bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mechanism with severing near barbed ends and annealing explains structure and dynamics of dendritic actin networks
Authors: Holz Danielle , Hall Aaron R. , Usukura Eiji , Yamashiro Sawako , Watanabe Naoki , Vavylonis Dimitrios 
Published: April 2021

ABSTRACTSingle molecule imaging has shown that part of actin disassembles within a few seconds after incorporation into the dendritic filament network in lamellipodia, suggestive of frequent destabilization near barbed ends. To investigate the mechanisms behind network remodeling, we created a stochastic model with polymerization, depolymerization, branching, capping, uncapping, severing, oligomer diffusion, annealing, and debranching. We find that filament severing, enhanced near barbed ends, can explain the single molecule actin lifetime distribution, if oligomer fragments reanneal to free ends with rate constants comparable to in vitro measurements. The same mechanism leads to actin networks consistent with measured filament, end, and branch concentrations. These networks undergo structural remodeling, leading to longer filaments away from the leading edge, at the +/- 35° orientation pattern. Imaging of actin speckle lifetimes at sub-second resolution verifies frequent disassembly of newly-assembled actin. We thus propose a unified mechanism that fits a diverse set of basic lamellipodia phenomenology.
ThePseudomonas aeruginosaphosphodiesterase genenbdAis transcriptionally regulated by RpoS and AmrZ
Authors: Gerbracht Katrin , Zehner Susanne , Frankenberg-Dinkel Nicole 
Published: April 2021

ABSTRACTPseudomonas aeruginosais an opportunistic pathogen causing serious infections in immune compromised persons. These infections are difficult to erase with antibiotics, due to the formation of biofilms. The biofilm lifecycle is regulated by the second messenger molecule c-di-GMP (bis-3,5-cyclic di-guanosine monophosphate).P. aeruginosaencodes 40 genes for enzymes presumably involved in the biosynthesis and degradation of c-di-GMP. A tight regulation of expression, subcellular localized function and protein interactions control the activity of these enzymes. In this work we elucidated the transcriptional regulation of the gene encoding the membrane-bound phosphodiesterase NbdA. We previously reported a transcriptional and posttranslational role of nitric oxide (NO) onnbdAand its involvement in biofilm dispersal. NO is released from macrophages during infections but can also be produced byP. aeruginosaitself during anaerobic denitrification. Recently however, contradictory results about the role of NbdA within NO-induced biofilm dispersal were published. Therefore, the transcriptional regulation ofnbdAwas reevaluated to obtain insights into this discrepancy. Determination of the transcriptional start site ofnbdAby 5’-RACE and subsequent identification of the promoter region revealed a shortened open reading frame (ORF) in contrast to the annotated one. In addition, putative binding sites for RpoS and AmrZ were discovered in the newly defined promoter region. Employing chromosomally integrated transcriptionallacZreporter gene fusions demonstrated a RpoS-dependent activation and AmrZ repression ofnbdAtranscription. In order to investigate the impact of NO onnbdAtranscription, conditions mimicking exogenous and endogenous NO were applied. While neither exogenous nor endogenous NO had an influence onnbdApromoter activity, deletion of the nitrite reductase genenirSstrongly increasednbdAtranscription independently of its enzymatic activity during denitrification. The latter supports a role of NirS inP. aeruginosaapart from its enzymatic function.IMPORTANCEThe opportunistic pathogenPseudomonas aeruginosapossesses a network of genes encoding proteins for the turnover of the second messenger c-di-GMP involved in regulating-among others-the lifestyle switch between planktonic, motile cells and sessile biofilms. Insight into the transcriptional regulation of these genes is important for the understanding of the protein function within the cell. Determination of the transcriptional start site of the phosphodiesterase genenbdArevealed a new promoter region and consequently a shortened open reading frame for the corresponding protein. Binding sites for RpoS and AmrZ were identifiedin silicoand confirmed experimentally. Previously reported regulation by nitric oxide was reevaluated and a strong influence of the moonlighting protein NirS identified.
Oxygen production by an ammonia-oxidizing archaeon
Authors: Kraft Beate , Jehmlich Nico , Larsen Morten , Bristow Laura , Könneke Martin , Thamdrup Bo , Canfield Donald E. 
Published: April 2021

