bluuebunny/crossref_metadata_2025 huggingface dataset:
Green and Red Fluorescent Dyes for Translational Applications in Imaging and Sensing Analytes: A Dual‐Color Flag
Authors: Oliveira Elisabete , Bértolo Emilia , Núñez Cristina , Pilla Viviane , Santos Hugo M. , Fernández‐Lodeiro Javier , Fernández‐Lodeiro Adrian , Djafari Jamila , Capelo José Luis , Lodeiro Carlos
Published: November 2017

Invited for this month's cover picture is the BIOSCOPE group of Professors Carlos Lodeiro and José Luis Capelo at the REQUIMTE/UCIBIO‐LAQv‐FCT University NOVA of Lisbon (Portugal), and their collaborators. The cover picture is devoted to Translational Research, and shows the Portuguese Flag represented by the interaction between cells and Janus gold/silver nanoparticles functionalized with rhodamine (red) and Fluorescein (green) dyes as tools for biomedical translational research. Read the full text of their Review at 10.1002/open.201700135.
Simultaneous Measurements of Geometric and Viscoelastic Properties of Hydrogel Microbeads Using Continuous‐Flow Microfluidics with Embedded Electrodes
Authors: Niu Ye , Zhang Xu , Si Ting , Zhang Yuntian , Qi Lin , Zhao Gang , Xu Ronald X. , He Xiaoming , Zhao Yi
Published: November 2017

Geometric and mechanical characterizations of hydrogel materials at the microscale are attracting increasing attention due to their importance in tissue engineering, regenerative medicine, and drug delivery applications. Contemporary approaches for measuring the these properties of hydrogel microbeads suffer from low‐throughput, complex system configuration, and measurement inaccuracy. In this work, a continuous‐flow device is developed to measure geometric and viscoelastic properties of hydrogel microbeads by flowing the microbeads through a tapered microchannel with an array of interdigitated microelectrodes patterned underneath the channel. The viscoelastic properties are derived from the trajectories of microbeads using a quasi‐linear viscoelastic model. The measurement is independent of the applied volumetric flow rate. The results show that the geometric and viscoelastic properties of Ca‐alginate hydrogel microbeads can be determined independently and simultaneously. The bulky high‐speed optical systems are eliminated, simplifying the system configuration and making it a truly miniaturized device. A throughput of up to 394 microbeads min−1 is achieved. This study may provide a powerful tool for mechanical profiling of hydrogel microbeads to support their wide applications.
Biotinylated Photopolymers for 3D‐Printed Unibody Lab‐on‐a‐Chip Optical Platforms
Authors: Credi Caterina , Griffini Gianmarco , Levi Marinella , Turri Stefano
Published: November 2017

The present work reports the first demonstration of straightforward fabrication of monolithic unibody lab‐on‐a‐chip (ULOCs) integrating bioactive micrometric 3D scaffolds by means of multimaterial stereolithography (SL). To this end, a novel biotin‐conjugated photopolymer is successfully synthesized and optimally formulated to achieve high‐performance SL‐printing resolution, as demonstrated by the SL‐fabrication of biotinylated structures smaller than 100 µm. By optimizing a multimaterial single‐run SL‐based 3D‐printing process, such biotinylated microstructures are incorporated within perfusion microchambers whose excellent optical transparency enables real‐time optical microscopy analyses. Standard biotin‐binding assays confirm the existence of biotin‐heads on the surfaces of the embedded 3D microstructures and allow to demonstrate that the biofunctionality of biotin is not altered during the SL‐printing, thus making it exploitable for further conjugation with other biomolecules. As a step forward, an in‐line optical detection system is designed, prototyped via SL‐printing and serially connected to the perfusion microchambers through customized world‐to‐chip connectors. Such detection system is successfully employed to optically analyze the solution flowing out of the microchambers, thus enabling indirect quantification of the concentration of target interacting biomolecules. The successful application of this novel biofunctional photopolymer as SL‐material enables to greatly extend the versatility of SL to directly fabricate ULOCs with intrinsic biofunctionality.
What’s in a Name
Authors: Parisi Andrew ,   Philosophy Documentation Center
Published: November 2017

This paper offers a response to Ramsey’s famous challenge to draw a logical, as opposed to merely syntactical, distinction between names and predicates. Three attempts to meet this challenge are considered, one from Dummett, one from Geach, and one from Brandom. It is shown that none of these adequately addresses Ramsey’s challenge. The paper concludes with a response to Ramsey that avoids the pitfalls of the other three replies. The advantage of the view proposed is that there is nothing preventing the set of sentences in consideration from consisting only of atomic sentences. The upshot of my solution is that the distinction between names and properties rests on the presence of relational predicates in a language and the validity of the structural rules of identity, contraction, and cut.
Muconato‐bridged Manganese Coordination Polymer exhibiting rare Distorted‐trigonal Prismatic Coordination Arrangement
Authors: Jaramillo‐García Jonathan , Sánchez‐Mendieta Víctor , García‐Orozco Iván , Morales‐Luckie Raúl A. , Martínez‐Otero Diego , Téllez‐López Antonio , Rosales‐Vázquez Luis D. , Escudero Roberto , Morales Francisco
Published: November 2017

