gebhart/patrepeval huggingface dataset:
A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning (2015)

CRM1 is a highly conserved, RanGTPase-driven exportin that carries proteins and RNPs from the nucleus to the cytoplasm. We now explored the cargo-spectrum of CRM1 in depth and identified surprisingly large numbers, namely >700 export substrates from the yeast S. cerevisiae, ≈1000 from Xenopus oocytes and >1050 from human cells. In addition, we quantified the partitioning of ≈5000 unique proteins between nucleus and cytoplasm of Xenopus oocytes. The data suggest new CRM1 functions in spatial control of vesicle coat-assembly, centrosomes, autophagy, peroxisome biogenesis, cytoskeleton, ribosome maturation, translation, mRNA degradation, and more generally in precluding a potentially detrimental action of cytoplasmic pathways within the nuclear interior. There are also numerous new instances where CRM1 appears to act in regulatory circuits. Altogether, our dataset allows unprecedented insights into the nucleocytoplasmic organisation of eukaryotic cells, into the contributions of an exceedingly promiscuous exportin and it provides a new basis for NES prediction.
Biochemical characterization and surfactant properties of horse allergens (2001)

A new allergen from horse dander, Equ c 5 has been purified. Its biochemical and biophysical properties have been characterized and compared with those of Equ c 1, Equ c 2 and Equ c 4. Their molecular masses, determined by mass spectrometry, were 22 kDa for Equ c 1, 16 kDa for Equ c 2, 18.7 kDa for Equ c 4 and 16.7 kDa for Equ c 5. Their pI values were between 3.8 and 5.25. Equ c 2 and Equ c 5 are not glycosylated, while Equ c 4 contains a tri-antennary tri-sialylated N-linked glycan. Linkages of terminal N-acetylneuraminic acid to galactose were: alpha-(2-->6) in Equ c 4, and both alpha-(2-->3) and alpha-(2-->6) in Equ c 1. Oligosaccharide portions of Equ c 1 or Equ c 4 were barely involved in IgE-immunoreactivity. Partial N-terminal sequence of Equ c 4 shares a significant sequence homology with the rat submandibular gland protein A. No matching was found for two internal peptides of Equ c 5. Surfactant properties of horse allergens as well as other proteins were investigated. In contrast to Equ c 2 and Equ c 3, solutions of Equ c 1, Equ c 4 and Equ c 5 significantly lowered the surface tension. Relationship between a property such as this, involving oriented hydrophobic patches of a molecule and allergenicity, is addressed.
The role of the E-cadherin/catenin complex in gastrointestinal cancer. (2000)

Cancer is a genetic disease. The unstable genome of cancer cells causes tumour progression through multiple alterations in suppressor and promoter genes, leading to loss of homeostatic and gain of oncogenic functions. Invasion is the critical step in the acquisition of malignancy. It implicates a continuous molecular conversation of the cancer cells with other cells and with the extracellular matrix in which adhesion molecules are crucial. One of these, E-cadherin, is discussed in the present review. E-cadherin is a transmembrane glycoprotein that forms a complex with cytoplasmic proteins, termed catenins because they link E-cadherin to the actin cytoskeleton. E-cadherin/catenin-mediated intercellular adhesion and communication is mainly homophylic homotypic. There is compelling evidence from experiments in vitro as well as in vivo to accept that the E-cadherin/catenin complex acts as an invasion suppressor. The mechanism of this action is not only through cell-cell adhesion but also through transduction of signals to the cell's motility system. In the replication error positive human colon cancer cell line HCT-8, the alpha E-catenin gene CTNNA1 is an invasion suppressor gene. Here, the transition from the non-invasive to the invasive state was prevented by introduction into the unstable non-invasive cells of either an extra CTNNA1 or a wild type hMSH6 mismatch repair gene. beta-catenin also participates at a complex which comprises the adenomatous polyposis cancer protein APC. In colorectal cancer, mutation of either APC or beta-catenin is oncogenic. Downregulation of the E-cadherin/catenin complex may occur in several ways amongst which are gene mutations, methylation of 5'CpG dinucleotides within the promotor region of E-cadherin, tyrosine phosphorylation of beta-catenin, cell surface expression of proteoglycans sterically hindering E-cadherin and proteolytic release of fragments from the extracellular part of E-cadherin. Upregulation of the E-cadherin/catenin complex has been realized with a series of agents, some of which can be used therapeutically. In most human gastrointestinal cancers the E-cadherin/catenin or related complexes are disturbed and this underscores their pivotal role in the progression of these tumours. Mutations of the E-cadherin gene, including germline mutations, occur in diffuse gastric carcinoma, CpG methylation around the promotor region of E-cadherin in hepatocellular carcinomas and mutations of the APC tumour suppressor gene or in the beta-catenin oncogene in most colorectal cancers. The literature agrees about the disturbance of immunohistochemical patterns of E-cadherin and catenin expression in gastrointestinal cancers. Conflicting opinions do, however, exist about the prognostic value of such immunohistochemical aberrations. We doubt that immunohistochemistry of E-cadherin or catenins add prognostic value to the already used histological grading systems. In our opinion the major benefit from understanding of the E-cadherin/catenin-mediated pathways of invasion will be the development of new anti-invasive treatment strategies.
Central CRF, urocortins and stress increase colonic transit via CRF1 receptors while activation of CRF2 receptors delays gastric transit in mice (2004)

