gebhart/patrepeval huggingface dataset:
Overlapping multi-site domains of the muscarinic cholinergic Hm1 receptor involved in signal transduction and sequestration. (1994)

Alanine mutagenesis scanning of the intracellular portion of the human muscarinic cholinergic Hm1 receptor was performed to identify domains mediating agonist induced receptor sequestration. Using these multiple alanine point mutants of Hm1, we had previously identified several receptor domains in the intracellular loops i1-3 that play a role in coupling to phosphatidyl inositol turnover, most notably, a lipophilic residue, Leu-131, in the conserved i2 loop domain DRYXXVXXPL (Moro, O., Lameh, J., Hogger, P., and Sadée, W. (1993) J. Biol. Chem. 268, 6862-6865). We now demonstrate that alanine substitutions in three of these domains, i.e. middle of the i2 loop and both junctions of the i3 loop, also result in defective sequestration (loss of surface receptor sites accessible to a polar tracer) in transfected human kidney U293 cells. The i2 loop was studied further by single point mutations. The strongest impairment of sequestration occurred with mutant L131A which was also highly defective in phosphatidyl inositol (PI) coupling. Substitution of Leu-131 with several distinct amino acids indicated that a bulky lipophilic residue is required for sequestration in this position, as shown for coupling to PI turnover. Further, the double point mutation, V127A/L131A, almost completely suppressed both sequestration and coupling of Hm1. In the beta 2 adrenoceptor, alanine substitution of the i2 residue Phe-139, equivalent to Leu-131 in Hm1, also resulted in impaired coupling to adenylyl cyclase and sequestration, indicating a general role for this conserved i2 loop residue in both processes. The combined results show that the multi-site domain involved in signal transduction of Hm1 is similar to and overlaps with that involved in sequestration. However, three Hm1 mutants that were moderately deficient in stimulating PI turnover displayed normal sequestration, suggesting distinct mechanisms. We propose that cellular mediators of receptor sequestration are structurally similar or identical to the heterotrimeric G proteins.
Ocular Gene Transfer with Self-Complementary AAV Vectors (2007)

These data suggest that scAAV vectors may be advantageous for ocular gene therapy, particularly in retinal diseases that require rapid and robust transgene expression in photoreceptor cells.
Cloning the interleukin 1 receptor from human T cells. (1989)

cDNA clones of the interleukin 1 (IL-1) receptor expressed in a human T-cell clone have been isolated by using a murine IL-1 receptor cDNA as a probe. The human and mouse receptors show a high degree of sequence conservation. Both are integral membrane proteins possessing a single membrane-spanning segment. Similar to the mouse receptor, the human IL-1 receptor contains a large cytoplasmic region and an extracellular, IL-1 binding portion composed of three immunoglobulin-like domains. When transfected into COS cells, the human IL-1 receptor cDNA clone leads to expression of two different affinity classes of receptors, with Ka values indistinguishable from those determined for IL-1 receptors in the original T-cell clone. An IL-1 receptor expressed in human dermal fibroblasts has also been cloned and sequenced and found to be identical to the IL-1 receptor expressed in T cells.
Functional assessment of control systems for cybernetic elbow prostheses. I. Description of the technique (1990)

This paper (Part I of II) presents a novel control scheme with which an amputee commands an elbow prosthesis using myoelectric activity. By mimicking some important characteristics of the intact neuromuscular system, the proposed controller attempts to make the prosthesis respond as the natural elbow to both voluntary commands from the amputee and applied moments from the environment. Also presented is the description of a novel experiment for functionally assessing elbow prosthesis controllers. The experimental design calls for an amputee to perform a constrained motion task while operating a prosthesis capable of implementing a wide variety of controllers. Due to the nature of the constraint, the task emphasizes the prosthesis response to both inputs: voluntary commands and external moments. Application of the experiment to assessment of the proposed control scheme and the control scheme used in a state-of-the-art prosthesis is presented in Part II.
Androgen replacement therapy in male patients with rheumatoid arthritis (1991)

