bluuebunny/crossref_metadata_2025 huggingface dataset:
Folk-economic beliefs: An evolutionary cognitive model
Authors: Boyer Pascal , Petersen Michael Bang
Published: October 2017

The domain of “folk-economics” consists in explicit beliefs about the economy held by laypeople, untrained in economics, about such topics as, for example, the causes of the wealth of nations, the benefits or drawbacks of markets and international trade, the effects of regulation, the origins of inequality, the connection between work and wages, the economic consequences of immigration, or the possible causes of unemployment. These beliefs are crucial in forming people's political beliefs and in shaping their reception of different policies. Yet, they often conflict with elementary principles of economic theory and are often described as the consequences of ignorance, irrationality, or specific biases. As we will argue, these past perspectives fail to predict the particular contents of popular folk-economic beliefs and, as a result, there is no systematic study of the cognitive factors involved in their emergence and cultural success. Here we propose that the cultural success of particular beliefs about the economy is predictable if we consider the influence of specialized, largely automatic inference systems that evolved as adaptations to ancestral human small-scale sociality. These systems, for which there is independent evidence, include free-rider detection, fairness-based partner choice, ownership intuitions, coalitional psychology, and more. Information about modern mass-market conditions activates these specific inference systems, resulting in particular intuitions, for example, that impersonal transactions are dangerous or that international trade is a zero-sum game. These intuitions in turn make specific policy proposals more likely than others to become intuitively compelling, and, as a consequence, exert a crucial influence on political choices.
The aerobic transition as an economic ratchet
Authors: Wallace Rodrick
Published: October 2017

Punctuated equilibrium, in the sense of Eldredge and Gould in 1972, and path dependence (Gould in 2002), dominate evolutionary processes, many of whose dynamics can be expressed in terms of interacting information sources (Wallace in 2010). Argument based on Feynman's (in 2000) characterization of information as a form of free energy leads to a close, if inverse, analogy between evolutionary transitions and economic ratchets. Driven by such a ‘self-referential’ mechanism, increases in available metabolic free energy – via the aerobic transition – led to the eukaryotic transition and to life as we know it. Formal analysis focuses on groupoid symmetries associated with the cognitive processes of gene expression, an extension of the symmetry breaking/making perspectives of physical science into biological phenomena. This suggests that understanding modalities of cognitive gene expression, as opposed to focus on genes themselves, provides the deepest insight into evolutionary phenomena, a perspective at some variance with current simplistic gene-centred views that constrain evolutionary theory.
Developing Standards for Post-Hoc Weighting in Population-Based Survey Experiments
Authors: Franco Annie , Malhotra Neil , Simonovits Gabor , Zigerell L. J.
Published: October 2017

Weighting techniques are employed to generalize results from survey experiments to populations of theoretical and substantive interest. Although weighting is often viewed as a second-order methodological issue, these adjustment methods invoke untestable assumptions about the nature of sample selection and potential heterogeneity in the treatment effect. Therefore, although weighting is a useful technique in estimating population quantities, it can introduce bias and also be used as a researcher degree of freedom. We review survey experiments published in three major journals from 2000–2015 and find that there are no standard operating procedures for weighting survey experiments. We argue that all survey experiments should report the sample average treatment effect (SATE). Researchers seeking to generalize to a broader population can weight to estimate the population average treatment effect (PATE), but should discuss the construction and application of weights in a detailed and transparent manner given the possibility that weighting can introduce bias.
IAEA Affirms Japan’s Fukushima-Related Radioactivity Monitoring
Authors: Hornyak Tim
Published: October 2017

Laboratories outside Japan have validated the results. Radioactivity levels from the nuclear disaster have fallen, but questions remain years after the meltdown.
Increasing AR by HIF-2α inhibitor (PT-2385) overcomes the side-effects of sorafenib by suppressing hepatocellular carcinoma invasion via alteration of pSTAT3, pAKT and pERK signals
Authors: Xu Junjie , Zheng Longbo , Chen Jiang , Sun Yin , Lin Hui , Jin Ren-an , Tang Minyue , Liang Xiao , Cai Xiujun
Published: October 2017

Although sorafenib is currently used as a standard treatment for advanced hepatocellular carcinoma, low response rate, transient and limited efficacy, primary and acquired resistance and negative side-effects gain increasing attentions, suggesting the need for better efficacious combination therapy. Here, we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible factor (HIF)-2α could bind to an hypoxia responsive element within 500 bp region of androgen receptor (AR) promoter and thus transcriptionally suppress AR. Importantly, In vitro and In vivo studies suggested a specific and potent HIF-2α inhibitor, PT-2385, could significantly enhance sorafenib efficacy by suppressing HIF-2α, increasing AR and suppressing downstream pSTAT3/pAKT/pERK pathways. Clinical samples further confirmed the role of HIF-2α and AR. It is promising that PT-2385 could alleviate the undesirable side-effects of sorafenib treatment by sorafenib-PT-2385 combination therapy, which may shed light for late-stage HCC patients.
Superoxide drives progression of Parkin/PINK1-dependent mitophagy following translocation of Parkin to mitochondria
Authors: Xiao Bin , Deng Xiao , Lim Grace G Y , Xie Shaoping , Zhou Zhi Dong , Lim Kah-Leong , Tan Eng-King
Published: October 2017

