bluuebunny/crossref_metadata_2025_split huggingface dataset:
The molecular principles of Piwi-mediated co-transcriptional silencing through the dimeric SFiNX complex
Authors: Schnabl Jakob , Wang Juncheng , Hohmann Ulrich , Gehre Maja , Batki Julia , Andreev Veselin I. , Purkhauser Kim , Fasching Nina , Duchek Peter , Novatchkova Maria , Mechtler Karl , Plaschka Clemens , Patel Dinshaw J. , Brennecke Julius 
Published: January 2021

AbstractNuclear Argonaute proteins, guided to nascent target RNAs by their bound small RNAs, elicit co-transcriptional silencing through heterochromatin formation at transposon insertions and repetitive genomic loci. The molecular mechanisms involved in this process are incompletely understood. Here, we propose that the SFiNX complex, a silencing mediator downstream of nuclear Piwi-piRNA complexes inDrosophila, enables co-transcriptional silencing via the formation of molecular condensates. Condensate formation is stimulated by nucleic acid binding and requires SFiNX dimerization, mediated by the dynein light chain protein, LC8/Cutup. LC8’s function within SFiNX can be bypassed with a heterologous dimerization domain, suggesting that dimerization is a constitutive feature of SFiNX. Mutations preventing LC8-mediated SFiNX dimerization result in loss of condensate formationin vitroand inability of Piwi to initiate heterochromatin formation and silence transposonsin vivo. Formation of molecular condensates might be a general mechanism that underlies effective heterochromatin establishment at small RNA target loci in a co-transcriptional manner.
From adverse to beneficial – contrasting dietary effects of freshwater mixotrophs on zooplankton
Authors: Vad Csaba F. , Schneider Claudia , Fischer Robert , Kainz Martin J. , Ptacnik Robert 
Published: January 2021

AbstractThe importance of mixotrophic algae as key bacterivores in microbial food webs is increasingly acknowledged, but their effects on the next trophic level remain poorly understood. Their high stoichiometric food quality is contrasted by anti-grazing strategies.We tested the quality of freshwater mixotrophs as prey for zooplankton, using four non-colonial chrysophyte species and a cryptophyte as a high quality reference food. We (1) analyzed the stoichiometric and biochemical (fatty acid) composition of the mixotrophs, and (2) quantified their dietary effects onDaphnia longispinasurvival.Survival ofD. longispinasignificantly depended on the identity of species provided as food, ranging from higher to lower as compared to starvation. This was not reflected in differences in cellular stoichiometry or fatty acid profiles of the mixotrophs. We suggest that toxicity may be the driver for the observed differences.Generalization of the dietary effects of mixotrophic chrysophytes does not appear straightforward. Besides fundamental species-specific differences, potential toxic effects may vary depending on environmental cues or physiological strategies. Notably in our study,Ochromonas tuberculata, a species previously reported to be deleterious turned out to be a beneficial food source, in terms of enabling high survival ofD. longispina.We challenge the generality of the assumption that chrysophytes are of low value as food for zooplankton. We recommend that future studies test how environmental conditions and physiological strategies shape the quality of mixotrophs as food for consumers at higher trophic levels, specifically focusing on effects of dietary toxicity.
To denoise or to cluster? That is not the question. Optimizing pipelines for COI metabarcoding and metaphylogeography
Authors: Antich A. , Palacin C. , Wangensteen O.S. , Turon X. 
Published: January 2021