A hypogonadic condition characterized by low serum testosterone levels has been identified in male patients with rheumatoid arthritis (RA). Seven men with active RA were treated daily for 6 months with oral testosterone undecanoate plus a nonsteroidal antiinflammatory drug in an attempt to evaluate the immunologic response, the overall clinical response, and the sex hormone response to such replacement therapy. At the end of the 6 months, there was a significant increase in serum testosterone levels (P less than 0.05), an increase in the number of CD8+ T cells, and a decrease in the CD4+:CD8+ T cell ratio. The IgM rheumatoid factor concentration decreased significantly (P less than 0.05). There was a concurrent significant reduction in the number of affected joints (P less than 0.05) and in the daily intake of nonsteroidal antiinflammatory drugs (P less than 0.01). The well-known immunosuppressive action of androgens probably contributed to our findings in these RA patients.
Scaffolding In Tissue Engineering (2005)

The growing interest in scaffolding design and increasing research programs dedicated to regenerative medicine corroborate the need for Scaffolding in Tissue Engineering. While certain books and journal articles address various aspects in the field, this is the first current, comprehensive text focusing on scaffolding for tissue engineering.<BR
STREAM CHANNEL PATTERN: A THRESHOLD MODEL (1988)

The focus of this research is the development of a model which explains channel pattern variability in streams. Since channel pattern is commonly regarded as a qualitative phenomenon, the research employs a logistic regression model, which is advocated as an alternative to traditional graphic/discriminant analysis, since the concepts of threshold and instability have very natural expressions in the logistic regression framework. The results demonstrate that channel gradient and mean discharge can effectively explain channel pattern (i.e., whether the channel is single or multithreaded) in an environment where there is a small range of bed material size. Sediment sorting is also shown to be related to channel pattern in the study environment. Models using valley gradient rather than channel gradient are shown to be distinctly inferior, and no advantage is found in using a stream power measure as opposed to separate gradient and discharge measures. [Key Words: fluvial geomorphology, stream channels, channel patterns, models.]
Repetitive hypoxia rapidly depresses cardio‐respiratory responses during active sleep but not quiet sleep in the newborn lamb (1999)

1. Arousal from sleep is an important protective response to hypoxia that becomes rapidly depressed in active sleep (AS) when hypoxia is repeated. This study questioned whether there might also be selective depression of cardio-respiratory responses to hypoxia during AS. 2. Nine newborn lambs (7-22 days of age) were studied over three successive nights. The first and third nights were baseline studies (inspired oxygen fraction, Fi,O2 = 0.21). During the second night, during every epoch of sleep, lambs were exposed to 60 s episodes of isocapnic hypoxia (Fi,O2 = 0.10). 3. During quiet sleep (QS), the probability of arousal in hypoxia exceeded the probability of spontaneous arousal (P < 0.001) throughout repeated exposures to hypoxia. Similarly, there were persisting increases in ventilation (135 +/- 25 %), blood pressure (3 +/- 1 %) and heart rate (3 +/- 1 %). 4. By contrast, rapid depression of all responses occurred during repetitive hypoxia in AS. Thus, the probability of arousal in hypoxia exceeded the probability of spontaneous arousal during the first 10 hypoxia exposures (P < 0.001) but not thereafter. Similarly, during the first 10 exposures to hypoxia, the changes in ventilation (88 +/- 15 %) and blood pressure (5 +/- 1 %) were greater than subsequent responses (P < 0.05). 5. We conclude that, when repeated, hypoxia rapidly becomes ineffective in stimulating protective arousal, ventilatory and blood pressure responses in AS, but not in QS. Selective depression of responses during AS may render the newborn particularly vulnerable to hypoxia in this state.
A functional assay for proteins involved in establishing an epithelial occluding barrier: identification of a uvomorulin-like polypeptide. (1986)

