bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the causal association of glycine with risk of cardio-metabolic diseases
Authors: Wittemans Laura B. L. , Lotta Luca A. , Oliver-Williams Clare , Stewart Isobel D. , Surendran Praveen , Karthikeyan Savita , Day Felix R. , Koulman Albert , Imamura Fumiaki , Zeng Lingyao , Erdmann Jeanette , Schunkert Heribert , Khaw Kay-Tee , Griffin Julian L. , Forouhi Nita G. , Scott Robert A. , Wood Angela M. , Burgess Stephen , Howson Joanna M. M. , Danesh John , Wareham Nicholas J. , Butterworth Adam S. , Langenberg Claudia 
Published: March 2019

AbstractCirculating levels of glycine have previously been associated with lower incidence of coronary heart disease (CHD) and type 2 diabetes (T2D) but it remains uncertain if glycine plays an aetiological role. We present a meta-analysis of genome-wide association studies for glycine in 80,003 participants and investigate the causality and potential mechanisms of the association between glycine and cardio-metabolic diseases using genetic approaches. We identify 27 genetic loci, of which 22 have not previously been reported for glycine. We show that glycine is genetically associated with lower CHD risk and find that this may be partly driven by blood pressure. Evidence for a genetic association of glycine with T2D is weaker, but we find a strong inverse genetic effect of hyperinsulinaemia on glycine. Our findings strengthen evidence for a protective effect of glycine on CHD and show that the glycine-T2D association may be driven by a glycine-lowering effect of insulin resistance.
Subtle changes in chromatin loop contact propensity are associated with differential gene regulation and expression
Authors: Greenwald William W. , Li He , Benaglio Paola , Jakubosky David , Matsui Hiroko , Schmitt Anthony , Selvaraj Siddarth , D’Antonio Matteo , D’Antonio-Chronowska Agnieszka , Smith Erin N. , Frazer Kelly A. 
Published: March 2019

AbstractWhile genetic variation at chromatin loops is relevant for human disease, the relationships between contact propensity (the probability that loci at loops physically interact), genetics, and gene regulation are unclear. We quantitatively interrogate these relationships by comparing Hi-C and molecular phenotype data across cell types and haplotypes. While chromatin loops consistently form across different cell types, they have subtle quantitative differences in contact frequency that are associated with larger changes in gene expression and H3K27ac. For the vast majority of loci with quantitative differences in contact frequency across haplotypes, the changes in magnitude are smaller than those across cell types; however, the proportional relationships between contact propensity, gene expression, and H3K27ac are consistent. These findings suggest that subtle changes in contact propensity have a biologically meaningful role in gene regulation and could be a mechanism by which regulatory genetic variants in loop anchors mediate effects on expression.
The Wolbachia mobilome in Culex pipiens includes a putative plasmid
Authors: Reveillaud Julie , Bordenstein Sarah R. , Cruaud Corinne , Shaiber Alon , Esen Özcan C. , Weill Mylène , Makoundou Patrick , Lolans Karen , Watson Andrea R. , Rakotoarivony Ignace , Bordenstein Seth R. , Eren A. Murat 
Published: March 2019

AbstractWolbachia is a genus of obligate intracellular bacteria found in nematodes and arthropods worldwide, including insect vectors that transmit dengue, West Nile, and Zika viruses. Wolbachia’s unique ability to alter host reproductive behavior through its temperate bacteriophage WO has enabled the development of new vector control strategies. However, our understanding of Wolbachia’s mobilome beyond its bacteriophages is incomplete. Here, we reconstruct near-complete Wolbachia genomes from individual ovary metagenomes of four wild Culex pipiens mosquitoes captured in France. In addition to viral genes missing from the Wolbachia reference genome, we identify a putative plasmid (pWCP), consisting of a 9.23-kbp circular element with 14 genes. We validate its presence in additional Culex pipiens mosquitoes using PCR, long-read sequencing, and screening of existing metagenomes. The discovery of this previously unrecognized extrachromosomal element opens additional possibilities for genetic manipulation of Wolbachia.
Pure PEDOT:PSS hydrogels
Authors: Lu Baoyang , Yuk Hyunwoo , Lin Shaoting , Jian Nannan , Qu Kai , Xu Jingkun , Zhao Xuanhe 
Published: March 2019