Reactive oxygen species (ROS) and mitophagy are profoundly implicated in the pathogenesis of neurodegenerative diseases, such as Parkinson’s disease (PD). Several studies have suggested that ROS are not involved in mitochondrial translocation of Parkin which primes mitochondria for autophagic elimination. However, whether ROS play a role in the execution of mitophagy is unknown. In the present study, we show that carbonyl cyanidem-chlorophenylhydrazone (CCCP) treatment induced both mitochondrial depolarization and generation of ROS that were needed for the mitophagy process. Cells failed to proceed to complete mitophagy if CCCP treatment was discontinued even after recruitment of Parkin and autophagy machinery to mitochondria. Notably, treatment of pro-oxidant was able to replace CCCP treatment to take mitophagy forward, while it alone was insufficient to induce translocation of Parkin to mitochondria or autophagic clearance of mitochondria. In addition, an SOD mimetic that attenuated the superoxide level suppressed mitophagy, while an SOD inhibitor accumulated cellular superoxide and promoted mitophagy. Furthermore, blockage of the p38 signaling pathway inhibited mitophagy induced by ROS, suggesting that it may contribute to the activation of ROS-mediated mitophagy. Together, our study sheds light on the link between ROS and mitophagy at a molecular level, and suggests the therapeutic potential of regulating mitophagy through the superoxide–p38–mitophagy axis.
Trehalose protects against cadmium-induced cytotoxicity in primary rat proximal tubular cells via inhibiting apoptosis and restoring autophagic flux
Authors: Wang Xin-Yu , Yang Heng , Wang Min-Ge , Yang Du-Bao , Wang Zhen-Yong , Wang Lin
Published: October 2017

Autophagy has an important renoprotective function and we recently found that autophagy inhibition is involved in cadmium (Cd)-induced nephrotoxicity. Here, we aimed to investigate the protective effect of trehalose (Tre), a novel autophagy activator, against Cd-induced cytotoxicity in primary rat proximal tubular (rPT) cells. First, data showed that Tre treatment significantly decreased Cd-induced apoptotic cell death of rPT cells via inhibiting caspase-dependent apoptotic pathway, evidenced by morphological analysis, flow cytometric and immunoblot assays. Also, administration with Tre protected rPT cells against Cd-induced lipid peroxidation. Inhibition of autophagic flux in Cd-exposed rPT cells was markedly restored by Tre administration, demonstrated by immunoblot analysis of autophagy marker proteins and GFP and RFP tandemly tagged LC3 method. Resultantly, Cd-induced autophagosome accumulation was obviously alleviated by Tre treatment. Meanwhile, blockage of autophagosome–lysosome fusion by Cd exposure was noticeably restored by Tre, which promoted the autophagic degradation in Cd-exposed rPT cells. Moreover, Tre treatment markedly recovered Cd-induced lysosomal alkalinization and impairment of lysosomal degradation capacity in rPT cells, demonstrating that Tre has the ability to restore Cd-impaired lysosomal function. Collectively, these findings demonstrate that Tre treatment alleviates Cd-induced cytotoxicity in rPT cells by inhibiting apoptosis and restoring autophagic flux.
Gadd45a opens up the promoter regions of miR-295 facilitating pluripotency induction
Authors: Li Linpeng , Chen Keshi , Wu Yi , Long Qi , Zhao Danyun , Ma Bochao , Pei Duanqing , Liu Xingguo
Published: October 2017

MicroRNAs (miRNAs) play crucial roles in the establishment of pluripotent state by controlling pluripotent network. However, the molecular mechanisms controlling miRNAs during somatic cell reprogramming remain obscure. In this study, we show Gadd45a (growth arrest and DNA-damage-inducible protein 45a) enhances reprogramming by activating miR-295. Furthermore, we show that Gadd45a binds the promoter regions of miR-295. Nuclease accessibility assay indicates that Gadd45a opens the promoter regions of miR-295. Levels of H3K9Ac and H3K27Ac on the promoter regions of miR-295 were also increased. In conclusion, our results indicate that Gadd45a relaxes the promoter regions of miR-295 and promotes the expression of miR-295 during reprogramming, implying a concise mechanism of Gadd45a and miR-290 cluster cooperation in cell-fate determination.
RANKL-mediated harmonious dialogue between fetus and mother guarantees smooth gestation by inducing decidual M2 macrophage polarization
Authors: Meng Yu-Han , Zhou Wen-Jie , Jin Li-Ping , Liu Li-Bing , Chang Kai-Kai , Mei Jie , Li Hui , Wang Jian , Li Da-Jin , Li Ming-Qing
Published: October 2017

Decidual macrophages (dMϕ) contribute to maternal–fetal tolerance. However, the mechanism of dMϕ differentiation during pregnancy is still largely unknown. Here, we report that receptor activator for nuclear factor-κ B ligand (RANKL), secreted by human embryonic trophoblasts and maternal decidual stromal cells (DSCs), polarizes dMϕ toward a M2 phenotype. This polarization is mediated through activation of Akt/signal transducer and activator of transcription 6 (STAT6) signaling, which is associated with the upregulation of histone H3 lysine-27 demethylase Jmjd3 and IRF4 in dMϕ. Such differentiated dMϕ can induce a Th2 bias that promotes maternal–fetal tolerance. Impaired expression of RANKL leads to dysfunction of dMϕ in vivo and increased rates of fetal loss in mice. Transfer of RANK+Mϕ reverses mouse fetal loss induced by Mϕ depletion. Compared with normal pregnancy, there are abnormally low levels of RANKL/RANK in villi and decidua from miscarriage patients. These results suggest that RANKL is a pivotal regulator of maternal–fetal tolerance by licensing dMϕ to ensure a successful pregnancy outcome. This observation provides a scientific basis on which a potential therapeutic strategy can be targeted to prevent pregnancy loss.
MBD2 upregulates miR-301a-5p to induce kidney cell apoptosis during vancomycin-induced AKI
Authors: Wang Juan , Li Huiling , Qiu Shuangfa , Dong Zheng , Xiang Xudong , Zhang Dongshan
Published: October 2017

