gebhart/patrepeval huggingface dataset:
Characterization of a point mutation in aspartylglucosaminidase gene: evidence for a readthrough of a translational stop codon (1994)

We have identified a novel aspartylglucosaminuria (AGU) mutation in the second exon of the aspartylglucosaminidase (AGA) gene resulting in a lysosomal storage disease in a Puerto Rican pedigree. This T192-->A transversion causes replacement of Cys64 with a premature translational stop codon and the patients' fibroblasts exhibit dramatically decreased steady-state levels of AGA mRNA. Immunofluorescence analysis and analysis of immunoprecipitated metabolically labelled AGA polypeptides from patient fibroblasts unexpectedly revealed traces of normally sized inactive AGA precursor polypeptide instead of the predicted short polypeptide of 40 amino acids, thus demonstrating readthrough due to suppression of the premature translational stop codon. The translated AGA precursor is not processed further and remains inactive. The Cys64 substitution evidently disturbs the folding of the nascent polypeptide in the endoplasmic reticulum, thus preventing activation by proteolytic cleavage.
Mechanisms of suppression of inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells by andrographolide (2000)

Andrographolide, an active component found in leaves of Andrographis paniculata, has been reported to exhibit nitric oxide (NO) inhibitory property in endotoxin-stimulated macrophages, however, the detailed mechanisms remain unclear. In the present study we investigated the effect of andrographolide on the expression of inducible NO synthase (iNOS) mRNA, protein, and enzyme activity in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma). RAW 264.7 cells stimulated with LPS/IFN-gamma activated NO production; in this condition andrographolide (1-100 microM) inhibited NO production in a dose-dependent manner with an IC(50) value of 17.4+/-1.1 microM. Andrographolide also reduces the expression of iNOS protein level but without a significant effect on iNOS mRNA. The reduction of iNOS activity is thought to be caused by decreased expression of iNOS protein. In a protein stability assay, andrographolide moderately but significantly reduced the amount of iNOS protein as suggested by accelerating degradation. Furthermore, andrographolide also inhibited total protein de novo synthesis as demonstrated by [(35)S]-methionine incorporation. As a whole, these data suggest that andrographolide inhibits NO synthesis in RAW 264.7 cells by reducing the expression of iNOS protein and the reduction could occur through two additional mechanisms: prevention of the de novo protein synthesis and decreasing the protein stability via a post-transcriptional mechanism. It is also possible that inhibition of iNOS protein expression and NO production under immune stimulation and/or bacteria infection may explain, in part, the beneficial effects of andrographolide as an anti-inflammatory agent.
Damping of CoxFe80−xB20 ultrathin films with perpendicular magnetic anisotropy (2013)

We use vector network analyzer ferromagnetic resonance to study the perpendicularly magnetized CoFeB films. We report the dependence of the anisotropy, the g-factor, and the damping upon the Fe-Co compositional ratio in the amorphous and crystalline states. The damping and the anisotropy increase upon crystallization but vary little with composition on the Fe-rich side. At high cobalt content, the anisotropy lowers while the damping and the sample inhomogeneity increase. The compositional dependences seem to extrapolate from the properties of bulk CoFe alloys, with differences that can be understood from the correlated impacts of spin-orbit interaction on anisotropy, g-factor, and damping.
TISSUE RENIN-ANGIOTENSIN SYSTEM:A Site of Drug Action? (1997)

In this review, we present background material that provides partial support for a tissue renin-angiotensin system (RAS). Evidence for the existence of this system relied in part on the use of drugs, which has entailed using low doses or concentrations of angiotensin-converting enzyme inhibitors, renin inhibitors, and angiotensin antagonists to block the RAS in vascular beds and in isolated arteries or organs. Other evidence for a tissue RAS has depended upon measurements of the components of the system, i.e. enzymes, substrates, and mRNAs for these proteins. All of these components were first believed to be present in the heart and blood vessels; however, it is now known that renin in the circulating blood derived from the kidney is used for the local synthesis of angiotensins. The main emphasis of the review is on the renal RAS because it is believed that the local RAS is most prominent in this organ. The renal RAS is probably involved in the long-rather than short-term regulation of renal vascular resistance and maintenance of normal blood pressure through the regulation of sodium reabsorption.
Structural and Spectroscopic Properties of Aryl Substituted Aminoboranes as Model Compounds and Synthons for B/C/N Materials and New Fluorescent Systems (2009)

