gebhart/patrepeval huggingface dataset:
Identification of fibronectin type I domains as amyloid-binding modules on tissue-type plasminogen activator and three homologs (2008)

The serine protease tissue-type plasminogen activator (tPA), a key enzyme in hemostasis, is activated by protein aggregates with amyloid-like properties. tPA is implicated in various pathologies, including amyloidoses. A major task is to further elucidate the mechanisms of amyloid pathology. We here show that the fibronectin type I domain of tPA mediates the interaction with amyloid protein aggregates. We found that in contrast to full-length tPA, a deletion-mutant of tPA, lacking the first three N-terminal domains (including the fibronectin type I domain), fails to activate in response to amyloid protein aggregates. Using recombinantly produced domains of tPA in direct binding assays, we subsequently mapped the amyloid-binding region to the fibronectin type I domain. This domain co-localized with congophilic plaques in brain sections from patients with Alzheimer's disease. Fibronectin type I domains from homologous proteases factor XII, hepatocyte growth factor activator and from the extracellular matrix protein fibronectin also bound to aggregated amyloidogenic peptides. Finally, we demonstrated that the isolated fibronectin type I domain inhibits amyloid-induced aggregation of blood platelets. The identification of the fibronectin type I domain as an amyloid-binding module provides new insights into the (patho-) physiological role of tPA and the homologous proteins which may offer new targets for intervention in amyloid pathology.
Profile of HBV antiviral resistance mutations with distinct evolutionary pathways against nucleoside/ nucleotide analogue treatment among Chinese chronic hepatitis B patients (2010)

One-third of the studied population harboured NA-resistant HBV with complicated mutation patterns. Monitoring HBV genotypic resistance mutation markers and patterns is therefore shown to be beneficial for optimizing antiviral therapies and for avoiding clinical deterioration.
S-Adenosyl-L-methionine–Dependent Restriction Enzymes (2004)

Restriction-modification (R-M) enzymes are classified into type I, II, III, and IV, based on their recognition sequence, subunit composition, cleavage position, and cofactor requirements. While the role of S-Adenosyl-L-methionine (AdoMet) as the methyl group donor in the methylation reaction is undisputed, its requirement in DNA cleavage reaction has been subject to intense study. AdoMet is a prerequisite for the DNA cleavage by most type I enzymes known so far, with the exception of R.EcoR124I. A number of new type II restriction enzymes belonging to the type IIB and IIG family were found to show AdoMet dependence for their cleavage reaction. The type III enzymes have been found to require AdoMet for their restriction function. AdoMet functions as an allosteric effector of the DNA cleavage reaction and has been shown to bring about conformational changes in the protein upon binding.
Aberrant trafficking of hepatitis B virus glycoproteins in cells in which N-glycan processing is inhibited (1997)

The role of N-glycan trimming in glycoprotein fate and function is unclear. We have recently shown that hepatitis B virus (HBV) DNA is not efficiently secreted from cells in which alpha-glucosidase mediated N-glycan trimming is inhibited. Here it is shown that, in cells in glucosidase-inhibited cells, viral DNA, accompanied by envelope and core proteins, most likely accumulate within lysosomal compartments. Pulse-chase experiments show that although the viral glycoproteins (L, M, and S) are dysfunctional, in the sense that they do not mediate virion egress and are not efficiently secreted from the cell, they all still leave the endoplasmic reticulum (ER). Surprisingly, however, the glycoproteins retained within the cell were not rapidly degraded, appearing as aggregates, enriched for L and M, with intracellular half-lives exceeding 20 h. Moreover, by 24 h after synthesis, a substantial fraction of the detained glycoproteins appeared to return to the ER, although a considerable amount was also found in the lysosomes. To our knowledge, this is the first report that shows, as a consequence of inhibiting glycosylation processing, certain glycoproteins (i) become dysfunctional and aggregate, yet still depart from the ER, and (ii) have extended rather than shortened half-lives. Taken together, these data suggest that proper intracellular routing of HBV glycoproteins requires ER glucosidase function. It is hypothesized that failure to process N-glycan causes HBV glycoproteins to aggregate and that impaired protein-protein interactions and trafficking are the result of misfolding.
Micropallet Arrays for the Separation of Single, Adherent Cells (2006)

