bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissecting super-enhancer hierarchy based on chromatin interactions
Authors: Huang Jialiang , Li Kailong , Cai Wenqing , Liu Xin , Zhang Yuannyu , Orkin Stuart H. , Xu Jian , Yuan Guo-Cheng 
Published: February 2018

AbstractRecent studies have highlighted super-enhancers (SEs) as important regulatory elements for gene expression, but their intrinsic properties remain incompletely characterized. Through an integrative analysis of Hi-C and ChIP-seq data, here we find that a significant fraction of SEs are hierarchically organized, containing both hub and non-hub enhancers. Hub enhancers share similar histone marks with non-hub enhancers, but are distinctly associated with cohesin and CTCF binding sites and disease-associated genetic variants. Genetic ablation of hub enhancers results in profound defects in gene activation and local chromatin landscape. As such, hub enhancers are the major constituents responsible for SE functional and structural organization.
A diminutive perinate European Enantiornithes reveals an asynchronous ossification pattern in early birds
Authors: Knoll Fabien , Chiappe Luis M. , Sanchez Sophie , Garwood Russell J. , Edwards Nicholas P. , Wogelius Roy A. , Sellers William I. , Manning Phillip L. , Ortega Francisco , Serrano Francisco J. , Marugán-Lobón Jesús , Cuesta Elena , Escaso Fernando , Sanz Jose Luis 
Published: February 2018

AbstractFossils of juvenile Mesozoic birds provide insight into the early evolution of avian development, however such fossils are rare. The analysis of the ossification sequence in these early-branching birds has the potential to address important questions about their comparative developmental biology and to help understand their morphological evolution and ecological differentiation. Here we report on an early juvenile enantiornithine specimen from the Early Cretaceous of Europe, which sheds new light on the osteogenesis in this most species-rich clade of Mesozoic birds. Consisting of a nearly complete skeleton, it is amongst the smallest known Mesozoic avian fossils representing post-hatching stages of development. Comparisons between this new specimen and other known early juvenile enantiornithines support a clade-wide asynchronous pattern of osteogenesis in the sternum and the vertebral column, and strongly indicate that the hatchlings of these phylogenetically basal birds varied greatly in size and tempo of skeletal maturation.
A browser-based tool for visualization and analysis of diffusion MRI data
Authors: Yeatman Jason D. , Richie-Halford Adam , Smith Josh K. , Keshavan Anisha , Rokem Ariel 
Published: February 2018

AbstractHuman neuroscience research faces several challenges with regards to reproducibility. While scientists are generally aware that data sharing is important, it is not always clear how to share data in a manner that allows other labs to understand and reproduce published findings. Here we report a new open source tool, AFQ-Browser, that builds an interactive website as a companion to a diffusion MRI study. Because AFQ-Browser is portable—it runs in any web-browser—it can facilitate transparency and data sharing. Moreover, by leveraging new web-visualization technologies to create linked views between different dimensions of the dataset (anatomy, diffusion metrics, subject metadata), AFQ-Browser facilitates exploratory data analysis, fueling new discoveries based on previously published datasets. In an era where Big Data is playing an increasingly prominent role in scientific discovery, so will browser-based tools for exploring high-dimensional datasets, communicating scientific discoveries, aggregating data across labs, and publishing data alongside manuscripts.
Cancer-associated fibroblasts induce antigen-specific deletion of CD8 + T Cells to protect tumour cells
Authors: Lakins Matthew A. , Ghorani Ehsan , Munir Hafsa , Martins Carla P. , Shields Jacqueline D. 
Published: February 2018

AbstractTumours have developed strategies to interfere with most steps required for anti-tumour immune responses. Although many populations contribute to anti-tumour responses, tumour-infiltrating cytotoxic T cells dominate, hence, many suppressive strategies act to inhibit these. Tumour-associated T cells are frequently restricted to stromal zones rather than tumour islands, raising the possibility that the tumour microenvironment, where crosstalk between malignant and “normal” stromal cells exists, may be critical for T cell suppression. We provide evidence of direct interactions between stroma and T cells driving suppression, showing that cancer-associated fibroblasts (CAFs) sample, process and cross-present antigen, killing CD8+T cells in an antigen-specific, antigen-dependent manner via PD-L2 and FASL. Inhibitory ligand expression is observed in CAFs from human tumours, and neutralisation of PD-L2 or FASL reactivates T cell cytotoxic capacity in vitro and in vivo. Thus, CAFs support T cell suppression within the tumour microenvironment by a mechanism dependent on immune checkpoint activation.
Convergent shifts in host-associated microbial communities across environmentally elicited phenotypes
Authors: Carrier Tyler J. , Reitzel Adam M. 
Published: February 2018

