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Article ; Online: Functionally Distinct Circuits Are Linked by Heterocellular Electrical Synapses in the Thalamic Reticular Nucleus.

Vaughn, Mitchell J / Laswick, Zachary / Wang, Huaixing / Haas, Julie S

2024 Volume 11, Issue 1

Abstract: The thalamic reticular nucleus (TRN) inhibits sensory thalamocortical relay neurons and is a key regulator of sensory attention as well as sleep and wake states. Recent developments have identified two distinct genetic subtypes of TRN neurons, calbindin- ... ...

Abstract	The thalamic reticular nucleus (TRN) inhibits sensory thalamocortical relay neurons and is a key regulator of sensory attention as well as sleep and wake states. Recent developments have identified two distinct genetic subtypes of TRN neurons, calbindin-expressing (CB) and somatostatin-expressing (SOM) neurons. These subtypes differ in localization within the TRN, electrophysiological properties, and importantly, targeting of thalamocortical relay channels. CB neurons send inhibition to and receive excitation from first-order thalamic relay nuclei, while SOM neurons send inhibition to and receive excitation from higher-order thalamic areas. These differences create distinct channels of information flow. It is unknown whether TRN neurons form electrical synapses between SOM and CB neurons and consequently bridge first-order and higher-order thalamic channels. Here, we use GFP reporter mice to label and record from CB-expressing and SOM-expressing TRN neurons. We confirm that GFP expression properly differentiates TRN subtypes based on electrophysiological differences, and we identified electrical synapses between pairs of neurons with and without common GFP expression for both CB and SOM types. That is, electrical synapses link both within and across subtypes of neurons in the TRN, forming either homocellular or heterocellular synapses. Therefore, we conclude that electrical synapses within the TRN provide a substrate for functionally linking thalamocortical first-order and higher-order channels within the TRN.
MeSH term(s)	Mice ; Animals ; Electrical Synapses/physiology ; Action Potentials/physiology ; Thalamic Nuclei/physiology ; Neurons/physiology ; Synapses/physiology ; Thalamus
Language	English
Publishing date	2024-01-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2800598-3
ISSN	2373-2822 ; 2373-2822
ISSN (online)	2373-2822
ISSN	2373-2822
DOI	10.1523/ENEURO.0269-23.2023
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Article: On the Diverse Functions of Electrical Synapses.

Vaughn, Mitchell J / Haas, Julie S

Frontiers in cellular neuroscience

2022 Volume 16, Page(s) 910015

Abstract: Electrical synapses are the neurophysiological product of gap junctional pores between neurons that allow bidirectional flow of current between neurons. They are expressed throughout the mammalian nervous system, including cortex, hippocampus, thalamus, ... ...

Abstract	Electrical synapses are the neurophysiological product of gap junctional pores between neurons that allow bidirectional flow of current between neurons. They are expressed throughout the mammalian nervous system, including cortex, hippocampus, thalamus, retina, cerebellum, and inferior olive. Classically, the function of electrical synapses has been associated with synchrony, logically following that continuous conductance provided by gap junctions facilitates the reduction of voltage differences between coupled neurons. Indeed, electrical synapses promote synchrony at many anatomical and frequency ranges across the brain. However, a growing body of literature shows there is greater complexity to the computational function of electrical synapses. The paired membranes that embed electrical synapses act as low-pass filters, and as such, electrical synapses can preferentially transfer spike after hyperpolarizations, effectively providing spike-dependent inhibition. Other functions include driving asynchronous firing, improving signal to noise ratio, aiding in discrimination of dissimilar inputs, or dampening signals by shunting current. The diverse ways by which electrical synapses contribute to neuronal integration merits furthers study. Here we review how functions of electrical synapses vary across circuits and brain regions and depend critically on the context of the neurons and brain circuits involved. Computational modeling of electrical synapses embedded in multi-cellular models and experiments utilizing optical control and measurement of cellular activity will be essential in determining the specific roles performed by electrical synapses in varying contexts.
Language	English
Publishing date	2022-06-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2022.910015
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Article ; Online: Ebola Virus Dose Response Model for Aerosolized Exposures: Insights from Primate Data.

