bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correction of multiple-blinking artefacts in photoactivated localisation microscopy
Authors: Jensen Louis G , Hoh Tjun Yee , Williamson David J , Griffié Juliette , Sage Daniel , Rubin-Delanchy Patrick , Owen Dylan M 
Published: March 2021

AbstractPhotoactivated localisation microscopy (PALM) produces an array of localisation coordinates by means of photoactivatable fluorescent proteins. However, observations are subject to fluorophore multiple-blinking and each protein is included in the dataset an unknown number of times at different positions, due to localisation error. This causes artificial clustering to be observed in the data. We present a workflow using calibration-free estimation of blinking dynamics and model-based clustering, to produce a corrected set of localisation coordinates now representing the true underlying fluorophore locations with enhanced localisation precision. These can be reliably tested for spatial randomness or analysed by other clustering approaches, and previously inestimable descriptors such as the absolute number of fluorophores per cluster are now quantifiable, which we validate with simulated data. Using experimental data, we confirm that the adaptor protein, LAT, is clustered at the T cell immunological synapse, with its nanoscale clustering properties depending on location and intracellular phosphorylatable tyrosine residues.
Investigations on regulation of miRNAs in rice reveal [Ca2+]cytsignal transduction regulated miRNAs
Authors: Kansal Shivani , Panwar Vaishali , Mutum Roseeta Devi , Raghuvanshi Saurabh 
Published: March 2021

AbstractMicroRNAs are critical components of the multi-dimensional regulatory networks in eukaryotic systems. They regulate a spectrum of developmental and metabolic processes in both plants and animals. Thus, it is quite apparent that the transcription, processing as well as activity of the miRNAs themselves is very dynamically regulated. One of the most important and universally implicated signalling molecule is [Ca2+]cyt. It is known to regulate a plethora of developmental and metabolic processes in both plants and animals, however their impact on the regulation of miRNA expression is relatively less explored. The current study employed a combination of internal and external calcium channel inhibitors, to establish that [Ca2+]cytsignatures actively regulate miRNA expression in rice. Involvement of [Ca2+]cytin regulation of miRNA expression was further confirmed by treatment with calcimycin, the calcium ionophore. Modulation of the cytosolic calcium levels was also found to regulate the drought responsive expression as well as ABA mediated response of miRNA genes in rice seedlings. The study further establishes the role of calmodulins and Calmodulin-binding Transcription Activators (CAMTAs) as important components of the signal transduction schema that regulates miRNA expression. Yeast-one-hybrid assay established that OsCAMTA4 & 6 are involved in the transcriptional regulation of miR156a and miR167h. Thus, the study was able to clearly establish that [Ca2+]cytis actively involved in regulating expression of miRNA genes both under control and stress conditions.
Taking full advantage of modelling to better assess environmental risk due to xenobiotics
Authors: Charles Sandrine , Ratier Aude , Baudrot Virgile , Multari Gauthier , Siberchicot Aurélie , Wu Dan , Lopes Christelle 
Published: March 2021

