bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Polyomavirus-Encoded Circular RNAs
Authors: Yang Rong , Lee Eunice E. , Kim Jiwoong , Choi Joon H. , Chen Yating , Crewe Clair , Scherer Philipp E. , Kolitz Elysha , Cockerell Clay , Smith Taylor R. , Rosen Leslie , Verlinden Louisa , Feltkamp Mariet C. , Sullivan Christopher S. , Wang Richard C. 
Published: December 2020

ABSTRACTCircular RNAs (circRNAs) are a conserved class of RNAs with diverse functions. A subset of circRNAs are translated into peptides. Here we describe circular RNAs encoded by human polyomaviruses (HPyVs), including circular forms of RNAs encoding variants of the previously described alternative large T antigen open reading frame (ALTO) gene. Circular ALTO RNAs (circALTOs) can be detected in virus positive Merkel cell carcinoma (VP-MCC) cell lines and tumor samples. CircALTOs are stable, predominantly located in the cytoplasm, and N6-methyladenosine (m6A) modified. MCPyV circALTOs produce ALTO protein in cultured cells. MCPyV ALTO promotes the transcription of co-transfected reporter genes. MCPyV circALTOs are enriched in exosomes derived from VP-MCC lines and circALTO-transfected 293T cells, and purified exosomes can mediate ALTO expression and transcriptional activation. The related trichodysplasia spinulosa polyomavirus (TSPyV) also expresses a circALTO that can be detected in infected tissues and produces ALTO protein in cultured cells. Thus, human polyomavirus circRNAs are expressed in human tumors and tissues, encode for proteins, and may contribute to the infectious and tumorigenic properties of these viruses.
Transcriptional and epi-transcriptional dynamics of SARS-CoV-2 during cellular infection
Authors: Chang Jessie J.-Y. , Rawlinson Daniel , Pitt Miranda E. , Taiaroa George , Gleeson Josie , Zhou Chenxi , Mordant Francesca L. , Paoli-Iseppi Ricardo De , Caly Leon , Purcell Damian F.J. , Stinear Tim P. , Londrigan Sarah L. , Clark Michael B. , Williamson Deborah A. , Subbarao Kanta , Coin Lachlan J.M. 
Published: December 2020

SummarySARS-CoV-2 uses subgenomic (sg)RNA to produce viral proteins for replication and immune evasion. We applied long-read RNA and cDNA sequencing toin vitrohuman and primate infection models to study transcriptional dynamics. Transcription-regulating sequence (TRS)-dependent sgRNA was upregulated earlier in infection than TRS-independent sgRNA. An abundant class of TRS-independent sgRNA consisting of a portion of ORF1ab containingnsp1joined to ORF10 and 3’UTR was upregulated at 48 hours post infection in human cell lines. We identified double-junction sgRNA containing both TRS-dependent and independent junctions. We found multiple sites at which the SARS-CoV-2 genome is consistently more modified than sgRNA, and that sgRNA modifications are stable across transcript clusters, host cells and time since infection. Our work highlights the dynamic nature of the SARS-CoV-2 transcriptome during its replication cycle. Our results are available via an interactive web-app athttp://coinlab.mdhs.unimelb.edu.au/.
Interplay between extreme drift and selection intensities favors the fixation of beneficial mutations in selfing maize populations
Authors: Desbiez-Piat Arnaud , Rouzic Arnaud Le , Tenaillon Maud I. , Dillmann Christine 
Published: December 2020

