, the Cardamine KCS: B. carinata high nervonic/highly reduced erucic transgenic seed oils will be the most suitable for testing in pharmaceutical/nutraceutical applications to improve human and animal health.
A Conserved Tyr Residue Is Required for Sugar Selectivity in a Pol α DNA Polymerase (2002)

Many DNA polymerases select their natural substrates, deoxy- as opposed to ribonucleoside triphosphates, with a selectivity greater than 10000-fold. The function of a highly conserved residue, Tyr416, in the palm domain of the parental enzyme, an exo(-) derivative of RB69 DNA polymerase (gp43), a member of the pol alpha DNA polymerase family, was examined for its role in helping the polymerase discriminate between ribo-, dideoxyribo-, and deoxyribonucleoside triphosphates. The parental enzyme selected dNTPs vs rNTPs with about the same preference as dNTPs vs ddNTPs. Pre-steady-state kinetic analysis was carried out with the parental enzyme and two mutants, Y416A and Y416F. The Y416A mutant incorporated ribonucleotide residues much more efficiently than the parental enzyme, whereas the Y416F mutant was more permissive toward ddNTP vs rNTP utilization than either the Y416A mutant or the parental enzyme. We also found that both dCDP and rCDP inhibited dCTP incorporation by the Y416A mutant, while only dCDP but not rCDP inhibited dCTP incorporation by the parental enzyme and the Y416F mutant. The parental enzyme and the Y416A and Y416F mutants were all able to add araCTP (1-beta-D-arabinofuranosylcytosine-5'-triphosphate) to a primer but with reduced efficiency relative to dCTP. Based on our kinetic results, interpreted in the context of the crystal structure of the RB69 gp43 ternary complex, we suggest that sugar discrimination is provided mainly by the Tyr416 side chain which can sterically block the 2'-OH group of an incoming rNTP.
Technetium-99m-labeled chemotactic peptides in acute infection and sterile inflammation. (1997)

fMLFK-HYNIC is retained in both acute infection and sterile inflammation by means of specific receptor binding if sufficient cellular infiltration is present.
The Natural History of Initially Untreated Low-Grade Non-Hodgkin's Lymphomas (1984)

To learn more about the natural history of low-grade non-Hodgkin's lymphoma, we have studied 83 patients in whom the advanced disease was initially managed without therapy. Actuarial survival was 82 per cent at 5 years and 73 per cent at 10 years. The median time until therapy was required was three years. Spontaneous regressions occurred in 19 untreated patients (23 per cent), including 30 per cent of patients with nodular, poorly differentiated lymphocytic lymphoma. Histologic transformation to an intermediate-grade or high-grade lymphoma occurred both before and after primary therapy. The actuarial risk of transformation among the initially untreated patients was similar to that in a group of patients treated at this institution immediately after diagnosis. Neither the time to histologic transformation nor the incidence of transformation was influenced by when therapy was started.
Analog study of dead-beat posicast control (1958)

A method is presented which eliminates the oscillations and overshoot in a lightly damped servomechanism in a time of considerably less than one cycle of the uncompensated oscillation. The frequency response of a resonant system compensated in this manner can be made flat up through and beyond the resonant frequency of the system. For dead-beat response in one-half period, the frequency response is down only 3 db at the resonant frequency. Systems designed to have dead-beat responses in much less than one-half period have correspondingly wider bandwidths. The posicast method involves splitting up the input excitation into several fragments. Each fragment is applied at such a time that the sum of all the transient terms is equal to zero after the last excitation. The method is general and can be applied to electrical, mechanical, and even pneumatic systems.
Expression of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (4F2hc) in oral squamous cell carcinoma and its precusor lesions. (2004)

LAT1 and 4F2hc may have an important role in the early stages of multistep oral carcinogenesis. In addition, the specific inhibition of LAT1 and 4F2hc might be a new rationale to suppress oral cancer progression.
Interaction of Hemojuvelin with Neogenin Results in Iron Accumulation in Human Embryonic Kidney 293 Cells (2005)

Type 2 hereditary hemochromatosis (HH) or juvenile hemochromatosis is an early onset, genetically heterogeneous, autosomal recessive disorder of iron overload. Type 2A HH is caused by mutations in the recently cloned hemojuvelin gene (HJV; also called HFE2) (Papanikolaou, G., Samuels, M. E., Ludwig, E. H., MacDonald, M. L., Franchini, P. L., Dube, M. P., Andres, L., MacFarlane, J., Sakellaropoulos, N., Politou, M., Nemeth, E., Thompson, J., Risler, J. K., Zaborowska, C., Babakaiff, R., Radomski, C. C., Pape, T. D., Davidas, O., Christakis, J., Brissot, P., Lockitch, G., Ganz, T., Hayden, M. R., and Goldberg, Y. P. (2004) Nat. Genet. 36, 77-82), whereas Type 2B HH is caused by mutations in hepcidin. HJV is highly expressed in both skeletal muscle and liver. Mutations in HJV are implicated in the majority of diagnosed juvenile hemochromatosis patients. In this study, we stably transfected HJV cDNA into human embryonic kidney 293 cells and characterized the processing of HJV and its effect on iron homeostasis. Our results indicate that HJV is a glycosylphosphatidylinositol-linked protein and undergoes a partial autocatalytic cleavage during its intracellular processing. HJV co-immunoprecipitated with neogenin, a receptor involved in a variety of cellular signaling processes. It did not interact with the closely related receptor DCC (deleted in Colon Cancer). In addition, the HJV G320V mutant implicated in Type 2A HH did not co-immunoprecipitate with neogenin. Immunoblot analysis of ferritin levels and transferrin-55Fe accumulation studies indicated that the HJV-induced increase in intracellular iron levels in human embryonic kidney 293 cells is dependent on the presence of neogenin in the cells, thus linking these two proteins to intracellular iron homeostasis.
Mining partially periodic event patterns with unknown periods (2002)

Periodic behavior is common in real-world applications. However in many cases, periodicities are partial in that they are present only intermittently. The authors study such intermittent patterns, which they refer to as p-patterns. The formulation of p-patterns takes into account imprecise time information (e.g., due to unsynchronized clocks in distributed environments), noisy data (e.g., due to extraneous events), and shifts in phase and/or periods. We structure mining for p-patterns as two sub-tasks: (1) finding the periods of p-patterns and (2) mining temporal associations. For (2), a level-wise algorithm is used. For (1), we develop a novel approach based on a chi-squared test, and study its performance in the presence of noise. Further we develop two algorithms for mining p-patterns based on the order in which the aforementioned sub-tasks are performed: the period-first algorithm and the association-first algorithm. Our results show that the association-first algorithm has a higher tolerance to noise; the period-first algorithm is more computationally efficient and provides flexibility as to the specification of support levels. In addition, we apply the period-first algorithm to mining data collected from two production computer networks, a process that led to several actionable insights.
On bandlimited signals with fractional Fourier transform (1996)

We study bandlimited signals with fractional Fourier transform (FRFT). We show that if a nonzero signal f is bandlimited with FRFT F/sub /spl alpha// for a certain real /spl alpha/, then it is not bandlimited with FRFT F/sub /spl beta// for any /spl beta/ with /spl beta//spl ne//spl plusmn//spl alpha/+n/spl pi/ for any integer n. This is a generalization of the fact that a nonzero signal can not be both timelimited and bandlimited. We also provide sampling theorems for bandlimited signals with FRFT that are similar to the Shannon sampling theorem.