bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery and Characterization of CD12681, a Potent RORγ Inverse Agonist, Preclinical Candidate for the Topical Treatment of Psoriasis
Authors: Ouvry Gilles , Atrux‐Tallau Nicolas , Bihl Franck , Bondu Aline , Bouix‐Peter Claire , Carlavan Isabelle , Christin Olivier , Cuadrado Marie‐Josée , Defoin‐Platel Claire , Deret Sophie , Duvert Denis , Feret Christophe , Forissier Mathieu , Fournier Jean‐François , Froude David , Hacini‐Rachinel Fériel , Harris Craig Steven , Hervouet Catherine , Huguet Hélène , Lafitte Guillaume , Luzy Anne‐Pascale , Musicki Branislav , Orfila Danielle , Ozello Benjamin , Pascau Coralie , Pascau Jonathan , Parnet Véronique , Peluchon Guillaume , Pierre Romain , Piwnica David , Raffin Catherine , Rossio Patricia , Spiesse Delphine , Taquet Nathalie , Thoreau Etienne , Vatinel Rodolphe , Vial Emmanuel , Hennequin Laurent François 
Published: January 2018

AbstractWith possible implications in multiple autoimmune diseases, the retinoic acid receptor‐related orphan receptor RORγ has become a sought‐after target in the pharmaceutical industry. Herein are described the efforts to identify a potent RORγ inverse agonist compatible with topical application for the treatment of skin diseases. These efforts culminated in the discovery of N‐(2,4‐dimethylphenyl)‐N‐isobutyl‐2‐oxo‐1‐[(tetrahydro‐2H‐pyran‐4‐yl)methyl]‐2,3‐dihydro‐1H‐benzo[d]imidazole‐5‐sulfonamide (CD12681), a potent inverse agonist with in vivo activity in an IL‐23‐induced mouse skin inflammation model.
Brain‐Cortex Microglia‐Derived Exosomes: Nanoparticles for Glioma Therapy
Authors: Murgoci Adriana‐Natalia , Cizkova Dasa , Majerova Petra , Petrovova Eva , Medvecky Lubomir , Fournier Isabelle , Salzet Michel 
Published: January 2018

AbstractThe function and integrity of the nervous system require interactive exchanges among neurons and glial cells. Exosomes and other extracellular vesicles (EVs) are emerging as a key mediator of intercellular communication, capable of transferring nucleic acids, proteins and lipids influencing numerous functional and pathological aspects of both donor and recipient cells. The immune response mediated by microglia‐derived exosomes is most prominently involved in the spread of neuroinflammation, neurodegenerative disorders, and brain cancer. Therefore, in the present study we describe a reproducible and highly efficient method for yielding purified primary microglia cells, followed by exosome isolation and their characterization. An in vitro biological assay demonstrates that microglia‐derived exosomes tested on a 3D spheroid glioma culture were able to inhibit tumor invasion in time course. These results evidence that brain microglia‐derived exosomes could be used as nanotherapeutic agents against glioma cells.
Sum rate–based relay selection strategy in FSO systems
Authors: Puri Parul , Garg Parul 
Published: January 2018

SummaryWe present a relay selection strategy for bidirectional free‐space optical (FSO) communication systems. A parallel relayed FSO network consisting of multiple decode‐and‐forward protocol based two‐way relays (TWRs) is considered. Using the proposed relay selection strategy, one TWR is selected to establish an FSO communication link between two non‐line‐of‐sight FSO transceivers. As the two‐way communication process is characterized by achievable sum rate of the system, the relay selection strategy is designed such that the achievable sum rate is maximum. Considering a Gamma‐Gamma distributed optical channel with path loss and pointing errors, we present a mathematical framework for the proposed relay selection strategy.
Flood effects on soil thermal regimes in contrasting cold‐desert river floodplains (Yampa and Green rivers, Colorado)
Authors: Andersen Douglas C. 
Published: January 2018

