gebhart/patrepeval huggingface dataset:
Cancer cell angiogenic capability is regulated by 3D culture and integrin engagement (2009)

Three-dimensional culture alters cancer cell signaling; however, the underlying mechanisms and importance of these changes on tumor vascularization remain unclear. A hydrogel system was used to examine the role of the transition from 2D to 3D culture, with and without integrin engagement, on cancer cell angiogenic capability. Three-dimensional culture recreated tumor microenvironmental cues and led to enhanced interleukin 8 (IL-8) secretion that depended on integrin engagement with adhesion peptides coupled to the polymer. In contrast, vascular endothelial growth factor (VEGF) secretion was unaffected by 3D culture with or without substrate adhesion. IL-8 diffused greater distances and was present in higher concentrations in the systemic circulation, relative to VEGF. Implantation of a polymeric IL-8 delivery system into GFP bone marrow-transplanted mice revealed that localized IL-8 up-regulation was critical to both the local and systemic control of tumor vascularization in vivo. In summary, 3D integrin engagement within tumor microenvironments regulates cancer cell angiogenic signaling, and controlled local and systemic blockade of both IL-8 and VEGF signaling may improve antiangiogenic therapies.
Electrophysiological analysis of the function of the mammalian renal peptide transporter expressed in xenopus laevis oocytes (1997)

1. To gain information on the mode of operation of the renal proton-coupled peptide transporter PepT2, voltage clamp studies were performed in Xenopus laevis oocytes expressing the rabbit renal PepT2. 2. Using differently charged glycyl-dipeptides we show that PepT2 translocates these dipeptides by an electrogenic pH-dependent process that is essentially independent of the substrate net charge. The apparent substrate affinities are in the micromolar range (2-50 microM) between pH 5.5 and 7.4 and membrane potentials of +/- 0 to -50 mV. 3. Maximal substrate-evoked inward currents (Imax) are affected by membrane voltage (Vm) and extracellular pH (pHo). Potential-dependent interactions of H+/H3O+ with PepT2 seem to be mediated by a single low affinity binding site and PepT2 remains pH dependent at all voltages. 4. The effects of voltage on apparent Imax and substrate affinity display an inverse relationship. As Vm is altered from -50 to -150 mV substrate affinities decrease 10- to 50-fold whereas apparent Imax increases almost 10-fold. 5. Even at saturating H+/H3O+ and dipeptide concentrations the I-V curves did not show saturation at negative membrane potentials, suggesting that other steps in the reaction cycle and not the ligand affinity changes are rate limiting. These are possibly the conformational changes of the empty and/or loaded transporters. 6. These findings demonstrate that not only substrate affinities but also other kinetic characteristics of PepT2 differ markedly from those of the intestinal peptide transporter isoform PepT1.
Solution structure of thanatin, a potent bactericidal and fungicidal insect peptide, determined from proton two‐dimensional nuclear magnetic resonance data (1998)

Thanatin is the first inducible insect peptide that has been found to have, at physiological concentrations, a broad range of activity against bacteria and fungi. Thanatin contains 21 amino acids including two cysteine residues that form a disulfide bridge. Two-dimensional (2D) 1H-NMR spectroscopy and molecular modelling have been used to determine its three-dimensional (3D) structure in water. Thanatin adopts a well-defined anti-parallel beta-sheet structure from residue 8 to the C-terminus, including the disulfide bridge. In spite of the presence of two proline residues, there is a large degree of structural variability in the N-terminal segment. The structure of thanatin is quite different from the known structures of other insect defence peptides, such as antibacterial defensin and antifungal drosomycin. It has more similarities with the structures of various peptides from different origins, such as brevinins, protegrins and tachyplesins, which have a two-stranded beta-sheet stabilized by one or two disulfide bridges. Combined with activity test experiments on several truncated isoforms of thanatin, carried out by Fehlbaum et al. [Fehlbaum, P., Bulet, P., Chernysh, S., Briand, J. P., Roussel, J. P., Letellier, L., Hétru, C. & Hoffmann, J. (1996) Proc. Natl Acad. Sci. USA 93, 1221-1225], our structural study evidences the importance of the beta-sheet structure and also suggests that anti-Gram-negative activity involves a site formed by the Arg20 side-chain embedded in a hydrophobic cluster.
Farnesoid X Receptor Modulates Renal Lipid Metabolism, Fibrosis, and Diabetic Nephropathy (2007)

