bluuebunny/crossref_metadata_2025_split huggingface dataset:
OncoGEMINI: Software for Investigating Tumor Variants From Multiple Biopsies With Integrated Cancer Annotations
Authors: Nicholas Thomas J. , Cormier Michael J. , Huang Xiaomeng , Qiao Yi , Marth Gabor T. , Quinlan Aaron R. 
Published: March 2020

AbstractDNA sequencing has unveiled extensive tumor heterogeneity in several different cancer types, with many exhibiting diverse subclonal populations. Identifying and tracing mutations throughout the expansion and progression of a tumor represents a significant challenge. Furthermore, prioritizing the subset of such mutations most likely to contribute to tumor evolution or that could serve as potential therapeutic targets represents an ongoing problem. Here we describe OncoGEMINI, a new tool designed for exploring the complex patterns and trajectory of somatic and inherited variation observed in heterogeneous tumors biopsied over the course of treatment. This is accomplished by creating a searchable database of variants that includes tumor sampling timepoints and allows for filtering methods that reflect specific changes in variant allele frequencies over time. Additionally, by incorporating existing annotations and resources that facilitate the interpretation of cancer mutations (e.g., CIViC, DGIdb), OncoGEMINI enables rapid searches for, and potential identification of, mutations that may be driving subclonal evolution.
Transcriptional repression of Myc underlies AGO1’s tumour suppressor function
Authors: Zaytseva Olga , Mitchell Naomi C. , Guo Linna , Marshall Owen J. , Parsons Linda M. , Hannan Ross D. , Levens David L. , Quinn Leonie M. 
Published: March 2020

AbstractHere we report novel tumour suppressor activity for theDrosophilaArgonaute family RNA binding protein AGO1, a component of the miRNA-dependent RNA-induced silencing complex (RISC). The mechanism for growth inhibition does not, however, involve canonical roles as part of the RISC; rather AGO1 controls cell and tissue growth by functioning as a direct transcriptional repressor of the master regulator of growth, Myc. AGO1 depletion in wing imaginal discs drives a significant increase in ribosome biogenesis, nucleolar expansion, and cell growth in a manner dependent on Myc abundance. Moreover, increasedMycpromoter activity and elevatedMycmRNA in AGO1 depleted animals requires RNA Pol II transcription. Further support for transcriptional AGO1 functions is provided by physical interaction with the RNA Pol II transcriptional machinery (chromatin remodelling factors and Mediator Complex), punctate nuclear localisation in euchromatic regions and overlap with Polycomb Group transcriptional silencing loci. Moreover, significant AGO1 enrichment is observed on theMycpromoter and AGO1 interacts with theMyctranscriptional activator Psi. Together our data show AGO1 functions outside of the RISC to repressMyctranscription and inhibit developmental cell and tissue growth.
Molecular basis of ubiquitination catalyzed by the bacterial transglutaminase MavC
Authors: Guan Hongxin , Fu Jiaqi , Yu Ting , Wang Zhao-Xi , Gan Ninghai , Huang Yini , Perčulija Vanja , Li Yu , Luo Zhao-Qing , Ouyang Songying 
Published: March 2020

SummaryTheLegionella pneumophilaeffector MavC is a transglutaminase that carries out atypical ubiquitination of the ubiquitin (Ub) E2 conjugation enzyme UBE2N by catalyzing the formation of an isopeptide bond between Gln40 of Ub and Lys92 (or to a less extent, Lys94) of UBE2N, which results in inhibition of UBE2N signaling in the NF-κB pathway. In the absence of UBE2N, MavC deamidates Ub at Gln40 or catalyzes self-ubiquitination. However, the mechanisms underlying these enzymatic activities of MavC are not fully understood at molecular level. In this study, we obtained the structure of the MavC-UBE2N-Ub ternary complex that represents a snapshot of covalent cross-linking of UBE2N and Ub catalyzed by MavC. The structure reveals the unique way by which the cross-linked catalytic product UBE2N-Ub binds mainly to the Insertion and the Tail domains of MavC prior to its release. Based on our structural, biochemical and mutational analyses, we proposed the catalytic mechanism for both the deamidase and the transglutaminase activities of MavC. Finally, by comparing the structures of MavC and MvcA, the homologous protein that reverses MavC-induced UBE2N ubiquitination, we identified several key regions of the two proteins responsible for their opposite enzymatic activity. Our results provide insights into the mechanisms for substrate recognition and ubiquitination mediated by MavC as well as explanations for the opposite activity of MavC and MvcA.
Biophysical forces rewire cell metabolism to guide microtubule-dependent cell mechanics
Authors: Torrino Stephanie , Audebert Stephane , Belhadj Ilyes , Lacoux Caroline , Pisano Sabrina , Abélanet Sophie , Brau Frederic , Chan Stephen Y. , Mari Bernard , Oldham William M , Bertero Thomas 
Published: March 2020