AbstractHydrogels of conducting polymers, particularly poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS), provide a promising electrical interface with biological tissues for sensing and stimulation, owing to their favorable electrical and mechanical properties. While existing methods mostly blend PEDOT:PSS with other compositions such as non-conductive polymers, the blending can compromise resultant hydrogels’ mechanical and/or electrical properties. Here, we show that designing interconnected networks of PEDOT:PSS nanofibrils via a simple method can yield high-performance pure PEDOT:PSS hydrogels. The method involves mixing volatile additive dimethyl sulfoxide (DMSO) into aqueous PEDOT:PSS solutions followed by controlled dry-annealing and rehydration. The resultant hydrogels exhibit a set of properties highly desirable for bioelectronic applications, including high electrical conductivity (~20 S cm−1 in PBS, ~40 S cm−1 in deionized water), high stretchability (> 35% strain), low Young’s modulus (~2 MPa), superior mechanical, electrical and electrochemical stability, and tunable isotropic/anisotropic swelling in wet physiological environments.
PIMKL: Pathway-Induced Multiple Kernel Learning
Authors: Manica Matteo , Cadow Joris , Mathis Roland , Rodríguez Martínez María 
Published: March 2019

AbstractReliable identification of molecular biomarkers is essential for accurate patient stratification. While state-of-the-art machine learning approaches for sample classification continue to push boundaries in terms of performance, most of these methods are not able to integrate different data types and lack generalization power, limiting their application in a clinical setting. Furthermore, many methods behave as black boxes, and we have very little understanding about the mechanisms that lead to the prediction. While opaqueness concerning machine behavior might not be a problem in deterministic domains, in health care, providing explanations about the molecular factors and phenotypes that are driving the classification is crucial to build trust in the performance of the predictive system. We propose Pathway-Induced Multiple Kernel Learning (PIMKL), a methodology to reliably classify samples that can also help gain insights into the molecular mechanisms that underlie the classification. PIMKL exploits prior knowledge in the form of a molecular interaction network and annotated gene sets, by optimizing a mixture of pathway-induced kernels using a Multiple Kernel Learning (MKL) algorithm, an approach that has demonstrated excellent performance in different machine learning applications. After optimizing the combination of kernels to predict a specific phenotype, the model provides a stable molecular signature that can be interpreted in the light of the ingested prior knowledge and that can be used in transfer learning tasks.
Succinyl-proteome profiling of Pyricularia oryzae, a devastating phytopathogenic fungus that causes rice blast disease
Authors: Wang Jiaoyu , Li Ling , Chai Rongyao , Zhang Zhen , Qiu Haiping , Mao Xueqin , Hao Zhongna , Wang Yanli , Sun Guochang 
Published: March 2019

AbstractPyricularia oryzae is the pathogen for rice blast disease, which is a devastating threat to rice production worldwide. Lysine succinylation, a newly identified post-translational modification, is associated with various cellular processes. Here, liquid chromatography tandem-mass spectrometry combined with a high-efficiency succinyl-lysine antibody was used to identify the succinylated peptides in P. oryzae. In total, 2109 lysine succinylation sites in 714 proteins were identified. Ten conserved succinylation sequence patterns were identified, among which, K*******Ksuc, and K**Ksuc, were two most preferred ones. The frequency of lysine succinylation sites, however, greatly varied among organisms, including plants, animals, and microbes. Interestingly, the numbers of succinylation site in each protein of P. oryzae were significantly greater than that of most previous published organisms. Gene ontology and KEGG analysis showed that these succinylated peptides are associated with a wide range of cellular functions, from metabolic processes to stimuli responses. Further analyses determined that lysine succinylation occurs on several key enzymes of the tricarboxylic acid cycle and glycolysis pathway, indicating that succinylation may play important roles in the regulation of basal metabolism in P. oryzae. Furthermore, more than 40 pathogenicity-related proteins were identified as succinylated proteins, suggesting an involvement of succinylation in pathogenicity. Our results provide the first comprehensive view of the P. oryzae succinylome and may aid to find potential pathogenicity-related proteins to control the rice blast disease. Significance Plant pathogens represent a great threat to world food security, and enormous reduction in the global yield of rice was caused by P. oryzae infection. Here, the succinylated proteins in P. oryzae were identified. Furthermore, comparison of succinylation sites among various species, indicating that different degrees of succinylation may be involved in the regulation of basal metabolism. This data facilitates our understanding of the metabolic pathways and proteins that are associated with pathogenicity.
Lissajous Scanning Two-photon Endomicroscope for In vivo Tissue Imaging
Authors: Kim Daniel Youngsuk , Hwang Kyungmin , Ahn Jinhyo , Seo Yeong-Hyeon , Kim Jae-Beom , Lee Soyoung , Yoon Jin-Hui , Kong Eunji , Jeong Yong , Jon Sangyong , Kim Pilhan , Jeong Ki-Hun 
Published: March 2019

