bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Galactic magnetic field and its lensing of ultrahigh energy and Galactic cosmic rays
Authors: Farrar Glennys R. 
Published: October 2016

AbstractIt has long been recognized that magnetic fields play an important role in many astrophysical environments, yet the strength and structure of magnetic fields beyond our solar system have been at best only qualitatively constrained. The Galactic magnetic field in particular is crucial for modeling the transport of Galactic CRs, for calculating the background to dark matter and CMB-cosmology studies, and for determining the sources of UHECRs. This report gives a brief overview of recent major advances in our understanding of the Galactic magnetic field (GMF) and its lensing of Galactic and ultrahigh energy cosmic rays.
Which way to the next frontier? Finding the most powerful cluster lenses
Authors: Ebeling Harald ,   the eMACS team
Published: October 2016

AbstractWhile the identification of a worthy topic or challenge is fundamental to the goal of conducting cutting-edge research, another ingredient is indispensable in the field of observational astronomy: the best possible target. Indeed, the ability to choose from a significant number of extremely powerful gravitational lenses was central to the success of the Frontier Fields project. We here briefly review the surveys that provided this crucial pool of targets, before focusing on the results of ongoing work to identify similarly extreme (if not more extreme) systems at higher redshift for the exploration of a yet more distant extragalactic frontier – with JWST and other, evermore ambitious missions.
Spatially resolved spectroscopy of lensed galaxies in the Frontier Fields
Authors: Jones Tucker ,   the GLASS collaboration
Published: October 2016

AbstractThe Grism Lens-Amplified Survey from Space (GLASS) has obtained slitless near-infrared spectroscopy of 10 galaxy clusters selected for their strong lensing properties, including all six Hubble Frontier Fields. Slitless grism spectra are ideal for mapping emission lines such as [O ii], [O iii], and Hα at z=1–3. The combination of strong gravitational lensing and Hubble's diffraction limit provides excellent sensitivity with spatial resolution as fine as 100 pc for highly magnified sources, and ~500 pc for less magnified sources near the edge of the field of view. The GLASS survey represents the largest spectroscopic sample with such high resolution at z > 1. GLASS and Hubble Frontier Field data provide the distribution of stellar mass, star formation, gas-phase metallicity, and other aspects of the physical structure of high redshift galaxies, reaching stellar masses as low as ~107 M⊙ at z=2. I discuss precise measurements of these physical properties and implications for galaxy evolution.
Glioblastoma, hypoxia and autophagy: a survival-prone ‘ménage-à-trois’
Authors: Jawhari Soha , Ratinaud Marie-Hélène , Verdier Mireille 
Published: October 2016

AbstractGlioblastoma multiforme is the most common and the most aggressive primary brain tumor. It is characterized by a high degree of hypoxia and also by a remarkable resistance to therapy because of its adaptation capabilities that include autophagy. This degradation process allows the recycling of cellular components, leading to the formation of metabolic precursors and production of adenosine triphosphate. Hypoxia can induce autophagy through the activation of several autophagy-related proteins such as BNIP3, AMPK, REDD1, PML, and the unfolded protein response-related transcription factors ATF4 and CHOP. This review summarizes the most recent data about induction of autophagy under hypoxic condition and the role of autophagy in glioblastoma.
Melatonin enhances sensitivity to fluorouracil in oesophageal squamous cell carcinoma through inhibition of Erk and Akt pathway
Authors: Lu Yun-Xin , Chen Dong-Liang , Wang De-Shen , Chen Le-Zong , Mo Hai-Yu , Sheng Hui , Bai Long , Wu Qi-Nian , Yu Hong-En , Xie Dan , Yun Jing-Ping , Zeng Zhao-Lei , Wang Feng , Ju Huai-Qiang , Xu Rui-Hua 
Published: October 2016

