bluuebunny/crossref_metadata_2025 huggingface dataset:
Harnessing synthetic lethality to predict the response to cancer treatment
Authors: Lee Joo Sang , Das Avinash , Jerby-Arnon Livnat , Arafeh Rand , Auslander Noam , Davidson Matthew , McGarry Lynn , James Daniel , Amzallag Arnaud , Park Seung Gu , Cheng Kuoyuan , Robinson Welles , Atias Dikla , Stossel Chani , Buzhor Ella , Stein Gidi , Waterfall Joshua J. , Meltzer Paul S. , Golan Talia , Hannenhalli Sridhar , Gottlieb Eyal , Benes Cyril H. , Samuels Yardena , Shanks Emma , Ruppin Eytan
Published: June 2018

While synthetic lethality (SL) holds promise in developing effective cancer therapies, SL candidates found via experimental screens often have limited translational value. Here we present a data-driven approach, ISLE (identification of clinically relevant synthetic lethality), that mines TCGA cohort to identify the most likely clinically relevant SL interactions (cSLi) from a given candidate set of lab-screened SLi. We first validate ISLE via a benchmark of large-scale drug response screens and by predicting drug efficacy in mouse xenograft models. We then experimentally test a select set of predicted cSLi via new screening experiments, validating their predicted context-specific sensitivity in hypoxic vs normoxic conditions and demonstrating cSLi’s utility in predicting synergistic drug combinations. We show that cSLi can successfully predict patients’ drug treatment response and provide patient stratification signatures. ISLE thus complements existing actionable mutation-based methods for precision cancer therapy, offering an opportunity to expand its scope to the whole genome.
Stable complete methane oxidation over palladium based zeolite catalysts
Authors: Petrov Andrey W. , Ferri Davide , Krumeich Frank , Nachtegaal Maarten , van Bokhoven Jeroen A. , Kröcher Oliver
Published: June 2018

Increasing the use of natural gas engines is an important step to reduce the carbon footprint of mobility and power generation sectors. To avoid emissions of unburnt methane and the associated severe greenhouse effect of lean-burn engines, the stability of methane oxidation catalysts against steam-induced sintering at low temperatures (<500 °C) needs to be improved. Here we demonstrate how the combination of catalyst development and improved process control yields a highly efficient solution for complete methane oxidation. We design a material based on palladium and hierarchical zeolite with fully sodium-exchanged acid sites, which improves the support stability and prevents steam-induced palladium sintering under reaction conditions by confining the metal within the zeolite. Repeated short reducing pulses enable the use of a highly active transient state of the catalyst, which in combination with its high stability provides excellent performance without deactivation for over 90 h in the presence of steam.
Continuous biomarker monitoring by particle mobility sensing with single molecule resolution
Authors: Visser Emiel W. A. , Yan Junhong , van IJzendoorn Leo J. , Prins Menno W. J.
Published: June 2018

Healthcare is in demand of technologies for real-time sensing in order to continuously guard the state of patients. Here we present biomarker-monitoring based on the sensing of particle mobility, a concept wherein particles are coupled to a substrate via a flexible molecular tether, with both the particles and substrate provided with affinity molecules for effectuating specific and reversible interactions. Single-molecular binding and unbinding events modulate the Brownian particle motion and the state changes are recorded using optical scattering microscopy. The technology is demonstrated with DNA and protein as model biomarkers, in buffer and in blood plasma, showing sensitivity to picomolar and nanomolar concentrations. The sensing principle is direct and self-contained, without consuming or producing any reactants. With its basis in reversible interactions and single-molecule resolution, we envisage that the presented technology will enable biosensors for continuous biomarker monitoring with high sensitivity, specificity, and accuracy.
Pervasive genetic interactions modulate neurodevelopmental defects of the autism-associated 16p11.2 deletion in Drosophila melanogaster
Authors: Iyer Janani , Singh Mayanglambam Dhruba , Jensen Matthew , Patel Payal , Pizzo Lucilla , Huber Emily , Koerselman Haley , Weiner Alexis T. , Lepanto Paola , Vadodaria Komal , Kubina Alexis , Wang Qingyu , Talbert Abigail , Yennawar Sneha , Badano Jose , Manak J. Robert , Rolls Melissa M. , Krishnan Arjun , Girirajan Santhosh
Published: June 2018

As opposed to syndromic CNVs caused by single genes, extensive phenotypic heterogeneity in variably-expressive CNVs complicates disease gene discovery and functional evaluation. Here, we propose a complex interaction model for pathogenicity of the autism-associated 16p11.2 deletion, where CNV genes interact with each other in conserved pathways to modulate expression of the phenotype. Using multiple quantitative methods in Drosophila RNAi lines, we identify a range of neurodevelopmental phenotypes for knockdown of individual 16p11.2 homologs in different tissues. We test 565 pairwise knockdowns in the developing eye, and identify 24 interactions between pairs of 16p11.2 homologs and 46 interactions between 16p11.2 homologs and neurodevelopmental genes that suppress or enhance cell proliferation phenotypes compared to one-hit knockdowns. These interactions within cell proliferation pathways are also enriched in a human brain-specific network, providing translational relevance in humans. Our study indicates a role for pervasive genetic interactions within CNVs towards cellular and developmental phenotypes.
Prioritizing network communities
Authors: Zitnik Marinka , Sosič Rok , Leskovec Jure
Published: June 2018