A functional assay has been developed to identify cell surface proteins involved in the formation of epithelial tight junctions. Transepithelial electrical resistance was used to measure the presence of intact tight junctions in monolayers of Madin-Darby canine kidney (MDCK) cells cultured on nitrocellulose filters. The strain I MDCK cells used have a transmonolayer resistance greater than 2,000 ohm . cm2. When the monolayers were incubated at 37 degrees C without Ca2+, the intercellular junctions opened and the transmonolayer resistance dropped to the value of a bare filter, i.e., less than 40 ohm . cm2. When Ca2+ was restored, the cell junctions resealed and the resistance recovered rapidly. Polyclonal antibodies raised against intact MDCK cells inhibited the Ca2+-dependent recovery of electrical resistance when applied to monolayers that had been opened by Ca2+ removal. Cross-linking of cell surface molecules was not required because monovalent Fab' fragments also inhibited. In contrast, a variety of other antibodies that recognize specific proteins on the MDCK cell surface failed to inhibit the recovery of resistance. Monoclonal antibodies have been raised and screened for their ability to inhibit resistance recovery. One such monoclonal antibody has been obtained that stained the lateral surface of MDCK cells. This antibody, rr1, recognized a 118-kD polypeptide in MDCK cell extracts and an 81-kD fragment released from the cell surface by trypsinization in the presence of Ca2+. Sequential immunoprecipitation with antibody rr1 and a monoclonal antibody to uvomorulin showed that this polypeptide is related to uvomorulin. The role of uvomorulin-like and liver cell adhesion molecule (L-CAM)-like polypeptides in the establishment of the epithelial occluding barrier is discussed.
Regulated expression in vitro of genes coding for formate hydrogenlyase components of Escherichia coli. (1994)

Purified FHLA, the transcriptional activator of the formate regulon from Escherichia coli, is able to efficiently stimulate transcription from the #-dependent promoters of the fdhF, hyp, and hyc transcriptional units. Expression was dependent on the presence of p, of the upstream activatory sequence (UAS), and of formate. Hypophosphite, a formate analogue, could substitute for formate in vitro suggesting that formate per se was active in regulation. The integration host factor (IHF) had a direct effect on the expression ( i n uiuo and in vitro) of the hyp and hyc genes but not of the fdhF gene. Binding of IHF within the region between the hyp and the hyc operon could be shown. A model is proposed for the transcriptional regulation of the inversely oriented hyp and hyc operons. It involves two upstream regulatory sequences, one between the hyp and the hyc operon (IRl), and the other between hycA and hycB (IR2). The UAS situated within IR1 is responsible for activation of the hyc operon, that within IR2 for activation of the hyp operon. A supramolecular transcription complex is proposed which involves the binding of IHF to a site located between the UAS and the promoter responsible for transcription of the hyc operon.
Triacsins, new inhibitors of acyl-CoA synthetase produced by Streptomyces sp. (1986)

Triacsins A and B, new inhibitors of acyl-CoA synthetase, were isolated from the cultured broth of Streptomyces sp. strain SK-1894. The structurally related compounds WS-1228 A and B, known as hypotensive vasodilators, were also found to inhibit acyl-CoA synthetase. The four compounds have in common a N-hydroxytriazene moiety in their structures. The IC50 values for triacsin A and WS-1228 A were 5.5 and 3.6 micrograms/ml, respectively.
Internalization and Processing of Bacillus anthracis Lethal Toxin by Toxin-sensitive and -resistant Cells (1989)

Anthrax lethal toxin consists of two separate proteins, protective antigen and lethal factor (LF). Certain macrophages and a mouse macrophage-like cell line, J774A.1, are lysed by low concentrations of lethal toxin. In contrast, another macrophage cell line, IC-21, and all other cell types tested were resistant to this toxin. To discover the basis for this difference, each step in the intoxication process was examined. No differences between sensitive and resistant cells were found in receptor binding or proteolytic activation of protective antigen, steps that are required prior to LF binding. To determine whether resistance results from a defect in translocation to the cytosol, we introduced LF into J774A.1 and IC-21 cells and a nonmacrophage cell line (L6 myoblast) by osmotic lysis of pinocytic vesicles. Only J774A.1 cells were lysed; no effect was observed in IC-21 and L6 cells. These results suggest that resistant cells either lack the intracellular target of LF or fail to process LF to an active form. The relatively low potency of LF introduced into J774A.1 cells by osmotic lysis suggests that protective antigen may also be required at a stage subsequent to endocytosis.
Corneal expression of the inflammatory mediator CAP37. (2002)

