bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astroglial major histocompatibility complex class I following immune activation leads to behavioral and neuropathological changes
Authors: Sobue Akira , Ito Norimichi , Nagai Taku , Shan Wei , Hada Kazuhiro , Nakajima Akira , Murakami Yuki , Mouri Akihiro , Yamamoto Yasuko , Nabeshima Toshitaka , Saito Kuniaki , Yamada Kiyofumi 
Published: January 2018

AbstractIn the central nervous system, major histocompatibility complex class I (MHCI) molecules are mainly expressed in neurons, and neuronal MHCI have roles in synapse elimination and plasticity. However, the pathophysiological significance of astroglial MHCI remains unclear. We herein demonstrate that MHCI expression is up‐regulated in astrocytes in the medial prefrontal cortex (mPFC) following systemic immune activation by an intraperitoneal injection of polyinosinic‐polycytidylic acid (polyI:C) or hydrodynamic interferon (IFN)‐γ gene delivery in male C57/BL6J mice. In cultured astrocytes, MHCI/H‐2D largely co‐localized with exosomes. To investigate the role of astroglial MHCI, H‐2D, or sH‐2D was expressed in the mPFC of male C57/BL6J mice using an adeno‐associated virus vector under the control of a glial fibrillary acidic protein promoter. The expression of astroglial MHCI in the mPFC impaired sociability and recognition memory in mice. Regarding neuropathological changes, MHCI expression in astrocytes significantly activated microglial cells, decreased parvalbumin‐positive cell numbers, and reduced dendritic spine density in the mPFC. A treatment with GW4869 that impairs exosome synthesis ameliorated these behavioral and neuropathological changes. These results suggest that the overexpression of MHCI in astrocytes affects microglial proliferation as well as neuronal numbers and spine densities, thereby leading to social and cognitive deficits in mice, possibly via exosomes created by astrocytes.
Sphingosine‐1‐Phosphate Modulates the Effect of Estrogen in Human Osteoblasts
Authors: Tantikanlayaporn Duangrat , Tourkova Irina L , Larrouture Quitterie , Luo Jianhua , Piyachaturawat Pawinee , Witt Michelle R , Blair Harry C , Robinson Lisa J 
Published: January 2018

ABSTRACTProduction of sphingosine‐1‐phosphate (S1P) is linked to 17β‐estradiol (E2) activity in many estrogen‐responsive cells; in bone development, the role of S1P is unclear. We studied effects of S1P on proliferation and differentiation of human osteoblasts (hOB). Ten nM E2, 1 μM S1P, or 1 μM of the S1P receptor 1 (S1PR1) agonist SEW2871 increased hOB proliferation at 24 hours. S1PR 1, 2, and 3 mRNAs are expressed by hOB but not S1PR4 or S1PR5. Expression of S1PR2 was increased at 7 and 14 days of differentiation, in correspondence with osteoblast‐related mRNAs. Expression of S1PR1 was increased by E2 or S1P in proliferating hOB, whereas S1PR2 mRNA was unaffected in proliferating cells; S1PR3 was not affected by E2 or S1P. Inhibiting sphingosine kinase (SPHK) activity with sphingosine kinase inhibitor (Ski) greatly reduced the E2 proliferative effect. Both E2 and S1P increased SPHK mRNA at 24 hours in hOB. S1P promoted osteoblast proliferation via activating MAP kinase activity. Either E2 or S1P increased S1P synthesis in a fluorescent S1P assay. Interaction of E2 and S1P signaling was indicated by upregulation of E2 receptor mRNA after S1P treatment. E2 and S1P also promoted alkaline phosphatase expression. During osteoblast differentiation, S1P increased bone‐specific mRNAs, similarly to the effects of E2. However, E2 and S1P showed differences in the activation of some osteoblast pathways. Pathway analysis by gene expression arrays was consistent with regulation of pathways of osteoblast differentiation; collagen and cell adhesion proteins centered on Rho/Rac small GTPase signaling and Map kinase or signal transducer and activator of transcription (Stat) intermediates. Transcriptional activation also included significant increases in superoxide dismutase 1 and 2 transcription by either S1P or E2. We demonstrate that the SPHK system is a co‐mediator for osteoblast proliferation and differentiation, which is mainly, but not entirely, complementary to E2, whose effects are mediated by S1PR1 and S1PR2. © 2018 The Authors JBMR Plus is published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
The long non‐coding RNA H19 rs217727 polymorphism is associated with PE susceptibility
Authors: Harati‐Sadegh Mahdiyeh , Kohan Leila , Teimoori Batool , Salimi Saeedeh 
Published: January 2018

