Journal articles on the topic 'CNRN'
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Tang, Yitai, and Richard H. Gomer. "A Protein with Similarity to PTEN Regulates Aggregation Territory Size by Decreasing Cyclic AMP Pulse Size during Dictyostelium discoideum Development." Eukaryotic Cell 7, no. 10 (August 1, 2008): 1758–70. http://dx.doi.org/10.1128/ec.00210-08.
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ABSTRACT An interesting but largely unanswered biological question is how eukaryotic organisms regulate the size of multicellular tissues. During development, a lawn of Dictyostelium cells breaks up into territories, and within the territories the cells aggregate in dendritic streams to form groups of ∼20,000 cells. Using random insertional mutagenesis to search for genes involved in group size regulation, we found that an insertion in the cnrN gene affects group size. Cells lacking CnrN (cnrN −) form abnormally small groups, which can be rescued by the expression of exogenous CnrN. Relayed pulses of extracellular cyclic AMP (cAMP) direct cells to aggregate by chemotaxis to form aggregation territories and streams. cnrN − cells overaccumulate cAMP during development and form small territories. Decreasing the cAMP pulse size by treating cnrN − cells with cAMP phosphodiesterase or starving cnrN − cells at a low density rescues the small-territory phenotype. The predicted CnrN sequence has similarity to phosphatase and tensin homolog (PTEN), which in Dictyostelium inhibits cAMP-stimulated phosphatidylinositol 3-kinase signaling pathways. CnrN inhibits cAMP-stimulated phosphatidylinositol 3,4,5-trisphosphate accumulation, Akt activation, actin polymerization, and cAMP production. Our results suggest that CnrN is a protein with some similarities to PTEN and that it regulates cAMP signal transduction to regulate territory size.
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Zhang, Zhongwei, Quanfei Meng, Ziping Li, Bitao Pan, Ravinder R. Regatte, and Mark E. Schweitzer. "Simultaneous Visualization of Nerves and Vessels of the Lower Extremities Using Magnetization-Prepared Susceptibility Weighted Magnetic Resonance Imaging at 3.0 T." Operative Neurosurgery 70, suppl_1 (July 15, 2011): ons1—ons7. http://dx.doi.org/10.1227/neu.0b013e31822da57f.
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Abstract BACKGROUND: Identifying the extent of involvement of the vessel and nerve, particularly in regard to preoperative evaluation and precise localization of the tumor and its relation to the structures of the extremities, has important applications for advancing the treatment of lower extremity diseases. OBJECTIVE: To review the technical feasibility of simultaneous visualization of nerves and vessels of the lower extremities by using magnetization-prepared susceptibility-weighted magnetic resonance (MR) imaging (MP-SWI) at 3.0T. METHODS: Ten healthy volunteers and 10 patients were studied. Optimized MP-SWI, MR neurography (MRN) based on 3D diffusion-weighted steady-state free precession imaging and contrast-enhanced MR angiography (CE-MRA) sequences were performed for each subject. The means of signal-to-noise ratio (SNR)n, SNRv, SNRm, contrast-to-noise ratio (CNR)n,m and CNRv,m were calculated and the certainty of identifying nerves and vessels was determined. CNRn,m between MP-SWI and MRN, and CNRv,m between MP-SWI and CE-MRA were compared. RESULTS: MP-SWI provides slightly poorer CNRv,m than CE-MRA, whereas MP-SWI provides a better CNRn,m than MRN. In thin-slice-thickness maximum-intensity projection arbitrary planes, the sciatic nerve and its branches were clearly identified (score 1 or 2 of 2) in 17 subjects (85%); the femoral artery and the main branches were identified (score 1 or 2 of 2) in all 20 subjects (100%). The nerves are isointense to slightly hypointense to muscle, and the vessels show a more obvious hyperintense signal than muscle in MP-SWI. CONCLUSION: The proposed MP-SWI demonstrates the feasibility of simultaneously visualizing nerves and vessels of the lower extremities without using an exogenous contrast agent. It may enable straightforward localization of a disease process to a specific nerve and vessel.
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Takahashi, Mihoko, Nobuyuki Haga, Todd Hennessey, Robert D. Hinrichsen, and Ritsuo Hara. "A gamma ray-induced non-excitable membrane mutant in Paramecium caudatum: a behavioral and genetic analysis." Genetical Research 46, no. 1 (August 1985): 1–10. http://dx.doi.org/10.1017/s0016672300022400.
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SUMMARYA new CNR (caudatum non-reversal) mutant of Paramecium caudatum was isolated after gamma ray mutagenesis. This CNR lacks not only the transient inward Ca2+ current but also the sustained Ca2+ current. It was shown to complement the three known CNR mutants of P. caudatum (cnrA, cnrB and cnrC) by crossbreeding analyses. Thus, this new mutant belongs to a 4th CNR locus, designated cnrD. The defect of cnrD can be partially rescued by microinjection of cytoplasm from any of the three CNR mutants or the three Pawns (pwA, pwB and pwC) in P. tetraurelia. Since the three CNR genes have been shown to be different from the three Pawn genes by cytoplasmic complementation test (Haga et al. 1983), this result suggests that cnrD is the 7th non-excitable mutant in Paramecium. Thus, there are at least seven genes controlling Ca2+ channel function in Paramecium.
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Grass, Gregor, Cornelia Große, and Dietrich H. Nies. "Regulation of the cnr Cobalt and Nickel Resistance Determinant from Ralstonia sp. Strain CH34." Journal of Bacteriology 182, no. 5 (March 1, 2000): 1390–98. http://dx.doi.org/10.1128/jb.182.5.1390-1398.2000.
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ABSTRACT Ralstonia sp. strain CH34 is resistant to nickel and cobalt cations. Resistance is mediated by the cnrdeterminant located on plasmid pMOL28. The cnr genes are organized in two clusters, cnrYXH and cnrCBA. As revealed by reverse transcriptase PCR and primer extension, transcription from these operons is initiated from promoters located upstream of the cnrY and cnrC genes. These two promoters exhibit conserved sequences at the −10 (CCGTATA) and −35 (CRAGGGGRAG) regions. The CnrH gene product, which is required for expression of both operons, is a sigma factor belonging to the sigma L family, whose activity seems to be governed by the membrane-bound CnrY and CnrX gene products in response to Ni2+. Half-maximal activation from the cnrCBAoperon was determined by using appropriate lacZ gene fusions and was shown to occur at an Ni2+ concentration of about 50 μM.
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Fukumoto, E., H. Sakai, S. Fukumoto, T. Yagi, O. Takagi, and Y. Kato. "Cadherin-related Neuronal Receptors in Incisor Development." Journal of Dental Research 82, no. 1 (January 2003): 17–22. http://dx.doi.org/10.1177/154405910308200105.
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Cadherins are cell adhesion molecules that are critical for tissue development. In this report, we identified members of the cadherin family cadherin-related neuronal receptors (CNRs) 1 and 5 expressed in rat incisors by the differential display method. Quantitative RT-PCR revealed that CNR1 mRNA is expressed in the secretory stage but reduced in the early-maturation stage, while CNR5 mRNA is expressed in both these stages. In situ hybridization showed that strong expression of CNR1 is strong in the secretory stage, but reduced in the early phase and diminished in the late phase of the early-maturation stage. CNR5 mRNA is expressed almost at the same levels in the secretory and in the early phase of the early-maturation stages but is absent in the late phase of the early-maturation stage. Both CNR1 and 5 mRNA are continuously expressed in odontoblasts. Immunohistology showed that CNR proteins are expressed in the secretory and early-maturation stages of ameloblasts, but no protein expression at the late-maturation stage was observed. CNR proteins were continuously expressed in odontoblasts. We found that recombinant CNR1 binds dental epithelial and mesenchymal cells through N-terminal domain EC1 in vitro. These results suggest that CNR1 and CNR5 may play an important role in enamel and dentin formation, probably through cell-cell and/or cell-matrix interactions.
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Tibazarwa, C., S. Wuertz, M. Mergeay, L. Wyns, and D. van der Lelie. "Regulation of the cnr Cobalt and Nickel Resistance Determinant of Ralstonia eutropha (Alcaligenes eutrophus) CH34." Journal of Bacteriology 182, no. 5 (March 1, 2000): 1399–409. http://dx.doi.org/10.1128/jb.182.5.1399-1409.2000.
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ABSTRACT The linked resistance to nickel and cobalt of Ralstonia eutropha-like strain CH34 (Alcaligenes eutrophusCH34) is encoded by the cnr operon, which is localized on the megaplasmid pMOL28. The regulatory genes cnrYXH have been cloned, overexpressed, and purified in Escherichia coli. CnrY fractionated as a 10.7-kDa protein in in vitro translation assays. CnrX, a periplasmic protein of 16.5 kDa, was overproduced and purified as a histidine-tagged fusion protein inE. coli. His-CnrX was found to posses a secondary structure content rich in alpha-helical and beta-sheet structures. CnrH, a sigma factor of the extracytoplasmic function family, was purified as an N-terminally histidine-tagged fusion. In gel shift mobility assays, His-CnrH, in the presence of E. coli core RNA polymerase enzyme, could retard at least two different promoter DNA targets,cnrYp and cnrHp, localized within thecnrYXH locus. These promoters and their transcription start sites were confirmed by primer extension. Purified His-CnrX did not inhibit the DNA-binding activity of His-CnrH and is therefore unlikely to be an anti-sigma factor, as previously hypothesized (EMBL M91650 description entry). To study the transcriptional response of the regulatory locus to metals and to probe promoter regions, transcriptional fusions were constructed between fragments ofcnrYXH and the luxCDABE, luciferase reporter genes. Nickel and cobalt specifically induced thecnrYXH-luxCDABE fusion at optimal concentrations of 0.3 mM Ni2+ and 2.0 mM Co2+ in a noncomplexing medium for metals. The two promoter regions PY (upstreamcnrY) and PH (upstream cnrH) were probed and characterized using this vector and were found to control the nickel-inducible regulatory response of the cnr operon. The cnrHp promoter was responsible for full transcription of the cnrCBA structural resistance genes, while thecnrYp promoter was necessary to obtain metal-inducible transcription from the cnrHp promoter. The zinc resistance phenotype (ZinB) of a spontaneous cnr mutant strain, AE963, was investigated and could be attributed to an insertion of IS1087, a member of the IS2 family of insertion elements, within the cnrY gene.