The findings in this study describe the extraneutrophilic expression of CAP37 in response to infection and suggest a role for CAP37 in host defense against infection in the eye.
Identification of multiple extracellular signal-regulated kinases (ERKs) with antipeptide antibodies. (1991)

A protein kinase characterized by its ability to phosphorylate microtubule-associated protein-2 (MAP2) and myelin basic protein (MBP) is thought to play a pivotal role in the transduction of signals from many receptors in response to their ligands. A kinase with such activity, named extracellular signal-regulated kinase 1 (ERK1), is activated rapidly by numerous extracellular signals, requires phosphorylation on tyrosine to be fully active, and in vitro can activate a kinase (a ribosomal S6 protein kinase) that is downstream in phosphorylation cascades. From the protein sequence predicted by the rat ERK1 cDNA, peptides were synthesized and used to elicit antibodies. The antibodies recognize both ERK1; a closely related kinase, ERK2; and a third novel ERK-related protein. Using these antibodies we have determined that ERK1 and ERK2 are ubiquitously distributed in rat tissues. Both enzymes are expressed most highly in brain and spinal cord as are their mRNAs. The third ERK protein was found in spinal cord and in testes. The antibodies detect ERKs in cell lines from multiple species, including human, mouse, dog, chicken, and frog, in addition to rat, indicating that the kinases are conserved across species. ERK1 and ERK2 have been separated by chromatography on Mono Q. Stimulation by insulin increases the phosphorylation of both kinases on tyrosine residues, as assessed by immunoblotting with phosphotyrosine antibodies, and retards their elution from Mono Q. Each of these ERKs appears to account for a distinct peak of MBP kinase activity. The activity in each peak is diminished by incubation with either phosphatase 2a or CD45. Therefore, both enzymes have similar modes of regulation and appear to contribute to the growth factor-stimulated MAP2/MBP kinase activity measured in cell extracts.
Evidence for probiotic potential of a capsular-producing Streptococcus thermophilus CHCC 3534 strain. (2009)

The purpose of this research was to evaluate the probiotic potential of an capsulated Streptococcus thermophilus CHCC 3534 strain. The strain tolerates 0.4% oxgall (bile) and was sufficiently resistant to pH as low as 2.5 for 3 hours of exposure. The strain demonstrated high adherence to human intestinal mucus, and showed unique resistance to different antibiotics. Crude extracts ofS. thermophilus CHCC 3534 contained a diffusible antimicrobial compound "bacteriocin" with a broad spectrum that inhibited the growth of closely related lactic acid bacteria and a number of food spoilage bacteria including Salmonella typhimurium and Staphylococcus aureus. The bacteriocin was heat stable, resistant to pH, inactivated by proteolytic enzymes, and resistant to a-amylase and lipase. A SDS-PAGE analysis of the partially purified bacteriocin revealed one component with a molecular weight ranging from 14.4 to 18.4 kDa. The strain may have industrial significance and represents an interesting candidate for use in biopreservation, probiotic food formulations and in the control of spoilage caused by food borne pathogens.
Adsorption of Water by Homoionic Exchange Forms of Wyoming Montmorillonite (SWy-1) (1989)

Abstract Adsorption isotherms for water on homoionic (Ca 2+ , Li + , Na + , and K + ) exchanged forms of Crook County, Wyoming, montmorillonite (CMS Source Clay SWy-1) were measured between 25° and 70°C using a vacuum microbalance having automated control of water vapor pressure. From these adsorption data, integral enthalpies and entropies of adsorption were calculated. Both quantities were negative, but decreased in magnitude with increasing amounts of adsorbed water. For all four cationic forms of the clay, the amount of initial water adsorption at 25°C and at low relative humidities was sensitive to the sample temperature during prior evacuation of water, less water being adsorbed by samples evacuated at 100°C compared with samples evacuated at 25°. For Ca- and Na-montmorillonite, these changes were reversible after several subsequent desorption/adsorption cycles, but recovery was not observed for the Li-SWy-1 clay, probably because of migration of Li + into the aluminosilicate structure.
Alpha-1-Antitrypsin Deficiency, the Serpinopathies and Conformational Disease (2000)

