bluuebunny/crossref_metadata_2025 huggingface dataset:
Combinatorial design of molecular seeds for chirality-controlled synthesis of single-walled carbon nanotubes
Authors: Tomada Joerg , Dienel Thomas , Hampel Frank , Fasel Roman , Amsharov Konstantin
Published: July 2019

The chirality-controlled synthesis of single-walled carbon nanotubes (SWCNTs) is a major challenge facing current nanomaterials science. The surface-assisted bottom-up fabrication from unimolecular CNT seeds (precursors), which unambiguously predefine the chirality of the tube during the growth, appears to be the most promising approach. This strategy opens a venue towards controlled synthesis of CNTs of virtually any possible chirality by applying properly designed precursor molecules. However, synthetic access to the required precursor molecules remains practically unexplored because of their complex structure. Here, we report a general strategy for the synthesis of molecular seeds for the controlled growth of SWCNTs possessing virtually any desired chirality by combinatorial multi-segmental assembly. The suggested combinatorial approach allows facile assembly of complex CNT precursors (with up to 100 carbon atoms immobilized at strictly predefined positions) just in one single step from complementary segments. The feasibility of the approach is demonstrated on the synthesis of the precursor molecules for 21 different SWCNT chiralities utilizing just three relatively simple building blocks.
The AAA + ATPase TorsinA polymerizes into hollow helical tubes with 8.5 subunits per turn
Authors: Demircioglu F. Esra , Zheng Weili , McQuown Alexander J. , Maier Nolan K. , Watson Nicki , Cheeseman Iain M. , Denic Vladimir , Egelman Edward H. , Schwartz Thomas U.
Published: July 2019

TorsinA is an ER-resident AAA + ATPase, whose deletion of glutamate E303 results in the genetic neuromuscular disease primary dystonia. TorsinA is an unusual AAA + ATPase that needs an external activator. Also, it likely does not thread a peptide substrate through a narrow central channel, in contrast to its closest structural homologs. Here, we examined the oligomerization of TorsinA to get closer to a molecular understanding of its still enigmatic function. We observe TorsinA to form helical filaments, which we analyzed by cryo-electron microscopy using helical reconstruction. The 4.4 Å structure reveals long hollow tubes with a helical periodicity of 8.5 subunits per turn, and an inner channel of ~ 4 nm diameter. We further show that the protein is able to induce tubulation of membranes in vitro, an observation that may reflect an entirely new characteristic of AAA + ATPases. We discuss the implications of these observations for TorsinA function.
Ultra-thin solid electrolyte interphase evolution and wrinkling processes in molybdenum disulfide-based lithium-ion batteries
Authors: Wan Jing , Hao Yang , Shi Yang , Song Yue-Xian , Yan Hui-Juan , Zheng Jian , Wen Rui , Wan Li-Jun
Published: July 2019

Molybdenum disulfide is considered one of the most promising anodes for lithium-ion batteries due to its high specific capacity; however, it suffers from an unstable solid electrolyte interphase. Understanding its structural evolution and reaction mechanism upon charging/discharging is crucial for further improvements in battery performance. Herein, the interfacial processes of solid electrolyte interphase film formation and lithiation/delithiation on ultra-flat monolayer molybdenum disulfide are monitored by in situ atomic force microscopy. The live formation of ultra-thin and dense films can be induced by the use of fluoroethylene carbonate as an additive to effectively protect the anode electrodes. The evolution of the fluoroethylene carbonate-derived solid electrolyte interphase film upon cycling is quantitatively analysed. Furthermore, the formation of wrinkle-structure networks upon lithiation process is distinguished in detailed steps, and accordingly, structure-reactivity correlations are proposed. These quantitative results provide an in-depth understanding of the interfacial mechanism in molybdenum disulfide-based lithium-ion batteries.
Methylation analysis of plasma DNA informs etiologies of Epstein-Barr virus-associated diseases
Authors: Lam W. K. Jacky , Jiang Peiyong , Chan K. C. Allen , Peng Wenlei , Shang Huimin , Heung Macy M. S. , Cheng Suk Hang , Zhang Haiqiang , Tse O. Y. Olivia , Raghupathy Radha , Ma Brigette B. Y. , Hui Edwin P. , Chan Anthony T. C. , Woo John K. S. , Chiu Rossa W. K. , Lo Y. M. Dennis
Published: July 2019

Epstein-Barr virus (EBV) is associated with a number of diseases, including malignancies. Currently, it is not known whether patients with different EBV-associated diseases have different methylation profiles of circulating EBV DNA. Through whole-genome methylation analysis of plasma samples from patients with nasopharyngeal carcinoma (NPC), EBV-associated lymphoma and infectious mononucleosis, we demonstrate that EBV DNA methylation profiles exhibit a disease-associated pattern. This observation implies a significant potential for the development of methylation analysis of plasma EBV DNA for NPC diagnostics. We further analyse the plasma EBV DNA methylome of NPC and non-NPC subjects from a prospective screening cohort. Plasma EBV DNA fragments demonstrate differential methylation patterns between NPC and non-NPC subjects. Combining such differential methylation patterns with the fractional concentration (count) and size of plasma EBV DNA, population screening of NPC is performed with an improved positive predictive value of 35.1%, compared to a count- and size-based only protocol.
Nanometer-precision non-local deformation reconstruction using nanodiamond sensing
Authors: Xia Kangwei , Liu Chu-Feng , Leong Weng-Hang , Kwok Man-Hin , Yang Zhi-Yuan , Feng Xi , Liu Ren-Bao , Li Quan
Published: July 2019

