bluuebunny/crossref_metadata_2025 huggingface dataset:
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

The 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

Erythrocytes 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 Summary

The 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

Navigation 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 statement

Natural 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.
Regulation of PD1 signaling is associated with prognosis in glioblastoma multiforme
Authors: Lopes-Ramos Camila , Belova Tatiana , Brunner Tess , Quackenbush John , Kuijjer Marieke L.
Published: February 2021

Glioblastoma is an aggressive cancer of the brain and spine. While analysis of glioblastoma ‘omics data has somewhat improved our understanding of the disease, it has not led to direct improvement in patient survival. Cancer survival is often characterized by differences in expression of particular genes, but the mechanisms that drive these differences are generally unknown. We therefore set out to model the regulatory mechanisms that associate with glioblastoma survival. We inferred individual patient gene regulatory networks using data from two different expression platforms from The Cancer Genome Atlas (n=522 and 431). We performed a comparative network analysis between patients with long- and short-term survival, correcting for patient age, sex, and neoadjuvant treatment status. We identified seven pathways associated with survival, all of which were involved in immune system signaling. Differential regulation of PD1 signaling was validated in an independent dataset from the German Glioma Network (n=70). We found that transcriptional repression of genes in this pathway—for which treatment options are available—was lost in short-term survivors and that this was independent of mutation burden and only weakly associated with T-cell infiltrate. These results provide a new way to stratify glioblastoma patients that uses network features as biomarkers to predict survival, and identify new potential therapeutic interventions, thus underscoring the value of analyzing gene regulatory networks in individual cancer patients.
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

The 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

The 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

Evolution 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

Differentiation 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

Plant 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.
Top-down attention modulates auditory-evoked neural responses in neurotypical, but not ADHD, young adults
Authors: Kwasa Jasmine A. C. , Noyce Abigail L. , Torres Laura M. , Shinn-Cunningham Barbara G.
Published: February 2021

Individuals differ in their ability to selectively attend to goal-relevant auditory stimuli. People with Attention-Deficit/Hyperactivity Disorder (ADHD) in particular tend to show cognitive deficits associated with distractibility and inefficiencies in inhibition and attention. We hypothesized that people with ADHD would exhibit poorer performance and weaker neural signatures of attentional control when undertaking a challenging auditory task that required strong top-down attention. Neurotypical (N = 20) and ADHD (N = 25) young adults with normal hearing listened to one of three concurrent, spatially separated speech streams and reported the order of the syllables presented while we recorded electroencephalography (EEG). We tested both the ability to sustain attentional focus on a single “target” stream and the ability to monitor the target but flexibly switch attention to an unpredictable “interrupter” stream from another direction if and when it appeared. Although both stimulus structure and task demands affected behavioral performance, ADHD status did not. In both groups, the interrupter evoked larger neural responses when it was to be attended compared to when it was irrelevant, including for the P3a “reorienting” response previously described as involuntary. This attentional modulation was weaker in ADHD listeners, even though their behavioral performance was no lower. Across the entire cohort, individual performance correlated with the degree of top-down modulation of neural responses. These results demonstrate that listeners differ in their ability to modulate neural representations of sound based on task goals. Adults with ADHD have weaker volitional control of attentional processes than their neurotypical counterparts.

Significance Statement

ADHD and neurotypical listeners attended to one speech stream among distractors while neural responses were measured with electroencephalography. Behavioral performance varied with stimulus structure and task demands, but not with ADHD status. In both groups, top-down attention modulated stimulus-evoked neural responses: interrupting sounds elicited weaker responses when the sounds were ignored compared to when they were attended. This modulation affected a late “orienting” response (P3a) that has been previously described as automatic and not dependent on internal state. Importantly, ADHD subjects showed weaker attentional filtering than did neurotypical controls. At the individual level, performance correlated with neural metrics. Our results demonstrate that people vary widely in how flexibly they can use attention to modulate sensory responses based on task goals.
Comprehensive phenotypic analysis of the Dp1Tyb mouse strain reveals a broad range of Down Syndrome-related phenotypes
Authors: Lana-Elola Eva , Cater Heather , Watson-Scales Sheona , Greenaway Simon , Müller-Winkler Jennifer , Gibbins Dorota , Nemes Mihaela , Slender Amy , Hough Tertius , Keskivali-Bond Piia , Scudamore Cheryl L , Herbert Eleanor , Banks Gareth T , Mobbs Helene , Canonica Tara , Tosh Justin , Noy Suzanna , Llorian Miriam , Nolan Patrick M. , Griffin Julian L. , Good Mark , Simon Michelle , Mallon Ann-Marie , Wells Sara , Fisher Elizabeth M. C. , Tybulewicz Victor L. J.
Published: February 2021

