bluuebunny/crossref_metadata_2025 huggingface dataset:
A CRISPR-based approach for targeted DNA demethylation
Authors: Xu Xingxing , Tao Yonghui , Gao Xiaobo , Zhang Lei , Li Xufang , Zou Weiguo , Ruan Kangcheng , Wang Feng , Xu Guo-liang , Hu Ronggui
Published: May 2016

In mammalian cells, DNA methylation critically regulates gene expression and thus has pivotal roles in myriad of physiological and pathological processes. Here we report a novel method for targeted DNA demethylation using the widely used clustered regularly interspaced short palindromic repeat (CRISPR)-Cas system. Initially, modified single guide RNAs (sgRNAs) (sgRNA2.0) were constructed by inserting two copies of bacteriophage MS2 RNA elements into the conventional sgRNAs, which would facilitate the tethering of the Tet1 catalytic domain (Tet-CD), in fusion with dCas9 or MS2 coat proteins, to the targeted gene loci. Subsequently, such system was shown to significantly upregulate transcription of the target genes, including RANKL, MAGEB2 or MMP2, which was in close correlation to DNA demethylation of their neighboring CpGs in the promoters. In addition, the dCas9/sgRNA2.0-directed demethylation system appeared to afford efficient demethylation of the target genes with tenuous off-target effects. Applications of this system would not only help us understand mechanistically how DNA methylation might regulate gene expression in specific contexts, but also enable control of gene expression and functionality with potential clinical benefits.
RubisCO of a nucleoside pathway known from Archaea is found in diverse uncultivated phyla in bacteria
Authors: Wrighton Kelly C , Castelle Cindy J , Varaljay Vanessa A , Satagopan Sriram , Brown Christopher T , Wilkins Michael J , Thomas Brian C , Sharon Itai , Williams Kenneth H , Tabita F Robert , Banfield Jillian F
Published: May 2016

Metagenomic studies recently uncovered form II/III RubisCO genes, originally thought to only occur in archaea, from uncultivated bacteria of the candidate phyla radiation (CPR). There are no isolated CPR bacteria and these organisms are predicted to have limited metabolic capacities. Here we expand the known diversity of RubisCO from CPR lineages. We report a form of RubisCO, distantly similar to the archaeal form III RubisCO, in some CPR bacteria from the Parcubacteria (OD1), WS6 and Microgenomates (OP11) phyla. In addition, we significantly expand the Peregrinibacteria (PER) II/III RubisCO diversity and report the first II/III RubisCO sequences from the Microgenomates and WS6 phyla. To provide a metabolic context for these RubisCOs, we reconstructed near-complete (>93%) PER genomes and the first closed genome for a WS6 bacterium, for which we propose the phylum name Dojkabacteria. Genomic and bioinformatic analyses suggest that the CPR RubisCOs function in a nucleoside pathway similar to that proposed in Archaea. Detection of form II/III RubisCO and nucleoside metabolism gene transcripts from a PER supports the operation of this pathway in situ. We demonstrate that the PER form II/III RubisCO is catalytically active, fixing CO2 to physiologically complement phototrophic growth in a bacterial photoautotrophic RubisCO deletion strain. We propose that the identification of these RubisCOs across a radiation of obligately fermentative, small-celled organisms hints at a widespread, simple metabolic platform in which ribose may be a prominent currency.
Global genetic capacity for mixotrophy in marine picocyanobacteria
Authors: Yelton Alexis P , Acinas Silvia G , Sunagawa Shinichi , Bork Peer , Pedrós-Alió Carlos , Chisholm Sallie W
Published: May 2016

The assimilation of organic nutrients by autotrophs, a form of mixotrophy, has been demonstrated in the globally abundant marine picocyanobacterial genera Prochlorococcus and Synechococcus. However, the range of compounds used and the distribution of organic compound uptake genes within picocyanobacteria are unknown. Here we analyze genomic and metagenomic data from around the world to determine the extent and distribution of mixotrophy in these phototrophs. Analysis of 49 Prochlorococcus and 18 Synechococcus isolate genomes reveals that all have the transporters necessary to take up amino acids, peptides and sugars. However, the number and type of transporters and associated catabolic genes differ between different phylogenetic groups, with low-light IV Prochlorococcus, and 5.1B, 5.2 and 5.3 Synechococcus strains having the largest number. Metagenomic data from 68 stations from the Tara Oceans expedition indicate that the genetic potential for mixotrophy in picocyanobacteria is globally distributed and differs between clades. Phylogenetic analyses indicate gradual organic nutrient transporter gene loss from the low-light IV to the high-light II Prochlorococcus. The phylogenetic differences in genetic capacity for mixotrophy, combined with the ubiquity of picocyanobacterial organic compound uptake genes suggests that mixotrophy has a more central role in picocyanobacterial ecology than was previously thought.
Culturing of ‘unculturable’ human microbiota reveals novel taxa and extensive sporulation
Authors: Browne Hilary P. , Forster Samuel C. , Anonye Blessing O. , Kumar Nitin , Neville B. Anne , Stares Mark D. , Goulding David , Lawley Trevor D.
Published: May 2016

Our intestinal microbiota harbours a diverse bacterial community required for our health, sustenance and wellbeing1,2. Intestinal colonization begins at birth and climaxes with the acquisition of two dominant groups of strict anaerobic bacteria belonging to the Firmicutes and Bacteroidetes phyla2. Culture-independent, genomic approaches have transformed our understanding of the role of the human microbiome in health and many diseases1. However, owing to the prevailing perception that our indigenous bacteria are largely recalcitrant to culture, many of their functions and phenotypes remain unknown3. Here we describe a novel workflow based on targeted phenotypic culturing linked to large-scale whole-genome sequencing, phylogenetic analysis and computational modelling that demonstrates that a substantial proportion of the intestinal bacteria are culturable. Applying this approach to healthy individuals, we isolated 137 bacterial species from characterized and candidate novel families, genera and species that were archived as pure cultures. Whole-genome and metagenomic sequencing, combined with computational and phenotypic analysis, suggests that at least 50–60% of the bacterial genera from the intestinal microbiota of a healthy individual produce resilient spores, specialized for host-to-host transmission. Our approach unlocks the human intestinal microbiota for phenotypic analysis and reveals how a marked proportion of oxygen-sensitive intestinal bacteria can be transmitted between individuals, affecting microbiota heritability.
Highly variable cancer subpopulations that exhibit enhanced transcriptome variability and metastatic fitness
Authors: Nguyen Alexander , Yoshida Mitsukuni , Goodarzi Hani , Tavazoie Sohail F.
Published: May 2016

