gebhart/patrepeval huggingface dataset:
Novel inhibitors of the calcineurin/NFATc hub - alternatives to CsA and FK506? (2009)

The drugs cyclosporine A (CsA) and tacrolimus (FK506) revolutionized organ transplantation. Both compounds are still widely used in the clinic as well as for basic research, even though they have dramatic side effects and modulate other pathways than calcineurin-NFATc, too. To answer the major open question - whether the adverse side effects are secondary to the actions of the drugs on the calcineurin-NFATc pathway - alternative inhibitors were developed. Ideal inhibitors should discriminate between the inhibition of (i) calcineurin and peptidyl-prolyl cis-trans isomerases (PPIases; the matchmaker proteins of CsA and FK506), (ii) calcineurin and the other Ser/Thr protein phosphatases, and (iii) NFATc and other transcription factors. In this review we summarize the current knowledge about novel inhibitors, synthesized or identified in the last decades, and focus on their mode of action, specificity, and biological effects.
MINIREVIEW: Interactions Among a Subfamily of Nuclear Hormone Receptors: The Regulatory Zipper Model (1990)

The nuclear hormone receptors comprise a superfamily of ligand-modulated transcription factors that regulate homeostasis, reproduction, development, and differentiation. Three amino acids within the zinc finger DNA binding motif determine target gene specificity. Groups of receptors exist with similar DNA binding specificity. A complex carboxy terminal region mediates ligand binding, dimerization, and hormone-relieved transcriptional inactivation. We summarize the current understanding of these phenomena and suggest a novel model that structurally and functionally links these events. This "regulatory zipper model" may explain the mechanism by which ligand activates nuclear hormone receptors.
Human Mesenchymal Stem Cells Protect Human Islets from Pro-Inflammatory Cytokines (2012)

Transplantation of human islets is an attractive alternative to daily insulin injections for patients with type 1 diabetes. However, the majority of islet recipients lose graft function within five years. Inflammation is a primary contributor to graft loss, and inhibiting pro-inflammatory cytokine activity can reverse inflammation mediated dysfunction of islet grafts. As mesenchymal stem cells (MSCs) possess numerous immunoregulatory properties, we hypothesized that MSCs could protect human islets from pro-inflammatory cytokines. Five hundred human islets were co-cultured with 0.5 or 1.0 × 10(6) human MSCs derived from bone marrow or pancreas for 24 hours followed by 48 hour exposure to interferon-γ, tumor necrosis factor-α and interleukin 1β. Controls include islets cultured alone (± cytokines) and with human dermal fibroblasts (± cytokines). For all conditions, glucose stimulated insulin secretion (GSIS), total islet cellular insulin content, islet β cell apoptosis, and potential cytoprotective factors secreted in the culture media were determined. Cytokine exposure disrupted human islet GSIS based on stimulation index and percentage insulin secretion. Conversely, culture with 1.0 × 10(6) bMSCs preserved GSIS from cytokine treated islets. Protective effects were not observed with fibroblasts, indicating that preservation of human islet GSIS after exposure to pro-inflammatory cytokines is MSC dependent. Islet β cell apoptosis was observed in the presence of cytokines; however, culture of bMSCs with islets prevented β cell apoptosis after cytokine treatment. Hepatocyte growth factor (HGF) as well as matrix metalloproteinases 2 and 9 were also identified as putative secreted cytoprotective factors; however, other secreted factors likely play a role in protection. This study, therefore, demonstrates that MSCs may be beneficial for islet engraftment by promoting cell survival and reduced inflammation.
G-CSF: From granulopoietic stimulant to bone marrow stem cell mobilizing agent (2014)

G-CSF was among the first cytokines to be identified and rapidly transitioned into clinical medicine. Initially used to promote the production of neutrophils in patients with chemotherapy-induced neutropenia it helped to revolutionize the delivery of cancer therapy. Its ability to mobilize hematopoietic stem cells from the bone marrow into the blood was subsequently exploited, changing the face of hematopoietic stem cell transplantation. Today the knowledge gained in unraveling the mechanisms of stem cell mobilization by G-CSF is being explored as a means to increase chemosensitivity in hematological malignancies. This review provides a brief history of G-CSF and then focuses on recent advances in our understanding of G-CSF-induced stem cell mobilization and the potential clinical application of this knowledge in chemo-sensitization.
Interaction of endothelial cell growth factor with heparin: characterization by receptor and antibody recognition. (1985)

