gebhart/patrepeval huggingface dataset:
Management of Breast Cancer: Is There a Role for Somatostatin and Its Analogs? (2001)

Somatostatin and related peptides are a family of peptides which are ubiquitous and function as endogenous growth inhibitors. Analogs have been developed through the introduction of a D-amino acid in the position 8 of somatostatin moiety which is more resistant to the action of endogenous peptidases than the parental moiety. Both somatostatin and its analogs interact with specific receptors on the cell surface. The five receptor subtypes, SSTR-1 to SSTR-5, which have been characterized so far, have a different affinity for somatostatin and its analogs. This and the fact that receptors are not homogeneously expressed in tissues account for the different activity of these compounds, all of which have demonstrated tumoristatic properties both in vitro and in vivo. The interaction of somatostatin and of somatostatin analogs with specific SSTR receptors is crucial to the antiproliferative mechanisms exerted by these compounds in vitro and in some animal models and the various pathways have been reviewed in detail. However, inhibition of angiogenesis and suppression of lactogenic hormones might represent alternative mechanisms, in particular in breast cancer. The rationale for the use of somatostatin and its analogs in breast cancer patients and to combine these peptides with antihormones, like antiestrogens or prolactin-lowering drugs, or cytotoxics has been reviewed together with the results obtained in phase II and comparative trials. The reasons for the limited efficacy shown by these compounds either when used alone or when used in combination with other drugs have also been critically reviewed in the perspective of new trials.
Suppressors of Cytokine Signaling Modulate JAK/STAT-Mediated Cell Responses During Atherosclerosis (2009)

SOCS expressed in atherosclerotic lesions are key regulators of vascular cell responses. Activation of this endogenous antiinflammatory pathway might be of interest in the treatment of atherosclerosis.
Binding of rapamycin analogs to calcium channels and FKBP52 contributes to their neuroprotective activities (2007)

Rapamycin is an immunosuppressive immunophilin ligand reported as having neurotrophic activity. We show that modification of rapamycin at the mammalian target of rapamycin (mTOR) binding region yields immunophilin ligands, WYE-592 and ILS-920, with potent neurotrophic activities in cortical neuronal cultures, efficacy in a rodent model for ischemic stroke, and significantly reduced immunosuppressive activity. Surprisingly, both compounds showed higher binding selectivity for FKBP52 versus FKBP12, in contrast to previously reported immunophilin ligands. Affinity purification revealed two key binding proteins, the immunophilin FKBP52 and the beta1-subunit of L-type voltage-dependent Ca(2+) channels (CACNB1). Electrophysiological analysis indicated that both compounds can inhibit L-type Ca(2+) channels in rat hippocampal neurons and F-11 dorsal root ganglia (DRG)/neuroblastoma cells. We propose that these immunophilin ligands can protect neurons from Ca(2+)-induced cell death by modulating Ca(2+) channels and promote neurite outgrowth via FKBP52 binding.
Direct Role of Adiponectin and Adiponectin Receptors in Endometrial Cancer: In Vitro and Ex Vivo Studies in Humans (2011)

Low adiponectin levels are an independent risk factor for and mediate the effect of obesity on endometrial cancer in epidemiology studies. The direct or indirect mechanisms underlying these findings remain to be elucidated. We first examined the expression of adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) in normal human endometrium and in endometrial cancer tissues ex vivo. We then used KLE and RL95-2 human endometrial cancer cell lines in vitro to study relative expression of AdipoRs, to investigate the effect of adiponectin on activating intracellular signaling pathways, and to assess its potential to alter malignant properties. We report for the first time that the relative expression level of AdipoR1 is higher than AdipoR2 in human endometrial cancer tissue, but the expression of AdipoRs is not statistically different from nonneoplastic tissues. We also show for the first time in endometrial cancer cell lines in vitro that adiponectin suppresses endometrial cancer proliferation acting through AdipoRs. Adiponectin also increases the expression of the adaptor molecule LKB1, which is required for adiponectin-mediated activation of AMPK/S6 axis and modulation of cell proliferation, colony formation, adhesion, and invasion of KLE and RL95-2 cell lines. These novel mechanistic studies provide for the first time in vitro and ex vivo evidence for a causal role of adiponectin in endometrial cancer.
Spinal opiate analgesia: Characteristics and principles of action (1981)

