gebhart/patrepeval huggingface dataset:
Insulin-like growth factor binding protein 2 enhances glioblastoma invasion by activating invasion-enhancing genes. (2003)

Comparison of gene expressing profiles between gliomas with different grades revealed frequent overexpression of insulin-like growth factor binding protein 2 (IGFBP2) in glioblastoma (GBM), the most advanced stage of glioma. To determine whether IGFBP2 is involved in the proliferative and invasive nature of GBM, we established stable SNB19 GBM cell lines that overexpress IGFBP2. Although there was no marked difference in the cell growth between IGFBP2 overexpressing SNB19(BP2) lines when compared with the control cells, these clones showed significantly increased invasive rates when compared with the parental or vector transfected SNB19 cells. Total RNAs from controls and SNB19(BP2) clones were used for microarray analysis to detect IGFBP2-mediated alterations in gene expression. When compared with parental or vector-transfected control cells, SNB19(BP2) cells consistently showed 3-5-fold increase in the expression of matrix metalloproteinase-2 (MMP-2) as well as other invasion related genes. Increased MMP-2 expression in SNB19(BP2) cells was subsequently confirmed by real time reverse-transcription PCR, Western blotting, and gelatin zymography. Furthermore, consistent with increased MMP-2 expression in SNB19(BP2) cells, transient transfection of a MMP-2 promoter/luciferase reporter also resulted in 3-6-fold higher luciferase activity in SNB19(BP2) cells than in parental or vector-transfected control cells. Finally, tissue microarray analysis of 68 GBM tissue specimens showed a significant correlation between the overexpression of IGFBP2 and elevated MMP-2 expression. Taken together, our data provide evidence that IGFBP2 contributes to glioma progression in part by enhancing MMP-2 gene transcription and in turn tumor cell invasion.
Common Profile for Presence (CPP) (2004)

At the time this document was written, numerous presence protocols were in use (largely as components of commercial instant messaging services), and little interoperability between services based on these protocols has been achieved. This specification defines common semantics and data formats for presence to facilitate the creation of gateways between presence services.
Inhibition of pulmonary metastasis by Z-100, an immunomodulatory lipid-arabinomannan extracted from Mycobacterium tuberculosis, in mice inoculated with B16 melanoma (1997)

The anti-metastatic effect of Z-100, an immunomodulatory arabinomannan extracted from Mycobacterium tuberculosis, was investigated in mice bearing B16 melanoma cells. Treatment of BF10 mice implanted with high metastatic B16F10 melanoma cells with a 10 mg/kg dose of Z-100 resulted in the reduction of experimental pulmonary metastasis as compared with that of BF10 mice treated with saline. The number of pulmonary metastatic colonies in BF1 mice (mice implanted with low metastatic B16F1 melanoma cells) was greatly increased after the inoculation of CD4+ CD11b+ CD281+ TCR alphabeta+ type 2 T cells (F10-Th2 cells) derived from BF10 mice, while only a few metastatic colonies were demonstrated in lungs of BF1 mice inoculated with naive CD4+ T cells. However, the numbers of metastatic colonies in BF1 mice were not increased when they were inoculated with the F10-Th2 cell fraction derived from Z-100-treated BF10 mice and the generation of F10-Th2 cells in BF10 mice was effectively suppressed by the Z-100 treatment. These results suggest that Z-100 inhibits pulmonary metastasis of B16 melanoma through the regulation of tumor-associated Th2 cells, which are a key cell in the acceleration of tumor metastasis.
The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bɛ at Ser539 and the microtubule-associated protein tau at Thr212: potential role for DYRK as a glycogen synthase kinase 3-priming kinase (2001)