Novel poly[Mn(H2O)(dmb)(muco)] (1) (H2muco = trans,trans‐muconic acid; dmb = 5,5′‐dimethyl‐2,2′‐bipyridine) was obtained by self‐assembly, one‐pot, solution reaction. 1 crystallizes in a monoclinic system with P21 space group and forms an infinite one‐dimensional (1D) polymer. Remarkably, the six‐coordinate MnII display a rare distorted trigonal prismatic configuration. This unusual coordination arrangement appears to be acquired due to the supramolecular interactions of the polymeric structure of 1, mainly throughout hydrogen bonding, giving rise to a 2D framework. Magnetic properties measurements reveal that 1 possesses weak antiferromagnetic interactions with θ(C–W) = –1.0 K and J = 458 cm–1.
Introduction
Authors: Wallis Jennifer
Published: November 2017

In this ‘Introduction’ Wallis highlights the importance of the asylum patient’s body to the study of mental disease in the late nineteenth century. The chapter questions why the body is often left out of histories of psychiatry, arguing that this is due to long-standing perceptions of the Victorian asylum as a place of incarceration and harsh treatment. Wallis asks how we can bring the body more meaningfully into histories of the asylum and suggests that we may achieve this by looking at scientific practices in the asylum. ‘Introduction’ concludes with a case study of the West Riding Lunatic Asylum, showing that this was an institution that fostered a research culture that was particularly concerned with the links between the body and mental disease.
Surface Plots for Cancer Survival
Authors: Rau Roland , Bohk-Ewald Christina , Muszyńska Magdalena M. , Vaupel James W.
Published: November 2017

While previous chapters focused only on the event of death, this chapter investigates the dynamics over age and time for the duration between being diagnosed with a specific cancer and death. We use five year survival as our indicator of survival in general, disease-specific survival and relative survival for selected cancer sites such as breast cancer, colorectal cancer, lung cancer or pancreatic cancer. The major impact of the stage of the tumor at the time of diagnosis for survival is illustrated using stage 1 and stage 4 of colorectal cancer as an example.
Surface Plots of Age-Specific Contributions to the Increase in Life Expectancy
Authors: Rau Roland , Bohk-Ewald Christina , Muszyńska Magdalena M. , Vaupel James W.
Published: November 2017

Rates of mortality improvement, as presented in the previous two chapters, are an excellent tool to illustrate mortality dynamics. They can not be directly translated to contributions to changes in life expectancy. Using Arriaga’s decomposition approach, we plot maps for selected countries from the Human Mortality Database, showing which ages contributed most to the respective change in life expectanc over time.
Back-to-back heavy quark pair production in semi-inclusive DIS
Authors: Zhang Guang-Peng
Published: November 2017

Abstract

The one-loop correction to heavy quark pair back-to-back production in unpolarized semi-inclusive deep inelastic scattering is given in this work in the framework of transverse momentum dependent(TMD) factorization. Both unpolarized and linearly polarized TMD gluon distribution functions are taken into account. A subtraction method based on diagram expansion is used to get finite hard coefficients. It is found the soft and collinear divergences of one-loop amplitude is proportional to tree level ones and can be expressed through several basic scalar triangle and bubble integrals. The subtraction of these divergences is spin independent. Beyond tree level an additional soft factor related to final heavy quark pair must be added into the factorization formula. This soft factor affects the azimuthal angle distribution of virtual photon in a nonperturbative way. Integrating over virtual photon azimuthal angle we construct three weighted cross sections, which depend on only three additional integrated soft factors. These weighted cross sections can be used to extract linearly polarized gluon distribution function. In addition, lepton azimuthal angle is unintegrated in this work, which provides more observables. All hard coefficients relevant to lepton and virtual photon azimuthal angle distributions are given at one-loop level.
A review of social media methods and lessons learned from the National Children’s Study
Authors: Burke-Garcia Amelia , Winseck Kate , Jouvenal Leslie Cooke , Hubble David , Kulbicki Kathryn M.
Published: November 2017

Introduction

Given the reach and influence of social media, the National Children’s Study Vanguard Study evaluated the feasibility, acceptability, and cost of using social media to support participant retention.

Methods

We describe a social media experiment designed to assess the impact of social media on participant retention, discuss several key considerations for integrating social media into longitudinal research, and review factors that may influence engagement in research-related social media.

Results

User participation varied but was most active when at launch. During the short life of the private online community, a total of 39 participants joined. General enthusiasm about the prospect of the online community was indicated. There were many lessons learned throughout the process in areas such as privacy, security, and Institutional Review Board clearance. These are described in detail.

Conclusions

The opportunity to engage participants in longitudinal research using online social networks is enticing; however, more research is needed to consider the feasibility of their use in an ongoing manner. Recommendations are presented for future research seeking to use social media to improve retention in longitudinal research.
Rural religion, religious places and local identities in Hispania: the sanctuary at Can Modolell (Cabrera de Mar, Barcelona)
Authors: Sinner Alejandro G. , Revilla Calvo Víctor
Published: November 2017

Rural cults are an aspect of the religion and culture of Roman Hispania that it is especially difficult to analyze given the paucity of epigraphic and archaeological evidence. This is quite a recent area of research; in addition, we are dealing with often modest religious practices that are difficult to identify in the archaeological record. Particularly problematic is the lack of information regarding cult places, despite the contribution made by some pioneering studies; yet the main problem has been the dominance of a paradigm that defines rural religion as a marginal space for social life, one that followed its own evolutionary rhythm influenced by a resistance to change. According to this paradigm, rural cults seem to comprise an unsystematic accumulation of traditional ritual practices whose preferred sphere of action would have been private.
Minerva, urban defenses, and the continuity of cult at Pompeii
Authors: van der Graaff Ivo , Ellis Steven J. R.
Published: November 2017

