bluuebunny/crossref_metadata_2025_split huggingface dataset:
A temperature-controlled, circular maintenance system for studying growth and development of pelagic tunicates (Salps)
Authors: Müller Svenja J. , Wessels Wiebke , Driscoll Sara , Pakhomov Evgeny A. , Auerswald Lutz , Michael Katharina , Meyer Bettina 
Published: July 2023

AbstractSalps are pelagic tunicates that are able to form large blooms under favorable conditions by alternating between sexual and asexual reproduction. While their role in the regional carbon cycle is receiving attention, our knowledge of their physiology is still limited. This knowledge gap is mainly due to their fragile gelatinous nature, which makes it difficult to capture intact specimens and maintain them in the laboratory. We present here a modified kreisel tank system, that was tested onboard using the Southern Ocean salpSalpa thompsoniand station-based using the Mediterranean speciesSalpa fusiformis. Successful maintenance over days to weeks allowed us to obtain comparable relative growth and developmental rates asin situ, and provided insight into their potential life cycle strategies. By providing a starting point for successful maintenance, we hope to stimulate future experimental research on this understudied taxonomic group.
Serotonergic and dopaminergic neurons in the dorsal raphe are differentially altered in a mouse model for parkinsonism
Authors: Boi Laura , Johansson Yvonne , Tonini Raffaella , Moratalla Rosario , Fisone Gilberto , Silberberg Gilad 
Published: July 2023

AbstractParkinson’s disease (PD) is characterized by motor impairments caused by degeneration of dopamine neurons in the substantia nigra pars compacta. In addition to these symptoms, PD patients often suffer from non-motor co-morbidities including sleep and psychiatric disturbances, which are thought to depend on concomitant alterations of serotonergic and noradrenergic transmission. A primary locus of serotonergic neurons is the dorsal raphe nucleus (DRN), providing brain-wide serotonergic input. Here, we identified electrophysiological and morphological parameters to classify serotonergic and dopaminergic neurons in the murine DRN under control conditions and in a PD model, following striatal injection of the catecholamine toxin, 6-hydroxydopamine (6-OHDA). Electrical and morphological properties of both neuronal populations were altered by 6-OHDA. In serotonergic neurons, most changes were reversed when 6-OHDA was injected in combination with desipramine, a noradrenaline reuptake inhibitor, protecting the noradrenergic terminals. Our results show that the depletion of both noradrenaline and dopamine in the 6-OHDA mouse model causes changes in the DRN neural circuitry.
Predicting the Beat Bin: Beta Oscillations Predict the Envelope Sharpness in a Rhythmic Sequence
Authors: Leske Sabine , Endestad Tor , Volehaugen Vegard , Foldal Maja D. , Blenkmann Alejandro O. , Solbakk Anne-Kristin , Danielsen Anne 
Published: July 2023

AbstractPeriodic sensory inputs entrain oscillatory brain activity, reflecting a neural mechanism that might be fundamental to temporal prediction and perception. Most environmental rhythms, such as music or speech, however, are rather quasi-periodic. Research has shown that neural tracking of speech is driven by modulations of the amplitude envelope, especially via sharp acoustic edges, which serve as prominent temporal landmarks. In the same vein, research on rhythm processing in music supports the notion that perceptual timing precision varies systematically with the sharpness of acoustic onset edges, conceptualized in the beat bin hypothesis. Increased envelope sharpness induces increased precision in localizing a sound in time. Despite this tight relationship between envelope shape and temporal processing, it is currently unknown how the brain uses predictive information about envelope features to optimize temporal perception.With the current study, we show that the predicted sharpness of the amplitude envelope is encoded by pre-target neural activity in the beta band (15–25 Hz), and has an impact on the temporal perception of sounds. Using probabilistic sound cues in an EEG experiment, we informed participants about the sharpness of the amplitude envelope of an upcoming target sound embedded in a quasi-isochronous beat. The predictive information about the envelope shape modulated the performance in the timing judgment task and pre-target beta power. Interestingly, these conditional beta-power modulations correlated positively with behavioral performance in the timing-judgment task and with perceptual temporal precision in a click-alignment task.This study provides new insight into the neural processes underlying prediction of the sharpness of the amplitude envelope during beat perception, which modulate the temporal perception of sounds. This finding could reflect a process that is involved in temporal prediction, exerting top-down control on neural entrainment via the prediction of acoustic edges in the auditory stream.
Exploring Liquid-Liquid Phase Separation in the organization of Golgi Matrix Proteins
Authors: Mendes Luis Felipe S. , Oliveira Carolina G. , Kava Emanuel , Costa-Filho Antonio J. 
Published: July 2023