Spatially resolved information about material deformation upon loading is critical to evaluating mechanical properties of materials, and to understanding mechano-response of live systems. Existing techniques may access local properties of materials at nanoscale, but not at locations away from the force-loading positions. Moreover, interpretation of the local measurement relies on correct modeling, the validation of which is not straightforward. Here we demonstrate an approach to evaluating non-local material deformation based on the integration of nanodiamond orientation sensing and atomic force microscopy nanoindentation. This approach features a 5 nm precision in the loading direction and a sub-hundred nanometer lateral resolution, high enough to disclose the surface/interface effects in the material deformation. The non-local deformation profile can validate the models needed for mechanical property determination. The non-local nanometer-precision sensing of deformation facilitates studying mechanical response of complex material systems ranging from impact transfer in nanocomposites to mechano-response of live systems.
Publisher Correction: Mediator complex interaction partners organize the transcriptional network that defines neural stem cells
Authors: Quevedo Marti , Meert Lize , Dekker Mike R. , Dekkers Dick H. W. , Brandsma Johannes H. , van den Berg Debbie L. C. , Ozgür Zeliha , van IJcken Wilfred F. J. , Demmers Jeroen , Fornerod Maarten , Poot Raymond A.
Published: July 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Predicting bacterial infection outcomes using single cell RNA-sequencing analysis of human immune cells
Authors: Bossel Ben-Moshe Noa , Hen-Avivi Shelly , Levitin Natalia , Yehezkel Dror , Oosting Marije , Joosten Leo A. B. , Netea Mihai G. , Avraham Roi
Published: July 2019

Complex interactions between different host immune cell types can determine the outcome of pathogen infections. Advances in single cell RNA-sequencing (scRNA-seq) allow probing of these immune interactions, such as cell-type compositions, which are then interpreted by deconvolution algorithms using bulk RNA-seq measurements. However, not all aspects of immune surveillance are represented by current algorithms. Here, using scRNA-seq of human peripheral blood cells infected withSalmonella, we develop a deconvolution algorithm for inferring cell-type specific infection responses from bulk measurements. We apply our dynamic deconvolution algorithm to a cohort of healthy individuals challenged ex vivo withSalmonella, and to three cohorts of tuberculosis patients during different stages of disease. We reveal cell-type specific immune responses associated not only with ex vivo infection phenotype but also with clinical disease stage. We propose that our approach provides a predictive power to identify risk for disease, and human infection outcomes.
Programmable responsive hydrogels inspired by classical conditioning algorithm
Authors: Zhang Hang , Zeng Hao , Priimagi Arri , Ikkala Olli
Published: July 2019

Living systems have inspired research on non-biological dynamic materials and systems chemistry to mimic specific complex biological functions. Upon pursuing ever more complex life-inspired non-biological systems, mimicking even the most elementary aspects of learning is a grand challenge. We demonstrate a programmable hydrogel-based model system, whose behaviour is inspired by associative learning, i.e., conditioning, which is among the simplest forms of learning. Algorithmically, associative learning minimally requires responsivity to two different stimuli and a memory element. Herein, nanoparticles form the memory element, where a photoacid-driven pH-change leads to their chain-like assembly with a modified spectral behaviour. On associating selected light irradiation with heating, the gel starts to melt upon the irradiation, originally a neutral stimulus. A logic diagram describes such an evolution of the material response. Coupled chemical reactions drive the system out-of-equilibrium, allowing forgetting and memory recovery. The findings encourage to search non-biological materials towards associative and dynamic properties.
A semiconducting layered metal-organic framework magnet
Authors: Yang Chongqing , Dong Renhao , Wang Mao , Petkov Petko St. , Zhang Zhitao , Wang Mingchao , Han Peng , Ballabio Marco , Bräuninger Sascha A. , Liao Zhongquan , Zhang Jichao , Schwotzer Friedrich , Zschech Ehrenfried , Klauss Hans-Henning , Cánovas Enrique , Kaskel Stefan , Bonn Mischa , Zhou Shengqiang , Heine Thomas , Feng Xinliang
Published: July 2019

The realization of ferromagnetism in semiconductors is an attractive avenue for the development of spintronic applications. Here, we report a semiconducting layered metal-organic framework (MOF), namely K3Fe2[(2,3,9,10,16,17,23,24-octahydroxy phthalocyaninato)Fe] (K3Fe2[PcFe-O8]) with spontaneous magnetization. This layered MOF features in-plane full π-d conjugation and exhibits semiconducting behavior with a room temperature carrier mobility of 15 ± 2 cm2 V−1 s−1 as determined by time-resolved Terahertz spectroscopy. Magnetization experiments and 57Fe Mössbauer spectroscopy demonstrate the presence of long-range magnetic correlations in K3Fe2[PcFe-O8] arising from the magnetic coupling between iron centers via delocalized π electrons. The sample exhibits superparamagnetic features due to a distribution of crystal size and possesses magnetic hysteresis up to 350 K. Our work sets the stage for the development of spintronic materials exploiting magnetic MOF semiconductors.
Absence of emergent supersymmetry at superconducting quantum critical points in Dirac and Weyl semimetals
Authors: Zhao Peng-Lu , Liu Guo-Zhu
Published: July 2019

