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	<title>bioRxiv Channel: SPARC</title>
	<link>https://biorxiv.org</link>
	<description>
	This feed contains articles for bioRxiv Channel "SPARC"
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	<prism:publicationName>bioRxiv</prism:publicationName>
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	<title>bioRxiv</title>
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	<item rdf:about="https://biorxiv.org/cgi/content/short/2020.07.06.189696v1?rss=1">
<title>
<![CDATA[
A DNA-based optical nanosensor for in vivo imaging of acetylcholine in the peripheral nervous system 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.07.06.189696v1?rss=1"
</link>
<description><![CDATA[
The ability to monitor the release of neurotransmitters during synaptic transmission would significantly impact the diagnosis and treatment of neurological disease. Here, we present a DNA-based enzymatic nanosensor for quantitative detection of acetylcholine (ACh) in the peripheral nervous system of living mice. ACh nanosensors consist of DNA as a scaffold, acetylcholinesterase as a recognition component, pH-sensitive fluorophores as signal generators, and -bungarotoxin as a targeting moiety. We demonstrate the utility of the nanosensors in the submandibular ganglia of living mice to sensitively detect ACh ranging from 0.228 M to 358 M. In addition, the sensor response upon electrical stimulation of the efferent nerve is dose-dependent, reversible, and we observe a reduction of ~76% in sensor signal upon pharmacological inhibition of ACh release. Equipped with an advanced imaging processing tool, we further spatially resolve ACh signal propagation on the tissue level. Our platform enables sensitive measurement and mapping of ACh transmission in the peripheral nervous system.
]]></description>
<dc:creator>Xia, J.</dc:creator>
<dc:creator>Yang, H.</dc:creator>
<dc:creator>Mu, M.</dc:creator>
<dc:creator>Micovic, N.</dc:creator>
<dc:creator>Poskanzer, K. E.</dc:creator>
<dc:creator>Monaghan, J. R.</dc:creator>
<dc:creator>Clark, H. A.</dc:creator>
<dc:date>2020-07-06</dc:date>
<dc:identifier>doi:10.1101/2020.07.06.189696</dc:identifier>
<dc:title><![CDATA[A DNA-based optical nanosensor for in vivo imaging of acetylcholine in the peripheral nervous system]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-07-06</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2019.12.21.885970v1?rss=1">
<title>
<![CDATA[
Optogenetic Stimulation of Pancreatic Function via Vagal Cholinergic Axons 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2019.12.21.885970v1?rss=1"
</link>
<description><![CDATA[
Previous studies have demonstrated stimulation of endocrine pancreas function by vagal nerve electrical stimulation. While this increases insulin secretion; concomitant reductions in circulating glucose do not occur. A complicating factor is the non-specific nature of electrical nerve stimulation. Optogenetic tools enable high specificity in neural stimulation using cell-type specific targeting of opsins and/or spatially shaped excitation light. Here, we demonstrate light-activated stimulation of the endocrine pancreas by targeting vagal parasympathetic axons. In a mouse model expressing ChannelRhodopsin2 (ChR2) in cholinergic cells, serum insulin and glucose were measured in response to both ultrasound image-guided optical stimulation of axon terminals in the pancreas and optical stimulation of axons of the cervical vagus nerve, together with ultrasound-based measures of pancreas blood flow. Measurements were made in basal-glucose and glucose-stimulated conditions. Significant increases in plasma insulin occurred relative to controls under both pancreas and vagal stimulation, accompanying rapid reductions in glycemic levels. Additionally, a significant increase in pancreatic blood flow was measured following optical stimulation. Together, these results demonstrate the utility of in-vivo optogenetics for studying the neural regulation of endocrine pancreas function and suggest therapeutic potential for the control of insulin secretion and glucose homeostasis.
]]></description>
<dc:creator>Fontaine, A. K.</dc:creator>
<dc:creator>Ramirez, D. G.</dc:creator>
<dc:creator>Littich, S. F.</dc:creator>
<dc:creator>Piscopio, R.</dc:creator>
<dc:creator>Kravets, V.</dc:creator>
<dc:creator>Caldwell, J. H.</dc:creator>
<dc:creator>Weir, R. F.</dc:creator>
<dc:creator>Benninger, R. K.</dc:creator>
<dc:date>2019-12-23</dc:date>
<dc:identifier>doi:10.1101/2019.12.21.885970</dc:identifier>
<dc:title><![CDATA[Optogenetic Stimulation of Pancreatic Function via Vagal Cholinergic Axons]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-12-23</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2020.06.26.173898v1?rss=1">
<title>
<![CDATA[
Selective Modulation of Heart and Respiration by Optical Control of Vagus Nerve Axons Innervating the Heart 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.06.26.173898v1?rss=1"
</link>
<description><![CDATA[
Targeting specifics subsets of peripheral pathways of the autonomic nervous system will enable new avenues to study organ control and develop new disease therapies. Vagus nerve stimulation (VNS) has shown many therapeutic benefits but current approaches involve imprecise electrical stimulation that gives rise to adverse effects, and the functionally relevant pathways are poorly understood. One method to overcome these limitations is the use of optogenetic techniques, which facilitate highly specific neural communication with light-sensitive actuators (opsins). Opsins can be targeted to cell populations of interest based on the location of viral delivery and genetic control of expression. Here, we tested whether holographic photostimulation of subsets of axons of the cervical vagus nerve that innervate the heart can be used to modulate cardiac function. Viral injection of retrograde adeno-associated virus (rAAV2-retro) in the heart resulted in robust, primarily afferent, opsin reporter expression in the vagus nerve, nodose ganglion, and brainstem. Selective holographic photostimulation of axons resulted in changes in heart rate, surface cardiac electrogram, and respiratory responses that were different from responses elicited by whole nerve photostimulation.Competing Interest StatementThe authors have declared no competing interest.View Full Text
]]></description>
<dc:creator>Fontaine, A. K.</dc:creator>
<dc:creator>Futia, G. L.</dc:creator>
<dc:creator>Rajendran, P. S.</dc:creator>
<dc:creator>Littich, S.</dc:creator>
<dc:creator>Mizoguchi, N.</dc:creator>
<dc:creator>Shivkumar, K.</dc:creator>
<dc:creator>Ardell, J. L.</dc:creator>
<dc:creator>Restrepo, D.</dc:creator>
<dc:creator>Caldwell, J. H.</dc:creator>
<dc:creator>Gibson, E. A.</dc:creator>
<dc:creator>Weir, R. F.</dc:creator>
<dc:date>2020-06-29</dc:date>
<dc:identifier>doi:10.1101/2020.06.26.173898</dc:identifier>
<dc:title><![CDATA[Selective Modulation of Heart and Respiration by Optical Control of Vagus Nerve Axons Innervating the Heart]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-06-29</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2020.07.29.227090v1?rss=1">
<title>
<![CDATA[
A spatially-tracked single cell transcriptomics map of neuronal networks in the intrinsic cardiac nervous system 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.07.29.227090v1?rss=1"
</link>
<description><![CDATA[
We developed a spatially-tracked single neuron transcriptomics map of an intrinsic cardiac ganglion - the right atrial ganglionic plexus (RAGP) that is a critical mediator of vagal control of the sinoatrial node (SAN) activity. We developed a 3D representation of RAGP with extensive mapping of neurons and used neuronal tracing to identify the spatial distribution of the subset of neurons that project to the SAN. RNAseq of laser capture microdissected neurons revealed a distinct composition of RAGP neurons compared to CNS neuronal subtypes. High-throughput qPCR of hundreds of laser capture microdissected single neurons led to a surprising finding that cholinergic and catecholaminergic neuronal markers Th and Chat were correlated, suggesting multipotential phenotypes that can drive neuroplasticity within RAGP. Interestingly, no single gene or module was an exclusive marker of RAGP neuronal connectivity to SAN. Neuropeptide-receptor coexpression analysis revealed a combinatorial paracrine neuromodulatory network within RAGP, informing follow-on studies on the vagal control of RAGP to regulate cardiac function in health and disease.
]]></description>
<dc:creator>Moss, A.</dc:creator>
<dc:creator>Robbins, S.</dc:creator>
<dc:creator>Achanta, S.</dc:creator>
<dc:creator>Kuttippurathu, L.</dc:creator>
<dc:creator>Turick, S.</dc:creator>
<dc:creator>Nieves, S.</dc:creator>
<dc:creator>Hanna, P.</dc:creator>
<dc:creator>Smith, E. H.</dc:creator>
<dc:creator>Hoover, D. B.</dc:creator>
<dc:creator>Chen, J.</dc:creator>
<dc:creator>Cheng, Z.</dc:creator>
<dc:creator>Ardell, J. L.</dc:creator>
<dc:creator>Shivkumar, K.</dc:creator>
<dc:creator>Schwaber, J. S.</dc:creator>
<dc:creator>Vadigepalli, R.</dc:creator>
<dc:date>2020-07-30</dc:date>
<dc:identifier>doi:10.1101/2020.07.29.227090</dc:identifier>
<dc:title><![CDATA[A spatially-tracked single cell transcriptomics map of neuronal networks in the intrinsic cardiac nervous system]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-07-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2020.07.29.227538v1?rss=1">
<title>
<![CDATA[
3D single cell scale anatomical map of sex-dependent variability of the rat intrinsic cardiac nervous system 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.07.29.227538v1?rss=1"
</link>
<description><![CDATA[
We developed and analyzed a single cell scale anatomical map of the rat intrinsic cardiac nervous system (ICNS) across 4 male and 3 female hearts. We find the ICNS has a reliable structural organizational plan across individuals that may provide the foundation for further analyses of the ICNS in cardiac function and disease. The distribution of the ICNS was evaluated by 3D visualization and using data-driven clustering. The pattern, distribution and clustering of ICNS neurons across all male and female rat hearts is highly conserved, demonstrating a coherent organizational plan in which distinct clusters of neurons are consistently localized. Female hearts had fewer neurons, lower packing density and slightly reduced distribution, but with the same localization. We registered the anatomical data from each heart to a geometric scaffold, normalizing their 3D coordinates for the standardization of common anatomical planes and providing the path where multiple experimental results and data types can be integrated and compared.