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Urrego, Daniela, Kylie Karmila Hornaday, Stephen L. Wood, and Donna Michelle Slater. "Expression of Cannabinoid Receptors in Mouse and Human Intrauterine Tissues: Insights into the Role of Endocannabinoid Signaling in Late Pregnancy." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A749—A750. http://dx.doi.org/10.1210/jendso/bvab048.1524.
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Abstract Introduction: Endocannabinoid signaling (ECS), mediated primarily by cannabinoid receptors (CNR) 1 and 2, is implicated in embryo implantation, decidualization, and placentation, but less is known about its role in late pregnancy or labour. Reports of elevated serum endocannabinoid concentrations during labour suggest that ECS may modulate uterine function leading up to and during parturition. Effects on uterine function likely vary depending on: the type of cannabinoid present, the intrauterine tissue, and CNR1/2 expression. Study of ECS gene expression in late pregnancy is therefore important to determine the contribution of this pathway to the normal and pathologic physiology of labour, for instance in preterm labour. Examining ECS gene expression in pregnancy may also contribute insight into the effects of exogenous cannabinoid consumption (reported in ~5% of pregnancies) on the late-pregnant uterus. To understand when and where cannabinoid signaling may impact uterine functions, we conducted an observational study on pregnant human and mouse intrauterine tissues. Methods: Human amnion, chorion, decidua, placenta, and upper/lower myometrium (n=6 participants) were biopsied at cesarean delivery (term, non-labour) to determine CNR expression by qPCR. Additional decidua (n=80) and upper/lower myometrium (n=82) samples were similarly obtained with and without labour, at term and preterm, for CNR expression analysis by qPCR. Mouse uteri for CNR expression analysis by qPCR were obtained from timed-mated C57BL6 mice at days 15-20 of pregnancy, in active labour, or post-partum. Human and mouse expression data were analyzed by Student’s t-test, one-way ANOVA (Bonferroni post-hoc), and Pearson’s correlation, as appropriate. Results: Term non-labour chorion, placenta, myometrium and decidua express CNRs, with 2-fold higher expression of CNR1 versus CNR2. In myometrium and decidua, neither CNR1 or CNR2 expression differed with labour status. CNR1 expression correlated positively with gestational age in decidua (r=0.346, p=0.0266) and lower segment myometrium (r=0.3667, p=0.0270) with labour. In mouse uteri, Cnr1 and Cnr2 expression significantly increased post-partum compared to mid/late pregnancy (vs day 19, p<0.0001 Cnr1; vs days 15-18, p<0.05 Cnr2). Conclusion: ECS may occur in the human decidua and myometrium throughout pregnancy and labour as CNR1 and CNR2 expression is maintained throughout. In our mouse model, higher Cnr1 and Cnr2 expression post-partum suggests that ECS may play a role in uterine resolution following delivery. Additional RNAseq analysis of the mouse tissues studied is underway to address whether expression of genes involved in production, transport or metabolism of cannabinoids are altered in late pregnancy or with the initiation of parturition.
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CANDELA, ANDREA. "THE EARLY STAGES OF URANIUM GEOLOGY IN POST-WWII ITALY." Earth Sciences History 38, no. 1 (April 1, 2019): 137–49. http://dx.doi.org/10.17704/1944-6178-38.1.137.
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ABSTRACT At the beginning of the industrial atomic age, launched by President Dwight Eisenhower's speech on the peaceful uses of nuclear energy (“Atoms for Peace”, addressed to the United Nations General Assembly, New York, 8 December 1953), and after the birth of the first atomic agencies in France (Commissariat a l'Énergie Atomique, 1945) and the United States (the U.S. Atomic Energy Commission, 1946), the Comitato Nazionale per le Ricerche Nucleari (National Committee for Nuclear Research–CNRN) was also established in Italy (1952). The new institution, in 1960 became a self-governing organization with a modified name, Comitato Nazionale per l'Energia Nucleare (National Committee for Nuclear Energy–CNEN). Its mission was to promote and develop Italian research in nuclear science and technology. Mining and mineral exploration were among the early activities that the National Committee undertook beginning in 1954, when the Divisione Geomineraria (Geology and Mining Division) was established. A regional-scale geochemical and geophysical prospecting survey for U-Th bearing ores involved different Italian regions both in northern and in southern Italy. Geological surveys, for instance, were systematically carried out in the Alps beginning in 1954. They were run by three main teams of geologists. The paper aims to analyze the key factors that contributed to fostering the emergence of a new field of research about uranium and nuclear geology in Italy during the years immediately after WWII.
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McGlinchey, Michael J. "2000 Alcan Award Lecture Adventures in organometallic NMR: steric restraints, slowed rotations, and skeletal rearrangements." Canadian Journal of Chemistry 79, no. 9 (September 1, 2001): 1295–309. http://dx.doi.org/10.1139/v01-117.
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The structures and NMR fluxionality of a wide variety of organometallic complexes (including tetrahedral cluster cations and systems of the type (CnRn)ML3, where R = Et, Ph) are discussed. Barriers to tripodal and peripheral substituent rotations are reported, and the relevance of correlated rotations to molecular machines is outlined. Haptotropic shifts in (cyclopenta[def]phenanthrenyl)MLn and (cyclopenta[l]phenanthrenyl)MLn complexes are rationalized in terms of the aromatic character of the transition states. Likewise, the barriers to silatropic shifts in polyindenylsilanes can be correlated with the aromaticity of the intermediate isoindenes. Finally, the use of cobalt clusters to control cyclohexane ring conformations is described.Key words: NMR ring currents, fluxionality, correlated rotations, molecular rearrangements, haptotropic shifts.
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Tang, Yitai, and Richard H. Gomer. "CnrN regulates Dictyostelium group size using a counting factor-independent mechanism." Communicative & Integrative Biology 1, no. 2 (October 2008): 185–87. http://dx.doi.org/10.4161/cib.1.2.7255.
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Nowin, Michele, and Judy Ozuna. "Role Delineation and Test Specification Validation Study for the CNRN Examination." Journal of Neuroscience Nursing 20, no. 5 (October 1988): 273–77. http://dx.doi.org/10.1097/01376517-198810000-00002.
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Weiss, Patricia, Edit Anna Porpaczy, Trang Le, Cathrin Skrabs, Michaela Gruber, Clemens Pausz, Ulrich Jäger, and Katrina Vanura. "Cannabinoid Receptor 1 in Chronic Lymphocytic Leukemia: Strong Prognostic Marker with Limited Therapeutic Use." Blood 120, no. 21 (November 16, 2012): 4565. http://dx.doi.org/10.1182/blood.v120.21.4565.4565.
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Abstract Abstract 4565 Cannabinoids, the active compounds of the marijuana plant Cannabis sativa L., have been used for their medical properties for thousands of years. They exert their function by binding to the two cannabinoid receptors (CNR1 and CNR2), CNR1 being expressed mostly in the nervous while CNR2 mainly is found in the immune system. Various studies reported that cannabinoids induce apoptosis and inhibit cell proliferation, invasion, and metastasis, and block angiogenesis in solid tumours. We and others (1, 2) have previously observed an overexpression of CNR1 and 2 and induction of apoptosis upon incubation with cannabinoids in hematologic malignancies, including chronic lymphocytic leukemia (CLL). These data led us to more thoroughly evaluate the role of the two receptors in CLL. A cohort of 102 well characterized CLL patients was screened by real-time PCR for CNR1 and 2 mRNA expression, expression was calculated relative to the mean of CD19 sorted healthy cells (N=4). Also, peripheral blood mononuclear cells (PBMC) from CLL patients (N=10–16) and healthy donors (HD) (N=2–3) were incubated with cannabinoids (ACEA, AM251, JWH-133, AM630, (−)-Cannabidiol, R-(+)-Methandamide) in suspension and co-culture with the mouse fibroblast cell line M2–10B4 at concentrations ranging from 5 to 100 μM for 48h. IC50 values were calculated based on standard viability assays. Although CNR2 mRNA expression was found to be overexpressed compared to healthy individuals (median 3.6, range 0.1–14.4), high or low gene expression (cut-off = 3.6) did not correlate with any clinical markers. In contrast, CNR1 which also was overexpressed in CLL patients (CNR1: median 1.34, range 0–140.4) was found to have prognostic value. With a cut-off set at median CNR1 expression (1.34), high CNR1 expression was associated with Binet stages B+C (p=0.049), unmutated IGHV (p= 0.006), and high CD38 expression (p=0.032). Furthermore, CNR1 high expressing patients had shorter overall (median 154.2 months vs. median not reached; p=0.002) and treatment free survival (median 53.6 vs. 141.4 months; p= 0.000). Based on these data, we evaluated CNR 1 & 2 as potential therapeutic targets. As shown in Table 1, in particular the antagonists reduced cell viability considerably in suspension culture. In co-culture, the microenvironment protected tumour cells from compound induced cytotoxicity except for methanandamide (RM), cannabidiol (CBD), and AM630 which retained their toxicity. However, some of the compounds also had significant impact on healthy cells showing in some instances IC50 values similar to that of CLL cells (Table 1). Interestingly, the sensitivity of samples to the cannabinoids was not associated with mRNA expression of either of the receptors. Taken together, we provide data that mRNA expression of CNR1 but not CNR2 is of prognostic value in CLL. Although some cannabinoids reduce viability in neoplastic cells considerably independent of CNR expression, also healthy cells are affected, indicating a poor therapeutic ratio in chronic lymphocytic leukemia. Table 1. IC50 values achieved after 48h incubation of primary CLL and HD cells and M2–10B4 mouse fibroblasts with cannabinoids. For comparison, IC50 values for fludarabine are included. Concentrations in μM, NR = 50% viability reduction not reached. Compound Action Primary CLL suspension Primary HD suspension Primary CLL co-culture M2-10B4 fibroblasts RM* CNR1 agonist 33.19 60.13 29.27 34.55 CBDμ CNR1 antagonist, CNR2 inverse agonist 21.74 15.09 16.78 13.52 ACEA CNR1 agonist 31.78 39.01 NR NR AM251 CNR1 antagonist 9.43 11.44 NR NR JWH133 CNR2 agonist 75.68 78.12 NR NR AM630 CNR2 antagonist, CNR2 inverse agonist, weak CNR1 agonist/inverse agonist 12.08 28.51 27.64 28.27 Fludarabine 4.18 7.08 5.36 103.15 * RM = R-(+)-Methanandamide. μ CBD = (−)-Cannabidiol. Disclosures: No relevant conflicts of interest to declare.