AbstractAmmonia-oxidizing archaea (AOA) are one of the most abundant groups of microbes in the world’s oceans and are key players in the nitrogen cycle. Their energy metabolism, the oxidation of ammonia to nitrite, requires oxygen. Nevertheless, AOA are abundant in environments where oxygen is undetectable. In incubation experiments, where oxygen concentrations were resolved to the nanomolar range, we show that Nitrosopumilus maritimus produces oxygen (O2) and dinitrogen (N2). The pathway is not completely resolved, but it has nitric oxide as a key intermediate. Part of the oxygen produced is directly used for ammonia oxidation, while some accumulates in the surrounding environment. N. maritimus joins a small handful of organisms known to produce oxygen in the dark, and based on this ability, we re-evaluate their role in oxygen-depleted marine environments.
Both transient and sustained MPK3/6 activities positively control expression of NLR genes in PTI and ETI
Authors: Lang Julien , Genot Baptiste , Bigeard Jean , Colcombet Jean 
Published: April 2021

AbstractArabidopsis thalianaMitogen Activated Protein Kinases 3 and 6 (MPK3/6) are known to be activated transiently in PAMP-Triggered Immunity (PTI) and durably in Effector-Triggered Immunity (ETI). However the functional differences between these two kinds of activation kinetics and how they allow coordination of the two layers of plant immunity remain poorly understood. Here, by analysing suppressors of the phenotype caused by a constitutively active form of MPK3, we demonstrate that ETI-mediating nucleotide-binding domain leucine-rich repeat receptors (NLRs) and NLR signaling can act downstream of MPK3 activities. Moreover we provide evidence that both sustained and transient MPK3/6 activities positively control the expression of at least two NLR genes, AT3G04220 and AT4G1110. We further show that the ETI regulators NDR1 and EDS1 also contribute to the upregulations of these two NLRs not only in an ETI context but also in a PTI context. Remarkably, while in ETI, MPK3/6 activities are dependent on NDR1 and EDS1, they are not in PTI, suggesting that if the same actors are involved in the two layers of immunity, the way they are interconnected is different. Finally we demonstrate that expression of the NLR AT3G04220 is sufficient to induce expression of defense genes from the SA branch. Overall this study enlarges our knowledge of MPK3/6 functions during immunity and gives a new insight into the intrication of PTI and ETI.
A SIMPLI (Single-cell Identification from MultiPLexed Images) approach for spatially resolved tissue phenotyping at single-cell resolution
Authors: Bortolomeazzi Michele , Montorsi Lucia , Temelkovski Damjan , Keddar Mohamed Reda , Acha-Sagredo Amelia , Pitcher Michael J. , Basso Gianluca , Laghi Luigi , Rodriguez-Justo Manuel , Spencer Jo , Ciccarelli Francesca D. 
Published: April 2021

ABSTRACTMultiplexed imaging technologies enable the study of biological tissues at single-cell resolution while preserving spatial information. Currently, high-dimension imaging data analysis is technology-specific and requires multiple tools, restricting analytical scalability and result reproducibility. Here we present SIMPLI (Single-cell Identification from MultiPlexed Images), a novel, flexible and technology-agnostic software that unifies all steps of multiplexed imaging data analysis. After raw image processing, SIMPLI performs a spatially resolved, single-cell analysis of the tissue slide as wells as cell-independent quantifications of marker expression to investigate features undetectable at the cell level. SIMPLI is highly customisable and can run on desktop computers as well as high-performance computing environments, enabling workflow parallelisation for large datasets. SIMPLI produces multiple tabular and graphical outputs at each step of the analysis. Its containerised implementation and minimum configuration requirements make SIMPLI a portable and reproducible solution for multiplexed imaging data analysis.SIMPLI is available at:https://github.com/ciccalab/SIMPLI.
A biophotoelectrochemical approach to unravelling the role of cyanobacterial cell structures in exoelectrogenesis
Authors: Wey Laura T. , Lawrence Joshua M. , Chen Xiaolong , Clark Robert , Lea-Smith David J. , Zhang Jenny Z. , Howe Christopher J. 
Published: April 2021

