bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knock-down of hippocampal DISC1 in immune-challenged mice impairs the prefrontal-hippocampal coupling and the cognitive performance throughout development
Authors: Xu Xiaxia , Song Lingzhen , Hanganu-Opatz Ileana L. 
Published: May 2020

AbstractDisrupted-in-Schizophrenia 1 (DISC1) gene represents an intracellular hub of developmental processes and has been related to cognitive dysfunction in psychiatric disorders. Mice with whole-brain DISC1 knock-down show memory and executive deficits as result of impaired prefrontal-hippocampal communication throughout development, especially when combined with early environmental stressors, such as maternal immune activation (MIA). While synaptic dysfunction of layer 2/3 pyramidal neurons in neonatal prefrontal cortex (PFC) has been recently identified as one source of abnormal long-range coupling in these mice, it is still unclear whether the hippocampus (HP) is also compromised during development. Here we aim to fill this knowledge gap by combiningin vivoelectrophysiology and optogenetics with morphological and behavioral assessment of immune-challenged mice with DISC1 knock-down either in the whole brain (GE) or restricted to pyramidal neurons in CA1 area of intermediate/ventral HP (i/vHP) (GHPE). Both groups of mice show abnormal network activity, sharp-waves (SPWs) and neuronal firing in CA1 area. Moreover, optogenetic stimulation of CA1 pyramidal neurons fails to activate the local circuits in the neonatal PFC. These deficits that persist until pre-juvenile development are due to dendrite sparsification and loss of spines of CA1 pyramidal neurons. As a long-term consequence, DISC1 knock-down in immune-challenged mice leads to poorer recognition memory at pre-juvenile age. Thus, besides PFC, hippocampal CA1 area has a critical role for the developmental miswiring and long-lasting cognitive impairment related to mental illness.Significance StatementDevelopmental miswiring within prefrontal-hippocampal networks has been proposed to account for cognitive impairment in mental disorders. Indeed, during development, long before the emergence of cognitive deficits, the functional coupling within these networks is reduced in mouse models of disease. However, the cellular mechanisms of dysfunction are largely unknown. Here we combine in vivo electrophysiology and optogenetics with behavioral assessment in immune-challenged mice with hippocampus-confined DISC1 knock-down and show that pyramidal neurons in CA1 area are critical for the developmental dysfunction of prefrontal-hippocampal communication and cognitive impairment.
A New Framework for MR Diffusion Tensor Distribution
Authors: Magdoom Kulam Najmudeen , Pajevic Sinisa , Dario Gasbarra , Basser Peter J. 
Published: May 2020

AbstractThe ability to characterize heterogeneous and anisotropic water diffusion processes within macro-scopic MRI voxels non-invasively andin vivois adesideratumin biology, neuroscience, and medicine. While an MRI voxel may contain approximately a microliter of tissue, our goal is to examine intravoxel diffusion processes on the order of picoliters. Here we propose a new theoretical framework and experimental design to describe and measure such intravoxel structural heterogeneity and anisotropy. We assume that a constrained normal tensor-variate distribution (CNTVD) describes the variability of positive definite diffusion tensors within a voxel which extends its applicability to a wide range of b-values unlike existing models. We use a Monte Carlo scheme to synthesize realistic numerical diffusion tensor distribution (DTD) phantoms and invert the MR signal. We show that the signal inversion is well-posed and estimate the CNTVD parameters parsimoniously by exploiting the different symmetries of the mean and covariance tensors of CNTVD. The robustness of the estimation pipeline is assessed by adding noise to calculated MR signals and compared with the ground truth. A family of invariant parameters which characterize microscopic shape, size and orientation heterogeneity within a voxel are also presented.
Metabolic and haemodynamic resting-state connectivity of the human brain: a high-temporal resolution simultaneous BOLD-fMRI and FDG-fPET multimodality study
Authors: Jamadar Sharna D , Ward Phillip GD , Liang Emma Xingwen , Orchard Edwina R , Chen Zhaolin , Egan Gary F 
Published: May 2020

