gebhart/patrepeval huggingface dataset:
High level transactivation by a modified Bombyx ecdysone receptor in mammalian cells without exogenous retinoid X receptor (1998)

Our studies of the Bombyx mori ecdysone receptor (BE) revealed that, unlike the Drosophila melanogaster ecdysone receptor (DE), treatment of BE with the ecdysone agonist tebufenozide stimulated high level transactivation in mammalian cells without adding an exogenous heterodimer partner. Gel mobility shift and transfection assays with both the ultraspiracle gene product (Usp) and retinoid X receptor heterodimer partners indicated that this property of BE stems from significantly augmented heterodimer complex formation and concomitant DNA binding. We have mapped this "gain of function" to determinants within the D and E domains of BE and demonstrated that, although the D domain determinant is sufficient for high affinity heterodimerization with Usp, both determinants are necessary for high affinity interaction with retinoid X receptor. Modified BE receptors alone used as replication-defective retroviruses potently stimulated separate "reporter" viruses in all cell types examined, suggesting that BE has potentially broad utility in the modulation of transgene expression in mammalian cells.
Tumor cells induce the cancer associated fibroblast phenotype via caveolin-1 degradation: Implications for breast cancer and DCIS therapy with autophagy inhibitors (2010)

Loss of stromal caveolin 1 (Cav-1) is a novel biomarker for cancer-associated fibroblasts that predicts poor clinical outcome in breast cancer and DCIS patients. We hypothesized that epithelial cancer cells may have the ability to drive Cav-1 downregulation in adjacent normal fibroblasts, thereby promoting the cancer associated fibroblast phenotype. To test this hypothesis directly, here we developed a novel co-culture model employing (i) human breast cancer cells (MCF7), and (ii) immortalized fibroblasts (hTERT-BJ1), which are grown under defined experimental conditions. Importantly, we show that co-culture of immortalized human fibroblasts with MCF7 breast cancer cells leads to Cav-1 downregulation in fibroblasts. These results were also validated using primary cultures of normal human mammary fibroblasts co-cultured with MCF7 cells. In this system, we show that Cav-1 downregulation is mediated by autophagic/lysosomal degradation, as pre-treatment with lysosome-specific inhibitors rescues Cav-1 expression. Functionally, we demonstrate that fibroblasts co-cultured with MCF7 breast cancer cells acquire a cancer associated fibroblast phenotype, characterized by Cav-1 downregulation, increased expression of myofibroblast markers and extracellular matrix proteins, and constitutive activation of TGFβ/Smad2 signaling. siRNA-mediated Cav-1 downregulation mimics several key changes that occur in co-cultured fibroblasts, clearly indicating that a loss of Cav-1 is a critical initiating factor, driving stromal fibroblast activation during tumorigenesis. As such, this co-culture system can now be used as an experimental model for generating "synthetic" cancer associated fibroblasts (CAFs). More specifically, these "synthetic" CAFs could be used for drug screening to identify novel therapeutics that selectively target the Cav-1-negative tumor micro-environment. Our findings also suggest that chloroquine, or other autophagy/lysosome inhibitors, may be useful as anti-cancer agents, to therapeutically restore the expression of stromal Cav-1 in cancer associated fibroblasts. We discuss this possibility, in light of the launch of a new clinical trial that uses chloroquine to treat DCIS patients: PINC (Preventing Invasive Breast Neoplasia with Cholorquine) [See http://clinicaltrials.gov/show/NCT01023477].
Recent advances in indole syntheses: New routes for a classic target (2011)

Indoles are the most abundant heterocycles in biologically active natural products, pharmaceuticals, agrochemicals, and are relevant substructures in functional materials. As a result, the development of methodologies that enable the synthesis of these compounds is continuously demanded. This review summarizes most recent and relevant approaches towards the preparation of this prevalent structural motif.
Reactions of N-ethylmaleimide with peptides and amino acids (1964)