ABSTRACTPopulation and quantitative genetic models provide useful approximations to predict long-term selection responses sustaining phenotypic shifts, and underlying multilocus adaptive dynamics. Valid across a broad range of parameters, their use for understanding the adaptive dynamics of small selfing populations undergoing strong selection intensity (thereafter High Drift-High selection regime, HDHS) remains to be explored. Saclay Divergent Selection Experiments (DSEs) on maize flowering time provide an interesting example of populations evolving under HDHS, with significant selection responses over 20 generations in two directions. We combined experimental data from Saclay DSEs, forward individual-based simulations, and theoretical predictions to dissect the evolutionary mechanisms at play in the observed selection responses. We asked two main questions: How do mutations arise, spread, and reach fixation in populations evolving under HDHS ? How does the interplay between drift and selection influence observed phenotypic shifts ? We showed that the long-lasting response to selection in small populations is due to the rapid fixation of mutations occurring during the generations of selection. Among fixed mutations, we also found a clear signal of enrichment for beneficial mutations revealing a limited cost of selection. Both environmental stochasticity and variation in selection coefficients likely contributed to exacerbate mutational effects, thereby facilitating selection grasp and fixation of small-effect mutations. Together our results highlight that despite a small number of polymorphic loci expected under HDHS, adaptive variation is continuously fueled by a vast mutational target. We discuss our results in the context of breeding and long-term survival of small selfing populations.
Ultra-high sensitivity mass spectrometry quantifies single-cell proteome changes upon perturbation
Authors: Brunner Andreas-David , Thielert Marvin , Vasilopoulou Catherine G. , Ammar Constantin , Coscia Fabian , Mund Andreas , Hoerning Ole B. , Bache Nicolai , Apalategui Amalia , Lubeck Markus , Richter Sabrina , Fischer David S. , Raether Oliver , Park Melvin A. , Meier Florian , Theis Fabian J. , Mann Matthias 
Published: December 2020

AbstractSingle-cell technologies are revolutionizing biology but are today mainly limited to imaging and deep sequencing1–3. However, proteins are the main drivers of cellular function and in-depth characterization of individual cells by mass spectrometry (MS)-based proteomics would thus be highly valuable and complementary4,5. Chemical labeling-based single-cell approaches introduce hundreds of cells into the MS, but direct analysis of single cells has not yet reached the necessary sensitivity, robustness and quantitative accuracy to answer biological questions6,7. Here, we develop a robust workflow combining miniaturized sample preparation, very low flow-rate chromatography and a novel trapped ion mobility mass spectrometer, resulting in a more than ten-fold improved sensitivity. We accurately and robustly quantify proteomes and their changes in single, FACS-isolated cells. Arresting cells at defined stages of the cell cycle by drug treatment retrieves expected key regulators such as CDK2NA, the E2 ubiquitin ligase UBE2S, DNA topoisomerases TOP2A/B and the chromatin regulator HMGA1. Furthermore, it highlights potential novel ones and allows cell phase prediction. Comparing the variability in more than 430 single-cell proteomes to transcriptome data revealed a stable core proteome despite perturbation, while the transcriptome appears volatile. This emphasizes substantial regulation of translation and sets the stage for its elucidation at the single cell level. Our technology can readily be applied to ultra-high sensitivity analyses of tissue material8, posttranslational modifications and small molecule studies to gain unprecedented insights into cellular heterogeneity in health and disease.
A neuronal circuit for vector computation builds an allocentric traveling-direction signal in theDrosophilafan-shaped body
Authors: Lyu Cheng , Abbott L.F. , Maimon Gaby 
Published: December 2020

AbstractMany behavioral tasks require the manipulation of mathematical vectors, but, outside of computational models1–8, it is not known how brains perform vector operations. Here we show how theDrosophilacentral complex, a region implicated in goal-directed navigation8–14, performs vector arithmetic. First, we describe neural signals in the fan-shaped body that explicitly track a fly’sallocentrictraveling direction, that is, the traveling direction in reference to external cues. Past work has identified neurons inDrosophila12,15–17and mammals18,19that track allocentric heading (e.g., head-direction cells), but these new signals illuminate how the sense of space is properly updated when traveling and heading angles differ. We then characterize a neuronal circuit that rotates, scales, and adds four vectors related to the fly’segocentrictraveling direction–– the traveling angle referenced to the body axis––to compute the allocentric traveling direction. Each two-dimensional vector is explicitly represented by a sinusoidal activity pattern across a distinct neuronal population, with the sinusoid’s amplitude representing the vector’s length and its phase representing the vector’s angle. The principles of this circuit, which performs an egocentric-to-allocentric coordinate transformation, may generalize to other brains and to domains beyond navigation where vector operations or reference-frame transformations are required.
The anatomy of a phenological mismatch: interacting consumer demand and resource characteristics determine the consequences of mismatching
Authors: Wilde Luke R. , Simmons Josiah E. , Swift Rose J. , Senner Nathan R. 
Published: December 2020

