bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep sequencing and pathway-focused analysis revealed multigene oncodriver signatures predicting survival outcomes in advanced colorectal cancer
Authors: De Nicola Francesca , Goeman Frauke , Pallocca Matteo , Sperati Francesca , Pizzuti Laura , Melucci Elisa , Casini Beatrice , Amoreo Carla Azzurra , Gallo Enzo , Diodoro Maria Grazia , Buglioni Simonetta , Mazzotta Marco , Vici Patrizia , Sergi Domenico , Di Lauro Luigi , Barba Maddalena , Pescarmona Edoardo , Ciliberto Gennaro , De Maria Ruggero , Fanciulli Maurizio , Maugeri-Saccà Marcello
Published: July 2018

Genomic technologies are reshaping the molecular landscape of colorectal cancer (CRC), revealing that oncogenic driver mutations (APC and TP53) coexist with still underappreciated genetic events. We hypothesized that mutational analysis of CRC-linked genes may provide novel information on the connection between genetically-deregulated pathways and clinical outcomes. We performed next-generation sequencing (NGS) analysis of 16 recurrently mutated genes in CRC exploiting tissue specimens from 98 advanced CRC patients. Multiple correspondence analysis (MCA) was used to identify gene sets characterizing negative and positive outliers (patients in the lowest and highest quartile of progression-free survival, PFS). Variables potentially affecting PFS and overall survival (OS) were tested in univariate and multivariate Cox proportional hazard models. Sensitivity analyses and resampling were used to assess the robustness of genomic predictors. MCA revealed that APC and TP53 mutations were close to the negative outlier group, whereas mutations in other WNT pathway genes were in proximity of the positive outliers. Reasoning that genetic alterations interact epistatically, producing greater or weaker consequences in combination than when individually considered, we tested whether patients whose tumors carried a genetic background characterized by APC and TP53 mutations without coexisting mutations in other WNT genes (AMER1, FBXW7, TCF7L2, CTNNB1, SOX9) had adverse survival outcomes. With this approach, we identified two oncodriver signatures (ODS1 and ODS2) associated with shorter PFS (ODS1 multivariate Cox for PFS: HR 2.16, 95%CI: 1.28–3.64, p = 0.004; ODS2 multivariate Cox for PFS: HR 2.61, 95%CI: 1.49–4.58, p = 0.001). Clinically-focused and molecularly-focused sensitivity analyses, resampling, and reclassification of mutations confirmed the stability of ODS1/2. Moreover, ODS1/2 negatively impacted OS. Collectively, our results point to co-occurring driver mutations as an adverse molecular factor in advanced CRC. This relationship depends on a broader genetic context highlighting the importance of genetic interactions.
Independent occurrence of de novo HSPD1 and HIP1 variants in brothers with different neurological disorders – leukodystrophy and autism
Authors: Yamamoto Toshiyuki , Yamamoto-Shimojima Keiko , Ueda Yuki , Imai Katsumi , Takahashi Yukitoshi , Imagawa Eri , Miyake Noriko , Matsumoto Naomichi
Published: July 2018

Consecutive occurrence of de novo variants in the same family is an extremely rare phenomenon. Two siblings, a younger brother with hypomyelinating leukodystrophy and an elder brother with severe intellectual disability and autistic features, had independent de novo variants ofHSPD1c.139T > G (p.Leu47Val) andHIP1c.1393G > A (p.Glu465Lys), respectively. These novel variants were predicted to be pathogenic. Both patients also had a knownMECP2variant, c.499C > T (p.Arg167Trp).
Direct observation of polymer surface mobility via nanoparticle vibrations
Authors: Kim Hojin , Cang Yu , Kang Eunsoo , Graczykowski Bartlomiej , Secchi Maria , Montagna Maurizio , Priestley Rodney D. , Furst Eric M. , Fytas George
Published: July 2018

Measuring polymer surface dynamics remains a formidable challenge of critical importance to applications ranging from pressure-sensitive adhesives to nanopatterning, where interfacial mobility is key to performance. Here, we introduce a methodology of Brillouin light spectroscopy to reveal polymer surface mobility via nanoparticle vibrations. By measuring the temperature-dependent vibrational modes of polystyrene nanoparticles, we identify the glass-transition temperature and calculate the elastic modulus of individual nanoparticles as a function of particle size and chemistry. Evidence of surface mobility is inferred from the first observation of a softening temperature, where the temperature dependence of the fundamental vibrational frequency of the nanoparticles reverses slope below the glass-transition temperature. Beyond the fundamental vibrational modes given by the shape and elasticity of the nanoparticles, another mode, termed the interaction-induced mode, was found to be related to the active particle–particle adhesion and dependent on the thermal behavior of nanoparticles.
Unperturbed expression bias of imprinted genes in schizophrenia
Authors: Gulyás-Kovács Attila , Keydar Ifat , Xia Eva , Fromer Menachem , Hoffman Gabriel , Ruderfer Douglas , Sachidanandam Ravi , Chess Andrew
Published: July 2018

How gene expression correlates with schizophrenia across individuals is beginning to be examined through analyses of RNA-seq from postmortem brains of individuals with disease and control brains. Here we focus on variation in allele-specific expression, following up on the CommonMind Consortium (CMC) RNA-seq experiments of nearly 600 human dorsolateral prefrontal cortex (DLPFC) samples. Analyzing the extent of allelic expression bias—a hallmark of imprinting—we find that the number of imprinted human genes is consistent with lower estimates (≈0.5% of all genes), and thus contradicts much higher estimates. Moreover, the handful of putatively imprinted genes are all in close genomic proximity to known imprinted genes. Joint analysis of the imprinted genes across hundreds of individuals allowed us to establish how allelic bias depends on various factors. We find that age and genetic ancestry have gene-specific, differential effect on allelic bias. In contrast, allelic bias appears to be independent of schizophrenia.
Finite temperature quantum annealing solving exponentially small gap problem with non-monotonic success probability
Authors: Mishra Anurag , Albash Tameem , Lidar Daniel A.
Published: July 2018

