bluuebunny/crossref_metadata_2025_split huggingface dataset:
The evolution and political use of élite domestic architecture at Poggio Civitate (Murlo)
Authors: Tuck Anthony 
Published: November 2017

The hill of Poggio Civitate is located immediately adjacent to the small mediaeval town of Murlo, c.25 km south of Siena (fig. 1). Situated at the juncture of Tuscany's mineralrich Colline metallifere and the agricultural abundance of the Crete senese, Poggio Civitate's inhabitants drew upon the area's vast resources to emerge as a regional center of power in the 8th through 6th c. B.C.Excavation in 2015 at the Etruscan site revealed a previously undocumented phase of monumental domestic architecture. The building in question lies immediately west of the Piano del Tesoro plateau, in the modern property zone known as Civitate A. Its architectural form, as well as the materials recovered both upon and beneath its floor, suggest that it dates earlier than the architectural complex known on the adjacent plateau.
Possible density dependent local variations in the IMF – CORRIGENDUM
Authors: Kavila Indulekha , George Babitha 
Published: November 2017

In the article by Kavila & George (2016) published in Proceedings IAU Symposium No. 315 there was an error with the author's affiliations. The correct affiliation is:
School of Pure & Applied Physics, Mahatma Gandhi University, KERALA 686560 INDIA email: indulekha@mgu.ac.in, kindulekha@gmail.com
Long non-coding RNA LINC00152 promotes cell proliferation, metastasis, and confers 5-FU resistance in colorectal cancer by inhibiting miR-139-5p
Authors: Bian Zehua , Zhang Jiwei , Li Min , Feng Yuyang , Yao Surui , Song Mingxun , Qi Xiaowei , Fei Bojian , Yin Yuan , Hua Dong , Huang Zhaohui 
Published: November 2017

AbstractLong intergenic non-coding RNA 152 (LINC00152) is a recently identified tumor-promoting long non-coding RNA. However, the biological functions of LINC00152 in colorectal cancer (CRC) remain unclear and require further research. The aim of the present study is to explore the roles of LINC00152 in cellular function and its possible molecular mechanism. In this study, we discovered that LINC00152 was overexpressed in CRC tissues and negatively related to the survival time of CRC patients. Functional analyses revealed that LINC00152 could promote cell proliferation. Furthermore, LINC00152 could increase the resistance of CRC cells to 5-fluorouracil (5-FU) by suppressing apoptosis. We also discovered that LINC00152 could enhance cell migration and invasion. Mechanistic studies demonstrated that LINC00152 could regulate the expression of NOTCH1 through sponging miR-139-5p and inhibiting its activity from promoting CRC progression and development. Altogether, our work points out a novel LINC00152/miR-139-5p/NOTCH1 regulatory axis in CRC progression and development.
Noninvasive liquid diet delivery of stable isotopes into mouse models for deep metabolic network tracing
Authors: Sun Ramon C. , Fan Teresa W.-M. , Deng Pan , Higashi Richard M. , Lane Andrew N. , Le Anh-Thu , Scott Timothy L. , Sun Qiushi , Warmoes Marc O. , Yang Ye 
Published: November 2017