Despite DNA methylation occurred in acute kidney injury (AKI), how it influenced progression of AKI remains unclear. Methyl-CpG-binding domain protein 2 (MBD2), a protein readers of methylation, was used to analyze the impact of DNA methylation on vancomycin (VAN)-induced AKI. Here, in cultured human kidney tubular epithelial cells (HK-2), we show that knockdown of MBD2 by siRNA attenuated VAN-induced apoptosis, caspase activity, and the expression of BAX and cleaved caspase 3. Interestingly, knockdown of MBD2 by siRNA was associated with the suppression of miR-301a-5p. Mechanistic studies confirmed MBD2 binds to these methylated CpG elements of miR-301a-5p promoter, and then activates miR-301a-5p promoter by suppressing methylation. Furthermore, anti-miR-301a-5p significantly blocked VAN-induced apoptosis and caspase activity in HK-2 cells, which was accompanied by downregulation of p53, and upregulation of MITF, HDGF and MDM-4 together. The latter genes were further identified as target genes of miR-301a-5p, and silencing of MDM-4 promoted p53 accumulation. In vivo, mice with MBD2 knockout (MBD2-KO) were counteracted to VAN-induced AKI, indicated by the analysis of renal function, histology, apoptosis and inflammation. MBD2-KO also significantly suppressed the expression of miR-301a-5p, p53, BAX and cleaved caspase 3, and restored the expression of MDM-4, MITF and HDGF. Finally, in vivo inhibition of miR-301a-5p also ameliorated VAN-induced AKI. Together, these results show the novel MBD2/miR-301a-5p/MITF, HDGF and MDM-4/p53 pathway in VAN-induced AKI.
Impairment of PTX3 expression in osteoblasts: a key element for osteoporosis
Authors: Scimeca Manuel , Salustri Antonietta , Bonanno Elena , Nardozi Daniela , Rao Cecilia , Piccirilli Eleonora , Feola Maurizio , Tancredi Virginia , Rinaldi Annamaria , Iolascon Giovanni , Orlandi Augusto , Gasbarra Elena , Maffulli Nicola , Brandi Maria Luisa , Tarantino Umberto
Published: October 2017

Pentraxin 3 (PTX3) is a multifunctional glycoprotein regulating inflammatory response, cell proliferation and migration and deposition and remodelling of the extracellular matrix by a variety of cells. In this study, we investigated the possible role of PTX3 in bone homeostasis. To this end, we compared the expression and function of PTX3 in human osteoblasts of osteoporotic, osteoarthritic patients and young subjects not affected by bone diseases. Immunohistochemical analysis performed on bone head biopsies showed a close association between bone health and the number of osteoblasts expressing PTX3. Noteworthy, the proportion of PTX3-positive osteoblasts resulted to be significantly lower in osteoporotic patients compared with both young patients and osteoarthritic patients of the same age. Ex vivo culture of osteoblasts isolated from the three groups of patients confirmed in vivo observation. Specifically, we observed rare runt-related transcription factor 2 (RUNX2) immunopositive osteoblasts expressing PTX3 in cell cultures derived from osteoporotic patients and western blotting analysis showed 80% reduction of PTX3 in the corresponding culture extracts compared with young and osteoarthritic patients. The treatment of human osteoblast primary cultures derived from young patients with anti-PTX3 antibody dramatically affected osteoblast behaviour. Indeed, they lost the morphological and molecular features typical of mature osteoblasts, acquiring fibroblast-like shape and highly decreasing nuclear factor kappa-B ligand (RANKL) and RUNX2 expression. Also, the inhibition of PTX3 negatively affected osteoblast proliferation and their ability to form cell clusters and microhydroxyapatite crystals. Altogether, these results suggest a central role of PTX3 in bone homeostasis showing its involvement in osteoblast proliferation, differentiation and function.
p38α MAPK antagonizing JNK to control the hepatic fat accumulation in pediatric patients onset intestinal failure
Authors: Xiao Yongtao , Wang Jun , Yan Weihui , Zhou Kejun , Cao Yi , Cai Wei
Published: October 2017

The p38α mitogen-activated protein kinase (MAPK) has been related to gluconeogenesis and lipid metabolism. However, the roles and related mechanisms of p38α MAPK in intestinal failure (IF)-associated liver steatosis remained poor understood. Here, our experimental evidence suggested that p38α MAPK significantly suppressed the fat accumulation in livers of IF patients mainly through two mechanisms. On the one hand, p38α MAPK increased hepatic bile acid (BA) synthesis by upregulating the expression of the rate-limiting enzyme cholesterol 7-α-hydroxylase (CYP7A1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which in turn activated the transcription of the CYP7A1. On the other hand, p38α MAPK promoted fatty acid (FA) β-oxidation via upregulating peroxisome proliferator-activated receptor alpha (PPARα) and its transcriptional target genes carnitine palmitoyltransferase 1A (CPT1A) and peroxisomal acyl-coenzyme aoxidase 1 (ACOX1). Dual luciferase assays indicated that p38α MAPK increased the transcription of PPARα, PGC-1α and CYP7A1 by upregulating their promoters’ activities. In addition, in vitro and in vivo assays indicated p38α MAPK negatively regulates the hepatic steatosis by controlling JNK activation. In conculsion, our findings demonstrate that hepatic p38α MAPK functions as a negative regulator of liver steatosis in maintaining BA synthesis and FAO by antagonizing the c-Jun N-terminal kinase (JNK).
MYCN contributes to the malignant characteristics of erythroleukemia through EZH2-mediated epigenetic repression of p21
Authors: Liu Li , Xu Feng , Chang Chun-Kang , He Qi , Wu Ling-Yun , Zhang Zheng , Li Xiao
Published: October 2017