AbstractIn the European Union, more than 100,000 man-made chemical substances are awaiting an environmental risk assessment (ERA). Simultaneously, ERA of chemicals has now entered a new era. Indeed, recent recommendations from regulatory bodies underline a crucial need for the use of mechanistic effect models, allowing assessments that are not only ecologically relevant, but also more integrative, consistent and efficient. At the individual level, toxicokinetic-toxicodynamic (TKTD) models are particularly encouraged for the regulatory assessment of pesticide-related risks on aquatic organisms. In this paper, we first propose a brief review of classical dose-response models to put into light the on-line MOSAIC tool offering all necessary services in a turnkey web platform whatever the type of data to analyze. Then, we focus on the necessity to account for the time-dimension of the exposure by illustrating how MOSAIC can support a robust calculation of bioaccumulation factors. At last, we show how MOSAIC can be of valuable help to fully complete the EFSA workflow regarding the use of TKTD models, especially with GUTS models, providing a user-friendly interface for calibrating, validating and predicting survival over time under any time-variable exposure scenario of interest. Our conclusion proposes a few lines of thought for an even easier use of modelling in ERA.Graphical art
Efficacy of a Broadly Neutralizing SARS-CoV-2 Ferritin Nanoparticle Vaccine in Nonhuman Primates
Authors: Joyce Michael G. , King Hannah A. D. , Naouar Ines Elakhal , Ahmed Aslaa , Peachman Kristina K. , Cincotta Camila Macedo , Subra Caroline , Chen Rita E. , Thomas Paul V. , Chen Wei-Hung , Sankhala Rajeshwer S. , Hajduczki Agnes , Martinez Elizabeth J. , Peterson Caroline E. , Chang William C. , Choe Misook , Smith Clayton , Lee Parker J. , Headley Jarrett A. , Taddese Mekdi G. , Elyard Hanne A. , Cook Anthony , Anderson Alexander , McGuckin-Wuertz Kathryn , Dong Ming , Swafford Isabella , Case James B. , Currier Jeffrey R. , Lal Kerri G. , O’Connell Robert J. , Molnar Sebastian , Nair Manoj S. , Dussupt Vincent , Daye Sharon P. , Zeng Xiankun , Barkei Erica K. , Staples Hilary M. , Alfson Kendra , Carrion Ricardo , Krebs Shelly J. , Paquin-Proulx Dominic , Karasavva Nicos , Polonis Victoria R. , Jagodzinski Linda L. , Amare Mihret F. , Vasan Sandhya , Scott Paul T. , Huang Yaoxing , Ho David D. , de Val Natalia , Diamond Michael S. , Lewis Mark G. , Rao Mangala , Matyas Gary R. , Gromowski Gregory D. , Peel Sheila A. , Michael Nelson L. , Bolton Diane L. , Modjarrad Kayvon 
Published: March 2021

The emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against coronavirus disease 2019 (COVID-19). We developed and evaluated an adjuvanted SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine in nonhuman primates (NHPs). High-dose (50µg) SpFN vaccine, given twice within a 28 day interval, induced a Th1-biased CD4 T cell helper response and a peak neutralizing antibody geometric mean titer of 52,773 against wild-type virus, with activity against SARS-CoV-1 and minimal decrement against variants of concern. Vaccinated animals mounted an anamnestic response upon high-dose SARS-CoV-2 respiratory challenge that translated into rapid elimination of replicating virus in their upper and lower airways and lung parenchyma. SpFN’s potent and broad immunogenicity profile and resulting efficacy in NHPs supports its utility as a candidate platform for SARS-like betacoronaviruses.One-Sentence SummaryA SARS-CoV-2 Spike protein ferritin nanoparticle vaccine, co-formulated with a liposomal adjuvant, elicits broad neutralizing antibody responses that exceed those observed for other major vaccines and rapidly protects against respiratory infection and disease in the upper and lower airways and lung tissue of nonhuman primates.
Genetic differentiation ofXylella fastidiosafollowing the introduction into Taiwan
Authors: Castillo Andreina I. , Tsai Chi-Wei , Su Chiou-Chu , Weng Ling-Wei , Lin Yu-Chen , Cho Shu-Ting , Almeida Rodrigo P. P. , Kuo Chih-Horng 
Published: March 2021

AbstractThe economically important plant pathogenXylella fastidiosahas been reported in multiple regions of the globe during the last two decades, threatening a growing list of crops and industries.Xylella fastidiosasubspeciesfastidiosacauses disease in grapevines (Pierce’s disease of grapevines, PD), a current problem in the United States (US), Spain, and Taiwan. We studied PD-causing subsp.fastidiosapopulations and compared the genome sequences of 33 isolates found in Central Taiwan with 171 isolates from the US and two from Spain.Phylogenetic relationships, haplotype network, and genetic diversity analyses confirm that subsp.fastidiosawas recently introduced into Taiwan from the Southeast US (i.e., the PD-I lineage in Georgia based on available data). Recent core genome recombination events were detected among introduced subsp.fastidiosaisolates in Taiwan and contributed to the development of genetic diversity, particularly in the Houli District of Taichung City in Central Taiwan. Unexpectedly, despite comprehensive sampling of all regions with high PD incidences in Taiwan, the genetic diversity observed include contributions through recombination from unknown donors, suggesting that higher diversity exists in the region. Nevertheless, no recombination event was detected betweenX. fastidiosasubsp.fastidiosaand the endemic sister speciesXylella taiwanensis. In summary, this study improved our understanding of the genetic diversity of PD-causing subsp.fastidiosaafter invasion to a new region.
ADAR2-mediated RNA editing of DNA:RNA hybrids is required for DNA double strand break repair
Authors: Jimeno Sonia , Prados-Carvajal Rosario , Fernández-Ávila María Jesús , Silva Sonia , Silvestris Domenico Alessandro , Endara-Coll Martín , Domingo-Prim Judit , Mejías-Navarro Fernando , Rodríguez-Real Guillermo , Romero-Franco Amador , Jimeno-González Silvia , Barroso Sonia , Cesarini Valeriana , Aguilera Andrés , Gallo Angela , Visa Neus , Huertas Pablo 
Published: March 2021

