bluuebunny/crossref_metadata_2025_split huggingface dataset:
How banks and other financial institutions think
Authors: Thompson M. 
Published: January 2018

AbstractConventional diagnoses of the 2007/8 Global Financial Crisis see it as “abnormal”, and then resort to explanations in terms of “irrational exuberance”, “animal spirits”, “herding behaviour” and so on. The prescription – “better regulation” – then follows automatically, as it has done after every such crisis, all the way back to tulipmania 400 years ago. But if there are different “seasons of risk”, and if financial sector actors are able to latch onto different risk-handling strategies, each appropriate to one of those seasons and inappropriate to the others, then we have a very different explanation: one in which, in contrast to both neoclassical and behavioural economics, rationality is no longer singular. This “anthropological” hypothesis has its roots in Mary Douglas’s book “How Institutions Think”, and the paper shows how it is well supported by historical evidence, agent-based modelling, and fieldwork among both financial sector firms and their regulators, as well as by parallels from ecology, organisation theory and evolutionary (i.e. Schumpeterian) economics.
Weed Management in Common Cottonwood (Populus deltoides) Nursery Plantation
Authors: Kaur H. , Kaur Navneet , Gill R. I. S. , Bhullar Makhan S. , Singh A. 
Published: January 2018

AbstractCommon cottonwood-based agroforestry system is widely adopted in Indian Indo-Gangetic plains. The stem cuttings of common cottonwood are raised in a nursery 10 to 12 months in rows spaced 0.5 mx0.5 m, before re-planting in the field. The longer duration of 10 to 12 months and wider spacing of stem cuttings in the nursery makes the entire transplants highly vulnerable to weed competition, especially during early establishment stages. The efficacy of preemergence herbicides and plastic and straw mulches for weed management in common cottonwood nursery was investigated at two sites in years 2014 and 2015. The major weed flora in the experimental field consisted of three grass weeds (crowfootgrass, feather lovegrass, and southern crabgrass), and four broadleaf weeds (scarlet pimpernel, garden spurge, niruri, and lesser swinecress). The integrated use of pendimethalin or alachlor applied PRE with paddy straw mulch significantly reduced density and biomass of both grass and broadleaf weeds compared to herbicide or straw mulch used alone, and provided similar level of weed control to hand weeding at both locations. Spreading of plastic mulch in the whole field after punching holes for common cottonwood stem cuttings, or in row spaces recorded similar weed control to hand-weeding. The integrated use of herbicides with straw mulch, and or plastic mulch alone significantly improved plant height, stem diameter, below- and above-ground biomass of common cottonwood plants compared to unweeded check. The study concluded that integrated use of herbicides plus paddy straw mulch or plastic mulch alone could be adopted for weed management in common cottonwood nursery plantations.
Age-associated microbiome shows the giant panda lives on hemicelluloses, not on cellulose
Authors: Zhang Wenping , Liu Wenbin , Hou Rong , Zhang Liang , Schmitz-Esser Stephan , Sun Huaibo , Xie Junjin , Zhang Yunfei , Wang Chengdong , Li Lifeng , Yue Bisong , Huang He , Wang Hairui , Shen Fujun , Zhang Zhihe 
Published: January 2018

Abstract
The giant panda feeds almost exclusively on bamboo, a diet highly enriched in lignin and cellulose, but is characterized by a digestive tract similar to carnivores. It is still large unknown if and how the giant panda gut microbiota contributes to lignin and cellulose degradation. Here we show the giant pandas’ gut microbiota does not significantly contribute to cellulose and lignin degradation. We found that no operational taxonomic unit had a nearest neighbor identified as a cellulolytic species or strain with a significant higher abundance in juvenile than cubs, a very low abundance of putative lignin and cellulose genes existed in part of analyzing samples but a significant higher abundance of genes involved in starch and hemicellulose degradation in juveniles than cubs. Moreover, a significant lower abundance of putative cellulolytic genes and a significant higher abundance of putative α-amylase and hemicellulase gene families were present in giant pandas than in omnivores or herbivores.
Targeting EHMT2 reverses EGFR-TKI resistance in NSCLC by epigenetically regulating the PTEN/AKT signaling pathway
Authors: Wang Lihui , Dong Xiaoyu , Ren Yong , Luo Juanjuan , Liu Pei , Su Dongsheng , Yang Xiaojun 
Published: January 2018

AbstractEpidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance is a major obstacle in the treatment of non-small cell lung cancer (NSCLC). Epigenetic alterations have been shown to be involved in NSCLC oncogenesis; however, their function in EGFR-TKI resistance remains uncharacterized. Here, we found that an EHMT2 inhibitor, UNC0638, can significantly inhibit cell growth and induce apoptosis in EGFR-TKI-resistant NSCLC cells. Additionally, we also found that EHMT2 expression and enzymatic activity levels were elevated in EGFR-TKI-resistant NSCLC cells. Moreover, we determined that genetic or pharmacological inhibition of EHMT2 expression enhanced TKI sensitivity and suppressed migration and tumor sphere formation in EGFR-TKI-resistant NSCLC cells. Further investigation revealed that EHMT2 contributed to PTEN transcriptional repression and thus facilitated AKT pathway activation. The negative relationship between EHMT2 and PTEN was confirmed by our clinical study. Furthermore, we determined that combination treatment with the EHMT2 inhibitor and Erlotinib resulted in enhanced antitumor effects in a preclinical EGFR-TKI-resistance model. We also found that high EHMT2 expression along with low PTEN expression can predict poor overall survival in patients with NSCLC. In summary, our findings showed that EHMT2 facilitated EGFR-TKI resistance by regulating the PTEN/AKT pathway in NSCLC cells, suggesting that EHMT2 may be a target in the clinical treatment of EGFR-TKI-resistant NSCLC.
microRNA-874 suppresses tumor proliferation and metastasis in hepatocellular carcinoma by targeting the DOR/EGFR/ERK pathway
Authors: Zhang Yi , Wei Yangchao , Li Xuan , Liang Xingsi , Wang Liming , Song Jun , Zhang Xiuzhong , Zhang Chong , Niu Jian , Zhang Pengbo , Ren Zeqiang , Tang Bo 
Published: January 2018

AbstractThe δ opioid receptor (DOR) is involved in the regulation of malignant transformation and tumor progression of hepatocellular carcinoma (HCC). However, regulation of the DOR in HCC remains poorly defined. We found that miR-874 was identified as a negative regulator of the DOR, which is a direct and functional target of miR-874 via its 3′ untranslated region (UTR). Moreover, miR-874 was downregulated in HCC and its expression was inversely correlated with DOR expression. Downregulation of miR-874 was also associated with larger tumor size, more vascular invasion, a poor TNM stage, poor tumor differentiation, and inferior patient outcomes. Functionally, overexpression of miR-874 in the HCC cell line SK-hep-1 inhibited cell growth, migration, in vitro invasion, and in vivo tumorigenicity. Furthermore, miR-874 overexpression suppressed the DOR, resulting in a downregulated epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK) phosphorylation. The EGFR activator—epidermal growth factor (EGF)—can rescue the proliferation and migration suppression induced by miR-874 overexpression, and the rescue effects of the EGF were blocked by an ERK inhibitor. Our study results suggest that miRNA-874 is a negative regulator of the DOR that can suppress tumor proliferation and metastasis in HCC by targeting the DOR/EGFR/ERK pathway, which may be a potential target for HCC treatment.
iPSC modeling of severe aplastic anemia reveals impaired differentiation and telomere shortening in blood progenitors
Authors: Melguizo-Sanchis Dario , Xu Yaobo , Taheem Dheraj , Yu Min , Tilgner Katarzyna , Barta Tomas , Gassner Katja , Anyfantis George , Wan Tengfei , Elango Ramu , Alharthi Sameer , El-Harouni Ashraf A. , Przyborski Stefan , Adam Soheir , Saretzki Gabriele , Samarasinghe Sujith , Armstrong Lyle , Lako Majlinda 
Published: January 2018

