Podcasts about biophysical

Play Episode Listen Later Aug 2, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.31.551259v1?rss=1 Authors: Starck, L., Sarem, M., Heimrich, B., Sawarkar, R., Ritz, M.-F., Hutter, G., Shastri, V. P. Abstract: While the direct biological factors underlying the progression of GBM, an aggressive form of brain cancer, have been extensively studied, emerging evidence suggests that indirect biological triggers, such as traumatic brain injury (TBI), may also have a role. Since reactive astrocytes are associated with TBI, and astroglial cells are the source of proteoglycans which contribute to changes in biophysical characteristics (stochastic topography, stiffness) of the brain, we postulated a role for stochastic nanoroughness in the induction of glioma. Using a model system to emulate such physical cues, we demonstrate that human cortical astrocytes undergo spontaneous organization into spheroids in response to nanoroughness and retain the spheroid phenotype even upon withdrawal of the physical cues. Furthermore, spheroids serve as aggregation foci for naive astrocytes; express activated MMP2, and disseminate upon implantation in mouse brain. RNA-seq revealed a tumoral phenotype with a gene expression pattern involving p53, ADAMTS proteases and fibronectin. Moreover, nanoroughness mediates a cross-talk between cancer cells and astrocytes through induced senescence. These findings implicate a role for stochastic biophysical cues in driving a potential malignant transformation of astrocytes. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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A Biophysical Model of Visual Rivalry Links Cellular Mechanisms to Signatures of Conscious Perception

Play Episode Listen Later Jul 15, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.13.548934v1?rss=1 Authors: Whyte, C. J., Munn, B. R., Aru, J., Larkum, M., John, Y., Muller, E. J., Shine, J. M. Abstract: Investigations into the neural basis of conscious perception span multiple scales and levels of analysis. There is, however, a theoretical and methodological gap between advances made at the microscopic scale in animal models and those made at the macroscopic scale in human cognitive neuroscience that places a fundamental limit on our understanding of the neurobiological basis of consciousness. Here, we use computational modelling to bridge this gap. Specifically, we show that the same mechanism that underlies threshold detection in mice - apical dendrite mediated burst firing in thick-tufted layer V pyramidal neurons - determines perceptual dominance in a thalamocortical model of binocular rivalry - a staple task in the cognitive neuroscience of consciousness. The model conforms to the constraints imposed by decades of previous research into binocular rivalry and generalises to the more sophisticated rivalry tasks studied in humans generating novel, testable, explanations of the role of expectation and attention in rivalry. Our model, therefore, provides an empirically-tractable bridge between cellular-level mechanisms and conscious perception. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Biophysical neural adaptation mechanisms enable deep learning models to capture dynamic retinal computation

The Talking With Dr. Toy Show

Play Episode Listen Later Jun 24, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.20.545728v1?rss=1 Authors: Idrees, S., Rieke, F., Field, G. D., Zylberberg, J. Abstract: Neural adaptation is a universal feature of neural systems that modulates the output based on input conditions, enabling efficient encoding of sensory inputs without saturation or loss. In contrast, conventional artificial neural networks (ANNs) lack these adaptational mechanisms, resulting in inaccurate neural predictions under changing input conditions. Can embedding neural adaptive mechanisms in ANNs improve their performance and generate biologically-plausible models? To address this question, we introduce a new type of convolutional neural network (CNN) layer incorporating photoreceptor biophysics and adaptation mechanisms to model light-dependent photoreceptor sensitivity and kinetics. Under changing input light conditions, CNNs that include the new photoreceptor layer integrated as a front-end perform better than conventional CNN models at predicting: (1) monkey and rat retinal ganglion cell responses; and (2) context-dependent changes in neural sensitivity. This study demonstrates the potential of embedding neural adaptive mechanisms in deep learning models, enabling them to adapt dynamically to evolving inputs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Talking With Dr. Toy: Mental Health Awareness--Protective Factors

Play Episode Listen Later May 29, 2023 34:07

Mental health issues are a reality and nurturing and cultivating protective factors are very important in preventing and improving mental health issues/symptoms. Protective factors have been defined as something that prevents problems and influences that make it less likely for individuals to develop mental health issues. There are various types of protective factors such as: Biophysical, psychological, social, and spiritual. For more information tune into the podcast via www.talkingwithdrtoy.com.