AbstractHeat transfer theory suggests that floodplain soils in dryland riverine ecosystems can be cooled by hyporheic flows generated during spring floods. I compared soil temperature cycles and associated hydrologic factors on a free‐flowing river to those on a river where flows and surface water temperatures are now regulated. Spring surface water temperatures were comparable on the 2 rivers, as was apparent diffusivity of the soil under mature Populus fremontii in a year when severe drought produced similar soil moisture regimes. Over 9 years of monitoring, mean annual maximum soil temperature was higher on the regulated river than on the free‐flowing river (10 cm depth: 33 vs. 23 °C; 40 cm depth: 30 vs. 20°C, respectively), and sinusoidal models of the annual temperature cycle at each depth indicated higher means and greater amplitudes on the regulated river. The annual maximum soil temperature was inversely related to peak flood discharge on the free‐flowing river but not on the regulated river. Temporal shifts in the lag between diel cycles at 40 and 10 cm depths—an index of soil thermal diffusivity—suggested that the capillary fringe is strongly involved in heat exchange. An increase in the lag during some water table declines suggested that shallow soils may undergo flood‐induced evaporative cooling. Hyporheic recharge can be an ecologically important determinant of growing‐season soil temperatures at plant rooting depth in dryland river floodplains. Reductions in spring flood magnitude due to river regulation, water abstraction, or climate change can increase these temperatures and thereby alter ecosystem structure and functioning.
A web‐based mental health promotion intervention for pharmacy staff to reduce stigmatising and discriminating attitudes
Authors: Wheeler Amanda J. , Mey Amary , Fowler Jane L. , Mihala Gabor , Kelly Fiona 
Published: January 2018

AbstractIssue addressedStigma and discrimination can have a significant impact on successful mental health recovery. This research evaluated the effectiveness of a web‐based mental health promotion intervention on stigma and discrimination in community pharmacies via assessment of staff attitudes, confidence and skills.MethodsGuided by the intervention mapping framework, we used experiential learning techniques, including pre‐recorded consumer/carer narratives, role‐plays and panel discussions accessed by participants in an innovative, flexible, web‐based, program of modules. A quasi‐experimental pre‐post design was used to evaluate the intervention effectiveness. Participants completed pre‐ (T1) and post‐intervention (T2) questionnaires that contained both validated measures and questions developed or adapted specifically for this evaluation.Results566 pharmacy staff (357 pharmacists, 209 support staff) completed the intervention between September 2012 and May 2013; pharmacists completed eight online modules (4‐hours total), support staff completed four (2‐hours total). After participating, staff attitudes about mental health had changed in a positive direction; their confidence and skills when working with consumers and their carers had increased overall, although support staff remained less confident than pharmacists.ConclusionThese results suggest that the involvement of consumers and carers in the intervention development and delivery was integral to reducing pharmacy staff stigma and enhancing confidence and communication skills.
Impact of HIV/aids epidemic on human capital development in West Africa
Authors: Dauda Rasaki Stephen 
Published: January 2018

SummaryWest Africa occupies the third position with respect to the burden of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) globally, after Southern and East Africa. About 5 million adults and children are infected with the disease in the subregion, while HIV prevalence in the general population hovers around 2% and 5%. This paper attempts to investigate the impact of HIV/AIDS epidemic on human capital development in 11 West African countries over the period 1990 to 2011. The study used a dynamic panel data modeling approach, using first difference, difference generalized methods of moment, and system generalized methods of moment estimating techniques. Four measures of HIV/AIDS and 2 human capital measures were used in the study. The findings revealed that HIV/AIDS pandemic had negative and significant impact on human capital in West Africa. However, the statistical significance was more pronounced on life expectancy (a measure of human capital), while the negative impact on school enrolment (another human capital measure) was not significant. It is therefore recommended that the spread of HIV/AIDS disease in West Africa should be effectively controlled, while the number of infected persons undergoing antiretroviral therapy in the subregion should be increased to a near 100% coverage.
Modelling surface‐water depression storage in a Prairie Pothole Region
Authors: Hay Lauren , Norton Parker , Viger Roland , Markstrom Steven , Steven Regan R. , Vanderhoof Melanie 
Published: January 2018