Departments of Neurosurgical Research and Pharmacology, Mayo Foundation, Rochester, Minn. 55905 U.S.A. Submitted May 18, 1981; accepted May 28, 1981.
ChemInform Abstract: ANTITUMOR COMPLEXES OF PLATINUM WITH CARRIER MOLECULES. 2. MIXED COMPLEXES OF F AMINO ACIDS AND TERT‐BUTYLAMINE (1985)

Abstract Die Synthese der Komplexe ′(II) mit zwei verschiedenen inerten Liganden in cis‐Stellung zueinander erfolgt wie aufgezeigt über den Komplex (I) mit tert.‐Butylamin als Liganden, der die Fettlöslichkeit der Verbindungen steigert.
CHROMOSOME STABILITY IN MAIZE (ZEA MAYS) TISSUE CULTURES AND SECTORING IN SOME REGENERATED PLANTS (1982)

Cytogenetic stability of maize (Zea mays L.) tissue cultures was assessed by meiotic analysis of plants regenerated from 4- and 8-month-old tissue cultures and by mitotic analysis of cultured cells 4 and 8 months after culture initiation. Cultures initiated from four embryos each of W22 R-nj R-nj × A188 and A188 × W22 R-nj R-nj were examined. After four months in culture, only one of 65 regenerated plants was abnormal; after eight months, only four of 59 regenerated plants were abnormal. Three of the five abnormal plants had normal and cytogenetically abnormal sectors in the tassels. Inheritance studies were conducted on 51 regenerated plants. Eight plants segregated in the S 1 for recessive mutations resulting in defective kernels, and one plant segregated for a recessive mutation resulting in a wilted phenotype. Eight different plants that produced normal S 1 progeny segregated for defective kernel mutations in some S 1 families, indicating a lack of concordance between male and female reproductive cells in the original regenerated plant. The cytogenetic stability observed in regenerated plants also was observed in vitro, indicating that selection at the time of regeneration did not occur. Four hundred and thirty-four (97%) of the 449 cells analyzed in 4-month-old cultures had the normal 20-chromosome complement; 377 (95%) of the 398 cells analyzed in 8-month-old cultures were normal. These results indicate that chromosome stability is maintained in tissue cultures of A188 × W22 R-nj R-nj maize.
RFLP mapping of genes conferring complete and partial resistance to blast in a durably resistant rice cultivar. (1994)

Moroberekan, a japonica rice cultivar with durable resistance to blast disease in Asia, was crossed to the highly susceptible indica cultivar, CO39, and 281 F7 recombinant inbred (RI) lines were produced by single seed descent. The population was evaluated for blast resistance in the greenhouse and the field, and was analyzed with 127 restriction fragment length polymorphism (RFLP) markers. Two dominant loci associated with qualitative resistance to five isolates of the fungus were tentatively named Pi-5(t) and Pi-7(t). They were mapped on chromosomes 4 and 11, respectively. To identify quantitative trait loci (QTLs) affecting partial resistance, RI lines were inoculated with isolate PO6-6 of Pyricularia oryzae in polycyclic tests. Ten chromosomal segments were found to be associated with effects on lesion number (P < 0.0001 and LOD > 6.0). Three of the markers associated with QTLs for partial resistance had been reported to be linked to complete blast resistance in previous studies. QTLs identified in greenhouse tests were good predictors of blast resistance at two field sites. This study illustrates the usefulness of RI lines for mapping a complex trait such as blast resistance and suggests that durable resistance in the traditional variety, Moroberekan, involves a complex of genes associated with both partial and complete resistance.
Long-term inhibition of Rho-kinase induces a regression of arteriosclerotic coronary lesions in a porcine model in vivo (2001)

