bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards a unifying framework for diversity and dissimilarity coefficients
Authors: Ricotta Carlo , Szeidl László , Pavoine Sandrine 
Published: January 2021

AbstractDiversity and dissimilarity within and between species assemblages have now been studied for more than half a century by community ecologists in relation to their connections with ecosystem functioning. However, a generalized framework that puts diversity and dissimilarity coefficients under the same formal umbrella is still lacking. In this paper, we show that generalized means represent an effective tool to develop a unifying formulation for the construction of a large array of parametric diversity and dissimilarity measures. These measures include some of the classical diversity coefficients, such as the Shannon entropy, the Gini-Simpson index or the parametric diversity of Patil and Taillie, together with a large number of dissimilarity coefficients of the Bray-Curtis family and can be further extended to the measurement of functional and phylogenetic differences within and between plots.
Mycorrhizal dominance reduces forest-tree species diversity
Authors: Carteron Alexis , Vellend Mark , Laliberté Etienne 
Published: January 2021

SUMMARYEctomycorrhizas and arbuscular mycorrhizas, the two most widespread plant-fungal symbioses, are thought to differentially influence tree species diversity, with positive plant-soil feedbacks favoring locally abundant ectomycorrhizal tree species and negative feedbacks promoting species coexistence and diversity in arbuscular mycorrhizal forests. While seedling recruitment studies and cross-biome patterns of plant diversity and mycorrhizal dominance support this hypothesis, it remains to be tested at the forest stand level over continental scales. Here, we analyze ∼85,000 forest plots across the United States to show that both ectomycorrhizal-dominated and arbuscular mycorrhizal-dominated forests show relatively low tree diversity, while forests with a mixture of mycorrhizal strategies support a higher number of tree species. Our findings suggest that mycorrhizal dominance, rather than mycorrhizal type, shapes tree diversity in forests.
LSTrAP-Kingdom: an automated pipeline to generate annotated gene expression atlases for kingdoms of life
Authors: Goh William , Mutwil Marek 
Published: January 2021

AbstractSummaryThere are now more than two million RNA sequencing experiments for plants, animals, bacteria and fungi publicly available, allowing us to study gene expression within and across species and kingdoms. However, the tools allowing the download, quality control and annotation of this data for more than one species at a time are currently missing. To remedy this, we present the Large-Scale Transcriptomic Analysis Pipeline in Kingdom of Life (LSTrAP-Kingdom) pipeline, which we used to process 134,521 RNA-seq samples, achieving ~12,000 processed samples per day. Our pipeline generated quality-controlled, annotated gene expression matrices that rival the manually curated gene expression data in identifying functionally-related genes.Availability and implementationLSTrAP-Kingdom is available from:https://github.com/wirriamm/plants-pipelineand is fully implemented in Python and Bash.
Adaptive immunity to human coronaviruses is widespread but low in magnitude
Authors: Tan Hyon-Xhi , Lee Wen Shi , Wragg Kathleen M , Nelson Christina , Esterbauer Robyn , Kelly Hannah G , Amarasena Thakshila , Jones Robert , Starkey Graham , Wang Bao Zhong , Yoshino Osamu , Tiang Thomas , Grayson M Lindsay , Opdam Helen , D’Costa Rohit , Vago Angela ,   The Austin Liver Transplant Perfusionist Group, Mackay Laura K , Gordon Claire L , Wheatley Adam K , Kent Stephen J , Juno Jennifer A 
Published: January 2021

AbstractEndemic human coronaviruses (hCoV) circulate worldwide but cause minimal mortality. Although seroconversion to hCoV is near ubiquitous during childhood, little is known about hCoV-specific T cell memory in adults. We quantified CD4 T cell and antibody responses to hCoV spike antigens in 42 SARS-CoV-2 uninfected individuals. T cell responses were widespread within conventional memory and cTFH compartments but did not correlate with IgG titres. SARS-CoV-2 cross-reactive T cells were observed in 48% of participants and correlated with HKU1 memory. hCoV-specific T cells exhibited a CCR6+ central memory phenotype in the blood, but were enriched for frequency and CXCR3 expression in human lung draining lymph nodes. Overall, hCoV-specific humoral and cellular memory are independently maintained, with a shared phenotype existing among coronavirus-specific CD4 T cells. This understanding of endemic coronavirus immunity provides insight into the homeostatic maintenance of immune responses that are likely to be critical components of protection against SARS-CoV-2.
Novel COVID-19 phenotype definitions reveal phenotypically distinct patterns of genetic association and protective effects
Authors: Roberts Genevieve H.L. , Partha Raghavendran , Rhead Brooke , Knight Spencer C. , Park Danny S. , Coignet Marie V. , Zhang Miao , Berkowitz Nathan , Turrisini David A. , Gaddis Michael , McCurdy Shannon R. , Pavlovic Milos , Ruiz Luong ,   AncestryDNA Science Team, Baltzell Asher K. Haug , Guturu Harendra , Girshick Ahna R. , Rand Kristin A. , Hong Eurie L. , Ball Catherine A. 
Published: January 2021