AbstractMechanical signals regulate cell shape and influence cell metabolism and behavior. Cells withstand external forces by adjusting the stiffness of its cytoskeleton. Microtubules (MTs) act as compression-bearing elements in response to mechanical cues. Therefore, MT dynamics affect cell mechanics. Yet, how mechanical loads control MT dynamics to adjust cell mechanics to its locally constrained environment has remained unclear. Here, we show that mechanical forces rewire glutamine metabolism to promote MT glutamylation and force cell mechanics, thereby modulating mechanodependent cell functions. Pharmacologic inhibition of glutamine metabolism decreased MT glutamylation and affected their mechanical stabilization. Similarly, depletion of the tubulin glutamylase TTLL4 or overexpression of tubulin mutants lacking glutamylation site(s) increased MT dynamics, cell compliance and contractility, and thereby impacted cell spreading, proliferation and migration. Together our results indicate that mechanical cues sustain cell mechanics through glutaminolysis-dependent MT glutamylation, linking cell metabolism to MT dynamics and cell mechanics. Furthermore, our results decipher part of the enigmatic tubulin code that coordinates the fine tunable properties of MT mechanics, allowing cells to adjust the stiffness of their cytoskeleton to the mechanical loads of their environment.
Less is more: Light sampling via throttled visual phototransduction robustly synchronizes theDrosophilacircadian clock in the absence of Cryptochrome
Authors: Ogueta Maite , Hardie Roger C , Stanewsky Ralf 
Published: March 2020

SummaryThe daily changes of light and dark exemplify a prominent cue for the synchronization of internal circadian clocks to external time. The match between external and internal time is crucial for the fitness of organisms and desynchronization has been linked to numerous physical and mental health problems in humans. Organisms therefore developed complex and not fully understood mechanisms to synchronize their circadian clock to light. In mammals and inDrosophilaboth the visual system and dedicated non-image forming photoreceptors contribute to light resetting of the circadian clock. In the fruit fly, light-dependent degradation of the clock protein TIMELESS (TIM) by the blue light photoreceptor Cryptochrome is considered the main mechanism for clock synchronization, although the visual system also contributes. In order to understand the nature of the visual system contribution, we generated a genetic variant exhibiting extremely slow phototransduction kinetics, yet normal sensitivity. We show that in this variant the visual system is able to contribute its full share to circadian clock entrainment, both with regard to behavioral and molecular synchronization to light:dark cycles. This function depends on an alternative Phospholipase C-ß enzyme, encoded byPLC21C, presumably playing a dedicated role in clock resetting by light. We show that this pathway requires the ubiquitin ligase CULLIN-3, presumably mediating CRY-independent degradation of TIM during light:dark cycles. Our results suggest that visual system contribution to circadian clock entrainment operates on a drastically slower time scale compared with fast, visual and image forming phototransduction. Our findings are therefore consistent with the general idea that the visual system samples light over prolonged periods of time (hours) in order to reliably synchronize their internal clocks with the external time.
Peripheral tolerance checkpoints imposed by ubiquitous antigen expression limit antigen-specific B-cell responses under strongly immunogenic conditions
Authors: Brooks Jeremy F. , Murphy Peter R. , Barber James E.M. , Wells James W. , Steptoe Raymond J. 
Published: March 2020