Closed-system quantum annealing is expected to sometimes fail spectacularly in solving simple problems for which the gap becomes exponentially small in the problem size. Much less is known about whether this gap scaling also impedes open-system quantum annealing. Here, we study the performance of a quantum annealing processor in solving such a problem: a ferromagnetic chain with sectors of alternating coupling strength that is classically trivial but exhibits an exponentially decreasing gap in the sector size. The gap is several orders of magnitude smaller than the device temperature. Contrary to the closed-system expectation, the success probability rises for sufficiently large sector sizes. The success probability is strongly correlated with the number of thermally accessible excited states at the critical point. We demonstrate that this behavior is consistent with a quantum open-system description that is unrelated to thermal relaxation, and is instead dominated by the system’s properties at the critical point.
Soluble RANKL contributes to osteoclast formation in adult mice but not ovariectomy-induced bone loss
Authors: Xiong Jinhu , Cawley Keisha , Piemontese Marilina , Fujiwara Yuko , Zhao Haibo , Goellner Joseph J. , O’Brien Charles A.
Published: July 2018

Receptor activator of NFkB ligand (RANKL) is a TNF-family cytokine required for osteoclast formation, as well as immune cell and mammary gland development. It is produced as a membrane-bound protein that can be shed to form a soluble protein. We created mice harboring a sheddase-resistant form of RANKL, in which soluble RANKL is undetectable in the circulation. Lack of soluble RANKL does not affect bone mass or structure in growing mice but reduces osteoclast number and increases cancellous bone mass in adult mice. Nonetheless, the bone loss caused by estrogen deficiency is unaffected by the lack of soluble RANKL. Lymphocyte number, lymph node development, and mammary gland development are also unaffected by the absence of soluble RANKL. These results demonstrate that the membrane-bound form of RANKL is sufficient for most functions of this protein but that the soluble form does contribute to physiological bone remodeling in adult mice.
Suppression of atom motion and metal deposition in mixed ionic electronic conductors
Authors: Qiu Pengfei , Agne Matthias T. , Liu Yongying , Zhu Yaqin , Chen Hongyi , Mao Tao , Yang Jiong , Zhang Wenqing , Haile Sossina M. , Zeier Wolfgang G. , Janek Jürgen , Uher Ctirad , Shi Xun , Chen Lidong , Snyder G. Jeffrey
Published: July 2018

Many superionic mixed ionic–electronic conductors with a liquid-like sublattice have been identified as high efficiency thermoelectric materials, but their applications are limited due to the possibility of decomposition when subjected to high electronic currents and large temperature gradients. Here, through systematically investigating electromigration in copper sulfide/selenide thermoelectric materials, we reveal the mechanism for atom migration and deposition based on a critical chemical potential difference. Then, a strategy for stable use is proposed: constructing a series of electronically conducting, but ion-blocking barriers to reset the chemical potential of such conductors to keep it below the threshold for decomposition, even if it is used with high electric currents and/or large temperature differences. This strategy not only opens the possibility of using such conductors in thermoelectric applications, but may also provide approaches to engineer perovskite photovoltaic materials and the experimental methods may be applicable to understanding dendrite growth in lithium ion batteries.
Higher activation barriers can lift exothermic rate restrictions in electron transfer and enable faster reactions
Authors: Mentel Kamila K. , Serra Arménio , Abreu Paulo E. , Arnaut Luis G.
Published: July 2018

Electron transfer reactions are arguably the simplest chemical reactions but they have not yet ceased to intrigue chemists. Charge-separation and charge-recombination reactions are at the core of life-sustaining processes, molecular electronics and solar cells. Intramolecular electron donor-acceptor systems capture the essential features of these reactions and enable their fundamental understanding. Here, we report intramolecular electron transfers covering a range of 100 kcal mol−1 in exothermicities that show an increase, then a decrease, and finally an increase in rates with the driving force of the reactions. Concomitantly, apparent activation energies change from positive, to negative and finally to positive. Reactions with positive activation energies are found to be faster than analogous reactions with negative effective activation energies. The increase of the reorganization energy with the driving force of the reactions can explain the peculiar free-energy relationship observed in this work.
Toroidal diamond anvil cell for detailed measurements under extreme static pressures
Authors: Dewaele Agnès , Loubeyre Paul , Occelli Florent , Marie Olivier , Mezouar Mohamed
Published: July 2018

Over the past 60 years, the diamond anvil cell (DAC) has been developed into a widespread high static pressure device. The adaptation of laboratory and synchrotron analytical techniques to DAC enables a detailed exploration in the 100 GPa range. The strain of the anvils under high load explains the 400 GPa limit of the conventional DAC. Here we show a toroidal shape for a diamond anvil tip that enables to extend the DAC use toward the terapascal pressure range. The toroidal-DAC keeps the assets for a complete, reproducible, and accurate characterization of materials, from solids to gases. Raman signal from the diamond anvil or X-ray signal from the rhenium gasket allow measurement of pressure. Here, the equations of state of gold, aluminum, and argon are measured with X-ray diffraction. The data are compared with recent measurements under similar conditions by two other approaches, the double-stage DAC and the dynamic ramp compression.
Saccade metrics reflect decision-making dynamics during urgent choices
Authors: Seideman Joshua A. , Stanford Terrence R. , Salinas Emilio
Published: July 2018