]]></description>
<dc:creator>Leung, C.</dc:creator>
<dc:creator>Robbins, S.</dc:creator>
<dc:creator>Moss, A.</dc:creator>
<dc:creator>Heal, M.</dc:creator>
<dc:creator>Osanlouy, M.</dc:creator>
<dc:creator>Christie, R.</dc:creator>
<dc:creator>Farahani, N.</dc:creator>
<dc:creator>Monteith, C.</dc:creator>
<dc:creator>Chen, J.</dc:creator>
<dc:creator>Hunter, P.</dc:creator>
<dc:creator>Tappan, S.</dc:creator>
<dc:creator>Vadigepalli, R.</dc:creator>
<dc:creator>Cheng, Z.</dc:creator>
<dc:creator>Schwaber, J. S.</dc:creator>
<dc:date>2020-07-30</dc:date>
<dc:identifier>doi:10.1101/2020.07.29.227538</dc:identifier>
<dc:title><![CDATA[3D single cell scale anatomical map of sex-dependent variability of the rat intrinsic cardiac nervous system]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-07-30</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2020.06.18.159939v1?rss=1">
<title>
<![CDATA[
Evidence of Superior and Inferior Sinoatrial Nodes in the Mammalian Heart 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.06.18.159939v1?rss=1"
</link>
<description><![CDATA[
The initiation of rhythmic heartbeat is the earliest manifestation of new life after conception. A normal heartbeat originates as an action potential in a group of pacemaker cells of the sinoatrial node (SAN)1. Pacemaker cells are evident since early embryogenesis when the entire sinus venosus exhibits electric automaticity and possesses specific gene expression profile distinct from that of working myocardium2,3. During the subsequent looping and ballooning stages of cardiac development, pacemaker cells eventually localize into SAN near the superior vena cava (SVC) when the two horns of the sinus venosus coil in formation of the atria2. The heart rate and anatomical site of origin of pacemaker activity dynamically change in response to various physiological input such as autonomic stimuli and pharmacological interventions4. However, the mechanisms of dominant pacemaker shift are not well understood. Here, we present functional and molecular evidence of two competing right atrial pacemakers localized near the SVC and the inferior vena cava (IVC), which we call the superior and inferior SANs: sSAN and iSAN. Using ex vivo optical mapping techniques and RNA sequencing of rat and human hearts, we demonstrate that sSAN and iSAN preferentially control the fast and slow heart rates during sympathetic or parasympathetic stimulation, respectively. RNAseq confirmed unique transcriptional profiles of sSAN and iSAN, which differs from both atria and ventricles. We speculate that the anatomical locations of sSAN and iSAN are a result of the way the two horns of the sinus venosus twist into a mature chambered heart. We anticipate these findings would clarify previously observed migration of dominant pacemaker and corresponding changes in P-wave morphology in many species. Furthermore, we expect these findings will shed light onto pathogenesis of aberrant pacemakers responsible for life-threatening arrhythmias near orifices of other major vessels: SVC and IVC, coronary sinus, pulmonary veins, aorta and the right ventricular outflow tract.Competing Interest StatementThe authors have declared no competing interest.View Full Text
]]></description>
<dc:creator>Brennan, J. A.</dc:creator>
<dc:creator>Chen, Q.</dc:creator>
<dc:creator>Gams, A.</dc:creator>
<dc:creator>Dyavanapalli, J.</dc:creator>
<dc:creator>Mendelowitz, D.</dc:creator>
<dc:creator>Peng, W.</dc:creator>
<dc:creator>Efimov, I. R.</dc:creator>
<dc:date>2020-06-20</dc:date>
<dc:identifier>doi:10.1101/2020.06.18.159939</dc:identifier>
<dc:title><![CDATA[Evidence of Superior and Inferior Sinoatrial Nodes in the Mammalian Heart]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-06-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2020.07.03.187211v1?rss=1">
<title>
<![CDATA[
Combinatorial transcriptional profiling of mouse and human enteric neurons identifies shared and disparate subtypes in situ. 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.07.03.187211v1?rss=1"
</link>
<description><![CDATA[
AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBACKGROUND & AIMSC_ST_ABSThe enteric nervous system (ENS) coordinates essential intestinal functions through the concerted action of diverse enteric neurons (EN). However, integrated molecular knowledge of EN subtypes is lacking. To compare human and mouse ENs, we transcriptionally profiled healthy ENS from adult humans and mice. We aimed to identify transcripts marking discrete neuron subtypes and visualize conserved EN subtypes for humans and mice in multiple bowel regions.

METHODSHuman myenteric ganglia and adjacent smooth muscle were isolated by laser-capture microdissection for RNA-Seq. Ganglia-specific transcriptional profiles were identified by computationally subtracting muscle gene signatures. Nuclei from mouse myenteric neurons were isolated and subjected to single-nucleus RNA-Seq (snRNA-Seq), totaling over four billion reads and 25,208 neurons. Neuronal subtypes were defined using mouse snRNA-Seq data. Comparative informatics between human and mouse datasets identified shared EN subtype markers, which were visualized in situ using hybridization chain reaction (HCR).

RESULTSSeveral EN subtypes in the duodenum, ileum, and colon are conserved between humans and mice based on orthologous gene expression. However, some EN subtype-specific genes from mice are expressed in completely distinct morphologically defined subtypes in humans. In mice, we identified several neuronal subtypes that stably express gene modules across all intestinal segments, with graded, regional expression of one or more marker genes.

CONCLUSIONSOur combined transcriptional profiling of human myenteric ganglia and mouse EN provides a rich foundation for developing novel intestinal therapeutics. There is congruency among some EN subtypes, but we note multiple species differences that should be carefully considered when relating findings from mouse ENS research to human GI studies.



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]]></description>
<dc:creator>May-Zhang, A. A.</dc:creator>
<dc:creator>Tycksen, E.</dc:creator>
<dc:creator>Southard-Smith, A. N.</dc:creator>
<dc:creator>Deal, K. K.</dc:creator>
<dc:creator>Benthal, J. T.</dc:creator>
<dc:creator>Buehler, D. P.</dc:creator>
<dc:creator>Adam, M.</dc:creator>
<dc:creator>Simmons, A. J.</dc:creator>
<dc:creator>Monaghan, J. R.</dc:creator>
<dc:creator>Matlock, B. K.</dc:creator>
<dc:creator>Flaherty, D. K.</dc:creator>
<dc:creator>Potter, S.</dc:creator>
<dc:creator>Lau, K. S.</dc:creator>
<dc:creator>Southard-Smith, E. M.</dc:creator>
<dc:date>2020-07-04</dc:date>
<dc:identifier>doi:10.1101/2020.07.03.187211</dc:identifier>
<dc:title><![CDATA[Combinatorial transcriptional profiling of mouse and human enteric neurons identifies shared and disparate subtypes in situ.]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-07-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2020.09.22.306670v1?rss=1">
<title>
<![CDATA[
A comprehensive, FAIR file format for neuroanatomical structure modeling 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.09.22.306670v1?rss=1"
</link>
<description><![CDATA[
With advances in microscopy and computer science, the technique of digitally reconstructing, modeling, and quantifying microscopic anatomies has become central to many fields of biological research. MBF Bioscience has chosen to openly document their digital reconstruction file format, Neuromorphological File Specification (4.0), available at www.mbfbioscience.com/filespecification (Angstman et al. 2020). One of such technologies, the format created and maintained by MBF Bioscience is broadly utilized by the neuroscience community. The data formats structure and capabilities have evolved since its inception, with modifications made to keep pace with advancements in microscopy and the scientific questions raised by worldwide experts in the field. More recent modifications to the neuromorphological data format ensure it abides by the Findable, Accessible, Interoperable, and Reusable (FAIR) data standards promoted by the International Neuroinformatics Coordinating Facility (INCF; Wilkinson et al. 2016). The incorporated metadata make it easy to identify and repurpose these data types for downstream application and investigation. This publication describes key elements of the file format and details their relevant structural advantages in an effort to encourage the reuse of these rich data files for alternative analysis or reproduction of derived conclusions.
]]></description>
<dc:creator>Sullivan, A. E.</dc:creator>
<dc:creator>Tappan, S. J.</dc:creator>
<dc:creator>Angstman, P. J.</dc:creator>
<dc:creator>Rodriguez, A.</dc:creator>
<dc:creator>Thomas, G. C.</dc:creator>
<dc:creator>Hoppes, D. M.</dc:creator>
<dc:creator>Abdul-Karim, M.-A.</dc:creator>
<dc:creator>Heal, M. L.</dc:creator>
<dc:creator>Glaser, J. R.</dc:creator>
<dc:date>2020-09-22</dc:date>
<dc:identifier>doi:10.1101/2020.09.22.306670</dc:identifier>
<dc:title><![CDATA[A comprehensive, FAIR file format for neuroanatomical structure modeling]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-09-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/661033v1?rss=1">
<title>
<![CDATA[
Comprehensive Integrated Anatomical And Molecular Atlas Of Rodent Intrinsic Cardiac Nervous System 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/661033v1?rss=1"
</link>
<description><![CDATA[
In this study, we developed, coordinated, and integrated several technologies including novel whole organ imaging, software development to support the very first precise 3D neuroanatomical mapping and molecular phenotyping of the intracardiac nervous system (ICN). While qualitative and gross anatomical descriptions of the anatomy of the ICN have been presented, we here bring forth the first comprehensive atlas at large scale of the entire ICN in rat at a single cell resolution. Our work for the first time provides a novel 3D model to precisely integrate anatomical, functional and molecular data in the 3D digitally reconstructed whole heart with high resolution at the micron scale. This work represents the cutting edge in a long history of attempts to understand the anatomical substrate upon which the neuronal control of cardiac function is built. To our knowledge, there has not yet been a comprehensive histological mapping to generate a neurocardiac atlas at cellular and molecular level for the whole heart of any species. We now display the full extent and the position of neuronal clusters on the base and posterior left atrium, and the distribution of molecular phenotypes in that context. In addition we display in this context distinct molecular phenotypes that are defined along the base-to-apex axis, and the present novel discovery of their phenotypical spatial gradients, have not been previously described. The development of these approaches needed to acquire these data has produced method pipelines which can not only achieve the goals of anatomical and molecular mapping of the heart, but also provide the method pipelines for mapping other organs (e.g., stomach, lung, kidney, and liver).