MYC proto-oncogene family including c-myc and n-myc (MYCN) are critical for normal cell development and tumorigenesis. Overexpression of c-myc causes acute erythroleukemia in vivo. However, the role of MYCN in acute erythroleukemia remains poorly understood. In this study, we found that the patients with erythroleukemia showed higher expression of MYCN than normal controls. In vitro experiments, knockdown of MYCN resulted in decreased cell proliferation, elevated autonomously cell apoptosis and increased P21-mediated cell senescence. On the contrary, overexpression of MYCN obviously promoted cell proliferation, and induced erythroid differentiation block and apoptosis resistance to cytotoxic agent. Further gene microarray and functional analysis revealed that EZH2 is a target of MYCN. Knockdown of MYCN inhibited the expression of EZH2, and then activated p21 expression through removal of H3K27me3 at the p21 promoter. Overexpression of ezh2 could antagonize the p21 activation caused by MYCN knockdown. In addition, Aurora inhibitor MLN8237 inhibited the proliferation of erythroleukemia cells through repression of MYCN/EZH2 axis, whereas it minimally affected the normal hematopoietic cells. In conclusion, MYCN contributes to the malignant characteristics of erythroleukemia through EZH2-meidated epigenetic repression of p21. MYCN may serve as a therapy target for the patients with acute erythroleukemia.
Erratum: Directly converting CO2 into a gasoline fuel
Authors: Wei Jian , Ge Qingjie , Yao Ruwei , Wen Zhiyong , Fang Chuanyan , Guo Lisheng , Xu Hengyong , Sun Jian
Published: October 2017

Nature Communications 8: Article number: 15174 (2017); Published 2 May 2017; Updated 12 October 2017 This Article contains an error in Fig. 3; in that, ‘Fe3C4’ in the orange semi-ellipse should be ‘Fe3O4’.
Cross-tissue integration of genetic and epigenetic data offers insight into autism spectrum disorder
Authors: Andrews Shan V. , Ellis Shannon E. , Bakulski Kelly M. , Sheppard Brooke , Croen Lisa A. , Hertz-Picciotto Irva , Newschaffer Craig J. , Feinberg Andrew P. , Arking Dan E. , Ladd-Acosta Christine , Fallin M. Daniele
Published: October 2017

Integration of emerging epigenetic information with autism spectrum disorder (ASD) genetic results may elucidate functional insights not possible via either type of information in isolation. Here we use the genotype and DNA methylation (DNAm) data from cord blood and peripheral blood to identify SNPs associated with DNA methylation (meQTL lists). Additionally, we use publicly available fetal brain and lung meQTL lists to assess enrichment of ASD GWAS results for tissue-specific meQTLs. ASD-associated SNPs are enriched for fetal brain (OR = 3.55; P < 0.001) and peripheral blood meQTLs (OR = 1.58; P < 0.001). The CpG targets of ASD meQTLs across cord, blood, and brain tissues are enriched for immune-related pathways, consistent with other expression and DNAm results in ASD, and reveal pathways not implicated by genetic findings. This joint analysis of genotype and DNAm demonstrates the potential of both brain and blood-based DNAm for insights into ASD and psychiatric phenotypes more broadly.
A homologue of the Parkinson’s disease-associated protein LRRK2 undergoes a monomer-dimer transition during GTP turnover
Authors: Deyaert Egon , Wauters Lina , Guaitoli Giambattista , Konijnenberg Albert , Leemans Margaux , Terheyden Susanne , Petrovic Arsen , Gallardo Rodrigo , Nederveen-Schippers Laura M. , Athanasopoulos Panagiotis S. , Pots Henderikus , Van Haastert Peter J. M. , Sobott Frank , Gloeckner Christian Johannes , Efremov Rouslan , Kortholt Arjan , Versées Wim
Published: October 2017

Mutations in LRRK2 are a common cause of genetic Parkinson’s disease (PD). LRRK2 is a multi-domain Roco protein, harbouring kinase and GTPase activity. In analogy with a bacterial homologue, LRRK2 was proposed to act as a GTPase activated by dimerization (GAD), while recent reports suggest LRRK2 to exist under a monomeric and dimeric form in vivo. It is however unknown how LRRK2 oligomerization is regulated. Here, we show that oligomerization of a homologous bacterial Roco protein depends on the nucleotide load. The protein is mainly dimeric in the nucleotide-free and GDP-bound states, while it forms monomers upon GTP binding, leading to a monomer-dimer cycle during GTP hydrolysis. An analogue of a PD-associated mutation stabilizes the dimer and decreases the GTPase activity. This work thus provides insights into the conformational cycle of Roco proteins and suggests a link between oligomerization and disease-associated mutations in LRRK2.
Experimental realization of two-dimensional Dirac nodal line fermions in monolayer Cu2Si
Authors: Feng Baojie , Fu Botao , Kasamatsu Shusuke , Ito Suguru , Cheng Peng , Liu Cheng-Cheng , Feng Ya , Wu Shilong , Mahatha Sanjoy K. , Sheverdyaeva Polina , Moras Paolo , Arita Masashi , Sugino Osamu , Chiang Tai-Chang , Shimada Kenya , Miyamoto Koji , Okuda Taichi , Wu Kehui , Chen Lan , Yao Yugui , Matsuda Iwao
Published: October 2017

