bluuebunny/crossref_metadata_2025_split huggingface dataset:
siRNA enrichment in Argonaute 2-depletedBlattella germanica
Authors: Montañés José Carlos , Rojano Carlos , Ylla Guillem , Piulachs Maria Dolors , Maestro José Luis 
Published: February 2021

ABSTRACTBackgroundRNA interference (RNAi) is a cellular mechanism used to fight various threats, including transposons, aberrant RNA, and some types of viruses. It relies on dsRNA detection and, through a mechanism involving Dicer-2 (Dcr-2) and Argonaute 2 (AGO2), together with a small RNA fragment (siRNA) as a complementary guide, binds to an RNA and cleaves it.MethodsUsing the cockroachBlattella germanicaas a model, we examined AGO2 activity by depleting its mRNA levels using RNAi and analyzing the phenotypes produced.ResultsSilencingAGO2expression had no remarkable effect on nymphal development or reproduction. dsRNA treatment triggered an immediate and transitory increase inAGO2expression, independently of Dcr-2 action. In addition, we analyzed the siRNAs generated after injecting a heterologous dsRNA in control andAGO2-depleted animals. The results revealed that siRNAs were distributed non-uniformly along the dsRNA sequence. InAGO2-depleted animals, the proportion of 22 nucleotide reads was higher and accumulations of reads appeared in areas less well-represented in the controls. We also detected a slight preference for cytosine as the first nucleotide in controls to be lost inAGO2-depleted individuals.Conclusions/General significanceThe siRNAs produced from a dsRNA are heterogeneously distributed along the length of the dsRNA and this arrangement depends on the sequence. AGO2 exerts its role as nuclease on the siRNA duplexes independently of its action on the homologous mRNA. This study sheds light on an extremely useful process for reverse genetics in laboratories, in addition to the design of more effective, specific, and eco-friendly pest-control strategies.Highlights-RNA interference is used to fight cellular threats including transposons and viruses-Silencing AGO2 inBlattella germanicadoes not affect development or reproduction-siRNA distribution along the dsRNA sequence is non-uniform and sequence dependent-AGO2 depletion increased the proportion of 22 nt reads in certain areas
Genetic determinants facilitating the evolution of resistance to carbapenem antibiotics
Authors: Ma Peijun , He Lorrie L. , Pironti Alejandro , Laibinis Hannah H. , Ernst Christoph M. , Manson Abigail L. , Bhattacharyya Roby P. , Earl Ashlee M. , Livny Jonathan , Hung Deborah T. 
Published: February 2021

AbstractIn this era of rising antibiotic resistance, in contrast to our increasing understanding of mechanisms that cause resistance, our understanding of mechanisms that influence the propensity to evolve resistance remains limited. Here, we identified genetic factors that facilitate the evolution of resistance to carbapenems, the antibiotic of “last resort,” inKlebsiella pneumoniae, the major carbapenem resistant species. In clinical isolates, we found that high-level transposon insertional mutagenesis plays an important role in contributing to high-level resistance frequencies in several major and emerging carbapenem-resistant lineages. A broader spectrum of resistance-conferring mutations for select carbapenems such as ertapenem also enables higher resistance frequencies and importantly, creates stepping-stones to achieve high-level resistance to all carbapenems. These mutational mechanisms can contribute to the evolution of resistance, in conjunction with the loss of systems that restrict horizontal resistance gene uptake, such as the CRISPR-Cas system. Given the need for greater antibiotic stewardship, these findings argue that in addition to considering the current efficacy of an antibiotic for a clinical isolate in antibiotic selection, considerations of future efficacy are also important. The genetic background of a clinical isolate and the exact antibiotic identity can and should also be considered as it is a determinant of a strain’s propensity to become resistant. Together, these findings thus provide a molecular framework for understanding acquisition of carbapenem resistance inK. pneumoniaewith important implications for diagnosing and treating this important class of pathogens.
Dlc1controls cardio-vascular development downstream of Vegfa/Kdrl/Nrp1 signaling in the zebrafish embryo
Authors: Linnerz Tanja , Bertrand Julien Y. 
Published: February 2021

