bluuebunny/crossref_metadata_2025 huggingface dataset:
An epigenetic predictor of death captures multi-modal measures of brain health
Authors: Hillary Robert F. , Stevenson Anna J. , Cox Simon R. , McCartney Daniel L. , Harris Sarah E. , Seeboth Anne , Higham Jon , Sproul Duncan , Taylor Adele M. , Redmond Paul , Corley Janie , Pattie Alison , Hernández Maria del. C. Valdés , Muñoz-Maniega Susana , Bastin Mark E. , Wardlaw Joanna M. , Horvath Steve , Ritchie Craig W. , Spires-Jones Tara L. , McIntosh Andrew M. , Evans Kathryn L. , Deary Ian J. , Marioni Riccardo E.
Published: December 2019

Individuals of the same chronological age exhibit disparate rates of biological ageing. Consequently, a number of methodologies have been proposed to determine biological age and primarily exploit variation at the level of DNA methylation (DNAm). A novel epigenetic clock, termed ‘DNAm GrimAge’ has outperformed its predecessors in predicting the risk of mortality as well as many age-related morbidities. However, the association between DNAm GrimAge and cognitive or neuroimaging phenotypes remains unknown. We explore these associations in the Lothian Birth Cohort 1936 (n = 709, mean age 73 years). Higher DNAm GrimAge was strongly associated with all-cause mortality over the eighth decade (Hazard Ratio per standard deviation increase in GrimAge: 1.81,P < 2.0 × 10−16). Higher DNAm GrimAge was associated with lower age 11 IQ (β = −0.11), lower age 73 general cognitive ability (β = −0.18), decreased brain volume (β = −0.25) and increased brain white matter hyperintensities (β = 0.17). There was tentative evidence for a longitudinal association between DNAm GrimAge and cognitive decline from age 70 to 79. Sixty-nine of 137 health- and brain-related phenotypes tested were significantly associated with GrimAge. Adjusting all models for childhood intelligence attenuated to non-significance a small number of associations (12/69 associations; 6 of which were cognitive traits), but not the association with general cognitive ability (33.9% attenuation). Higher DNAm GrimAge associates with lower cognitive ability and brain vascular lesions in older age, independently of early-life cognitive ability. This epigenetic predictor of mortality associates with different measures of brain health and may aid in the prediction of age-related cognitive decline.
Replicability of structural brain alterations associated with general psychopathology: evidence from a population-representative birth cohort
Authors: Romer Adrienne L. , Knodt Annchen R. , Sison Maria L. , Ireland David , Houts Renate , Ramrakha Sandhya , Poulton Richie , Keenan Ross , Melzer Tracy R. , Moffitt Terrie E. , Caspi Avshalom , Hariri Ahmad R.
Published: December 2019

Transdiagnostic research has identified a general psychopathology factor—often called the ‘p’ factor—that accounts for shared variation across internalizing, externalizing, and thought disorders in diverse samples. It has been argued that the p factor may reflect dysfunctional thinking present in serious mental illness. In support of this, we previously used a theory-free, data-driven multimodal neuroimaging approach to find that higher p factor scores are associated with structural alterations within a cerebello-thalamo-cortical circuit (CTCC) and visual association cortex, both of which are important for monitoring and coordinating information processing in the service of executive control. Here we attempt to replicate these associations by conducting region-of-interest analyses using data from 875 members of the Dunedin Longitudinal Study, a five-decade study of a population-representative birth cohort, collected when they were 45 years old. We further sought to replicate a more recent report that p factor scores can be predicted by patterns of distributed cerebellar morphology as estimated through independent component analysis. We successfully replicated associations between higher p factor scores and both reduced gray matter volume of the visual association cortex and fractional anisotropy of pontine white matter pathways within the CTCC. In contrast, we failed to replicate prior associations between cerebellar structure and p factor scores. Collectively, our findings encourage further focus on the CTCC and visual association cortex as core neural substrates and potential biomarkers of general psychopathology.
Characterization of novel, recurrent genomic rearrangements as sensitive MRD targets in childhood B-cell precursor ALL
Authors: zur Stadt Udo , Alawi Malik , Adao Manuela , Indenbirken Daniela , Escherich Gabriele , Horstmann Martin A.
Published: November 2019

B-cell precursor (BCP) ALL carry a variety of classical V(D)J rearrangements as well as genomic fusions and translocations. Here, we assessed the value of genomic capture high-throughput sequencing (gc-HTS) in BCP ALL (n = 183) for the identification and implementation of targets for minimal residual disease (MRD) testing. For TRδ, a total of 300 clonal rearrangements were detected in 158 of 183 samples (86%). Beside clonal Vδ2-Dδ3, Dδ2-Dδ3, and Vδ2-Jα we identified a novel group of recurrent Dδ-Jα rearrangements, comprising Dδ2 or Dδ3 segments fused predominantly to Jα29. For IGH-JH, 329 clonal rearrangements were identified in 172 of 183 samples (94%) including novel types of V(D)J joining. Oligoclonality was found in ~1/3 (n = 57/183) of ALL samples. Genomic breakpoints were identified in 71 BCP-ALL. A distinct MRD high-risk subgroup of IGH-V(D)J-germline ALL revealed frequent deletions of IKZF1 (n = 7/11) and the presence of genomic fusions (n = 10/11). Quantitative measurement using genomic fusion breakpoints achieved equivalent results compared to conventional V(D)J-based MRD testing and could be advantageous upon persistence of a leukemic clone. Taken together, selective gc-HTS expands the spectrum of suitable MRD targets and allows for the identification of genomic fusions relevant to risk and treatment stratification in childhood ALL.
Transcription elongation factor AFF2/FMR2 regulates expression of expanded GGGGCC repeat-containing C9ORF72 allele in ALS/FTD
Authors: Yuva-Aydemir Yeliz , Almeida Sandra , Krishnan Gopinath , Gendron Tania F. , Gao Fen-Biao
Published: November 2019

