bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ocean Access to Zachariæ Isstrøm Glacier, Northeast Greenland, Revealed by OMG Airborne Gravity
Authors: Yang Junjun , Luo Zhicai , Tu Liangcheng 
Published: October 2020

AbstractSeafloor topography shapes the pathways of ocean currents transporting ocean heat and, thus, is a fundamental boundary condition for modeling ocean‐ice interactions. However, few ship bathymetric data are available on the inner continental shelf of northeast Greenland due to the year‐round presence of sea ice. We infer seafloor topography of this region from airborne gravity anomaly measured by National Aeronautics and Space Administration's Oceans Melting Greenland (OMG) mission through a nonlinear inversion method called simulated annealing and results in a model with 1.95–3.9 km resolution and 52 m accuracy. The model provides a view of the seafloor near Zachariæ Isstrøm and reveals previously unknown topographic features such as a 370–560 m deep trough that enables warm subsurface water to reach Jøkelbugten fjord into which Zachariæ Isstrøm drains. Present bathymetric models do not show deep enough troughs near Jøkelbugten fjord allowing the inflow of warm water.
Temporal and spatial dynamics in the apple flower microbiome in the presence of the phytopathogen Erwinia amylovora
Authors: Cui Zhouqi , Huntley Regan B , Zeng Quan , Steven Blaire 
Published: October 2020

Abstract
Plant microbiomes have important roles in plant health and productivity. However, despite flowers being directly linked to reproductive outcomes, little is known about the microbiomes of flowers and their potential interaction with pathogen infection. Here, we investigated the temporal spatial dynamics of the apple stigma microbiome when challenged with a phytopathogen Erwinia amylovora, the causal agent of fire blight disease. We profiled the microbiome from the stigmas of individual flowers, greatly increasing the resolution at which we can characterize shifts in the composition of the microbiome. Individual flowers harbored unique microbiomes at the operational taxonomic unit level. However, taxonomic analysis of community succession showed a population gradually dominated by bacteria within the families Enterobacteriaceae and Pseudomonadaceae. Flowers inoculated with E. amylovora established large populations of the phytopathogen, with pathogen-specific gene counts of &gt;3.0 × 107 in 90% of the flowers. Yet, only 42% of inoculated flowers later developed fire blight symptoms. This reveals that pathogen abundance on the stigma is not sufficient to predict disease outcome. Our data demonstrate that apple flowers represent an excellent model in which to characterize how plant microbiomes establish, develop, and correlate with biological processes such as disease progression in an experimentally tractable plant organ.
Disruption of Firmicutes and Actinobacteria abundance in tomato rhizosphere causes the incidence of bacterial wilt disease
Authors: Lee Sang-Moo , Kong Hyun Gi , Song Geun Cheol , Ryu Choong-Min 
Published: October 2020

Abstract
Enrichment of protective microbiota in the rhizosphere facilitates disease suppression. However, how the disruption of protective rhizobacteria affects disease suppression is largely unknown. Here, we analyzed the rhizosphere microbial community of a healthy and diseased tomato plant grown &lt;30-cm apart in a greenhouse at three different locations in South Korea. The abundance of Gram-positive Actinobacteria and Firmicutes phyla was lower in diseased rhizosphere soil (DRS) than in healthy rhizosphere soil (HRS) without changes in the causative Ralstonia solanacearum population. Artificial disruption of Gram-positive bacteria in HRS using 500-μg/mL vancomycin increased bacterial wilt occurrence in tomato. To identify HRS-specific and plant-protective Gram-positive bacteria species, Brevibacterium frigoritolerans HRS1, Bacillus niacini HRS2, Solibacillus silvestris HRS3, and Bacillus luciferensis HRS4 were selected from among 326 heat-stable culturable bacteria isolates. These four strains did not directly antagonize R. solanacearum but activated plant immunity. A synthetic community comprising these four strains displayed greater immune activation against R. solanacearum and extended plant protection by 4 more days in comparison with each individual strain. Overall, our results demonstrate for the first time that dysbiosis of the protective Gram-positive bacterial community in DRS promotes the incidence of disease.
Nme1 and Nme2 genes exert metastasis-suppressor activities in a genetically engineered mouse model of UV-induced melanoma
Authors: Pamidimukkala Nidhi , Puts Gemma S. , Kathryn Leonard M. , Snyder Devin , Dabernat Sandrine , De Fabo Edward C. , Noonan Frances P. , Slominski Andrzej , Merlino Glenn , Kaetzel David M. 
Published: October 2020