AbstractDelivering isotopic tracers for metabolic studies in rodents without overt stress is challenging. Current methods achieve low label enrichment in proteins and lipids. Here, we report noninvasive introduction of13C6-glucose via a stress-free, ad libitum liquid diet. Using NMR and ion chromatography-mass spectrometry, we quantify extensive13C enrichment in products of glycolysis, the Krebs cycle, the pentose phosphate pathway, nucleobases, UDP-sugars, glycogen, lipids, and proteins in mouse tissues during 12 to 48 h of13C6-glucose feeding. Applying this approach to patient-derived lung tumor xenografts (PDTX), we show that the liver supplies glucose-derived Gln via the blood to the PDTX to fuel Glu and glutathione synthesis while gluconeogenesis occurs in the PDTX. Comparison of PDTX with ex vivo tumor cultures and arsenic-transformed lung cells versus xenografts reveals differential glucose metabolism that could reflect distinct tumor microenvironment. We further found differences in glucose metabolism between the primary PDTX and distant lymph node metastases.
Structure-based design of native-like HIV-1 envelope trimers to silence non-neutralizing epitopes and eliminate CD4 binding
Authors: Kulp Daniel W. , Steichen Jon M. , Pauthner Matthias , Hu Xiaozhen , Schiffner Torben , Liguori Alessia , Cottrell Christopher A. , Havenar-Daughton Colin , Ozorowski Gabriel , Georgeson Erik , Kalyuzhniy Oleksandr , Willis Jordan R. , Kubitz Michael , Adachi Yumiko , Reiss Samantha M. , Shin Mia , de Val Natalia , Ward Andrew B. , Crotty Shane , Burton Dennis R. , Schief William R. 
Published: November 2017

AbstractElicitation of broadly neutralizing antibodies (bnAbs) is a primary HIV vaccine goal. Native-like trimers mimicking virion-associated spikes present nearly all bnAb epitopes and are therefore promising vaccine antigens. However, first generation native-like trimers expose epitopes for non-neutralizing antibodies (non-nAbs), which may hinder bnAb induction. We here employ computational and structure-guided design to develop improved native-like trimers that reduce exposure of non-nAb epitopes in the V3-loop and trimer base, minimize both CD4 reactivity and CD4-induced non-nAb epitope exposure, and increase thermal stability while maintaining bnAb antigenicity. In rabbit immunizations with native-like trimers of the 327c isolate, improved trimers suppress elicitation of V3-directed and tier-1 neutralizing antibodies and induce robust autologous tier-2 neutralization, unlike a first-generation trimer. The improved native-like trimers from diverse HIV isolates, and the design methods, have promise to assist in the development of a HIV vaccine.
A multiplexable TALE-based binary expression system for in vivo cellular interaction studies
Authors: Toegel Markus , Azzam Ghows , Lee Eunice Y. , Knapp David J. H. F. , Tan Ying , Fa Ming , Fulga Tudor A. 
Published: November 2017

AbstractBinary expression systems have revolutionised genetic research by enabling delivery of loss-of-function and gain-of-function transgenes with precise spatial-temporal resolution in vivo. However, at present, each existing platform relies on a defined exogenous transcription activator capable of binding a unique recognition sequence. Consequently, none of these technologies alone can be used to simultaneously target different tissues or cell types in the same organism. Here, we report a modular system based on programmable transcription activator-like effector (TALE) proteins, which enables parallel expression of multiple transgenes in spatially distinct tissues in vivo. Using endogenous enhancers coupled to TALE drivers, we demonstrate multiplexed orthogonal activation of several transgenes carrying cognate variable activating sequences (VAS) in distinct neighbouring cell types of the Drosophila central nervous system. Since the number of combinatorial TALE–VAS pairs is virtually unlimited, this platform provides an experimental framework for highly complex genetic manipulation studies in vivo.
UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells
Authors: Maschalidi Sophia , Nunes-Hasler Paula , Nascimento Clarissa R , Sallent Ignacio , Lannoy Valérie , Garfa-Traore Meriem , Cagnard Nicolas , Sepulveda Fernando E. , Vargas Pablo , Lennon-Duménil Ana-Maria , van Endert Peter , Capiod Thierry , Demaurex Nicolas , Darrasse-Jèze Guillaume , Manoury Bénédicte 
Published: November 2017