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Pandelides, Zacharias, Neelakanteswar Aluru, Cammi Thornton, Haley E. Watts, and Kristine L. Willett. "Transcriptomic Changes and the Roles of Cannabinoid Receptors and PPARγ in Developmental Toxicities Following Exposure to Δ9-Tetrahydrocannabinol and Cannabidiol." Toxicological Sciences 182, no. 1 (April 21, 2021): 44–59. http://dx.doi.org/10.1093/toxsci/kfab046.
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Abstract Human consumption of cannabinoid-containing products during early life or pregnancy is rising. However, information about the molecular mechanisms involved in early life stage Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) toxicities is critically lacking. Here, larval zebrafish (Danio rerio) were used to measure THC- and CBD-mediated changes on transcriptome and the roles of cannabinoid receptors (Cnr) 1 and 2 and peroxisome proliferator activator receptor γ (PPARγ) in developmental toxicities. Transcriptomic profiling of 96-h postfertilization (hpf) cnr+/+ embryos exposed (6 − 96 hpf) to 4 μM THC or 0.5 μM CBD showed differential expression of 904 and 1095 genes for THC and CBD, respectively, with 360 in common. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched in the THC and CBD datasets included those related to drug, retinol, and steroid metabolism and PPAR signaling. The THC exposure caused increased mortality and deformities (pericardial and yolk sac edemas, reduction in length) in cnr1−/− and cnr2−/− fish compared with cnr+/+ suggesting Cnr receptors are involved in protective pathways. Conversely, the cnr1−/− larvae were more resistant to CBD-induced malformations, mortality, and behavioral alteration implicating Cnr1 in CBD-mediated toxicity. Behavior (decreased distance travelled) was the most sensitive endpoint to THC and CBD exposure. Coexposure to the PPARγ inhibitor GW9662 and CBD in cnr+/+ and cnr2−/− strains caused more adverse outcomes compared with CBD alone, but not in the cnr1−/− fish, suggesting that PPARγ plays a role in CBD metabolism downstream of Cnr1. Collectively, PPARγ, Cnr1, and Cnr2 play important roles in the developmental toxicity of cannabinoids with Cnr1 being the most critical.
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Gaffal, Evelyn, Andrea M. Kemter, Stefanie Scheu, Rafael Leite Dantas, Jens Vogt, Bernhard Baune, Thomas Tüting, Andreas Zimmer, and Judith Alferink. "Cannabinoid Receptor 2 Modulates Maturation of Dendritic Cells and Their Capacity to Induce Hapten-Induced Contact Hypersensitivity." International Journal of Molecular Sciences 21, no. 2 (January 11, 2020): 475. http://dx.doi.org/10.3390/ijms21020475.
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Contact hypersensitivity (CHS) is an established animal model for allergic contact dermatitis. Dendritic cells (DCs) play an important role in the sensitization phase of CHS by initiating T cell responses to topically applied haptens. The cannabinoid receptors 1 (CB1) and 2 (CB2) modulate DC functions and inflammatory skin responses, but their influence on the capacity of haptenized DCs to induce CHS is still unknown. We found lower CHS responses to 2,4-dinitro-1-fluorobenzene (DNFB) in wild type (WT) mice after adoptive transfer of haptenized Cnr2−/− and Cnr1−/−/Cnr2−/− bone marrow (BM) DCs as compared to transfer of WT DCs. In contrast, induction of CHS was not affected in WT recipients after transfer of Cnr1−/− DCs. In vitro stimulated Cnr2−/− DCs showed lower CCR7 and CXCR4 expression when compared to WT cells, while in vitro migration towards the chemokine ligands was not affected by CB2. Upregulation of MHC class II and co-stimulatory molecules was also reduced in Cnr2−/− DCs. This study demonstrates that CB2 modulates the maturation phenotype of DCs but not their chemotactic capacities in vitro. These findings and the fact that CHS responses mediated by Cnr2−/− DCs are reduced suggest that CB2 is a promising target for the treatment of inflammatory skin conditions.
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Sun, Xiaofei, Monica Cappelletti, Yingju Li, Christopher L. Karp, Senad Divanovic, and Sudhansu K. Dey. "Cnr2 Deficiency Confers Resistance to Inflammation-Induced Preterm Birth in Mice." Endocrinology 155, no. 10 (October 1, 2014): 4006–14. http://dx.doi.org/10.1210/en.2014-1387.
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Abstract Infection-induced inflammation, frequently associated with increased production of proinflammatory cytokines, is considered a significant contributor to preterm birth. A G protein-coupled cannabinoid receptor 2 (CB2), encoded by Cnr2, is expressed in various immune cells and was shown to modulate immune responses. We show here that Cnr2, but not Cnr1, deficient mice are resistant to lipopolysaccharide (LPS)-driven preterm birth and suppression of serum progesterone levels. After LPS challenge, Cnr2−/− mice exhibited increased serum levels of IL-10 with decreased IL-6 levels. These changes were associated with reduced LPS-induced Ptgs2 expression at the maternal-conceptus interface on day 16 of pregnancy. LPS stimulation of Cnr2−/− dendritic cells in vitro resulted in increased IL-10 with reduced IL-6 production and correlated with increased cAMP accumulation. Collectively, our results suggest that increased IL-10 production occurring via augmented cAMP accumulation represents a potential mechanism for the resistance of Cnr2−/− mice to LPS-induced preterm birth. These results may have clinical relevance, because currently, there are limited options to prevent preterm birth.
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Li, Jun-Xian, Feng-Ji Xie, Chia-Hui Chen, Kuan-Ming Chen, and Chia-Jung Tsai. "Dual-Energy Computed Tomography for Evaluation of Breast Cancer Follow-Ups: Comparison of Virtual Monoenergetic Images and Iodine-Map." Diagnostics 12, no. 4 (April 10, 2022): 946. http://dx.doi.org/10.3390/diagnostics12040946.
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Differentiating tumor tissue from dense breast tissue can be difficult. Dual-energy CT (DECT) could be suitable for making diagnoses at breast cancer follow-ups. This study investigated the contrast in DECT images and iodine maps for patients with breast cancer being followed-up. Chest CT images captured in 2019 were collected. Five cases of metastatic breast cancer in the lungs were analyzed; the contrast-to-noise ratio (for breast tissue and muscle: CNRb and CNRm, respectively), tumor-to-breast mammary gland ratio (T/B), and tumor-to-muscle ratio (T/M) were calculated. For 84 cases of no metastasis, monochromatic spectral and iodine maps were obtained to compare differences under various breast densities using the K-means algorithm. The optimal T/B, T/M, and CNRb (related to mammary glands) were achieved for the 40-keV image. Conversely, CNRm (related to lungs) was better for higher energy. The optimal balance was achieved at 80 keV. T/B, T/M, and CNR were excellent for iodine maps, particularly for density > 25%. In conclusion, energy of 80 keV is the parameter most suitable for observing the breast and lungs simultaneously by using monochromatic spectral images. Adding iodine mapping can be appropriate when a patient’s breast density is greater than 25%.
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Austrich-Olivares, Amaya, María Salud García-Gutiérrez, Lucía Illescas, Ani Gasparyan, and Jorge Manzanares. "Cannabinoid CB1 Receptor Involvement in the Actions of CBD on Anxiety and Coping Behaviors in Mice." Pharmaceuticals 15, no. 4 (April 13, 2022): 473. http://dx.doi.org/10.3390/ph15040473.
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The anxiolytic and antidepressant properties of cannabidiol (CBD) have been evaluated in several studies. However, the molecular mechanisms involved in these actions remain unclear. A total of 130 male mice were used. CBD’s ability to modulate emotional disturbances (anxiety and depressive-like behaviors) was evaluated at different doses in wild-type (CD1; 10, 20 and 30 mg/kg; i.p.) and knockout (CB1KO, CB2KO; GPR55KO; 20 mg/kg) mice. Moreover, CBD effects (20 mg/kg; i.p.) were evaluated in mice previously treated with the CB1r-antagonist SR141716A (2mg/kg; i.p.). Relative gene expression analyses of Cnr1 and Cnr2, Gpr55 and GABA(A)α2 and γ2 receptor subunits were performed in the amygdala (AMY) and hippocampus (HIPP) of CD1 mice. CBD (10 and 20 mg/kg) showed anxiolytic and antidepressant actions in CD1 mice, being more effective at 20 mg/kg. Its administration did not induce anxiolytic actions in CB1KO mice, contrary to CB2KO and GPR55KO. In all of them, the lack of cannabinoid receptors did not modify the antidepressant activity of CBD. Interestingly, the administration of the CB1r antagonist SR141716A blocked the anxiolytic-like activity of CBD. Real-time PCR studies revealed a significant reduction in Cnr1 and GABA(A)α2 and γ2 gene expression in the HIPP and AMY of CD1 mice treated with CBD. Opposite changes were observed in the Cnr2. Indeed, Gpr55 was increased in the AMY and reduced in the HIPP. CB1r appears to play a relevant role in modulating the anxiolytic actions of CBD. Moreover, this study revealed that CBD also modified the gene expression of GABA(A) subunits α2 and γ2 and CB1r, CB2r and GPR55, in a dose- and brain-region-dependent manner, supporting a multimodal mechanism of action for CBD.
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Kaim, Wolfgang, Thomas Roth, Barbara Olbrich-Deussner, Renate Gross-Lannert, Jeanne Jordanov, and Eberhard K. H. Roth. "Unexpected paramagnetism of mono- and polynuclear 18 valence electron metal carbonyl complexes [(CnRn)(CO)2M]k(L), M = chromium, manganese; k = 1, 2, 4. Implications for photoreactivity." Journal of the American Chemical Society 114, no. 14 (July 1992): 5693–97. http://dx.doi.org/10.1021/ja00040a031.