A perceptual judgment is typically characterized by constructing psychometric and chronometric functions, i.e., by mapping the accuracies and reaction times of motor choices as functions of a sensory stimulus feature dimension. Here, we show that various saccade metrics (e.g., peak velocity) are similarly modulated as functions of sensory cue viewing time during performance of an urgent-decision task. Each of the newly discovered functions reveals the dynamics of the perceptual evaluation process inherent to the underlying judgment. Remarkably, saccade peak velocity correlates with statistical decision confidence, suggesting that saccade kinematics reflect the degree of certainty with which an urgent perceptual decision is made. The data were explained by a race-to-threshold model that also replicates standard performance measures and cortical oculomotor neuronal activity in the task. The results indicate that, although largely stereotyped, saccade metrics carry subtle but reliable traces of the underlying cognitive processes that give rise to each oculomotor choice.
Structural and topological nature of plasticity in sheared granular materials
Authors: Cao Yixin , Li Jindong , Kou Binquan , Xia Chengjie , Li Zhifeng , Chen Rongchang , Xie Honglan , Xiao Tiqiao , Kob Walter , Hong Liang , Zhang Jie , Wang Yujie
Published: July 2018

Upon mechanical loading, granular materials yield and undergo plastic deformation. The nature of plastic deformation is essential for the development of the macroscopic constitutive models and the understanding of shear band formation. However, we still do not fully understand the microscopic nature of plastic deformation in disordered granular materials. Here we used synchrotron X-ray tomography technique to track the structural evolutions of three-dimensional granular materials under shear. We establish that highly distorted coplanar tetrahedra are the structural defects responsible for microscopic plasticity in disordered granular packings. The elementary plastic events occur through flip events which correspond to a neighbor switching process among these coplanar tetrahedra (or equivalently as the rotation motion of 4-ring disclinations). These events are discrete in space and possess specific orientations with the principal stress direction.
Dietary compounds have potential in controlling atherosclerosis by modulating macrophage cholesterol metabolism and inflammation via miRNA
Authors: Shao Dongyan , Lian Ziyang , Di Yichao , Zhang Lei , Rajoka Muhammad shahid riaz , Zhang Yudan , Kong Jie , Jiang Chunmei , Shi Junling
Published: July 2018

Atherosclerosis (AS) is a typical example of a widespread fatal cardiovascular disease. Accumulation of cholesterol-laden macrophages in the artery wall forms the starting point of AS. Increased influx of oxidized low-density lipoprotein to macrophages and decreased efflux of free cholesterol out of macrophages constitute major factors promoting the development of AS. Inflammation further aggravates the development of AS along or via interaction with the cholesterol metabolism. Many microRNAs (miRNAs) are related to the regulation of macrophage in AS in aspects of cholesterol metabolism and inflammation signaling. Dietary compounds perform AS inhibitory effects via miRNAs in the cholesterol metabolism (miR-19b, miR-378, miR-10b, miR-33a, and miR-33b) and two miRNAs in the inflammation signaling (miR-155 and miR-146a). The targeted miRNAs in the cholesterol metabolism vary greatly among different food compounds; however, in inflammation signaling, most food compounds target miR-155. Many receptors are involved in macrophages via miRNAs, including ABCA1 and ABCG1 as major receptors in the cholesterol metabolism, while nuclear factor-κB (NF-κB) and Nrf2 signaling and PI3K/AKT signaling pathways are targeted during inflammation. This article reviews current literature to investigate possible AS therapy with dietary compounds via targeting miRNAs. Currently existing problems were also discussed to guide further studies.
Facile, environmentally benign and scalable approach to produce pristine few layers graphene suitable for preparing biocompatible polymer nanocomposites
Authors: George Gejo , Sisupal Suja Bhargavan , Tomy Teenu , Kumaran Alaganandam , Vadivelu Prabha , Suvekbala Vemparthan , Sivaram Swaminathan , Ragupathy Lakshminarayanan
Published: July 2018

The success of developing graphene based biomaterials depends on its ease of synthesis, use of environmentally benign methods and low toxicity of the chemicals involved as well as biocompatibility of the final products/devices. We report, herein, a simple, scalable and safe method to produce defect free few layers graphene using naturally available phenolics i.e. curcumin/tetrahydrocurcumin/quercetin, as solid-phase exfoliating agents with a productivity of ∼45 g/batch (D/G ≤ 0.54 and D/D′ ≤ 1.23). The production method can also be employed in liquid-phase using a ball mill (20 g/batch, D/G ≤ 0.23 and D/D′ ≤ 1.12) and a sand grinder (10 g/batch, D/G ≤ 0.11 and D/D∼ ≤ 0.78). The combined effect of π-π interaction and charge transfer (from curcumin to graphene) is postulated to be the driving force for efficient exfoliation of graphite. The yielded graphene was mixed with the natural rubber (NR) latex to produce thin film nanocomposites, which show superior tensile strength with low modulus and no loss of % elongation at break. In-vitro and in-vivo investigations demonstrate that the prepared nanocomposite is biocompatible. This approach could be useful for the production of materials suitable in products (gloves/condoms/catheters), which come in contact with body parts/body fluids.
Infant temperament and family socio-economic status in relation to the emergence of attention regulation
Authors: Conejero Ángela , Rueda M. Rosario
Published: July 2018

