bluuebunny/crossref_metadata_2025_split huggingface dataset:
Left and right ventricular function by echocardiography, tissue Doppler imaging, carotid intima-media thickness, and asymmetric dimethyl arginine levels in obese adolescents with metabolic syndrome
Authors: Aslan Eyup , Sert Ahmet , Buyukinan Muammer , Pirgon Mustafa Ozgur , Kurku Huseyin , Yilmaz Hakan , Odabas Dursun 
Published: January 2019

AbstractPurposeThe aim of our study was to assess left ventricle and right ventricle systolic and diastolic functions in obese adolescents with metabolic syndrome using conventional echocardiography and pulsed-wave tissue Doppler imaging and to investigate carotis intima-media thickness, and asymmetric dimethyl arginine levels.MethodsA total of 198 obese adolescents were enrolled in the study. The obese patients were divided into metabolic syndrome group and non-metabolic syndrome group. All subjects underwent laboratory blood tests, including asymmetric dimethyl arginine, complete two-dimensional, pulsed, and tissue Doppler echocardiography, and measurement of the carotid intima-media thickness.ResultsObese adolescents were characterised by enlarged left end-diastolic, end-systolic and left atrial diameters, thicker left and right ventricular walls compared with non-obese adolescents. The metabolic syndrome group had normal left ventricle systolic function, impaired diastolic function, and altered global systolic and diastolic myocardial performance. In the metabolic syndrome obese group patients, left ventricle mass was found positively correlated with body mass index, waist and hip circumferences, diastolic blood pressure, age, and waist-to-hip circumference ratio. The carotid intima-media thickness was found positively correlated with waist and hip circumferences and total cholesterol levels. Asymmetric dimethyl arginine levels were found positively correlated with systolic blood pressure, waist-to-hip circumference ratio, and diastolic blood pressure.ConclusionsThe results of this study demonstrate that metabolic syndrome in adolescence is associated with significant changes in myocardial geometry and function. In addition, it has been associated with a high level of asymmetric dimethyl arginine concentration and thicker carotid intima-media thickness reflecting endothelial dysfunction.
Determinants of second pillar pension reforms: economic crisis and globalization
Authors: Fong Joelle H. , Leibrecht Markus 
Published: January 2019

AbstractIn this paper, we examine reforms characterized by the establishment of mandatory funded privately-managed schemes in the social security framework. We construct a new dataset to analyze the determinants of pension reforms over 1980–2012 in about 100 medium and large economies around the world. Our results highlight the fundamental importance of economic forces in explaining the speed of reforms after adjusting for the confounding effects of demographic and geopolitical factors. Countries with greater globalization growth and a history of economic crisis experienced a shorter time until reform. These findings are robust to variations in empirical methodology.
Meteorological Scale Correlation Relationship of the Ionospheric Longitudinal Structure Wavenumber 4 and Upper Atmospheric Daily DE3 Tide
Authors: Li Xing , Wan Weixing , Cao Jinbin , Ren Zhipeng 
Published: January 2019

AbstractIn order to analyze the relationship between atmospheric tides and the ionospheric day‐to‐day variations, this paper mainly presents the meteorological scale (period is shorter than 60 days) correlation relationship between the daily longitudinal structure wavenumber 4 (WN4) in the ionosphere and the daily diurnal eastward propagating with zonal wavenumber 3 (DE3) tide in the upper atmosphere. We deduce the latitudinal integration of total electron content from the global ionospheric maps in the middle‐ to low‐latitude ionosphere and the upper atmospheric temperature from Thermosphere‐Ionosphere‐Mesosphere Energetics and Dynamics\Sounding of the Atmosphere using Broadband Emission Radiometry observations in the MLT region. Applying new techniques proposed by Li et al. (2015, https://doi.org/10.1002/2015JA021577), we extract the daily WN4 structure and daily DE3 tide, respectively. We found that (1) the meteorological scale cross‐correlation coefficients are symmetric about the equator and dominate at the low latitudes; (2) there is a remarkable valley value around sunrise: the amplitudes in day time are a little larger than those at night; the phases in day time are stable and change slowly at night and dramatically before dawn; (3) they vary gradually with altitudes, and the vertical propagating wavelength is about 35‐km altitude; (4) they present an obvious annual variation that the amplitudes are larger from June solstice to early north autumn, and the phases are stable in these months; and (5) they display an obvious quasi‐biennial oscillation phenomenon, and in June to August of 2008–2009 the amplitudes almost disappear before dawn.
Are drivers of root-associated fungal community structure context specific?
Authors: Alzarhani A Khuzaim , Clark Dave R , Underwood Graham J C , Ford Hilary , Cotton T E Anne , Dumbrell Alex J 
Published: January 2019