The religious landscapes of Republican-era urban communities in central and southern Italy were built on complex relationships between the inhabitants and their sacred spaces. The critical need to defend sacred sites such as temples, shrines and altars contributed directly to the shaping of urban centers and the formation of their cultural identities. Many urban centers had a separate citadel where communities protected their sanctuaries behind fortifications. In a reciprocal process the gods protected settlements. Some city gates (e.g., Volterra, Perugia, Falerii Novi) still carry prominent adornments in the form of busts and reliefs that evoke implicit civic and religious associations. The deities' presence implies a complex political and social interaction between the population, protective gods, and fortifications. As tutelary deities, their manipulation whether by a local élite or by a power such as Rome was an important part of the definition and appropriation of local identity.
Investigating the “Villa degli Antonini” at Lanuvium
Authors: Chatr Aryamontri Deborah , Renner Timothy
Published: November 2017

The archaeological site known as the “Villa degli Antonini” lies in the SE sector of the Alban Hills within the modern comune of Genzano di Roma and some 1.5 km north of the ancient urban center of Lanuvium (Lanuvio) (fig. 1). It is c.400 m south of the Via Appia between that road's 18th and 19th milestones (it seems to have been connected to the Via Appia by a side road traceable in historic aerial photographs and of which a section is still preserved) and c.1 km south of the rim of the volcanic lake of Nemi, from which the ground slopes gently down towards the coastal plain of Latium. To the west and east are two scoria cones, Monte Due Torri and Montecagnoletto, the latter of which was once separated from our site by a N-S valley c.100 m in width.
Tituli picti su due fronti di cava nel distretto di Bacakale a Docimium (Iscehisar, Afyonkarahisar)
Authors: Bruno Matthias
Published: November 2017

Il distretto estrattivo di Iscehisar, da cui proveniva il marmor phrygium (pavonazzetto), è uno dei più grandi dell'antichità romana nonché uno dei più studiati e documentati. Il primo ad interessarsi alle cave di Docimium fu J. Röder, che effettuò una ricognizione sistematica delle cave con la conseguente produzione della prima pianta topografica dell'antico sito estrattivo, allora ancora in gran parte integro anche con i rispettivi cumuli detritici. M. Waelkens rivolse la propria attenzione non solo alle cave, ma anche alla loro produzione, mentre J. C. Fant affronto soprattutto l'analisi dei corredi epigrafici dei blocchi di cava in modo da comprendere l'organizzazione delle attività estrattive di queste grandi cave imperiali. Le iscrizioni di cava sono state oggetto inoltre degli studi approfonditi di M. Christol e T. Drew-Bear, che non di rado si ponevano in forte contrasto e dissenso con quelli di Fant, e, negli ultimi anni, di P. Pensabene.
Categorical improvement in functional impairment in depressed patients treated with desvenlafaxine
Authors: Soares Claudio N. , Zhang Min , Boucher Matthieu
Published: November 2017

Objective

This post-hoc pooled analysis evaluated categorical change in functional impairment in patients with major depressive disorder (MDD) treated with desvenlafaxine versus placebo and examined whether early improvement in functioning predicted functional outcomes at study endpoint.

Methods

Data were pooled from eight randomized, double-blind, placebo-controlled studies of desvenlafaxine for the treatment of MDD, including adults who were randomly assigned to receive desvenlafaxine 50 or 100 mg/d or placebo (N=3,384). Shift tables were generated for categorical changes in functional impairment from baseline based on Sheehan Disability Scale (SDS) subscale scores. The categories were none/mild (0–3), moderate (4–6), and marked/extreme (7–10). Treatment comparisons for prespecified shifts of interest and predictive value of week 2 or 4 improvement in SDS subscale scores for functional outcome at week 8 were assessed using logistic regression.

Results

Greater proportions of patients receiving desvenlafaxine 50 and 100 mg achieved improvement from baseline to week 8 for each prespecified shift endpoint versus placebo (allp≤ 0.02). Early improvement in SDS subscale scores was a statistically significant predictor of functional outcome at week 8, both overall and for each treatment group (allp<0.0001).

Conclusions

Treatment with desvenlafaxine 50 or 100 mg/d led to significantly greater categorical improvement in functional impairment versus placebo, and improvement in SDS subscale scores significantly predicted functional outcome. Monitoring patient progress early in the course of antidepressant treatment using a functional assessment such as the SDS may help clinicians determine whether or not treatment adjustments are needed.
Structural basis for xenobiotic extrusion by eukaryotic MATE transporter
Authors: Miyauchi Hirotake , Moriyama Satomi , Kusakizako Tsukasa , Kumazaki Kaoru , Nakane Takanori , Yamashita Keitaro , Hirata Kunio , Dohmae Naoshi , Nishizawa Tomohiro , Ito Koichi , Miyaji Takaaki , Moriyama Yoshinori , Ishitani Ryuichiro , Nureki Osamu
Published: November 2017

Mulitidrug and toxic compound extrusion (MATE) family transporters export xenobiotics to maintain cellular homeostasis. The human MATE transporters mediate the excretion of xenobiotics and cationic clinical drugs, whereas some plant MATE transporters are responsible for aluminum tolerance and secondary metabolite transport. Here we report the crystal structure of the eukaryotic MATE transporter from Arabidopsis thaliana, at 2.6 Å resolution. The structure reveals that its carboxy-terminal lobe (C-lobe) contains an extensive hydrogen-bonding network with well-conserved acidic residues, and their importance is demonstrated by the structure-based mutational analysis. The structural and functional analyses suggest that the transport mechanism involves the structural change of transmembrane helix 7, induced by the formation of a hydrogen-bonding network upon the protonation of the conserved acidic residue in the C-lobe. Our findings provide insights into the transport mechanism of eukaryotic MATE transporters, which is important for the improvement of the pharmacokinetics of the clinical drugs.
3D collagen architecture induces a conserved migratory and transcriptional response linked to vasculogenic mimicry
Authors: Velez D. O. , Tsui B. , Goshia T. , Chute C. L. , Han A. , Carter H. , Fraley S. I.
Published: November 2017