ABSTRACTThe recent blooming of metabarcoding applications to biodiversity studies comes with some relevant methodological debates. One such issue concerns the treatment of reads by denoising or by clustering methods, which have been wrongly presented as alternatives. It has also been suggested that denoised sequence variants should replace clusters as the basic unit of metabarcoding analyses, missing the fact that sequence clusters are a proxy for species-level entities, the basic unit in biodiversity studies. We argue here that methods developed and tested for ribosomal markers have been uncritically applied to highly variable markers such as cytochrome oxidase I (COI) without conceptual or operational (e.g., parameter setting) adjustment. COI has a naturally high intraspecies variability that should be assessed and reported, as it is a source of highly valuable information. We contend that denoising and clustering are not alternatives. Rather, they are complementary and both should be used together in COI metabarcoding pipelines. Using a typical dataset from benthic marine communities, we compared two denoising procedures (based on the UNOISE3 and the DADA2 algorithms), set suitable parameters for denoising and clustering COI datasets, and compared the outcome of applying these processes in different orders. Our results indicate that denoising based on the UNOISE3 algorithm preserves a higher intra-cluster variability. We suggest and test ways to improve this algorithm taking into account the natural variability of each codon position in coding genes. The order of the steps (denoising and clustering) has little influence on the final outcome. We recommend researchers to consider reporting their results in terms of both denoised sequences (a proxy for haplotypes) and clusters formed (a proxy for species), and to avoid collapsing the sequences of the latter into a single representative. This will allow studies at the cluster (ideally equating species-level diversity) and at the intra-cluster level, and will ease additivity and comparability between studies.
Extracellular vimentin as a target against SARS-CoV-2 host cell invasion
Authors: Suprewicz Łukasz , Swoger Maxx , Gupta Sarthak , Piktel Ewelina , Byfield Fitzroy J. , Iwamoto Daniel V. , Germann Danielle , Reszeć Joanna , Marcińczyk Natalia , Carroll Robert J. , Lenart Marzena , Pyrc Krzysztof , Janmey Paul , Schwarz J.M. , Bucki Robert , Patteson Alison 
Published: January 2021

AbstractInfection of human cells by pathogens, including SARS-CoV-2, typically proceeds by cell surface binding to a crucial receptor. In the case of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2) has been identified as a necessary receptor, but not all ACE2-expressing cells are equally infected, suggesting that other extracellular factors are involved in host cell invasion by SARS-CoV-2. Vimentin is an intermediate filament protein that is increasingly recognized as being present on the extracellular surface of a subset of cell types, where it can bind to and facilitate pathogens’ cellular uptake. Here, we present evidence that extracellular vimentin might act as a critical component of the SARS-CoV-2 spike protein-ACE2 complex in mediating SARS-CoV-2 cell entry. We demonstrate direct binding between vimentin and SARS-CoV-2 pseudovirus coated with the SARS-CoV-2 spike protein and show that antibodies against vimentin blockin vitroSARS-CoV-2 pseudovirus infection of ACE2-expressing cells. Our results suggest new therapeutic strategies for preventing and slowing SARS-CoV-2 infection, focusing on targeting cell host surface vimentin.
HBO1-MLL interaction promotes AF4/ENL/P-TEFb-mediated leukemogenesis
Authors: Takahashi Satoshi , Kanai Akinori , Okuda Hiroshi , Miyamoto Ryo , Kawamura Takeshi , Matsui Hirotaka , Inaba Toshiya , Takaori-Kondo Akifumi , Yokoyama Akihiko 
Published: January 2021

AbstractLeukemic oncoproteins cause uncontrolled self-renewal of hematopoietic progenitors by aberrant gene activation, eventually causing leukemia. However, the molecular mechanism of aberrant gene activation remains elusive. Here, we showed that leukemic MLL fusion proteins associate with the HBO1 histone acetyltransferase (HAT) complex through their TRX2 domain. Among many MLL fusions, MLL-ELL particularly depended on its association with the HBO1 complex for leukemic transformation. The C-terminal portion of ELL provided a binding platform for multiple factors including AF4, EAF1 and p53. MLL-ELL activated gene expression by loading an AF4 /ENL/P-TEFb complex (AEP) onto the target promoters. The HBO1 complex promoted the use of AEP over EAF1 and p53. Moreover, the NUP98-HBO1 fusion protein exerted its oncogenic properties via interaction with MLL but not its intrinsic HAT activity. Thus, the interaction between HBO1 and MLL is an important nexus in leukemic transformation, which may serve as a therapeutic target for drug development.
Spatiotemporal Determination of Metabolite Activities in Multiple Corneal Epithelium Barriers on a Chip
Authors: Abdalkader Rodi , Chaleckis Romanas , Wheelock Craig E. , Kamei Ken-ichiro 
Published: January 2021