Expanded GGGGCC (G4C2) repeats in C9ORF72 cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). How RNAs containing expanded G4C2 repeats are transcribed in human neurons is largely unknown. Here we describe a Drosophila model in which poly(GR) expression in adult neurons causes axonal and locomotor defects and premature death without apparent TDP-43 pathology. In an unbiased genetic screen, partial loss of Lilliputian (Lilli) activity strongly suppresses poly(GR) toxicity by specifically downregulating the transcription of GC-rich sequences in Drosophila. Knockout of AFF2/FMR2 (one of four mammalian homologues of Lilli) with CRISPR-Cas9 decreases the expression of the mutant C9ORF72 allele containing expanded G4C2 repeats and the levels of repeat RNA foci and dipeptide repeat proteins in cortical neurons derived from induced pluripotent stem cells of C9ORF72 patients, resulting in rescue of axonal degeneration and TDP-43 pathology. Thus, AFF2/FMR2 regulates the transcription and toxicity of expanded G4C2 repeats in human C9ORF72-ALS/FTD neurons.
An interhemispheric neural circuit allowing binocular integration in the optic tectum
Authors: Gebhardt Christoph , Auer Thomas O. , Henriques Pedro M. , Rajan Gokul , Duroure Karine , Bianco Isaac H. , Del Bene Filippo
Published: November 2019

Binocular stereopsis requires the convergence of visual information from corresponding points in visual space seen by two different lines of sight. This may be achieved by superposition of retinal input from each eye onto the same downstream neurons via ipsi- and contralaterally projecting optic nerve fibers. Zebrafish larvae can perceive binocular cues during prey hunting but have exclusively contralateral retinotectal projections. Here we report brain activity in the tectal neuropil ipsilateral to the visually stimulated eye, despite the absence of ipsilateral retinotectal projections. This activity colocalizes with arbors of commissural neurons, termed intertectal neurons (ITNs), that connect the tectal hemispheres. ITNs are GABAergic, establish tectal synapses bilaterally and respond to small moving stimuli. ITN-ablation impairs capture swim initiation when prey is positioned in the binocular strike zone. We propose an intertectal circuit that controls execution of the prey-capture motor program following binocular localization of prey, without requiring ipsilateral retinotectal projections.
Enzyme-mimetic self-catalyzed polymerization of polypeptide helices
Authors: Song Ziyuan , Fu Hailin , Baumgartner Ryan , Zhu Lingyang , Shih Kuo-Chih , Xia Yingchun , Zheng Xuetao , Yin Lichen , Chipot Christophe , Lin Yao , Cheng Jianjun
Published: November 2019

Enzymes provide optimal three-dimensional structures for substrate binding and the subsequent accelerated reaction. Such folding-dependent catalytic behaviors, however, are seldom mechanistically explored with reduced structural complexity. Here, we demonstrate that the α-helix, a much simpler structural motif of enzyme, can facilitate its own growth through the self-catalyzed polymerization ofN-carboxyanhydride (NCA) in dichloromethane. The reversible binding between the N terminus of α-helical polypeptides and NCAs promotes rate acceleration of the subsequent ring-opening reaction. A two-stage, Michaelis–Menten-type kinetic model is proposed by considering the binding and reaction between the propagating helical chains and the monomers, and is successfully utilized to predict the molecular weights and molecular-weight distributions of the resulting polymers. This work elucidates the mechanism of helix-induced, enzyme-mimetic catalysis, emphasizes the importance of solvent choice in the discovery of new reaction type, and provides a route for rapid production of well-defined synthetic polypeptides by taking advantage of self-accelerated ring-opening polymerizations.
Parametrization of energy sharing distributions in direct double photoionization of He
Authors: Andersson J. , Zagorodskikh S. , Roos A. Hult , Talaee O. , Squibb R. J. , Koulentianos D. , Wallner M. , Zhaunerchyk V. , Singh R. , Eland J. H. D. , Rost J. M. , Feifel R.
Published: November 2019

We present experimental results on the characteristic sharing of available excess energy, ranging from 11–221 eV, between two electrons in single-photon direct double ionization of He. An effective parametrization of the sharing distributions is presented along with an empirical model that describes the complete shape of the distribution based on a single experimentally determinable parameter. The measured total energy sharing distributions are separated into two distributions representing the shake-off and knock-out parts by simulating the sharing distribution curves expected from a pure wave collapse after a sudden removal of the primary electron. In this way, empirical knock-out distributions are extracted and both the shake-off and knock-out distributions are parametrized. These results suggest a simple method that can be applied to other atomic and molecular systems to experimentally study important aspects of the direct double ionization process.
Prenatal electroporation-mediated gene transfer restores Slc26a4 knock-out mouse hearing and vestibular function
Authors: Takeda Hiroki , Miwa Toru , Kim Min Young , Choi Byung Yoon , Orita Yorihisa , Minoda Ryosei
Published: November 2019