AbstractA series of layered peripheral checkpoints maintain self-reactive B cells in an unresponsive state. Autoantibody production occurs when these checkpoints are breached, however, when and how this occurs is largely unknown. In particular, how self-reactive B cells are restrained during bystander inflammation in otherwise healthy individuals is poorly understood. A weakness has been the unavailability of methods capable of dissecting physiologically-relevant B-cell responses, without the use of an engineered B-cell receptor. Resolving this will provide insights that decipher how this process goes awry during autoimmunity or could be exploited for therapy. Here we use a strong adjuvant to provide bystander innate and adaptive signals that promote B-cell responsiveness, in conjunction with newly developed B cell detection tools to study in detail the ways that peripheral tolerance mechanisms limit the expansion and function of self-reactive B cells activated under these conditions. We show that although autoreactive B cells are recruited into the germinal centre, their development does not proceed, possibly through rapid counter-selection. Consequently, differentiation of plasma cells is blunted, and autoantibody responses are transient and devoid of affinity maturation. We propose this approach and these tools can be more widely applied to track antigen-specific B cell responses to more disease relevant antigens, without the need for BCR transgenic mice, in settings where tolerance pathways are compromised or have been genetically manipulated to drive stronger insights into the biology underlying B cell-mediated autoimmunity.
Fact retrieval or compacted procedures in arithmetic – a neurophysiological investigation of two hypotheses
Authors: Grabner Roland H. , Brunner Clemens , Lorenz Valerie , Vogel Stephan E. , De Smedt Bert 
Published: March 2020

ABSTRACTThere is broad consensus that adults solve single-digit multiplication problems almost exclusively by fact retrieval (i.e., retrieval of the solution from an arithmetic fact network). In contrast, there has been a long-standing debate on the cognitive processes involved in solving single-digit addition problems. This debate has evolved around two theoretical accounts. Thefact-retrieval accountpostulates that these are solved through fact retrieval, just like multiplications, whereas thecompacted-procedure accountproposes that solving very small additions (i.e., problems with operands between 1 and 4) involves highly automatized and unconscious compacted procedures. In the present electroencephalography (EEG) study, we put these two accounts to the test by comparing neurophysiological correlates of solving very small additions and multiplications. A sample of 40 adults worked on an arithmetic production task involving all (non-tie) single-digit additions and multiplications. Afterwards, participants completed trial-by-trial strategy self-reports. In our EEG analyses, we focused on induced activity (event-related synchronization/desynchronization, ERS/ERD) in three frequency bands (theta, lower alpha, upper alpha). Across all frequency bands, we found higher evidential strength for similar rather than different neurophysiological processes accompanying the solution of very small addition and multiplication problems. This was also true whenn+ 1 andn× 1 problems were excluded from the analyses. In two additional analyses, we showed that ERS/ERD can differentiate between self-reported problem-solving strategies (retrieval vs. procedure) and even betweenn+ 1 andn+mproblems in very small additions, demonstrating its high sensitivity to cognitive processes in arithmetic. The present findings clearly support the fact-retrieval account, suggesting that both very small additions and multiplications are solved through fact retrieval.HIGHLIGHTSNeurophysiological test of fact retrieval and compacted procedures accountInduced EEG data are sensitive to cognitive processes in arithmetic problem solvingBoth very small additions and multiplications are solved through fact retrieval
The murine Microenvironment Cell Population counter method to estimate abundance of tissue-infiltrating immune and stromal cell populations in murine samples using gene expression
Authors: Petitprez Florent , Lévy Sacha , Sun Cheng-Ming , Meylan Maxime , Linhard Christophe , Becht Etienne , Elarouci Nabila , Roumenina Lubka T. , Ayadi Mira , Sautès-Fridman Catherine , Fridman Wolf H. , de Reyniès Aurélien 
Published: March 2020

AbstractQuantifying tissue-infiltrating immune and stromal cells provides clinically relevant information for various diseases, notably cancer. While numerous methods allow to quantify immune or stromal cells in human tissue samples based on transcriptomic data, very few are available for mouse studies. Here, we introduce murine Microenvironment Cell Population counter (mMCP-counter), a method based on highly specific transcriptomic markers that allow to accurately quantify 12 immune and 4 stromal murine cell populations. We validated mMCP-counter with flow cytometry data. We also showed that mMCP-counter outperforms existing methods. We showed in mouse models of mesothelioma and kidney cancer that mMCP-counter quantification scores are predictive of response to immune checkpoint blockade Finally, we illustrated mMCP-counter’s potential to analyze immune impacts of Alzheimer’s disease. mMCP-counter is available as an R package from GitHub:https://github.com/cit-bioinfo/mMCP-counter.
DE NOVOSEQUENCING AND ANALYSIS OF THERANA CHENSINENSISTRANSCRIPTOME TO DISCOVER PUTATIVE GENES ASSOCIATED WITH POLYUNSATURATED FATTY ACIDS
Authors: Sun Jingmeng , Wang Zhuoming , Zhang Weiyu 
Published: March 2020