Individual cells within a tumour can exhibit distinct genetic and molecular features. The impact of such diversification on metastatic potential is unknown. Here we identify clonal human breast cancer subpopulations that display different levels of morphological and molecular diversity. Highly variable subpopulations are more proficient at metastatic colonization and chemotherapeutic survival. Through single-cell RNA-sequencing, inter-cell transcript expression variability is identified as a defining feature of the highly variable subpopulations that leads to protein-level variation. Furthermore, we identify high variability in the spliceosomal machinery gene set. Engineered variable expression of the spliceosomal gene SNRNP40 promotes metastasis, attributable to cells with low expression. Clinically, low SNRNP40 expression is associated with metastatic relapse. Our findings reveal transcriptomic variability generation as a mechanism by which cancer subpopulations can diversify gene expression states, which may allow for enhanced fitness under changing environmental pressures encountered during cancer progression.
Message in a molecule
Authors: Sarkar Tanmay , Selvakumar Karuthapandi , Motiei Leila , Margulies David
Published: May 2016

Since ancient times, steganography, the art of concealing information, has largely relied on secret inks as a tool for hiding messages. However, as the methods for detecting these inks improved, the use of simple and accessible chemicals as a means to secure communication was practically abolished. Here, we describe a method that enables one to conceal multiple different messages within the emission spectra of a unimolecular fluorescent sensor. Similar to secret inks, this molecular-scale messaging sensor (m-SMS) can be hidden on regular paper and the messages can be encoded or decoded within seconds using common chemicals, including commercial ingredients that can be obtained in grocery stores or pharmacies. Unlike with invisible inks, however, uncovering these messages by an unauthorized user is almost impossible because they are protected by three different defence mechanisms: steganography, cryptography and by entering a password, which are used to hide, encrypt or prevent access to the information, respectively.
DNA defects, epigenetics, and gene expression in cancer-adjacent breast: a study from The Cancer Genome Atlas
Authors: Troester Melissa A , Hoadley Katherine A , D’Arcy Monica , Cherniack Andrew D , Stewart Chip , Koboldt Daniel C , Robertson A Gordon , Mahurkar Swapna , Shen Hui , Wilkerson Matthew D , Sandhu Rupninder , Johnson Nicole B , Allison Kimberly H , Beck Andrew H , Yau Christina , Bowen Jay , Sheth Margi , Hwang E Shelley , Perou Charles M , Laird Peter W , Ding Li , Benz Christopher C
Published: May 2016

Recurrence rates after breast-conserving therapy may depend on genomic characteristics of cancer-adjacent, benign-appearing tissue. Studies have not evaluated recurrence in association with multiple genomic characteristics of cancer-adjacent breast tissue. To estimate the prevalence of DNA defects and RNA expression subtypes in cancer-adjacent, benign-appearing breast tissue at least 2 cm from the tumor margin, cancer-adjacent, pathologically well-characterized, benign-appearing breast tissue specimens from The Cancer Genome Atlas project were analyzed for DNA sequence, copy-number variation, DNA methylation, messenger RNA (mRNA) sequence, and mRNA/microRNA expression. Additional samples were also analyzed by at least one of these genomic data types and associations between genomic characteristics of normal tissue and overall survival were assessed. Approximately 40% of cancer-adjacent, benign-appearing tissues harbored genomic defects in DNA copy number, sequence, methylation, or in RNA sequence, although these defects did not significantly predict 10-year overall survival. Two mRNA/microRNA expression phenotypes were observed, including an active mRNA subtype that was identified in 40% of samples. Controlling for tumor characteristics and the presence of genomic defects, this active subtype was associated with significantly worse 10-year survival among estrogen receptor (ER)-positive cases. This multi-platform analysis of breast cancer-adjacent samples produced genomic findings consistent with current surgical margin guidelines, and provides evidence that extratumoral RNA expression patterns in cancer-adjacent tissue predict overall survival among patients with ER-positive disease.
Accurate Electron Affinity of Iron and Fine Structures of Negative Iron ions
Authors: Chen Xiaolin , Luo Zhihong , Li Jiaming , Ning Chuangang
Published: May 2016

Ionization potential (IP) is defined as the amount of energy required to remove the most loosely bound electron of an atom, while electron affinity (EA) is defined as the amount of energy released when an electron is attached to a neutral atom. Both IP and EA are critical for understanding chemical properties of an element. In contrast to accurate IPs and structures of neutral atoms, EAs and structures of negative ions are relatively unexplored, especially for the transition metal anions. Here, we report the accurate EA value of Fe and fine structures of Fe− using the slow electron velocity imaging method. These measurements yield a very accurate EA value of Fe, 1235.93(28) cm−1 or 153.236(34) meV. The fine structures of Fe− were also successfully resolved. The present work provides a reliable benchmark for theoretical calculations and also paves the way for improving the EA measurements of other transition metal atoms to the sub cm−1 accuracy.
Molecular Imaging of Activated Platelets Allows the Detection of Pulmonary Embolism with Magnetic Resonance Imaging
Authors: Heidt Timo , Ehrismann Simon , Hövener Jan-Bernd , Neudorfer Irene , Hilgendorf Ingo , Reisert Marco , Hagemeyer Christoph E. , Zirlik Andreas , Reinöhl Jochen , Bode Christoph , Peter Karlheinz , von Elverfeldt Dominik , von zur Muhlen Constantin
Published: May 2016