AbstractAplastic Anemia (AA) is a bone marrow failure (BMF) disorder, resulting in bone marrow hypocellularity and peripheral pancytopenia. Severe aplastic anemia (SAA) is a subset of AA defined by a more severe phenotype. Although the immunological nature of SAA pathogenesis is widely accepted, there is an increasing recognition of the role of dysfunctional hematopoietic stem cells in the disease phenotype. While pediatric SAA can be attributable to genetic causes, evidence is evolving on previously unrecognized genetic etiologies in a proportion of adults with SAA. Thus, there is an urgent need to better understand the pathophysiology of SAA, which will help to inform the course of disease progression and treatment options. We have derived induced pluripotent stem cell (iPSC) from three unaffected controls and three SAA patients and have shown that this in vitro model mimics two key features of the disease: (1) the failure to maintain telomere length during the reprogramming process and hematopoietic differentiation resulting in SAA-iPSC and iPSC-derived-hematopoietic progenitors with shorter telomeres than controls; (2) the impaired ability of SAA-iPSC-derived hematopoietic progenitors to give rise to erythroid and myeloid cells. While apoptosis and DNA damage response to replicative stress is similar between the control and SAA-iPSC-derived-hematopoietic progenitors, the latter show impaired proliferation which was not restored by eltrombopag, a drug which has been shown to restore hematopoiesis in SAA patients. Together, our data highlight the utility of patient specific iPSC in providing a disease model for SAA and predicting patient responses to various treatment modalities.
Human papillomavirus E7 induces p63 expression to modulate DNA damage response
Authors: Eldakhakhny Sahar , Zhou Qing , Crosbie Emma J. , Sayan Berna S. 
Published: January 2018

AbstractCervical cancer is the third most common malignancy diagnosed in women worldwide. The major aetiological factor underlying the malignant transformation of cervical cells is the persistent infection with high-risk human papillomaviruses (HR-HPV), with more than 99% of cases expressing viral sequences. Here, we report a previously unknown mechanism driven by high-risk human papillomavirus E7 protein to modulate response to DNA damage in cervical cancer cells. Our data shows that HR-HPV E7 oncoprotein induces the transcription of the p53-family member p63, which modulates DNA damage response pathways, to facilitate repair of DNA damage. Based on our findings, we proposed a model, where HR-HPV could interfere with the sensitivity of transformed cells to radiation therapy by modulating DNA damage repair efficiency. Importantly, we have shown for the first time a critical role for p63 in response to DNA damage in cervical cancer cells.
FLI1 and PKC co-activation promote highly efficient differentiation of human embryonic stem cells into endothelial-like cells
Authors: Zhao Hao , Zhao Yan , Li Zili , Ouyang Qi , Sun Yi , Zhou Di , Xie Pingyuan , Zeng Sicong , Dong Lingfeng , Wen Hua , Lu Guangxiu , Lin Ge , Hu Liang 
Published: January 2018

AbstractRationale-endothelial cells (ECs) play important roles in various regeneration processes and can be used in a variety of therapeutic applications, such as cardiac regeneration, gene therapy, tissue-engineered vascular grafts and prevascularized tissue transplants. ECs can be acquired from pluripotent and adult stem cells. To acquire ECs from human embryonic stem cells (hESCs) in a fast, efficient and economic manner. We established a conditional overexpression system in hESCs based on 15 transcription factors reported to be responsible for hematopoiesis lineage. Among them, only overexpression of FLI1 could induce hESCs to a hematopoietic lineage. Moreover, simultaneous overexpression of FLI1 and activation of PKC rapidly and efficiently induced differentiation of hESCs into induced endothelial cells (iECs) within 3 days, while neither FLI1 overexpression nor PKC activation alone could derive iECs from hESCs. During induction, hESCs differentiated into spindle-like cells that were consistent in appearance with ECs. Flow cytometric analysis revealed that 92.2–98.9% and 87.2–92.6% of these cells were CD31+ and CD144+, respectively. Expression of vascular-specific genes dramatically increased, while the expression of pluripotency genes gradually decreased during induction. iECs incorporated acetylated low-density lipoproteins, strongly expressed vWF and bound UEA-1. iECs also formed capillary-like structures both in vitro and in vivo. RNA-seq analysis verified that these cells closely resembled their in vivo counterparts. Our results showed that co-activation of FLI1 and PKC could induce differentiation of hESCs into iECs in a fast, efficient and economic manner.
Downregulation of MCL-1 and upregulation of PUMA using mTOR inhibitors enhance antitumor efficacy of BH3 mimetics in triple-negative breast cancer
Authors: Li Haolong , Liu Lei , Chang Haocai , Zou Zhengzhi , Xing Da 
Published: January 2018