These results indicate that Rho-kinase is substantially involved in constrictive remodeling and vasospastic activity of the arteriosclerotic coronary artery, both of which could be reversed by long-term inhibition of the molecule in vivo. Thus, Rho-kinase may be regarded as a novel therapeutic target for arteriosclerotic vascular disease.
METHYLATION OF THE ECORI RECOGNITION SITE DOES NOT ALTER DNA CONFORMATION. THE CRYSTAL STRUCTURE OF D(CGCGAM6ATTCGCG) AT 2.0 ANGSTROMS RESOLUTION (1988)

Methylation of nucleic acid bases is known to prevent the cleavage of DNA by restriction endonucleases. The effect on the conformation of the DNA molecule itself and hence its interactions with other DNA binding proteins has been a subject of general interest. To help address this question, we have solved the crystal structure at 2.0 A of the methylated dodecamer, d(CGCGAm6ATTCGCG), which contains the EcoRI recognition sequence and have compared the conformation of the methylated molecule with that of its nonmethylated counterpart. This methylation produces a bulky hydrophobic patch on the floor of the major groove of B-DNA which plays an important role in the mechanism of inhibition of EcoRI restriction activity. However, with the exception of small perturbations in the immediate vicinity of the methyl groups, the structure is virtually unchanged. Given the lack of a conformational change upon methylation, we have extended this thesis of the recognition process to other types of restriction systems and found that different restriction enzymes seem to have their own characteristic protein-DNA interactions. The relative spatial orientations of methylation sites and cleavage sites must play a major role in ordering protein secondary structure elements as well as subunit-subunit interactions along the DNA strand.
Mesenchymal stem cells enhance autophagy and increase β-amyloid clearance in Alzheimer disease models (2013)

Current evidence suggests a central role for autophagy in Alzheimer disease (AD), and dysfunction in the autophagic system may lead to amyloid-β (Aβ) accumulation. Using in vitro and in vivo AD models, the present study investigated whether mesenchymal stem cells (MSCs) could enhance autophagy and thus exert a neuroprotective effect through modulation of Aβ clearance In Aβ-treated neuronal cells, MSCs increased cellular viability and enhanced LC3-II expression compared with cells treated with Aβ only. Immunofluorescence revealed that MSC coculture in Aβ-treated neuronal cells increased the number of LC3-II-positive autophagosomes that were colocalized with a lysosomal marker. Ultrastructural analysis revealed that most autophagic vacuoles (AVs) in Aβ-treated cells were not fused with lysosomes, whereas a large portion of autophagosomes were conjoined with lysosomes in MSCs cocultured with Aβ-treated neuronal cells. Furthermore, MSC coculture markedly increased Aβ immunoreactivity colocalized within lysosomes and decreased intracellular Aβ levels compared with Aβ-treated cells. In Aβ-treated animals, MSC administration significantly increased autophagosome induction, final maturation of late AVs, and fusion with lysosomes. Moreover, MSC administration significantly reduced the level of Aβ in the hippocampus, which was elevated in Aβ-treated mice, concomitant with increased survival of hippocampal neurons. Finally, MSC coculture upregulated BECN1/Beclin 1 expression in AD models. These results suggest that MSCs significantly enhance autolysosome formation and clearance of Aβ in AD models, which may lead to increased neuronal survival against Aβ toxicity. Modulation of the autophagy pathway to repair the damaged AD brain using MSCs would have a significant impact on future strategies for AD treatment.
Effects of Chronic Central Nervous System Administration of Agouti-Related Protein in Pair-Fed Animals (2001)