Down syndrome (DS), trisomy 21, results in many complex phenotypes including cognitive deficits, heart defects and craniofacial alterations. Phenotypes arise from an extra copy of human chromosome 21 (Hsa21) genes. However, causative genes remain mostly unknown. Animal models enable identification of these genes and pathological mechanisms. The Dp1Tyb mouse model of DS has an extra copy of 63% of Hsa21-orthologous mouse genes. Here, we comprehensively phenotype Dp1Tyb mice and find wide-ranging DS-like phenotypes including aberrant megakaryopoiesis, reduced bone density, and deficits in memory, locomotion, hearing and sleep. Thus, Dp1Tyb mice are an excellent model for studies of many complex DS phenotypes.
ChEC-seq produces robust and specific maps of transcriptional regulators
Authors: Zentner Gabriel E. , Policastro Robert A. , Henikoff Steven
Published: February 2021

We previously introduced chromatin endogenous cleavage and high-throughput sequencing (ChEC-seq), which uses fusion of a chromatin-binding protein of interest to micrococcal nuclease (MNase) and high-throughput sequencing to generate genome-wide maps of factor binding. Here, we respond to concerns that have been raised about the specificity of the method relative to its negative control when a single long calcium incubation time is used. Through reanalysis of our previously published datasets, we show that short-duration ChEC-seq experiments provide robust, specific maps of transcriptional regulators across the budding yeast genome. Our analyses also confirm that consideration of MNase digestion kinetics is important for proper design and interpretation of ChEC-seq experiments.
The genetic basis of adaptation through the evolution of self-fertilization
Authors: Xu Kuangyi
Published: February 2021

Although adaptation can be realized through the fixation of beneficial alleles that increase viability, many plant populations may adapt through the evolution of self-fertilization, especially when pollination becomes inefficient. However, the genetic basis of adaptation through the evolution of selfing remains unclear. Using population genetic models, I study adaptation through the fixation of alleles that increase the selfing rate (selfing modifiers) from new mutations or/and standing variation. For adaptive alleles unrelated to selfing, it is known that selfing promotes adaptation from a new mutation only when the beneficial alleles are recessive, and the probability of adaptation from standing variation is nearly independent of dominance, and always decreases with the selfing rate. In contrast, for adaptation through the evolution of selfing, when it occurs by fixation of a newly arisen mutation, a population that already has a high selfing rate may be more (less) likely to adapt than outcrossers even when the modifier is dominant (recessive) if the modifier is weakly (strongly) selected. Also, adaptation from standing variation is more likely through recessive modifier alleles, with the highest fixation probability found in partially selfing populations, but fixation is fastest when dominance is intermediate. When there are multiple modifiers, adaptation through new mutations is more likely when selfing is controlled by few large-effect rather than many slight-effect modifiers. This study suggests that to understand the genetic basis of adaptation, it is necessary to determine the ecological and genetic advantages of adaptive alleles.

Significance statement

This study, by deriving the selective coefficient and effective population size, investigated the genetic basis of adaptation through fixation of modifier alleles that increase the selfing rate, which is shown to differ in several aspects from that through evolution of mating-unrelated alleles. Specifically, when adaptation is from new mutations, the dominance of a selfing modifier allele below which selfing increases the fixation probability depends on the strength of pollen limitation and pollen discounting. Adaptation from standing variation is more likely through recessive modifier alleles and in populations with an intermediate selfing rate. This work suggests it is important to have a mechanistic understanding of how adaptive alleles increase individual fitness in environment that is unfavorable to the population.
Annotation of snoRNA abundance across human tissues reveals complex snoRNA-host gene relationships
Authors: Fafard-Couture Étienne , Bergeron Danny , Couture Sonia , Abou Elela Sherif , Scott Michelle S
Published: February 2021

Background

Small nucleolar RNAs (snoRNAs) are mid-size non-coding RNAs required for ribosomal RNA modification, implying a ubiquitous tissue distribution linked to ribosome synthesis. However, increasing numbers of studies identify extra-ribosomal roles of snoRNAs in modulating gene expression, suggesting more complex snoRNA abundance patterns. Therefore, there is a great need for mapping the snoRNome in different human tissues as the blueprint for snoRNA functions.

