bluuebunny/crossref_metadata_2025_split huggingface dataset:
APPROXIMATION OF -ANALYTIC TORSION FOR ARITHMETIC QUOTIENTS OF THE SYMMETRIC SPACE
Authors: Matz Jasmin , Müller Werner 
Published: February 2018

In [31] we defined a regularized analytic torsion for quotients of the symmetric space$\operatorname{SL}(n,\mathbb{R})/\operatorname{SO}(n)$by arithmetic lattices. In this paper we study the limiting behavior of the analytic torsion as the lattices run through sequences of congruence subgroups of a fixed arithmetic subgroup. Our main result states that for principal congruence subgroups and strongly acyclic flat bundles, the logarithm of the analytic torsion, divided by the index of the subgroup, converges to the$L^{2}$-analytic torsion.
Between art and information: communicating world health, 1948–70
Authors: Medcalf Alexander 
Published: February 2018

AbstractWith the advent of new media technologies and approaches in the twentieth century, public health officials became convinced that health needed mass media support. The World Health Organization believed that educating people, as well as informing them about the health situation around the world, could assist in the enduring fight against disease. Yet in an increasingly competitive media landscape, the agency recognized the need to persuade people and hold their attention through attractive presentation. Public information, the name given to the multiple strategies used to communicate with the public, was rarely straightforward and required the agency not only to monitor the impact of its own efforts but also to identify opportunities to further enhance its reputation, especially when this was in danger of damage or misappropriation. The WHO’s understanding of public information provides insights into the development of international information, communication, and education networks and practices after 1945, as well as the increasingly central position of these processes in generating support for and evincing the value of international organizations.
Managing the world: the United Nations, decolonization, and the strange triumph of state sovereignty in the 1950s and 1960s
Authors: Muschik Eva-Maria 
Published: February 2018

AbstractThis article examines a 1956 United Nations effort to respond to decolonization, by supplying newly independent governments with international administrators to help build sovereign nation-states out of the disintegrating European empires and anchor them firmly within the capitalist world. The article reveals the UN as a significant historical actor during the Cold War beyond the organization’s function of providing a forum for intergovernmental debates and lobbying. While the initiative never resulted in a large-scale response to decolonization, it ultimately effected a substantial shift in the practice of development assistance: from advisory services to a more paternalist approach that focused on ‘getting the work done’ on behalf of aid recipients. Recovering this history helps account for the strange triumph of state sovereignty in the second half of the twentieth century: its global proliferation at a time when international actors became increasingly active in the management of the public affairs of developing countries.
Iron and phosphorus deprivation induce sociality in the marine bloom-forming cyanobacterium Trichodesmium
Authors: Tzubari Yael , Magnezi Liel , Be’er Avraham , Berman-Frank Ilana 
Published: February 2018

Abstract
Trichodesmium spp. are diazotrophic cyanobacteria that exist as single filaments (trichomes) and as macroscopic colonies of varying shapes formed by aggregating trichomes. The causes and dynamics of colony formation and disassociation are not yet elucidated. we demonstrate that limited availability of dissolved phosphorus (P) or iron (Fe) stimulated trichome mobility and induced colony formation in Trichodesmium erythraeum IMS101 cultures. The specific nutrient limitation differentially affected the rate of colony formation and morphology of the colonies. Fe starvation promoted rapid colony formation (10–48 h from depletion) while 5–7 days were required for colonies to form in P-depleted cultures. Video analyses confirmed that the probability of trichomes to cluster increased from 12 to 35% when transferred from nutrient replete to Fe-depleted conditions. Moreover, the probability for Fe-depleted aggregates to remain colonial increased to 50% from only 10% in nutrient replete cultures. These colonies were also characterized by stronger attachment forces between the trichomes. Enrichment of nutrient-depleted cultures with the limited nutrient-stimulated colony dissociation into single trichomes. We postulate that limited P and Fe availability enhance colony formation of Trichodesmium and primarily control the abundance and distribution of its different morphologies in the nutrient-limited surface ocean.
Long non-coding RNA PVT1 predicts poor prognosis and induces radioresistance by regulating DNA repair and cell apoptosis in nasopharyngeal carcinoma
Authors: He Yi , Jing Yizhou , Wei Fang , Tang Yanyan , Yang Liting , Luo Jia , Yang Pei , Ni Qianxi , Pang Jinmeng , Liao Qianjin , Xiong Fang , Guo Can , Xiang Bo , Li Xiaoling , Zhou Ming , Li Yong , Xiong Wei , Zeng Zhaoyang , Li Guiyuan 
Published: February 2018