AbstractH19 is an imprinted gene transcribing a long noncoding RNA which was previously reported to be involved in some diseases. However, the association between the H19 polymorphisms and Pre‐eclampsia (PE) susceptibility has remained elusive. This study aimed to evaluate the association between three H19 haplotype SNPs (rs3741219, rs217727, and rs2107425) and the risk of PE. The present case control study consisted of 193 PE women and 201 controls. The H19 rs3741219 and rs217727 polymorphisms were genotyped with PCR‐RFLP (Polymerase chain reaction‐restriction fragment length polymorphism) and the H19 rs2107425 polymorphism with ARMS‐PCR (Amplification refractory mutation system) methods. The frequency of alleles and genotypes of H19 rs3741219 and rs2107425 polymorphisms did not differ between PE women and controls. The frequency of the H19 rs217727T allele was significantly higher in PE women (P < 0.0001). The H19 rs217727 polymorphism was associated with higher PE susceptibility in the Co‐dominant (OR = 12.1, 95% CI = 5.7‐24.5, P < 0.0001 for CT genotype and OR = 29.7, 95% CI = 12.9‐68.1, P < 0.0001 for TT genotype), Dominant (OR = 15.1, 95% CI = 7.5‐30.3, P = P < 0.0001), Recessive (OR = 4.5, 95% CI = 2.6‐7.9, P = < 0.0001), and Over‐dominant (OR = 2.1, 95% CI = 1.4‐3.1, P = 0.0006) models. Furthermore, the CCC, TCT, TCC, and CCT haplotypes of H19 rs3741219, rs217727, rs2107425 were associated with lower risk of PE; however, the CTC, TTC, and TTT haplotypes were associated with higher risk of PE. In conclusion, the present study found the relationship between H19 rs217727 but not rs3741219 and rs2107425 polymorphisms and PE susceptibility. In addition, the CTC, TTC, and TTT haplotypes were associated with the higher risk of PE.
Integrin alpha V beta 3 targeted dendrimer‐rapamycin conjugate reduces fibroblast‐mediated prostate tumor progression and metastasis
Authors: Hill Elliott E. , Kim Jin Koo , Jung Younghun , Neeley Chris K. , Pienta Kenneth J. , Taichman Russell S. , Nor Jacques E. , Baker James R. , Krebsbach Paul H. 
Published: January 2018

AbstractTherapeutic strategies targeting both cancer cells and associated cells in the tumor microenvironment offer significant promise in cancer therapy. We previously reported that generation 5 (G5) dendrimers conjugated with cyclic‐RGD peptides target cells expressing integrin alpha V beta 3. In this study, we report a novel dendrimer conjugate modified to deliver the mammalian target of rapamycin (mTOR) inhibitor, rapamycin. In vitro analyses demonstrated that this drug conjugate, G5‐FI‐RGD‐rapamycin, binds to prostate cancer (PCa) cells and fibroblasts to inhibit mTOR signaling and VEGF expression. In addition, G5‐FI‐RGD‐rapamycin inhibits mTOR signaling in cancer cells more efficiently under proinflammatory conditions compared to free rapamycin. In vivo studies established that G5‐FI‐RGD‐rapamycin significantly inhibits fibroblast‐mediated PCa progression and metastasis. Thus, our results suggest the potential of new rapamycin‐conjugated multifunctional nanoparticles for PCa therapy.
Retracted: Upregulation of Klotho potentially inhibits pulmonary vascular remodeling by blocking the activation of the Wnt signaling pathway in rats with PM2.5‐induced pulmonary arterial hypertension
Authors: Cong Lu‐Hong , Du Shi‐Yu , Wu Yi‐Na , Liu Ying , Li Tao , Wang Hui , Li Gang , Duan Jun 
Published: January 2018