AbstractNME1 is a metastasis-suppressor gene (MSG), capable of suppressing metastatic activity in cell lines of melanoma, breast carcinoma and other cancer origins without affecting their growth in culture or as primary tumours. Herein, we selectively ablated the tandemly arranged Nme1 and Nme2 genes to assess their individual impacts on metastatic activity in a mouse model (HGF:p16−/−) of ultraviolet radiation (UVR)-induced melanoma. Metastatic activity was strongly enhanced in both genders of Nme1- and Nme2-null mice, with stronger activity in females across all genotypes. The study ascribes MSG activity to Nme2 for the first time in an in vivo model of spontaneous cancer, as well as a novel metastasis-suppressor function to Nme1 in the specific context of UVR-induced melanoma.
Lysine demethylase 2A expression in cancer-associated fibroblasts promotes breast tumour growth
Authors: Chen Jing-Yi , Li Chien-Feng , Lai You-Syuan , Hung Wen-Chun 
Published: October 2020

Abstract
Background
Our previous study demonstrated that lysine demethylase 2A (KDM2A) enhances stemness in breast cancer cells. This demethylase is also highly expressed in cancer-associated fibroblasts (CAFs). However, its clinical significance is unclear.

Methods
The expression of KDM2A in CAFs was studied using immunohistochemical staining and its association with clinicopathological features and patient’s survival was tested. Overexpression and knockdown strategies were used to investigate KDM2A-regulated genes in fibroblasts. Senescent cells were detected by using β-galactosidase staining. The in vivo tumour-promoting activity of stromal KDM2A was confirmed by animal study.

Results
Increase of stromal KDM2A is associated with advanced tumour stage and poor clinical outcome in breast cancer patients. Cancer-derived cytokines stimulated KDM2A expression in normal fibroblasts and transformed them into CAFs. Upregulation of KDM2A induced p53-dependent senescence in fibroblasts and enhanced the release of cytokines, which reciprocally promoted cancer cell proliferation. Additionally, KDM2A upregulated programmed death-ligand 1 (PD-L1) expression via transcriptional activation in fibroblasts. Knockdown of KDM2A completely abolished the tumour-promoting activity of CAFs on breast tumour growth in vivo and diminished PD-L1 expression in the stroma of tumour tissues.

Conclusions
Stromal KDM2A plays an oncogenic role in breast cancer and inhibition of KDM2A reduces fibroblast senescence and suppresses tumour growth.
LncRNA LL22NC03-N14H11.1 promoted hepatocellular carcinoma progression through activating MAPK pathway to induce mitochondrial fission
Authors: Yi Tingzhuang , Luo Hongcheng , Qin Fengxue , Jiang Qi , He Shougao , Wang Tonghua , Su Jianwei , Song Sien , Qin Xiaoshan , Qin Yueqiu , Zhou Xihan , Huang Zansong 
Published: October 2020

AbstractInvolvement of long non-coding RNAs (lncRNAs) in hepatocarcinogenesis has been largely documented. Mitochondrial dynamics is identified to impact survival and metastasis in tumors including hepatocellular carcinoma (HCC), but the underlying mechanism remains poorly understood. This study planned to explore the regulation of lncRNA LL22NC03-N14H11.1 on HCC progression and mitochondrial fission. Dysregulated lncRNAs in HCC are identified through circlncRNAnet and GEPIA bioinformatics tools. Biological function of LL22NC03-N14H11.1 in HCC was detected by CCK-8 assay, flow cytometry analysis, transwell invasion, and wound healing assays. Molecular interactions were determined by RNA immunoprecipitation, RNA pull-down, and co-immunoprecipitation assays. Results showed that LL22NC03-N14H11.1 was upregulated in HCC tissues and cells. Functionally, LL22NC03-N14H11.1 contributed to cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) in HCC. Moreover, LL22NC03-N14H11.1 facilitated mitochondrial fission in HCC cells. Mechanistically, LL22NC03-N14H11.1 recruited Myb proto-oncogene (c-Myb) to repress the transcription of leucine zipper-like transcription regulator 1 (LZTR1), so as to inhibit LZTR1-mediated ubiquitination of H-RAS (G12V), leading to the activation of mitogen-activated protein kinase (MAPK) signaling and induction of p-DRP1 (Serine 616). In conclusion, this study firstly revealed that lncRNA LL22NC03-N14H11.1 promoted HCC progression through activating H-RAS/MAPK pathway to induce mitochondrial fission, indicating LL22NC03-N14H11.1 as a novel potential biomarker for HCC treatment.
A gene expression signature of TREM2hi macrophages and γδ T cells predicts immunotherapy response
Authors: Xiong Donghai , Wang Yian , You Ming 
Published: October 2020

