bluuebunny/crossref_metadata_2025 huggingface dataset:
Contested evidence: a Dutch reimbursement decision taken to court
Authors: Moes Floortje , Houwaart Eddy , Delnoij Diana , Horstman Klasien
Published: November 2016

This paper examines a remarkable lawsuit in health care rationing. The Patients Association for Interstitial Cystitis sued the Dutch National Health Care Institute for alleged misconduct against Interstitial Cystitis patients, as the Institute decided that bladder instillations with chondroitin sulphate or hyaluronic acid are no longer covered by the basic health insurance. The patients’ organisation challenged the Institute for basing its standpoint on scientific evidence; overruling clinical expertise and patients’ experiences. While scientific advice is often solicited in public health issues, simultaneously, the authority of scientific advice is increasingly being questioned in the public domain. Also, the judiciary is frequently called upon to adjudicate in rationing decisions. Based on an ethnographic study of the National Health Care Institute, drawing on insights from the field of Science and Technology Studies, we analyse this lawsuit as a negotiation of what knowledge counts in reimbursement decisions.
Teaching Sensitive Topics in the Secondary Classics Classroom
Authors: Hunt Steven
Published: November 2016

This article examines how a number of teachers of Classics at secondary school level say they deal with sensitive topics, such as violence, religious belief, death and sex and sexuality. In the secondary school original texts are read partly for improving the students' understanding of the language and partly for the study of other aspects of the ancient society, such as the subject matter and the process of a legal case, for example. Therefore, sensitive topics often arise incidentally during the reading of a text rather than because they are the particular feature of the reading. Should teachers brush past such an topic for fear of causing offence or getting into trouble with school authorities or parents, or should they use the topic to develop their students' understanding of the topic at hand – and if the latter, how far should they go?
Coastal Observations from a New Vantage Point
Authors: Salisbury Joseph , Davis Curtiss , Erb Angela , Hu Chuanmin , Gatebe Charles , Jordan Carolyn , Lee Zhongping , Mannino Antonio , Mouw Colleen , Schaaf Crystal , Schaeffer Blake , Tzortziou Maria
Published: November 2016

The NASA Geostationary Coastal and Air Pollution Events satellite mission plans to keep an eye on short-term processes that affect coastal communities and ecosystems.
Carbon Tax Initiative Fails in Washington State
Authors: Heisman Rebecca
Published: November 2016

Environmental groups were divided over the nation's first carbon tax ballot measure.
NANOG reprograms prostate cancer cells to castration resistance via dynamically repressing and engaging the AR/FOXA1 signaling axis
Authors: Jeter Collene R , Liu Bigang , Lu Yue , Chao Hsueh-Ping , Zhang Dingxiao , Liu Xin , Chen Xin , Li Qiuhui , Rycaj Kiera , Calhoun-Davis Tammy , Yan Li , Hu Qiang , Wang Jianmin , Shen Jianjun , Liu Song , Tang Dean G
Published: November 2016

The pluripotency transcription factor NANOG has been implicated in tumor development, and NANOG-expressing cancer cells manifest stem cell properties that sustain tumor homeostasis, mediate therapy resistance and fuel tumor progression. However, how NANOG converges on somatic circuitry to trigger oncogenic reprogramming remains obscure. We previously reported that inducible NANOG expression propels the emergence of aggressive castration-resistant prostate cancer phenotypes. Here we first show that endogenous NANOG is required for the growth of castration-resistant prostate cancer xenografts. Genome-wide chromatin immunoprecipitation sequencing coupled with biochemical assays unexpectedly reveals that NANOG co-occupies a distinctive proportion of androgen receptor/Forkhead box A1 genomic loci and physically interacts with androgen receptor and Forkhead box A1. Integrative analysis of chromatin immunoprecipitation sequencing and time-resolved RNA sequencing demonstrates that NANOG dynamically alters androgen receptor/Forkhead box A1 signaling leading to both repression of androgen receptor-regulated pro-differentiation genes and induction of genes associated with cell cycle, stem cells, cell motility and castration resistance. Our studies reveal global molecular mechanisms whereby NANOG reprograms prostate cancer cells to a clinically relevant castration-resistant stem cell-like state driven by distinct NANOG-regulated gene clusters that correlate with patient survival. Thus, reprogramming factors such as NANOG may converge on and alter lineage-specific master transcription factors broadly in somatic cancers, thereby facilitating malignant disease progression and providing a novel route for therapeutic resistance.
Multidimensional heritability analysis of neuroanatomical shape
Authors: Ge Tian , Reuter Martin , Winkler Anderson M. , Holmes Avram J. , Lee Phil H. , Tirrell Lee S. , Roffman Joshua L. , Buckner Randy L. , Smoller Jordan W. , Sabuncu Mert R.
Published: November 2016

In the dawning era of large-scale biomedical data, multidimensional phenotype vectors will play an increasing role in examining the genetic underpinnings of brain features, behaviour and disease. For example, shape measurements derived from brain MRI scans are multidimensional geometric descriptions of brain structure and provide an alternate class of phenotypes that remains largely unexplored in genetic studies. Here we extend the concept of heritability to multidimensional traits, and present the first comprehensive analysis of the heritability of neuroanatomical shape measurements across an ensemble of brain structures based on genome-wide SNP and MRI data from 1,320 unrelated, young and healthy individuals. We replicate our findings in an extended twin sample from the Human Connectome Project (HCP). Our results demonstrate that neuroanatomical shape can be significantly heritable, above and beyond volume, and can serve as a complementary phenotype to study the genetic determinants and clinical relevance of brain structure.
Smectic phase in suspensions of gapped DNA duplexes
Authors: Salamonczyk Miroslaw , Zhang Jing , Portale Giuseppe , Zhu Chenhui , Kentzinger Emmanuel , Gleeson James T. , Jakli Antal , De Michele Cristiano , Dhont Jan K. G. , Sprunt Samuel , Stiakakis Emmanuel
Published: November 2016