AbstractDendritic cells (DC) have the unique ability to present exogenous antigens via the major histocompatibility complex class I pathway to stimulate naive CD8+ T cells. In DCs with a non-functional mutation in Unc93b1 (3d mutation), endosomal acidification, phagosomal maturation, antigen degradation, antigen export to the cytosol and the function of the store-operated-Ca2+-entry regulator STIM1 are impaired. These defects result in compromised antigen cross-presentation and anti-tumor responses in 3d-mutated mice. Here, we show that UNC93B1 interacts with the calcium sensor STIM1 in the endoplasmic reticulum, a critical step for STIM1 oligomerization and activation. Expression of a constitutively active STIM1 mutant, which no longer binds UNC93B1, restores antigen degradation and cross-presentation in 3d-mutated DCs. Furthermore, ablation of STIM1 in mouse and human cells leads to a decrease in cross-presentation. Our data indicate that the UNC93B1 and STIM1 cooperation is important for calcium flux and antigen cross-presentation in DCs.
DNA methylation signatures follow preformed chromatin compartments in cardiac myocytes
Authors: Nothjunge Stephan , Nührenberg Thomas G. , Grüning Björn A. , Doppler Stefanie A. , Preissl Sebastian , Schwaderer Martin , Rommel Carolin , Krane Markus , Hein Lutz , Gilsbach Ralf 
Published: November 2017

AbstractStorage of chromatin in restricted nuclear space requires dense packing while ensuring DNA accessibility. Thus, different layers of chromatin organization and epigenetic control mechanisms exist. Genome-wide chromatin interaction maps revealed large interaction domains (TADs) and higher order A and B compartments, reflecting active and inactive chromatin, respectively. The mutual dependencies between chromatin organization and patterns of epigenetic marks, including DNA methylation, remain poorly understood. Here, we demonstrate that establishment of A/B compartments precedes and defines DNA methylation signatures during differentiation and maturation of cardiac myocytes. Remarkably, dynamic CpG and non-CpG methylation in cardiac myocytes is confined to A compartments. Furthermore, genetic ablation or reduction of DNA methylation in embryonic stem cells or cardiac myocytes, respectively, does not alter genome-wide chromatin organization. Thus, DNA methylation appears to be established in preformed chromatin compartments and may be dispensable for the formation of higher order chromatin organization.
Switching between H- and J-type electronic coupling in single conjugated polymer aggregates
Authors: Eder Theresa , Stangl Thomas , Gmelch Max , Remmerssen Klaas , Laux Dirk , Höger Sigurd , Lupton John M. , Vogelsang Jan 
Published: November 2017

AbstractThe aggregation of conjugated polymers and electronic coupling of chromophores play a central role in the fundamental understanding of light and charge generation processes. Here we report that the predominant coupling in isolated aggregates of conjugated polymers can be switched reversibly between H-type and J-type coupling by partially swelling and drying the aggregates. Aggregation is identified by shifts in photoluminescence energy, changes in vibronic peak ratio, and photoluminescence lifetime. This experiment unravels the internal electronic structure of the aggregate and highlights the importance of the drying process in the final spectroscopic properties. The electronic coupling after drying is tuned between H-type and J-type by changing the side chains of the conjugated polymer, but can also be entirely suppressed. The types of electronic coupling correlate with chain morphology, which is quantified by excitation polarization spectroscopy and the efficiency of interchromophoric energy transfer that is revealed by the degree of single-photon emission.
Biosynthesis of helvolic acid and identification of an unusual C-4-demethylation process distinct from sterol biosynthesis
Authors: Lv Jian-Ming , Hu Dan , Gao Hao , Kushiro Tetsuo , Awakawa Takayoshi , Chen Guo-Dong , Wang Chuan-Xi , Abe Ikuro , Yao Xin-Sheng 
Published: November 2017