AbstractThe Golgi apparatus is a critical organelle in protein sorting and lipid metabolism. Characterized by its stacked, flattened cisternal structure, the Golgi exhibits distinct polarity with itscis- andtrans-faces orchestrating various protein maturation and transport processes. At the heart of its structural integrity and organization are the Golgi Matrix Proteins (GMPs), predominantly comprising Golgins and GRASPs. These proteins contribute to this organelle’s unique stacked and polarized structure and ensure the precise localization of Golgi-resident enzymes, which is crucial for accurate protein processing. Despite over a century of research since its discovery, the Golgi architecture’s intricate mechanisms still need to be fully understood. Here, we demonstrate that GMPs present a significant tendency to form biocondensates through Liquid-Liquid Phase Separation (LLPS) across different Eukaryotic lineages. Moreover, we validated experimentally that members of the GRASP family also exhibit a strong tendency for LLPS. Our findings offer a new perspective on the possible roles of protein disorder and LLPS of GMPs in the Golgi organization.
Molecular responses of agroinfiltratedNicotiana benthamianaleaves expressing suppressor of silencing P19 and influenza virus-like particles
Authors: Hamel Louis-Philippe , Tardif Rachel , Poirier-Gravel Francis , Rasoolizadeh Asieh , Brosseau Chantal , Giroux Geneviève , Lucier Jean-François , Goulet Marie-Claire , Barrada Adam , Roussel Élise , Comeau Marc-André , Lavoie Pierre-Olivier , Moffett Peter , Michaud Dominique , D’Aoust Marc-André 
Published: July 2023

SummaryThe production of influenza vaccines in plants is achieved through transientAgrobacterium-mediated expression of viral hemagglutinins (HAs). These proteins are produced and matured through the secretory pathway of plant cells, before being trafficked to the plasma membrane where they induce formation of virus-like particles (VLPs). Production of VLPs unavoidably impacts plant cells, as do viral suppressors of RNA silencing (VSRs) that are often co-expressed to increase protein yields. However, little information is available on host molecular responses to these foreign proteins. The present work provides a comprehensive overview of transcriptomic, metabolic, and signaling changes occurring inNicotiana benthamianaleaf cells transiently expressing the VSR P19, or co-expressing P19 and an influenza HA. Our data identifies generic responses toAgrobacterium-mediated expression of foreign proteins, including shutdown of chloroplast gene expression, activation of oxidative stress responses, and reinforcement of the plant cell wall through lignification. Our results also indicate that P19 expression promotes salicylic acid (SA) signaling, a process apparently antagonized by co-expression of HA. As the latter induces specific signatures, with effects on lipid metabolism, lipid distribution, and oxylipin signaling, dampening of P19 responses suggests crosstalk between SA and oxylipin pathways. Consistent with the upregulation of oxidative stress-related genes and proteins, we finally show that reduction of oxidative stress damage through exogenous application of ascorbic acid improves plant biomass quality during production of VLPs.One-sentence summaryAgrobacterium-mediated expression of influenza virus-like particles induces a unique molecular signature inNicotiana benthamianaleaf cells.
Cryogenic Soft Landing Improves Structural Preservation of Protein Complexes
Authors: Westphall Michael S. , Lee Kenneth W. , Hemme Colin , Salome Austin Z. , Mertz Keaton , Grant Timothy , Coon Joshua J. 
Published: July 2023

ABSTRACTWe describe an apparatus for the cryogenic landing of particles from the ion beam of a mass spectrometer onto transmission electron microscope grids for cryo-electron microscopy. This system also allows for the controlled formation of thin films of amorphous ice on the grid surface. We demonstrate that as compared to room temperature landings, use of this cryogenic landing device greatly improves the structural preservation of deposited protein–protein complexes. Further, landing under cryogenic conditions can increase the diversity of particle orientations, allowing for improved 3D structural interpretation. Finally, we conclude that this approach allows for the direct coupling of mass spectrometry with cryo-electron microscopy.
Sequencing 4.3 million mutations in wheat promoters to understand and modify gene expression
Authors: Zhang Junli , Xiong Hongchun , Burguener Germán F. , Vasquez-Gross Hans , Liu Qiujie , Debernardi Juan M. , Akhunova Alina , Campbell-Garland Kim , Kianian Shahryar F. , Brown-Guedira Gina , Pozniak Curtis , Faris Justin D. , Akhunov Eduard , Dubcovsky Jorge 
Published: July 2023

