A three-dimensional, population-based average of the C57BL/6 mouse brain from DAPI-stained coronal slices

Social media has become a popular means for people to consume and share the news. At the same time, however, it has also enabled the wide dissemination of fake news, that is, news with intentionally false information, causing significant negative effects on society. To mitigate this problem, the research of fake news detection has recently received a lot of attention. Despite several existing computational solutions on the detection of fake news, the lack of comprehensive and community-driven fake news data sets has become one of major roadblocks. Not only existing data sets are scarce, they do not contain a myriad of features often required in the study such as news content, social context, and spatiotemporal information. Therefore, in this article, to facilitate fake news-related research, we present a fake news data repository FakeNewsNet, which contains two comprehensive data sets with diverse features in news content, social context, and spatiotemporal information. We present a comprehensive description of the FakeNewsNet, demonstrate an exploratory analysis of two data sets from different perspectives, and discuss the benefits of the FakeNewsNet for potential applications on fake news study on social media.

The hippocampus plays a critical role in learning and memory and higher cognitive functions, and its dysfunction has been implicated in various neuropathological disorders. Electrophysiological recording undertaken in live brain slices is one of the most powerful tools for investigating hippocampal cellular and network activities. The plane for cutting the slices determines which afferent and/or efferent connections are best preserved, and there are three commonly used slices: hippocampal-entorhinal cortex (HEC), coronal and transverse. All three slices have been widely used for studying the major afferent hippocampal pathways including the perforant path (PP), the mossy fibers (MFs) and the Schaffer collaterals (SCs). Surprisingly, there has never been a systematic investigation of the anatomical and functional consequences of slicing at a particular angle. In the present study, we focused on how well fiber pathways are preserved from the entorhinal cortex (EC) to the hippocampus, and within the hippocampus, in slices generated by sectioning at different angles. The postmortem neural tract tracer 1,1′-dioctadecyl-3,3,3′3′-tetramethylindocarbocyanine perchlorate (DiI) was used to label afferent fibers to hippocampal principal neurons in fixed slices or whole brains. Laser scanning confocal microscopy was adopted for imaging DiI-labeled axons and terminals. We demonstrated that PP fibers were well preserved in HEC slices, MFs in both HEC and transverse slices and SCs in all three types of slices. Correspondingly, field excitatory postsynaptic potentials (fEPSPs) could be consistently evoked in HEC slices when stimulating PP fibers and recorded in stratum lacunosum-moleculare (sl-m) of area CA1, and when stimulating the dentate granule cell layer (gcl) and recording in stratum lucidum (sl) of area CA3. The MF evoked fEPSPs could not be recorded in CA3 from coronal slices. In contrast to our DiI-tracing data demonstrating severely truncated PP fibers in coronal slices, fEPSPs could still be recorded in CA1 sl-m in this plane, suggesting that an additional afferent fiber pathway other than PP might be involved. The present study increases our understanding of which hippocampal pathways are best preserved in the three most common brain slice preparations, and will help investigators determine the appropriate slices to use for physiological studies depending on the subregion of interest.

Publication bias has the potential to adversely impact clinical decision making and patient health if alternative decisions would have been made had there been complete publication of evidence. The objective of our analysis was to determine if earlier publication of the complete evidence on rosiglitazone's risk of myocardial infarction (MI) would have changed clinical decision making at an earlier point in time. We tested several methods for adjustment of publication bias to assess the impact of potential time delays to identifying the MI effect. We then performed a cumulative meta-analysis (CMA) for both published studies (published-only data set) and all studies performed (comprehensive data set). We then created an adjusted data set using existing methods of adjustment for publication bias (Harbord regression, Peter's regression, and the nonparametric trim and fill method) applied to the limited data set. Finally, we compared the time to the decision threshold for each data set using CMA. Although published-only and comprehensive data sets did not provide notably different final summary estimates [OR=1.4 (95 percent confidence interval [CI]: .95-2.05) and 1.42 (95 percent CI: 1.03-1.97)], the comprehensive data set reached the decision threshold 36months earlier than the published-only data set. All three adjustment methods tested did not show a differential time to decision threshold versus the published-only data set. Complete access to studies capturing MI risk for rosiglitazone would have led to the evidence reaching a clinically meaningful decision threshold 3years earlier.