Supersymmetry plays a crucial role in superstring theory and high-energy physics, but has never been observed in experiments. Recently, an effective space–time supersymmetry (SUSY) was argued to emerge in the low-energy region by tuning Dirac or Weyl semimetal to approach a superconducting (SC) quantum critical point (QCP), at which the Dirac or Weyl fermion and the bosonic order parameter are both massless. Here, we study under what circumstances can SUSY be realized at a quantum critical point. We demonstrate that the Yukawa-type coupling between the massless fermion and massless boson can dynamically generate an infinite number of non-supersymmetric terms in the effective field theory of the boson. Owing to these terms, no space–time supersymmetry emerges at the SC QCPs. The results provide important constraint on the exploration of emergent SUSY in condensed matter systems.
Cryptic inoviruses revealed as pervasive in bacteria and archaea across Earth’s biomes
Authors: Roux Simon , Krupovic Mart , Daly Rebecca A. , Borges Adair L. , Nayfach Stephen , Schulz Frederik , Sharrar Allison , Matheus Carnevali Paula B. , Cheng Jan-Fang , Ivanova Natalia N. , Bondy-Denomy Joseph , Wrighton Kelly C. , Woyke Tanja , Visel Axel , Kyrpides Nikos C. , Eloe-Fadrosh Emiley A.
Published: July 2019

Bacteriophages from the Inoviridae family (inoviruses) are characterized by their unique morphology, genome content and infection cycle. One of the most striking features of inoviruses is their ability to establish a chronic infection whereby the viral genome resides within the cell in either an exclusively episomal state or integrated into the host chromosome and virions are continuously released without killing the host. To date, a relatively small number of inovirus isolates have been extensively studied, either for biotechnological applications, such as phage display, or because of their effect on the toxicity of known bacterial pathogens including Vibrio cholerae and Neisseria meningitidis. Here, we show that the current 56 members of the Inoviridae family represent a minute fraction of a highly diverse group of inoviruses. Using a machine learning approach leveraging a combination of marker gene and genome features, we identified 10,295 inovirus-like sequences from microbial genomes and metagenomes. Collectively, our results call for reclassification of the current Inoviridae family into a viral order including six distinct proposed families associated with nearly all bacterial phyla across virtually every ecosystem. Putative inoviruses were also detected in several archaeal genomes, suggesting that, collectively, members of this supergroup infect hosts across the domains Bacteria and Archaea. Finally, we identified an expansive diversity of inovirus-encoded toxin–antitoxin and gene expression modulation systems, alongside evidence of both synergistic (CRISPR evasion) and antagonistic (superinfection exclusion) interactions with co-infecting viruses, which we experimentally validated in a Pseudomonas model. Capturing this previously obscured component of the global virosphere may spark new avenues for microbial manipulation approaches and innovative biotechnological applications.
Transcriptome sequencing, molecular markers, and transcription factor discovery of Platanus acerifolia in the presence of Corythucha ciliata
Authors: Li Fengqi , Wu Chunyan , Gao Mengzhu , Jiao Mengmeng , Qu Cheng , Gonzalez-Uriarte Asier , Luo Chen
Published: July 2019

The London Planetree (Platanus acerifolia) are present throughout the world. The tree is considered a greening plant and is commonly planted in streets, parks, and courtyards. The Sycamore lace bug (Corythucha ciliata) is a serious pest of this tree. To determine the molecular mechanism behind the interaction between the London Planetree and the Sycamore lace bug, we generated a comprehensive RNA-seq dataset (630,835,762 clean reads) for P. acerifolia by sequencing both infected and non-infected leaves of C. ciliata using the Illumina Hiseq 4000 system. We assembled the transcriptomes using the Trinity De Novo assembly followed by annotation. In total, 121,136 unigenes were obtained, and 80,559 unigenes were successfully annotated. From the 121,136 unigenes, we identified 3,010,256 SNPs, 39,097 microsatellites locus, and 1,916 transcription factors. The transcriptomic dataset we present are the first reports of transcriptome information in Platanus species and will be incredibly useful in future studies with P. acerifolia and other Platanus species, especially in the areas of genomics, molecular biology, physiology, and population genetics.
Modeling Zika Virus Transmission Dynamics: Parameter Estimates, Disease Characteristics, and Prevention
Authors: Rahman Munsur , Bekele-Maxwell Kidist , Cates LeAnna L. , Banks H. T. , Vaidya Naveen K.
Published: July 2019

Because of limited data, much remains uncertain about parameters related to transmission dynamics of Zika virus (ZIKV). Estimating a large number of parameters from the limited information in data may not provide useful knowledge about the ZIKV. Here, we developed a method that utilizes a mathematical model of ZIKV dynamics and the complex-step derivative approximation technique to identify parameters that can be estimated from the available data. Applying our method to epidemic data from the ZIKV outbreaks in French Polynesia and Yap Island, we identified the parameters that can be estimated from these island data. Our results suggest that the parameters that can be estimated from a given data set, as well as the estimated values of those parameters, vary from Island to Island. Our method allowed us to estimate some ZIKV-related parameters with reasonable confidence intervals. We also computed the basic reproduction number to be from 2.03 to 3.20 across islands. Furthermore, using our model, we evaluated potential prevention strategies and found that peak prevalence can be reduced to nearly 10% by reducing mosquito-to-human contact by at least 60% or increasing mosquito death by at least a factor of three of the base case. With these preventions, the final outbreak-size is predicted to be negligible, thereby successfully controlling ZIKV epidemics.
Regulation of stomatal opening and histone modification by photoperiod in Arabidopsis thaliana
Authors: Aoki Saya , Toh Shigeo , Nakamichi Norihito , Hayashi Yuki , Wang Yin , Suzuki Takamasa , Tsuji Hiroyuki , Kinoshita Toshinori
Published: July 2019

