bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogenous adhesion of follower cells affects tension profile and velocity of leader cells in primary keratocyte collective cell migration
Authors: Mukherjee Baishali , Chakraborty Madhura , Biswas Arikta , Nayak Rajesh Kumble , Sinha Bidisha 
Published: December 2020

AbstractSingle cell studies demonstrate membrane tension to be a central regulator of lamellipodia-driven motility bringing in front-coherence. During collective cell migration, however, tension mapping or existence of intracellular tension-gradients and the effect of cell-cell interactions have remained unexplored. In this study of membrane fluctuations and fluctuation-tension of migrating primary keratocyte cell-sheets, we first show that some leader cells are followed by followers which remain de-adhered from the substrate while being attached to other cells and thus appear to be “taking a ride”. A subtle yet significant enhanced long-timescale velocity in these leaders indicate increased directionality. Intriguingly, such leaders mostly have front-high tension gradients like single keratocytes, while followers and other leaders usually display front-low membrane tension gradients. The front-high tension gradient and higher membrane tension observed in these leaders, despite the high cell-to-cell variability in membrane tension demonstrate how leader-follower interactions and heterogenous adhesion profiles are key in collective cell migration.
Evolving Structure and Diversity of Human Narratives in the Journal of Stories in Science
Authors: Mach Reilly Q. , Tsai Jessica W. , Muindi Fanuel J. 
Published: December 2020

AbstractFundamentally, science is about people. The stories of the people behind the science are just as important as the results themselves, even though the results are often what get more attention. Despite the growth of databases storing such stories across diverse mediums, a detailed assessment of those databases is missing. To continue innovating science storytelling, we provide the first assessment of the structure and diversity of the narratives published in the Journal of Stories in Science. In this assessment, a total of 170 published stories authored by 158 authors between 2016 and 2020 are analyzed. Majority (67%) of the authors are women from North America and in the life sciences. The narratives most commonly feature authors from academia (e.g., 23% graduate students, 13% post-doctoral fellows and 21% professors). However, there is also a growing number of authors with PhDs that are working outside of academia (15%). Nearly a quarter (23%) of the database authors come from racial groups (African American, Latino, and Hispanic) that have been shown to be underrepresented in health-related sciences in the United States. Using the industry standard Flesch Reading Ease Score, we found that 74% of the stories included in the analysis fall in the target range of 50-70, which represents readability by students in grades 8-12. The analysis here provides the first deep look into one of the databases publishing diverse stories in science using a wide range of mediums. In summary, there is a need for more emphasis on both expanding and studying such databases given the continuous demand for these stories and their inclusion into K-12 curriculums.
constclust: Consistent Clusters for scRNA-seq
Authors: Virshup Isaac , Choi Jarny , Lê Cao Kim-Anh , Wells Christine A 
Published: December 2020

1AbstractUnsupervised clustering to identify distinct cell types is a crucial step in the analysis of scRNA-seq data. Current clustering methods are dependent on a number of parameters whose effect on the resulting solution’s accuracy and reproducibility are poorly understood. The adjustment of clustering parameters is therefore ad-hoc, with most users deviating minimally from default settings.constclustis a novel meta-clustering method based on the idea that if the data contains distinct populations which a clustering method can identify, meaningful clusters should be robust to small changes in the parameters used to derive them. By reconciling solutions from a clustering method over multiple parameters, we can identify locally robust clusters of cells and their corresponding regions of parameter space. Rather than assigning cells to a single partition of the data set, this approach allows for discovery of discrete groups of cells which can correspond to the multiple levels of cellular identity. Additionallyconstclustrequires significantly fewer computational resources than current consensus clustering methods for scRNA-seq data. We demonstrate the utility, accuracy, and performance ofconstclustas part of the analysis workflow.constclustis available athttps://github.com/ivirshup/constclust1.
Pseudodesulfovibrio cashewsp. nov., a novel deep-sea sulfate-reducing bacterium, linking heavy metal resistance and sulfur cycle
Authors: Zheng Rikuan , Sun Chaomin 
Published: December 2020