Results

We used a low structure bias RNA-Seq approach to accurately quantify snoRNAs and compare them to the entire transcriptome in seven healthy human tissues (breast, ovary, prostate, testis, skeletal muscle, liver and brain). We identified 475 expressed snoRNAs categorized in two abundance classes that differ significantly in their function, conservation level and correlation with their host gene: 390 snoRNAs are uniformly expressed and 85 are enriched in the brain or reproductive tissues. Most tissue-enriched snoRNAs are embedded in lncRNAs and display strong correlation of abundance with them, whereas uniformly expressed snoRNAs are mostly embedded in protein-coding host genes and are mainly non- or anticorrelated with them. 59% of the non-correlated or anticorrelated protein-coding host gene/snoRNA pairs feature dual-initiation promoters, as opposed to only 16% of the correlated non-coding host gene/snoRNA pairs.

Conclusions

Our results demonstrate that snoRNAs are not a single homogeneous group of housekeeping genes but include highly regulated tissue-enriched RNAs. Indeed, our work indicates that the architecture of snoRNA host genes varies to uncouple the host and snoRNA expressions in order to meet the different snoRNA abundance levels and functional needs of human tissues.
The structure of the human cell cycle
Authors: Stallaert Wayne , Kedziora Katarzyna M. , Taylor Colin D. , Zikry Tarek M. , Sobon Holly K. , Taylor Sovanny R. , Young Catherine L. , Limas Juanita C. , Cook Jeanette G. , Purvis Jeremy E.
Published: February 2021

The human cell cycle is conventionally depicted as a five-phase model consisting of four proliferative phases (G1, S, G2, M) and a single state of arrest (G0). However, recent studies show that individual cells can take different paths through the cell cycle and exit into distinct arrest states, thus necessitating an update to the canonical model. We combined time lapse microscopy, highly multiplexed single cell imaging and manifold learning to determine the underlying “structure” of the human cell cycle under multiple growth and arrest conditions. By visualizing the cell cycle as a complete biological process, we identified multiple points of divergence from the proliferative cell cycle into distinct states of arrest, revealing multiple mechanisms of cell cycle exit and re-entry and the molecular routes to senescence, endoreduplication and polyploidy. These findings enable the visualization and comparison of alternative cell cycles in development and disease.

One-sentence summary

A systems-level view of single-cell states reveals the underlying architecture of the human cell cycle
Gys1 antisense therapy rescues neuropathological bases of murine Lafora disease
Authors: Ahonen Saija , Nitschke Silvia , Grossman Tamar R. , Kordasiewicz Holly , Wang Peixiang , Zhao Xiaochu , Guisso Dikran R. , Kasiri Sahba , Nitschke Felix , Minassian Berge A.
Published: February 2021

Lafora disease is a fatal progressive myoclonus epilepsy. At root, it is due to constant acquisition of branches that are too long in a subgroup of glycogen molecules, leading them to precipitate and accumulate into Lafora bodies, which drive a neuroinflammatory response and neurodegeneration. As a potential therapy, we aimed to downregulate glycogen synthase, the enzyme responsible for glycogen branch elongation, in the disease’s mouse models. We synthesized an antisense oligonucleotide (Gys1-ASO) that targets the mRNA of the brain-expressed glycogen synthase 1 gene (Gys1). We administered Gys1-ASO by intracerebroventricular injection and analyzed the pathological hallmarks of Lafora disease, namely glycogen accumulation, Lafora body formation, and neuroinflammation. Gys1-ASO prevented Lafora body formation in young mice that had not yet formed them. In older mice that already exhibited Lafora bodies, Gys1-ASO inhibited further accumulation, markedly preventing large Lafora bodies characteristic of advanced disease. Inhibition of Lafora body formation was associated with prevention of astrogliosis and strong trends towards correction of dysregulated expression of disease immune and neuroinflammatory markers. Lafora disease manifests gradually in previously healthy teenagers. Our work provides proof of principle that an antisense oligonucleotide targeting the GYS1 mRNA could prevent, and halt progression of, this catastrophic epilepsy.
A versatile Tn7 transposon-based bioluminescence tagging tool for quantitative and spatial detection of bacteria in plants
Authors: Matsumoto Ayumi , Schlüter Titus , Melkonian Katharina , Takeda Atsushi , Nakagami Hirofumi , Mine Akira
Published: February 2021