INTRODUCTION PARAGRAPHMultiple large COVID-19 genome-wide association studies (GWAS) have identified reproducible genetic associations indicating that some infection susceptibility and severity risk is heritable.1-5 Most of these studies ascertained COVID-19 cases in medical clinics and hospitals, which can lead to an overrepresentation of cases with severe outcomes, such as hospitalization, intensive care unit admission, or ventilation. Here, we demonstrate the utility and validity of deep phenotyping with self-reported outcomes in a population with a large proportion of mild and subclinical cases. Using these data, we defined eight different phenotypes related to COVID-19 outcomes: four that align with previously studied COVID-19 definitions and four novel definitions that focus on susceptibility given exposure, mild clinical manifestations, and an aggregate score of symptom severity. We assessed replication of 13 previously identified COVID-19 genetic associations with all eight phenotypes and found distinct patterns of association, most notably related to the chr3/SLC6A20/LZTFL1 and chr9/ABO regions. We then performed a discovery GWAS, which suggested some novel phenotypes may better capture protective associations and also identified a novel association in chr11/GALNT18 that reproduced in two fully independent populations.
Chest wall abnormalities in Swiss childhood cancer survivors
Authors: Kasteler Rahel , Lichtensteiger Christa , Schindera Christina , Ansari Marc , Kuehni Claudia E. ,   for the Swiss Pediatric Oncology Group (SPOG)
Published: January 2021

AbstractBackgroundChest wall abnormalities are a poorly studied complication after treatment for childhood cancer. Chest wall abnormalities are not well described in the literature, and little is known on the impact on daily life of survivors.MethodsWe investigated chest wall abnormalities in the nationwide, population-based cohort study (Swiss Childhood Cancer Survivor Study) with a questionnaire survey to describe prevalence and risk factors. We then interviewed a nested sample of survivors to understand types of chest wall abnormalities and their impact on daily life of survivors.Results48 of 2,382 (95%CI 2%–3%) survivors reported a chest wall abnormality. Risk factors were older age at cancer diagnosis (16–20 years; OR 2.5, 95%CI 1.0– 6.1), lymphoma (OR 3.8, 95%CI 1.2–11.4), and central nervous system tumors (OR 9.5, 95%CI 3.0–30.1) as underlying disease, and treatment with thoracic radiotherapy (OR 2.0, 95%CI 1.0–4.2), surgery to the chest (OR 4.5, 95%CI 1.8–11.5), or chemotherapy (OR 2.9, 95%CI 1.0–8.1) .The nature of the chest wall abnormalities varied and included thoracic wall deformities (30%), deformations of the spine (5%) or both (55%), and scars (10%). Chest wall abnormalities affected the daily life in two thirds (13/20) of those who reported these problems, and 15 (75%) had required chest wall abnormalities-related medical attention.ConclusionIt is important that during follow-up care physicians pay attention to chest wall abnormalities, which are rare late-effect of cancer treatment, but can considerably affect well-being of cancer survivors.
Nuclear cholesterol is required for transcriptional repression by BASP1
Authors: Loats Amy E. , Carrera Samantha , Fleming Anna F. , Roberts Abigail R.E. , Sherrard Alice , Toska Eneda , Medler Kathryn F. , Roberts Stefan G. E. 
Published: January 2021