Early and reliable detection of pulmonary embolism (PE) is critical for improving patient morbidity and mortality. The desire for low-threshold screening for pulmonary embolism is contradicted by unfavorable radiation of currently used computed tomography or nuclear techniques, while standard magnetic resonance imaging still struggles to provide sufficient diagnostic sensitivity in the lung. In this study we evaluate a molecular-targeted contrast agent against activated platelets for non-invasive detection of murine pulmonary thromboembolism using magnetic resonance imaging. By intravenous injection of human thrombin, pulmonary thromboembolism were consistently induced as confirmed by immunohistochemistry of the lung. Magnetic resonance imaging after thrombin injection showed local tissue edema in "Equation missing" weighted images which co-localized with the histological presence of pulmonary thromboembolism. Furthermore, injection of a functionalized contrast agent targeting activated platelets provided sensitive evidence of focal accumulation of activated platelets within the edematous area, which, ex vivo, correlated well with the size of the pulmonary embolism. In summary, we here show delivery and specific binding of a functionalized molecular contrast agent against activated platelets for targeting pulmonary thromboembolism. Going forward, molecular imaging may provide new opportunities to increase sensitivity of magnetic resonance imaging for detection of pulmonary embolism.
Dislocation Majorana zero modes in perovskite oxide 2DEG
Authors: Chung Suk Bum , Chan Cheung , Yao Hong
Published: May 2016

Much of the current experimental efforts for detecting Majorana zero modes have been centered on probing the boundary of quantum wires with strong spin-orbit coupling. The same type of Majorana zero mode can also be realized at crystalline dislocations in 2D superconductors with the nontrivial weak topological indices. Unlike at an Abrikosov vortex, at such a dislocation, there is no other low-lying midgap state than the Majorana zero mode so that it avoids usual complications encountered in experimental detections such as scanning tunneling microscope (STM) measurements. We will show that, using the anisotropic dispersion of the t2g orbitals of Ti or Ta atoms, such a weak topological superconductivity can be realized when the surface two-dimensional electronic gas (2DEG) of SrTiO3 or KTaO3 becomes superconducting, which can occur through either intrinsic pairing or proximity to existing s-wave superconductors.
New Hosts of The Lassa Virus
Authors: Olayemi Ayodeji , Cadar Daniel , Magassouba N’Faly , Obadare Adeoba , Kourouma Fode , Oyeyiola Akinlabi , Fasogbon Samuel , Igbokwe Joseph , Rieger Toni , Bockholt Sabrina , Jérôme Hanna , Schmidt-Chanasit Jonas , Garigliany Mutien , Lorenzen Stephan , Igbahenah Felix , Fichet Jean-Nicolas , Ortsega Daniel , Omilabu Sunday , Günther Stephan , Fichet-Calvet Elisabeth
Published: May 2016

Lassa virus (LASV) causes a deadly haemorrhagic fever in humans, killing several thousand people in West Africa annually. For 40 years, the Natal multimammate rat, Mastomys natalensis, has been assumed to be the sole host of LASV. We found evidence that LASV is also hosted by other rodent species: the African wood mouse Hylomyscus pamfi in Nigeria, and the Guinea multimammate mouse Mastomys erythroleucus in both Nigeria and Guinea. Virus strains from these animals were isolated in the BSL-4 laboratory and fully sequenced. Phylogenetic analyses of viral genes coding for glycoprotein, nucleoprotein, polymerase and matrix protein show that Lassa strains detected in M. erythroleucus belong to lineages III and IV. The strain from H. pamfi clusters close to lineage I (for S gene) and between II & III (for L gene). Discovery of new rodent hosts has implications for LASV evolution and its spread into new areas within West Africa.
An effective colorimetric and ratiometric fluorescent probe based FRET with a large Stokes shift for bisulfite
Authors: Wu Wen-Li , Wang Zhao-Yang , Dai Xi , Miao Jun-Ying , Zhao Bao-Xiang
Published: May 2016

Bisulfite plays crucial roles in diverse physiological processes. Therefore, the efficient detection of bisulfite is very important. In this study, we report a colorimetric and ratiometric fluorescent probe (CPT) with a large Stokes shift (162 nm) for bisulfite (HSO3−) based FRET mechanism. The probe can quantitatively detect HSO3− with low detection limit (45 nM) and high specificity over other common anions and biothiols. A nucleophilic addition reaction was proposed for the sensing mechanism, which was confirmed by HRMS spectra. The test strips of the probe were made and used easily. Moreover, probe CPT was used to ratiometric fluorescent imaging of exogenous and endogenous HSO3− in living cells.
Combined sodium ion sensitivity in agonist binding and internalization of vasopressin V1b receptors
Authors: Koshimizu Taka-aki , Kashiwazaki Aki , Taniguchi Junichi
Published: May 2016