AbstractPhotosynthetic microorganisms can export electrons outside their cells, a phenomenon called exoelectrogenesis, which can be harnessed for solar energy conversion. However, the route electrons take from thylakoid membranes to the cell exterior is not understood. Electrochemistry is a powerful analytical technique for studying electron transfer pathways. Here, we show how photoelectrochemistry can be used to compare electron flux from cyanobacterial cells of different growth stages, species and with the outer layers systematically removed. We show that the periplasmic space contributes significantly to the photocurrent profile complexity of whole cells, indicating that it gates electron transfer in exoelectrogenesis. We found that although components of the type IV pili machinery do not have a role in exoelectrogenesis, they contribute significantly to cell-electrode adherence. This study establishes that analytical photoelectrochemistry and molecular microbiology provide a powerful combination to study exoelectrogenesis, enabling future studies to answer biological questions and advance solar energy conversion applications.
Establishing a Role of the Semantic Control Network in Social Cognitive Processing: A Meta-analysis of Functional Neuroimaging Studies
Authors: Diveica Veronica , Koldewyn Kami , Binney Richard J. 
Published: April 2021

AbstractMost leading models of socio-cognitive processing devote little discussion to the nature and neuroanatomical correlates of cognitive control mechanisms. Recently, it has been proposed that the regulation of social behaviours could rely on brain regions specialised in the controlled retrieval of semantic information, namely the anterior inferior frontal gyrus (IFG) and posterior middle temporal gyrus. Accordingly, we set out to investigate whether the neural activation commonly found in social functional neuroimaging studies extends to these ‘semantic control’ regions. We conducted five coordinate-based meta-analyses to combine results of over 500 fMRI/PET experiments and identified the brain regions consistently involved in semantic control, as well as four social abilities: theory of mind, trait inference, empathy and moral reasoning. This allowed an unprecedented parallel review of the neural networks associated with each of these cognitive domains. The results confirmed that the anterior left IFG region involved in semantic control is reliably engaged in all four social domains. This suggests that social cognition could be partly regulated by the neurocognitive system underpinning semantic control.
Identification of Biochemical and Molecular Markers of Early Aging in Childhood Cancer Survivors
Authors: Ravera Silvia , Vigliarolo Tiziana , Bruno Silvia , Morandi Fabio , Marimpietri Danilo , Sabatini Federica , Dagnino Monica , Petretto Andrea , Bartolucci Martina , Muraca Monica , Biasin Eleonora , Haupt Riccardo , Zecca Marco , Fagioli Franca , Cilloni Daniela , Podestà Marina , Frassoni Francesco 
Published: April 2021

ABSTRACTPurposeSurvival rates of Childhood Cancer Patients have improved tremendously over the past four decades. However, cancer treatments are associated with an increased risk of developing an anticipated onset of chronic diseases typical of aging. Thus, we aimed to identify molecular/metabolic cellular alterations responsible for early aging in Childhood Cancer Survivors (CCS).Patients and MethodsBiochemical, proteomic and molecular biology analyses were conducted on mononuclear cells (MNCs) isolated from peripheral blood of 196 CCS, comparing the results with those obtained on MNCs of 154 healthy subjects.ResultsData demonstrate that CCS-MNCs show: i) inefficient oxidative phosphorylation associated with low energy status and a metabolic switch to lactate fermentation compared with age-matched normal controls; ii) increment of lipid peroxidation due to an unbalance among the oxidative stress production and the activation of the antioxidant defenses; (iii) significantly lower expression of genes and proteins involved in mitochondrial biogenesis and metabolism regulation, such as CLUH, PGC1-α, and SIRT6 in CCS, not observed in the age-matched healthy or elderly subjects. The application of a mathematical model based on biochemical parameters predicts that CCS have a biological age significantly increased by decades compared to the chronological age. Overall, the results show that the impact of chemo/chemoradiotherapy on mitochondria efficiency in 196 CCS was rather homogeneous, irrespective of cancer type, treatment protocols, and time elapsed from the end of the curative period.ConclusionsOur study identifies some biochemical and molecular alterations possibly contributing to the pathophysiology of anticipated aging and metabolic deficiency described in CCS. These results may be useful in identifying approaches to restore the mitochondrial function, slowing down the aging and the associated pathological conditions in CCS.
Comparative anatomy of leaf petioles in temperate trees and shrubs
Authors: Filartiga Arinawa Liz , Klimeš Adam , Altman Jan , Nobis Michael Peter , Crivellaro Alan , Schweingruber Fritz , Doležal Jiří 
Published: April 2021

