bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin-11 signaling underlies fibrosis, parenchymal dysfunction, and chronic inflammation of the airway
Authors: Ng Benjamin , Cook Stuart A. , Schafer Sebastian 
Published: December 2020

AbstractInterleukin (IL)-11 evolved as part of the innate immune response. In the human lung, IL-11 upregulation has been associated with viral infections and a range of fibroinflammatory diseases, including idiopathic pulmonary fibrosis. Transforming growth factor-beta (TGFβ) and other disease factors can initiate an autocrine loop of IL-11 signaling in pulmonary fibroblasts, which, in a largely ERK-dependent manner, triggers the translation of profibrotic proteins. Lung epithelial cells also express the IL-11 receptor and transition into a mesenchymal-like state in response to IL-11 exposure. In mice, therapeutic targeting of IL-11 with antibodies can arrest and reverse bleomycin-induced pulmonary fibrosis and inflammation. Intriguingly, fibroblast-specific blockade of IL-11 signaling has anti-inflammatory effects, which suggests that lung inflammation is sustained, in part, through IL-11 activity in the stroma. Proinflammatory fibroblasts and their interaction with the damaged epithelium may represent an important but overlooked driver of lung disease. Initially thought of as a protective cytokine, IL-11 is now increasingly recognized as an important determinant of lung fibrosis, inflammation, and epithelial dysfunction.
Superchiral near fields detect virus structure
Authors: Kakkar Tarun , Keijzer Chantal , Rodier Marion , Bukharova Tatyana , Taliansky Michael , Love Andrew J. , Milner Joel J. , Karimullah Affar S. , Barron Laurence D. , Gadegaard Nikolaj , Lapthorn Adrian J. , Kadodwala Malcolm 
Published: December 2020

AbstractOptical spectroscopy can be used to quickly characterise the structural properties of individual molecules. However, it cannot be applied to biological assemblies because light is generally blind to the spatial distribution of the component molecules. This insensitivity arises from the mismatch in length scales between the assemblies (a few tens of nm) and the wavelength of light required to excite chromophores (≥150 nm). Consequently, with conventional spectroscopy, ordered assemblies, such as the icosahedral capsids of viruses, appear to be indistinguishable isotropic spherical objects. This limits potential routes to rapid high-throughput portable detection appropriate for point-of-care diagnostics. Here, we demonstrate that chiral electromagnetic (EM) near fields, which have both enhanced chiral asymmetry (referred to as superchirality) and subwavelength spatial localisation (∼10 nm), can detect the icosahedral structure of virus capsids. Thus, they can detect both the presence and relative orientation of a bound virus capsid. To illustrate the potential uses of the exquisite structural sensitivity of subwavelength superchiral fields, we have used them to successfully detect virus particles in the complex milieu of blood serum.
FOXO3a-driven miRNA signatures suppresses VEGF-A/NRP1 signaling and breast cancer metastasis
Authors: Song Ying , Zeng Shanshan , Zheng Guopei , Chen Danyang , Li Pan , Yang Mingqiang , Luo Kai , Yin Jiang , Gu Yixue , Zhang Zhijie , Jia Xiaoting , Qiu Ni , He Zhimin , Li Hongsheng , Liu Hao 
Published: December 2020

AbstractMetastasis remains the major obstacle to improved survival for breast cancer patients. Downregulation of FOXO3a transcription factor in breast cancer is causally associated with the development of metastasis through poorly understood mechanisms. Here, we report that FOXO3a is functionally related to the inhibition of VEGF-A/NRP1 signaling and to the consequent suppression of breast cancer metastasis. We show that FOXO3a directly induces miR-29b-2 and miR-338 expression. Ectopic expression of miR-29b-2/miR-338 significantly suppresses EMT, migration/invasion, and in vivo metastasis of breast cancer. Moreover, we demonstrate that miR-29b-2 directly targets VEGF-A while miR-338 directly targets NRP1, and show that regulation of miR-29b-2 and miR-338 mediates the ability of FOXO3a to suppress VEGF-A/NRP1 signaling and breast cancer metastasis. Clinically, our results show that the FOXO3a-miR-29b-2/miR-338-VEGF-A/NRP1 axis is dysregulated and plays a critical role in disease progression in breast cancer. Collectively, our findings propose that FOXO3a functions as a metastasis suppressor, and define a novel signaling axis of FOXO3a-miRNA-VEGF-A/NRP1 in breast cancer, which might be potential therapeutic targets for breast cancer.
Putting Warburg to work: how imaging of tumour acidosis could help predict metastatic potential in breast cancer
Authors: Rolver Michala Gylling , Pedersen Stine Falsig 
Published: December 2020