AbstractMorphological plasticity is a genotype-by-environment interaction that enables organisms to increase fitness across varying environments. Symbioses with diverse microbiota may aid in acclimating to this variation, but whether the associated bacteria community is phenotype specific remains understudied. Here we induce morphological plasticity in three species of sea urchin larvae and measure changes in the associated bacterial community. While each host species has unique bacterial communities, the expression of plasticity results in the convergence on a phenotype-specific microbiome that is, in part, driven by differential association with α- and γ-proteobacteria. Furthermore, these results suggest that phenotype-specific signatures are the product of the environment and are correlated with ingestive and digestive structures. By manipulating diet quantity over time, we also show that differentially associating with microbiota along a phenotypic continuum is bidirectional. Taken together, our data support the idea of a phenotype-specific microbial community and that phenotypic plasticity extends beyond a genotype-by-environment interaction.
Elucidating anionic oxygen activity in lithium-rich layered oxides
Authors: Xu Jing , Sun Meiling , Qiao Ruimin , Renfrew Sara E. , Ma Lu , Wu Tianpin , Hwang Sooyeon , Nordlund Dennis , Su Dong , Amine Khalil , Lu Jun , McCloskey Bryan D. , Yang Wanli , Tong Wei 
Published: February 2018

AbstractRecent research has explored combining conventional transition-metal redox with anionic lattice oxygen redox as a new and exciting direction to search for high-capacity lithium-ion cathodes. Here, we probe the poorly understood electrochemical activity of anionic oxygen from a material perspective by elucidating the effect of the transition metal on oxygen redox activity. We study two lithium-rich layered oxides, specifically lithium nickel metal oxides where metal is either manganese or ruthenium, which possess a similar structure and discharge characteristics, but exhibit distinctly different charge profiles. By combining X-ray spectroscopy with operando differential electrochemical mass spectrometry, we reveal completely different oxygen redox activity in each material, likely resulting from the different interaction between the lattice oxygen and transition metals. This work provides additional insights into the complex mechanism of oxygen redox and development of advanced high-capacity lithium-ion cathodes.
The Seasonality of Acute Attack of Primary Angle-Closure Glaucoma in Beijing, China
Authors: Zhu Jingyuan , Xu Yang , Wang Hongyuan , Liu Dongjing , Zhu Jingbo , Wu Huijuan 
Published: February 2018

AbstractIn this study, the seasonality of acute attack of primary angle-closure glaucoma (PACG) was analysed. This retrospective case series included 283 patients (200 women, 83 men; mean age, 68.2 ± 10.3 years; range, 37–96 years) with acute attack of PACG from a university-based clinic over 4 years. Patients’ age and sex, and the date and season of onset of PACG attack, were analysed. Descriptive analysis and von Mises distribution were used for statistical analysis. The highest incidence of acute attack of PACG was observed in those aged 60–69 years (34.6%). Descriptive analysis showed that the incidence was greater in June and July for men, November for women, and November for the entire sample. An angular plot (using von Mises distribution) of the individual dates of onset revealed the estimated peak onset on September 11, November 8, and October 28 for men, women, and both, respectively. Integration of the results from the two analyses revealed the incidence to be higher in the summer and winter for men, and in the winter for women and for the entire sample. More females than males were affected. Monthly and seasonal variations in onset were observed, which might be related to weather changes.
A retrospective study of community-acquired Clostridium difficile infection in southwest China
Authors: Liao Feng , Li Wenge , Gu Wenpeng , Zhang Wenzhu , Liu Xiaoshu , Fu Xiaoqing , Xu Wen , Wu Yuan , Lu Jinxing 
Published: February 2018