Abstract
The composition and structure of plant-root-associated fungal communities are determined by local abiotic and biotic conditions. However, the relative influence and identity of relationships to abiotic and biotic factors may differ across environmental and ecological contexts, and fungal functional groups. Thus, understanding which aspects of root-associated fungal community ecology generalise across contexts is the first step towards a more predictive framework. We investigated how the relative importance of biotic and abiotic factors scale across environmental and ecological contexts using high-throughput sequencing (ca. 55 M Illumina metabarcoding sequences) of &gt;260 plant-root-associated fungal communities from six UK salt marshes across two geographic regions (South-East and North-West England) in winter and summer. Levels of root-associated fungal diversity were comparable with forests and temperate grasslands, quadrupling previous estimates of salt-marsh fungal diversity. Whilst abiotic variables were generally most important, a range of site- and spatial scale-specific abiotic and biotic drivers of diversity and community composition were observed. Consequently, predictive models of diversity trained on one site, extrapolated poorly to others. Fungal taxa from the same functional groups responded similarly to the specific drivers of diversity and composition. Thus site, spatial scale and functional group are key factors that, if accounted for, may lead to a more predictive understanding of fungal community ecology.
Bacterial and protozoan dynamics upon thawing and freezing of an active layer permafrost soil
Authors: Schostag Morten , Priemé Anders , Jacquiod Samuel , Russel Jakob , Ekelund Flemming , Jacobsen Carsten Suhr 
Published: January 2019

Abstract
The active layer of soil overlaying permafrost in the Arctic is subjected to annual changes in temperature and soil chemistry, which we hypothesize to affect the overall soil microbial community. We investigated changes in soil microorganisms at different temperatures during warming and freezing of the active layer soil from Svalbard, Norway. Soil community data were obtained by direct shotgun sequencing of total extracted RNA. No changes in soil microbial communities were detected when warming from −10 to −2 °C or when freezing from −2 to −10 °C. In contrast, within a few days we observed changes when warming from −2 to +2 °C with a decrease in fungal rRNA and an increase in several OTUs belonging to Gemmatimonadetes, Bacteroidetes and Betaproteobacteria. Even more substantial changes occurred when incubating at 2 °C for 16 days, with declines in total fungal potential activity and decreases in oligotrophic members from Actinobacteria and Acidobacteria. Additionally, we detected an increase in transcriptome sequences of bacterial phyla Bacteriodetes, Firmicutes, Betaproteobacteria and Gammaproteobacteria—collectively presumed to be copiotrophic. Furthermore, we detected an increase in putative bacterivorous heterotrophic flagellates, likely due to predation upon the bacterial community via grazing. Although this grazing activity may explain relatively large changes in the bacterial community composition, no changes in total 16S rRNA gene copy number were observed and the total RNA level remained stable during the incubation. Together, these results are showing the first comprehensive ecological evaluation across prokaryotic and eukaryotic microbial communities on thawing and freezing of soil by application of the TotalRNA technique.
High cholesterol triggers white matter alterations and cognitive deficits in a mouse model of cerebrovascular disease: benefits of simvastatin
Authors: Tong Xin-Kang , Trigiani Lianne J. , Hamel Edith 
Published: January 2019