The substrate specificity of glycogen synthase kinase 3 (GSK3) is unusual in that efficient phosphorylation only occurs if another phosphoserine or phosphothreonine residue is already present four residues C-terminal to the site of GSK3 phosphorylation. One such substrate is the epsilon-subunit of rat eukaryotic protein-synthesis initiation factor 2B (eIF2Bepsilon), which is inhibited by the GSK3-catalysed phosphorylation of Ser(535). There is evidence that GSK3 is only able to phosphorylate eIF2Bepsilon at Ser(535) if Ser(539) is already phosphorylated by another protein kinase. However, no protein kinases capable of phosphorylating Ser(539) have so far been identified. Here we show that Ser(539) of eIF2Bepsilon, which is followed by proline, is phosphorylated specifically by two isoforms of dual-specificity tyrosine phosphorylated and regulated kinase (DYRK2 and DYRK1A), but only weakly or not at all by other 'proline-directed' protein kinases tested. We also establish that phosphorylation of Ser(539) permits GSK3 to phosphorylate Ser(535) in vitro and that eIF2Bepsilon is highly phosphorylated at Ser(539) in vivo. The DYRK isoforms also phosphorylate human microtubule-associated protein tau at Thr(212) in vitro, a residue that is phosphorylated in foetal tau and hyperphosphorylated in filamentous tau from Alzheimer's-disease brain. Phosphorylation of Thr(212) primes tau for phosphorylation by GSK3 at Ser(208) in vitro, suggesting a more general role for DYRK isoforms in priming phosphorylation of GSK3 substrates.
Protocols for Oligonucleotides and Analogs (1993)

When first conceived, not only was the aim of Protocols for Oligo­ nucleotides and Analogs to provide wide coverage of the ohgonuc- otide chemistry field for readers who are well versed within the field, but also to give investigators just entering into the field a new perspective. The very first book on this topic was edited and published by Michael Gait in 1984, in whose laboratory I encountered the newer aspects of oligonucleotide chemistry. Since then, oligonucleotide research has developed to such an extent that its uses extend far beyond basic studies, and now find wide application throughout clinical science as well. Until recently, the major application of oligonucleotides has been in the area of DNA-based diagnostic and "antisense oligonucleotid- based therapeutic approaches. However, oligonucleotides are now also being used as therapeutic agents and are thus frequently found in clinical trials in humans. Synthesis of unmodified oligonucleotides using automated synthe­ sizers has become a common practice in numerous laboratories. How­ ever, improvements on the existing techniques and the introduction of ever newer methods for oligonucleotide synthesis is constantly driving ahead in the leading research laboratories. And several new oligonucle­ otide analogs have been synthesized and studied for their individual prop­ erties in recent years. The present volume strives to bring the readers the most up-to-date information on the newest aspects of synthesis of oligo­ nucleotides and their analogs. A separate volume covers synthesis of oligonucleotide conjugates, along with most of the analytical techniques presently used for analysis of oligonucleotides
The brain‐specific protein MLC1 implicated in megalencephalic leukoencephalopathy with subcortical cysts is expressed in glial cells in the murine brain (2003)

The human MLC1 gene (also known as KIAA0027 and WKL1) and its murine orthologue (Mlc1) encode a putative transmembrane protein expressed primarily in brain. Recessive mutations within human MLC1 cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), whereas a missense mutation resulting in a methionine substitution within a transmembrane leucine string of MLC has been implicated in catatonic schizophrenia in a large pedigree. To gain insight into the function of the MLC protein and to elucidate the pathophysiology of these severe neurodegenerative disorders, information on the cellular and regional distribution of the murine Mlc1, as well as the developmental pattern of Mlc1 expression in brain, is required. Using in situ hybridization (ISH), Mlc1 mRNA was exclusively detected in glial cells of the adult murine brain, such as astrocytes, Bergmann glia, and ependymal cells. ISH, Northern blot analysis, and quantitative real-time polymerase chain reaction (PCR) demonstrated that Mlc1 mRNA is broadly distributed in the adult mouse brain, with highest concentrations of expression in the cerebellum and olfactory bulb. Furthermore, differential expression patterns during brain development were revealed. Overall brain Mlc1 mRNA concentrations exhibited a substantial increase in the perinatal period reaching adult concentrations at postnatal day 5. At the cellular level, highest Mlc1 expression was found during the pre- and perinatal period in multipotential neural precursor cells, especially in the subventricular zone of the lateral ventricle, whereas in adulthood highest Mlc1 mRNA concentrations were revealed in Bergmann glia cells. Because the temporal expression profile of Mlc1 indicates that, in contrast to developing and mature astrocytes, oligodendrocytes are devoid of Mlc1 expression, white matter tract abnormalities observed in these disorders may result from a primary astrocytic defect. Detailed information on Mlc1 expression in brain is likely to lead to a better understanding of Mlc1 involvement in the pathogenesis of both MLC and catatonic schizophrenia.
Definition of Receptor Binding Domains in Interferon-α (1992)