Stomatal movements are regulated by many environmental signals, such as light, CO2, temperature, humidity, and drought. Recently, we showed that photoperiodic flowering components have positive effects on light-induced stomatal opening in Arabidopsis thaliana. In this study, we determined that light-induced stomatal opening and increased stomatal conductance were larger in plants grown under long-day (LD) conditions than in those grown under short-day (SD) conditions. Gene expression analyses using purified guard cell protoplasts revealed that FT and SOC1 expression levels were significantly increased under LD conditions. Interestingly, the enhancement of light-induced stomatal opening and increased SOC1 expression in guard cells due to LD conditions persisted for at least 1 week after plants were transferred to SD conditions. We then investigated histone modification using chromatin immunoprecipitation–PCR, and observed increased trimethylation of lysine 4 on histone 3 (H3K4) around SOC1. We also found that LD-dependent enhancement of light-induced stomatal opening and H3K4 trimethylation in SOC1 were suppressed in the ft-2 mutant. These results indicate that photoperiod is an important environmental cue regulating stomatal opening, and that LD conditions enhance light-induced stomatal opening and epigenetic modification (H3K4 trimethylation) around SOC1, a positive regulator of stomatal opening, in an FT-dependent manner. Thus, this study provides novel insights into stomatal responses to photoperiod.
Functional spectroscopic imaging reveals specificity of glutamate response in mouse brain to peripheral sensory stimulation
Authors: Seuwen Aline , Schroeter Aileen , Grandjean Joanes , Schlegel Felix , Rudin Markus
Published: July 2019

Non-invasive investigation of physiological changes and metabolic events associated with brain activity in mice constitutes a major challenge. Conventionally, fMRI assesses neuronal activity by evaluating activity-evoked local changes in blood oxygenation levels (BOLD). In isoflurane-anaethetized mice, however, we found that BOLD signal changes during paw stimulation appear to be dominated by arousal responses even when using innocuous stimuli. Widespread responses involving both hemispheres have been observed in response to unilateral stimulation. MRS allows probing metabolic changes associated with neuronal activation and provides a complementary readout to BOLD fMRI for investigating brain activity. In this study we evaluated the sensitivity of a free induction decay (FID) based spectroscopic imaging (MRSI) protocol for the measurement of alterations in glutamate levels elicited by unilateral electrical paw stimulation at different current amplitudes. Coronal MRSI maps of glutamate distribution with 17 × 17 voxels of 1 µl volume have been recorded with a temporal resolution of 12 min. Significant region-specific increases in glutamate levels have been observed in the contralateral but not in the ispiateral S1 somatosensory cortex upon stimulation. The amplitude of glutamate changes increased in a dose-dependent manner with the stimulus amplitude. The study demonstrates feasibility of functional MRSI in mice for studying activity-evoked glutamate changes in a temporo-spatially resolved manner.
Surgical anatomy of the ovine sural nerve for facial nerve regeneration and reconstruction research
Authors: Niimi Yosuke , Fukuda Satoshi , Gilbert Ryan S. , Baljinnyam Tuvshintugs , Niimi Yu , Matsumine Hajime , Liu Keibun , Jacob Sam , Hawkins Hal K. , Cox Robert A. , Herndon David N. , Prough Donald S. , Enkhbaatar Perenlei
Published: July 2019

The lack of a clinically relevant animal models for research in facial nerve reconstruction is challenging. In this study, we investigated the surgical anatomy of the ovine sural nerve as a potential candidate for facial nerve reconstruction, and performed its histological quantitative analysis in comparison to the buccal branch (BB) of the facial nerve using cadaver and anesthetized sheep. The ovine sural nerve descended to the lower leg along the short saphenous vein. The length of the sural nerve was 14.3 ± 0.5 cm. The distance from the posterior edge of the lateral malleolus to the sural nerve was 7.8 ± 1.8 mm. The mean number of myelinated fibers in the sural nerve was significantly lower than that of the BB (2,311 ± 381vs. 5,022 ± 433, respectively. p = 0.003). The number of fascicles in the sural nerve was also significantly lower than in the BB (10.5 ± 1.7 vs. 21.3 ± 2.7, respectively. p = 0.007). The sural nerve was grafted to the BB with end-to-end neurorrhaphy under surgical microscopy in cadaver sheep. The surgical anatomy and the number of fascicles of the ovine sural nerve were similar of those reported in humans. The results suggest that the sural nerve can be successfully used for facial nerve reconstruction research in a clinically relevant ovine model.
Virus Genotype-Dependent Transcriptional Alterations in Lipid Metabolism and Inflammation Pathways in the Hepatitis C Virus-infected Liver
Authors: d’Avigdor W. M. H. , Budzinska M. A. , Lee M. , Lam R. , Kench J. , Stapelberg M. , McLennan S. V. , Farrell G. , George J. , McCaughan G. W. , Tu T. , Shackel N. A.
Published: July 2019

Despite advances in antiviral therapy, molecular drivers of Hepatitis C Virus (HCV)-related liver disease remain poorly characterised. Chronic infection with HCV genotypes (1 and 3) differ in presentation of liver steatosis and virological response to therapies, both to interferon and direct acting antivirals. To understand what drives these clinically important differences, liver expression profiles of patients with HCV Genotype 1 or 3 infection (n = 26 and 33), alcoholic liver disease (n = 8), and no liver disease (n = 10) were analysed using transcriptome-wide microarrays. In progressive liver disease, HCV genotype was the major contributor to altered liver gene expression with 2151 genes differentially expressed >1.5-fold between HCV Genotype 1 and 3. In contrast, only 6 genes were altered between the HCV genotypes in advanced liver disease. Induction of lipogenic, lipolytic, and interferon stimulated gene pathways were enriched in Genotype 1 injury whilst a broad range of immune-associated pathways were associated with Genotype 3 injury. The results are consistent with greater lipid turnover in HCV Genotype 1 patients. Moreover, the lower activity in inflammatory pathways associated with HCV genotype 1 is consistent with relative resistance to interferon-based therapy. This data provides a molecular framework to explain the clinical manifestations of HCV-associated liver disease.
Experimental Characterization of the Ultrafast, Tunable and Broadband Optical Kerr Nonlinearity in Graphene
Authors: Thakur Siddharatha , Semnani Behrooz , Safavi-Naeini Safieddin , Majedi Amir Hamed
Published: July 2019