Small-angle x-ray scattering (SAXS) imaging can differentiate tissue types based on their nanoscale molecular structure. However, characterization of the coherent scattering cross-section profile of relevant tissues is needed to optimally design SAXS imaging techniques for a variety of biomedical applications. Reported measured nervous tissue x-ray scattering cross sections under a synchrotron source have had limited agreement. We report a set of x-ray cross-section measurements obtained from planar SAXS imaging of 1 mm thick mouse brain (APP/PS1 wild-type) coronal slices using an 8 keV laboratory x-ray source. Two characteristic peaks were found at 0.96 and 1.60 nm−1 attributed to myelin. The peak intensities varied by location in the slice. We found that regions of gray matter, white matter, and corpus callosum could be segmented by their increasing intensities of myelin peaks respectively. Measured small-angle x-ray scattering cross sections were then used to define brain tissue scattering properties in a GPU-accelerated Monte Carlo simulation of SAXS computed tomography (CT) using a higher monochromatic x-ray energy (20 keV) to study design trade-offs for noninvasive in vivo SAXS imaging on a small-animal head including radiation dose, signal-to-noise ratio (SNR), and the effect of skull presence on the previous two metrics. Simulation results show the estimated total dose to the mouse head for a single SAXS-CT slice was 149.4 mGy. The pixel SNR was approximately 30.8 for white matter material whether or not a skull was present. In this early-stage proof-of-principle work, we have demonstrated our brain cross-section data and simulation tools can be used to assess optimal instrument parameters for dedicated small-animal SAXS-CT prototypes.

Scanning small spots of laser light allows mapping of synaptic circuits in brain slices from transgenic mice expressing channelrhodopsin-2 (ChR2). These light spots photostimulate presynaptic neurons expressing ChR2, while postsynaptic responses can be monitored in neurons that do not express ChR2. Correlating the location of the light spot with the amplitude of the postsynaptic response elicited at that location yields maps of the spatial organization of the synaptic circuits. This approach yields maps within minutes, which is several orders of magnitude faster than can be achieved with conventional paired electrophysiological methods. We have applied this high-speed technique to map local circuits in many brain regions. In cerebral cortex, we observed that maps of excitatory inputs to pyramidal cells were qualitatively different from those measured for interneurons within the same layers of the cortex. In cerebellum, we have used this approach to quantify the convergence of molecular layer interneurons on to Purkinje cells. The number of converging interneurons is reduced by treatment with gap junction blockers, indicating that electrical synapses between interneurons contribute substantially to the spatial convergence. Remarkably, gap junction blockers affect convergence in sagittal cerebellar slices but not in coronal slices, indicating sagittal polarization of electrical coupling between interneurons. By measuring limb movement or other forms of behavioral output, this approach also can be used in vivo to map brain circuits non-invasively. In summary, ChR2-mediated high-speed mapping promises to revolutionize our understanding of brain circuitry.

Labeling and Identification of Living Donor Cells in Brain Slices of Recipient Hemiparkinsonian Model Rats for Physiological Recordings: Methods for Physiological Assessments of Neural Transplantation

Source: Bosch, D., et al. Ex Vivo Optogenetic Dissection of Fear Circuits in Brain Slices. J. Vis. Exp. (2016). This video demonstrates the preparation of thin coronal brain slices from a murine brain, exposing the amygdala regions rich in synaptic connections from the medial prefrontal cortex. The slices are then recovered in oxygenated artificial cerebrospinal fluid to maintain neuronal viability.