AbstractWe evaluated the effects of Klotho on pulmonary vascular remodeling and cell proliferation and apoptosis in rat models with PM2.5‐induced pulmonary arterial hypertension (PAH) via the Wnt signaling pathway. After establishing rat models of PM2.5‐induced PAH, these Sprague‐Dawley male rats were randomized into control and model groups. Cells extracted from the model rats were sub‐categorized into different groups. Activation of Wnt/β‐catenin signaling transcription factor was detected by a TOPFlash/FOPFlash assay. A serial of experiment was conducted to identify the mechanism of Klotho on PHA via the Wnt signaling pathway. VEGF levels and PaCO2 content were higher in the model group, while PaO2, NO2−/NO3− content and Klotho level was lower compared to the control group. In comparison to the control group, the model group had decreased Klotho and Bax levels, and elevated Wnt‐1, β‐catenin, bcl‐2, survivin, and PCNA expression, VEGF, IL‐6, TNF‐α, TNF‐β1, and bFGF levels, as well as the percentage of pulmonary artery ring contraction. The Klotho vector, DKK‐1 and DKK‐1 + Klotho vector groups exhibited reduced cell proliferation, luciferase activity, and the expression of Wnt‐1, β‐catenin, bcl‐2, survivin, and PCNA, as well as shortened S phase compared with the blank and NC groups. Compared with the Klotho vector and DKK‐1 groups, the DKK‐1 + Klotho vector groups had reduced cell proliferation, luciferase activity, and the expression of Wnt‐1, β‐catenin, bcl‐2, survivin, and PCNA, as well as a shortened S phase. Conclusively, Klotho inhibits pulmonary vascular remodeling by inactivation of Wnt signaling pathway.
hmSOD1 gene mutation‐induced disturbance in iron metabolism is mediated by impairment of Akt signalling pathway
Authors: Halon‐Golabek Malgorzata , Borkowska Andzelika , Kaczor Jan J. , Ziolkowski Wieslaw , Flis Damian J. , Knap Narcyz , Kasperuk Kajetan , Antosiewicz Jedrzej 
Published: January 2018

AbstractBackgroundRecently, skeletal muscle atrophy, impairment of iron metabolism, and insulin signalling have been reported in rats suffering from amyotrophic lateral sclerosis (ALS). However, the interrelationship between these changes has not been studied. We hypothesize that an impaired Akt–FOXO3a signalling pathway triggers changes in the iron metabolism in the muscles of transgenic animals.MethodsIn the present study, we used transgenic rats bearing the G93A hmSOD1 gene and their non‐transgenic littermates. The study was performed on the muscles taken from animals at three different stages of the disease: asymptomatic (ALS I), the onset of the disease (ALS II), and the terminal stage of the disease (ALS III). In order to study the molecular mechanism of changes in iron metabolism, we used SH‐SY5Y and C2C12 cell lines stably transfected with pcDNA3.1, SOD1 WT and SOD1 G93A, or FOXO3a TM‐ER.ResultsA significant decrease in P‐Akt level and changes in iron metabolism were observed even in the group of ALS I animals. This was accompanied by an increase in the active form of FOXO3a, up‐regulation of atrogin‐1, and catalase. However, significant muscle atrophy was observed in ALS II animals. An increase in ferritin L and H was accompanied by a rise in PCBP1 and APP protein levels. In SH‐SY5Y cells stably expressing SOD1 or SOD1 G93A, we observed elevated levels of ferritin L and H and non‐haem iron. Interestingly, insulin treatment significantly down‐regulated ferritin L and H proteins in the cell. Conversely, cells transfected with small interfering RNA against Akt 1, 2, 3, respectively, showed a significant increase in the ferritin and FOXO3a levels. In order to assess the role of FOXO3a in the ferritin expression, we constructed a line of SH‐SY5Y cells that expressed a fusion protein made of FOXO3a fused at the C‐terminus with the ligand‐binding domain of the oestrogen receptor (TM‐ER) being activated by 4‐hydroxytamoxifen. Treatment of the cells with 4‐hydroxytamoxifen significantly up‐regulated ferritin L and H proteins level.ConclusionsOur data suggest that impairment of insulin signalling and iron metabolism in the skeletal muscle precedes muscle atrophy and is mediated by changes in Akt/FOXO3a signalling pathways.
Ra‐224 labeling of calcium carbonate microparticles for internal α‐therapy: Preparation, stability, and biodistribution in mice
Authors: Westrøm Sara , Malenge Marion , Jorstad Ida Sofie , Napoli Elisa , Bruland Øyvind S. , Bønsdorff Tina B. , Larsen Roy H. 
Published: January 2018