Reducing Na+ in the extracellular environment may lead to two beneficial effects for increasing agonist binding to cell surface G-protein coupled receptors (GPCRs): reduction of Na+-mediated binding block and reduce of receptor internalization. However, such combined effects have not been explored. We used Chinese Hamster Ovary cells expressing vasopressin V1b receptors as a model to explore Na+ sensitivity in agonist binding and receptor internalization. Under basal conditions, a large fraction of V1b receptors is located intracellularly and a small fraction is in the plasma membrane. Decreases in external Na+ increased cell surface [3H]AVP binding and decreased receptor internalization. Substitution of Na+ by Cs+ or NH4+ inhibited agonist binding. To suppress receptor internalization, the concentration of NaCl, but not of CsCl, had to be less than 50 mM, due to the high sensitivity of the internalization machinery to Na+ over Cs+. Iso-osmotic supplementation of glucose or NH4Cl maintained internalization of the V1b receptor, even in a low-NaCl environment. Moreover, iodide ions, which acted as a counter anion, inhibited V1b agonist binding. In summary, we found external ionic conditions that could increase the presence of high-affinity state receptors at the cell surface with minimum internalization during agonist stimulations.
Resveratrol Inhibition of Rac1-Derived Reactive Oxygen Species by AMPK Decreases Blood Pressure in a Fructose-Induced Rat Model of Hypertension
Authors: Cheng Pei-Wen , Lee Hui-Chieh , Lu Pei-Jung , Chen Hsin-Hung , Lai Chi-Cheng , Sun Gwo-Ching , Yeh Tung-Chen , Hsiao Michael , Lin Yu-Te , Liu Chun-Peng , Tseng Ching-Jiunn
Published: May 2016

Recent studies have reported that the activation of AMP-activated protein kinase (AMPK) suppressed oxidative stress. The aim of this study was to examine whether the activation of AMPK in the brain decreased Rac1-induced ROS generation, thereby reducing blood pressure (BP) in rats with fructose-induced hypertension. The inhibition of ROS by treatment with an AMPK activator (oral resveratrol, 10 mg/kg/day) for 1 week decreased the BP and increased the NO production in the rostral ventrolateral medulla (RVLM) of fructose-fed rats but not in control Wistar-Kyoto (WKY) rats. In addition, resveratrol treatment abolished the Rac1-induced increases in the activity of the NADPH oxidase subunits p22-phox and reduced the activity of SOD2, while treatment with an AMPK inhibitor (compound C, 40 μM/day) had the opposite effect, in the fructose-fed rats. Interestingly, the activation of AMPK abolished Rac1 activation and decreased BP by inducing the activities of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and ribosomal protein S6 kinase (RSK) and nNOS phosphorylation in the fructose-fed rats. We conclude that the activation of AMPK decreased BP, abolished ROS generation and enhanced ERK1/2-RSK-nNOS pathway activity by negatively regulating Racl-induced NADPH oxidase levels in the RVLM during oxidative stress–associated hypertension.
Expression levels of ROS1/ALK/c-MET and therapeutic efficacy of cetuximab plus chemotherapy in advanced biliary tract cancer
Authors: Chiang Nai-Jung , Hsu Chiun , Chen Jen-Shi , Tsou Hsiao-Hui , Shen Ying-Ying , Chao Yee , Chen Ming-Huang , Yeh Ta-Sen , Shan Yan-Shen , Huang Shiu-Feng , Chen Li-Tzong
Published: May 2016

Aberrant expression of ROS1, ALK or c-MET (RAM) is implicated in carcinogenesis and cancer drug resistance. We retrospectively evaluated the effect of RAM expression on outcomes for advanced biliary tract cancer patients, who were treated with gemcitabine plus oxaliplatin (GEMOX), with or without cetuximab, in a randomized phase II trial. RAM expression levels on archived tissue sections were scored using immunohistochemistry (IHC). Of 110 tumors with IHC staining for all three markers, 18 were RAMhigh (IHC intensity 3+ for any markers). Ninety-two tumors were RAMlow (IHC intensity <3+ for all markers). All RAMhigh tumors were intra-hepatic cholangiocarcinomas (IHCC). Of the patients with IHCC (n = 80), median overall survival (OS) of RAMhigh group was inferior to that of the RAMlow group (5.7 vs. 11.7 months, p = 0.021). In multivariate analysis RAMhigh remained an independently adverse prognostic factor, with a hazard ratio of 2.01 (p = 0.039). In the RAMlow group, GEMOX treatment with cetuximab significantly improved the disease control rate (68% vs. 41%, p = 0.044), median progression-free survival (7.3 vs. 4.9 months, p = 0.026), and marginally prolonged median OS (14.1 vs 9.6 months, p = 0.056), compared to GEMOX treatment alone. Future trials of anti-EGFR inhibitors for IHCC may consider RAM expression as a patient stratification factor.
The Complex QT/RR Relationship in Mice
Authors: Roussel Julien , Champeroux Pascal , Roy Jérôme , Richard Sylvain , Fauconnier Jérémy , Le Guennec Jean-Yves , Thireau Jérôme
Published: May 2016

The QT interval reflects the time between the depolarization of ventricles until their repolarization and is usually used as a predictive marker for the occurrence of arrhythmias. This parameter varies with the heart rate, expressed as the RR interval (time between two successive ventricular depolarizations). To calculate the QT independently of the RR, correction formulae are currently used. In mice, the QT-RR relationship as such has never been studied in conscious animals, and correction formulas are mainly empirical. In the present paper we studied how QT varies when the RR changes physiologically (comparison of nocturnal and diurnal periods) or after dosing mice with tachycardic agents (norepinephrine or nitroprusside). Our results show that there is significant variability of QT and RR in a given condition, resulting in the need to average at least 200 consecutive complexes to accurately compare the QT. Even following this method, no obvious shortening of the QT was observed with increased heart rate, regardless of whether or not this change occurs abruptly. In conclusion, the relationship between QT and RR in mice is weak, which renders the use of correction formulae inappropriate and misleading in this species.
Epigenetically regulated miR-449a enhances hepatitis B virus replication by targeting cAMP-responsive element binding protein 5 and modulating hepatocytes phenotype
Authors: Zhang Xiaoyong , Liu Hongyan , Xie Zhanglian , Deng Wangyu , Wu Chunchen , Qin Bo , Hou Jinlin , Lu Mengji
Published: May 2016