The topographical organization of collagen within the tumor microenvironment has been implicated in modulating cancer cell migration and independently predicts progression to metastasis. Here, we show that collagen matrices with small pores and short fibers, but not Matrigel, trigger a conserved transcriptional response and subsequent motility switch in cancer cells resulting in the formation of multicellular network structures. The response is not mediated by hypoxia, matrix stiffness, or bulk matrix density, but rather by matrix architecture-induced β1-integrin upregulation. The transcriptional module associated with network formation is enriched for migration and vasculogenesis-associated genes that predict survival in patient data across nine distinct tumor types. Evidence of this gene module at the protein level is found in patient tumor slices displaying a vasculogenic mimicry (VM) phenotype. Our findings link a collagen-induced migration program to VM and suggest that this process may be broadly relevant to metastatic progression in solid human cancers.
mDia1 senses both force and torque during F-actin filament polymerization
Authors: Yu Miao , Yuan Xin , Lu Chen , Le Shimin , Kawamura Ryo , Efremov Artem K. , Zhao Zhihai , Kozlov Michael M. , Sheetz Michael , Bershadsky Alexander , Yan Jie
Published: November 2017

Formins, an important family of force-bearing actin-polymerizing factors, function as homodimers that bind with the barbed end of actin filaments through a ring-like structure assembled from dimerized FH2 domains. It has been hypothesized that force applied to formin may facilitate transition of the FH2 ring from an inhibitory closed conformation to a permissive open conformation, speeding up actin polymerization. We confirm this hypothesis for mDia1 dependent actin polymerization by stretching a single-actin filament in the absence of profilin using magnetic tweezers, and observe that increasing force from 0.5 to 10 pN can drastically speed up the actin polymerization rate. Further, we find that this force-promoted actin polymerization requires torsionally unconstrained actin filament, suggesting that mDia1 also senses torque. As actin filaments are subject to complex mechanical constraints in living cells, these results provide important insights into how formin senses these mechanical constraints and regulates actin organization accordingly.
The HSF1–PARP13–PARP1 complex facilitates DNA repair and promotes mammary tumorigenesis
Authors: Fujimoto Mitsuaki , Takii Ryosuke , Takaki Eiichi , Katiyar Arpit , Nakato Ryuichiro , Shirahige Katsuhiko , Nakai Akira
Published: November 2017

Poly(ADP-ribose) polymerase 1 (PARP1) is involved in DNA repair, chromatin structure, and transcription. However, the mechanisms that regulate PARP1 distribution on DNA are poorly understood. Here, we show that heat shock transcription factor 1 (HSF1) recruits PARP1 through the scaffold protein PARP13. In response to DNA damage, activated and auto-poly-ADP-ribosylated PARP1 dissociates from HSF1–PARP13, and redistributes to DNA lesions and DNA damage-inducible gene loci. Histone deacetylase 1 maintains PARP1 in the ternary complex by inactivating PARP1 through deacetylation. Blocking ternary complex formation impairs redistribution of PARP1 during DNA damage, which reduces gene expression and DNA repair. Furthermore, ternary complex formation and PARP1 redistribution protect cells from DNA damage by promoting DNA repair, and support growth of BRCA1-null mammary tumors, which are sensitive to PARP inhibitors. Our findings identify HSF1 as a regulator of genome integrity and define this function as a guarding mechanism for a specific type of mammary tumorigenesis.
Surface plasmon induced direct detection of long wavelength photons
Authors: Tong Jinchao , Zhou Wei , Qu Yue , Xu Zhengji , Huang Zhiming , Zhang Dao Hua
Published: November 2017

Millimeter and terahertz wave photodetectors have long been of great interest due to a wide range of applications, but they still face challenges in detection performance. Here, we propose a new strategy for the direct detection of millimeter and terahertz wave photons based on localized surface-plasmon-polariton (SPP)-induced non-equilibrium electrons in antenna-assisted subwavelength ohmic metal–semiconductor–metal (OMSM) structures. The subwavelength OMSM structure is used to convert the absorbed photons into localized SPPs, which then induce non-equilibrium electrons in the structure, while the antenna increases the number of photons coupled into the OMSM structure. When the structure is biased and illuminated, the unidirectional flow of the SPP-induced non-equilibrium electrons forms a photocurrent. The energy of the detected photons is determined by the structure rather than the band gap of the semiconductor. The detection scheme is confirmed by simulation and experimental results from the devices, made of gold and InSb, and a room temperature noise equivalent power (NEP) of 1.5 × 10−13 W Hz−1/2 is achieved.
The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis
Authors: Fusella Federica , Seclì Laura , Busso Elena , Krepelova Anna , Moiso Enrico , Rocca Stefania , Conti Laura , Annaratone Laura , Rubinetto Cristina , Mello-Grand Maurizia , Singh Vijay , Chiorino Giovanna , Silengo Lorenzo , Altruda Fiorella , Turco Emilia , Morotti Alessandro , Oliviero Salvatore , Castellano Isabella , Cavallo Federica , Provero Paolo , Tarone Guido , Brancaccio Mara
Published: November 2017