AbstractThe long non-coding RNA, plasmacytoma variant translocation 1 (PVT1), is highly expressed in a variety of tumors, and is believed to be a potential oncogene. However, the role and mechanism of action of PVT1 in the carcinogenesis and progression of nasopharyngeal carcinomas (NPCs) remains unclear. In this study, for the first time, we have discovered that PVT1 shows higher expression in NPCs than in normal nasopharyngeal epithelial tissue, and patients with NPCs who show higher expression of PVT1 have worse progression-free and overall survivals. Additionally, we observed that the proliferation of NPC cells decreased, and their rate of apoptosis increased; these results indicated that the knockdown of PVT1 expression in the NPC cells induced radiosensitivity. Further, we have shown that the knockdown of PVT1 expression can induce apoptosis in the NPC cells by influencing the DNA damage repair pathway after radiotherapy. In general, our study shows that PVT1 may be a novel biomarker for prognosis and a new target for the treatment of NPCs. Additionally, targeting PVT1 may be a potential strategy for the clinical management of NPC and for the improvement of the curative effect of radiation in NPCs.
Microfluidic cell sorting by stiffness to examine heterogenic responses of cancer cells to chemotherapy
Authors: Islam Muhymin , Mezencev Roman , McFarland Brynn , Brink Hannah , Campbell Betsy , Tasadduq Bushra , Waller Edmund K. , Lam Wilbur , Alexeev Alexander , Sulchek Todd 
Published: February 2018

AbstractCancers consist of a heterogeneous populations of cells that may respond differently to treatment through drug-resistant sub-populations. The scarcity of these resistant sub-populations makes it challenging to understand how to counter their resistance. We report a label-free microfluidic approach to separate cancer cells treated with chemotherapy into sub-populations enriched in chemoresistant and chemosensitive cells based on the differences in cellular stiffness. The sorting approach enabled analysis of the molecular distinctions between resistant and sensitive cells. Consequently, the role of multiple mechanisms of drug resistance was identified, including decreased sensitivity to apoptosis, enhanced metabolism, and extrusion of drugs, and, for the first time, the role of estrogen receptor in drug resistance of leukemia cells. To validate these findings, several inhibitors for the identified resistance pathways were tested with chemotherapy to increase cytotoxicity sevenfold. Thus, microfluidic sorting can identify molecular mechanisms of drug resistance to examine heterogeneous responses of cancers to therapies.
A novel autophagy inhibitor berbamine blocks SNARE-mediated autophagosome-lysosome fusion through upregulation of BNIP3
Authors: Fu Ruoqiu , Deng Qin , Zhang Hongwei , Hu Xiaoye , Li Yunong , Liu Yanxia , Hu Jinjiao , Luo Qingsong , Zhang Yanhao , Jiang Xiuxing , Li Lirong , Yang Chong , Gao Ning 
Published: February 2018

AbstractIncreasing evidences reveal that autophagy inhibitor could enhance the effect of chemotherapy to cancer. However, few autophagy inhibitors are currently approved for clinical application in humans. Berbamine (BBM) is a natural compound extracted from traditional Chinese medicine that is widely used for treatment of a variety of diseases without any obvious side effects. Here we found that BBM is a novel auophagy inhibitor, which potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human breast cancer cells. Mechanistically, we found that BBM blocked autophagosome-lysosome fusion by inhibiting the interaction of SNAP29 and VAMP8. Furthermore, BBM induced upregulation of BNIP3 and the interaction between SNAP29 and BNIP3. BNIP3 depletion or SNAP29 overexpression abrogated BBM-mediated blockade of autophagosome-lysosome fusion through the interaction between SNAP29 and VAMP8, whereas BNIP3 overexpression blocked autophagosome-lysosome fusion through inhibition of the interaction between SNAP29 and VAMP8. These findings suggest that upregulation of BNIP3 and interaction between BNIP3 and SNAP29 could be involved in BBM-mediated blockade of autophagosome-lysosome fusion through inhibition of the interaction between SNAP29 and VAMP8. Our findings identify the critical role of BNIP3 in blockade of autophagosome-lysosome fusion mediated by BBM, and suggest that BBM could potentially be further developed as a novel autophagy inhibitor, which could enhance the effect of chemotherapy to cancer.
Non-toxic engineered carbon nanodiamond concentrations induce oxidative/nitrosative stress, imbalance of energy metabolism, and mitochondrial dysfunction in microglial and alveolar basal epithelial cells
Authors: Fresta Claudia G. , Chakraborty Aishik , Wijesinghe Manjula B. , Amorini Angela M. , Lazzarino Giacomo , Lazzarino Giuseppe , Tavazzi Barbara , Lunte Susan M. , Caraci Filippo , Dhar Prajnaparamita , Caruso Giuseppe 
Published: February 2018