Smectic ordering in aqueous solutions of monodisperse stiff double-stranded DNA fragments is known not to occur, despite the fact that these systems exhibit both chiral nematic and columnar mesophases. Here, we show, unambiguously, that a smectic-A type of phase is formed by increasing the DNA’s flexibility through the introduction of an unpaired single-stranded DNA spacer in the middle of each duplex. This is unusual for a lyotropic system, where flexibility typically destabilizes the smectic phase. We also report on simulations suggesting that the gapped duplexes (resembling chain-sticks) attain a folded conformation in the smectic layers, and argue that this layer structure, which we designate as smectic-fA phase, is thermodynamically stabilized by both entropic and energetic contributions to the system’s free energy. Our results demonstrate that DNA as a building block offers an exquisitely tunable means to engineer a potentially rich assortment of lyotropic liquid crystals.
Bivalence Mn5O8 with hydroxylated interphase for high-voltage aqueous sodium-ion storage
Authors: Shan Xiaoqiang , Charles Daniel S. , Lei Yinkai , Qiao Ruimin , Wang Guofeng , Yang Wanli , Feygenson Mikhail , Su Dong , Teng Xiaowei
Published: November 2016

Aqueous electrochemical energy storage devices have attracted significant attention owing to their high safety, low cost and environmental friendliness. However, their applications have been limited by a narrow potential window (∼1.23 V), beyond which the hydrogen and oxygen evolution reactions occur. Here we report the formation of layered Mn5O8 pseudocapacitor electrode material with a well-ordered hydroxylated interphase. A symmetric full cell using such electrodes demonstrates a stable potential window of 3.0 V in an aqueous electrolyte, as well as high energy and power performance, nearly 100% coulombic efficiency and 85% energy efficiency after 25,000 charge–discharge cycles. The interplay between hydroxylated interphase on the surface and the unique bivalence structure of Mn5O8 suppresses the gas evolution reactions, offers a two-electron charge transfer via Mn2+/Mn4+ redox couple, and provides facile pathway for Na-ion transport via intra-/inter-layer defects of Mn5O8.
BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity
Authors: Rasmussen Rikke D. , Gajjar Madhavsai K. , Tuckova Lucie , Jensen Kamilla E. , Maya-Mendoza Apolinar , Holst Camilla B. , Møllgaard Kjeld , Rasmussen Jane S. , Brennum Jannick , Bartek Jiri , Syrucek Martin , Sedlakova Eva , Andersen Klaus K. , Frederiksen Marie H. , Bartek Jiri , Hamerlik Petra
Published: November 2016

Oncogene-evoked replication stress (RS) fuels genomic instability in diverse cancer types. Here we report that BRCA1, traditionally regarded a tumour suppressor, plays an unexpected tumour-promoting role in glioblastoma (GBM), safeguarding a protective response to supraphysiological RS levels. Higher BRCA1 positivity is associated with shorter survival of glioma patients and the abrogation of BRCA1 function in GBM enhances RS, DNA damage (DD) accumulation and impairs tumour growth. Mechanistically, we identify a novel role of BRCA1 as a transcriptional co-activator of RRM2 (catalytic subunit of ribonucleotide reductase), whereby BRCA1-mediated RRM2 expression protects GBM cells from endogenous RS, DD and apoptosis. Notably, we show that treatment with a RRM2 inhibitor triapine reproduces the BRCA1-depletion GBM-repressive phenotypes and sensitizes GBM cells to PARP inhibition. We propose that GBM cells are addicted to the RS-protective role of the BRCA1-RRM2 axis, targeting of which may represent a novel paradigm for therapeutic intervention in GBM.
Massively parallel sequencing analysis of synchronous fibroepithelial lesions supports the concept of progression from fibroadenoma to phyllodes tumor
Authors: Piscuoglio Salvatore , Geyer Felipe C , Burke Kathleen A , Murray Melissa P , Ng Charlotte KY , Mota Alba , Marchio Caterina , Berman Samuel H , Norton Larry , Brogi Edi , Weigelt Britta , Reis-Filho Jorge S
Published: November 2016