NF-κB is a transcription factor involved in the regulation of multiple physiological and pathological cellular processes, including inflammation, cell survival, proliferation, and cancer cell metastasis. NF-κB is frequently hyperactivated in several cancers, including triple-negative breast cancer. Here we show that NF-κB activation in breast cancer cells depends on the presence of the CHORDC1 gene product Morgana, a previously unknown component of the IKK complex and essential for IκBα substrate recognition. Morgana silencing blocks metastasis formation in breast cancer mouse models and this phenotype is reverted by IκBα downregulation. High Morgana expression levels in cancer cells decrease recruitment of natural killer cells in the first phases of tumor growth and induce the expression of cytokines able to attract neutrophils in the primary tumor, as well as in the pre-metastatic lungs, fueling cancer metastasis. In accordance, high Morgana levels positively correlate with NF-κB target gene expression and poor prognosis in human patients.
Mrg15 stimulates Ash1 H3K36 methyltransferase activity and facilitates Ash1 Trithorax group protein function in Drosophila
Authors: Huang Chang , Yang Fu , Zhang Zhuqiang , Zhang Jing , Cai Gaihong , Li Lin , Zheng Yong , Chen She , Xi Rongwen , Zhu Bing
Published: November 2017

Ash1 is a Trithorax group protein that possesses H3K36-specific histone methyltransferase activity, which antagonizes Polycomb silencing. Here we report the identification of two Ash1 complex subunits, Mrg15 and Nurf55. In vitro, Mrg15 stimulates the enzymatic activity of Ash1. In vivo, Mrg15 is recruited by Ash1 to their common targets, and Mrg15 reinforces Ash1 chromatin association and facilitates the proper deposition of H3K36me2. To dissect the functional role of Mrg15 in the context of the Ash1 complex, we identify an Ash1 point mutation (Ash1-R1288A) that displays a greatly attenuated interaction with Mrg15. Knock-in flies bearing this mutation display multiple homeotic transformation phenotypes, and these phenotypes are partially rescued by overexpressing the Mrg15-Nurf55 fusion protein, which stabilizes the association of Mrg15 with Ash1. In summary, Mrg15 is a subunit of the Ash1 complex, a stimulator of Ash1 enzymatic activity and a critical regulator of the TrxG protein function of Ash1 in Drosophila.
First-principles screening of structural properties of intermetallic compounds on martensitic transformation
Authors: Lee Joohwi , Ikeda Yuji , Tanaka Isao
Published: November 2017

Martensitic transformation with good structural compatibility between parent and martensitic phases are required for shape memory alloys (SMAs) in terms of functional stability. In this study, first-principles-based materials screening is systematically performed to investigate the intermetallic compounds with the martensitic phases by focusing on energetic and dynamical stabilities as well as structural compatibility with the parent phase. The B2, D03, and L21crystal structures are considered as the parent phases, and the 2H and 6M structures are considered as the martensitic phases. In total, 3384 binary and 3243 ternary alloys with stoichiometric composition ratios are investigated. It is found that 187 alloys survive after the screening. Some of the surviving alloys are constituted by the chemical elements already widely used in SMAs, but other various metallic elements are also found in the surviving alloys. The energetic stability of the surviving alloys is further analyzed by comparison with the data in Materials Project Database (MPD) to examine the alloys whose martensitic structures may cause further phase separation or transition to the other structures.
Prioritising the application of genomic medicine
Authors: Doble Brett , Schofield Deborah J. , Roscioli Tony , Mattick John S.
Published: November 2017

The clinical translation of genomic sequencing is hampered by the limited information available to guide investment into those areas where genomics is well placed to deliver improved health and economic outcomes. To date, genomic medicine has achieved its greatest successes through applications to diseases that have a high genotype–phenotype correlation and high penetrance, with a near certainty that the individual will develop the condition in the presence of the genotype. It has been anticipated that genomics will play an important role in promoting population health by targeting at-risk individuals and reducing the incidence of highly prevalent, costly, complex diseases, with potential applications across screening, prevention, and treatment decisions. However, where primary or secondary prevention requires behavioural changes, there is currently very little evidence to support reduction in disease incidence. A better understanding of the relationship between genomic variation and complex diseases will be necessary before effective genomic risk identification and management of the risk of complex diseases in healthy individuals can be carried out in clinical practice. Our recommended approach is that priority for genomic testing should focus on diseases where there is strong genotype–phenotype correlation, high or certain penetrance, the effects of the disease are serious and near-term, there is the potential for prevention and/or treatment, and the net costs incurred are acceptable for the health gains achieved.
IGF-1-mediated PKM2/β-catenin/miR-152 regulatory circuit in breast cancer
Authors: Wen Yi-Yang , Liu Wei-Tao , Sun Hao-Ran , Ge Xin , Shi Zhu-Mei , Wang Min , Li Wei , Zhang Jian-Ying , Liu Ling-Zhi , Jiang Bing-Hua
Published: November 2017

Dysregulation of miRNAs is important in breast cancer initiation and malignant progression. Recently we showed that miR-152 downregulation is associated with breast cancer development, yet the underlying mechanism of miR-152 remains to be well elucidated. In this study, we identified β-catenin as a new direct target of miR-152. MiR-152 inhibited cell proliferation by targeting and inhibiting both β-catenin and PKM2 expression. We found that miR-152 expression sensitized the breast cancer cells to paclitaxel treatment by inhibiting β-catenin and PKM2 expression. Intriguingly, IGF-1 induced β-catenin and PKM2 expression and enhanced β-catenin and PKM2 interaction. Subsequently, IGF-1-induced β-catenin and PKM2 complex translocated into the nucleus, which in turn activated expression of miR-152. These results suggested a regulatory circuit between miR-152, β-catenin and PKM2 in breast cancer. By using human clinical specimens, we also showed that miR-152 expression levels were negatively correlated with β-catenin and PKM2 levels in breast cancer tissues. Our findings provide new insights into a mechanism of miR-152 involved in β-catenin and PKM2 inhibition which would have clinical implication for the cancer development and new treatment option in the future.
Results of a 15-year systematic survey of commensal rodents in English dwellings
Authors: Lambert M. , Vial F. , Pietravalle S. , Cowan D.
Published: November 2017