These results therefore indicate a new and important role for FXR in the kidney and provide new therapeutic avenues for the treatment of diabetic nephropathy.
Predominant CD4 T-lymphocyte tropism of human herpesvirus 6-related virus (1989)

Human herpesvirus 6 (HHV-6)-related virus was isolated from CD4+ CD8- and CD3+ CD4+ mature T lymphocytes but could not be isolated from CD4- CD8+, CD4- CD8-, and CD3- T cells in the peripheral blood of exanthem subitum patients. HHV-6-related virus predominantly infected CD4+ CD8+, CD4+ CD8-, and CD3+ CD4+ cells with mature phenotypes and rarely infected CD4- CD8+ cells from cord blood mononuclear cells, which suggested predominant CD4 mature T-lymphocyte tropism of HHV-6-related virus.
Electron Transfer through DNA: Site‐Specific Modification of Duplex DNA with Ruthenium Donors and Acceptors (1995)

The rate of the electron transfer between two ruthenium centers at the ends of an octanucleotide duplex (metal‐to‐metal distance = 21 Å) was determined to be 1.6(4) × 10 6 s −1 . By using automated DNA synthesis techniques, modified oligonucleotides were prepared with a protected phosphoroamidite of 2′‐amino‐2′‐deoxyuridine. The NH 2 ‐modified oligonucleotides were hybridized with complementary DNA sequences to protect nucleotide bases, and then treated with ruthenium complexes. In this way the ruthenium complex was bound only to the free NH 2 group.
Vaccine-Stimulated, Adoptively Transferred CD8+ T Cells Traffic Indiscriminately and Ubiquitously while Mediating Specific Tumor Destruction (2004)

It has been suggested that antitumor T cells specifically traffic to the tumor site, where they effect tumor destruction. To test whether tumor-reactive CD8(+) T cells specifically home to tumor, we assessed the trafficking of gp100-specific pmel-1 cells to large, vascularized tumors that express or do not express the target Ag. Activation of tumor-specific CD8(+) pmel-1 T cells with IL-2 and vaccination with an altered peptide ligand caused regression of gp100-positive tumors (B16), but not gp100-negative tumors (methylcholanthrene 205), implanted on opposing flanks of the same mouse. Surprisingly, we found approximately equal and very large numbers of pmel-1 T cells (>25% of all lymphocytes) infiltrating both Ag-positive and Ag-negative tumors. We also found evidence of massive infiltration and proliferation of activated antitumor pmel-1 cells in a variety of peripheral tissues, including lymph nodes, liver, spleen, and lungs, but not peripheral blood. Most importantly, evidence for T cell function, as measured by production of IFN-gamma, release of perforin, and activation of caspase-3 in target cells, was confined to Ag-expressing tumor. We thus conclude that CD8(+) T cell-mediated destruction of tumor is the result of specific T cell triggering at the tumor site. The ability to induce ubiquitous homing and specific tumor destruction may be important in the case of noninflammatory metastatic tumor foci.
Nurr1 and Retinoid X Receptor Ligands Stimulate Ret Signaling in Dopamine Neurons and Can Alleviate α-Synuclein Disrupted Gene Expression (2015)

How α-synuclein, a protein enriched in Lewy bodies in Parkinson's disease, is causing neuropathology in dopamine neurons remains unclear. This study elucidated how α-synuclein is influencing gene expression and how Nurr1, a transcription factor known to protect dopamine neurons against α-synuclein toxicity, can counteract these effects. Moreover, given the protective role of Nurr1, this study also investigated how Nurr1 could be pharmacologically targeted via bexarotene, a ligand of Nurr1's heterodimerization partner retinoid X receptor (RXR). The results showed that RXR ligands could increase neurotrophic signaling, but provided a mixed picture of its potential in a Parkinson's disease rat model in vivo. However, this study clearly emphasized Nurr1's neuroprotective role and indicated that other RXR ligands could have therapeutic potential in Parkinson's disease.
Nck-Interacting Ste20 Kinase Couples Eph Receptors to c-Jun N-Terminal Kinase and Integrin Activation (2000)