Endothelial cell growth factor (ECGF) binds specifically in vitro to membrane receptors present on the surface of several cell types, including murine and human endothelial cells and fibroblasts. Monoclonal antibodies prepared against ECGF that inhibit the mitogenic activity of the growth factor prevent receptor occupancy by the ligand. Heparin interacts structurally with ECGF [Maciag, T., Mehlman, T., Friesel, R. & Schreiber, A. B. (1984) Science 225, 932-935], potentiates the mitogenic activity of the polypeptide, restores the biological activity to inactivate ECGF, enhances the affinity of the ligand to cell surface receptors, and modifies antibody recognition of ECGF. These data suggest that the association between heparin and ECGF induces a conformational change in the polypeptide that increases or stabilizes the biological activity of the mitogen.
Management of varicella zoster infections in immunocompetent hosts. (1988)

Varicella in otherwise healthy children usually requires no antiviral treatment. In severe cases, however, such as are seen in neonates and adults, treatment must be given. Anecdotal evidence suggests the efficacy of intravenous acyclovir in such patients. Herpes zoster in immunocompetent patients may be severe enough to warrant antiviral therapy, particularly in elderly patients. Both idoxuridine and acyclovir have been investigated in placebo-controlled double-blind studies. Due to its low toxicity, ease of administration, and the possibility of systemic administration, acyclovir has largely replaced older antivirals in the management of herpes zoster in the normal host. Recent studies have shown the efficacy of oral acyclovir. In addition, oral acyclovir may prevent the ocular complications of ophthalmic zoster. When acyclovir is given, it should be administered as early as possible, preferably no later than four days after the onset of the rash. The combination of acyclovir and prednisolone for the prevention of post-herpetic neuralgia has not proved effective.
Murine marrow‐derived mesenchymal stem cell: isolation, in vitro expansion, and characterization (2003)

In spite of the attention given to the study of mesenchymal stem cells (MSCs) derived from the bone marrow (BM) of humans and other species, there is a lack of information about murine MSCs. We describe the establishment of conditions for the in vitro expansion of plastic-adherent cells from murine BM for over 50 passages, and provide their characterization regarding morphology, surface marker profile and growth kinetics. These cells were shown to differentiate along osteogenic and adipogenic pathways, and to support the growth and differentiation of haematopoietic stem cells, and were thus operationally defined as murine mesenchymal stem cells (mMSCs). mMSCs were positive for the surface markers CD44, CD49e, CD29 and Sca-1, and exhibited a homogeneous, distinctive morphology. Their frequency in the BM of adult BALB/c and C57Bl/6 mice, normal or knockout for the alpha-L-iduronidase (IDUA) gene, was preliminarily estimated to be 1 per 11,300-27,000 nucleated cells. The emergence of a defined methodology for the culture of mMSCs, as well as a comprehensive understanding of their biology, will make the development of cellular and genetic therapy protocols in murine models possible, and provide new perspectives in the field of adult stem cells research.
Evaluation of a New, Rapid Bedside Test for Quantitative Determination of B-Type Natriuretic Peptide (2001)

Congestive heart failure (CHF) is among the most frequently encountered cardiac diagnoses, with an estimated prevalence of 1% (1). Plasma concentrations of B-type natriuretic peptide (BNP) and its precursor, N-terminal pro-BNP (NT pro-BNP), are increased in patients with CHF and have been shown to accurately predict clinical severity and left ventricular ejection fraction (LVEF) as well as morbidity and mortality in those patients (2)(3). A major limitation in the routine determination of natriuretic peptides is the time-consuming nature of analytical techniques, e.g., extraction procedures, long incubation times, or radioactive labeling (4)(5)(6)(7)(8). A rapid bedside test for determination of BNP was introduced recently (Triage BNP; Biosite Diagnostics, San Diego, CA). We evaluated the assay and compared it, in samples from patients with suspected CHF, with other assay systems for determination of either BNP (Shionoria BNP; CIS Diagnostics) or NT pro-BNP (Roche Diagnostics, Tutzing, Germany).