Uncovering modular structure in networks is fundamental for systems in biology, physics, and engineering. Community detection identifies candidate modules as hypotheses, which then need to be validated through experiments, such as mutagenesis in a biological laboratory. Only a few communities can typically be validated, and it is thus important to prioritize which communities to select for downstream experimentation. Here we develop CRank, a mathematically principled approach for prioritizing network communities. CRank efficiently evaluates robustness and magnitude of structural features of each community and then combines these features into the community prioritization. CRank can be used with any community detection method. It needs only information provided by the network structure and does not require any additional metadata or labels. However, when available, CRank can incorporate domain-specific information to further boost performance. Experiments on many large networks show that CRank effectively prioritizes communities, yielding a nearly 50-fold improvement in community prioritization.
Prevalence of Parkinson’s disease across North America
Authors: Marras C. , Beck J. C. , Bower J. H. , Roberts E. , Ritz B , Ross G. W. , Abbott R. D. , Savica R. , Van Den Eeden S. K. , Willis A. W. , Tanner CM ,   on behalf of the Parkinson’s Foundation P4 Group
Published: June 2018

Estimates of the prevalence of Parkinson’s disease in North America have varied widely and many estimates are based on small numbers of cases and from small regional subpopulations. We sought to estimate the prevalence of Parkinson’s disease in North America by combining data from a multi-study sampling strategy in diverse geographic regions and/or data sources. Five separate cohort studies in California (2), Minnesota (1), Hawaii USA (1), and Ontario, Canada (1) estimated the prevalence of PD from health-care records (3), active ascertainment through facilities, large group, and neurology practices (1), and longitudinal follow-up of a population cohort (1). US Medicare program data provided complementary estimates for the corresponding regions. Using our age- and sex-specific meta-estimates from California, Minnesota, and Ontario and the US population structure from 2010, we estimate the overall prevalence of PD among those aged ≥45 years to be 572 per 100,000 (95% confidence interval 537–614) that there were 680,000 individuals in the US aged ≥45 years with PD in 2010 and that that number will rise to approximately 930,000 in 2020 and 1,238,000 in 2030 based on the US Census Bureau population projections. Regional variations in prevalence were also observed in both the project results and the Medicare-based calculations with which they were compared. The estimates generated by the Hawaiian study were lower across age categories. These estimates can guide health-care planning but should be considered minimum estimates. Some heterogeneity exists that remains to be understood.
Uhlmann curvature in dissipative phase transitions
Authors: Carollo Angelo , Spagnolo Bernardo , Valenti Davide
Published: June 2018

A novel approach based on the Uhlmann curvature is introduced for the investigation of non-equilibrium steady-state quantum phase transitions (NESS-QPTs). Equilibrium phase transitions fall invariably into two markedly non-overlapping categories: classical phase transitions and quantum phase transitions. NESS-QPTs offer a unique arena where such a distinction fades off. We propose a method to reveal and quantitatively assess the quantum character of such critical phenomena. We apply this tool to a paradigmatic class of lattice fermion systems with local reservoirs, characterised by Gaussian non-equilibrium steady states. The relations between the behaviour of the Uhlmann curvature, the divergence of the correlation length, the character of the criticality and the dissipative gap are demonstrated. We argue that this tool can shade light upon the nature of non equilibrium steady state criticality in particular with regard to the role played by quantum vs classical fluctuations.
HrpE, the major component of the Xanthomonas type three protein secretion pilus, elicits plant immunity responses
Authors: Gottig Natalia , Vranych Cecilia V. , Sgro Germán G. , Piazza Ainelén , Ottado Jorgelina
Published: June 2018

Like several pathogenic bacteria, Xanthomonas infect host plants through the secretion of effector proteins by the Hrp pilus of the Type Three Protein Secretion System (T3SS). HrpE protein was identified as the major structural component of this pilus. Here, using the Xanthomonas citri subsp. citri (Xcc) HrpE as a model, a novel role for this protein as an elicitor of plant defense responses was found. HrpE triggers defense responses in host and non-host plants revealed by the development of plant lesions, callose deposition, hydrogen peroxide production and increase in the expression levels of genes related to plant defense responses. Moreover, pre-infiltration of citrus or tomato leaves with HrpE impairs later Xanthomonas infections. Particularly, HrpE C-terminal region, conserved among Xanthomonas species, was sufficient to elicit these responses. HrpE was able to interact with plant Glycine-Rich Proteins from citrus (CsGRP) and Arabidopsis (AtGRP-3). Moreover, an Arabidopsis atgrp-3 knockout mutant lost the capacity to respond to HrpE. This work demonstrate that plants can recognize the conserved C-terminal region of the T3SS pilus HrpE protein as a danger signal to defend themselves against Xanthomonas, triggering defense responses that may be mediated by GRPs.
The adiponectin promoter activator NP-1 induces high levels of circulating TNFα and weight loss in obese (fa/fa) Zucker rats
Authors: Decara Juan , Serrano Antonia , Pavón Francisco Javier , Rivera Patricia , Arco Rocio , Gavito Ana , Vargas Antonio , Navarro Juan A. , Tovar Ruben , Lopez-Gambero Antonio J. , Martínez Ana , Suárez Juan , Rodríguez de Fonseca Fernando , Baixeras Elena
Published: June 2018

