bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuropeptide Y signaling regulates recurrent excitation in the auditory midbrain
Authors: Silveira Marina A. , Drotos Audrey C. , Pirrone Trinity M. , Versalle Trevor S. , Bock Amanda , Roberts Michael T. 
Published: May 2023

AbstractNeuropeptides play key roles in shaping the organization and function of neuronal circuits. In the inferior colliculus (IC), which is located in the auditory midbrain, Neuropeptide Y (NPY) is expressed by a large class of GABAergic neurons that project locally as well as outside the IC. The IC integrates information from numerous auditory nuclei making the IC an important hub for sound processing. Most neurons in the IC have local axon collaterals, however the organization and function of local circuits in the IC remains largely unknown. We previously found that neurons in the IC can express the NPY Y1 receptor (Y1R+) and application of the Y1R agonist, [Leu31, Pro34]-NPY (LP-NPY), decreases the excitability of Y1R+neurons. To investigate how Y1R+neurons and NPY signaling contribute to local IC networks, we used optogenetics to activate Y1R+neurons while recording from other neurons in the ipsilateral IC. Here, we show that 78.4% of glutamatergic neurons in the IC express the Y1 receptor, providing extensive opportunities for NPY signaling to regulate excitation in local IC circuits. Additionally, Y1R+neuron synapses exhibit modest short-term synaptic plasticity, suggesting that local excitatory circuits maintain their influence over computations during sustained stimuli. We further found that application of LP-NPY decreases recurrent excitation in the IC, suggesting that NPY signaling strongly regulates local circuit function in the auditory midbrain. Together, our data show that excitatory neurons are highly interconnected in the local IC and their influence over local circuits is tightly regulated by NPY signaling.
Structure and dynamics of cholesterol-mediated aquaporin-0 arrays and implications for lipid rafts
Authors: Chiu Po-Lin , Orjuela Juan D. , de Groot Bert L. , Aponte-Santamaría Camilo , Walz Thomas 
Published: May 2023

AbstractAquaporin-0 (AQP0) tetramers form square arrays in lens membranes through a yet unknown mechanism, but lens membranes are enriched in sphingomyelin and cholesterol. Here, we determined electron crystallographic structures of AQP0 in sphingomyelin/cholesterol membranes and performed molecular dynamics (MD) simulations to establish that the observed cholesterol positions represent those seen around an isolated AQP0 tetramer and that the AQP0 tetramer largely defines the location and orientation of most of its associated cholesterol molecules. At a high concentration, cholesterol increases the hydrophobic thickness of the annular lipid shell around AQP0 tetramers, which may thus cluster to mitigate the resulting hydrophobic mismatch. Moreover, neighboring AQP0 tetramers sandwich a cholesterol deep in the center of the membrane. MD simulations show that the association of two AQP0 tetramers is necessary to maintain the deep cholesterol in its position and that the deep cholesterol increases the force required to laterally detach two AQP0 tetramers, not only due to protein–protein contacts but also due to increased lipid–protein complementarity. Since each tetramer interacts with four such ‘glue’ cholesterols, avidity effects may stabilize larger arrays. The principles proposed to drive AQP0 array formation could also underlie protein clustering in lipid rafts.
T-FINDER: A highly sensitive, pan-HLA platform for functional T cell receptor and ligand discovery
Authors: Schmid Theresa , Cetin Miray , Pinamonti Veronica , Fuentes Ana Mellado , Kromer Kristina , Lerner Taga , Zhang Jing , Boschert Tamara , Herzig Yonatan , Ehlert Christopher , Fisch Laura , Dragan Valeriia , Kouwenhoven Arlette , Schoubroeck Bertrand Van , Wils Hans , Hove Carl Van , Platten Michael , Green Edward , Stevenaert Frederik , Felix Nathan J. , Lindner John M. 
Published: May 2023

