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Text of the page (random words):
hat achieved ecs preservation using perfusion it s still not entirely clear to me why perfusion doesn t usually achieve ecs preservation but it seems like it probably depends on the osmotic concentration of the perfusate cragg 1980 is 30 years old now it would be ideal if it could be replicated and the phenomenon understood better rate this andy brain banking molecular neuroscience june 25 2022 july 25 2022 2 minutes prenatal epigenetic age acceleration in down syndrome that s a result of xu et al 2022 accelerated epigenetic aging in newborns with down syndrome this study furthers our understanding of a syndrome of accelerated aging the authors show a significant acceleration of an epigenetic aging marker in the blood of people with down syndrome furthermore they show that this effect is present at birth and is significantly stronger in newborns who have down syndrome plus gata1 mutations this association with gata1 mutations is intriguing as gata1 mutations are associated with transient abnormal myelopoiesis one thing that this study does not do is investigate the mechanism by which this age acceleration occurs one hypothesis based on this finding is that it might help explain why people with down syndrome have an increased susceptibility to alzheimer s disease lore has long been that this is due to the triplication of amyloid precursor protein however this study suggests that age acceleration may also play at least a part in the increased susceptibility of people with down syndrome to aging associated cognitive impairment and alzheimer type neuropathology from https onlinelibrary wiley com doi 10 1111 acel 13652 rate this andy aging alzheimers disease june 7 2022 1 minute correlating immunohistochemistry with serial block face electron microscopy of neurons in talapka et al 2022 application of the mirror technique for block face scanning electron microscopy the authors use a modified mirror technique to combine immunohistochemistry for labeling of dendrites and ultrastructural analysis in 3d em of osmicated sections this relies on the finding that the surface of a tissue block can still be imaged using confocal microscopy the authors show that the cell body of a somatostatin immunopositive neuron and one of the emerging dendrites can be clearly visualized and reconstructed after the use of their technique it is likely that the dendritic arbor of a large number of neurons can be analyzed using this technique the technique combines the advantages of a high resolution approach and of a labeling method for specific cellular markers the morphological preservation of the structures seen on the surfaces of tissue sections such as blood vessels will in part determine the quality of the images here is one of the figures from their paper image from https link springer com article 10 1007 s00429 022 02506 w rate this andy uncategorized june 2 2022 1 minute integrating synchrotron microtomography with electron microscopy in the study of mammalian brain tissue bosch et al 2022 functional and multiscale 3d structural investigation of brain tissue through correlative in vivo physiology synchrotron microtomography and volume electron microscopy is an interesting study that brings x ray microscopy to bear on the problem of correlating structure and function the authors studied hippocampal ca1 and olfactory bulb circuits via multiple imaging modalities including 2 photon calcium imaging x ray microscopy and serial block face electron microscopy in all cases the imaging modalities had different strengths in identifying different circuit elements and the authors were able to correlate structure and function in interesting ways the interplay between structural functional and molecular level data will be increasingly critical in systems neuroscience and this study highlights some important points the authors should be commended on showing that x ray microscopy can be used without causing significant damage on fixed and osmium uranium lead en bloc em embedded tissue which is an important advance the authors also showed that x ray microscopy can be used at high resolution on thick mammalian brain tissues this is important because x ray microscopy has the potential to provide structural details at the level of individual dendrites which is possible with volume electron microscopy but less easily scalable finally the authors point out that staining protein and lipid distributions defines the ultrastructure of the tissue this is an important point that is often missed figure 4 from bosch et al https www nature com articles s41467 022 30199 6 rate this andy uncategorized may 26 2022 1 minute question 21 how far would a typical molecule diffuse in a millisecond what is diffusion diffusion is a type of passive transport that involves the net movement of molecules or ions from an area of higher concentration to an area of lower concentration down a concentration gradient the concentration gradient is the difference in concentration between two points in biology diffusion plays an important role in many biological events such as molecular transport cell signaling and neurotransmitter movement across a synaptic cleft how far would a typical molecule diffuse in a millisecond a second an hour diffusion is a description of how molecules will randomly move around in a liquid their movement will be limited if they hit a barrier or randomly collide with another molecule and react which is not described by diffusion the distance a molecule will diffuse in a certain amount of time depends on the size of the molecule the viscosity of the fluid and the temperature this can be explained by the stokes einstein relation d kt 6πηa where d the diffusion constant k the boltzmann constant t the temperature η the viscosity coefficient of the fluid a the radius of the diffusing molecule the constant value is 6 assuming that the radius of the diffusing molecule is greater than the radius of the solvent assuming that we are talking about diffusion at 25 c and in water then there is a nice calculator on physiologyweb com that lists diffusion coefficients for different ions and molecules https www physiologyweb com calculators diffusion_time_calculator html if we are talking about the diffusion of a small molecule neurotransmitter such as glutamate it has a mw of 147 which is close to glucose s mw of 180 so we can use glucose s diffusion coefficient as a rough guide for the diffusion of some types of small molecule neurotransmitters this calculator suggests that glucose will diffuse 1000 nm in a millisecond 31 000 nm 31 μm in a second or 1 900 000 nm 1 9 mm in an hour molecular diffusion rates are helpful when building intuition about what structural information is necessary to be able to infer in brain preservation because in the way that i think about it molecular events that occur more slowly than rapid long term memory recall can be instantiated which conservatively can occur in 500 1000 ms cannot be uniquely necessary for the structural information describing it inspired by caltech s question 21 for cognitive scientists what is diffusion how far would a typical molecule diffuse in a millisecond a second an hour how does the diffusion equation differ from the cable equation rate this andy 100 questions molecular neuroscience february 13 2022 2 minutes question 20 what does the cable equation mean for neurons cable theory as applied to a neurite https en wikipedia org