Cellular microRNAs (miRNAs) are able to influence hepatitis B virus (HBV) replication directly by binding to HBV transcripts or indirectly by targeting cellular factors. Here, we investigate the effect of epigenetically regulated miR-449a on HBV replication and the underlying mechanisms. miR-449a expression was lower in human hepatocellular carcinoma (HCC) cells than in primary hepatocytes and could be induced by trichostatin A. Ectopic miR-449a expression in HCC cells strongly enhanced HBV replication, transcription, progeny virions secretion and antigen expression in a dose-dependent manner. miR-449a directly targeted cAMP-responsive element binding protein 5 (CREB5), which in turn induced the expression of farnesoid X receptor α (FXRα), a transcription factor that facilitates HBV replication. CREB5 knockdown and overexpression demonstrated that it is a negative regulator of HBV replication. Additionally, miR-449a overexpression inhibited proliferation, caused cell cycle arrest and promoted HCC cell differentiation. The results indicated that epigenetically regulated miR-449a targets CREB5 to increase FXRα expression, thereby promoting HBV replication and gene expression. Our findings provide a new understanding of the role of miRNAs in HBV replication.
A clinically applicable molecular classification for high-grade serous ovarian cancer based on hormone receptor expression
Authors: Feng Zheng , Wen Hao , Bi Rui , Ju Xingzhu , Chen Xiaojun , Yang Wentao , Wu Xiaohua
Published: May 2016

To establish an effective hormone receptor-based molecular classification of high-grade serous ovarian cancer (HGSC), we retrospectively examined 875 consecutive HGSC patients who underwent primary surgery at our hospital and constructed tissue microarrays from these specimens. The expression levels of the hormone receptors were as follows: ER 64.4%, PR 12.6%, AR 35.6%, FSHR 54.5%, LHR 34.8%, and GnRHR 88.3%. Based on clustering of their expression patterns, we classified patients into five subgroups with distinctive clinical features (PR+, PR − ER + AR+, PR − ER + AR−, PR − ER − AR+, and PR − ER − AR−). Patients in the PR + group were younger compared to those in the other groups (p < 0.001). More patients were of advanced stage in the PR − ER + AR− group than the other groups (p = 0.020). A greater proportion of patients were sensitive to platinum-based chemotherapy in the PR − ER − AR + group compared with the other groups (p = 0.034). A trend of increasing risk of death was observed among these subgroups (p < 0.001). In the multivariate analysis, patients also had orderly increased hazard ratios for death in the PR + (HR = 2.256, 95% CI, 0.983–5.175), PR − ER + AR + (HR = 2.188, 95% CI, 1.004–4.796), PR − ER − AR− (HR = 2.316, 95% CI, 1.097–5.082) and PR − ER + AR− (HR = 2.928, 95% CI, 1.366–6.276) subgroups compared to the PR − ER − AR+ subgroup. Our classification could help predict patient clinical outcomes, guide individual treatments and stratify patients in future clinical trials.
Sex, offspring and carcass determine antimicrobial peptide expression in the burying beetle
Authors: Jacobs Chris G. C. , Steiger Sandra , Heckel David G. , Wielsch Natalie , Vilcinskas Andreas , Vogel Heiko
Published: May 2016

The burying beetle Nicrophorus vespilloides has emerged as a model system for the investigation of adaptations that allow the utilization of carrion as a diet and as a resource for reproduction. The survival of beetles and their offspring given their exposure to soil-dwelling and cadaver-borne microbes requires mechanisms that reduce bacterial contamination in the diet and that achieve sanitation of the microhabitat. To explore the role of antimicrobial peptides (AMPs) in this context, we analyzed burying beetle males and females at different stages of their breeding cycle using the RNA-Seq and proteomics approaches. To address variation in immune functions, we investigated the impact of adult sex, the presence or absence of offspring (social context), and the presence of carrion (environmental context) on the expression of the identified immune effector genes. We found that particular AMPs are sex-specific and tightly regulated by the presence of a carcass or offspring and identified the two most context-dependent antimicrobial proteins in anal secretions. The context-specific expression dynamics of particular AMPs and lysozymes reveals a complex regulatory system, reflecting adaptations to specific ecological niches. This study highlights how burying beetles cope with microorganisms found on carrion and identifies candidates for both internal and external immunity.
Multi-Order Investigation of the Nonlinear Susceptibility Tensors of Individual Nanoparticles
Authors: Schmidt Cédric , Riporto Jérémy , Uldry Aline , Rogov Andrii , Mugnier Yannick , Dantec Ronan Le , Wolf Jean-Pierre , Bonacina Luigi
Published: May 2016

We use Hyper Rayleigh Scattering and polarization resolved multiphoton microscopy to investigate simultaneously the second and third-order nonlinear response of Potassium Niobate and Bismuth Ferrite harmonic nanoparticles. We first derive the second-to-third harmonic intensity ratio for colloidal ensembles and estimate the average third-order efficiency of these two materials. Successively, we explore the orientation dependent tensorial response of individual nanoparticles fixed on a substrate. The multi-order polarization resolved emission curves are globally fitted with an analytical model to retrieve individual elements of susceptibility tensors.
Surface fractal dimension, water adsorption efficiency and cloud nucleation activity of insoluble aerosol
Authors: Laaksonen Ari , Malila Jussi , Nenes Athanasios , Hung Hui-Ming , Chen Jen-Ping
Published: May 2016

Surface porosity affects the ability of a substance to adsorb gases. The surface fractal dimension D is a measure that indicates the amount that a surface fills a space and can thereby be used to characterize the surface porosity. Here we propose a new method for determining D, based on measuring both the water vapour adsorption isotherm of a given substance and its ability to act as a cloud condensation nucleus when introduced to humidified air in aerosol form. We show that our method agrees well with previous methods based on measurement of nitrogen adsorption. Besides proving the usefulness of the new method for general surface characterization of materials, our results show that the surface fractal dimension is an important determinant in cloud drop formation on water insoluble particles. We suggest that a closure can be obtained between experimental critical supersaturation for cloud drop activation and that calculated based on water adsorption data, if the latter is corrected using the surface fractal dimension of the insoluble cloud nucleus.
Financial difficulties but not other types of recent negative life events show strong interactions with 5-HTTLPR genotype in the development of depressive symptoms
Authors: Gonda X , Eszlari N , Kovacs D , Anderson I M , Deakin J F W , Juhasz G , Bagdy G
Published: May 2016