Topological nodal line semimetals, a novel quantum state of materials, possess topologically nontrivial valence and conduction bands that touch at a line near the Fermi level. The exotic band structure can lead to various novel properties, such as long-range Coulomb interaction and flat Landau levels. Recently, topological nodal lines have been observed in several bulk materials, such as PtSn4, ZrSiS, TlTaSe2 and PbTaSe2. However, in two-dimensional materials, experimental research on nodal line fermions is still lacking. Here, we report the discovery of two-dimensional Dirac nodal line fermions in monolayer Cu2Si based on combined theoretical calculations and angle-resolved photoemission spectroscopy measurements. The Dirac nodal lines in Cu2Si form two concentric loops centred around the Γ point and are protected by mirror reflection symmetry. Our results establish Cu2Si as a platform to study the novel physical properties in two-dimensional Dirac materials and provide opportunities to realize high-speed low-dissipation devices.
Controlling the bioactivity of a peptide hormone in vivo by reversible self-assembly
Authors: Ouberai Myriam M. , Dos Santos Ana L. Gomes , Kinna Sonja , Madalli Shimona , Hornigold David C. , Baker David , Naylor Jacqueline , Sheldrake Laura , Corkill Dominic J. , Hood John , Vicini Paolo , Uddin Shahid , Bishop Steven , Varley Paul G. , Welland Mark E.
Published: October 2017

The use of peptides as therapeutic agents is undergoing a renaissance with the expectation of new drugs with enhanced levels of efficacy and safety. Their clinical potential will be only fully realised once their physicochemical and pharmacokinetic properties have been precisely controlled. Here we demonstrate a reversible peptide self-assembly strategy to control and prolong the bioactivity of a native peptide hormone in vivo. We show that oxyntomodulin, a peptide with potential to treat obesity and diabetes, self-assembles into a stable nanofibril formulation which subsequently dissociates to release active peptide and produces a pharmacological effect in vivo. The subcutaneous administration of the nanofibrils in rats results in greatly prolonged exposure, with a constant oxyntomodulin bioactivity detectable in serum for at least 5 days as compared to free oxyntomodulin which is undetectable after only 4 h. Such an approach is simple, cost-efficient and generic in addressing the limitations of peptide therapeutics.
Apical surface supracellular mechanical properties in polarized epithelium using noninvasive acoustic force spectroscopy
Authors: Cartagena-Rivera Alexander X. , Van Itallie Christina M. , Anderson James M. , Chadwick Richard S.
Published: October 2017

Abstract

Maintenance of epithelial tissue integrity requires coordination between cell–cell adherens junctions, tight junctions (TJ), and the perijunctional actomyosin cytoskeleton. Here we addressed the hypothesis that alterations in TJ structure and remodeling of the actomyosin cytoskeleton modify epithelial mechanics. Current methods to measure supracellular mechanical properties disrupt intact monolayers, therefore, we developed a novel method using noncontact acoustic frequency-modulation atomic force microscopy (FM-AFM) and tested it on MDCK polarized monolayers. Our results show that double knockdown (dKD) of ZO-1/ZO-2 elevates the apical epithelial tension and effective viscosity. Interestingly, epithelial tension is more sensitive to inhibition of myosin II ATPase activity than to inhibition of ROCK activity, but viscosity is highly sensitive to both. Additionally, we showed epithelial intercellular pulling forces at tricellular junctions and adhesion forces in dKD cells are elevated with an increase in contractility. In conclusion, FM-AFM enables the physiological and quantitative investigation of mechanics in intact epithelium.
Younger Dryas ice margin retreat triggered by ocean surface warming in central-eastern Baffin Bay
Authors: Oksman Mimmi , Weckström Kaarina , Miettinen Arto , Juggins Stephen , Divine Dmitry V. , Jackson Rebecca , Telford Richard , Korsgaard Niels J. , Kucera Michal
Published: October 2017

The transition from the last ice age to the present-day interglacial was interrupted by the Younger Dryas (YD) cold period. While many studies exist on this climate event, only few include high-resolution marine records that span the YD. In order to better understand the interactions between ocean, atmosphere and ice sheet stability during the YD, more high-resolution proxy records from the Arctic, located proximal to ice sheet outlet glaciers, are required. Here we present the first diatom-based high-resolution quantitative reconstruction of sea surface conditions from central-eastern Baffin Bay, covering the period 14.0–10.2 kyr BP. Our record reveals warmer sea surface conditions and strong interactions between the ocean and the West Greenland ice margin during the YD. These warmer conditions were caused by increased Atlantic-sourced water inflow combined with amplified seasonality. Our results emphasize the importance of the ocean for ice sheet stability under the current changing climate.
Hyperconnected molecular glass network architectures with exceptional elastic properties
Authors: Burg Joseph A. , Oliver Mark S. , Frot Theo J. , Sherwood Mark , Lee Victor , Dubois Geraud , Dauskardt Reinhold H.
Published: October 2017

Hyperconnected network architectures can endow nanomaterials with remarkable mechanical properties that are fundamentally controlled by designing connectivity into the intrinsic molecular structure. For hybrid organic–inorganic nanomaterials, here we show that by using 1,3,5 silyl benzene precursors, the connectivity of a silicon atom within the network extends beyond its chemical coordination number, resulting in a hyperconnected network with exceptional elastic stiffness, higher than that of fully dense silica. The exceptional intrinsic stiffness of these hyperconnected glass networks is demonstrated with molecular dynamics models and these model predictions are calibrated through the synthesis and characterization of an intrinsically porous hybrid glass processed from 1,3,5(triethoxysilyl)benzene. The proposed molecular design strategy applies to any materials system wherein the mechanical properties are controlled by the underlying network connectivity.
APOBEC3H structure reveals an unusual mechanism of interaction with duplex RNA
Authors: Bohn Jennifer A. , Thummar Keyur , York Ashley , Raymond Alice , Brown W. Clay , Bieniasz Paul D. , Hatziioannou Theodora , Smith Janet L.
Published: October 2017