AbstractTo identify the prevalence and characteristics of community-acquiredClostridium difficileinfection (CA-CDI) in southwest China, we conducted a cross-sectional study. 978 diarrhea patients were enrolled and stool specimens’ DNA was screened for virulence genes. Bacterial culture was performed and isolates were characterized by PCR ribotyping and multilocus sequence typing. Toxin genestcdAand/ortcdBwere found in 138/978 (14.11%) cases for fecal samples. A total of 55 C. difficilestrains were isolated (5.62%). The positive rate of toxin genes and isolation results had no statistical significance between children and adults groups. However, some clinical features, such as fecal property, diarrhea times before hospital treatment shown difference between two groups. The watery stool was more likely found in children, while the blood stool for adults; most of children cases diarrhea ≤3 times before hospital treatment, and adults diarrhea >3 times. Independent risk factor associated with CA-CDI was patients with fever. ST35/RT046 (18.18%), ST54/RT012 (14.55%), ST3/RT001 (14.55%) and ST3/RT009 (12.73%) were the most distributed genotype profiles. ST35/RT046, ST3/RT001 and ST3/RT009 were the commonly found in children patients but ST54/RT012 for adults. The prevalence of CA-CDI in Yunnan province was relatively high, and isolates displayed heterogeneity between children and adults groups.
Circuit-specific and neuronal subcellular-wide E-I balance in cortical pyramidal cells
Authors: Yang Weiguo , Sun Qian-Quan 
Published: February 2018

AbstractWe used ChR2-assisted circuit mapping (CRACM) to examine neuronal/compartmental excitatory and inhibitory synaptic balance (E-I balance) in pyramidal cells (PCs) located in several brain regions (including both neocortices and paleocortices). Within the vS1, different inputs on the same neurons, or the same inputs formed on different targets, induced different E/I ratios. E/I ratios in PCs from different regions were largely different. Chemogenetic silencing of somatostatin (SOM)- or parvalbumin (PV)-containing interneurons (INs) while optogenetically activating long-range M1 inputs demonstrated differential contribution of PV and SOM INs to the E/I ratios in a layer-specific manner in S1. Our results thus demonstrate that there are both universal subcellular-wide E-I balance within single PC and high specificity in the value of E/I ratios across different circuits (i.e. visual, somatosensory, piriform and hippocampal). Specificity of E/I balance are likely caused by unique glutamatergic innervation of interneurons. The dichotomy of high specificity and generalization of subcellular E-I balance in different circuits forms the basis for further understanding of neuronal computation under physiological conditions and various neuro-psychiatric disease-states.
Recombinant RNA-Dependent RNA Polymerase Complex of Ebola Virus
Authors: Tchesnokov Egor P. , Raeisimakiani Parisa , Ngure Marianne , Marchant David , Götte Matthias 
Published: February 2018

AbstractHere we report on the expression, purification and characterization of recombinant ebola virus RNA-dependent RNA polymerase (EBOV RdRp). Active protein complexes composed of the large L protein and viral protein VP35 were isolated from insect cells and analyzed using a short primer/template substrate that allowed benchmarking against related enzymes. RNA synthesis by multiprotein complexes of EBOV, influenza B, respiratory syncytial virus (RSV) and monomeric enzymes of hepatitis C and Zika (ZIKV) viruses required a 5′-phosporylated primer. The minimum length of the primer varied between two and three nucleotides in this system. The EBOV enzyme utilizes Mg2+ as a co-factor and the D742A substitution provides an active site mutant that likely affects binding of the catalytic metal ions. Selectivity measurements with nucleotide analogues translate our assay into quantitative terms and facilitate drug discovery efforts. The related EBOV and RSV enzymes are not able to efficiently discriminate against ara-cytidine-5′-triphosphate. We demonstrate that this compound acts like a non-obligate chain-terminator.
Changes in global translation elongation or initiation rates shape the proteome via the Kozak sequence
Authors: Acevedo Julieta M. , Hoermann Bernhard , Schlimbach Tilo , Teleman Aurelio A. 
Published: February 2018

AbstractThe sequence context surrounding the AUG start codon of an open reading frame - the ‘Kozak sequence’ - affects the probability with which a scanning ribosome will recognize the start codon and start translating there. A significant number of transcripts in animals such as Drosophila contain weak Kozak sequences. This is predicted to cause constitutively low translation of these transcripts. We study here the additional possibility that these mRNAs have weak Kozak sequences to allow for the regulation of their translation in response to stress or altered cellular signaling. We find that transcripts with weak Kozak sequences are less sensitive to drops in global elongation rates and more sensitive to drops in global initiation rates compared to transcripts with strong Kozak sequences. This provides a mechanism by which changes in these global translation parameters differentially affect different pools of mRNAs depending on their Kozak sequence, thereby shaping the proteome. Interestingly, mRNAs with weak Kozak sequences are enriched for genes involved in neurobiology, suggesting that they constitute a functional group that can be translationally co-regulated.
Prediction of pKa Values for Neutral and Basic Drugs based on Hybrid Artificial Intelligence Methods
Authors: Li Mengshan , Zhang Huaijing , Chen Bingsheng , Wu Yan , Guan Lixin 
Published: February 2018