The otocyst, an anlage of the inner ear, presents an attractive target to study treatment strategies for genetic hearing loss and inner ear development. We have previously reported that electroporation-mediated transuterine gene transfer of Connexin30, utilizing a monophasic pulse into Connexin30−/− mouse otocysts at embryonic day 11.5, is able to prevent putative hearing deterioration. However, it is not clear whether supplementary gene transfer can rescue significant morphological changes, caused by genetic deficits. In addition, with the transuterine gene transfer technique utilized in our previous report, the survival rate of embryos and their mothers after treatment was low, which became a serious obstacle for effective in vivo experiments. Here, we set out to elucidate the feasibility of supplementation therapy in Slc26a4 deficient mice, utilizing biphasic pulses, optimized by modifying pulse conditions. Modification of the biphasic pulse conditions during electroporation increased the survival rate. In addition, supplementation of the target gene cDNA into the otocysts of homozygous Slc24a4 knockout mice significantly prevented enlargement of the endolymphatic space in the inner ear areas; moreover, it rescued hearing and vestibular function of mice in vivo.
Practical Resistance of Ostrinia nubilalis (Lepidoptera: Crambidae) to Cry1F Bacillus thuringiensis maize discovered in Nova Scotia, Canada
Authors: Smith Jocelyn L. , Farhan Yasmine , Schaafsma Arthur W.
Published: December 2019

Transgenic maize, Zea mays L., modified to express insecticidal proteins from the bacterium Bacillus thuringiensis Berliner, was introduced in 1996 to control Ostrinia nubilalis Hübner (Lepidoptera: Crambidae), a key maize pest in North America. The high-dose/refuge concept, developed to delay or prevent resistance evolution to this technology, has been exemplified by O. nubilalis as no cases of practical resistance were identified in >20 years. This study documents the first case of practical resistance to Cry1F Bt maize by O. nubilalis in North America. Four collections of O. nubilalis were made from Cry1F maize in Nova Scotia, Canada with unexpected injury (UXI) ranging from 30–70%. Greater survival of UXI collections was observed when larvae were exposed to the highest concentration of 200 ng Cry1F cm−2 in diet-overlay bioassays compared to susceptible laboratory colonies. Larvae also fed and survived on Cry1F leaf tissue in 7 d bioassays. A collection from non-Bt maize, 120 km west of the UXI region, also survived 200 ng Cry1F cm−2, but was susceptible to Cry1F leaf tissue. Detection of Cry1F-resistant O. nubilalis in what might be considered an insignificant maize-growing region indicates that a number of preventable causal factors may have been related to inadequate stewardship of Bt maize technology.
Altered generation of ciliated cells in chronic obstructive pulmonary disease
Authors: Gohy Sophie , Carlier François M. , Fregimilicka Chantal , Detry Bruno , Lecocq Marylène , Ladjemi Maha Zohra , Verleden Stijn , Hoton Delphine , Weynand Birgit , Bouzin Caroline , Pilette Charles
Published: November 2019

In COPD, epithelial changes are prominent features in the airways, such as goblet cell hyperplasia and squamous metaplasia. In contrast, it remains unclear whether ciliated cells are reduced and which pathways dysregulate epithelial differentiation. We hypothesized that bronchial epithelial cell lineage specification is dysregulated in COPD because of an aberrant reprogramming through transforming growth factor (TGF)-β1. Surgical lung tissue from 81 COPD and 61 control (smokers and non-smokers) patients was assessed for bronchial epithelial cell phenotyping by immunohistochemistry, both in situ and in vitro in reconstituted air-liquid interface (ALI) cultures. The role of TGF-β1 was studied in vitro. COPD epithelium in large airways, when compared to controls, showed decreased β-tubulin IV + ciliated cells (4.4%, 2.5–8.8% versus 8.5%, 6.3–11.8% of surface staining, median and IQR, p = 0.0009) and increased MUC5AC + goblet cells (34.8%, 24.4–41.9% versus 10.3%, 5.1–17.6%, p < 0.0001). Both features were recapitulated in the ALI-cultured epithelium from COPD patients. Exogenous TGF-β1 reduced mucociliary differentiation while neutralizing TGF-β1 during ALI increased both specialized cell types. The COPD airway epithelium displays altered differentiation for ciliated cells, which recapitulates in vitro, at least in part through TGF-β1.
Warming and elevated CO2 alter the transcriptomic response of maize (Zea mays L.) at the silking stage
Authors: Huang Yulan , Fang Rui , Li Yansheng , Liu Xiaobing , Wang Guanghua , Yin Kuide , Jin Jian , Herbert Stephen J.
Published: November 2019

Exploring the transcriptome of crops in response to warming and elevated CO2 (eCO2) is important to gaining insights of botanical adaption and feedback to climate change. This study deployed Illumina sequencing technology to characterize transcriptomic profile of maize plants at the silking stage, which were grown under warming (2 °C higher than ambient temperature) and eCO2 (550 ppm) conditions. The treatment of ambient temperature and ambient CO2 concentration was considered as control (CK). Warming, eCO2 and warming plus eCO2 resulted in 2732, 1966 and 271 genes expressing differently (DEGs) compared to the CK, respectively. Among the DEGs, 48, 47 and 36 gene ontology (GO) terms were enriched in response to warming, eCO2 and warming plus eCO2 compared to the CK, respectively. The majority of genes were assigned to the biological process category and the cellular component category. Elevated CO2 significantly inhibited gene expressions in terms of photosynthesis and carbohydrate biosynthesis pathways. Warming not only negatively affected expressions of these genes, but also secondary pathways of nitrogen (N) metabolism, including key enzymes of GST30, GST7, GST26, GST15, GLUL and glnA. These results indicated the negative biochemical regulation and physiological functions in maize in response to warming and eCO2, highlighting the necessity to improve the genetic adaptability of plant to future climate change.
Presynaptic dopamine function measured with [18F]fluorodopa and L-DOPA effects on impulsive choice
Authors: Petzold Johannes , Lee Ying , Pooseh Shakoor , Oehme Liane , Beuthien-Baumann Bettina , London Edythe D. , Goschke Thomas , Smolka Michael N.
Published: November 2019