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Talking With Dr. Toy: Mental Health Awareness--The Reality of Risk Factors

The Talking With Dr. Toy Show

Play Episode Listen Later May 22, 2023 34:52

Mental health issues are a reality and awareness and attending to risk factors are very important in improving mental health. Risk factors have been defined as anything that creates problems and make it more likely for the development of mental health issues. There are various types of risk factors such as: Biophysical, psychological, social, and spiritual. For more information tune into the podcast via www.talkingwithdrtoy.com.

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Basolateral amygdala oscillations enable fear learning in a biophysical model

Play Episode Listen Later Apr 28, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.28.538604v1?rss=1 Authors: Cattani, A., Arnold, D. B., McCarthy, M., Kopell, N. Abstract: Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Inferring parameters of pyramidal neuronexcitability in mouse models of Alzheimer'sdisease using biophysical modeling and deeplearning

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Play Episode Listen Later Apr 19, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.18.537149v1?rss=1 Authors: Saghafi, S., Rumbell, T. H., Gurev, V., Kozloski, J. C., Tamagnini, F., Wedgwood, K. C., Diekman, C. O. Abstract: Alzheimer's disease (AD) is believed to occur when abnormal amounts of the proteins amyloid beta and tau aggregate in the brain, resulting in a progressive loss of neuronal function. Hippocampal neurons in transgenic mice with amyloidopathy or tauopathy exhibit altered intrinsic excitability properties. We introduce a novel parameter inference technique, deep hybrid modeling (DeepHM), that combines deep learning with biophysical modeling to map experimental data recorded from hippocampal CA1 neurons in transgenic AD mice and age-matched wildtype littermate controls to the parameter space of a conductance-based CA1 model. Although mechanistic modeling and machine learning methods are by themselves powerful tools for approximating biological systems and making accurate predictions from data, when used in isolation these approaches suffer from distinct shortcomings: model and parameter uncertainty limit mechanistic modeling, whereas machine learning methods disregard the underlying biophysical mechanisms. DeepHM addresses these shortcomings by using conditional generative adversarial networks (cGANs) to provide an inverse mapping of data to mechanistic models that identifies the distributions of mechanistic modeling parameters coherent to the data. Here, we demonstrate that DeepHM accurately infers parameter distributions of the conductance-based model and outperforms a Markov chain Monte Carlo method on several test cases using synthetic data. We then use DeepHM to estimate parameter distributions corresponding to the experimental data and infer which ion channels are altered in the Alzheimer's mouse models compared to their wildtype controls at 12 and 24 months. We find that the conductances most disrupted by tauopathy, amyloidopathy, and aging are delayed rectifier potassium, transient sodium, and hyperpolarization-activated potassium, respectively. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Reproducibility of biophysical in silico neuron states and spikes from event-based partial histories

Play Episode Listen Later Apr 16, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.15.536945v1?rss=1 Authors: Cudone, E., Lower, A., McDougal, R. A. Abstract: Biophysically detailed simulations attempting to reproduce neuronal activity often rely on solving large systems of differential equations; in some models, these systems have tens of thousands of states per cell. Numerically solving these equations is computationally intensive and requires making assumptions about the initial cell states. Additional realism from incorporating more biological detail is achieved at the cost of increasingly more states, more computational resources, and more modeling assumptions. We show that for both point and morphologically-detailed cell models, the presence and timing of future action potentials is probabilistically well-characterized by the relative timings of a small number of recent synaptic events alone. Knowledge of initial conditions or full synaptic input history is not a requirement. While model time constants, etc. impact the specifics, we demonstrate that for both individual spikes and sustained cellular activity, the uncertainty in spike response decreases to the point of approximate determinism. Further, we show cellular model states are reconstructable from ongoing synaptic events, despite unknown initial conditions. We propose that a strictly event-based modeling framework is capable of representing the full complexity of cellular dynamics of the differential-equations models with significantly less per-cell state variables, thus offering a pathway toward utilizing modern data-driven modeling to scale up to larger network models while preserving individual cellular biophysics. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Controlling morpho-electrophysiological variability of neurons with detailed biophysical models

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Play Episode Listen Later Apr 6, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.06.535923v1?rss=1 Authors: Arnaudon, A., Reva, M., Zbili, M., Markram, H., Van Geit, W., Kanari, L. Abstract: Variability is a universal feature among biological units such as neuronal cells as they enable a robust encoding of a high volume of information in neuronal circuits and prevent hyper synchronizations such as epileptic seizures. While most computational studies on electrophysiological variability in neuronal circuits were done with simplified neuron models, we instead focus on the variability of detailed biophysical models of neurons. With measures of experimental variability, we leverage a Markov chain Monte Carlo method to generate populations of electrical models able to reproduce the variability from sets of experimental recordings. By matching input resistances of soma and axon initial segments with the one of dendrites, we produce a compatible set of morphologies and electrical models that faithfully represent a given morpho-electrical type. We demonstrate our approach on layer 5 pyramidal cells with continuous adapting firing type and show that morphological variability is insufficient to reproduce electrical variability. Overall, this approach provides a strong statistical basis to create detailed models of neurons with controlled variability. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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S6E11 - Worlds Primer 6 Imperial & CIS with Biophysical