Earlier studies from this laboratory had identified three regions in interferon-alpha (IFN-alpha) that influence the active conformation of the molecule. These domains are associated with the amino acid residues 10-35, 78-107, and 123-166. In this report, we define these domains more accurately by identifying their critical clusters of amino acids. Using a panel of IFN-alpha 2a variants in antiviral, growth inhibitory, and receptor binding studies, we are able to show that these three domains, defined by residues 29-35, 78-95, and 123-140, are likely located on the surface of the molecule, with domains 29-35 and 123-140 in close spatial proximity. We conclude that the 29-35 and 123-140 domains are responsible for IFN-alpha receptor binding interactions and constitute receptor recognition sites in IFN-alpha. Extrapolating from our biological activity data, in the context of a number of predictive algorithms that provide insights into the hydrophobicity/hydrophilicity, surface probability, and flexibility of amino acid clusters, we infer that the residues 29-35 influence the active configuration of IFN-alpha most significantly. This region likely represents a loop structure that is relatively rigid in configuration. The carboxy-terminally located strategic domain, 123-140, is comprised of two clusters of amino acid residues, one that forms part of a rigid alpha-helix, the other a more flexible loop structure. Similarly, the 78-95 domain comprises a portion of an alpha-helical structure that is followed by a loop structure. Close examination of the amino acid sequences in all three regions among the different species of IFN-alpha s and human IFN-beta indicate that the 29-35 and 123-140 domains are most highly conserved, yet some variance is apparent in the 78-95 domain. We propose that the 78-95 region influences species specificity among the murine and human IFN-alpha s and determines the differential specificity of action between human IFN-alpha and human IFN-beta.
Prognostic Factors for Generalized Peritonitis Secondary to Colonic Perforation (2003)

Purpose: The prognosis following colonic perforation is generally regarded as worse than it is for upper gastrointestinal perforation. Moreover, the increasing incidence of colon cancer associated perforation is another reason for the present study of colonic perforation in the present study. We reviewed and analyzed various types of colonic perforations to determine which prognostic factors were still useful for the treatment of colonic perforation. Methods: Thirty six patients (mean age, 51.5; 24 males) with generalized peritonitis secondary to a colonic perforation were studied retrospectively. All the patients had undergone an exploratory laparotomy. The severity of the clinical condition was recorded according to the APACHE III scoring system for all the patients when they were first seen. Mortality and morbidity were analyzed for possible prognostic factors, such as age, type of operation, association with malignancy, and APACHE-III score. Results: Penetrating trauma was the leading cause of perforation (27.8%), and iatrogenic perforations accounted for 19.4% of the total. Among nontraumatic perforations, malignancy was the major pathology (25.0%). The sigmoid colon was the most frequent site of perforation. Types of surgical treatment varied according to the general conditions of the patients. In 22 patients, the operation was finished with primary closure alone. A colonic resection was performed in 14 patients, and a proximal diversion was performed in 19 patients (after either a resection or primary closure). Analysis of the various clinical variables showed that old age (＞60), underlying malignancy, and the APACHE III score were significant prognostic factors for the surgical outcome. Conclusions: These results suggest that penetrating injuries are still the main cause of colonic perforation and that iatrogenic and malignancy-related perforations are increasing. Among other variables, old age, underlying malignancy and the APACHE III score are significant prognostic factors for the surgical outcome.
Myristylation site in Pr65gag is essential for virus particle formation by Moloney murine leukemia virus. (1986)