We previously reported that L-DOPA effects on reward-based decision-making in a randomized, placebo-controlled, double-blind, crossover study were consistent with an inverted U-shaped function whereby both low and high extremes of dopamine signaling are associated with high-impulsive choice. To test this hypothesis, we performed [18F]DOPA positron emission tomography in 60 of the 87 participants in that study, and measured the effective distribution volume ratio (EDVR) of [18F]DOPA influx rate to [18F]dopamine washout rate, an index of presynaptic dopaminergic function. Participants with higher baseline EDVR self-reported lower impulsivity, and discounted rewards as a function of delay more strongly after receiving L-DOPA, whereas the opposite was detected for those with lower baseline EDVR. Our findings support a relationship of striatal dopaminergic activity to trait impulsivity, and the view that there is a non-linear, possibly inverted U-shaped relationship of striatal dopaminergic function with delay discounting. Individuals with optimal dopamine signaling would become more impulsive when receiving dopamine-enhancing drugs, whereas those with suboptimal dopaminergic signaling would benefit and exhibit less impulsive choice. Consideration of differences in endogenous dopamine signaling and possibly also other neurotransmitter activity may be crucial to advance understanding of the neurobiochemical mechanisms of impulsive decision-making and related mental disorders.
Observation of a comb-shaped filamentary plasma array under subcritical condition in 303-GHz millimetre-wave air discharge
Authors: Fukunari Masafumi , Tanaka Shunsuke , Shinbayashi Ryuji , Yamaguchi Yuusuke , Tatematsu Yoshinori , Saito Teruo
Published: November 2019

Gas breakdown in the millimetre-wave frequency band is an interesting phenomenon in nonlinear dynamics such as self-organized structure formation. We observed the transition between two types of filamentary plasma arrays in air discharge driven by a 303-GHz millimetre wave. Plasma is ignited at a parabolic mirror’s focal point in the overcritical condition. One array parallel to the electric field vector appears with a spacing of λ/4 at the focal point. Filaments then separate into plasma lumps ~10 μs after ignition. At 20 μs, a new comb-shaped array grows in the subcritical condition. Filaments are parallel to the incident beam with spacing of 0.96 λ and elongate towards the incident beam. This comb-shaped array appears only in the electric field plane; bulk plasma with a sharp vertex forms in the magnetic field plane. This array is created by a standing wave structure generated by waves diffracted from the plasma surface. Filamentary plasma array formations can influence the energy absorption by the plasma, which is important for engineering applications such as beamed energy propulsion.
Automated identification of Myxobacterial genera using Convolutional Neural Network
Authors: Sajedi Hedieh , Mohammadipanah Fatemeh , Pashaei Ali
Published: December 2019

The Myxococcales order consist of eleven families comprising30 genera, and are featured by the formation of the highest level of differential structure aggregations called fruiting bodies. These multicellular structures are essential for their resistance in ecosystems and is used in the primitive identification of these bacteria while their accurate taxonomic position is confirmed by the nucleotide sequence of 16SrRNA gene. Phenotypic classification of these structures is currently performed based on the stereomicroscopic observations that demand personal experience. The detailed phenotypic features of the genera with similar fruiting bodies are not readily distinctive by not particularly experienced researchers. The human examination of the fruiting bodies requires high skill and is error-prone. An image pattern analysis of schematic images of these structures conducted us to the construction of a database, which led to an extractable recognition of the unknown fruiting bodies. In this paper, Convolutional Neural Network (CNN) was considered as a baseline for recognition of fruiting bodies. In addition, to enhance the result the classifier, part of CNN is replaced with other classifiers. By employing the introduced model, all 30 genera of this order could be recognized based on stereomicroscopic images of the fruiting bodies at the genus level that not only does not urge us to amplify and sequence gene but also can be attained without preparation of microscopic slides of the vegetative cells or myxospores. The accuracy of 77.24% in recognition of genera and accuracy of 88.92% in recognition of suborders illustrate the applicability property of the proposed machine learning model.
Lithospheric mantle buoyancy: the role of tectonic convergence and mantle composition
Authors: Boonma K. , Kumar A. , Garcia-Castellanos D. , Jiménez-Munt I. , Fernández M.
Published: November 2019

Plate subduction and delamination, two key processes driving plate tectonics, are thought to be controlled by the buoyancy of the lithospheric mantle relative to the underlying asthenosphere. Most mantle delamination models consider a lithospheric density higher than the asthenosphere to ensure negative buoyancy (slab pull). However, mineral physics show that the continental lithospheric mantle density is lighter than the asthenosphere, and that only its pressure-temperature-composition dependence makes it become denser and unstable when sinking adiabatically. Here, we explore the controls on buoyancy using a 2D thermal-diffusive model of plate convergence, considering five chemical compositions and tectonothermal ages, namely Archon (>2.5 Ga), Proton (2.5–1.0 Ga), Tecton (<1.0 Ga), and two oceanic lithospheric plates of 30 Ma and 120 Ma. While the advection of colder rock in oceanic-like plates always results in negative buoyancy, Protons and Tectons exhibit an ability to slowly flip from negative to positive buoyancy at low convergence rates: they first favour the sinking due to advection and then become more buoyant because they are thinner and heat up faster during subduction. In contrast, the lighter density of cratons overprints this effect and hinders delamination or subduction, regardless of the convergence rate. This may explain why Archons are more stable during the Wilson cycle.
Hyperventilation-induced heart rate response as a potential marker for cardiovascular disease
Authors: Hawkins Selwynne M. , Guensch Dominik P. , Friedrich Matthias G. , Vinco Giulia , Nadeshalingham Gobinath , White Michel , Mongeon Francois-Pierre , Hillier Elizabeth , Teixeira Tiago , Flewitt Jacqueline A. , Eberle Balthasar , Fischer Kady
Published: November 2019