Mitchell, Jade / Dean, Kara / Haas, Charles

Risk analysis : an official publication of the Society for Risk Analysis

2020 Volume 40, Issue 11, Page(s) 2390–2398

Abstract: This study develops dose-response models for Ebolavirus using previously published data sets from the open literature. Two such articles were identified in which three different species of nonhuman primates were challenged by aerosolized Ebolavirus in ... ...

Abstract	This study develops dose-response models for Ebolavirus using previously published data sets from the open literature. Two such articles were identified in which three different species of nonhuman primates were challenged by aerosolized Ebolavirus in order to study pathology and clinical disease progression. Dose groups were combined and pooled across each study in order to facilitate modeling. The endpoint of each experiment was death. The exponential and exact beta-Poisson models were fit to the data using maximum likelihood estimation. The exact beta-Poisson was deemed the recommended model because it more closely approximated the probability of response at low doses though both models provided a good fit. Although transmission is generally considered to be dominated by person-to-person contact, aerosolization is a possible route of exposure. If possible, this route of exposure could be particularly concerning for persons in occupational roles managing contaminated liquid wastes from patients being treated for Ebola infection and the wastewater community responsible for disinfection. Therefore, this study produces a necessary mathematical relationship between exposure dose and risk of death for the inhalation route of exposure that can support quantitative microbial risk assessment aimed at informing risk mitigation strategies including personal protection policies against occupational exposures.
MeSH term(s)	Aerosols ; Animals ; Disease Models, Animal ; Ebolavirus/pathogenicity ; Hemorrhagic Fever, Ebola/transmission ; Humans ; Occupational Exposure/prevention & control ; Poisson Distribution ; Primates ; Risk Assessment
Chemical Substances	Aerosols
Language	English
Publishing date	2020-07-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	778660-8
ISSN	1539-6924 ; 0272-4332
ISSN (online)	1539-6924
ISSN	0272-4332
DOI	10.1111/risa.13551
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Article ; Online: Where the leatherbacks roam

Mitchell J. Rider / Larisa Avens / Heather L. Haas / Joshua M. Hatch / Samir H. Patel / Christopher R. Sasso

Frontiers in Marine Science, Vol

movement behavior analyses reveal novel foraging locations along the Northwest Atlantic shelf

2024 Volume 11

Abstract: Leatherback sea turtles (Dermochelys coriacea) migrate along the east coast of the United States, traversing the South and Mid-Atlantic Bights (SAB and MAB) while traveling to and from well-known northern foraging areas off Southern New England (SNE) and ...

Abstract	Leatherback sea turtles (Dermochelys coriacea) migrate along the east coast of the United States, traversing the South and Mid-Atlantic Bights (SAB and MAB) while traveling to and from well-known northern foraging areas off Southern New England (SNE) and Nova Scotia. However, there is limited information on leatherback movement behavior in these regions. To identify leatherback movement patterns, we fit hidden Markov models (HMMs) to satellite transmitter data from 52 leatherbacks tagged between 2017 and 2022 off the coasts of Massachusetts and North Carolina to estimate locations of area restricted searching (ARS) and transient behaviors. Depth-temperature profiles were then paired to locations associated with ARS behavior to understand the vertical use of the water column. We observed leatherbacks displaying ARS behavior in SNE as expected, but also in the MAB and SAB. The HMM results indicated that leatherbacks were primarily foraging in SNE between Nantucket and Long Island Sound and depth-temperature plots from ARS behavior on Nantucket Shoals implied turtles foraging throughout the entire water column. In the MAB, ARS behavior was concentrated between Cape Hatteras, North Carolina, and the mouth of Delaware Bay during the summer. Turtles were closely associated with a well-defined thermocline, but still appeared to dive to deeper cooler waters, which may be a sign of thermoregulatory behavior. There was evidence of foraging in the SAB along the coast as well as along the continental shelf edge. The ARS behavior we documented within the MAB and SAB is the first published empirical evidence that both areas may be important foraging grounds. Our results lay a path for future research to understand how leatherbacks use these areas and the potential anthropogenic threats encountered while moving through these regions.
Keywords	satellite telemetry ; leatherback turtle ; movement ecology ; foraging ; migration ; Mid-Atlantic Bight ; Science ; Q ; General. Including nature conservation ; geographical distribution ; QH1-199.5
Subject code	551
Language	English
Publishing date	2024-02-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Design of a Computed Tomography Automation Architecture

Nicholas Hashem / Mitchell Pryor / Derek Haas / James Hunter

Applied Sciences, Vol 11, Iss 2858, p

2021 Volume 2858

Abstract: This paper presents a literature review on techniques related to the computed tomography procedure that incorporate automation elements in their research investigations or industrial applications. Computed tomography (CT) is a non-destructive testing ( ... ...