AbstractOesophageal squamous cell carcinoma (ESCC) is the sixth most common cause of cancer-associated death in the world and novel therapeutic alternatives are urgently warranted. In this study, we investigated the anti-tumour activity and underlying mechanisms of melatonin, an indoleamine compound secreted by the pineal gland as well as naturally occurring plant products, in ESCC cells and revealed that melatonin inhibited proliferation, migration, invasion and induced mitochondria-dependent apoptosis of ESCC cells in vitro and suppressed tumour growth in the subcutaneous mice model in vivo. Furthermore, after treatment with melatonin, the expressions of pMEK, pErk, pGSK3β and pAkt were significantly suppressed. In contrast, treatment of the conventional chemotherapeutic drug fluorouracil (5-Fu) resulted in activation of Erk and Akt, which could be reversed by co-treatment with melatonin. Importantly, melatonin effectively enhanced cytotoxicity of 5-Fu to ESCC in vitro and in vivo. Together, these results suggested that inhibition of Erk and Akt pathway by melatonin have an important role in sensitization of ESCC cells to 5-Fu. Combined 5-Fu and melatonin treatment may be appreciated as a useful approach for ESCC therapy that warrants further investigation.
Metformin protects against apoptosis and senescence in nucleus pulposus cells and ameliorates disc degeneration in vivo
Authors: Chen Deheng , Xia Dongdong , Pan Zongyou , Xu Daoliang , Zhou Yifei , Wu Yaosen , Cai Ningyu , Tang Qian , Wang Chenggui , Yan Meijun , Zhang Jing Jie , Zhou Kailiang , Wang Quan , Feng Yongzeng , Wang Xiangyang , Xu Huazi , Zhang Xiaolei , Tian Naifeng 
Published: October 2016

AbstractIntervertebral disc degeneration (IDD) is a complicated process that involves both cellular apoptosis and senescence. Metformin has been reported to stimulate autophagy, whereas autophagy is shown to protect against apoptosis and senescence. Therefore, we hypothesize that metformin may have therapeutic effect on IDD through autophagy stimulation. The effect of metformin on IDD was investigated both in vitro and in vivo. Our study showed that metformin attenuated cellular apoptosis and senescence induced by tert-butyl hydroperoxide in nucleus pulposus cells. Autophagy, as well as its upstream regulator AMPK, was activated by metformin in nucleus pulposus cells in a dose- and time-dependent manner. Inhibition of autophagy by 3-MA partially abolished the protective effect of metformin against nucleus pulposus cells’ apoptosis and senescence, indicating that autophagy was involved in the protective effect of metformin on IDD. In addition, metformin was shown to promote the expression of anabolic genes such as Col2a1 and Acan expression while inhibiting the expression of catabolic genes such as Mmp3 and Adamts5 in nucleus pulposus cells. In vivo study illustrated that metformin treatment could ameliorate IDD in a puncture-induced rat model. Thus, our study showed that metformin could protect nucleus pulposus cells against apoptosis and senescence via autophagy stimulation and ameliorate disc degeneration in vivo, revealing its potential to be a therapeutic agent for IDD.
Desferrioxamine reduces ultrahigh-molecular-weight polyethylene-induced osteolysis by restraining inflammatory osteoclastogenesis via heme oxygenase-1
Authors: Kang Hui , Yan Yufei , Jia Peng , Yang Kai , Guo Changjun , Chen Hao , Qi Jin , Qian Niandong , Xu Xing , Wang Fei , Li Changwei , Guo Lei , Deng Lianfu 
Published: October 2016

AbstractAs wear particles-induced osteolysis still remains the leading cause of early implant loosening in endoprosthetic surgery, and promotion of osteoclastogenesis by wear particles has been confirmed to be responsible for osteolysis. Therapeutic agents targeting osteoclasts formation are considered for the treatment of wear particles-induced osteolysis. In the present study, we demonstrated for the first time that desferrioxamine (DFO), a powerful iron chelator, could significantly alleviate osteolysis in an ultrahigh-molecular-weight polyethylene (UHMWPE) particles-induced mice calvaria osteolysis model. Furthermore, DFO attenuated calvaria osteolysis by restraining enhanced inflammatory osteoclastogenesis induced by UHMWPE particles. Consistent with the in vivo results, we found DFO was also able to inhibit osteoclastogenesis in a dose-dependent manner in vitro, as evidenced by reduction of osteoclasts formation and suppression of osteoclast specific genes expression. In addition, DFO dampened osteoclasts differentiation and formation at early stage but not at late stage. Mechanistically, the reduction of osteoclastogenesis by DFO was due to increased heme oxygenase-1 (HO-1) expression, as decreased osteoclasts formation induced by DFO was significantly restored after HO-1 was silenced by siRNA, while HO-1 agonist COPP treatment enhanced DFO-induced osteoclastogenesis inhibition. In addition, blocking of p38 mitogen-activated protein kinase (p38MAPK) signaling pathway promoted DFO-induced HO-1 expression, implicating that p38 signaling pathway was involved in DFO-mediated HO-1 expression. Taken together, our results suggested that DFO inhibited UHMWPE particles-induced osteolysis by restraining inflammatory osteoclastogenesis through upregulation of HO-1 via p38MAPK pathway. Thus, DFO might be used as an innovative and safe therapeutic alternative for treating wear particles-induced aseptic loosening.
Increased expression of EHF via gene amplification contributes to the activation of HER family signaling and associates with poor survival in gastric cancer
Authors: Shi Jing , Qu Yiping , Li Xinru , Sui Fang , Yao Demao , Yang Qi , Shi Bingyin , Ji Meiju , Hou Peng 
Published: October 2016