The melanocortin receptor (MC3-R and MC4-R) antagonist, agouti-related protein (AGRP), is a potent stimulant of food intake. We examined the effect of chronic intracerebroventricular (ICV) AGRP treatment on energy metabolism and pituitary function in ad libitum fed rats and rats administered AGRP and then pair-fed to a saline control group. Chronic ICV AGRP (83-132) administration (1 nmol/day for 7 days) significantly increased food intake and body weight in ad libitum fed animals compared with saline-treated controls (body weight on day 7: 272 +/- 6 [saline] vs. 319 +/- 8 g [AGRP ad libitum fed]; P < 0.001). A significant increase in the epididymal fat pad weight, interscapular brown adipose tissue (BAT) weight, and plasma leptin was also observed in the ad libitum fed group. In the AGRP pair-fed group, a significant increase in the epididymal fat pad weight, BAT weight, and plasma leptin was again observed, suggesting that AGRP caused metabolic changes independent of increased food intake. BAT uncoupling protein 1 (UCP-1) content was significantly decreased compared with saline controls in both the AGRP ad libitum fed (21 +/- 8% of saline control; P < 0.01) and AGRP pair-fed groups (24 +/- 7% of saline control; P < 0.01). Plasma thyroid-stimulating hormone (TSH) was significantly suppressed compared with saline controls in both the AGRP ad libitum fed and AGRP pair-fed groups (3.5 +/- 0.3 [saline] vs. 2.7 +/- 0.4 [AGRP ad libitum fed] vs. 2.1 +/- 0.2 ng/ml [AGRP pair-fed]; P < 0.01). This study demonstrates that independent of its orexigenic effects, chronic AGRP treatment decreased BAT UCP-1, suppressed plasma TSH, and increased fat mass and plasma leptin, suggesting that it may play a role in energy expenditure.
EARLY ENGINE EMISSION REDUCTION TEST RESULTS WITH RAPRENOX (1991)

The objective of this program is to develop a RAPRENOX aftertreatment system for heavy duty diesel engines which will produce 80% NOx reduction and will allow engine design to be focused on performance, durability, and reliability. This is expected to be accomplished through an improved understanding of the basic parameters controlling the system, developing practical improvements in the system, and by designing, constructing, and engine testing prototypes from the above work. For the covering abstract of the proceedings see IRRD 853538.
Cellular mechanisms of neural fold formation and morphogenesis in the chick embryo (2001)

The mechanisms underlying neural fold formation and morphogenesis are complex, and how these processes occur is not well understood. Although both intrinsic forces (i.e., generated by the neuroepithelium) and extrinsic forces (i.e., generated by non-neuroepithelial tissues) are known to be important in these processes, the series of events that occur at the neural ectoderm-epidermal ectoderm (NE-EE) transition zone, resulting in the formation of two epithelial layers from one, have not been fully elucidated. Moreover, the region-specific differences that exist in neural fold formation and morphogenesis along the rostrocaudal extent of the neuraxis have not been systematically characterized. In this study, we map the rostrocaudal movements of cells that contribute to the neural folds at three distinct brain and spinal cord levels by following groups of dye-labeled cells over time. In addition, we examine the morphology of the neural folds at the NE-EE transition zone at closely-spaced temporal intervals for comparable populations of neural-fold cells at each of the three levels. Finally, we track the lateral-to-medial displacements that occur in the epidermal ectoderm during neural groove closure. The results demonstrate that neural fold formation and morphogenesis consist of a series of processes comprising convergent-extension movements, as well as epithelial ridging, kinking, delamination, and apposition at the NE-EE transition zone. Regional differences along the length of the neuraxis in the respective roles of these processes are described.
CRISPR/Cas9 in Genome Editing and Beyond (2016)

The Cas9 protein (CRISPR-associated protein 9), derived from type II CRISPR (clustered regularly interspaced short palindromic repeats) bacterial immune systems, is emerging as a powerful tool for engineering the genome in diverse organisms. As an RNA-guided DNA endonuclease, Cas9 can be easily programmed to target new sites by altering its guide RNA sequence, and its development as a tool has made sequence-specific gene editing several magnitudes easier. The nuclease-deactivated form of Cas9 further provides a versatile RNA-guided DNA-targeting platform for regulating and imaging the genome, as well as for rewriting the epigenetic status, all in a sequence-specific manner. With all of these advances, we have just begun to explore the possible applications of Cas9 in biomedical research and therapeutics. In this review, we describe the current models of Cas9 function and the structural and biochemical studies that support it. We focus on the applications of Cas9 for genome editing, regulation, and imaging, discuss other possible applications and some technical considerations, and highlight the many advantages that CRISPR/Cas9 technology offers.
N-(Triisopropylsilyl)pyrrole. A progenitor "par excellence" of 3-substituted pyrroles (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTN-(Triisopropylsilyl)pyrrole. A progenitor "par excellence" of 3-substituted pyrrolesBrian L. Bray, Peter H. Mathies, Reto Naef, Dennis R. Solas, Thomas T. Tidwell, Dean R. Artis, and Joseph M. MuchowskiCite this: J. Org. Chem. 1990, 55, 26, 6317–6328Publication Date (Print):December 1, 1990Publication History Published online1 May 2002Published inissue 1 December 1990https://pubs.acs.org/doi/10.1021/jo00313a019https://doi.org/10.1021/jo00313a019research-articleACS PublicationsRequest reuse permissionsArticle Views6470Altmetric-Citations218LEARN 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
Photochemical surface modification of polymers for improved adhesion (1995)