Abstract	This paper presents a literature review on techniques related to the computed tomography procedure that incorporate automation elements in their research investigations or industrial applications. Computed tomography (CT) is a non-destructive testing (NDT) technique in that the imaging and inspection are performed without damaging the sample, allowing for additional or repeated analysis if necessary. The reviewed literature is organized based on the steps associated with a general NDT task in order to define an end-to-end computed tomography automation architecture. The process steps include activities prior to image collection, during the scan, and after the data are collected. It further reviews efforts related to repeating this process based on a previous scan result. By analyzing the multiple existing but disparate efforts found in the literature, we present a framework for fully automating NDT procedures and discuss the remaining technical gaps in the developed framework.
Keywords	computed tomography ; radiography ; automation ; robotics ; radiation imaging ; X-ray ; Technology ; T ; Engineering (General). Civil engineering (General) ; TA1-2040 ; Biology (General) ; QH301-705.5 ; Physics ; QC1-999 ; Chemistry ; QD1-999
Subject code	670
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Notch signaling induces either apoptosis or cell fate change in multiciliated cells during mucociliary tissue remodeling.

Tasca, Alexia / Helmstädter, Martin / Brislinger, Magdalena Maria / Haas, Maximilian / Mitchell, Brian / Walentek, Peter

Developmental cell

2021 Volume 56, Issue 4, Page(s) 525–539.e6

Abstract: Multiciliated cells (MCCs) are extremely highly differentiated, presenting >100 cilia and basal bodies. Therefore, MCC fate is thought to be terminal and irreversible. We analyzed how MCCs are removed from the airway-like mucociliary Xenopus epidermis ... ...

Abstract	Multiciliated cells (MCCs) are extremely highly differentiated, presenting >100 cilia and basal bodies. Therefore, MCC fate is thought to be terminal and irreversible. We analyzed how MCCs are removed from the airway-like mucociliary Xenopus epidermis during developmental tissue remodeling. We found that a subset of MCCs undergoes lateral line-induced apoptosis, but that the majority coordinately trans-differentiate into goblet secretory cells. Both processes are dependent on Notch signaling, while the cellular response to Notch is modulated by Jak/STAT, thyroid hormone, and mTOR signaling. At the cellular level, trans-differentiation is executed through the loss of ciliary gene expression, including foxj1 and pcm1, altered proteostasis, cilia retraction, basal body elimination, as well as the initiation of mucus production and secretion. Our work describes two modes for MCC loss during vertebrate development, the signaling regulation of these processes, and demonstrates that even cells with extreme differentiation features can undergo direct fate conversion.
MeSH term(s)	Animals ; Apoptosis ; Autophagy ; Basal Bodies/metabolism ; Basal Bodies/ultrastructure ; Cell Lineage ; Cell Transdifferentiation ; Cilia/metabolism ; Cilia/ultrastructure ; Epidermal Cells/metabolism ; Janus Kinases/metabolism ; Lateral Line System/metabolism ; Organ Specificity ; Receptors, Notch/metabolism ; STAT Transcription Factors/metabolism ; Signal Transduction ; Xenopus Proteins/metabolism ; Xenopus laevis/embryology ; Xenopus laevis/metabolism
Chemical Substances	Receptors, Notch ; STAT Transcription Factors ; Xenopus Proteins ; Janus Kinases (EC 2.7.10.2)
Language	English
Publishing date	2021-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2054967-2
ISSN	1878-1551 ; 1534-5807
ISSN (online)	1878-1551
ISSN	1534-5807
DOI	10.1016/j.devcel.2020.12.005
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Book ; Online: Lane-Level Route Planning for Autonomous Vehicles

Jones, Mitchell / Haas-Heger, Maximilian / Berg, Jur van den

2022

Abstract: We present an algorithm that, given a representation of a road network in lane-level detail, computes a route that minimizes the expected cost to reach a given destination. In doing so, our algorithm allows us to solve for the complex trade-offs ... ...