The mammalian Ste20 kinase Nck-interacting kinase (NIK) specifically activates the c-Jun amino-terminal kinase (JNK) mitogen-activated protein kinase module. NIK also binds the SH3 domains of the SH2/SH3 adapter protein Nck. To determine whether Nck functions as an adapter to couple NIK to a receptor tyrosine kinase signaling pathway, we determined whether NIK is activated by Eph receptors (EphR). EphRs constitute the largest family of receptor tyrosine kinases (RTK), and members of this family play important roles in patterning of the nervous and vascular systems. In this report, we show that NIK kinase activity is specifically increased in cells stimulated by two EphRs, EphB1 and EphB2. EphB1 kinase activity and phosphorylation of a juxtamembrane tyrosine (Y594), conserved in all Eph receptors, are both critical for NIK activation by EphB1. Although pY594 in the EphB1R has previously been shown to bind the SH2 domain of Nck, we found that stimulation of EphB1 and EphB2 led predominantly to a complex between NIK/Nck, p62(dok), RasGAP, and an unidentified 145-kDa tyrosine-phosphorylated protein. Tyrosine-phosphorylated p62(dok) most probably binds directly to the SH2 domain of Nck and RasGAP and indirectly to NIK bound to the SH3 domain of Nck. We found that NIK activation is also critical for coupling EphB1R to biological responses that include the activation of integrins and JNK by EphB1. Taken together, these findings support a model in which the recruitment of the Ste20 kinase NIK to phosphotyrosine-containing proteins by Nck is an important proximal step in the signaling cascade downstream of EphRs.
Mechanistic studies of RNA modifying enzymes. RNA pseudouridine synthase and m5Cytosine methyl tranferase (2000)

RNA has numerous post-transcriptional modifications, but relatively little is known about the enzymes that catalyze such modifications or about the functions of the modified residues. Our laboratory has been engaged in studies of the structure and function of enzymes that catalyze the conversion of Urd residues in RNA to pseudouridine (psi Synthase), and Cyd to 5-methylcytidine methyl transferase (RNA m5C Mtase). The presentation will summarize recent results from our laboratory.
High Expression of Macrophage Colony-Stimulating Factor-1 Receptor in Peritumoral Liver Tissue Is Associated with Poor Outcome in Hepatocellular Carcinoma After Curative Resection (2010)

Peritumoral CSF-1R is associated with intrahepatic metastasis, tumor recurrence, and patient survival after hepatectomy, highlighting the critical role of the peritumoral liver milieu in HCC progression. CSF-1R may become a potential therapeutic target for postoperative adjuvant treatment.
Radiographic assessment of progression in osteoarthritis (1987)

Abstract We evaluated methods of grading radiologic progression of osteoarthritis (OA). Sets of radiographs were assessed separately by 8 readers who were blinded to the time sequence. Included were radiographs of patients with OA of the hands (24 pairs), hips (40 pairs), and knees (32 pairs). Most films were taken 12–60 months apart. The relative contribution of individual joints (such as particular interphalangeal joints), of observations (such as narrowing or spurs), and of a single joint compartment (such as the medial or lateral compartment of the knee) toward evidence of OA progression was evaluated, as well as the reliability and concordance of scoring, and the sensitivity in detecting change. In assessing OA of the hand, the greatest sensitivity was achieved by reading a single posteroanterior bilateral hand radiograph for narrowing, spurs, and erosions, and scoring 10 joints (second and third distal interphalangeal, second and third proximal interphalangeal, and trapeziometacarpal joints, bilaterally), using a scale of 0–3. In OA of the hip, a single anteroposterior radiograph assessed for joint space narrowing and cyst formation yielded the greatest sensitivity. In OA of the knee, an anteroposterior radiograph, with weight‐bearing, assessed for narrowing, spurs, and sclerosis in both the medial and lateral compartments yielded the greatest sensitivity. These techniques will be useful to the investigator in designing experimental studies and to the clinician in determining the rate of disease progression in an individual patient.
Progressive Motor Deficit is Mediated by the Denervation of Neuromuscular Junctions and Axonal Degeneration in Transgenic Mice Expressing Mutant (P301S) Tau Protein (2017)

