bluuebunny/crossref_metadata_2025_split huggingface dataset:
The AFB1 auxin receptor controls rapid auxin signaling and root growth through membrane depolarization inArabidopsis thaliana
Authors: Serre Nelson BC , Kralík Dominik , Yun Ping , Shabala Sergey , Slouka Zdeněk , Fendrych Matyáš 
Published: January 2021

AbstractThe existence of an electric gradient across membranes is essential for a cell operation. In plants, application of the growth regulator auxin (IAA) causes almost instantaneous membrane depolarization in various cell types, making membrane depolarization a hallmark of the rapid non-transcriptional responses to IAA. Auxin triggers rapid root growth inhibition; a process that underlies gravitropic bending. The growth and depolarization responses to auxin show remarkable similarities in dynamics, requirement of auxin influx and the involvement of the TIR1/AFB auxin coreceptors, but whether auxin-induced depolarization participates in root growth inhibition remains unanswered. Here, we established a toolbox to dynamically visualize membrane potentialin vivoinArabidopsis thalianaroots by combining the DISBAC2(3) fluorescent probe with microfluidics and vertical stage microscopy. This way we show that auxin-induced membrane depolarization tightly correlates with rapid root growth inhibition and that the cells of the transition zone/early elongation zone are the most responsive to auxin. Further, we demonstrate that auxin cycling in and out of the cells through AUX1 influx and PIN2 efflux is not essential for membrane depolarization and rapid root growth inhibition but acts as a facilitator of these responses. The rapid membrane depolarization by auxin instead strictly depends on the AFB1 auxin receptor, while the other TIR1/AFB paralogues contribute to this response. The lack of membrane depolarization in the afb1 mutant explains the lack of the immediate root growth inhibition. Finally, we show that AFB1 is required for the rapid depolarization and rapid growth inhibition of cells at the lower side of the gravistimulated root. These results are instrumental in understanding the physiological significance of membrane depolarization for the gravitropic response of the root and clarify the role of AFB1 as the receptor central for rapid auxin responses, adding another piece to the puzzle in understanding the biology of the phytohormone auxin.
Protist and Fungal Metaxin-like Proteins: Relationship to Vertebrate Metaxins that Function in Protein Import into Mitochondria
Authors: Adolph Kenneth W. 
Published: January 2021

ABSTRACTMetaxin-like proteins are shown to be encoded in the genomes of a wide range of protists and fungi. The metaxin proteins were originally described in humans and mice, and were experimentally demonstrated to have a role in the import of nascent proteins into mitochondria. In this study, metaxin-like proteins of protists and fungi predicted from genome sequences were identified by criteria including their sequence homology with vertebrate metaxin proteins and the existence of distinctive metaxin protein domains. Protists of diverse taxa, including amoebae, protozoa, phytoplankton, downy mildews, water molds, and algae, were found to possess genes for metaxin-like proteins. With fungi, the important taxonomic divisions (phyla) of Ascomycota, Basidiomycota, Chytridiomycota, Mucoromycota, and Zoopagomycota had species with metaxin-like protein genes. The presence of distinctive GST_N_Metaxin, GST_C_Metaxin, and Tom37 domains in the predicted proteins indicates that the protist and fungal proteins are related to the vertebrate metaxins. However, the metaxin-like proteins are not direct homologs of vertebrate metaxins 1, 2, or 3, but have similarity to each of the three. The alignment of the metaxin-like proteins of a variety of protists with vertebrate metaxins 1 and 2 showed about 26% and 19% amino acid identities, respectively, while for fungal metaxin-like proteins, the identities were about 29% and 23%. The different percentages with the two vertebrate metaxins indicates that the metaxin-like proteins are both metaxin 1-like and, to a lesser degree, metaxin 2-like. The secondary structures of protist and fungal metaxin-like proteins both consist of nine α-helical segments, the same as for the vertebrate metaxins, with a negligible contribution from β-strand. Phylogenetic analysis demonstrated that the protist and fungal metaxin-like proteins and the vertebrate metaxins form distinct and separate groups, but that the groups are derived from a common ancestral protein sequence.
Taxonomy-aware, sequence similarity ranking reliably predicts phage-host relationships
Authors: Zielezinski Andrzej , Barylski Jakub , Karlowski Wojciech M. 
Published: January 2021

