scholarly journals Frameshift mutations of YPEL3 alter sensory circuit function in Drosophila

2019 ◽  
Author(s):  
Jung Hwan Kim ◽  
Monika Singh ◽  
Geng Pan ◽  
Adrian Lopez ◽  
Nicholas Zito ◽  
...  
Keyword(s):  
Frameshift Mutation ◽  
Synaptic Contact ◽  
Synaptic Connection ◽  
Allyl Isothiocyanate ◽  
Nociceptive Response ◽  
Presynaptic Mechanisms ◽  
Human Disorder ◽  
Neurological Conditions ◽  
Dendritic Development ◽  
Circuit Function

ABSTRACTA frameshift mutation in Yippee-like (YPEL) 3 was recently found from a rare human disorder with peripheral neurological conditions including hypotonia and areflexia. The YPEL gene family is highly conserved from yeast to human, but their functions are poorly defined. Moreover, the pathogenicity of the human YPEL3 variant is completely unknown. To tackle these issues, we generated a Drosophila model of human YPEL3 variant by CRISPR-mediated In-del mutagenesis. Gene-trap analysis suggests that Drosophila YPEL3 (dYPEL3) is predominantly expressed in subsets of neurons, including nociceptors. Analysis on chemical nociception induced by allyl-isothiocyanate (AITC), a natural chemical stimulant, revealed a reduced nociceptive response in dYPEL3 mutants. Subsequent circuit analysis showed a reduction in the activation of second-order neurons (SONs) in the pathway without affecting nociceptor activation upon AITC treatment. Although the gross axonal and dendritic development of nociceptors was not affected, the synaptic contact between nociceptors and SONs were decreased by dYPEL3 mutations. Together, these suggest that the frameshift mutation in human YPEL3 causes neurological conditions by weakening synaptic connection through presynaptic mechanisms.

Lateral Hypothalamic-Induced Alpha-Adrenoceptor Modulation Occurs in a Model of Inflammatory Pain in Rats

2009 ◽  
Vol 10 (4) ◽  
pp. 331-339 ◽  
Author(s):  
Younhee Jeong ◽  
Janean E. Holden
Keyword(s):  
Dorsal Horn ◽  
Inflammatory Pain ◽  
Antinociceptive Effect ◽  
Allyl Isothiocyanate ◽  
Spinal Cord Dorsal Horn ◽  
Mustard Oil ◽  
Control Group ◽  
Nociceptive Response ◽  
Sprague Dawley ◽  
Alpha Adrenoceptor

Previous work from our lab showed that stimulation of the lateral hypothalamus (LH) produces analgesia (antinociception) in a model of thermal nociceptive pain. This antinociceptive effect is mediated by α2-adrenoceptors in the spinal cord dorsal horn. However, a concomitant, opposing hyperalgesic (pro-nociceptive) response also occurs, which is mediated by α1-adrenoceptors in the dorsal horn. Antinociception predominates but is attenuated by the pronociceptive response. To determine whether such an effect occurs in a model of inflammatory pain, we applied mustard oil (allyl isothiocyanate; 20 μl) to the left ankle of female Sprague-Dawley rats. We then stimulated the LH using carbamylcholine chloride (carbachol; 125 nmol). The foot withdrawal latencies were measured. Some rats received intrathecal α-adrenoceptor antagonists to determine whether the opposing α-adrenoceptor response was present. Mustard oil application produced hyperalgesia in the affected paw, while the LH stimulation increased the foot withdrawal latencies for the mustard oil paw as compared to the control group. Following carbachol microinjection in the LH, WB4101, an α1-adrenoceptor antagonist, produced significantly longer foot withdrawal latencies compared to saline controls, while yohimbine, an α2-antagonist, decreased the foot withdrawal latencies from 10 min postinjection ( p < .05). These findings support the hypothesis that the LH-induced nociceptive modulation is mediated through an α-adrenoceptor opposing response in a model of inflammatory pain.

Microfabrication research at the National Submicron Facility

1983 ◽  
Vol 41 ◽  
pp. 86-89
Author(s):  
E.D. Wolf
Keyword(s):  
Integrated Circuits ◽  
Particle Physics ◽  
High Speed ◽  
New Technology ◽  
High Energy ◽  
High Energy Particle ◽  
New Science ◽  
Wide Range ◽  
Intermediate Domain ◽  
Circuit Function

Most microelectronics devices and circuits operate faster, consume less power, execute more functions and cost less per circuit function when the feature-sizes internal to the devices and circuits are made smaller. This is part of the stimulus for the Very High-Speed Integrated Circuits (VHSIC) program. There is also a need for smaller, more sensitive sensors in a wide range of disciplines that includes electrochemistry, neurophysiology and ultra-high pressure solid state research. There is often fundamental new science (and sometimes new technology) to be revealed (and used) when a basic parameter such as size is extended to new dimensions, as is evident at the two extremes of smallness and largeness, high energy particle physics and cosmology, respectively. However, there is also a very important intermediate domain of size that spans from the diameter of a small cluster of atoms up to near one micrometer which may also have just as profound effects on society as “big” physics.