Several studies indicate that 5-HTTLPR mediates the effect of childhood adversity in the development of depression, while results are contradictory for recent negative life events. For childhood adversity the interaction with genotype is strongest for sexual abuse, but not for other types of childhood maltreatment; however, possible interactions with specific recent life events have not been investigated separately. The aim of our study was to investigate the effect of four distinct types of recent life events in the development of depressive symptoms in a large community sample. Interaction between different types of recent life events measured by the List of Threatening Experiences and the 5-HTTLPR genotype on current depression measured by the depression subscale and additional items of the Brief Symptom Inventory was investigated in 2588 subjects in Manchester and Budapest. Only a nominal interaction was found between life events overall and 5-HTTLPR on depression, which failed to survive correction for multiple testing. However, subcategorising life events into four categories showed a robust interaction between financial difficulties and the 5-HTTLPR genotype, and a weaker interaction in the case of illness/injury. No interaction effect for the other two life event categories was present. We investigated a general non-representative sample in a cross-sectional approach. Depressive symptoms and life event evaluations were self-reported. The 5-HTTLPR polymorphism showed a differential interaction pattern with different types of recent life events, with the strongest interaction effects of financial difficulties on depressive symptoms. This specificity of interaction with only particular types of life events may help to explain previous contradictory findings.
Intensified vmPFC surveillance over PTSS under perturbed microRNA-608/AChE interaction
Authors: Lin T , Simchovitz A , Shenhar-Tsarfaty S , Vaisvaser S , Admon R , Hanin G , Hanan M , Kliper E , Bar-Haim Y , Shomron N , Fernandez G , Lubin G , Fruchter E , Hendler T , Soreq H
Published: May 2016

Trauma causes variable risk of posttraumatic stress symptoms (PTSS) owing to yet-unknown genome–neuronal interactions. Here, we report co-intensified amygdala and ventromedial prefrontal cortex (vmPFC) emotional responses that may overcome PTSS in individuals with the single-nucleotide polymorphism (SNP) rs17228616 in the acetylcholinesterase (AChE) gene. We have recently shown that in individuals with the minor rs17228616 allele, this SNP interrupts AChE suppression by microRNA (miRNA)-608, leading to cortical elevation of brain AChE and reduced cortisol and the miRNA-608 target GABAergic modulator CDC42, all stress-associated. To examine whether this SNP has effects on PTSS and threat-related brain circuits, we exposed 76 healthy Israel Defense Forces soldiers who experienced chronic military stress to a functional magnetic resonance imaging task of emotional and neutral visual stimuli. Minor allele individuals predictably reacted to emotional stimuli by hyperactivated amygdala, a hallmark of PTSS and a predisposing factor of posttraumatic stress disorder (PTSD). Despite this, minor allele individuals showed no difference in PTSS levels. Mediation analyses indicated that the potentiated amygdala reactivity in minor allele soldiers promoted enhanced vmPFC recruitment that was associated with their limited PTSS. Furthermore, we found interrelated expression levels of several miRNA-608 targets including CD44, CDC42 and interleukin 6 in human amygdala samples (N=7). Our findings suggest that miRNA-608/AChE interaction is involved in the threat circuitry and PTSS and support a model where greater vmPFC regulatory activity compensates for amygdala hyperactivation in minor allele individuals to neutralize their PTSS susceptibility.
In-syringe reversed dispersive liquid–liquid microextraction coupled to high performance liquid chromatography for the determination of sulfonylurea herbicide residues in cereal samples
Authors: Ngaosi Niphaphon , Seebunrueng Ketsarin , Srijaranai Supalax
Published: May 2016

A rapid and sensitive method, IS-R-DLLME coupled to HPLC, has been developed for the determination of sulfonylurea herbicides in cereal samples.
Promotion of 1,3-dipolar cycloaddition between azides and β-enaminones by deep eutectic solvents
Authors: Martins Marcos Antonio Pinto , Paveglio Guilherme Caneppele , Rodrigues Leticia Valvassori , Frizzo Clarissa Piccinin , Zanatta Nilo , Bonacorso Helio Gauze
Published: May 2016

The metal-free, high selectivity and efficient synthesis of 4-acyl triazoles in a DES (ChCl:ethylene glycol) is reported.
Mechanical signatures of microbial biofilms in micropillar-embedded growth chambers
Authors: Chew S. C. , Kundukad B. , Teh W. K. , Doyle P. , Yang L. , Rice S. A. , Kjelleberg S.
Published: May 2016

Biofilms are surface-attached communities of microorganisms embedded in an extracellular matrix and are essential for the cycling of organic matter in natural and engineered environments.
Fabrication of living soft matter by symbiotic growth of unicellular microorganisms
Authors: Das Anupam A. K. , Bovill James , Ayesh Maram , Stoyanov Simeon D. , Paunov Vesselin N.
Published: May 2016

We have produced a living biomaterial by a symbiotic growth of the bacteria,Acetobacter aceti, and the microalgae,C. reinhardtii, which integratein situinto the produced bacterial cellulose gel.
Early apoptosis real-time detection by label-free SERS based on externalized phosphatidylserine
Authors: Zhou Haibo , Wang Qiqin , Yuan Detian , Wang Jinyong , Huang Yang , Wu Huihui , Jian Jingyi , Yang Danting , Huang Ning , Haisch Christoph , Jiang Zhengjin , Chen Shanze
Published: May 2016