Attention regulation refers to the ability to control attention according to goals and intentions. Disengagement of attention is one of the first mechanisms of attention regulation that emerges in infancy, involving attention control and flexibility. Disengaging attention from emotional stimuli (such as threat-related cues) is of particular interest given its implication for self-regulation. A second mechanism of attention control is the ability to flexibly switch attention according to changing conditions. In our study, we investigated 9 to 12-month-olds’ disengagement and flexibility of attention, and examined the contribution of both temperament and socioeconomic status (SES) to individual differences in the emergence of these attention regulation skills at the end of the first year of life. Our results show that both difficulty to disengage from fearful faces and poorer attention flexibility were associated with higher levels of temperamental Negative Affectivity (NA). Additionally, attention flexibility moderated the effect of NA on disengagement from fearful faces. Infants with higher NA and poorer attention flexibility showed the greatest difficulty to disengage. Low SES was also associated with poorer attention flexibility, association that was mediated by infants’ NA. These results suggest that attention flexibility together with temperament and environmental factors are key to understand individual differences in attention regulation from threat-related stimuli as early as from infancy. Our findings also stress the importance of interactions between environmental and constitutional factors for understanding individual differences in the emergence of attention regulation.
The association between different domains of quality of life and symptoms in primary care patients with emotional disorders
Authors: González-Blanch César , Hernández-de-Hita Fernando , Muñoz-Navarro Roger , Ruíz-Rodríguez Paloma , Medrano Leonardo Adrián , Cano-Vindel Antonio
Published: July 2018

Despite the importance of quality of life (QoL) in primary care patients with emotional disorders, the specific influence of the symptoms of these disorders and the sociodemographic characteristics of patients on the various QoL domains has received scant attention. The aim of the present study of primary care patients with emotional disorders was to analyse the associations between four different QoL domains and the most prevalent clinical symptoms (i.e., depression, anxiety and somatization), while controlling for sociodemographic variables. A total of 1241 participants from 28 primary care centres in Spain were assessed with the following instruments: the Patient Health Questionnaire (PHQ)-9 to evaluate depression; the Generalized Anxiety Disorder Scale (GAD)-7 for anxiety; PHQ-15 for somatization; and the World Health Organization Quality of Life Instrument-Short Form (WHOQOL-Bref) to assess four broad QoL domains: physical health, psychological health, social relationships, and environment. The associations between the symptoms and QoL domains were examined using hierarchical regression analyses. Adjusted QoL mean values as a function of the number of overlapping diagnoses were calculated. The contribution of sociodemographic variables to most QoL domains was modest, explaining anywhere from 2% to 11% of the variance. However, adding the clinical variables increased the variance explained by 12% to 40% depending on the specific QoL domain. Depression was the strongest predictor for all domains. The number of overlapping diagnoses adversely affected all QoL domains, with each additional diagnosis reducing the main QoL subscales by 5 to 10 points. In primary care patients with a diagnostic impression of an emotional disorders as identified by their treating GP, clinical symptoms explained more of the variance in QoL than sociodemographic factors such as age, sex, level of education, marital status, work status, and income. Given the strong relationship between depressive symptoms and QoL, treatment of depression may constitute a key therapeutic target to improve QoL in people with emotional disorders in primary care.
Intradermal immunization by Ebola virus GP subunit vaccines using microneedle patches protects mice against lethal EBOV challenge
Authors: Liu Ying , Ye Ling , Lin Fang , Gomaa Yasmine , Flyer David , Carrion Ricardo , Patterson Jean L. , Prausnitz Mark R. , Smith Gale , Glenn Gregory , Wu Hua , Compans Richard W. , Yang Chinglai
Published: July 2018

Development of a safe and efficacious filovirus vaccine is of high importance to public health. In this study, we compared immune responses induced by Ebola virus (EBOV) glycoprotein (GP) subunit vaccines via intradermal immunization with microneedle (MN) patches and the conventional intramuscular (IM) injection in mice, which showed that MN delivery of GP induced higher levels and longer lasting antibody responses against GP than IM injection. Further, we found that EBOV GP in formulation with a saponin-based adjuvant, Matrix-M, can be efficiently loaded onto MN patches. Co-delivery of Matrix-M with GP significantly enhanced induction of antibody responses by MN delivery, as also observed for IM injection. Results from challenge studies showed that all mice that received the GP/adjuvant formulation by MN or IM immunizations were protected from lethal EBOV challenge. Further, 4 out of 5 mice vaccinated by MN delivery of unadjuvanted GP also survived the challenge, whereas only 1 out of 5 mice vaccinated by IM injection of unadjuvanted GP survived the challenge. These results demonstrate that MN patch delivery of EBOV GP subunit vaccines, which is expected to enable improved safety and thermal stability, can confer effective protection against EBOV infection that is superior to IM vaccination.
Dynamic multistimuli-responsive reversible chiral transformation in supramolecular helices
Authors: Goskulwad Santosh , La Duong Duc , Kobaisi Mohammad Al , Bhosale Sidhanath V. , Bansal Vipul , Vinu Ajayan , Ariga Katsuhiko , Bhosale Sheshanath V.
Published: July 2018

The design of new chiral chromophores that allow tunable assembly of higher order helical structures by using natural stimuli offers promising avenue in understanding various biological processes. In particular, access to dynamic multistimuli-responsive systems can provide real-time monitoring of chiral transformation in chemical and biological systems. We report on the synthesis of naphthalenediimide appended L-glutamate (NDI-L-Glu) that self-assembles into chiral supramolecular structures under physiological conditions. Specifically, NDI-L-Glu shows a mixture of left- and right-handed helices under physiological conditions, and any deviation from the ambient biochemical environment has a remarkable influence on the chirality of these structures. For instance, acidic environments shift the helicity to left-handedness while the alkaline conditions reversed the helical structures to right-handedness, thereby mimicking the molecular virulence mechanism of tobacco mosaic virus (TMV). The chirality of these supramolecular assemblies can also be controllably tuned by using temperature as an external stimulus, allowing reversible flip of helicity.
Anti-angiogenic drug scheduling optimisation with application to colorectal cancer
Authors: Sturrock M. , Miller I. S. , Kang G. , Hannis Arba’ie N. , O’Farrell A. C. , Barat A. , Marston G. , Coletta P. L. , Byrne A. T. , Prehn J. H.
Published: July 2018