AbstractAn endomicroscope opens new frontiers of non-invasive biopsy for in vivo imaging applications. Here we report two-photon laser scanning endomicroscope for in vivo cellular and tissue imaging using a Lissajous fiber scanner. The fiber scanner consists of a piezoelectric (PZT) tube, a single double-clad fiber (DCF) with high fluorescence collection, and a micro-tethered-silicon-oscillator (MTSO) for the separation of biaxial resonant scanning frequencies. The endomicroscopic imaging exhibits 5 frames/s with 99% in scanning density by using the selection rule of scanning frequencies. The endomicroscopic scanner was compactly packaged within a stainless tube of 2.6 mm in diameter with a high NA gradient-index (GRIN) lens, which can be easily inserted into the working channel of a conventional laparoscope. The lateral and axial resolutions of the endomicroscope are 0.70 µm and 7.6 μm, respectively. Two-photon fluorescence images of a stained kidney section and miscellaneous ex vivo and in vivo organs from wild type and green fluorescent protein transgenic (GFP-TG) mice were successfully obtained by using the endomicroscope. The endomicroscope also obtained label free images including autofluorescence and second-harmonic generation of an ear tissue of Thy1-GCaMP6 (GP5.17) mouse. The Lissajous scanning two-photon endomicroscope can provide a compact handheld platform for in vivo tissue imaging or optical biopsy applications.
miR-124 dosage regulates prefrontal cortex function by dopaminergic modulation
Authors: Kozuka Takashi , Omori Yoshihiro , Watanabe Satoshi , Tarusawa Etsuko , Yamamoto Haruka , Chaya Taro , Furuhashi Mayu , Morita Makiko , Sato Tetsuya , Hirose Shinichi , Ohkawa Yasuyuki , Yoshimura Yumiko , Hikida Takatoshi , Furukawa Takahisa 
Published: March 2019

AbstractMicroRNA-124 (miR-124) is evolutionarily highly conserved among species and one of the most abundantly expressed miRNAs in the developing and mature central nervous system (CNS). Previous studies reported that miR-124 plays a role in CNS development, such as neuronal differentiation, maturation, and survival. However, the role of miR-124 in normal brain function has not yet been revealed. Here, we subjected miR-124-1+/− mice, to a comprehensive behavioral battery. We found that miR-124-1+/− mice showed impaired prepulse inhibition (PPI), methamphetamine-induced hyperactivity, and social deficits. Whole cell recordings using prefrontal cortex (PFC) slices showed enhanced synaptic transmission in layer 5 pyramidal cells in the miR-124-1+/− PFC. Based on the results of behavioral and electrophysiological analysis, we focused on genes involved in the dopaminergic system and identified a significant increase of Drd2 expression level in the miR-124-1+/− PFC. Overexpression or knockdown of Drd2 in the control or miR-124-1+/− PFC demonstrates that aberrant Drd2 signaling leads to impaired PPI. Furthermore, we identified that expression of glucocorticoid receptor gene Nr3c1, which enhances Drd2 expression, increased in the miR-124-1+/− PFC. Taken together, the current study suggests that miR-124 dosage modulates PFC function through repressing the Drd2 pathway, suggesting a critical role of miR-124 in normal PFC function.
PLD-dependent phosphatidic acid microdomains are signaling platforms for podosome formation
Authors: Bolomini-Vittori Matteo , Mennens Svenja F. B. , Joosten Ben , Fransen Jack , Du Guangwei , van den Dries Koen , Cambi Alessandra 
Published: March 2019