Recently characterized selective agonists and developed antagonists for the corticotropin releasing factor (CRF) receptors are new tools to investigate stress-related functional changes. The influence of mammalian CRF and related peptides injected intracerebroventricularly (i.c.v.) on gastric and colonic motility, and the CRF receptor subtypes involved and their role in colonic response to stress were studied in conscious mice. The CRF(1)/CRF(2) agonists rat urocortin 1 (rUcn 1) and rat/human CRF (r/h CRF), the preferential CRF(1) agonist ovine CRF (oCRF), and the CRF(2) agonist mouse (m) Ucn 2, injected i.c.v. inhibited gastric emptying and stimulated distal colonic motor function (bead transit and defecation) while oCRF(9-33)OH (devoid of CRF receptor affinity) showed neither effects. mUcn 2 injected peripherally had no colonic effect. The selective CRF(2) antagonist astressin(2)-B (i.c.v.), at a 20 : 1 antagonist: agonist ratio, blocked i.c.v. r/hCRF and rUcn 1 induced inhibition of gastric transit and reduced that of mUcn 2, while the CRF(1) antagonist NBI-35965 had no effect. By contrast, the colonic motor stimulation induced by i.c.v. r/hCRF and rUcn 1 and 1h restraint stress were antagonized only by NBI-35965 while stimulation induced by mUcn 2 was equally blocked by both antagonists. None of the CRF antagonists injected i.c.v. alone influenced gut transit. These data establish in mice that brain CRF(1) receptors mediate the stimulation of colonic transit induced by central CRF, urocortins (1 and 2) and restraint stress, while CRF(2) receptors mediate the inhibitory actions of these peptides on gastric transit.
Type-common and type-specific monoclonal antibody to herpes simplex virus type 1 (1980)

Hybridoma cells produced by fusing mouse myeloma cells with spleen cells from mice primed with herpes simplex virus (HSV) type 1 yielded five clones producing neutralizing antibody against homologous virus. Two clones, HCl and HC2, produced antibody capable of precipitating glycoprotein C and its precursor, whereas three clones, HD1, HD2, and HD3, produced antibody capable of precipitating glycoprotein D and its precursor. Antibody produced by the HC1 and HC2 clones neutralized HSV type 1 but not HSV type 2 or HSV type 1 strain MP, which is known to lack glycoprotein C. Antibody produced by the HD1 and HD2 clones neutralized both HSV type 1 and HSV type 2, whereas antibody produced by the HD3 clone neutralized HSV type 1 but not HSV type 2. The two clones which produced antibody to glycoprotein C and the two clones which produced type-common antibody to glycoprotein D were independently derived and not clonally related inasmuch as the antibody in each pair belonged to a different subclass of immunoglobulin.
Molecular cloning of a novel C or γ type chemokine, SCM‐1 (1995)