AbstractPetioles are important plant organs connecting stems with leaf blades and affecting light-harvesting leaf ability as well as transport of water, nutrient and biochemical signals. Despite petiole’s high diversity in size, shape and anatomical settings, little information is available about their structural adaptations across evolutionary lineages and environmental conditions. To fill our knowledge gap, we investigated the variation of petiole morphology and anatomy in 95 European woody plant species using phylogenetic comparative models. Two major axes of variation were related to leaf area (from large and soft to small and tough leaves), and plant size (from cold-adapted shrubs to warm-adapted tall trees). Larger and softer leaves are found in taller trees of more productive habitats. Their petioles are longer, with a circular outline, thin cuticles without trichomes, and are anatomically characterised by the predominance of sclerenchyma, larger vessels, interfascicular areas with fibers, indistinct phloem rays, and the occurrence of prismatic crystals and druses. In contrast, smaller and tougher leaves are found in shorter trees and shrubs of colder or drier habitats. Their petioles are characterized by teret outline, thick cuticle, simple and non-glandular trichomes, epidermal cells smaller than cortex cells, phloem composed of small cells and radially arranged vessels, fiberless xylem, lamellar collenchyma, acicular crystals and secretory elements. Individual anatomical traits were linked to different internal and external drivers. The petiole length and vessel conduit size increase, while cuticle thickness decreases, with increasing leaf blade area. Epidermis cell walls are thicker in leaves with higher specific leaf area. Collenchyma becomes absent with increasing temperature, epidermis cell size increases with plant height and temperature, and petiole outline becomes polygonal with increasing precipitation. We conclude that species temperature and precipitation optima, plant height, leaf area and thickness exerted a significant control on petiole anatomical and morphological structures not confounded by phylogenetic inertia. Unrelated species with different evolutionary histories but similar thermal and hydrological requirements have converged to similar petiole anatomical structures. Our findings contribute to improving current knowledge about the functional morphoanatomy of the petiole as the key organ that plays a crucial role in the hydraulic pathways in plants.
Fine-tuning the Spike: Role of the nature and topology of the glycan shield in the structure and dynamics of the SARS-CoV-2 S
Authors: Harbison Aoife M. , Fogarty Carl A. , Phung Toan K. , Satheesan Akash , Schulz Benjamin L. , Fadda Elisa 
Published: April 2021

AbstractThe dense glycan shield is an essential feature of the SARS-CoV-2 spike (S) architecture, key to immune evasion and to the activation of the prefusion conformation. Recent studies indicate that the occupancy and structures of the SARS-CoV-2 S glycans depend not only on the nature of the host cell, but also on the structural stability of the trimer; a point that raises important questions about the relative competence of different glycoforms. Moreover, the functional role of the glycan shield in the SARS-CoV-2 pathogenesis suggests that the evolution of the sites of glycosylation is potentially intertwined with the evolution of the protein sequence to affect optimal activity. Our results from multi-microsecond molecular dynamics simulations indicate that the type of glycosylation at N234, N165 and N343 greatly affects the stability of the receptor binding domain (RBD) open conformation, and thus its exposure and accessibility. Furthermore, our results suggest that the loss of glycosylation at N370, a newly acquired modification in the SARS-CoV-2 S glycan shield’s topology, may have contributed to increase the SARS-CoV-2 infectivity as we find that N-glycosylation at N370 stabilizes the closed RBD conformation by binding a specific cleft on the RBD surface. We discuss how the absence of the N370 glycan in the SARS-CoV-2 S frees the RBD glycan binding cleft, which becomes available to bind cell-surface glycans, potentially increases host cell surface localization.
Increasing role of pyrethroid-resistant Anopheles funestus in malaria transmission in the Lake Zone, Tanzania: implications for the evaluation of novel vector control products
Authors: Matowo Nancy S. , Martin Jackline , Kulkarni Manisha A. , Mosha Jacklin F. , Lukole Eliud , Isaya Gladness , Shirima Boniface , Kaaya Robert , Moyes Catherine , Hancock Penelope A. , Rowland Mark , Manjurano Alphaxard , Mosha Franklin W , Protopopoff Natacha , Messenger Louisa A. 
Published: April 2021