Bevacizumab (bvz) is a first choice anti-angiogenic drug in oncology and is primarily administered in combination with chemotherapy. It has been hypothesized that anti-angiogenic drugs enhance efficacy of cytotoxic drugs by “normalizing” abnormal tumor vessels and improving drug penetration. Nevertheless, the clinical relevance of this phenomenon is still unclear with several studies over recent years suggesting an opposing relationship. Herein, we sought to develop a new computational tool to interrogate anti-angiogenic drug scheduling with particular application in the setting of colorectal cancer (CRC). Specifically, we have employed a mathematical model of vascular tumour growth which interrogates the impact of anti-angiogenic treatment and chemotherapeutic treatment on tumour volume. Model predictions were validated using CRC xenografts which underwent treatment with a clinically relevant combinatorial anti-angiogenic regimen. Bayesian model selection revealed the most appropriate term for capturing the effect of treatments on the tumour size, and provided insights into a switch-like dependence of FOLFOX delivery on the tumour vasculature. Our experimental data and mathematical model suggest that delivering chemotherapy prior to bvz may be optimal in the colorectal cancer setting.
Determination of system level alterations in host transcriptome due to Zika virus (ZIKV) Infection in retinal pigment epithelium
Authors: Singh Pawan Kumar , Khatri Indu , Jha Alokkumar , Pretto Carla D. , Spindler Katherine R. , Arumugaswami Vaithilingaraja , Giri Shailendra , Kumar Ashok , Bhasin Manoj K.
Published: July 2018

Previously, we reported that Zika virus (ZIKV) causes ocular complications such as chorioretinal atrophy, by infecting cells lining the blood-retinal barrier, including the retinal pigment epithelium (RPE). To understand the molecular basis of ZIKV-induced retinal pathology, we performed a meta-analysis of transcriptome profiles of ZIKV-infected human primary RPE and other cell types infected with either ZIKV or other related flaviviruses (Japanese encephalitis, West Nile, and Dengue). This led to identification of a unique ZIKV infection signature comprising 43 genes (35 upregulated and 8 downregulated). The major biological processes perturbed include SH3/SH2 adaptor activity, lipid and ceramide metabolism, and embryonic organ development. Further, a comparative analysis of some differentially regulated genes (ABCG1, SH2B3, SIX4, and TNFSF13B) revealed that ZIKV induced their expression relatively more than dengue virus did in RPE. Importantly, the pharmacological inhibition of ABCG1, a membrane transporter of cholesterol, resulted in reduced ZIKV infectivity. Interestingly, the ZIKV infection signature revealed the downregulation of ALDH5A1 and CHML, genes implicated in neurological (cognitive impairment, expressive language deficit, and mild ataxia) and ophthalmic (choroideremia) disorders, respectively. Collectively, our study revealed that ZIKV induces differential gene expression in RPE cells, and the identified genes/pathways (e.g., ABCG1) could potentially contribute to ZIKV-associated ocular pathologies.
L-Carnitine and extendin-4 improve outcomes following moderate brain contusion injury
Authors: Chen Hui , Chan Yik Lung , Linnane Claire , Mao Yilin , Anwer Ayad G. , Sapkota Arjun , Annissa Tiara F. , Herok George , Vissel Bryce , Oliver Brian G. , Saad Sonia , Gorrie Catherine A.
Published: July 2018

There is a need for pharmaceutical agents that can reduce neuronal loss and improve functional deficits following traumatic brain injury (TBI). Previous research suggests that oxidative stress and mitochondrial dysfunction play a major role in neuronal damage after TBI. Therefore, this study aimed to investigate two drugs known to have antioxidant effects, L-carnitine and exendin-4, in rats with moderate contusive TBI. L-carnitine (1.5 mM in drinking water) or exendin-4 (15 µg/kg/day, ip) were given immediately after the injury for 2 weeks. Neurological function and brain histology were examined (24 h and 6 weeks post injury). The rats with TBI showed slight sensory, motor and memory functional deficits at 24 h, but recovered by 6 weeks. Both treatments improved sensory and motor functions at 24 h, while only exendin-4 improved memory. Both treatments reduced cortical contusion at 24 h and 6 weeks, however neither affected gliosis and inflammatory cell activation. Oxidative stress was alleviated and mitochondrial reactive oxygen species was reduced by both treatments, however only mitochondrial functional marker protein transporter translocase of outer membrane 20 was increased at 24 h post injury. In conclusion, L-carnitine and exendin-4 treatments immediately after TBI can improve neurological functional outcome and tissue integrity by reducing oxidative stress.
Epidemiology of intussusception before and after rotavirus vaccine introduction in Fiji
Authors: Ratu Felisita Tupou , Reyburn Rita , Tuivaga Evelyn , Tuiketei Asena , Jenkins Kylie , Mulholland Kim , Jenney Adam , Russell Fiona
Published: July 2018

In 2012, Fiji introduced rotavirus vaccine (Rotarix, GSK) into the national immunisation schedule. We describe the intussusception epidemiology prior to rotavirus vaccine, temporal association of intussusception cases to administration of rotavirus vaccine, and estimate the additional number of intussusception cases that may be associated with rotavirus vaccine. A retrospective review of intussusception cases for children aged <24 months old was undertaken between January 2007 and October 2012 pre-vaccine. All admissions and deaths with a discharge diagnosis of intussusception, bowel obstruction, paralytic ileus, or intussusception ICD10-AM codes were extracted from national databases and hospital records. Nationwide active intussusception surveillance was established for three years post-vaccine (2013–2015). There were 24 definite intussusception cases in the pre-rotavirus vaccine period, 96% were confirmed by surgery. The median age was 6.5 months. The incidence rate was 22.2 (95% CI: 13.9–33.7) per 100,000 infants. There were no deaths. Active surveillance identified 25 definite intussusception cases, 96% of which were among children who were age-eligible for rotavirus vaccine. None were potentially vaccine related. We estimated one to five additional  cases of intussusception every five years. The incidence of intussusception pre-rotavirus vaccine in Fiji is low. Intussusception associated with rotavirus vaccine is likely a rare event in Fiji.
Extracting the multi-timescale activity patterns of online financial markets
Authors: Kobayashi Teruyoshi , Sapienza Anna , Ferrara Emilio
Published: July 2018