]]></description>
<dc:creator>Achanta, S.</dc:creator>
<dc:creator>Gorky, J. M.</dc:creator>
<dc:creator>Leung, C.</dc:creator>
<dc:creator>Moss, A.</dc:creator>
<dc:creator>Robbins, S.</dc:creator>
<dc:creator>Eisenman, L.</dc:creator>
<dc:creator>Chen, J.</dc:creator>
<dc:creator>Tappan, S.</dc:creator>
<dc:creator>Heal, M.</dc:creator>
<dc:creator>Farhani, N.</dc:creator>
<dc:creator>Huffman, T.</dc:creator>
<dc:creator>Cheng, Z.</dc:creator>
<dc:creator>Vadigepalli, R.</dc:creator>
<dc:creator>Schwaber, J. S.</dc:creator>
<dc:date>2019-06-05</dc:date>
<dc:identifier>doi:10.1101/661033</dc:identifier>
<dc:title><![CDATA[Comprehensive Integrated Anatomical And Molecular Atlas Of Rodent Intrinsic Cardiac Nervous System]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-06-05</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2020.08.09.242792v1?rss=1">
<title>
<![CDATA[
Input-output signal processing plasticity of vagal motorneurons in response to cardiac ischemic injury 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.08.09.242792v1?rss=1"
</link>
<description><![CDATA[
Vagal stimulation is emerging as the next frontier in bioelectronic medicine to modulate peripheral organ health and treat disease. The neuronal molecular phenotypes in the dorsal motor nucleus of the vagus (DMV) remain largely unexplored, limiting the potential for harnessing the DMV plasticity for therapeutic interventions. We developed a mesoscale single cell transcriptomics data from hundreds of DMV neurons under homeostasis and following physiological perturbations. Our results revealed that homeostatic DMV neuronal states can be organized into distinguishable input-output signal processing units. Remote ischemic preconditioning induced a distinctive shift in the neuronal states towards diminishing the role of inhibitory inputs, with concomitant changes in regulatory microRNAs miR-218a and miR-495. Chronic cardiac ischemic injury resulted in a dramatic shift in DMV neuronal states suggestive of enhanced neurosecretory function. We propose a DMV molecular network mechanism that integrates combinatorial neurotransmitter inputs from multiple brain regions and humoral signals to modulate cardiac health.
]]></description>
<dc:creator>Gorky, J. M.</dc:creator>
<dc:creator>Moss, A.</dc:creator>
<dc:creator>Balycheva, M.</dc:creator>
<dc:creator>Vadigepalli, R.</dc:creator>
<dc:creator>Schwaber, J.</dc:creator>
<dc:date>2020-08-10</dc:date>
<dc:identifier>doi:10.1101/2020.08.09.242792</dc:identifier>
<dc:title><![CDATA[Input-output signal processing plasticity of vagal motorneurons in response to cardiac ischemic injury]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-08-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2020.07.14.199653v1?rss=1">
<title>
<![CDATA[
High-density Neural Recordings from Feline Sacral Dorsal Root Ganglia with Thin-film Array 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.07.14.199653v1?rss=1"
</link>
<description><![CDATA[
Objective: Dorsal root ganglia (DRG) are promising sites for recording sensory activity. Current technologies for DRG recording are stiff and typically do not have sufficient site density for high-fidelity neural data techniques. Approach: In acute experiments, we demonstrate single-unit neural recordings in sacral DRG of anesthetized felines using a 4.5 m-thick, high-density flexible polyimide microelectrode array with 60 sites and 30-40 m site spacing. We delivered arrays into DRG with ultrananocrystalline diamond shuttles designed for high stiffness affording a smaller footprint. We recorded neural activity during sensory activation, including cutaneous brushing and bladder filling, as well as during electrical stimulation of the pudendal nerve and anal sphincter. We used specialized neural signal analysis software to sort densely packed neural signals. Main results: We successfully delivered arrays in five of six experiments and recorded single-unit sensory activity in four experiments. The median neural signal amplitude was 55 V peak-to-peak and the maximum unique units recorded at one array position was 260, with 157 driven by sensory or electrical stimulation. In one experiment, we used the neural analysis software to track eight sorted single units as the array was retracted ~500 m. Significance: This study is the first demonstration of ultrathin, flexible, high-density electronics delivered into DRG, with capabilities for recording and tracking sensory information that are a significant improvement over conventional DRG interfaces.
]]></description>
<dc:creator>Sperry, Z. J.</dc:creator>
<dc:creator>Na, K.</dc:creator>
<dc:creator>Jun, J.</dc:creator>
<dc:creator>Madden, L. R.</dc:creator>
<dc:creator>Socha, A.</dc:creator>
<dc:creator>Yoon, E.</dc:creator>
<dc:creator>Seymour, J. P.</dc:creator>
<dc:creator>Bruns, T. M.</dc:creator>
<dc:date>2020-07-15</dc:date>
<dc:identifier>doi:10.1101/2020.07.14.199653</dc:identifier>
<dc:title><![CDATA[High-density Neural Recordings from Feline Sacral Dorsal Root Ganglia with Thin-film Array]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-07-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/435800v1?rss=1">
<title>
<![CDATA[
Novel diamond shuttle to deliver flexible bioelectronics with reduced tissue compression 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/435800v1?rss=1"
</link>
<description><![CDATA[
The ability to deliver flexible biosensors through the toughest membranes of the central and peripheral nervous system is an important challenge in neuroscience and neural engineering. Bioelectronic devices implanted through dura mater and thick epineurium would ideally create minimal compression and acute damage as they reach the neurons of interest. We demonstrate that a three-dimensional diamond shuttle can be easily made with a vertical support to deliver ultra-compliant polymer microelectrodes (4.5 m thick) in-vivo through dura mater and thick epineurium. The diamond shuttle has 54% less cross-sectional area than an equivalently stiff silicon shuttle, which we simulated will result in a 37% reduction in blood vessel damage. We also discovered that higher frequency oscillation of the shuttle (200 Hz) significantly reduced tissue compression regardless of the insertion speed, while slow speeds also independently reduced tissue compression. Insertion and recording performance are demonstrated in rat and feline models, but the large design space of these tools are suitable for research in a variety of animal models and nervous system targets.
]]></description>
<dc:creator>Na, K.</dc:creator>
<dc:creator>Sperry, Z. J.</dc:creator>
<dc:creator>Lu, J.</dc:creator>
<dc:creator>Voeroeslakos, M.</dc:creator>
<dc:creator>Parizi, S. S.</dc:creator>
<dc:creator>Bruns, T. M.</dc:creator>
<dc:creator>Yoon, E.</dc:creator>
<dc:creator>Seymour, J. P.</dc:creator>
<dc:date>2018-10-16</dc:date>
<dc:identifier>doi:10.1101/435800</dc:identifier>
<dc:title><![CDATA[Novel diamond shuttle to deliver flexible bioelectronics with reduced tissue compression]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2018-10-16</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2020.05.15.098301v1?rss=1">
<title>
<![CDATA[
Multi-channel intraneural vagus nerve recordings with a novel high-density carbon fiber microelectrode array 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.05.15.098301v1?rss=1"
</link>
<description><![CDATA[
Autonomic nerves convey essential neural signals that regulate vital body functions. Recording clearly distinctive physiological neural signals from autonomic nerves will help develop new treatments for restoring regulatory functions. However, this is very challenging due to the small nature of autonomic nerves and the low-amplitude signals from their small axons. We developed a multi-channel, high-density, intraneural carbon fiber microelectrode array (CFMA) with ultra-small electrodes (8-9 m in diameter, 150-250 m in length) for recording physiological action potentials from small autonomic nerves. In this study, we inserted CFMA with up to 16 recording carbon fibers in the cervical vagus nerve of 22 isoflurane-anesthetized rats. We recorded action potentials with peak-to-peak amplitudes of 15.1-91.7 V and signal-to-noise ratios of 2.0-8.3 on multiple carbon fibers per experiment, determined conduction velocities of some vagal signals in the afferent (0.7-4.4 m/sec) and efferent (0.7-8.8 m/sec) directions, and monitored firing rate changes in breathing and blood glucose modulated conditions. Overall, these experiments demonstrated that CFMA is a novel interface for in-vivo intraneural action potential recordings. This work is considerable progress towards the comprehensive understanding of physiological neural signaling in vital regulatory functions controlled by autonomic nerves.