ABSTRACTRana chensinensis(R. chensinensis) is an important wild animal found in China, and a precious animal in Chinese herbal medicine.R. chensinensisis rich in polyunsaturated fatty acids (PUFAS). However, information regarding the genes ofR. chensinensisrelated to the synthesis of PUFAs is limited. To identify these genes, we performed Illumina sequencing ofR. chensinensisRNA from the skin and Oviductus Ranae. The Illumina Hiseq 2000 platform was used for sequencing, and the I-Sanger cloud platform was used for transcriptomede novosequencing and information analysis to generate a database. Through the database generated by the transcriptome and the pathway map, we found the pathway for the biosynthesis ofR. chensinensisPUFAs. The Pearson coefficient method was used to analyze the correlation of gene expression levels between samples, and the similarity of gene expression in different tissues and the characteristics in their respective tissues were found. Twelve differentially expressed genes of PUFA in skin and Oviductus Ranae were screened by gene differential expression analysis. The 12 unigenes expression levels of qRT-PCR were used to verify the results of gene expression levels consistent with transcriptome analysis. Based on the sequencing, key genes involved in biosynthesis of unsaturated fatty acids were isolated, which established a biotechnological platform for further research onR. chensinensis.
In silico Design of novel Multi-epitope recombinant Vaccine based on Coronavirus surface glycoprotein
Authors: Behbahani Mandana 
Published: March 2020

AbstractIt is of special significance to find a safe and effective vaccine against coronavirus disease 2019 (COVID-19) that can induce T cell and B cell -mediated immune responses. There is currently no vaccine to prevent COVID-19. In this project, a novel multi-epitope vaccine for COVID-19 virus based on surface glycoprotein was designed through application of bioinformatics methods. At the first, seventeen potent linear B-cell and T-cell binding epitopes from surface glycoprotein were predicted in silico, then the epitopes were joined together via different linkers. The ability of the selected epitopes to induce interferon-gamma was evaluate using IFNepitope web server. One final vaccine was constructed which composed of 398 amino acids and attached to 50S ribosomal protein L7/L12 as adjuvant. Physicochemical properties, as well as antigenicity in the proposed vaccines, were checked for defining the vaccine stability and its ability to induce cell-mediated immune responses. Three-dimensional structure of the mentioned vaccine was subjected to the molecular docking studies with MHC-I and MHC-II molecules. The results proposed that the multi-epitope vaccine with 50S ribosomal protein L7/L12 was a stable construct with high aliphatic content and high antigenicity.
Effects of environmental variables on the distribution of juvenile cubomedusaeCarybdea marsupialisin the coastal Western Mediterranean
Authors: Bordehore Cesar , Fonfría Eva S. , Alonso Cristina , Rubio-Tortosa Beatriz , Acevedo Melissa J. , Canepa Antonio , Falcó Silvia , Rodilla Miguel , Fuentes Verónica 
Published: March 2020

AbstractRelationships between environmental factors and oscillations in jellyfish abundance, especially in the early life stages, could help to interpret past increases and also predict scenarios in a changing future. For the first time, we present cubozoan spatial and temporal distributions in the earliest stages and their relationships with different factors. Abundances ofCarybdea marsupialismedusae showed high interannual variability from 2008 to 2014 along the Dénia coast (SE Spain, W Mediterranean). During 2015, samples were collected from 11 beaches along 17 km of coastline, 8 times from January to November in order to determine the effects of environmental factors on the distribution of juvenileC. marsupialis. Juveniles (≤ 15 mm diagonal bell width) were present from May to July, with more sampled near shore (0 – 15 m). Most of them occurred in June when their numbers were unequal among beaches (average 0.05 ind m−3, maximum 6.71 ind m−3). We tested distributions of juveniles over time and space versus temperature, salinity, nutrients (N, P and Si), chlorophyll-a(Chl-a), and zooplankton abundance. Temperature and cladocerans (zooplankton group) were significantly positively correlated with juvenile distribution, whereas Chl-aconcentration was weakly negative. By contrast, in 2014, high productivity areas (Chl-aand zooplankton) overlapped the maximum adult abundance (5.2 ind m−3). The distribution of juveniles during 2015 did not spatially coincide with the areas where ripe adults were located the previous year, suggesting that juveniles drift with the currents upon release from the cubopolyps. Our results yield important insights into the complexity of cubozoan distributions.
Differential vaginalLactobacillusspecies metabolism of glucose, L and D-lactate by13C-nuclear magnetic resonance spectroscopy
Authors: Amabebe Emmanuel , Anumba Dilly O. , Reynolds Steven 
Published: March 2020