Phyllodes tumors (PTs) and fibroadenomas (FAs) are fibroepithelial lesions (FELs) of the breast. Although mutations affecting exon 2 of MED12 are highly recurrent in FAs and PTs, TERT promoter hotspot mutations are frequently found in PTs but are vanishingly rare in FAs. Malignant transformation of benign PTs is well-documented, but the progression from FA to PT remains a matter of contention. Here we report on the somatic genetic alterations in multiple ipsilateral synchronous FELs (three FAs, one benign PT, and one malignant PT) occurring in the same patient. DNA samples extracted from each tumor and matched normal tissue were subjected to targeted massively parallel sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay. This analysis revealed MED12 mutations in all lesions. One FA and the benign PT harbored a MED12Gly44Val mutation, whereas another FA and the malignant PT displayed a MED12Gly44Asp mutation. The remaining FA had an independent distinct MED12Gly44Cys mutation. A formal clonality analysis suggested a clonal relationship between the FELs with identical MED12 mutations (P<0.05). A clonal TERT promoter hotspot mutation was identified exclusively in the malignant PT. The identification of distinct MED12 mutations in multifocal ipsilateral and synchronous FELs supports the notion that co-existing mammary fibroepithelial tumors can arise independently. Conversely, the co-existence of identical MED12 mutations indicates clonal relatedness among FAs and PTs, corroborating the hypothesis that FAs may constitute the substrate from which PTs develop. Our findings also support the notion that acquisition of TERT promoter mutations may drive the progression of FELs.
An efficient cell free enzyme-based total synthesis of a meningococcal vaccine candidate
Authors: Fiebig Timm , Romano Maria Rosaria , Oldrini Davide , Adamo Roberto , Tontini Marta , Brogioni Barbara , Santini Laura , Berger Monika , Costantino Paolo , Berti Francesco , Gerardy-Schahn Rita
Published: November 2016

Invasive meningococcal disease (IMD) is a global health problem and vaccination has proven the most effective way of disease control. Neisseria meningitidis serogroup X (NmX) is an emerging threat in the African sub-Saharan meningitis belt, but no vaccine is available today. Leading vaccines against Nm are glycoconjugates, in which capsular polysaccharides isolated from large-scale pathogen cultures are conjugated to adjuvant proteins. Though safe and efficacious even in infants, high costs and biohazard associated with the production limit abundant application of glycoconjugate vaccines particularly in the most afflicted nations. An existing NmX vaccine candidate (CPSXn-CRM197) produced by established protocols from NmX capsule polysaccharide (CPSX) has been shown to elicit high bactericidal immunoglobulin G titres in mice. Here we describe the scalable in vitro synthesis of CPSXiv from chemically pure precursors by the use of recombinant NmX capsule polymerase. Application of the described coupling chemistry gives CPSXiv-CRM197, which in mouse vaccination experiments behaves identical to the benchmark CPSXn-CRM197. Excluding any biohazards, this novel process represents a paradigm shift in vaccine production and a premise towards vaccine manufacturing in emerging economies.
Habitual coffee consumption and risk of type 2 diabetes, ischemic heart disease, depression and Alzheimer’s disease: a Mendelian randomization study
Authors: Kwok Man Ki , Leung Gabriel M. , Schooling C. Mary
Published: November 2016

Observationally, coffee is inversely associated with type 2 diabetes mellitus (T2DM), depression and Alzheimer’s disease, but not ischemic heart disease (IHD). Coffee features as possibly protective in the 2015 Dietary Guidelines for Americans. Short-term trials suggest coffee has neutral effect on most glycemic traits, but raises lipids and adiponectin. To clarify we compared T2DM, depression, Alzheimer’s disease, and IHD and its risk factors by genetically predicted coffee consumption using two-sample Mendelian randomization applied to large extensively genotyped case-control and cross-sectional studies. Childhood cognition was used as a negative control outcome. Genetically predicted coffee consumption was not associated with T2DM (odds ratio (OR) 1.02, 95% confidence interval (CI) 0.76 to 1.36), depression (0.89, 95% CI 0.66 to 1.21), Alzheimer’s disease (1.17, 95% CI 0.96 to 1.43), IHD (0.96, 95% CI 0.80 to 1.14), lipids, glycemic traits, adiposity or adiponectin. Coffee was unrelated to childhood cognition. Consistent with observational studies, coffee was unrelated to IHD, and, as expected, childhood cognition. However, contrary to observational findings, coffee may not have beneficial effects on T2DM, depression or Alzheimer’s disease. These findings clarify the role of coffee with relevance to dietary guidelines and suggest interventions to prevent these complex chronic diseases should be sought elsewhere.
Gesture recognition by instantaneous surface EMG images
Authors: Geng Weidong , Du Yu , Jin Wenguang , Wei Wentao , Hu Yu , Li Jiajun
Published: November 2016

Gesture recognition in non-intrusive muscle-computer interfaces is usually based on windowed descriptive and discriminatory surface electromyography (sEMG) features because the recorded amplitude of a myoelectric signal may rapidly fluctuate between voltages above and below zero. Here, we present that the patterns inside the instantaneous values of high-density sEMG enables gesture recognition to be performed merely with sEMG signals at a specific instant. We introduce the concept of an sEMG image spatially composed from high-density sEMG and verify our findings from a computational perspective with experiments on gesture recognition based on sEMG images with a classification scheme of a deep convolutional network. Without any windowed features, the resultant recognition accuracy of an 8-gesture within-subject test reached 89.3% on a single frame of sEMG image and reached 99.0% using simple majority voting over 40 frames with a 1,000 Hz sampling rate. Experiments on the recognition of 52 gestures of NinaPro database and 27 gestures of CSL-HDEMG database also validated that our approach outperforms state-of-the-arts methods. Our findings are a starting point for the development of more fluid and natural muscle-computer interfaces with very little observational latency. For example, active prostheses and exoskeletons based on high-density electrodes could be controlled with instantaneous responses.
Non-uniform Evolving Hypergraphs and Weighted Evolving Hypergraphs
Authors: Guo Jin-Li , Zhu Xin-Yun , Suo Qi , Forrest Jeffrey
Published: November 2016

