Measurement of Subcellular Force Generation in Neurons

AbstractForces are important for neuronal outgrowth during the initial wiring of the nervous system and after trauma, yet subcellular force generation over the microtubule-rich region at the rear of the growth cone and along the axon has never, to our knowledge, been directly measured. Because previous studies have indicated microtubule polymerization and the microtubule-associated proteins Kinesin-1 and dynein all generate forces that push microtubules forward, a major question is whether the net forces in these regions are contractile or expansive. A challenge in addressing this is that measuring local subcellular force generation is difficult. Here we develop an analytical mathematical model that describes the relationship between unequal subcellular forces arranged in series within the neuron and the net overall tension measured externally. Using force-calibrated towing needles to measure and apply forces, in combination with docked mitochondria to monitor subcellular strain, we then directly measure force generation over the rear of the growth cone and along the axon of chick sensory neurons. We find the rear of the growth cone generates 2.0 nN of contractile force, the axon generates 0.6 nN of contractile force, and that the net overall tension generated by the neuron is 1.3 nN. This work suggests that the forward bulk flow of the cytoskeletal framework that occurs during axonal elongation and growth-cone pauses arises because strong contractile forces in the rear of the growth cone pull material forward

Direct evidence for coherent low velocity axonal transport of mitochondria

Axonal growth depends on axonal transport. We report the first global analysis of mitochondrial transport during axonal growth and pauses. In the proximal axon, we found that docked mitochondria attached to the cytoskeletal framework that were stationary relative to the substrate and fast axonal transport fully accounted for mitochondrial transport. In the distal axon, we found both fast mitochondrial transport and a coherent slow transport of the mitochondria docked to the axonal framework (low velocity transport [LVT]). LVT was distinct from previously described transport processes; it was coupled with stretching of the axonal framework and, surprisingly, was independent of growth cone advance. Fast mitochondrial transport decreased and LVT increased in a proximodistal gradient along the axon, but together they generated a constant mitochondrial flux. These findings suggest that the viscoelastic stretching/creep of axons caused by tension exerted by the growth cone, with or without advance, is seen as LVT that is followed by compensatory intercalated addition of new mitochondria by fast axonal transport

Why Donald Trump’s election may mean we see more liberal conspiracy theories about the government

In 2016, conspiracy theories seem to have become part of politics’ new normal. But what kinds of people are more likely to believe in certain conspiracy theories? In new research, Joanne M. Miller, Kyle L. Saunders and Christina E. Farhart find that conservatives are more likely to endorse ideologically motivated conspiracy theories – such as the idea that President Obama was not born in the US – if they have low levels of trust in government and greater political knowledge. Liberals, on the other hand, are less likely to endorse liberal conspiracy theories if they have both greater political knowledge and more trust in government

3D Mapping with an Unmanned Aerial Vehicle

Missionary aviation pilots often have to land their planes on remote airstrips that might be unsafe due to runway obstructions such as encroaching vegetation or large objects that were unknowingly placed on the runway. The Falcon Unmanned Aerial Vehicle (UAV) team is partnering with ITEC to develop an imaging system using a UAV to scan these airstrips to detect these obstructions. ITEC was founded by Steve Saint, the son of martyred missionary Nate Saint, to develop technologies to aid missionaries in their work. This video highlights the work of the Falcon UAV team and the basic terms and definitions for understanding the work of the team. The Falcon UAV team focuses primarily on the use of automated 3D mapping and photogrammetry by drones to help identify obstructions to pilots landing on remote airstrips. In this video, we will explore 3D mapping and compare different options for drones to purchase and software to use in the process of mapping information.https://mosaic.messiah.edu/engr2020/1007/thumbnail.jp

Evaluation of the 20 L Dust Explosibility Testing Chamber and Comparison to a Modified 38 L Vessel for Underground Coal

The phenomenon of combustible dust explosions is present within many industries. Tests for explosibility of dust clouds per ASTM E1226 use a 20 L explosive chamber that places the combustible dust directly below the dispersion nozzle which generates a thorough mixture for testing purposes. However, in the underground coal mining industry, there are a number of geologic, mining, and regulatory factors that change the deposition scheme of combustible coal dust. This causes the atmosphere of a coal mine to have a variable rock dust-coal dust mixture at the time of ignition. To investigate the impact of this variable atmosphere, a series of lean explosibility tests were conducted on a sample of Pittsburgh Pulverized coal dust. These explosibility tests were conducted in a 38 L chamber with a 5 kJ Sobbe igniter. The 38 L chamber generates a variable air-dust mixture prior to ignition. The test results indicate that the 38 L chamber experiences reduced explosive pressures, and lower explosibility index values when compared to the 20 L chamber

Slowing of axonal regeneration is correlated with increased axonal viscosity during aging

<p>Abstract</p> <p>Background</p> <p>As we age, the speed of axonal regeneration declines. At the biophysical level, why this occurs is not well understood.</p> <p>Results</p> <p>To investigate we first measured the rate of axonal elongation of sensory neurons cultured from neonatal and adult rats. We found that neonatal axons grew 40% faster than adult axons (11.5 µm/hour vs. 8.2 µm/hour). To determine how the mechanical properties of axons change during maturation, we used force calibrated towing needles to measure the viscosity (stiffness) and strength of substrate adhesion of neonatal and adult sensory axons. We found no significant difference in the strength of adhesions, but did find that adult axons were 3 times intrinsically stiffer than neonatal axons.</p> <p>Conclusions</p> <p>Taken together, our results suggest decreasing axonal stiffness may be part of an effective strategy to accelerate the regeneration of axons in the adult peripheral nervous system.</p