AbstractLipids are present within the cell nucleus where they engage with factors involved in gene regulation. Cholesterol associates with chromatin in vivo and stimulates nucleosome packing in-vitro, but its effects on specific transcriptional responses are not clear. Here we show that the lipidated WT1 transcriptional corepressor, BASP1, interacts with cholesterol in the cell nucleus through a conserved cholesterol interaction motif. We demonstrate that BASP1 directly recruits cholesterol to the promoter region of WT1 target genes. Mutation of BASP1 to ablate its interaction with cholesterol or the treatment of cells with drugs that block cholesterol biosynthesis inhibit the transcriptional repressor function of BASP1. We find that the BASP1-cholesterol interaction is required for BASP1-dependent chromatin remodelling and the direction of transcription programs that control cell differentiation. Our study uncovers a mechanism for gene-specific targeting of cholesterol where it is required to mediate transcriptional repression.SignificanceCholesterol is present within the cell nucleus where it associates with chromatin but to date, a direct role for cholesterol in nuclear processes has not been identified. We demonstrate that the transcriptional repressor BASP1 directly interacts with cholesterol within the cell nucleus through a consensus cholesterol interaction motif. BASP1 recruits cholesterol to the promoter region of target genes where it is required to mediate chromatin remodelling and transcriptional repression. Our work demonstrates that nuclear cholesterol plays a direct role in transcriptional regulation.
Spike-in normalization for single-cell RNA-seq reveals dynamic global transcriptional activity mediating anti-cancer drug response
Authors: Wang Xin , Frederick Jane , Wang Hongbin , Hui Sheng , Backman Vadim , Ji Zhe 
Published: January 2021

ABSTRACTThe transcriptional plasticity of cancer cells promotes intercellular heterogeneity in response to anti-cancer drugs and facilitates the generation of subpopulation surviving cells. Characterizing single-cell transcriptional heterogeneity after drug treatments can provide mechanistic insights into drug efficacy. Here we used single-cell RNA-seq to examine transcriptomic profiles of cancer cells treated with paclitaxel, celecoxib, and the combination of the two drugs. By normalizing the expression of endogenous genes to spike-in molecules, we found that celluar mRNA abundance shows dynamic regulation after drug treatment. Using a random forest model, we identified gene signatures classifying single cells into three states: transcriptional repression, amplification, and control-like. Treatment with paclitaxel or celecoxib alone generally repressed gene transcription across single cells. Interestingly, the drug combination resulted in transcriptional amplification and hyperactivation of mitochondrial oxidative phosphorylation pathway linking to enhanced cell killing efficiency. Finally, we identified a regulatory module enriched with metabolism and inflammation-related genes activated in a subpopulation of paclitaxel-treated cells, the expression of which predicted paclitaxel efficacy across cancer cell lines andin vivopatient samples. Our study highlights the dynamic global transcriptional activity driving single-cell heterogeneity during drug response and emphasizes the importance of adding spike-in molecules to study gene expression regulation using single-cell RNA-seq.
Heterogeneity in PHGDH protein expression potentiates cancer cell dissemination and metastasis
Authors: Rossi Matteo , Doglioni Ginevra , Bornes Laura , Broekaert Dorien , Planque Mélanie , Fernández-García Juan , Rinaldi Gianmarco , Van Elsen Joke , Nittner David , Jauset Cristina , Rizzollo Francesca , Domingo Carla Riera , Orth Martin F , Dobrolecki Lacey E , Van Brussel Thomas , Teoh Shao Thing , Aurora Arin B , Eelen Guy , Karras Panagiotis , Sotlar Karl , Bartsch Harald , Marine Jean-Christophe , Carmeliet Peter , Morrison Sean J , Lewis Michael T , Hannon Gregory J , Mazzone Massimiliano , Lambrechts Diether , van Rheenen Jacco , Grünewald Thomas G P , Lunt Sophia Y , Fendt Sarah-Maria 
Published: January 2021