AbstractThe biological function of E26 transformation-specific (ETS) transcription factor EHF/ESE-3 in human cancers remains largely unknown, particularly gastric cancer. The aim of this study was to explore the role of EHF in tumorigenesis and its potential as a therapeutic target in gastric cancer. By using quantitative RT-PCR (qRT-PCR), immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays, we investigated the expression and copy number of EHF in a cohort of gastric cancers and control subjects. Specific EHF siRNAs was used to determine the biologic impacts and mechanisms of altered EHF expression in vitro and in vivo. Dual-luciferase reporter, chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) assays were performed to identify its downstream targets. Our results demonstrated that EHF was significantly upregulated and frequently amplified in gastric cancer tissues as compared with control subjects. Moreover, EHF amplification was positively correlated with its overexpression and significantly associated with poor clinical outcomes of gastric cancer patients. We also found that EHF knockdown notably inhibited gastric cancer cell proliferation, colony formation, migration, invasion and tumorigenic potential in nude mice and induced cell cycle arrest and apoptosis. Importantly, we identified EHF as a new HER2 transcription factor and the modulator of HER3 and HER4 in gastric cancer. Collectively, our findings suggest that EHF is a novel functional oncogene in gastric cancer by regulating the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases and may represent a potential prognostic marker and therapeutic target for this cancer.
T cell receptor recognition of CD1b presenting a mycobacterial glycolipid
Authors: Gras Stephanie , Van Rhijn Ildiko , Shahine Adam , Cheng Tan-Yun , Bhati Mugdha , Tan Li Lynn , Halim Hanim , Tuttle Kathryn D. , Gapin Laurent , Le Nours Jérôme , Moody D. Branch , Rossjohn Jamie 
Published: October 2016

AbstractCD1 proteins present microbial lipids to T cells. Germline-encoded mycolyl lipid-reactive (GEM) T cells with conserved αβ T cell receptors (TCRs) recognize CD1b presenting mycobacterial mycolates. As the molecular basis underpinning TCR recognition of CD1b remains unknown, here we determine the structure of a GEM TCR bound to CD1b presenting glucose-6-O-monomycolate (GMM). The GEM TCR docks centrally above CD1b, whereby the conserved TCR α-chain extensively contacts CD1b and GMM. Through mutagenesis and study of T cells from tuberculosis patients, we identify a consensus CD1b footprint of TCRs present among GEM T cells. Using both the TCR α- and β-chains as tweezers to surround and grip the glucose moiety of GMM, GEM TCRs create a highly specific mechanism for recognizing this mycobacterial glycolipid.
Engineered AAA+ proteases reveal principles of proteolysis at the mitochondrial inner membrane
Authors: Shi Hui , Rampello Anthony J. , Glynn Steven E. 
Published: October 2016

AbstractThe human YME1L protease is a membrane-anchored AAA+ enzyme that controls proteostasis at the inner membrane and intermembrane space of mitochondria. Understanding how YME1L recognizes substrates and catalyses ATP-dependent degradation has been hampered by the presence of an insoluble transmembrane anchor that drives hexamerization of the catalytic domains to form the ATPase active sites. Here, we overcome this limitation by replacing the transmembrane domain with a soluble hexameric coiled coil to produce active YME1L hexamers that can be studied in vitro. We use these engineered proteases to reveal principles of substrate processing by YME1L. Degradation by YME1L requires substrates to present an accessible signal sequence and is not initiated simply by substrate unfolding. The protease is also capable of processively unfolding substrate proteins with substantial thermodynamic stabilities. Lastly, we show that YME1L discriminates between degradation signals by amino acid composition, implying the use of sequence-specific signals in mitochondrial proteostasis.
Delayed electron emission in strong-field driven tunnelling from a metallic nanotip in the multi-electron regime
Authors: Yanagisawa Hirofumi , Schnepp Sascha , Hafner Christian , Hengsberger Matthias , Kim Dong Eon , Kling Matthias F. , Landsman Alexandra , Gallmann Lukas , Osterwalder Jürg 
Published: October 2016

