bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruption of G3BP1 Granules Promotes Mammalian CNS and PNS Axon Regeneration
Authors: Sahoo Pabitra K. , Agrawal Manasi , Hanovice Nicholas , Ward Patricia , Desai Meghal , Smith Terika P. , SiMa HaoMin , Dulin Jennifer N. , Vaughn Lauren S. , Tuszynski Mark , Welshhans Kristy , Benowitz Larry , English Arthur , Houle John D. , Twiss Jeffery L. 
Published: June 2024

ABSTRACTDepletion or inhibition of core stress granule proteins, G3BP1 in mammals and TIAR-2 inC. elegans, increases axon regeneration in injured neurons, showing spontaneous regeneration. Inhibition of G3BP1 by expression of its acidic or ‘B-domain’ accelerates axon regeneration after nerve injury, bringing a potential therapeutic intervention to promote neural repair in the peripheral nervous system. Here, we asked if G3BP1 inhibition is a viable strategy to promote regeneration in injured mammalian central nervous system where axons do not regenerate spontaneously. G3BP1 B-domain expression was found to promote axon regeneration in the transected spinal cord provided with a permissive peripheral nerve graft (PNG) as well as in crushed optic nerve. Moreover, a cell-permeable peptide (CPP) to a subregion of B-domain (rodent G3BP1 amino acids 190-208) accelerated axon regeneration after peripheral nerve injury and promoted regrowth of reticulospinal axons into the distal transected spinal cord through a bridging PNG. G3BP1 CPP promoted axon growth from rodent and human neurons cultured on permissive substrates, and this function required alternating Glu/Asp-Pro repeats that impart a unique predicted tertiary structure. The G3BP1 CPP disassembles axonal G3BP1, G3BP2, and FMRP, but not FXR1, granules and selectively increases axonal protein synthesis in cortical neurons. These studies identify G3BP1 granules as a key regulator of axon growth in CNS neurons and demonstrate that disassembly of these granules promotes retinal axon regeneration in injured optic nerve and reticulospinal axon elongation into permissive environments after CNS injury. This work highlights G3BP1 granule disassembly as a potential therapeutic strategy for enhancing axon growth and neural repair.SIGNIFICANCE STATEMENTThe central nervous system (CNS) axon does not have the capacity for spontaneous axon regeneration, as seen in the peripheral nervous system (PNS). We previously showed that stress granule-like aggregates of G3BP1 are present in uninjured PNS axons, and these slow nerve regeneration. We now report that CNS axons contain G3BP1 granules, and G3BP1 granule disassembling strategies promote axon regeneration in the injured sciatic nerve, transected spinal cord with a peripheral nerve graft, and injured optic nerve. Thus, G3BP1 granules are a barrier to axon regeneration and can be targeted for stimulating neural repair following traumatic injury, including in the regeneration refractory CNS.
The “don’t eat me” signal CD47 contributes to microglial phagocytosis defects and autism-like behaviors in 16p11.2 deletion mice
Authors: Ju Jun , Pan Yifan , Yang Xinyi , Li Xuanyi , Chen Jinghong , Wu Shiyu , Hou Sheng-Tao 
Published: June 2024