]]></description>
<dc:creator>Jiman, A. A.</dc:creator>
<dc:creator>Ratze, D. C.</dc:creator>
<dc:creator>Welle, E. J.</dc:creator>
<dc:creator>Patel, P. R.</dc:creator>
<dc:creator>Richie, J. M.</dc:creator>
<dc:creator>Bottorff, E. C.</dc:creator>
<dc:creator>Seymour, J. P.</dc:creator>
<dc:creator>Chestek, C. A.</dc:creator>
<dc:creator>Bruns, T. M.</dc:creator>
<dc:date>2020-05-16</dc:date>
<dc:identifier>doi:10.1101/2020.05.15.098301</dc:identifier>
<dc:title><![CDATA[Multi-channel intraneural vagus nerve recordings with a novel high-density carbon fiber microelectrode array]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-05-16</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/607242v1?rss=1">
<title>
<![CDATA[
Machine learning prediction of emesis and gastrointestinal state in ferrets 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/607242v1?rss=1"
</link>
<description><![CDATA[
Although electrogastrography (EGG) could be a critical tool in the diagnosis and treatment of patients with gastrointestinal (GI) disease, it remains under-utilized. The lack of spatial and temporal resolution using current EGG methods presents a significant roadblock to more widespread usage. Human and preclinical studies have shown that GI myoelectric electrodes can record signals containing significantly more information than can be derived abdominal surface electrodes. The current study sought to assess the efficacy of multi-electrode arrays, surgically implanted on the serosal surface of the GI tract, from gastric fundus to duodenum, in recording myoelectric signals. It also examines the potential for machine learning algorithms to predict functional states, such as retching and emesis, from GI signal features. Studies were performed using ferrets, a gold standard model for emesis testing. Our results include simultaneous recordings from up to six GI recording sites in both anesthetized and chronically implanted free-moving ferrets. Testing conditions to produce different gastric states included gastric distension, intragastric infusion of emetine (a prototypical emetic agent), and feeding. Despite the observed variability in GI signals, machine learning algorithms, including k nearest neighbors and support vector machines, were able to detect the state of the stomach with high overall accuracy (>80%). The present study is the first demonstration of machine learning algorithms to detect the physiological state of the stomach and onset of retching and could provide insight into methodologies to treat GI diseases and control symptoms such as nausea and vomiting.
]]></description>
<dc:creator>Nanivadekar, A. C.</dc:creator>
<dc:creator>Miller, D. M.</dc:creator>
<dc:creator>Fulton, S.</dc:creator>
<dc:creator>Wong, L.</dc:creator>
<dc:creator>Ogren, J.</dc:creator>
<dc:creator>Chitnis, G.</dc:creator>
<dc:creator>McLaughlin, B.</dc:creator>
<dc:creator>Zhai, S.</dc:creator>
<dc:creator>Fisher, L. E.</dc:creator>
<dc:creator>Yates, B. J.</dc:creator>
<dc:creator>Horn, C. C.</dc:creator>
<dc:date>2019-04-12</dc:date>
<dc:identifier>doi:10.1101/607242</dc:identifier>
<dc:title><![CDATA[Machine learning prediction of emesis and gastrointestinal state in ferrets]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-04-12</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2020.09.18.303958v1?rss=1">
<title>
<![CDATA[
A neuroskeletal atlas of the mouse limb 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.09.18.303958v1?rss=1"
</link>
<description><![CDATA[
Nerves in bone play well-established roles in pain and vasoregulation and have been associated with progression of skeletal disorders including osteoporosis, fracture, arthritis and tumor metastasis. However, isolation of the region-specific mechanisms underlying these relationships is limited by our lack of comprehensive maps of skeletal innervation. To overcome this, we mapped sympathetic adrenergic and sensory peptidergic axons within the limb in two strains of mice (B6 and C3H). In the periosteum, these maps were related to the surrounding musculature, including entheses and myotendinous attachments to bone. Locally, three distinct patterns of innervation (Type I, II, III) were defined within established sites that are important for bone pain, bone repair, and skeletal homeostasis. In addition, we mapped the major nerve branches and areas of specialized mechanoreceptors. This work is intended to serve as a guide during the design, implementation, and interpretation of future neuroskeletal studies and was compiled as a resource for the field as part of the NIH SPARC consortium.
]]></description>
<dc:creator>Lorenz, M. R.</dc:creator>
<dc:creator>Brazill, J. M.</dc:creator>
<dc:creator>Beeve, A.</dc:creator>
<dc:creator>Shen, I.</dc:creator>
<dc:creator>Scheller, E. L.</dc:creator>
<dc:date>2020-09-19</dc:date>
<dc:identifier>doi:10.1101/2020.09.18.303958</dc:identifier>
<dc:title><![CDATA[A neuroskeletal atlas of the mouse limb]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-09-19</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2020.06.19.161851v1?rss=1">
<title>
<![CDATA[
Lung at a Glance: an integrative web toolset of lung ontology, imaging and single cell omics 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.06.19.161851v1?rss=1"
</link>
<description><![CDATA[
Recent advances in single-cell omics and high-resolution imaging have provided unanticipated data resources for the elucidation of genes underlying the complex biological processes critical for organ formation and function. However, processing and integrating large amounts of single-cell omics and imaging data presents a major challenge for most researchers. There is a critical need for ready-to-use computational tools for data/knowledge integration and visualization. Here we present "Lung-at-a-glance", an easy-to-use web toolset for visualizing and interoperating complex omics and imaging data, providing an interactive web interface to bridge lung anatomic ontology classifications to lung histology and immunofluorescence confocal images, and cell-type-specific gene expression. "Lung-at-a-glance" contains three interactive components: 1) "Region at a glance", 2) "Cell at a glance" and 3) "Gene at a glance". "Lung-at-a-glance" and other newly developed web tools for lung-related data query, integration and visualization are publicly available on LGEA web portal v3 https://research.cchmc.org/pbge/lunggens/mainportal.html.
]]></description>
<dc:creator>Du, Y.</dc:creator>
<dc:creator>Ouyang, W.</dc:creator>
<dc:creator>Kitzmiller, J.</dc:creator>
<dc:creator>Guo, M.</dc:creator>
<dc:creator>Zhao, S.</dc:creator>
<dc:creator>Whitsett, J. A.</dc:creator>
<dc:creator>Xu, Y.</dc:creator>
<dc:date>2020-06-20</dc:date>
<dc:identifier>doi:10.1101/2020.06.19.161851</dc:identifier>
<dc:title><![CDATA[Lung at a Glance: an integrative web toolset of lung ontology, imaging and single cell omics]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-06-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/784199v1?rss=1">
<title>
<![CDATA[
Identification of the lymphangioleiomyomatosis cell and its uterine origin 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/784199v1?rss=1"
</link>
<description><![CDATA[
Lymphangioleiomyomatosis (LAM) is a metastasizing neoplasm of reproductive age women that causes cystic lung remodeling and progressive respiratory failure. The source of LAM cells that invade the lung and the reasons that LAM targets women have remained elusive. We employed single cell and single nuclei RNA sequencing on LAM lesions within explanted LAM lungs, known to contain smooth muscle like cells bearing mTOR activating mutations in TSC1 or TSC2, and identified a unique population of cells that were readily distinguished from those of endogenous lung cells. LAMCORE cells shared closest transcriptomic similarity to normal uterus and neural crest. Immunofluorescence microscopy demonstrated the expression of LAMCORE cell signature genes within LAM lesions in both lung and uterus. Serum aptamer proteomics and ELISA identified biomarkers predicted to be secreted by LAMCORE cells. Single cell transcriptomics strongly supports a uterine neural crest origin of LAMCORE cells; providing insights into disease pathogenesis and informing future treatment strategies for LAM.nnSIGNIFICANCEPresent study identified a novel population of LAMCORE cells, which is likely originated from uterine neural crest; identified novel LAM cell-specific secretome proteins that hold promise as potential biomarkers and therapeutic targets. Advancing the understanding of LAM pathogenesis and metastasis model may yield broader insights into the biology of cancer.
]]></description>
<dc:creator>Guo, M.</dc:creator>
<dc:creator>Yu, J. J.</dc:creator>
<dc:creator>Perl, A. K.</dc:creator>
<dc:creator>Wikenheiser-Brokamp, K. A.</dc:creator>
<dc:creator>Riccetti, M.</dc:creator>
<dc:creator>Zhang, E. Y.</dc:creator>
<dc:creator>Sudha, P.</dc:creator>
<dc:creator>Adam, M.</dc:creator>
<dc:creator>Potter, A.</dc:creator>
<dc:creator>Kopras, E. J.</dc:creator>
<dc:creator>Giannikou, K.</dc:creator>
<dc:creator>Potter, S. S.</dc:creator>
<dc:creator>Sherman, S.</dc:creator>
<dc:creator>Hammes, S. R.</dc:creator>
<dc:creator>Kwiatkowski, D. J.</dc:creator>
<dc:creator>Whitsett, J. A.</dc:creator>
<dc:creator>McCormack, F. X.</dc:creator>
<dc:creator>Xu, Y.</dc:creator>
<dc:date>2019-10-08</dc:date>
<dc:identifier>doi:10.1101/784199</dc:identifier>
<dc:title><![CDATA[Identification of the lymphangioleiomyomatosis cell and its uterine origin]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-10-08</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2020.06.04.133843v1?rss=1">
<title>
<![CDATA[
Imaging fascicular organization of peripheral nerves with fast neural Electrical Impedance Tomography (EIT) 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.06.04.133843v1?rss=1"
</link>
<description><![CDATA[
Imaging of the compound action potential (CAP) in fascicles in peripheral nerves could help avoid side effects in neuromodulation by selective stimulation of identified fascicles. Existing methods have low resolution, limited imaging depth, or are invasive. We propose fast neural electrical impedance tomography (EIT), which allows fascicular CAP imaging with a high resolution of [~]200 m, <1 ms. This uses a non-penetrating flexible cuff electrode array with 14 circumferential electrodes. This has been validated in rat sciatic nerve by comparison to micro-computed tomography (microCT) and histology with fluorescent dextran tracers (n=5). With EIT, there were reproducible localized changes in tissue impedance in response to stimulation of individual fascicles (tibial, peroneal and sural). The reconstructed EIT images corresponded to microCT scans and neural tracer histology, with significant separation between the fascicles (p<0.01), and no significant difference between techniques. The standard deviation from the mean fascicle position for EIT was 86 m (6% of nerve diameter). This suggests fast neural EIT can reliably image the functional fascicular anatomy of the nerves and so aid selective neuromodulation.
