bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unveiling molecular interactions that stabilize bacterial adhesion pili
Authors: Dahlberg Tobias , Baker Joseph L. , Bullitt Esther , Andersson Magnus 
Published: January 2022

AbstractAdhesion pili assembled by the chaperone-usher pathway are superelastic helical filaments on the surface of bacteria, optimized for attachment to target cells. Here, we investigate the biophysical function and structural interactions that stabilize P pili from uropathogenic bacteria. Using optical tweezers we measure P pilus subunit-subunit interaction dynamics and show that pilus compliance is contour-length dependent. Atomic details of subunit-subunit interactions of pili under tension are shown using steered molecular dynamics (sMD) simulations. sMD results also indicate that the N-terminal “staple” region of P pili significantly stabilizes the helical filament structure, consistent with previous structural data, suggesting more layer-to-layer interactions could compensate for the lack of a staple in Type 1 pili. This study informs our understanding of essential structural and dynamic features of adhesion pili, supporting the hypothesis that the biophysical function of pili is niche-adapted rather than a direct consequence of genetic similarity or diversity.
Astrocyte glutamate transport is modulated by motor learning and regulates neuronal correlations and movement encoding by motor cortex neurons
Authors: Delepine Chloe , Li Keji , Shih Jennifer , Gaudeaux Pierre , Sur Mriganka 
Published: January 2022

ABSTRACTWhile motor cortex is crucial for learning precise and reliable movements, whether and how astrocytes contribute to its plasticity and function during motor learning is unknown. Here we report that primary motor cortex (M1) astrocytes in mice show in vivo plasticity during learning of a lever push task, as revealed by transcriptomic and functional modifications. In particular, we observe changes in expression of glutamate transporter genes and increased coincidence of intracellular calcium events. Astrocyte-specific manipulations of M1 are sufficient to alter motor learning and execution, and neuronal population coding, in the same task. Mice expressing decreased levels of the astrocyte glutamate transporter GLT1 show impaired and variable movement trajectories. Mice with increased astrocyte Gq signaling show decreased performance rates, delayed response times and impaired trajectories, along with abnormally high levels of GLT1. In both groups of mice, M1 neurons have altered inter-neuronal correlations and impaired population representations of task parameters, including response time and movement trajectories. Thus, astrocytes have a specific role in coordinating M1 neuronal activity during motor learning, and control learned movement execution and dexterity through mechanisms that importantly include fine regulation of glutamate transport.
Sialic acid and fucose residues on the SARS-CoV-2 receptor binding domain modulate IgG reactivity
Authors: Samuelsson Ebba , Mirgorodskaya Ekaterina , Nyström Kristina , Bäckström Malin , Liljeqvist Jan-Åke , Nordén Rickard 
Published: January 2022

AbstractThe receptor binding domain (RBD) of the SARS-CoV-2 spike protein is a conserved domain and a target for neutralizing antibodies. We defined the carbohydrate content of recombinant RBD produced in different mammalian cells. We found a higher degree of complex type N-linked glycans, with less sialylation and more fucosylation, when the RBD was produced in Human embryonic kidney cells compared to the same protein produced in Chinese hamster ovary cells. The carbohydrates on the RBD proteins were enzymatically modulated and the effect on antibody reactivity was evaluated with serum samples from SARS-CoV-2 positive patients. Removal of all carbohydrates diminished antibody reactivity while removal of only sialic acids or terminal fucoses improved the reactivity. The RBD produced in Lec3.2.8.1-cells, which generate carbohydrate structures devoid of sialic acids and with reduced fucose content, exhibited enhanced antibody reactivity verifying the importance of these specific monosaccharides. The results can be of importance for the design of future vaccine candidates, indicating that it might be possible to enhance the immunogenicity of recombinant viral proteins.
Basal amygdala inputs to the medial prefrontal cortex mediate fear memory strengthening
Authors: Einarsson Einar Ö. , Flores Africa , Jercog Daniel , Herry Cyril 
Published: January 2022