AbstractFusidane-type antibiotics represented by helvolic acid, fusidic acid and cephalosporin P1 are a class of bacteriostatic agents, which have drawn renewed attention because they have no cross-resistance to commonly used antibiotics. However, their biosynthesis is poorly understood. Here, we perform a stepwise introduction of the nine genes from the proposed gene cluster for helvolic acid into Aspergillus oryzae NSAR1, which enables us to isolate helvolic acid (~20 mg L−1) and its 21 derivatives. Anti-Staphylococcus aureus assay reveals that the antibacterial activity of three intermediates is even stronger than that of helvolic acid. Notably, we observe an unusual C-4 demethylation process mediated by a promiscuous short-chain dehydrogenase/reductase (HelC) and a cytochrome P450 enzyme (HelB1), which is distinct from the common sterol biosynthesis. These studies have set the stage for using biosynthetic approaches to expand chemical diversity of fusidane-type antibiotics.
Cisplatin is retained in the cochlea indefinitely following chemotherapy
Authors: Breglio Andrew M. , Rusheen Aaron E. , Shide Eric D. , Fernandez Katharine A. , Spielbauer Katie K. , McLachlin Katherine M. , Hall Matthew D. , Amable Lauren , Cunningham Lisa L. 
Published: November 2017

AbstractCisplatin chemotherapy causes permanent hearing loss in 40–80% of treated patients. It is unclear whether the cochlea has unique sensitivity to cisplatin or is exposed to higher levels of the drug. Here we use inductively coupled plasma mass spectrometry (ICP-MS) to examine cisplatin pharmacokinetics in the cochleae of mice and humans. In most organs cisplatin is detected within one hour after injection, and is eliminated over the following days to weeks. In contrast, the cochlea retains cisplatin for months to years after treatment in both mice and humans. Using laser ablation coupled to ICP-MS, we map cisplatin distribution within the human cochlea. Cisplatin accumulation is consistently high in the stria vascularis, the region of the cochlea that maintains the ionic composition of endolymph. Our results demonstrate long-term retention of cisplatin in the human cochlea, and they point to the stria vascularis as an important therapeutic target for preventing cisplatin ototoxicity.
Selenoprotein P-neutralizing antibodies improve insulin secretion and glucose sensitivity in type 2 diabetes mouse models
Authors: Mita Yuichiro , Nakayama Kaho , Inari Shogo , Nishito Yukina , Yoshioka Yuya , Sakai Naoko , Sotani Kanade , Nagamura Takahiro , Kuzuhara Yuki , Inagaki Kumi , Iwasaki Miki , Misu Hirofumi , Ikegawa Masaya , Takamura Toshinari , Noguchi Noriko , Saito Yoshiro 
Published: November 2017

AbstractSelenoprotein P (SeP) functions as a selenium (Se)-supply protein. SeP is identified as a hepatokine, promoting insulin resistance in type 2 diabetes. Thus, the suppression of Se-supply activity of SeP might improve glucose metabolism. Here, we develop an anti-human SeP monoclonal antibody AE2 as with neutralizing activity against SeP. Administration of AE2 to mice significantly improves glucose intolerance and insulin resistance that are induced by human SeP administration. Furthermore, excess SeP administration significantly decreases pancreas insulin levels and high glucose-induced insulin secretion, which are improved by AE2 administration. Epitope mapping reveals that AE2 recognizes a region of human SeP adjacent to the first histidine-rich region (FHR). A polyclonal antibody against the mouse SeP FHR improves glucose intolerance and insulin secretion in a mouse model of diabetes. This report describes a novel molecular strategy for the development of type 2 diabetes therapeutics targeting SeP.
DNA nanomapping using CRISPR-Cas9 as a programmable nanoparticle
Authors: Mikheikin Andrey , Olsen Anita , Leslie Kevin , Russell-Pavier Freddie , Yacoot Andrew , Picco Loren , Payton Oliver , Toor Amir , Chesney Alden , Gimzewski James K. , Mishra Bud , Reed Jason 
Published: November 2017

AbstractProgress in whole-genome sequencing using short-read (e.g., <150 bp), next-generation sequencing technologies has reinvigorated interest in high-resolution physical mapping to fill technical gaps that are not well addressed by sequencing. Here, we report two technical advances in DNA nanotechnology and single-molecule genomics: (1) we describe a labeling technique (CRISPR-Cas9 nanoparticles) for high-speed AFM-based physical mapping of DNA and (2) the first successful demonstration of using DVD optics to image DNA molecules with high-speed AFM. As a proof of principle, we used this new “nanomapping” method to detect and map precisely BCL2–IGH translocations present in lymph node biopsies of follicular lymphoma patents. This HS-AFM “nanomapping” technique can be complementary to both sequencing and other physical mapping approaches.
Optically driven ultra-stable nanomechanical rotor
Authors: Kuhn Stefan , Stickler Benjamin A. , Kosloff Alon , Patolsky Fernando , Hornberger Klaus , Arndt Markus , Millen James 
Published: November 2017