AbstractThe corneal epithelial barrier maintains the metabolic activities of the ocular surface by regulating membrane transporters and metabolic enzymes responsible for the homeostasis of the eye as well as the pharmacokinetic behavior of drugs. Despite its importance, no established biomimetic in vitro methods are available to perform the spatiotemporal investigation of corneal metabolism and determine the transportation of endogenous and exogenous molecules. This study introduces multiple corneal epithelium barriers on a chip, namely, Cornea-Chip, which enables the spatiotemporal collection as well as analysis of micro-scaled extracellular metabolites from both the apical and basolateral sides of the barriers. Longitudinal samples collected during 48 h period were analyzed using untargeted liquid chromatography–mass spectrometry metabolomics method, and 104 metabolites were annotated. The shifts in extracellular metabolites and quantitative analysis of the mRNA associated with membrane transporters could allow the investigation of the correlation between the expression of and the secretion and transportation of metabolites across the polarized corneal epithelial barrier. The Cornea-Chip might provide a non-invasive, simple, and effectively informative method to determine pharmacokinetics and pharmacodynamics as well as to discover novel biomarkers for drug toxicological and safety tests as an alternative to animal experiments.
UCsim2: 2D Structured Illumination Microscopy using UC2
Authors: Wang Haoran , Lachmann René , Marsikova Barbora , Heintzmann Rainer , Diederich Benedict 
Published: January 2021

AbstractState-of-the-art microscopy techniques enable the imaging of sub-diffraction barrier biological structures at the price of high-costs or lacking transparency. We try to reduce some of these barriers by presenting a super-resolution upgrade to our recently presented open-source optical toolbox UC2. Our new injection moulded parts allow larger builds with higher precision. The 4× lower manufacturing tolerance compared to 3D printing makes assemblies more reproducible. By adding consumer-grade available open-source hardware such as digital mirror devices (DMD) and laser projectors we demonstrate a compact 3D multimodal setup that combines image scanning microscopy (ISM) and structured illumination microscopy (SIM). We demonstrate a gain in resolution and optical sectioning using the two different modes compared to the widefield limit by imaging Alexa Fluor 647- and SiR-stained HeLa cells. We compare different objective lenses and by sharing the designs and manuals of our setup, we make super-resolution imaging available to everyone.
LuxT controls specific quorum-sensing-regulated behaviors inVibrionaceaespp. via repression ofqrr1, encoding a small regulatory RNA
Authors: Eickhoff Michaela J. , Fei Chenyi , Huang Xiuliang , Bassler Bonnie L. 
Published: January 2021

AbstractQuorum sensing (QS) is a process of chemical communication bacteria use to transition between individual and collective behaviors. QS depends on the production, release, and synchronous response to signaling molecules called autoinducers (AIs). The marine bacteriumVibrio harveyimonitors AIs using a signal transduction pathway that relies on five small regulatory RNAs (called Qrr1-5) that post-transcriptionally control target genes. Curiously, the small RNAs function redundantly making it difficult to understand the necessity for five of them. Here, we identify LuxT as a transcriptional repressor ofqrr1. LuxT does not regulateqrr2-5, demonstrating thatqrrgenes can be independently controlled to drive unique downstream QS gene expression patterns. LuxT reinforces its control over the same genes it regulates indirectly via repression ofqrr1, through a second transcriptional control mechanism. Genes dually regulated by LuxT specify public goods including an aerolysin-type pore-forming toxin. Phylogenetic analyses reveal that LuxT is conserved amongVibrionaceaeand sequence comparisons predict that LuxT repressesqrr1 in additional species. The present findings reveal that redundant QS regulatory RNAs can carry out both shared and unique functions to endow bacteria with plasticity in their output behaviors.Author SummaryBacteria communicate and count their cell numbers using a process called quorum sensing (QS). In response to changes in cell density, QS bacteria alternate between acting as individuals and participating in collective behaviors.Vibrio harveyiis used as a model organism to understand QS-mediated communication. Five small RNAs lie at the heart of theV. harveyiQS system, and they regulate the target genes that underlie the QS response. The small RNAs function redundantly making it difficult to understand whyV. harveyirequires five of them. Here, we discover a regulator, called LuxT, that exclusively represses the gene encoding one of the QS small RNAs. LuxT regulation of one QS small RNA enables unique control of a specific subset of QS target genes. LuxT is broadly conserved amongVibrionaceae. Our findings show how redundant regulatory components can possess both common and unique roles that provide bacteria with plasticity in their behaviors.
Fatty acid oxidation participates of the survival to starvation, cell cycle progression and differentiation in the insect stages ofTrypanosoma cruzi
Authors: Souza Rodolpho Ornitz Oliveira , Damasceno Flávia Silva , Marsiccobetre Sabrina , Biran Marc , Murata Gilson , Curi Rui , Bringaud Frédéric , Silber Ariel Mariano 
Published: January 2021