AbstractWheat is an important contributor to global food security, and further improvements are required to feed a growing human population. New functional genetics and genomics tools can help us to understand the function of different genes and to engineer beneficial changes. In this study, we used a promoter capture assay to sequence 2-kb regions upstream of all high-confidence annotated genes from 1,513 mutagenized plants from the tetraploid wheat variety Kronos. We identified 4.3 million induced mutations with an accuracy of 99.8%, resulting in a mutation density of 41.9 mutations per kb. We also remapped Kronos exome capture reads to Chinese Spring RefSeq v1.1, identified 4.7 million mutations, and predicted their effects on annotated genes. Using these predictions, we identified 59% more non-synonymous substitutions and 49% more truncation mutations than in the original study. To show the biological value of the new promoter dataset, we selected two mutations within the promoter of theVRN-A1vernalization gene. Both mutations, located within transcription factor binding sites, significantly alteredVRN-A1expression, and one reduced the number of spikelets per spike. These publicly available sequenced mutant datasets provide rapid and inexpensive access to induced variation in the promoters and coding regions of most wheat genes. These mutations can be used to understand and modulate gene expression and phenotypes for both basic and commercial applications, where limited governmental regulations can facilitate deployment. These mutant collections, together with gene editing, provide valuable tools to accelerate functional genetic studies in this economically important crop.Significance StatementWe sequenced 4.3 million induced mutations in the promoters and 4.7 million in the coding regions of most wheat genes. We also show how this public resource can be used to understand gene function, modulate gene expression, and generate changes in valuable wheat agronomic traits.
Salmonella injectisome penetration of macrophages triggers rapid translation of transcription factors and protection against cell death
Authors: Wood George , Johnson Rebecca , Powell Jessica , Bryant Owain J. , Lastovka Filip , Brember Matt , Tourlomousis Pani , Carr John P. , Bryant Clare E. , Chung Betty Y.W. 
Published: July 2023

AbstractDuring bacterial infection both the host cell and its invader must divert intracellular resources to synthesise specific proteins in a timely manner. For the host, these factors may be needed for innate immune responses, including programmed cell death, and in the bacteria newly synthesized proteins may be survival factors needed to counteract host responses.Salmonellais an important food-borne bacterial pathogen that invades and multiplies within host cells. It is well established that invasion of epithelial cells is dependent upon the SPI-1 Type III injectisome, a biological needle that penetrates and secretes effectors into host cells to promote internalization. However, the importance of the SPI-1 injectisome in infection of professional phagocytes such as macrophages, which are the predominant host cell type during systemic infection, is less clear. Through time resolved parallel transcriptomic and translatomic studies of macrophage infection, we revealed that SPI-1 injectisome-dependent infection of macrophages triggers rapid translation of transcription factor mRNAs, including Early Growth Response 1 (Egr1). Despite the short half-life of EGR1 protein, its swift synthesis within the initial hour of infection is sufficient to inhibit transcription of pro-inflammatory genes and thereby restrain inflammatory responses and programmed cell death within the first hour of during early infection. This transient period of inflammatory suppression in macrophages is exploited bySalmonellato establish infection and sheds new insight on the importance of translational activation in host-pathogen dynamics duringSalmonellainfection.
Reactive oxygen species acceleratede novoacquisition of antibiotic resistance inE. coli
Authors: Qi Wenxi , Jonker Martijs J. , de Leeuw Wim , Brul Stanley , ter Kuile Benno H. 
Published: July 2023