AbstractNanomechanical devices have attracted the interest of a growing interdisciplinary research community, since they can be used as highly sensitive transducers for various physical quantities. Exquisite control over these systems facilitates experiments on the foundations of physics. Here, we demonstrate that an optically trapped silicon nanorod, set into rotation at MHz frequencies, can be locked to an external clock, transducing the properties of the time standard to the rod’s motion with a remarkable frequency stability fr/Δfr of 7.7 × 1011. While the dynamics of this periodically driven rotor generally can be chaotic, we derive and verify that stable limit cycles exist over a surprisingly wide parameter range. This robustness should enable, in principle, measurements of external torques with sensitivities better than 0.25 zNm, even at room temperature. We show that in a dilute gas, real-time phase measurements on the locked nanorod transduce pressure values with a sensitivity of 0.3%.
Intranasal infection and contact transmission of Zika virus in guinea pigs
Authors: Deng Yong-Qiang , Zhang Na-Na , Li Xiao-Feng , Wang Ya-Qing , Tian Min , Qiu Ye-Feng , Fan Jun-Wan , Hao Jia-Nan , Huang Xing-Yao , Dong Hao-Long , Fan Hang , Wang Yu-Guang , Zhang Fu-Chun , Tong Yi-Gang , Xu Zhiheng , Qin Cheng-Feng 
Published: November 2017

AbstractZika virus (ZIKV) is primarily transmitted to humans through mosquito bites or sexual contact. The excretion and persistence of contagious ZIKV in various body fluids have been well documented in ZIKV patients; however, the risk of direct contact exposure remains unclear. Here, we show that guinea pigs are susceptible to ZIKV infection via subcutaneous inoculation route; infected guinea pigs exhibit seroconversion and significant viral secretion in sera, saliva, and tears. Notably, ZIKV is efficiently transmitted from infected guinea pigs to naïve co-caged animals. In particular, intranasal inoculation of ZIKV is fully capable of establishing infection in guinea pigs, and viral antigens are detected in multiple tissues including brain and parotid glands. Cynomolgus macaques also efficiently acquire ZIKV infection via intranasal and intragastric inoculation routes. These collective results from animal models highlight the risk of exposure to ZIKV contaminants and raise the possibility of close contact transmission of ZIKV in humans.
Outcomes of patients with sarcoma enrolled in clinical trials of pazopanib combined with histone deacetylase, mTOR, Her2, or MEK inhibitors
Authors: Dembla Vikas , Groisberg Roman , Hess Ken , Fu Siqing , Wheler Jennifer , Hong David S. , Janku Filip , Zinner Ralph , Piha-Paul Sarina Anne , Ravi Vinod , Benjamin Robert S. , Patel Shreyaskumar , Somaiah Neeta , Herzog Cynthia E. , Karp Daniel D. , Roszik Jason , Meric-Bernstam Funda , Subbiah Vivek 
Published: November 2017