AbstractIn this study, the Precipitation‐Runoff Modelling System (PRMS) was used to simulate changes in surface‐water depression storage in the 1,126‐km2 Upper Pipestem Creek basin located within the Prairie Pothole Region of North Dakota, USA. The Prairie Pothole Region is characterized by millions of small water bodies (or surface‐water depressions) that provide numerous ecosystem services and are considered an important contribution to the hydrologic cycle. The Upper Pipestem PRMS model was extracted from the U.S. Geological Survey's (USGS) National Hydrologic Model (NHM), developed to support consistent hydrologic modelling across the conterminous United States. The Geospatial Fabric database, created for the USGS NHM, contains hydrologic model parameter values derived from datasets that characterize the physical features of the entire conterminous United States for 109,951 hydrologic response units. Each hydrologic response unit in the Geospatial Fabric was parameterized using aggregated surface‐water depression area derived from the National Hydrography Dataset Plus, an integrated suite of application‐ready geospatial datasets. This paper presents a calibration strategy for the Upper Pipestem PRMS model that uses normalized lake elevation measurements to calibrate the parameters influencing simulated fractional surface‐water depression storage. Results indicate that inclusion of measurements that give an indication of the change in surface‐water depression storage in the calibration procedure resulted in accurate changes in surface‐water depression storage in the water balance. Regionalized parameterization of the USGS NHM will require a proxy for change in surface‐storage to accurately parameterize surface‐water depression storage within the USGS NHM.
The determination of the carbonic anhydrases activators in vitro effect of mixed donor crown ethers
Authors: Akkemik Ebru , Cicek Baki , Camadan Yasemin , Calisir Umit , Onbasioglu Zekai 
Published: January 2018

AbstractCarbonic anhydrases (CAs) play an important function in various physiological and pathological processes. Therefore, many researchers work in this field in order to design and synthesize new drugs. Both inhibitors and activators of CAs, which are associated with the diagnosis and treatment of many diseases, are very important. The emergence of the use of CA activators in the treatment of Alzheimer has led many scholars to work on this issue. In this study, CA activators and inhibitors are determined. The crown ethers compounds (1, 2, 3, 6, 7, 8, and 9) were found to cause activation on enzyme activities of hCA I and II. The AC50 values on hCA I and II of the compounds are in the range of 4.6565–374.979 μM. The 4 (IC50; 1.301 and 3.215 μM for hCA I and II) and 5 (IC50; 73.96 and 378.5 μM for hCA I and II) compounds were found to cause inhibition on enzyme activities of hCA I and II.
Enhanced Lysis of [125l]5-lodo-2′- Deoxyuridine-Labeled Target Cells in the Presence of Normal Macrophages: Possible Mechanisms of Action
Authors: Evans Robert , Eidlen Denise M 
Published: January 2018

Abstract
The potential mechanisms involved during the faster release of [125l]-iodo-2′- deoxyuridine (125ldUrd)-labeled target sarcoma cells in the presence of normal C57BL/6J peritoneal macrophages were investigated. Maximum (= 90%) “spontaneous” release of 125l from target cells cultured alone occurred over a period of about 10 days. However, after about 3 days, confluent sheets of target cells developed. In the presence of normal macrophages, 90% of the 125l was released between 3 and 7 days, again with the formation of confluent sheets of target cells. This enhanced 125I release was not influenced by increasing the relative concentration of IdUrd using the nonradioactive isotope 127ldUrd. Established mechanisms of target cell destruction were investigated but no evidence was found for the involvement of superoxide anion, hydrogen peroxide, or regulation by prostaglandin synthesis. The macrophage-mediated effect was abrogated by incorporating hydrocortisone-acetate (10−7 to 10−4M) into the culture medium but this did not affect target cell proliferation. The use of serum-free culture medium suggested that macrophages secreted a soluble mediator that was not derived from or dependent on the presence of fetal bovine serum. In addition, macrophage-conditioned medium was able to induce the faster 125l release. The failure to precipitate with 20% trichloroacetic acid the 125l released from target cells cultured in the presence of macrophages indicated that the radioactive component had been separated from the precipitable DNA. The data are discussed in light of two possible hypotheses: that macrophages recognized subtle changes in IdUrd-labeled cells and exacerbate radiotoxicity, and that the faster release reflected proliferative death caused by stimulated growth.
Effects of Essential Fatty Acid Deficiency and Indomethacin on Histologic, Ultrastructural, and Phagocytic Responses of Hepatic Macrophages to Glucan
Authors: Way C F , Dougherty W J , Cook J A 
Published: January 2018

