bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dust Transport to the Taylor Glacier, Antarctica, During the Last Interglacial
Authors: Aarons S. M. , Aciego S. M. , McConnell J. R. , Delmonte B. , Baccolo G. 
Published: February 2019

AbstractChanges in the composition of dust trapped in ice provide evidence of past atmospheric circulation and earth surface conditions. Investigations of dust provenance in Antarctic ice during glacial and interglacial periods indicate that South America is the primary dust source during both climate regimes. Here, we present results from a new ice core dust archive extracted from the Taylor Glacier in coastal East Antarctica during the deglacial transition from Marine Isotope Stage 6 to 5e. Radiogenic strontium and neodymium isotopes indicate that last interglacial dust is young and volcanic, in contrast to the observed preindustrial and Holocene (Marine Isotope Stage 1) dust composition. The dust composition differences from the last interglacial and current interglacial period at the site require a profound difference in atmospheric transport and environmental conditions. We consider several potential causes for enhanced transport of volcanic material to the site, including increased availability of volcanic material and large‐scale atmospheric circulation changes.
Climatic Factors and Their Availability in Estimating Long‐Term Variations of Fine Particle Distributions Over East China
Authors: Wang Yanyu , Duan Junyan , Xie Xin , He Qianshan , Cheng Tiantao , Mu Haizhen , Gao Wei , Li Xiang 
Published: February 2019

AbstractConcerns about air pollutions in China have made fine particulate matter (PM2.5) estimation a hot research topic in recent years. Using satellite‐based PM2.5 data obtained over East China in 2000–2015, climatic factors affecting the PM2.5 variability were revealed in different seasons. Relevant climatic factors were used to estimate seasonal PM2.5 distributions by combining empirical orthogonal function with stepwise regression. The assessment results indicate a greater impact by climatic factors on PM2.5 variability in western East China than over coastal areas, and more significant influence by climatic factors on PM2.5 variability also occurs in summer and autumn than spring and winter. Our favorable results for PM2.5 estimation in 2016 further validate the capability of the estimation method for PM2.5 distributions based on climatic factors. Individual contributions of dominant climatic factors to PM2.5 variability over East China during the past 16 years range from 5% to 30%. In conclusion, climatic factors play nonnegligible roles in modulating PM2.5 concentrations, and they can feasibly be considered as predictors in the estimation of PM2.5 concentrations in East China. Our work underscores the importance of climate change impacts on air pollutions and improves air quality forecasts over East China.
Spectral Analysis of the September 2017 Solar Energetic Particle Events
Authors: Bruno A. , Christian E. R. , de Nolfo G. A. , Richardson I. G. , Ryan J. M. 
Published: February 2019

AbstractAn interval of exceptional solar activity was registered in early September 2017, late in the decay phase of solar cycle 24, involving the complex Active Region 12673 as it rotated across the western hemisphere with respect to Earth. A large number of eruptions occurred between 4 and 10 September, including four associated with X‐class flares. The X9.3 flare on 6 September and the X8.2 flare on 10 September are currently the two largest during cycle 24. Both were accompanied by fast coronal mass ejections and gave rise to solar energetic particle (SEP) events measured by near‐Earth spacecraft. In particular, the partially occulted solar event on 10 September triggered a ground‐level enhancement (GLE), the second GLE of cycle 24. A further, much less energetic SEP event was recorded on 4 September. In this work we analyze observations by the Advanced Composition Explorer (ACE) and the Geostationary Operational Environmental Satellites (GOES), estimating the SEP event‐integrated spectra above 300 keV and carrying out a detailed study of the spectral shape temporal evolution. Derived spectra are characterized by a low‐energy break at few/tens of MeV; the 10 September event spectrum, extending up to ∼1 GeV, exhibits an additional rollover at several hundred MeV. We discuss the spectral interpretation in the scenario of shock acceleration and in terms of other important external influences related to interplanetary transport and magnetic connectivity, taking advantage of multipoint observations from the Solar Terrestrial Relations Observatory. Spectral results are also compared with those obtained for the 17 May 2012 GLE event.
Warming Alters Hydrologic Heterogeneity: Simulated Climate Sensitivity of Hydrology‐Based Microrefugia in the Snow‐to‐Rain Transition Zone
Authors: Marshall A. M. , Link T. E. , Abatzoglou J. T. , Flerchinger G. N. , Marks D. G. , Tedrow L. 
Published: February 2019