ABSTRACTBackgroundSimilar regions in virus and host genomes provide strong evidence for phage-host interaction, and BLAST is one of the leading tools to predict prokaryotic hosts from phage sequences. However, BLAST-based host prediction has three major limitations: (i) top-scoring sequences do not always point to the actual host, (ii) mosaic phage genomes may match to many, typically related, bacteria, and (iii) phage and host sequences may diverge beyond the point where their relationship can be detected by a BLAST alignment.ResultsWe created an extension to BLAST, named Phirbo, that improves host prediction quality beyond what is obtainable from standard BLAST searches. The tool harnesses information concerning sequence similarity and bacteria relatedness to predict phage-host interactions. Phirbo was evaluated on three benchmark sets of known phage-host pairs, and it improved precision and recall by 11-40 percentage points over currently available, state-of-the-art, alignment-based, alignment-free, and machine learning host prediction tools. Moreover, the discriminatory power of Phirbo for the recognition of phage-host relationships surpassed the results of other tools by at least 10 percentage points (Area Under the Curve = 0.95), yielding a mean host prediction accuracy of 57% and 68% at the genus and family levels respectively, and drops by 12 percentage points when using only a fraction of phage genome sequences (3 kb). Finally, we provide insights into a repertoire of protein and ncRNA genes that are shared between phages and hosts and may be prone to horizontal transfer during infection.ConclusionsOur results suggest that Phirbo is a simple and effective tool for predicting phage host relationships.
Reducing disease and producing food: Effects of 13 agrochemicals on snail biomass and human schistosomes
Authors: Haggerty Christopher J E , Halstead Neal , Civitello David J. , Rohr Jason R 
Published: January 2021

AbstractAgrochemical use is predicted to increase 2-5 fold by 2050 to meet food demand. Evidence suggests that agrochemical pollution could increase snails that transmit the disease schistosomiasis to 250 million people, but most agrochemicals remain unexamined. Here we quantify the relative effects of fertilizer, six insecticides, and six herbicides on snail genera responsible for 90% of global schistosomiasis cases. We identified fertilizers and 4 of 6 insecticides as high risk for increasing snail biomass by increasing snail resources (vegetative habitat and periphytic food) and reducing snail predators, respectively. Herbicides generally had negative effects on snails by reducing vegetative habitat, with two herbicides increasing snails in the absence of aquatic vegetation. Parasite production, which reflects human infection risk, scaled positively to snail biomass. Our findings suggest that fertilizers and insecticides are more likely to increase human schistosomiasis than herbicides and revealed several low risk agrochemicals that might increase crop production without increasing schistosomiasis.
Source identity shapes spatial preference in primary auditory cortex during active navigation
Authors: Amaro Diana , Ferreiro Dardo N. , Grothe Benedikt , Pecka Michael 
Published: January 2021

SummaryLocalizing and identifying sensory objects while navigating the environment are fundamental brain functions. However, how individual objects are neuronally represented during unrestricted self-motion is mostly unexplored. We trained gerbils on a behavioral foraging paradigm that required localization and identification of sound-sources during free navigation. Chronic multi-electrode recordings in primary auditory cortex during task performance revealed previously unreported sensory object representations. Strikingly, the egocentric angle preference of the majority of spatially sensitive neurons changed significantly depending on the task-specific identity (outcome association) of the sound-source. Spatial tuning also exhibited larger temporal complexity. Moreover, we encountered egocentrically untuned neurons whose response magnitude differed between source identities. Using a neural network decoder we show that together, these neuronal response ensembles provide spatio-temporally co-existent information about both the egocentric location and the identity of individual sensory objects during self-motion, revealing a novel cortical computation principle for naturalistic sensing.HighlightsLocalization task during free navigation prompts diverse spatial tuning in gerbil A1Spatial preference of individual neurons changes with sound-source identityEgo- and allocentric information are spatio-temporally coexistent in A1 ensemblesActive sensing reveals new cortical representations for sensory object identification
Environmental enrichment delays the development of stereotypic behavior and reduces variability in behavioral experiments using California mice (Peromyscus californicus)
Authors: Minie Vanessa , Ramos-Maciel Stephanie , Wright Emily , Petric Radmila , Trainor Brian , Duque-Wilckens Natalia 
Published: January 2021