Online financial markets can be represented as complex systems where trading dynamics can be captured and characterized at different resolutions and time scales. In this work, we develop a methodology based on non-negative tensor factorization (NTF) aimed at extracting and revealing the multi-timescale trading dynamics governing online financial systems. We demonstrate the advantage of our strategy first using synthetic data, and then on real-world data capturing all interbank transactions (over a million) occurred in an Italian online financial market (e-MID) between 2001 and 2015. Our results demonstrate how NTF can uncover hidden activity patterns that characterize groups of banks exhibiting different trading strategies (normal vs. early vs. flash trading, etc.). We further illustrate how our methodology can reveal “crisis modalities” in trading triggered by endogenous and exogenous system shocks: as an example, we reveal and characterize trading anomalies in the midst of the 2008 financial crisis.
Weighted Symbolic Dependence Metric (wSDM) for fMRI resting-state connectivity: A multicentric validation for frontotemporal dementia
Authors: Moguilner Sebastian , García Adolfo M. , Mikulan Ezequiel , Hesse Eugenia , García-Cordero Indira , Melloni Margherita , Cervetto Sabrina , Serrano Cecilia , Herrera Eduar , Reyes Pablo , Matallana Diana , Manes Facundo , Ibáñez Agustín , Sedeño Lucas
Published: July 2018

The search for biomarkers of neurodegenerative diseases via fMRI functional connectivity (FC) research has yielded inconsistent results. Yet, most FC studies are blind to non-linear brain dynamics. To circumvent this limitation, we developed a “weighted Symbolic Dependence Metric” (wSDM) measure. Using symbolic transforms, we factor in local and global temporal features of the BOLD signal to weigh a robust copula-based dependence measure by symbolic similarity, capturing both linear and non-linear associations. We compared this measure with a linear connectivity metric (Pearson’s R) in its capacity to identify patients with behavioral variant frontotemporal dementia (bvFTD) and controls based on resting-state data. We recruited participants from two international centers with different MRI recordings to assess the consistency of our measure across heterogeneous conditions. First, a seed-analysis comparison of the salience network (a specific target of bvFTD) and the default-mode network (as a complementary control) between patients and controls showed that wSDM yields better identification of resting-state networks. Moreover, machine learning analysis revealed that wSDM yielded higher classification accuracy. These results were consistent across centers, highlighting their robustness despite heterogeneous conditions. Our findings underscore the potential of wSDM to assess fMRI-derived FC data, and to identify sensitive biomarkers in bvFTD.
Temperature responsiveness of gilthead sea bream bone; an in vitro and in vivo approach
Authors: Riera-Heredia Natàlia , Martins Rute , Mateus Ana Patrícia , Costa Rita A. , Gisbert Enric , Navarro Isabel , Gutiérrez Joaquim , Power Deborah M. , Capilla Encarnación
Published: July 2018

This study aimed to characterize the molecules involved in osteogenesis in seabream and establish using in vitro/in vivo approaches the responsiveness of selected key genes to temperature. The impact of a temperature drop from 23 to 13 °C was evaluated in juvenile fish thermally imprinted during embryogenesis. Both, in vitro/in vivo, Fib1a, appeared important in the first stages of bone formation, and Col1A1, ON and OP, in regulating matrix production and mineralization. OCN mRNA levels were up-regulated in the final larval stages when mineralization was more intense. Moreover, temperature-dependent differential gene expression was observed, with lower transcript levels in the larvae at 18 °C relative to those at 22 °C, suggesting bone formation was enhanced in the latter group. Results revealed that thermal imprinting affected the long-term regulation of osteogenesis. Specifically, juveniles under the low and low-to-high-temperature regimes had reduced levels of OCN when challenged, indicative of impaired bone development. In contrast, gene expression in fish from the high and high-to-low-temperature treatments was unchanged, suggesting imprinting may have a protective effect. Overall, the present study revealed that thermal imprinting modulates bone development in seabream larvae, and demonstrated the utility of the in vitro MSC culture as a reliable tool to investigate fish osteogenesis.
Superior Strength and Multiple Strengthening Mechanisms in Nanocrystalline TWIP Steel
Authors: Kim Jung Gi , Enikeev Nariman A. , Seol Jae Bok , Abramova Marina M. , Karavaeva Marina V. , Valiev Ruslan Z. , Park Chan Gyung , Kim Hyoung Seop
Published: July 2018

The strengthening mechanism of the metallic material is related to the hindrance of the dislocation motion, and it is possible to achieve superior strength by maximizing these obstacles. In this study, the multiple strengthening mechanism-based nanostructured steel with high density of defects was fabricated using high-pressure torsion at room and elevated temperatures. By combining multiple strengthening mechanisms, we enhanced the strength of Fe-15 Mn-0.6C-1.5 Al steel to 2.6 GPa. We have found that solute segregation at grain boundaries achieves nanograined and nanotwinned structures with higher strength than the segregation-free counterparts. The importance of the use of multiple deformation mechanism suggests the development of a wide range of strong nanotwinned and nanostructured materials via severe plastic deformation process.
Runx1-Stat3-Tgfb3 signaling network regulating the anterior palatal development
Authors: Sarper Safiye E. , Kurosaka Hiroshi , Inubushi Toshihiro , Ono Minagi Hitomi , Kuremoto Koh-ichi , Sakai Takayoshi , Taniuchi Ichiro , Yamashiro Takashi
Published: July 2018