It was previously reported that the gag proteins of mammalian type C retroviruses are modified by the addition of myristate to the N-terminal glycine residue. We have performed oligonucleotide-directed mutagenesis to change this glycine codon in the Moloney murine leukemia virus genome to an alanine codon and also to specifically delete the glycine codon. Upon transfection into mammalian cells, these mutant genomes direct the synthesis of gag proteins, but these proteins are not myristylated. The mutants do not form virus particles or any recognizable virus-specific structures visible in thin sections with the electron microscope. Further, the mutant gag proteins appear to remain in the cytosol, whereas the wild type is found principally in particulate fractions of the cell. The results are consistent with the theory that myristate is required for the association of the gag protein with the plasma membrane and that this association is necessary for virus assembly.
[Observation of the clinical effects of two kinds of resin materials for restoring the defects of maxillary incisor]. (2004)

To analyse and compare the effects of the resin materials of etched and nonetched groups in restoring the defect of maxillary incisor. 120 teeth were divided into two groups and filled by two kinds of materials. One year follow up results was studied. The effects of retention had no significant difference between the two groups, but the nonetched group had a lower stimulation to the pulp than the other one in restoring middle to deep caries. Compared to the etched group, the nonetched materials of resin has lower stimulation to pulp, more adhesion and higher success rate.
Bicarbonate Alters Bacterial Susceptibility to Antibiotics by Targeting the Proton Motive Force (2017)

The antibacterial properties of sodium bicarbonate have been known for years, yet the molecular understanding of its mechanism of action is still lacking. Utilizing chemical-chemical combinations, we first explored the effect of bicarbonate on the activity of conventional antibiotics to infer on the mechanism. Remarkably, the activity of 8 classes of antibiotics differed in the presence of this ubiquitous buffer. These interactions and a study of mechanism of action revealed that, at physiological concentrations, bicarbonate is a selective dissipater of the pH gradient of the proton motive force across the cytoplasmic membrane of both Gram-negative and Gram-positive bacteria. Further, while components that make up innate immunity have been extensively studied, a link to bicarbonate, the dominant buffer in the extracellular fluid, has never been made. Here, we also explored the effects of bicarbonate on components of innate immunity. Although the immune response and the buffering system have distinct functions in the body, we posit there is interplay between these, as the antimicrobial properties of several components of innate immunity were enhanced by a physiological concentration of bicarbonate. Our findings implicate bicarbonate as an overlooked potentiator of host immunity in the defense against pathogens. Overall, the unique mechanism of action of bicarbonate has far-reaching and predictable effects on the activity of innate immune components and antibiotics. We conclude that bicarbonate has remarkable power as an antibiotic adjuvant and suggest that there is great potential to exploit this activity in the discovery and development of new antibacterial drugs by leveraging testing paradigms that better reflect the physiological concentration of bicarbonate.
Volume polarization in reaction field theory (1998)

In continuum reaction field models of solvation, unconstrained quantum mechanical calculation of the solute electronic structure inevitably leads to penetration of some solute charge density outside the cavity and into the solvent dielectric region. This produces a rarely recognized or treated volume polarization that contributes in addition to the commonly considered surface polarization. In this work a new practical implementation is described for quantitatively evaluating both volume and surface polarization contributions to the solute-solvent interaction with an irregularly shaped cavity surface. For illustration, numerical results are presented on several representative small neutral, cation, and anion solutes. The volume polarization contributions to energies and dipole moments are found to be somewhat smaller than those from surface polarization, but not negligible. The results are also used to test several charge renormalization approaches that have been previously proposed in the literature. Compared to the exact volume polarization correction, these can sometimes lead to energy corrections of the wrong sign. A previously proposed method of simulating volume polarization through an additional surface polarization generally produces corrections of the right sign and of about the right magnitude.
Conditional gene expression in secretory tissues and skin of transgenic mice using the MMTV‐LTR and the tetracycline responsive system (1995)