ABSTRACTSulfur cycling is primarily driven by sulfate reduction mediated by sulfate-reducing bacteria (SRB) in marine sediments. The dissimilatory sulfate reduction drives the production of enormous quantities of reduced sulfide and thereby the formation of highly insoluble metal sulfides in marine sediments. Here, a novel sulfate-reducing bacterium designatedPseudodesulfovibrio cashewSRB007 was isolated and purified from the deep-sea cold seep and proposed to represent a novel species in the genus ofPseudodesulfovibrio.A detailed description of the phenotypic traits, phylogenetic status and central metabolisms of strain SRB007, allowing the reconstruction of the metabolic potential and lifestyle of a novel member of deep-sea SRB. Notably,P. cashewSRB007 showed a strong ability to resist and remove different heavy metal ions including Fe3+, Co2+, Ni2+, Cu2+, Cd2+and Hg2+. And the dissimilatory sulfite reduction was demonstrated to contribute to the prominent removal capability ofP. cashewSRB007 against different heavy metals via forming insoluble metal sulfides.IMPORTANCEThe dissimilatory sulfate reduction driven by sulfate-reducing bacteria (SRB) was ubiquitous in marine sediments, and was proposed to couple with heavy metal ions removal through forming insoluble metal sulfides. The deep-sea cold seep is a very special environment where is rich in sulfate and novel species of SRB that possessing many unknown mechanisms toward sulfur cycle. Here, a novel sulfate-reduction bacteriumPseudodesulfovibrio cashewSRB007 was isolated from the deep-sea cold seep and proposed as the type strain for a novel species. The taxonomy and typical physiological properties closely related to sulfur cycle, heavy metal resistance and their co-relationship were disclosed through a combination of genomic and biochemical methods. Given the absence of pure cultures of typical SRB isolated from the deep-sea cold seep, our work provides a good model to study the sulfur cycle which coupling with other elements and a potential candidate to develop bioremediation product in the future.
Protease-mediated processing of Argonaute proteins controls small RNA association
Authors: Gudipati Rajani Kanth , Braun Kathrin , Gypas Foivos , Hess Daniel , Schreier Jan , Carl Sarah H. , Ketting René F. , Großhans Helge 
Published: December 2020

SummarySmall RNA pathways defend the germlines of animals against selfish genetic elements and help to maintain genomic integrity. At the same time, their activity needs to be well-controlled to prevent silencing of ‘self’ genes. Here, we reveal a proteolytic mechanism that controls endogenous small interfering (22G) RNA activity in the Caenorhabditis elegans germline to protect genome integrity and maintain fertility. We find that WAGO-1 and WAGO-3 Argonaute (Ago) proteins are matured through proteolytic processing of their unusually proline-rich N-termini. In the absence of DPF-3, a P-granule-localized N-terminal dipeptidase orthologous to mammalian DPP8/9, processing fails, causing a change of identity of 22G RNAs bound to these WAGO proteins. Desilencing of repeat- and transposon-derived transcripts, DNA damage and acute sterility ensue. These phenotypes are recapitulated when WAGO-1 and WAGO-3 are rendered resistant to DFP-3-mediated processing, identifying them as critical substrates of DPF-3. We conclude that N-terminal processing of Ago proteins regulates their activity and promotes discrimination of self from non-self by ensuring association with the proper complement of small RNAs.Graphical Abstract: The role of DPF-3 in the fertility of the animalsIn wild type animals, the WAGO-1 and WAGO-3 Argonaute proteins are produced as immature pro-proteins with N-termini (N) that are unusually rich in prolines (P). N-terminal processing by DPF-3 is required for loading of the proper small RNA cargo and stabilization of WAGO-3. Accordingly, loss of this processing activity causes desilencing of transposable elements (TE), cell death and sterility.
Removal of KCNQ2 from Parvalbumin-expressing Interneurons Improves Anti-Seizure Efficacy of Retigabine
Authors: Jing Junzhan , Dunbar Corrinne , Sonesra Alina , Chavez Ana , Park Suhyeorn , Soh Heun , Lee Maxwell , Tzingounis Anastasios , Cooper Edward C. , Jiang Xiaolong , Maheshwari Atul 
Published: December 2020