Investigation of plant-bacteria interactions requires quantification ofin plantabacterial titers by means of colony counting assays. However, colony counting assays are cumbersome and time-consuming, and are unable to detect spatial patterns of bacterial colonization in plants. Here, to overcome these shortcomings, we devised a broadly applicable genetic engineering tool for bioluminescence-based quantitative and spatial detection of bacteria in plants. We developed plasmid vectors that have broad host ranges and enable Tn7transposon-mediated integration of theluxCDABEluciferase operon into a specific genomic location ubiquitously found across bacterial phyla. These vectors allowed for generation of bioluminescent transformants of various plant pathogenic bacteria belonging to the generaPseudomonas, Rhizobium(Agrobacterium), andRalstonia. The bioluminescent transformant ofPseudomonas syringaepv.tomatoDC3000 (Pto-lux) was as virulent inArabidopsis thalianaas its parental strain. Direct luminescence measurements ofPto-lux-inoculated plant tissues reported bacterial titers inA. thaliana, Solanum lycopersicum, Nicotiana benthamiana, andMarchantia polymorphaas accurately as conventional colony counting assays. We further showed the utility of our vectors for converting the previously generatedPtoderivatives to isogenic bioluminescent strains. Importantly, quantitative bioluminescence assays using thesePto-lux strains accurately reported the effects of plant immunity and bacterial effectors on bacterial growth with a dynamic range of 4 orders of magnitude. Moreover, macroscopic bioluminescence imaging illuminated spatial colonization patterns of thePto-lux in/on inoculated plant tissues. Taken together, our vectors offer untapped opportunities for developing bioluminescence-based quantitative and spatial analysis of bacterial growth in a variety of plant-bacteria interactions.

SIGNIFICANCE STATEMENT

We developed broad-host-range plasmid vectors that integrate the luciferase operon,luxCDABE, into a specific genomic location ubiquitously found across bacterial phyla. Using these vectors, we established a high-throughput method for bioluminescence-based quantitative assays ofin plantabacterial growth with a dynamic range of 4 orders of magnitude and visualized spatiotemporal patterns of bacterial colonization in/on inoculated plant tissues.
The relationship between affective visual mismatch negativity and interpersonal difficulties across autism and schizotypal traits
Authors: Ford Talitha C. , Hugrass Laila E. , Jack Bradley N.
Published: February 2021

Objective

Sensory deficits are a feature of autism and schizophrenia, as well as the upper end of their non-clinical spectra. The mismatch negativity (MMN), an index of pre-attentive auditory processing, is particularly sensitive in detecting such deficits; however, little is known about the relationship between the visual MMN (vMMN) to emotional faces and autism and schizophrenia spectrum symptom domains.

Methods

We probed the vMMN to happy, sad, and neutral faces in 77 young adults (18-40 years, 41 female), and evaluated their degree of autism and schizophrenia spectrum traits using the Autism Spectrum Quotient (AQ) and Schizotypal Personality Questionnaire (SPQ). Results: The vMMN to happy faces was significantly larger than the vMMNs to sad and neutral faces (p> 0.05). The vMMN to happy faces was associated with interpersonal difficulties as indexed by AQ Communication and Attention to Detail subscales, and SPQ Interpersonal Features (p< 0.05,uncorrected), such that a larger vMMN was associated with more interpersonal difficulties.

Conclusions

Pre-attentive processing of positive affect might be more specific to the interpersonal features associated with autism and schizophrenia.

Significance

These findings add valuable insights into the growing body of literature investigating symptom-specific neurobiological markers of autism and schizophrenia spectrum conditions.