Exploiting the information content offered by geoelectric data in an efficient manner requires careful selection of the electrode configurations to be used. This can be achieved using sequential experimental design techniques proposed over the past few years. However, these techniques become impractical when large-scale 2D or 3D experiments have to be designed. Even if sequential experimental design were applicable, acquisition of the resulting data sets would require an unreasonably large effort using traditional multielectrode arrays. We present a new, fully parallelized pole-bipole measuring strategy by which large amounts of data can be acquired swiftly. Furthermore, we introduce a new experimental design concept that is based on “complete” data sets in terms of linear independence. Complete data sets include a relatively small number of basis electrode configurations, from which any other configuration can be reconstructedby superposition. The totality of possible configurations is referred to as the comprehensive data set. We demonstrate the benefits of such reconstructions using eigenvalue analyses for the case of noise-free data. In the presence of realistic noise, such reconstructions lead to unstable results when only four-point (bipole-bipole) configurations are considered. In contrast, complete three-point (pole-bipole) data sets allow more stable reconstructions. Moreover, complete pole-bipole data sets can be acquired very efficiently with a fully parallelized system. Resolution properties of complete pole-bipole data sets are illustrated using both noise-free and noisy synthetic data sets. We also show results from a field survey performed over a buried waste disposal site, which further demonstrates the usefulness of our approach. Although this paper is restricted to 2D examples, it is trivial to extend the concept to 3D surveys, where the advantages of parallelized pole-bipole data acquisition become very significant.

Integrating neuroscience into psychiatric residency training

The dentate gyrus (DG) is a gateway that regulates seizure activity in the hippocampus. We investigated the site of action of lamotrigine (LTG), an effective anticonvulsant, in the regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) receptor-mediated excitatory synaptic transmission on DG. Evoked AMPA and NMDA receptor-mediated excitatory postsynaptic currents (eEPSCampa and eEPSCnmda) were recorded by whole-cell patch-clamp recording from the granule cells of DG in brain slice preparation of young Wistar rats (60-120 g). Exogenously applied AMPA and NMDA-induced currents and AMPA receptor-mediated miniature EPSC (mEPSCampa) were recorded in the presence of specific antagonists. LTG inhibited both eEPSCampa and eEPSCnmda, and had no effect on exogenously applied NMDA-induced current indicating LTG inhibited glutamate release. Previous studies demonstrated that alteration in glutamate concentration in synaptic cleft causes parallel changes of eEPSCampa and eEPSCnmda. Our results showed that LTG inhibited eEPSCampa significantly more than eEPSCnmda (p < 0.05), suggesting that LTG may also have blocked the postsynaptic AMPA receptor. The hypothesis is further supported by the facts that; (1) LTG (30-100 microM) inhibited direct exogenously applied AMPA-induced currents (to 90%), (2) LTG significantly reduced the amplitude, but not the frequency of mEPSCampa and asynchronous (EPSC), and (3) LTG-induced reduction of eEPSCampa was not associated with a modification of the paired-pulse ratio. To sum up, LTG exerts a postsynaptic inhibitory mechanism on the AMPA receptor. Our results demonstrate that LTG suppresses postsynaptic AMPA receptors and reduces glutamate release in granule cells of DG. The postsynaptic effect can be one of the underlying mechanisms of LTG's anticonvulsant action.