Longitudinal patterns of emerging literacy in beginning deaf and hearing readers

The emerging reading and spelling abilities of 24 deaf and 23 hearing beginning readers were followed over 2 years. The deaf children varied in their language backgrounds and preferred mode of communication. All children were given a range of literacy, cognitive and language-based tasks every 12 months. Deaf and hearing children made similar progress in literacy in the beginning stages of reading development and then their trajectories began to diverge. The longitudinal correlates of beginning reading in the deaf children were earlier vocabulary, letter-sound knowledge, and speechreading. Earlier phonological awareness was not a longitudinal correlate of reading ability once earlier reading levels were controlled. Only letter name knowledge was longitudinally related to spelling ability. Speechreading was also a strong longitudinal correlate of reading and spelling in the hearing children. The findings suggested that deaf and hearing children utilize slightly different reading strategies over the first 2 years of schooling

Explosive Dust Test Vessel Comparison using Pulverized Pittsburgh Coal

Explosions of coal dust are a major safety concern within the coal mining industry. The explosion and subsequent fires caused by coal dust can result in significant property damage, loss of life in underground coal mines and damage to coal processing facilities. The United States Bureau of Mines conducted research on coal dust explosions until 1996 when it was dissolved. In the following years, the American Society for Testing and Materials (ASTM) developed a test standard, ASTM E1226, to provide a standard test method characterizing the “explosibility” of particulate solids of combustible materials suspended in air. The research presented herein investigates the explosive characteristic of Pulverized Pittsburgh Coal dust using the ASTM E1226-12 test standard. The explosibility characteristics include: maximum explosion pressure, (Pmax); maximum rate of pressure rise, (dP/dt)max; and explosibility index, (Kst). Nine Pulverized Pittsburgh Coal dust concentrations, ranging from 30 to 1,500 g/m3 , were tested in a 20-Liter Siwek Sphere. The newly recorded dust explosibility characteristics are then compared to explosibility characteristics published by the Bureau of Mines in their 20 liter vessel and procedure predating ASTM E1126-12. The information presented in this paper will allow for structures and devices to be built to protect people from the effects of coal dust explosions

Brominated Flame Retardants: Spatial and Temporal Patterns and Trends in Seabird eggs from the Nearshore Pacific Coast of Canada

Brominated flame retardants (BFRs) have been widely used to reduce fire hazards. One class, the polybrominated diphenyl ethers (PBDEs), are particularly persistent bioaccumulative and toxic chemicals, now classified as POPs under the Stockholm Convention. Marine ecosystems are the ultimate sink for POPs, and thus there is a continuing need to monitor such contamination. Eggs of marine birds have proven to be an efficient and effective means of measuring and tracking xenobiotic compounds which are transferred from the female bird to the egg via yolk lipids or proteins. Here we report and discuss data from long term monitoring of and mercury in seabird eggs from the northeast Pacific. For this program, the marine system was divided, and representative species selected. The nearshore subsurface is monitored using two cormorant, Phalacrocorax, species, auritus and pelagicus, both feed on a variety of benthic and pelagic fish. The inshore and estuarine zone is monitored using the great blue heron, Adea Herodias. Nearshore data will be compared to data from the offshore subsurface monitored using the rhinoceros auklet, Cerorhinca monocerata, a feeder mainly on small pelagic fishes, and the offshore surface species, the Leach’s storm-petrel, Oceanodroma leucorhoa, which feeds mainly on surface plankton and larval fishes. At three breeding colonies each along the Pacific coast of Canada and at four year intervals 15 eggs are collected and archived. Data from a recent retrospective study, using archived samples collected from 1990 to 2011, shows, as reported for more polluted environments, that PBDEs increased in continental shelf ranging auklet eggs until the early 2000s and have declined since then, in response to restrictions on usage. In contrast, another BFR compound, HBCD (hexabromocyclododecane), increased steadily in eggs of both near and offshore species. The possible role of dietary variation, potentially related to marine regime shifts, will be examined by use of stable isotopes in variation in contaminant levels in these monitored seabirds

Intrathecal enzyme replacement for Hurler syndrome: biomarker association with neurocognitive outcomes.

PurposeAbnormalities in cerebrospinal fluid (CSF) have been reported in Hurler syndrome, a fatal neurodegenerative lysosomal disorder. While no biomarker has predicted neurocognitive response to treatment, one of these abnormalities, glycosaminoglycan nonreducing ends (NREs), holds promise to monitor therapeutic efficacy. A trial of intrathecal enzyme replacement therapy (ERT) added to standard treatment enabled tracking of CSF abnormalities, including NREs. We evaluated safety, biomarker response, and neurocognitive correlates of change.MethodsIn addition to intravenous ERT and hematopoietic cell transplantation, patients (N = 24) received intrathecal ERT at four peritransplant time points; CSF was evaluated at each point. Neurocognitive functioning was quantified at baseline, 1 year, and 2 years posttransplant. Changes in CSF biomarkers and neurocognitive function were evaluated for an association.ResultsOver treatment, there were significant decreases in CSF opening pressure, biomarkers of disease activity, and markers of inflammation. Percent decrease in NRE from pretreatment to final intrathecal dose posttransplant was positively associated with percent change in neurocognitive score from pretreatment to 2 years posttransplant.ConclusionIntrathecal ERT was safe and, in combination with standard treatment, was associated with reductions in CSF abnormalities. Critically, we report evidence of a link between a biomarker treatment response and neurocognitive outcome in Hurler syndrome