AbstractSimultaneous FDG-PET/fMRI ([18F]-fluorodeoxyglucose positron emission tomography functional magnetic resonance imaging) provides the capacity to image two sources of energetic dynamics in the brain – glucose metabolism and haemodynamic response. Functional fMRI connectivity has been enormously useful for characterising interactions between distributed brain networks in humans. Metabolic connectivity based on static FDG-PET has been proposed as a biomarker for neurological disease; but static FDG-PET cannot be used to estimate subjectlevel measures ofconnectivity, only across-subjectcovariance. Here, we applied high-temporal resolution constant infusion fPET to measure subject-level metabolic connectivity simultaneously with fMRI connectivity. fPET metabolic connectivity was characterised by fronto-parietal connectivity within and between hemispheres. fPET metabolic connectivity showed moderate similarity with fMRI primarily in superior cortex and frontoparietal regions. Significantly, fPET metabolic connectivity showed little similarity with static FDG-PET metabolic covariance, indicating that metabolic brain connectivity is a non-ergodic process whereby individual brain connectivity cannot be inferred from group level metabolic covariance. Our results highlight the complementary strengths of fPET and fMRI in measuring the intrinsic connectivity of the brain, and open up the opportunity for novel fundamental studies of human brain connectivity as well as multi-modality biomarkers of neurological diseases.
Actin reorganization at the centrosomal area and the immune synapse regulates polarized secretory traffic of multivesicular bodies in T lymphocytes
Authors: Bello-Gamboa Ana , Velasco Marta , Moreno Solange , Herranz Gonzalo , Ilie Roxana , Huetos Silvia , Dávila Sergio , Sánchez Alicia , de la Serna Jorge Bernardino , Calvo Víctor , Izquierdo Manuel 
Published: May 2020

ABSTRACTT-cell receptor stimulation induces the convergence of multivesicular bodies towards the microtubule-organizing center (MTOC) and the polarization of the MTOC to the immune synapse (IS). These events lead to exosome secretion at the IS. We describe here that upon IS formation centrosomal area F-actin decreased concomitantly with MTOC polarization to the IS. PKCδ-interfered T cell clones showed a sustained level of centrosomal area F-actin associated with defective MTOC polarization. We analysed the contribution of two actin cytoskeleton-regulatory proteins, FMNL1 and paxillin, to the regulation of cortical and centrosomal F-actin networks. FMNL1β phosphorylation and F-actin reorganization at the IS were inhibited in PKCδ-interfered clones. F-actin depletion at the central region of the IS, a requirement for MTOC polarization, was associated with FMNL1β phosphorylation at its C-terminal, autoregulatory region. Interfering all FMNL1 isoforms prevented MTOC polarization; nonetheless, FMNL1β re-expression restored MTOC polarization in a centrosomal area F-actin reorganization-independent manner. Moreover, PKCδ-interfered clones exhibited decreased paxillin phosphorylation at the MTOC, which suggests an alternative actin cytoskeleton regulatory pathway. Our results infer that PKCδ regulates MTOC polarization and secretory traffic leading to exosome secretion in a coordinated manner by means of two distinct pathways, one involving FMNL1β regulation and controlling F-actin reorganization at the IS, and the other, comprising paxillin phosphorylation potentially controlling centrosomal area F-actin reorganization.
Uclacyanin proteins are required for lignified nanodomain formation within Casparian strips
Authors: Reyt Guilhem , Chao Zhenfei , Flis Paulina , Castrillo Gabriel , Chao Dai-Yin , Salt David E. 
Published: May 2020