SUMMARYSurvival critically depends on the memorization of stimuli recurrently predicting pleasant or aversive experiences. Memory strengthening by additional learning is a critical process allowing the long-term stabilization of learned aversive experience. However, the underlying neuronal circuits and mechanisms are still largely unknown. Using a combination of single unit recordings and optogenetic manipulations, we observed that strengthened fear responses following successive fear learning episodes led to a remapping in the population of basal amygdala (BA) neurons encoding the conditioned stimulus. Moreover, strengthened fear responses were preferentially carried by BA neurons projecting to the medial prefrontal cortex (mPFC). Selective optogenetic inhibition of BA terminals in the mPFC during a second learning episode prevented fear memory strengthening. Together, our findings suggest that fear memory strengthening with additional training critically depends on the selective remapping of a subpopulation of BA neurons projecting to the mPFC.
Exo-Enzymatic Cell-Surface Glycan Labeling for Capturing Glycan-Protein Interactions through Photo-Crosslinking
Authors: Babulic Jonathan L. , Capicciotti Chantelle J. 
Published: January 2022

AbstractTools to interrogate glycoconjugate-protein interactions in the context living cells are highly attractive for the identification of critically important functional binding partners of glycan-binding proteins. These interactions are challenging to interrogate due to low affinity and rapid dissociation rates of glycan-protein binding events. The use of photo-crosslinkers to capture glycan-protein interaction complexes has shown great promise for identifying binding partners involved in these interactions. Current methodologies use metabolic oligosaccharide engineering (MOE) to incorporate photo-crosslinking sugars. However, these MOE strategies are not amenable to all cell types and can result in low incorporation and cell-surface display of the photo-crosslinking probe, limiting their utility for studying many types of interactions. We describe here an exo-enzymatic strategy for selectively introducing photo-crosslinking probes into cell-surface glycoconjugates using the recombinant human sialyltransferase ST6GAL1 and a diazirine-linked CMP-Neu5Ac derivative. Probe introduction is highly efficient, amenable to different cell types and resulted in improved crosslinking when compared to MOE. This exo-enzymatic labeling approach can selectively introduce the photo-crosslinking sugar on to specific glycan epitopes and subclasses by harnessing the specificity of the sialyltransferase employed, underscoring its potential as a tool to interrogate and identify glycoconjugate ligands for diverse glycan-binding proteins.
Mutation of Vsx genes in zebrafish highlights the robustness of the retinal specification network
Authors: Letelier Joaquín , Buono Lorena , Almuedo-Castillo María , Zang Jingjing , González-Díaz Sergio , Polvillo Rocío , Sanabria-Reinoso Estefanía , Diez del Corral Ruth , Neuhauss Stephan C. F. , Martínez-Morales Juan R. 
Published: January 2022

AbstractGenetic studies in human and mice have established a dual role for Vsx genes in retina development: an early function in progenitors’ specification, and a later requirement for bipolar-cells fate determination. Despite their conserved expression patterns, it is currently unclear to which extent Vsx functions are also conserved across vertebrates, as mutant models are available only in mammals. To gain insight into vsx function in teleosts, we have generated vsx1 and vsx2 CRISPR-Cas9 double knockouts (vsxKO) in zebrafish. Our electrophysiological and histological analyses indicate severe visual impairment and bipolar cells depletion in vsxKO larvae, with retinal precursors being rerouted towards photoreceptor or Müller glia fates. Surprisingly, neural retina is properly specified and maintained in mutant embryos, which do not display microphthalmia. We show that although important cis-regulatory remodelling occurs in vsxKO retinas during early specification, this has little impact at a transcriptomic level. Our observations point to genetic redundancy as an important mechanism sustaining the integrity of the retinal specification network, and to Vsx genes regulatory weight varying substantially among vertebrate species.Brief Summary Statement for use in emailed and online tables of content alertsThe mutation of vsx genes in zebrafish confirms a conserved role in bipolar cells specification across vertebrates, but do not interfere with the specification of the neural retina domain. Our data reveal the unexpected robustness of the genetic network sustaining the identity of the neural retina.
Tubulin glutamylation is key to axon guidance via selective tuning of microtubule-severing enzymes
Authors: Martin Daniel Ten , Jardin Nicolas , Vougny Juliette , Giudicelli François , Gasmi Laïla , Henriot Véronique , Lebrun Laura , Haumaître Cécile , Kneussel Matthias , Nicol Xavier , Janke Carsten , Magiera Maria , Hazan Jamilé , Fassier Coralie 
Published: January 2022