Research Article| June 01 1964 Reactions of N-ethylmaleimide with peptides and amino acids DG Smyth; DG Smyth Search for other works by this author on: This Site PubMed Google Scholar OO Blumenfeld; OO Blumenfeld Search for other works by this author on: This Site PubMed Google Scholar W Konigsberg W Konigsberg Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1964) 91 (3): 589–595. https://doi.org/10.1042/bj0910589 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation DG Smyth, OO Blumenfeld, W Konigsberg; Reactions of N-ethylmaleimide with peptides and amino acids. Biochem J 1 June 1964; 91 (3): 589–595. doi: https://doi.org/10.1042/bj0910589 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1964 The Biochemical Society1964 Article PDF first page preview Close Modal You do not currently have access to this content.
Cervical Cytomegalovirus Excretion in Pregnant and Nonpregnant Women: Suppression in Early Gestation (1975)

Comparison of 659 pregnant and 202 nonpregnant women with similar demographic characteristics showed overall rates of cervical cytomegalovirus excretion that were identical (9.5% vs. 9.4%) and were surprisingly high, especially since 89% of the pregnant group possessed antibody to cytomegalovirus when admitted to the study. Prevalence of cytomegalovirus among gravidas was significantly lower during the first (1.6%) than during the third (11.3%) trimester. Thus, early pregnancy appeared to exert a suppressive effect on viral excretion that waned with advancing gestation. A similar but less significant occurrence was observed in the two groups with respect to viuria. Increasing age also appeared to suppress the virologic expression of cervical and urinary tract infection, whereas multiparity seemingly produced such an effect only in the cervix. Among both cervical and urinary excreters, a few shed virus thoughout pregnancy, and others shed virus intermittently; however, viral shedding most commonly began in late gestation and frequently continued into the postpartum period. Primary infection was not documented, and antibody status remained unchanged with the advent of viral excretion in most cases. Thus, reactivation of endogenous virus seems the most likely explanation for viral shedding in our population. Similar rates of isolation of Neisseria gonorrhoeae in excreters and nonexcreters further argue against the other major possibility, venereal reinfection.
Evaluation of a rapid bedside test for the quantitative determination of C-reactive protein (2005)

Regardless of its origin, any condition associated with inflammation is accompanied by an increase in serum C-reactive protein levels. This study compared the results of a rapid test for the bedside assay of C-reactive protein (QuikRead CRP, Orion Corporation, Orion Diagnostica, Espoo, Finland) with those of a standard laboratory assay in samples taken from 231 children aged less than 14 years (126 males; median age 4.7 years) attending the Emergency Department of Milan University's Institute of Pediatrics because of acute respiratory infection. The two methods showed similar median C-reactive protein levels (standard laboratory assay: 34.7 mg/L, range 4-199 mg/L; QuikRead CRP: 33.3 mg/L, range <8-196 mg/L; p = 0.779) and a similar distribution of children with C-reactive protein levels of <20 mg/L, 20-70 mg/L and >70 mg/L. This study shows for the first time that the rapid QuikRead CRP test can be performed at the bedside or in an outpatient clinic and, in less than 5 min, gives the same quantitative results as those obtained using a more complex routine laboratory method.
General algorithm of phase-shifting interferometry by iterative least-squares fitting (1995)

A new numerical phase-measuring algorithm for digital phases-hifting interferometry is presented. In this algorithm, the actual values of phase shifts are taken as unknowns together with the wavefront phases ultimately to be determined, and they are computed through iterative spatial and serial least-squares fittings. The algorithm is more general than existing methods in that any arbitrary number of unequal phase shifts may be adopted with no prescriptive restrictions on their spacings. The algorithm is therefore found inherently free from any errors of phase shifts, allowing accurate measurement even in harsh environmental conditions with vibratory disturbances.
ENVIRONMENTAL SENSING OF CHEMICAL AND BIOLOGICAL WARFARE AGENTS IN THE THz REGION (2002)