The Triage BNP test is an immunofluorometric assay for quantitative determination of BNP in EDTA-anticoagulated whole blood or plasma (9)(10). A murine recombinant polyclonal antibody is bound to the fluorescent label, and a murine monoclonal antibody against the disulfide bond-mediated ring structure of BNP 32 is bound to the solid phase.

Briefly, after the addition of 250 μL of EDTA-anticoagulated whole blood, the plasma is separated and allowed to react with fluorescent antibody conjugates within a reaction chamber. After an incubation period, complexes of the analyte and fluorescent antibody conjugates are captured on a detection lane. The concentration of BNP in the specimen is proportional to the fluorescence bound to the detection lane, which is determined quantitatively by a handheld fluorescence instrument (Triage Meter) as described in detail elsewhere (11 …
Increased accumulation of drugs in multidrug-resistant cells induced by liposomes. (1992)

A multidrug-resistant cell such as the human lymphoblastic leukemic cell CEM/VLB100 accumulates far less vinblastine (VLB) than its drug-sensitive parent, CEM. When CEM/VLB100 cells are exposed to liposomes consisting of the phospholipids cardiolipin, dioleoylphosphatidic acid, or phosphatidylinositol bearing unsaturated fatty acids and then tested for uptake of VLB, accumulation of drug rapidly rises to levels approaching those of CEM cells, which are relatively unaffected by the liposome treatment. The liposomes are not carriers of entrapped drug. Phosphatidylserine, phosphatidylcholine, and phosphatidylethanolamine are inactive, and the addition of cholesterol to liposomes inhibits uptake. Exposure of cells to liposomes does not appear to alter the efflux of drugs. We suggest that the liposomal lipids, introduced into the plasma membranes of CEM/VLB100 cells, change their properties so that accumulation of drugs by cells is largely restored. The cytotoxicity of VLB in CEM/VLB100 cells is increased approximately 10-fold by cardiolipin liposomes.
Structural and Functional Characterization of a Multifunctional Alanine-Rich Peptide Analogue from Pleuronectes americanus (2012)

Recently, defense peptides that are able to act against several targets have been characterized. The present work focuses on structural and functional evaluation of the peptide analogue Pa-MAP, previously isolated as an antifreeze peptide from Pleuronectes americanus. Pa-MAP showed activities against different targets such as tumoral cells in culture (CACO-2, MCF-7 and HCT-116), bacteria (Escherichia coli ATCC 8739 and Staphylococcus aureus ATCC 25923), viruses (HSV-1 and HSV-2) and fungi (Candida parapsilosis ATCC 22019, Trichophyton mentagrophytes (28d&E) and T. rubrum (327)). This peptide did not show toxicity against mammalian cells such as erythrocytes, Vero and RAW 264.7 cells. Molecular mechanism of action was related to hydrophobic residues, since only the terminal amino group is charged at pH 7 as confirmed by potentiometric titration. In order to shed some light on its structure-function relations, in vitro and in silico assays were carried out using circular dichroism and molecular dynamics. Furthermore, Pa-MAP showed partial unfolding of the peptide changes in a wide pH (3 to 11) and temperature (25 to 95°C) ranges, although it might not reach complete unfolding at 95°C, suggesting a high conformational stability. This peptide also showed a conformational transition with a partial α-helical fold in water and a full α-helical core in SDS and TFE environments. These results were corroborated by spectral data measured at 222 nm and by 50 ns dynamic simulation. In conclusion, data reported here show that Pa-MAP is a potential candidate for drug design against pathogenic microorganisms due to its structural stability and wide activity against a range of targets.
Molecular mechanism of action of metformin: old or new insights? (2013)