Mynock Squadron Podcast

Play Episode Listen Later Mar 21, 2023 71:30

This week we bring on Biophysical, the master of the Empire, to talk about how the bad guys can win worlds. Then we fumble in the dark trying to discuss Separatists. Check out Ryan's Game on Kickstarter! https://www.kickstarter.com/projects/almanacgames/encounters-shattered-wastes

Laminar Specificity of the Auditory Perceptual Awareness Negativity: A Biophysical Modeling Study

Play Episode Listen Later Mar 8, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.06.531459v1?rss=1 Authors: Fernandez Pujol, C., Blundon, E. G., Dykstra, A. R. Abstract: How perception of sensory stimuli emerges from brain activity is a fundamental question of neuroscience. To date, two disparate lines of research have examined this question. On one hand, human neuroimaging studies have helped us understand the large-scale brain dynamics of perception. On the other hand, work in animal models (mice, typically) has led to fundamental insight into the micro-scale neural circuits underlying perception. However, translating such fundamental insight from animal models to humans has been challenging. Here, using biophysical modeling, we show that the auditory awareness negativity (AAN), an evoked response associated with perception of target sounds in noise, can be accounted for by synaptic input to the supragranular layers of auditory cortex (AC) that is present when target sounds are heard but absent when they are missed. This additional input likely arises from cortico-cortical feedback and/or non-lemniscal thalamic projections and targets the apical dendrites of layer-V pyramidal neurons (PNs). In turn, this leads to increased local field potential activity, increased spiking activity in layer-V PNs, and the AAN. The results are consistent with current cellular models of conscious processing and help bridge the gap between the macro and micro levels of perception-related brain activity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Biophysical characterization and modeling of SCN1A gain-of-function predicts interneuron hyperexcitability and a predisposition to network instability through homeostatic plasticity

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Play Episode Listen Later Feb 21, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.20.529310v1?rss=1 Authors: Berecki, G., Bryson, A., Polster, T., Petrou, S. Abstract: SCN1A gain-of-function variants are associated with early onset developmental and epileptic encephalopathies (DEEs) that possess distinct clinical features compared to Dravet syndrome caused by SCN1A loss-of-function. However, it is unclear how SCN1A gain-of-function may predispose to cortical hyper-excitability and seizures. Here, we first report the clinical features of a patient carrying a de novo SCN1A variant (T162I) associated with neonatal-onset DEE, and then characterize the biophysical properties of T162I and three other SCN1A variants associated with neonatal-onset or early infantile DEE (I236V, P1345S, R1636Q). In voltage clamp experiments, three variants (T162I, P1345S and R1636Q) exhibited changes in activation and inactivation properties that enhanced window current, consistent with gain-of-function. Dynamic action potential clamp experiments utilising model neurons incorporating Nav1.1. channels supported a gain-of-function mechanism for all four variants. Here, the T162I, I236V, P1345S, and R1636Q variants exhibited higher peak firing rates relative to wild type and the T162I and R1636Q variants produced a hyperpolarized threshold and reduced neuronal rheobase. To explore the impact of these variants upon cortical excitability, we used a spiking network model containing an excitatory pyramidal cell (PC) and parvalbumin positive (PV) interneuron population. SCN1A gain-of-function was modeled by enhancing the excitability of PV interneurons and then incorporating three simple forms of homeostatic plasticity that restored pyramidal cell firing rates. We found that homeostatic plasticity mechanisms exerted differential impact upon network function, with changes to PV-to-PC and PC-to-PC synaptic strength predisposing to network instability. Overall, our findings support a role for SCN1A gain-of-function and inhibitory interneuron hyperexcitability in early onset DEE. We propose a mechanism through which homeostatic plasticity pathways can predispose to pathological excitatory activity and contribute to phenotypic variability in SCN1A disorders. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Alternative Cancer Therapies Are A Biophysical Challenge AND DEMAND A Deep Autonomic Reset OR They Will FAIL!!!- Show 609

Medici Medicine

Play Episode Listen Later Feb 3, 2023 27:16

https://medicienterprises.com/2023/01/21/show-609/

Biophysical modeling of the electric field magnitude and distribution induced by electrical stimulation with intracerebral electrodes