Molecular mechanisms of development and disease can be studied in transgenic animals. Controlling the spatial and temporal expression patterns of transgenes, however, is a prerequisite for the elucidation of gene function in the whole organism. Previously we reported that mice carrying a tetR/VP16 hybrid gene (tTA), under the control of the human cytomegalovirus immediate early 1 (HCMV-IE1) gene promoter, can be used to temporally activate the expression of transgenes under the control of a promoter containing tetop sequences. We now show that the MMTV-LTR can be used to target expression of tTA to the epithelial cells of secretory organs and skin in transgenic mice. Notably, nearly uniform expression of a tetop-lacZ transgene was found in seminal vesicle, salivary gland, and Leydig cells of mice carrying also the MMTV-tTA transgene. More heterogeneous patterns of gene expression were observed in mammary epithelial cells and basal cells of the epidermis. Different MMTV-tTA lines had comparable tissue expression patterns. Transcriptional activation mediated by tTA was up to several hundredfold, and it was abrogated after the administration of tetracycline. The MMTV-tTA mice established in this work will be useful for experiments examining the roles of biological factors at defined developmental stages in the epithelial cells of salivary gland, seminal vesicle, mammary gland, and skin and the Leydig cells of testes. In addition, in combination with the CRE/lox recombination system, these mice wil be useful to achieve gene deletions at defined time points in these organs.
Fecal Microbiota Transplantation for Ulcerative Colitis: A Systematic Review and Meta-Analysis (2016)

FMT provides a promising effect for UC with few adverse events. Successful FMT may be associated with an increase in microbiota diversity and richness, similarity, and certain change of bacterial composition.
PNA-based artificial nucleases as antisense and anti-miRNA oligonucleotide agents (2011)

Because of its interesting chemical, physical and biological properties, Peptide Nucleic Acid (PNA) has attracted major attention in molecular biology, for diagnostics purposes and development of biosensors. PNAs have become candidates for gene therapeutic drugs in ANTISENSE (AO) strategy with favorable in vivo biochemical properties. Recently, antisense PNA oligonucleotides have been described in anti-miRNA approach (AMO). We propose PNA-based nucleases as AO and AMO agents. We report the design, synthesis and characterization of two kinds of artificial nucleases composed of a PEG-PNA-PEG domain conjugated to HGG·Cu (A) and DETA (B) as well known cleavage sites. Qualitative (MALDI-TOF) and quantitative (HTS) assays were planned to study nuclease activity of constructs A and B on RNA-3'-FAM target sequence. The results have highlighted the best performance of nuclease B and the relevance of the PEG spacer, in particular for conjugate A, in terms of efficiency of the cleavage, suggesting that conjugates A and B also act as potential antisense and anti-miRNA agents.
Interaction of decorin with CNBr peptides from collagens I and II (2002)

Decorin is a small leucine-rich chondroitin/dermatan sulfate proteoglycan reported to interact with fibrillar collagens through its protein core and to localize at d and e bands of the collagen fibril banding pattern. Using a solid-phase assay, we have determined the interaction of peptides derived by CNBr cleavage of type I and type II collagen with decorin extracted from bovine tendon and its protein core and with a recombinant decorin preparation. At least five peptides have been found to interact with all three decorin samples. The interaction of peptides with tendon decorin has a dissociation constant in the nanomolar range. The triple helical conformation of the peptide trimeric species is a necessary requisite for the binding. All positive peptides have a region within the d and e bands of collagen fibrils. Two chemical derivatives of collagens and of positive peptides were prepared by N-acetylation and N-methylation of the primary amino group of Lys/Hyl side chains. Chemical modifications performed in mild conditions do not significantly alter the thermal stability of peptide trimeric species whereas they affect the interaction with decorin: N-acetylation eliminates both the positive charge and the binding to decorin, whereas N-methylation preserves the cationic character and modulates the binding. We conclude that decorin makes contacts with multiple sites in type I collagen and probably also in type II collagen and that some collagen Lys/Hyl residues are essential for the binding.