Highlights

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The visual Mismatch Negativity (vMMN) is larger in response to happy compared to sad or neutral facial expressions

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The vMMN to happy facial expressions is specifically associated with more social communication difficulties

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vMMN to positive affect may be a neural mechanism associated with social communication difficulties in autism and schizophrenia
Physical phenotype of blood cells is altered in COVID-19
Authors: Kubánková Markéta , Hohberger Bettina , Hoffmanns Jakob , Fürst Julia , Herrmann Martin , Guck Jochen , Kräter Martin
Published: February 2021

Clinical syndrome coronavirus disease 2019 (COVID-19) induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by rapid spreading and high mortality worldwide. While the pathology is not yet fully understood, hyper-inflammatory response and coagulation disorders leading to congestions of microvessels are considered to be key drivers of the still increasing death toll. Until now, physical changes of blood cells have not been considered to play a role in COVID-19 related vascular occlusion and organ damage. Here we report an evaluation of multiple physical parameters including the mechanical features of five frequent blood cell types, namely erythrocytes, lymphocytes, monocytes, neutrophils, and eosinophils. More than 4 million blood cells of 17 COVID-19 patients at different levels of severity, 24 volunteers free from infectious or inflammatory diseases, and 14 recovered COVID-19 patients were analyzed. We found significant changes in erythrocyte deformability, lymphocyte stiffness, monocyte size, and neutrophil size and deformability. While some of these changes recovered to normal values after hospitalization, others persisted for months after hospital discharge, evidencing the long-term imprint of COVID-19 on the body.
Selective inhibition reveals the regulatory function of DYRK2 in protein synthesis and calcium entry
Authors: Wei Tiantian , Wang Jue , Liang Ruqi , Chen Wendong , He An , Du Yifei , Zhou Wenjing , Zhang Zhiying , Ma Mingzhe , Lu Jin , Guo Xing , Chen Xiaowei , Tian Ruijun , Xiao Junyu , Lei Xiaoguang
Published: February 2021

The dual-specificity tyrosine phosphorylation-regulated kinase DYRK2 has emerged as a key regulator of cellular processes such as proteasome-mediated protein degradation. To gain further insights into its function, we took a chemical biology approach and developed C17, a potent small-molecule DYRK2 inhibitor, through multiple rounds of structure-based optimization guided by a number of co-crystallized structures. C17 displayed an effect on DYRK2 at a single-digit nanomolar IC50and showed outstanding selectivity for the human kinome containing 467 other human kinases. Using C17 as a chemical probe, we further performed quantitative phosphoproteomic assays and identified several novel DYRK2 targets, including eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and stromal interaction molecule 1 (STIM1). DYRK2 phosphorylated 4E-BP1 at multiple sites, and the combined treatment of C17 with AKT and MEK inhibitors showed synergistic 4E-BP1 phosphorylation suppression. The phosphorylation of STIM1 by DYRK2 substantially increased the interaction of STIM1 with the ORAI1 channel, and C17 impeded the store-operated calcium entry process. Collectively, these studies further expand our understanding of DYRK2 and provide a valuable tool to further pinpoint its biological function.
Elucidating vimentin interaction with zinc ions and its interplay with oxidative modifications through crosslinking assays and molecular dynamics simulations
Authors: Mónico Andreia , Guzmán-Caldentey Joan , Pajares María A. , Martín-Santamaría Sonsoles , Pérez-Sala Dolores
Published: February 2021

The intermediate filament protein vimentin is involved in essential cellular processes, including cell division and stress responses. Vimentin oxidative modifications impact network reorganization and its single cysteine residue, Cys328, acts as a redox sensor. Vimentin binds zinc, which influences its assembly by undefined mechanisms. Here, results from combined biochemical and molecular dynamics studies support that zinc ions interact with Cys328 in its thiolate form, whereas Glu329 and Asp331 stabilize zinc coordination. Vimentin oxidation can induce disulfide crosslinking, implying a close proximity of cysteine residues in certain vimentin associations, validated by our computational models. Notably, micromolar zinc concentrations selectively prevent Cys328 alkylation and crosslinking. These effects are not mimicked by magnesium, consistent with the fewer magnesium ions hosted at the cysteine region. Altogether, our results pinpoint the region surrounding Cys328, highly conserved in type III intermediate filaments, as a hot spot for zinc binding, which modulates Cys328 reactivity and vimentin assembly.
The bacterial iron sensor IdeR recognizes its DNA targets by indirect readout
Authors: Marcos-Torres Francisco Javier , Maurer Dirk , Griese Julia J.
Published: February 2021