From human PBMC stimulated with PHA, we have isolated cDNA clones encoding a novel cytokine named SCM-1, which is significantly related to the CC and the CXC chemokines but has only the 2nd and the 4th of the four cysteines conserved in these proteins. Its gene is also distinctly mapped to human chromosome 1. SCM-1 is strongly induced in human PBMC and Jurkat T cells by PHA stimulation. Among various human tissues, SCM-1 is expressed most strongly in spleen. SCM-1 is found to be 60.5% identical to lymphotactin, a recently described murine lymphocyte-specific chemokine, which also retains only two cysteines. SCM-1 and lymphotactin may thus represent the human and murine prototypes of a novel C or gamma type chemokine family.
Regulated expression of the GAL4 activator gene in yeast provides a sensitive genetic switch for glucose repression. (1991)

Glucose (catabolite) repression is mediated by multiple mechanisms that combine to regulate transcription of the GAL genes over at least a thousandfold range. We have determined that this is due predominantly to modest glucose repression (4- to 7-fold) of expression of GAL4, the gene encoding the transcriptional activator of the GAL genes. GAL4 regulation is affected by mutations in several genes previously implicated in the glucose repression pathway; it is not dependent on GAL4 or GAL80 protein function. GAL4 promoter sequences that mediate glucose repression were found to lie downstream of positively acting elements that may be "TATA boxes." Two nearly identical sequences (10/12 base pairs) in this region that may be binding sites for the MIG1 protein were identified as functional glucose-control elements. A 4-base-pair insertion in one of these sites causes constitutive GAL4 synthesis and leads to substantial relief (50-fold) of glucose repression of GAL1 expression. Furthermore, promoter deletions that modestly reduce GAL4 expression, and therefore presumably the amount of GAL4 protein synthesized, cause much greater reductions in GAL1 expression. These results suggest that GAL4 works synergistically to activate GAL1 expression. Thus, glucose repression of GAL1 expression is due largely to a relatively small reduction of GAL4 protein levels caused by reduced GAL4 transcription. This illustrates how modest regulation of a weakly expressed regulatory gene can act as a sensitive genetic switch to produce greatly amplified responses to environmental changes.
Comprehensive Insights into the Catalytic Mechanism of Middle East Respiratory Syndrome 3C-Like Protease and Severe Acute Respiratory Syndrome 3C-Like Protease (2020)

Coronavirus 3C-like protease (3CL<sup>Pro</sup>) is a highly conserved cysteine protease employing a catalytic dyad for its functions. 3CL<sup>Pro</sup> is essential to the viral life cycle and, therefore, is an attractive target for developing antiviral agents. However, the detailed catalytic mechanism of coronavirus 3CL<sup>Pro</sup> remains largely unknown. We took an integrated approach of employing X-ray crystallography, mutational studies, enzyme kinetics study, and inhibitors to gain insights into the mechanism. Such experimental work is supplemented by computational studies, including the prereaction state analysis, the ab initio calculation of the critical catalytic step, and the molecular dynamic simulation of the wild-type and mutant enzymes. Taken together, such studies allowed us to identify a residue pair (Glu-His) and a conserved His as critical for binding; a conserved GSCGS motif as important for the start of catalysis, a partial negative charge cluster (PNCC) formed by Arg-Tyr-Asp as essential for catalysis, and a conserved water molecule mediating the remote interaction between PNCC and catalytic dyad. The data collected and our insights into the detailed mechanism have allowed us to achieve a good understanding of the difference in catalytic efficiency between 3CL<sup>Pro</sup> from SARS and MERS, conduct mutational studies to improve the catalytic activity by 8-fold, optimize existing inhibitors to improve the potency by 4-fold, and identify a potential allosteric site for inhibitor design. All such results reinforce each other to support the overall catalytic mechanism proposed herein.
An Audio View of (L A )TE XD ocuments (1992)

