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Advancements in brain imaging techniques have significantly expanded the size and complexity of real-time neuroimaging and behavioral data. However, identifying patterns, trends and synchronies within these datasets presents a significant computational challenge. Here, we demonstrate an approach that can translate time-varying neuroimaging data into unique audiovisualizations consisting of audible representations of dynamic data merged with simplified, color-coded movies of spatial components and behavioral recordings. Multiple variables can be encoded as different musical instruments, letting the observer differentiate and track multiple dynamic parameters in parallel. This representation enables intuitive assimilation of these datasets for behavioral correlates and spatiotemporal features such as patterns, rhythms and motifs that could be difficult to detect through conventional data interrogation methods. These audiovisual representations provide a novel perception of the organization and patterns of real-time activity in the brain, and offer an intuitive and compelling method for complex data visualization for a wider range of applications. [ABSTRACT FROM AUTHOR]

Nonlocal thermal transport in magnetized plasmas is studied theoretically and numerically with the Vlasov–Fokker–Planck (VFP) model, in which the magnetic field has nonzero components both perpendicular to and along the temperature gradient. Nonlocal heat transport is found in both the longitudinal and transverse directions, provided the temperature gradients are sufficiently large. The magnetic field tends to reduce the nonlocality of the thermal transport in the direction perpendicular to the magnetic field, i.e., the difference between the heat fluxes predicted by the Braginskii theory and the VFP simulation decreases with increasing magnetic field strength. When the initial temperature gradient is steep, the nonlocal heat flux depends not only on the present temperature profile, but also on its time history. Moreover, the contribution of high-order terms in the spherical harmonic expansion of the electron distribution function becomes important for a magnetized plasma, in particular for thermal transport in the direction perpendicular to the temperature gradient. [ABSTRACT FROM AUTHOR]

The cognitive abilities that characterize humans are thought to emerge from unique features of the cortical circuit architecture of the human brain, which include increased cortico–cortical connectivity. However, the evolutionary origin of these changes in connectivity and how they affected cortical circuit function and behaviour are currently unknown. The human-specific gene duplication SRGAP2C emerged in the ancestral genome of the Homo lineage before the major phase of increase in brain size1,2. SRGAP2C expression in mice increases the density of excitatory and inhibitory synapses received by layer 2/3 pyramidal neurons (PNs)3–5. Here we show that the increased number of excitatory synapses received by layer 2/3 PNs induced by SRGAP2C expression originates from a specific increase in local and long-range cortico–cortical connections. Mice humanized for SRGAP2C expression in all cortical PNs displayed a shift in the fraction of layer 2/3 PNs activated by sensory stimulation and an enhanced ability to learn a cortex-dependent sensory-discrimination task. Computational modelling revealed that the increased layer 4 to layer 2/3 connectivity induced by SRGAP2C expression explains some of the key changes in sensory coding properties. These results suggest that the emergence of SRGAP2C at the birth of the Homo lineage contributed to the evolution of specific structural and functional features of cortical circuits in the human cortex.The human-specific gene duplication SRGAP2C is identified as a modifier of structural and functional features of cortical circuits leading to improved behavioural performance that may have allowed the emergence of cognitive properties characterizing the human brain. [ABSTRACT FROM AUTHOR]

Our understanding of signaling pathways regulating the cell fate of human embryonic stem cells (hESCs) is limited. Calcineurin‐NFAT signaling is associated with a wide range of biological processes and diseases. However, its role in controlling hESC fate remains unclear. Here, we report that calcineurin A gamma and the NFATc3/SRPX2 axis control the expression of lineage and epithelial–mesenchymal transition (EMT) markers in hESCs. Knockdown of PPP3CC, the gene encoding calcineurin A gamma, or NFATC3, downregulates certain markers both at the self‐renewal state and during differentiation of hESCs. Furthermore, NFATc3 interacts with c‐JUN and regulates the expression of SRPX2, the gene encoding a secreted glycoprotein known as a ligand of uPAR. We show that SRPX2 is a downstream target of NFATc3. Both SRPX2 and uPAR participate in controlling expression of lineage and EMT markers. Importantly, SRPX2 knockdown diminishes the upregulation of multiple lineage and EMT markers induced by co‐overexpression of NFATc3 and c‐JUN in hESCs. Together, this study uncovers a previously unknown role of calcineurin A gamma and the NFATc3/SRPX2 axis in modulating the fate determination of hESCs. [ABSTRACT FROM AUTHOR]