Graphene’s giant nonlinear optical response along with its integrability has made it a vaunted material for on-chip photonics. Despite a multitude of studies confirming its strong nonlinearity, there is a lack of reports examining the fundamental processes that govern the response. Addressing this gap in knowledge we analyse the role of experimental parameters by systematically measuring the near-infrared spectral dependence, the sub-picosecond temporal evolution and pulse-width dependence of the effective Kerr coefficient (n2,eff) of graphene in hundreds of femtosecond regime. The spectral dependence measured using the Z-scan technique is corroborated by a density matrix quantum theory formulation to extract a n2,eff ∝ λ2 dependence. The temporal evolution obtained using the time-resolved Z-scan measurement shows the nonlinearity peaking at zero delay time and relaxing on a time-scale of carrier relaxation. The dependence of the n2,eff on pulse duration is obtained by expanding the input pulse using a prism-pair set-up. Our results provide an avenue for controllable tunability of the nonlinear response in graphene, which is limited in silicon photonics.
Thermodynamic study of the effect of ions on the interaction between dengue virus NS3 helicase and single stranded RNA
Authors: Cababie Leila A. , Incicco J. Jeremías , González-Lebrero Rodolfo M. , Roman Ernesto A. , Gebhard Leopoldo G. , Gamarnik Andrea V. , Kaufman Sergio B.
Published: July 2019

Dengue virus nonstructural protein 3 (NS3) fulfills multiple essential functions during the viral replication and constitutes a prominent drug target. NS3 is composed by a superfamily-2 RNA helicase domain joined to a serine protease domain. Quantitative fluorescence titrations employing a fluorescein-tagged RNA oligonucleotide were used to investigate the effect of salts on the interaction between NS3 and single stranded RNA (ssRNA). We found a strong dependence of the observed equilibrium binding constant, Kobs, with the salt concentration, decreasing at least 7-fold for a 1-fold increase on cation concentration. As a result of the effective neutralization of ~10 phosphate groups, binding of helicase domain of NS3 to ssRNA is accompanied by the release of 5 or 7 monovalent cations from an oligonucleotide or a polynucleotide, respectively and of 3 divalent cations from the same oligonucleotide. Such estimates are not affected by the type of cation, either monovalent (KCl, NaCl and RbCl) or divalent (MgCl2 and CaCl2), nor by the presence of the protease domain or the fluorescein label. Combined effect of mono and divalent cations was well described by a simple equilibrium binding model which allows to predict the values of Kobs at any concentration of cations.
Female Blow Flies As Vertebrate Resource Indicators
Authors: Owings Charity G. , Banerjee Aniruddha , Asher Travis M. D. , Gilhooly William P. , Tuceryan Anais , Huffine Mary , Skaggs Christine L. , Adebowale Iyun M. , Manicke Nicholas E. , Picard Christine J.
Published: July 2019

Rapid vertebrate diversity evaluation is invaluable for monitoring changing ecosystems worldwide. Wild blow flies naturally recover DNA and chemical signatures from animal carcasses and feces. We demonstrate the power of blow flies as biodiversity monitors through sampling of flies in three environments with varying human influences: Indianapolis, IN and two national parks (the Great Smoky Mountains and Yellowstone). Dissected fly guts underwent vertebrate DNA sequencing (12S and 16S rRNA genes) and fecal metabolite screening. Integrated Nested Laplace Approximation (INLA) was used to determine the most important abiotic factor influencing fly-derived vertebrate richness. In 720 min total sampling time, 28 vertebrate species were identified, with 42% of flies containing vertebrate resources: 23% DNA, 5% feces, and 14% contained both. The species of blow fly used was not important for vertebrate DNA recovery, however the use of female flies versus male flies directly influenced DNA detection. Temperature was statistically relevant across environments in maximizing vertebrate detection (mean = 0.098, sd = 0.048). This method will empower ecologists to test vertebrate community ecology theories previously out of reach due practical challenges associated with traditional sampling.
Macaques preferentially attend to visual patterns with higher fractal dimension contours
Authors: Finn Kelly R. , Crutchfield James P. , Bliss-Moreau Eliza
Published: July 2019

Animals’ sensory systems evolved to efficiently process information from their environmental niches. Niches often include irregular shapes and rough textures (e.g., jagged terrain, canopy outlines) that must be navigated to find food, escape predators, and master other fitness-related challenges. For most primates, vision is the dominant sensory modality and thus, primates have evolved systems for processing complicated visual stimuli. One way to quantify information present in visual stimuli in natural scenes is evaluating their fractal dimension. We hypothesized that sensitivity to complicated geometric forms, indexed by fractal dimension, is an evolutionarily conserved capacity, and tested this capacity in rhesus macaques (Macaca mulatta). Monkeys viewed paired black and white images of simulated self-similar contours that systematically varied in fractal dimension while their attention to the stimuli was measured using noninvasive infrared eye tracking. They fixated more frequently on, dwelled for longer durations on, and had attentional biases towards images that contain boundary contours with higher fractal dimensions. This indicates that, like humans, they discriminate between visual stimuli on the basis of fractal dimension and may prefer viewing informationally rich visual stimuli. Our findings suggest that sensitivity to fractal dimension may be a wider ability of the vertebrate vision system.
Novel strategy for rapid functional in vivo validation of oncogenic drivers in haematological malignancies
Authors: Pieters Tim , T’Sas Sara , Demoen Lisa , Almeida André , Haenebalcke Lieven , Matthijssens Filip , Lemeire Kelly , D’Hont Jinke , Van Rockeghem Frederique , Hochepied Tino , Lintermans Beatrice , Reunes Lindy , Lammens Tim , Berx Geert , Haigh Jody J. , Goossens Steven , Van Vlierberghe Pieter
Published: July 2019