Discrimination between hazardous materials in the environment and ambient constituents is a fundamental problem in environmental sensing. The ubiquity of naturally occurring bacteria, plant pollen, fungi, and other airborne materials makes the task of sensing for biological warfare (BW) agents particularly challenging. The spectroscopic properties of the chemical warfare (CW) agents in the long wavelength infrared (LWIR) region are important physical properties that have been successfully exploited for environmental sensing. However, in the case of BW agents, the LWIR region affords less distinction between hazardous and ambient materials. Recent studies of the THz spectroscopic properties of biological agent simulants, particularly bacterial spores, have yielded interesting and potentially useful spectral signatures of these materials. It is anticipated that with the advent of new THz sources and detectors, a novel environmental sensor could be designed that exploits the peculiar spectral properties of the biological materials. We will present data on the molecular spectroscopy of several CW agents and simulants as well as some THz spectroscopy of the BW agent simulants that we have studied to date, and discuss the prospectus with regard to detection probabilities through the application of sensor system modeling.
Mechanistic insights into editing-site specificity of ADARs (2012)

Adenosine deaminases that act on RNA (ADARs) deaminate adenosines in dsRNA to produce inosines. ADARs are essential in mammals and are particularly important in the nervous system. Altered levels of adenosine-to-inosine (A-to-I) editing are observed in several diseases. The extent to which an adenosine is edited depends on sequence context. Human ADAR2 (hADAR2) has 5' and 3' neighbor preferences, but which amino acids mediate these preferences, and by what mechanism, is unknown. We performed a screen in yeast to identify mutations in the hADAR2 catalytic domain that allow editing of an adenosine within a disfavored triplet. Binding affinity, catalytic rate, base flipping, and preferences were monitored to understand the effects of the mutations on ADAR reactivity. Our data provide information on the amino acids that affect preferences and point to a conserved loop as being of key importance. Unexpectedly, our data suggest that hADAR2's preferences derive from differential base flipping rather than from direct recognition of neighboring bases. Our studies set the stage for understanding the basis of altered editing levels in disease and for developing therapeutic reagents.
Regulation of cytotoxic T cells by ecto-nicotinamide adenine dinucleotide (NAD) correlates with cell surface GPI-anchored/arginine ADP-ribosyltransferase. (1994)

This report demonstrates that incubation of cytotoxic T cells with NAD causes suppression of their ability to proliferate in response to stimulator cells or to lyse targets. Effects are evident after incubation for 3 h with concentrations of NAD as low as 1 microM and are sustained for many hours after removal of NAD from culture media. Suppression is a result of the failure of CTL to form specific conjugates with targets as well as a lower level of activation in response to TCR-mediated stimulation, although TCR-mediated transmembrane signaling is demonstrable. Metabolites of NAD such as nicotinamide, ADP-ribose, and cyclic-ADP-ribose have no detectable effect, indicating that NAD-glycohydrolase or ADP-ribose cyclase do not mediate suppression. Incubation of intact CTL with [32P]NAD leads to incorporation of 32P into a particulate, subcellular fraction, a reaction that is not inhibitable by ADP-ribose. Hydroxylamine, but not mercuric ion releases [32P]ADP-ribose, whereas phosphodiesterase releases [32P]AMP from the particulate subcellular fraction, suggesting that labeling is a result of enzymatic mono-ADP-ribosylation of arginines. In support of this, treatment of intact CTL with phosphatidylinositol-specific phospholipase C releases an arginine-specific ADP-ribosyltransferase and causes insensitivity to ecto-NAD suppression. These results suggest that a GPI-anchored ADP-ribosyltransferase uses ecto-NAD to ADP-ribosylate proteins that regulate CTL function.
Synthesis, Structure, and Spectroscopic Properties of Bismuth Citrate Compounds and the Bismuth-Containing Ulcer-Healing Agent Colloidal Bismuth Subcitrate (CBS). 4. Crystal Structure and Solution Behavior of a Unique Dodecanuclear Cluster (NH4)12[Bi12O8(cit)8](H2O)10 (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis, Structure, and Spectroscopic Properties of Bismuth Citrate Compounds and the Bismuth-Containing Ulcer-Healing Agent Colloidal Bismuth Subcitrate (CBS). 4. Crystal Structure and Solution Behavior of a Unique Dodecanuclear Cluster (NH4)12[Bi12O8(cit)8](H2O)10Eiji Asato, Kosho Katsura, Masahiro Mikuriya, Urho Turpeinen, Ilpo Mutikainen, and Jan ReedijkCite this: Inorg. Chem. 1995, 34, 9, 2447–2454Publication Date (Print):April 1, 1995Publication History Published online1 May 2002Published inissue 1 April 1995https://pubs.acs.org/doi/10.1021/ic00113a028https://doi.org/10.1021/ic00113a028research-articleACS PublicationsRequest reuse permissionsArticle Views729Altmetric-Citations67LEARN 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
Image-Based Control of the Magnetic Resonance Imaging-Guided Focused Ultrasound Thermotherapy (2006)