Population trends for commensal rodents are the subject of interest and speculation but accurate data are rarely available. Here we report data from a 15-year systematic survey of rats and mice in English dwellings and present national-level estimates of prevalence for 1996–2010. We found evidence for peaks in prevalence of mice inside and rats around dwellings in 2002 and 2008. Models containing twelve variables relating to the dwelling and local area explained some but not all of the variation in prevalence. Older dwellings, those in rural areas, those with litter, drainage faults and pets or other animals outdoors tended to have higher levels of rodent prevalence. Regional differences were found but there were no seasonal trends apart from lower prevalence of mice during summer. Rodent prevalence was generally higher in rented (compared to owner-occupied) dwellings, although apparently not due to reduced tendency to carry out rodent control. The percentage of households having taken some form of action against active rodent problems varied according to prevalence at the national level, and therefore appropriate data on number of rodent control treatments carried out each year could likely act as a useful index of household rodent prevalence.
Whole Exome Sequencing reveals new candidate genes in host genomic susceptibility to Respiratory Syncytial Virus Disease
Authors: Salas Antonio , Pardo-Seco Jacobo , Cebey-López Miriam , Gómez-Carballa Alberto , Obando-Pacheco Pablo , Rivero-Calle Irene , Currás-Tuala María-José , Amigo Jorge , Gómez-Rial José , Martinón-Torres Federico ,   GENDRES network, Justicia-Grande Antonio , Morillo Beatriz , Redondo-Collazo Lorenzo , Rodríguez-Tenreiro Carmen , Barral-Arca Ruth , Pischedda Sara , Peña-Guitián José , Curros Novo Carmen , Puente-Puig Miriam , Leis-Trabazo Rosaura , Martinón-Torres Nazareth , Martinón-Sánchez José María , Fraga-Rodríguez Máximo Francisco , Antúnez José Ramón , Bernaola-Iturbe Enrique , Moreno-Galarraga Laura , Álvarez Jorge , González-López Teresa , Suarez-Vázquez Delfina , Vázquez Vázquez Ángela , Rey-García Susana , Giménez-Sánchez Francisco , Forte Miguel Sánchez , Calvo-Rey Cristina , García-García María Luz , Oulego-Erroz Ignacio , Naranjo Vivas David , Lapeña Santiago , Alonso-Quintela Paula , Martínez-Sáenz de Jubera Jorge , Garrido-García Estibaliz , Calvo Monge Cristina , Oñate-Vergara Eider , de la Cruz Moreno Jesús , Martínez-Padilla Maria del Carmen , Baca-Cots Manuel , Moreno-Pérez David , Beatriz-Reyes Susana , León-León María Cruz
Published: November 2017

Respiratory syncytial virus (RSV) is an important cause of serious lower respiratory tract disease in infants. Several studies have shown evidence pointing to the genome of the host as an important factor determining susceptibility to respiratory disease caused by RSV. We sequenced the complete exomes of 54 patients infected by RSV that needed hospitalization due to development of severe bronchiolitis. The Iberian sample (IBS) from The 1000 Genomes Project (1000G) was used as control group; all the association results were pseudo-replicated using other 1000G-European controls and Spanish controls. The study points to SNP rs199665292 in the olfactory receptor (OR) geneOR13C5as the best candidate variant (P-value = 1.16 × 10−12; OR = 5.56). Genetic variants at HLA genes (HLA-DQA1,HLA-DPB1), and in the mucin 4 gene (MUC4) also emerge as susceptibility candidates. By collapsing rare variants in genes and weighing by pathogenicity, we obtained confirmatory signals of association in the OR geneOR8U1/OR8U8, the taste receptorTAS2R19, and another mucin gene (MUC6). Overall, we identified new predisposition variants and genes related to RSV infection. Of special interest is the association of RSV to olfactory and taste receptors; this finding is in line with recent evidence pointing to their role in viral infectious diseases.
An organic fluorophore-nanodiamond hybrid sensor for photostable imaging and orthogonal, on-demand biosensing
Authors: Purdey Malcolm S. , Capon Patrick K. , Pullen Benjamin J. , Reineck Philipp , Schwarz Nisha , Psaltis Peter J. , Nicholls Stephen J. , Gibson Brant C. , Abell Andrew D.
Published: November 2017

Organic fluorescent probes are widely used to detect key biomolecules; however, they often lack the photostability required for extended intracellular imaging. Here we report a new hybrid nanomaterial (peroxynanosensor, PNS), consisting of an organic fluorescent probe bound to a nanodiamond, that overcomes this limitation to allow concurrent and extended cell-based imaging of the nanodiamond and ratiometric detection of hydrogen peroxide. Far-red fluorescence of the nanodiamond offers continuous monitoring without photobleaching, while the green fluorescence of the organic fluorescent probe attached to the nanodiamond surface detects hydrogen peroxide on demand. PNS detects basal production of hydrogen peroxide within M1 polarised macrophages and does not affect macrophage growth during prolonged co-incubation. This nanosensor can be used for extended bio-imaging not previously possible with an organic fluorescent probe, and is spectrally compatible with both Hoechst 33342 and MitoTracker Orange stains for hyperspectral imaging.
Dual-Mode Manipulating Multicenter Photoluminescence in a Single-Phased Ba9Lu2Si6O24:Bi3+, Eu3+ Phosphor to Realize White Light/Tunable Emissions
Authors: Guo Yue , Park Sung Heum , Choi Byung Chun , Jeong Jung Hyun , Kim Jung Hwan
Published: November 2017