Chronic NP-1 administration reduces body weight and hepatic steatosis despite induction of tolerance in adiponectin gene transcription with respect to the acute actions of this drug. This study explored the hypothesis that NP-1 could exert these effects through mechanisms independent of adiponectin. To this aim, we took advantage of the Zucker (fa/fa) rat model, which exhibits obesity, fatty liver and elevated leptin and adiponectin levels. Body weight and food intake were reduced after chronic NP-1 treatment. Plasma TNFα concentrations were elevated but no increase in adiponectin was found. Even so, NP-1 ameliorated fatty liver and corrected dyslipidemia by mechanisms probably associated with reduced feeding, transcription of Cpt1 and down-regulation of Hmgcr-CoA expression. In brown fat tissue NP-1 increased Dnmt1 (inhibitor of Adipoq) while it reduced Ucp1 expression and heat production, which excludes thermogenesis as a mechanism of the NP-1 slimming effect. The anti-obesity action of chronic NP-1 administration might be mediated by TNFα, which is known to have anorectic actions in the hypothalamus and to regulate both Dmnt1 and Ucp1 expression in adipose tissues. This finding opens up the possibility of using NP-1-mediated TNFα-induced weight loss as an innovative treatment of complicated obesity under strict pharmacologic control.
Increased nuclear DNA damage precedes mitochondrial dysfunction in peripheral blood mononuclear cells from Huntington’s disease patients
Authors: Askeland Georgina , Dosoudilova Zaneta , Rodinova Marie , Klempir Jiri , Liskova Irena , Kuśnierczyk Anna , Bjørås Magnar , Nesse Gaute , Klungland Arne , Hansikova Hana , Eide Lars
Published: June 2018

Huntington’s disease (HD) is a progressive neurodegenerative disorder primarily affecting the basal ganglia and is caused by expanded CAG repeats in the huntingtin gene. Except for CAG sizing, mitochondrial and nuclear DNA (mtDNA and nDNA) parameters have not yet proven to be representative biomarkers for disease and future therapy. Here, we identified a general suppression of genes associated with aerobic metabolism in peripheral blood mononuclear cells (PBMCs) from HD patients compared to controls. In HD, the complex II subunit SDHB was lowered although not sufficiently to affect complex II activity. Nevertheless, we found decreased level of factors associated with mitochondrial biogenesis and an associated dampening of the mitochondrial DNA damage frequency in HD, implying an early defect in mitochondrial activity. In contrast to mtDNA, nDNA from HD patients was four-fold more modified than controls and demonstrated that nDNA integrity is severely reduced in HD. Interestingly, the level of nDNA damage correlated inversely with the total functional capacity (TFC) score; an established functional score of HD. Our data show that PBMCs are a promising source to monitor HD progression and highlights nDNA damage and diverging mitochondrial and nuclear genome responses representing early cellular impairments in HD.
Conformation-dependent binding of a Tetrastatin peptide to αvβ3 integrin decreases melanoma progression through FAK/PI3K/Akt pathway inhibition
Authors: Lambert Eléonore , Fuselier Eloïse , Ramont Laurent , Brassart Bertrand , Dukic Sylvain , Oudart Jean-Baptiste , Dupont-Deshorgue Aurélie , Sellier Christèle , Machado Carine , Dauchez Manuel , Monboisse Jean-Claude , Maquart François-Xavier , Baud Stéphanie , Brassart-Pasco Sylvie
Published: June 2018

Tetrastatin, a 230 amino acid sequence from collagen IV, was previously demonstrated to inhibit melanoma progression. In the present paper, we identified the minimal active sequence (QKISRCQVCVKYS: QS-13) that reproduced the anti-tumor effects of whole Tetrastatin in vivo and in vitro on melanoma cell proliferation, migration and invasion. We demonstrated that QS-13 binds to SK-MEL-28 melanoma cells through the αvβ3 integrin using blocking antibody and β3 integrin subunit siRNAs strategies. Relevant QS-13 conformations were extracted from molecular dynamics simulations and their interactions with αVβ3 integrin were analyzed by docking experiments to determine the binding areas and the QS-13 amino acids crucial for the binding. The in silico results were confirmed by in vitro experiments. Indeed, QS-13 binding to SK-MEL-28 was dependent on the presence of a disulfide-bound as shown by mass spectroscopy and the binding site on αVβ3 was located in close vicinity to the RGD binding site. QS-13 binding inhibits the FAK/PI3K/Akt pathway, a transduction pathway that is largely involved in tumor cell proliferation and migration. Taken together, our results demonstrate that the QS-13 peptide binds αvβ3 integrin in a conformation-dependent manner and is a potent antitumor agent that could target cancer cells through αVβ3.
Reciprocal cross-species induction of outer membrane vesicle biogenesis via secreted factors
Authors: Horspool Alexander M. , Schertzer Jeffrey W.
Published: June 2018

Delivery of cargo to target cells is fundamental to bacterial competitiveness. One important but poorly understood system, ubiquitous among Gram-negative organisms, involves packaging cargo into outer membrane vesicles (OMVs). These biological nanoparticles are involved in processes ranging from toxin delivery to cell-cell communication. Despite this, we know comparatively little about how OMVs are formed. Building upon the discovery that the Pseudomonas Quinolone Signal (PQS) stimulates OMV biogenesis in Pseudomonas aeruginosa, we proposed a model where PQS interacts with the outer membrane to induce curvature and ultimately OMV formation. Though this model is well supported in P. aeruginosa, it remained unclear whether other organisms produce similar compounds. Here we describe the development of a tightly controlled experimental system to test the interaction of bacterially-produced factors with target cells. Using this system, we show that multiple species respond to PQS by increasing OMV formation, that PQS accumulates in the induced vesicles, and that other bacteria secrete OMV-promoting factors. Analysis of induced vesicles indicates that recipient-mediated mechanisms exist to control vesicle size and that relatedness to the producer organism can dictate susceptibility to OMV-inducing compounds. This work provides evidence that small molecule induced OMV biogenesis is a widely conserved process and that cross-talk between systems may influence OMV production in neighboring bacteria.
Optimization-based design of an elastostatic cloaking device
Authors: Fachinotti Víctor D. , Peralta Ignacio , Albanesi Alejandro E.
Published: June 2018