AbstractDomesticated mice and rats have shown to be powerful model systems for biomedical research, but there are cases in which the biology of species is a poor match for the hypotheses under study. The California mouse (Peromyscus californicus) has unique physiological and behavioral traits and has emerged as a powerful model for studying sex differences in the biology of psychiatric disease, which is particularly relevant considering the new NIH guidelines that require the inclusion of sex as a biological variable. Despite its growing role in preclinical research, there is a lack of studies assessing species-specific housing needs, which presents a challenge for research facilities seeking to ensure good welfare and obtaining high-quality experimental data. Indeed, captive California mice present a high prevalence of stereotypic backflipping behavior, a common consequence of suboptimal housing and a potential source of experimental outcome variability. Using three different cage systems, the present studies show that increasing housing space as well as social and environmental complexity can delay the development of stereotypic behavior in male and female California mice. Critically, this reduction in stereotypy is accompanied by increased effect sizes of stress in an established model for social anxiety. These results suggest that increased cage size and enrichment could enhance welfare in California mice while simultaneously increasing the quality of behavioral experiments.
The skin environment controls local dendritic cell differentiation and function through innate IL-13
Authors: Mayer Johannes U , Lamiable Olivier , Hilligan Kerry L , Chandler Jodie S , Old Samuel I , Eccles David A , Yang Jianping , Webb Greta R , Domingues Rita G , Munoz-Erazo Luis , Wakelin Kirsty A , Hyde Evelyn J , Tang Shiau-Choot , Chappell Sally C , Mackay Charles R , Brombacher Frank , Sher Alan , Tussiwand Roxane , Connor Lisa M , Jankovic Dragana , Hepworth Matthew R , Le Gros Graham , Ronchese Franca 
Published: January 2021

ABSTRACTThe signals driving the adaptation of type-2 dendritic cells (DC2s) to diverse peripheral environments are not well understood. We show that the development of CD11blowmigratory DC2s, a DC2 population unique to the dermis, requires STAT6- and KLF4-dependent IL-13 signaling, whereas DC2s in lung and small intestine are STAT6-independent. Dermal IL-13 is mostly derived from innate lymphoid cells expressing a resting ICOS+ KLRG1-ST2-phenotype. Analysis of public datasets indicates that human skin DC2s also express an IL-4/IL-13 gene signature compared to blood or spleen, suggesting a similar developmental pathway in mice and humans. In the absence of IL-13 signaling, dermal DC2s are stable in number but remain CD11bhiand show defective activation in response to allergen with diminished ability to support IL-4+ GATA3+ Th development, whereas anti-fungal IL-17+ RORγt+ responses are increased. Thus, steady-state IL-13 fosters a non-inflammatory and pro-allergic environment in healthy skin via conditioning of local DC2s.
Physical theory of biological noise buffering by multi-component phase separation
Authors: Deviri Dan , Safran Samuel A. 
Published: January 2021

AbstractMaintaining homeostasis is a fundamental characteristic of living systems. In cells, this is contributed to by assembly of biochemically-distinct organelles, many of whom are not membrane-bound, but form by the physical process of liquid-liquid phase separation (LLPS). By analogy with LLPS in binary solutions, cellular LLPS was hypothesized to contribute to homeostasis by facilitating “concentration buffering”, which renders the local protein concentration within the organelle robust to global variations in the average, cellular concentration (e.g. due to expression noise). Interestingly, concentration buffering was experimentally measured in vivo, in a simple organelle with a single solute, while it was observed not to be obeyed in one with several solutes. Here, we formulate theoretically and solve analytically a physical model of LLPS in a ternary solution of two solutes (A and B) that interact both homotypically (A-A attractions) and heterotypically (A-B attractions). Our physical theory predicts how the equilibrium concentrations in LLPS are related to expression noise and thus generalizes the concept of concentration buffering to multi-component systems. This allows us to reconcile the seemingly contradictory experimental observations. Furthermore, we predict that incremental changes of the homotypic and heterotypic interactions among the molecules that undergo LLPS, such as those that are caused by mutations in the genes encoding the proteins, may increase the efficiency of concentration buffering of a given system. Thus, we hypothesize that evolution may optimize concentration buffering as an efficient mechanism to maintain LLPS homeostasis, and suggest experimental approaches to test this in different systems.SignificanceThe stochastic nature of transcription/translation implies that the concentrations of cellular proteins are “noisy” and not constant in time or across cell populations. Liquid-liquid phase separation (LLPS), can reduce or “buffer” this noise by maintaining well-defined concentrations, even in the presence of concentration distributions. However, this idea was recently challenged experimentally in multicomponent systems. Our physical theory of LLPS in ternary systems (solutes A and B in a solvent), predicts their LLPS properties as a function of the A-A (homotypic) and A-B (heterotypic) interaction strengths. We show how buffering can be effective if the noise distribution aligns with the tie-lines of the phase diagram and suggest that evolution may optimize concentration buffering by selecting mutations that lead to this.
Monod law is insufficient to explain biomass growth in nitrogen-limited yeast fermentation
Authors: Henriques David , Balsa-Canto Eva 
Published: January 2021