In cancer research, it remains challenging to functionally validate putative novel oncogenic drivers and to establish relevant preclinical models for evaluation of novel therapeutic strategies. Here, we describe an optimized and efficient pipeline for the generation of novel conditional overexpression mouse models in which putative oncogenes, along with an eGFP/Luciferase dual reporter, are expressed from the endogenous ROSA26 (R26) promoter. The efficiency of this approach was demonstrated by the generation and validation of novel R26 knock-in (KI) mice that allow conditional overexpression of Jarid2, Runx2, MN1 and a dominant negative allele of ETV6. As proof of concept, we confirm that MN1 overexpression in the hematopoietic lineage is sufficient to drive myeloid leukemia. In addition, we show that T-cell specific activation of MN1 in combination with loss of Pten increases tumour penetrance and stimulates the formation of Lyl1+ murine T-cell lymphoblastic leukemias or lymphomas (T-ALL/T-LBL). Finally, we demonstrate that these luciferase-positive murine AML and T-ALL/T-LBL cells are transplantable into immunocompromised mice allowing preclinical evaluation of novel anti-leukemic drugs in vivo.
Tracking the Growth of Superparamagnetic Nanoparticles with an In-Situ Magnetic Particle Spectrometer (INSPECT)
Authors: Malhotra Ankit , von Gladiss Anselm , Behrends André , Friedrich Thomas , Neumann Alexander , Buzug Thorsten M. , Lüdtke-Buzug Kerstin
Published: July 2019

Magnetic Particle Spectroscopy (MPS) is a measurement technique to determine the magnetic properties of superparamagnetic iron oxide nanoparticles (SPIONs) in an oscillating magnetic field as applied in Magnetic Particle Imaging (MPI). State of the art MPS devices are solely capable of measuring the magnetization response of the SPIONs to an oscillatory magnetic excitation retrospectively, i.e. after the synthesis process. In this contribution, a novel in-situ magnetic particle spectrometer (INSPECT) is presented, which can be used to monitor the entire synthesis process from particle genesis via growth to the stable colloidal suspension of the nanoparticles in real time. The device is suitable for the use in a biochemistry environment. It has a chamber size of 72 mm such that a 100 ml reaction flask can be used for synthesis. For an alkaline-based precipitation, the change of magnetic properties of SPIONs during the nucleation and growth phase of the synthesis is demonstrated. The device is able to record the changes in the amplitude and phase spectra, and, in turn, the hysteresis. Hence, it is a powerful tool for an in-depth understanding of the nanoparticle formation dynamics during the synthesis process.
Targeted detection of Dehalococcoides mccartyi microbial protein biomarkers as indicators of reductive dechlorination activity in contaminated groundwater
Authors: Solis Manuel I. Villalobos , Abraham Paul E. , Chourey Karuna , Swift Cynthia M. , Löffler Frank E. , Hettich Robert L.
Published: July 2019

Dehalococcoides mccartyi (Dhc) bacterial strains expressing active reductive dehalogenase (RDase) enzymes play key roles in the transformation and detoxification of chlorinated pollutants, including chlorinated ethenes. Site monitoring regimes traditionally rely on qPCR to assess the presence of Dhc biomarker genes; however, this technique alone cannot directly inform about dechlorination activity. To supplement gene-centric approaches and provide a more reliable proxy for dechlorination activity, we sought to demonstrate a targeted proteomics approach that can characterize Dhc mediated dechlorination in groundwater contaminated with chlorinated ethenes. Targeted peptide selection was conducted in axenic cultures of Dhc strains 195, FL2, and BAV1. These experiments yielded 37 peptides from housekeeping and structural proteins (i.e., GroEL, EF-TU, rpL7/L2 and the S-layer), as well as proteins involved in the reductive dechlorination activity (i.e., FdhA, TceA, and BvcA). The application of targeted proteomics to a defined bacterial consortium and contaminated groundwater samples resulted in the detection of FdhA peptides, which revealed active dechlorination with Dhc strain-level resolution, and the detection of RDases peptides indicating specific reductive dechlorination steps. The results presented here show that targeted proteomics can be applied to groundwater samples and provide protein level information about Dhc dechlorination activity.
Ex Vivo and In Vivo Biocompatibility Assessment (Blood and Tissue) of Three-Dimensional Bacterial Nanocellulose Biomaterials for Soft Tissue Implants
Authors: Osorio M. , Cañas A. , Puerta J. , Díaz L. , Naranjo T. , Ortiz I. , Castro C.
Published: July 2019