AbstractTriple-negative breast cancer (TNBC) shows a higher malignant and poorer clinical outcome compared with other breast cancer subtypes. Albeit that chemotherapy is the first choice for TNBC treatment, rapid emergence of chemoresistance and variability of chemotherapeutic responses in TNBC patients call for novel therapeutic strategies. Here, we reported evidences highlighting that combination of BH3 mimetics and mTOR inhibitors could be a promising therapeutic strategy to improve TNBC treatment. Our results showed that combination of the BH3 mimetic ABT263 and typical mTOR inhibitors, BEZ235 or AZD8055, leads to efficient apoptosis in vitro. Tumor regression was significantly improved by combination therapy compared with either drug alone in the xenograft model. Further mechanistic investigations revealed that mTOR inhibitors induced the suppression of MCL-1; concomitantly, the expression level of PUMA was significantly upregulated in a FOXO3a-dependent manner. The specific changes of MCL-1 and PUMA facilitated the release of the apoptotic regulators, such as BIM, BAX, and BAK, to induce the activation of mitochondrial apoptotic pathway, thereby sensitizing the ABT263 activity in TNBC. Therefore, our findings provided evidences that mTOR inhibitors can enhance antitumor efficacy of BH3 mimetics via downregulating MCL-1 and upregulating PUMA in TNBC; it could be a promising therapeutic strategy to treat TNBC.
Synergistic effect of a novel autophagy inhibitor and Quizartinib enhances cancer cell death
Authors: Ouchida Amanda Tomie , Li Yingbo , Geng Jiefei , Najafov Ayaz , Ofengeim Dimitry , Sun Xiaoxiao , Yu Qiang , Yuan Junying 
Published: January 2018

AbstractDrug combinations have been increasingly applied in chemotherapy as a strategy to enhance the efficacy of anti-cancer treatment. The appropriate drug combinations may achieve synergistic effects beyond monotherapies alone. AC220 (Quizartinib), an FLT3 receptor tyrosine kinase inhibitor, developed for the treatment of AML, has been tested in phase II human clinical trials. However, AC220 as a monotherapy is not efficacious enough. In this study, we performed a small-molecule screening of 12 640 compounds in order to find a compound that increase the AC220 efficacy in chemotherapy. We identified that TAK-165, a HER2 inhibitor, even when used at low nanomolar doses in combination with AC220, was able to induce cell death in different cancer cells, but not in non-cancer cell lines. We showed that TAK-165 and AC220 act synergistically to downregulate key signaling pathways and potently induce cancer cell death. Furthermore, we demonstrated that TAK-165 inhibited autophagy in a HER2-independent manner. Finally, we showed that the combination of TAK-165 and AC220 induced cell death in cancer cells through the activation of chaperone-mediated autophagy. Overall, these findings support the strategy for using AC220 and an autophagy inhibitor such as TAK-165 in a combinatorial treatment to enhance the efficacy of cancer therapies.
Uptake, distribution, clearance, and toxicity of iron oxide nanoparticles with different sizes and coatings
Authors: Feng Qiyi , Liu Yanping , Huang Jian , Chen Ke , Huang Jinxing , Xiao Kai 
Published: January 2018

AbstractIron oxide nanoparticles (IONPs) have been increasingly used in biomedical applications, but the comprehensive understanding of their interactions with biological systems is relatively limited. In this study, we systematically investigated the in vitro cell uptake, cytotoxicity, in vivo distribution, clearance and toxicity of commercially available and well-characterized IONPs with different sizes and coatings. Polyethylenimine (PEI)-coated IONPs exhibited significantly higher uptake than PEGylated ones in both macrophages and cancer cells, and caused severe cytotoxicity through multiple mechanisms such as ROS production and apoptosis. 10 nm PEGylated IONPs showed higher cellular uptake than 30 nm ones, and were slightly cytotoxic only at high concentrations. Interestingly, PEGylated IONPs but not PEI-coated IONPs were able to induce autophagy, which may play a protective role against the cytotoxicity of IONPs. Biodistribution studies demonstrated that all the IONPs tended to distribute in the liver and spleen, and the biodegradation and clearance of PEGylated IONPs in these tissues were relatively slow (>2 weeks). Among them, 10 nm PEGylated IONPs achieved the highest tumor uptake. No obvious toxicity was found for PEGylated IONPs in BALB/c mice, whereas PEI-coated IONPs exhibited dose-dependent lethal toxicity. Therefore, it is crucial to consider the size and coating properties of IONPs in their applications.
Design and synthesis of coumarin-based organoselenium as a new hit for myeloprotection and synergistic therapeutic efficacy in adjuvant therapy
Authors: Patra Arup Ranjan , Roy Somnath Singha , Basu Abhishek , Bhuniya Avishek , Bhattacharjee Arin , Hajra Subhadip , Sk Ugir Hossain , Baral Rathindranath , Bhattacharya Sudin 
Published: January 2018