AbstractIn complex terrain, drifting snow contributes to ecohydrologic landscape heterogeneity and ecological refugia. In this study, we assessed the climate sensitivity of hydrological dynamics in a semiarid mountainous catchment in the snow‐to‐rain transition zone. This catchment includes a distinct snow drift‐subsidized refugium that comprises a small portion (14.5%) of the watershed but accounts for a disproportionate amount (modeled average 56%) of hydrological flux generation. We conducted climate sensitivity experiments using a physically based hydrologic model to assess responses of a suite of hydrologic metrics across the watershed. Experiments with an imposed 3.5 °C warming showed reductions in average maximum snow water equivalent of 58–68% and deep percolation by 72%. While relative decreases were similar across the watershed, much greater absolute decreases in snowpack occurred in the drift‐subsidized site than the surrounding landscape. In drift‐subsidized locations, warming caused a shift from a regime that included both energy‐ and water‐limited evapotranspiration conditions to exclusively water‐limited conditions. Warming also resulted in altered interannual variability of hydrologic metrics. The drift‐subsidized unit was more sensitive to warming than the surrounding landscape, with reduced potential for the effects of warming to be offset by increased precipitation. Despite spatially homogeneous changes in climate, the effects of climate change on the hydrological dynamics were spatially heterogeneous in this watershed due to the presence of lateral water transport in the form of drifting snow. These findings suggest an increase in hydrologic homogeneity across the landscape and relatively large changes in snow drift‐subsidized refugia.
Mechanism of the natural product moracin-O derived MO-460 and its targeting protein hnRNPA2B1 on HIF-1α inhibition
Authors: Soung Nak-Kyun , Kim Hye-Min , Asami Yukihiro , Kim Dong Hyun , Cho Yangrae , Naik Ravi , Jang Yerin , Jang Kusic , Han Ho Jin , Ganipisetti Srinivas Rao , Cha-Molstad Hyunjoo , Hwang Joonsung , Lee Kyung Ho , Ko Sung-Kyun , Jang Jae-Hyuk , Ryoo In-Ja , Kwon Yong Tae , Lee Kyung Sang , Osada Hiroyuki , Lee Kyeong , Kim Bo Yeon , Ahn Jong Seog 
Published: February 2019

AbstractHypoxia-inducible factor-1α (HIF-1α) mediates tumor cell adaptation to hypoxic conditions and is a potentially important anticancer therapeutic target. We previously developed a method for synthesizing a benzofuran-based natural product, (R)-(-)-moracin-O, and obtained a novel potent analog, MO-460 that suppresses the accumulation of HIF-1α in Hep3B cells. However, the molecular target and underlying mechanism of action of MO-460 remained unclear. In the current study, we identified heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) as a molecular target of MO-460. MO-460 inhibits the initiation of HIF-1α translation by binding to the C-terminal glycine-rich domain of hnRNPA2B1 and inhibiting its subsequent binding to the 3’-untranslated region of HIF-1α mRNA. Moreover, MO-460 suppresses HIF-1α protein synthesis under hypoxic conditions and induces the accumulation of stress granules. The data provided here suggest that hnRNPA2B1 serves as a crucial molecular target in hypoxia-induced tumor survival and thus offer an avenue for the development of novel anticancer therapies.
Development of frontoparietal connectivity predicts longitudinal symptom changes in young people with autism spectrum disorder
Authors: Lin Hsiang-Yuan , Perry Alistair , Cocchi Luca , Roberts James A. , Tseng Wen-Yih Isaac , Breakspear Michael , Gau Susan Shur-Fen 
Published: February 2019