We present a new method for the design of devices to manipulate the displacement field in Elastic materials. It consists of solving a nonlinear optimization problem where the objective function defines the error in matching a desired displacement field, and the design variables determine the required material distribution within the device. In order to facilitate fabrication, the material at a given point of the device is chosen from a set of predefined materials, giving raise to a discrete optimization problem that is converted into a continuous one using the Discrete Material Optimization technique. The candidate materials maybe simple, isotropic materials, but the device made of them behaves as a whole as a metamaterial, enabling the manipulation of the displacement field in ways that are inconceivable in nature. As an example of application, a device for elastostatic cloaking or unfeelability is designed.
Differential preservation of endogenous human and microbial DNA in dental calculus and dentin
Authors: Mann Allison E. , Sabin Susanna , Ziesemer Kirsten , Vågene Åshild J. , Schroeder Hannes , Ozga Andrew T. , Sankaranarayanan Krithivasan , Hofman Courtney A. , Fellows Yates James A. , Salazar-García Domingo C. , Frohlich Bruno , Aldenderfer Mark , Hoogland Menno , Read Christopher , Milner George R. , Stone Anne C. , Lewis Cecil M. , Krause Johannes , Hofman Corinne , Bos Kirsten I. , Warinner Christina
Published: June 2018

Dental calculus (calcified dental plaque) is prevalent in archaeological skeletal collections and is a rich source of oral microbiome and host-derived ancient biomolecules. Recently, it has been proposed that dental calculus may provide a more robust environment for DNA preservation than other skeletal remains, but this has not been systematically tested. In this study, shotgun-sequenced data from paired dental calculus and dentin samples from 48 globally distributed individuals are compared using a metagenomic approach. Overall, we find DNA from dental calculus is consistently more abundant and less contaminated than DNA from dentin. The majority of DNA in dental calculus is microbial and originates from the oral microbiome; however, a small but consistent proportion of DNA (mean 0.08 ± 0.08%, range 0.007–0.47%) derives from the host genome. Host DNA content within dentin is variable (mean 13.70 ± 18.62%, range 0.003–70.14%), and for a subset of dentin samples (15.21%), oral bacteria contribute > 20% of total DNA. Human DNA in dental calculus is highly fragmented, and is consistently shorter than both microbial DNA in dental calculus and human DNA in paired dentin samples. Finally, we find that microbial DNA fragmentation patterns are associated with guanine-cytosine (GC) content, but not aspects of cellular structure.
Multi-centennial fluctuations of radionuclide production rates are modulated by the Earth’s magnetic field
Authors: Pavón-Carrasco F. J. , Gómez-Paccard M. , Campuzano S. A. , González-Rouco J. F. , Osete M. L.
Published: June 2018

The production of cosmogenic isotopes offers a unique way to reconstruct solar activity during the Holocene. It is influenced by both the solar and Earth magnetic fields and thus their combined effect needs to be disentangled to infer past solar irradiance. Nowadays, it is assumed that the long-term variations of cosmogenic production are modulated by the geomagnetic field and that the solar field dominates over shorter wavelengths. In this process, the effects of the non-dipolar terms of the geomagnetic field are considered negligible. Here we analyse these assumptions and demonstrate that, for a constant solar modulation potential, the geomagnetic field exerts a strong modulation of multi-centennial to millennial wavelengths (periods of 800 and 2200 yr). Moreover, we demonstrate that the non-dipole terms derived from the harmonic degree 3 and above produce maximum differences of 7% in the global average radiocarbon production rate. The results are supported by the identification, for the first time, of a robust coherence between the production rates independently estimated from geomagnetic reconstructions and that inferred from natural archives. This implies the need to review past solar forcing reconstructions, with important implications both for the assessment of solar-climate relationships as well as for the present and future generation of paleoclimate models.
Correction of center of rotation and projection angle in synchrotron X-ray computed tomography
Authors: Cheng Chang-Chieh , Ching Yu-Tai , Ko Pai-Hung , Hwu Yeukuang
Published: June 2018

An error in tomographic reconstruction parameters can result considerable artifacts in the reconstructed image, particularly in micro-computed tomography and nano-computed tomography. This study involved designing an automatic method for efficiently correcting errors resulting from incorrectly determined rotational axes and projection angles. In this method, errors are corrected by minimizing the “total variation” of a reconstructed image, and minimization is accomplished by using the gradient descent method. Compared with two previous methods, the proposed method achieved the best reconstruction results.
High pressure minerals in the Château-Renard (L6) ordinary chondrite: implications for collisions on its parent body
Authors: Baziotis Ioannis , Asimow Paul D. , Hu Jinping , Ferrière Ludovic , Ma Chi , Cernok Ana , Anand Mahesh , Topa Dan
Published: June 2018

We report the first discoveries of high-pressure minerals in the historical L6 chondrite fall Château-Renard, based on co-located Raman spectroscopy, scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy and electron backscatter diffraction, electron microprobe analysis, and transmission electron microscopy (TEM) with selected-area electron diffraction. A single polished section contains a network of melt veins from ~40 to ~200 μm wide, with no cross-cutting features requiring multiple vein generations. We find high-pressure minerals in veins greater than ~50 μm wide, including assemblages of ringwoodite + wadsleyite, ringwoodite + wadsleyite + majorite-pyropess, and ahrensite + wadsleyite. In association with ahrensite + wadsleyite at both SEM and TEM scale, we find a sodic pyroxene whose Raman spectrum is indistinguishable from that of jadeite but whose composition and structure are those of omphacite. We discuss constraints on the impact record of this meteorite and the L-chondrites in general.
The extent of extra-axonal tissue damage determines the levels of CSPG upregulation and the success of experimental axon regeneration in the CNS
Authors: Kim Juhwan , Sajid Muhammad S. , Trakhtenberg Ephraim F.
Published: June 2018