Abstract	We present an algorithm that, given a representation of a road network in lane-level detail, computes a route that minimizes the expected cost to reach a given destination. In doing so, our algorithm allows us to solve for the complex trade-offs encountered when trying to decide not just which roads to follow, but also when to change between the lanes making up these roads, in order to -- for example -- reduce the likelihood of missing a left exit while not unnecessarily driving in the leftmost lane. This routing problem can naturally be formulated as a Markov Decision Process (MDP), in which lane change actions have stochastic outcomes. However, MDPs are known to be time-consuming to solve in general. In this paper, we show that -- under reasonable assumptions -- we can use a Dijkstra-like approach to solve this stochastic problem, and benefit from its efficient $O(n \log n)$ running time. This enables an autonomous vehicle to exhibit lane-selection behavior as it efficiently plans an optimal route to its destination. Comment: Appeared at the 15th International Workshop on the Algorithmic Foundations of Robotics (WAFR) 2022
Keywords	Computer Science - Robotics
Publishing date	2022-06-06
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Relationship Between Radiographic Lumbosacral Spine Mensuration and Chronic Low Back Pain Intensity: A Cross-sectional Study.

Shortz, Savannah K / Haas, Mitchell

Journal of chiropractic medicine

2018 Volume 17, Issue 1, Page(s) 1–6

Abstract: Objective: The purpose of this study was to investigate correlative factors affecting chronic low back pain (CLBP), with special emphasis on the radiographic postural findings in the sagittal lumbosacral spine.: Methods: A cross-sectional study ... ...

Abstract	Objective: The purpose of this study was to investigate correlative factors affecting chronic low back pain (CLBP), with special emphasis on the radiographic postural findings in the sagittal lumbosacral spine. Methods: A cross-sectional study alongside a randomized trial was conducted. Standing lateral lumbar spine radiographs from 352 patients with CLBP enrolled in a randomized trial were analyzed and radiographic mensuration of lumbar lordosis, lumbosacral disc angle, and sacral inclination performed. These angles were correlated with baseline variables, including CLBP intensity, age, and sex. Multiple polynomial regressions were performed in which CLBP intensity was regressed on linear and quadratic terms of lumbar lordosis to investigate the possibility of greater pain with hypo- and/or hyperlordosis. Results: There was no significant correlation of the angles with pain and age ( Conclusion: This study determined that there was no correlation between lumbar lordosis and pain levels for people with CLBP; thus, use of lumbar spine radiographic mensuration in the management of pain for people with CLBP is not recommended.
Language	English
Publishing date	2018-01-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2365038-2
ISSN	1556-3715 ; 1556-3707
ISSN (online)	1556-3715
ISSN	1556-3707
DOI	10.1016/j.jcm.2017.10.005
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Article ; Online: Genomic Analysis of Vancomycin-Resistant Staphylococcus aureus Isolates from the 3rd Case Identified in the United States Reveals Chromosomal Integration of the

Haas, Wolfgang / Singh, Navjot / Lainhart, William / Mingle, Lisa / Nazarian, Elizabeth / Mitchell, Kara / Nattanmai, Geetha / Kohlerschmidt, Donna / Dickinson, Michelle C / Kacica, Marilyn / Dumas, Nellie / Musser, Kimberlee A

Microbiology spectrum

2023 , Page(s) e0431722

Abstract: Vancomycin-resistant Staphylococcus aureus (VRSA) is a human pathogen of significant public health concern. Although the genome sequences of individual VRSA isolates have been published over the years, very little is known about the genetic changes of ... ...