AbstractVarious pathological characteristics of autism spectrum disorder (ASD) stem from abnormalities in brain resident immune cells, specifically microglia, to prune unnecessary synapses or neural connections during early development. Animal models of ASD exhibit an abundance of synapses in different brain regions, which is strongly linked to the appearance of ASD behaviors. Overexpression of CD47 on neurons acts as a “don’t eat me” signal, safeguarding synapses from inappropriate pruning by microglia. Indeed, CD47 overexpression occurs in 16p11.2 deletion carriers, causing decreased synaptic phagocytosis and the manifestation of ASD characteristics. However, the role of CD47 in synaptic pruning impairment leading to ASD phenotypes in the 16p11.2 deletion mouse model is unclear. Moreover, whether blocking CD47 can alleviate ASD mice’s behavioral deficits remains unknown. Here, we demonstrate a strong link between increased CD47 expression, decreased microglia phagocytosis capacity, and increased impairment in social novelty preference in the 16p11.2 deletion mice. The reduction in microglia phagocytosis caused a rise in excitatory synapses and transmission in the prefrontal cortex of 16p11.2 deletion mice. Importantly, blocking CD47 using a specific CD47 antibody or reducing CD47 expression using a specific shRNA enhanced the microglia phagocytosis and reduced excitatory transmission. Reduction in CD47 expression improved social novelty preference deficits in 16p11.2 mice. These findings demonstrate that CD47 contributes to the ASD phenotypes in the 16p11.2 deletion mice and could be a promising target for the development of treatment for ASD.Significance StatementAutism spectrum disorder (ASD) is a neurological developmental condition characterized by stereotyped behaviors and cognitive deficits. However, therapeutic options for ASD remain limited. Activation of the classical complement system, an innate immune signaling pathway component, supports microglia-mediated synaptic pruning during development and disease. In particular, CD47, a “don’t eat me” signal, protects synapses from inappropriate clearance. Here, we investigated the role of CD47 in microglial phagocytosis using the 16p11.2 deletion mouse model, demonstrating that reducing CD47 signaling enhances microglial phagocytose synapses in the prefrontal cortex. This enhancement leads to improved synaptic function and reduced social behavioral deficits. These findings provide mechanistic insights into the role of CD47, laying the groundwork for developing more effective treatments for ASD.
SpyDen: Automating molecular and structural analysis across spines and dendrites
Authors: Eggl Maximilian F. , Wagle Surbhit , Filling Jean P. , Chater Thomas E. , Goda Yukiko , Tchumatchenko Tatjana 
Published: June 2024

AbstractInvestigating the molecular composition across neural compartments such as axons, dendrites, or synapses is critical for our understanding of learning and memory. State-of-the-art microscopy techniques can now resolve individual molecules and pinpoint their position with micrometre or even nanometre resolution across tens or hundreds of micrometres, allowing the labelling of multiple structures of interest simultaneously. Algorithmically, tracking individual molecules across hundreds of micrometres and determining whether they are inside any cellular compartment of interest can be challenging. Historically, microscopy images are annotated manually, often using multiple software packages to detect fluorescence puncta (e.g. labelled mRNAs) and then trace and quantify cellular compartments of interest. Advanced ANN-based automated tools, while powerful, are often able to help only with selected parts of the data analysis pipeline, may be optimised for specific spatial resolutions or cell preparations or may not be fully open source and open access to be sufficiently customisable. To address these challenges, we developed SpyDen. SpyDen is a Python package based upon three principles:i)ease of use for multi-task scenarios,ii)open-source accessibility and data export to a common, open data format,iii)the ability to edit any software-generated annotation and generalise across spatial resolutions. Equipped with a graphical user interface and accompanied by video tutorials, SpyDen provides a collection of powerful algorithms that can be used for neurite and synapse detection as well as fluorescent puncta and intensity analysis. We validated SpyDen using expert annotation across numerous use cases to prove a powerful, integrated platform for efficient and reproducible molecular imaging analysis.
Crystal structure of a MarR family transcriptional regulator protein
Authors: Goswami Arpita , Ravindranath Kannika Byadarahalli , Shankar Madan Kumar 
Published: June 2024

AbstractThe multiple antibiotic resistance regulator (MarR) family of transcription factor proteins form a large group of multitasking bio-molecules in pathogenicEscherichia coli(E. coli). HosA is one of these MarR transcription factors reported in dozens of pathogenicE. coliwith highly conserved sequence profiles. The HosA from the enteropathogenicE. coliO127:H6 (strain E2348/69), a predominantly monomeric protein, was overexpressed inE. coliand purified. The HosA protein crystals were obtained in microbatch under oil method at 4° C. The X-rays of the diffracted spots were extended to 2.21 Å resolution. The crystal belongs to the space groupP4322, with unit-cell parametersa= 67.16 Å,b= 67.16 Å,c= 95.66 Å and α = β = γ = 90°. In the asymmetric unit, monomeric HosA protein was crystallized and confirmed with the Matthew coefficient analysis (3.48 Å3Da-1). The monomeric structure is compared with previously solved structures of other homologous transcription factors. This confirmed the winged loop at the DNA binding region of the HosA protein.
HCNetlas: Human cell network atlas enabling cell type-resolved disease genetics
Authors: Yu Jiwon , Cha Junha , Koh Geon , Lee Insuk 
Published: June 2024