AbstractIlluminating a nano-sized metallic tip with ultrashort laser pulses leads to the emission of electrons due to multiphoton excitations. As optical fields become stronger, tunnelling emission directly from the Fermi level becomes prevalent. This can generate coherent electron waves in vacuum leading to a variety of attosecond phenomena. Working at high emission currents where multi-electron effects are significant, we were able to characterize the transition from one regime to the other. Specifically, we found that the onset of laser-driven tunnelling emission is heralded by the appearance of a peculiar delayed emission channel. In this channel, the electrons emitted via laser-driven tunnelling emission are driven back into the metal, and some of the electrons reappear in the vacuum with some delay time after undergoing inelastic scattering and cascading processes inside the metal. Our understanding of these processes gives insights on attosecond tunnelling emission from solids and should prove useful in designing new types of pulsed electron sources.
Mechanisms on the morphology variation of hematite crystals by Al substitution: The modification of Fe and O reticular densities
Authors: Li Wei , Liang Xiaoliang , An Pengfei , Feng Xionghan , Tan Wenfeng , Qiu Guohong , Yin Hui , Liu Fan 
Published: October 2016

AbstractAl substitution in hematite is ubiquitous in soils. With the increase of Al amount, the hematite morphology changes from rhombohedral crystals to disk-shaped ones, but the underlying mechanism is poorly understood. Herein, a series of Al-substituted hematite were synthesized and characterized by synchrotron X-ray diffraction (SXRD), field emission scanning electron microscopy (FESEM), high resolution electron transmission microscopy (HRTEM) and extended X-ray absorption fine structure (EXAFS) spectroscopy, to investigate the effects of Al3+ substitution on the hematite structure and morphology. EXAFS and Rietveld structural refinement analyses find an increase in face-sharing (along c axis) Fe-Me (Me = Al, Fe) distances, edge-sharing (in a-b plane) Fe-Me (Me = Al, Fe) distances, and O-O average distances. Moreover, the face-sharing Fe-Me distances and O-O distances along c axis increase more significantly. This indicates a more apparent decrease in the reticular densities of Fe and O along the direction of c axis, which facilitates faster crystal growth along c axis and results in the evolution of morphology of Al-substituted hematite to disk-shaped crystals. The above results provide new insights into the morphology changes and environmental geochemistry behaviors of Al-contained hematite in soils, and are benefit for the control of crystal morphologies during its application as environmentally-friendly materials.
NOGO-A/RTN4A and NOGO-B/RTN4B are simultaneously expressed in epithelial, fibroblast and neuronal cells and maintain ER morphology
Authors: Rämö Olli , Kumar Darshan , Gucciardo Erika , Joensuu Merja , Saarekas Maiju , Vihinen Helena , Belevich Ilya , Smolander Olli-Pekka , Qian Kui , Auvinen Petri , Jokitalo Eija 
Published: October 2016

AbstractReticulons (RTNs) are a large family of membrane associated proteins with various functions. NOGO-A/RTN4A has a well-known function in limiting neurite outgrowth and restricting the plasticity of the mammalian central nervous system. On the other hand, Reticulon 4 proteins were shown to be involved in forming and maintaining endoplasmic reticulum (ER) tubules. Using comparative transcriptome analysis and qPCR, we show here that NOGO-B/RTN4B and NOGO-A/RTN4A are simultaneously expressed in cultured epithelial, fibroblast and neuronal cells. Electron tomography combined with immunolabelling reveal that both isoforms localize preferably to curved membranes on ER tubules and sheet edges. Morphological analysis of cells with manipulated levels of NOGO-B/RTN4B revealed that it is required for maintenance of normal ER shape; over-expression changes the sheet/tubule balance strongly towards tubules and causes the deformation of the cell shape while depletion of the protein induces formation of large peripheral ER sheets.
Hi-C-constrained physical models of human chromosomes recover functionally-related properties of genome organization
Authors: Di Stefano Marco , Paulsen Jonas , Lien Tonje G. , Hovig Eivind , Micheletti Cristian 
Published: October 2016