AbstractEngineered nanoparticles are finding a wide spectrum of biomedical applications, including drug delivery and capacity to trigger cytotoxic phenomena, potentially useful against tumor cells. The full understanding of their biosafety and interactions with cell processes is mandatory. Using microglial (BV-2) and alveolar basal epithelial (A549) cells, in this study we determined the effects of engineered carbon nanodiamonds (ECNs) on cell viability, nitric oxide (NO) and reactive oxygen species (ROS) production, as well as on energy metabolism. Particularly, we initially measured decrease in cell viability as a function of increasing ECNs doses, finding similar cytotoxic ECN effects in the two cell lines. Subsequently, using apparently non-cytotoxic ECN concentrations (2 µg/mL causing decrease in cell number < 5%) we determined NO and ROS production, and measured the concentrations of compounds related to energy metabolism, mitochondrial functions, oxido-reductive reactions, and antioxidant defences. We found that in both cell lines non-cytotoxic ECN concentrations increased NO and ROS production with sustained oxidative/nitrosative stress, and caused energy metabolism imbalance (decrease in high energy phosphates and nicotinic coenzymes) and mitochondrial malfunctioning (decrease in ATP/ADP ratio).These results underline the importance to deeply investigate the molecular and biochemical changes occurring upon the interaction of ECNs (and nanoparticles in general) with living cells, even at apparently non-toxic concentration. Since the use of ECNs in biomedical field is attracting increasing attention the complete evaluation of their biosafety, toxicity and/or possible side effects both in vitro and in vivo is mandatory before these highly promising tools might find the correct application.
Dural effects of oxidative stress on cardiomyogenesis via Gata4 transcription and protein ubiquitination
Authors: Li Tao , Zhang Xia , Jiang Kesheng , Liu Jing , Liu Zhiqiang 
Published: February 2018

Abstract
Oxidative stress generates reactive oxygen species (ROS) that can promote or inhibit cardiac differentiation of stem cells dependent on the intensity of stimuli as well as cellular context in redox and differentiation status. In the current study, we confirmed that suitable intensity of hydrogen peroxide at the formation stage of embryoid bodies (EBs) effectively favored the formation of spontaneously beating cardiomyocytes from P19 embryonal carcinoma cells. Mechanistic studies implicated that extrinsic ROS enhanced the Caspase-mediated degradation of Oct4 and Nanog, two factors that governing pluripotent property. Further experiments suggested that a cohort of Nanog together with histone deacetylase 4 (Hdac4) played a critical role in establishing and maintaining the silent transcriptional status of Gata4 and Nkx2.5 in undifferentiated cells. Thus, an impulse of hydrogen peroxide depleted Nanog and Hdac4 via a caspase-dependent manner to ameliorate the repression on Gata4 and Nkx2.5 promoters, thereby generating a persistent activation on cardiac differentiation program. Meanwhile, we found that excessive ROS-activated JNK cascade to facilitate the ubiquitination and subsequent degradation of Gata4 protein. Overall, our results indicate that suitable ROS promotes the activation of Gata4 in transcription, while excessive ROS targets Gata4 protein for proteasome-dependent degradation. Gata4 is an important modulator balancing the promoting and inhibitory effects of oxidative stress on differentiation program of cardiomyogenesis.
Temporal requirements for ISL1 in sympathetic neuron proliferation, differentiation, and diversification
Authors: Zhang Qingquan , Huang Ru , Ye Youqiong , Guo Xiaoxia , Lu Jun , Zhu Fugui , Gong Xiaohui , Zhang Qitong , Yan Jie , Luo Lina , Zhuang Shaowei , Chen Yihan , Zhao Xiaodong , Evans Sylvia M. , Jiang Cizhong , Liang Xingqun , Sun Yunfu 
Published: February 2018