wiki file cable_theory_neuron_rc_circuit_v3 svg a simplified explanation of capacitance in neuronal membranes is that higher capacitance will tend to will cause a flow of ions towards the membrane on the cytoplasmic side due to the difference in charge across the membrane called a displacement current https en wikipedia org wiki cable_theory media file neuroncapacitancerev jpg cable theory can be derived in part from ohm s law the fundamental theory of electricity that models the current flowing between two points as equal to the voltage distance between the two points divided by the material s resistance or in other words the classic equation v ir the greater the cross sectional area of the neurite s cytosol the interior part of it containing biomolecules electrolytes and other ions the easier an ion can flow through it so the neurite s longitudinal resistance r_l will be lower if the cell membrane is more resistant to ion flow into or out of the cell due to high membrane resistance r_m then charge will tend to accumulate inside the cell and it will have a higher ionic current flowing down longer distances in the neurite this is often represented by a paremeter called the length current λ equal to the square root of r_m divided by r_l if a cell membrane has a lower membrane capacitance c_m which is usually a fairly constant value then the relative ion flow down the neurite will be greater due to a lower displacement current how quickly the membrane voltage changes in response to a current injected at at given point can be predicted by the time constant τ equal to the product of c_m times r_m an electrotonic potential results from a local change in ion conductance e g after a synaptic event that does not propagate it becomes exponentially smaller as it spreads this is opposed to an action potential which reaches the voltage threshold by which it does propagate down the neurite due to the opening of voltage gated ion channels and then spreads like a wave dendritic trees can perform non linear integration of signals that can be predicted on the basis of cable theory the existence of subthreshold membrane potential fluctuations in dendrites which based on my understanding should dominate neuronal signaling can allow variations in synaptic weight distributions and input timing to encode a substantial amount of information within a single neuron inspired by caltech s question 20 for cognitive scientists derive the cable equation for a uniform cylinder with optimal boundary conditions what does it mean for neurons rate this andy 100 questions january 17 2022 january 17 2022 2 minutes question 19 ion channel biophysics what are the biophysics of voltage gated sodium channels sodium channels are a major component of excitable membranes they are an intrinsic component of excitable tissue that allows them to generate and propagate action potentials these electrical signals are essential for proper neuronal communication the channel looks like a barrel with 4 fold symmetry and a diameter of about 10 nm the channel has an activation gate through which sodium ions can flow through if the activation gate is closed no ions can pass through but if it is open ions can pass through the pore the channel is closed at rest wherein the membrane voltage potential is polarized when a sufficient voltage depolarization across the membrane occurs the membrane will draw the gates open allowing sodium ions to flow through and leading to further depolarization when enough sodium has passed the further voltage change causes the inactivation gate to close thus stopping the flow of sodium ions and leading to repolarization sodium channels are selective for sodium ions because the inner filter of the pore is highly negatively charged the na ion has a positive charge and will bind well to the inner filter k ions while also positively charged cannot pass through because of a size restriction the gate is not large enough for them to fit through for ions to pass they need to be smaller than the diameter of the filter for ions with a larger diameter to pass the filter would need to enlarge however the size of the filter cannot increase because the pore has a fixed size these are the unique properties of the sodium channel that allow it to selectively conduct sodium sodium channels are good targets for many drugs and toxins for example tetrodotoxin specifically binds to voltage gated sodium channels and can stop sodium channels from opening thereby blocking all neural signaling what are the biophysics of transmitter gated channels transmitter gated channels are opened by transmitters they are then generally ion selective to open the channel the transmitter needs to bind to the receptor the transmitter binding causes an allosteric change that allows another part of the channel to open known as the ion channel gate when open the ion channel gate allows specific ions to pass through a special example is the nmda receptor under normal circumstances the nmda receptor is blocked by mg2 and zn2 ions when the post synaptic neuron is depolarized however mg2 and zn2 ions are repelled in this case the receptor can be activated by glutamate when activated the nmda receptor allows positive ions to pass through k na and ca2 ions which can help sustain depolarization and lead to intracellular signaling events such as long term potentiation nmda receptors are often called coincidence detectors because these two events must occur together for the channel to open first the nmda receptor must be activated by the post synaptic being depolarized and second glutamate must be released model of an ndma channel green https journals plos org plosone article id 10 1371 journal pone 0177686 another example is the nicotinic acetylcholine receptor when acetylcholine binds to the receptor the channel opens this allows sodium and potassium ions to pass through which leads to depolarization and therefore a neural signal most types of ion channel activity in the brain need regulation regulation can occur post translationally through the addition of a phosphate group to one or more amino acids the addition of a phosphate group to a particular location of the ampa receptor for example has been shown to increase the probability of ampa channel opening the ca2 calmodulin kinase ii pathway is able to phosphorylate the glua1 ampa receptor subunit at ser831 causing an increase in ampa channel conductance in addition to the post translational regulation of channel activity many channels are regulated by endogenous compounds in the brain serotonin is a monoamine neurotransmitter that regulates various types of sodium channels and potassium channels dopamine is also a monoamine neurotransmitter and it can be found in extrasynaptic regions dopamine has been shown to increase potassium channel activity by activating dopamine d1 receptors in axons together the biophysics of ion channels allow for neural signaling by allowing for the passage of ions into and out of the cell this allows for changes in membrane potential and intracellular signaling inspired by caltech s question 19 for cognitive scientists describe the main biophysical characteristics of ionic channels how does its biophysical properties contribute to its physiological function what is thought to be the basis for the channels ion selectivity rate this andy 100 questions january 16 2022 3 minutes posts navigation older posts about about this blog categories 100 questions aging alzheimers disease autism spectrum brain ba...