Early apoptosis real-time detection by label-free SERS based on externalized phosphatidylserine usingin situsynthesized silver nanoparticles.
Solid phase microextraction–comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry: a new tool for determining PAHs in airport runoff water samples
Authors: Sulej-Suchomska Anna Maria , Polkowska Żaneta , Chmiel Tomasz , Dymerski Tomasz Marcin , Kokot Zenon Józef , Namieśnik Jacek
Published: May 2016

Analysis of a new type of environmental sample – airport stormwater, a new analytical protocol (SPME/GC × GC-TOFMS) for tracking the environmental fate of PAHs.
Determination of compounds with varied volatilities from aqueous samples using a polymeric ionic liquid sorbent coating by direct immersion-headspace solid-phase microextraction
Authors: Merib Josias , Yu Honglian , Carasek Eduardo , Anderson Jared L.
Published: May 2016

The use of highly robust polymeric ionic liquid (PIL) sorbent coatings combined with direct immersion (DI) and headspace (HS) modes in a single solid-phase microextraction (SPME) procedure coupled to gas chromatography (GC) is reported.
Simultaneous determination of seven acrylates in food contact paper products by GC/MS and modified QuEChERS
Authors: Xun Zhiqing , Huang Jinfeng , Li Xiu-Ying , Lin Senyu , He Shuang , Guo Xindong , Xian Yanping
Published: May 2016

A new method was established to determine acrylates in food contact paper products by utilizing modified QuEChERS technology and GC/MS.
A simple label-free aptamer-based method for C-reactive protein detection
Authors: Wu Bin , Chen Nandi , Wang Qing , Yang Xiaohai , Wang Kemin , Li Wenshan , Li Qing , Liu Wenjing , Fang Hongmei
Published: May 2016

We developed a simple label-free aptamer-based method for C-reactive protein (CRP) detection.
Oxo-rhenium catalyzed reductive coupling and deoxygenation of alcohols
Authors: Kasner Gabrielle R. , Boucher-Jacobs Camille , Michael McClain J. , Nicholas Kenneth M.
Published: May 2016

Representative benzylic, allylic and α-keto alcohols are deoxygenated to alkanes and/or reductively coupled to alkane dimers by reaction with PPh3catalyzed by (PPh3)2ReIO2(1).
One-pot assembly of metal/organic-acid sites on amine-functionalized ligands of MOFs for photocatalytic hydrogen peroxide splitting
Authors: Qin Lei , Li Zhaowen , Hu Qiong , Xu Zehai , Guo Xinwen , Zhang Guoliang
Published: May 2016

A one-pot organic-acid-directed post-synthetic modification allows molecular iron/citric acid complexes to be anchored into amine-functionalized MOFs by a liquid spraying method.
NIR light/H2O2-triggered nanocomposites for a highly efficient and selective synergistic photodynamic and photothermal therapy against hypoxic tumor cells
Authors: Zhang Yu , Shen Ting-Ting , Kirillov Alexander M. , Liu Wei-Sheng , Tang Yu
Published: May 2016

Smart nanocomposites were designed and applied for an efficient synergistic photodynamic and photothermal therapy under single NIR laser excitation to overcome the hypoxia-induced drug resistance.
Enantioselective construction of imidazolines having vicinal tetra-substituted stereocenters by direct Mannich reaction of α-substituted α-isocyanoacetates with ketimines
Authors: Nakamura Shuichi , Yamaji Ryota , Iwanaga Masaru
Published: May 2016

Enantioselective direct Mannich-type reaction of ketimines with α-substituted α-isocyanoacetates gave imidazolines having vicinal tetra-substituted stereocenters with high stereoselectivity.
Photoacid-mediated ring opening polymerization driven by visible light
Authors: Fu Changkui , Xu Jiangtao , Boyer Cyrille
Published: May 2016

Visible light regulated ring opening polymerization in the presence of reversible merocyanine-based photoacid is reported in this article.
Tunable DNA cleavage activity promoted by copper(ii) ternary complexes with N-donor heterocyclic ligands
Authors: Bortolotto T. , Silva-Caldeira P. P. , Pich C. T. , Pereira-Maia E. C. , Terenzi H.
Published: May 2016

UV-light exposure can greatly enhance the DNA cleavage activity promoted by ternary copper(ii) complexes.
A through-space description of substituent effects leads to inaccurate molecular electrostatic potentials and cation⋯π interactions in extended aromatic systems
Authors: Cabaleiro-Lago Enrique M. , Rodríguez-Otero Jesús
Published: May 2016

The effect of substituents in extended aromatic systems spreads to the whole molecule. Predictions based on the currently accepted through-space model give significant deviations on the strength of cation⋯π interactions.
Markedly different adsorption behaviors of gas molecules on defective monolayer MoS2: a first-principles study
Authors: Li Hongxing , Huang Min , Cao Gengyu
Published: May 2016

Different gas molecules adsorbed on monolayer MoS2with single S vacancy behave differently. Particularly, NO2dissociates on defective MoS2with low activation barrier energy forming NO molecule and O atom filling in S vacancy.
Polymorphism in α-sexithiophene crystals: relative stability and transition path
Authors: Klett Bernhard , Cocchi Caterina , Pithan Linus , Kowarik Stefan , Draxl Claudia
Published: May 2016

We theoretically and experimentally determine the relative stability between sexithiophene crystal polymorphs, and estimate the transition barrier between them.
Electrochemical activity and high ionic conductivity of lithium copper pyroborate Li6CuB4O10
Authors: Strauss Florian , Rousse Gwenaëlle , Alves Dalla Corte Daniel , Ben Hassine Mohamed , Saubanère Matthieu , Tang Mingxue , Vezin Hervé , Courty Matthieu , Dominko Robert , Tarascon Jean-Marie
Published: May 2016

Conductivity of Li6CuB4O10 as function of temperature highlighting a reversible structural transition leading to a high ionic conductivity of ∼1.4 mS cm−1 at 500 °C.
First-principles study of thermal properties of borophene
Authors: Sun Hongyi , Li Qingfang , Wan X. G.
Published: May 2016