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Xu, Xiaohong, Michael M. Scott, and Evan S. Deneris. "Shared Long-Range Regulatory Elements Coordinate Expression of a Gene Cluster Encoding Nicotinic Receptor Heteromeric Subtypes." Molecular and Cellular Biology 26, no. 15 (August 1, 2006): 5636–49. http://dx.doi.org/10.1128/mcb.00456-06.
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ABSTRACT The nicotinic acetylcholine receptor (nAChR) β4/α3/α5 gene cluster encodes several heteromeric transmitter receptor subtypes that are essential for cholinergic synaptic transmission in adrenal gland, autonomic ganglia, pineal gland, and several nuclei in the central nervous system. However, the transcriptional mechanisms coordinating expression of these subunit genes in different cell populations are unknown. Here, we used transgenic methods to investigate long-range transcriptional control of the cluster. A 132-kb P1-derived artificial chromosome (PAC) encoding the rat cluster recapitulated the neurally- and endocrine-restricted expression patterns of the endogenous β4/α3/α5 genes. Mutation of ETS factor binding sites in an enhancer, β43′, embedded in the β4 3′-untranslated exon resulted in greatly diminished β4, α3, and α5 expression in adrenal gland and to a lesser extent in the superior cervical ganglion (SCG) but not in other tissues. Phylogenetic sequence analyses revealed several conserved noncoding regions (CNRs) upstream of β4 and α5. Deletion of one of them (CNR4) located 20 kb upstream of β4 resulted in a dramatic decrease in β4 and α3 expression in the pineal gland and SCG. CNR4 was sufficient to direct LacZ transgene expression to SCG neurons, which express the endogenous β4α3α5 subunits, and pineal cells, which express the endogenous β4α3 combination. Finally, CNR4 was able to direct transgene expression to major sites of expression of the endogenous cluster in the brain. Together, our findings support a model in which cell type-specific shared long-range regulatory elements are required for coordinate expression of clustered nAChR genes.
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Takei, Yutaka, Shun Hamada, Kouji Senzaki, Tetsuji Mutoh, Hidehiko Sugino, and Takeshi Yagi. "Two Novel CNRs from the CNR Gene Cluster Have Molecular Features Distinct from Those of CNR1 to 8." Genomics 72, no. 3 (March 2001): 321–30. http://dx.doi.org/10.1006/geno.2000.6468.
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Portugalov, Anna, Hiba Zaidan, Inna Gaisler-Salomon, Cecilia J. Hillard, and Irit Akirav. "FAAH Inhibition Restores Early Life Stress-Induced Alterations in PFC microRNAs Associated with Depressive-Like Behavior in Male and Female Rats." International Journal of Molecular Sciences 23, no. 24 (December 17, 2022): 16101. http://dx.doi.org/10.3390/ijms232416101.
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Early life stress (ELS) increases predisposition to depression. We compared the effects of treatment with the fatty acid amide hydrolase (FAAH) inhibitor URB597, and the selective serotonin reuptake inhibitor paroxetine, on ELS-induced depressive-like behavior and the expression of microRNAs (miRs) associated with depression in the medial prefrontal cortex (mPFC), hippocampal CA1 area, lateral habenula and dorsal raphe in rats. We also examined the mRNA expression of serotonergic (htr1a and slc6a4) and endocannabinoid (cnr1, cnr2 and faah) targets in the mPFC following ELS and pharmacological treatment. Adult males and females exposed to the ‘Limited Bedding and Nesting’ ELS paradigm demonstrated a depressive-like phenotype and late-adolescence URB597 treatment, but not paroxetine, reversed this phenotype. In the mPFC, ELS downregulated miR-16 in males and miR-135a in females and URB597 treatment restored this effect. In ELS females, the increase in cnr2 and decrease in faah mRNAs in the mPFC were reversed by URB597 treatment. We show for the first time that URB597 reversed ELS-induced mPFC downregulation in specific miRs and stress-related behaviors, suggesting a novel mechanism for the beneficial effects of FAAH inhibition. The differential effects of ELS and URB597 on males and females highlight the importance of developing sex-specific treatment approaches.
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Poznanski, Piotr, Joanna Giebultowicz, Justyna Durdzinska, Tomasz Kocki, Mariusz Sacharczuk, Magdalena Bujalska-Zadrozny, and Anna Lesniak. "Mechanisms Underlining Inflammatory Pain Sensitivity in Mice Selected for High and Low Stress-Induced Analgesia—The Role of Endocannabinoids and Microglia." International Journal of Molecular Sciences 23, no. 19 (October 2, 2022): 11686. http://dx.doi.org/10.3390/ijms231911686.
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In this work we strived to determine whether endocannabinoid system activity could account for the differences in acute inflammatory pain sensitivity in mouse lines selected for high (HA) and low (LA) swim-stress-induced analgesia (SSIA). Mice received intraplantar injections of 5% formalin and the intensity of nocifensive behaviours was scored. To assess the contribution of the endocannabinoid system, mice were intraperitoneally (i.p.) injected with rimonabant (0.3–3 mg/kg) prior to formalin. Minocycline (45 and 100 mg/kg, i.p.) was administered to investigate microglial activation. The possible involvement of the endogenous opioid system was investigated with naloxone (1 mg/kg, i.p.). Cannabinoid receptor types 1 and 2 (Cnr1, Cnr2) and opioid receptor subtype (Oprm1, Oprd1, Oprk1) mRNA levels were quantified by qPCR in the structures of the central nociceptive circuit. Levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were measured by liquid chromatography coupled with the mass spectrometry method (LC-MS/MS). In the interphase, higher pain thresholds in the HA mice correlated with increased spinal anandamide and 2-AG release and higher Cnr1 transcription. Downregulation of Oprd1 and Oprm1 mRNA was noted in HA and LA mice, respectively, however no differences in naloxone sensitivity were observed in either line. As opposed to the LA mice, inflammatory pain sensitivity in the HA mice in the tonic phase was attributed to enhanced microglial activation, as evidenced by enhanced Aif1 and Il-1β mRNA levels. To conclude, Cnr1 inhibitory signaling is one mechanism responsible for decreased pain sensitivity in HA mice in the interphase, while increased microglial activation corresponds to decreased pain thresholds in the tonic inflammatory phase.
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Li, Yingju, Fenghua Bian, Xiaofei Sun, and Sudhansu K. Dey. "Mice Missing Cnr1 and Cnr2 Show Implantation Defects." Endocrinology 160, no. 4 (February 18, 2019): 938–46. http://dx.doi.org/10.1210/en.2019-00024.
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Kaim, Wolfgang, Ralf Reinhardt, and Monika Sieger. "Chemical and Electrochemical Generation of Hydride-Forming Catalytic Intermediates (bpy)M(CnRn): M = Rh, Ir (n = 5); M = Ru, Os (n = 6). Coordinatively Unsaturated Ground State Models of MLCT Excited States?" Inorganic Chemistry 33, no. 20 (September 1994): 4453–59. http://dx.doi.org/10.1021/ic00098a009.
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Sun, Qi, Min-jun Dong, Xiao-feng Tao, Meng-da Jiang, and Chi Yang. "Selection and application of coils in temporomandibular joint MRI." Dentomaxillofacial Radiology 49, no. 3 (March 2020): 20190002. http://dx.doi.org/10.1259/dmfr.20190002.
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Objective: To compare and evaluate the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR) values between a 15-channel phased array head coil and 6-channel dS Flex M surface coil in the MRI of temporomandibular joint. Methods: 300 patients were randomly assigned to two groups: 150 patients were examined by using a 15-channel phased array head coil and the other 150 patients were scanned by using a 6-channel dS Flex M surface coil. All of the data were set in the same 6 regions of interest including the temporal lobe, condyle neck, lateral pterygoid muscle, parotid gland, the adipose area and an area of the background noise）. SNR and CNR values were measured respectively. Results: The numerical variation law of SNR and CNR values measured in regionsof interest of each group was similar, although different coils were used. There were statistically significant differences of SNR values in all of the oblique sagittal (OSag) proton density-weighted imaging, the part of OSag T 2 weighted image (T 2WI) except for SNR4 and SNR5. and oblique coronal (OCor) T 2WI sequence except for SNR2. On the contrary, SNR4 and SNR5 values in the OCor T 2WI and SNR5 values in OSag T 2WI sequences by using the surface coil were higher than those by using the head coil. There were no statistically significant intergroup differences of CNR values in OSag proton density-weighted imaging sequence except CNR1 and in OSag T 2WI sequence except CNR5. But, statistically significant differences of all the values in the OCor T 2WI sequence except for CNR1 were observed. Conclusion: Both the phased array head coil and dS Flex M surface coil can be used for temporomandibular joint MRI.
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Kong, Xiangjuan, Qingshan Miao, Xiaozi Lu, Zeng Zhang, Min Chen, Jinxiang Zhang, and Jinguo Zhai. "The association of endocannabinoid receptor genes (CNR1 and CNR2) polymorphisms with depression." Medicine 98, no. 46 (November 2019): e17403. http://dx.doi.org/10.1097/md.0000000000017403.
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Peiró, Ana M., María S. García-Gutiérrez, Beatriz Planelles, Teresa Femenía, Carlos Mingote, Luis Jiménez-Treviño, Sara Martínez-Barrondo, et al. "Association of cannabinoid receptor genes (CNR1 and CNR2) polymorphisms and panic disorder." Anxiety, Stress, & Coping 33, no. 3 (March 2, 2020): 256–65. http://dx.doi.org/10.1080/10615806.2020.1732358.
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Notarstefano, Valentina, Giorgia Gioacchini, Elisabetta Giorgini, Nina Montik, Andrea Ciavattini, Anna Rita Polidori, Fulvia Antonia Candela, Lisa Vaccari, Maurizio Cignitti, and Oliana Carnevali. "The Impact of Controlled Ovarian Stimulation Hormones on the Metabolic State and Endocannabinoid System of Human Cumulus Cells." International Journal of Molecular Sciences 21, no. 19 (September 27, 2020): 7124. http://dx.doi.org/10.3390/ijms21197124.