ABSTRACTThe family ofdeleted-in-liver-cancer (dlc)genes encodes RhoGTPases and plays pivotal roles in cardiovascular development, but animal models for studying their functions are sparse due to early embryonic lethality. Gain and loss of function ofdlc1anddlc3severely altered the growth of intersegmental vessels in the trunk of zebrafish embryos. Additionally, overexpression ofdlc1affected the growth of the common cardinal veins, but could rescue the arrest of angiogenesis induced by Vegfr2 inhibition, placingdlc1downstream ofkdrlsignaling. Loss ofdlc1negatively affected the lumenization of the first aortic arch arteries and the lateral dorsal aortae.dlc1mutants displayed a full obstruction in the early outflow tract during cardiac morphogenesis, which models to alterations in DLC1 detected in congenital heart defects in human patients. This study provides a functionalin vivocharacterization ofdlc1anddlc3during vertebrate embryogenesis and placesdlc1as a key gene to control vascular development.
Dorsal striatal dopamine induces fronto-cortical hypoactivity and implies reduced anxiety and compulsive behaviors in rats
Authors: Casado-Sainz Agata , Gudmundsen Frederik , Baerentzen Simone L. , Lange Denise , Ringsted Annemette , Martinez-Tajada Isabel , Medina Siria , Lee Hedok , Svarer Claus , Keller Sune H. , Schain Martin , Kjaerby Celia , Fisher Patrick M. , Cumming Paul , Palner Mikael 
Published: February 2021

AbstractDorsal striatal dopamine transmission engages the cortico-striato-thalamo-cortical (CSTC) circuit, which is implicated in many neuropsychiatric diseases, including obsessive-compulsive disorder (OCD). Yet it is unknown if dorsal striatal dopamine hyperactivity is the cause or consequence of changes elsewhere in the CSTC circuit. Classical pharmacological and neurotoxic manipulations of the CSTC and other brain circuits suffer from various drawbacks related to off-target effects and adaptive changes. Chemogenetics, on the other hand, enables a highly selective targeting of specific neuronal populations within a given circuit. In this study, we developed a chemogenetic method for selective activation of dopamine neurons in the substantia nigra, which innervating the rat dorsal striatum. We used this model to investigate effects of targeted dopamine activation on CSTC circuit function, especially in fronto-cortical regions. We found that chemogenetic activation of these neurons increased movement, as expected from dopamine release, rearings and time spend in center, while it also lowered self-grooming and increased prepulse inhibition in females. Remarkably, we observed reduced [18F]FDG metabolism in frontal cortex, following dopamine activation in the dorsal striatum, yet total glutamate levels-in this region were increased. A finding which may help explain the contradiction in some clinical studies of increased [18F]FDG metabolism and lower glutamate levels in diseases like OCD. Taken together, these results establish the importance of nigro-striatal dopamine transmission for modulating CSTC function, especially with respect to fronto-cortical activity, glutamate levels and behaviors related anxiety and compulsive actions.One Sentence SummaryDorsal striatum dopamine induce fronto-cortical hypoactivity and reduce compulsive behaviors in rats
Cytidine triphosphate promotes efficient ParB-dependent DNA condensation by facilitating one-dimensional spreading fromparS
Authors: de Asis Balaguer Francisco , Aicart-Ramos Clara , Fisher Gemma LM , de Bragança Sara , Pastrana Cesar L. , Dillingham Mark S. , Moreno-Herrero Fernando 
Published: February 2021