]]></description>
<dc:creator>Ravagli, E.</dc:creator>
<dc:creator>Mastitkaya, S.</dc:creator>
<dc:creator>Thompson, N.</dc:creator>
<dc:creator>Iacoviello, F.</dc:creator>
<dc:creator>Shearing, P. R.</dc:creator>
<dc:creator>Perkins, J.</dc:creator>
<dc:creator>Gourine, A. V.</dc:creator>
<dc:creator>Aristovich, K.</dc:creator>
<dc:creator>Holder, D.</dc:creator>
<dc:date>2020-06-05</dc:date>
<dc:identifier>doi:10.1101/2020.06.04.133843</dc:identifier>
<dc:title><![CDATA[Imaging fascicular organization of peripheral nerves with fast neural Electrical Impedance Tomography (EIT)]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-06-05</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2020.10.28.359109v1?rss=1">
<title>
<![CDATA[
Innervation and Neuronal Control of the Mammalian Sinoatrial Node: A Comprehensive Atlas 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.10.28.359109v1?rss=1"
</link>
<description><![CDATA[
Cardiac function is under exquisite intrinsic cardiac neural control. Neuroablative techniques to modulate control of cardiac function are currently being studied in patients, albeit with variable and sometimes deleterious results. Recognizing the major gaps in our understanding of cardiac neural control, we sought to evaluate neural regulation of impulse initiation in the sinoatrial node as an initial discovery step. Here, we report an in-depth, multi-scale structural and functional characterization of the innervation of the sinoatrial node (SAN) by the right atrial ganglionated plexus (RAGP) in porcine and human hearts. Combining intersectional strategies including tissue clearing, immunohistochemical and ultrastructural techniques, we have delineated a comprehensive neuroanatomic atlas of the RAGP-SAN complex. The RAGP shows significant phenotypic diversity of neurons while maintaining predominant cholinergic innervation. Cellular and tissue-level electrophysiologic mapping and ablation studies demonstrate interconnected ganglia with synaptic convergence within the RAGP to modulate SAN automaticity, atrioventricular (AV) conduction and left ventricular (LV) contractility. For the first time, we demonstrate that intrinsic cardiac neurons influence the pacemaking site in the heart. This provides an experimental demonstration of a discrete neuronal population controlling a specific geographic region of the heart (SAN) that can serve as a framework for further exploration of other parts of the intrinsic cardiac nervous system (ICNS) in mammalian hearts and for developing targeted therapies.
]]></description>
<dc:creator>Hanna, P.</dc:creator>
<dc:creator>Dacey, M. J.</dc:creator>
<dc:creator>Brennan, J.</dc:creator>
<dc:creator>Moss, A.</dc:creator>
<dc:creator>Robbins, S.</dc:creator>
<dc:creator>Achanta, S.</dc:creator>
<dc:creator>Biscola, N. P.</dc:creator>
<dc:creator>Swid, M. A.</dc:creator>
<dc:creator>Rajendran, P. S.</dc:creator>
<dc:creator>Mori, S.</dc:creator>
<dc:creator>Hadaya, J.</dc:creator>
<dc:creator>Smith, E. H.</dc:creator>
<dc:creator>Peirce, S. G.</dc:creator>
<dc:creator>Chen, J.</dc:creator>
<dc:creator>Havton, L. A.</dc:creator>
<dc:creator>Cheng, Z.</dc:creator>
<dc:creator>Vadigepalli, R.</dc:creator>
<dc:creator>Schwaber, J.</dc:creator>
<dc:creator>Lux, R. L.</dc:creator>
<dc:creator>Efimov, I.</dc:creator>
<dc:creator>Tompkins, J. D.</dc:creator>
<dc:creator>Hoover, D. B.</dc:creator>
<dc:creator>Ardell, J. L.</dc:creator>
<dc:creator>Shivkumar, K.</dc:creator>
<dc:date>2020-10-29</dc:date>
<dc:identifier>doi:10.1101/2020.10.28.359109</dc:identifier>
<dc:title><![CDATA[Innervation and Neuronal Control of the Mammalian Sinoatrial Node: A Comprehensive Atlas]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-10-29</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2020.10.26.352740v1?rss=1">
<title>
<![CDATA[
Sex-specific classification of drug-induced Torsade de Pointes susceptibility using cardiac simulations and machine learning 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.10.26.352740v1?rss=1"
</link>
<description><![CDATA[
Torsade de Pointes (TdP), a rare but lethal ventricular arrhythmia, is a toxic side effect of many drugs. To assess TdP risk, safety regulatory guidelines require quantification of hERG channel block in vitro and QT interval prolongation in vivo for all new therapeutic compounds. Unfortunately, these have proven to be poor predictors of torsadogenic risk, and are likely to have prevented safe compounds from reaching clinical phases. While this has stimulated numerous efforts to define new paradigms for cardiac safety, none of the recently developed strategies accounts for patient conditions. In particular, despite being a well-established independent risk factor for TdP, female sex is vastly underrepresented in both basic research and clinical studies, and thus current TdP metrics are likely biased toward the male sex. Here, we apply statistical learning to synthetic data, generated by simulating drug effects on cardiac myocyte models capturing male and female electrophysiology, to develop new sex-specific classification frameworks for TdP risk. We show that (1) TdP classifiers require different features in females vs. males; (2) malebased classifiers perform more poorly when applied to female data; (3) female-based classifier performance is largely unaffected by acute effects of hormones (i.e., during various phases of the menstrual cycle). Notably, when predicting TdP risk of intermediate drugs on female simulated data, male-biased predictive models consistently underestimate TdP risk in women. Therefore, we conclude that pipelines for preclinical cardiotoxicity risk assessment should consider sex as a key variable to avoid potentially lifethreatening consequences for the female population.
]]></description>
<dc:creator>Fogli Iseppe, A.</dc:creator>
<dc:creator>Ni, H.</dc:creator>
<dc:creator>Zhu, S.</dc:creator>
<dc:creator>Zhang, X.</dc:creator>
<dc:creator>Coppini, R.</dc:creator>
<dc:creator>Yang, P.-C.</dc:creator>
<dc:creator>Srivatsa, U.</dc:creator>
<dc:creator>Clancy, C. E.</dc:creator>
<dc:creator>Edwards, A. G.</dc:creator>
<dc:creator>Morotti, S.</dc:creator>
<dc:creator>Grandi, E.</dc:creator>
<dc:date>2020-10-27</dc:date>
<dc:identifier>doi:10.1101/2020.10.26.352740</dc:identifier>
<dc:title><![CDATA[Sex-specific classification of drug-induced Torsade de Pointes susceptibility using cardiac simulations and machine learning]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-10-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2020.11.18.375741v1?rss=1">
<title>
<![CDATA[
Preliminary Minimum Reporting Requirements for Reporting In-Vivo Neural Interface Research: I. Implantable Neural Interfaces 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.11.18.375741v1?rss=1"
</link>
<description><![CDATA[
The pace of research and development in neuroscience, neurotechnology, and neurorehabilitation is rapidly accelerating, with the number of publications doubling every 4.2 years. Maintaining this progress requires technological standards and scientific reporting guidelines to provide frameworks for communication and interoperability. The present lack of such standards for neurotechnologies limits the transparency, reproducibility, and meta-analysis of this growing body of research, posing an ongoing barrier to research, clinical, and commercial objectives.

Continued neurotechnological innovation requires the development of some minimal standards to promote integration between this broad spectrum of technologies and therapies. To preserve design freedom and accelerate the translation of research into safe and effective technologies with maximal user benefit, such standards must be collaboratively co-developed by a full spectrum of neuroscience and neurotechnology stakeholders. This paper summarizes the preliminary recommendations of IEEE Working Group P2794, developing a Reporting Standard for in-vivo Neural Interface Research (RSNIR).

Impact StatementThis work provides a preliminary set of reporting guidelines for implantable neural interface research, developed by IEEE WG P2794 in open collaboration between a range of stakeholders to accelerate the research, development, and integration of innovative neurotechnologies.
]]></description>
<dc:creator>Eiber, C. D.</dc:creator>
<dc:creator>Delbeke, J.</dc:creator>
<dc:creator>Cardoso, J.</dc:creator>
<dc:creator>de Neeling, M.</dc:creator>
<dc:creator>John, S.</dc:creator>
<dc:creator>Lee, C. W.</dc:creator>
<dc:creator>Skefos, J.</dc:creator>
<dc:creator>Sun, A.</dc:creator>
<dc:creator>Prodanov, D.</dc:creator>
<dc:creator>McKinney, Z.</dc:creator>
<dc:date>2020-11-20</dc:date>
<dc:identifier>doi:10.1101/2020.11.18.375741</dc:identifier>
<dc:title><![CDATA[Preliminary Minimum Reporting Requirements for Reporting In-Vivo Neural Interface Research: I. Implantable Neural Interfaces]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-11-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2020.12.11.421743v1?rss=1">
<title>
<![CDATA[
Automatic Assessment of Human Gastric Motility and Emptying from Dynamic 3D Magnetic Resonance Imaging 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.12.11.421743v1?rss=1"
</link>
<description><![CDATA[
BackgroundTime-sequenced magnetic resonance imaging (MRI) of the stomach is an emerging technique for non-invasive assessment of gastric emptying and motility. However, an automated and systematic image processing pipeline for analyzing dynamic 3D (i.e., 4D) gastric MRI data is not yet available. This study introduces an MRI protocol for imaging the stomach with high spatiotemporal isotropic resolution and provides an integrated pipeline for assessing gastric emptying and motility simultaneously.