The APOBEC3 family of cytidine deaminases cause lethal hypermutation of retroviruses via deamination of newly reverse-transcribed viral DNA. Their ability to bind RNA is essential for virion infiltration and antiviral activity, yet the mechanisms of viral RNA recognition are unknown. By screening naturally occurring, polymorphic, non-human primate APOBEC3H variants for biological and crystallization properties, we obtained a 2.24-Å crystal structure of pig-tailed macaque APOBEC3H with bound RNA. Here, we report that APOBEC3H forms a dimer around a short RNA duplex and, despite the bound RNA, has potent cytidine deaminase activity. The structure reveals an unusual RNA-binding mode in which two APOBEC3H molecules at opposite ends of a seven-base-pair duplex interact extensively with both RNA strands, but form no protein–protein contacts. CLIP-seq analysis revealed that APOBEC3H preferentially binds to sequences in the viral genome predicted to contain duplexes, a property that may facilitate both virion incorporation and catalytic activity.
Erratum: Non-quasiparticle transport and resistivity saturation: a view from the large-N limit
Authors: Werman Yochai , Kivelson Steven A. , Berg Erez
Published: October 2017

Erratum to: doi:10.1038/s41535-017-0009-8
Collimated protons accelerated from an overdense gas jet irradiated by a 1 µm wavelength high-intensity short-pulse laser
Authors: Chen S. N. , Vranic M. , Gangolf T. , Boella E. , Antici P. , Bailly-Grandvaux M. , Loiseau P. , Pépin H. , Revet G. , Santos J. J. , Schroer A. M. , Starodubtsev Mikhail , Willi O. , Silva L. O. , d’Humières E. , Fuchs J.
Published: October 2017

We have investigated proton acceleration in the forward direction from a near-critical density hydrogen gas jet target irradiated by a high intensity (1018 W/cm2), short-pulse (5 ps) laser with wavelength of 1.054 μm. We observed the signature of the Collisionless Shock Acceleration mechanism, namely quasi-monoenergetic proton beams with small divergence in addition to the more commonly observed electron-sheath driven proton acceleration. The proton energies we obtained were modest (~MeV), but prospects for improvement are offered through further tailoring the gas jet density profile. Also, we observed that this mechanism is very robust in producing those beams and thus can be considered as a future candidate in laser-driven ion sources driven by the upcoming next generation of multi-PW near-infrared lasers.
Long-term passive acoustic recordings track the changing distribution of North Atlantic right whales (Eubalaena glacialis) from 2004 to 2014
Authors: Davis Genevieve E. , Baumgartner Mark F. , Bonnell Julianne M. , Bell Joel , Berchok Catherine , Bort Thornton Jacqueline , Brault Solange , Buchanan Gary , Charif Russell A. , Cholewiak Danielle , Clark Christopher W. , Corkeron Peter , Delarue Julien , Dudzinski Kathleen , Hatch Leila , Hildebrand John , Hodge Lynne , Klinck Holger , Kraus Scott , Martin Bruce , Mellinger David K. , Moors-Murphy Hilary , Nieukirk Sharon , Nowacek Douglas P. , Parks Susan , Read Andrew J. , Rice Aaron N. , Risch Denise , Širović Ana , Soldevilla Melissa , Stafford Kate , Stanistreet Joy E. , Summers Erin , Todd Sean , Warde Ann , Van Parijs Sofie M.
Published: October 2017

Given new distribution patterns of the endangered North Atlantic right whale (NARW;Eubalaena glacialis) population in recent years, an improved understanding of spatio-temporal movements are imperative for the conservation of this species. While so far visual data have provided most information on NARW movements, passive acoustic monitoring (PAM) was used in this study in order to better capture year-round NARW presence. This project used PAM data from 2004 to 2014 collected by 19 organizations throughout the western North Atlantic Ocean. Overall, data from 324 recorders (35,600 days) were processed and analyzed using a classification and detection system. Results highlight almost year-round habitat use of the western North Atlantic Ocean, with a decrease in detections in waters off Cape Hatteras, North Carolina in summer and fall. Data collected post 2010 showed an increased NARW presence in the mid-Atlantic region and a simultaneous decrease in the northern Gulf of Maine. In addition, NARWs were widely distributed across most regions throughout winter months. This study demonstrates that a large-scale analysis of PAM data provides significant value to understanding and tracking shifts in large whale movements over long time scales.
Structural analysis of variant of Helicobacter pylori MotB in its activated form, engineered as chimera of MotB and leucine zipper
Authors: Andrews Daniel A. , Nesmelov Yuri E. , Wilce Matthew C. , Roujeinikova Anna
Published: October 2017

Rotation of the bacterial flagellum is powered by a proton influx through the peptidoglycan (PG)-tethered stator ring MotA/B. MotA and MotB form an inner-membrane complex that does not conduct protons and does not bind to PG until it is inserted into the flagellar motor. The opening of the proton channel involves association of the plug helices in the periplasmic region of the MotB dimer into a parallel coiled coil. Here, we have characterised the structure of a soluble variant of full-length Helicobacter pylori MotB in which the plug helix was engineered to be locked in a parallel coiled coil state, mimicking the open state of the stator. Fluorescence resonance energy transfer measurements, combined with PG-binding assays and fitting of the crystal structures of MotB fragments to the small angle X-ray scattering (SAXS) data revealed that the protein’s C-terminal domain has a PG-binding-competent conformation. Molecular modelling against the SAXS data suggested that the linker in H. pylori MotB forms a subdomain between the plug and the C-terminal domain, that ‘clamps’ the coiled coil of the plug, thus stabilising the activated form of the protein. Based on these results, we present a pseudo-atomic model structure of full-length MotB in its activated form.
The Effects of Exoskeleton Assisted Knee Extension on Lower-Extremity Gait Kinematics, Kinetics, and Muscle Activity in Children with Cerebral Palsy
Authors: Lerner Zachary F. , Damiano Diane L. , Bulea Thomas C.
Published: October 2017