SUMMARYFaithful segregation of bacterial chromosomes relies on the ParABS partitioning system and the SMC complex. In this work, we used single molecule techniques to investigate the role of cytidine triphosphate (CTP) binding and hydrolysis in the critical interaction between centromere-likeparSDNA sequences and the ParB CTPase. Using a combined dual optical tweezers confocal microscope, we observe the specific interaction of ParB withparSdirectly. Binding aroundparSis enhanced 4-fold by the presence of CTP or the non-hydrolysable analogue CTPγS. However, ParB proteins are also detected at a lower density in distal non-specific regions of DNA. This requires the presence of aparSloading site and is prevented by roadblocks on DNA, consistent with one dimensional diffusion by a sliding clamp. Magnetic tweezers experiments show that the spreading activity, which has an absolute requirement for CTP binding but not hydrolysis, results in the condensation ofparS-containing DNA molecules at low nanomolar protein concentrations. We propose a model in which ParB-CTP-Mg2+complexes move along DNA following loading atparSsites and protein:protein interactions result in the localised condensation of DNA within ParB networks.
Importance of viscosity contrast for the motion of erythrocytes in microcapillaries
Authors: Dasanna Anil K. , Mauer Johannes , Gompper Gerhard , Fedosov Dmitry A. 
Published: February 2021

ABSTRACTThe dynamics and deformation of red blood cells (RBCs) in microcirculation affect the flow resistance and transport properties of whole blood. One of the key properties that can alter RBC dynamics in flow is the contrast λ (or ratio) of viscosities between RBC cytosol and blood plasma. Here, we study the dependence of RBC shape and dynamics on the viscosity contrast in tube flow, using mesoscopic hydrodynamics simulations. State diagrams of different RBC dynamical states, including tumbling cells, parachutes, and tank-treading slippers, are constructed for various viscosity contrasts and wide ranges of flow rates and tube diameters (or RBC confinements). Despite similarities in the classification of RBC behavior for different viscosity contrasts, there are notable differences in the corresponding state diagrams. In particular, the region of parachutes is significantly larger for λ = 1 in comparison to λ = 5. Furthermore, the viscosity contrast strongly affects the tumbling-to-slipper transition, thus modifying the regions of occurrence of these states as a function of flow rate and RBC confinement. Also, an increase in cytosol viscosity leads to a reduction in membrane tension induced by flow stresses. Physical mechanisms that determine these differences in RBC dynamical states as a function of λ are discussed.
Red Blood Cells Function as DNA Sensors
Authors: Lam Metthew , Murphy Sophia , Kokkinaki Dimitra , Venosa Alessandro , Sherrill-Mix Scott , Casu Carla , Rivella Stefano , Weiner Aaron , Park Jeongho , Shin Sunny , Vaughan Andrew , Hahn Beatrice H. , John Audrey R. Odom , Meyer Nuala J. , Hunter Christopher A. , Worthen G. Scott , Mangalmurti Nilam S. 
Published: February 2021

AbstractErythrocytes have long been mistaken as exclusively inert oxygen carriers lacking immune function. Here we show that red blood cells (RBCs) serve as immune sensors through surface expression of the nucleic acid-sensing toll-like receptor 9 (TLR9), a classically endosomal receptor that initiates immune responses following the detection of unmethylated CpG motifs present in pathogen and mitochondrial DNA. Mammalian RBCs express TLR9 on their surface and bind CpG-containing bacterial, malarial, and mitochondrial DNA. Erythrocyte-bound CpG DNA increases during infection, and CpG-carrying RBCs trigger accelerated erythrophagocytosis and innate immune activation characterized by RBC-TLR9 dependent local and systemic cytokine production. Thus, RBC nucleic acid detection and capture regulates red cell clearance and immune responses and provides evidence for RBCs as innate immune sentinels during pathologic states.One Sentence SummaryThe ability of RBCs to detect and bind cell-free nucleic acids contributes to immunity during acute inflammatory states.
Predicting behavior from eye movement and whisking asymmetry
Authors: Bergmann Ronny , Sehara Keisuke , Dominiak Sina E. , Kremkow Jens , Larkum Matthew E. , Sachdev Robert N.S. 
Published: February 2021