There are errors in Figs 1D and 3C. The incorrect reference protein blot images were included for Fig 1D; IB: -tubulin and Fig 3C; IB: -tubulin. Please see the correct figures here: Graph: Fig 1 LSD1 catalyzes lysine demethylation of IFITM3 at K88.(A) HEK293T cells grown in six-well plates were transfected with HA-IFITM3 and FLAG-LSD1. [Extracted from the article]

The histone demethylase LSD1 has been known as a key transcriptional coactivator for DNA viruses such as herpes virus. Inhibition of LSD1 was found to block viral genome transcription and lytic replication of DNA viruses. However, RNA virus genomes do not rely on chromatin structure and histone association, and the role of demethylase activity of LSD1 in RNA virus infections is not anticipated. Here, we identify that, contrary to its role in enhancing DNA virus replication, LSD1 limits RNA virus replication by demethylating and activating IFITM3 which is a host restriction factor for many RNA viruses. We have found that LSD1 is recruited to demethylate IFITM3 at position K88 under IFNα treatment. However, infection by either Vesicular Stomatitis Virus (VSV) or Influenza A Virus (IAV) triggers methylation of IFITM3 by promoting its disassociation from LSD1. Accordingly, inhibition of the enzymatic activity of LSD1 by Trans-2-phenylcyclopropylamine hydrochloride (TCP) increases IFITM3 monomethylation which leads to more severe disease outcomes in IAV-infected mice. In summary, our findings highlight the opposite role of LSD1 in fighting RNA viruses comparing to DNA viruses infection. Our data suggest that the demethylation of IFITM3 by LSD1 is beneficial for the host to fight against RNA virus infection. [ABSTRACT FROM AUTHOR]

Although resting-state functional magnetic resonance imaging (fMRI) studies have observed dynamically changing brain-wide networks of correlated activity, fMRI's dependence on hemodynamic signals makes results challenging to interpret. Meanwhile, emerging techniques for real-time recording of large populations of neurons have revealed compelling fluctuations in neuronal activity across the brain that are obscured by traditional trial averaging. To reconcile these observations, we use wide-field optical mapping to simultaneously record pan-cortical neuronal and hemodynamic activity in awake, spontaneously behaving mice. Some components of observed neuronal activity clearly represent sensory and motor function. However, particularly during quiet rest, strongly fluctuating patterns of activity across diverse brain regions contribute greatly to interregional correlations. Dynamic changes in these correlations coincide with changes in arousal state. Simultaneously acquired hemodynamics depict similar brain-state-dependent correlation shifts. These results support a neural basis for dynamic resting-state fMRI, while highlighting the importance of brain-wide neuronal fluctuations in the study of brain state. [Display omitted] • Interregional neural correlations reveal a compelling functional cortical topography • Ongoing neural activity shows time-varying correlation structure across the cortex • Neural activity correlation patterns can predict behavioral states and arousal levels • Brain hemodynamics recapitulate the dynamics of neuronal correlation patterns Shahsavarani et al. investigate the dynamic correlation structure of cortex-wide neuronal activity and hemodynamics in awake mice using wide-field optical mapping. They demonstrate a relationship between neuronal correlation dynamics, arousal level, and behavior that is reproduced by hemodynamic correlations. Results support a neural basis for fMRI-based dynamic functional connectivity mapping. [ABSTRACT FROM AUTHOR]

Although modern techniques such as two-photon microscopy can now provide cellular-level three-dimensional imaging of the intact living brain, the speed and fields of view of these techniques remain limited. Conversely, two-dimensional wide-field optical mapping (WFOM), a simpler technique that uses a camera to observe large areas of the exposed cortex under visible light, can detect changes in both neural activity and haemodynamics at very high speeds. Although WFOM may not provide single-neuron or capillarylevel resolution, it is an attractive and accessible approach to imaging large areas of the brain in awake, behaving mammals at speeds fast enough to observe widespread neural firing events, as well as their dynamic coupling to haemodynamics. Although such wide-field optical imaging techniques have a long history, the advent of genetically encoded fluorophores that can report neural activity with high sensitivity, as well as modern technologies such as light emitting diodes and sensitive and high-speed digital cameras have driven renewed interest in WFOM. To facilitate the wider adoption and standardization of WFOM approaches for neuroscience and neurovascular coupling research, we provide here an overview of the basic principles of WFOM, considerations for implementation of wide-field fluorescence imaging of neural activity, spectroscopic analysis and interpretation of results. [ABSTRACT FROM AUTHOR]