Bacterial nanocellulose (BNC) is a promising biomedical material. However, the haemocompatibility (haemolysis and thrombogenicity) and acute and sub-chronic immune responses to three-dimensional (3D) BNC biomaterials have not been evaluated. Accordingly, this manuscript focused on the effect of 3D microporosity on BNC haemocompatibility and a comparison with 2D BNC architecture, followed by the evaluation of the immune response to 3D BNC. Blood ex vivo studies indicated that compared with other 2D and 3D BNC architectures, never-dried 2D BNC presented antihemolytic and antithrombogenic effects. Nevertheless, in vivo studies indicated that 3D BNC did not interfere with wound haemostasis and elicited a mild acute inflammatory response, not a foreign body or chronic inflammatory response. Moreover, compared with the polyethylene controls, the implant design with micropores ca. 60 µm in diameter showed a high level of collagen, neovascularization and low fibrosis. Cell/tissue infiltration increased to 91% after 12 weeks and was characterized by fibroblastic, capillary and extracellular matrix infiltration. Accordingly, 3D BNC biomaterials can be considered a potential implantable biomaterial for soft tissue augmentation or replacement.
AIM2 inflammasome-derived IL-1β induces postoperative ileus in mice
Authors: Hupa Kristof Johannes , Stein Kathy , Schneider Reiner , Lysson Mariola , Schneiker Bianca , Hornung Veit , Latz Eicke , Iwakura Yoichiro , Kalff Jörg C. , Wehner Sven
Published: July 2019

Postoperative ileus (POI) is an intestinal dysmotility frequently occurring after abdominal surgery. An orchestrated neuroimmune response within the muscularis externa (ME) involves activation of resident macrophages, enteric glia and infiltration of blood-derived leukocytes. Interleukin-1 receptor type-I (IL1R1) signalling on enteric glia has been shown to be involved in POI development. Herein we investigated the distinct role of the IL1R1 ligands interleukin (IL) -1α and IL-1β and focused on the mechanism of IL-1β production. IL-1α and IL-1β deficient mice were protected from POI. Bone-marrow transplantation studies indicated that IL-1α originated from radio-resistant cells while IL-1β was released from the radio-sensitive infiltrating leukocytes. Mouse strains deficient in inflammasome formation identified the absent in melanoma 2 (AIM2) inflammasome to be crucial for IL-1β production in POI. Mechanistically, antibiotic-treated mice revealed a prominent role of the microbiome in IL-1β production. Our study provides new insights into distinct roles of IL-1α and IL-1β signalling during POI. While IL-1α release is most likely an immediate passive response to the surgical trauma, IL-1β production depends on AIM2 inflammasome formation and the microbiome. Selective interaction in this pathway might be a promising target to prevent POI in surgical patients.
High Serum Cyclophilin C levels as a risk factor marker for Coronary Artery Disease
Authors: Alfonso Amparo , Bayón Jeremías , Gegunde Sandra , Alonso Eva , Alvariño Rebeca , Santás-Álvarez Melisa , Testa-Fernández Ana , Rios-Vázquez Ramón , González-Juanatey Carlos , Botana Luis M.
Published: July 2019

Cyclophilins (Cyps) are ubiquitous proteins that belong to the immunophilins family consistently associated with inflammatory and cardiovascular diseases. While levels of CypA have been extensively studied, less data are available for other Cyps. The purpose of this case-control study was to determine the relationship of Cyps (A, B, C and D) with coronary artery disease (CAD) and eight inflammation markers. Serum levels of Cyps, interleukins and metalloproteinases were measured in serum collected from 84 subjects. Participants were divided into two sub-groups based on CAD diagnosis: 40 CAD patients and 44 control volunteers. Serum levels of CypA, CypB and CypC, IL-1β and IL-6 were significantly higher in CAD patients. Bivariate correlation analysis revealed a significant positive correlation between Cyps and several blood and biochemical parameters. When the ability of Cyps levels for CAD diagnosis was evaluated, higher sensitivity and selectivity values were obtained with CypC (c-statistic 0.891, p < 0.001) indicating that it is a good marker of CAD disease, while less conclusive results were obtained with CypA (c-statistic 0.748, p < 0.001) and CypB (c-statistic 0.655, p < 0.014). In addition, significant correlations of traditional CAD risk factors and CypC were observed. In summary, high levels of CypC are a risk factor for CAD and therefore it can be proposed as a new biomarker for this disease.
Optical coherence tomography complements confocal microscopy for investigation of multicellular tumour spheroids
Authors: Hari Neelam , Patel Priyanka , Ross Jacqueline , Hicks Kevin , Vanholsbeeck Frédérique
Published: July 2019

Knowledge of optical properties, such as the refractive index (RI), of biological tissues is important in optical imaging, as they influence the distribution and propagation of light in tissue. To accurately study the response of cancerous cells to drugs, optimised imaging protocols are required. This study uses a simple custom-built spectral domain optical coherence tomography (OCT) system to conduct RI measurements of multicellular spheroids, three-dimensional (3D) in-vitro culture systems, of the cell line HCT116. The spheroid RIs are compared to study the effect of growth over time. To improve confocal microscopy imaging protocols, two immersion media (glycerol and ScaleView-A2) matching the spheroid RIs were trialled, with the aim to reduce the RI mismatch between the spheroid and the immersion medium and thus improve imaging depth with confocal microscopy. ScaleView-A2 (n = 1.380) aided in achieving greater depths of imaging of the multicellular spheroids under confocal microscopy. This improvement in imaging depth confirmed the utility of our RI measurements, proving the promising outlook of OCT as a complementary tool to microscopy in cancer research.
Identification of novel breakpoints for locus- and region-specific translocations in 293 cells by molecular cytogenetics before and after irradiation
Authors: Binz Regina L. , Tian Erming , Sadhukhan Ratan , Zhou Daohong , Hauer-Jensen Martin , Pathak Rupak
Published: July 2019