AbstractNavigation through complex environments requires motor planning, motor preparation and the coordination between multiple sensory–motor modalities. For example, the stepping motion when we walk is coordinated with motion of the torso, arms, head and eyes. In rodents, movement of the animal through the environment is often coordinated with whisking. Here we trained head fixed mice – navigating a floating Airtrack plus maze – to overcome their directional preference and use cues indicating the direction of movement expected in each trial. Once cued, mice had to move backward out of a lane, then turn in the correct direction, and enter a new lane. In this simple paradigm, as mice begin to move backward, they position their whiskers asymmetrically: whiskers on one side of the face protract, and on the other side they retract. This asymmetry reflected the turn direction. Additionally, on each trial, mice move their eyes conjugately in the direction of the upcoming turn. Not only do they move their eyes, but saccadic eye movement is coordinated with the asymmetric positioning of the whiskers. Our analysis shows that the asymmetric positioning of the whiskers predicts the direction of turn that mice will make at an earlier stage than eye movement does. We conclude that, when mice move or plan to move in complex real-world environments, their motor plan and behavioral state can be read out in the movement of both their whiskers and eyes.Significance statementNatural behavior occurs in multiple sensory and motor dimensions. When we move through our environment we coordinate the movement of our body, head, eyes and limbs. Here we show that when mice navigate a maze, they move their whiskers and eyes; they position their whiskers asymmetrically, and use saccadic eye movements. The position of the eyes and whiskers predicts the direction mice will turn in. This work suggests that when mice move through their environment, they coordinate the visual-motor and somatosensory-motor systems.
SARS-CoV-2 variants B.1.351 and B.1.1.248: Escape from therapeutic antibodies and antibodies induced by infection and vaccination
Authors: Hoffmann Markus , Arora Prerna , Groß Rüdiger , Seidel Alina , Hörnich Bojan , Hahn Alexander , Krüger Nadine , Graichen Luise , Hofmann-Winkler Heike , Kempf Amy , Winkler Martin Sebastian , Schulz Sebastian , Jäck Hans-Martin , Jahrsdörfer Bernd , Schrezenmeier Hubert , Müller Martin , Kleger Alexander , Münch Jan , Pöhlmann Stefan 
Published: February 2021

SUMMARYThe global spread of SARS-CoV-2/COVID-19 is devastating health systems and economies worldwide. Recombinant or vaccine-induced neutralizing antibodies are used to combat the COVID-19 pandemic. However, recently emerged SARS-CoV-2 variants B.1.1.7 (UK), B.1.351 (South Africa) and B.1.1.248 (Brazil) harbor mutations in the viral spike (S) protein that may alter virus-host cell interactions and confer resistance to inhibitors and antibodies. Here, using pseudoparticles, we show that entry of UK, South Africa and Brazil variant into human cells is susceptible to blockade by entry inhibitors. In contrast, entry of the South Africa and Brazil variant was partially (Casirivimab) or fully (Bamlanivimab) resistant to antibodies used for COVID-19 treatment and was less efficiently inhibited by serum/plasma from convalescent or BNT162b2 vaccinated individuals. These results suggest that SARS-CoV-2 may escape antibody responses, which has important implications for efforts to contain the pandemic.
Alternative female and male developmental trajectories in the dynamic balance of human visual perception
Authors: Ziman Gergő , Aleshin Stepan , Unoka Zsolt , Braun Jochen , Kovács Ilona 
Published: February 2021

AbstractThe numerous multistable phenomena in vision, hearing and touch attest that the inner workings of perception are prone to instability. We investigated a visual example – binocular rivalry – with an accurate no-report paradigm, and uncovered developmental and maturational lifespan trajectories that were specific for age and sex. To interpret these trajectories, we hypothesized that conflicting objectives of visual perception – such asstabilityof appearance,sensitivityto visual detail, andexplorationof fundamental alternatives – change in relative importance over the lifespan. Computational modelling of our empirical results allowed us to estimate this putative development of stability, sensitivity, and exploration over the lifespan. Our results confirmed prior findings of developmental psychology and appear to quantify important aspects of neurocognitive phenotype. Additionally, we report atypical function of binocular rivalry in autism spectrum disorder and borderline personality disorder. Our computational approach offers new ways of quantifying neurocognitive phenotypes both in development and in dysfunction.
Cone mitochondria act as microlenses to enhance light delivery and confer Stiles-Crawford-like direction sensitivity
Authors: Ball John M. , Chen Shan , Li Wei 
Published: February 2021