AbstractThe microtubule cytoskeleton is a major driving force of neuronal circuit development. Fine-tuned remodelling of this network by selective activation of microtubule-regulating proteins, including microtubule severers, emerged as a central process in neuronal wiring. Tubulin posttranslational modifications control both microtubule properties and the activities of their interacting proteins. However, whether and how tubulin posttranslational modifications may contribute to neuronal connectivity has not yet been addressed. During zebrafish embryogenesis, we show that the microtubule severers p60-katanin and spastin play specific roles in axon guidance and identify a key role for tubulin polyglutamylation in their functional specificity. Furthermore, our work reveals that polyglutamylases with undistinguishable activitiesin vitro, TTLL6 and TTLL11, play exclusive roles in axon navigation by selectively tuning p60-katanin and spastin activities. We confirm the selectivity of TTLL11 towards spastin activation in mammalian cortical neurons and establish its relevance in preventing axonal degeneration triggered by spastin haploinsufficiency. Our work thus provides mechanistic insight on the control of microtubule-driven neuronal development and homeostasis, and opens novel avenues for developing therapeutic strategies in spastin-associated hereditary spastic paraplegia.
MaxQuant and MSstats in Galaxy enable reproducible cloud-based analysis of quantitative proteomics experiments for everyone
Authors: Pinter Niko , Glätzer Damian , Fahrner Matthias , Fröhlich Klemens , Johnson James , Grüning Björn Andreas , Warscheid Bettina , Drepper Friedel , Schilling Oliver , Föll Melanie Christine 
Published: January 2022

ABSTRACTQuantitative mass spectrometry-based proteomics has become a high-throughput technology for the identification and quantification of thousands of proteins in complex biological samples. Two de facto standard tools, MaxQuant and MSstats, allow for the analysis of raw data and finding proteins with differential abundance between conditions of interest. To enable accessible and reproducible quantitative proteomics analyses in a cloud environment, we have integrated MaxQuant (including TMTpro 16/18plex), Proteomics Quality Control (PTXQC), MSstats and MSstatsTMT into the open-source Galaxy framework. This enables the web-based analysis of label-free and isobaric labeling proteomics experiments via Galaxy’s graphical user interface on
public clouds. MaxQuant and MSstats in Galaxy can be applied in conjunction with thousands of existing Galaxy tools and integrated into standardized, sharable workflows. Galaxy tracks all metadata and intermediate results in analysis histories, which can be shared privately for collaborations or publicly, allowing full reproducibility and transparency of published analysis. To further increase accessibility, we provide detailed hands-on training materials. The integration of MaxQuant and MSstats into the Galaxy framework enables their usage in a reproducible way on accessible large computational infrastructures, hence realizing the foundation for high throughput proteomics data science for everyone.
A mixed generative model of auditory word repetition
Authors: Sajid Noor , Holmes Emma , Costa Lancelot Da , Price Cathy , Friston Karl 
Published: January 2022

AbstractIn this paper, we introduce a word repetition generative model (WORM), which—when combined with an appropriate belief updating scheme—is capable of inferring the word that should be spoken when presented with an auditory cue. Our generative model takes a deep temporal form, combining both discrete and continuous states. This allows a (synthetic) WORM agent to perform categorical inference on continuous acoustic signals, and—based on the same model—to repeat heard words at the appropriate time. From the perspective of word production, the model simulates how high-level beliefs about discrete lexical, prosodic and context attributes give rise to continuous acoustic signals at the sensory level. From the perspective of word recognition, it simulates how continuous acoustic signals are recognised as words and, how (and when) they should be repeated. We establish the face validity of our generative model by simulating a word repetition paradigm in which a synthetic agent or a human subject hears a target word and subsequently reproduces that word. The repeated word should be the target word but differs acoustically. The results of these simulations reveal how the generative model correctly infers what must be repeated, to the extent it can successfully interact with a human subject. This provides a formal process theory of auditory perception and production that can be deployed in health and disease. We conclude with a discussion of how the generative model could be scaled-up to include a larger phonetic and phonotactic repertoire, complex higher-level attributes (e.g., semantic, concepts, etc.), and produce more elaborate exchanges.
Parallel multicopy-suppressor screens reveal convergent evolution of phage-encoded single gene lysis proteins
Authors: Adler Benjamin A. , Chamakura Karthik , Carion Heloise , Krog Jonathan , Deutschbauer Adam M. , Young Ryland F , Mutalik Vivek K. , Arkin Adam P. 
Published: January 2022