Internal therapy with α‐emitters should be well suited for micrometastatic disease. Radium‐224 emits multiple α‐particles through its decay and has a convenient 3.6 days of half‐life. Despite its attractive properties, the use of 224Ra has been limited to bone‐seeking applications because it cannot be stably bound to a targeting molecule. Alternative delivery systems for 224Ra are therefore of considerable interest. In this study, calcium carbonate microparticles are proposed as carriers for 224Ra, designed for local therapy of disseminated cancers in cavitary regions, such as peritoneal carcinomatosis. Calcium carbonate microparticles were radiolabeled by precipitation of 224Ra on the particle surface, resulting in high labeling efficiencies for both 224Ra and daughter 212Pb and retention of more than 95% of these nuclides for up to 1 week in vitro. The biodistribution after intraperitoneal administration of the 224Ra‐labeled CaCO3 microparticles in immunodeficient mice revealed that the radioactivity mainly remained in the peritoneal cavity. In addition, the systemic distribution of 224Ra was found to be strongly dependent on the amount of administered microparticles, with a reduced skeletal uptake of 224Ra with increasing dose. The results altogether suggest that the 224Ra‐labeled CaCO3 microparticles have promising properties for use as a localized internal α‐therapy of cavitary cancers.
Quantitative susceptibility mapping (QSM) as a means to monitor cerebral hematoma treatment
Authors: Zhang Yuyao , Wei Hongjiang , Sun Yawen , Cronin Matthew J. , He Naying , Xu Jianrong , Zhou Yan , Liu Chunlei 
Published: January 2018

BackgroundQuantitative susceptibility mapping (QSM) offers a consistent hemorrhage volume measurement independent of imaging parameters.PurposeTo investigate the magnetic susceptibility of intracerebral hemorrhage (ICH) as a quantitative measurement for monitoring treatment in hematoma patients.Study TypeProspective.PopulationTwenty‐six patients with acute ICH were recruited and enrolled in treatment including surgery or medication (mannitol) for 1 week.Field Strength/SequenceA 3D gradient echo sequence at 3.0T.AssessmentThe hematoma volumes on computed tomography (CT) and QSM were calculated and used for correlation analysis. Magnetic susceptibility changes from pre‐ to posttreatment were calculated and compared to the National Institutes of Health stroke scale (NIHSS) measure of neurological deficit for each patient.Statistical TestsMean susceptibility values were calculated over each region of interest (ROI). A one‐sample t‐test was used to assess the changes of total volumes and mean magnetic susceptibility of ICH identified between pre‐ and posttreatment images (P < 0.05 was considered significant) and the Bland–Altman analysis with 95% limits of agreement (average difference, ±1.96 SD of the difference). Regression of volume measurements on QSM vs. CT and fitted linear regression of mean susceptibility vs. CT signal intensity for hematoma regions were conducted in all patients.ResultsGood correlation was found between hemorrhage volumes calculated from CT and QSM (CT volume = 0.94*QSM volume, r = 0.98). Comparison of QSM pre‐ and posttreatment showed that the mean ICH volume was reduced by a statistically insignificant amount from 5.74 cm3 to 5.45 cm3 (P = 0.21), while mean magnetic susceptibility was reduced significantly from 0.48 ppm to 0.38 ppm (P = 0.004). A significant positive association was found between changes in magnetic susceptibility values and NIHSS following hematoma treatment (P < 0.01).Data ConclusionsQSM in hematoma assessment, as compared with CT, offers a comparably accurate volume measurement; however, susceptibility measurements may enable improved monitoring of ICH treatment compared to volume measurements alone.Level of Evidence: 2Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2018;48:907–915.
Evaluation of regional very heavy precipitation events during the summer season using NARCCAP contemporary simulations
Authors: Kawazoe Sho , Gutowski William J. 
Published: January 2018

ABSTRACTRegional climate models (RCMs) from the North American Regional Climate Change Assessment Program (NARCCAP) are compared with the two gridded precipitation data sets [Climate Prediction Center (CPC) and the University of Washington (UW)] and the North American regional reanalysis (NARR) to examine if RCMs are able to reproduce very heavy precipitation under similar physical conditions seen in observations. The analysis focuses on contemporary climate (1982–1999) in an upper Mississippi region during the summer (June–July–August) months and utilizes output from NARCCAP RCMs forced with a reanalysis and atmosphere–ocean global climate models (AOGCMs).The NARCCAP models generally reproduce the precipitation frequency versus intensity spectrum seen in observations up to around 25 mm day−1, before producing overly strong precipitation at high intensities. CRCM simulations produce lower precipitation amounts than the rest of the models and observations past the 25 mm day−1 threshold. Further analysis focuses on precipitation events exceeding the 99.5th percentile that occur simultaneously at several points in the region, yielding ‘widespread events’. Apart from the CRCM and EPC2 simulations, models and observations produce peaks in widespread events during 0300–0900 UTC, although the models typically produce slightly weaker intensities compared to observations. Widespread precipitation falls too frequently throughout the day, especially between 1500 and 2100 UTC, compared to observations. Composite precipitation shows inter‐model differences in magnitude and location of widespread events. Examination of additional fields shows that NARCCAP models produce credible representations of very heavy precipitation and their supporting environments when compared to the NARR.
Forecasting seasonal rainfall characteristics and onset months over South Africa
Authors: Phakula Steven , Landman Willem A. , Beraki Asmerom F. 
Published: January 2018