MethodsDiet contrast-enhanced MRI images were acquired from seventeen healthy humans after they consumed a naturalistic contrast meal. An automated image processing pipeline was developed to correct for respiratory motion, to segment and compartmentalize the lumen-enhanced stomach, to quantify total gastric and compartmental emptying, and to compute and visualize gastric motility on the surface of the stomach.

Key ResultsThe gastric segmentation reached an accuracy of 91.10{+/-}0.43% with the Type-I error and Type-II error being 0.11{+/-}0.01% and 0.22{+/-}0.01%, respectively. Gastric volume decreased 34.64{+/-}2.8% over 1 hour where the emptying followed a linear-exponential pattern. The gastric motility showed peristaltic patterns with a median = 4 wave-fronts (range 3 - 6) and a mean frequency of 3.09{+/-}0.07 cycles per minute (CPM). Further, the contractile amplitude was stronger in the antrum than in the corpus (antrum vs. corpus: 5.18{+/-}0.24 vs. 3.30{+/-}0.16 mm; p < .001).

Conclusions & InferencesThe automated, streamlined software can process dynamic 3D MRI images and produce comprehensive and personalized profiles of gastric motility and emptying. This software will facilitate the application of MRI for monitoring gastric dynamics in research and clinical settings.
]]></description>
<dc:creator>Lu, K.-H.</dc:creator>
<dc:creator>Liu, Z.</dc:creator>
<dc:creator>Jaffey, D.</dc:creator>
<dc:creator>Wo, J.</dc:creator>
<dc:creator>Mosier, K.</dc:creator>
<dc:creator>Cao, J.</dc:creator>
<dc:creator>Wang, X.</dc:creator>
<dc:creator>Powley, T. L.</dc:creator>
<dc:date>2020-12-11</dc:date>
<dc:identifier>doi:10.1101/2020.12.11.421743</dc:identifier>
<dc:title><![CDATA[Automatic Assessment of Human Gastric Motility and Emptying from Dynamic 3D Magnetic Resonance Imaging]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-12-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2020.12.17.423297v1?rss=1">
<title>
<![CDATA[
Quantitative cross-species translators of cardiac myocyte electrophysiology: model training, experimental validation, and applications 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.12.17.423297v1?rss=1"
</link>
<description><![CDATA[
Animal experimentation is key in the evaluation of cardiac efficacy and safety of novel therapeutic compounds. However, inter-species differences in the mechanisms regulating excitation-contraction coupling can limit the translation of experimental findings from animal models to human physiology, and undermine the assessment of drugs efficacy and safety. Here, we built a suite of translators for quantitatively mapping electrophysiological responses in ventricular myocytes across species. We trained these statistical operators using a broad dataset obtained by simulating populations of our biophysically detailed computational models of action potential and Ca2+ transient in mouse, rabbit, and human. We then tested our translators against experimental data describing the response to stimuli, such as ion channel block, change in beating rate, and {beta}-adrenergic challenge. We demonstrate that this approach is well suited to predicting the effects of perturbations across different species or experimental conditions, and suggest its integration into mechanistic studies and drug development pipelines.
]]></description>
<dc:creator>Morotti, S.</dc:creator>
<dc:creator>Liu, C.</dc:creator>
<dc:creator>Hegyi, B.</dc:creator>
<dc:creator>Ni, H.</dc:creator>
<dc:creator>Fogli Iseppe, A.</dc:creator>
<dc:creator>Wang, L.</dc:creator>
<dc:creator>Ripplinger, C. M.</dc:creator>
<dc:creator>Bers, D. M.</dc:creator>
<dc:creator>Edwards, A. G.</dc:creator>
<dc:creator>Grandi, E.</dc:creator>
<dc:date>2020-12-18</dc:date>
<dc:identifier>doi:10.1101/2020.12.17.423297</dc:identifier>
<dc:title><![CDATA[Quantitative cross-species translators of cardiac myocyte electrophysiology: model training, experimental validation, and applications]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-12-18</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/856989v1?rss=1">
<title>
<![CDATA[
Functional Vagotopy in the Cervical Vagus Nerve of the Domestic Pig: Implications for Vagus Nerve Stimulation 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/856989v1?rss=1"
</link>
<description><![CDATA[
Given current clinical interest in vagus nerve stimulation, there are surprisingly few studies characterizing the anatomy of the vagus nerve in large animal models as it pertains to on-and off-target engagement of local fibers. We sought to address this gap by evaluating vagal anatomy in the domestic pig, whose vagus nerve organization and size approximates the human cervical vagus nerve. We provide data on key features across the cervical vagus nerve including diameter, number and diameter of fascicles, and distance of fascicles from the epineural surface where stimulating electrodes are placed. We also characterized the relative locations of the superior and recurrent laryngeal branches of the vagus nerve that have been implicated in therapy limiting side effects with common electrode placement. We identified key variants across the cohort that may be important for vagus nerve stimulation with respect to changing sympathetic/parasympathetic tone, such as cross-connections to the sympathetic trunk. We discovered that cell bodies of pseudo-unipolar cells aggregate together to form a very distinct grouping within the nodose ganglion. This distinct grouping gives rise to a larger number of smaller fascicles as one moves caudally down the cervical vagus nerve. This often leads to a distinct bimodal organization, or  vagotopy that may be advantageous to exploit in design of electrodes/stimulation paradigms. Finally, we placed our data in context of historic and recent histology spanning mouse, rat, canine, pig, non-human primate and human models, thus providing a comprehensive resource to understand similarities and differences across species.
]]></description>
<dc:creator>Settell, M. L.</dc:creator>
<dc:creator>Knudsen, B. E.</dc:creator>
<dc:creator>Dingle, A. M.</dc:creator>
<dc:creator>McConico, A. L.</dc:creator>
<dc:creator>Nicolai, E. N.</dc:creator>
<dc:creator>Trevathan, J. K.</dc:creator>
<dc:creator>Ross, E. K.</dc:creator>
<dc:creator>Pelot, N. A.</dc:creator>
<dc:creator>Grill, W. M.</dc:creator>
<dc:creator>Gustafson, K. J.</dc:creator>
<dc:creator>Shoffstall, A. J.</dc:creator>
<dc:creator>Williams, J. C.</dc:creator>
<dc:creator>Zeng, W.</dc:creator>
<dc:creator>Poore, S. O.</dc:creator>
<dc:creator>Populin, L. C.</dc:creator>
<dc:creator>Suminski, A. J.</dc:creator>
<dc:creator>Ludwig, K. A.</dc:creator>
<dc:date>2019-11-27</dc:date>
<dc:identifier>doi:10.1101/856989</dc:identifier>
<dc:title><![CDATA[Functional Vagotopy in the Cervical Vagus Nerve of the Domestic Pig: Implications for Vagus Nerve Stimulation]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2019-11-27</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2020.12.24.424256v1?rss=1">
<title>
<![CDATA[
In vivo visualization of pig vagus nerve 'vagotopy' using ultrasound 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.12.24.424256v1?rss=1"
</link>
<description><![CDATA[
BackgroundPlacement of the clinical vagus nerve stimulating cuff is a standard surgical procedure based on anatomical landmarks, with limited patient specificity in terms of fascicular organization or vagal anatomy. As such, the therapeutic effects are generally limited by unwanted side effects of neck muscle contractions, demonstrated by previous studies to result from stimulation of 1) motor fibers near the cuff in the superior laryngeal and 2) motor fibers within the cuff projecting to the recurrent laryngeal.

ObjectiveThe use of patient-specific visualization of vagus nerve fascicular organization could better inform clinical cuff placement and improve clinical outcomes.

MethodsThe viability of ultrasound, with the transducer in the surgical pocket, to visualize vagus nerve fascicular organization (i.e. vagotopy) was characterized in a pig model. Ultrasound images were matched to post-mortem histology to confirm the utility of ultrasound in identifying fascicular organization.

ResultsHigh-resolution ultrasound accurately depicted the vagotopy of the pig vagus nerve intra-operatively, as confirmed via histology. The stereotypical pseudo-unipolar cell body aggregation at the nodose ganglion was identifiable, and these sensory afferent fascicular bundles were traced down the length of the vagus nerve. Additionally, the superior and recurrent laryngeal nerves were identified via ultrasound.

ConclusionsIntraoperative visualization of vagotopy and surrounding nerves using ultrasound is a novel approach to optimize stimulating cuff placement, avoid unwanted activation of motor nerve fibers implicated in off-target effects, and seed patient-specific models of vagal fiber activation to improve patient outcomes.