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Play Episode Listen Later Jan 13, 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.13.523921v1?rss=1 Authors: Alonso, F., Mercadal, B., Salvador, R., Ruffini, G., Bartolomei, F., Wendling, F., Modolo, J. Abstract: Intracranial electrodes are used clinically for diagnostic or therapeutic purposes, notably in drug-refractory epilepsy (DRE) among others. Visualization and quantification of the energy delivered through such electrodes is key to understanding how the resulting electric fields modulate neuronal excitability, i.e. the ratio between excitation and inhibition. Quantifying the electric field induced by electrical stimulation in a patient-specific manner is challenging, because these electric fields depend on a number of factors: electrode trajectory with respect to folded brain anatomy, biophysical (electrical conductivity / permittivity) properties of brain tissue and stimulation parameters such as electrode contacts position and intensity. Here, we aimed to evaluate various biophysical models for characterizing the electric fields induced by electrical stimulation in DRE patients undergoing stereoelectroencephalography (SEEG) recordings in the context of pre-surgical evaluation. This stimulation was performed with multiple-contact intracranial electrodes used in routine clinical practice. We introduced realistic 3D models of electrode geometry and trajectory in the neocortex. For the electrodes, we compared point (0D) and line (1D) sources approximations. For brain tissue, we considered three configurations of increasing complexity: a 6-layer spherical model, a toy model with a sulcus representation, replicating results from previous approaches; and went beyond the state-of-the-art by using a realistic head model geometry. Electrode geometry influenced the electric field distribution at close distances (~3 mm) from the electrode axis. For larger distances, the volume conductor geometry and electrical conductivity dominated electric field distribution. These results are the first step towards accurate and computationally tractable patient-specific models of electric fields induced by neuromodulation and neurostimulation procedures. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

A selectivity filter in the EMC limits protein mislocalization to the ER

Play Episode Listen Later Dec 1, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.29.518402v1?rss=1 Authors: Pleiner, T., Hazu, M., Tomaleri, G. P., Nguyen, V. N., Januszyk, K., Voorhees, R. M. Abstract: Tail anchored proteins (TAs) play essential roles at both the ER and mitochondria, and their accurate localization is critical to proteostasis. Biophysical similarities lead to mistargeting of mitochondrial TAs to the ER, where they are delivered to the ER membrane protein complex (EMC). We showed that the EMC directly contributes to sorting fidelity of mitochondrial TAs and multipass substrates that contain positively charged soluble domains. Leveraging an improved structural model of the human EMC, we used mutagenesis and site-specific crosslinking to map the path of a TA from its cytosolic capture by methionine-rich loops to its membrane insertion through a hydrophilic vestibule. Positively charged residues at the entrance to the vestibule function as a selectivity filter that uses charge-repulsion to reject mitochondrial TAs. Substrate discrimination by the EMC provides a biochemical explanation for one role of charge in TA sorting and protects compartment identity by limiting protein misinsertion. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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472: Caulobacter Condensates Compartmentalize Kinase

BacterioFiles

Play Episode Listen Later Nov 21, 2022 15:53

This episode: Bacteria can use blobs of disordered proteins to quickly adapt to new conditions! Thanks to Dr. Saumya Saurabh for his contribution! Download Episode (10.9 MB, 15.9 minutes) Show notes: Microbe of the episode: Drosophila melanogaster Micropia virus Takeaways Bacteria can adapt to environmental fluctuations via mechanisms operating at the various levels of the central dogma, or metabolism (stringent response). Recently, researchers at Stanford University discovered a mechanism that allows bacteria to sense and rapidly adapt to nutrient fluctuations by simply tuning protein self-assembly as a function of nutrient availability. Termed membraneless organelles or condensates, these proteinaceous assemblies can dynamically sequester key signaling enzymes within them in response to environmental cues. Biophysical adaptation mediated by organelles is fast, reversible, and facile; thereby representing a crucial step in the mechanistic understanding of microbial adaptation. Journal Paper: Saurabh S, Chong TN, Bayas C, Dahlberg PD, Cartwright HN, Moerner WE, Shapiro L. 2022. ATP-responsive biomolecular condensates tune bacterial kinase signaling. Sci Adv 8:eabm6570. Other interesting stories: Bacteria produce biofuel from carbon dioxide, light, and solar power-generated electricity Vine that can mimic leaves of different trees may get info from bacteria (paper) Email questions or comments to bacteriofiles at gmail dot com. Thanks for listening! Subscribe: Apple Podcasts, Google Podcasts, Android, or RSS. Support the show at Patreon, or check out the show at Twitter or Facebook.