Abstract	Vancomycin-resistant Staphylococcus aureus (VRSA) is a human pathogen of significant public health concern. Although the genome sequences of individual VRSA isolates have been published over the years, very little is known about the genetic changes of VRSA within a patient over time. A total of 11 VRSA, 3 vancomycin-resistant enterococci (VRE), and 4 methicillin-resistant S. aureus (MRSA) isolates, collected over a period of 4.5 months in 2004 from a patient in a long-term-care facility in New York State, were sequenced. A combination of long- and short-read sequencing technologies was used to obtain closed assemblies for chromosomes and plasmids. Our results indicate that a VRSA isolate emerged as the result of the transfer of a multidrug resistance plasmid from a coinfecting VRE to an MRSA isolate. The plasmid then integrated into the chromosome via homologous recombination mediated between two regions derived from remnants of transposon Tn
Language	English
Publishing date	2023-03-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.04317-22
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Article ; Online: Early Increases in Blood Pressure and Major Adverse Cardiovascular Events in Patients With Renal Cell Carcinoma and Thyroid Cancer Treated With VEGFR TKIs.

Narayan, Vivek / Liu, Tao / Song, Yunjie / Mitchell, Joshua / Sicks, JoRean / Gareen, Ilana / Sun, Lova / Denduluri, Srinivas / Fisher, Ciaran / Manikowski, Jesse / Wojtowicz, Mark / Vadakara, Joseph / Haas, Naomi / Margulies, Kenneth B / Ky, Bonnie

Journal of the National Comprehensive Cancer Network : JNCCN

2023 Volume 21, Issue 10, Page(s) 1039–1049.e10

Abstract: Background: Although VEGFR tyrosine kinase inhibitors (TKIs) are a preferred systemic treatment approach for patients with advanced renal cell carcinoma (RCC) and thyroid carcinoma (TC), treatment-related cardiovascular (CV) toxicity is an important ... ...

Abstract	Background: Although VEGFR tyrosine kinase inhibitors (TKIs) are a preferred systemic treatment approach for patients with advanced renal cell carcinoma (RCC) and thyroid carcinoma (TC), treatment-related cardiovascular (CV) toxicity is an important contributor to morbidity. However, the clinical risk assessment and impact of CV toxicities, including early significant hypertension, among real-world advanced cancer populations receiving VEGFR TKI therapies remain understudied. Methods: In a multicenter, retrospective cohort study across 3 large and diverse US health systems, we characterized baseline hypertension and CV comorbidity in patients with RCC and those with TC who are newly initiating VEGFR TKI therapy. We also evaluated baseline patient-, treatment-, and disease-related factors associated with the risk for treatment-related early hypertension (within 6 weeks of TKI initiation) and major adverse CV events (MACE), accounting for the competing risk of death in an advanced cancer population, after VEGFR TKI initiation. Results: Between 2008 and 2020, 987 patients (80.3% with RCC, 19.7% with TC) initiated VEGFR TKI therapy. The baseline prevalence of hypertension was high (61.5% and 53.6% in patients with RCC and TC, respectively). Adverse CV events, including heart failure and cerebrovascular accident, were common (occurring in 14.9% of patients) and frequently occurred early (46.3% occurred within 1 year of VEGFR TKI initiation). Baseline hypertension and Black race were the primary clinical factors associated with increased acute hypertensive risk within 6 weeks of VEGFR TKI initiation. However, early significant "on-treatment" hypertension was not associated with MACE. Conclusions: These multicenter, real-world findings indicate that hypertensive and CV morbidities are highly prevalent among patients initiating VEGFR TKI therapies, and baseline hypertension and Black race represent the primary clinical factors associated with VEGFR TKI-related early significant hypertension. However, early on-treatment hypertension was not associated with MACE, and cancer-specific CV risk algorithms may be warranted for patients initiating VEGFR TKIs.
MeSH term(s)	Humans ; Carcinoma, Renal Cell/drug therapy ; Carcinoma, Renal Cell/epidemiology ; Kidney Neoplasms/drug therapy ; Kidney Neoplasms/epidemiology ; Blood Pressure ; Retrospective Studies ; Protein Kinase Inhibitors/adverse effects ; Thyroid Neoplasms/drug therapy ; Thyroid Neoplasms/epidemiology ; Hypertension/chemically induced ; Hypertension/epidemiology ; Hypertension/drug therapy
Chemical Substances	Protein Kinase Inhibitors
Language	English
Publishing date	2023-10-19
Publishing country	United States
Document type	Multicenter Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2250759-0
ISSN	1540-1413 ; 1540-1405
ISSN (online)	1540-1413
ISSN	1540-1405
DOI	10.6004/jnccn.2023.7047
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