AbstractClimate change has caused shifts in seasonally recurring biological events and the temporal decoupling of consumer-resource pairs – i.e., phenological mismatching (hereafter, ‘mismatching’). Despite the hypothetical risk mismatching poses to consumers, it does not invariably lead to individual- or population-level effects. This may stem from how mismatches are typically defined, where an individual or population are ‘matched or mismatched’ based on the degree of asynchrony with a resource pulse. However, because both resource availability and consumer demands change over time, this categorical definition can obscure within- or among-individual fitness effects. We investigated the effects of resource characteristics on the growth, daily survival, and fledging rates of Hudsonian godwit (Limosa haemastica) chicks hatched near Beluga River, Alaska. To do this, we developed models to identify the effects of resource characteristics on individual- and population-level processes and determine how the strength of these effects change throughout a consumer’s early development. We found that at the individual-level, chick growth and survival improved following periods of higher invertebrate abundance but were increasingly dependent on the availability of larger prey as chicks aged. At the population level, seasonal fledging rates were best explained by a model including age-structured consumer demand. Our study suggests that modelling the effects of mismatching as a disrupted interaction between consumers and their resources provides a biological mechanism for how mismatching occurs and clarifies when it matters to individuals and populations. Given the variable responses to mismatching exhibited by consumer populations, such tools for predicting how populations may respond under future climatic conditions will be critical for conservation planning.
Characterizing intra-tumor and inter-tumor variability of immune cell infiltrates in murine syngeneic tumors
Authors: Mojtahedzadeh Sepideh , Opsahl Alan , Aguilar Joan-Kristel , Li Dingzhou , Streiner Nicole , Wang Jinwei , Trajkovic Dusko , Boucher Germaine , Coskran Timothy , O’Neil Shawn P. , Ram Sripad 
Published: December 2020

ABSTRACTBy using serial-sectioning methodology combined with immunohistochemistry (IHC) and whole-slide digital image analysis (DIA), we present a systematic analysis of intra-tumor and inter-tumor variability in the abundance of nine immune cell biomarkers in multiple murine tumor models. Our analysis shows that inter-tumor variability is typically the dominant source of variation in measurements of immune cell densities. Statistical power analysis reveals how group size and variance in immune cell density estimates affect the predictive power for detecting a statistically meaningful fold-change in immune cell density. Inter-tumor variability in the ratio of immune cell densities show distinct patterns in select tumor models and reveal the existence of strong correlations between select biomarker pairs. Further, we show that the relative proportion of immune cells at different depths across tumor samples is preserved in some but not all tumor models thereby revealing the existence of compositional heterogeneity. The results and analyses presented here reveal the complex nature of immunologic heterogeneity that exists in murine tumor models and provide guidelines for designing preclinical studies for immuno-oncology research and drug development.
A WD40 repeat-like protein pathway connects F-BOX STRESS INDUCED (FBS) proteins to the NIGT1.1 transcriptional repressor in Arabidopsis
Authors: Sepulveda-Garcia Edgar , Fulton Elena C , Parlan Emily V , Brauning Ashley A , O’Connor Lily E , Fleming Anneke A , Replogle Amy J , Rocha-Sosa Mario , Gendron Joshua M , Thines Bryan 
Published: December 2020

ABSTRACTSCF-type E3 ubiquitin ligases use F-box (FBX) proteins as interchangeable substrate adaptors to recruit protein targets for ubiquitylation. FBX proteins almost universally have structure with two domains. A conserved N-terminal F-box domain interacts with a SKP protein and connects the FBX protein to the core SCF complex, while a C-terminal domain interacts with the protein target and facilitates recruitment. The F-BOX STRESS INDUCED (FBS) subfamily of four plant FBX proteins has atypical domain structure, however, with a centrally located F-box domain and additional conserved regions at both the N- and C-termini. FBS proteins have been linked to environmental stress networks, but no ubiquitylation target(s) or exact biological function has been established for this subfamily. We have identified two WD40 repeat-like proteins in Arabidopsis that are highly conserved in plants and interact with FBS proteins, which we have named FBS INTERACTING PROTEINs (FBIPs). FBIPs interact exclusively with the N-terminus of FBS proteins, and this interaction occurs in the nucleus. FBS1 destabilizes FBIP1, consistent with FBIPs being ubiquitylation targets of SCFFBScomplexes. Furthermore, we found that FBIP1 interacts with NIGT1.1, a GARP-type transcriptional repressor that regulates nitrate and phosphate starvation signaling and responses. Collectively, these interactions between FBS, FBIP, and NIGT1.1 proteins delineate a previously unrecognized SCF-connected transcription regulation module that works in the context of phosphate and nitrate starvation, and possibly other environmental stresses. Importantly, this work also identified two uncharacterized WD40 repeat-like proteins as new tools with which to probe how an atypical SCF complex, SCFFBS, functions via FBX protein N-terminal interaction events.
Creation and validation of 3D-printed head molds for stereotaxic injections of neonatal mouse brains
Authors: Chervonski Ethan , Brockman Asa A. , Khurana Rohit , Chen Yuhao , Greenberg Sabrina , Hay Madeleine S. , Luo Yifu , Miller Jason , Patelis Deanna , Whitney Sarah K. , Walker Matthew , Ihrie Rebecca A. 
Published: December 2020