AbstractIdentifying factors underlying resistance to immune checkpoint therapy (ICT) is still challenging. Most cancer patients do not respond to ICT and the availability of the predictive biomarkers is limited. Here, we re-analyze a publicly available single-cell RNA sequencing (scRNA-seq) dataset of melanoma samples of patients subjected to ICT and identify a subset of macrophages overexpressing TREM2 and a subset of gammadelta T cells that are both overrepresented in the non-responding tumors. In addition, the percentage of a B cell subset is significantly lower in the non-responders. The presence of these immune cell subtypes is corroborated in other publicly available scRNA-seq datasets. The analyses of bulk RNA-seq datasets of the melanoma samples identify and validate a signature - ImmuneCells.Sig - enriched with the genes characteristic of the above immune cell subsets to predict response to immunotherapy. ImmuneCells.Sig could represent a valuable tool for clinical decision making in patients receiving immunotherapy.
Origin and adaptation to high altitude of Tibetan semi-wild wheat
Authors: Guo Weilong , Xin Mingming , Wang Zihao , Yao Yingyin , Hu Zhaorong , Song Wanjun , Yu Kuohai , Chen Yongming , Wang Xiaobo , Guan Panfeng , Appels Rudi , Peng Huiru , Ni Zhongfu , Sun Qixin 
Published: October 2020

AbstractTibetan wheat is grown under environmental constraints at high-altitude conditions, but its underlying adaptation mechanism remains unknown. Here, we present a draft genome sequence of a Tibetan semi-wild wheat (Triticum aestivum ssp. tibetanum Shao) accession Zang1817 and re-sequence 245 wheat accessions, including world-wide wheat landraces, cultivars as well as Tibetan landraces. We demonstrate that high-altitude environments can trigger extensive reshaping of wheat genomes, and also uncover that Tibetan wheat accessions accumulate high-altitude adapted haplotypes of related genes in response to harsh environmental constraints. Moreover, we find that Tibetan semi-wild wheat is a feral form of Tibetan landrace, and identify two associated loci, including a 0.8-Mb deletion region containing Brt1/2 homologs and a genomic region with TaQ-5A gene, responsible for rachis brittleness during the de-domestication episode. Our study provides confident evidence to support the hypothesis that Tibetan semi-wild wheat is de-domesticated from local landraces, in response to high-altitude extremes.
Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis
Authors: Pfisterer Ulrich , Petukhov Viktor , Demharter Samuel , Meichsner Johanna , Thompson Jonatan J. , Batiuk Mykhailo Y. , Asenjo-Martinez Andrea , Vasistha Navneet A. , Thakur Ashish , Mikkelsen Jens , Adorjan Istvan , Pinborg Lars H. , Pers Tune H. , von Engelhardt Jakob , Kharchenko Peter V. , Khodosevich Konstantin 
Published: October 2020