AbstractThe maintenance of genomic stability requires the coordination of multiple cellular tasks upon the appearance of DNA lesions. RNA editing, the post-transcriptional sequence alteration of RNA, has a profound effect on cell homeostasis, but its implication in the response to DNA damage was not previously explored. Here we show that, in response to DNA breaks, an overall change of the Adenosine-to-Inosine RNA editing is observed, a phenomenon we call theRNAEditingDAmageResponse (REDAR). REDAR relies on the checkpoint kinase ATR and the recombination factor CtIP. Moreover, depletion of the RNA editing enzyme ADAR2 renders cells hypersensitive to genotoxic agents, increases genomic instability and hampers homologous recombination by impairing DNA resection. Such a role of ADAR2 in DNA repair goes beyond the recoding of specific transcripts, but depends on ADAR2 editing DNA:RNA hybrids to ease their dissolution.One sentence summary:DNA recombination requires RNA editing of DNA:RNA hybrids to ease their melting and facilitate DNA end resection
Modelling nonlinear dendritic processing of facilitation in a dragonfly target-tracking neuron
Authors: Bekkouche Bo M. B. , Shoemaker Patrick A. , Fabian Joseph M. , Rigosi Elisa , Wiederman Steven D. , O’Carroll David C. 
Published: March 2021

AbstractDragonflies are highly skilled and successful aerial predators that are even capable of selectively attending to one target within a swarm. Detection and tracking prey is likely to be driven by small target motion detector (STMD) neurons identified from several insect groups. Prior work has shown that dragonfly STMD responses are facilitated by targets moving on a continuous path, enhancing the response gain at the present and predicted future location of targets. In this study, we combined detailed morphological data with computational modelling to test whether a combination of dendritic morphology combined with the nonlinear properties of NMDA receptors could explain these observations. We developed a hybrid neuronal model of neurons within the dragonfly optic lobe, which integrates numerical and morphological components. The model was able to generate potent facilitation for targets moving on continuous trajectories, including a localized spotlight of maximal sensitivity close to the last seen target location, as also measured duringin vivorecordings. The model did not, however, include a mechanism capable of producing a traveling or spreading wave of facilitation. Our data support a strong role for the high dendritic density seen in the dragonfly neuron in enhancing non-linear facilitation. An alternative model based on morphology of an unrelated type of motion processing neuron from a dipteran fly required more than 3 times higher synaptic gain in order to elicit similar levels of facilitation, despite having only 20% fewer synapses. Our data supports a potential role for NMDA receptors in target tracking and also demonstrates the feasibility of combining biologically plausible dendritic computations with more abstract computational models for basic processing as used in earlier studies.
A year in the life of the Eastern Mediterranean: Monthly dynamics of phytoplankton and bacterioplankton in an ultra-oligotrophic sea
Authors: Reich Tom , Ben-Ezra Tal , Belkin Natalya , Tsemel Anat , Aharonovich Dikla , Roth-Rosenberg Dalit , Givati Shira , Bialik Or , Herut Barak , Berman-Frank Ilana , Frada Miguel , Krom Michael D. , Lehahn Yoav , Rahav Eyal , Sher Daniel 
Published: March 2021

