gebhart/patrepeval huggingface dataset:
μ opioid and CB1 cannabinoid receptor interactions: reciprocal inhibition of receptor signaling and neuritogenesis (2006)

Several studies have described functional interactions between opioid and cannabinoid receptors; the underlying mechanism(s) have not been well explored. One possible mechanism is direct receptor-receptor interactions, as has been demonstrated for a number of G-protein-coupled receptors. In order to investigate interactions between opioid and cannabinoid receptors, we epitope tagged mu, delta and kappa opioid receptors with Renilla luciferase and CB1 cannabinoid or CCR5 chemokine receptors with yellow fluorescent protein and examined the extent of substrate hydrolysis induced bioluminescence resonance energy transfer (BRET) signal. We find that coexpression of opioid receptors with cannabinoid receptors, but not with chemokine receptors, leads to a significant increase in the level of BRET signal, suggesting that the opioid-cannabinoid interactions are receptor specific. In order to examine the implications of these interactions to signaling, we used GTPgammaS binding and mitogen-activated protein kinase (MAPK) phosphorylation assays and examined the effect of receptor activation on signaling. We find that the mu receptor-mediated signaling is attenuated by the CB1 receptor agonist; this effect is reciprocal and is seen in heterologous cells and endogenous tissue expressing both receptors. In order to explore the physiological consequences of this interaction, we examined the effect of receptor activation on the extent of Src and STAT3 phosphorylation and neuritogenesis in Neuro-2A cells. We find that the simultaneous activation of mu opioid and CB1 cannabinoid receptors leads to a significant attenuation of the response seen upon activation of individual receptors, implicating a role for receptor-receptor interactions in modulating neuritogenesis.
Epidermal Growth Factor Receptor Activation of Calpain Is Required for Fibroblast Motility and Occurs via an ERK/MAP Kinase Signaling Pathway (2000)

To become migratory, cells must reorganize their connections to the substratum, and during locomotion they must break rear attachments. The molecular and biochemical mechanisms underlying these biophysical processes are unknown. Recent studies have implicated both extracellular signal-regulated kinase/mitogen-activated protein (ERK/MAP) kinase and calpain (EC 3.4.22.17) in these processes, but it is uncertain whether these are two distinct pathways acting on different modes of motility. We report that cell deadhesion involved in epidermal growth factor (EGF) receptor-mediated fibroblast motility requires activation of M-calpain downstream of ERK/MAP kinase signaling. NR6 fibroblasts expressing full-length wild type epidermal growth factor receptor required both calpain and ERK activation, as demonstrated by pharmacological inhibitors (calpeptin and calpain inhibitor I and PD98059, respectively) for EGF-induced deadhesion and motility. EGF induced rapid activation of calpain that was preventable by molecular inhibition of the Ras-Raf-MEK but not phospholipase Cgamma signaling pathway, and calpain was stimulated by transfection of constitutively active MEK. Enhanced calpain activity was not mirrored by increased calpain protein levels or decreased levels of its endogenous inhibitor calpastatin. The link between ERK/MAP kinase signaling and cell motility required the M-isoform of calpain (calpain II), as determined by specific antisense-mediated down-regulation. These data promote a previously undescribed signaling pathway of ERK/MAP kinases activating calpain to destabilize cell-substratum adhesions in response to EGF stimulation.
Absence of the p75 Neurotrophin Receptor Alters the Pattern of Sympathosensory Sprouting in the Trigeminal Ganglia of Mice Overexpressing Nerve Growth Factor (1999)