IdeR is the main transcriptional regulator controlling iron homeostasis genes in Actinobacteria, including species from theCorynebacterium, Mycobacterium, andStreptomycesgenera, as well as the erythromycin-producing bacteriumSaccharopolyspora erythraea.Despite being a well-studied transcription factor since the identification of the Diphtheria toxin repressor DtxR three decades ago, the details of how IdeR proteins recognize their highly conserved 19-bp DNA target remain to be elucidated. The results of our structural and mutational studies support a model wherein IdeR uses an indirect readout mechanism, identifying its targets via the sequence-specific DNA backbone structure rather than through direct contacts with the DNA bases. Furthermore, we show that IdeR efficiently recognizes a shorter palindromic sequence corresponding to a half binding site as compared to the full 19-bp target previously reported, expanding the number of potential target genes controlled by IdeR proteins.
Crystal structure and Hirshfeld surface analysis of 2-benzyl-4,5-dibromo-2,3,3a,4,5,6,7,7a-octahydro-3a,6-epoxy-1H-isoindol-1-one
Authors: Mertsalov Dmitriy F. , Zaytsev Vladimir P. , Pokazeev Kuzma M. , Grigoriev Mikhail S. , Bachinsky Alexander V. , Çelikesir Sevim Türktekin , Akkurt Mehmet , Mlowe Sixberth
Published: February 2021

The title compound, C15H15Br2NO2, crystallizes with two molecules in the asymmetric unit of the unit cell. In both molecules, the tetrahydrofuran rings adopt an envelope conformation with the O atom as the flap and the pyrrolidine rings adopt an envelope conformation. In the crystal, molecules are linked by weak C—H...O hydrogen bonds, forming sheets lying parallel to the (002) plane. These sheets are connected only by weak van der Waals interactions. The most important contributions to the surface contacts are from H...H (44.6%), Br...H/H...Br (24.1%), O...H/H...O (13.5%) and C...H/H...C (11.2%) interactions, as concluded from a Hirshfeld surface analysis.
Building organizational resilience through human capital management strategy
Authors: Douglas Stephanie
Published: February 2021

Purpose

This paper examines the role of human capital management strategy in shaping organizational resilience. Resilient organizations thrive in uncertain and adverse conditions. The organization’s capacity for resilience can be developed through human capital management strategies that are focused on employee capabilities, training, and development. When individual capabilities and resilience are developed, those can be aggregated at an organizational level to develop the capacity in an organization for resilience.

Design/methodology/approach

A review of relevant studies and literature was conducted to develop strategies and insight into developing the human capital of an organization to support organizational resilience.

Findings

Supporting individual capability development and resilience builds the organization’s capacity for resilience. By shifting human capital management strategies to building capabilities and then skills, organizations develop individual resilience and then organizational resilience. The implications of how to build such human capital management strategies are presented.

Originality/value

This paper provides support and guidelines for building individual capability and resilience to enhance an organization’s resilience.
Genetic algorithm based cooling energy optimization of data centers
Authors: Athavale Jayati , Yoda Minami , Joshi Yogendra
Published: February 2021

Purpose

This study aims to present development of genetic algorithm (GA)-based framework aimed at minimizing data center cooling energy consumption by optimizing the cooling set-points while ensuring that thermal management criteria are satisfied.

Design/methodology/approach

Three key components of the developed framework include an artificial neural network-based model for rapid temperature prediction (Athavale et al., 2018a, 2019), a thermodynamic model for cooling energy estimation and GA-based optimization process. The static optimization framework informs the IT load distribution and cooling set-points in the data center room to simultaneously minimize cooling power consumption while maximizing IT load. The dynamic framework aims to minimize cooling power consumption in the data center during operation by determining most energy-efficient set-points for the cooling infrastructure while preventing temperature overshoots.

Findings

Results from static optimization framework indicate that among the three levels (room, rack and row) of IT load distribution granularity, Rack-level distribution consumes the least cooling power. A test case of 7.5 h implementing dynamic optimization demonstrated a reduction in cooling energy consumption between 21%–50% depending on current operation of data center.

Research limitations/implications

The temperature prediction model used being data-driven, is specific to the lab configuration considered in this study and cannot be directly applied to other scenarios. However, the overall framework can be generalized.

Practical implications

The developed framework can be implemented in data centers to optimize operation of cooling infrastructure and reduce energy consumption.

Originality/value

This paper presents a holistic framework for improving energy efficiency of data centers which is of critical value given the high (and increasing) energy consumption by these facilities.
Assessment of vortex generator shapes for enhancing thermohydraulic performance of fluid flow in a channel equipped with perforated chevron plate-fin
Authors: Nejati Barzoki Faezeh , Sheikhzadeh Ghanbar Ali , Khoshvaght Aliabadi Morteza , Abbasian Arani Ali Akbar
Published: February 2021

Purpose

The purpose of this paper is to investigate thermohydraulic characteristics of turbulent flow of water (4,000 = Re = 10,000) in a rectangular channel equipped with perforated chevron plat-fin (PCPF) with different vortex generators (VGs) shapes.