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The Judy Torel Show Series 6 Ep 4: Monitoring Biophysical Outputs is VERY Important When Over 60!

The Judy Torel Show

Play Episode Listen Later Nov 17, 2022 18:24

Monitoring biophysical outputs is VERY important when over 60. RHR, HRV, Body temperature, and metrics such as HR and pace. Learn what needs to be tracked and why in this video.

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A Biophysical Basis for Learning and Transmitting Sensory Predictions

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Play Episode Listen Later Nov 1, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.31.514538v1?rss=1 Authors: Muller, S. Z., Abbott, L. F., Sawtell, N. B. Abstract: Homeostatic (anti-Hebbian) forms of synaptic are effective at eliminating "prediction errors" that signal the differences between predicted and actual sensory input. However, such mechanisms appear to preclude the possibility of transmitting the resulting predictions to downstream circuits, severely limiting their utility. Using modeling and recordings from the electrosensory lobe of mormyrid fish, we reveal interactions between axonal and dendritic spikes that support both the learning and transmission of predictions. We find that sensory input modulates the rate of dendritic spikes by adjusting the amplitude of backpropagating axonal action potentials. Homeostatic plasticity counteracts these effects through changes in the underlying membrane potential, allowing the dendritic spike rate to be restored to equilibrium while simultaneously transmitting predictions through modulation of the axonal spike rate. These results reveal how two types of spikes dramatically enhance the computational power of single neurons in support of an ethologically relevant multi-layer computation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Episode 13. Functional Fertility And Preconception Health With Special Guest Dr Shefali Verma

They Say It Takes A Village

Play Episode Play 39 sec Highlight Listen Later Oct 31, 2022 70:11

In today's episode have the pleasure of interviewing Dr. Shefali Verma As we talk at length about functional fertility and preconception health and how making small changes in lifestyle can positively impact your fertility journey and overall well being. Dr Shefali is integrated Medical Biohacker, Educator and Medical Director of the Institute for Biophysical. As well as her private practice Dr. Shefali is passionate in the education space and has held many prestigious appointments, providing private consultations for major corporate organisations, government offices and private clients including working with the Ministry of Foreign Affairs and Future. She is passionate about educating on the importance of creating a health culture within the corporate sector with a key focus on proactive health as opposed to being reactive. At the start of her career after she completed her Masters in Sports medicine she also looked after several athletes at Internatiknal competitions as well as more recently those selected to participate in the Government Games 2020 before the pandemic. In 2017, Dr Shefali was awarded one the top 50 Outstanding Women in Healthcare which was presented at the Worlds Health and Wellness Congress and Awards in Mumbai and then she was awarded one of the top 100 Leaders in Healthcare at the same conference for the following two years in a row. Dr Shefali Verma continues to support organisations and schools, teaching on the process of disease and espousing the philosophy that “An Ounce of Prevention Is Worth A Pound Of Cure” and enjoys empowering her audience in the management of one's own health in Dubai as well as globally.For those of you that would like to have a consultation with Dr Shefali head over to the Institute For Biophysical Medicine and make an appointment. Phone: 044322188

Cross-attractor modeling of resting-state functional connectivity in psychiatric disorders reveals disturbances in excitation, inhibition, and energy gaps

Play Episode Listen Later Oct 31, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.29.514373v1?rss=1 Authors: Sun, Y., Zhang, M., Saggar, M. Abstract: Resting-state functional connectivity (RSFC) is altered across various psychiatric disorders. Biophysical network modeling (BNM) has the potential to reveal the neurobiological underpinnings of such abnormalities by dynamically modeling the structure-function relationship and examining biologically relevant parameters after fitting the models with real data. Although innovative BNM approaches have been developed, two main issues need to be further addressed. First, previous BNM approaches are primarily limited to simulating noise-driven dynamics near a chosen attractor (or a stable brain state). Such approaches miss out on the multi(or cross)-attractor dynamics that have been shown to better capture non-stationarity and switching between states in the resting brain. Second, previous BNM work is limited to characterizing one disorder at a time. Given the large degree of co-morbidity across psychiatric disorders, comparing BNMs across disorders might provide a novel avenue to generate insights regarding the dynamical features that are common across (vs. specific to) disorders. Here, we address these issues by (1) examining the layout of the attractor repertoire over the entire multi-attractor landscape using a recently developed cross-attractor BNM approach; and (2) characterizing and comparing multiple disorders (schizophrenia, bipolar, and ADHD) with healthy controls using an openly available and moderately large multimodal dataset from the UCLA Consortium for Neuropsychiatric Phenomics. Both global and local differences were observed across disorders. Specifically, the highest local excitation (across groups) was observed in the ADHD group, whereas the lowest local inhibition was observed in the bipolar group. In line with these results, the ADHD group had the lowest switching costs (energy gaps) across groups. Overall, this study provides preliminary evidence supporting transdiagnostic multi-attractor BNM approaches to better understand psychiatric disorders' pathophysiology. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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Reduced oriens-lacunosum/moleculare (OLM)cell model identifies biophysical currentbalances for in vivo theta frequency spikingresonance

