Modulation of Ion Channels in the Axon: Mechanisms and Function

The axon is responsible for integrating synaptic signals, generating action potentials (APs), propagating those APs to downstream synapses and converting them into patterns of neurotransmitter vesicle release. This process is mediated by a rich assortment of voltage-gated ion channels whose function can be affected on short and long time scales by activity. Moreover, neuromodulators control the activity of these proteins through G-protein coupled receptor signaling cascades. Here, we review cellular mechanisms and signaling pathways involved in axonal ion channel modulation and examine how changes to ion channel function affect AP initiation, AP propagation, and the release of neurotransmitter. We then examine how these mechanisms could modulate synaptic function by focusing on three key features of synaptic information transmission: synaptic strength, synaptic variability, and short-term plasticity. Viewing these cellular mechanisms of neuromodulation from a functional perspective may assist in extending these findings to theories of neural circuit function and its neuromodulation

Clustering in mixing flows

We calculate the Lyapunov exponents for particles suspended in a random three-dimensional flow, concentrating on the limit where the viscous damping rate is small compared to the inverse correlation time. In this limit Lyapunov exponents are obtained as a power series in epsilon, a dimensionless measure of the particle inertia. Although the perturbation generates an asymptotic series, we obtain accurate results from a Pade-Borel summation. Our results prove that particles suspended in an incompressible random mixing flow can show pronounced clustering when the Stokes number is large and we characterise two distinct clustering effects which occur in that limit.Comment: 5 pages, 1 figur

Author Correction: The CaMKII/NMDA receptor complex controls hippocampal synaptic transmission by kinase-dependent and independent mechanisms.

The originally published version of this Article contained errors in Figure 5, for which we apologise. In panel c, the scatter graph was inadvertently replaced with a scatter graph comprising a subset of data points from panel d. Furthermore, the legends to Figures 5c and 5d were inverted. These errors have now been corrected in both the PDF and HTML versions of the Article, and the incorrect version of Fig. 5c is presented in the Author Correction associated with this Article

The CaMKII/NMDA receptor complex controls hippocampal synaptic transmission by kinase-dependent and independent mechanisms.

CaMKII is one of the most studied synaptic proteins, but many critical issues regarding its role in synaptic function remain unresolved. Using a CRISPR-based system to delete CaMKII and replace it with mutated forms in single neurons, we have rigorously addressed its various synaptic roles. In brief, basal AMPAR and NMDAR synaptic transmission both require CaMKIIα, but not CaMKIIβ, indicating that, even in the adult, synaptic transmission is determined by the ongoing action of CaMKIIα. While AMPAR transmission requires kinase activity, NMDAR transmission does not, implying a scaffolding role for the CaMKII protein instead. LTP is abolished in the absence of CaMKIIα and/or CaMKIIβ and with an autophosphorylation impaired CaMKIIα (T286A). With the exception of NMDAR synaptic currents, all aspects of CaMKIIα signaling examined require binding to the NMDAR, emphasizing the essential role of this receptor as a master synaptic signaling hub

Temporal invariance of social-ecological catchments

Natural resources such as waterbodies, public parks, and wildlife refuges attract people from varying distances on the landscape, creating “social-ecological catchments.” Catchments have provided great utility for understanding physical and social relationships within specific disciplines. Yet, catchments are rarely used across disciplines, such as its application to understand complex spatiotemporal dynamics between mobile human users and patchily distributed natural resources. We collected residence ZIP codes from 19,983 angler parties during 2014–2017 to construct seven angler–waterbody catchments in Nebraska, USA. We predicted that sizes of dense (10% utilization distribution) and dispersed (95% utilization distribution) angler–waterbody catchments would change across seasons and years as a function of diverse resource selection among mobile anglers. Contrary to expectations, we revealed that catchment size was invariant. We discuss how social (conservation actions) and ecological (low water quality, reduction in species diversity) conditions are expected to impact landscape patterns in resource use. We highlight how this simple concept and user-friendly technique can inform timely landscape-level conservation decisions within coupled social-ecological systems that are currently difficult to study and understand

Some methods for computing component distribution probabilities in relational structures