AbstractCasparian strips (CS) are cell wall modifications of vascular plants restricting extracellular free diffusion into and out the vascular system. This barrier plays a critical role in controlling the acquisition of nutrients and water necessary for normal plant development. CS are formed by the precise deposition of a band of lignin approximately 2 μm wide and 150 nm thick spanning the apoplastic space between adjacent endodermal cells. Here, we identified a copper-containing protein, Uclacyanin1 (UCC1) that is sub-compartmentalised within the CS. UCC1 forms a central CS nanodomain in comparison with other CS-located proteins that are found to be mainly accumulated at the periphery of the CS. We found that loss-of-function of two uclacyanins (UCC1andUCC2) reduces lignification specifically in this central CS nanodomain, revealing a nano-compartmentalised machinery for lignin polymerisation. This lack of lignification leads to increased endodermal permeability, and consequently to a loss of mineral nutrient homeostasis.
Versatile live-cell activity analysis platform for characterization of neuronal dynamics at single-cell and network level
Authors: Yuan Xinyue , Schröter Manuel , Obien Marie Engelene J. , Fiscella Michele , Gong Wei , Kikuchi Tetsuhiro , Odawara Aoi , Noji Shuhei , Suzuki Ikuro , Takahashi Jun , Hierlemann Andreas , Frey Urs 
Published: May 2020

AbstractChronic imaging of neuronal networksin vitrohas provided fundamental insights into mechanisms underlying neuronal function. Existing labeling and optical imaging methods, however, cannot be used for continuous and long-term recordings of the dynamics and evolution of neuronal networks, as fluorescence indicators can cause phototoxicity. Here, we introduce a versatile platform for label-free, comprehensive and detailed electrophysiological live-cell imaging of various neurogenic cells and tissues over extended times. We report on a novel dual-mode high-density microelectrode array, which can simultaneously record in i) full-frame mode with 19,584 recording sites and ii) high-signal-to-noise mode with 246 channels. We set out to demonstrate the capabilities of this platform with recordings from primary and iPSC-derived neuronal cultures and tissue preparations over several weeks, providing detailed morpho-electrical phenotypic parameters at subcellular, cellular and network level. Moreover, we developed reliable analysis tools with drastically increased throughput for extracting axonal morphology and conduction parameters.
Examining the neural antecedents of tics in Tourette syndrome using electroencephalography
Authors: Maiquez Barbara Morera , Jackson Georgina M. , Jackson Stephen R. 
Published: May 2020

AbstractTourette syndrome (TS) is a neurological disorder of childhood onset that is characterised by the occurrence of motor and vocal tics. TS is associated with cortical-striatal-thalamic-cortical circuit [CSTC] dysfunction and hyper-excitability of cortical limbic and motor regions that are thought to lead to the occurrence of tics. Importantly, individuals with TS often report that their tics are preceded by ‘premonitory sensory/urge phenomena’ (PU) that are described as uncomfortable bodily sensations that precede the execution of a tic and are experienced as a strong urge for motor discharge. While tics are most often referred to as involuntary movements, it has been argued that tics should be viewed as voluntary movements that are executed in response to the presence of PU and bring temporary relief from the uncomfortable bodily sensations that are associated with PU. This issue remains unresolved but has very important implications for the design of clinical interventions for TS. To investigate this issue further, we conducted a study using electroencephalography (EEG). Specifically, we recorded movement-related EEG (mu and beta band oscillations) during (a) the immediate period leading up to the execution of voluntary movements by a group of individuals with TS and a group of matched healthy control participants, and (b) the immediate period leading up to the execution of a tic in a group of individuals with TS. We demonstrate that movement-related mu and beta band oscillations arenotobserved prior to tics in individuals with TS. We interpret this effect as reflecting the greater involvement of a network of brain areas, including the insular and cingulate cortices, basal ganglia nuclei, and the cerebellum, in the generation of tics in TS. We also show that beta-band desynchronization does occur when individuals with TS initiate voluntary movements, but, in contrast to healthy controls, desynchronization of mu-band oscillations is not observed during the execution of voluntary movements for individuals with TS. We interpret this finding as reflecting a dysfunction of physiological inhibition in TS, thereby contributing to an impaired ability to suppress neuronal populations that may compete with movement preparation processes.
A new species ofMesopolobusWestwood (Hymenoptera, Pteromalidae) from black locust crops
Authors: László Zoltán , Lakatos K. Tímea , Dénes Avar-Lehel 
Published: May 2020