AbstractEpilepsy is one of the most common neurological disorders, yet its pathophysiology is poorly understood due to the high complexity of affected neuronal circuits. To identify dysfunctional neuronal subtypes underlying seizure activity in the human brain, we have performed single-nucleus transcriptomics analysis of >110,000 neuronal transcriptomes derived from temporal cortex samples of multiple temporal lobe epilepsy and non-epileptic subjects. We found that the largest transcriptomic changes occur in distinct neuronal subtypes from several families of principal neurons (L5-6_Fezf2 and L2-3_Cux2) and GABAergic interneurons (Sst and Pvalb), whereas other subtypes in the same families were less affected. Furthermore, the subtypes with the largest epilepsy-related transcriptomic changes may belong to the same circuit, since we observed coordinated transcriptomic shifts across these subtypes. Glutamate signaling exhibited one of the strongest dysregulations in epilepsy, highlighted by layer-wise transcriptional changes in multiple glutamate receptor genes and strong upregulation of genes coding for AMPA receptor auxiliary subunits. Overall, our data reveal a neuronal subtype-specific molecular phenotype of epilepsy.
In primary airway epithelial cells, the unjamming transition is distinct from the epithelial-to-mesenchymal transition
Authors: Mitchel Jennifer A. , Das Amit , O’Sullivan Michael J. , Stancil Ian T. , DeCamp Stephen J. , Koehler Stephan , Ocaña Oscar H. , Butler James P. , Fredberg Jeffrey J. , Nieto M. Angela , Bi Dapeng , Park Jin-Ah 
Published: October 2020

AbstractThe epithelial-to-mesenchymal transition (EMT) and the unjamming transition (UJT) each comprises a gateway to cellular migration, plasticity and remodeling, but the extent to which these core programs are distinct, overlapping, or identical has remained undefined. Here, we triggered partial EMT (pEMT) or UJT in differentiated primary human bronchial epithelial cells. After triggering UJT, cell-cell junctions, apico-basal polarity, and barrier function remain intact, cells elongate and align into cooperative migratory packs, and mesenchymal markers of EMT remain unapparent. After triggering pEMT these and other metrics of UJT versus pEMT diverge. A computational model attributes effects of pEMT mainly to diminished junctional tension but attributes those of UJT mainly to augmented cellular propulsion. Through the actions of UJT and pEMT working independently, sequentially, or interactively, those tissues that are subject to development, injury, or disease become endowed with rich mechanisms for cellular migration, plasticity, self-repair, and regeneration.
Single-cell RNA sequencing highlights the role of inflammatory cancer-associated fibroblasts in bladder urothelial carcinoma
Authors: Chen Zhaohui , Zhou Lijie , Liu Lilong , Hou Yaxin , Xiong Ming , Yang Yu , Hu Junyi , Chen Ke 
Published: October 2020

AbstractAlthough substantial progress has been made in cancer biology and treatment, clinical outcomes of bladder carcinoma (BC) patients are still not satisfactory. The tumor microenvironment (TME) is a potential target. Here, by single-cell RNA sequencing on 8 BC tumor samples and 3 para tumor samples, we identify 19 different cell types in the BC microenvironment, indicating high intra-tumoral heterogeneity. We find that tumor cells down regulated MHC-II molecules, suggesting that the downregulated immunogenicity of cancer cells may contribute to the formation of an immunosuppressive microenvironment. We also find that monocytes undergo M2 polarization in the tumor region and differentiate. Furthermore, the LAMP3 + DC subgroup may be able to recruit regulatory T cells, potentially taking part in the formation of an immunosuppressive TME. Through correlation analysis using public datasets containing over 3000 BC samples, we identify a role for inflammatory cancer-associated fibroblasts (iCAFs) in tumor progression, which is significantly related to poor prognosis. Additionally, we characterize a regulatory network depending on iCAFs. These results could help elucidate the protumor mechanisms of iCAFs. Our results provide deep insight into cancer immunology and provide an essential resource for drug discovery in the future.
Experimental and in silico evidence suggests vaccines are unlikely to be affected by D614G mutation in SARS-CoV-2 spike protein
Authors: McAuley Alexander J. , Kuiper Michael J. , Durr Peter A. , Bruce Matthew P. , Barr Jennifer , Todd Shawn , Au Gough G. , Blasdell Kim , Tachedjian Mary , Lowther Sue , Marsh Glenn A. , Edwards Sarah , Poole Timothy , Layton Rachel , Riddell Sarah-Jane , Drew Trevor W. , Druce Julian D. , Smith Trevor R. F. , Broderick Kate E. , Vasan S. S. 
Published: October 2020