AbstractAnti-seizure drug (ASD) targets are widely expressed in both excitatory and inhibitory neurons. It remains unknown if the action of an ASD upon inhibitory neurons could counteract its beneficial effects on excitatory neurons (or vice versa), thereby reducing the efficacy of the ASD. Here, we examine whether the efficacy of the ASD retigabine (RTG) is altered after removal of the Kv7 potassium channel subunit KCNQ2, one of its drug targets, from parvalbumin-expressing interneurons (PV-INs). Parvalbumin-Cre (PV-Cre) mice were crossed withKcnq2-floxed (Kcnq2fl/fl) mice to conditionally deleteKcnq2from PV-INs. In these conditional knockout mice (cKO, PV-Kcnq2fl/fl), RTG (10 mg/kg, i.p.) significantly delayed the onset of either picrotoxin (PTX, 10 mg/kg, i.p)- or kainic acid (KA, 30mg/kg, i.p.)-induced convulsive seizures compared to vehicle, while RTG was not effective in wild-type littermates (WT). Immunostaining for KCNQ2 and KCNQ3 revealed that both subunits were enriched at axon initial segments (AISs) of hippocampal CA1 PV-INs, and their specific expression was selectively abolished in cKO mice. Accordingly, the M-currents recorded from CA1 PV-INs and their sensitivity to RTG were significantly reduced in cKO mice. While the ability of RTG to suppress CA1 excitatory neurons in hippocampal slices was unchanged in cKO mice, its suppressive effect on the spike activity of CA1 PV-INs was significantly reduced compared with WT mice. In addition, the RTG-induced suppression on intrinsic membrane excitability of PV-INs in WT mice was significantly reduced in cKO mice. These findings suggest that preventing RTG from suppressing PV-INs improves its anticonvulsant effect.Significance StatementOne out of three patients with epilepsy remain resistant to anti-seizure drugs (ASD). Therefore, strategies that can enhance the efficacy of current ASDs or aid in the development of novel ASDs are in high demand. Here we show that by sparing a subset of inhibitory neurons, the ASD retigabine becomes more efficacious. These findings indicate that developing the ASDs that have relatively greater effects on excitatory over inhibitory neurons may be an effective strategy to improve the efficacy of ASDs.
Sparse Coding in Temporal Association Cortex Improves Complex Sound Discriminability
Authors: Feigin L , Tasaka G , Maor I , Mizrahi A 
Published: December 2020

AbstractThe mouse auditory cortex is comprised of several auditory fields spanning the dorso-ventral axis of the temporal lobe. The ventral most auditory field is the temporal association cortex (TeA), which remains largely unstudied. Using Neuropixels probes, we simultaneously recorded from primary auditory cortex (AUDp), secondary auditory cortex (AUDv) and TeA, characterizing neuronal responses to pure tones and frequency modulated (FM) sweeps in awake head-restrained mice. As compared to primary and secondary auditory cortices, single unit responses to pure tones in TeA were sparser, delayed and prolonged. Responses to FMs were also sparser. Population analysis showed that the sparser responses in TeA render it less sensitive to pure tones, yet more sensitive to FMs. When characterizing responses to pure tones under anesthesia, the distinct signature of TeA was changed considerably as compared to that in awake mice, implying that responses in TeA are strongly modulated by non-feedforward connections. Together with the known connectivity profile of TeA, these findings suggest that sparse representation of sounds in TeA supports selectivity to higher-order features of sounds and more complex auditory computations.
Bacterial sirtuin CobB and PRPP synthase crosstalk in regulation of protein acetylation
Authors: Walter Beata M. , Morcinek-Orłowska Joanna , Szulc Aneta , Lovering Andrew L. , Banzhaf Manuel , Glinkowska Monika 
Published: December 2020