AbstractReactive oxygen species (ROS) produced as a secondary effect of bactericidal antibiotics are hypothesized to play a role in killing bacteria. However, the role of ROS in the development ofde novoresistance as a result of sublethal levels of bactericidal antibiotics has barely been investigated. Here, we report that single-gene knockout strains with reduced ROS scavenging exhibited enhanced ROS accumulation and more rapid acquisition of resistance when exposed to sublethal levels of bactericidal antibiotics. Consistent with this observation, the ROS scavenger thiourea in the medium decelerated resistance development. Thiourea downregulated the transcriptional level of error-prone DNA polymerase and DNA glycosylase MutM, which counters the incorporation and accumulation of 8-hydroxy-2’-deoxyguanosine (8-HOdG) in the genome. The level of 8-HOdG significantly increased following incubation with bactericidal antibiotics but decreased after treatment with the ROS scavenger thiourea. These observations suggest that inE. colisublethal levels of ROS stimulatede novodevelopment of resistance, providing a mechanistic basis for hormetic responses induced by antibiotics.ImportanceExposure to sublethal concentrations of antimicrobials is known to result inde novoresistance development against the specific compound. Particularly, the use of antibiotics as feed additives to enhance productivity may result in the development of drug resistance in environmental and veterinary microorganisms, which could subsequently transfer to human populations. Nevertheless, the mechanisms underlyingde novoresistance development have not been extensively explored. In this study, we indicate the role of ROS in promoting the formation of resistance to bactericidal antibiotics and show the potential of ROS scavengers to reduce mutation rates and slow down resistance formation under long-term selection. Thus, the supplementary use of antioxidants during prolonged antibiotic administration potentially contributes to mitigating the emergence of antimicrobial resistance.
hnRNPUL1 ensures efficient Integrator-mediated cleavage of snRNAs and is mutated in amyotrophic lateral sclerosis
Authors: Yonchev Ivaylo D. , Apostol Carmen V. , Griffith Llywelyn , Li Ang , Butler Larissa , Patrick Helen , Aguilar-Martinez Elisa , Whelan Ashleigh G. R. , Evans Caroline , Dickman Mark J. , Cooper-Knock Johnathan , Shaw Pamela J. , West Steven , Barbaric Ivana , Sudbery Ian M. , Wilson Stuart A. 
Published: July 2023

AbstractIntegrator cleaves nascent RNA, triggering RNA polymerase II transcription termination, but how cleavage is regulated is poorly understood. Here we show hnRNPUL1 ensures efficient Integrator-mediated cleavage of nascent RNA downstream of snRNA genes and, in the case of U2 snRNA, binds a terminal stem-loop involved in this process. In the nucleoplasm, hnRNPUL1 binds U4 snRNA and SART3 and enables efficient reformation of the U4:U6 di-snRNP for further rounds of pre-mRNA splicing. Sustained hnRNPUL1 loss leads to reduced levels of snRNAs, defects in histone mRNA 3′ end processing and loss of Cajal bodies. hnRNPUL1 binds RNA through multiple domains, including a globular central domain comprising tightly juxtaposed SPRY and dead polynucleotide kinase folds. This latter fold allows binding to 5′-monophosphorylated RNAs in a mutually exclusive manner with ATP binding and functions as an XRN2 antagonist when overexpressed. We identify a cohort of amyotrophic lateral sclerosis patients harbouring disruptive mutations in hnRNPUL1. SMN loss in spinal muscular atrophy and hnRNPUL1 loss both disrupt snRNP biogenesis, leading to motor neuron death, suggesting a common aetiology.
A functional microbiome catalog crowdsourced from North American rivers
Authors: Borton Mikayla A. , McGivern Bridget B. , Willi Kathryn R. , Woodcroft Ben J. , Mosier Annika C. , Singleton Derick M. , Bambakidis Ted , Pelly Aaron , Liu Filipe , Edirisinghe Janaka N. , Faria José P. , Leleiwi Ikaia , Daly Rebecca A. , Goldman Amy E. , Wilkins Michael J. , Hall Ed K. , Pennacchio Christa , Roux Simon , Eloe-Fadrosh Emiley A. , Good Stephen P. , Sullivan Matthew B. , Henry Christopher S. , Wood-Charlson Elisha M. , Ross Matthew R.V. , Miller Christopher S. , Crump Byron C. , Stegen James C. , Wrighton Kelly C. 
Published: July 2023