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Different Follicle Stimulating Hormone (FSH) formulation and Luteinizing Hormone (LH) are used in Assisted Reproductive Technology (ART) to induce follicles development and oocytes maturation, but it is still under debate which protocol is to be preferred. In the present study, the different effects on cumulus cells (CCs) of three controlled ovarian stimulation (COS) protocols, based on urinary FSH, recombinant FSH, or human Menopausal Gonadotropin (hMG) administration, were assessed. CCs were obtained from 42 normal-responders women undergoing COS, randomly divided into three groups according to the used gonadotropin formulation. Differences were found in the expression of genes belonging to the endocannabinoid system (the receptors CNR1, CNR2 and TRPV1, and the enzymes involved in the metabolisms of anandamide, NAPE-PLD and FAAH, and 2-acylglycerol, DAGL and MAGL); consistently, changes in lipid (PPARα, and FASN) and carbohydrate (GLUT1 and GLUT9) metabolisms, in CCs’ macromolecules composition (highlighted by Fourier Transform Infrared Microspectroscopy, FTIRM), and in the number of retrieved oocytes were found. For the first time, statistically significant evidence on the differences related to each COS protocol on the endocannabinoid system, metabolism and macromolecular composition of CCs was found, representing a proof of concept to be further confirmed in a larger cohort of patients.
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Chioccarelli, Teresa, Giovanna Cacciola, Lucia Altucci, Sheena E. M. Lewis, Luke Simon, Giulia Ricci, Catherine Ledent, et al. "Cannabinoid Receptor 1 Influences Chromatin Remodeling in Mouse Spermatids by Affecting Content of Transition Protein 2 mRNA and Histone Displacement." Endocrinology 151, no. 10 (September 1, 2010): 5017–29. http://dx.doi.org/10.1210/en.2010-0133.
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Marijuana smokers and animals treated with Δ9-tetrahydrocannabinol, the principal component of marijuana, show alterations of sperm morphology suggesting a role for cannabinoids in sperm differentiation and/or maturation. Because the cannabinoid receptor 1 (CNR1) activation appears to play a pivotal role in spermiogenesis, the developmental stage where DNA is remodeled, we hypothesized that CNR1 receptors might also influence chromatin quality in sperm. We used Cnr1 null mutant (Cnr1−/−) mice to study the possible role of endocannabinoids on sperm chromatin during spermiogenesis. We demonstrated that CNR1 activation regulated chromatin remodeling of spermatids by either increasing Tnp2 levels or enhancing histone displacement. Comparative analysis of wild-type, Cnr1+/−, and Cnr1−/− animals suggested the possible occurrence of haploinsufficiency for Tnp2 turnover control by CNR1, whereas histone displacement was disrupted to a lesser extent. Furthermore, flow cytometry analysis demonstrated that the genetic loss of Cnr1 decreased sperm chromatin quality and was associated with sperm DNA fragmentation. This damage increased during epididymal transit, from caput to cauda. Collectively, our results show that the expression/activity of CNR1 controls the physiological alterations of DNA packaging during spermiogenesis and epididymal transit. Given the deleterious effects of sperm DNA damage on male fertility, we suggest that the reproductive function of marijuana users may also be impaired by deregulation of the endogenous endocannabinoid system.
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Zhang, Ruijie, Shenghua Sun, Fuyun Ji, Chun Liu, Hua Lin, Lihua Xie, Honghui Yang, et al. "CNTN-1 Enhances Chemoresistance in Human Lung Adenocarcinoma Through Induction of Epithelial-Mesenchymal Transition by Targeting the PI3K/Akt Pathway." Cellular Physiology and Biochemistry 43, no. 2 (2017): 465–80. http://dx.doi.org/10.1159/000480473.
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Background/Aims: Chemoresistance has been a major obstacle to the effective treatment of lung cancer. Previously, we found that contactin-1 (CNTN-1) is related to cisplatin resistance in lung adenocarcinoma. Here, we aimed to investigate the underlying mechanism behind the role of CNTN-1 in cisplatin resistance in lung adenocarcinoma. Methods: EMT-associated phenotypes, including alterations in cellular morphology and marker (E-cadherin, N-cadherin and Vimentin) expression, were compared between A549 cells and A549/DDP cells (a cisplatin-resistant cell line of lung adenocarcinoma with abnormal CNTN-1 expression) by using real-time time PCR and Western blotting. Other methods, including CNTN-1 overexpression in A549 cells and CNTN-1 knockdown in A549/DDP cells, were also used to investigate the role of CNTN-1 in mediating the EMT phenotype and thr resulting cisplatin resistance and malignant progression of cancer cells in vitro and in vivo. Results: A549/DDP cells exhibited an EMT phenotype and aggravated malignant behaviors. CNTN-1 knockdown in A549/DDP cells partly reversed the EMT phenotype, increased drug sensitivity, and attenuated the malignant progression whereas CNTN-1 overexpression in A549 cells resulted in the opposite trend. Furthermore, the PI3K/Akt pathway was involved in the effects of CNTN-1 on EMT progression in A549/DDP cells, verified by the xenograft mouse model. Conclusion: CNTN-1 promotes cisplatin resistance in human cisplatin-resistant lung adenocarcinoma through inducing the EMT process by activating the PI3K/Akt signaling pathway. CNTN-1 may be a potential therapeutic target to reverse chemoresistance in cisplatin-resistant lung adenocarcinoma.
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Löfgren, Patrik, Eva Sjölin, Kerstin Wåhlen, and Johan Hoffstedt. "Human Adipose Tissue Cannabinoid Receptor 1 Gene Expression Is Not Related to Fat Cell Function or Adiponectin Level." Journal of Clinical Endocrinology & Metabolism 92, no. 4 (April 1, 2007): 1555–59. http://dx.doi.org/10.1210/jc.2006-2240.
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Abstract Context: The cannabinoid receptor 1 gene (CNR1) is implicated in adipocyte function. Objective: We investigated human adipose tissue CNR1 mRNA in relation to obesity, clinical and metabolic variables, adipocyte function, and adiponectin (ADIPOQ) levels. Methods: We assessed sc fat biopsies from 96 obese and nonobese subjects and omental fat biopsies from 82 obese and nonobese subjects. Results: The sc and omental adipose CNR1 gene expression were similar in obese and nonobese subjects. No association between either sc or omental adipose CNR1 mRNA levels and body mass index, waist circumference, plasma levels of glucose and insulin, lipids, or blood pressure was found. The sc and omental maximal adrenergic lipolytic activation as well as lipolytic adrenoceptor sensitivity were not related to CNR1 gene expression. Lipogenesis in sc adipocytes also showed no association with CNR1 mRNA levels. Finally, no relation was found between adipose CNR1 gene expression and ADIPOQ mRNA, adipose tissue adiponectin secretion, or circulating adiponectin. Conclusion: We found no association of human adipose tissue CNR1 mRNA expression with measures of body fat, metabolic parameters, fat cell function, or ADIPOQ expression. These data do not suggest a major role of human adipose CNR1 in fat cell function or metabolic disease development.
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Yu, Ji-Wei, Sheng-Hua Wu, Rui-qi Lu, Ju-gang Wu, Xiao-Chun Ni, Gou-cai Zhou, Hai-guang Jiang, et al. "Expression and Significances of Contactin-1 in Human Gastric Cancer." Gastroenterology Research and Practice 2013 (2013): 1–10. http://dx.doi.org/10.1155/2013/210205.
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Background. This study aimed at determining the relationship between vascular endothelial growth factor-C (VEGF-C), vascular endothelial growth factor receptor-3 (VEGFR-3), and contactin-1 (CNTN-1) expression in gastric cancer (GC).Methods. The expression level of CNTN-1 mRNA and CNTN-1 protein of 33 cases was determined using RT-PCR and Western Blot. And 105 cases were immunohistochemically examined for VEGF-C, VEGFR-3, and CNTN-1 expressions. Assessment of lymphatic vessel density (LVD) was also performed by D2-40 immunostaining. Then we analyzed the relationships between VEGF-C, VEGFR-3, and CNTN-1, as well as their correlations with clinicopathologic features, LVD, and survival time.Results. The positivity rate of VEGF-C, VEGFR-3, and CNTN-1 in primary tumor was 56.19%, 64.76%, and 58.09%. The expression of CNTN-1 significantly correlated with VEGF-C (P<0.001) and VEGFR-3 (P<0.001). All of them were closely related to TNM stage, lymphatic invasion, and lymph node involvement (P<0.05). LVD was significantly correlated with VEGF-C (P=0.001), VEGFR-3 (P=0.011), and CNTN-1 expression (P<0.001). VEGF-C, VEGFR-3, and CNTN-1 expression significantly associated with poorer prognosis (P<0.001,P=0.034,P=0.012, resp.).Conclusion. CNTN-1 associated with VEGF-C and VEGFR-3 expression in GC. All of them correlated with lymphatic metastasis, which might play an important role in the lymphatic invasion via lymphangiogenesis pathway in GC.
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Zhao, Liguang, Ruishen Fan, Peng Li, Li Ding, Yazhong Song, Jianwei Li, Yuekun Wang, Tuo Dai, Dayu Deng, and Hongxing Gui. "Impact of N,N ′ -Methylene-bis-Morpholine on the Preservation of Natural Rubber Latex." International Journal of Polymer Science 2023 (March 1, 2023): 1–10. http://dx.doi.org/10.1155/2023/5194052.