The failure of mature central nervous system (CNS) projection neurons to regenerate axons over long distances drastically limits the recovery of functions lost after various CNS injuries and diseases. Although a number of manipulations that stimulate some degree of axon regeneration that overcomes the inhibitory environment after CNS injury have been discovered, the extent of regeneration remains very limited, emphasizing the need for improved therapies. Regenerating axons need nerve tissue environment capable of supporting their growth, and severe extra-axonal tissue damage and remodeling after injury may disrupt such environment. Here, we used traumatic injury to the mouse optic nerve as a model system to investigate how the extent of extra-axonal tissue damage affects experimental axon regeneration. Axon regeneration was stimulated by the shRNA-mediated knockdown (KD) of Pten gene expression in the retinal ganglion cells, and the extent of extra-axonal tissue damage was varied by changing the duration of optic nerve crush. Although no axons were spared using either 1 or 5 seconds crush, we found that Pten KD-stimulated axon regeneration was significantly reduced in 5 seconds compared with 1 second crush. The more severe extra-axonal tissue damage did not cause tissue atrophy, but led to significantly higher upregulation of axon growth-inhibiting chondroitin sulfate proteoglycan (CSPG) in the glial scar and also enlarged glial scar size, compared with less severely damaged tissue. Thus, the success of axon-regenerating approaches that target neuronal intrinsic mechanisms of axon growth is dependent on the preservation of appropriate extra-axonal tissue environment, which may need to be co-concurrently repaired by tissue remodeling methods.
Multiplex STR amplification sensitivity in a silicon microchip
Authors: Cornelis Senne , Fauvart Maarten , Gansemans Yannick , Vander Plaetsen Ann-Sophie , Colle Frederik , Wiederkehr Rodrigo S. , Deforce Dieter , Stakenborg Tim , Van Nieuwerburgh Filip
Published: June 2018

The demand for solutions to perform forensic DNA profiling outside of centralized laboratories is increasing. We here demonstrate highly sensitive STR amplification using a silicon micro-PCR (µPCR) chip. Exploiting industry-standard semiconductor manufacturing processes, a device was fabricated that features a small form factor thanks to an integrated heating element covering three parallel micro-reactors with a reaction volume of 0.5 µl each. Diluted reference DNA samples (1 ng–31 pg) were amplified on the µPCR chip using the forensically validated AmpFISTR Identifier Plus kit, followed by conventional capillary electrophoresis. Complete STR profiles were generated with input DNA quantities down to 62 pg. Occasional allelic dropouts were observed from 31 pg downward. On-chip STR profiles were compared with those of identical samples amplified using a conventional thermal cycler for direct comparison of amplification sensitivity in a forensic setting. The observed sensitivity was in line with kit specifications for both µPCR and conventional PCR. Finally, a rapid amplification protocol was developed. Complete STR profiles could be generated in less than 17 minutes from as little as 125 pg template DNA. Together, our results are an important step towards the development of commercial, mass-produced, relatively cheap, handheld devices for on-site testing in forensic DNA analysis.
Evaluation at scale of microbiome-derived metabolites as biomarker of flavan-3-ol intake in epidemiological studies
Authors: Ottaviani Javier I. , Fong Redmond , Kimball Jennifer , Ensunsa Jodi L. , Britten Abigail , Lucarelli Debora , Luben Robert , Grace Philip B. , Mawson Deborah H. , Tym Amy , Wierzbicki Antonia , Khaw Kay-Tee , Schroeter Hagen , Kuhnle Gunter G. C.
Published: June 2018

The accurate assessment of dietary intake is crucial to investigate the effect of diet on health. Currently used methods, relying on self-reporting and food composition data, are known to have limitations and might not be suitable to estimate the intake of many bioactive food components. An alternative are nutritional biomarkers, which can allow an unbiased assessment of intake. They require a careful evaluation of their suitability, including: (a) the availability of a precise, accurate and robust analytical method, (b) their specificity (c) a consistent relationship with actual intake. We have evaluated human metabolites of a microbiome-derived flavan-3-ol catabolite, 5-(3′,4′-dihydroxyphenyl)-[gamma]-valerolactone (gVL), as biomarker of flavan-3-ol intake in large epidemiological studies. Flavan-3-ols are widely consumed plant bioactives, which have received considerable interest due to their potential ability to reduce CVD risk. The availability of authentic standards allowed the development of a validated high-throughput method suitable for large-scale studies. In dietary intervention studies, we could show that gVL metabolites are specific for flavan-3-ols present in tea, fruits, wine and cocoa-derived products, with a strong correlation between intake and biomarker (Spearman’s r = 0.90). This biomarker will allow for the first time to estimate flavan-3-ol intake and further investigation of associations between intake and disease risk.
Vesicle-associated membrane protein 7-mediated eosinophil degranulation promotes allergic airway inflammation in mice
Authors: Willetts Lian , Felix Lindsey C. , Jacobsen Elizabeth A. , Puttagunta Lakshmi , Condjella Rachel M. , Zellner Katie R. , Ochkur Sergei I. , Kim John D. , Luo Huijun , Lee Nancy A. , Lee James J. , Moqbel Redwan , Lacy Paige
Published: June 2018