AbstractCell type-specific actions of disease genes add a significant layer of complexity to the genetic architecture underlying diseases, obscuring our understanding of disease mechanisms. Single-cell omics have revealed the functional roles of genes at the cellular level, identifying cell types critical for disease progression. Often, a gene impact on disease through its altered network within specific cell types, rather than mere changes in expression levels. To explore the cell type-specific roles of disease genes, we developed HCNetlas (human cell network atlas), a resource cataloging cell type-specific gene networks (CGNs) for various healthy tissue cells. We also devised three network analysis methods to investigate cell type-specific functions of disease genes. These methods involve comparing HCNetlas CGNs with those derived from disease-affected tissue samples. These methods find that systemic lupus erythematosus genes predominantly function in myeloid cells, and Alzheimer’s disease genes mainly play roles in inhibitory and excitatory neurons. Moreover, they show many lung cancer genes exert their roles in immune cells. These findings suggest that HCNetlas has the potential to link disease-associated genes to cell types of action, facilitating development of cell type-resolved diagnostics and therapeutic strategies for complex human diseases.
Genomic Insights and Biocontrol Potential of Ten Bacterial Strains from the Tomato Core Microbiome
Authors: Nicotra Daniele , Ghadamgahi Farideh , Ghosh Samrat , Anzalone Alice , Dimaria Giulio , Mosca Alexandros , Massimino Maria Elena , Vetukuri Ramesh Raju , Catara Vittoria 
Published: June 2024

AbstractDespite their adverse environmental effects, modern agriculture relies heavily on agrochemicals to manage diseases and pests and enhance plant growth and productivity. Some of these functions could instead be fulfilled by endophytes from the plant microbiota, which have diverse activities beneficial for plant growth and health. We therefore used a microbiome-guided top-down approach to select ten bacterial strains from different taxa in the core microbiome of tomato plants in the production chain for evaluation as potential bioinoculants. These taxa included some that are commonly used as biofertilizers and biocontrol agents (PseudomonasandBacillus) as well as the less studied generaLeclercia, Chryseobacterium, Glutamicibacter,andPaenarthorbacter. When inoculated in the tomato rhizosphere, these strains promoted plant growth and reduced the severity of Fusarium Crown and Root Rot and Bacterial Spot infections. High-quality genomes for each strain were obtained using Oxford Nanopore long-read and Illumina short-read sequencing, enabling the dissection of their genetic makeup to identify phyto-beneficial traits. This yielded a comprehensive inventory of genes from each strain related to processes including colonization, biofertilization, phytohormones, and plant signaling. Traits directly relevant to fertilization including phosphate solubilization and acquisition of nitrogen and iron were also identified. Moreover, the strains carried several functional genes putatively involved in abiotic stress alleviation and biotic stress management, traits that indirectly foster plant health and growth. The gathered genomic information will be instrumental in planning the use of these bacteria individually or in consortia to enhance plant growth by coupling strains with different traits, effects, and mechanisms of action.
DNA methylation contributes to plant acclimation to naturally fluctuating light
Authors: Emmerson Robyn A , Bechtold Ulrike , Zabet Nicolae Radu , Lawson Tracy 
Published: June 2024

AbstractPlants in the natural environment experience continuous dynamic changes in light intensity. We have limited understanding on how plants adapt to such variable conditions. Here, we exposedArabidopsis thalianaplants to naturally fluctuating light regimes alongside traditional square light regimes such as those often found in control environment growth chambers. The physiological response was highly consistent across experiments, indicating the involvement of an epigenetic mechanism, leading us to investigated differences in DNA methylation. Our results identified a large number of alterations in DNA methylation patterns between fluctuating light acclimated plants, and square light acclimated plants, demonstrating natural fluctuations in light impacts the plant epigenetic mechanisms. Most importantly, there are more differences in DNA methylation patterns between different light pattern regimes than between different light intensities. These differences in DNA methylation were accompanied by significant changes in gene expression, some of which correlated with altered DNA methylation. Interestingly, several transposable elements which displayed differential methylation were found to be differentially expressed between light regimes. Our data suggests DNA methylation plays a role in acclimation to natural light which may directly regulate gene expression and impact transposable element activation.
Should I stay or should I go? Spatio-temporal dynamics of bacterial biofilms in confined flows
Authors: Benbelkacem Massinissa , Ramos Gabriel , El Garah Fatima , Abidine Yara , Roques Christine , Davit Yohan 
Published: June 2024