AbstractThe pKa value of drugs is an important parameter in drug design and pharmacology. In this paper, an improved particle swarm optimization (PSO) algorithm was proposed based on the population entropy diversity. In the improved algorithm, when the population entropy was higher than the set maximum threshold, the convergence strategy was adopted; when the population entropy was lower than the set minimum threshold the divergence strategy was adopted; when the population entropy was between the maximum and minimum threshold, the self-adaptive adjustment strategy was maintained. The improved PSO algorithm was applied in the training of radial basis function artificial neural network (RBF ANN) model and the selection of molecular descriptors. A quantitative structure-activity relationship model based on RBF ANN trained by the improved PSO algorithm was proposed to predict the pKa values of 74 kinds of neutral and basic drugs and then validated by another database containing 20 molecules. The validation results showed that the model had a good prediction performance. The absolute average relative error, root mean square error, and squared correlation coefficient were 0.3105, 0.0411, and 0.9685, respectively. The model can be used as a reference for exploring other quantitative structure-activity relationships.
Low intensity repetitive transcranial magnetic stimulation modulates skilled motor learning in adult mice
Authors: Tang Alexander D. , Bennett William , Hadrill Claire , Collins Jessica , Fulopova Barbora , Wills Karen , Bindoff Aidan , Puri Rohan , Garry Michael I. , Hinder Mark R. , Summers Jeffery J. , Rodger Jennifer , Canty Alison J. 
Published: February 2018

AbstractRepetitive transcranial magnetic stimulation (rTMS) is commonly used to modulate cortical plasticity in clinical and non-clinical populations. Clinically, rTMS is delivered to targeted regions of the cortex at high intensities (>1 T). We have previously shown that even at low intensities, rTMS induces structural and molecular plasticity in the rodent cortex. To determine whether low intensity rTMS (LI-rTMS) alters behavioural performance, daily intermittent theta burst LI-rTMS (120 mT) or sham was delivered as a priming or consolidating stimulus to mice completing 10 consecutive days of skilled reaching training. Relative to sham, priming LI-rTMS (before each training session), increased skill accuracy (~9%) but did not alter the rate of learning over time. In contrast, consolidating LI-rTMS (after each training session), resulted in a small increase in the rate of learning (an additional ~1.6% each day) but did not alter the daily skill accuracy. Changes in behaviour with LI-rTMS were not accompanied with long lasting changes in brain-derived neurotrophic factor (BDNF) expression or in the expression of plasticity markers at excitatory and inhibitory synapses for either priming or consolidation groups. These results suggest that LI-rTMS can alter specific aspects of skilled motor learning in a manner dependent on the timing of intervention.
Cedratvirus getuliensis replication cycle: an in-depth morphological analysis
Authors: Silva Ludmila Karen dos Santos , Andrade Ana Cláudia dos Santos Pereira , Dornas Fábio Pio , Rodrigues Rodrigo Araújo Lima , Arantes Thalita , Kroon Erna Geessien , Bonjardim Cláudio Antônio , Abrahão Jônatas Santos 
Published: February 2018

AbstractThe giant viruses are the largest and most complex viruses in the virosphere. In the last decade, new members have constantly been added to this group. Here, we provide an in-depth descriptive analysis of the replication cycle of Cedratvirus getuliensis, one of the largest viruses known to date. We tracked the virion entry, the early steps of virus factory and particles morphogenesis, and during this phase, we observed a complex and unique sequential organization of immature particle elements, including horseshoe and rectangular compartments, revealed by transverse and longitudinal sections, respectively, until the formation of the final ovoid-shaped striped virion. The genome and virion proteins are incorporated through a longitudinal opening in the immature virion, followed by the incorporation of the second cork and thickening of the capsid well. Moreover, many cell modifications occur during viral infection, including intense membrane trafficking important to viral morphogenesis and release, as evidenced by treatment using brefeldin A. Finally, we observed that Cedratvirus getuliensis particles are released after cellular lysis, although we obtained microscopic evidence that some particles are released by exocytosis. The present study provides new information on the unexplored steps in the life cycle of cedratviruses.
Comparative efficacy of corticosteroid injection and non-invasive treatments for plantar fasciitis: a systematic review and meta-analysis
Authors: Chen Chien-Min , Lee Meng , Lin Chia-Hung , Chang Chia-Hao , Lin Chu-Hsu 
Published: February 2018