The selection and collection of single cells from within a heterogeneous population is required to produce genetically engineered cell lines, to develop new stem cell lines, and for single-cell studies. We describe a new platform for the positive selection of single live mammalian cells while the cells remain adherent to their growth surface. Cells were grown on arrays of microfabricated, releasable elements composed of SU-8 polymer termed "cell pallets". The presence of air between the elements restricted the cells to the top surfaces of the pallets. Single pallets situated within large arrays of pallets were released on demand using a single, focused, laser pulse. The laser pulses were low in energy (2-5 muJ) and did not detach nearby, nontargeted pallets. Since the SU-8 pallets and the underlying glass substrate were optically transparent, the cells on the pallets could be visualized by microscopy before and after release. Over 90% of cells remained attached to the pallet during laser-based release. The feasibility of growing the cells from the released pallets into clonal colonies was demonstrated. The pallet array system permits adherent cells to be inspected using conventional microscopy and selected cells released for further analysis. The ability to assess cells while they remain adherent to a surface will broaden the number of attributes that can be utilized for cell separation, for example, cell shape, cytoskeletal properties, and other attributes.
[Chemotherapy with cisplatinum, carboplatin and 5FU-folinic acid, followed by concomitant chemo-radiotherapy in unresectable esophageal carcinomas]. (2001)

neutropenia grade 3-4 (32%), thrombopenia grade 3-4 (18%). More important, a lymphopenia (< 500/mm3) was noted in 12 patients (43%). Accordingly, 4 serious infectious complications were observed, with three toxic deaths. Objective response rate: 44% after initial chemotherapy; 75% after chemoradiotherapy, with 8 complete responses (38%). Median survival was 7.4 months, with a one- and two-year survival of 33% and 17,8%, respectively. Conclusion. This association of cisplatin, carboplatin, and 5FU did not offer a better response rate than the classical 5FU-cisplatinum association. But serious infectious complications occurred during the trial. We do not recommended further evaluation of this biplatinum therapy with 5FU in advanced esophageal carcinomas.
Enhanced Apoptosis and Tumor Growth Suppression Elicited by Combination of MEK (Selumetinib) and mTOR Kinase Inhibitors (AZD8055) (2012)

The mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase/AKT signaling pathways interact at multiple nodes in cancer, including at mTOR complexes, suggesting an increased likelihood of redundancy and innate resistance to any therapeutic effects of single pathway inhibition. In this study, we investigated the therapeutic effects of combining the MAPK extracellular signal-regulated kinase (MEK)1/2 inhibitor selumetinib (AZD6244) with the dual mTORC1 and mTORC2 inhibitor (AZD8055). Concurrent dosing in nude mouse xenograft models of human lung adenocarcinoma (non-small cell lung cancers) and colorectal carcinoma was well tolerated and produced increased antitumor efficacy relative to the respective monotherapies. Pharmacodynamic analysis documented reciprocal pathway inhibition associated with increased apoptosis and Bim expression in tumor tissue from the combination group, where key genes such as DUSP6 that are under MEK functional control were also modulated. Our work offers a strong rationale to combine selumetinib and AZD8055 in clinical trials as an attractive therapeutic strategy.
RANKL-induced DC-STAMP Is Essential for Osteoclastogenesis (2004)

Osteoclasts are bone-resorbing, multinucleated giant cells that are essential for bone remodeling and are formed through cell fusion of mononuclear precursor cells. Although receptor activator of nuclear factor-kappaB ligand (RANKL) has been demonstrated to be an important osteoclastogenic cytokine, the cell surface molecules involved in osteoclastogenesis are mostly unknown. Here, we report that the seven-transmembrane receptor-like molecule, dendritic cell-specific transmembrane protein (DC-STAMP) is involved in osteoclastogenesis. Expression of DC-STAMP is rapidly induced in osteoclast precursor cells by RANKL and other osteoclastogenic stimulations. Targeted inhibition of DC-STAMP by small interfering RNAs and specific antibody markedly suppressed the formation of multinucleated osteoclast-like cells. Overexpression of DC-STAMP enhanced osteoclastogenesis in the presence of RANKL. Furthermore, DC-STAMP directly induced the expression of the osteoclast marker tartrate-resistant acid phosphatase. These data demonstrate for the first time that DC-STAMP has an essential role in osteoclastogenesis.
Cut-Blot-Coagulate (1982)