AbstractStructural neuroimaging studies suggest altered brain maturation in autism spectrum disorder (ASD) compared with typically developing controls (TDC). However, the prognostic value of whole-brain structural connectivity analysis in ASD has not been established. Diffusion magnetic imaging data were acquired in 27 high-functioning young ASD participants (2 females) and 29 age-matched TDC (12 females; age 8–18 years) at baseline and again following 3–7 years. Whole-brain structural connectomes were reconstructed from these data and analyzed using a longitudinal statistical model. We identified distinct patterns of widespread brain connections that exhibited either significant increases or decreases in connectivity over time (p < 0.001). There was a significant interaction between diagnosis and time in brain development (p < 0.001). This was expressed by a decrease in structural connectivity within the frontoparietal network—and its broader connectivity—in ASD during adolescence and early adulthood. Conversely, these connections increased with time in TDC. Crucially, stronger baseline connectivity in this subnetwork predicted a lower symptom load at follow-up (p = 0.048), independent of the expression of symptoms at baseline. Our findings suggest a clinically meaningful relationship between the atypical development of frontoparietal structural connections and the dynamics of the autism phenotype through early adulthood. These results highlight a potential marker of future outcome.
Three-dimensional alteration of neurites in schizophrenia
Authors: Mizutani Ryuta , Saiga Rino , Takeuchi Akihisa , Uesugi Kentaro , Terada Yasuko , Suzuki Yoshio , De Andrade Vincent , De Carlo Francesco , Takekoshi Susumu , Inomoto Chie , Nakamura Naoya , Kushima Itaru , Iritani Shuji , Ozaki Norio , Ide Soichiro , Ikeda Kazutaka , Oshima Kenichi , Itokawa Masanari , Arai Makoto 
Published: February 2019

AbstractPsychiatric symptoms of schizophrenia suggest alteration of cerebral neurons. However, the physical basis of the schizophrenia symptoms has not been delineated at the cellular level. Here, we report nanometer-scale three-dimensional analysis of brain tissues of schizophrenia and control cases. Structures of cerebral tissues of the anterior cingulate cortex were visualized with synchrotron radiation nanotomography. Tissue constituents visualized in the three-dimensional images were traced to build Cartesian coordinate models of tissue constituents, such as neurons and blood vessels. The obtained Cartesian coordinates were used for calculating curvature and torsion of neurites in order to analyze their geometry. Results of the geometric analyses indicated that the curvature of neurites is significantly different between schizophrenia and control cases. The mean curvature of distal neurites of the schizophrenia cases was ~1.5 times higher than that of the controls. The schizophrenia case with the highest neurite curvature carried a frame shift mutation in the GLO1 gene, suggesting that oxidative stress due to the GLO1 mutation caused the structural alteration of the neurites. The differences in the neurite curvature result in differences in the spatial trajectory and hence alter neuronal circuits. It has been shown that the anterior cingulate cortex analyzed in this study has emotional and cognitive functions. We suggest that the structural alteration of neurons in the schizophrenia cases should reflect psychiatric symptoms of schizophrenia.
KIAA1199 is a secreted molecule that enhances osteoblastic stem cell migration and recruitment
Authors: Chen Li , Shi Kaikai , Andersen Thomas Levin , Qiu Weimin , Kassem Moustapha 
Published: February 2019

AbstractFactors mediating mobilization of osteoblastic stem and progenitor cells from their bone marrow niche to be recruited to bone formation sites during bone remodeling are poorly known. We have studied secreted factors present in the bone marrow microenvironment and identified KIAA1199 (also known as CEMIP, cell migration inducing hyaluronan binding protein) in human bone biopsies as highly expressed in osteoprogenitor reversal cells (Rv.C) recruited to the eroded surfaces (ES), which are the future bone formation sites. In vitro, KIAA1199 did not affect the proliferation of human osteoblastic stem cells (also known as human bone marrow skeletal or stromal stem cells, hMSCs); but it enhanced cell migration as determined by scratch assay and trans-well migration assay. KIAA1199 deficient hMSCs (KIAA1199down) exhibited significant changes in cell size, cell length, ratio of cell width to length and cell roundness, together with reduction of polymerization actin (F-actin) and changes in phos-CFL1 (cofflin1), phos-LIMK1 (LIM domain kinase 1) and DSTN (destrin), key factors regulating actin cytoskeletal dynamics and cell motility. Moreover, KIAA1199downhMSC exhibited impaired Wnt signaling in TCF-reporter assay and decreased expression of Wnt target genes and these effects were rescued by KIAA1199 treatment. Finally, KIAA1199 regulated the activation of P38 kinase and its associated changes in Wnt-signaling. Thus, KIAA1199 is a mobilizing factor that interacts with P38 and Wnt signaling, and induces changes in actin cytoskeleton, as a mechanism mediating recruitment of hMSC to bone formation sites.
High mobility group box 1 promotes radioresistance in esophageal squamous cell carcinoma cell lines by modulating autophagy
Authors: Ma Hongbing , Zheng Shuyu , Zhang Xiaozhi , Gong Tuotuo , Lv Xin , Fu Shenbo , Zhang Shuqun , Yin Xiaoran , Hao Jingcan , Shan Changyou , Huang Shan 
Published: February 2019