Till now, (LA)TEX has been used to generate typeset documents. This paper points out an alternative view — the generation of audio renderings. The (LA)TEX typesetting source captures a lot of document structure which is then used to typeset the document. This can be exploited to convey document structure in audio renderings of the document as well. This becomes especially important when dealing with mathematical documents. Our approach attempts to develop notions of audio formatting similar to the well-understood notions of visual formatting and layout. Our goal is to do for the audio document what (LA)TE Xh as done for the printed document.
Resolution of discrete and continuous molecular size distributions by means of diffusion-ordered 2D NMR spectroscopy (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTResolution of discrete and continuous molecular size distributions by means of diffusion-ordered 2D NMR spectroscopyKevin F. Morris and Charles S. Johnson Jr.Cite this: J. Am. Chem. Soc. 1993, 115, 10, 4291–4299Publication Date (Print):May 1, 1993Publication History Published online1 May 2002Published inissue 1 May 1993https://pubs.acs.org/doi/10.1021/ja00063a053https://doi.org/10.1021/ja00063a053research-articleACS PublicationsRequest reuse permissionsArticle Views2198Altmetric-Citations322LEARN 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
Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response (2001)

This study investigated whether soluble paracrine factors mediated Salmonella-induced IL-8 expression in polarized model intestinal epithelia. We found that the basolateral media of model epithelia that had been apically infected with Salmonella typhimurium for a short period (10 minutes) could activate IL-8 secretion in virgin model epithelia, demonstrating that a proinflammatory factor (PIF) was indeed present. Initial characterization found that PIF was a heat-stable protein with a molecular mass of about 50 kDa that acts on the basolateral, but not apical, surface of model intestinal epithelia to elicit IL-8 secretion. PIF was not present in the media of model epithelia stimulated with other inducers of IL-8 secretion (TNF-alpha or carbachol) but was present in S. typhimurium supernatants, indicating PIF is of bacterial origin. PIF was purified from bacterial culture supernatants by anion/cation exchange chromatography and SDS-PAGE and found by using microsequencing to be the protein flagellin. In support of this finding, flagellin-deficient S. typhimurium mutants did not secrete detectable levels of PIF (i.e., a bioactivity that induced IL-8 secretion when placed basolaterally on model epithelia). Furthermore, viable flagellin-deficient mutant organisms (fliC/fljB and flhD) failed to elicit IL-8 secretion when added apically to model intestinal epithelia. These findings indicate that translocation of flagellin across epithelia, subsequent to apical epithelial-S. typhimurium interaction, is likely a major means of activating a mucosal inflammatory response.
Effects of S -Glutathionylation and S -Nitrosylation on Calmodulin Binding to Triads and FKBP12 Binding to Type 1 Calcium Release Channels (2005)

This study shows that the combination of glutathione (GSH) plus hydrogen peroxide (H2O2) promotes the S-glutathionylation of ryanodine receptor type 1 (RyR1) Ca2+ release channels, and confirms their joint S-glutathionylation and S-nitrosylation by S-nitrosoglutathione (GSNO). In addition, we show that 35S-labeled 12-kDa FK506-binding protein ([35S]FKBP12) bound with a Kd of 13.1 nM to RyR1 present in triads or heavy sarcoplasmic reticulum vesicles; RyR1 S-nitrosylation by NOR-3 or GSNO, but not S-glutathionylation, specifically increased by four- to fivefold this Kd value. RyR1 redox modifications also increased the Kd of [35S]calmodulin binding to triads without affecting Bmax. RyR1 S-glutathionylation (induced by GSH plus H2O2) or RyR1 S-nitrosylation (produced by NOR-3) increased by approximately six- or twofold, respectively, the Kd of apocalmodulin (apoCaM) or Ca2+-calmodulin (CaCaM) binding to triads. Likewise, the combined S-glutathionylation and S-nitrosylation of RyR1 induced by GSNO increased by fourfold the Kd of CaCaM binding to triads and abolished apoCaM binding. As both FKBP12 and CaCaM inhibit RyR1, decreased FKBP12 binding to RyR1 and/or decreased CaCaM binding to either RyR1 or dihydropyridine receptor in triad preparations may cause the reported enhanced activation of Ca2+-induced Ca2+ release kinetics mediated by S-glutathionylation/S-nitrosylation. We discuss possible consequences of these redox modifications on RyR1-mediated Ca2+ release in physiological or pathological conditions.
Automatic Atrial Threshold Measurement and Adjustment in Pediatric Patients (2009)