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Natural rubber latex (NRL) preserved by high ammonia (HA) presents substantial pollution issues despite its good all-around properties. Cleaning preservation of NRL is critical in the modern rubber industry. In this study, NRL was preserved using N,N ′ -methylene-bis-morpholine (MBM), and the impact of MBM on the preservation and characteristics of NRL was investigated. The results showed that when the MBM dose was greater than 0.15 wt%, the volatile fatty acid value (VFA No.) and viscosity value of fresh NRL were lower, and it could be stored for longer than 5 days without losing stability. Furthermore, MBM demonstrated a favorable preservation effect on concentrated NRL (CNRL). To be effective, MBM must be administered at a dosage greater than 0.3 wt%. The mechanical stability test (MST) and VFA No. of the low-ammonia (LA)-CNRL prepared by MBM combined with ammonia were somewhat lower, whereas the viscosity value was greater. The research showed that the dose of lauric acid soap needs to be increased to improve the stability of ultra-LA-CNRL made by MBM–ammonia composite preservation. After pre-vulcanization treatment, the stability of LA-CNRL preserved by MBM–ammonia composite was drastically reduced. As the stabilizer dose was increased, the CNRL viscosity value decreased, whereas the MST and heat stability improved. The LA-CNRL vulcanized film has excellent mechanical properties similar to HA-CNRL. Furthermore, the infrared spectrum of the LA-CNRL raw rubber film was similar to that of the HA-CNRL film. The thermal degradation curve and characteristic temperature were also similar to that of the HA film. The study indicates that MBM has an outstanding preservation effect on fresh NRL and LA-CNRL, and the findings constitute a significant step forward in the development of the CNRL sector.
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Held, Thomas, Sati Akbaba, Kristin Lang, Semi Harrabi, Denise Bernhardt, Christian Freudlsperger, Steffen Kargus, et al. "Clinical Management of Blood–Brain Barrier Disruptions after Active Raster-Scanned Carbon Ion Re-Radiotherapy in Patients with Recurrent Head-and-Neck Cancer." Cancers 11, no. 3 (March 19, 2019): 383. http://dx.doi.org/10.3390/cancers11030383.
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Purpose: The aim of the current evaluation was to assess central nervous system necrosis (CNSN) after re-irradiation with carbon ions (CR) in two-hundred seventeen (n = 217) patients with recurrent head-and-neck cancer (HNC). Methods: Thirty-six (n = 36) patients with CNSN were assessed retrospectively regarding clinical symptoms and radiographic response. Results: CNSN were classified according to clinical management in line with the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. At a median follow-up of 25.3 months (range 3.3–79.9 months), the median time interval until occurrence of grade I, II, and III CNSN was 9.2 months (range 2.8–75.0 months), 10.2 months (range 2.3–60.5 months), and 16.6 months (range 8.7–32.5 months), respectively. In one patient with an adenocarcinoma infiltrating the frontal lobe, an extensive CNSN grade IV was suspected but the patient declined surgical intervention. Radiographic response after treatment of CNSN grade I, II, and III, defined as ≥25% reduction of the T2 alteration on Magnetic Resonance Imaging (MRI), was observed in 4 (16.0%), 5 (29.4%), and 4 (80%) patients, respectively. Conclusion: CNSN occurred late and frequent after re-irradiation with carbon ions in patients with HNC infiltrating the base of skull. The clinical outcome with adequate treatment was encouraging but correct diagnosis of CNSN remains challenging.
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Okahisa, Y., M. Kodama, M. Takaki, T. Inada, N. Uchimura, M. Yamada, N. Iwata, et al. "Association Study of Two Cannabinoid Receptor Genes, CNR1 and CNR2, with Methamphetamine Dependence." Current Neuropharmacology 9, no. 1 (March 1, 2011): 183–89. http://dx.doi.org/10.2174/157015911795017191.
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Chen, Binshen, Yiming Zhang, Chaoming Li, Peng Xu, Yubo Gao, and Yawen Xu. "CNTN-1 promotes docetaxel resistance and epithelial-to-mesenchymal transition via the PI3K/Akt signaling pathway in prostate cancer." Archives of Medical Science 17, no. 1 (January 5, 2021): 152–65. http://dx.doi.org/10.5114/aoms.2020.92939.
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IntroductionTherapy options for prostate cancer (PCa) typically are centered on docetaxel-based chemotherapy but are limited by the effects of multi-drug resistance. Recent advances have illustrated a role of contactin-1 (CNTN-1) in tumor chemoresistance, while the function and mechanism of CNTN-1 in the resistance of docetaxel in prostate cancer have not yet been elucidated.Material and methodsDocetaxel (Dox)-resistant PCa cell lines of PC3 (PC3-DR) and DU145 (DU145-DR) were established, and short hairpin RNA (shRNA) constructs targeting CNTN-1 were generated to analyze the effect of knockdown of CNTN-1 on PCa progression. Cell Counting Kit-8 (CCK-8), flow cytometry, wound-healing, transwell and western blotting analysis were used to analyze cell proliferation, apoptosis, migration, invasion and related protein expression levels, respectively.ResultsKnockdown of CNTN-1 in PC3-DR and DU145-DR cells attenuated cell proliferation, migration, invasion, EMT phenotype, and drug resistance, and increased cell apoptosis further reduced the tumorigenic phenotype. Knockdown of CNTN-1 resulted in an anti-tumor effect in the xenograft tumor model, and decreased activity of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway both in vitro and in vivo.ConclusionsThe results of the present study suggest that downregulation of CNTN-1 may be an important mechanism to reverse chemoresistance in Dox-resistant PCa progression, thus shedding light on the development of novel anti-tumor therapeutics for the treatment of PCa.
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Nichols, James Matthew, and Barbara Kaplan. "The role of CB1 in experimental autoimmune encephalomyelitis (EAE)." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 180.12. http://dx.doi.org/10.4049/jimmunol.202.supp.180.12.
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Abstract It is well known that cannabinoid receptors have critical roles in immune homeostasis. This includes the CB1 receptor, which is encoded on by the Cnr1 gene. Previous work by others using the EAE model in ABH Cnr1−/− mice showed that while disease severity and onset were similar between wild type (WT) and Cnr1−/− mice, recovery from a relapse was better in WT mice suggesting a level of neuroprotection mediated by the CB1 receptor. In this study, we used the active EAE model in Cnr1−/− and WT C57BL/6 littermates to determine the importance of the CB1 receptor in disease progression by examining both the peripheral and neural immune response. We found clinical disease to be more severe in Cnr1−/− mice as compared to WT mice, which corresponded with significant increases of IFNγ from supernatants of restimulated splenocytes as determined by ELISA. Our results also showed that IL17A was modestly higher in the serum and culture supernatants of the Cnr1−/− mice as compared to WT mice, and histologic analysis of spinal sections showed modestly higher levels of neuroinflammation in Cnr1−/− mice as compared to WT mice. This suggests that CB1 receptors may have an immunoregulatory effect in the peripheral immune response of EAE, which combined with the neuroprotective effect via CB1 found in the other study, ultimately leads to less severe clinical disease in WT mice.
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Licitra, Rosario, Marco Martinelli, Luigi Petrocchi Jasinski, Maria Marchese, Claudia Kiferle, and Baldassare Fronte. "In Vivo Evaluation of Cannabis sativa Full Extract on Zebrafish Larvae Development, Locomotion Behavior and Gene Expression." Pharmaceuticals 14, no. 12 (November 25, 2021): 1224. http://dx.doi.org/10.3390/ph14121224.
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Historically, humans have been using Cannabis sativa for both recreational and medical purposes. Nowadays, cannabis-based products have gained scientific interest due to their beneficial effects on several syndromes and illnesses. The biological activity of cannabinoids is essentially due to the interaction with the endocannabinoid system, and zebrafish (Danio rerio) is a very well-known and powerful in vivo model for studying such specific interactions. The aim of the study was to investigate the effects of different doses of a Cannabis sativa whole extract [dissolved in dimethyl sulfoxide (DMSO)] on zebrafish eggs’ hatchability, embryo post-hatching survival, larvae locomotion behavior and mRNA gene expression. The results showed the absence of toxicity, and no significant differences were observed between treatments for both embryo hatching and survival rate. In addition, larvae exposed to the cannabis extract at the highest dose [containing 1.73 nM and 22.3 nM of ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD), respectively] showed an increased locomotion compared to the control and DMSO treated groups. Moreover, qRT-PCR analysis showed that the highest dosage of cannabis induced an over-expression of cnr1 and cnr2 cannabinoid receptors. In conclusion, the exposition of zebrafish larvae to the whole extract of Cannabis sativa showed no negative effects on embryo development and survival and enhanced the larvae’s locomotor performances. These findings may open up possible Cannabis sativa applications in human pharmacology as well as in other animal sectors.
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Ndaw, D., C. T. Bop, G. Dieye, N. A. Boye Faye, and F. Lique. "The excitation of CNCN in the interstellar medium: hyperfine resolved rate coefficients and non-LTE modelling." Monthly Notices of the Royal Astronomical Society 503, no. 4 (March 18, 2021): 5976–83. http://dx.doi.org/10.1093/mnras/stab775.
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ABSTRACT The recent detections of CNCN and HNCCN+ are seen as further evidence of the large abundance of NCCN in the interstellar medium. The accurate determination of the abundance of these chemically related compounds from the observational spectra requires the prior calculation of collisional rate coefficients. In this work, we aimed at computing hyperfine resolved rate coefficients for the CNCN–He collisional system. First, we determined a new potential energy surface for the CNCN–He van der Waals complex from which we computed rotationally resolved excitation cross-sections for energies up to 800 cm−1 using the quantum mechanical close-coupling approach. Then, hyperfine resolved transitions between the 30 low-lying pure rotational levels of CNCN were computed for temperatures ranging from 5 to 150 K using an improved infinite order sudden approach. The analysis of the scattering results showed a propensity rule in favour of Δj = ΔF1 = ΔF for the hyperfine transitions and a slight dominance of the odd Δj transitions. Using these data, we carried out non-LTE radiative transfer calculations to simulate the excitation of CNCN in molecular clouds and to constrain the physical conditions of cold dark clouds. Preliminary results showed that the abundance of CNCN derived from observational spectra has to be revisited using these new collisional data.
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Michou, M., D. Saint-Martin, H. Teyssèdre, A. Alias, F. Karcher, D. Olivié, A. Voldoire, et al. "A new version of the CNRM Chemistry-Climate Model, CNRM-CCM: description and improvements from the CCMVal-2 simulations." Geoscientific Model Development 4, no. 4 (October 6, 2011): 873–900. http://dx.doi.org/10.5194/gmd-4-873-2011.