AbstractThe first choice of treatment for patients with plantar fasciitis is non-invasive treatment, rather than corticosteroid injection (CSI). However, no comprehensive study has compared the effectiveness of CSI with non-invasive treatments for plantar fasciitis. We conducted a meta-analysis comparing CSI and non-invasive treatment effects on plantar fasciitis. The primary outcome was pain reduction. Nine randomized controlled trials comparing CSI with 4 non-invasive treatment types were included. A trend favoring CSI over non-invasive treatments was indicated regarding reduction in the visual analogue scale (VAS) score at 1–1.5 (mean difference (MD), 1.70; 95% confidence interval (CI) = 0.39–3.01; P = 0.01) and 2–3 months (MD, 1.67; 95% CI = 0.58–2.76; P = 0.003). At 1.5-month follow-up, CSI was associated with improved VAS score compared with physical therapy (PT) (MD, 2.5; 95% CI = 0.1–4.9; P = 0.04). No significant differences in the VAS score reduction were observed between CSI and shock wave therapy within 3 months. In summary, CSI tends to be more effective for pain reduction than non-invasive treatments within 3 months. Moreover, CSI provides significant pain relief at 1.5 months after treatment compared with PT. This study provides important clinical information for selecting therapeutics.
Night Sleep Duration and Risk of Incident Anemia in a Chinese Population: A Prospective Cohort Study
Authors: Liu Xiaoxue , Song Qiaofeng , Hu Wanning , Han Xiaochen , Gan Jianhui , Zheng Xiang , Wang Xizhu , Wu Shouling 
Published: February 2018

AbstractThe purpose was to study the association between sleep duration and the prevalence of anemia in Chinese people. There were 84,791 participants (men: 79.1%; women: 20.9%) aged 18–98 years in the prospective study. We divided the participants into five categories based on the individual sleep duration: ≤5 h, 6 h, 7 h(reference), 8 h, and ≥9 h. Anemia was defined based on hemoglobin <12 g/dL for men and <11 g/dL for women. The Cox proportional hazards model was used to assess the association between sleep duration and anemia. During median follow-up of 7.9 years, 2698 cases of anemia had occurred. The HRand (95% CI) of anemia (7 h as the reference group) for individuals reporting ≤5 h, 6 h, 8 h, and ≥9 h were 1.23(1.04–1.45), 1.26(1.11–1.44), 1.04(0.92–1.16) and 1.42(1.08–1.86), respectively. It showed that there was a significant interaction on the risk of anemia between sleep duration and sex in the secondary analysis (p < 0.001).The significant association between long sleepduration and anemia was found in women (HR, 2.29; 95% CI, 1.56–3.37), not in men(HR, 0.90; 95% CI, 0.60–1.34). Both short and long night sleep duration were associated with increased risk of anemia.
Use of Ultrasonic Device in Cervical and Thoracic Laminectomy: a Retrospective Comparative Study and Technical Note
Authors: Chen Yu , Chang Zhengqi , Yu Xiuchun , Song Ruoxian , Huang Weimin 
Published: February 2018

AbstractMultilevel severe compressive myelopathy is a challenging disorder for the surgeons, the aim of this study is to assess the efficacy and safety of a newly designed ultrasonic burr as an assistant tool to the ultrasonic scalpel in laminectomy for this disease. This is a retrospective comparative study, the included subjects were patients who received cervical and thoracic laminectomy using ultrasonic device (LUD, n = 9, 10 surgeries) and controls with the high-speed burr (LHB, n = 16). Fifteen patients (60.0%) showed severe cord occupancy and the average number of laminae operated was 3.5. Ultrasonic devices caused less blood loss (P = 0.02) and quicker operative time per level (P < 0.001) than LHB, and was associated with more operated laminae (P = 0.04). Preoperative JOA scores (P = 0.51), improvement rate (P = 0.47), and dural injury (P = 0.51) were not related to LUD. Our experience indicates ultrasonic devices are safe and effective for laminectomy treating multilevel and severe compressive myelopathy, the instrument could be used with ease especially for cases with ossified posterior longitudinal ligament and ossification of the ligamentum flavum, proper utility of the instrument is crucial to prevent complications.