Abstract Tetraphenylaminoborane ( 1 ) and carbazonyldiphenylborane ( 2 ) are examples for isolated BN bonds completely substituted by aryl ligands, which enable π‐interactions. Such systems can serve as building blocks for new fluorescent polymers and are also suitable precursors for B/C/N materials. The compounds were characterized by multinuclear NMR spectroscopy, UV/Vis spectroscopy, and single‐crystal X‐ray diffractometry. Both compounds 1 and 2 are principal structures for tricoordinate, aryl substituted BN bonds. Compound 1 crystallizes in the monoclinic crystal system in the space group P 2 1 , with two formula units per unit cell with a = 9.8236(9) Å, b = 9.2743(8) Å, c = 10.7426(10) Å; α = 90°, β = 107.228(4)°, γ = 90°, Z = 2, V = 934.81(15) Å 3 (final R indices [ I &gt; 2 σ ( I )]: R 1 = 0.0597; wR 2 = 0.1489) and compound 2 crystallizes in the monoclinic crystal system of the space group C 2/ c . The unit cell contains four formula units as a set of two pairs of diastereomers. The cell parameters are a = 17.404(4) Å, b = 11.020(2) Å, c = 9.4195(19) Å; α = 90°, β = 91.45(3)°, γ = 90°, Z = 4, V = 1805.9(6) Å 3 (final R indices [ I &gt; 2 σ ( I )]: R 1 = 0.038; wR 2 = 0.0847). The UV/Vis spectra of 1 and 2 reveal strong absorptions (240 nm and 285 nm) for 1 and broad features (260 nm and 290 nm) for 2 . The 11 B NMR spectroscopic data of 1 (48.7 ppm) and 2 (53.0 ppm) clearly indicate tricoordinate BN systems in solution with a weaker BN π‐interaction compared to dialkylborylamines.
Textile Sensing Interfaces for Cardiopulmonary Signs Monitoring (2005)

A wearable system able to monitor cardiopulmonary vital signs is presented. The innovative technological core of the system is based on the use of a textile conformable sensing cloth, where conducting and piezoresistive materials are integrated in form of fibres and yarns, giving rise to fabric sensors, electrodes and connections. Electrocardiogram and impedance pneumography signals are acquired through the same textile electrodes, while to discriminate between abdominal and thoracic activity, two piezoresistive fabric sensors are placed below the lower end of the sternum and at the level of the navel for recording the thorax and the abdominal pattern of breathing. The use of impedance pneumography methodology reduces the artefacts due to the movement, phonation and rib cage expansions disjointed from respiratory mechanics. All the signals are acquired simultaneously allowing a comparative control of the cardiopulmonary activity and artefacts rejection.
Immunization Against Urinary Tract Infection with a Multi-Valent Vaginal Vaccine (1991)

Systemic and local immune responses are thought to play an important role in susceptibility to urinary tract infection. In an attempt to boost local immunity, a vaccine was administered parenterally or vaginally to two mouse strains. Both routes of immunization increased the number of splenic antibody-forming cells against the bacterial strains in the vaccine. Following vaginal or parenteral immunization and subsequent induction of cystitis with live E. coli, immunized animals had fewer viable bladder E. coli than non-immunized animals.
X-ray Structure of the 154-Amino-Acid Form of Recombinant Human Basic Fibroblast Growth Factor. Comparison with the Truncated 146-Amino-Acid Form (1997)