Sympathetic axons invade the trigeminal ganglia of mice overexpressing nerve growth factor (NGF) (NGF/p75(+/+) mice) and surround sensory neurons having intense NGF immunolabeling; the growth of these axons appears to be directional and specific (). In this investigation, we provide new insight into the neurochemical features and receptor requirements of this sympathosensory sprouting. Using double-antigen immunohistochemistry, we demonstrate that virtually all (98%) trigeminal neurons that exhibit a sympathetic plexus are trk tyrosine kinase receptor (trkA)-positive. In addition, the majority (86%) of those neurons enveloped by sympathetic fibers is also calcitonin gene-related peptide (CGRP)-positive; a smaller number of plexuses (14%) surrounded other somata lacking this neuropeptide. Our results show that sympathosensory interactions form primarily between noradrenergic sympathetic efferents and the trkA/CGRP-expressing sensory somata. To assess the contribution of the p75 neurotrophin receptor (p75(NTR)) in sympathosensory sprouting, a hybrid strain of mice was used that overexpresses NGF but lacks p75(NTR) expression (NGF/p75(-/-) mice). The trigeminal ganglia of NGF/p75(-/-) mice, like those of NGF/p75(+/+) mice, have increased levels of NGF protein and display a concomitant ingrowth of sympathetic axons. In contrast to the precise pattern of sprouting seen in the ganglia of NGF/p75(+/+) mice, sympathetic axons course randomly throughout the ganglionic neuropil of NGF/p75(-/-) mice, forming few perineuronal plexuses. Our results indicate that p75(NTR) is not required to initiate or sustain the growth of sympathetic axons into the NGF-rich trigeminal ganglia but rather plays a role in regulating the directional patterns of axon growth.
One active C1r subunit is sufficient for the activity of the complement C1 complex: stabilization of C1r in the zymogen form by point mutations. (1999)

The binding of C1 (the first component of complement) to immune complexes leads to the autoactivation of C1r through the cleavage of the Arg463-Ile464 bond in the catalytic domain. Spontaneous activation of C1r (and C1) also occurs in the fluid phase, preventing the characterization of the zymogen form of C1r. To overcome this difficulty, the zymogen form of human C1r was stabilized by mutating the Arg in the Arg463-Ile464 bond to Gln. This mutant was designated as mutant QI. Recombinant C1r (wild type (wt) or mutant) was expressed in insect cells using serum-free medium in functionally pure form; therefore, the cell culture supernatant was suitable to reconstruct C1 for the hemolytic assay. Mutant QI was a stable, nonactivable zymogen and showed no hemolytic activity in reconstituted C1. However, this stable zymogen C1r mutant could form an active mixed dimer with the wt C1r, indicating that one active C1r subunit in the C1 complex is sufficient for the full activity of the entire complex. Our experiments also showed that the exchange of C1r monomers between the C1r dimers is completed in less than 16 h even at pH 7 and 4 degrees C. Two other mutants were also constructed by changing Arg463 to Lys, or Ile464 to Phe, and were designated as mutants KI and RF, respectively. Although these substitutions did increase the stability of the proenzyme in the cell culture supernatant, the mutant proteins retained their ability to autoactivate, and both had a wt-like hemolytic activity.
Sensor Development for Agricultural Vehicle Guidance (1993)

&lt;div class="htmlview paragraph"&gt;The potential exists for significantly reducing operating costs by minimizing missing and overlap in successive agricultural field operations, particularly in areas where the equipment is pull-behind and widths of over fifteen meters are common.&lt;/div&gt; &lt;div class="htmlview paragraph"&gt;This paper reports on the development of a sensor, consisting of a video camera and image processing system, to detect the location of the demarcation line between tilled-and-untilled soil and cut-and-standing crop. The development of hardware and software to achieve real-time operation under a variety of crop, soil and ambient lighting conditions is described.&lt;/div&gt;
A Survey of Validation Strategies for CRISPR-Cas9 Editing (2018)

The T7 endonuclease 1 (T7E1) mismatch detection assay is a widely used method for evaluating the activity of site-specific nucleases, such as the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system. To determine the accuracy and sensitivity of this assay, we compared the editing estimates derived by the T7E1 assay with that of targeted next-generation sequencing (NGS) in pools of edited mammalian cells. Here, we report that estimates of nuclease activity determined by T7E1 most often do not accurately reflect the activity observed in edited cells. Editing efficiencies of CRISPR-Cas9 complexes with similar activity by T7E1 can prove dramatically different by NGS. Additionally, we compared editing efficiencies predicted by the Tracking of Indels by Decomposition (TIDE) assay and the Indel Detection by Amplicon Analysis (IDAA) assay to that observed by targeted NGS for both cellular pools and single-cell derived clones. We show that targeted NGS, TIDE, and IDAA assays predict similar editing efficiencies for pools of cells but that TIDE and IDAA can miscall alleles in edited clones.
Shape Control of Manipulators with Hyper Degrees of Freedom (1999)