ABSTRACTAspects of forecast skill in predicting seasonal characteristics using global climate models (GCMs) are assessed over South Africa. The GCMs output is configured to predict number of rainfall days at South African Weather Service stations exceeding pre‐defined threshold values for the austral summer seasons and to predict the rainfall totals of the onset months of the rainy seasons for eight homogeneous rainfall regions of South Africa. Using canonical correlation analysis (CCA) as statistical downscaling technique through model output statistics, the forecast skill levels of coupled ocean–atmosphere and uncoupled atmospheric models are determined through retro‐actively generated hindcasts. Both downscaled models have skill in predicting low and high number of rainfall days exceeding pre‐defined thresholds for the austral summer seasons as well as rainfall totals of onset months. In addition to the forecast verification results, CCA pattern is performed to determine the dominating atmospheric circulation systems predicted to be controlling rainfall variations for the seasons and months of interest. CCA patterns for both the GCMs indicate that usually when there are anomalously negative (positive) predicted 850 hPa geopotential heights over South Africa, there are anomalously wet (dry) conditions over most parts of South Africa. The work has paved the way for the operational production of seasonal rainfall characteristics over South Africa in real time.
Superensemble seasonal forecasting of soil moisture by NMME
Authors: Yao Mengna , Yuan Xing 
Published: January 2018

ABSTRACTSoil moisture affects hydro‐climate processes by altering water and energy exchanges between land surface and atmosphere. Understanding of the predictability of soil moisture is not only important for a skillful forecasting of seasonal hydro‐climate, but also for agricultural drought early warning. This paper assesses seasonal forecast skill and potential predictability of soil moisture directly produced by climate models, and investigates an optimal combination of different models over China. A set of 29‐year hindcasts for soil moisture from six North American Multi‐model Ensemble (NMME) models are verified against ERA Interim reanalysis. Results show that soil moisture predictability, which is defined by anomaly correlation under a perfect model assumption, is higher than forecast skill in all models, suggesting that soil moisture prediction may have a room for improvement. Except the CESM model, NMME climate forecast models with higher predictability also have higher forecast skill, where predictability is positively correlated with forecast skill with p < 0.01 across different lead times. Soil moisture forecast skill from NMME simple arithmetic mean is higher than any individual models, and the skill is further improved through an optimization of model weights with a cross validation procedure. As compared with simple ensemble mean, the optimized superensemble mean reduces root mean squared error by 19 and 7% for seasonal mean soil moisture forecast during winter and summer seasons, respectively, and increases correlation by about 10%. This study suggests that soil moisture forecasts directly produced by climate models, when combined appropriately, can provide useful information for climate service.
Sequentially shifted excitation: A tool for suppression of laser‐induced fluorescence in mineralogical applications using portable Raman spectrometers
Authors: Culka Adam , Jehlička Jan 
Published: January 2018

AbstractLaser‐induced fluorescence is a phenomenon that can be encountered in the Raman spectra of minerals, and it complicates the acquisition of high quality Raman spectra when using portable instruments. A novel portable Raman spectrometer utilizing sequentially shifted excitation was used for analyses of the minerals anhydrite, apatite, and zircon that frequently exhibit laser‐induced fluorescence, especially when 785 nm excitation is used. Fluorescence centers, responsible for the laser‐induced fluorescence in these minerals, are generated primarily by the presence of rare earth elements. The narrow and intense fluorescence bands that arise can be confused with or mask the Raman bands of the minerals when analyzing with the conventional 785 nm excitation. It has been found that the fluorescence is completely removed in those spectral regions containing no Raman bands of the minerals. In the areas of those Raman spectra of minerals where the fluorescence and Raman bands coincide, the sequentially shifted excitation was able to suppress effectively the fluorescence. In some cases, the fluorescence removal process in the final spectra of the most fluorescence samples introduced new instrumental artifact bands. Nevertheless, the sequentially shifted excitation was able to suppress this specific laser‐induced fluorescence quite effectively; and Raman features became well pronounced, especially for the zircon specimens. This novel approach of obtaining high quality Raman spectra of minerals containing trace amounts of fluorescence‐inducing components (such as rare earth elements) with portable instrumentation opens up new possibilities for in situ spectroscopic analyses in the fields of mineralogy and geology.