AbstractIn contrast to dsDNA phages where multiple proteins are involved in programmed host lysis, lysis in ssRNA Fiersviridae and ssDNA Microviridae phages requires only a single gene (sgl for single gene lysis) to meet the size constraints of some of the smallest genomes in the biosphere. To achieve lysis, Sgl proteins exploit evolutionary “weak spots” in bacterial cell wall biogenesis. In several cases, this is done by inhibiting specific steps in Lipid II synthesis. Recently metatranscriptomics has revealed thousands of novel ssRNA phage genomes, each of which must carry at least one sgl gene. Determining the targets of these Sgl proteins could reveal novel vulnerabilities in bacterial envelope biogenesis and may lead to new antibiotics. Here, we employ a high-throughput genetic screen to uncover genome-wide host suppressors of Sgl activity and apply it to a set of diverse Sgls with unknown molecular targets. In addition to validating known molecular mechanisms, we determined that the Sgl of PP7, an ssRNA phage of P. aeruginosa, targets MurJ, the flippase responsible for Lipid II export which was previously shown to be the target of the Sgl of coliphage M. These two Sgls, which are unrelated and predicted to have opposite membrane topology, thus represent a case of convergent evolution. Another set of Sgls which are thought to cause lysis without inhibiting cell wall synthesis elicit a common set of multicopy suppressors, suggesting these Sgls act by the same or similar mechanism.
Caulobacter requires anionic sphingolipids and deactivation of fur to lose lipid A
Authors: Zik Justin J. , Yoon Sung Hwan , Guan Ziqiang , Skidmore Gabriele Stankeviciute , Gudoor Ridhi R. , Davies Karen M. , Deutschbauer Adam M. , Goodlett David R. , Klein Eric A. , Ryan Kathleen R. 
Published: January 2022

SummaryLipid A, the membrane-anchored portion of lipopolysaccharide, is an essential component of the outer membrane (OM) of nearly all Gram-negative bacteria. Here, we identify regulatory and structural factors that together permit Caulobacter crescentus to eliminate lipid A from its OM. Mutations in the ferric uptake regulator fur allow Caulobacter to survive in the absence of either LpxC, which catalyzes an early step of lipid A synthesis, or CtpA, a tyrosine phosphatase homolog which we find is needed for wild-type lipid A structure and abundance. Alterations in Fur-regulated processes, rather than iron status per se, underlie the ability to eliminate lipid A. Fitness of lipid A-deficient Caulobacter requires a previously uncharacterized anionic sphingolipid, ceramide phosphoglycerate (CPG), which also mediates sensitivity to the antibiotic colistin. Our results demonstrate that, in an altered regulatory landscape, anionic sphingolipids can support the integrity of a lipid A-deficient OM.
Research on the temporal evolution track and influence of green development in the last decade
Authors: Chen Yunfang , Lai Qingkui , Ji Xuan , zhang Cunyu , Xiao Mengxiong 
Published: January 2022