A Bi3+ and Eu3+ ion co-doped Ba9Lu2Si6O24 single-phased phosphor was synthesized successfully via a conventional high-temperature solid-state reaction. X-ray diffraction, crystal structure analysis, diffuse reflectance and luminescent spectra, quantum efficiency measurements, and thermal stability analysis were applied to investigate the phase, structure, luminescent and thermal stability properties. From the analyses of the crystal structure and luminescent spectra, we observed four discernible Bi3+ luminescent centers with peaks at ~363.3, ~403.1, ~437.7, and ~494.5 nm. Moreover, due to the complex energy transfer processes among these Bi3+ centers, their relative emission intensity tightly depended on the incident excitation wavelength. Interestingly, the as-prepared phosphor could generate warm white light/tunable emission by changing the concentration of Eu3+ ions or adjusting the excitation wavelength. The energy transfer mechanism from Bi3+ to Eu3+ was confirmed via an electric dipole-dipole interaction, the energy transfer efficiencies $$({\eta }_{T})$$
(

η

T

)
from Bi3+ to Eu3+ were 50.84% and 40.17% monitoring at 410 and 485 nm, respectively. The internal quantum efficiency of the optimized Ba9Lu2Si6O24:Bi3+, Eu3+ phosphor was calculated to be 42.6%. In addition, the configurational coordinate model was carried out to explain the energy decrease of the phonon-electron coupling effect.
Physicochemical characteristics and toxicity of surface-modified zinc oxide nanoparticles to freshwater and marine microalgae
Authors: Yung Mana M. N. , Fougères Paul-Antoine , Leung Yu Hang , Liu Fangzhou , Djurišić Aleksandra B. , Giesy John P. , Leung Kenneth M. Y.
Published: November 2017

Because of wide applications of surface-modified zinc oxide nanoparticles (ZnO-NPs) in commercial sunscreens and their easiness of being released into water, concerns have been raised over their potential effects on aquatic organisms. This study compared physicochemical properties of silane-coated and uncoated ZnO-NPs to elucidate their toxic potencies toward three freshwater and three marine microalgae. Surfaces of ZnO-NPs (20 nm) were modified by coating with 3-aminopropyltrimethoxysilane (A-ZnO-NPs) that provides the particles with a more hydrophilic surface, or dodecyltrichlorosilane (D-ZnO-NPs) that turns the particles to hydrophobic. Uncoated ZnO-NPs formed larger aggregates and released more Zn2+ than did either of the two coated ZnO-NPs. The three nanoparticles formed larger aggregates but released less Zn2+ at pH 8 than at pH 7. Although sensitivities varied among algal species, A-ZnO-NPs and uncoated ZnO-NPs were more potent at inhibiting growth of algal cells than were D-ZnO-NPs after 96-h exposure to ZnO, uncoated ZnO-NPs, each of the coated ZnO-NPs or ZnSO4 at 10 concentrations ranging from 0.1 to 100 mg/L. The marine diatom Thalassiosira pseudonana exposed to ZnO-NPs, A-ZnO-NPs or D-ZnO-NPs resulted in differential expressions of genes, suggesting that each of the coatings resulted in ZnO-NPs acting through different mechanisms of toxic action.
Encoding of menstrual pain experience with theta oscillations in women with primary dysmenorrhea
Authors: Lee Pin-Shiuan , Low Intan , Chen Yong-Sheng , Tu Cheng-Hao , Chao Hsiang-Tai , Hsieh Jen-Chuen , Chen Li-Fen
Published: November 2017

Theta oscillation (4–7 Hz) is well documented for its association with neural processes of memory. Pronounced increase of theta activity is commonly observed in patients with chronic neurogenic pain. However, its association with encoding of pain experience in patients with chronic pain is still unclear. The goal of the present study is to investigate the theta encoding of sensory and emotional information of long-term menstrual pain in women with primary dysmenorrhea (PDM). Forty-six young women with PDM and 46 age-matched control subjects underwent resting-state magnetoencephalography study during menstrual and periovulatory phases. Our results revealed increased theta activity in brain regions of pain processing in women with PDM, including the right parahippocampal gyrus, right posterior insula, and left anterior/middle cingulate gyrus during the menstrual phase and the left anterior insula and the left middle/inferior temporal gyrus during the periovulatory phase. The correlations between theta activity and the psychological measures pertaining to pain experience (depression, state anxiety, and pain rating index) implicate the role of theta oscillations in emotional and sensory processing of pain. The present study provides evidence for the role of theta oscillations in encoding the immediate and sustained effects of pain experience in young women with PDM.
Via mucosa incision EUS-guided sampling for the diagnosis of conventional endoscopic biopsy-negative gastric wall thickening
Authors: Shan Hongbo , Gao Xiaoyan , Luo Guangyu , Xiang Jieqing , Zhong Bilv , Qiu Xiaofang , Lin Shiyong , Li Shuhong , Li Yin , Xu Guoliang , Zhang Rong
Published: November 2017