AbstractEffective, unbiased, high-throughput methods to functionally identify both class II and class I HLA-presented T cell epitopes and their cognate T cell receptors (TCRs) are essential for and prerequisite to diagnostic and therapeutic applications, yet remain underdeveloped. Addressing this bottleneck, we established T-FINDER (T cell Functional Identification and (Neo)-antigen Discovery of Epitopes and Receptors), a platform that rapidly deconvolutes CD4 and CD8 TCR reactivities to targets physiologically processed and presented by an individual’s unmanipulated, complete HLA haplotype. By using a highly sensitive TCR signaling reporter capable of detecting even low-affinity TCR:ligand interactions, T-FINDER not only robustly identifies unknown peptide:HLA ligands from complex antigen libraries, but also rapidly screens and functionally validates the specificity of complex TCR libraries against known or predicted targets. To demonstrate its pan-HLA presentation capacity, we apply the platform to multiple TCR-based applications, including glioma, celiac disease, and rheumatoid arthritis, providing unique biological insights and showcasing T-FINDER’s potency and versatility.
CRISPR-based diagnostics detects invasive insect pests
Authors: Shashank Pathour R. , Parker Brandon M. , Rananaware Santosh R. , Plotkin David , Couch Christian , Yang Lilia G. , Nguyen Long T. , Prasannakumar N. R. , Braswell W. Evan , Jain Piyush K. , Kawahara Akito Y. 
Published: May 2023

AbstractRapid identification of organisms is essential across many biological and medical disciplines, from understanding basic ecosystem processes and how organisms respond to environmental change, to disease diagnosis and detection of invasive pests. CRISPR-based diagnostics offers a novel and rapid alternative to other identification methods and can revolutionize our ability to detect organisms with high accuracy. Here we describe a CRISPR-based diagnostic developed with the universal cytochrome-oxidase 1 gene (CO1). The CO1 gene is the most sequenced gene among Animalia, and therefore our approach can be adopted to detect nearly any animal. We tested the approach on three difficult-to-identify moth species (Keiferia lycopersicella, Phthorimaea absoluta, andScrobipalpa atriplicella) that are major invasive pests globally. We designed an assay that combines recombinase polymerase amplification (RPA) with CRISPR for signal generation. Our approach has a much higher sensitivity than other real time-PCR assays and achieved 100% accuracy for identification of all three species, with a detection limit of up to 120 fM forP. absolutaand 400 fM for the other two species. Our approach does not require a lab setting, reduces the risk of cross-contamination, and can be completed in less than one hour. This work serves as a proof of concept that has the potential to revolutionize animal detection and monitoring.
The emergence of human gastrulation uponin vitroattachment
Authors: De Santis Riccardo , Rice Eleni , Croft Gist , Yang Min , Rosado-Olivieri Edwin A. , Brivanlou Ali H. 
Published: May 2023

AbstractWhile studied extensively in model systems, human gastrulation remains obscure. This process starts upon blastocyst implantation into the uterine wall, which is assumed to occur after 14 days post-fertilization. The scarcity and limited access to fetal biological material as well as ethical considerations limit our understanding of the cellular and molecular portrait of human gastrulation.In vitroculture of natural human blastocysts shed light on the second week of human development, unveiling an unexpected level of self-organization embedded in the pre-gastrulating embryo, yet whether they can undergo gastrulation uponin vitroattachment remains elusive. Blastocyst models calledblastoids, which are derived from human pluripotent stem cells, provide the opportunity to reconstitute post-implantation human developmentin vitrowith unlimited biological material. Here we show that humanblastoidsbreak symmetry and undergo gastrulation uponin vitroattachment. scRNA-seq of these models replicate the transcriptomic signature of the natural human gastrula, recapitulating aspects of the second to the third week of human development. Surprisingly, analysis of developmental timing reveals that in bothblastoidmodels and naturalin vitroattached human embryos, the onset of gastrulation as defined by molecular makers, can be traced to time scales equivalent to 12 days post-fertilization, which appeals for a reconsideration of the onset of human gastrulation upon extendedin vitroculture.
Gametophytic epigenetic regulators MEDEA and DEMETER synergistically suppress ectopic shoot formation in Arabidopsis
Authors: Rajabhoj Mohit , Sankar Sudev , Bondada Ramesh , Shanmukhan Anju P , Prasad Kalika , Maruthachalam Ravi 
Published: May 2023