This paper provides a theoretical framework for controlling a manipulator with hyper degrees of freedom (HDOF). An HDOF manipulator has the capability to achieve various kinds of tasks. To make full use of its capability, shape control is proposed here; that is, not only the tip of a manipulator, but also its whole body is controlled. To formulate control objectives for shape control, we define a shape correspondence between an HDOF manipulator and a spatial curve that prescribes a desired shape. The shape correspondence is defined by using solutions of a nonlinear optimization problem termed the shape-inverse problem. We give theorems on the existence of the solutions, and on an existence region that allows us to convert shape-control problems into more tractable ones. A shape-regulation control problem is considered first to bring an HDOF manipulator onto a given time-invariant curve. The idea of estimating the desired curve parameters is the crucial key to solving the problem by Lyapunov design. The derived shape-regulation law includes the estimator, which infers the desired curve parameters corresponding to the desired joint positions on the curve. The idea of the desired curve-parameter estimation is also effective for shape tracking where a time-varying curve is used for prescribing a moving desired shape. Considering an estimator with second-order dynamics enables us to find two shape-tracking control laws by utilizing conventional tracking methods in manipulator control. We show the simulation results of applying the derived shape-tracking control laws to a 20-DOF manipulator.
Improving Drug Delivery to Intracerebral Tumor and Surrounding Brain in a Rodent Model: A Comparison of Osmotic versus Bradykinin Modification of the Blood-Brain and/or Blood-Tumor Barriers (1998)

BBBD resulted in global delivery of a variety of agents in a wide range of sizes. In this human brain tumor xenograft model, bradykinin was not effective at increasing delivery to the tumor of any agent tested.
Dexmedetomidine for opioid and benzodiazepine withdrawal in pediatric patients (2011)

A limited body of published evidence from retrospective studies and case reports suggests a potential role for dexmedetomidine as an adjunct therapy to provide sedation and analgesia to reduce narcotic withdrawal symptoms in pediatric patients.
Liposomal Delivery of CTL Epitopes to Dendritic Cells (2002)

The induction of strong and long lasting T-cell response, CD4+ or CD8+, is a major requirement in the development of efficient vaccines. An important aspect involves delivery of antigens to dendritic cells (DCs) as antigen presenting cells (APCs) for the induction of potent antigen-specific CD8+ T lymphocyte (CTLs) responses. Protein or peptide-based vaccines become an attractive alternative to the use of live cell vaccines to stimulate CTL responses for the treatment of viral diseases or malignancies. However, vaccination with proteins or synthetic peptides representing discrete CTL epitopes have failed in most instances due to the inability for exogenous antigens to be properly presented to T cells via major histocompatibility complex (MHC) class I molecules. Modern vaccines, based on either synthetic or natural molecules, will be designed in order to target appropriately professional APCs and to co-deliver signals able to facilitate activation of DCs. In this review, we describe the recent findings in the development of lipid-based formulations containing a combination of these attributes able to deliver tumor- or viral-associated antigens to the cytosol of DCs. We present in vitro and pre-clinical studies reporting specific immunity to viral, parasitic infection and tumor growth.
[Test of efficacy of an oxalate-binding anion exchanger Colestid in healthy subjects for use in idiopathic calcium-oxalate urolithiasis]. (1981)

Sodium oxalate (402 mg) was administered in a single dose to 10 healthy volunteers receiving a controlled diet. Half the group received 3 times 10 g Colestid and the other half 4 times 2 g Andursil. On the 5th day the oxalate load was repeated. Urine was collected within 32 hours following oxalate application in 8 fractions. In each fraction the levels of oxalate, calcium, phosphate and uric acid were determined. The amount of oxalate, phosphate and uric acid measured in the group receiving Colestid was lower in all fractions. Peak excretions of oxalate found in unmedicated volunteers were suppressed following oxalate load. In the group receiving Andursil, only the excretion of phosphate was decreased. The results presented suggest that Colestid may be promising in the prevention of calcium-oxalate-urolithiasis.
Activation of Nuclear Orphan Receptor NURR1 Transcription by NF-κB and Cyclic Adenosine 5′-Monophosphate Response Element-Binding Protein in Rheumatoid Arthritis Synovial Tissue (2002)