AbstractIntroductionCervicovaginal dysbiosis can lead to infection-associated spontaneous preterm birth.ObjectiveTo determine whether vaginalLactobacillusspecies,L. crispatusandL. jensenii, differentially metabolise glucose, L- and/or D-lactate to propagate their survival/dominance.MethodsBacteria were incubated anaerobically for 24h at 37°C, with13Cu-glucose,13C3-D-lactate or13C3-L-lactate (singularly or combined) for 24h.13C-spectra were acquired using a 9.4T NMR spectrometer.ResultsL. crispatusandL. jensenii(n=6 each) metabolised13C-glucose to13C-lactate and13C-acetate.L. jenseniiconverted more13C3-D- or13C3-L-lactate to13C-acetate thanL. crispatus, p<0.001.ConclusionConversion of glucose and lactate to acetate byL. jenseniicompared toL. crispatus, suggests a possibly important pathomechanism of dysbiosis and infection-associated spontaneous preterm birth.
Drinking biodiversity: a choice experiment on Franciacorta sparkling wines
Authors: Ruggeri Giordano , Mazzocchi Chiara , Corsi Stefano 
Published: March 2020

PurposeConsumers' concerns about the environmental impacts of food production have been increasing over the last years, and several certification systems for environment-friendly food products have been created. This research investigates wine consumers' preferences for a certification that guarantees the use of agricultural practices that better protect the biodiversity in the vineyard during the production of grapes.Design/methodology/approachUsing a choice experiment, we investigate consumer preferences and willingness to pay for biodiversity-friendly wines on a sample of 334 wine consumers. The experiment was carried out by direct interviews at a wine-tasting event in an Italian winery located in the Franciacorta area, in northern Italy. A between-subject design and two different questionnaires were used, one presenting the Brut bottle and one the Satén bottle.FindingsEstimates from a mixed logit model reveal that consumers are generally willing to pay a higher price for biodiversity-friendly wines, but they have stronger preferences for organic certification and quality indications. When consumers perceive a specific product as having high quality, i.e. Satèn, they might be less willing to pay for further environment-friendly certifications. Moreover, preferences depend on sociodemographic and attitudinal variables such as gender, wine consumption frequency, wine education and knowledge degree of the labels.Originality/valueThis paper broadens the knowledge about consumer preferences and willingness to pay for biodiversity-friendly wines, focusing on a specific market segment of Italian sparkling wines.
Business buyers are people too: exploring how geodemographics affects business-to-business selling effectiveness
Authors: Mier Joel , Carlson Jeffrey , Bellenger Danny Norton , Johnston Wesley J. 
Published: March 2020

Purpose
Drawing from the contingency model, this study aims to investigate the moderating effects of business-to-business (B2B) buyer personal characteristics on the relationship between sales activities and sales effectiveness.

Design/methodology/approach
As an application of engaged scholarship, this study leverages a years’ worth of sales activity and results from a Fortune 500 financial services company for 2,710 dyads; personal characteristics (i.e. geodemographics) were appended for the customers/prospects of the dyads. The data was analyzed with hierarchical regression, and subgroups were tested using the Chow test.

Findings
The results support that geodemographic segments – as a proxy for personal characteristics – moderate the strength of the relationship between selling activities and sales effectiveness. Overall, the results demonstrate that selling activities have varying impacts on sales effectiveness within geodemographic segments and buyclass scenarios.

Practical implications
While it has been long held that understanding the personal characteristics of the B2B purchasing decision-maker is critical for sales effectiveness, little guidance has been provided on how to accomplish this to scale. The present study provides a framework and process for practitioner operationalization.

Originality/value
This research contributes to the literature that has explored personal characteristics of buying center members. Additionally, the results suggest that personal characteristics of the purchase decision-maker may transcend business-to-consumer and B2B purchasing contexts.