AbstractTransgenic mice overexpressing transforming growth factor-β1 (TGF mice) display impaired cerebrovascular reactivity, cerebral hypoperfusion and neurovascular uncoupling, but no overt cognitive deficits until old age. Cardiovascular diseases are a major risk factor for vascular cognitive impairment and dementia (VCID). We investigated the impact of a high cholesterol diet (HCD) on cerebrovascular and cognitive function in adult (6 months) and aged (12 months) TGF mice, together with the potential benefit of simvastatin (SV), an anti-cholesterol drug with pleiotropic effects, in adult mice. HCD increased blood, but not brain, cholesterol levels in treated mice, which SV did not reduce. In WT mice, HCD induced small, albeit significant, impairment in endothelium-dependent dilatory function. In TGF mice, HCD worsened the established brain vessel dilatory dysfunction in an age-dependent manner and increased the number of string vessels in the white matter (WM), alterations respectively normalized and significantly countered by SV. HCD triggered cognitive decline only in TGF mice at both ages, a deficit prevented by SV. Concurrently, HCD upregulated galectin−3 immunoreactivity in WM microglial cells, a response significantly reduced in SV-treated TGF mice. Grey matter astrogliosis and microgliosis were not affected by HCD or SV. In the subventricular zone of adult HCD-treated TGF mice, SV promoted oligogenesis and migration of oligodendrocyte progenitor cells. The results demonstrate that an underlying cerebrovascular pathology increases vulnerability to cognitive failure when combined to another risk factor for dementia, and that WM alterations are associated with this loss of function. The results further indicate that myelin repair mechanisms, as triggered by SV, may bear promise in preventing or delaying cognitive decline related to VCID.
ASF1a inhibition induces p53-dependent growth arrest and senescence of cancer cells
Authors: Wu Yujiao , Li Xidan , Yu Jingya , Björkholm Magnus , Xu Dawei 
Published: January 2019

AbstractAnti-silencing function 1a (ASF1a) is a histone H3–H4 chaperone isoform involved in chromatin assembling and transcription regulation. Recently, ASF1a has been shown to be up-regulated in certain human malignancies and required for the expression of telomerase reverse transcriptase (TERT), a factor essential for the immortal phenotype of cancer cells; however, its role in oncogenesis remains poorly defined. In the present study, we determine whether ASF1a is required for the unlimited proliferation of cancer cells, a key cancer hallmark. Elevated ASF1a mRNA expression was observed in hepatocellular carcinoma (HCC) tumors. The overexpression of ASF1a was similarly found in 20 cancer types contained in TCGA and GTEx datasets. ASF1a knockdown led to growth arrest and senescence of wild-type (wt) p53-carrying HCC and prostate cancer cells. Cellular senescence mediated by ASF1a inhibition resulted from the robust up-regulation of p53 and p21cip1 expression, but without detectable changes in TERT expression. p53 inhibition attenuated p21cip1 induction caused by ASF1a depletion. Mechanistically, ASF1a-knocked down cells displayed widespread DNA damage. The TCGA dataset analysis revealed a negative correlation between ASF1a and p21cip1 expression in multiple types of primary tumors, including HCC, prostate, gastric, and breast cancer. Higher ASF1a and lower p21cip1 expression predicted a poor outcome in patients with HCC. Our results reveal that ASF1a overexpression is widespread in human malignancies and is required for the infinite proliferation of cancer cells, whereas its inhibition induces DNA damage and subsequent up-regulation of p53-p21cip1 expression, thereby triggering cellular senescence. Thus, ASF1a may serve as a potential target in cancer therapy.
Hypoxia-induced 26S proteasome dysfunction increases immunogenicity of mesenchymal stem cells
Authors: Abu-El-Rub Ejlal , Sequiera Glen Lester , Sareen Niketa , Yan Weiang , Moudgil Meenal , Sabbir Mohammad Golam , Dhingra Sanjiv 
Published: January 2019