An increase of heart rate to physical or mental stress reflects the ability of the autonomous nervous system and the heart to respond adequately. Hyperventilation is a user-controlled breathing maneuver that has a significant impact on coronary function and hemodynamics. Thus, we aimed to investigate if the heart rate response to hyperventilation (HRRHV) can provide clinically useful information. A pooled analysis of the HRRHV after 60 s of hyperventilation was conducted in 282 participants including healthy controls; patients with heart failure (HF); coronary artery disease (CAD); a combination of both; or patients suspected of CAD but with a normal angiogram. Hyperventilation significantly increased heart rate in all groups, although healthy controls aged 55 years and older (15 ± 9 bpm) had a larger HRRHV than each of the disease groups (HF: 6 ± 6, CAD: 8 ± 8, CAD+/HF+: 6 ± 4, and CAD−/HF−: 8 ± 6 bpm, p < 0.001). No significant differences were found between disease groups. The HRRHV may serve as an easily measurable additional marker of cardiovascular health. Future studies should test its diagnostic potential as a simple, inexpensive pre-screening test to improve patient selection for other diagnostic exams.
The Assessment of Twitter’s Potential for Outbreak Detection: Avian Influenza Case Study
Authors: Yousefinaghani Samira , Dara Rozita , Poljak Zvonimir , Bernardo Theresa M. , Sharif Shayan
Published: December 2019

Social media services such as Twitter are valuable sources of information for surveillance systems. A digital syndromic surveillance system has several advantages including its ability to overcome the problem of time delay in traditional surveillance systems. Despite the progress made with using digital syndromic surveillance systems, the possibility of tracking avian influenza (AI) using online sources has not been fully explored. In this study, a Twitter-based data analysis framework was developed to automatically monitor avian influenza outbreaks in a real-time manner. The framework was implemented to find worrisome posts and alerting news on Twitter, filter irrelevant ones, and detect the onset of outbreaks in several countries. The system collected and analyzed over 209,000 posts discussing avian influenza on Twitter from July 2017 to November 2018. We examined the potential of Twitter data to represent the date, severity and virus type of official reports. Furthermore, we investigated whether filtering irrelevant tweets can positively impact the performance of the system. The proposed approach was empirically evaluated using a real-world outbreak-reporting source. We found that 75% of real-world outbreak notifications of AI were identifiable from Twitter. This shows the capability of the system to serve as a complementary approach to official AI reporting methods. Moreover, we observed that one-third of outbreak notifications were reported on Twitter earlier than official reports. This feature could augment traditional surveillance systems and provide a possibility of early detection of outbreaks. This study could potentially provide a first stepping stone for building digital disease outbreak warning systems to assist epidemiologists and animal health professionals in making relevant decisions.
Promising Hybrid Graphene-Silver Nanowire Composite Electrode for Flexible Organic Light-Emitting Diodes
Authors: Li Huiying , Liu Yunfei , Su Anyang , Wang Jintao , Duan Yu
Published: November 2019

Thanks to its high transparency, high carrier mobility, and thermal conductivity, graphene is often used as transparent conductive electrode (TCE) in optoelectronic devices. However, the low carrier concentration and high resistance caused by vacancy defects, grain boundaries, and superposed folds in typical graphene films limit its application. In this study, we propose a method to increase both the conductivity and carrier concentration in single-layer graphene (SLG) by blending it with silver nanowires (AgNWs). AgNWs provide connections between grain boundaries of graphene to improve charge-carrier transport. The AgNWs in this study can reduce the resistance of SLG from 650 Ω/◻ to 27 Ω/◻ yet still maintain a transmittance of 86.7% (at 550 nm). Flexible organic light-emitting diode, with a maximum 15000 cd m−2 luminance was successfully fabricated using such graphene and AgNWs composite transparent electrodes.
In vitro assessment of immunomodulatory and anti-Campylobacter activities of probiotic lactobacilli
Authors: Taha-Abdelaziz Khaled , Astill Jake , Kulkarni Raveendra R. , Read Leah R. , Najarian Afsaneh , Farber Jeffrey M. , Sharif Shayan
Published: November 2019

The present study was undertaken to assess the antimicrobial activity ofLactobacillusspp. (L. salivarius,L. johnsonii,L. reuteri,L. crispatus, andL. gasseri) againstCampylobacter jejunias well as their immunomodulatory capabilities. The results demonstrated that lactobacilli exhibit differential antagonistic effects againstC. jejuniand vary in their ability to elicit innate responses in chicken macrophages. All lactobacilli exerted inhibitory effects onC. jejunigrowth, abrogated the production of the quorum sensing molecule autoinducer-2 (AI-2) byC. jejuniand inhibited the invasion ofC. jejuniin human intestinal epithelial cells. Additionally, all lactobacilli, exceptL. reuteri, significantly reduced the expression of virulence-related genes inC. jejuni, including genes responsible for motility (flaA, flaB, andflhA), invasion (ciaB), and AI-2 production (luxS). All lactobacilli enhancedC. jejuniphagocytosis by macrophages and increased the expression of interferon (IFN)-γ, interleukin (IL)-1β, IL-12p40, IL-10, and chemokine (CXCLi2) in macrophages. Furthermore,L. salivarius, L. reuteri, L. crispatus, and a mixture of all lactobacilli significantly increased expression of the co-stimulatory molecules CD40, CD80, and CD86 in macrophages. In conclusion, these findings demonstrate that lactobacilli possess anti-Campylobacterand immunomodulatory activities. Further studies are needed to assess their protective efficacy against intestinal colonization byC. jejuniin broiler chickens.
A method for hand-foot-mouth disease prediction using GeoDetector and LSTM model in Guangxi, China
Authors: Gu Jiangyan , Liang Lizhong , Song Hongquan , Kong Yunfeng , Ma Rui , Hou Yane , Zhao Jinyu , Liu Junjie , He Nan , Zhang Yang
Published: November 2019