Abnormal thickened lesions of the gastric wall are usually covered with normal mucosa. Conventional endoscopic biopsies often do not yield sufficient positive histological results for clinical treatment. To increase the rate of diagnosis of conventional endoscopic biopsy-negative gastric wall thickening, we used an endoscopic submucosal dissection (ESD)-like sampling method under endoscopic ultrasound (EUS) guidance to obtain tissue of gastric wall-thickening lesions. Between 2012 and 2016, patients with gastric wall thickening (as identified by computed tomography (CT), EUS or other imaging methods that showed no positive findings in repeating conventional endoscopic biopsy) underwent via mucosa incision EUS-guided sampling. Final diagnosis was determined after surgical or biopsy pathology. A total of 10 patients with gastric wall thickening were included in this study. Eight cases received definite results, whereas in two cases the biopsy results were ambiguous and in these two patients poorly differentiated adenocarcinoma was determined by postoperative pathology. The results of the cases presented in this study demonstrated that via mucosa incision EUS-guided sampling provided a complementary option for the diagnosis of conventional endoscopic biopsy-negative gastric wall thickening.
Overexpression of suppressive microRNAs, miR-30a and miR-200c are associated with improved survival of breast cancer patients
Authors: Kawaguchi Tsutomu , Yan Li , Qi Qianya , Peng Xuan , Gabriel Emmanuel M. , Young Jessica , Liu Song , Takabe Kazuaki
Published: November 2017

Some microRNAs (miRNAs) are known to suppress breast cancer. However, whether the expressions of these tumor suppressive miRNAs translate to patient survival were not investigated in large cohort. Nine miRNAs (miR-30a, miR-30c, miR-31, miR-126, miR-140, miR-146b, miR-200c, miR-206, and miR-335) known to be tumor suppressive miRNAs in breast cancer were investigated in Genomic Data Common data portal miRNA-Seq dataset and The Cancer Genome Atlas (TCGA) (n = 1052). Of the 9 miRNAs, miR-30a, miR-30c, miR-126, miR-140, miR-206, and miR-335 were found to have significantly lower expression in breast cancer tissues compared to paired normal breast tissue. High expression of miR-30a or miR-200c was associated with significantly better overall survival (OS). Gene Set Enrichment Analysis (GSEA) demonstrated that low expression levels of miR-30a had the tendency to associate with gene enrichment of EMT, while miR-200c did not, in TCGA cohort, and our findings support the need of validation using large cohort to use miRNA as prognostic biomarker for patients with breast cancer.
The LATERAL ORGAN BOUNDARIES Domain gene family in grapevine: genome-wide characterization and expression analyses during developmental processes and stress responses
Authors: Grimplet Jérôme , Pimentel Diana , Agudelo-Romero Patricia , Martinez-Zapater Jose Miguel , Fortes Ana Margarida
Published: November 2017

LATERAL ORGAN BOUNDARIES (LOB) DOMAIN (LBD) constitute a family of plant-specific transcription factors with key roles in the regulation of plant organ development, pollen development, plant regeneration, pathogen response, and anthocyanin and nitrogen metabolisms. However, the role of LBDs in fruit ripening and in grapevine (Vitis vinifera L.) development and stress responses is poorly documented. By performing a model curation of LBDs in the latest genome annotation 50 genes were identified. Phylogenetic analysis showed that LBD genes can be grouped into two classes mapping on 16 out of the 19 V. vinifera chromosomes. New gene subclasses were identified that have not been characterized in other species. Segmental and tandem duplications contributed significantly to the expansion and evolution of the LBD gene family in grapevine as noticed for other species. The analysis of cis-regulatory elements and transcription factor binding sites in the VviLBD promoter regions suggests the involvement of several hormones in the regulation of LBDs expression. Expression profiling suggest the involvement of LBD transcription factors in grapevine development, berry ripening and stress responses. Altogether this study provides valuable information and robust candidate genes for future functional analysis aiming to clarify mechanisms responsible for the onset of fruit ripening and fruit defense strategies.
Identification of microRNAs as potential cellular monocytic biomarkers in the early phase of myocardial infarction: a pilot study
Authors: Parahuleva Mariana S. , Euler Gerhild , Mardini Amar , Parviz Behnoush , Schieffer Bernhard , Schulz Rainer , Aslam Muhammad
Published: November 2017

MicroRNA has been increasingly suggested to be involved in vascular inflammation. The aim of this study was to assess the expression profile of miRs as possible novel cellular biomarkers in circulating monocytes in patients with ST-segment elevation myocardial infarction (STEMI). Microarray techniques and TaqMan polymerase chain reaction were used to analyse the global expression of 352 miRNAs in peripheral blood monocytes from healthy donors (n = 20) and patients (n = 24) with acute STEMI. The expression level of miR-143 in monocytes from STEMI patients compared to healthy controls was increased, whereas the expression of miR-1, -92a, -99a, and -223 was reduced significantly. During 3.5 ± 1.5 months of follow-up miR-1 and -223 were back to baseline, whereas miR-92a and -99a return to normal levels over 3 months, but remained lower than healthy controls. Furthermore, monocytic expression of miR-143 was positively correlated with hs-CRP (R2 = 0.338; P < 0.031), but not with cTnT. Importantly, treatment of monocytes isolated from healthy individuals with INFγ, but not LPS or TNFα caused an upregulation of miR-143 and downregulation of miR-1. Our findings identify circulating monocytes as putative biomarkers and as novel carriers for the cell-specific transfer of miRs in the early phase of myocardial infarction.
Remediation mechanisms for Cd-contaminated soil using natural sepiolite at the field scale
Authors: Yin Xiuling , Xu Yingming , Huang Rong , Huang Qingqing , Xie Zhonglei , Cai Yanming , Liang Xuefeng
Published: November 2017

Remediation of heavy metal polluted agricultural soil is essential for human health and ecological safety and remediation mechanisms at the microscopic level are vital for their large-scale utilization.