SummarySolid tumours are often highly acidic compared to normal tissue, and tumour extracellular acidosis contributes to multiple aspects of cancer progression. Now, Anemone et al. in this issue of the British Journal of Cancer provide in vivo evidence that the degree to which various breast cancer cell lines acidify their environment correlates with their ability to metastasise to the lungs. This indicates that measurements of tumour extracellular acidosis have the potential to become a clinical tool for assessing the risk of metastasis.
Postoperative, but not preoperative, inflammation-based prognostic markers are prognostic factors in stage III colorectal cancer patients
Authors: Yasui Kohei , Shida Dai , Nakamura Yuya , Ahiko Yuka , Tsukamoto Shunsuke , Kanemitsu Yukihide 
Published: December 2020

Abstract
Background
Recent evidence suggests that both preoperative and postoperative inflammation-based prognostic markers are useful for predicting the survival of colorectal cancer (CRC) patients. However, associations between longitudinal changes in inflammation-based prognostic markers and prognosis are controversial.

Methods
The subjects of this study were 568 patients with stage III CRC between 2008 and 2014. Preoperative and postoperative neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein/albumin ratio (CAR) and lymphocyte-to-C-reactive protein ratio (LCR) were calculated to assess the inflammatory state of subjects. Subjects were stratified into three groups for each marker: preoperatively low inflammatory state (normal group), preoperatively high but postoperatively low inflammatory state (normalised group) and persistently high inflammatory state (elevated group). Multivariable analyses for overall survival (OS) and recurrence-free survival (RFS) were performed to adjust for well-established clinicopathologic factors.

Results
For all assessed markers, the normalised group had a significantly better prognosis than the elevated group and a similar prognosis as the normal group for both OS and RFS.

Conclusions
Postoperative, but not preoperative, inflammation-based prognostic markers more accurately predict OS and RFS in patients with stage III CRC.
Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection
Authors: Yao Hangping , Sun Yao , Deng Yong-Qiang , Wang Nan , Tan Yongcong , Zhang Na-Na , Li Xiao-Feng , Kong Chao , Xu Yan-Peng , Chen Qi , Cao Tian-Shu , Zhao Hui , Yan Xintian , Cao Lei , Lv Zhe , Zhu Dandan , Feng Rui , Wu Nanping , Zhang Wenhai , Hu Yuhao , Chen Keda , Zhang Rong-Rong , Lv Qingyu , Sun Shihui , Zhou Yunhua , Yan Run , Yang Guan , Sun Xinglu , Liu Chanjuan , Lu Xiangyun , Cheng Linfang , Qiu Hongying , Huang Xing-Yao , Weng Tianhao , Shi Danrong , Jiang Weidong , Shao Junbin , Wang Lei , Zhang Jie , Jiang Tao , Lang Guojun , Qin Cheng-Feng , Li Lanjuan , Wang Xiangxi 
Published: December 2020

AbstractStructural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.
Identification of key gene networks controlling organic acid and sugar metabolism during watermelon fruit development by integrating metabolic phenotypes and gene expression profiles
Authors: Umer Muhammad Jawad , Bin Safdar Luqman , Gebremeskel Haileslassie , Zhao Shengjie , Yuan Pingli , Zhu Hongju , Kaseb M. O. , Anees Muhammad , Lu Xuqiang , He Nan , Gong Chengsheng , Liu Wenge 
Published: December 2020