AbstractThe gametophyte to sporophyte transition facilitates the alternation of generations in a plant life cycle. The epigenetic regulators DEMETER(DME) and MEDEA(MEA) synergistically control central cell proliferation and differentiation, ensuring proper gametophyte to sporo-phyte transition inArabidopsis. Mutant alleles ofDMEandMEAare female gametophyte lethal, eluding the recovery of recessive homozygotes to examine their role in the sporophyte. Here, we exploited the paternal transmission of these mutant alleles coupled with CENH3-haploid inducer to generatemea-1;dme-2 sporophytes. Strikingly, the simultaneous loss of function of MEA and DME leads to the emergence of ectopic shoot meristems at the apical pole of the plant body axis.DMEandMEAare expressed in the developing shoot apex and regulate the expression of various shoot-promoting factors. Chromatin immunoprecipitation(ChIP), DNA methylation and gene expression analysis revealed several shoot regulators as potential targets of MEA and DME. Knockdown of upregulated shoot-promoting factors STM, CUC2, and PLT5 rescued the ectopic shoot phenotypes. Our findings reveal a previously unrecognized synergistic role of MEA and DME in restricting the meristematic activity at the shoot apex during sporophytic development to orchestrate the plant architecture.
Longitudinal analysis of memory T follicular helper cells and antibody response following CoronaVac vaccination
Authors: Zhou Pengcheng , Cao Cheng , Ji Tuo , Zheng Ting , Dai Yaping , Liu Min , Jiang Junfeng , Sun Daoqi , Bai Zhonghu , Lu Xiaojie , Gong Fang 
Published: May 2023

AbstractThe inactivated vaccine CoronaVac is one of the most widely used COVID-19 vaccines globally. However, the longitudinal evolution of the immune response induced by CoronaVac remains elusive compared to other vaccine platforms. Here, we recruited 88 healthy individuals that received 3 doses of CoronaVac vaccine. We longitudinally evaluated their polyclonal and antigen-specific CD4+T cells and neutralizing antibody response after receiving each dose of vaccine for over 300 days. Both the 2ndand 3rddose of vaccination induced robust spike-specific neutralizing antibodies, with a 3rdvaccine further increased the overall magnitude of antibody response, and neutralization against Omicron sub-lineages B.1.1.529, BA.2, BA.4/BA.5 and BA.2.75.2. Spike-specific CD4+T cell and circulating T follicular helper (cTFH) cells were markedly increased by the 2ndand 3rddose of CoronaVac vaccine, accompanied with altered composition of functional cTFHcell subsets with distinct effector and memory potential. Additionally, cTFHcells are positively correlated with neutralizing antibody titers. Our results suggest that CoronaVac vaccine-induced spike-specific T cells are capable of supporting humoral immunity for long-term immune protection.
Spatial Multiomics Reveal the Role of Wnt Modulator, Dkk2, in Palatogenesis
Authors: Oliver Piña Jeremie , Raju Resmi , Roth Daniela M. , Winchester Emma Wentworth , Padilla Cameron , Iben James , Faucz Fabio R. , Cotney Justin L. , D’Souza Rena N. 
Published: May 2023

ABSTRACTMultiple genetic and environmental etiologies contribute to the pathogenesis of cleft palate, which constitutes the most common among the inherited disorders of the craniofacial complex. Insights into the molecular mechanisms regulating osteogenic differentiation and patterning in the palate during embryogenesis are limited and needed for the development of innovative diagnostics and cures. This study utilized thePax9-/-mouse model with a consistent phenotype of cleft secondary palate to investigate the role ofPax9in the process of palatal osteogenesis. While prior research had identified upregulation of Wnt pathway modulatorsDkk1andDkk2inPax9-/-palate mesenchyme, limitations of spatial resolution and technology restricted a more robust analysis. Here, data from single-nucleus transcriptomics and chromatin accessibility assays validated byin situhighly multiplex targeted single-cell spatial profiling technology suggest a distinct relationship betweenPax9+and osteogenic populations. Loss ofPax9results in spatially restricted osteogenic domains bounded byDkk2, which normally interfaces withPax9in the mesenchyme. These results suggest that Pax9-dependent Wnt signaling modulators influence osteogenic programming during palate formation, potentially contributing to the observed cleft palate phenotype.
A rapid workflow for neuron counting in combined light sheet microscopy and magnetic resonance histology
Authors: Tian Yuqi , Johnson G Allan , Williams Robert W , White Leonard 
Published: May 2023