Runx1 deficiency results in an anteriorly specific cleft palate at the boundary between the primary and secondary palates and in the first rugae area of the secondary palate in mice. However, the cellular and molecular pathogenesis underlying such regional specificity remain unknown. In this study, Runx1 epithelial-specific deletion led to the failed disintegration of the contacting palatal epithelium and markedly downregulated Tgfb3 expression in the primary palate and nasal septum. In culture, TGFB3 protein rescued the clefting of the mutant. Furthermore, Stat3 phosphorylation was disturbed in the corresponding cleft regions in Runx1 mutants. The Stat3 function was manifested by palatal fusion defects in culture following Stat3 inhibitor treatment with significant downregulation of Tgfb3. Tgfb3 is therefore a critical target of Runx1 signaling, and this signaling axis could be mediated by Stat3 activation. Interestingly, the expression of Socs3, an inhibitor of Stat3, was specific in the primary palate and upregulated by Runx1 deficiency. Thus, the involvement of Socs3 in Runx1-Tgfb3 signaling might explain, at least in part, the anteriorly specific downregulation of Tgfb3 expression and Stat3 activity in Runx1 mutants. This is the first study to show that the novel Runx1-Stat3-Tgfb3 axis is essential in anterior palatogenesis.
Fast and non-destructive Raman spectroscopic determination of multi-walled carbon nanotube (MWCNT) contents in MWCNT/polydimethylsiloxane composites
Authors: Ryoo Donghyun , Kim Jong Yun , Duy Pham Khac , Cho Sang Hoon , Chung Hoeil , Yoon Tae Hyun
Published: July 2018

A versatile Raman spectroscopic method to determine the contents of carbon nanotubes (CNTs) in CNT/polydimethylsiloxane (PDMS) composites is demonstrated, and important issues directly related to the accuracy of the measurement were investigated.
Effective procedures for the determination of As, Cd, Cu, Fe, Hg, Mg, Mn, Ni, Pb, Se, Th, Zn, U and rare earth elements in plants and foodstuffs
Authors: Paniz Fernanda Pollo , Pedron Tatiana , Freire Bruna Moreira , Torres Daiane Placido , Silva Fábio Ferreira , Batista Bruno Lemos
Published: July 2018

There are several international regulations regarding trace elements. The use of ICP-MS for their determination is usually a difficult task, especially when Hg is one of the target elements.
Activation of carbon suboxide (C3O2) by U(iii) to form a cyclobutane-1,3-dione ring
Authors: Tsoureas Nikolaos , Cloke F. Geoffrey N.
Published: July 2018

[U(η5-C5H4SiMe3)3] reductively couples three C3O2molecules to form a tetranuclear complex with a central cyclobutane-1,3-dione ring,viaan intermediate bridging ketene complex.
Janus-faced role of water in defining nanostructure of choline chloride/glycerol deep eutectic solvent
Authors: Weng Lindong , Toner Mehmet
Published: July 2018

Effect of hydration on deep eutectic solvent properties.
Phosphomolybdic acid supported single-metal-atom catalysis in CO oxidation: first-principles calculations
Authors: Yu Ming-an , Feng Yingxin , Gao Liye , Lin Sen
Published: July 2018

Highly active phosphomolybdic acid supported single-metal-atom catalysts for CO oxidation.
Synthesis, properties, and optoelectronic applications of two-dimensional MoS2and MoS2-based heterostructures
Authors: Wang Hongmei , Li Chunhe , Fang Pengfei , Zhang Zulei , Zhang Jin Zhong
Published: July 2018

As a two-dimensional (2D) material, molybdenum disulfide (MoS2) exhibits unique electronic and optical properties useful for a variety of optoelectronic applications including light harvesting.
A review on the catalytic decomposition of NO to N2 and O2: catalysts and processes
Authors: Sun Qiang , Wang Zhong , Wang Da , Hong Zhe , Zhou Mingdong , Li Xuebing
Published: July 2018

Recent advances in the catalytic decomposition of NO have been overviewed and divided into three categories: metal oxide catalysts (including perovskites and rare earth oxides), supported metal oxide catalysts (including alkali metals, cobalt oxide and noble metals) and Cu-ZSM-5.
Competing mechanisms and origins of chemo- and stereo-selectivities of NHC-catalyzed reactions of enals with 2-aminoacrylates
Authors: Wang Yang , Wang Yanyan , Wang Xinghua , Li Xue , Qu Ling-Bo , Wei Donghui
Published: July 2018

A DFT study on competing mechanisms of NHC-catalyzed reactions of enals with 2-aminoacrylates has been performed for the first time.
Lactoferrin attenuates high-fat diet-induced hepatic steatosis and lipid metabolic dysfunctions by suppressing hepatic lipogenesis and down-regulating inflammation in C57BL/6J mice
Authors: Xiong Ling , Ren Fazheng , Lv Jiayi , Zhang Hao , Guo Huiyuan
Published: July 2018

Lactoferrin was reported to exert modulatory effects on lipid metabolism, but the regulatory mechanisms remain unclear.
Hydroxysafflor yellow A (HSYA) targets the NF-κB and MAPK pathways and ameliorates the development of osteoarthritis
Authors: Hu Zhi-Chao , Xie Zhong-Jie , Tang Qian , Li Xiao-Bin , Fu Xin , Feng Zhen-Hua , Xuan Jiang-Wei , Ni Wen-Fei , Wu Ai-Min
Published: July 2018