AbstractLocal membrane phospholipid enrichment serves as docking platform for signaling proteins involved in many processes including cell adhesion and migration. Tissue-resident dendritic cells (DCs) assemble actomyosin-based structures called podosomes, which mediate adhesion and degradation of extracellular matrix for migration and antigen sampling. Recent evidence suggested the involvement of phospholipase D (PLD) and its product phosphatidic acid (PA) in podosome formation, but the spatiotemporal control of this process is poorly characterized. Here we determined the role of PLD1 and PLD2 isoforms in regulating podosome formation and dynamics in human primary DCs by combining PLD pharmacological inhibition with a fluorescent PA sensor and fluorescence microscopy. We found that ongoing PLD2 activity is required for the maintenance of podosomes, whereas both PLD1 and PLD2 control the early stages of podosome assembly. Furthermore, we captured the formation of PA microdomains accumulating at the membrane cytoplasmic leaflet of living DCs, in dynamic coordination with nascent podosome actin cores. Finally, we show that both PLD1 and PLD2 activity are important for podosome-mediated matrix degradation. Our results provide novel insight into the isoform-specific spatiotemporal regulation of PLD activity and further our understanding of the role of cell membrane phospholipids in controlling localized actin polymerization and cell protrusion.
Dynamic plant height QTL revealed in maize through remote sensing phenotyping using a high-throughput unmanned aerial vehicle (UAV)
Authors: Wang Xiaqing , Zhang Ruyang , Song Wei , Han Liang , Liu Xiaolei , Sun Xuan , Luo Meijie , Chen Kuan , Zhang Yunxia , Yang Hao , Yang Guijun , Zhao Yanxin , Zhao Jiuran 
Published: March 2019

AbstractPlant height (PH) is a key factor in maize (Zea maysL.) yield, biomass, and plant architecture. We investigated the PH of diverse maize inbred lines (117 temperate lines, 135 tropical lines) at four growth stages using unmanned aerial vehicle high-throughput phenotypic platforms (UAV-HTPPs). We extracted PH data using an automated pipeline based on crop surface models and orthomosaic model. The correlation between UAV and manually measured PH data reached 0.95. Under temperate field conditions, temperate maize lines grew faster than tropical maize lines at early growth stages, but tropical lines grew faster at later growth stages and ultimately became taller than temperate lines. A genome-wide association study identified 68 unique quantitative trait loci (QTLs) for seven PH-related traits, and 35% of the QTLs coincided with those previously reported to control PH. Generally, different QTLs controlled PH at different growth stages, but eight QTLs simultaneously controlled PH and growth rate at multiple growth stages. Based on gene annotations and expression profiles, we identified candidate genes controlling PH. The PH data collected by the UAV-HTPPs were credible and the genetic mapping power was high. Therefore, UAV-HTPPs have great potential for use in studies on PH.
Partially spatially coherent digital holographic microscopy and machine learning for quantitative analysis of human spermatozoa under oxidative stress condition
Authors: Dubey Vishesh , Popova Daria , Ahmad Azeem , Acharya Ganesh , Basnet Purusotam , Mehta Dalip Singh , Ahluwalia Balpreet Singh 
Published: March 2019

AbstractSemen quality assessed by sperm count and sperm cell characteristics such as morphology and motility, is considered to be the main determinant of men’s reproductive health. Therefore, sperm cell selection is vital in assisted reproductive technology (ART) used for the treatment of infertility. Conventional bright field optical microscopy is widely utilized for the imaging and selection of sperm cells based on the qualitative analysis by experienced clinicians. In this study, we report the development of a highly sensitive quantitative phase microscopy (QPM) using partially spatially coherent light source, which is a label-free, non-invasive and high-resolution technique to quantify various biophysical parameters. The partial spatial coherence nature of light source provides a significant improvement in spatial phase sensitivity and hence reconstruction of the phase of the entire sperm cell is demonstrated, which was otherwise not possible using highly spatially coherent light source. High sensitivity of the system enables quantitative phase imaging of the specimens having very low refractive index contrast with respect to the medium like tail of the sperm cells. Further, it also benefits with accurate quantification of 3D-morphological parameters of sperm cells which might be helpful in the infertility treatment. The quantitative analysis of more than 2500 sperm cells under hydrogen peroxide (H2O2) induced oxidative stress condition is demonstrated. It is further correlated with motility of sperm cell to study the effect of oxidative stress on healthy sperm cells. The results exhibit a decrease in the maximum phase values of the sperm head as well as decrease in the sperm cell’s motility with increasing oxidative stress, i.e., H2O2concentration. Various morphological and texture parameters were extracted from the phase maps and subsequently support vector machine (SVM) based machine learning algorithm is employed for the classification of the control and the stressed sperms cells. The algorithm achieves an area under the receiver operator characteristic (ROC) curve of 89.93% based on the all morphological and texture parameters with a sensitivity of 91.18%. The proposed approach can be implemented for live sperm cells selection in ART procedure for the treatment of infertility.
The 1997 Mars Pathfinder Spacecraft Landing Site: Spillover Deposits from an Early Mars Inland Sea
Authors: Rodriguez J. A. P. , Baker V. R. , Liu T. , Zarroca M. , Travis B. , Hui T. , Komatsu G. , Berman D. C. , Linares R. , Sykes M. V. , Banks M. E. , Kargel J. S. 
Published: March 2019