The crystal structure of the 154-amino-acid form of human basic fibroblast growth factor (hbFGF154), probably representing the intact form of hbFGF as deduced from the open reading frame of hbFGF cDNA, was determined by X-ray crystallography and refined to a crystallographic residual of 19.0% for all data between 20.0 and 2.0 A resolution. Crystals were obtained from recombinant hbFGF154 expressed in E. coli. hbFGF154 has the same overall structure as the N-terminus truncated 146-amino-acid form. The structure has a Kunitz-type fold and is built of 12 beta-strands of which six antiparallel strands form a beta-sheet barrel. In the structure it was possible to locate two additional residues at the N terminus and the last three C-terminal amino-acid residues, which seem to be disordered in all but one of the reported structures of the truncated form of hbFGF. The C-terminal amino-acid residues are part of the last beta-strand through the formation of a hydrogen bond between the main-chain amide group of Ala152 and the carbonyl O atom of Pro28. An apparent phosphate ion is bound within the basic region on the surface of the molecule and has as ligands the side chains of Asn35, Arg128 and Lys133 and two water molecules. A slightly different hydrogen-bonding pattern to the phosphate ion is observed as compared with the sulfate ions in the truncated forms [Eriksson, Cousens & Matthews (1993). Protein Sci. 2, 1274-1284; Zhang, Cousens, Barr & Sprang (1991). Proc. Natl Acad. Sci. USA, 88, 3446-3450]. One molecule of beta-mercaptoethanol forms a disulfide bridge to Cys77.
Pheromone Signalling in Saccharomyces cerevisiae Requires the Small GTP-Binding Protein Cdc42p and Its Activator CDC24 (1995)

Pheromone signalling in Saccharomyces cerevisiae is mediated by the STE4-STE18 G-protein beta gamma subunits. A possible target for the subunits is Ste20p, whose structural homolog, the serine/threonine kinase PAK, is activated by GTP-binding p21s Cdc42 and Rac1. The putative Cdc42p-binding domain of Ste20p, expressed as a fusion protein, binds human and yeast GTP-binding Cdc42p. Cdc42p is required for alpha-factor-induced activation of FUS1.cdc24ts strains defective for Cdc42p GDP/GTP exchange show no pheromone induction at restrictive temperatures but are partially rescued by overexpression of Cdc42p, which is potentiated by Cdc42p12V mutants. Epistatic analysis indicates that CDC24 and CDC42 lie between STE4 and STE20 in the pathway. The two-hybrid system revealed that Ste4p interacts with Cdc24p. We propose that Cdc42p plays a pivotal role both in polarization of the cytoskeleton and in pheromone signalling.
Immunoregulatory Effects of Glandular Kallikrein from the Salivary Submandibular Gland of Rats (1997)

A protein of 40 kD molecular weight was isolated from the salivary submandibular glands of male rats. The protein catalyzed the hydrolysis of alpha-N-benzoyl-L-arginine ethyl ester. This esterase activity was inhibitable with the protease inhibitor aprotinin. The sequence of the first 25 amino acids of this protein was identical to that of rat glandular kallikrein (rGK). When added to cultures of murine lymph node cells suboptimally stimulated with the T cell mitogen concanavalin A, rGK markedly stimulated the proliferative activity of these cells. When injected into mice, rGK suppressed the contact sensitivity response to picryl chloride, a form of delayed-type hypersensitivity. Similar in vitro and in vivo effects were induced with GK from porcine pancreas (pGK). Moreover, the aforementioned in vitro and in vivo effects were abolished by aprotinin either added to the tissue culture medium or injected into the animals immediately before rGK or pGK. This demonstrates that the enzymatic activity of rGK and pGK is important for the induction of immunoregulatory effects. These results suggest that rGK is a systemic immunoregulatory enzyme with immunosuppressive potential. GK is the first example for systemic immunoregulation by an enzyme, the secretion of which is under neuroendocrine control.
Structural and functional analysis of a promoter of the human granulin/epithelin gene (1996)

Granulins (grns) or epithelins (epis) are peptides with molecular masses of approx. 6 kDa that modulate the growth of cells. The precursor for the grns/epis, which might itself be biologically active, is a secreted glycoprotein containing multiple repeats of the grn/epi motif. Grn/epi mRNA occurs widely in vivo, particularly in tissues rich in epithelial and haematopoietic cells. To understand better the role of the gene products for grn/epi it is important to determine the patterns of grn/epi gene expression and how this is regulated. To assist in this we have obtained the 5' sequence of the human grn/epi gene, and using chimaeras of the grn/epi -5' sequence and the chloramphenicol acetyltransferase gene we have shown a strong promoter activity associated with the 5' sequence of the human grn/epi gene. We have further delineated regions of the 5' sequence that confer high-level expression on the chimaeric gene.
Promotion of Mitochondrial Membrane Complex Assembly by a Proteolytically Inactive Yeast Lon (1996)