Very recently, a new single-element two-dimensional (2D) material borophene was successfully grown on a silver surface under pristine ultrahigh vacuum conditions which attracts tremendous interest.
Mechanistic insight into the nucleation and growth of oleic acid capped lead sulphide quantum dots
Authors: Shrestha Aabhash , Spooner Nigel A. , Qiao Shi Zhang , Dai Sheng
Published: May 2016

In this study, we present a detailed understanding on synthesis mechanism of PbS QDs so as to provide guidance for future QDs synthesis.
Lanthanide-directed synthesis of luminescent self-assembly supramolecular structures and mechanically bonded systems from acyclic coordinating organic ligands
Authors: Barry Dawn E. , Caffrey David F. , Gunnlaugsson Thorfinnur
Published: May 2016

This review focuses on recent developments made in the area of lanthanide directed synthesis/formation of supramolecular self-assembly structures including the formation of complexes/bundles, helicates, MOFs and interlocked molecules.
The conversion of levulinic acid into γ-valerolactone using Cu–ZrO2 catalysts
Authors: Jones Daniel R. , Iqbal Sarwat , Ishikawa Satoshi , Reece Christian , Thomas Liam M. , Miedziak Peter J. , Morgan David J. , Edwards Jennifer K. , Bartley Jonathon K. , Willock David J. , Hutchings Graham J.
Published: May 2016

A series of Cu–ZrO2 catalysts prepared by a co-precipitation method were studied for the hydrogenation of levulinic acid to give γ-valerolactone (GVL).
Li0.6[Li0.2Sn0.8S2] – a layered lithium superionic conductor
Authors: Holzmann T. , Schoop L. M. , Ali M. N. , Moudrakovski I. , Gregori G. , Maier J. , Cava R. J. , Lotsch B. V.
Published: May 2016

Implementing vacant sites enhances the Li mobility in lithium tin sulfide enormously as demonstrated by the increase in Li conductivity from 10−5 S cm−1 in Li1.0[Li0.33Sn0.67S2] to 10−2 S cm−1 in Li0.6[Li0.2Sn0.8S2].
A carbon dot–hemoglobin complex-based biosensor for cholesterol detection
Authors: Bui Trang Thi , Park Soo-Young
Published: May 2016

In the present study, a carbon dot/hemoglobin (CD/Hb) complex is used as a bio-receptor in an optical cholesterol biosensor.
Cooperative rare earth metal–zinc based heterometallic catalysts for copolymerization of CO2 and cyclohexene oxide
Authors: Qin Jie , Xu Bin , Zhang Yong , Yuan Dan , Yao Yingming
Published: May 2016

Significant cooperation was observed in rare earth metal–zinc heterotrinuclear complexes when initiating the copolymerization of CO2 and cyclohexene oxide.
Structural analysis of oncogenic mutation of isocitrate dehydrogenase 1
Authors: Rajendran Vidya
Published: May 2016

Arginine to histidine mutation at position 132 (R132H) in isocitrate dehydrogenase 1 (IDH1) led to reduced affinity of the respective enzymes for isocitrate and increased affinity for α-ketoglutarate (AKG) and NADPH.
Thioester-appended organosilatranes: synthetic investigations and application in the modification of magnetic silica surfaces
Authors: Singh Gurjaspreet , Rani Sunita , Arora Aanchal , Aulakh Darpandeep , Wriedt Mario
Published: May 2016

Thioester tethered organosilatranes were synthesized. The substituent effect on the absorption spectra and potential for binding with Cu2+were explored.
Niobium pentoxide nanotube powder for efficient dye-sensitized solar cells
Authors: Liu Xiaolin , Yuan Renlong , Liu Yongsheng , Zhu Shu , Lin Jia , Chen Xianfeng
Published: May 2016

Niobium pentoxide nanotube powder was obtained by continuous anodization and applied as the photoanode in dye-sensitized solar cells.
Mono- and bis-N-heterocyclic carbene complexes of tantalum and niobium with high oxidation states
Authors: Wei ZhenHong , Zhang Wenbiao , Luo Guangming , Xu Feng , Mei YingXuan , Cai Hu
Published: May 2016

Reactions of two free NHCs 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) and 1,3-dimesitylimidazol-2-yliden (IMes) with group VB metals MCl5 (M = Ta, Nb) gave a mono-(NHC) complex 1 and two bis-(NHC) complexes 2 and 3 with the high oxidation states of Nb(v) and Ta(v).
Multifunctional core–shell hybrid nano-composites made using Pickering emulsions: a new design for therapeutic vectors
Authors: Fontecave Thomas , Bourbousson Manon , Chaneac Corinne , Wilhelm Claire , Espinosa Ana , Fortin Marc-André , Sanchez Clément , Boissiere Cédric
Published: May 2016

A model of therapeutic nanovectors was developed for creating original prodrug@Fe2O3@porous silica architectures. Fe2O3 catalytic and magnetic properties were used for controlling the kinetics of drug release.
Concise synthesis of calystegines B2 and B3via intramolecular Nozaki–Hiyama–Kishi reaction
Authors: Wang Hong-Yao , Kato Atsushi , Kinami Kyoko , Li Yi-Xian , Fleet George W. J. , Yu Chu-Yi
Published: May 2016

Calystegines B2 and B3 were synthesized with a concise and efficient strategy, which features an intramolecular Nozaki–Hiyama–Kishi (NHK) reaction as the key step.
In situ generated nickel on cerium oxide nanoparticle for efficient catalytic reduction of 4-nitrophenol
Authors: Vivek S. , Arunkumar P. , Babu K. Suresh
Published: May 2016

Absorption spectra recorded using UV-visible spectrometer during the reduction process of 4-nitrophenol to 4-aminophenol in the presence of reducing agent (NaBH4) and catalyst (Ni(NO3)2/CeO2).