AbstractThe ‘D614G’ mutation (Aspartate-to-Glycine change at position 614) of the SARS-CoV-2 spike protein has been speculated to adversely affect the efficacy of most vaccines and countermeasures that target this glycoprotein, necessitating frequent vaccine matching. Virus neutralisation assays were performed using sera from ferrets which received two doses of the INO-4800 COVID-19 vaccine, and Australian virus isolates (VIC01, SA01 and VIC31) which either possess or lack this mutation but are otherwise comparable. Through this approach, supported by biomolecular modelling of this mutation and the commonly-associated P314L mutation in the RNA-dependent RNA polymerase, we have shown that there is no experimental evidence to support this speculation. We additionally demonstrate that the putative elastase cleavage site introduced by the D614G mutation is unlikely to be accessible to proteases.
A cross-country database of COVID-19 testing
Authors: Hasell Joe , Mathieu Edouard , Beltekian Diana , Macdonald Bobbie , Giattino Charlie , Ortiz-Ospina Esteban , Roser Max , Ritchie Hannah 
Published: October 2020

AbstractOur understanding of the evolution of the COVID-19 pandemic is built upon data concerning confirmed cases and deaths. This data, however, can only be meaningfully interpreted alongside an accurate understanding of the extent of virus testing in different countries. This new database brings together official data on the extent of PCR testing over time for 94 countries. We provide a time series for the daily number of tests performed, or people tested, together with metadata describing data quality and comparability issues needed for the interpretation of the time series. The database is updated regularly through a combination of automated scraping and manual collection and verification, and is entirely replicable, with sources provided for each observation. In providing accessible cross-country data on testing output, it aims to facilitate the incorporation of this crucial information into epidemiological studies, as well as track a key component of countries’ responses to COVID-19.
Addressing the “minimum parking” problem for on-demand mobility
Authors: Kondor Dániel , Santi Paolo , Le Diem-Trinh , Zhang Xiaohu , Millard-Ball Adam , Ratti Carlo 
Published: October 2020

AbstractParking infrastructure is pervasive and occupies large swaths of land in cities. However, on-demand (OD) mobility has started reducing parking needs in urban areas around the world. This trend is expected to grow significantly with the advent of autonomous driving, which might render on-demand mobility predominant. Recent studies have started looking at expected parking reductions with on-demand mobility, but a systematic framework is still lacking. In this paper, we apply a data-driven methodology based on shareability networks to address what we call the “minimum parking” problem: what is the minimum parking infrastructure needed in a city for given on-demand mobility needs? While solving the problem, we also identify a critical tradeoff between two public policy goals: less parking means increased vehicle travel from deadheading between trips. By applying our methodology to the city of Singapore we discover that parking infrastructure reduction of up to 86% is possible, but at the expense of a 24% increase in traffic measured as vehicle kilometers travelled (VKT). However, a more modest 57% reduction in parking is achievable with only a 1.3% increase in VKT. We find that the tradeoff between parking and traffic obeys an inverse exponential law which is invariant with the size of the vehicle fleet. Finally, we analyze parking requirements due to passenger pick-ups and show that increasing convenience produces a substantial increase in parking for passenger pickup/dropoff. The above findings can inform policy-makers, mobility operators, and society at large on the tradeoffs required in the transition towards pervasive on-demand mobility.
Human spatial memory implicitly prioritizes high-calorie foods
Authors: de Vries Rachelle , Morquecho-Campos Paulina , de Vet Emely , de Rijk Marielle , Postma Elbrich , de Graaf Kees , Engel Bas , Boesveldt Sanne 
Published: October 2020

AbstractAll species face the important adaptive problem of efficiently locating high-quality nutritional resources. We explored whether human spatial cognition is enhanced for high-calorie foods, in a large multisensory experiment that covertly tested the location memory of people who navigated a maze-like food setting. We found that individuals incidentally learned and more accurately recalled locations of high-calorie foods – regardless of explicit hedonic valuations or personal familiarity with foods. In addition, the high-calorie bias in human spatial memory already became evident within a limited sensory environment, where solely odor information was available. These results suggest that human minds continue to house a cognitive system optimized for energy-efficient foraging within erratic food habitats of the past, and highlight the often underestimated capabilities of the human olfactory sense.