AbstractDuring its complex life cycle,Trypanosoma cruzicolonizes different niches in its insect and mammalian hosts. This characteristic determined the types of parasites that adapted to face challenging environmental cues. The primary environmental challenge, particularly in the insect stages, is poor nutrient availability. TheseT. cruzistages could be exposed to fatty acids originating from the degradation of the perimicrovillar membrane. In this study, we revisit the metabolic fate of fatty acid breakdown inT. cruzi. Herein, we show that during parasite proliferation, the glucose concentration in the medium can regulate the fatty acid metabolism. At the stationary phase, the parasites fully oxidize fatty acids. [U-14C]-palmitate can be taken up from the medium, leading to CO2production via beta-oxidation. Lastly, we also show that fatty acids are degraded through beta-oxidation. Additionally, through beta-oxidation, electrons are fed directly to oxidative phosphorylation, and acetyl-CoA is supplied to the tricarboxylic acid cycle, which can be used to feed other anabolic pathways such as thede novobiosynthesis of fatty acids.Author SummaryTrypanosoma cruziis a protist parasite with a life cycle involving two types of hosts, a vertebrate one (which includes humans, causing Chagas disease) and an invertebrate one (kissing bugs, which vectorize the infection among mammals). In both hosts, the parasite faces environmental challenges such as sudden changes in the metabolic composition of the medium in which they develop, severe starvation, osmotic stress and redox imbalance, among others. Because kissing bugs feed infrequently in nature, an intriguing aspect ofT. cruzibiology (it exclusively inhabits the digestive tube of these insects) is how they subsist during long periods of starvation. In this work, we show that this parasite performs a metabolic switch from glucose consumption to lipid oxidation, and it is able to consume lipids and the lipid-derived fatty acids from both internal origins as well as externally supplied compounds. When fatty acid oxidation is chemically inhibited by etomoxir, a very well-known drug that inhibits the translocation of fatty acids into the mitochondria, the proliferative insect stage of the parasites has dramatically diminished survival under severe metabolic stress and its differentiation into its infective forms is impaired. Our findings place fatty acids in the centre of the scene regarding their extraordinary resistance to nutrient-depleted environments.
Role of extracellular mycobacteria in blood-retinal barrier invasion in a zebrafish model of ocular TB
Authors: Damera Santhosh Kumar , Panigrahi Ranjan K. , Mitra Sanchita , Basu Soumyava 
Published: January 2021

AbstractIntraocular inflammation following mycobacterial dissemination to the eye is common in tuberculosis (TB)-endemic countries. However, the early host-pathogen interactions during ocular dissemination are unknown. In this study, we investigate the early events during mycobacterial invasion of the blood-retinal barriers (BRB) with fluorescent taggedMycobacterium marinum(Mm), host macrophages and retinal vasculature in a zebrafish model of ocular TB. We found thatMminvaded the vascular endothelium either in extracellular or intracellular (inside phagocytes) state, typically 3-4 days post-injection (dpi). ExtracellularMmare phagocytosed in the retinal tissue, and progress to form a compact granuloma around 6 dpi. IntracellularMmcrossing the BRB are likely to be less virulent, and either persist inside solitary macrophages (most cases), or progress to loosely arranged granuloma (rare). The early interactions between mycobacteria and host immune cells can thus determine the course of disease during mycobacterial dissemination to the eye.
Evolution in salmon life-history induced by direct and indirect effects of fishing
Authors: Czorlich Y. , Aykanat T. , Erkinaro J. , Orell P. , Primmer CR. 
Published: January 2021