Magnetic resonance imaging (MRI)-guided focused ultrasound surgery (FUS) is a full noninvasive approach for localized thermal ablation of deep tissues, coupling the following: (1) a versatile, nonionizing physical agent for therapy and (2) a state-of-the art diagnosis and on-line monitoring tool. A commercially available, Food and Drug Administration-approved device using the MRI-guided FUS exists since 2004 for the ablation of benign tumors (uterine fibroids); however, the ultimate goal of the technological, methodological, and medical research in this field is to provide a clinical-routine tool for fighting localized cancer. When addressing cancer applications, the accurate spatial control of the delivered thermal dose is mandatory. Contiguous destruction of the target volume must be achieved in a minimum time, whereas sparing as much as possible the neighboring healthy tissues and especially when some adjacent regions are critical. This paper reviews some significant developments reported in the literature related to the image-based control of the FUS therapy for kidney, breast, prostate, and brain, including the own experience of the authors on the active feedback control of the temperature during FUS ablation. In addition, preliminary results of an original study of MRI-guided FUS ablation of VX2 carcinoma in kidney, under active temperature control, are described here.
A nude mouse model of massive liver and lymph node metastasis of human colon cancer. (2000)

Liver and lymph nodes metastasis are the main causes of treatment failure for advanced colon cancer. However, currently-available animal models of human colon cancer do not demonstrate sufficient metastasis to represent highly malignant colon cancer that extensively metastasizes to these sites. A liver metastasis from a patient with highly malignant, poorly differentiated adenocarcinoma of the colon was established in nude mice by surgical orthotopic implantation to the mouse colon. The human origin of the tumor growing in nude mice was confirmed by in situ hybridization of human DNA. After 20 passages from the first implantation, massive liver and lymph nodes metastasis, occurred in 100% of the transplanted animals. Lymph nodes metastasis were found at the sites of lymph node drainage of the liver: celiac, portal and mediastinal lymph nodes. However no mesenteric and retroperitoneal nodes or lung tissue metastases were observed. Our data suggest that the mediastinal, celiac and hepatic lymph nodes metastases are derived form the liver metastasis, confirming the concept of metastasis of metastases or "remetastasis" of colon cancer.
Adenovirus-Mediated Type I Interferon Expression Delays and Reduces Disease Signs in Cattle Challenged with Foot-and-Mouth Disease Virus (2003)