Firstly, this paper proposes a non-uniform evolving hypergraph model with nonlinear preferential attachment and an attractiveness. This model allows nodes to arrive in batches according to a Poisson process and to form hyperedges with existing batches of nodes. Both the number of arriving nodes and that of chosen existing nodes are random variables so that the size of each hyperedge is non-uniform. This paper establishes the characteristic equation of hyperdegrees, calculates changes in the hyperdegree of each node, and obtains the stationary average hyperdegree distribution of the model by employing the Poisson process theory and the characteristic equation. Secondly, this paper constructs a model for weighted evolving hypergraphs that couples the establishment of new hyperedges, nodes and the dynamical evolution of the weights. Furthermore, what is obtained are respectively the stationary average hyperdegree and hyperstrength distributions by using the hyperdegree distribution of the established unweighted model above so that the weighted evolving hypergraph exhibits a scale-free behavior for both hyperdegree and hyperstrength distributions.
Occurrence and source apportionment of Per- and poly-fluorinated compounds (PFCs) in North Canal Basin, Beijing
Authors: Zhang Yi-Zhe , Wang Bin , Wang Wei , Li Wen-Chao , Huang Jun , Deng Shu-Bo , Wang Yu-Jue , Yu Gang
Published: November 2016

Various per- and poly-fluorinated compounds (PFCs) were first systematically investigated in North Canal Basin, Beijing, China. A total of 68 surface water samples were collected from North Canal Basin, Beijing, at high spatial resolution. The seasonal disparity was compared and associated with source variation. PFCs concentrations in low-water period ranged from 26 to 207 ng/L, and significantly declined levels were found in high-water period. The individual component proportions among different sites varied less in high-water period, when runoff played a role in mixing and diluting PFCs. A methodology combined with principal component analysis (PCA), heat map-hierarchical cluster analysis (HM-HCA), and correlation analysis were introduced to discriminate sources of PFCs in surface water. The statistical results agreed with each other, and daily domestic consumption, fire-fighting products and related industries were identified as sources of PFCs in this region. In addition, two composition ratios were proposed through the methodology to distinguish the impact of nonpoint source, and the outcome demonstrates that great disparities exist in compositional profiles between nonpoint source and others. Overall, the results showed that this comprehensive analysis method has great potential for source apportionment in surface water and other environmental compartments.
Evidence for strong, widespread chlorine radical chemistry associated with pollution outflow from continental Asia
Authors: Baker Angela K. , Sauvage Carina , Thorenz Ute R. , van Velthoven Peter , Oram David E. , Zahn Andreas , Brenninkmeijer Carl A. M. , Williams Jonathan
Published: November 2016

The chlorine radical is a potent atmospheric oxidant, capable of perturbing tropospheric oxidative cycles normally controlled by the hydroxyl radical. Significantly faster reaction rates allow chlorine radicals to expedite oxidation of hydrocarbons, including methane, and in polluted environments, to enhance ozone production. Here we present evidence, from the CARIBIC airborne dataset, for extensive chlorine radical chemistry associated with Asian pollution outflow, from airborne observations made over the Malaysian Peninsula in winter. This region is known for persistent convection that regularly delivers surface air to higher altitudes and serves as a major transport pathway into the stratosphere. Oxidant ratios inferred from hydrocarbon relationships show that chlorine radicals were regionally more important than hydroxyl radicals for alkane oxidation and were also important for methane and alkene oxidation (>10%). Our observations reveal pollution-related chlorine chemistry that is both widespread and recurrent, and has implications for tropospheric oxidizing capacity, stratospheric composition and ozone chemistry.
Role of thioredoxin reductase 1 in dysplastic transformation of human breast epithelial cells triggered by chronic oxidative stress
Authors: Dong Chaoran , Zhang Lei , Sun Ruoxuan , Liu Jianying , Yin Hanwei , Li Xiaoxiao , Zheng Xiaoqing , Zeng Huihui
Published: November 2016

Thioredoxin reductase 1 (TrxR1) is a pivotal intracellular redox sensor and antioxidant enzyme. On the other hand, overexpression of TrxR1 is closely correlated with the initiation of various tumors including breast cancer, though the detailed mechanism remains unclear. Here we investigated the role of TrxR1 in dysplastic transformation of human breast epithelial cell line MCF-10A induced by chronic oxidative stress. Not surprisingly, sustained exposure to H2O2 significantly augmented the expression and activity of TrxR1 in MCF-10A cells. The dysplastically transformed MCF-10A (MCF-10AT) cells undergoing 8-week H2O2 treatment exhibited a certain degree of malignancy in tumorigenicity evaluation. Moreover, TrxR1 inhibitor ethaselen (BBSKE) could partially reverse some malignant phenotypes including epithelial to mesenchymal transition (EMT) of MCF-10AT as well as MCF-7 cells. Collectively, our results supported the considerable involvement of TrxR1 in the onset of breast cancer and BBSKE may be a promising agent against breast cancer.
Cancer derived peptide of vacuolar ATPase ‘a2’ isoform promotes neutrophil migration by autocrine secretion of IL-8
Authors: Ibrahim Safaa A. , Kulshrestha Arpita , Katara Gajendra K. , Amin Magdy A. , Beaman Kenneth D.
Published: November 2016