AbstractResistance to radiotherapy results in relapse and treatment failure in locally advanced esophageal squamous cell carcinoma (ESCC). High mobility group box 1 (HMGB1) is reported to be associated with the radioresistance in bladder and breast cancer. However, the role of HMGB1 in the radiotherapy response in ESCC has not been fully elucidated. Here, we investigated the role of HMGB1 to radioresistance in ESCC clinical samples and cell lines. We found that HMGB1 expression was associated with tumor recurrence after postoperative radiotherapy in locally advanced ESCC patients. HMGB1 knockdown in ESCC cells resulted in increased radiosensitivity both in vitro and in vivo. Autophagy level was found depressed in HMGB1 inhibition cells and activation of autophagy brought back cell’s radioresistance. Our results demonstrate that HMGB1 activate autophagy and consequently promote radioresistance. HMGB1 may be used as a predictor of poor response to radiotherapy in ESCC patients. Our finding also highlights the importance of the utility of HMGB1 in ESCC radiosensitization.
A30P mutant α-synuclein impairs autophagic flux by inactivating JNK signaling to enhance ZKSCAN3 activity in midbrain dopaminergic neurons
Authors: Lei Zhinian , Cao Guangliang , Wei Gang 
Published: February 2019

AbstractMutations in α-synuclein gene have been linked to familial early-onset Parkinson’s disease (PD) with Lewy body pathology. A30P mutant α-synuclein is believed to suppress autophagic progression associated with PD pathogenesis. However, the mechanistic link between A30P mutation and autophagy inhibition in PD remains poorly understood. In this study, we identified that A30P mutant α-synuclein resulted in reduced autophagy flux through promoting the decrease of autophagosomal membrane-associated protein LC3 and the increase of SQSTM1/p62 protein levels in midbrain dopaminergic neuron, due to the transcriptional repressor ZKSCAN3 trafficking from the cytoplasm to the nucleus. Moreover, the results demonstrated that A30P mutant α-synuclein not only decreased the phospho-c-Jun N-terminal Kinase (p-JNK) levels in midbrain dopaminergic neuron but also interfered autophagy without influencing the activities of AMPK and mTOR. Collectively, the present study reveals a novel autophagy inhibition mechanism induced by A30P mutant α-synuclein via transcriptional activation of the ZKSCAN3 in a JNK-dependent manner.
ER stress sensor, glucose regulatory protein 78 (GRP78) regulates redox status in pancreatic cancer thereby maintaining “stemness”
Authors: Dauer Patricia , Sharma Nikita S. , Gupta Vineet K. , Durden Brittany , Hadad Roey , Banerjee Santanu , Dudeja Vikas , Saluja Ashok , Banerjee Sulagna 
Published: February 2019

AbstractEndoplasmic reticulum (ER) stress and the unfolded protein response (UPR) signaling have been shown to be dysregulated in multiple cancer types. Glucose regulatory protein 78 (GRP78), the master regulator of the UPR, plays a role in proliferation, invasion, and metastasis in cancer. Cancer stem cells (CSCs) make up a crucial component of the tumor heterogeneity in pancreatic cancer, as well as other cancers. “Stemness” in pancreatic cancer defines a population of cells within the tumor that have increased therapeutic resistance as well as survival advantage. In the current study, we investigated how GRP78 was responsible for maintaining “stemness” in pancreatic cancer thereby contributing to its aggressive biology. We determined that GRP78 downregulation decreased clonogenicity and self-renewal properties in pancreatic cancer cell lines in vitro. In vivo studies resulted in delayed tumor initiation frequency, as well as smaller tumor volume in the shGRP78 groups. Additionally, downregulation of GRP78 resulted in dysregulated fatty acid metabolism in pancreatic tumors as well as the cells. Further, our results showed that shGRP78 dysregulates multiple transcriptomic and proteomic pathways that involve DNA damage, oxidative stress, and cell death, that were reversed upon treatment with a ROS inhibitor, N-acetylcysteine. This study thus demonstrates for the first time that the heightened UPR in pancreatic cancer may be responsible for maintenance of the “stemness” properties in these cells that are attributed to aggressive properties like chemoresistance and metastasis.
LncRNA MIAT sponges miR-149-5p to inhibit efferocytosis in advanced atherosclerosis through CD47 upregulation
Authors: Ye Zi-ming , Yang Shuai , Xia Yuan-peng , Hu Rui-ting , Chen Shengcai , Li Bo-wei , Chen Shao-li , Luo Xue-ying , Mao Ling , Li Yanan , Jin Huijuan , Qin Chao , Hu Bo 
Published: February 2019