AbstractCancer metastasis requires the transient activation of cellular programs enabling dissemination and seeding in distant organs. Genetic, transcriptional and translational intra-tumor heterogeneity contributes to this dynamic process. Beyond this, metabolic intra-tumor heterogeneity has also been observed, yet its role for cancer progression remains largely elusive. Here, we discovered that intra-tumor heterogeneity in phosphoglycerate dehydrogenase (PHGDH) protein expression drives breast cancer cell dissemination and metastasis formation. Specifically, we observed intra-tumor heterogeneous PHGDH expression in primary breast tumors, with low PHGDH expression being indicative of metastasis in patients. In mice, Phgdh protein, but not mRNA, expression is low in circulating tumor cells and early metastatic lesions, leading to increased dissemination and metastasis formation. Mechanistically, low PHGDH protein expression induces an imbalance in glycolysis that can activate sialic acid synthesis. Consequently, cancer cells undergo a partial EMT and show increased p38 as well as SRC phosphorylation, which activate cellular programs of dissemination. In turn, inhibition of sialic acid synthesis through knock-out of cytidine monophosphate N-acetylneuraminic acid synthetase (CMAS) counteracts the increased cancer cell dissemination and metastasis induced by low PHGDH expression. In conclusion, we find that heterogeneity in PHGDH protein expression promotes cancer cell dissemination and metastasis formation.
Optimization of Ethanol-Assisted Aqueous Oil Extraction from aCicadidae Sp
Authors: Mahmoudi-Kordi Farzaneh , Balvardi Mohammad , Akhavan Hamid-Reza 
Published: January 2021

AbstractEdible insects have been considering as a rich resource of high-quality protein and lipid content and at the same time a low-cost nutritious resource acquiring the least expenditure during farming, breeding, rearing and harvesting. On the other hand, organic solvent consumptions in industrial areas need to be limited; being flammable by environmental hazards. That is why seeking for alternative non-toxic solvents is highly substantial. In this study ethanol-aqueous extraction method applied at three different levels to find the optimum yield of edible oil extracted of Homoptera Cicadidae Magicicada, a seasonal insect residing underground, which is consuming locally as a whole meal. These levels set using Design of expert software to variables as pH, ethanol-concentration and solvent/sample ratio and the maximum yield extracted respectively at 6, 50 and 5, by the yield of 19.5%, that is comparable to oil extracted by conventional hexane oil extraction method at 27%. Fatty acids profile of recent method and hexane extraction method analyzed using GC-MS method and the physicochemical properties of either alternative method investigated. The results were on the standard ranges. Fatty acid profile of HCM was for the most part consisted of oleic acid, following by palmitic and linoleic acid 66.5, 19.2 and 7.8 respectively in hexane extraction method and 66.3, 17.7 and 9.5 in ethanol aqueous extraction method. The Iodine Value of HCM oil was noticeably high which introduces a medicinal applicatory besides the rich amount of MUFAs and PUFAs essential oils that are well-known for their incredible health benefits.
Ecological consequences of urbanization on a legume-rhizobia mutualism
Authors: Murray-Stoker David , Johnson Marc T. J. 
Published: January 2021

AbstractMutualisms are key determinants of community assembly and composition, but urbanization can alter the dynamics of these interactions and associated effects on ecosystem functions. Legume-rhizobia mutualisms are a model interaction to evaluate the ecological and ecosystem-level effects of urbanization, particularly urban-driven eutrophication and nitrogen (N) deposition. Here, we evaluated how urbanization affected the ecology of the mutualism between white clover (Trifolium repens) and its rhizobial symbiont (Rhizobium leguminosarumsymbiovartrifolii) along an urbanization gradient. We found that the abundance of rhizobium nodules on white clover decreased with urbanization. White clover acquired N from mixed sources of N fixation and uptake from the soil for the majority of the urbanization gradient, but white clover primarily acquired N from the soil rather than N fixation by rhizobia at the urban and rural limits of the gradient. Importantly, we identified soil N as a critical nexus for urban-driven changes in the white clover-rhizobium mutualism. Taken together, our results demonstrate that urbanization alters the ecological consequences of a legume-rhizobium mutualism, with direct and indirect effects of the urban landscape on an ecologically-important mutualistic interaction.
P4HA2-induced prolyl hydroxylation suppresses YAP1-mediated prostate cancer cell migration, invasion, and metastasis
Authors: Zhu Ming , Peng Ruiqing , Liang Xin , Lan Zhengdao , Tang Ming , Hou Pingping , Song Jian H. , Mak Celia Sze Ling , Park Jiwon , Zheng Shui-er , Huang Ailing , Ma Xingdi , Chen Ruidong , Chang Qing , Logothetis Christopher J. , Jain Abhinav K. , Lin Sue-Hwa , Katayama Hiroyuki , Hanash Samir M. , Wang Guocan 
Published: January 2021