Afg3p and Rca1p are adenosine triphosphate (ATP)-dependent metalloproteases in yeast mitochondria. Cells lacking both proteins exhibit defects in respiration-dependent growth, degradation of mitochondrially synthesized proteins, and assembly of inner-membrane complexes. Defects in growth and protein assembly, but not in degradation, were suppressed by overproduction of yeast mitochondrial Lon, an ATP-dependent serine protease. Suppression by Lon was enhanced by inactivation of the proteolytic site and was prevented by mutation of the ATP-binding site. It is suggested that the mitochondrial proteases Lon, Afg3p, and Rca1p can also serve a chaperone-like function in the assembly of mitochondrial protein complexes.
Assessing the Disease-Liability of Mutations in CFTR (2012)

Over 1900 mutations have been reported in the cystic fibrosis transmembrane conductance regulator (CFTR), the gene defective in patients with cystic fibrosis. These mutations have been discovered primarily in individuals who have features consistent with the diagnosis of CF. In some cases, it has been recognized that the mutations are not causative of cystic fibrosis but are responsible for disorders with features similar to CF, and these conditions have been termed CFTR-related disorders or CFTR-RD. There are also mutations in CFTR that do not contribute to any known disease state. Distinguishing CFTR mutations according to their penetrance for an abnormal phenotype is important for clinical management, structure/function analysis of CFTR, and understanding the molecular and cellular mechanisms underlying CF.
Negative Influence of IL3 on the Expansion of Human Cord Blood In Vivo Long-Term Repopulating Stem Cells (2000)

Identification of culture conditions that support expansion or even long-term maintenance of in vivo repopulating human hematopoietic stem cells is still a major challenge. Using a combination of FLT3 ligand (FL), Stem Cell Factor (SCF), Thrombopoietin (TPO) and Interleukin 6 (IL6), we cultured cord blood (CB) CD34+ cells for up to 12 weeks and transplanted their progeny into sublethally irradiated NOD/SCID mice. Bone marrow engraftment was considered successful when recipients contained measurable numbers of human CD45+, CD71+ and Glycophorin A+(GpA) cells 8 weeks after transplantation. Twelve-week expanded cells with FL+SCF+TPO+IL6 successfully engrafted all of the recipients and human CD45(+)+CD71(+)+GpA(+) cells represented 4.3 to 22.4% of bone marrow. Substitution of IL6 with IL3 led to an even better expansion of cells and a similar clonogenic progenitor output in the first 8 weeks of culture; however, LTC-IC output increased up to week 6 and then decreased and disappeared. By contrast, with FL+SCF+TPO+IL6, LTC-IC kept increasing up to week 12. Four-week cultured cells with FL+SCF+TPO+IL3 less efficiently engrafted NOD/SCID mice, both as measured by frequency of positive recipients (4 out of 10) and percentage of engrafted human cells (< or =2%). Six-week expanded cells failed to engraft. This study provides evidence that many, but not all, of the so-called "early acting" cytokines, can sustain long-term maintenance and even expansion of human primitive in vivo repopulating stem cells. In particular, in the culture conditions used in this study, the presence of IL3 greatly reduces the repopulating potential of expanded CD34+ CB cells.
Gilbert multiplier as an active mixer with conversion gain bandwidth of up to 17 GHz (1991)

A monolithically integrated mixer based on a Gilbert cell multiplier for ultra-broadband applications has been produced in self-aligning 1 μm silicon bipolar technology. Positive power conversion gain bandwidths for RF and LO up to 17.3 GHz and for the intermediate frequency (IF) up to 13 GHz were measured. The corresponding −3dB frequencies are 9 GHz for RF and LO (IF = 100 MHz) and 8 GHz(fLO = 1 GHz) for IF.
Significance of different J chain profiles in human tissues: generation of IgA and IgM with binding site for secretory component is related to the J chain expressing capacity of the total local immunocyte population, including IgG and IgD producing cells, and depends on the clinical state of the tissue. (1984)