AbstractProtein lysine acetylation, regulates a wide range of cellular functions and is controlled by protein deacetylases called sirtuins. In eukaryotes, sirtuins activity is coupled to the spatiotemporally-controlled NAD+ level. However, regulation of the bacterial sirtuin CobB and its coupling to the NAD+ metabolism is not well understood. In this work we show that such coordination inEscherichia colicells is achieved through a CobB interaction with PRPP synthase Prs, an enzyme necessary for NAD+ synthesis. Probing CobB protein-protein interactions, we demonstrate that it forms a stable complex with Prs. This assembly stimulates CobB deacetylase activity and partially protects it from inhibition by nicotinamide. We provide evidence that Prs acetylation is not necessary for CobB binding but affects the global acetylome and CobB activityin vivo. Consequently, we show that Prs acetylation status affects bacterial growth under different metabolic regimes. Therefore, we propose that CobB-Prs crosstalk orchestrates the NAD+ metabolism and protein acetylation in response to environmental cues.
The tardigradeHypsibius exemplarisas an emerging model to study the mitochondrial alternative oxidase at animal organismal level
Authors: Grobys Daria , Roszkowska Milena , Kaczmarek Łukasz , Jarmuszkiewicz Wiesława , Karachitos Andonis , Kmita Hanna 
Published: December 2020

AbstractMitochondrial alternative oxidase (AOX) is present in mitochondria of many invertebrates. Independently of the reason concerning the enzyme occurrence in animal mitochondria, expression of AOX in human mitochondria is regarded as a potential therapeutic strategy. Till now, relevant data were obtained due to heterologous AOX expression in cells and animals without natively expressed AOX. Application of animals natively expressing AOX importantly contribute the research. Thus, we investigatedHypsibius exemplarisas a model for AOX activity analysis. We observed thatH. exemplaristolerance to the blockage of the MRC complexes was diminished in the presence of AOX inhibitor and the inhibitor-sensitive respiration enabled the tardigrade respiration under condition of the blockage. Furthermore, although detection of AOX at protein level and pronounced oxygraphic registration of its activity required the MRC complex blockage, the obtained data indicated that AOX clearly contributed animal functioning. We demonstrated that AOX activity in tardigrades, can be monitored by measurement of intact specimen whole-body respiration. Furthermore, it was also possible to monitor the impact of the MRC complex IV blockage on AOX expression and AOX inhibition in the absence of the blockage on animal functioning. Thus,H. exemplarisis applied as a whole-animal model suitable to study AOX.
CLEAN AND FOLDED: OPTIMIZED PRODUCTION OF HIGH QUALITY RECOMBINANT HUMAN INTERFERON-Λ1
Authors: Shaldzhyan Aram , Yolshin Nikita , Zabrodskaya Yana , Kudling Tatiana , Lozhkov Alexey , Plotnikova Marina , Ramsay Edward , Taraskin Aleksandr , Nekrasov Peter , Grudinin Mikhail , Vasin Andrey 
Published: December 2020

ABSTRACTType III interferons exhibit antiviral activity against influenza viruses, coronaviruses, rotaviruses, and others. In addition, this type of interferon theoretically has therapeutic advantages, in comparison with type I interferons, due to its ability to activate a narrower group of genes in a relatively small group of target cells. Hence, it can elicit more targeted antiviral or immunomodulatory responses. Obtaining biologically-active interferon lambda (hIFN-λ1) is fraught with difficulties at the stage of expression in soluble form or, in the case of expression in the form of inclusion bodies, at the stage of refolding. In this work, hIFN-λ1was expressed in the form of inclusion bodies, and a simple, effective refolding method was developed. Efficient and scalable methods for chromatographic purification of recombinant hIFN-λ1were also developed. High-yield, high-purity product was obtained through optimization of several processes including: recombinant protein expression; metal affinity chromatography; cation exchange chromatography; and an intermediate protein refolding stage. The obtained protein was shown to have expected, specific biological activity in line with published effects: induction of MxA gene expression in A549 cells.
Millimeter-resolution mapping of citrate exuded from soil grown roots using a novel, low-invasive sampling technique
Authors: Tiziani Raphael , Puschenreiter Markus , Smolders Erik , Mimmo Tanja , Herrera José Carlos , Cesco Stefano , Santner Jakob 
Published: December 2020