]]></description>
<dc:creator>Settell, M. L.</dc:creator>
<dc:creator>Kasole, M.</dc:creator>
<dc:creator>Skubal, A. C.</dc:creator>
<dc:creator>Knudsen, B. E.</dc:creator>
<dc:creator>Nicolai, E. N.</dc:creator>
<dc:creator>Huang, C.</dc:creator>
<dc:creator>Zhou, C.</dc:creator>
<dc:creator>Trevathan, J. K.</dc:creator>
<dc:creator>Pelot, N. A.</dc:creator>
<dc:creator>Grill, W. M.</dc:creator>
<dc:creator>Upadhye, A.</dc:creator>
<dc:creator>Kolluru, C.</dc:creator>
<dc:creator>Shoffstall, A. J.</dc:creator>
<dc:creator>Williams, J. C.</dc:creator>
<dc:creator>Suminski, A. J.</dc:creator>
<dc:creator>Chen, S.</dc:creator>
<dc:creator>Ludwig, K. A.</dc:creator>
<dc:date>2020-12-24</dc:date>
<dc:identifier>doi:10.1101/2020.12.24.424256</dc:identifier>
<dc:title><![CDATA[In vivo visualization of pig vagus nerve 'vagotopy' using ultrasound]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-12-24</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2020.01.15.907246v1?rss=1">
<title>
<![CDATA[
Sources of Off-Target Effects of Vagus Nerve Stimulation Using the Helical Clinical Lead in Domestic Pigs 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2020.01.15.907246v1?rss=1"
</link>
<description><![CDATA[
Clinical data suggest that efficacious vagus nerve stimulation (VNS) is limited by side effects such as cough and dyspnea that have stimulation thresholds lower than those for therapeutic outcomes. VNS side effects are putatively caused by activation of nearby muscles within the neck, via direct muscle activation or activation of nerve fibers innervating those muscles. Our goal was to determine the thresholds at which various VNS-evoked effects occur in the domestic pig--an animal model with vagus anatomy similar to human--using the bipolar helical lead deployed clinically. Intrafascicular electrodes were placed within the vagus nerve to record electroneurographic (ENG) responses, and needle electrodes were placed in the vagal-innervated neck muscles to record electromyographic (EMG) responses. Contraction of the cricoarytenoid muscle occurred at low amplitudes ([~]0.3 mA) and resulted from activation of motor nerve fibers in the cervical vagus trunk within the electrode cuff which bifurcate into the recurrent laryngeal branch of the vagus. At higher amplitudes ([~]1.4 mA), contraction of the cricoarytenoid and cricothyroid muscles was generated by current leakage outside the cuff to activate motor nerve fibers running within the nearby superior laryngeal branch of the vagus. Activation of these muscles generated artifacts in the ENG recordings that may be mistaken for compound action potentials representing slowly conducting A{delta}-, B-, and C-fibers. Our data resolve conflicting reports of the stimulation amplitudes required for C-fiber activation in large animal studies (>10 mA) and human studies (<250 {micro}A). After removing muscle-generated artifacts, ENG signals with post-stimulus latencies consistent with A{delta}- and B-fibers occurred in only a small subset of animals, and these signals had similar thresholds to those that caused bradycardia. By identifying specific neuroanatomical pathways that cause off-target effects and characterizing the stimulation dose-response curves for on- and off-target effects, we hope to guide interpretation and optimization of clinical VNS.
]]></description>
<dc:creator>Nicolai, E. N.</dc:creator>
<dc:creator>Settell, M. L.</dc:creator>
<dc:creator>Knudsen, B. E.</dc:creator>
<dc:creator>McConico, A. L.</dc:creator>
<dc:creator>Gosink, B. A.</dc:creator>
<dc:creator>Trevathan, J. K.</dc:creator>
<dc:creator>Baumgart, I. W.</dc:creator>
<dc:creator>Ross, E. K.</dc:creator>
<dc:creator>Pelot, N. A.</dc:creator>
<dc:creator>Grill, W. M.</dc:creator>
<dc:creator>Gustafson, K. J.</dc:creator>
<dc:creator>Shoffstall, A. J.</dc:creator>
<dc:creator>Williams, J. C.</dc:creator>
<dc:creator>Ludwig, K. A.</dc:creator>
<dc:date>2020-01-15</dc:date>
<dc:identifier>doi:10.1101/2020.01.15.907246</dc:identifier>
<dc:title><![CDATA[Sources of Off-Target Effects of Vagus Nerve Stimulation Using the Helical Clinical Lead in Domestic Pigs]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2020-01-15</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2021.01.21.427697v1?rss=1">
<title>
<![CDATA[
Sharpened and mechanically robust carbon fiber electrode arrays for neural interfacing 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2021.01.21.427697v1?rss=1"
</link>
<description><![CDATA[
Bioelectric medicine treatments target disorders of the nervous system unresponsive to pharmacological methods. While current stimulation paradigms effectively treat many disorders, the underlying mechanisms are relatively unknown, and current neuroscience recording electrodes are often limited in their specificity to gross averages across many neurons or axons. Here, we develop a novel, durable carbon fiber electrode array adaptable to many neural structures for precise neural recording. Carbon fibers were sharpened using a reproducible blowtorch method that uses the reflection of fibers against the surface of a water bath. The arrays were developed by partially embedding carbon fibers in medical-grade silicone to improve durability. We recorded acute spontaneous electrophysiology from the rat cervical vagus nerve (CVN), feline dorsal root ganglia (DRG), and rat brain. Blowtorching resulted in fibers of 72.3 {+/-} 33.5 degree tip angle with 146.8 {+/-} 17.7 m exposed carbon. Silicone-embedded carbon fiber arrays were durable with 87.5% of fibers remaining after 50,000 passes. Observable neural clusters were recorded using sharpened carbon fiber electrodes from rat CVN (41.8 Vpp), feline DRG (101.1 Vpp), and rat brain (80.7 Vpp). Recordings from the feline DRG included physiologically-relevant signals from increased bladder pressure and cutaneous brushing. These results suggest that this carbon fiber array is a uniquely durable and adaptable neural recording device. In the future, this device may be useful as a bioelectric medicine tool for diagnosis and closed-loop neural control of therapeutic treatments and monitoring systems.
]]></description>
<dc:creator>Welle, E. J.</dc:creator>
<dc:creator>Woods, J. E.</dc:creator>
<dc:creator>Jiman, A. A.</dc:creator>
<dc:creator>Richie, J. M.</dc:creator>
<dc:creator>Bottorff, E. C.</dc:creator>
<dc:creator>Ouyang, Z.</dc:creator>
<dc:creator>Seymour, J. P.</dc:creator>
<dc:creator>Patel, P. R.</dc:creator>
<dc:creator>Bruns, T. M.</dc:creator>
<dc:creator>Chestek, C. A.</dc:creator>
<dc:date>2021-01-22</dc:date>
<dc:identifier>doi:10.1101/2021.01.21.427697</dc:identifier>
<dc:title><![CDATA[Sharpened and mechanically robust carbon fiber electrode arrays for neural interfacing]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-01-22</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2021.02.19.431879v1?rss=1">
<title>
<![CDATA[
Selective stimulation of the ferret abdominal vagus nerve with multi-contact nerve cuff electrodes 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2021.02.19.431879v1?rss=1"
</link>
<description><![CDATA[
Dysfunction and diseases of the gastrointestinal (GI) tract are a major driver of medical care. The vagus nerve innervates and controls multiple organs of the GI tract and vagus nerve stimulation (VNS) could provide a means for affecting GI function and treating disease. However, the vagus nerve also innervates many other organs throughout the body, and off-target effects of VNS could cause major side effects such as changes in blood pressure. In this study, we aimed to achieve selective stimulation of populations of vagal afferents using a multi-contact cuff electrode wrapped around the abdominal trunks of the vagus nerve. Four-contact nerve cuff electrodes were implanted around the dorsal (N=3) or ventral (N=3) abdominal vagus nerve in six ferrets, and the response to stimulation was measured via a 32-channel microelectrode array (MEA) inserted into the nodose ganglion. Selectivity was characterized by the ability to evoke responses in MEA channels through one bipolar pair of cuff contacts but not through the other bipolar pair. We demonstrated that is was possible to selectively activate subpopulations of vagal afferents using abdominal VNS. Additionally, we quantified the conduction velocity of evoked responses to determine what types of nerve fibers (i.e. A{delta} vs. C) responded to stimulation. We also quantified the spatial organization of evoked responses in the nodose MEA to determine if there is somatotopic organization of the neurons in that ganglion. Finally, we demonstrated in a separate set of three ferrets that stimulation of the abdominal vagus via a four-contact cuff could selectively alter gastric myoelectric activity, suggesting that abdominal VNS can potentially be used to control GI function.
]]></description>
<dc:creator>Shulgach, J. A.</dc:creator>
<dc:creator>Beam, D. W.</dc:creator>
<dc:creator>Nanivadekar, A. C.</dc:creator>
<dc:creator>Miller, D. M.</dc:creator>
<dc:creator>Fulton, S.</dc:creator>
<dc:creator>Sciullo, M.</dc:creator>
<dc:creator>Ogren, J.</dc:creator>
<dc:creator>Wong, L.</dc:creator>
<dc:creator>McLaughlin, B.</dc:creator>
<dc:creator>Yates, B. J.</dc:creator>
<dc:creator>Horn, C.</dc:creator>
<dc:creator>Fisher, L.</dc:creator>
<dc:date>2021-02-20</dc:date>
<dc:identifier>doi:10.1101/2021.02.19.431879</dc:identifier>
<dc:title><![CDATA[Selective stimulation of the ferret abdominal vagus nerve with multi-contact nerve cuff electrodes]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-02-20</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2021.04.01.438136v1?rss=1">
<title>
<![CDATA[
The SPARC DRC: Building a resource for the autonomic nervous system community 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2021.04.01.438136v1?rss=1"
</link>
<description><![CDATA[
The Data and Resource Center (DRC) of the NIH-funded SPARC program is developing databases, connectivity maps and simulation tools for the mammalian autonomic nervous system. The experimental data and mathematical models supplied to the DRC by the SPARC consortium are curated, annotated and semantically linked via a single knowledgebase. A data portal has been developed that allows discovery of data and models both via semantic search and via an interface that includes Google Map-like 2D flatmaps for displaying connectivity, and 3D anatomical organ scaffolds that provide a common coordinate framework for cross-species comparisons. We discuss examples that illustrate the data pipeline, which includes data upload, curation, segmentation (for image data), registration against the flatmaps and scaffolds, and finally display via the web portal, including the link to freely available online computational facilities that will enable neuromodulation hypotheses to be investigated by the autonomic neuroscience community and device manufacturers.