AbstractPredicting elemental cycles and maintaining water quality under increasing anthropogenic influence requires understanding the spatial drivers of river microbiomes. However, the unifying microbial processes governing river biogeochemistry are hindered by a lack of genome-resolved functional insights and sampling across multiple rivers. Here we employed a community science effort to accelerate the sampling, sequencing, and genome-resolved analyses of river microbiomes to create the Genome Resolved Open Watersheds database (GROWdb). This resource profiled the identity, distribution, function, and expression of thousands of microbial genomes across rivers covering 90% of United States watersheds. Specifically, GROWdb encompasses 1,469 microbial species from 27 phyla, including novel lineages from 10 families and 128 genera, and defines the core river microbiome for the first time at genome level. GROWdb analyses coupled to extensive geospatial information revealed local and regional drivers of microbial community structuring, while also presenting a myriad of foundational hypotheses about ecosystem function. Building upon the previously conceived River Continuum Concept1, we layer on microbial functional trait expression, which suggests the structure and function of river microbiomes is predictable. We make GROWdb available through various collaborative cyberinfrastructures2, 3so that it can be widely accessed across disciplines for watershed predictive modeling and microbiome-based management practices.
Assessing the impact of autologous neutralizing antibodies on viral rebound in postnatally SHIV-infected ART-treated infant rhesus macaques
Authors: Mainou Ellie , Berendam Stella J , Obregon-Perko Veronica , Uffman Emilie A , Phan Caroline T , Shaw George M , Bar Katherine J , Kumar Mithra R , Fray Emily J , Siliciano Janet M , Siliciano Robert F , Silvestri Guido , Permar Sallie R , Fouda Genevieve G , McCarthy Janice , Chahroudi Ann , Conway Jessica M , Chan Cliburn 
Published: July 2023

AbstractWhile the benefits of early antiretroviral therapy (ART) initiation in perinatally infected infants are well documented, early ART initiation is not always possible in postnatal pediatric HIV infections, which account for the majority of pediatric HIV cases worldwide. The timing of onset of ART initiation is likely to affect the size of the latent viral reservoir established, as well as the development of adaptive immune responses, such as the generation of neutralizing antibody responses against the virus. How these parameters impact the ability of infants to control viremia and the time to viral rebound after ART interruption is unclear. To gain insight into the dynamics, we utilized mathematical models to investigate the effect of time of ART initiation via latent reservoir size and autologous virus neutralizing antibody responses in delaying viral rebound when treatment is interrupted. We used an infant nonhuman primate Simian/Human Immunodeficiency Virus (SHIV) infection model that mimics breast milk HIV transmission in human infants. Infant Rhesus macaques (RMs) were orally challenged with SHIV.C.CH505 375H dCT and either given ART at 4-7 days post-infection (early ART condition), at 2 weeks post-infection (intermediate ART condition), or at 8 weeks post-infection (late ART condition). These infants were then monitored for up to 60 months post-infection with serial viral load and immune measurements. We develop a stochastic mathematical model to investigate the joint effect of latent reservoir size, the autologous neutralizing antibody potency, and CD4+ T cell levels on the time to viral rebound and control of post-rebound viral loads. We find that the latent reservoir size is an important determinant in explaining time to viral rebound by affecting the growth rate of the virus. The presence of neutralizing antibodies also can delay rebound, but we find this effect for high potency antibody responses only.
Polyreactivity of antibodies from different B cell subpopulations is determined by distinct sequence patterns of variable region
Authors: Lecerf Maxime , Lacombe Robin V. , Dimitrov Jordan D. 
Published: July 2023

AbstractAn antibody molecule that is able to bind to multiple distinct antigens is defined as polyreactive. In the present study we performed statistical analyses to assess sequence correlates of polyreactivity of >600 antibodies cloned from different B cell types of healthy humans. The data reveled a number of sequence patterns of variable regions of heavy and light immunoglobulin chains that determine polyreactivity. The most prominent identified patterns were increased number of basic amino acid residues, reduced frequency of acidic residues, increased number of aromatic and hydrophobic residues, as well as longer length of CDR L1. Importantly, our study revealed that antibodies isolated from different B cell population used distinct sequence patterns (or combinations of them) for polyreactive antigen binding. Furthermore, we combined the data from sequence analyses with molecular modeling of selected polyreactive antibodies, and demonstrate that human antibodies can use multiple pathways for achieving antigen binding promiscuity. These data reconcile some contradictions in literature regarding the determinants of antibody polyreactivity. Moreover, our study demonstrates that mechanism of polyreactivity of antibodies evolves during immune response and might be tailored to specific functional properties of different B cell compartments. Finally, these data can be of use for efforts in development and engineering of therapeutic antibodies.