Neutrophils play significant regulatory roles within the tumor microenvironment by directly promoting tumor progression that leads to poor clinical outcomes. Identifying the tumor associated molecules that regulate neutrophil infiltration into tumors may provide new and specific therapeutic targets for cancer treatment. The a2-isoform of vacuolar ATPase (a2V) is uniquely and highly expressed on cancer cell plasma membrane. Cancer cells secrete a peptide from a2V (a2NTD) that promotes the pro-tumorigenic properties of neutrophils. This provides a2V the propensity to control neutrophil migration. Here, we report that the treatment of human neutrophils with recombinant a2NTD leads to neutrophil adherence and polarization. Moreover, a2NTD treatment activates surface adhesion receptors, as well as FAK and Src kinases that are essential regulators of the migration process in neutrophils. Functional analysis reveals that a2NTD can act as a chemo-attractant and promotes neutrophil migration. In addition, a2Neuɸ secrete high levels of IL-8 via NF-κB pathway activation. Confirmatory assays demonstrate that the promoted migration of a2Neuɸ was dependent on the autocrine secretion of IL-8 from a2Neuɸ. These findings demonstrate for the first time the direct regulatory role of cancer associated a2-isoform V-ATPase on neutrophil migration, suggesting a2V as a potential target for cancer therapy.
Transcriptome analysis of Arabidopsis mutants suggests a crosstalk between ABA, ethylene and GSH against combined cold and osmotic stress
Authors: Kumar Deepak , Hazra Saptarshi , Datta Riddhi , Chattopadhyay Sharmila
Published: November 2016

The involvement of ethylene and abscisic acid in providing stress tolerance and defence response to plants is widely recognized. However, little is known about the cross-talk between glutathione with ethylene and abscisic acid to combat stress in planta. Here, transcriptome analysis of combined cold and osmotic stress treated Arabidopsis mutants were carried out to elucidate the crosstalk between the abscisic acid, ethylene and glutathione. Microarray experiment revealed the differential regulation of about 2313 and 4131 transcripts in ein2 (ethylene insensitive mutant) and aba1.6 (abscisic acid mutant) respectively. Functional analysis exposed common down-regulated stress and defence, secondary metabolite biosynthesis viz. phenylpropanoid, lignin and flavonols, redox and transcription factors related genes in ein2, aba1.6 and pad2.1 (glutathione mutant) in response to combined stress treatment. The reduced glutathione content was less in stress treated mutants in comparison to Col-0. Again, selective down-regulated transcripts in stress treated mutants were noted up-regulated after glutathione feeding. Some of the important differentially expressed genes were also validated by comparative proteomics analysis of stress treated mutants. In summary, our results suggested the role of ethylene and abscisic acid in inducing stress-responsive genes and proteins by activating glutathione biosynthesis to combat abiotic stress conditions in plant system.
Effect of bio-engineering on size, shape, composition and rigidity of bacterial microcompartments
Authors: Mayer Matthias J. , Juodeikis Rokas , Brown Ian R. , Frank Stefanie , Palmer David J. , Deery Evelyne , Beal David M. , Xue Wei-Feng , Warren Martin J.
Published: November 2016

Bacterial microcompartments (BMCs) are proteinaceous organelles that are found in a broad range of bacteria and are composed of an outer shell that encases an enzyme cargo representing a specific metabolic process. The outer shell is made from a number of different proteins that form hexameric and pentameric tiles, which interact to allow the formation of a polyhedral edifice. We have previously shown that the Citrobacter freundii BMC associated with 1,2-propanediol utilization can be transferred into Escherichia coli to generate a recombinant BMC and that empty BMCs can be formed from just the shell proteins alone. Herein, a detailed structural and proteomic characterization of the wild type BMC is compared to the recombinant BMC and a number of empty BMC variants by 2D-gel electrophoresis, mass spectrometry, transmission electron microscopy (TEM) and atomic force microscopy (AFM). Specifically, it is shown that the wild type BMC and the recombinant BMC are similar in terms of composition, size, shape and mechanical properties, whereas the empty BMC variants are shown to be smaller, hollow and less malleable.
A Preliminary Study of the Carbon Emissions Reduction Effects of Land Use Control
Authors: Chuai Xiaowei , Huang Xianjin , Qi Xinxian , Li Jiasheng , Zuo Tianhui , Lu Qinli , Li Jianbao , Wu Changyan , Zhao Rongqin
Published: November 2016

Land use change not only directly influences carbon storage in terrestrial ecosystems but can also cause energy-related carbon emissions. This study examined spatiotemporal land use change across Jiangsu Province, China; calculated vegetation carbon storage loss caused by land use change and energy-related carbon emissions; analysed the relationship among land use change, carbon emissions and social-economic development; and optimized land use structure to maximize carbon storage. Our study found that 13.61% of the province’s land area underwent a change in type of land use between 1995 and 2010, mainly presented as built-up land expansion and cropland shrinkage, especially in southern Jiangsu. Land use change caused a 353.99 × 104 t loss of vegetation carbon storage loss. Energy-related carbon emissions increased 2.5 times from 1995 to 2013; the energy consumption structure has been improved to some extent while still relying on coal. The selected social-economic driving forces have strong relationships with carbon emissions and land use changes, while there are also other determinants driving land use change, such as land use policy. The optimized land use structure will slow the rate of decline in vegetation carbon storage compared with the period between 1995 and 2010 and will also reduce energy-related carbon emissions by 12%.
Discriminating cancer-related and cancer-unrelated chemoradiation-response genes for locally advanced rectal cancers
Authors: Guo You , Cheng Jun , Ao Lu , Li Xiangyu , Guan Qingzhou , Zhang Juan , Yan Haidan , Cai Hao , Gao Qiao , Jiang Weizhong , Guo Zheng
Published: November 2016