]]></description>
<dc:creator>Osanlouy, M.</dc:creator>
<dc:creator>Bandrowski, A.</dc:creator>
<dc:creator>de Bono, B.</dc:creator>
<dc:creator>Brooks, D.</dc:creator>
<dc:creator>Cassara, A. M.</dc:creator>
<dc:creator>Christie, R.</dc:creator>
<dc:creator>Ebrahimi, N.</dc:creator>
<dc:creator>Gillespie, T.</dc:creator>
<dc:creator>Grethe, J. S.</dc:creator>
<dc:creator>Guercio, L. A.</dc:creator>
<dc:creator>Heal, M.</dc:creator>
<dc:creator>Lin, M.</dc:creator>
<dc:creator>Kuster, N.</dc:creator>
<dc:creator>Martone, M. E.</dc:creator>
<dc:creator>Neufeld, E.</dc:creator>
<dc:creator>Nickerson, D. P.</dc:creator>
<dc:creator>Soltani, E. G.</dc:creator>
<dc:creator>Tappan, S.</dc:creator>
<dc:creator>Wagenaar, J. B.</dc:creator>
<dc:creator>Zhuang, K.</dc:creator>
<dc:creator>Hunter, P. J.</dc:creator>
<dc:date>2021-04-04</dc:date>
<dc:identifier>doi:10.1101/2021.04.01.438136</dc:identifier>
<dc:title><![CDATA[The SPARC DRC: Building a resource for the autonomic nervous system community]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-04-04</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2021.04.30.442206v1?rss=1">
<title>
<![CDATA[
High-density spinal cord stimulation selectively activates lower urinary tract afferents 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2021.04.30.442206v1?rss=1"
</link>
<description><![CDATA[
Epidural spinal cord stimulation (SCS) has recently been reported as a potential intervention to improve limb and autonomic functions, with lumbar stimulation improving locomotion and thoracic stimulation regulating blood pressure. We asked whether sacral SCS could be used to target the lower urinary tract. Here we show that high-density epidural SCS over the sacral spinal cord and cauda equina of anesthetized cats evokes responses in nerves innervating the bladder and urethra and that these nerves can be activated selectively. Sacral epidural SCS always recruited the pelvic and pudendal nerves and selectively recruited these nerves in all but one animal. Individual branches of the pudendal nerve were always recruited as well. Electrodes that selectively recruited specific peripheral nerves were spatially clustered on the arrays, suggesting anatomically organized sensory pathways. This selective recruitment demonstrates a mechanism to directly modulate bladder and urethral function through known reflex pathways, which could be used to restore bladder and urethral function after injury or disease.
]]></description>
<dc:creator>Jantz, M. K.</dc:creator>
<dc:creator>Gopinath, C.</dc:creator>
<dc:creator>Kumar, R.</dc:creator>
<dc:creator>Chin, C.</dc:creator>
<dc:creator>Wong, L.</dc:creator>
<dc:creator>Ogren, J. I.</dc:creator>
<dc:creator>Fisher, L. E.</dc:creator>
<dc:creator>McLaughlin, B. L.</dc:creator>
<dc:creator>Gaunt, R. A.</dc:creator>
<dc:date>2021-05-01</dc:date>
<dc:identifier>doi:10.1101/2021.04.30.442206</dc:identifier>
<dc:title><![CDATA[High-density spinal cord stimulation selectively activates lower urinary tract afferents]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-05-01</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2021.02.10.430563v1?rss=1">
<title>
<![CDATA[
SPARC Data Structure: Rationale and Design of a FAIR Standard for Biomedical Research Data 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2021.02.10.430563v1?rss=1"
</link>
<description><![CDATA[
The NIH Common Funds Stimulating Peripheral Activity to Relieve Conditions (SPARC) initiative is a large-scale program that seeks to accelerate the development of therapeutic devices that modulate electrical activity in nerves to improve organ function. Integral to the SPARC program are the rich anatomical and functional datasets produced by investigators across the SPARC consortium that provide key details about organ-specific circuitry, including structural and functional connectivity, mapping of cell types and molecular profiling. These datasets are provided to the research community through an open data platform, the SPARC Portal. To ensure SPARC datasets are Findable, Accessible, Interoperable and Reusable (FAIR), they are all submitted to the SPARC portal following a standard scheme established by the SPARC Curation Team, called the SPARC Data Structure (SDS). Inspired by the Brain Imaging Data Structure (BIDS), the SDS has been designed to capture the large variety of data generated by SPARC investigators who are coming from all fields of biomedical research. Here we present the rationale and design of the SDS, including a description of the SPARC curation process and the automated tools for complying with the SDS, including the SDS validator and Software to Organize Data Automatically (SODA) for SPARC. The objective is to provide detailed guidelines for anyone desiring to comply with the SDS. Since the SDS are suitable for any type of biomedical research data, it can be adopted by any group desiring to follow the FAIR data principles for managing their data, even outside of the SPARC consortium. Finally, this manuscript provides a foundational framework that can be used by any organization desiring to either adapt the SDS to suit the specific needs of their data or simply desiring to design their own FAIR data sharing scheme from scratch.
]]></description>
<dc:creator>Bandrowski, A.</dc:creator>
<dc:creator>Grethe, J. S.</dc:creator>
<dc:creator>Pilko, A.</dc:creator>
<dc:creator>Gillespie, T. H.</dc:creator>
<dc:creator>Pine, G.</dc:creator>
<dc:creator>Patel, B.</dc:creator>
<dc:creator>Surles-Zeiglera, M.</dc:creator>
<dc:creator>Martone, M. E.</dc:creator>
<dc:date>2021-02-10</dc:date>
<dc:identifier>doi:10.1101/2021.02.10.430563</dc:identifier>
<dc:title><![CDATA[SPARC Data Structure: Rationale and Design of a FAIR Standard for Biomedical Research Data]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-02-10</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2021.11.09.467343v1?rss=1">
<title>
<![CDATA[
Fascicles split or merge every ~560 microns within the human cervical vagus nerve 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2021.11.09.467343v1?rss=1"
</link>
<description><![CDATA[
1Vagus nerve stimulation (VNS) is FDA approved for stroke rehabilitation, epilepsy, and depression; however, the vagus functional anatomy underlying the implant is poorly understood. We used microCT to quantify fascicular structure and neuroanatomy within human cervical vagus nerves. Fascicles split or merged every ~560 m (17.8 {+/-} 6.1 events/cm). The high degree of fascicular splitting and merging in humans may explain the clinical heterogeneity in patient responses.
]]></description>
<dc:creator>Upadhye, A. R.</dc:creator>
<dc:creator>Kolluru, C.</dc:creator>
<dc:creator>Druschel, L.</dc:creator>
<dc:creator>Al Lababidi, L.</dc:creator>
<dc:creator>Ahmad, S.</dc:creator>
<dc:creator>Menendez, D.</dc:creator>
<dc:creator>Buyukcelik, O. N.</dc:creator>
<dc:creator>Settell, M. L.</dc:creator>
<dc:creator>Jenkins, M. W.</dc:creator>
<dc:creator>Wilson, D.</dc:creator>
<dc:creator>Zhang, J.</dc:creator>
<dc:creator>Tatsuoka, C.</dc:creator>
<dc:creator>Grill, W. M.</dc:creator>
<dc:creator>Pelot, N. A.</dc:creator>
<dc:creator>Ludwig, K.</dc:creator>
<dc:creator>Gustafson, K. J.</dc:creator>
<dc:creator>Shoffstall, A. J.</dc:creator>
<dc:date>2021-11-11</dc:date>
<dc:identifier>doi:10.1101/2021.11.09.467343</dc:identifier>
<dc:title><![CDATA[Fascicles split or merge every ~560 microns within the human cervical vagus nerve]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2021-11-11</prism:publicationDate>
<prism:section></prism:section>
</item>
<item rdf:about="https://biorxiv.org/cgi/content/short/2022.02.24.480770v1?rss=1">
<title>
<![CDATA[
Comparative transcriptomics reveal highly conserved regional programs between porcine and human colonic enteric nervous system 
]]>
</title>
<link>
https://biorxiv.org/cgi/content/short/2022.02.24.480770v1?rss=1"
</link>
<description><![CDATA[
The porcine gut is increasingly regarded as a useful translational model. The enteric nerve system (ENS) in the colon coordinates diverse functions. However, knowledge of the molecular profiling of porcine ENS and its similarity to that of human is limited. We identified the distinct transcriptional programs associated with functional characteristics between inner submucosal and myenteric ganglia (ISG, MG) in porcine proximal and distal colon (p-pC, p-dC) using bulk RNA sequencing (RNA-seq) and single-cell RNA-seq. Comparative transcriptomics of MG in corresponding colonic regions of porcine and human revealed highly conserved programs existing in p-pC and p-dC, which explained >90% of their transcriptomic responses to vagal nerve stimulation (VNS), suggesting that p-pC and p-dC could serve as predictors in translational studies. The conserved programs specific for inflammatory modulation were displayed in porcine with VNS. This study provides a valuable transcriptomic resource for understanding of human colonic functions and neuromodulation using porcine model.
]]></description>
<dc:creator>Li, T.</dc:creator>
<dc:creator>Morselli, M.</dc:creator>
<dc:creator>Su, T.</dc:creator>
<dc:creator>Mulugeta, M.</dc:creator>
<dc:creator>Larauche, M.</dc:creator>
<dc:creator>Tache, Y.</dc:creator>
<dc:creator>Yuan, P.-Q.</dc:creator>
<dc:date>2022-02-25</dc:date>
<dc:identifier>doi:10.1101/2022.02.24.480770</dc:identifier>
<dc:title><![CDATA[Comparative transcriptomics reveal highly conserved regional programs between porcine and human colonic enteric nervous system]]></dc:title>
<dc:publisher>Cold Spring Harbor Laboratory Press</dc:publisher>
<prism:publicationDate>2022-02-25</prism:publicationDate>
<prism:section></prism:section>
</item>
</rdf:RDF>