AbstractMalformations of the sympathetic nervous system have been associated with cardiovascular instability, gastrointestinal dysfunction, and neuroblastoma. A better understanding of the factors regulating sympathetic nervous system development is critical to the development of potential therapies. Here, we have uncovered a temporal requirement for the LIM homeodomain transcription factor ISL1 during sympathetic nervous system development by the analysis of two mutant mouse lines: an Isl1 hypomorphic line and mice with Isl1 ablated in neural crest lineages. During early development, ISL1 is required for sympathetic neuronal fate determination, differentiation, and repression of glial differentiation, although it is dispensable for initial noradrenergic differentiation. ISL1 also plays an essential role in sympathetic neuron proliferation by controlling cell cycle gene expression. During later development, ISL1 is required for axon growth and sympathetic neuron diversification by maintaining noradrenergic differentiation, but repressing cholinergic differentiation. RNA-seq analyses of sympathetic ganglia from Isl1 mutant and control embryos, together with ISL1 ChIP-seq analysis on sympathetic ganglia, demonstrated that ISL1 regulates directly or indirectly several distinct signaling pathways that orchestrate sympathetic neurogenesis. A number of genes implicated in neuroblastoma pathogenesis are direct downstream targets of ISL1. Our study revealed a temporal requirement for ISL1 in multiple aspects of sympathetic neuron development, and suggested Isl1 as a candidate gene for neuroblastoma.
Loss of NDRG2 in liver microenvironment inhibits cancer liver metastasis by regulating tumor associate macrophages polarization
Authors: Li Mengyang , Lai Xiaofeng , Zhao Ying , Zhang Yuan , Li Minghui , Li Danxiu , Kong Jing , Zhang Yong , Jing Pengyu , Li Huichen , Qin Hongyan , Shen Liangliang , Yao Libo , Li Jipeng , Dou Kefeng , Zhang Jian 
Published: February 2018

AbstractThe liver is the predominant metastatic site for several types of malignancies. Tumor-associated macrophages (TAMs) in the liver play crucial roles in the metastasis process. Shifting tumor-promoting M2-like TAMs toward the M1-like phenotype, which exerts tumor suppressor functions via phagocytosis and the secretion of inhibitory factors, may be a potential therapeutic strategy for liver cancer metastasis treatment.We first cloned NDRG2 (N-myc downstream-regulated gene 2) and verified its tumor suppressor role in multiple solid tumors, including colorectal cancer and hepatocellular carcinoma. However, its role in the tumor-associated liver microenvironment, especially in TAMs, has not been illustrated. By establishing a liver cancer metastasis model in wild-type (WT) and Ndrg2 knockout (Ndrg2−/−) mice, we found that the loss of the tumor suppressor Ndrg2 in liver microenvironment significantly suppressed the growth of liver colonies. In addition, this process was accompanied by a higher proportion of M1-like TAM infiltration in Ndrg2−/− mice. Interestingly, bone marrow (BM) transplantation revealed that BM-derived macrophages (BMDMs) rather than liver resident Kupffer cells were responsible for the inhibitory effect. We further demonstrated that loss of Ndrg2 influenced TAM polarization via the NF-κB pathway. Inhibition of IκBα phosphorylation in cancer cell-conditioned medium-stimulated BMDMs decreased M1 marker expression in Ndrg2−/− macrophages. Finally, in vitro, invasion, migration, and proliferation assays confirmed that NF-κB participated in the tumor suppressor function of Ndrg2−/− macrophages. Collectively, our findings highlight the role of NDRG2 in the regulation of TAM polarization and its function in promoting cancer liver metastasis.
Impaired autophagic flux is associated with the severity of trauma and the role of A2AR in brain cells after traumatic brain injury
Authors: Zeng Xu-Jia , Li Ping , Ning Ya-Lei , Zhao Yan , Peng Yan , Yang Nan , Zhao Zi-Ai , Chen Jiang-Fan , Zhou Yuan-Guo 
Published: February 2018

AbstractRecent studies have shown that after traumatic brain injury (TBI), the number of autophagosomes is markedly increased in brain cells surrounding the wound; however, whether autophagy is enhanced or suppressed by TBI remains controversial. In our study, we used a controlled cortical impact system to establish models of mild, moderate and severe TBI. In the mild TBI model, the levels of autophagy-related protein 6 (Beclin1) and autophagy-related protein 12 (ATG12)-autophagy-related protein 5 (ATG5) conjugates were increased, indicating the enhanced initiation of autophagy. Furthermore, the level of the autophagic substrate sequestosome 1 (SQSTM1) was decreased in the ipsilateral cortex. This result, together with the results observed in tandem mRFP-GFP-LC3 adeno-associated virus (AAV)-infected mice, indicates that autophagosome clearance was also increased after mild TBI. Conversely, following moderate and severe TBI, there was no change in the initiation of autophagy, and autophagosome accumulation was observed. Next, we used chloroquine (CQ) to artificially impair autophagic flux in the injured cortex of the mild TBI model and found that the severity of trauma was obviously exacerbated. In addition, autophagic flux and trauma severity were significantly improved in adenosine A2A receptor (A2AR) knockout (KO) mice subjected to moderate TBI. Thus, A2AR may be involved in regulating the impairment of autophagic flux in response to brain injury. Our findings suggest that whether autophagy is increased after TBI is associated with whether autophagic flux is impaired, and the impairment of autophagic flux exacerbates the severity of trauma. Furthermore, A2AR may be a target for alleviating the impairment in autophagic flux after TBI.
Flubendazole inhibits glioma proliferation by G2/M cell cycle arrest and pro-apoptosis
Authors: Zhou Xumin , Liu Jumei , Zhang Jinming , Wei Yong , Li Hua 
Published: February 2018