AbstractThe vast majority of bacteria live in sessile biofilms that colonize the channels, pores and crevices of confined structures. Flow in these structures carries the nutrients necessary for growth, but also generates stresses and detachment from surfaces. Conversely, bacteria tend to occupy a large part of the available space and, in so doing, increase resistance to flow and modify transport properties. Although the importance of advective transport and hydrodynamic forces on bacteria is well known, the complex feedback effects that control development in confined geome-tries are much less understood. Here, we study how couplings between flow and bacterial development control the spatio-temporal dynamics ofPseudomonas aeruginosain microchannel flows. We demonstrate that nutrient limitation drives the longitudinal distribution of biomass, while a competition between growth and flow-induced detachment controls the maximum clogging and the temporal dynamics. We find that successive cycles of sloughing and growth cause persistent fluctuations of the hydraulic resistance and prevent the system from ever reaching a true steady-state. Our results indicate that these self-sustained fluctuations are a signature effect of biofilm development in confined flows and could thus be a key component of the spreading of biofilms in infections, environmental processes and engineering applications. Consistent with the description of other bursting events, such as earthquakes or avalanches, we further show that the dynamics of sloughing can be described as a jump stochastic process with a gamma distribution of interevent times. This stochastic modeling approach opens the way towards a new quantitative approach to the characterization of the apparent randomness and irreproducibility of biofilm experiments in such systems.
Date palm acclimates to aridity by diverting organic osmolytes for root osmotic adjustment in parallel with leaf membrane remodeling and ROS scavenging
Authors: Franzisky Bastian L. , Mueller Heike M. , Du Baoguo , Lux Thomas , White Philip J. , Carpentier Sebastien Christian , Winkler Jana Barbro , Schnitzler Joerg-Peter , Kudla Jörg , Kangasjärvi Jaakko , Reichelt Michael , Mithöfer Axel , Mayer Klaus F.X. , Rennenberg Heinz , Ache Peter , Hedrich Rainer , Messerer Maxim , Geilfus Christoph-Martin 
Published: June 2024

AbstractHighlight statementOsmotic strength of date palm roots increases with soil desiccation, for which the accumulation of organic osmolytes, such as sugars, is essential in complement to energetically cheap mineral osmotics.Date palm (Phoenix dactyliferaL.) is an important crop in arid regions that is well-adapted to desert ecosystems. To understand the remarkable ability to grow and yield in water-limited environments, experiments were conducted in a simulated desert environment with water-withholding for up to four weeks. In response to drought, root, rather than leaf, osmotic strength increased, with sugars contributing more to the osmolyte increase than minerals. Consistently, carbon and amino acid metabolism was acclimated toward biosynthesis at both the transcriptional and translational levels. In leaves, a remodeling of membrane systems was observed, suggesting changes in thylakoid lipid composition, which together with the restructuring of the photosynthetic apparatus, indicated an acclimation preventing oxidative damage. Thus, xerophilic date palm avoids oxidative damage under drought by combined prevention and rapid detoxification of oxygen radicals. Although minerals were expected to serve as cheap key osmotics, date palm also relies on organic osmolytes for osmotic adjustment of the roots during desiccation. The diversion of these resources away from growth is consistent with date palm’s strategy of generally slow growth in harsh environments and clearly indicates a trade-off between growth and stress-related physiological responses.
Association of GLOD4 with Alzheimer’s Disease in Humans and Mice
Authors: Utyro Olga , Włoczkowska-Łapińska Olga , Jakubowski Hieronim 
Published: June 2024