AbstractEvolution endeavors to maximize the function of biological structures in organisms, and the vertebrate eye is no exception. Cone photoreceptors in the retina are among the most energy-demanding cells in our body, necessitating numerous mitochondria. Intriguingly, these mitochondria adopt a peculiar spatial aggregation immediately beneath the cone outer segment (OS) that houses light-sensitive opsin molecules. Here we demonstrate,viadirect live imaging and computational modeling of ground squirrel cones, that such mitochondria bundles concentrate light to enter the OS for detection. This “microlens”-like feature of cone mitochondria produces an angular dependence of light intensity quantitively consistent with the Stiles-Crawford effect, a psychophysical phenomenon believed to improve visual resolution. Thus, in addition to their function as a necessary powerhouse, cone mitochondria play a critical optical role.
Comparative Chromatin Dynamics of Stem Cell Differentiation in Human and Rat
Authors: Thai Christina Wilcox , Jiang Shan , Roxas Yuka , McGill Cassandra , Ma Savanna , Mortazavi Ali 
Published: February 2021

ABSTRACTDifferentiation of cell types homologous between species are controlled by conserved networks of regulatory elements driving gene expression. In order to identify conservation of gene expression and chromatin accessibility during cell differentiation in two different species. We collected a daily time-course of gene expression and chromatin accessibility in rat and human to quantify conserved and species-specific chromatin dynamics during embryonic stem cell differentiation to definitive endoderm (DE) as well as to neuronal progenitor cells (NPC). We identify shared and cell-type specific transient differentiation markers in each species, including key transcription factors that may regulate differentiation into each cell-type and their candidate cis-regulatory elements (cCREs). Our analysis shows that DE differentiation has higher conservation of gene expression and chromatin accessibility than NPC differentiation. We provide the first global comparison of transcriptional complexity and chromatin dynamics between human and rat for DE and NPC differentiation.
Coordination between growth and stress responses by DELLA in the liverwortMarchantia polymorpha
Authors: Hernández-García Jorge , Sun Rui , Serrano-Mislata Antonio , Inoue Keisuke , Vargas-Chávez Carlos , Esteve-Bruna David , Arbona Vicent , Yamaoka Shohei , Nishihama Ryuichi , Kohchi Takayuki , Blázquez Miguel A. 
Published: February 2021

SummaryPlant survival depends on the optimal use of resources under variable environmental conditions. Among the mechanisms that mediate the balance between growth, differentiation and stress responses, the regulation of transcriptional activity by DELLA proteins stands out. In angiosperms, DELLA accumulation promotes defense against biotic and abiotic stress and represses cell division and expansion, while loss of DELLA function is associated with increased plant size and sensitivity towards stress1. Given that DELLA protein stability is dependent on gibberellin (GA) levels2, and GA metabolism is influenced by the environment3, this pathway is proposed to relay environmental information to the transcriptional programs that regulate growth and stress responses in angiosperms4,5. However,DELLAgenes are also found in bryophytes, whereas canonical GA receptors appeared only in vascular plants6–10. Thus, it is not clear whether these regulatory functions of DELLA predated or emerged with typical GA signaling. Here we show that, as in vascular plants, the only DELLA in the liverwortMarchantia polymorphaalso participates in the regulation of growth and key developmental processes, and promotes the tolerance towards oxidative stress. Moreover, part of these effects is likely caused by the conserved physical interaction with the MpPIF transcription factor. Therefore, we suggest that the role in the coordination of growth and stress responses was already encoded in DELLA from the common ancestor of land plants, and the importance of this function is justified by its conservation over the past 450 M years.