Miamt, Fla. * Information on availability on request. † Hand switch disposable models are also available. 9000 N.E. 2nd Avenue Miami Shores, Fla. 33138
Living three-dimensional micro fabricated constructs for the replacement of vital organ function (2004)

We report the first demonstration of high-resolution three-dimensional constructs of living tissue suitable for transplantation for vital organ replacement devices. This work invokes a microfluidic approach, in which the blood supply of the liver or kidney is simulated using computational fluid dynamics; the vascular supply is then fabricated by replica molding of thin sheets of biopolymers stacked to form three-dimensional channel networks. These vascular networks are lined with endothelial cells in capillary-like structures that permeate the polymer construct with a rich bed of blood vessels. Organ function is achieved by arranging organ-specific cells in compartments adjacent to the blood vessels, which are separated by nanoporous polymer membranes. Initial results demonstrate that rat hepatocytes are sustained and retain their function for periods of weeks when oxygenated medium is perfused through the engineered capillary networks, a promising first step towards the ultimate goal of organ replacement.
Structural Redesigning Arabidopsis Lignins into Alkali-Soluble Lignins through the Expression of p-Coumaroyl-CoA:Monolignol Transferase PMT (2016)

Grass lignins can contain up to 10% to 15% by weight of p-coumaric esters. This acylation is performed on monolignols under the catalysis of p-coumaroyl-coenzyme A monolignol transferase (PMT). To study the impact of p-coumaroylation on lignification, we first introduced the Brachypodium distachyon Bradi2g36910 (BdPMT1) gene into Arabidopsis (Arabidopsis thaliana) under the control of the constitutive maize (Zea mays) ubiquitin promoter. The resulting p-coumaroylation was far lower than that of lignins from mature grass stems and had no impact on stem lignin content. By contrast, introducing either the BdPMT1 or the Bradi1g36980 (BdPMT2) gene into Arabidopsis under the control of the Arabidopsis cinnamate-4-hydroxylase promoter boosted the p-coumaroylation of mature stems up to the grass lignin level (8% to 9% by weight), without any impact on plant development. The analysis of purified lignin fractions and the identification of diagnostic products confirmed that p-coumaric acid was associated with lignins. BdPMT1-driven p-coumaroylation was also obtained in the fah1 (deficient for ferulate 5-hydroxylase) and ccr1g (deficient for cinnamoyl-coenzyme A reductase) lines, albeit to a lower extent. Lignins from BdPMT1-expressing ccr1g lines were also found to be feruloylated. In Arabidopsis mature stems, substantial p-coumaroylation of lignins was achieved at the expense of lignin content and induced lignin structural alterations, with an unexpected increase of lignin units with free phenolic groups. This higher frequency of free phenolic groups in Arabidopsis lignins doubled their solubility in alkali at room temperature. These findings suggest that the formation of alkali-leachable lignin domains rich in free phenolic groups is favored when p-coumaroylated monolignols participate in lignification in a grass in a similar manner.
A VIEW OF SUR/KIR6.X, KATP CHANNELS (1998)

ATP-sensitive potassium channels, termed KATP channels, link the electrical activity of cell membranes to cellular metabolism. These channels are heteromultimers of sulfonylurea receptor (SUR) and KIR6.X subunits associated with a 1:1 stoichiometry as a tetramer (SUR/KIR6.X forms the pores, whereas SUR regulates their activity. Changes in [ATP]i and [ADP]i gate the channel. The diversity of KATP channels results from the assembly of SUR and KIR6.X subtypes KIR6.1-based channels differ from KIR6.2 channels mainly by their smaller unitary conductance. SUR1- and SUR2-based channels are distinguished by their differential sensitivity to sulfonylureas, whereas SUR2A-based channels are distinguished from SUR2B channels by their differential sensitivity to diazoxide. Mutations that result in the loss of KATP channels in pancreatic beta-cells have been identified in SUR1 and KIR6.2. These mutations lead to familial hyperinsulinism. Understanding the mutations in SUR and KIR6.X is allowing insight into how these channels respond to nucleotides, sulfonylureas, and potassium channel openers, KCOs.
Ubiquitin-specific Cysteine Protease 2a (USP2a) Regulates the Stability of Aurora-A (2011)