Hand-foot-mouth disease (HFMD) is a common infectious disease in children and is particularly severe in Guangxi, China. Meteorological conditions are known to play a pivotal role in the HFMD. Previous studies have reported numerous models to predict the incidence of HFMD. In this study, we proposed a new method for the HFMD prediction using GeoDetector and a Long Short-Term Memory neural network (LSTM). The daily meteorological factors and HFMD records in Guangxi during 2014–2015 were adopted. First, potential risk factors for the occurrence of HFMD were identified based on the GeoDetector. Then, region-specific prediction models were developed in 14 administrative regions of Guangxi, China using an optimized three-layer LSTM model. Prediction results (the R-square ranges from 0.39 to 0.71) showed that the model proposed in this study had a good performance in HFMD predictions. This model could provide support for the prevention and control of HFMD. Moreover, this model could also be extended to the time series prediction of other infectious diseases.
Assessing the reliability of gene expression measurements in very-low-numbers of human monocyte-derived macrophages
Authors: Geiß Carsten , Alanis-Lobato Gregorio , Andrade-Navarro Miguel , Régnier-Vigouroux Anne
Published: November 2019

Tumor-derived primary cells are essential for in vitro and in vivo studies of tumor biology. The scarcity of this cellular material limits the feasibility of experiments or analyses and hence hinders basic and clinical research progress. We set out to determine the minimum number of cells that can be analyzed with standard laboratory equipment and that leads to reliable results, unbiased by cell number. A proof-of-principle study was conducted with primary human monocyte-derived macrophages, seeded in decreasing number and constant cell density. Gene expression of cells stimulated to acquire opposite inflammatory states was analyzed by quantitative PCR. Statistical analysis indicated the lack of significant difference in the expression profile of cells cultured at the highest (100,000 cells) and lowest numbers (3,610 cells) tested. Gene Ontology, pathway enrichment and network analysis confirmed the reliability of the data obtained with the lowest cell number. This statistical and computational analysis of gene expression profiles indicates that low cell number analysis is as dependable and informative as the analysis of a larger cell number. Our work demonstrates that it is possible to employ samples with a scarce number of cells in experimental studies and encourages the application of this approach on other cell types.
Improved Alere Determine Lipoarabinomannan Antigen Detection Test for the Diagnosis of Human and Bovine Tuberculosis by Manipulating Urine and Milk
Authors: García Juan Ignacio , Kelley Holden V. , Meléndez Johanna , de León Rosa Alejandra Alvarez , Castillo Alejandra , Sidiki Sabeen , Yusoof Kizil A. , Nunes Elizabete , Téllez Cesar López , Mejía-Villatoro Carlos Rodolfo , Ikeda Janet , García-Basteiro Alberto L. , Wang Shu-Hua , Torrelles Jordi B.
Published: November 2019

Tuberculosis (TB) disease still kills 1-person every 21-seconds. Few TB diagnostic tests are considered truly appropriate for point of care settings. The WHO-endorsed immunodiagnostic Alere Determine Lipoarabinomannan Ag-test (LAM-test) detects Mycobacterium tuberculosis complex LAM in urine, and its use is recommended for TB diagnosis among HIV co-infected individuals with low CD4 T-cell counts. Here we found that a simple 15-minute enzymatic treatment at room temperature of LAM-spiked urine with α-mannosidase (for human TB), and LAM-spiked milk with combined lactase and caseinase (for bovine TB), enhanced 10-fold the detection levels of the LAM-test and thus, improved the detection of LAM by the LAM-test in urine and milk that otherwise could be missed in the field. Future separate clinical research studies specifically designed to address the potential of these findings are required.
Age-related decrease in collagen proton fraction in tibial tendons estimated by magnetization transfer modeling of ultrashort echo time magnetic resonance imaging (UTE-MRI)
Authors: Jerban Saeed , Ma Yajun , Namiranian Behnam , Ashir Aria , Shirazian Hoda , Wei Zhao , Le Nicole , Wu Mei , Cai Zhenyu , Du Jiang , Chang Eric Y.
Published: November 2019

Clinical magnetic resonance imaging (MRI) sequences are not often capable of directly visualizing tendons. Ultrashort echo time (UTE) MRI can acquire high signal from tendons thus enabling quantitative assessments. Magnetization transfer (MT) modeling combined with UTE-MRI—UTE-MT-modeling—can indirectly assess macromolecular protons in the tendon. This study aimed to determine if UTE-MT-modeling is a quantitative technique sensitive to the age-related changes of tendons. The legs of 26 young healthy (29 ± 6 years old) and 22 elderly (75 ± 8 years old) female subjects were imaged using UTE sequences on a 3T MRI scanner. Institutional review board approval was obtained, and all recruited subjects provided written informed consent. T1 and UTE-MT-modeling were performed on anterior tibialis tendons (ATT) and posterior tibialis tendons (PTT) as two representative human leg tendons. A series of MT pulse saturation powers (500–1500°) and frequency offsets (2–50 kHz) were used to measure the macromolecular fraction (MMF) and macromolecular T2 (T2MM). All measurements were repeated by three independent readers for a reproducibility study. MMF demonstrated significantly lower values on average in the elderly cohort compared with the younger cohort for both ATT (decreased by 16.8%, p = 0.03) and PTT (decreased by 23.0%, p < 0.01). T2MMand T1 did not show a significant nor a consistent difference between the young and elderly cohorts. For all MRI parameters, intraclass correlation coefficient (ICC) was higher than 0.98, indicating excellent consistency between measurements performed by independent readers. MMF serving as a surrogate measure for collagen content, showed a significant decrease in elderly leg tendons. This study highlighted UTE-MRI-MT techniques as a useful quantitative method to assess the impact of aging on human tendons.
Seed yield can be explained by altered yield components in field-grown western wheatgrass (Pascopyrum smithii Rydb.)
Authors: Chen Zhao , Niu Junpeng , Cao Xinlong , Jiang Wenbo , Cui Jian , Wang Quanzhen , Zhang Quan
Published: November 2019