For patients with locally advanced rectal cancer (LARC) treated with preoperation chemoradiation (pCRT), identifying differentially expressed (DE) genes between non-responders and responders is a common approach for investigating mechanisms of chemoradiation resistance. However, some of such DE genes might be irrelevant to cancer itself but simply reflect the pharmacokinetic differences of the normal tissues. In this study, we adopted the RankComp algorithm to identify DE genes for each of LARC sample compared with its own normal state. Then, we identified genes with significantly different deregulation frequencies between the non-responders and responders, defined as cancer-related pCRT-response genes. Pathway enrichment and protein-protein interaction analyses showed that these genes specifically and intensively interacted with currently known effective genes of pCRT, involving in DNA replication, cell cycle and DNA repair. In contrast, after excluding the cancer-related pCRT-response genes, the other DE genes between non-responders and responders were enriched in many pathways of drug and protein metabolisms and transports, and interacted with both the known effective genes and pharmacokinetic genes. Hence, these two types of DE genes should be distinguished for investigating mechanisms of pCRT response in LARCs.
Ecotypic differentiation matters for latitudinal variation in energy metabolism and flight performance in a butterfly under climate change
Authors: Van Dyck Hans , Holveck Marie-Jeanne
Published: November 2016

Life histories of organisms may vary with latitude as they experience different thermal constraints and challenges. This geographic, intraspecific variation could be of significance for range dynamics under climate change beyond edge-core comparisons. In this study, we did a reciprocal transplant experiment between the temperature-regimes of two latitudes with an ectotherm insect, examining the effects on energy metabolism and flight performance.Pararge aegeriaexpanded its ecological niche from cool woodland (ancestral) to warmer habitat in agricultural landscape (novel ecotype). Northern males had higher standard metabolic rates than southern males, but in females these rates depended on their ecotype. Southern males flew for longer than northern ones. In females, body mass-corrected flight performance depended on latitude and thermal treatment during larval development and in case of the southern females, their interaction. Our experimental study provides evidence for the role of ecological differentiation at the core of the range to modulate ecophysiology and flight performance at different latitudes, which in turn may affect the climatic responsiveness of the species.
Integrins outside focal adhesions transmit tensions during stable cell adhesion
Authors: Wang Yongliang , Wang Xuefeng
Published: November 2016

Integrins coupled with other proteins form protein complexes named focal adhesions (FA) which are considered as the primary sites for cellular forces transduction during cell stable adhesion. Cell traction forces transmitted by FAs and integrin tensions inside FAs have been extensively studied. However, it remains unknown whether integrins outside FAs can transmit tension, and if so, what is the tension range. We previously developed a tension sensor named tension gauge tether (TGT). To calibrate integrin tensions outside FAs, here we applied multiplex TGT (mTGT) to simultaneously monitor integrin tensions at separate levels. mTGT unambiguously revealed that integrins outside FAs also transmit tension after FA formation. These tensions are mainly located in the range of 43 ~ 54 pN which is lower than integrin tensions inside FAs. Integrin tensions both inside and outside FAs substantially contribute to bulk cellular forces and they respond independently to actin and myosin II inhibition, serum deprivation and microtubule inhibition, indicating their different tension sources and independent dynamics. Our work identified integrin tensions outside FAs and calibrated the tension range for the first time. We also demonstrated that mTGT is a valuable tool to monitor integrin tension profile in a broad detection range of 10 ~ 60 pN.
Computational Drug Target Screening through Protein Interaction Profiles
Authors: Vilar Santiago , Quezada Elías , Uriarte Eugenio , Costanzi Stefano , Borges Fernanda , Viña Dolores , Hripcsak George
Published: November 2016

The development of computational methods to discover novel drug-target interactions on a large scale is of great interest. We propose a new method for virtual screening based on protein interaction profile similarity to discover new targets for molecules, including existing drugs. We calculated Target Interaction Profile Fingerprints (TIPFs) based on ChEMBL database to evaluate drug similarity and generated new putative compound-target candidates from the non-intersecting targets in each pair of compounds. A set of drugs was further studied in monoamine oxidase B (MAO-B) and cyclooxygenase-1 (COX-1) enzyme through molecular docking and experimental assays. The drug ethoxzolamide and the natural compound piperlongumine, present in Piper longum L, showed hMAO-B activity with IC50values of 25 and 65 μM respectively. Five candidates, including lapatinib, SB-202190, RO-316233, GW786460X and indirubin-3′-monoxime were tested against human COX-1. Compounds SB-202190 and RO-316233 showed a IC50in hCOX-1 of 24 and 25 μM respectively (similar range as potent inhibitors such as diclofenac and indomethacin in the same experimental conditions). Lapatinib and indirubin-3′-monoxime showed moderate hCOX-1 activity (19.5% and 28% of enzyme inhibition at 25 μM respectively). Our modeling constitutes a multi-target predictor for large scale virtual screening with potential in lead discovery, repositioning and drug safety.
Mutation tendency of mutator Plasmodium berghei with proofreading-deficient DNA polymerase δ
Authors: Honma Hajime , Niikura Mamoru , Kobayashi Fumie , Horii Toshihiro , Mita Toshihiro , Endo Hiroyoshi , Hirai Makoto
Published: November 2016