AbstractInformation on regional variation in cell numbers and densities in the CNS provides critical insight into structure, function, and the progression of CNS diseases. However, variability can be real or can be a consequence of methods that do not account for technical biases, including morphologic deformations, errors in the application of cell type labels and boundaries of regions, errors of counting rules and sampling sites. We address these issues of by introducing a workflow that consists of the following steps: 1. Magnetic resonance histology (MRH) to establish the size, shape, and regional morphology of the mouse brain in situ. 2. Light-sheet microscopy (LSM) to selectively label all neurons or other cells in the entire brain without sectioning artifacts. 3. Register LSM volumes to MRH volumes to correct for dissection errors and morphological deformations. 4. Implement novel protocol for automated sampling and counting of cells in 3D LSM volumes. This workflow can analyze the cells density of one brain region in less than 1 min and is highly replicable to cortical and subcortical gray matter regions and structures throughout the brain. We report deformation-corrected neuron (NeuN) counts and neuronal density in 13 representative regions in 5 C57B6/6J and 2 BXD strains. The data represent the variability among cases for the same brain region and across regions within case. Our data are consistent with previous studies. We demonstrate the application of our workflow to a mouse model of aging. This workflow improves the accuracy of neuron counting and the assessment of neuronal density on a region-by-region basis, with broad applications in how genetics, environment, and development across the lifespan impact brain structure.
Rhythmic entrainment of saccadic eye-movements in macaque FEF
Authors: Shaverdi Yeganeh , Setarehdan Seyed Kamaledin , Treue Stefan , Esghaei Moein 
Published: May 2023

AbstractSaccadic eye movements play a key role in gaining information about the surrounding environment. However, the neural mechanisms underlying the timing of these eye movements remain poorly understood. Here, we investigated the entrainment of saccadic eye movement by oscillatory neural activities in rhesus monkeys performing a visual foraging task. We found that saccades are phase-locked to beta LFP oscillations (16-22 Hz) in the frontal eye field (FEF), 100 ms before saccade onset, supporting a causal role of these oscillations in saccade timing. Furthermore, we show that the alignment between saccades and FEF LFPs varies, depending on the spatial relationship between the saccade target and the response field (RF) of neurons in the FEF. These findings suggest that the phase of the oscillatory neural activities determines the timing and direction of saccades.
SARS-CoV-2 infection leads to Tau pathological signature in neurons
Authors: Di Primio Cristina , Quaranta Paola , Mignanelli Marianna , Siano Giacomo , Bimbati Matteo , Piazza Carmen Rita , Spezia Piero Giorgio , Perrera Paola , Basolo Fulvio , Poma Anello Marcello , Costa Mario , Pistello Mauro , Cattaneo Antonino 
Published: May 2023

ABSTRACTBackgroundThe coronavirus disease 19 (COVID-19) has represented an issue for global health since its outbreak in March 2020. It is now evident that the SARS-CoV-2 infection results in a wide range of long-term neurological symptoms and is worryingly associated with the aggravation of Alzheimer’s disease. Little is known about the molecular basis of these manifestations.MethodsSeveral SARS-CoV-2 strain variants were used to infect SH-SY5Y neuroblastoma cells and K18-hACE C57BL/6J mice. The Tau phosphorylation profile and aggregation propensity upon infection were investigated using immunoblot and immunofluorescence on cellular extracts, subcellular fractions, and brain tissue. The viral proteins Spike, Nucleocapsid, and Membrane were overexpressed in SH-SY5Y cells and the direct effect on Tau phosphorylation was checked using immunoblot experiments.ResultsUpon infection, Tau is phosphorylated at several pathological epitopes associated with Alzheimer’s disease and other tauopathies. Moreover, this event increases Tau’s propensity to form insoluble aggregates and alters its subcellular localization.ConclusionsOur data support the evidence that SARS-CoV-2 infection in the Central Nervous System triggers downstream effects altering Tau function, eventually leading to the impairment of neuronal function.
Acute effect of transcranial direct current stimulation (tDCS) on postural control of trained athletes: a randomized controlled trial
Authors: Giancatarina Mary , Grandperrin Yohan , Nicolier Magali , Gimenez Philippe , Vidal Chrystelle , Tio Gregory , Haffen Emmanuel , Bennabi Djamila , Grosprêtre Sidney 
Published: May 2023