AbstractBackgroundGlyoxalase domain containing protein 4 (GLOD4), a protein of an unknown function, is associated with Alzheimer’s disease (AD). Three GLOD4 isoforms are known. The mechanism underlying GLOD4’s association with AD was unknown.ObjectiveTo assess GLOD4’s role in the central nervous system by studying GLOD4 isoforms expression in human frontal cerebral cortical tissues from AD patients and in brains ofBlmh−/−5xFAD mouse AD model of AD.MethodsGLOD4 protein and mRNA were quantified in human and mouse brains by western blotting and RT-qPCR, respectively. Mouse brain amyloid β (Aβ) was quantified by western blotting. Behavioral assessments of mice were performed by cognitive/neuromotor testing.Glod4gene in mouse neuroblastoma N2a-APPswe cells was silenced by RNA interference and Glod4 protein/mRNA, Aβ precursor protein (Aβpp)/mRNA,Atg5,p62, andLc3mRNAs were quantified.ResultsGLOD4mRNA and protein isoforms were downregulated in cortical tissues from AD patients compared to non-AD controls.Glod4mRNA was downregulated in brains ofBlmh−/−5xFAD mice compared toBlmh+/+5xFAD sibling controls, but not inBlmh−/−mice without the 5xFAD transgene compared toBlmh+/+sibling controls. The 5xFAD transgene downregulated Glod4 mRNA inBlmh−/−mice of both sexes and inBlmh+/+males but not females. Attenuated Glod4 was associated with elevated Aβ and worsened memory/sensorimotor performance inBlmh−/−5xFAD mice. Glod4 depletion in N2a-APPswe cells upregulated AβPP and downregulated autophagy-relatedAtg5,p62, andLc3genes.ConclusionsThese findings suggest that GLOD4 interacts with AβPP and the autophagy pathway, and that disruption of these interactions leads to Aβ accumulation and cognitive/neurosensory deficits.
High-resolution, high-throughput analysis ofDrosophilageotactic behavior
Authors: Canic Tijana , Lopez Juan , Ortiz-Vega Natalie , Zhai R. Grace , Syed Sheyum 
Published: June 2024

AbstractDrosophilainnate response to gravity, geotaxis, has been previously used to assess the impact of aging and disease on motor performance. Despite its rich history, fly geotaxis continues to be largely measured manually and assessed through simplistic metrics. The manual nature of this assay introduces substantial experimental variability while simplistic metrics provide limited analytic insights into the behavior. To address these shortcomings, we have constructed a fully automated, programable apparatus, and developed a multi-object tracking software capable of following sub-second movements of individual flies, thus allowing reproducible, detailed, and quantitative analysis of geotactic behavior. The apparatus triggers and monitors geotaxis of 10 fly cohorts simultaneously, with each cohort consisting of up to 7 flies. The tracking program isolates cohorts and records individual fly coordinate outputs allowing for simultaneous multi-group, multifly tracks per experiment, greatly improving throughput and resolution. The algorithm tracks individual flies during the entire run with ∼97% accuracy, yielding detailed climbing curve, speed, and movement direction with 1/30 second resolution. Our tracking also allows the construction of multi-variable metrics and the detection of transitory movement phenotypes, such as slips and falls, which have thus far been neglected in geotaxis studies due to limited spatio-temporal resolution. Through a combination of automation and robust tracking, the platform is therefore poised to advanceDrosophilageotaxis assay into a comprehensive assessment of locomotor behavior.
TLR4 deficiency does not alter glaucomatous progression in a mouse model of chronic glaucoma
Authors: Zhang Chi , Simón Marina , Harder Jeffrey M. , Lim Haeyn , Montgomery Christa , Wang Qing , John Simon W.M. 
Published: June 2024

AbstractGlaucoma is a leading cause of irreversible blindness worldwide. Toll-like receptor 4 (TLR4) is a pattern-recognition transmembrane receptor that induces neuroinflammatory processes in response to injury.Tlr4is highly expressed in ocular tissues and is known to modulate inflammatory processes in both anterior and posterior segment tissues. TLR4 activation can lead to mitochondrial dysfunction and metabolic deficits in inflammatory disorders. Due to its effects on inflammation and metabolism, TLR4 is a candidate to participate in glaucoma pathogenesis. It has been suggested as a therapeutic target based on studies using acute models, such as experimentally raising IOP to ischemia-inducing levels. Nevertheless, its role in chronic glaucoma needs further evaluation. In the current study, we investigated the role of TLR4 in an inherited mouse model of chronic glaucoma, DBA/2J. To do this, we analyzed the effect ofTlr4knockout (Tlr4−/−) on glaucoma-associated phenotypes in DBA/2J mice. Our studies found no significant differences in intraocular pressure, iris disease, or glaucomatous progression inTlr4−/−compared toTlr4+/+DBA/2J mice. These data do not identify a role for TLR4 in this chronic glaucoma, but further research is warranted to understand its role in other glaucoma models and different genetic contexts.