Eosinophil degranulation is a determining factor in allergy-mediated airway pathology. Receptor-mediated degranulation in eosinophils requires vesicle-associated membrane protein 7 (VAMP-7), a principal component of the SNARE fusion machinery. The specific contribution of eosinophil degranulation to allergen-induced airway responses remains poorly understood. We generated mice withVAMP-7gene deficiency exclusively in eosinophils (eoCRE/V7) from a cross using eosinophil-specificCrerecombinase-expressing mice crossed withVAMP-7f/fmice. Eosinophils fromeoCRE/V7mice showed deficient degranulation responses in vitro, and responses continued to be decreased following ex vivo intratracheal adoptive transfer ofeoCRE/V7eosinophils intoIL-5/hE2/EPX−/−mice. Consistent with diminished degranulation responses, reduced airway hyperresponsiveness was observed in ovalbumin-sensitized and challengedeoCRE/V7mice following methacholine inhalation. Therefore, VAMP-7 mediates eosinophil degranulation both in vitro and ex vivo, and this event augments airway hyperresponsiveness.
rGO/AuNPs/tetraphenylporphyrin nanoconjugate-based electrochemical sensor for highly sensitive detection of cadmium ions
Authors: Si Yanmei , Liu Jing , Chen Yuan , Miao Xufeng , Ye Fang , Liu Zhigang , Li Jishan
Published: June 2018

rGO/AuNPs/TPP nanoconjugates were prepared and used to construct a novel electrochemical sensor for the sensitive and selective detection of cadmium ions.
Mechanism of NO–CO reaction over highly dispersed cuprous oxide on γ-alumina catalyst using a metal–support interfacial site in the presence of oxygen: similarities to and differences from biological systems
Authors: Fukuda Ryoichi , Sakai Shogo , Takagi Nozomi , Matsui Masafuyu , Ehara Masahiro , Hosokawa Saburo , Tanaka Tsunehiro , Sakaki Shigeyoshi
Published: June 2018

The NO–CO reaction mechanism over the Cu/γ-Al2O3 catalyst was elucidated using DFT and a cluster model.
Palladium-catalysed carboxytelomerisation of β-myrcene to highly branched C21-esters
Authors: Vogelsang Dennis , Dittmar Morten , Seidensticker Thomas , Vorholt Andreas J.
Published: June 2018

The first example of the highly-efficient palladium-catalysed carboxytelomerisation of β-myrcene to branched C21-esters is presented.
The epithelial barrier-protecting properties of a soy hydrolysate
Authors: Kiewiet Mensiena B. G. , González Rodríguez Martín I. , Dekkers Renske , Gros Marjan , Ulfman Laurien H. , Groeneveld Andre , de Vos Paul , Faas Marijke M.
Published: June 2018

A soy hydrolysate protects the epithelial cell layer from an increase in permeability in a barrier disruptor specific manner.
Diagnosis of immunomarkersin vivo viamultiplexed surface enhanced Raman spectroscopy with gold nanostars
Authors: Ou Yu-Chuan , Webb Joseph A. , O'Brien Christine M. , Pence Isaac J. , Lin Eugene C. , Paul Eden P. , Cole Danielle , Ou Shih-Hao , Lapierre-Landry Maryse , DeLapp Rossane C. , Lippmann Ethan S. , Mahadevan-Jansen Anita , Bardhan Rizia
Published: June 2018

In this work biomarkers PD-L1 and EGFR are diagnosed in mouse tumorsin vivoandex vivowith surface-enhanced Raman spectroscopy.
Understanding quantum emitters in plasmonic nanocavities with conformal transformation: Purcell enhancement and forces
Authors: Pacheco-Peña V. , Navarro-Cía M.
Published: June 2018

Insights into the Purcell enhancement and self-induced trapping of colloidal quantum dots inside bowtie nanocavities using conformal transformation.
Probing the nanoscale light emission properties of a CVD-grown MoS2monolayer by tip-enhanced photoluminescence
Authors: Okuno Yoshito , Lancry Ophélie , Tempez Agnès , Cairone Cristina , Bosi Matteo , Fabbri Filippo , Chaigneau Marc
Published: June 2018

The concurrent analysis of the morphological and optical properties demonstrates that TEPL is a unique tool to study 2D materials at the nanoscale.
Highly improved photoelectrocatalytic efficiency and stability of WO3 photoanodes by the facile in situ growth of TiO2 branch overlayers
Authors: Zeng Qingyi , Gao Yaowen , Lyu Lai , Chang Sheng , Hu Chun
Published: June 2018

A novel TiO2 branch decorated WO3 nanoplate (TWNP) photoanode was prepared by a simple and facile in situ wet chemical growth method and used as a highly efficient and stable photoelectrode for photoelectrocatalytic applications.
M13 bacteriophage spheroids as scaffolds for directed synthesis of spiky gold nanostructures
Authors: Ngo-Duc Tam-Triet , Plank Joshua M. , Chen Gongde , Harrison Reed E. S. , Morikis Dimitrios , Liu Haizhou , Haberer Elaine D.
Published: June 2018

A gold-binding filamentous virus was converted to its spheroidal form and investigated as a versatile template of nanostructure formation.
Continuous wave pumped single-mode nanolasers in inorganic perovskites with robust stability and high quantum yield
Authors: Jiang Li , Liu Renming , Su Rongling , Yu Ying , Xu Haofei , Wei Yuming , Zhou Zhang-Kai , Wang Xuehua
Published: June 2018

A one-step and surfactant-free method is proposed to synthesize inorganic perovskite (CsPbX3, X = Cl, Br, I) nanowires at room temperature. The as-prepared CsPbX3 nanowires exhibit high lasing quantum yield, single-mode lasing with ultra-narrow linewidth.
Novel applications of fluorescent brighteners in aqueous visible-light photopolymerization: high performance water-based coating and LED-assisted hydrogel synthesis
Authors: Zuo Xiaoling , Morlet-Savary Fabrice , Schmitt Michael , Le Nouën Didier , Blanchard Nicolas , Goddard Jean-Philippe , Lalevée Jacques
Published: June 2018