Metformin is the first-line drug treatment for type 2 diabetes. Globally, over 100 million patients are prescribed this drug annually. Metformin was discovered before the era of target-based drug discovery and its molecular mechanism of action remains an area of vigorous diabetes research. An improvement in our understanding of metformin's molecular targets is likely to enable target-based identification of second-generation drugs with similar properties, a development that has been impossible up to now. The notion that 5' AMP-activated protein kinase (AMPK) mediates the anti-hyperglycaemic action of metformin has recently been challenged by genetic loss-of-function studies, thrusting the AMPK-independent effects of the drug into the spotlight for the first time in more than a decade. Key AMPK-independent effects of the drug include the mitochondrial actions that have been known for many years and which are still thought to be the primary site of action of metformin. Coupled with recent evidence of AMPK-independent effects on the counter-regulatory hormone glucagon, new paradigms of AMPK-independent drug action are beginning to take shape. In this review we summarise the recent research developments on the molecular action of metformin.
Construction of a 600-kilobase cosmid clone contig and generation of a transcriptional map surrounding the lung cancer tumor suppressor gene (TSG) locus on human chromosome 3p21.3: progress toward the isolation of a lung cancer TSG. (1996)

The critical region on human chromosome 3p21.3 harboring a putative lung cancer tumor suppressor gene (TSG) was previously defined by allelotyping and recently refined by overlapping homozygous deletions. We report the construction of a 700-kb (cosmid and one P1 phage) clone contig covering the deletion overlap and its flanks. The minimal set of 23 cosmids comprises 600 kb and is extended by one P1 phage to 700 kb to cover the distal breakpoint of the overlap. The clone contig was extensively characterized by restriction and expression mapping to produce high resolution physical and transcription maps of the cloned region. Potential transcribed fragments were detected by hybridization with PCR-amplified cDNA libraries, direct cDNA selection "zoo" blotting, cDNA screening, and identification of 24 CpG islands. Thus far, 15 new genes represented by partial or full-length cDNAs were isolated, characterized, and precisely positioned on the contig. Two previously cloned genes, namely GNAI-2 and GNAT-1, were also positioned. In addition, the telomeric breakpoint of the NCI H740 deletion and centromeric breakpoint of the overlapping GLC20 deletion were discovered and mapped to define precisely the candidate TSG region. This large cosmid clone contig and high resolution maps will prove crucial in the identification of the lung cancer TSG(s).
Proteomics-based signature for human benign prostate hyperplasia and prostate adenocarcinoma (2011)

Prostate adenocarcinoma often presents at a late stage, due to a lack of early clinical symptoms and lack of accurate objective markers. This study aimed to identify and validate proteomics-based biomarkers useful for prostate cancer diagnosis and to establish a marker-panel for prostate cancer and benign prostate hyperplasia (BPH). Global protein expression patterns in fresh tissue specimens from 8 patients with prostate carcinoma and 16 with BPH were analyzed by two-dimensional gel electrophoresis. Differentially expressed proteins were identified by MALDI-TOF mass spectrometry. We compared our results with those of published studies and defined a set of common biomarkers. We identified 22 differentially expressed proteins between BPH and prostate carcinomas. The up-regulated proteins in cancer compared to BPH included protein disulfide-isomerase, 14-3-3-protein, Enoyl CoA-hydrase, prohibitin and B-tubulin β-2. Keratin-II, desmin, HSP71, ATP-synthase-β-chain and creatine kinase-β-chain were down-regulated. Survey of the literature showed that 15 of our 22 identified proteins have been previously reported to differ in their expression levels between BPH and prostate cancer by other laboratories. The expression patterns of these biomarkers could successfully cluster BPH and adenocarcinomas as well as prostate cancer of low and high Gleason scores. This study validates protein-biomarkers that can be useful for accurate diagnosis and prognostic monitoring of prostate adenocarcinoma. Despite varied prevalence of the disease between different ethnic populations (i.e., high in Sweden, low in Saudi Arabia); the biomarkers indicate that BPH and prostate cancers are biologically 'homogeneous' in their protein expression patterns across wide geographical regions.
Fmoc Amino Acid Fluorides: Convenient Reagents for the Solid-PhaseAssembly of Peptides Incorporating Sterically Hindered Residues (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFmoc Amino Acid Fluorides: Convenient Reagents for the Solid-PhaseAssembly of Peptides Incorporating Sterically Hindered ResiduesHolger Wenschuh, Michael Beyermann, Eberhard Krause, Michael Brudel, Ruediger Winter, Michael Schuemann, Louis A. Carpino, and Michael BienertCite this: J. Org. Chem. 1994, 59, 12, 3275–3280Publication Date (Print):June 1, 1994Publication History Published online1 May 2002Published inissue 1 June 1994https://pubs.acs.org/doi/10.1021/jo00091a011https://doi.org/10.1021/jo00091a011research-articleACS PublicationsRequest reuse permissionsArticle Views981Altmetric-Citations99LEARN 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
Progress in Exosome Isolation Techniques (2017)