Design/methodology/approach

First, three general shapes of VGs including rectangular, triangular and half circle, are compared to each other. Then, the various shapes of rectangular VGs, (horizontal, vertical and square) and triangular VGs, (forward, backward and symmetric) are evaluated. To comprehensively evaluate the thermohydraulic performance of the PCPF with various VG shapes, the relationship between the Colburn factor and the friction factor (j/f) is presented, then a performance index (η) is applied using these factors.

Findings

Results show that the enhanced models of the PCPF, which are equipped with VGs, have higher values of j/f ratio and η as compared with the reference model (R). Further, the half-circle VG with the lowest pressure drop values (about 2.4% and 4.9%, averagely as compared with the S and ST vortex generators), shows the highest thermohydraulic performance among the proposed shapes. The maximum of performance index of 1.14 is found for the HC vortex generator at Re = 4,000. It is also found that the square and forward triangular VGs, have the best thermohydraulic performance among the rectangular and triangular VGs respectively and the highest performance index of 1.13 and 1.11 are reported for these VGs.

Originality/value

The thermohydraulic performance of the PCPF with different vortex generators VGs shapes have been investigated.
Digital tools to promote remote lesson study
Authors: Weaver Joanna C. , Matney Gabriel , Goedde Allison M. , Nadler Jeremy R. , Patterson Nancy
Published: February 2021

Purpose

The authors propose that a digital instructional delivery format of lesson study (LS) may have the potential to amplify particular aspects of traditional, face-to-face LS.

Design/methodology/approach

This is a qualitative case study, using data triangulation, member checking and an inductive approach to open-coding utilizing grounded theory to identify codes and themes.

Findings

Digital tools promoted LS and learning, allowing for rigorous collaboration, synchronous observations, data collection and feedback, leading to deeper understanding.

Research limitations/implications

Digital tools used in the online LS process changed how instructional planning can be researched, analyzed and written collaboratively and impacted the fluidity of a lesson, the ease of observation and reflection, student engagement and the researchers' and students' ability to share ideas in real time.

Practical implications

LS can be integrated into online teacher education programs to engage students in online learning and promotes engagement, peer interaction and student voice. The use of these digital tools is not restricted just to remote instructional contexts.

Social implications

LS reduces teacher isolation, builds a collaborative community of teachers and increases instructional motivation. Educators across schools, universities or districts can integrate online LS into remote teacher education programs and online courses.

Originality/value

This study is original work that has not been published elsewhere.
Coaching in the time of coronavirus 2019: how simulations spark reflection
Authors: Wernick Ann Marie , Conry Jillian Marie , Ware Paige Daniel
Published: February 2021

Purpose

This study investigates how debrief conversations unfold during virtual coaching sessions that provide embedded opportunities to practice teaching within a mixed reality simulation (MRS). We examine how teacher and coach topical episodes function (agreeing, explaining, clarifying, probing, recapping, reflecting and suggesting) to activate reflection as part of virtual coaching.

Design/methodology/approach

Grounded in Vygotsky's sociocultural theory and the belief that learning is collaborative and impacts how pre- and in-service teachers construct knowledge, this exploratory case study draws on insights from 15 graduate students (5 pre-service teachers (PSTs) and 10 in-service teachers (ISTs)) who participated in virtual coaching with embedded practice opportunities. Data sources were video recordings and transcripts of 15 virtual coaching sessions, and one-on-one postcoaching interviews. Coding categories were determined through the constant comparative analysis method.

Findings

Findings indicate that an MRS provides an immediate context for reflection, which guided the debrief conversations. Additionally, functions occurred with varying frequency among PSTs and ISTs, and across both groups, probing questions often led directly to reflecting and recapping the shared simulation context.

Research limitations/implications

This study had a small sample (n = 15) and the use of an MRS, while widely used, is not necessarily a scalable practice.

Originality/value

In times of remote teaching, like during corona virus 2019 (COVID-19), opportunities to simulate clinical experiences become vital. With a limited research base, learning how teachers engage with and learn from simulated experiences is a key to creating rich learning opportunities for teachers.