Commercial fluorescent brighteners are shown to be active photoinitiators in aqueous visible-light photopolymerization.
Mitochondria-targeted half-sandwich rutheniumII diimine complexes: anticancer and antimetastasis via ROS-mediated signalling
Authors: Xu Zhishan , Kong Deliang , He Xiangdong , Guo Lihua , Ge Xingxing , Liu Xicheng , Zhang Hairong , Li Juanjuan , Yang Yuliang , Liu Zhe
Published: June 2018

Two half-sandwich RuII diimine complexes combine features of bioimaging, anticancer and antimetastasis properties into one molecule. The complexes target mitochondria and damage mitochondrial integrity.
Ultrafine molybdenum phosphide nanocrystals on a highly porous N,P-codoped carbon matrix as an efficient catalyst for the hydrogen evolution reaction
Authors: Ren Jin-Tao , Chen Lei , Weng Chen-Chen , Yuan Zhong-Yong
Published: June 2018

Ultrafine MoP nanocrystals on N,P-codoped carbon matrix are fabricated by a one-step carbothermal-phosphorization strategy, exhibiting high electrocatalytic activity.
CO2-switchable response of protein microtubules: behaviour and mechanism
Authors: Yang Guang , Hu Rongting , Ding Hong-ming , Kochovski Zdravko , Mei Shilin , Lu Yan , Ma Yu-qiang , Chen Guosong , Jiang Ming
Published: June 2018

In this study, a new mechanism on CO2-responsiveness of protein microtubules constructed by dual non-covalent interactions has been demonstrated.
Capacitive performance of vertically aligned reduced titania nanotubes coated with Mn2O3 by reverse pulse electrodeposition
Authors: Samsudin Nurul Asma , Zainal Zulkarnain , Lim Hong Ngee , Sulaiman Yusran , Chang Sook-Keng , Lim Ying-Chin , Ayal Asmaa Kadim , Mohd Amin Wardatun Nadrah
Published: June 2018

Mn2O3 was coated onto reduced titania nanotubes by reverse pulse electrodeposition, showing smooth and homogenous deposits without covering the opening of the nanotubes.
Synthesis of non-toxic, biocompatible, and colloidal stable silver nanoparticle using egg-white protein as capping and reducing agents for sustainable antibacterial application
Authors: Thiyagarajan Kalaiyarasan , Bharti Vijay K. , Tyagi Shruti , Tyagi Pankaj K. , Ahuja Anami , Kumar Krishna , Raj Tilak , Kumar Bhuvnesh
Published: June 2018

For nearly a decade, silver nanoparticles (AgNPs) have been the most prevalent commercial nanomaterials products widely used in different biomedical applications due to their broad-spectrum antimicrobial activity.
The synthesis of imidazo[1,5-a]quinolinesviaa decarboxylative cyclization under metal-free conditions
Authors: Yan Zicong , Wan Changfeng , Yang Yu , Zha Zhenggen , Wang Zhiyong
Published: June 2018

An iodine-mediated decarboxylative cyclization was developed from α-amino acids and 2-methyl quinolines under metal-free conditions, affording a variety of imidazo[1,5-a]quinolines with moderate to good yields.
Facile synthesis and microwave absorption investigation of activated carbon@Fe3O4 composites in the low frequency band
Authors: Yin Pengfei , Deng Yu , Zhang Limin , Li Ning , Feng Xing , Wang Jian , Zhang Yi
Published: June 2018

Activated carbon@Fe3O4 composites with good electromagnetic wave absorbing performances in the low frequency range were synthesized via a hydrothermal method.
Facile access to deep red/near-infrared emissive AIEgens for efficient non-doped OLEDs
Authors: Lee Will W. H. , Zhao Zheng , Cai Yuanjing , Xu Zeng , Yu Ying , Xiong Yu , Kwok Ryan T. K. , Chen Yue , Leung Nelson L. C. , Ma Dongge , Lam Jacky W. Y. , Qin Anjun , Tang Ben Zhong
Published: June 2018

Design of an efficient DR/NIR solid emitter with a shortened conjugation length but long emission wavelength for non-doped NIR OLEDs.
Synthesis of mesoporous LiMn2O4and LiMn2−xCoxO4thin films using the MASA approach as efficient water oxidation electrocatalysts
Authors: Balci Fadime Mert , Karakaya Irmak , Alsaç Elif Pınar , Yaman Muammer Yusuf , Saat Gülbahar , Karadas Ferdi , Ülgüt Burak , Dag Ömer
Published: June 2018

The molten-salt assisted self-assembly (MASA) process is applicable to fabricate high quality mesoporous metal lithiate thin films that exhibit excellent performance as electrocatalysts for water oxidation.
An easily coatable temperature responsive cholesteric liquid crystal oligomer for making structural colour patterns
Authors: Zhang Pei , Kragt Augustinus J. J. , Schenning Albertus P. H. J. , de Haan Laurens T. , Zhou Guofu
Published: June 2018

A crosslinkable, temperature-responsive cholesteric main-chain liquid crystal oligomer was prepared, and used to make patterned coatings.
Back-to-back symmetric Schottky type UVA photodetector based on ternary alloy BeZnO
Authors: Su Longxing , Zhu Yuan , Xu Xiaojie , Chen Hongyu , Tang Zikang , Fang Xiaosheng
Published: June 2018