AbstractThe organoleptic qualities of watermelon fruit are defined by the sugar and organic acid contents, which undergo considerable variations during development and maturation. The molecular mechanisms underlying these variations remain unclear. In this study, we used transcriptome profiles to investigate the coexpression patterns of gene networks associated with sugar and organic acid metabolism. We identified 3 gene networks/modules containing 2443 genes highly correlated with sugars and organic acids. Within these modules, based on intramodular significance and Reverse Transcription Quantitative polymerase chain reaction (RT-qPCR), we identified 7 genes involved in the metabolism of sugars and organic acids. Among these genes,Cla97C01G000640,Cla97C05G087120andCla97C01G018840(r2= 0.83 with glucose content) were identified as sugar transporters (SWEET,EDR6andSTP) andCla97C03G064990(r2=0.92 with sucrose content) was identified as a sucrose synthase from information available for other crops. Similarly,Cla97C07G128420,Cla97C03G068240andCla97C01G008870, having strong correlations with malic (r2= 0.75) and citric acid (r2= 0.85), were annotated as malate and citrate transporters (ALMT7,CS, andICDH). The expression profiles of these 7 genes in diverse watermelon genotypes revealed consistent patterns of expression variation in various types of watermelon. These findings add significantly to our existing knowledge of sugar and organic acid metabolism in watermelon.
A CCAAT-binding factor, SlNFYA10, negatively regulates ascorbate accumulation by modulating the d-mannose/l-galactose pathway in tomato
Authors: Chen Weifang , Hu Tixu , Ye Jie , Wang Bing , Liu Genzhong , Wang Ying , Yuan Lei , Li Jiaming , Li Fangman , Ye Zhibiao , Zhang Yuyang 
Published: December 2020

AbstractAscorbic acid (AsA), an important antioxidant and growth regulator, and it is essential for plant development and human health. Specifically, humans have to acquire AsA from dietary sources due to their inability to synthesize it. The AsA biosynthesis pathway in plants has been elucidated, but its regulatory mechanism remains largely unknown. In this report, we biochemically identified a CCAAT-box transcription factor (SlNFYA10) that can bind to the promoter of SlGME1, which encodes GDP-Man-3’,5’-epimerase, a pivotal enzyme in the d-mannose/l-galactose pathway. Importantly, SlNFYA10 simultaneously binds to the promoter of SlGGP1, a downstream gene of SlGME1 in the d-mannose/l-galactose pathway. Binding assays in yeast and functional analyses in plants have confirmed that SlNFYA10 exerts a negative effect on the expression of both SlGME1 and SlGGP1. Transgenic tomato lines overexpressing SlNFYA10 show decreased levels of SlGME1 and SlGGP1 abundance and AsA concentration in their leaves and fruits, accompanied by enhanced sensitivity to oxidative stress. Overall, SlNFYA10 is the first CCAAT-binding factor identified to date to negatively regulate the AsA biosynthetic pathway at multiple sites and modulate plant responses to oxidative stress.
Melon short internode (CmSi) encodes an ERECTA-like receptor kinase regulating stem elongation through auxin signaling
Authors: Yang Sen , Zhang Kaige , Zhu Huayu , Zhang Xiaojing , Yan Wenkai , Xu Nana , Liu Dongming , Hu Jianbin , Wu Yufeng , Weng Yiqun , Yang Luming 
Published: December 2020