The ubiquitin/proteasome pathway plays critical roles in virtually all aspects of cell biology. Enzymes of the ubiquitin pathway add (ligases) or remove (deubiquitinases) ubiquitin tags to or from their target proteins in a selective fashion. USP2a is a member of a subfamily of deubiquitinases, called ubiquitin-specific cysteine proteases (USPs). Although USP2a has been reported to be a bona fide oncogene that regulates the stability of MDM2, MDMX, and FAS, it is likely that there are other unidentified substrates for USP2a. In this study, we show that USP2a mediates mitotic progression by regulating the stability of Aurora-A. Through cell-based screening of a USP siRNA library, we discovered that knockdown of USP2a reduced the protein levels of Aurora-A. USP2a interacts with Aurora-A directly in vitro and in vivo. In addition, Aurora-A is a substrate for USP2a in vitro and in vivo. Our study provides a novel mechanism for the role of USP2a in mediating the stability of Aurora-A.
Parathyroid Hormone (1–84) and Treatment of Osteoporosis (2005)

PTH (1-84), when given intermittently as a subcutaneous injection, appears to be a safe and efficacious treatment option for osteoporosis. Further trials are needed to determine its specific place in therapy compared with other treatment options.
Topoisomerase II levels and drug sensitivity in adult acute myelogenous leukemia (1994)

The topoisomerase (topo) II-directed agents etoposide, daunorubicin (DNR), and amsacrine (m-AMSA) are widely used in the treatment of acute myelogenous leukemia (AML). In the present study, multiple aspects of topo II-mediated drug action were examined in marrows from adult AML patients. Colony-forming assays revealed that the dose of etoposide, DNR, or m-AMSA required to diminish leukemic colony formation by 90% (LD90) varied over a greater than 20-fold range between different pretreatment marrows. Measurement of nuclear DNR accumulation in the absence and presence of quinidine revealed evidence of P-glycoprotein (Pgp) function in 8 of 82 samples at diagnosis and 5 of 36 samples at first relapse, but the largest quinidine-induced increment in DNR accumulation (&lt; 2-fold) was too small to explain the variations in drug sensitivity. Restriction enzyme-based assays and sequencing of partial topo II alpha and topo II beta cDNAs from the most highly resistant specimens failed to demonstrate topo II gene mutations that could account for resistance. Western blotting of marrow samples containing greater than 80% blasts revealed that the content of the two topo II isoenzymes varied over a greater than 20-fold range, but did not correlate with drug sensitivity in vitro or in vivo. In addition, levels of topo II alpha and topo II beta in 46 of 47 clinical samples were lower than in human AML cell lines. Immunoperoxidase staining showed that these low topo II levels were accompanied by marked cell-to- cell heterogeneity, with topo II alpha being abundant in some blasts and diminished or absent from others. There was a trend toward increasing percentages of topo II alpha-positive cells in pretreatment marrows that contained more S-phase cells. Consistent with this observation, treatment of patients with granulocyte-macrophage colony- stimulating factor for 3 days before chemotherapy resulted in increases in topo II alpha-positive cells concomitant with increases in the number of cells traversing the cell cycle. These observations have implications for the regulation of topo II in AML, for the use of topo II-directed chemotherapy, and for future attempts to relate drug sensitivity to topo II levels in clinical material.
Accumulation of Very-Long-Chain Fatty Acids in Membrane Glycerolipids Is Associated with Dramatic Alterations in Plant Morphology (1998)

Anthony A. Millar, Mercedes Wrischer, Ljerka Kunst, Accumulation of Very-Long-Chain Fatty Acids in Membrane Glycerolipids Is Associated with Dramatic Alterations in Plant Morphology, The Plant Cell, Vol. 10, No. 11 (Nov., 1998), pp. 1889-1902
Electrophysiological Brain Changes Associated With Cognitive Improvement in a Pediatric Attention Deficit Hyperactivity Disorder Digital Artificial Intelligence-Driven Intervention: Randomized Controlled Trial (2021)

ISRCTN Registry ISRCTN71041318; https://www.isrctn.com/ISRCTN71041318.
Dephosphorylation of the guanylyl cyclase-A receptor causes desensitization. (1992)