AbstractBone marrow-derived allogeneic (donor derived) mesenchymal stem cells (MSCs) are immunoprivileged and are considered to be prominent candidates for regenerative therapy for numerous degenerative diseases. Even though the outcome of initial allogeneic MSCs based clinical trials was encouraging, the overall enthusiasm, of late, has dimmed down. This is due to failure of long-term survival of transplanted cells in the recipient. In fact, recent analyses of allogeneic MSC-based studies demonstrated that cells after transplantation turned immunogenic and were subsequently rejected by host immune system. The current study reveals a novel mechanism of immune switch in MSCs. We demonstrate that hypoxia, a common denominator of ischemic tissues, induces an immune shift in MSCs from immunoprivileged to immunogenic state. The immunoprivilege of MSCs is preserved by downregulation or the absence of major histocompatibility complex class II (MHC-II) molecules. We found that 26S proteasome-mediated intracellular degradation of MHC-II helps maintain the absence of MHC-II expression on cell surface in normoxic MSCs and preserves their immunoprivilege. The exposure to hypoxia leads to dissociation of 19S and 20S subunits, and inactivation of 26S proteasome. This prevented the degradation of MHC-II and, as a result, the MSCs became immunogenic. Furthermore, we found that hypoxia-induced decrease in the levels of a chaperon protein HSP90α is responsible for inactivation of 26S proteasome. Maintaining HSP90α levels in hypoxic MSCs preserved the immunoprivilege of MSCs. Therefore, hypoxia-induced inactivation of 26S proteasome assembly instigates loss of immunoprivilege of allogeneic mesenchymal stem cells. Maintaining 26S proteasome activity in mesenchymal stem cells preserves their immunoprivilege.
Differential effects of N-acetylcysteine on retinal degeneration in two mouse models of normal tension glaucoma
Authors: Sano Hiroki , Namekata Kazuhiko , Kimura Atsuko , Shitara Hiroshi , Guo Xiaoli , Harada Chikako , Mitamura Yoshinori , Harada Takayuki 
Published: January 2019

AbstractN-acetylcysteine (NAC) is widely used as a mucolytic agent and as an antidote to paracetamol overdose. NAC serves as a precursor of cysteine and stimulates the synthesis of glutathione in neural cells. Suppressing oxidative stress in the retina may be an effective therapeutic strategy for glaucoma, a chronic neurodegenerative disease of the retinal ganglion cells (RGCs) and optic nerves. Here we examined the therapeutic potential of NAC in two mouse models of normal tension glaucoma, in which excitatory amino-acid carrier 1 (EAAC1) or glutamate/aspartate transporter (GLAST) gene was deleted. EAAC1 is expressed in retinal neurons including RGCs, whereas GLAST is mainly expressed in Müller glial cells. Intraperitoneal administration of NAC prevented RGC degeneration and visual impairment in EAAC1-deficient (knockout; KO) mice, but not in GLAST KO mice. In EAAC1 KO mice, oxidative stress and autophagy were suppressed with increased glutathione levels by NAC treatment. Our findings suggest a possibility that systemic administration of NAC may be available for some types of glaucoma patients.
Cancer cell-derived immunoglobulin G activates platelets by binding to platelet FcγRIIa
Authors: Miao Shuo , Shu Dan , Zhu Ying , Lu Meng , Zhang Qingsong , Pei Youliang , He Ao-Di , Ma Rong , Zhang Bixiang , Ming Zhang-Yin 
Published: January 2019

AbstractTumor-associated thrombosis is the second leading risk factor for cancer patient death, and platelets activity is abnormal in cancer patients. Discovering the mechanism of platelet activation and providing effective targets for therapy are urgently needed. Cancer cell- derived IgG has been reported to regulate development of tumors. However, studies on the functions of cancer cell-derived IgG are quite limited. Here we investigated the potential role of cancer cell-derived IgG in platelet activation. We detected the expression of CD62P on platelets by flow cytometry and analyzed platelet function by platelets aggregation and ATP release. The content of IgG in cancer cell supernatants was detected by enzyme-linked immune sorbent assay. The distribution of cancer-derived IgG in cancer cells was analyzed by immunofluorescence assay. Western blot was performed to quantify the relative expression of FcγRIIa, syk, PLCγ2. The interaction between cancer cell-derived IgG and platelet FcγRIIa was analyzed by co-immunoprecipitation. The results showed that higher levels of CD62P were observed in cancer patients’ platelets compared with that of healthy volunteers. Cancer cell culture supernatants increased platelet CD62P and PAC-1 expression, sensitive platelet aggregation and ATP release in response to agonists, while blocking FcγRIIa or knocking down IgG reduced the activation of platelets. Coimmunoprecipitation results showed that cancer cell-derived IgG interacted directly with platelet FcγRIIa. In addition, platelet FcγRIIa was highly expressed in liver cancer patients. In summary, cancer cell-derived IgG interacted directly with FcγRIIa and activated platelets; targeting this interaction may be an approach to prevent and treat tumor-associated thrombosis.
TMEM97 and PGRMC1 do not mediate sigma-2 ligand-induced cell death
Authors: Zeng Chenbo , Weng Chi-Chang , Schneider Mark E. , Puentes Laura , Riad Aladdin , Xu Kuiying , Makvandi Mehran , Jin Linda , Hawkins William G. , Mach Robert H. 
Published: January 2019