Exosomes are one type of membrane vesicles secreted into extracellular space by most types of cells. In addition to performing many biological functions particularly in cell-cell communication, cumulative evidence has suggested that several biological entities in exosomes like proteins and microRNAs are closely associated with the pathogenesis of most human malignancies and they may serve as invaluable biomarkers for disease diagnosis, prognosis, and therapy. This provides a commanding impetus and growing demands for simple, efficient, and affordable techniques to isolate exosomes. Capitalizing on the physicochemical and biochemical properties of exosomes, a number of techniques have been developed for the isolation of exosomes. This article summarizes the advances in exosome isolation techniques with an emphasis on their isolation mechanism, performance, challenges, and prospects. We hope that this article will provide an overview of exosome isolation techniques, opening up new perspectives towards the development more innovative strategies and devices for more time saving, cost effective, and efficient isolations of exosomes from a wide range of biological matrices.
Guillain-Barre Syndrome, Influenza, and Influenza Vaccination: The Epidemiologic Evidence (2014)

Guillain-Barré syndrome (GBS) is the most common cause of acute flaccid paralysis worldwide, and is thought to be immune-mediated. It is preceded by upper respiratory or gastrointestinal infection in about two-thirds of cases and is associated with some viral infections, including influenza. GBS has also been associated with the 1976 swine-influenza vaccine. Thereafter, some studies have shown a small increased risk of GBS following receipt of seasonal and 2009 H1N1 monovalent influenza vaccines. Studies over the years have also shown an increased risk of GBS following influenza infection, and the magnitude of risk is several times greater than that following influenza vaccination. Because GBS is rare, and even rarer following vaccination, it is difficult to estimate precise risk. We try to shed light on the complex relationship of GBS and its association with influenza and influenza vaccines over the past 35 years.
Bone morphogenetic proteins-2 and -4 are involved in the retinoic acid-induced differentiation of embryonal carcinoma cells. (1992)

Bone morphogenetic proteins-2 and -4 (BMPs-2 and -4) are transforming growth factor beta-related proteins that can induce bone formation in vivo. We observed that the level of endogenous BMP-2 mRNA increased an average of 11-fold on differentiation of F9 embryonal carcinoma cells into parietal endoderm after treatment with retinoic acid (RA) and cAMP, whereas the message for the closely related BMP-4 decreased 12-fold after this treatment. Therefore, the effects of exogenous recombinant BMP-2 protein on the RA-induced differentiation of F9 embryonal carcinoma cells were investigated. BMP-2 addition altered the growth and morphology of RA-treated but not untreated cells. Moreover, the abundance of several messages was affected by exogenous BMP-2 treatment. Notably, the BMP-2 and -4 messages themselves were reduced by the addition of exogenous BMP-2. The observations suggest that RA, which is known to affect bone morphogenesis, may regulate the osteoinductive proteins, BMP-2 and -4. Furthermore, BMP-2 and -4 may be involved in preimplantation embryogenesis.
Medical treatment of inflammatory bowel diseases. (2005)

In conclusion, medical therapy of inflammatory bowel diseases is a constantly moving field and recent evolutions will undoubtedly change clinical practice in the years to come.
Silicon Photonics-Based 100  Gbit/s, PAM4, DWDM Data Center Interconnects (2018)

In this paper we discuss the nature of and requirements for data center interconnects. We then demonstrate a switch-pluggable, 4.5&#x00A0;W, 100&#x00A0;Gbit/s, silicon-photonics-based, PAM4, QSFP-28 module to transport Ethernet data directly over DWDM for layer 2/3 connection between switches at data centers up to 120&#x00A0;km apart, thereby eliminating the need for a separate optical transport layer. The module, based on the direct detect modulation format, is of much reduced complexity, power, and cost compared to the coherent systems that are currently being deployed for this application.