A method using photoactivatable reagents is described to modify organic polymer surfaces without changing the bulk properties of the material. The reagents contain a benzophenone or other photoactivatable group which, when exposed to light of appropriate wavelength, generates highly reactive intermediates that covalently bond with nearly any organic material. Some general surface characteristics that can be achieved by this approach, on a wide range of materials, are good wettability, good lubricity, passivation, and priming for either adhesion or immobilization of other molecules. This technology provides tremendous flexibility for tailoring surface characteristics for a broad range of applications. Some materials that have desirable bulk properties for specific applications, however, have surface characteristics that make bonding them to other materials difficult. By photocoupling water-soluble polymers onto the surfaces of such materials, the surface properties can be modified to achieve greatly increased bond strengths with conventional adhesives. For example, using such techniques, the strength of bonding two pieces of high-density polyethylene to each other using a cyanoacrylate adhesive was increased by about 17-fold. Similarly, in preliminary experiments, the bond strengths of silicone rubber to polyvinyl chloride, using cyanoacrylate adhesive, were increased by more than 18-fold. This technology offers great potential for surface modification for improved adhesion.
Mutational analysis of F1F0 ATPase: catalysis and energy coupling. (1998)

Escherichia coli ATP synthase has eight subunits and functions through transmission of conformational changes between subunits. Extensive mutational analyses identified essential residues for catalysis and conformation transmission. Pseudorevertant studies revealed that beta/alpha and beta/gamma subunits interactions are important for the energy coupling between catalysis and H+ translocation. In this article, we discuss mechanism of catalysis and energy coupling based on our recent mutation studies.
Nucleotide Sequence and Secondary Structure of Citrus Exocortis and Chrysanthemum Stunt Viroid (1982)

The complete nucleotide sequence of citrus exocortis viroid (CEV, propagated in Gymura) and chrysanthemum stunt viroid (CSV, propagated in Cineraria) has been established, using labelling in vitro and direct RNA sequencing methods and a new screening procedure for the rapid selection of suitable RNA fragments from limited digests. The covalently closed circular single-stranded viroid RNAs consist of 371 (CEV) and 354 (CSV) nucleotides, respectively. As previously shown for potato spindle tuber viroid (PSTV, 359 nucleotides), CEV and CSV also contain a long polypurine sequence. Maximal base-pairing of the established CEV and CSV sequences results in an extended rod-like secondary structure similar to that previously established for PSTV and as predicted from detailed physicochemical studies of all these viroids. Although the three viroid species sequenced to date differ in size and nucleotide sequence, there is 60--73% homology between them. As PSTV, CEV and CSV also contain conserved complementary sequences which are separated from each other in the native secondary structure. We postulate that the resulting 'secondary' hairpins, being formed and observed in vitro during the complex process of thermal denaturation of viroid RNA, must have a vital, although yet unknown, function in vivo. The possible origin and function of viroids are discussed on the basis of the characteristic structural features and of a considerable homology with U1a RNA found for a region highly conserved in the three viroids.
Surface Electromyography for Speech and Swallowing Systems: Measurement, Analysis, and Interpretation (2012)

Despite the challenges discussed, application of sEMG to speech and swallowing has potential as a clinical and research tool when used correctly and is specifically suited to noninvasive clinical studies using between-condition or between-group comparisons for which detection of specific isolated muscle activities is not necessary.
Magnetic resonance without nuclei? (1984)

Magnetic resonance without nuclei?PA Bottomley and WA EdelsteinAudio Available | Share