ABSTRACTThe Indian Ocean region is one among the six major cyclone prone regions in the world with an annual average of about five to six cyclones. Prior studies conducted for this region are location‐specific and confined to storm surge characteristic and associated inundation. A detailed study to develop precomputed scenarios on storm surge and inundation maps for the entire Indian coast is still lacking for emergency preparedness. An effort in this direction can drastically reduce preparedness time in the eventuality of a real cyclone approaching its landfall location for effective coastal zone management measures. The present study is a motivation in this direction leading to the generation of a comprehensive data set on storm surges and associated coastal flooding for entire Odisha coast located in the east coast of India and that can be extended to other coastal regions as well. Historically, the Odisha State experiences highest number of cyclone strikes with the highest risk of exposure to storm surge and inundation. The novelty of this study is in the preparation of a comprehensive storm data set using synthetic tracks simulated with various combinations of landfall location, angle of attack, intensity, and forward translation speed. It also generates possible storm surge and inundation associated with intensified cyclones expected in a changing climate scenario. Further, the study also correlates power dissipation index with storm tide all along this coast. The distribution of surge height follows a third‐order polynomial to wind speed. An in‐depth analysis was also carried out to understand the characteristics of storm surge height and extent of coastal inundation with respect to coastal geomorphology, angle of attack, and varying forward speed of cyclones. The authors believe that information and analysis from this comprehensive data set will have immense potential in understanding the impacts from tropical cyclone climatology and disaster management applications.

THINGS-data reflects three large-scale neuroimaging and behavioral datasets of object processing in humans, comprising densely sampled functional MRI and magnetoencephalographic recordings, as well as 4.70 million similarity judgments in response to thousands of photographic images for up to 1854 objects.

This thesis presents a critical appraisal of several differing approaches to the design and testing of fault detection (FD) algorithms monitoring the instrumentation used in the alternated aerobic/anoxic cycles (AC) process for nitrogen removal. Several features are selected as the basis of the FD, involving the slope and the timing of the process measurements of the various nitrogen compounds. Two separate FD algorithms have been developed for the anoxic and the aerobic phases, requiring a separate tuning but sharing the same principles: first some low-level checks are performed on the raw signals, discriminating gross malfunctions like missing data and spikes, then more sophisticated methods are used to investigate the presence of more subtle anomalies that were not detected by the previous screening. The FD problem is treated either in terms of classification problem, testing different algorithms such as binary trees, support vector machines (SVM) and principal component analysis (PCA), or as a forecasting one, using the Bayesian theory to predict the faulty or normal state of the process based on the previous records. An operational data set obtained from a municipal plant was used to first train the algorithm. However, due to the fairly limited information which could be extracted, a more comprehensive data set was created building an AC model based on the standard Benchmark simulation model with improved nitrogen kinetics and seasonal temperature variations. Detailed sensor models were also included, so that the occurrence of faults could be totally controlled, both in kind and timing. The performances of the various methods on either the operational and the synthetic datasets have been assessed comparing the anomalies detected by the methods with those actually observed. While the great majority of the gross faults is successfully detected by the preliminary screening, differing performances of the subsequent finer detection are obtained, depending on both the quality of data set and the detection method used: poorer results are observed using the plant data, in part due to an insufficient characterization of the fault events and in part due to the limited number of signals monitored. The higher availability of measurements provided by the numerical model, instead, enhances the discrimination capabilities of the tested methods, especially the nonlinear SVM, while the PCA-based approach and the Bayesian predictor results less affected by a change in the combination of diagnostic parameters used.

Neurons rely on the electric insulation and trophic support of myelinating oligodendrocytes. Despite the importance of oligodendrocytes, the advanced tools currently used to study neurons, have only partly been taken on by oligodendrocyte researchers. Cell type-specific staining by viral transduction is a useful approach to study live organelle dynamics. This paper describes a protocol for visualizing oligodendrocyte mitochondria in organotypic brain slices by transduction with adeno-associated virus (AAV) carrying genes for mitochondrial targeted fluorescent proteins under the transcriptional control of the myelin basic protein promoter. It includes the protocol for making organotypic coronal mouse brain slices. A procedure for time-lapse imaging of mitochondria then follows. These methods can be transferred to other organelles and may be particularly useful for studying organelles in the myelin sheath. Finally, we describe a readily available technique for visualization of unstained myelin in living slices by Confocal Reflectance microscopy (CoRe). CoRe requires no extra equipment and can be useful to identify the myelin sheath during live imaging.

Rapid quantification of ischaemic injury and cerebroprotection in brain slices using densitometric assessment of 2,3,5-triphenyltetrazolium chloride staining