AbstractAnopheles funestus is playing an increasing role in malaria transmission in parts of sub-Saharan Africa, where An. gambiae s.s. has been effectively controlled by long-lasting insecticidal nets. We investigated vector population bionomics, insecticide resistance and malaria transmission dynamics in 86 study clusters in North-West Tanzania. An. funestus s.l. represented 94.5% (4740/5016) of all vectors and was responsible for the majority of malaria transmission (96.5%), with a sporozoite rate of 3.4% and average monthly entomological inoculation rate (EIR) of 4.57 per house. Micro-geographical heterogeneity in species composition, abundance and transmission was observed across the study district in relation to key ecological differences between northern and southern clusters, with significantly higher densities, proportions and EIR of An. funestus s.l. collected from the south. An. gambiae s.l. (5.5%) density, principally An. arabiensis (81.1%) and An. gambiae s.s. (18.9%), was much lower and closely correlated with seasonal rainfall. Both An. funestus s.l. and An. gambiae s.l. were similarly resistant to alpha-cypermethrin and permethrin. Overexpression of CYP9K1, CYP6P3, CYP6P4 and CYP6M2 and high L1014F-kdr mutation frequency were detected in An. gambiae s.s. populations. Study findings highlight the urgent need for novel vector control tools to tackle persistent malaria transmission in the Lake Region of Tanzania.
Growth-rate dependency of ribosome abundance and translation elongation rate inCorynebacterium glutamicumdiffers fromEscherichia coli
Authors: Matamouros Susana , Gensch Thomas , Cerff Martin , Sachs Christian C. , Abdollahzadeh Iman , Hendriks Johnny , Horst Lucas , Tenhaef Niklas , Noack Stephan , Graf Michaela , Takors Ralf , Nöh Katharina , Bott Michael 
Published: April 2021

AbstractThe growth rate µ of bacteria depends on the protein synthesis capacity of the cell and thus on the number of active ribosomes and their translation elongation rate. The relationship between these fundamental growth parameters have only been described for a few bacterial species, in particularEscherichia coli, but are missing for most bacterial phyla. In this study, we systematically analysed the growth-rate dependency of ribosome abundance and translation elongation rate forCorynebacterium glutamicum, a gram-positive model species differing fromE. coliby a lower growth temperature optimum and a lower µmax. Ribosomes were quantified via single-molecule localization microscopy (SMLM) using fluorescently tagged ribosomal proteins and via RNA/protein ratio. Both methods revealed a non-linear relationship with little change in ribosome abundance below µ = 0.4 h-1and a steep increase at higher µ. UnlikeE. coli,C. glutamicumkeeps a large pool of active ribosomes at low µ, but the translation elongation rate declines from ∼9 amino acids s-1at µmaxto <2 aa s-1at µ < 0.1 h-1. A model-based approach shows that depletion of translation precursors at low growth rates can explain the observed decrease in translation elongation rate. Nutrient up-shift experiments support the hypothesis that maintenance of excess ribosomes during poor nutrient conditions enablesC. glutamicumto quickly restart growth when conditions improve.
Impact of sulfamethoxazole on a riverine microbiome
Authors: Borsetto C. , Raguideau S. , Travis E. , Kim D.W. , Lee D.H. , Bottrill A. , Stark R. , Song L. , Cha J.C. , Pearson J. , Quince C. , Singer A.C. , Wellington E.M.H. 
Published: April 2021

AbstractThe continued emergence of bacterial pathogens presenting antimicrobial resistance is widely recognised as a global health threat and recent attention focused on potential environmental reservoirs of antibiotic resistance genes (ARGs). Freshwater environments such as rivers represent a potential hotspot for ARGs and antibiotic resistant bacteria as they are receiving systems for effluent discharges from wastewater treatment plants (WWTPs). Effluent also contains low levels of different antimicrobials including antibiotics and biocides. Sulfonamides are antibacterial chemicals widely used in clinical, veterinary and agricultural settings and are frequently detected in sewage sludge and manure in addition to riverine ecosystems. The impact of such exposure on ARG prevalence and diversity is unknown, so the aim of this study was to investigate the release of a sub-lethal concentration of the sulfonamide compound sulfamethoxazole (SMX) on the river bacterial microbiome using a flume system. This system was a semi-naturalin vitroflume using river water (30 L) and sediment with circulation to mimic river flow. A combination of ‘omics’ approaches were conducted to study the impact of SMX exposure on the microbiomes within the flumes. Metagenomic analysis showed that the addition of low concentrations of SMX (<4 μg L−1) had a limited effect on the bacterial resistome in the water fraction only, with no impact observed in the sediment. Metaproteomics did not show differences in ARGs expression with SMX exposure in water. Overall, the river bacterial community was resilient to short term exposure to sub-lethal concentrations of SMX which mimics the exposure such communities experience downstream of WWTPs throughout the year.