AbstractFlubendazole, FDA-approved anthelmintic, has been widely used in treating testinal parasites. In the recent years, Flubendazole has been reported to exert anticancer activities. On the other hand, little was known about the effects of Flubendazole on gliomas. Here we demonstrated a novel effect of flubendazole on glioma cells. We found that Flubendazole inhibited cell proliferation and promoted cell apoptosis of glioma cell lines in vitro, and suppressed tumor growth in xenograft models by intraperitoneal injection. However, Flubendazole might have no influence on cell migration. Mechanism study reaveled that Flubendazole caused cell cycle arrest in G2/M phase, which partly account for the suppressed proliferation. Consistently, Flubendazole induced P53 expression and reduced Cyclin B1 and p-cdc2 expression in glioma cells. In addition, Flubendazole promoted cell apoptosis by regulating the classical apoptosis protein BCL-2 expression. These observations suggest that Flubendazole exerts anti-proliferation and pro-apoptosis effects in Glioma through affecting the cell cycle and intrinsic apoptotic signaling, and indicate a novel utilization of Flubendazole in the treatment of Glioma.
Prostaglandin D2 amplifies lupus disease through basophil accumulation in lymphoid organs
Authors: Pellefigues Christophe , Dema Barbara , Lamri Yasmine , Saidoune Fanny , Chavarot Nathalie , Lohéac Charlotte , Pacreau Emeline , Dussiot Michael , Bidault Caroline , Marquet Florian , Jablonski Mathieu , Chemouny Jonathan M. , Jouan Fanny , Dossier Antoine , Chauveheid Marie-Paule , Gobert Delphine , Papo Thomas , Karasuyama Hajime , Sacré Karim , Daugas Eric , Charles Nicolas 
Published: February 2018

AbstractIn systemic lupus erythematosus (SLE), autoantibody production can lead to kidney damage and failure, known as lupus nephritis. Basophils amplify the synthesis of autoantibodies by accumulating in secondary lymphoid organs. Here, we show a role for prostaglandin D2(PGD2) in the pathophysiology of SLE. Patients with SLE have increased expression of PGD2receptors (PTGDR) on blood basophils and increased concentration of PGD2metabolites in plasma. Through an autocrine mechanism dependent on both PTGDRs, PGD2induces the externalization of CXCR4 on basophils, both in humans and mice, driving accumulation in secondary lymphoid organs. Although PGD2can accelerate basophil-dependent disease, antagonizing PTGDRs in mice reduces lupus-like disease in spontaneous and induced mouse models. Our study identifies the PGD2/PTGDR axis as a ready-to-use therapeutic modality in SLE.
Extraction condition optimization and effects of drying methods on physicochemical properties and antioxidant activities of polysaccharides from Astragalus cicer L.
Authors: Shang Hongmei , Wang Menghan , Li Ran , Duan Mengying , Wu Hongxin , Zhou Haizhu 
Published: February 2018

AbstractResponse surface methodology (RSM) including three variables was performed to optimize the extraction parameters of Astragalus cicer L. polysaccharides (ACPs). The influence of different drying techniques on the physicochemical properties and antioxidant abilities of ACPs were evaluated. The ACPs were dried with hot air (HD), vacuum (VD) and freeze drying (FD) methods. The optimal conditions for ACPs extraction were as follows: water to raw material ratio of 25 mL/g, extraction time of 61 min and temperature of 75 °C. Under these parameters, an ACPs yield of 10.97% was obtained. HPLC analysis showed that the monosaccharide compositions of the three ACPs dried with HD, VD or FD techniques were identical. The three ACPs exhibited antioxidant abilities in a concentration-dependent manner. ACPs dried with the FD method (FD-ACPs) had the best antioxidant activities, which might be related to their smaller molecular weight and higher uronic acid content. At the determined concentration of 1 mg/mL, the ferric reducing power, and DPPH and ABTS free radical scavenging capacities of FD-ACPs were 0.762, 75.30% and 99.21%, respectively. Therefore, FD was a good choice for the drying of Astragalus cicer L. polysaccharides.