Modulation of the NURR subfamily of nuclear receptors may be an important mechanism regulating pathways associated with inflammatory joint disease. We examined the signaling mechanisms through which inflammatory mediators, produced by rheumatoid arthritis (RA) synovial tissue, contribute to the regulation of the NURR subfamily. Markedly enhanced expression of NURR1 is observed in synovial tissue of patients with RA compared with normal subjects. Modulation by proinflammatory mediators in primary RA and normal synoviocytes shows that PGE(2), IL-1beta, and TNF-alpha markedly enhance NURR1 mRNA and protein levels in contrast to other subfamily members, NUR77 and NOR-1. We have established that transcriptional activation of the NURR1 gene by IL-1beta and TNF-alpha requires a proximal promoter region that contains a consensus NF-kappaB DNA-binding motif. IL-1beta- and TNF-alpha-induced NF-kappaB binding to this site is due predominantly to p65-p50 heterodimer and p50 homodimer subunit protein complexes. We further demonstrate a direct CREB-1-dependent regulation by PGE(2) situated at promoter region -171/-163. Moreover, analyses confirm the presence of CREB-1 and NF-kappaB p50 and p65 subunit binding to the NURR1 promoter under basal conditions in freshly explanted RA synovial tissue. In summary, enhanced NF-kappaB- and CREB-1-binding activity on the NURR1 promoter by inflammatory mediators delineates novel mechanisms in the regulation of NURR1 transcription. PGE(2)-, TNF-alpha-, and IL-1beta-dependent stimulation of the NURR1 gene implies that NURR1 induction represents a point of convergence of at least two distinct signaling pathways, suggesting an important common role for this transcription factor in mediating multiple inflammatory signals.
Single-molecule denaturation mapping of DNA in nanofluidic channels (2010)

Here we explore the potential power of denaturation mapping as a single-molecule technique. By partially denaturing YOYO-1-labeled DNA in nanofluidic channels with a combination of formamide and local heating, we obtain a sequence-dependent "barcode" corresponding to a series of local dips and peaks in the intensity trace along the extended molecule. We demonstrate that this structure arises from the physics of local denaturation: statistical mechanical calculations of sequence-dependent melting probability can predict the barcode to be observed experimentally for a given sequence. Consequently, the technique is sensitive to sequence variation without requiring enzymatic labeling or a restriction step. This technique may serve as the basis for a new mapping technology ideally suited for investigating the long-range structure of entire genomes extracted from single cells.
Programmed death-1 pathway blockade produces a synergistic antitumor effect: combined application in ovarian cancer (2017)

Programmed death-1 (PD-1) and its ligand are part of the immune checkpoint pathway that down-regulates effector T cells in immune response, thereby causing immune suppression. The PD-1/programmed death-ligand 1 (PD-L1) pathway can be blocked by antibodies to reverse tumor-mediated immunosuppression. However, advanced cancers such as stage III-IV ovarian cancer (OC) and certain types such as ID8 OC (a clone of C57BL/6 mouse OC) may hijack the PD-1/PD-L1 pathway to escape immune attack. When combined with chemotherapy, radiotherapy, targeted therapy, immunotherapy, or other agents, these PD-1/PD-L1 pathway blockages can produce a synergistic antitumor response in OC. Combined immunotherapy significantly prolongs overall survival by changing the tumor microenvironment through processes such as increasing the number of CD4⁺ or CD8⁺ T cells or cytokines in mice with OC and decreasing the number of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). OC patients treated with combined immunotherapy received better prognoses than those treated with monotherapy. This review reflects the move toward novel therapy combinations for OC and discusses these promising immunotherapeutic approaches, which are more cost-effective and effective than other approaches.
Review of the Molecular Requirements of Endotoxic Actions (1987)