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26614/1/0000155.pd

cis sequence effects on gene expression

<p>Abstract</p> <p>Background</p> <p>Sequence and transcriptional variability within and between individuals are typically studied independently. The joint analysis of sequence and gene expression variation (genetical genomics) provides insight into the role of linked sequence variation in the regulation of gene expression. We investigated the role of sequence variation in <it>cis </it>on gene expression (<it>cis </it>sequence effects) in a group of genes commonly studied in cancer research in lymphoblastoid cell lines. We estimated the proportion of genes exhibiting <it>cis </it>sequence effects and the proportion of gene expression variation explained by <it>cis </it>sequence effects using three different analytical approaches, and compared our results to the literature.</p> <p>Results</p> <p>We generated gene expression profiling data at N = 697 candidate genes from N = 30 lymphoblastoid cell lines for this study and used available candidate gene resequencing data at N = 552 candidate genes to identify N = 30 candidate genes with sufficient variance in both datasets for the investigation of <it>cis </it>sequence effects. We used two additive models and the haplotype phylogeny scanning approach of Templeton (Tree Scanning) to evaluate association between individual SNPs, all SNPs at a gene, and diplotypes, with log-transformed gene expression. SNPs and diplotypes at eight candidate genes exhibited statistically significant (p < 0.05) association with gene expression. Using the literature as a "gold standard" to compare 14 genes with data from both this study and the literature, we observed 80% and 85% concordance for genes exhibiting and not exhibiting significant <it>cis </it>sequence effects in our study, respectively.</p> <p>Conclusion</p> <p>Based on analysis of our results and the extant literature, one in four genes exhibits significant <it>cis </it>sequence effects, and for these genes, about 30% of gene expression variation is accounted for by <it>cis </it>sequence variation. Despite diverse experimental approaches, the presence or absence of significant <it>cis </it>sequence effects is largely supported by previously published studies.</p

A Regularized Graph Layout Framework for Dynamic Network Visualization

Many real-world networks, including social and information networks, are dynamic structures that evolve over time. Such dynamic networks are typically visualized using a sequence of static graph layouts. In addition to providing a visual representation of the network structure at each time step, the sequence should preserve the mental map between layouts of consecutive time steps to allow a human to interpret the temporal evolution of the network. In this paper, we propose a framework for dynamic network visualization in the on-line setting where only present and past graph snapshots are available to create the present layout. The proposed framework creates regularized graph layouts by augmenting the cost function of a static graph layout algorithm with a grouping penalty, which discourages nodes from deviating too far from other nodes belonging to the same group, and a temporal penalty, which discourages large node movements between consecutive time steps. The penalties increase the stability of the layout sequence, thus preserving the mental map. We introduce two dynamic layout algorithms within the proposed framework, namely dynamic multidimensional scaling (DMDS) and dynamic graph Laplacian layout (DGLL). We apply these algorithms on several data sets to illustrate the importance of both grouping and temporal regularization for producing interpretable visualizations of dynamic networks.Comment: To appear in Data Mining and Knowledge Discovery, supporting material (animations and MATLAB toolbox) available at http://tbayes.eecs.umich.edu/xukevin/visualization_dmkd_201

IMC-Denoise: A content aware denoising pipeline to enhance Imaging Mass Cytometry

Imaging Mass Cytometry (IMC) is an emerging multiplexed imaging technology for analyzing complex microenvironments using more than 40 molecularly-specific channels. However, this modality has unique data processing requirements, particularly for patient tissue specimens where signal-to-noise ratios for markers can be low, despite optimization, and pixel intensity artifacts can deteriorate image quality and downstream analysis. Here we demonstrate an automated content-aware pipeline, IMC-Denoise, to restore IMC images deploying a differential intensity map-based restoration (DIMR) algorithm for removing hot pixels and a self-supervised deep learning algorithm for shot noise image filtering (DeepSNiF). IMC-Denoise outperforms existing methods for adaptive hot pixel and background noise removal, with significant image quality improvement in modeled data and datasets from multiple pathologies. This includes in technically challenging human bone marrow; we achieve noise level reduction of 87% for a 5.6-fold higher contrast-to-noise ratio, and more accurate background noise removal with approximately 2 × improved F1 score. Our approach enhances manual gating and automated phenotyping with cell-scale downstream analyses. Verified by manual annotations, spatial and density analysis for targeted cell groups reveal subtle but significant differences of cell populations in diseased bone marrow. We anticipate that IMC-Denoise will provide similar benefits across mass cytometric applications to more deeply characterize complex tissue microenvironments

TOI-150: A transiting hot Jupiter in the TESS southern CVZ

We report the detection of a hot Jupiter ($M_{p}=1.75_{-0.17}^{+0.14}\ M_{J}$,$R_{p}=1.38\pm0.04\ R_{J}$) orbiting a middle-aged star ($\log g=4.152^{+0.030}_{-0.043}$) in the Transiting Exoplanet Survey Satellite (TESS) southern continuous viewing zone ($\beta=-79.59^{\circ}$). We confirm the planetary nature of the candidate TOI-150.01 using radial velocity observations from the APOGEE-2 South spectrograph and the Carnegie Planet Finder Spectrograph, ground-based photometric observations from the robotic Three-hundred MilliMeter Telescope at Las Campanas Observatory, and Gaia distance estimates. Large-scale spectroscopic surveys, such as APOGEE/APOGEE-2, now have sufficient radial velocity precision to directly confirm the signature of giant exoplanets, making such data sets valuable tools in the TESS era. Continual monitoring of TOI-150 by TESS can reveal additional planets and subsequent observations can provide insights into planetary system architectures involving a hot Jupiter around a star about halfway through its main-sequence life.Comment: 13 pages, 3 figures, 2 tables, accepted to ApJ