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Abstract. This paper presents a new version of the Météo-France CNRM Chemistry-Climate Model, so-called CNRM-CCM. It includes some fundamental changes from the previous version (CNRM-ACM) which was extensively evaluated in the context of the CCMVal-2 validation activity. The most notable changes concern the radiative code of the GCM, and the inclusion of the detailed stratospheric chemistry of our Chemistry-Transport model MOCAGE on-line within the GCM. A 47-yr transient simulation (1960–2006) is the basis of our analysis. CNRM-CCM generates satisfactory dynamical and chemical fields in the stratosphere. Several shortcomings of CNRM-ACM simulations for CCMVal-2 that resulted from an erroneous representation of the impact of volcanic aerosols as well as from transport deficiencies have been eliminated. Remaining problems concern the upper stratosphere (5 to 1 hPa) where temperatures are too high, and where there are biases in the NO2, N2O5 and O3 mixing ratios. In contrast, temperatures at the tropical tropopause are too cold. These issues are addressed through the implementation of a more accurate radiation scheme at short wavelengths. Despite these problems we show that this new CNRM CCM is a useful tool to study chemistry-climate applications.
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Michou, M., D. Saint-Martin, H. Teyssèdre, A. Alias, F. Karcher, D. Olivié, A. Voldoire, et al. "A new version of the CNRM Chemistry-Climate Model, CNRM-CCM: description and improvements from the CCMVal-2 simulations." Geoscientific Model Development Discussions 4, no. 2 (May 31, 2011): 1129–83. http://dx.doi.org/10.5194/gmdd-4-1129-2011.
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Abstract. This paper presents a new version of the Météo-France CNRM Chemistry-Climate Model, so-called CNRM-CCM. It includes some fundamental changes from the previous version (CNRM-ACM) which was extensively evaluated in the context of the CCMVal-2 validation activity. The most notable changes concern the radiative code of the GCM, and the inclusion of the detailed stratospheric chemistry of our Chemistry-Transport model MOCAGE on-line within the GCM. A 47-yr transient simulation (1960–2006) is the basis of our analysis. CNRM-CCM generates satisfactory dynamical and chemical fields in the stratosphere. Several shortcomings of CNRM-ACM simulations for CCMVal-2 that resulted from an erroneous representation of the impact of volcanic aerosols as well as from transport deficiencies have been eliminated. Remaining problems concern the upper stratosphere (5 to 1 hPa) where temperatures are too high, and where there are biases in the NO2, N2O5 and O3 mixing ratios. In contrast, temperatures at the tropical tropopause are too cold. These issues are addressed through the implementation of a more accurate radiation scheme at short wavelengths. Despite these problems we show that this new CNRM CCM is a useful tool to study chemistry-climate applications.
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Iorio-Morin, C., M. Kameda-Smith, SU Ahmed, M. Bigder, A. Dakson, C. Elliott, D. Guha, et al. "P.019 Report from the Canadian Neurosurgery Research Collaborative – One year of resident-led multicentre research initiatives." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 44, S2 (June 2017): S18. http://dx.doi.org/10.1017/cjn.2017.104.
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Background: The Canadian Neurosurgery Research Collaborative (CNRC) was founded in November 2015 as a resident-led national network for multicentre research. We present an annual report of our activities. Methods: CNRC meetings and publications were reviewed and summarized. The status of ongoing and future studies was collected from project leaders. Results: In its first year, the CNRC produced two papers accepted for publication in the Canadian Journal of Neurological Sciences: A CNRC launch letter and a study of operative volume at Canadian neurosurgery residency programs. Three manuscripts are in preparation: 1) a study of the demographics of Canadian neurosurgery residents, 2) an assessment of mobile devices usage patterns and 3) a validation study of the most utilized neurosurgery mobile apps. In addition, protocols for two multi-centre studies are currently undergoing national Research Ethics Board review: A retrospective study of the incidence and predictors of cerebellar mutism and a prospective registry of external ventricular drain procedures and complications. The network is now a registered not-for-profit organization endorsed by the Canadian Neurosurgical Society. Conclusions: The CNRC is a feasibile, relevant and productive resident-led national research network. As the CNRC matures, we look forward to expanding the scope and impact of its projects.
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Wu, Junzhen, Yongming Xu, Shaofeng Pu, Jin Zhou, Yingying Lv, Cheng Li, and Dongping Du. "US-Guided Transforaminal Cervical Nerve Root Block: A Novel Lateral in-Plane Approach." Pain Medicine 22, no. 9 (January 27, 2021): 1940–45. http://dx.doi.org/10.1093/pm/pnab008.
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Abstract Objective The aim of the present study was to investigate the effectiveness and safety of a novel lateral in-plane approach for ultrasound-guided transforaminal cervical nerve root block (US-guided TF-CNRB) in the treatment of cervical radiculopathic pain. Design The design of the present study consisted of an institutional, retrospective case series. Setting The present study was conducted at a university hospital. Subjects Thirty-two patients with cervical radiculopathy who were resistant to conservative therapies and regular US-guided CNRB were included as participants. Methods The included patients were treated with US-guided TF-CNRB. During the treatments, using real-time fluoroscopy, we monitored the spreading patterns of a contrast medium and double confirmed the positions of needle tips. Pain numeric rating scales (NRS) and symptom relief grades were determined via telephone interviews at one, four, and 12 weeks after the procedures. Results US-guided TF-CNRB was performed at the C5 level in six patients, the C6 level in 18 patients, and the C7 level in eight patients. Compared with NRS at baseline, pain scores decreased throughout the observation period. Symptom relief rates of US-guided TF-CNRB at one, four, and 12 weeks were 72%, 69%, and 63%, respectively. Venous blood was aspirated during the procedures in two patients, and the needle tips were corrected. No intravascular injections or neurologic injuries were observed. Conclusion US-guided TF-CNRB produced circumferential spreading around the involved cervical nerve root and showed significant clinical effectiveness in patients resistant to regular US-guided CNRB.
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Onwuameze, O. E., K. W. Nam, E. A. Epping, T. H. Wassink, S. Ziebell, N. C. Andreasen, and B. C. Ho. "MAPK14 and CNR1 gene variant interactions: effects on brain volume deficits in schizophrenia patients with marijuana misuse." Psychological Medicine 43, no. 3 (July 31, 2012): 619–31. http://dx.doi.org/10.1017/s0033291712001559.
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BackgroundAdolescent marijuana use is associated with increased risk for schizophrenia. We previously reported that marijuana misuse in conjunction with specific cannabinoid receptor 1 (CNR1) genetic variants (rs12720071-G-allele carriers) contributed to white-matter (WM) brain volume deficits in schizophrenia patients. In this study, we assessed the influence of another cannabinoid-related gene, mitogen-activated protein kinase 14 (MAPK14), and potential MAPK14–CNR1 gene–gene interactions in conferring brain volume abnormalities among schizophrenia patients with marijuana abuse/dependence. MAPK14 encodes a member of the MAPK family involved in diverse cellular processes, including CNR1-induced apoptosis.MethodWe genotyped 235 schizophrenia patients on nine MAPK14 tag single nucleotide polymorphisms (tSNPs). Approximately one quarter of the sample had marijuana abuse or dependence. Differential effects of MAPK14 tSNPs on brain volumes across patients with versus without marijuana abuse/dependence were examined using ANCOVA.ResultsOf the MAPK14 tSNPs, only rs12199654 had significant genotype effects and genotype × marijuana misuse interaction effects on WM volumes. rs12199654-A homozygotes with marijuana abuse/dependence had significantly smaller total cerebral and lobar WM volumes. The effects of MAPK14 rs12199654 on WM volume deficits remained significant even after controlling for the CNR1 rs12720071 genotype. There were significant main effects of the MAPK14 CNR1 diplotype and diplotype × marijuana interaction on WM brain volumes, with both genetic variants having additive contributions to WM volume deficits only in patients with marijuana misuse.ConclusionsGiven that CNR1-induced apoptosis is preceded by increased MAPK phosphorylation, our study suggests that potential MAPK14–CNR1 gene–gene interactions may mediate brain morphometric features in schizophrenia patients with heavy marijuana use.
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Zammit, Stanley, Gillian Spurlock, Hywel Williams, Nadine Norton, Nigel Williams, Michael C. O'Donovan, and Michael J. Owen. "Genotype effects of CHRNA7, CNR1 and COMT in schizophrenia: interactions with tobacco and cannabis use." British Journal of Psychiatry 191, no. 5 (November 2007): 402–7. http://dx.doi.org/10.1192/bjp.bp.107.036129.
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BackgroundGenetic variations might modify associations between schizophrenia and cannabis or tobacco use.AimsTo examine whether variants within the cannabinoid receptor (CNR1) and α7 nicotinic receptor (CHRNA7) genes are associated with schizophrenia, and whether these effects vary according to cannabis or tobacco use. We also examined a putative interaction between cannabis and Val158Met within the catechol-O-methyltransferase gene (COMT).MethodGenotype effects of CHRNA7 and CNR1 were studied in a case–control sample of 750 individuals with schizophrenia and 688 controls, with interactions for these genes studied in small subsamples. A case-only design of 493 of the schizophrenia group was used to examine interactions between cannabis use and COMT.ResultsThere was no evidence of association between schizophrenia and CNR1 (OR=0.97, 95% CI 0.82–1.13) or CHRNA7 (OR=1.07, 95% CI 0.77–1.49) genotypes, or of interactions between tobacco use and CHRNA7, or cannabis use and CNR1 or COMT genotypes.ConclusionsNeither CNR1 nor CHRNA7 variation appears to alter the risk of schizophrenia. Furthermore, our results do not support the presence of different effects of cannabis use on schizophrenia according to variation within COMT.
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Séférian, Roland, Christine Delire, Bertrand Decharme, Aurore Voldoire, David Salas y Melia, Matthieu Chevallier, David Saint-Martin, et al. "Development and evaluation of CNRM Earth system model – CNRM-ESM1." Geoscientific Model Development 9, no. 4 (April 19, 2016): 1423–53. http://dx.doi.org/10.5194/gmd-9-1423-2016.