ABSTRACTThe yeastSaccharomyces cerevisiaeis an essential microorganism in food biotechnology; particularly, in wine and beer making. During wine fermentation, yeasts transform sugars present in the grape juice into ethanol and carbon dioxide. The process occurs in batch conditions and is, for the most part, an anaerobic process. Previous studies linked limited-nitrogen conditions with problematic fermentations, with negative consequences for the performance of the process and the quality of the final product. It is, therefore, of the highest interest to anticipate such problems through mathematical models. Here we propose a model to explain problematic fermentations under nitrogen-limited anaerobic conditions. We separated the biomass formation into two phases: growth and carbohydrate accumulation. Growth was modelled using the well-known Monod law while carbohydrate accumulation was modelled by an empirical function, analogous to a proportional controller activated by the limitation of available nitrogen. We also proposed to formulate the fermentation rate as a function of the total protein content when relevant data are available. The final model was used to successfully explain a series of experiments taken from the literature, performed under normal and nitrogen-limited conditions. Our results revealed that Monod law is insufficient to explain biomass formation kinetics in nitrogen-limited fermentations ofS. cerevisiae. The goodness-of-fit of the herewith proposed model is superior to that of previously published models, offering the means to predict, and thus control, problematic fermentations.IMPORTANCEProblematic fermentations still occur in the winemaking industrial practise. Problems include sluggish rates of fermentation, which have been linked to insufficient levels of assimilable nitrogen. Data and relevant models can help anticipate poor fermentation performance. In this work, we proposed a model to predict biomass growth and fermentation rate under nitrogen-limited conditions and tested its performance with previously published experimental data. Our results show that the well-known Monod law does not suffice to explain biomass formation. A second term accounting for carbohydrate accumulation is required to predict successfully, and thus control, problematic fermentations.
Antiviral activity of bacterial TIR domains via signaling molecules that trigger cell death
Authors: Ofir Gal , Herbst Ehud , Baroz Maya , Cohen Daniel , Millman Adi , Doron Shany , Tal Nitzan , Malheiro Daniel B. A. , Malitsky Sergey , Amitai Gil , Sorek Rotem 
Published: January 2021

AbstractThe Toll/interleukin-1 receptor (TIR) domain is a canonical component of animal and plant immune systems. In plants, intracellular pathogen sensing by immune receptors triggers their TIR domains to generate a molecule which is a variant of cyclic ADP-ribose (v-cADPR). This molecule is hypothesized to activate plant cell death via a yet unresolved pathway. TIR domains were recently also shown to be involved in a bacterial anti-phage defense system called Thoeris, but the mechanism of Thoeris defense remained unknown. In this study we report that phage infection triggers Thoeris TIR-domain proteins to produce an isomer of cyclic ADP-ribose. This molecular signal activates a second protein, ThsA, which then depletes the cell of the essential molecule nicotinamide adenine dinucleotide (NAD) and leads to abortive infection and cell death. We further show that similar to eukaryotic innate immune systems, bacterial TIR-domain proteins determine the immunological specificity to the invading pathogen. Our results describe a new antiviral signaling pathway in bacteria, and suggest that generation of intracellular signaling molecules is an ancient immunological function of TIR domains conserved in both plant and bacterial immunity.
West Nile virus detection in horses in three Brazilian states
Authors: Costa Erica Azevedo , Giovanetti Marta , Catenacci Lilian Silva , Fonseca Vagner , Aburjaile Flavia , Iani Felipe Melo Campos , da Cunha e Silva Vieira Marcelo Adriano , Henriques Danielle Freitas , de Almeida Daniele Barbosa , Coelho Guedes Maria Isabel Maldonado , da Silva Ramos Beatriz Senra Álvares , Silva Aila Solimar Gonçalves , de Oliveira Tulio , Jardim Cavalcante Karina Ribeiro Leite , de Moura Noely Fabiana Oliveira , Romano Alessandro Pecego Martins , de Albuquerque Carlos F. Campelo , Feitosa Lauro César Soares , Bayeux José Joffre Martins , Teixeira Raffaella Bertoni Cavalcanti , Lobato Osmaikon Lisboa , da Costa Silva Silvokleio , Lourenço José , Alcantara Luiz Carlos Junior 
Published: January 2021