AbstractBackgroundAn increasing number of rodent model systems use injection of DNA or viral constructs in the neonatal brain. However, approaches for reliable positioning and stereotaxic injection at this developmental stage are limited, typically relying on handheld positioning or molds that must be re-aligned for use in a given laboratory.New methodA complete protocol and open source software pipeline for generating 3D-printed head molds derived from a CT scan of a neonatal mouse head cast, together with a universal adapter that can be placed on a standard stereotaxic stage.ResultsA series of test injections with adenovirus encoding red fluorescent protein were conducted using original clay molds and newly generated 3D printed molds. Several metrics were used to compare spread and localization of targeted injections.Comparison with existing methodsThe new method of head mold generation gave comparable results to the field standard, but also allowed the rapid generation of additional copies of each head mold with standardized positioning of the head each time.ConclusionsThis 3D printing pipeline can be used to rapidly develop a series of head molds with standardized injection coordinates across multiple laboratories. More broadly, this pipeline can easily be adapted to other perinatal ages or species.
Structural basis for the dimerization-dependent CRISPR-Cas12f nuclease
Authors: Xiao Renjian , Li Zhuang , Wang Shukun , Han Ruijie , Chang Leifu 
Published: December 2020

ABSTRACTCas12f, also known as Cas14, is an exceptionally small type V-F CRISPR-Cas nuclease that is roughly half the size of comparable nucleases of this type. To reveal the mechanisms underlying substrate recognition and cleavage, we determined the cryo-EM structures of the Cas12f-sgRNA-target DNA and Cas12f-sgRNA complexes at 3.1 Å and 3.9 Å, respectively. An asymmetric Cas12f dimer is bound to one sgRNA for recognition and cleavage of dsDNA substrate with a T-rich PAM sequence. Despite its dimerization, Cas12f adopts a conserved activation mechanism among the type V nucleases which requires coordinated conformational changes induced by the formation of the crRNA-target DNA heteroduplex, including the close-to-open transition in the lid motif of the RuvC domain. Only one RuvC domain in the Cas12f dimer is activated by substrate recognition, and the substrate bound to the activated RuvC domain is captured in the structure. Structure-assisted truncated sgRNA, which is less than half the length of the original sgRNA, is still active for target DNA cleavage. Our results expand our understanding of the diverse type V CRISPR-Cas nucleases and facilitate potential genome editing applications using the miniature Cas12f.
Intra-Ramanome Correlation Analysis Unveils Metabolite Conversion Network from an Isogenic Cellular Population
Authors: He Yuehui , Huang Shi , Zhang Peng , Ji Yuetong , Xu Jian 
Published: December 2020