AbstractCombining genome-wide structural models with phenomenological data is at the forefront of efforts to understand the organizational principles regulating the human genome. Here, we use chromosome-chromosome contact data as knowledge-based constraints for large-scale three-dimensional models of the human diploid genome. The resulting models remain minimally entangled and acquire several functional features that are observedin vivoand that were never used as input for the model. We find, for instance, that gene-rich, active regions are drawn towards the nuclear center, while gene poor and lamina associated domains are pushed to the periphery. These and other properties persist upon adding local contact constraints, suggesting their compatibility with non-local constraints for the genome organization. The results show that suitable combinations of data analysis and physical modelling can expose the unexpectedly rich functionally-related properties implicit in chromosome-chromosome contact data. Specific directions are suggested for further developments based on combining experimental data analysis and genomic structural modelling.
Surgical technique for allogeneic uterus transplantation in macaques
Authors: Obara Hideaki , Kisu Iori , Kato Yojiro , Yamada Yohei , Matsubara Kentaro , Emoto Katsura , Adachi Masataka , Matoba Yusuke , Umene Kiyoko , Nogami Yuya , Banno Kouji , Tsuchiya Hideaki , Itagaki Iori , Kawamoto Ikuo , Nakagawa Takahiro , Ishigaki Hirohito , Itoh Yasushi , Ogasawara Kazumasa , Saiki Yoko , Sato Shin-ichi , Nakagawa Kenshi , Shiina Takashi , Aoki Daisuke , Kitagawa Yuko 
Published: October 2016

AbstractNo study has reported an animal model of uterus transplantation (UTx) using cynomolgus macaques. We aimed to establish a surgical technique of allogeneic UTx assuming the recovery of a uterus from a deceased donor in cynomolgus macaques. Four allogeneic UTxs were performed in female cynomolgus macaques. Donor surgeries comprised en bloc recovery of organs with iliac vessels on both sides, and/or abdominal aorta/vena cava after sufficient perfusion from one femoral artery or external iliac artery. Before perfusion, 150 mL of whole blood was obtained from the donor for subsequent blood transfusion to the recipient. Four uterine grafts were orthotopically transplanted to recipients. End-to-side anastomosis was performed to the iliac vessels on one side in case 1 and iliac vessels on both sides in case 2; aorto-aorto/cavo-caval anastomosis was performed in cases 3 and 4. Arterial blood flow of the uterine grafts was determined by intraoperative indocyanine green (ICG) angiography. ICG angiography results showed sufficient blood flow to all uterine grafts, and anaemia did not progress. Under appropriate immune suppression, all recipients survived for more than 90 days post-transplantation, without any surgical complications. We describe a surgical technique for allogeneic UTx in cynomolgus macaques.
Available sustainable alternatives replace endangered animal horn based on their proteomic analysis and bio-effect evaluation
Authors: Liu Rui , Wang Fei , Huang Qiong , Duan Jin-ao , Liu Pei , Shang Erxin , Zhu Dong , Wen Hongmei , Qian Dawei 
Published: October 2016

AbstractThe use of endangered animal products in traditional Chinese medicine (TCM) and other ethno-medicines is culturally widespread across many regions of Asia. In the present study, traditional efficacies of seven types of animal horn including antipyretic, sedative and procoagulant activities were evaluated. Shotgun proteomic analysis was performed on material from horns following separation into soluble and insoluble fractions. Over 200 proteins were identified in each sample using nano LC-MS/MS, and these were classified according to their molecular function and cellular component using principal component analysis (PCA). The results indicated that seven horns showed antipyretic, sedative and procoagulant effect. Proteomic analysis showed that YH and WBH were similar to RH in terms of protein profile, and GH was similar to SAH. In addition, YH and GH were similar to RH in their cellular component classification profile. PCA based on the composition of keratin and keratin-associated proteins showed that constituents of WBH and GH were similar to RH and SAH, respectively. This is the first analysis of the protein content of animal horns used in TCM, and it is effective to substitute the horn of endangered animals with sustainable alternatives from domestic animals.