AbstractThe Eastern Mediterranean Sea (EMS) is a poorly studied ultra-oligotrophic marine environment, dominated by small-size phyto- and bacterioplankton. Here, we describe the dynamics of a single annual cycle (2018-19) of phyto- and bacterioplankton (abundances, pigments and productivity) in relation to the physical and chemical conditions in the photic water column at an offshore EMS site (Station THEMO-2, ∼1,500m depth, 50km offshore). We show that phytoplankton biomass (as chlorophyll a), primary and bacterial productivity differed between the mixed winter (January-April) and the thermally stratified (May-December) periods.ProchlorococcusandSynechococcusnumerically dominated the picophytoplankton populations, with each clade revealing different temporal and depth changes indicative to them, while pico-eukaryotes (primarily haptophytes) were less abundant, yet likely contributed significant biomass. Estimated primary productivity (∼32 gC m-2y-1) was lower compared with other well-studied oligotrophic locations, including the north Atlantic and Pacific (BATS and HOT observatories), the western Mediterranean (DYFAMED observatory) and the Red Sea, and was on-par with the ultra-oligotrophic South Pacific Gyre. In contrast, integrated bacterial production (∼11 gC m-2y-1) was similar to other oligotrophic locations. Phytoplankton seasonal dynamics were similar to those at BATS and the Red Sea, suggesting an observable effect of winter mixing in this ultra-oligotrophic location. These results highlight the ultra-oligotrophic conditions in the EMS and provide, for the first time in this region, a full-year baseline and context to ocean observatories in the region.HighlightsBacterioplankton dynamics were assessed monthly in the Eastern Mediterranean SeaSmall-sized picophytoplankton numerically dominated the phytoplankton communitySeasonal phytoplankton dynamics are similar to BATS and Red Sea, but not to HOTAnnual primary productivity is among the lowest in the world’s oceansBacterial to primary production ratio is higher than most oligotrophic seas
Searching match for single-cell open-chromatin profiles in large pools of single-cell transcriptomes and epigenomes for reference supported analysis
Authors: Mishra Shreya , Pandey Neetesh , Chawla Smriti , SenGupta Debarka , Natrajan Kedar Nath , Kumar Vibhor 
Published: March 2021

AbstractThe true benefits of large datasets of the single-cell transcriptome and epigenome profiles can be availed only with their inclusion and search for annotating individual cells. Matching a single cell epigenome profile to a large pool of reference cells remains a major challenge. We developed a method (scEpiSearch) to resolve the challenges of searching and comparing single-cell open-chromatin profiles against large pools of single-cell expression and open chromatin datasets. scEpiSearch is more accurate than other methods when comparing single cell open-chromatin profiles to single-cell transcriptomes and epigenomes. scEpiSearch also provides a robust method for reference-supported co-embedding of single-cell open chromatin profiles. In performance benchmarks, scEpiSearch outperformed multiple methods for the low dimensional co-embedding of single-cell open-chromatin profiles irrespective of platforms and species. scEpiSearch works with both reference single-cell expression and epigenome profiles, enabling classification of single-cell open-chromatin profiles. Here we demonstrate the unconventional utilities of scEpiSearch by applying it on single-cell epigenome profiles of K562 cells and samples from patients with acute leukaemia to reveal different aspects of their heterogeneity, multipotent behaviour and de-differentiated states. Applying scEpiSearch on our single-cell open-chromatin profiles from embryonic stem cells(ESCs), we identified ESC subpopulations with more activity and poising for endoplasmic reticulum stress and unfolded protein response. Thus, scEpiSearch solves the non-trivial problem of amalgamating information from a large pool of single-cells to identify and study the regulatory states of cells using their single-cell epigenomes.The true benefits of large datasets of the single-cell transcriptome and epigenome profiles can be availed only with their inclusion and search for annotating individual cells.
Profiling DNA break sites and transcriptional changes in response to contextual fear learning
Authors: Stott Ryan T. , Kritsky Oleg , Tsai Li-Huei 
Published: March 2021

AbstractNeuronal activity generates DNA double-strand breaks (DSBs) at specific lociin vitroand this facilitates the rapid transcriptional induction of early response genes (ERGs). Physiological neuronal activity, including exposure of mice to learning behaviors, also cause the formation of DSBs, yet the distribution of these breaks and their relation to brain function remains unclear. Here, following contextual fear conditioning (CFC) in mice, we profiled the locations of DSBs genome-wide in the medial prefrontal cortex and hippocampus using γH2AX ChIP-Seq. Remarkably, we found that DSB formation is widespread in the brain compared to cultured primary neurons and they are predominately involved in synaptic processes. We observed increased DNA breaks at genes induced by CFC in neuronal and non-neuronal nuclei. Activity-regulated and proteostasis-related transcription factors appear to govern some of these gene expression changes across cell types. Finally, we find that glia but not neurons have a robust transcriptional response to glucocorticoids, and many of these genes are sites of DSBs. Our results indicate that learning behaviors cause widespread DSB formation in the brain that are associated with experience-driven transcriptional changes across both neuronal and glial cells.
The species-specificity of energy landscapes for soaring birds, and its consequences for transferring suitability models across species
Authors: Scacco Martina , Arrondo Eneko , Donázar J. Antonio , Flack Andrea , Sánchez-Zapata J. Antonio , Duriez Olivier , Wikelski Martin , Safi Kamran 
Published: March 2021