Tauopathies include a variety of neurodegenerative diseases associated with the pathological aggregation of hyperphosphorylated tau, resulting in progressive cognitive decline and motor impairment. The underlying mechanism for motor deficits related to tauopathy is not yet fully understood. Here, we use a novel transgenic tau mouse line, Tau 58/4, with enhanced neuron-specific expression of P301S mutant tau to investigate the motor abnormalities in association with the peripheral nervous system. Using stationary beam, gait, and rotarod tests, motor deficits were found in Tau 58/4 mice already 3 months after birth, which deteriorated during aging. Hyperphosphorylated tau was detected in the cell bodies and axons of motor neurons. At the age of 9 and 12 months, significant denervation of the neuromuscular junction in the extensor digitorum longus muscle was observed in Tau 58/4 mice, compared to wild-type mice. Muscle hypotrophy was observed in Tau 58/4 mice at 9 and 12 months. Using electron microscopy, we observed ultrastructural changes in the sciatic nerve of 12-month-old Tau 58/4 mice indicative of the loss of large axonal fibers and hypomyelination (assessed by g-ratio). We conclude that the accumulated hyperphosphorylated tau in the axon terminals may induce dying-back axonal degeneration, myelin abnormalities, neuromuscular junction denervation, and muscular atrophy, which may be the mechanisms responsible for the deterioration of the motor function in Tau 58/4 mice. Tau 58/4 mice represent an interesting neuromuscular degeneration model, and the pathological mechanisms might be responsible for motor signs observed in some human tauopathies.
US Valuation of the EQ-5D Health States (2005)

The D1 model best predicts the values for observed health states. The resulting preference weight estimates represent a significant enhancement of the EQ-5D's utility for health status assessment and economic analysis in the US.
A critical role for extracellular protein disulfide isomerase during thrombus formation in mice (2008)

Thiol isomerases, including protein disulfide isomerase (PDI), catalyze disulfide oxidation, reduction, and isomerization, thereby playing an important role in protein synthesis. To determine whether extracellular PDI mediates thrombus formation in an animal model, PDI expression, platelet accumulation, and fibrin generation were monitored in the blood vessels of mice by intravital fluorescence microscopy following laser-induced arteriolar injury. A time-dependent increase in PDI was observed in murine thrombi following injury. Infusion of the PDI inhibitor bacitracin or a blocking monoclonal antibody against PDI inhibited platelet thrombus formation and fibrin generation. Fibrin deposition is normal in mice lacking the G protein-coupled platelet receptor Par4, although there is no stable accumulation of platelets. Infusion of monoclonal antibodies against PDI into the circulation of Par4(-/-) mice prior to vessel wall injury inhibited fibrin generation. These results indicate that PDI is required in vivo in mice for both fibrin generation and platelet thrombus formation.
Effects of Sodium Chloride Particles, Ozone, UV, and Relative Humidity on Atmospheric Corrosion of Silver (2010)

The corrosion of Ag contaminated with NaCl particles in gaseous environments containing humidity and ozone was investigated. In particular, the effects of relative humidity and UV light illumination were quantitatively analyzed using a coulometric reduction technique. The atmospheric corrosion of Ag was greatly accelerated in the presence of ozone and UV light. Unlike bare Ag (i.e., with no NaCl particles on the surface), Ag with NaCl exhibited fast corrosion even in the dark, with no UV in the presence of ozone. Samples exposed to different outdoor environments and samples exposed in a salt spray chamber were studied for comparison. Ag corroded at extremely low rates in a salt spray chamber partly because of the combined absence of light and oxidizing agents such as ozone.
HKL-3000: the integration of data reduction and structure solution – from diffraction images to an initial model in minutes (2006)