ABSTRACTTranscranial direct current stimulation (tDCS) is used to modulate the brain function in targeted brain areas, and can acutely modulate motor control, such as postural control. While the acute effect of tDCS is well documented on patients, little is still known whether tDCS can alter the motor control of healthy populations with an already high level of motor skills. This study aimed to assess the acute effect of tDCS on postural control of trained athletes. Eighteen parkour practitioners, known for their good balance abilities, were tested on three occasions in the laboratory for each stimulation condition (2 mA ; 20 minutes) – primary motor cortex (M1), prefrontal cortex (dlPFC) and sham (placebo). Postural control was evaluated PRE and POST each stimulation by measuring Center of Pressure (CoP) displacements on a force platform during static conditions (bipedal and unipedal stance). Following M1 stimulation, significant decreases were observed in CoP area in unipedal (P=0.003) and bipedal (P<0.001) stances. As well, the CoP total length was significantly reduced in bipodal (P=0.005) as well as in unipedal stance (P<0.001), only after M1 stimulation. Relative pre-post changes observed after M1 stimulation were negatively correlated to experience in parkour only after unipedal stance (r=0.715, P<0.001), meaning that the more participants were trained the less tDCS was effective. No significant changes were noticed after sham and dlPFC stimulation. These results suggested that the modulation of gait performance in athletes following an acute intervention of tDCS is specific to the targeted brain region, and that more complex postures (such as unipedal stance) were more sensitive to the effect of tDCS according to the level of practice.
Single nuclei transcriptomics in human and non-human primate striatum implicates neuronal DNA damage and proinflammatory signaling in opioid use disorder
Authors: Phan BaDoi N. , Ray Madelyn H. , Xue Xiangning , Fu Chen , Fenster Robert J. , Kohut Stephen J. , Bergman Jack , Haber Suzanne N. , McCullough Kenneth M. , Fish Madeline K. , Glausier Jill R. , Su Qiao , Tipton Allison E. , Lewis David A. , Freyberg Zachary , Tseng George C. , Russek Shelley J. , Alekseyev Yuriy , Ressler Kerry J. , Seney Marianne L. , Pfenning Andreas R. , Logan Ryan W. 
Published: May 2023

AbstractThe striatum in the brain is involved in various behavioral functions, including reward, and disease processes, such as opioid use disorder (OUD). Further understanding of the role of striatal subregions in reward behaviors and their potential associations with OUD requires molecular identification of specific striatal cell types in human brain. The human striatum contains subregions based on different anatomical, functional, and physiological properties, with the dorsal striatum further divided into caudate and putamen. Both caudate and putamen are involved in altered reward processing, formation of habits, and development of negative affect states associated with OUD. Using single nuclei RNA-sequencing of human postmortem caudate and putamen, we identified canonical neuronal cell types in striatum (e.g.,dopamine receptor 1 or 2 expressing neurons, D1 or D2) and less abundant subpopulations, including D1/D2-hybrid neurons and multiple classes of interneurons. By comparing unaffected subjects to subjects with OUD, we found neuronal-specific differences in pathways related to neurodegeneration, interferon response, and DNA damage. DNA damage markers were also elevated in striatal neurons of rhesus macaques following chronic opioid administration. We also identified sex-dependent differences in the expression of stress-induced transcripts among astrocytes and oligodendrocytes from female subjects with OUD. Thus, we describe striatal cell types and leverage these data to gain insights into molecular alterations in human striatum associated with opioid addiction.
Decomposing bulk signals to reveal hidden information in processive enzyme reactions: A case study in mRNA translation
Authors: Haase Nadin , Christ Simon , Heinemann Dag , Rudorf Sophia 
Published: May 2023

AbstractProcessive enzymes, such as polymerases or ribosomes, are often studied in en-semble or bulk experiments through the monitoring of time-dependent signals, such as fluorescence time traces. However, ensemble signals are a superposition of the time traces of all molecules in the reaction and can exhibit less distinct features than individual single-molecule signals due to the stochasticity of biomolecular processes. Here, we demonstrate that under certain conditions, bulk signals from processive reactions can still be decomposed to reveal hidden information about individual reaction steps. Using mRNA translation as a case study for processive biochemical reactions, we explore the limits of least-squares approaches for ensemble fluorescence signal decomposition. Specifically, we show that decomposing a noisy ensemble signal generated by the translation of mRNAs containing more than a few codons represents an ill-posed problem, which can be addressed through Tikhonov regularization. Our findings can help to increase the information content extracted from bulk experiments, thereby expanding the range of these time- and cost-efficient methods.