AbstractA newly designed organoselenium compound, methyl substituted umbelliferone selenocyanate (MUS), was synthesized as a primary hit against the myelotoxic activity of carboplatin. MUS was administered at 6 mg/kg b.wt, p.o. in concomitant and pretreatment schedules with carboplatin (12 mg/kg b.wt, i.p. for 10 days) in female Swiss albino mouse. MUS treatment reduced (P < 0.001) the percentage of chromosomal aberrations, micronuclei formation, DNA damage and apoptosis in murine bone marrow cells and also enhanced (P < 0.001) the bone marrow cell proliferation of the carboplatin-treated mice. These activities cumulatively restored the viable bone marrow cell count towards normalcy. Myeloprotection by MUS was achieved, in part, due to a significant reduction in the ROS/RNS formation and restoration of glutathione redox pool. Additionally, MUS synergistically enhanced the cytotoxicity of carboplatin against two human cancer cell lines (MCF-7 and Colo-205). Furthermore, MUS can effectively potentiate the antitumour activity of carboplatin against two murine cancers (Dalton’s Lymphoma and Sarcoma-180) in vivo. These preclinical findings clearly indicate that MUS can improve the therapeutic index of carboplatin and ensures more effective therapeutic strategy against cancer for clinical development.
The paxillin-plectin-EPLIN complex promotes apical elimination of RasV12-transformed cells by modulating HDAC6-regulated tubulin acetylation
Authors: Kasai Nobuhiro , Kadeer Ailijiang , Kajita Mihoko , Saitoh Sayaka , Ishikawa Susumu , Maruyama Takeshi , Fujita Yasuyuki 
Published: January 2018

AbstractRecent studies have revealed that newly emerging RasV12-transformed cells are often apically extruded from the epithelial layer. During this cancer preventive process, cytoskeletal proteins plectin and Epithelial Protein Lost In Neoplasm (EPLIN) are accumulated in RasV12 cells that are surrounded by normal cells, which positively regulate the apical elimination of transformed cells. However, the downstream regulators of the plectin-EPLIN complex remain to be identified. In this study, we have found that paxillin binds to EPLIN specifically in the mix culture of normal and RasV12-transformed cells. In addition, paxillin is accumulated in RasV12 cells surrounded by normal cells. Paxillin, plectin and EPLIN mutually influence their non-cell-autonomous accumulation, and paxillin plays a crucial role in apical extrusion of RasV12 cells. We also demonstrate that in RasV12 cells surrounded by normal cells, acetylated tubulin is accumulated. Furthermore, acetylation of tubulin is promoted by paxillin that suppresses the activity of histone deacetylase (HDAC) 6. Collectively, these results indicate that in concert with plectin and EPLIN, paxillin positively regulates apical extrusion of RasV12-transformed cells by promoting microtubule acetylation. This study shed light on the unexplored events occurring at the initial stage of carcinogenesis and would potentially lead to a novel type of cancer preventive medicine.
Magnesium prevents vascular calcification in vitro by inhibition of hydroxyapatite crystal formation
Authors: ter Braake Anique D. , Tinnemans Paul T. , Shanahan Catherine M. , Hoenderop Joost G. J. , de Baaij Jeroen H. F. 
Published: January 2018

AbstractMagnesium has been shown to effectively prevent vascular calcification associated with chronic kidney disease. Magnesium has been hypothesized to prevent the upregulation of osteoblastic genes that potentially drives calcification. However, extracellular effects of magnesium on hydroxyapatite formation are largely neglected. This study investigated the effects of magnesium on intracellular changes associated with transdifferentiation and extracellular crystal formation. Bovine vascular smooth muscle cells were calcified using β-glycerophosphate. Transcriptional analysis, alkaline phosphatase activity and detection of apoptosis were used to identify transdifferentiation. Using X-ray diffraction and energy dispersive spectroscopy extracellular crystal composition was investigated. Magnesium prevented calcification in vascular smooth muscle cells. β-glycerophosphate increased expression of osteopontin but no other genes related to calcification. Alkaline phosphatase activity was stable and apoptosis was only detected after calcification independent of magnesium. Blocking of the magnesium channel TRPM7 using 2-APB did not abrogate the protective effects of magnesium. Magnesium prevented the formation of hydroxyapatite, which formed extensively during β-glycerophosphate treatment. Magnesium reduced calcium and phosphate fractions of 68% and 41% extracellular crystals, respectively, without affecting the fraction of magnesium. This study demonstrates that magnesium inhibits hydroxyapatite formation in the extracellular space, thereby preventing calcification of vascular smooth muscle cells.