Old and new data are compiled to confirm earlier claims and to substantiate new concepts regarding the structural requirements of endotoxic reactions. The major points can be summarized as follows. (1) Recent results obtained by the use of synthetic analogues of lipid A structures proved unequivocally that the lipid moiety of the endotoxin is the carrier of toxic properties. Incomplete or attenuated structures are inactive in some or all toxic reactions, depending on the extent of deviations from the structure of the native product. (2) On the other hand, some beneficial reactions can be initiated not only by the complete structures but by their structural remains, which are no longer toxic. (3) Some of the split products in the lipid-free and polysaccharide-rich preparations can induce beneficial reactions. (4) Gram-negative bacteria can produce endotoxin-unrelated and beneficial compounds. Conventional endotoxin preparations are heterogeneous and often contain some of these unrelated substances. (5) Elucidation of the exact structural requirements of endotoxic reactions has just begun. It appears to be safe to predict that individual reactions will require highly specific structures or physicochemical properties. The potential rewards of such research might be quite significant by facilitating our understanding of the molecular events of the beneficial effects of endotoxins and by directing the search for preparations with therapeutic applications.
Relation between solvation as expressed by the Walden product and cation exchange selectivity in water-dimethylsulfoxide (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRelation between solvation as expressed by the Walden product and cation exchange selectivity in water-dimethylsulfoxideRobert. Smits, Pierre. Van den Winkel, D. L. Massart, Jean. Juillard, and J. P. MorelCite this: Anal. Chem. 1973, 45, 2, 339–342Publication Date (Print):February 1, 1973Publication History Published online1 May 2002Published inissue 1 February 1973https://pubs.acs.org/doi/10.1021/ac60324a002https://doi.org/10.1021/ac60324a002research-articleACS PublicationsRequest reuse permissionsArticle Views48Altmetric-Citations9LEARN 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
Catabolism of leucine to branched-chain fatty acids in Staphylococcus xylosus (2004)

The metabolic information obtained is extremely important in connection with a future biotechnological design of starter cultures for production of fermented meat.
Studies on Multiplex RT-PCR for Detection of Avian Influenza Virus Type A Group and Specific H5 and H7 Subtypes (2012)

A multiplex Reverse Transcription Polymerase Chain Reaction (mRT-PCR) for Avian Influenza Virus (AIV) has been developed to simultaneously Detect Nucleoprotein (NP) genes common to all AIV subtypes or type A influenza viruses by AIV NP gene or group primers and hemagglutinin (HA) protein genes specific to H5 and H7 subtypes by H5 and H7 primers, respectively. The AIV group primer bases were selected from conserved regions of AIV NP genes determined by sequence comparison and alignment using DNA STAR primer software (DNA STAR Inc., WI). Primers specific to H5 and H7 subtypes were designed on conserved sequences of HA protein genes of H5 and H7 subtypes, respectively. The mRT-PCR products amplified by AIV group primers gave a 750bp fragment, by H7 primers gave a 518bp fragment and by H5 primers gave a 410bp fragment. Evaluation test of the mRT-PCR for AIV indicated that all AIV subtypes H1 through H7 and H9 tested were specifically amplified by AIV group primers, H5 subtypes were amplified by both group primers and H5 primers, and H7 subtypes were amplified by both group and H7 primers. Non-H5 or H7 subtypes were not amplified by the use of H5 or H7 primers. Samples contained both H5 and H7 subtypes were amplified by all 3 primer sets of AIV group, H5 and H7 primers simultaneously in one assay. Other avian viruses had no reaction to any of the AIV primers. The mRT-PCR for AIV detected as low as 2 x 10-3 ng of RNA extracted from H7N2 and H5N2 subtypes or as low as 2.2-2.5 Log10 ELD50 of these two viruses. Sensitivity (Se) and Specificity (Sp) of the mRT-PCR for AIV were measured as 92% and 100%, respectively, in comparison with virus isolation in Embryonated Chicken Eggs (ECE).