Most IgA producing cells in normal intestinal and nasal mucosa synthesize dimers or larger polymers as evidenced by 90% cytoplasmic affinity for secretory component (SC) in vitro and almost 100% J chain positivity. The comparable median figures for normal exocrine glands (salivary, lacrimal, lactating mammary) were 84% and 92%, respectively. Conversely, IgA immunocytes in the subepithelial areas of palatine tonsils and in other extraglandular tissues, such as inflamed gingiva and intestinal submucosa, showed only 16-28% SC binding capacity and 18-51% J chain positivity. Similarly decreasing J chain expression, from glandular to extraglandular sites, was revealed not only for IgM immunocytes but also for those producing IgD or IgG, particularly the latter. This observation indicated more extensive overall clonal maturation in tissues without glandular elements since J chain expression seems to be a feature of relatively early memory B cells. The results were supported by studies in patients with selective IgA deficiency. Inflammatory disease caused significantly reduced SC binding capacity of IgA cells, both in intestinal mucosa and tonsils; this change was paralleled by decreased J chain expression, not only for mucosal and tonsillar IgA cells but also for mucosal IgG cells, suggesting local appearance of more mature clones. The resulting change to production of monomeric IgA may adversely affect secretory immunity and thus contribute to perpetuation of chronic inflammatory disease.
Chemistry at the Nano−Bio Interface (2009)

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTChemistry at the Nano−Bio InterfaceThomas E. Mallouk and Peidong YangCite this: J. Am. Chem. Soc. 2009, 131, 23, 7937–7939Publication Date (Web):June 10, 2009Publication History Published online10 June 2009Published inissue 17 June 2009https://doi.org/10.1021/ja9038104Copyright © 2009 American Chemical SocietyRequest reuse permissions This publication is free to access through this site. Learn MoreArticle Views8189Altmetric-Citations21LEARN 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 InReddit PDF (67 KB) Get e-AlertscloseSUBJECTS:Cells,Drug delivery,Genetics,Metal nanoparticles,Nanoparticles Get e-Alerts
Blocking Periodontal Disease Progression by Inhibiting Tissue‐Destructive Enzymes: A Potential Therapeutic Role for Tetracyclines and Their Chemically‐Modified Analogs (1993)

Tetracyclines (TCs) have wide therapeutic usage as antimicrobial agents; these drugs (e.g., minocycline, doxycycline) remain useful as adjuncts in periodontal therapy. However, TCs also have non-antimicrobial properties which appear to modulate host response. In that regard, TCs and their chemically-modified analogs (CMTs) have been shown to inhibit the activity of the matrix metalloproteinase (MMP), collagenase. The activity of this enzyme appears crucial in the destruction of the major structural protein of connective tissues, collagen. Such pathologic collagenolysis may be a common denominator in tissue destructive diseases such as rheumatoid and Osteoarthritis, diabetes mellitus, bullous dermatologic diseases, corneal ulcers, and periodontitis. The mechanisms by which TCs affect and, possibly, diminish bone resorption (a key event in the pathogenesis of periodontal and other diseases) are not yet understood. However, a number of possibilities remain open for investigation including the following: TCs may 1) directly inhibit the activity of extracellular collagenase and other MMPs such as gelatinase; 2) prevent the activation of its proenzyme by scavenging reactive oxygen species generated by other cell types (e.g. PMNs, osteoclasts); 3) inhibit the secretion of other collagenolytic enzymes (i.e. lysosomal cathepsins); and 4) directly affect other aspects of osteoclast structure and function. Several recent studies have also addressed the therapeutic potential of TCs and CMTs in periodontal disease. These drugs reduced excessive gingival collagenase activity and severity of periodontal breakdown in rats infected with Porphyromonas gingivalis and in diabetic rats. Furthermore, the latter drug (CMT) was not associated with the emergence of TC-resistant microorganisms. In human clinical trials, low-dose doxycycline therapy substantially reduced collagenase activity in the gingiva and GCF, and prevented the loss of attachment in adult periodontitis. Clearly, the non-antimicrobial properties of TCs have enormous medical and dental therapeutic potential since these drugs can inhibit the activity of MMPs and their degradation of non-osseous and osseous connective tissues. J Periodontol 1993; 64:819-827.