SummaryPlant height is one of the most important agronomic traits that directly determines plant architecture, and compact or dwarf plants can allow for increased planting density and land utilization as well as increased lodging resistance and economic yield. At least four dwarf/semidwarf genes have been identified in different melon varieties, but none of them have been cloned, and little is known about the molecular mechanisms underlying internode elongation in melon. Here, we report map-based cloning and functional characterization of the first semidwarf gene short internode (Cmsi) in melon, which encodes an ERECTA-like receptor kinase regulating internode elongation. Spatial-temporal expression analyses revealed that CmSI exhibited high expression in the vascular bundle of the main stem during internode elongation. The expression level of CmSI was positively correlated with stem length in the different melon varieties examined. Ectopic expression of CmSI in Arabidopsis and cucumber suggested CmSI as a positive regulator of internode elongation in both species. Phytohormone quantitation and transcriptome analysis showed that the auxin content and the expression levels of a number of genes involved in the auxin signaling pathway were altered in the semidwarf mutant, including several well-known auxin transporters, such as members of the ABCB family and PIN-FORMED genes. A melon polar auxin transport protein CmPIN2 was identified by protein–protein interaction assay as physically interacting with CmSI to modulate auxin signaling. Thus, CmSI functions in an auxin-dependent regulatory pathway to control internode elongation in melon. Our findings revealed that the ERECTA family gene CmSI regulates stem elongation in melon through auxin signaling, which can directly affect polar auxin transport.
Online sonification improves cycling performance through kinematic and muscular reorganisations
Authors: O’Brien Benjamin , Hardouin Romain , Rao Guillaume , Bertin Denis , Bourdin Christophe 
Published: December 2020

AbstractBased on a previous study that demonstrated the beneficial effects of sonification on cycling performance, this study investigated which kinematic and muscular activities were changed to pedal effectively. An online error-based sonification strategy was developed, such that, when negative torque was applied to the pedal, a squeak sound was produced in real-time in the corresponding headphone. Participants completed four 6-min cycling trials with resistance values associated with their first ventilatory threshold. Different auditory display conditions were used for each trial (Silent, Right, Left, Stereo), where sonification was only presented for 20 s at the start of minutes 1, 2, 3, and 4. Joint kinematics and right leg muscular activities of 10 muscles were simultaneously recorded. Our results showed participants were more effective at pedalling when presented sonification, which was consistent with previously reported findings. In comparison to the Silent condition, sonification significantly limited ankle and knee joint ranges of motion and reduced muscular activations. These findings suggest performance-based sonification significantly affected participants to reduce the complexity of the task by altering the coordination of the degrees of freedom. By making these significant changes to their patterns, participants improved their cycling performance despite lowering joint ranges of motion and muscular activations.
Analyzing the effects of memory biases and mood disorders on social performance
Authors: Sreenivas Nanda Kishore , Rao Shrisha 
Published: December 2020

AbstractRealistic models of decision-making and social interactions, considering the nature of memory and biases, continue to be an area of immense interest. Emotion and mood are a couple of key factors that play a major role in decisions, nature of social interactions, size of the social network, and the level of engagement. Most of the prior work in this direction focused on a single trait, behavior, or bias. However, this work builds an integrated model that considers multiple traits such as loneliness, the drive to interact, the memory, and mood biases in an agent. The agent system comprises of rational, manic, depressed, and bipolar agents. The system is modeled with an interconnected network, and the size of the personal network of each agent is based on its nature. We consider a game of iterated interactions where an agent cooperates based on its past experiences with the other agent. Through simulation, the effects of various biases and comparative performances of agent types is analyzed. Taking the performance of rational agents as the baseline, manic agents do much better, and depressed agents do much worse. The payoffs also exhibit an almost-linear relationship with the extent of mania. It is also observed that agents with stronger memory perform better than those with weaker memory. For rational agents, there is no significant difference between agents with a positive bias and those with a negative bias. Positive bias is linked with higher payoffs in manic and bipolar agents. In depressed agents, negative bias is linked with higher payoffs. In manic agents, an intermediate value of mood dependence offers the highest payoff. But the opposite is seen in depressed agents. In bipolar agents, agents with weak mood dependence perform the best.
Control of response interference: caudate nucleus contributes to selective inhibition
Authors: Schmidt Claudia C. , Timpert David C. , Arend Isabel , Vossel Simone , Fink Gereon R. , Henik Avishai , Weiss Peter H. 
Published: December 2020