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Play Episode Listen Later Oct 21, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.20.513073v1?rss=1 Authors: Sun, Z., Crompton, D., Lankarany, M., Skinner, F. Abstract: Conductance-based models have played an important role in the development of modern neuroscience. These mathematical models are powerful 'tools' that enable theoretical explorations in experimentally untenable situations, and can lead to the development of novel hypotheses and predictions. With advances in cell imaging and computational power, multi-compartment models with morphological accuracy are becoming common practice. However, as more biological details are added, they make extensive explorations and analyses more challenging largely due to their huge computational expense. Here, we focus on oriens-lacunosum/moleculare (OLM) cell models. OLM cells can contribute to functionally relevant theta rhythms in the hippocampus by virtue of their ability to express spiking resonance at theta frequencies, but what characteristics underlie this is far from clear. We converted a previously developed detailed multi-compartment OLM cell model into a reduced single compartment model that retained biophysical fidelity with its underlying ion currents. We showed that the reduced OLM cell model can capture complex output that includes spiking resonance in in vivo-like scenarios as previously obtained with the multi-compartment model. Using the reduced model, we were able to greatly expand our in vivo-like scenarios. Applying spike-triggered average analyses, we were thus able to to determine that it is a combination of hyperpolarization-activated cation and muscarinic type potassium currents that specifically allow OLM cells to exhibit spiking resonance at theta frequencies. Further, we developed a robust Kalman Filtering (KF) method to estimate parameters of the reduced model in real-time. We showed that it may be possible to directly estimate conductance parameters from experiments since this KF method can reliably extract parameter values from model voltage recordings. Overall, our work showcases how the contribution of cellular biophysical current details could be determined and assessed for spiking resonance. As well, our work shows that it may be possible to directly extract these parameters from current clamp voltage recordings. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

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DO 83 - Panel on biophysical realities and cultural potentials

Doomer Optimism

Play Episode Listen Later Oct 12, 2022 97:05

Jason moderates this panel on the topic of biophysical realities and cultural potentials. Greg Cassel @gregsc1 of @neighbour_hoods community open source #p2p inclusive organizing / protocols not platforms; communication not control/ #permaculture #madhyamika #panentheism Ellie at Common Action @sellieyoung making climate cool again. move fast and fix things. get your CA orb: https://ca.refiorb.com join us in Slack: http://tinyurl.com/42dnwub6 Nathan @tornadonate is a licensed psychotherapist and co-host of Altered States of Context, a podcast about psychedelics, science and psychotherapy. He also practices regenerative ranching and writes from his family's farm in rural west-central Illinois. Richard Flyer @Richard_Flyer Fall 2022 Launching Symbiotic Culture Lab. From Symbiosis -- Intentional Mutual Benefit at all scales. Global Commonwealth of Bioregional Economies. Jason Snyder @cognazor Metamodern localist | homesteading, permaculture, bioregional regeneration | meditation, self inquiry, embodied cognition | PhD from Michigan State University, faculty Appalachian State University.

A multiplex platform to identify mechanisms and modulators of proteotoxicity in neurodegeneration

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Play Episode Listen Later Sep 19, 2022