In this study, we investigated the mutation tendency of a mutator rodent malaria parasite, Plasmodium berghei, with proofreading-deficient DNA polymerase δ. Wild-type and mutator parasites were maintained in mice for over 24 weeks, and the genome-wide accumulated mutations were determined by high-throughput sequencing. The mutator P. berghei had a significant preference for C/G to A/T substitutions; thus, its genome had a trend towards a higher AT content. The mutation rate was influenced by the sequence context, and mutations were markedly elevated at TCT. Some genes mutated repeatedly in replicate passage lines. In particular, knockout mutations of the AP2-G gene were frequent, which conferred strong growth advantages on parasites during the blood stage but at the cost of losing the ability to form gametocytes. This is the first report to demonstrate a biased mutation tendency in malaria parasites, and its results help to promote our basic understanding of Plasmodium genetics.
Guatemala paleoseismicity: from Late Classic Maya collapse to recent fault creep
Authors: Brocard Gilles , Anselmetti Flavio S. , Teyssier Christian
Published: November 2016

We combine ‘on-fault’ trench observations of slip on the Polochic fault (North America-Caribbean plate boundary) with a 1200 years-long ‘near-fault’ record of seismo-turbidite generation in a lake located within 2 km of the fault. The lake record indicates that, over the past 12 centuries, 10 earthquakes reaching ground-shaking intensities ≥ VI generated seismo-turbidites in the lake. Seismic activity was highly unevenly distributed over time and noticeably includes a cluster of earthquakes spread over a century at the end of the Classic Maya period. This cluster may have contributed to the piecemeal collapse of the Classic Maya civilization in this wet, mountainous southern part of the Maya realm. On-fault observations within 7 km of the lake show that soils formed between 1665 and 1813 CE were displaced by the Polochic fault during a long period of seismic quiescence, from 1450 to 1976 CE. Displacement on the Polochic fault during at least the last 480 years included a component of slip that was aseismic, or associated with very light seismicity (magnitude <5 earthquakes). Seismicity of the plate boundary is therefore either non-cyclic, or dominated by long-period cycles (>1 ky) punctuated by destructive earthquake clusters.
MiR-101 Targets the EZH2/Wnt/β-Catenin the Pathway to Promote the Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells
Authors: Wang Hongrui , Meng Yake , Cui Quanjun , Qin Fujun , Yang Haisong , Chen Yu , Cheng Yajun , Shi Jiangang , Guo Yongfei
Published: November 2016

Mounting evidence indicates that microRNAs (miRNAs) are involved in multiple processes of osteogenic differentiation. MicroRNA-101 (miR-101), identified as a tumor suppressor, has been implicated in the pathogenesis of several types of cancer. However, the expression of miR-101 and its roles in the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) remain unclear. We found that the miR-101 expression level was significantly increased during the osteogenic differentiation of hBMSCs. MiR-101 depletion suppressed osteogenic differentiation, whereas the overexpression of miR-101 was sufficient to promote this process. We further demonstrated that enhancer of zeste homolog 2 (EZH2) was a target gene of miR-101. EZH2 overexpression and depletion reversed the promoting or suppressing effect of osteogenic differentiation of hBMSCs, respectively, caused by miR-101. In addition, we showed that miR-101 overexpression promoted the expression of Wnt genes, resulting in the activation of the Wnt/β-catenin signaling pathway by targeting EZH2, while the activity of β-catenin and the Wnt/β-catenin signaling pathway was inhibited by ICG-001, a β-Catenin inhibitor, which reversed the promoting effect of miR-101. Finally, miR-101 also promotes in vivo bone formation by hBMSCs. Collectively, these data suggest that miR-101 is induced by osteogenic stimuli and promotes osteogenic differentiation at least partly by targeting the EZH2/Wnt/β-Catenin signaling pathway.
Critical Role of Energy Transfer Between Terbium Ions for Suppression of Back Energy Transfer in Nonanuclear Terbium Clusters
Authors: Omagari Shun , Nakanishi Takayuki , Kitagawa Yuichi , Seki Tomohiro , Fushimi Koji , Ito Hajime , Meijerink Andries , Hasegawa Yasuchika
Published: November 2016

Lanthanide (Ln(III)) complexes form an important class of highly efficient luminescent materials showing characteristic line emission after efficient light absorption by the surrounding ligands. The efficiency is however lowered by back energy transfer from Ln(III) ion to the ligands, especially at higher temperatures. Here we report a new strategy to reduce back energy transfer losses. Nonanuclear lanthanide clusters containing terbium and gadolinium ions, TbnGd9−n clusters ([TbnGd9−n(μ-OH)10(butylsalicylate)16]+NO3−, n = 0, 1, 2, 5, 8, 9), were synthesized to investigate the effect of energy transfer between Tb(III) ions on back energy transfer. The photophysical properties of TbnGd9−n clusters were studied by steady-state and time-resolved spectroscopic techniques and revealed a longer emission lifetime with increasing number of Tb(III) ions in TbnGd9−n clusters. A kinetic analysis of temperature dependence of the emission lifetime show that the energy transfer between Tb(III) ions competes with back energy transfer. The experimental results are in agreement with a theoretical rate equation model that confirms the role of energy transfer between Tb(III) ions in reducing back energy transfer losses. The results provide a new strategy in molecular design for improving the luminescence efficiency in lanthanide complexes which is important for potential applications as luminescent materials.
Slow reduction of IP-10 Levels predicts HBeAg seroconversion in chronic hepatitis B patients with 5 years of entecavir treatment
Authors: Guo Renyong , Mao Hejun , Hu Xiao , Zheng Nengneng , Yan Dong , He Jianqin , Yang Jiezuan
Published: November 2016