Individuals with cerebral palsy often exhibit crouch gait, a debilitating and inefficient walking pattern marked by excessive knee flexion that worsens with age. To address the need for improved treatment, we sought to evaluate if providing external knee extension assistance could reduce the excessive burden placed on the knee extensor muscles as measured by knee moments. We evaluated a novel pediatric exoskeleton designed to provide appropriately-timed extensor torque to the knee joint during walking in a multi-week exploratory clinical study. Seven individuals (5–19 years) with mild-moderate crouch gait from cerebral palsy (GMFCS I-II) completed the study. For six participants, powered knee extension assistance favorably reduced the excessive stance-phase knee extensor moment present during crouch gait by a mean of 35% in early stance and 76% in late stance. Peak stance-phase knee and hip extension increased by 12° and 8°, respectively. Knee extensor muscle activity decreased slightly during exoskeleton-assisted walking compared to baseline, while knee flexor activity was elevated in some participants. These findings support the use of wearable exoskeletons for the management of crouch gait and provide insights into their future implementation.
A Pilot Study on Tocilizumab for Treating Refractory Adult-Onset Still’s Disease
Authors: Li Ting , Gu Liyang , Wang Xiaodong , Guo Li , Shi Hui , Yang Chengde , Chen Sheng
Published: October 2017

To investigate the efficacy and safety of Tocilizumab (TCZ) in patients with refractory adult-onset Still’s disease (AOSD). We enrolled 8 female patients from October 2013 to July 2014. All patients fulfilled Japan’s Yamaguch AOSD classification and recognized as refractory AOSD. All Patients received TCZ treatment 4–8 mg/kg every 4 weeks. Evaluation of efficacy was conducted after 3 months and 6 months, including clinical manifestations of AOSD patients, improvement of inflammatory markers as well as glucocorticoids dosage adjustments. Treatment-related adverse events were also recorded. Patients treated with Tocilizumab with average age 41.1 years old, the average disease duration 23.6 months. Two patients drop off due to infusion side effects. Others were followed at least 6 months. After 3 months of follow-up, remission rates of fever, arthritis and rashes from 8 patients were 87.5%, 100% and 87.5%. White blood cell counts, erythrocyte sedimentation rate, C-reactive protein and ferritin levels were decreased (P < 0.01) significantly compared to treatment before. Furthermore, the average dose of prednisone was reduced from 51.7 ± 38.4 mg/d to 12.9 ± 7.7 mg/d (P < 0.01). Our findings suggest that tocilizumab could alleviate the clinical manifestations of refractory AOSD rapidly and efficiently.
Dissecting the Underlying Pharmaceutical Mechanism of Chinese Traditional Medicine Yun-Pi-Yi-Shen-Tong-Du-Tang Acting on Ankylosing Spondylitis through Systems Biology Approaches
Authors: Xie Duoli , Huang Lin , Zhao Guanghui , Yu Yiran , Gao Jiawei , Li Haichang , Wen Chengping
Published: October 2017

Traditional Chinese Medicine (TCM) has been served as complementary medicine for Ankylosing Spondylitis (AS) treatment for a long time. Yun-Pi-Yi-Shen-Tong-Du-Tang (Y-Y-T) is a novel empirical formula designed by Prof. Chengping Wen. In this study, a retrospective investigation supported efficacy of Y-Y-T and then we deciphered the underlying molecular mechanism of the efficacy. Herbal ingredients and targeting proteins were collected from TCMID. PPI networks were constructed to further infer the relationship among Y-Y-T, drugs used for treating AS, differentially expressed genes of AS patients and AS disease proteins. Finally, it was suggested that TLR signaling pathway and T cell receptor signaling pathway may involve in the biological processes of AS progression and contribute to the curative effect and proteins such as JAK2, STAT3, HSP90AA1, TNF and PTEN were the key targets. Our systemic investigation to infer therapeutic mechanism of Y-Y-T for AS treatment provides a new insight in understanding TCM pharmacology.
Eosinophilia and clinical outcome of chronic obstructive pulmonary disease: a meta-analysis
Authors: Ho Jeffery , He Wajia , Chan Matthew T. V. , Tse Gary , Liu Tong , Wong Sunny H. , Leung Czarina C. H. , Wong Wai T. , Tsang Sharon , Zhang Lin , Chan Rose Y. P , Gin Tony , Leung Joseph , Lau Benson W. M. , Wu William K. K. , Ngai Shirley P. C.
Published: October 2017