The inflammatory environment has been demonstrated to be strongly associated with the progression of osteoarthritis (OA).
Bi2Se3-assisted membrane crystallization
Authors: Macedonio Francesca , Politano Antonio , Drioli Enrico , Gugliuzza Annarosa
Published: July 2018

Water uptake in Bi2S3 vacancies assists ion aggregation during membrane crystallization.
E-Selective synthesis of vinyl sulfones via silver-catalyzed sulfonylation of styrenes
Authors: Gui Qingwen , Han Kang , Liu Zhuoliang , Su Zhaohong , He Xiaoli , Jiang Hongmei , Tian Bufan , Li Yangyan
Published: July 2018

An efficient and highly E-selective protocol for the synthesis of vinyl sulfones is described.
Unveiling controlled breaking of the mirror symmetry of Eu(fod)3 with α-/β-pinene and BINAP by circularly polarised luminescence (CPL), CPL excitation, and 19F-/31P{1H}-NMR spectra and Mulliken charges
Authors: Jalilah Abd Jalil , Asanoma Fumio , Fujiki Michiya
Published: July 2018

The first CPL signals at f–f transitions of Eu(fod)3 in α- and β-pinene as chiral solvents and with BINAP (1 : 1) in chloroform were detected.
Metabolic profiling putatively identifies plasma biomarkers of male infertility using UPLC-ESI-IT-TOFMS
Authors: Zeng F. J. , Ji H. C. , Zhang Z. M. , Luo J. K. , Lu H. M. , Wang Y.
Published: July 2018

Ultra-performance liquid chromatography-electrospray ionization-ion trap-time of flight mass spectrometry combined with chemometrics methods was used to discover potential biomarkers of male infertility based on untargeted plasma metabolomics.
The genusCapsicum: a phytochemical review of bioactive secondary metabolites
Authors: Antonio A. S. , Wiedemann L. S. M. , Veiga Junior V. F.
Published: July 2018

TheCapsicumgenus is economically important due to its chemical profile which is rich in capsaicinoids, carotenoids and flavonoids. Its unique chemical composition allows this genus to be applied from food additives to medicinal application.
Detection of resveratrol by phosphorescence quantum dots without conjunction and mutual impact exploration
Authors: Qin Jin , Zheng Ji , Fang Xiaoxing , Yan Guiqin
Published: July 2018

In this study, a convenient and sensitive method for the detection of resveratrol was established based on phosphorescence quenching of resveratrol for MPA-capped Mn:ZnS QDs.
MoS2 formation induced by amorphous MoS3 species under lubricated friction
Authors: Oumahi C. , De Barros-Bouchet M. I. , Le Mogne T. , Charrin C. , Loridant S. , Geantet C. , Afanasiev P. , Thiebaut B.
Published: July 2018

In order to investigate the decomposition mechanism of amide molybdate, two series of experimental friction tests have been performed, varying the temperature and pressure.
Copper(i) reagent-promoted hydroxytrifluoromethylation of enamides: flexible synthesis of substituted-3-hydroxy-2-aryl-3-(2,2,2-trifluoro-1-arylethyl)isoindolin-1-one
Authors: Wang Qing , Shi Peng , Zeng Runsheng
Published: July 2018

A novel CuBr-catalyzed hydroxytrifluoromethylation reaction was investigated. Substituted 3-benzylidene-2-arylisoindolin-1-ones were reacted with sodium trifluoromethanesulfinate to afford substituted-3-hydroxy-2-aryl-3-(2,2,2-trifluoro-1-arylethyl)isoindolin-1-one.
A DOX-loaded polymer micelle for effectively inhibiting cancer cells
Authors: Feng Huayang , Chu Dandan , Li Zhanrong , Guo Zhihua , Jin Lin , Fan Bingbing , Zhang Junjie , Li Jingguo
Published: July 2018

A novel triblock polymer is synthesized and self-assembled with doxorubicin to form DOX-loaded micelles.
New insights into the surface plasmon resonance (SPR) driven photocatalytic H2 production of Au–TiO2
Authors: Nie Jinlin , Schneider Jenny , Sieland Fabian , Zhou Long , Xia Shuwei , Bahnemann Detlef W.
Published: July 2018

The Surface Plasmon Resonance (SPR) driven photocatalytic H2 production upon visible light illumination (≥500 nm) was investigated on gold-loaded TiO2 (Au–TiO2).
Cooking with active oxygen and solid alkali facilitates lignin degradation in bamboo pretreatment
Authors: Ding Ning , Song Xiaoqiang , Jiang Yetao , Luo Bin , Zeng Xianhai , Sun Yong , Tang Xing , Lei Tingzhou , Lin Lu
Published: July 2018

By using HSQC NMR, delignification of the CAOSA process was described, which paves the way for developing new eco-friendly pulping technology.
Electric field induced gelation in aqueous nanoclay suspensions
Authors: Gadige Paramesh , Bandyopadhyay Ranjini
Published: July 2018

Liquid-like aqueous colloidal LAPONITE® clay suspensions rapidly transform into soft solids due to the application of DC electric fields.
Layer-by-layer assembled multilayers of charged polyurethane and graphene oxide platelets for flexible and stretchable gas barrier films
Authors: Noh Min Ji , Oh Min Jun , Choi Jae Ho , Yu Jae Chul , Kim Woo-Jae , Park Juhyun , Chang Young-Wook , Yoo Pil J.
Published: July 2018

To improve stretchability of gas barrier films without sacrificing the barrier property, alternatively charged and highly flexible polyurethane chains were layer-by-layer self-assembled with graphene oxide nano-platelets.
Modular approach to microswimming
Authors: Niu Ran , Palberg Thomas
Published: July 2018

Modular approach flexibly makes a variety of microswimmers by combining active and inactive components.