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.19.508444v1?rss=1 Authors: Resnick, S. J., Qamar, S. S., Sheng, J., Huang, L. H., Nixon-Abell, J., Melore, S., Chung, C. W., Li, X., Wang, J., Zhang, N., Shneider, N. A., Kaminski, C. F., Ruggeri, F. S., Schierle, G. S. K., St George-Hyslop, P., Chavez, A. Abstract: Neurodegenerative disorders are a family of diseases that remain poorly treated despite their growing global health burden. A shared feature of many neurodegenerative disorders is the accumulation of toxic misfolded proteins. To gain insight into the mechanisms and modulators of protein misfolding, we developed a multiplex reverse genetics platform. Using this novel platform 29 cell-based models expressing proteins that undergo misfolding in neurodegeneration were probed against more than a thousand genetic modifiers. The resulting data provide insight into the nature of modifiers that act on multiple misfolded proteins as compared to those that show activity on only one. To illustrate the utility of this platform, we extensively characterized a potent hit from our screens, the human chaperone DNAJB6. We show that DNAJB6 is a general modifier of the toxicity and solubility of multiple amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD)-linked RNA-binding proteins (RBPs), including FUS, TDP-43, and hnRNPA1. Biophysical examination of DNAJB6 demonstrated that it co-phase separates with, and alters the behavior of FUS containing condensates by locking them into a loose gel-like state which prevents their fibrilization. Domain mapping and a deep mutational scan of DNAJB6 support the critical importance for DNAJB6 phase separation in its effects on multiple RNA-binding proteins. Crucially, these studies also suggest that this property can be further tuned to generate novel variants with enhanced activity that might illuminate potential avenues for clinical translation. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Episode 250: Is Hop Terroir a Marketing Construct and/or a Biophysical Reality?

Master Brewers Podcast

Play Episode Listen Later Jun 20, 2022 43:45

A recent Master Brewers Technical Quarterly paper explores the answer. Special Guests: Aaron Staples, Alec Mull, Alex Adams, Rob Sirrine, and Scott Stuhr.

“Antepartum Fetal Testing, Part 2: Nonstress Test & Biophysical Profile” – with Kelly Zafman, MD

Healthful Woman Podcast

Play Episode Listen Later Mar 14, 2022 38:08

In part two of this episode, Dr. Kelly Zafman and Dr. Fox continue their discussion of antepartum testing. Dr. Zafman explains nonstress tests, which compares a baby's heart rate with contractions. She also reviews the biophysical profile, or BPP, as well as a modified biophysical profile.

testing profile fetal bpp biophysical

How to Biodesign #20: Harvesting solar energy with living materials

HOW TO BIODESIGN AUDIO RECAP

Play Episode Listen Later Jan 4, 2022 70:23

☀️When focussing on solar energy, we can list the possibilities from nature. How do bioneers use these possibilities in their designs and how to tackle challenges like durability and storage when using living materials to harvest solar energy? Listen back to the stories of: Huub de Groot: Professor of Biophysical organic chemistry & PhD. Miguel Mayorga: CEO of @greenfluidics, a Mexican startup, developing revolutionary solar biopanels that use microalgae and nanofluids.