Atrial natriuretic peptide (ANP) binds to the guanylyl cyclase-A (GC-A) receptor found in tissues such as the kidney and adrenal gland, resulting in marked elevations of the intracellular signaling molecule, cGMP. Here, GC-A is shown to exist as a phosphoprotein when expressed in human embryonic 293 cells. The 32P is principally associated with phosphoserine, with only trace amounts of phosphothreonine. The addition of ANP causes a time-dependent dephosphorylation of the receptor, as well as desensitization, which is not due to an ANP-mediated decrease in the amount of receptor protein. The mobility of GC-A on sodium dodecyl sulfate-polyacrylamide gel electrophoresis increases after treatment of cells with ANP, and protein phosphatase 2A induces the same mobility shift. The protein phosphatase also catalyzes dephosphorylation of GC-A, and this is directly correlated with decreases in ANP-stimulatable guanylyl cyclase activity. Okadaic acid, an inhibitor of protein phosphatase 2A, blocks both the dephosphorylation and the desensitization. Therefore, in contrast to many other cell surface receptors, GC-A is desensitized by ligand-induced dephosphorylation.
Pathogenesis of the toxic shock syndrome: T cell mediated lethal shock caused by the superantigen TSST‐1 (1993)

The pathogenesis of the toxic shock syndrome (TSS) is only incompletely understood. We now present evidence that TSS toxin-1 (TSST-1), one of the superantigens produced by Staphylococcus aureus, induces lethal shock in D-galactosamine sensitized mice. In this model TSS is dependent on T cells, since cyclosporin A (CsA) completely blocked development of shock, and since T cell-deficient SCID mice did not show signs of disease upon injection with TSST-1. However, SCID mice repopulated with T cells succumbed to lethal shock. The disease is characterized by a burst of lymphokines like interleukin-2 (IL-2) and tumor necrosis factor (TNF) released into the sera of TSST-1-treated animals. Already 1-2 h after TSST-1 application TNF serum levels peaked and IL-2 levels peaked around 4 h after treatment. TNF appears as key mediator of TSS, because anti-TNF monoclonal antibodies protected TSST-1-challenged mice. Interestingly, the burst of TNF in serum was noted well in advance of detectable markers of T cell activation. Thus, about 5% of all peripheral T cells started to express the IL-2 receptors as late as 4 h after treatment. Comparing TSST-1- and endotoxin-induced shock we conclude that TNF effects shock in both diseases. However, the type of cells involved appears distinct in that T cells cause TSS triggered by the exotosin TSST-1 while macrophages mediate the shock induced by endotoxins.
Ester Quats: The Novel Class of Cationic Fabric Softeners (2007)

Esterquats, which are quaternary ammonium compounds having two long (C(16)-C(18)) fatty acid chains with 2 weak ester linkages, represent a new generation of fabric softening agents, having replaced the dialkyldimethylammonium salts (e.g. DTDMAC and DSDMAC). The inclusion of ester linkages into the aliphatic chains has significantly improved the kinetics of biodegradation of the cationic surfactants, lowering the environmental exposure levels. This new generation of fabric softening agents combines a good environmental profile with the structural features required for an effective fabric conditioner. The present paper reviews the synthesis, types, actives combines a good environmental profile with the structural features required for a properties and applications of esterquats.
Recombinant DNA Technology and Applications (1991)

Part I: Cloning Techniques & Applications: Cloning in Bacteria, Vectors and Techniques. Part II: Applications of Recombinant and other Related Technologies in Medicine. Part III: Improving Product Expression and Recovery. Part IV: Bioprocessing: Reactors & Facilities. Part V: Societal Issues.
The Representation of Polysemy: MEG Evidence (2006)

Most words in natural language are polysemous, that is, they can be used in more than one way. For example, paper can be used to refer to a substance made out of wood pulp or to a daily publication printed on that substance. Although virtually every sentence contains polysemy, there is little agreement as to how polysemy is represented in the mental lexicon. Do different uses of polysemous words involve access to a single representation or do our minds store distinct representations for each different sense? Here we investigated priming between senses with a combination of behavioral and magnetoencephalographic measures in order to test whether different senses of the same word involve identity or mere formal and semantic similarity. Our results show that polysemy effects are clearly distinct from similarity effects bilaterally. In the left hemisphere, sense-relatedness elicited shorter latencies of the M350 source, which has been hypothesized to index lexical activation. Concurrent activity in the right hemisphere, on the other hand, peaked later for sense-related than for unrelated target stimuli, suggesting competition between related senses. The obtained pattern of results supports models in which the representation of polysemy involves both representational identity and difference: Related senses connect to same abstract lexical representation, but are distinctly listed within that representation.