AbstractAtherosclerotic cardio-cerebrovascular disease and death remain the leading cause of morbidity and mortality worldwide. Defective efferocytosis, the clearance of apoptotic cells by macrophages, is thought to lead to increased inflammation and necrotic core formation in atherosclerotic lesions. However, very little is known about the role of long noncoding RNA (lncRNA) during this process. Here we show that lncRNA myocardial infarction associated transcript (MIAT) was markedly elevated in the serum of patients with symptoms of vulnerable atherosclerotic plaque and the macrophages of necrotic cores in an advanced atherosclerosis mouse model. MIAT knockdown attenuated atherosclerosis progression, reduced necrotic core size, and increased plaque stability in vivo. Furthermore, MIAT knockdown promoted clearance of apoptotic cells by macrophages in vivo and in vitro. Mechanistic studies revealed that MIAT acted as a micro RNA (miRNA) sponge to positively modulate the expression of anti-phagocytic molecule CD47 through sponging miR-149-5p. Together, these findings identified a macrophage MIAT/miR-149-5p /CD47 pathway as a key factor in the development of necrotic atherosclerotic plaques.
Hypoxia preconditioning promotes bone marrow mesenchymal stem cells survival by inducing HIF-1α in injured neuronal cells derived exosomes culture system
Authors: Luo Zucheng , Wu Fangfang , Xue Enxing , Huang Linlin , Yan Ping , Pan Xiaoyun , Zhou Yulong 
Published: February 2019

AbstractBone marrow derived stem cells (BMSCs) transplantation are viewed as a promising therapeutic candidate for spinal cord injury (SCI). However, the inflammatory microenvironment in the spinal cord following SCI limits the survival and efficacy of transplanted BMSCs. In this study, we investigate whether injured neuronal cells derived exosomes would influence the survival of transplanted BMSCs after SCI. In order to mimic the microenvironment in SCI that the neuronal cells or transplanted BMSCs suffer in vivo, PC12 cells conditioned medium and PC12 cell’s exosomes collected from H2O2-treated PC12 cell’s culture medium were cultured with BMSCs under oxidative stress in vitro. PC12 cells conditioned medium and PC12 cell’s exosomes significantly accelerated the apoptosis of BMSCs induced by H2O2. Moreover, the cleaved caspase-3, cytochrome (Cyt) C, lactate dehydrogenase (LDH) releases, and apoptotic percentage were increased, and the ratio of Bcl-2/Bax and cell viability were decreased. Inhibition of exosome secretion via Rab27a small interfering RNA prevented BMSCs apoptosis in vitro. In addition, hypoxia-preconditioned promoted the survival of BMSCs under oxidative stress both in vivo after SCI and in vitro. Our results also indicate that HIF-1α plays a central role in the survival of BMSCs in hypoxia pretreatment under oxidative stress conditions. siRNA-HIF-1α increased apoptosis of BMSCs; in contrast, HIF-1α inducer FG-4592 attenuated apoptosis of BMSCs. Taken together, we found that the injured PC12 cells derived exosomes accelerate BMSCs apoptosis after SCI and in vitro, hypoxia pretreatment or activating expression of HIF-1α to be important in the survival of BMSCs after transplantation, which provides a foundation for application of BMSCs in therapeutic potential for SCI.
Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors
Authors: Yang Yang , Wang Huanan , Kouadir Mohammed , Song Houhui , Shi Fushan 
Published: February 2019

AbstractThe NLRP3 inflammasome is a multimeric protein complex that initiates an inflammatory form of cell death and triggers the release of proinflammatory cytokines IL-1β and IL-18. The NLRP3 inflammasome has been implicated in a wide range of diseases, including Alzheimer’s disease, Prion diseases, type 2 diabetes, and some infectious diseases. It has been found that a variety of stimuli including danger-associated molecular patterns (DAMPs, such as silica and uric acid crystals) and pathogen-associated molecular patterns (PAMPs) can activate NLRP3 inflammasome, but the specific regulatory mechanisms of NLRP3 inflammasome activation remain unclear. Understanding the mechanisms of NLRP3 activation will enable the development of its specific inhibitors to treat NLRP3-related diseases. In this review, we summarize current understanding of the regulatory mechanisms of NLRP3 inflammasome activation as well as inhibitors that specifically and directly target NLRP3.