AbstractThe Martian outflow channels comprise some of the largest known channels in the Solar System. Remote-sensing investigations indicate that cataclysmic floods likely excavated the channels ~3.4 Ga. Previous studies show that, in the southern circum-Chryse region, their flooding pathways include hundreds of kilometers of channel floors with upward gradients. However, the impact of the reversed channel-floor topography on the cataclysmic floods remains uncertain. Here, we show that these channel floors occur within a vast basin, which separates the downstream reaches of numerous outflow channels from the northern plains. Consequently, floods propagating through these channels must have ponded, producing an inland sea, before reaching the northern plains as enormous spillover discharges. The resulting paleohydrological reconstruction reinterprets the 1997 Pathfinder landing site as part of a marine spillway, which connected the inland sea to a hypothesized northern plains ocean. Our flood simulation shows that the presence of the sea would have permitted the propagation of low-depth floods beyond the areas of reversed channel-floor topography. These results explain the formation at the landing site of possible fluvial features indicative of flow depths at least an order of magnitude lower than those apparent from the analyses of orbital remote-sensing observations.
Wide-field choroidal thickness in myopes and emmetropes
Authors: Hoseini-Yazdi Hosein , Vincent Stephen J. , Collins Michael J. , Read Scott A. , Alonso-Caneiro David 
Published: March 2019

AbstractThere is a paucity of knowledge regarding the normal in-vivo thickness of the choroid beyond the macula (~17°). In this study, the choroidal thickness of 27 healthy young adults was examined across the macular (the central 5 mm including the fovea, parafovea, and perifovea) and extra-macular (a 5–14 mm annulus including the near-periphery and periphery) regions using wide-field optical coherence tomography, and compared between emmetropes (n = 14) and myopes (n = 13). The choroid progressively thinned beyond the parafovea (350 ± 86 µm) towards the periphery (264 ± 44 µm), and was thickest superiorly (355 ± 76 µm) and thinnest nasally (290 ± 79 µm). Choroidal thickness also varied with refractive error; myopes exhibited a thinner choroid than emmetropes in the macular region (311 ± 88 vs. 383 ± 66 µm), however, this difference diminished towards the periphery (251 ± 48 vs. 277 ± 37 µm). Meridional variations in choroidal thickness were not different between myopes and emmetropes. In conclusion, the choroid was thickest within the perifovea; thinned substantially towards the periphery, and exhibited the minimum and maximum peripheral thinning superiorly and nasally across a 55° region respectively. Choroidal thinning associated with myopia was more pronounced in the macular than extra-macular regions.
Short- and Long-term Risks of Highly Active Antiretroviral Treatment with Incident Opportunistic Infections among People Living with HIV/AIDS
Authors: Yen Yung-Feng , Chen Marcelo , Jen I.-An , Chuang Pei-Hung , Lee Chun-Yuan , Lin Su-I. , Chen Yi-Ming Arthur 
Published: March 2019

AbstractHighly active antiretroviral therapy (HAART) causes a rapid increase of CD4 + T cells counts during the first 3–6 months of treatment and may enhance the development of opportunistic infections (OIs). However, the short- and long-term effects of HAART exposure on the development of incident OIs has not been extensively studied. This nationwide longitudinal study followed up a total of 26,258 people living with HIV/AIDS (PLWHA) to ascertain the short- and long-term effects of HAART on incident OIs. During 150,196 person-years of follow-up, 6,413 (24.4%) PLWHA had new onset of OIs. After adjusting for demographics, comorbidities, and AIDS status, PLWHA who received HAART were more likely to develop OIs than those who did not receive HAART. Considering the short- and long-term effects of HAART on the development of OIs, HAART was found to be a risk factor for developing OIs during the first 90 days of treatment, but a protective factor against OIs after 180 days of HAART use. The risk for the development of active OIs significantly decreased as the duration of HAART increased (P < 0.001). Our study suggests that HAART is a risk factor for developing OIs in the short term, but is a protective factor in the long term.