Alpha-1-antitrypsin deficiency results from point mutations that distort the structure of the protein to allow a unique protein-protein interaction that we have termed loopsheet polymerisation. Polymers of Z alpha 1-antitrypsin accumulate within hepatocytes to form inclusion bodies that are associated with juvenile cirrhosis and hepatocellular carcinoma. The lack of circulating protein predisposes the Z alpha 1-antitrypsin homozygote to emphysema. This process also occurs in other members of the serine proteinase inhibitor (serpin) superfamily, antithrombin, C1-inhibitor and alpha 1-antichymotrypsin, in association with thrombosis, angioedema and chronic obstructive pulmonary disease, respectively, and we have recently shown that it underlies a novel inclusion body dementia. The interaction provides a useful paradigm for other 'conformational diseases' such as Huntington's disease, Creutzfeldt-Jakob disease and the amyloidoses.
Translocation of Diacylglycerol Kinase θ from Cytosol to Plasma Membrane in Response to Activation of G Protein-coupled Receptors and Protein Kinase C (2005)

Diacylglycerol kinase (DGK) phosphorylates the second messenger diacylglycerol (DAG) to phosphatidic acid. We previously identified DGK as one of nine mammalian DGK isoforms and reported on its regulation by interaction with RhoA and by translocation to the plasma membrane in response to noradrenaline. Here, we have investigated how the localization of DGK, fused to green fluorescent protein, is controlled upon activation of G protein-coupled receptors in A431 cells. Extracellular ATP, bradykinin, or thrombin induced DGK translocation from the cytoplasm to the plasma membrane within 2-6 min. This translocation, independent of DGK activity, was preceded by protein kinase C (PKC) translocation and was blocked by PKC inhibitors. Conversely, activation of PKC by 12-O-tetradecanoylphorbol-13-acetate induced DGK translocation. Membrane-permeable DAG (dioctanoylglycerol) also induced DGK translocation but in a PKC (staurosporin)-independent fashion. Mutations in the cysteine-rich domains of DGK abrogated its hormone- and DAG-induced translocation, suggesting that these domains are essential for DAG binding and DGK recruitment to the membrane. We show that DGK interacts selectively with and is phosphorylated by PKCepsilon and -eta and that peptide agonist-induced selective activation of PKCepsilon directly leads to DGK translocation. Our data are consistent with the concept that hormone-induced PKC activation regulates the intracellular localization of DGK, which may be important in the negative regulation of PKCepsilon and/or PKCeta activity.
Differential Alteration in Intestinal Epithelial Cell Expression of Toll-Like Receptor 3 (TLR3) and TLR4 in Inflammatory Bowel Disease (2000)

Initiation and perpetuation of the inflammatory intestinal responses in inflammatory bowel disease (IBD) may result from an exaggerated host defense reaction of the intestinal epithelium to endogenous lumenal bacterial flora. Intestinal epithelial cell lines constitutively express several functional Toll-like receptors (TLRs) which appear to be key regulators of the innate response system. The aim of this study was to characterize the expression pattern of TLR2, TLR3, TLR4, and TLR5 in primary intestinal epithelial cells from patients with IBD. Small intestinal and colonic biopsy specimens were collected from patients with IBD (Crohn's disease [CD], ulcerative colitis [UC]) and controls. Non-IBD specimens were assessed by immunofluorescence histochemistry using polyclonal antibodies specific for TLR2, TLR3, TLR4, and TLR5. Primary intestinal epithelial cells (IEC) of normal mucosa constitutively expressed TLR3 and TLR5, while TLR2 and TLR4 were only barely detectable. In active IBD, the expression of TLR3 and TLR4 was differentially modulated in the intestinal epithelium. TLR3 was significantly downregulated in IEC in active CD but not in UC. In contrast, TLR4 was strongly upregulated in both UC and CD. TLR2 and TLR5 expression remained unchanged in IBD. These data suggest that IBD may be associated with distinctive changes in selective TLR expression in the intestinal epithelium, implying that alterations in the innate response system may contribute to the pathogenesis of these disorders.