AbstractSigma-2 receptors have been implicated in both tumor proliferation and neurodegenerative diseases. Recently the sigma-2 receptor was identified as transmembrane protein 97 (TMEM97). Progesterone receptor membrane component 1 (PGRMC1) was also recently reported to form a complex with TMEM97 and the low density lipoprotein (LDL) receptor, and this trimeric complex is responsible for the rapid internalization of LDL. Sigma-2 receptor ligands with various structures have been shown to induce cell death in cancer cells. In the current study, we examined the role of TMEM97 and PGRMC1 in mediating sigma-2 ligand-induced cell death. Cell viability and caspase-3 assays were performed in control, TMEM97 knockout (KO), PGRMC1 KO, and TMEM97/PGRMC1 double KO cell lines treated with several sigma-2 ligands. The data showed that knockout of TMEM97, PGRMC1, or both did not affect the concentrations of sigma-2 ligands that induced 50% of cell death (EC50), suggesting that cytotoxic effects of these compounds are not mediated by TMEM97 or PGRMC1. Sigma-1 receptor ligands, (+)-pentazocine and NE-100, did not block sigma-2 ligand cytotoxicity, suggesting that sigma-1 receptor was not responsible for sigma-2 ligand cytotoxicity. We also examined whether the alternative, residual binding site (RBS) of 1,3-Di-o-tolylguanidine (DTG) could be responsible for sigma-2 ligand cytotoxicity. Our data showed that the binding affinities (Ki) of sigma-2 ligands on the DTG RBS did not correlate with the cytotoxicity potency (EC50) of these ligands, suggesting that the DTG RBS was not fully responsible for sigma-2 ligand cytotoxicity. In addition, we showed that knocking out TMEM97, PGRMC1, or both reduced the initial internalization rate of a sigma-2 fluorescent ligand, SW120. However, concentrations of internalized SW120 became identical later in the control and knockout cells. These data suggest that the initial internalization process of sigma-2 ligands does not appear to mediate the cell-killing effect of sigma-2 ligands. In summary, we have provided evidence that sigma-2 receptor/TMEM97 and PGRMC1 do not mediate sigma-2 ligand cytotoxicity. Our work will facilitate elucidating mechanisms of sigma-2 ligand cytotoxicity.
The prodomain of caspase-3 regulates its own removal and caspase activation
Authors: Ponder Katelyn G. , Boise Lawrence H. 
Published: January 2019

AbstractCaspase-3 is a cysteine–aspartic acid protease that cleaves cellular targets and executes cell death. Our current understanding is caspase-3 is activated by the cleavage of the interdomain linker and then subsequent cleavage of the N-terminal prodomain. However, previous reports have suggested that removal of the prodomain can result in the constitutive activation of caspase-3, although other studies have not observed this. To address this question in a more physiological setting, we developed an inducible doxycycline system to express a mutant form of caspase-3 that lacks the prodomain (∆28). We found that the removal of the prodomain renders the cells more susceptible to death signals, but the caspase is not constitutively active. To elucidate the regions of the prodomain that regulate activity, we created deletion constructs that remove 10 and 19 N-terminal amino acids. Surprisingly, removal of the first 10 amino acids renders caspase-3 inactive. Following serum withdrawal, the interdomain linker is cleaved, however, the remaining prodomain is not removed. Therefore, there is a specific amino acid or stretch of amino acids within the first 10 that are important for prodomain removal and caspase-3 function. We created different point mutations within the prodomain and found amino acid D9 is vital for caspase-3 function. We hypothesize that an initial cleavage event at D9 is required to allow cleavage at D28 that causes the complete removal of the prodomain allowing for full caspase activation. Together these findings demonstrate a previously unknown role of the prodomain in caspase activation.