Recent success in the derivation of haploid embryonic stem cells (haESCs) from mouse via parthenogenesis and androgenesis has enabled genetic screening in mammalian cells and generation of gene-modified animals. However, whether haESCs can be derived from primates remains unknown. Here, we report the derivation of haESCs from parthenogenetic blastocysts of Macaca fascicularis monkeys. These cells, termed as PG-haESCs, are pluripotent and can differentiate to cells of three embryonic germ layers in vitro or in vivo. Interestingly, the haploidy of one monkey PG-haESC line (MPH1) is more stable compared with that of the other one (MPH2), as shown by the existence of haploid cells for more than 140 days without fluorescence-activated cell sorting (FACS) enrichment of haploid cells. Importantly, transgenic monkey PG-haESC lines can be generated by lentivirus- and piggyBac transposon-mediated gene transfer. Moreover, genetic screening is feasible in monkey PG-haESCs. Our results demonstrate that PG-haESCs can be generated from monkeys, providing an ideal tool for genetic analyses in primates. [ABSTRACT FROM AUTHOR]

Objective: Although amyloid-beta (Aβ) peptide deposition into insoluble plaques is a pathological hallmark of Alzheimer disease; soluble oligomeric Aβ has been hypothesized to more directly underlie impaired learning and memory in dementia of the Alzheimer type. However, the lack of a sensitive, specific, and quantitative assay for Aβ oligomers has hampered rigorous tests of this hypothesis.Methods: We developed a plate-based single molecule counting fluorescence immunoassay for oligomeric Aβ sensitive to low pg/ml concentrations of synthetic Aβ dimers using the same Aβ-specific monoclonal antibody to both capture and detect Aβ. The Aβ oligomer assay does not recognize monomeric Aβ, amyloid precursor protein, or other non-Aβ peptide oligomers.Results: Aβ oligomers were detected in aqueous cortical lysates from patients with dementia of the Alzheimer type and nondemented patients with Aβ plaque pathology. However, Aβ oligomer concentrations in demented patients' lysates were tightly correlated with Aβ plaque coverage (r = 0.88), but this relationship was weaker in those from nondemented patients (r = 0.30) despite equivalent Aβ plaque pathology. The ratio of Aβ oligomer levels to plaque density fully distinguished demented from nondemented patients, with no overlap between groups in this derived variable. Other Aβ and plaque measures did not distinguish demented from nondemented patients. Aβ oligomers were not detected in cerebrospinal fluid with this assay.Interpretation: The results raise the intriguing hypothesis that the linkage between plaques and oligomers may be a key pathophysiological event underlying dementia of the Alzheimer type. This Aβ oligomer assay may be useful for many tests of the oligomer hypothesis. [ABSTRACT FROM AUTHOR]

Objective: Although amyloid-beta (Aβ) peptide deposition into insoluble plaques is a pathological hallmark of Alzheimer disease; soluble oligomeric Aβ has been hypothesized to more directly underlie impaired learning and memory in dementia of the Alzheimer type. However, the lack of a sensitive, specific, and quantitative assay for Aβ oligomers has hampered rigorous tests of this hypothesis. Methods: We developed a plate-based single molecule counting fluorescence immunoassay for oligomeric Aβ sensitive to low pg/ml concentrations of synthetic Aβ dimers using the same Aβ-specific monoclonal antibody to both capture and detect Aβ. The Aβ oligomer assay does not recognize monomeric Aβ, amyloid precursor protein, or other non-Aβ peptide oligomers. Results: Aβ oligomers were detected in aqueous cortical lysates from patients with dementia of the Alzheimer type and nondemented patients with Aβ plaque pathology. However, Aβ oligomer concentrations in demented patients' lysates were tightly correlated with Aβ plaque coverage ( r = 0.88), but this relationship was weaker in those from nondemented patients ( r = 0.30) despite equivalent Aβ plaque pathology. The ratio of Aβ oligomer levels to plaque density fully distinguished demented from nondemented patients, with no overlap between groups in this derived variable. Other Aβ and plaque measures did not distinguish demented from nondemented patients. Aβ oligomers were not detected in cerebrospinal fluid with this assay. Interpretation: The results raise the intriguing hypothesis that the linkage between plaques and oligomers may be a key pathophysiological event underlying dementia of the Alzheimer type. This Aβ oligomer assay may be useful for many tests of the oligomer hypothesis. ANN NEUROL 2013 [ABSTRACT FROM AUTHOR]