Numerous studies have investigated the association between eosinophilia and clinical outcome of patients with chronic obstructive pulmonary disease (COPD) but the evidence is conflicting. We conducted a pooled analysis of outcome measures comparing eosinophilic and non-eosinophilic COPD patients. We searched articles indexed in four databases using Medical Subject Heading or Title and Abstract words including COAD, COPD, eosinophil, eosinophilia, eosinopenia from inception to December 2016. Observational studies and randomized controlled trials with parallel groups comparing COPD patients with and without eosinophilia were included. Comparing to the non-eosinophilic group, those with eosinophilic COPD had a similar risk for exacerbation in 12 months [Odds ratio = 1.07, 95% confidence interval (CI) 0.86–1.32, P = 0.55] and in-hospital mortality [OR = 0.52, 95% CI 0.25–1.07]. Eosinophilia was associated with reduced length of hospital stay (P = 0.04). Subsequent to therapeutic interventions, eosinophilic outpatients performed better in pulmonary function tests [Mean Difference = 1.64, 95% CI 0.05–3.23, P < 0.001]. Inclusion of hospitalized patients nullified the effect. Improvement of quality of life was observed in eosinophilic subjects [Standardized Mean Difference = 1.83, 95% CI 0.02–3.64, P = 0.05], independent of hospitalization status. In conclusion, blood eosinophilia may be predictive of favorable response to steroidal and bronchodilator therapies in patients with stable COPD.
Open Source 3D Multipurpose Measurement System with Submillimetre Fidelity and First Application in Magnetic Resonance
Authors: Han Haopeng , Moritz Raphael , Oberacker Eva , Waiczies Helmar , Niendorf Thoralf , Winter Lukas
Published: October 2017

Magnetic resonance imaging (MRI) is the mainstay of diagnostic imaging, a versatile instrument for clinical science and the subject of intense research interest. Advancing clinical science, research and technology of MRI requires high fidelity measurements in quantity, location and time of the given physical property. To meet this goal a broad spectrum of commercial measurement systems has been made available. These instruments frequently share in common that they are costly and typically employ closed proprietary hardware and software. This shortcoming makes any adjustment for a specified application difficult if not prohibitive. Recognizing this limitation this work presents COSI Measure, an automated open source measurement system that provides submillimetre resolution, robust configuration and a large working volume to support a versatile range of applications. The submillimetre fidelity and reproducibility/backlash performance were evaluated experimentally. Magnetic field mapping of a single ring Halbach magnet, a 3.0 T and a 7.0 T MR scanner as well as temperature mapping of a radio frequency coil were successfully conducted. Due to its open source nature and versatile construction, the system can be easily modified for other applications. In a resource limited research setting, COSI Measure makes efficient use of laboratory space, financial resources and collaborative efforts.
Structure of melanins from the fungi Ochroconis lascauxensis and Ochroconis anomala contaminating rock art in the Lascaux Cave
Authors: De la Rosa José Maria , Martin-Sanchez Pedro M. , Sanchez-Cortes Santiago , Hermosin Bernardo , Knicker Heike , Saiz-Jimenez Cesareo
Published: October 2017

Two novel species of the fungal genus Ochroconis, O. lascauxensis and O. anomala have been isolated from the walls of the Lascaux Cave, France. The interest in these fungi and their melanins lies in the formation of black stains on the walls and rock art which threatens the integrity of the paintings. Here we report solid-state cross polarization magic-angle spinning 13C and 15N nuclear magnetic resonance (NMR) spectroscopy and surface-enhanced Raman spectroscopy (SERS) of the melanins extracted from the mycelia of O. lascauxensis and O. anomala in order to known their chemical structure. The melanins from these two species were compared with those from other fungi. The melanins from the Ochroconis species have similar SERS and 13C and 15N NMR spectra. Their chemical structures as suggested by the data are not related to 3,4-dihydroxyphenylalanine, 5,6-dihydroxyindole or 1,8-dihydroxynaphthalene precursors and likely the building blocks from the melanins have to be based on other phenols that react with the N-terminal amino acid of proteins. The analytical pyrolysis of the acid hydrolysed melanin from O. lascauxensis supports this assumption.
Phase-driven charge manipulation in Hybrid Single-Electron Transistor
Authors: Enrico Emanuele , Strambini Elia , Giazotto Francesco
Published: October 2017

Phase-tunable hybrid devices, built upon nanostructures combining normal metal and superconductors, have been the subject of intense studies due to their numerous combinations of different charge and heat transport configurations. They exhibit solid applications in quantum metrology and coherent caloritronics. Here we propose and realize a new kind of hybrid device with potential application in single charge manipulation and quantized current generation. We show that by tuning superconductivity on two proximized nanowires, coupled via a Coulombic normal-metal island, we are able to control its charge state configuration. This device supports a one-control-parameter cycle being actuated by the sole magnetic flux. In a voltage biased regime, the phase-tunable superconducting gaps can act as energy barriers for charge quanta leading to an additional degree of freedom in single electronics. The resulting configuration is fully electrostatic and the current across the device is governed by the quasiparticle populations in the source and drain leads. Notably, the proposed device can be realized using standard nanotechniques opening the possibility to a straightforward coupling with the nowadays well developed superconducting electronics.
Association of anaemia with Helicobacter pylori infection: a retrospective study
Authors: Xu Mei-Yan , Cao Bing , Yuan Bao-Shi , Yin Jian , Liu Lan , Lu Qing-Bin
Published: October 2017

The role of Helicobacter pylori (H. pylori) infection in haematological system diseases is not well understood. We conducted this retrospective study to explore the association between H. pylori infection and anaemia in the Chinese population. This retrospective study was performed in Aerospace Center Hospital in Beijing. We derived the data from the registration system of the physical population between 2012–2016. Logistic regression models were used to explore the association between H. pylori infection and anaemia. Among 17,791 subjects, there were 7,804 (43.9%) subjects with H. pylori infection and 950 (5.3%) with anaemia. The prevalence of anaemia in the H. pylori (+) group was significantly higher than in the H. pylori (−) group after adjusting for age, sex, marriage, underlying diseases and body mass index. Compared to H. pylori (−), the OR of H. pylori (+) was 1.39 for moderate-to-severe anaemia and 1.05 for mild anaemia. The level of haemoglobin was lower in the H. pylori (+) group than in the H. pylori (−) group. This study indicates that H. pylori infection may be related to anaemia and haemoglobin level in the Chinese population.