AbstractWe report genetic evidence of WNV circulation from southern and northeastern Brazilian states isolated from equine red blood cells. In the northeastern state the tenth human case was also detected, presenting neuroinvasive disease compatible with WNV infection. Our analyses demonstrate that much is still unknown on the virus’ local epidemiology. We advocate for a shift to active surveillance, to ensure adequate control for future epidemics with spill-over potential to humans.
Tetherin antagonism by SARS-CoV-2 enhances virus release: multiple mechanisms including ORF3a-mediated defective retrograde traffic
Authors: Stewart Hazel , Palmulli Roberta , Johansen Kristoffer H. , McGovern Naomi , Shehata Ola M. , Carnell George W. , Jackson Hannah K. , Lee Jin S. , Brown Jonathan C. , Burgoyne Thomas , Heeney Jonathan L. , Okkenhaug Klaus , Firth Andrew E. , Peden Andrew A. , Edgar James R. 
Published: January 2021

AbstractThe antiviral restriction factor, tetherin, blocks the release of several different families of enveloped viruses, including theCoronaviridae. Tetherin is an interferon-induced protein that forms parallel homodimers between the host cell and viral particles, linking viruses to the surface of infected cells and inhibiting their release. We demonstrated that SARS-CoV-2 infection causes tetherin downregulation, and that tetherin depletion from cells enhances SARS-CoV-2 viral titres. We investigated the potential viral proteins involved in abrogating tetherin function and found that SARS- CoV-2 ORF3a reduces tetherin localisation within biosynthetic organelles via reduced retrograde recycling and increases tetherin localisation to late endocytic organelles. By removing tetherin from the Coronavirus budding compartments, ORF3a enhances virus release. We also found expression of Spike protein caused a reduction in cellular tetherin levels. Our results confirm that tetherin acts as a host restriction factor for SARS-CoV-2 and highlight the multiple distinct mechanisms by which SARS-CoV-2 subverts tetherin function.Author SummarySince it was identified in 2019, SARS-CoV-2 has displayed voracious transmissibility which has resulted in rapid spread of the virus and a global pandemic. SARS-CoV-2 is a member of theCoronaviridaefamily whose members are encapsulated by a host-derived protective membrane shell. Whilst the viral envelope may provide protection for the virus, it also provides an opportunity for the host cell to restrict the virus and stop it spreading. The anti-viral restriction factor, tetherin, acts to crosslink viruses to the surface of infected cells and prevent their spread to uninfected cells. Here, we demonstrate that SARS-CoV-2 undergoes viral restriction by tetherin, and that SARS-CoV-2 moves tetherin away from the site of Coronavirus budding to enhance its ability to escape and infect naïve cells. Tetherin depletion from cells enhanced SARS-CoV-2 viral release and increased propagation of the virus. We found that the SARS-CoV-2 protein, ORF3a, redirects tetherin away from the biosynthetic organelles where tetherin would become incorporated to newly forming SARS-CoV-2 virions – and instead relocalises tetherin to late endocytic organelles. We also found that SARS-CoV-2 Spike downregulates tetherin. These two mechanisms, in addition to the well described antagonism of interferon and subsequent ISGs highlight the multiple mechanisms by which SARS-CoV-2 abrogates tetherin function. Our study provides new insights into how SARS-CoV-2 subverts human antiviral responses and escapes from infected cells.