AbstractUnderstanding the drivers of evolution is a fundamental aim in biology. However, identifying the evolutionary impacts of human activities, both direct and indirect, is challenging because of lack of temporal data and limited knowledge of the genetic basis of most traits1. Atlantic salmon is a species exposed to intense anthropogenic pressures during its anadromous life cycle2. Previous research has shown that salmon age at maturity has evolved towards earlier maturation over the last 40 years, with an 18% decrease3in the allele associated with late maturation at the large-effectvgll3locus4; but the drivers of this change remain unknown. Here, we link genetic and phenotypic changes in a large Atlantic salmon population with salmon prey species biomass in the Barents Sea, temperature, and fishing effort in order to identify drivers of age at maturity evolution. We show that age at maturity evolution is associated with two different types of fisheries induced evolution acting in opposing directions: an indirect effect linked with commercial harvest of a salmon prey species (capelin) at sea (selection against late maturation), and a direct effect due to temporal changes in net fishing pressure in the river (surprisingly, selection against early maturation). Although the potential for direct and indirect evolutionary effects of fishing have been acknowledged, empirical evidence for induced changes at the genetic level has been lacking5. As capelin are primarily harvested to produce fish meal and oil for aquaculture6, we hereby identify an indirect path by which Atlantic salmon aquaculture may negatively affect wild populations.
Genetic influences on brain activation and large-scale functional connectivity during nociceptive processing: a twin study
Authors: Kastrati Gránit , Rosén Jörgen , Thompson William H. , Chen Xu , Larsson Henrik , Nichols Thomas E. , Tracey Irene , Fransson Peter , Åhs Fredrik , Jensen Karin B. 
Published: January 2021

AbstractNociceptive processing in the human brain is a signal that enables harm avoidance, with large interindividual variance. The relative contributions of genes and environment to the neural structures that support nociception have not been studied in twins previously. Here, we employed a classic twin-design to determine brain structures influenced by additive genetics. We found genetic influences on nociceptive processing in the midcingulate cortex, bilateral posterior insulae and thalamus. In addition to brain activations, we found genetic contributions to large-scale functional connectivity during nociceptive processing. We conclude that additive genetics influence specific aspects of nociceptive processing, which improves our understanding of human nociceptive processing.
compaRe, an ultra-fast and robust suite for multiparametric screening, identifies phenotypic drug responses in acute myeloid leukemia
Authors: Hajkarim Morteza Chalabi , Karjalainen Ella , Osipovitch Mikhail , Dimopoulos Konstantinos , Gordon Sandra Leigh , Ambri Francesca , Rasmussen Kasper Dindler , Grønbæk Kirsten , Helin Kristian , Wennerberg Krister , Won Kyoung Jae 
Published: January 2021

AbstractMultiparametric phenotypic screening of cells, for example assessing their responses to small molecules or knockdown/knockout of specific genes, is a powerful approach to understanding cellular systems and identifying potential new therapeutic strategies. However, automated tools for analyzing similarities and differences between a large number of tested conditions have not been readily available. Methods designed for clustering cells cannot identify differences between samples effectively. We introducecompaRefor ultra-fast and robust analysis of multiparametric high-throughput screening. Applying a mass-aware gridding algorithm using hypercubes,compaReperforms automatic and effective similarity comparison for hundreds to thousands of tests and provides information about the treatment effect. Particularly for screening data,compaReis equipped with modules to remove various sources of bias.Benchmarking tests show thatcompaRecan circumvent batch effects and perform a similarity analysis substantially faster than conventional analysis tools. ApplyingcompaReto high-throughput flow cytometry screening data, we were able to distinguish subtle phenotypic drug responses in a human sample and a genetically engineered mouse model with acute myeloid leukemia (AML).compaRerevealed groups of drugs with similar responses even though their mechanisms are distinct from each other. In another screening,compaReeffectively circumvented batch effects and grouped samples from AML and myelodysplastic syndrome (MDS) patients using clinical flow cytometry data.