Abstract
Glucan administration in the rat induces a hyperplasia and hypertrophy of the reticuloendothelial system (RES) and a concomitant leukocytosis. Increased phagocytic function and lysozymal immunoreactivity of macrophages are also characteristic of the glucan effect. The potential role of archidonic acid metabolites in mediating this hepatic inflammatory response induced by the RES stimulant glucan was assessed in the present study by two experimental approaches. In one study, rats were depleted of archidonic acid by rendering them deficient in essential fatty acids (EFA). In another study, rats were pre- treated with the fatty acid cyclooxygenase inhibitor indomethacin. Both treatment interventions markedly attenuated the hepatic Kupffer cell proliferative and granulomatous response to glucan and the associated leukocytosis. Ly- sozyme immunoreactivity of the Kupffer cells and rates of colloidal carbon clearance (T/2), however, were enhanced by the above treatments. Supplementation of EFA-deficient rats with ethyl arachidonate restored their glucan response to an extent that was not significantly different from nondeficient rats. Marked hepatic proliferative responses were apparent only in those treatment groups characterized by leukocytosis, which suggests that extrahepatic recruitment is an important component of the glucan response in normal, nutritionally adequate rats. Collectively these data suggest that arachidonic acid metabolites may play a role in modulating this extrahepatic recruitment and the associated cellular proliferative and granulomatous responses following glucan administration of the rat.
Regulation of Macrophage Lysosomal Secretion by Adenosine, Adenosine Phosphate Esters, and Related Structural Analogues of Adenosine
Authors: Riches David W H , Watkins Jane L , Henson Peter M , Stanworth Denis R 
Published: January 2018

Abstract
Zymosan particle-stimulated β -galactosidase secretion by mouse peritoneal macrophages was found to be inhibited by micromolar concentrations of adenosine, AMP, ADP, and ATP. Inhibition by all four agents was increased to approximately 80% by adding erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA; 10 μM) an adenosine deaminase inhibitor, to the incubation medium. The inhibition of lysosomal enzyme secretion by ATP, ADP, and AMP was reversed by adding α,β -methylene ADP (100 μM), a 5′-nucleotidase inhibitor, to the incubation medium. Inhibition by adenosine, however, was unaffected byα,β -methylene ADP indicating that the inhibition by AMP, ADP, and ATP only occurred after they had been converted to adenosine by cell surface phosphohydrolases, including 5′-nucleotidase. Theophylline, a competitive antagonist of the binding of adenosine to plasma membrane adenosine receptors, failed to reverse the inhibitory effect of adenosine indicating the probable site of adenosine action to be intracellular. Other purine nucleosides, e.g., guanosine, and several purine and ribose- modified structural analogues of adenosine also inhibited zymosan-stimulated β -galactosidase secretion, while xanthosine and certain pyrimidine nucleosides, e.g., thymidine, were inactive in this respect.
Secretion of Colony-Stimulating Factors by Human Monocytes and Bone Marrow Cells After In Vitro Treatment With Biological Response Modifiers
Authors: Schlick E , Hartung K , Stevenson H C , Chirigos M A 
Published: January 2018

Abstract
The results of this study indicate that human interferons (hlFNs) may have bimodal effects in vitro on human myelopoiesis. Low concentrations of hlFNα (1–10 U/ml), hlFNβ (1–100 U/ml), and hlFNℽ (1 U/ml) stimulated in vitro increased secretion of colony-stimulating factors (CSF) by human blood monocytes, which induced growth and differentiation of granulocyte-macrophage progenitor cells. High concentrations of hlFNsα,β,ℽ (&gt; 100 U/ml), however, had direct antiproliferative effects on granulocyte-macrophage progenitors. Both effects could be blocked by monoclonal antibodies against hlFNa and hlFNℽ, as well as by heteroantiserum against hlFNβ. Human IFNs did not appear to be involved in mediating the response to the chemically defined biological response modifiers (BRMs) poly ICLC (polyriboinosinic-polycytidylic acid poly-L-lysine) and BM 41.332 (2-cyano-1-[(2-methoxy-6-methyl-pyridin-3yl)- methyl]-aziridine), since neutralizing antibodies against the human IFNs (anti- IFNα,β,ℽ) did not block the poly ICLC and BM 41.332-induced secretion of CSF by human blood monocytes. In contrast to hlFNs, poly ICLC and BM 41.332 also stimulated adherent human mononuclear bone marrow cells to secrete CSF, which induced growth and differentiation of nonadherent granulocyte- macrophage progenitors. The studies presented here thus support the concept that selected BRMs might be useful to stimulate in vivo secretion of myelo-poietic growth factors and thereby promote granulocyte and monocyte/macrophage functions.
Dorsal Lateral Plate Mesoderm Influences Proliferation and Differentiation of Hemopoietic Stem Cells Derived From Ventral Lateral Plate Mesoderm During Early Development of Xenopus laevis Embryos
Authors: Turpen James B , Smith Paula B 
Published: January 2018