AbstractSoaring birds use the energy available in the environment in the form of atmospheric uplifts, to subsidize their flight. Their dependence on soaring opportunities makes them extremely sensitive to anthropogenic wind energy development. Predictive modelling is now considered instrumental to forecast the impact of wind farms on single species of concern. However, as multiple species often coexist in the same area, there is clear need to overcome the limitations of single species approaches.We looked for converging patterns in the way two obligate soaring species use the energy available in the landscape to soar, using movement data from 57 white storks,Ciconia ciconia, and 27 griffon vultures,Gyps fulvus. We first compared the soaring efficiency of the two species. We then tested the accuracy of topographic features, important correlates of collision risk in soaring birds, in predicting their soaring behaviour. We finally tested the transferability of soaring suitability models across species.Topography alone can predict and map the soaring opportunities available to storks across Europe, but not as efficiently in vultures. Only 20.5% of the study area was suitable to both species to soar, suggesting the existence of species-specific requirements in the use of the landscape for soaring. Storks relied on uplift occurrence while vultures on uplift quality, needing stronger uplifts to support their higher body mass and wing loading.Synthesis and applications:Our results indicate that the flight of highly specialized soaring species is more dependent on atmospheric conditions than on static features, and that more knowledge is required to accurately predict their behaviour. Despite the superficially similar soaring behaviour, the two species have different environmental requirements, suggesting that energy landscapes are species-specific. Our models provide a base to explore the effects that changes in the landscape have on the flight behaviour of different soaring species and suggest that there is no reliable and responsible way to shortcut risk assessment in areas where multiple species might be at risk by anthropogenic structures.
Transcriptional and cellular signatures of cortical morphometric similarity remodelling in chronic pain
Authors: Martins Daniel , Dipasquale Ottavia , Veronese Mattia , Turkheimer Federico , Loggia Marco L. , McMahon Stephen , Howard Matthew A , Williams Steven CR 
Published: March 2021

AbstractChronic pain is a highly debilitating and poorly understood condition. Here, we attempt to advance our understanding of the brain mechanisms driving chronic pain by investigating alterations in morphometric similarity (MS) and corresponding transcriptomic and cellular signatures, in three cohorts of patients with distinct chronic pain syndromes (knee osteoarthritis, low back pain and fibromyalgia). We uncover a novel pattern of cortical MS remodelling involving mostly MS increases in the insula and limbic cortex, which cuts across the boundaries of specific pain syndromes. We show that cortical MS remodelling in chronic pain spatially correlates with the brain-wide expression of genes involved in the glial immune response and neuronal plasticity. Cortical remodelling in chronic pain might involve a disruption of multiple elements of the cellular architecture of the brain. Therefore, multi-target therapeutic approaches tackling both glial activation and neuronal hyperexcitability might better encompass the full neurobiology of chronic pain.
Class I Histone Deacetylases (HDAC1–3) are Histone Lysine Delactylases
Authors: Moreno-Yruela Carlos , Zhang Di , Wei Wei , Bæk Michael , Gao Jinjun , Nielsen Alexander L. , Bolding Julie E. , Yang Lu , Jameson Samuel T. , Wong Jiemin , Olsen Christian A. , Zhao Yingming 
Published: March 2021

AbstractLysinel-lactylation [K(l-la)] is a newly discovered histone mark that can be stimulated under conditions of high glycolysis, such as the Warburg effect. K(l-la) is associated with functions that are different from the widely studied histone acetylation. While K(l-la) can be introduced by the acetyltransferase p300, histone delactylase enzymes remain unknown. Here, we report the systematic evaluation of zinc- and NAD+-dependent HDACs for their ability to cleave ε-N-l-lactyllysine marks. Our screens identified HDACs 1–3 and SIRT1–3 as delactylases in vitro. HDACs 1–3 show robust activity toward not only K(l-la) but also K(d-la) and diverse short-chain acyl modifications. We further confirmed the de-l-lactylase activity of HDACs 1 and 3 in cells. Identification of p300 and HDAC3 as regulatory enzymes suggests that histone lactylation is installed and removed by enzymes as opposed to spontaneous chemical reactivity. Our results therefore represent an important step toward full characterization of this pathway’s regulatory elements.