ABSTRACTYes-associated protein 1 (YAP1), a key player in the Hippo pathway, has been shown to play a critical role in tumor progression. However, the role of YAP1 in prostate cancer cell invasion, migration, and metastasis is not well defined. Through functional, transcriptomic, epigenomic, and proteomic analyses, we showed that prolyl hydroxylation of YAP1 plays a critical role in the suppression of cell migration, invasion, and metastasis in prostate cancer. Knockdown (KD) or knockout (KO) ofYAP1led to an increase in cell migration, invasion, and metastasis in prostate cancer cells. Microarray analysis showed that the EMT pathway was activated inYap1-KD cells. ChIP-seq analysis showed that YAP1 target genes are enriched in pathways regulating cell migration. Mass spectrometry analysis identified P4H prolyl hydroxylase in the YAP1 complex and YAP1 was hydroxylated at multiple proline residues. Proline-to-alanine mutations of YAP1 isoform 3 identified proline 174 as a critical residue, and its hydroxylation suppressed cell migration, invasion, and metastasis. KO ofP4ha2led to an increase in cell migration and invasion, which was reversed uponYap1KD. Our study identified a novel regulatory mechanism of YAP1 by which P4HA2-dependent prolyl hydroxylation of YAP1 determines its transcriptional activities and its function in prostate cancer metastasis.
rtcisE2F drives liver TIC self-renewal and metastasis via m6A-modulated mRNA stability ofE2F6andE2F3
Authors: Chen Zhenzhen , Liu Benyu , Huang Lan , Zhong Xiang , Yan Zhongyi , Zhu Pingping 
Published: January 2021

AbstractBackgroundLiver tumor initiating cells (TICs) harbor self-renewal and differentiation capacities, and well contribute to liver tumorigenesis, metastasis and heterogeneity. However, the molecular mechanisms of liver TIC self-renewal are unclear. N6-methyladenosine is the most abundant modification of RNA molecules, and is involved in RNA stability and translation, but the molecular mechanisms of m6A regulation remain largely unknown.MethodscircRNA expression was detected byin situhybridization, fluorescencein situhybridization, quantitative real-time PCR and Northern blot. Target gene expression was examined by microarray analyses, quantitative real-time PCR and Western blot. CRISPR, CRISPR interference (CRISPRi) and short-hairpin RNA (shRNA) were used for circRNA/target gene knockout and knockdown. Liver TICs were enriched through sphere formation and FACS using CD133 as a marker, and liver TIC activity was assessed by tumor propagation, sphere formation, tumor-initiating, and transwell assays. Quantitative real-time PCR and Northern blot were used to determine mRNA stability. RNA–protein interactions were examined by RNA pulldown, RNA immunoprecipitation, Tagged RNA affinity purification (TRAP) and electrophoretic mobility shift assays (EMSA).ResultsHere, we identified a functional rt-circRNA, termed rtcisE2F, that is highly expressed in liver cancer and liver TICs. rtcisE2F plays essential roles in the self-renewal and activities of liver TICs. rtcisE2F targetsE2F6andE2F3mRNAs, attenuates mRNA turnover, and increases E2F6/E2F3 expression. Mechanistically, rtcisE2F functions as a scaffold of m6A reader IGF2BP2 andE2F6/E2F3mRNA, promotes the association ofE2F6/E2F3mRNAs with IGF2BP2, and then inhibits their association with another m6A reader, YTHDF2. IGF2BP2 inhibitsE2F6/E2F3mRNA decay, whereas YTHDF2 promotesE2F6/E2F3mRNA decay. By switching m6A readers, rtcisE2F enhancesE2F6/E2F3mRNA stability. E2F6 and E2F3 are both required for liver TIC self-renewal and Wnt/β-catenin activation, and inhibition of these pathways is a potential strategy for preventing liver tumorigenesis and metastasis.ConclusionThis work identified rtcisE2F as a key modulator in liver cancer and liver TICs, providing evidence for the biological function of rt-circRNA and unveiling a new regulatory layer for liver TIC self-renewal. rtcisE2F is involved in E2F6/E2F3 stability by switching their binding to the m6A readers IGF2BP2 and YTHDF2, providing a competitive mechanism between RNA molecules and m6A readers. Both E2F6 and E2F3 are required for liver TIC self-renewal and serve as therapeutic targets for liver TIC elimination.