A new approach that integrates data collection, data reduction, phasing and model building significantly accelerates the process of structure determination and on average minimizes the number of data sets and synchrotron time required for structure solution. Initial testing of the HKL-3000 system (the beta version was named HKL-2000_ph) with more than 140 novel structure determinations has proven its high value for MAD/SAD experiments. The heuristics for choosing the best computational strategy at different data resolution limits of phasing signal and crystal diffraction are being optimized. The typical end result is an interpretable electron-density map with a partially built structure and, in some cases, an almost complete refined model. The current development is oriented towards very fast structure solution in order to provide feedback during the diffraction experiment. Work is also proceeding towards improving the quality of phasing calculation and model building.
pH and Chemotherapy (2001)

In vivo pH measurements by magnetic resonance spectroscopy reveal the presence of large regions of acidic extracellular pH in tumours, with the intracellular pH being maintained in the neutral-to-alkaline range. This acid-outside plasmalemmal pH gradient acts to exclude weak base drugs such as the anthracyclines and vinca alkaloids, a behaviour that is predicted by the decrease in octanol-water partition coefficients of mitoxantrone and doxorubicin with decreasing solution pH. This pH gradient can be reduced or eliminated in mouse models of breast cancer by systemic treatment with sodium bicarbonate. We have demonstrated tumour alkalinization following chronic ad libitum administration of NaHCO3 and acute intraperitoneal administration of NaHCO3 to tumour-bearing mice. Chronic treatment of tumour-bearing SCID mice with NaHCO3 results in an enhancement in MCF-7 tumour xenograft response to doxorubicin. Intraperitoneal administration of NaHCO3 to tumour-bearing C3H/Hen mice prior to treatment with mitoxantrone results in a greater-than 4.5-fold increase in cell-kill in the syngeneic C3H mammary tumour model. Most combination chemotherapy regimens include at least one weak base drug. Our results suggest that agents such as sodium bicarbonate, Carbicarb and the diuretic furosemide--which are known to induce metabolic alkalosis in humans--may be useful in enhancing the efficacy of these treatment regimens in humans.
A20 as an immune tolerance factor can determine islet transplant outcomes (2019)

Islet transplantation can restore lost glycemic control in type 1 diabetes subjects but is restricted in its clinical application by a limiting supply of islets and the need for heavy immune suppression to prevent rejection. TNFAIP3, encoding the ubiquitin editing enzyme A20, regulates the activation of immune cells by raising NF-κB signaling thresholds. Here, we show that increasing A20 expression in allogeneic islet grafts resulted in permanent survival for ~45% of recipients, and > 80% survival when combined with subtherapeutic rapamycin. Allograft survival was dependent upon Tregs and was antigen specific, and grafts showed reduced expression of inflammatory factors. Transplantation of islets with A20 containing a loss-of-function variant (I325N) resulted in increased RIPK1 ubiquitination and NF-κB signaling, graft hyperinflammation, and acute allograft rejection. Overexpression of A20 in human islets potently reduced expression of inflammatory mediators, with no impact on glucose-stimulated insulin secretion. Therapeutic administration of A20 raises inflammatory signaling thresholds to favor immune tolerance and promotes islet allogeneic survival. Clinically, this would allow for reduced immunosuppression and support the use of alternate islet sources.
Porphocyanine: an expanded tetrapyrrolic macrocycle (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPorphocyanine: an expanded tetrapyrrolic macrocycleDavid Dolphin, Steven J. Rettig, Hang Tang, Tilak Wijesekera, and Lily Yun XieCite this: J. Am. Chem. Soc. 1993, 115, 20, 9301–9302Publication Date (Print):October 1, 1993Publication History Published online1 May 2002Published inissue 1 October 1993https://pubs.acs.org/doi/10.1021/ja00073a061https://doi.org/10.1021/ja00073a061research-articleACS PublicationsRequest reuse permissionsArticle Views221Altmetric-Citations32LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Effect of the Benzylic Structure of Lignan on Antioxidant Activity (2007)

The effect of the benzylic structure of lignan on antioxidant activity was evaluated. Secoisolariciresinol (1) and 3,4-bis(4-hydroxy-3-methoxybenzyl)tetrahydrofuran (2), which have two secondary benzylic positions without oxygen, showed the highest antioxidant activity. Optically active verrucosin (4) was synthesized for the first time in this experiment.