A back-to-back symmetric Schottky type BeZnO based UVA photodetector with ultra-low dark current and rapid response time has been realized.
Adenylyl cyclase 6 is required for maintaining acid–base homeostasis
Authors: Poulsen Søren Brandt , Marin De Evsikova Caralina , Murali Sathish Kumar , Praetorius Jeppe , Chern Yijuang , Fenton Robert A. , Rieg Timo
Published: June 2018

Adenylyl cyclase (AC) isoform 6 (AC6) is highly expressed throughout the renal tubule and collecting duct (CD), catalyzes the synthesis of cAMP and contributes to various aspects of renal transport. Several proteins involved in acid–base homeostasis are regulated by cAMP. In the present study, we assess the relative contribution of AC6 to overall acid–base regulation using mice with global deletion of AC6 (AC6−/−) or newly generated mice lacking AC6 in the renal tubule and CD (AC6loxloxPax8Cre). Higher energy expenditure in AC6−/− relative to wild-type (WT) mice, was associated with lower urinary pH, mild alkalosis in conjunction with elevated blood HCO3− concentrations, and significantly higher renal abundance of the H+-ATPase B1 subunit. In contrast with WT mice, AC6−/− mice have a less pronounced increase in urinary pH after 8 days of HCO3− challenge, which is associated with increased blood pH and HCO3− concentrations. Immunohistochemistry demonstrated that AC6 was expressed in intercalated cells (IC), but subcellular distribution of the H+-ATPase B1 subunit, pendrin, and the anion exchangers 1 and 2 in AC6−/− mice was normal. In the AC6−/− mice, H+-ATPase B1 subunit levels after HCO3− challenge were greater, which correlated with a higher number of type A IC. In contrast with the AC6−/− mice, AC6loxloxPax8Cre mice had normal urinary pH under baseline conditions but higher blood HCO3− than controls after HCO3− challenge. In conclusion, AC6 is required for maintaining normal acid–base homeostasis and energy expenditure. Under baseline conditions, renal AC6 is redundant for acid–base balance but becomes important under alkaline conditions.
A novel variant in TAF1 affects gene expression and is associated with X-linked TAF1 intellectual disability syndrome
Authors: Hurst Sarah E. , Liktor-Busa Erika , Moutal Aubin , Parker Sara , Rice Sydney , Szelinger Szabolcs , Senner Grant , Hammer Michael F. , Johnstone Laurel , Ramsey Keri , Narayanan Vinodh , Perez-Miller Samantha , Khanna May , Dahlin Heather , Lewis Karen , Craig David , Wang Edith H. , Khanna Rajesh , Nelson Mark A.
Published: June 2018

We investigated the genome of a 5-year-old male who presented with global developmental delay (motor, cognitive, and speech), hypotonia, possibly ataxia, and cerebellar hypoplasia of unknown origin. Whole genome sequencing (WGS) and mRNA sequencing (RNA-seq) were performed on a family having an affected proband, his unaffected parents, and maternal grandfather. To explore the molecular and functional consequences of the variant, we performed cell proliferation assays, quantitative real-time PCR (qRT-PCR) array, immunoblotting, calcium imaging, and neurite outgrowth experiments in SH-SY5Y neuroblastoma cells to compare the properties of the wild-type TATA-box-binding protein factor 1 (TAF1), deletion of TAF1, and TAF1 variant p.Ser1600Gly samples. The whole genome data identified several gene variants. However, the genome sequence data failed to implicate a candidate gene as many of the variants were of unknown significance. By combining genome sequence data with transcriptomic data, a probable candidate variant, p.Ser1600Gly, emerged in TAF1. Moreover, the RNA-seq data revealed a 90:10 extremely skewed X-chromosome inactivation (XCI) in the mother. Our results showed that neuronal ion channel genes were differentially expressed between TAF1 deletion and TAF1 variant p.Ser1600Gly cells, when compared with their respective controls, and that the TAF1 variant may impair neuronal differentiation and cell proliferation. Taken together, our data suggest that this novel variant in TAF1 plays a key role in the development of a recently described X-linked syndrome, TAF1 intellectual disability syndrome, and further extends our knowledge of a potential link between TAF1 deficiency and defects in neuronal cell function.
Assessment of Subjective Visual Vertical (SVV) Using the “Bucket Test” and the Virtual SVV System
Authors: Michelson Patricia L. , McCaslin Devin L. , Jacobson Gary P. , Petrak Michelle , English Lauren , Hatton Kelsey
Published: June 2018

Objective

The purpose of this study was to describe the variability and test–retest reliability of a commercially available subjective visual vertical (SVV) system known as Virtual SVV (Interacoustics). In addition, the study aimed to compare the reliability of the Virtual system with a previously established bucket test of SVV.

Study Design

Fifteen participants with normal hearing, normal middle ear function, and normal utricular function were included in the study. Each participant underwent static SVV testing using both the Virtual system and the bucket test. Subjects completed 2 testing sessions to determine test–retest reliability. For each test, data were collected with the head at 0°, tilted 45° to the right, and tilted 45° to the left.

Setting

This study was conducted in a balance function laboratory embedded in a large, tertiary care otology clinic.

Results

The mean SVV values obtained with the Virtual system were within 1°–2° from 0 with the head positioned at 0°, which is in agreement with many other studies of SVV with the head at 0° (Akin & Murnane, 2009; Halmagyi & Curthoys, 1999; Zwergal, Rettinger, Frenzel, Dieterich, & Strupp, 2009). Using the intraclass correlation coefficient, test–retest reliability of the Virtual system was excellent in the 45° left position and fair to good in the 45° right and 0° position. Test–retest reliability of the bucket test was poor in all head positions.

Conclusions

The Virtual system is a more reliable measure of static SVV than the bucket test. Therefore, the Virtual system could be utilized as a screening device for utricular dysfunction in busy clinical settings.