AbstractA new species of the genusMesopolobusWestwood,Mesopolobus robiniaesp. n., is described and illustrated from east-central Europe (Romania and Hungary). The species was reared from black locust (Robinia pseudoacacia) seedpod samples, where it most likely parasitizes the black locust’s seed predatorBruchophagus robiniaeZerova, 1970. Here we present the new species and report on its ecological relationships within the European seed predator community of black locust. We also give details regarding type material and type locality, a detailed description with images, a differential diagnosis of the new species, and a modification to the identification key published by Graham (1969), that distinguishes this new species from closely related species. In addition, we provide information on the distribution, biology and results of barcoding analysis. We also provide the DNA sequence data to complement the morphological taxonomy.
Adult-born granule cells support pathological microcircuits in the chronically epileptic dentate gyrus
Authors: Sparks FT , Liao Z , Li W , Soltesz I , Losonczy A 
Published: May 2020

AbstractTemporal lobe epilepsy (TLE) is characterized by recurrent seizures driven by synchronous neuronal activity. The dentate gyrus (DG) region of the hippocampal formation is highly reorganized in chronic TLE; in particular, pathological remodeling of the “dentate gate” is thought to open up pathological conduction pathways for synchronous discharges and seizures in the mesial temporal lobe. However, this pathophysiological framework lacks a mechanistic explanation of how macroscale synchronous dynamics emerge from alterations of the DG at the microcircuit level. In particular, the relative contribution of developmentally defined subpopulations of adult-born (abGCs) and mature (mGCs) granule cells to epileptiform network events remains unknown. To address this question, we optically recorded activity dynamics of identified populations of abGCs and mGCs during interictal epileptiform discharges (IEDs) in mice with chronic TLE. We find that disjoint subsets of IEDs differentially recruit abGC and mGC populations. We used these observations to develop a neural topic modeling framework, under which we find that the epileptic DG network organizes into disjoint, cell-type specific pathological ensembles, a subset of which are recruited by each IED. We found that statistics of this ensemble structure are highly conserved across animals, with abGCs disproportionately driving network activity in the epileptic DG during IEDs. Our results provide the firstin vivocharacterization of activity dynamics of identified GC subpopulations in the epileptic DG, the first microcircuit-level correlates of IEDsin vivo, and reveal a specific contribution of abGCs to interictal epileptic events.HighlightsWe relate electrographic signatures of epilepsy to microcircuit dynamics at single-cell resolutionThe chronically epileptic dentate gyrus granule cell network is organized in lineage-specific pathological ensemblesA novel generative model framework for ensemble recruitment relates local field potential signatures to microcircuit activation during interictal epileptiform dischargesAdult-born granule cell-dominated ensembles are disproportionately represented among the inferred ensemblesThe most active ensemble during an interictal epileptiform discharge can be decoded directly from the local field potential spectrumThis Latent Ensemble Recruitment model of cell recruitment by interictal events is the first application of Bayesian topic modeling toin vivotwo-photon calcium imaging data
Pre-target oculomotor inhibition reflects temporal orienting rather than certainty
Authors: Tal-Perry Noam , Yuval-Greenberg Shlomit 
Published: May 2020

AbstractRecent studies suggested that eye movements are linked to temporal predictability. These studies manipulated predictability by setting the cue-target interval (foreperiod) to be fixed or random throughout block. Findings showed that pre-target oculomotor behavior was reduced in the fixed relative to the random condition. This effect was interpreted as reflecting the formation of temporal expectation. However, it is unknown whether the effect is driven by target-specific temporal orienting, or rather a result of a more context-dependent state of certainty that participants may experience during blocks with a high predictability rate.In thus study we dissociated certainty and orienting in a tilt-discrimination task. In each trial, a temporal cue (fixation color change) was followed by a tilted grating-patch. The foreperiod distribution was varied between blocks to be either fully fixed (same foreperiod in 100% of trials), mostly fixed (80% of trials with one foreperiod and 20% with another) or random (five foreperiods in equal probabilities). The two hypotheses led to different prediction models which were tested against the experimental data.Results were consistent with the orienting hypothesis and inconsistent with the certainty hypothesis, supporting the link between oculomotor inhibition and temporal orienting and its validity as a temporal expectations marker.
Integrator terminates promoter-proximal Pol II to generateC. eleganspiRNA precursors
Authors: Beltran Toni , Pahita Elena , Ghosh Subhanita , Lenhard Boris , Sarkies Peter 
Published: May 2020