ACM measures atrial thresholds reliably in pediatric patients with both endocardial and epicardial leads, allowing its use in both. Constant high intrinsic atrial rate may prevent automatic threshold measurement in young children.
An Euclidean distance measure between covariance matrices of speech cepstra for text-independent speaker recognition (2002)

It has been shown that similarity measures between covariance matrices of speech cepstra provide good speaker recognition. We propose a transformation from covariance matrices to vectors in Euclidean space, which allows the use of the Euclidean distance measure. We show how this measure is related to the Gaussian log-likelihood measure between covariance matrices and we compare the performance. The Euclidean measure has comparable performance and allows various manipulations in Euclidean space.
Studies on the Biosynthesis of the Antibiotic Moenomycin A (2000)

Feeding experiments ( 13C and 15N-labeled precursors) shed light on the biosynthetic origin of the chromophore (unit A of 1), the N-acetyl groups, the 4-C-methyl group of the moenuronamide unit (part F of 1), the sugar units, and the lipid part (unit I of 1) of the antibiotic moenomycin A(1). The lipid part is completely isoprenoid and is constructed via the non-mevalonate pathway. The central C 10 part originates from a precursor like geranyl or linalyl diphosphate and is formed by a route involving ring formation between C-2 and C-6 of the monoterpene unit, two successive rearrangements to give a 7-membered ring intermediate and cleavage of the ring between C-5 and C-11 (moenocinol numbering).
Assisting network intrusion detection with reconfigurable hardware (2003)

String matching is used by Network Intrusion Detection Systems (NIDS) to inspect incoming packet payloads for hostile data. String-matching speed is often the main factor limiting NIDS performance. String-matching performance can be dramatically improved by using Field-Programmable Gate Arrays (FPGAs); accordingly, a "regular-expression to FPGA circuit" module generator has been developed. The module generator extracts strings from the Snort NIDS rule-set, generates a regular expression that matches all extracted strings, synthesizes a FPGA-based string matching circuit, and generates an EDIF netlist that can be processed by Xilinx software to create an FPGA bitstream. The feasibility of this approach is demonstrated by comparing the performance of the FPGA-based string matcher against the software-based GNU regex program. The FPGA-based string matcher exceeds the performance of the software-based system by 600x for large patterns.
Design considerations for high-frequency continuous-time filters and implementation of an antialiasing filter for digital video (1990)

An approach that has made possible the integration of video frequency continuous-time filters with wide dynamic range is discussed. The tuning scheme necessary to maintain the stable and accurate frequency response in the presence of temperature variations, process tolerance, and aging is described. Detailed design techniques specific to high-frequency operation are introduced to implement a 5-V, seventh-order elliptic analog magnitude filter for antialiasing in digital video applications. The filter, based on a G/sub m/-C technique, exhibits a dynamic range of 61 dB and dissipates a power of 75 mW. Ninety-two chips from various wafers and two different process runs were tested. Seventy-five percent of the fabricated chips were functional, and 63% of them met the commercial-grade specifications in spite of an error in the layout which forced the phase control circuitry to perform suboptimally.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
GSK3β mediates muscle pathology in myotonic dystrophy (2012)

Myotonic dystrophy type 1 (DM1) is a complex neuromuscular disease characterized by skeletal muscle wasting, weakness, and myotonia. DM1 is caused by the accumulation of CUG repeats, which alter the biological activities of RNA-binding proteins, including CUG-binding protein 1 (CUGBP1). CUGBP1 is an important skeletal muscle translational regulator that is activated by cyclin D3-dependent kinase 4 (CDK4). Here we show that mutant CUG repeats suppress Cdk4 signaling by increasing the stability and activity of glycogen synthase kinase 3β (GSK3β). Using a mouse model of DM1 (HSA(LR)), we found that CUG repeats in the 3' untranslated region (UTR) of human skeletal actin increase active GSK3β in skeletal muscle of mice, prior to the development of skeletal muscle weakness. Inhibition of GSK3β in both DM1 cell culture and mouse models corrected cyclin D3 levels and reduced muscle weakness and myotonia in DM1 mice. Our data predict that compounds normalizing GSK3β activity might be beneficial for improvement of muscle function in patients with DM1.