Cortical spreading depolarizations (CSDs) are increasingly suspected to play an exacerbating role in a range of acute brain injuries, including stroke, possibly through their interactions with cortical blood flow. We use simultaneous wide-field imaging of neural activity and hemodynamics in Thy1-GCaMP6f mice to explore the neurovascular dynamics of CSDs during and following Rose Bengal-mediated photothrombosis. CSDs are observed in all mice as slow-moving waves of GCaMP fluorescence extending far beyond the photothrombotic area. Initial CSDs are accompanied by profound vasoconstriction and leave residual oligemia and ischemia in their wake. Later, CSDs evoke variable responses, from constriction to biphasic to vasodilation. However, CSD-evoked vasoconstriction is found to be more likely during rapid, high-amplitude CSDs in regions with stronger oligemia and ischemia, which, in turn, worsens after each repeated CSD. This feedback loop may explain the variable but potentially devastating effects of CSDs in the context of acute brain injury. [Display omitted] • Pan-cortical imaging of neural activity in mice reveals CSDs after photothrombosis • Simultaneous hemodynamic imaging reveals varying vascular responses to each CSD • Successive CSDs induce worsening oligemia and ischemia in distal cortical areas • Vascular response dependence on baseline cortical state may exacerbate damage Zhao et al. use wide-field optical mapping of neuronal and hemodynamic activity in mice, capturing CSDs immediately following photothrombosis. Initial CSDs are accompanied by strong vasoconstriction, leaving persistent oligemia and ischemia. Region-dependent neurovascular responses to subsequent CSDs demonstrate a potential vicious cycle of CSD-dependent damage in acute brain injury. [ABSTRACT FROM AUTHOR]

Diffusely infiltrating gliomas are known to cause alterations in cortical function, vascular disruption, and seizures. These neurological complications present major clinical challenges, yet their underlying mechanisms and causal relationships to disease progression are poorly characterized. Here, we follow glioma progression in awake Thy1-GCaMP6f mice using in vivo wide-field optical mapping to monitor alterations in both neuronal activity and functional hemodynamics. The bilateral synchrony of spontaneous neuronal activity gradually decreases in glioma-infiltrated cortical regions, while neurovascular coupling becomes progressively disrupted compared to uninvolved cortex. Over time, mice develop diverse patterns of high amplitude discharges and eventually generalized seizures that appear to originate at the tumors' infiltrative margins. Interictal and seizure events exhibit positive neurovascular coupling in uninfiltrated cortex; however, glioma-infiltrated regions exhibit disrupted hemodynamic responses driving seizure-evoked hypoxia. These results reveal a landscape of complex physiological interactions occurring during glioma progression and present new opportunities for exploring novel biomarkers and therapeutic targets. • Glioma disrupts neural synchrony between bilateral cortical regions • Tumor development is accompanied by local changes in neurovascular coupling • Wide-field GCaMP imaging reveals glioma-induced interictal discharges and seizures • Altered neurovascular coupling drives hypoperfusion of the tumor during seizures The glioma microenvironment involves multiple cell types. Montgomery et al. utilize in vivo wide-field cortical imaging in awake mice to characterize both neuronal activity and hemodynamics during glioma progression. Observed tumor-localized alterations in neuronal synchrony and neurovascular coupling, interictal events, and seizures reveal potential functional contributions to glioma progression. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Histone demethylase LSD1 restricts influenza A virus infection by erasing IFITM3-K88 monomethylation" which appeared in the 2017 issue.