Western wheatgrass (Pascopyrum smithii Rydb.) is an important cool-season forage and turfgrass. However, due to seed dormancy and poor seedling vigor, it is difficult to develop high seed yield production systems, and assessing these components in response to seed yield. Based on multifactor orthogonally designed field experimental plots under various field management regimes, the effects of numbers of fertile tillers m−2 (Y1), spikelets/fertile tiller (Y2), florets/spikelet (Y3), seed numbers/spikelet (Y4), and seed weight (Y5) on seed yield (Z) were determined over three successive years. Correlation analysis indicated that fertile tillers (Y1) was the most important seed yield component. And the biggest contribution of those five yield component is fertile tillers (Y1), followed by seed numbers/spikelet (Y4), spikelets/fertile tiller (Y2), florets/spikelet (Y3) and seed weight (Y5), respectively. By using ridge regression analysis, we have developed an accurate model of seed yield with its five components. Finally, the results of synergism and antagonism among these yield components on seed yield showed that fertile tillers and seed numbers/spikelet had an antagonistic effect on seed yield. Therefore, selection for high seed yield by direct selection for large values of fertile tillers and seed numbers/spikelet would be the most effective breeding strategy for western wheatgrass.
Etiology and Visual Prognosis in Open Globe Injuries: Results of A Tertiary Referral Center in Turkey
Authors: Ozturk Taylan , Cetin Dora Golgem , Ayhan Ziya , Kaya Mahmut , Arikan Gul , Yaman Aylin
Published: November 2019

We aimed to analyse the clinical characteristics of OGI and evaluate the correlation between baseline ocular trauma score (OTS) and visual outcomes in cases with OGI. The charts of 257 OGI patients who had at least six months of follow-up were reviewed retrospectively. Demographics, data about the etiology, localization and size of the OGI, baseline and final best-corrected visual acuity (BCVA) were noted. At the time of approval OTS was calculated and compared with final BCVA. All analysis was performed in both entire study population and our pediatric subgroup. A total of 261 eyes of 257 patients with a mean age of 34.9 ± 19.8 years were enrolled. Globe injury with a mean size of 6.7 ± 4.5 mm was within zone I in 46.7% of the eyes. Older age (p < 0.001, OR = 1.029, 95% CI = 1.015–1.043), higher baseline logMAR BCVA scores (p < 0.001, OR = 4.460, 95% CI = 2.815–7.065), bigger wound size (p < 0.001, OR = 1.159, 95% CI = 1.084–1.240), relative afferent pupillary defect (RAPD) positiveness (p < 0.001, OR = 0.021 95% CI = 0.005–0.087), lower OTS (p < 0.001, OR = 27.034, 95% CI = 6.299–116.021), presence of concomitant retinal detachment (p < 0.001, OR = 0.157, 95% CI = 0.080–0.306), and endophthalmitis (p = 0.045, OR = 0.207, 95% CI = 0.044–0.962) were found to be related to poor visual prognosis. Cases with OGI caused by a sharp object (p = 0.007, OR = 0.204, 95% CI = 0.065–0.641) and those injured by a glass (p = 0.039, OR = 0.229, 95% CI = 0.056–0.931) had more favorable final vision. This study highlights that baseline BCVA, wound size, RAPD, retinal detachment, and OTS were the most significant markers for poor visual outcomes in both the entire population and pediatric subgroup. In cases with OGI, OTS was also found effective in predicting visual prognosis.
Circulating tumor cells detection in tumor draining vein of breast cancer patients
Authors: Hattori Masaya , Nakanishi Hayao , Yoshimura Mayumi , Iwase Madoka , Yoshimura Akiyo , Adachi Yayoi , Gondo Naomi , Kotani Haruru , Sawaki Masataka , Fujita Nao , Yatabe Yasushi , Iwata Hiroji
Published: December 2019

Circulating tumor cells (CTCs) in tumor draining vein blood (DB) are potential sources for liquid biopsy. However, the identification of CTCs in DB of breast cancer has not been attempted. In this study, we investigated the feasibility of CTC detection in DB of breast cancer patients using a newly developed filtration-based microfluidic CTC detection device. Samples of peripheral vein blood (PB) and DB drawn from the lateral thoracic vein of the resected breast tissue were collected during the perioperative period. We investigated 41 breast cancer patients who underwent breast surgery with axillary lymph node dissection. DB was successfully collected in 36 patients (87.8%), with a mean amount of 0.85 ml. CTCs were detected in 58.3% of PB samples and 80.6% of DB samples. DB had significant higher number of CTCs compared with PB (p < 0.001). CTCs were detected in 75.0% of DB samples and 50.0% of PB samples from patients achieving pathological complete response after neoadjuvant chemotherapy. These results suggest that abundant CTCs are released into the DB of breast cancer patients, indicating that CTCs in DB would be alternative sources for liquid biopsy and potential indicators for monitoring of treatment response and prognosis in breast cancer patients.
Preserved wake-dependent cortical excitability dynamics predict cognitive fitness beyond age-related brain alterations
Authors: Van Egroo Maxime , Narbutas Justinas , Chylinski Daphne , Villar González Pamela , Ghaemmaghami Pouya , Muto Vincenzo , Schmidt Christina , Gaggioni Giulia , Besson Gabriel , Pépin Xavier , Tezel Elif , Marzoli Davide , Le Goff Caroline , Cavalier Etienne , Luxen André , Salmon Eric , Maquet Pierre , Bahri Mohamed Ali , Phillips Christophe , Bastin Christine , Collette Fabienne , Vandewalle Gilles
Published: December 2019