AbstractWhile the role of cortical regions in cognitive control processes is well accepted, the contribution of subcortical structures (e.g., the striatum), especially to the control of response interference, remains controversial. Therefore, the present study aimed to investigate the cortical and particularly subcortical neural mechanisms of response interference control (including selective inhibition). Thirteen healthy young participants underwent event-related functional magnetic resonance imaging while performing a unimanual version of the Simon task. In this task, successful performance required the resolution of stimulus–response conflicts in incongruent trials by selectively inhibiting interfering response tendencies. The behavioral results show an asymmetrical Simon effect that was more pronounced in the contralateral hemifield. Contrasting incongruent trials with congruent trials (i.e., the overall Simon effect) significantly activated clusters in the right anterior cingulate cortex, the right posterior insula, and the caudate nucleus bilaterally. Furthermore, a region of interest analysis based on previous patient studies revealed that activation in the bilateral caudate nucleus significantly co-varied with a parameter of selective inhibition derived from distributional analyses of response times. Our results corroborate the notion that the cognitive control of response interference is supported by a fronto-striatal circuitry, with a functional contribution of the caudate nucleus to the selective inhibition of interfering response tendencies.
Longitudinal time-lapse in vivo micro-CT reveals differential patterns of peri-implant bone changes after subclinical bacterial infection in a rat model
Authors: Stadelmann Vincent A. , Thompson Keith , Zeiter Stephan , Camenisch Karin , Styger Ursula , Patrick Sheila , McDowell Andrew , Nehrbass Dirk , Richards R. Geoff , Moriarty T. Fintan 
Published: December 2020

AbstractSubclinical infection associated with orthopedic devices can be challenging to diagnose. The goal of this study was to evaluate longitudinal, microcomputed tomography (microCT) imaging in a rat model of subclinical orthopedic device-related infection caused byStaphylococcus epidermidisand four differentCutibacterium(previouslyPropionibacterium)acnesstrains, and compare outcomes with non-inoculated and historicalS. aureus-inoculated controls. Sterile screws or screws colonized with bacteria were placed in the tibia of 38 adult Wistar rats [n = 6 sterile screws; n = 6S. epidermidis-colonized screws; n = 26C. acnes-colonized screws (covering all three main subspecies)]. Regular microCT scans were taken over 28 days and processed for quantitative time-lapse imaging with dynamic histomorphometry. At euthanasia, tissues were processed for semiquantitative histopathology or quantitative bacteriology. All rats receiving sterile screws were culture-negative at euthanasia and displayed progressive bony encapsulation of the screw. All rats inoculated withS. epidermidis-colonized screws were culture-positive and displayed minor changes in peri-implant bone, characteristic of subclinical infection. Five of the 17 rats in theC. acnesinoculated group were culture positive at euthanasia and displayed bone changes at the interface of the screw and bone, but not deeper in the peri-implant bone. Dynamic histomorphometry revealed significant differences in osseointegration, bone remodeling and periosteal reactions between groups that were not measurable by visual observation of still microCT images. Our study illustrates the added value of merging 3D microCT data from subsequent timepoints and producing inherently richer 4D data for the detection and characterization of subclinical orthopedic infections, whilst also reducing animal use.
Dynamic constitutive model of frozen soil that considers the evolution of volume fraction of ice
Authors: Xie Qijun , Su Lijun , Zhu Zhiwu 
Published: December 2020

AbstractA new constitutive model for frozen soils under high strain rate is developed. By taking the frozen soil as a composite material and considering the adiabatic temperature rise and interfacial debonding damage, the nonlinear dynamic response (NDR) of the frozen soil is predicted. At the same time, the relationship between instantaneous temperature and unfrozen water content is given, and an evolution rule of the volume fraction of ice particles is obtained. This relationship shows good agreement with experimental data. Using this new constitutive model, the stress–strain relationship of frozen soil under impact loading at temperatures of − 3 °C, − 8 °C, − 18 °C, and − 28 °C is calculated. There is good agreements between the results based on this new constitutive model and the data of dynamic impact.