AbstractPazopanib is US FDA approved for the treatment of advanced soft tissue sarcomas. All patients with this disease ultimately develop resistance to therapy. Mechanisms of resistance include activation of the mTOR, histone deacetylase (HDAC), MAPK, and ERBB4 pathways. We hypothesized that combining pazopanib with other targeted agents inhibiting these pathways would increase response rates. We retrospectively evaluated the safety and efficacy of pazopanib plus vorinostat, everolimus, lapatinib or trastuzumab, and MEK inhibitor in patients with advanced sarcoma. The Cancer Geneome Atlas (TCGA) data was analyzed for HDAC, PI3K, HER2, and MAPK/RAS/RAF gene alterations from sarcoma TCGA. Of the 44 advanced sarcoma patients in these trials, 27 (61%) were male; 18 (41%) had bone sarcoma, and 26 (59%) had soft tissue sarcoma. Best response was partial response (PR) in four patients [(overall response rate (ORR) = 9%, 95% confidence interval [CI] 3% to 22%)]. The median progression-free survival (PFS) for all patients was 9.6 weeks (95% CI 8.0 to 15.7 weeks). Analysis of TCGA data revealed HDAC, PI3K, HER2, and MAPK/RAS/RAF gene alterations in 112/243 (46%) of patients predominantly HDAC1–11 (41%) alterations. Pazopanib combinations did demonstrate safety in combination with other agents. TCGA data suggests further evaluation of epigenetic pathway inhibitors in sarcoma.
Whey Protein Concentrate Renders MDA-MB-231 Cells Sensitive to Rapamycin by Altering Cellular Redox State and Activating GSK3β/mTOR Signaling
Authors: Cheng Shih-Hsuan , Tseng Yang-Ming , Wu Szu-Hsien , Tsai Shih-Meng , Tsai Li-Yu 
Published: November 2017

AbstractWhey protein concentrate (WPC) is an amino acid-rich supplement that has been shown to increase cellular antioxidant capacity. Mammalian target of rapamycin (mTOR) is a crucial regulator of signaling in mammalian cells, and serves as a therapeutic target for triple-negative breast cancer (TNBC). This study was designed to investigate the effect of combining WPC with rapamycin on MDA-MB-231 human breast cancer cells. These cells were found to be insensitive to rapamycin and exhibited higher glutathione (GSH) and reactive oxygen species levels than non-tumorigenic MCF-10A cells. However, for MDA-MB-231 cells, the half maximal inhibitory concentration of rapamycin was lower when this drug was administered in combination with WPC than when used alone. Furthermore, combining WPC with rapamycin depleted GSH levels and reduced Nrf2 nuclear accumulation. In addition, WPC activated GSK3β/mTOR signaling, and GSK3β appeared to be involved in the WPC-mediated Nrf2 reduction and mTOR activation. In conclusion, WPC induced rapamycin sensitivity in MDA-MB-231 cells by altering their redox state and activating GSK3β/mTOR signaling. These results not only suggest a novel therapeutic approach for breast cancer treatment, but also provide insight into the critical pathways affecting the resistance to mTOR inhibition observed in a subgroup of TNBC patients.
Detection of Somatic Mutations in Exome Sequencing of Tumor-only Samples
Authors: Hsu Yu-Chin , Hsiao Yu-Ting , Kao Tzu-Yuan , Chang Jan-Gowth , Shieh Grace S. 
Published: November 2017

AbstractDue to lack of normal samples in clinical diagnosis and to reduce costs, detection of small-scale mutations from tumor-only samples is required but remains relatively unexplored. We developed an algorithm (GATKcan) augmenting GATK with two statistics and machine learning to detect mutations in cancer. The averaged performance of GATKcan in ten experiments outperformed GATK in detecting mutations of randomly sampled 231 from 241 TCGA endometrial tumors (EC). In external validations, GATKcan outperformed GATK in TCGA breast cancer (BC), ovarian cancer (OC) and melanoma tumors, in terms of Matthews correlation coefficient (MCC) and precision, where MCC takes both sensitivity and specificity into account. Further, GATKcan reduced high fractions of false positives detected by GATK. In mutation detection of somatic variants, classified commonly by VarScan 2 and MuTect from the called variants in BC, OC and melanoma, ranked by adjusted MCC (adjusted precision) GATKcan was the top 1, followed by MuTect, VarScan 2 and GATK. Importantly, GATKcan enables detection of mutations when alternate alleles exist in normal samples. These results suggest that GATKcan trained by a cancer is able to detect mutations in future patients with the same type of cancer and is likely applicable to other cancers with similar mutations.