Foot-and-mouth disease (FMD) is an economically important disease of livestock. Eliminating FMD outbreaks in previously disease-free countries often relies on restriction of animal movement and massive slaughter of infected and in-contact susceptible animals. To develop a more effective and humane FMD control strategy, we explored the possibility of using type I interferon (IFN-α/β) as a novel anti-FMD agent. We have demonstrated previously that swine inoculated with replication-defective human adenovirus type 5 (Ad5) vector expressing porcine IFN-α (Ad5-PoIFN-α) were completely protected from FMD virus (FMDV) challenge. To extend this approach to bovines, we constructed Ad5 vectors that express bovine IFN-α or IFN-β (Ad5-BoIFN-α and Ad5-BoIFN-β). Cells infected with these viruses produced high levels of biologically active BoIFN-α/β, but despite expression in vitro, no detectable IFN-induced biologic activity was found in cattle inoculated with Ad5-BoIFN-α. Because PoIFN-α inhibits FMDV replication in bovine cells, we evaluated the potential use of PoIFN-α against FMD in cattle. In cattle inoculated with Ad5-PoIFN-α, the appearance of vesicles was delayed after challenge with FMDV and disease was less severe than in control animals. One Ad5-PoIFN-α-inoculated animal never developed clinical disease. Similarly, although all the Ad5-PoIFN-α-inoculated animals developed viremia, it was delayed for 1 day as compared with the control group. These results suggest that in vivo expression of PoIFN-α partially protected cattle from FMD.
Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. (1977)

The properties of Na channels of the node of Ranvier are altered by neutral, amine, and quaternary local anesthetic compounds. The kinetics of the Na currents are governed by a composite of voltage- and time-dependent gating processes with voltage- and time-dependent block of channels by drug. Conventional measurements of steady-state sodium inactivation by use of 50-ms prepulses show a large negative voltage shift of the inactivation curve with neutral benzocaine and with some ionizable amines like lidocaine and tetracaine, but no shift is seen with quaternary OX-572. However, when the experiment is done with repetitive application of a prepulse-testpulse waveform, a shift with the quaternary cations (applied internally) is seen as well. 1-min hyperpolarizations of lidocaine- or tetracaine-treated fibers restore two to four times as many channels to the conducting pool as 50-ms hyperpolarizations. Raising the external Ca++ concentration also has a strong unblocking effect. These manipulations do not relieve block in fibers treated with internal quaternary drugs. The results are interpreted in terms of a single receptor in Na channels for the different drug types. Lipid-soluble drug forms are thought to come and go from the receptor via a hydrophobic region of the membrane, while charged and less lipid-soluble forms pass via a hydrophilic region (the inner channel mouth). The hydrophilic pathway is open only when the gates of the channel are open. Any drug form in the channel increases the probability of closing the inactivation gate which, in effect, is equivalent to a negative shift of the voltage dependence of inactivation.
Circulating Concentrations of Growth-Differentiation Factor 15 in Apparently Healthy Elderly Individuals and Patients with Chronic Heart Failure as Assessed by a New Immunoradiometric Sandwich Assay (2006)

Abstract Background: Growth-differentiation factor 15 (GDF15) is a member of the transforming growth factor β (TGF-β) cytokine superfamily. There has been increasing interest in using circulating GDF15 as a biomarker in patients, for example those with cardiovascular disease. Methods: We developed an IRMA that uses a polyclonal, affinity chromatography–purified goat antihuman GDF15 IgG antibody, assessed the preanalytic characteristics of GDF15, and determined circulating GDF15 concentrations in 429 apparently healthy elderly individuals and 153 patients with chronic heart failure (CHF). Results: The assay had a detection limit of 20 ng/L, an intraassay imprecision of ≤10.6%, and an interassay imprecision of ≤12.2%. Specificity was demonstrated with size-exclusion chromatography, parallel measurements with polyclonal and monoclonal anti-GDF15 antibody, and lack of cross-reactivity with TGF-β. The assay was not appreciably influenced by the anticoagulant matrix or unrelated biological substances. GDF15 was stable at room temperature for 48 h and resistant to 4 freeze-thaw cycles. Apparently healthy, elderly individuals presented with a median GDF15 concentration of 762 ng/L (25th–75th percentiles, 600–959 ng/L). GDF15 concentrations were associated with age and with cystatin C and C-reactive protein concentrations. CHF patients had increased GDF15 concentrations that were closely related to disease severity. Conclusion: The IRMA can detect GDF15 in human serum and plasma with excellent sensitivity and specificity. The reference limits and confounding variables defined for apparently healthy elderly individuals and the favorable preanalytic characteristics of GDF15 are expected to facilitate future studies of GDF15 as a biomarker in various disease settings, including CHF.