AbstractThe reliable sampling of root exudates in soil grown plants is experimentally challenging. This study aimed at developing a citrate sampling and mapping technique with millimetre-resolution using DGT (diffusive gradients in thin films) ZrOH binding gels. Citrate adsorption kinetics, DGT capacity and stability of ZrOH gels were evaluated. ZrOH gels were applied to generate 2D maps of citrate exuded by white lupin roots grown in rhizotrosn in a phosphorus deficient soil. Citrate was adsorbed quantitatively and rapidly by the ZrOH gels, these gels can be stored after sampling for several weeks prior to analysis. The DGT capacity of the ZrOH gel for citrate depends on the ionic strength and the pH of the soil solution but was suitable for citrate sampling. 2D citrate maps of rhizotron grown plants have been generated for the first time at a millimetre resolution to measure an illustrated plant response to P fertilization. DGT-based citrate sampling is suitable for studying the root exudation in soil environments, at unprecedented spatial resolution. By changing binding material, the technique is also applicable to other exudate classes and might be used for the evaluation of whole root exudation crucial in specific cultivar breeding.HighlightWe present a novel, reliable, easy to use, non-destructive citrate sampling- and two-dimensional high-resolution imaging technique for soil grown plant roots.
CytoGLMM: Conditional Differential Analysis for Flow and Mass Cytometry Experiments
Authors: Seiler Christof , Ferreira Anne-Maud , Kronstad Lisa M. , Simpson Laura J. , Gars Mathieu Le , Vendrame Elena , Blish Catherine A. , Holmes Susan 
Published: December 2020

AbstractBackgroundFlow and mass cytometry are important modern immunology tools for measuring expression levels of multiple proteins on single cells. The goal is to better understand the mechanisms of responses on a single cell basis by studying differential expression of proteins. We focus on cell-specific differential analysis and one fixed cell type. In contrast, most current methods learn cell types and perform differential analysis jointly. Our narrower field of application allows us to define a more specific statistical model with easier to control statistical guarantees.ResultsDifferential analysis of marker expressions can be difficult due to marker correlations and inter-individual heterogeneity, particularly for studies of human immunology. We address these challenges with two multiple regression strategies: A bootstrapped generalized linear model and a generalized linear mixed model. On simulated datasets, we compare the robustness towards marker correlations and heterogeneity of both strategies. For paired experiments, we find that both strategies maintain the target false discovery rate under medium correlations and that mixed models are statistically more powerful under the correct model specification. For unpaired experiments, our results indicate that much larger patient sample sizes are required to detect differences. We illustrate theCytoGLMMRpackage and workflow for both strategies on a pregnancy dataset.ConclusionsOur approach to find differential proteins in flow and mass cytometry data reduces biases arising from maker correlations and safeguards against false discoveries induced by patient heterogeneity.
EVI/WLS function is regulated by ubiquitination and linked to ER-associated degradation by ERLIN2
Authors: Wolf Lucie , Lambert Annika , Haenlin Julie , Boutros Michael 
Published: December 2020

ABSTRACTWnt signalling is important for development in all metazoan animals and associated with various human diseases. The Ubiquitin-Proteasome System (UPS) and regulatory ER-associated degradation (ERAD) has been implicated in the secretion of WNT proteins. Here, we investigated how the WNT secretory factor EVI/WLS is ubiquitinated, recognised by ERAD components, and subsequently removed from the secretory pathway. We performed a focused, immunoblot-based RNAi screen for factors that influence EVI/WLS protein stability. We identified the VCP-binding proteins FAF2 and UBXN4 as novel interaction partners of EVI/WLS and showed that ERLIN2 links EVI/WLS to the ubiquitination machinery. Interestingly, we found in addition that EVI/WLS is ubiquitinated and degraded in cells irrespective of their level of WNT production. K11, K48, and K63-linked ubiquitination is mediated by the E2 ubiquitin conjugating enzymes UBE2J2, UBE2N, and UBE2K, but independent of the E3 ligases HRD1/SYVN. Taken together, our study identified factors that link UPS to the WNT secretory pathway and provides mechanistic details on the fate of an endogenous substrate of regulatory ERAD in mammalian cells.