The human kidney embryonic 293 cell line (293 cells) is extensively used in biomedical and pharmaceutical research. These cells exhibit a number of numerical and structural chromosomal anomalies. However, the breakpoints responsible for these structural chromosomal rearrangements have not been comprehensively characterized. In addition, it is not known whether chromosomes with structural rearrangement are more sensitive to external toxic agents, such as ionizing radiation. We used G-banding, spectral karyotyping (SKY), and locus- and region-specific fluorescence in situ hybridization (FISH) probes designed in our lab or obtained from commercial vendor to address this gap. Our G-banding analysis revealed that the chromosome number varies from 66 to 71, with multiple rearrangements and partial additions and deletions. SKY analysis confirmed 3 consistent rearrangements, two simple and one complex in nature. Multicolor FISH analysis identified an array of breakpoints responsible for locus- and region-specific translocations. Finally, SKY analysis revealed that radio-sensitivity of structurally rearranged chromosomes is dependent on radiation dose. These findings will advance our knowledge in 293 cell biology and will enrich the understanding of radiation biology studies.
Enhanced cardiac repair by telomerase reverse transcriptase over-expression in human cardiac mesenchymal stromal cells
Authors: Le Thi Yen Loan , Pickett Hilda A. , Yang Andrian , Ho Joshua W. K. , Thavapalachandran Sujitha , Igoor Sindhu , Yang Sile F. , Farraha Melad , Voges Holly K. , Hudson James E. , dos Remedios Cristobal G. , Bryan Tracy M. , Kizana Eddy , Chong James J. H.
Published: July 2019

We have previously reported a subpopulation of mesenchymal stromal cells (MSCs) within the platelet-derived growth factor receptor-alpha (PDGFRα)/CD90 co-expressing cardiac interstitial and adventitial cell fraction. Here we further characterise PDGFRα/CD90-expressing cardiac MSCs (PDGFRα + cMSCs) and use human telomerase reverse transcriptase (hTERT) over-expression to increase cMSCs ability to repair the heart after induced myocardial infarction. hTERT over-expression in PDGFRα + cardiac MSCs (hTERT + PDGFRα + cMSCs) modulates cell differentiation, proliferation, survival and angiogenesis related genes. In vivo, transplantation of hTERT + PDGFRα + cMSCs in athymic rats significantly increased left ventricular function, reduced scar size, increased angiogenesis and proliferation of both cardiomyocyte and non-myocyte cell fractions four weeks after myocardial infarction. In contrast, transplantation of mutant hTERT + PDGFRα + cMSCs (which generate catalytically-inactive telomerase) failed to replicate this cardiac functional improvement, indicating a telomerase-dependent mechanism. There was no hTERT + PDGFRα + cMSCs engraftment 14 days after transplantation indicating functional improvement occurred by paracrine mechanisms. Mass spectrometry on hTERT + PDGFRα + cMSCs conditioned media showed increased proteins associated with matrix modulation, angiogenesis, cell proliferation/survival/adhesion and innate immunity function. Our study shows that hTERT can activate pro-regenerative signalling within PDGFRα + cMSCs and enhance cardiac repair after myocardial infarction. An increased understanding of hTERT’s role in mesenchymal stromal cells from various organs will favourably impact clinical regenerative and anti-cancer therapies.
USP10 is a critical factor for Tau-positive stress granule formation in neuronal cells
Authors: Piatnitskaia Svetlana , Takahashi Masahiko , Kitaura Hiroki , Katsuragi Yoshinori , Kakihana Taichi , Zhang Lu , Kakita Akiyoshi , Iwakura Yuriko , Nawa Hiroyuki , Miura Takeshi , Ikeuchi Takeshi , Hara Toshifumi , Fujii Masahiro
Published: July 2019

Tau aggregates in neurons of brain lesions is a hallmark pathology of tauopathies, including Alzheimer’s disease (AD). Recent studies suggest that the RNA-binding protein TIA1 initiates Tau aggregation by inducing the formation of stress granules (SGs) containing Tau. SGs are stress-inducible cytoplasmic protein aggregates containing many RNA-binding proteins that has been implicated as an initial site of multiple pathogenic protein aggregates in several neurodegenerative diseases. In this study, we found that ubiquitin-specific protease 10 (USP10) is a critical factor for the formation of Tau/TIA1/USP10-positive SGs. Proteasome inhibition or TIA1-overexpression in HT22 neuronal cells induced the formation of TIA1/Tau-positive SGs, and the formations were severely attenuated by depletion of USP10. In addition, the overexpression of USP10 without stress stimuli in HT22 cells induced TIA1/Tau/USP10-positive SGs in a deubiquitinase-independent manner. In AD brain lesions, USP10 was colocalized with Tau aggregates in the cell body of neurons. The present findings suggest that USP10 plays a key role in the initiation of pathogenic Tau aggregation in AD through SG formation.
Discovering consensus genomic regions in wheat for root-related traits by QTL meta-analysis
Authors: Soriano Jose Miguel , Alvaro Fanny
Published: July 2019

Root system architecture is crucial for wheat adaptation to drought stress, but phenotyping for root traits in breeding programmes is difficult and time-consuming owing to the belowground characteristics of the system. Identifying quantitative trait loci (QTLs) and linked molecular markers and using marker-assisted selection is an efficient way to increase selection efficiency and boost genetic gains in breeding programmes. Hundreds of QTLs have been identified for different root traits in the last few years. In the current study, consensus QTL regions were identified through QTL meta-analysis. First, a consensus map comprising 7352 markers was constructed. For the meta-analysis, 754 QTLs were retrieved from the literature and 634 of them were projected onto the consensus map. Meta-analysis grouped 557 QTLs in 94 consensus QTL regions, or meta-QTLs (MQTLs), and 18 QTLs remained as singletons. The recently published genome sequence of wheat was used to search for gene models within the MQTL peaks. As a result, gene models for 68 of the 94 Root_MQTLs were found, 35 of them related to root architecture and/or drought stress response. This work will facilitate QTL cloning and pyramiding to develop new cultivars with specific root architecture for coping with environmental constraints.