AbstractPiwi-interacting RNAs (piRNAs) play key roles in germline development and genome defence in metazoans. InC. elegans, piRNAs are transcribed from >15000 discrete genomic loci by RNA polymerase II, resulting in 28 nt short-capped piRNA precursors. Here we investigate transcription termination at piRNA loci. We show that the Integrator complex, which terminates snRNA transcription, is recruited to piRNA loci. We show that the catalytic activity of Integrator cleaves nascent capped piRNA precursors associated with promoter-proximal Pol II, resulting in termination of transcription. Loss of Integrator activity, however, does not result in transcriptional readthrough at the majority of piRNA loci. Our results draw new parallels between snRNA and piRNA biogenesis in nematodes, and provide evidence of a role for the Integrator complex as a terminator of promoter-proximal RNA polymerase II.Highlights- Integrator localises to sites of piRNA biogenesis in nematodes- Integrator cleaves nascent RNAs associated with promoter-proximal Pol II at piRNA loci to release short capped piRNA precursors from chromatin- Repression of Pol II elongation at the majority of piRNA loci is independent of Integrator
Shared genetic etiology of age of menarche and socioeconomic variables: No evidence for genetic overlap with psychiatric traits
Authors: Steppan Martin 
Published: May 2020

AbstractEarlier research has shown observational associations of early pubertal timing and poor mental health. Mendelian randomization (MR) studies demonstrated a transient effect of pubertal timing on mental health during adolescence, but not later in life. MR studies also showed that there is a likely causal association of pubertal timing with life history traits. However, the strongest causal effects and genetic correlations with age of menarche have been found for Body Mass Index (BMI). As high BMI is associated with lower socioeconomic status and with poor mental health, the shared genetic etiology of socioeconomic status, BMI and poor mental health is not yet fully understood. BMI correlates negatively with socioeconomic status and several mental health outcomes. Despite their substantial genetic overlap, the underlying genetic etiology of these phenotypes remains unclear. In this study we applied Linkage Disequi-librium score regression to test genetic correlations of age of menarche with 33 socioeconomic, life history, social interaction, personality and psychiatric traits, and BMI. We further applied spectral decomposition and hierarchical clustering to the genetic correlation matrix. After controlling for multiple testing, we could only identify significant genetic correlations with BMI and three socioeconomic traits (household income, deprivation and parental longevity). The results suggest that genome-wide association studies on age of menarche also contain socioeconomic information. Future MR studies aiming to test the unconfounded effect of pubertal timing should make sure that genetic instruments have no pleiotropic effect on socioeconomic variables, or (if possible) also control for socioeconomic status on the observational level.
Constitutive activation of cellular immunity underlies the evolution of resistance to infection
Authors: Leitão Alexandre B. , Arunkumar Ramesh , Day Jonathan P. , Geldman Emma M. , Jiggins Francis M. 
Published: May 2020

AbstractOrganisms rely on inducible and constitutive immune defences to combat infection. Constitutive immunity enables a rapid response to infection but may carry a cost for uninfected individuals, leading to the prediction that it will be favoured when infection rates are high. When we exposed populations ofDrosophila melanogasterto intense parasitism by the parasitoid waspLeptopilina boulardi, they evolved resistance by developing a more reactive cellular immune response. Using single-cell RNA sequencing, we found that immune-inducible genes had become constitutively upregulated. This was the result of resistant larvae differentiating precursors of specialized immune cells called lamellocytes that were previously only produced after infection. Therefore, populations evolved resistance by genetically hard-wiring an induced immune response to become constitutive.