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Abstract. We document the first version of the Centre National de Recherches Météorologiques Earth system model (CNRM-ESM1). This model is based on the physical core of the CNRM climate model version 5 (CNRM-CM5) model and employs the Interactions between Soil, Biosphere and Atmosphere (ISBA) and the Pelagic Interaction Scheme for Carbon and Ecosystem Studies (PISCES) as terrestrial and oceanic components of the global carbon cycle. We describe a preindustrial and 20th century climate simulation following the CMIP5 protocol. We detail how the various carbon reservoirs were initialized and analyze the behavior of the carbon cycle and its prominent physical drivers. Over the 1986–2005 period, CNRM-ESM1 reproduces satisfactorily several aspects of the modern carbon cycle. On land, the model captures the carbon cycling through vegetation and soil, resulting in a net terrestrial carbon sink of 2.2 Pg C year−1. In the ocean, the large-scale distribution of hydrodynamical and biogeochemical tracers agrees with a modern climatology from the World Ocean Atlas. The combination of biological and physical processes induces a net CO2 uptake of 1.7 Pg C year−1 that falls within the range of recent estimates. Our analysis shows that the atmospheric climate of CNRM-ESM1 compares well with that of CNRM-CM5. Biases in precipitation and shortwave radiation over the tropics generate errors in gross primary productivity and ecosystem respiration. Compared to CNRM-CM5, the revised ocean–sea ice coupling has modified the sea-ice cover and ocean ventilation, unrealistically strengthening the flow of North Atlantic deep water (26.1 ± 2 Sv). It results in an accumulation of anthropogenic carbon in the deep ocean.
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Kamworapan, Suchada, and Chinnawat Surussavadee. "Evaluation of CMIP5 Global Climate Models for Simulating Climatological Temperature and Precipitation for Southeast Asia." Advances in Meteorology 2019 (September 25, 2019): 1–18. http://dx.doi.org/10.1155/2019/1067365.
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This study evaluates the performances of all forty different global climate models (GCMs) that participate in the Coupled Model Intercomparison Project Phase 5 (CMIP5) for simulating climatological temperature and precipitation for Southeast Asia. Historical simulations of climatological temperature and precipitation of the 40 GCMs for the 40-year period of 1960–1999 for both land and sea and those for the century of 1901–1999 for land are evaluated using observation and reanalysis datasets. Nineteen different performance metrics are employed. The results show that the performances of different GCMs vary greatly. CNRM-CM5-2 performs best among the 40 GCMs, where its total error is 3.25 times less than that of GCM performing worst. The performance of CNRM-CM5-2 is compared with those of the ensemble average of all 40 GCMs (40-GCM-Ensemble) and the ensemble average of the 6 best GCMs (6-GCM-Ensemble) for four categories, i.e., temperature only, precipitation only, land only, and sea only. While 40-GCM-Ensemble performs best for temperature, 6-GCM-Ensemble performs best for precipitation. 6-GCM-Ensemble performs best for temperature and precipitation simulations over sea, whereas CNRM-CM5-2 performs best over land. Overall results show that 6-GCM-Ensemble performs best and is followed by CNRM-CM5-2 and 40-GCM-Ensemble, respectively. The total errors of 6-GCM-Ensemble, CNRM-CM5-2, and 40-GCM-Ensemble are 11.84, 13.69, and 14.09, respectively. 6-GCM-Ensemble and CNRM-CM5-2 agree well with observations and can provide useful climate simulations for Southeast Asia. This suggests the use of 6-GCM-Ensemble and CNRM-CM5-2 for climate studies and projections for Southeast Asia.
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Camilleri, Michael, Gururaj J. Kolar, Maria I. Vazquez-Roque, Paula Carlson, Duane D. Burton, and Alan R. Zinsmeister. "Cannabinoid receptor 1 gene and irritable bowel syndrome: phenotype and quantitative traits." American Journal of Physiology-Gastrointestinal and Liver Physiology 304, no. 5 (March 1, 2013): G553—G560. http://dx.doi.org/10.1152/ajpgi.00376.2012.
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Genetic variations in metabolism of endocannabinoids and in CNR1 (gene for cannabinoid 1 receptor) are associated with symptom phenotype, colonic transit, and left colon motility in irritable bowel syndrome (IBS). Our aim was to evaluate associations between two variations in CNR1 genotype (rs806378 and [AAT]n triplets) with symptom phenotype, small bowel and colonic transit, and rectal sensations in 455 patients with IBS and 228 healthy controls. Small bowel and colonic transit were measured by scintigraphy, rectal sensation by isobaric distensions. Associations with genotype were assessed by χ2 test (symptom phenotype) and ANCOVA (quantitative traits) based on a dominant genetic model. Significant association of CNR1 rs806378 (but not CNR1 [AAT]n) genotype and symptom phenotype was observed (χ2 P = 0.028). There was significant association of CNR1 rs806378 ( P = 0.014; CC vs. CT/TT) with colonic transit in IBS-diarrhea (IBS-D) group; the TT group had the fastest colonic transit at 24 and 48 h. There was significant overall association of CNR1 rs806378 with sensation rating of gas ( P = 0.025), but not pain; the strongest associations for gas ratings were in IBS-D ( P = 0.002) and IBS-alternating ( P = 0.025) subgroups. For CNR1 (AAT)n, gene-by-phenotype interactions were observed for colonic transit at 24 ( P = 0.06) and 48 h ( P = 0.002) and gas ( P = 0.046, highest for IBS-D, P = 0.034), but not pain sensation; the strongest association with transit was in controls, not in IBS. These data support the hypothesis that cannabinoid receptors may play a role in control of colonic transit and sensation in humans and deserve further study as potential mediators or therapeutic targets in lower functional gastrointestinal disorders.
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Gallhofer, Sonja. "Going beyond western dualism: towards corporate nature responsibility reporting." Accounting, Auditing & Accountability Journal 31, no. 8 (October 15, 2018): 2110–34. http://dx.doi.org/10.1108/aaaj-12-2015-2358.
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Purpose The purpose of this paper is to outline an ecofeminist lens for the analysis of accounting, which is applied to: first, the critique of corporate social responsibility reporting (CSRR); second, the elaboration of elements of a framework for a new accounting – corporate nature responsibility reporting (CNRR) – as a response to the critique of CSRR; and, third, the consideration of elements of an enabling and emancipatory praxis in the context of CNRR, including a sketch of a research agenda. Design/methodology/approach The paper presents a critical application of aspects of the ecofeminist critique of Western dualism and its emphasis on wholeness, interconnectedness and relatedness, including its particular delineation of nature, to the critique and design of accounting. Findings Insights from the application of an ecofeminist lens to the critique of CSRR raise questions about the suitability of the western notion of corporate social responsibility (CSR) and its associated accounting currently in use. In order to go beyond critique, the paper introduces the notions of corporate nature responsibility (CNR) and CNRR and offers an outline of key elements of CNRR and an emancipatory praxis in the context of CNRR, including a sketch of a research agenda. The author’s elaborations suggest that in order to overcome the limitations of CSR and CSRR, a corporation ought to be concerned about its broader and holistic CNR. And, it should provide a CNR report, as part of a holistic CNRR concerned with the performance of the company in the context of CNR. Social implications Through creating new visibilities, CNRR has the potential to enhance the well-being of people and nature more generally. Originality/value Ecofeminism’s critique of western dichotomous thinking has been given little consideration in prior studies of accounting. The paper thus draws attention to the relevance of an ecofeminist theoretical lens for the critique and design of accounting by focussing on CSRR. The paper introduces the concepts of CNR and CNRR to address the limitations of CSRR as currently practiced.
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Ikoma, Naruhiko, Jeannelyn Estrella, Mariela A. Blum Murphy, Hsiang-Chun Chen, Xuemei Wang, Keith F. Fournier, Paul F. Mansfield, Jaffer A. Ajani, and Brian D. Badgwell. "Lymph node metastasis in gastric cancer: Location of positive station to predict survival after preoperative therapy." Journal of Clinical Oncology 35, no. 4_suppl (February 1, 2017): 166. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.166.
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166 Background: We sought to determine the association between the identification of positive lymph nodes on D2 lymph node dissection (LND) with stage and outcomes, in the era of preoperative treatment for gastric cancer. Methods: We reviewed data from a prospectively maintained database of gastric cancer patients who underwent resection of gastric or gastroesophageal cancer at our institution from 2005-2016. Central lymph nodes (CnLN) were defined as common hepatic, celiac, and proximal splenic artery lymph nodes (stations #8, 9, and 11p). Risk factors for CnLN metastases, and overall survival (OS) were examined. Results: We identified 356 patients, median age was 64 years (IQR 54-71) and 59% were male. Preoperative therapy was given in 66% of patients. D2 LND was performed in 80% of patients, and the median number of LN examined was 25 (IQR 18-34). Most patients (N = 244, 68%) had separately-examined CnLN in pathology and the median number of examined LNs was higher in this group (27 vs 19; p < 0.001). The CnLN positivity rate was 9.1% (22/244; #8: 4.8%, #9: 6.1%, and #11p: 4.8%), which was higher in advanced pT stage patients (pT0 - 3%, pT1 - 0%, pT2 - 6%, pT3 - 18%, pT4 - 13%; p = 0.001). If we assume that D2 LND was not performed on these patients, a total of 7 (3%, 7/244) patients would have had pN stage down-migration (6 with N1 to N0, 1 with N2 to N1). Of the 22 CnLN-positive patients, 10 (45%) had pN1, 2 (9%) had pN2, and 10 (45%) had pN3 stages. On multivariate analysis, EUS N stage (positive) was associated with positive CnLNs (OR 2.86 [95%CI 1.08-7.58]). Among 342 patients who had R0 resection, the median follow-up was 3.6 years, and the median OS was 11.6 years. Among patients who received preoperative therapy, pT3/4 stage (HR 2.44 [1.27-4.69]; p = 0.01) and positive CnLN (HR 5.44 [2.36-12.52]; p < 0.001) were negatively associated with OS by multivariate analysis. Conclusions: CnLN metastases are uncommon in gastric cancer, and are associated with an adverse impact on OS. However, long-term survival is still possible in patients with positive CnLN whom underwent a D2 lymph node dissection. Larger multi-institutional studies are needed to determine if CnLN positivity requires a separate staging category.