Abstract
The developmental pattern of dorsal and ventral lateral plate mesoderm was examined by explanting these regions and culturing them in serum-free conditions for 10 days. Under these circumstances, ventral lateral plate mesoderm gave rise to hemopoietic cells, and dorsal lateral plate mesoderm gave rise to stromal cells. Comparison of the differentiation pattern observed when dorsal and ventral mesoderm were cultured separately versus the pattern observed when dorsal and ventral mesoderm were cultured together revealed that dorsal mesoderm influenced the differentiation of ventral-derived hemopoietic cells. Ventral mesoderm cultured alone gave rise to erythrocytes and granulocytes. However, in the presence of dorsal mesoderm, ventral mesoderm gave rise to erythrocytes, monocytes, and granuloyctes. Moreover, dorsal mesoderm functioned to maintain the proliferation and differentiation potential of progenitor cells as determined using a colony-forming cell assay (CFU-c).
KI-M2R, a New Specific Monoclonal Antibody, Discriminates Tissue Macrophages From Reticulum Cells and Monocytes In Vivo and In Vitro
Authors: Wacker Hans-Heinrich , Radzun Heinz Joachim , Parwaresch Mohammad Reza 
Published: January 2018

Abstract
Utilizing rat peritoneal macrophages as the immunogen, a new monoclonal antibody enabling differential monitoring of the mononuclear phagocyte system (MPS) by immunohistochemistry has been raised. Designated Ki-M2R, this antigen could be detected with the immune alkaline phosphatase reaction on all macrophages including those of bone marrow, lymphatic sinuses, lymphoid follicles, splenic red pulp, and von Kupffer cells of the liver, as well as on macrophages of connective tissue, renal interstitial tissue, serous cavities, and gastrointestinal tract. Langerhans cells—the MPS-derived reticulum cells of the epidermis—interdigitating reticulum cells, and dendritic reticulum cells of lymphoid follicles were invariably negative. Blood monocytes were rendered positive only after evolving into macrophages upon appropriate stimulation. Thus, Ki-M2R selectively labels monocytes after transformation into macrophages.
Effect of Maturation and Age on Lymphocyte Proliferation Induced by A23187 Through an Interleukin-Independent Pathway
Authors: Wu Wutong , Pahlavani Mohammad , Richardson Arlan , Cheung H Tak 
Published: January 2018

Abstract
Lymphocyte proliferation induced by lectins declines drastically with age. It has been suggested that the reduction of interleukin production by lymphocytes from old individuals is responsible for the decline in proliferation. In this study, lymphocyte proliferation was stimulated by the calcium ionophore, A23187. A23187 induced the proliferation of spleen lymphocytes from rats through an interleukin-independent pathway; depletion of spleen lymphocytes of macrophages, addition of exogenous interleukin 2 (IL 2), and addition of anti-IL 2 monoclonal antibodies had no effect on the proliferation stimulated by A23187. Spleen lymphocytes from male Fischer F344 male rats of 5, 13, 22, and 30 months of age were stimulated with either concanavalin A (Con A) or A23187. A 50% decrease in Con A- and A23187-induced proliferation was observed between 5 months and 13 months of age. A23187-induced proliferation decreased only slightly between 13 months and 30 months of age (14%), while Con A-induced proliferation decreased by 34%. This is the first report to show that the induction of lymphocyte proliferation through an interleukin-independent pathway decreases with increasing age. In addition, these results suggest that a decrease in the responsiveness of cells to calcium ions might be an important factor in the age-related decline in lymphocyte proliferation.
Phagocytosis of Unopsonized Zymosan by Human Monocyte-Derived Macrophages: Maturation and Inhibition by Mannan
Authors: Speert David P , Silverstein Samuel C 
Published: January 2018

Abstract
Human monocyte-derived macrophages phagocytosed zymosan in the absence of serum opsonins. The capacity to ingest zymosan developed after the cells were cultured in vitro for 3 days and was inhibited completely by mannan. We conclude that human monocyte-derived macrophages phagocytose unopsonized zymosan predominantly via mannose receptors.