Age-related cognitive decline arises from alterations in brain structure as well as in sleep-wake regulation. Here, we investigated whether preserved wake-dependent regulation of cortical function could represent a positive factor for cognitive fitness in aging. We quantified cortical excitability dynamics during prolonged wakefulness as a sensitive marker of age-related alteration in sleep-wake regulation in 60 healthy older individuals (50–69 y; 42 women). Brain structural integrity was assessed with amyloid-beta- and tau-PET, and with MRI. Participants’ cognition was investigated using an extensive neuropsychological task battery. We show that individuals with preserved wake-dependent cortical excitability dynamics exhibit better cognitive performance, particularly in the executive domain which is essential to successful cognitive aging. Critically, this association remained significant after accounting for brain structural integrity measures. Preserved dynamics of basic brain function during wakefulness could therefore be essential to cognitive fitness in aging, independently from age-related brain structural modifications that can ultimately lead to dementia.
Repression of phagocytosis by human CD33 is not conserved with mouse CD33
Authors: Bhattacherjee Abhishek , Rodrigues Emily , Jung Jaesoo , Luzentales-Simpson Matthew , Enterina Jhon R. , Galleguillos Danny , St. Laurent Chris D. , Nakhaei-Nejad Maryam , Fuchsberger Felix F. , Streith Laura , Wang Qian , Kawasaki Norihito , Duan Shiteng , Bains Arjun , Paulson James C. , Rademacher Christoph , Giuliani Fabrizio , Sipione Simonetta , Macauley Matthew S.
Published: December 2019

CD33 is an immunomodulatory receptor linked to Alzheimer’s disease (AD) susceptibility via regulation of phagocytosis in microglia. Divergent features between human CD33 (hCD33) and murine CD33 (mCD33) include a unique transmembrane lysine in mCD33 and cytoplasmic tyrosine in hCD33. The functional consequences of these differences in restraining phagocytosis remains poorly understood. Using a new αmCD33 monoclonal antibody, we show that mCD33 is expressed at high levels on neutrophils and low levels on microglia. Notably, cell surface expression of mCD33 is entirely dependent on Dap12 due to an interaction with the transmembrane lysine in mCD33. In RAW264.7 cultured macrophages, BV-2 cultured microglia, primary neonatal and adult microglia, uptake of cargo — including aggregated Aβ1–42 — is not altered upon genetic ablation of mCD33. Alternatively, deletion of hCD33 in monocytic cell lines increased cargo uptake. Moreover, transgenic mice expressing hCD33 in the microglial cell lineage showed repressed cargo uptake in primary microglia. Therefore, mCD33 and hCD33 have divergent roles in regulating phagocytosis, highlighting the importance of studying hCD33 in AD susceptibility.
Isolation and characterisation of a stable 2-azaphenalenyl azomethine ylide
Authors: Katayama Koji , Konishi Akihito , Horii Koki , Yasuda Makoto , Kitamura Chitoshi , Nishida Jun-ichi , Kawase Takeshi
Published: November 2019

Although azomethine ylides have been fully exploited as versatile reactive intermediates in dipolar cycloaddition reactions to construct a variety of heterocyclic compounds involving a nitrogen atom, little is known about their structural and electronic properties. Here a method is developed for the preparation, isolation and characterization of a stable 2-azaphenalenyl based azomethine ylide. N-Phenyl-5,8-di-t-butyl-2-azaphenalenyl cannot be isolated because it undergoes rapid dimerization by C–C bond formation at the 1 and 3 positions. In contrast, sterically bulkier N-2,6-di(isopropyl)phenyl-5,8-di-t-butyl-2-azaphenalenyl can be generated and isolated as deep green crystals under deoxygenated conditions. X-ray crystal analysis of this stable azomethine ylide reveals that its azaphenalenyl skeleton has very small bond alternation and structural deformation. The results of spectroscopic and electrochemical theoretical studies indicate that N-2,6-di(isopropyl)phenyl-5,8-di-t-butyl-2-azaphenalenyl has electronic features that are similar to those of phenalenyl anion and it possesses an extremely high HOMO energy.
Latin American Food Labelling: Review and Recent Developments
Authors: Reyes Marcela , Corvalan Camila
Published: December 2019

The problem of malnutrition has spread throughout the world, with more than three-quarters of non-communicable diseases (NCDs: diabetes, hypertension, cancer, etc.) occurring in low- and middle-income countries. Latin American countries are also facing an epidemic of overweight and diet-driven NCDs, whilst problems associated with undernutrition are still a matter of significant concern. The epidemiology of Latin American countries is characterised predominately by all forms of malnutrition as well as a significant burden from NCDs. Moreover, there is increased manufacture and consumption of ultra-processed foods, high in sugars, saturated and trans fats and sodium, which are linked to poor diet and low micronutrient and protein intakes. Several calls for action have targeted structural measures to improve diets through better nutrition labelling (i.e. more visible and understandable). However, to date, only three countries have implemented mandatory front-of-package (FOP) labelling in the Latin American region (i.e. Mexico, Ecuador and Chile). This chapter focuses on use of FOP labelling in Latin America, as a tool for improving diets, communicating potential health benefits, and giving examples from countries that have implemented these approaches.