The Lateral Giant Fiber to Motor Giant Fiber Synapse in Crayfish

1972 ◽  
Vol 30 ◽  
pp. 170-171
Author(s):  
Charles A. Stirling
Keyword(s):  
Synaptic Vesicles ◽  
Procambarus Clarkii ◽  
Synaptic Contact ◽  
Giant Fiber ◽  
Synaptic Junctions

The lateral giant (LG) to motor giant (MoG) synapses in crayfish (Procambarus clarkii) abdominal ganglia are the classic electrotonic synapses. They have previously been described as having synaptic vesicles and as having them on both the pre- and postsynaptic sides of symmetrical synaptic junctions. This positioning of vesicles would make these very atypical synapses, but in the present work on the crayfish Astacus pallipes the motor giant has never been found to contain any type of vesicle at its synapses with the lateral giant fiber.The lateral to motor giant fiber synapses all occur on short branches off the main giant fibers. Closely associated with these giant fiber synapses are two small presynaptic nerves which make synaptic contact with both of the giant fibers and with their small branches.

Inbox: Elevator Speeches for Neurological Conditions

ASHA Leader ◽  
2014 ◽  
Vol 19 (1) ◽  
pp. 6-6
Author(s):  
Charles Ellis Jr.
Keyword(s):  
Neurological Conditions

Somatic hMLH3 frameshift mutation in colorectal cancers with microsatellite instability

2001 ◽  
Vol 120 (5) ◽  
pp. A295-A295
Author(s):  
D CHANG ◽  
A GOEL ◽  
L RICCIARDIELLO ◽  
C ARNOLD ◽  
C BOLAND
Keyword(s):  
Microsatellite Instability ◽  
Frameshift Mutation ◽  
Colorectal Cancers

Neurological consultations and diagnoses in a large, dedicated COVID-19 university hospital

2020 ◽  
Vol 78 (8) ◽  
pp. 494-500 ◽  
Author(s):  
Adalberto STUDART-NETO ◽  
Bruno Fukelmann GUEDES ◽  
Raphael de Luca e TUMA ◽  
Antonio Edvan CAMELO FILHO ◽  
Gabriel Taricani KUBOTA ◽  
...  
Keyword(s):  
Neurological Diseases ◽  
Neuromuscular Disorders ◽  
Neurological Symptoms ◽  
University Hospital ◽  
Special Treatment ◽  
Nasal Swabs ◽  
Neurological Exam ◽  
Neurological Conditions ◽  
De Medicina

ABSTRACT Background: More than one-third of COVID-19 patients present neurological symptoms ranging from anosmia to stroke and encephalopathy. Furthermore, pre-existing neurological conditions may require special treatment and may be associated with worse outcomes. Notwithstanding, the role of neurologists in COVID-19 is probably underrecognized. Objective: The aim of this study was to report the reasons for requesting neurological consultations by internists and intensivists in a COVID-19-dedicated hospital. Methods: This retrospective study was carried out at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil, a 900-bed COVID-19 dedicated center (including 300 intensive care unit beds). COVID-19 diagnosis was confirmed by SARS-CoV-2-RT-PCR in nasal swabs. All inpatient neurology consultations between March 23rd and May 23rd, 2020 were analyzed. Neurologists performed the neurological exam, assessed all available data to diagnose the neurological condition, and requested additional tests deemed necessary. Difficult diagnoses were established in consensus meetings. After diagnosis, neurologists were involved in the treatment. Results: Neurological consultations were requested for 89 out of 1,208 (7.4%) inpatient COVID admissions during that period. Main neurological diagnoses included: encephalopathy (44.4%), stroke (16.7%), previous neurological diseases (9.0%), seizures (9.0%), neuromuscular disorders (5.6%), other acute brain lesions (3.4%), and other mild nonspecific symptoms (11.2%). Conclusions: Most neurological consultations in a COVID-19-dedicated hospital were requested for severe conditions that could have an impact on the outcome. First-line doctors should be able to recognize neurological symptoms; neurologists are important members of the medical team in COVID-19 hospital care.

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