AbstractRevealing dynamic features of cellular systems, such as links among metabolic phenotypes, typically requires a time- or condition-series set of samples. Here Intra-Ramanome Correlation analysis (IRCA) was proposed to achieve this goal from just one snapshot of an isogenic population, by pairwise correlating among cells all the thousands of Raman bands from Single-cell Raman Spectra (SCRS), i.e., based on the intrinsic inter-cellular metabolic heterogeneity. IRCA ofChlamydomonas reinhardtiiunder nitrogen depletion revealed a metabolite conversion network at each time point and its temporal dynamics that feature protein-to-starch conversion followed by starch-to-TAG conversion (plus conversion of membrane lipids to TAG). Such correlation patterns in IRCA were abrased by knocking out the starch-biosynthesis pathway yet fully restored by genetic complementation. Extension to 64 ramanomes from microalgae, fungi and bacteria under various conditions suggests IRCA-derived metabolite conversion network as an intrinsic, reliable, species-resolved and state-sensitive metabolic signature of isogenic cellular population. The high throughput, low cost, excellent scalability and broad extendibility of IRCA suggest its broad application in cellular systems.
New look at RSV infection : tissue clearing and 3D imaging of the entire mouse lung at cellular resolution
Authors: Frétaud Maxence , Descamps Delphyne , Laubreton Daphné , Rameix-Welti Marie-Anne , Eléouët Jean-François , Larcher Thibaut , Galloux Marie , Langevin Christelle 
Published: December 2020

AbstractBackgroundRespiratory Syncytial Virus (RSV) is the major cause of severe acute respiratory tract illness in young children worldwide and a main pathogen for the elderly and immune-compromised people. In the absence of vaccines or effective treatments, a better characterization of the pathogenesis of RSV infection is required. To date, the pathophysiology of the disease and its diagnosis mostly relied on chest x-ray and genome detection in nasopharyngeal swabs. The development of new imaging approaches is instrumental to further the description of RSV spread, virus-host interactions and related acute respiratory disease, at the level of the entire lung.MethodsBy combining tissue clearing, 3D microscopy and image processing, we developed a novel visualization tool of RSV infection in undissected mouse lungs.ResultsWhole tissue analysis allowed the identification of infected cell subtypes, based on both morphological traits and position within the cellular network. Furthermore, 3D imaging was also valuable to detect the cytoplasmic viral factories, also called inclusion bodies, a hallmark of RSV infection.ConclusionsWhole lung clearing and 3D deep-imaging represents an unprecedented visualization method of infected lungs to allow insight into RSV pathophysiology and improve the 2D histology analyses.
Unveiling a postcolonial neoliberalism: hybridised controls and emancipatory potentials for tea-plucking women in Sri Lanka
Authors: Ranasinghe Seuwandhi Buddhika , Wickramasinghe Danture 
Published: December 2020

PurposeDrawing on the ideas of postcolonial hybridity and postcolonial feminism, the purpose of this paper is to explore a contextual variant of neoliberalism, which the authors call postcolonial neoliberalism. It unpacks the peculiarities of hybridised practices of management controls therein to reflect on its construction and consequences.Design/methodology/approachA seven-month ethnographic study was carried out in a Sri Lankan tea estate to understand both the nature and the practices of these controls.FindingsPostcolonial neoliberalism has been animated by a hybrid form of management controls encompassing colonial action controls, postcolonial cultural controls and neoliberal results controls. This created an emancipatory space for female workers to engage in some confrontations to attain some compromises.Originality/valueThe message is that the hybridised controls are central to the construction of this form of postcolonial neoliberalism and to its reproduction. However, as these controls accompany a gendered form, female workers find a condition of possibility for some emancipatory potentials within the neoliberal development policy.
Differences in game consumption patterns between North and South China
Authors: Wei Lei , Hao Yiting (Demi) , Zhu Hong , Li Jun (Justin) 
Published: December 2020

PurposeThe 2019 novel coronavirus (COVID-19) pandemic has affected many countries around the world. Due to the debate on the source of the outbreak, wildlife meat consumption has gained international attention and become an area that requires further exploration. The purpose of this research is to explore the differences in game consumption motivations and behaviours among populations in northern and southern China.Design/methodology/approachAn online survey on wild meat awareness with (potential) game consumers across the country as target groups was conducted.FindingsResults from this study showed that consumers in the southern region have a preference for wildlife. This preference was determined by factors such as natural environment, history and culture and the level of economic development. However, there was no significant difference in the frequency of game consumption between the north and south since game meat is not a major component of the daily diet.Practical implicationsThe government should consider banning this trade permanently to prevent future disease outbreaks caused by wildlife-to-human transmissions.Originality/valueThe consumption of game meat is regional, but the animals in game trades live across a wider area, and thus, game trades have a global influence on ecological systems and human health. Therefore, this epidemic is also a global concern, which might lead people to display a highly negative attitude towards consuming game meat.