The aim of this study was to determine the correlation between dynamic changes in serum cytokine/chemokine expression levels in response to entecavir (ETV) treatment and HBV e antigen (HBeAg) seroconversion in patients with chronic hepatitis B (CHB). Four cytokines (interleukin [IL]-4, IL-6, IL-8, and interferon-γ) and five chemokines (macro-phage inflammatory protein [MIP]-1α, MIP-1β, platelet derived growth factor-BB, and interferon-inducible protein 10 [IP-10]) before ETV therapy and at 3, 6, 12, 24, 36 and 60 months during therapy in 105 CHB patients were analyzed. The results showed that the low decrease rate of IP-10 levels after 1 year of ETV treatment was an independent predictor of HBeAg seroconversion at year 5 (Hazard ratio = 0.972). The area under the receiver operating characteristic curves for the decrease rate of IP-10 levels after 1 year of treatment to discriminate a year-5 HBeAg seroconversion was 0.752 (p = 0.005). The results indicate that higher IP-10 level at year one of ETV treatment is associated with an increased probability of HBeAg seroconversion. Quantification of IP-10 during ETV treatment may help to predict long-term HBeAg seroconversion in patients with CHB.
Analysis of Serum Metabolites to Diagnose Bicuspid Aortic Valve
Authors: Wang Wenshuo , Maimaiti Aikebaier , Zhao Yun , Zhang Lingfei , Tao Hongyue , Nian Hui , Xia Limin , Kong Biao , Wang Chunsheng , Liu Mofang , Wei Lai
Published: November 2016

Bicuspid aortic valve (BAV) is the most common congenital heart disease. The current study aims to construct a diagnostic model based on metabolic profiling as a non-invasive tool for BAV screening. Blood serum samples were prepared from an estimation group and a validation group, each consisting of 30 BAV patients and 20 healthy individuals, and analyzed by liquid chromatography-mass spectrometry (LC-MS). In total, 2213 metabolites were detected and 41 were considered different. A model for predicting BAV in the estimation group was constructed using the concentration levels of monoglyceride (MG) (18:2) and glycerophospho-N-oleoyl ethanolamine (GNOE). A novel model named Zhongshan (ZS) was developed to amplify the association between BAV and the two metabolites. The area under curve (AUC) of ZS for BAV prediction was 0.900 (0.782–0.967) and was superior to all single-metabolite models when applied to the estimation group. Using optimized cutoff (−0.1634), ZS model had a sensitivity score of 76.7%, specificity score of 90.0%, positive predictive value of 80% and negative predictive value of 85.0% for the validation group. These results support the use of serum-based metabolomics profiling method as a complementary tool for BAV screening in large populations.
Avoidance, escape and microstructural adaptations of the tea green leafhopper to water droplets
Authors: Lin Meizhen , Vasseur Liette , Yang Guang , Gurr Geoff M. , You Minsheng
Published: November 2016

Rain and dew droplets can dislodge or drown small insects and may be important factors that drive adaptations for avoidance and escape. Studying the microstructure of small insects and insect behaviour can help understand these adaptations. We quantified avoidance behaviour and entrapment of nymphs and adults of the tea green leafhopper (Empoasca onukii) using simulated rainfall onto host plant foliage and made observations of pretarsi and abdomen microstructures. Adults responded rapidly to simulated rainfall and escaped by jumping whilst most young nymphs were washed from water-sprayed leaves though older nymphs tended to remain on leaves and subsequently escaped from water droplets. Adults had denser covering of water-repelling brochosomes on pretarsi and abdomen surface than nymphs, and were able to stand on water film whilst most nymphs had multiple penetrating tarsi. Removal of brochosomes from the abdomen of adults reduced hydrophobicity, demonstrating the hydrophobic significance of brochosomes in the capacity of leafhopper to escape from water droplets. Nymphs exhibited a higher pull-off force than adults. This research is one of the few studies to focus on the wettability and water avoidance of small insect pests and has implications for pest management.
Neuroprotection Mediated through GluN2C-Containing N-methyl-D-aspartate (NMDA) Receptors Following Ischemia
Authors: Chung Connie , Marson John D. , Zhang Quan-Guang , Kim Jimok , Wu Wei-Hua , Brann Darrell W. , Chen Bo-Shiun
Published: November 2016

Post-ischemic activation of NMDA receptors (NMDARs) has been linked to NMDAR subunit-specific signaling that mediates pro-survival or pro-death activity. Although extensive studies have been performed to characterize the role of GluN2A and GluN2B following ischemia, there is less understanding regarding the regulation of GluN2C. Here, we show that GluN2C expression is increased in acute hippocampal slices in response to ischemia. Strikingly, GluN2C knockout mice, following global cerebral ischemia, exhibit greater neuronal death in the CA1 area of the hippocampus and reduced spatial working memory compared to wild-type mice. Moreover, we find that GluN2C-expressing hippocampal neurons show marked resistance to NMDA-induced toxicity and reduced calcium influx. Using both in vivo and in vitro experimental models of ischemia, we demonstrate a neuroprotective role of GluN2C, suggesting a mechanism by which GluN2C is upregulated to promote neuronal survival following ischemia. These results may provide insights into development of NMDAR subunit-specific therapeutic strategies to protect neurons from excitotoxicity.