AbstractGreen development is important to realize the coordinated development of local ecological environment, economy and society, but also an important way to promote the harmony between human and land. This study utilizes projection pursuit model (PPM) measure, as well as the system gray prediction model GM (1, N), and other measurement methods, build an evaluation system from three dimensions of green fortune, green growth and green benefits to analyze the temporal evolution, development trend and its influencing factors of Baoshan’s ecological engineering of project acres, the results show: (1)The overall level of the green development system in Baoshan, Yunnan Province, is relatively good and shows an increasing trend year by year, with an average growth rate of 18.3%, and there is a synergistic coupling effect among the three subsystems. (2) Regional green development has achieved remarkable progress, but problems and pressure among the three subsystems are still grim. The sub-system of green growth and green benefits declined from 2010 to 2016, with an annual decline rate of 12%, and then picked up slightly in the next three years, reflecting the pressure of resources and ecological environment in this region and the difficulty of the sub-system of green wealth growth. (3) The prediction analysis shows that the green development index in Baoshan, Yunnan Province will keep a steady rise in the next two years, and the predicted value will be 4.51 in 2020, with an average growth rate of 15.1%, and the regional green development system is in good condition. (4) Green development is mainly affected by environmental pollution, industrial structure, urbanization, population, market and other factors from the three subsystems of local ecology, ecology, economy and social benefits. This paper puts forward suggestions in terms of popularizing the concept of green development, improving the level of ecological economic development and promoting the regional environment bearing capacity, green development model of ecological engineering area is also built. It aims to have some practical reference value for prompting regional ecological civilization construction and green development. And provide regional support for the post-2020 Global Biodiversity Framework and the Achievement of the United Nations Sustainable Development Goals.
Pore-C Simultaneously Captures Genome-wide Multi-way Chromatin Interaction and Associated DNA Methylation Status in Arabidopsis
Authors: Li Zhuowen , Long Yanping , Yu Yiming , Zhang Fei , Zhang Hong , Liu Zhijian , Jia Jinbu , Mo Weipeng , Tian Simon Zhongyuan , Zheng Meizhen , Zhai Jixian 
Published: January 2022

AbstractIn the past decade, genome-wide characterization of the three-dimensional chromatin structure in plants using high-throughput methods has greatly advanced our knowledge in plant genome architecture (Liu and Weigel, 2015; Ouyang et al., 2020). However, due to the limitation of Illumina short-read sequencing, the genome-wide contact map obtained by Hi-C/ChIA-PET is pairwise, and the multi-way interaction can only be inferred from the two-way data. To directly capture multi-way interaction in Arabidopsis, we applied a long-read-based method called Pore-C that directly sequences the DNA fragments joined by proximity-based ligation (Ulahannan et al., 2019).
GM1a functions as a coreceptor/ attachment factor for Dengue virus during infection in mammalian systems
Authors: Tantirimudalige Sarala Neomi , Raghuvamsi Palur Venkata , Wei Bao Jonathan Chua , Anand Ganesh S. , Wohland Thorsten 
Published: January 2022

AbstractDengue virus (DENV) is a flavivirus causing an estimated 390 million infections per year around the world. Despite the immense global health and economic impact of this virus, its true receptor(s) for internalization into live cells has not yet been identified, and no successful antivirals or treatments have been isolated to this date. This study aims to improve our understanding of virus entry routs by exploring the sialic acid-based cell surface molecule GM1a and its role in DENV infection. The interaction of the virus with GM1a was studied using fluorescence correlation spectroscopy (FCS), fluorescence cross correlation spectroscopy (FCCS), imaging FCS (ImFCS) and amide hydrogen/deuterium exchange mass spectrometry (HDXMS), and the effect on infectivity and movement of the virus during infection was explored using plaque assays and fluorescence-based imaging and single particle tracking (SPT). GM1a was deemed to interact with DENV at domain I (DI) and domain II (DII) of the E protein of the protein coat at quaternary contacts of a fully assembled virus, leading to a ten-fold increase and seven-fold increase in infectivity for DENV1 and DENV2 in mammalian cell systems respectively. The interaction of virus with GM1a triggers a speeding up of virus movement on live cell surfaces, possibly resulting from a reduction in rigidity of cellular rafts during infection, and functions as a coreceptor/ attachment factor for DENV during infection in mammalian systems.Author SummaryDengue virus (DENV) is a flavivirus causing an estimated 390 million infections per year around the world. Despite the immense global health and economic impact of this virus, no successful antivirals or treatments have been isolated to this date. This may be due to the incomplete understanding of the virus infection mechanism, including a lack of an identified ‘true’ receptor and entry related attachment factors or co-receptors responsible for internalization of the virus. This work focuses on the early infection stage of DENV1 and DENV2 strains, to identify how the virus moves on cell surfaces in its search for its receptors, and identifies the critical role of the sialic acid ganglioside GM1a during internalization of the virus.