phd mexican materials harvesting solar energy huub biodesign biophysical

054 Fetal Growth Restriction (FGR)

True Birth

Play Episode Listen Later Nov 22, 2021 36:24

What's the cause of fetal growth restriction? How can you prevent it? In this episode of True Birth, we will talk about fetal growth restriction/FGR previously termed IUGR or Inner Uterine Growth Restriction. What is FGR? [1:36] It is when the baby falls below the 10th percentile for weight. 10% of babies will be below the 10th percentile, by definition. Hence, 10% of babies will be classified as fetal growth restricted. It's important for you to know that because 10% of babies are not in a pathological situation. They're not in a bad situation. They're not in a situation where they're not growing. [2:35] It's important to consider each woman and her partner uniquely in pregnancy. A women that is 5'9 with women and a woman that is 5 feet tall will have different size expectations and patterns when it comes to pregnancy. Possible reasons that the baby is small [4:17] The number one reason that a baby could be on the smaller side is that the mother is small and the father of the baby is maybe not the tallest guy. We use the term FGR/Fetal Growth Restriction when they're in utero, but once they're delivered, we call them SGA/Small for Gestational Age. [5:06] When you find the baby's not growing well, this will generally be after 20 weeks Babies are generally the same size until 20 weeks. [6:08] Another reason the baby is small is that it's supposed to be small and there's nothing wrong. The number two reason is placental perfusion. It has a problem with the baby getting enough blood flow and nutrients. It is just not getting enough of what it needs to grow well. And there are many reasons why the placenta won't function. So when you see a small baby, especially in the third trimester after 27 weeks, 30 weeks, start thinking, "Oh, how are her blood pressures? She's spilling protein. Is there something going on with this patient that's pointing me towards preeclampsia?" [8:07] TORCH is an acronym that stands for toxoplasmosis, rubella cytomegalovirus, herpes simplex, and HIV. Cytomegalovirus is a virus that's very common in the population. Most people have been exposed to cytomegalovirus. T Ultrasound tools [12:09] To understand Dopplers without getting into the physics of what the Doppler effect is, you can take your transducer, you could put it over the cord, and you can turn on the Doppler and you could see the blood flow through the cord. [13:48] When you look at a Doppler, and you see the blood flowing the way it should, before the next heartbeat, you measure how fast it's going right before the next heartbeat. [15:14] When you talk about fetal growth restriction, you can't just talk about the baby's size because there's only one piece of it. The other piece is what is the placenta telling you? What are the Dopplers telling you? [15:34] Biometry is when you measure the femur and the abdomen and measure the head to get the size and weight of the baby and estimated fetal weight. Guidelines about how to approach Fetal Growth Restriction [18:12] If you're below the third percentile, even if everything else is okay, that's the baby you got to deliver at 37 weeks. You can't just sit around and look at that baby for 37 weeks get the baby out. If your baby is above the third percentile and the Dopplers are elevated but not absent, get the baby up. And if there's no flow, the blood stops, that's even more concerning. If you see the reverse flow, you're dealing with a much more ominous situation and you don't want to go past 32 weeks. If you don't think the baby's doing well, you might have to come out even earlier. Biophysical profile [22:09] One of the things that some patients might have to consider in other practices is that they would need to start having biophysical profiles done. A biophysical profile is when you're checking for a series of four different things and looking to ensure that the baby is reassuring overall. What is the baby's movement? What is fetal breathing, which is an exercise the baby does to inhale and exhale fluid? What is his tone? Is the baby flex or the floppy? Or if you feel the baby's not moving, these are things that you have to consider. [23:51] One of the things you're looking for when talking about growth restriction is you want to see how the baby is handling the uterine environment? How's the baby doing on the inside? These tests will wish to you to identify a baby that's not doing well or not getting enough blood flow. You need to know if you can wait on it and let the baby stay inside, or is it time to get the baby out? Because then the baby will do better outside of the womb. Recommendations [24:20] The recommendation is that if you recognize growth restriction, you should at least be monitoring weekly, that might be nonstress tests, or that might be a biophysical every week. And if you have a severe growth that restricts a baby under the third percentile or abnormal Dopplers or accident, then twice a week. If you have reversed outside flow, put those patients in the hospital because they need to be monitored around the clock and you got to pull the baby out before it's too late. [29:08] The most reliable and consistent way to assess blood flow to the baby is the umbilical artery. Look at the ductus phimosis. When the umbilical cord hits the baby's belly button, a big part of the vein goes up into the heart carrying the birth at heart, and you can see if there's resistance, or even at the umbilical vein. Here is the photo that we have permission to share. Visit https://www.truebirthpodcast.com/ to listen more episodes! Maternal Resources Social Facebook: https://www.facebook.com/maternalresourceshackensack |nstagram: @maternalresources Subscribe to the podcast on Apple Podcasts, Spotify, Google Podcasts, & Stitcher and leave a review!

Rob McConnell Interviews - Freddy Silva - Crop Circle in the Fields

The Best of The 'X' Zone Radio/TV Show with Rob McConnell

Play Episode Listen Later Sep 24, 2021 41:28

For over a decade Crop Circle Secrets has led the way in helping the public make an informed decision on the origin of crop circles. Its factual research has provided an antidote to deliberate falsification of the genuine phenomenon by skeptics, hoaxers and their allies in the media. Crop circles are scientifically proven to be manifestations of energy under intelligent guidance. Over 80 eyewitnesses describe them to be made by tubes of light in less than fifteen seconds, as proved by a Japanese camera crew in 1989. The evidence for crop circles as a genuine phenomenon is found in Freddy Silva's book Secrets In The Fields. Contrary to popular perception, crop circles are not a modern phenomenon. They were witnessed by policemen and farmers as far back as 1890, they exist in the folklore of South Africa and China, and are mentioned in 17th Century academic texts. Over eighty eyewitnesses have seen crop circles forming in under fifteen seconds. Around 1980 they re-appeared as simple circles and rings in southern England, where 75% of designs are reported. By the late 1980s they developed into pictograms, not unlike the petroglyphs found at sacred sites. After 1990 the designs developed exponentially in complexity, and today the crop glyphs display as fractals and elements expressing fourth dimensional processes in quantum physics. To quell the public's growing interest in crop circles, the British Military presented two individuals named Doug and Dave to the media via a fictitious press agency, as the makers of all crop circles. The majority of their claims were later proved to have been fabricated, but never reported in the media. So, what exactly lies behind real crop circles? In genuine formations the stems are not broken but bent and swirled; they are subjected to a short and intense burst of heat that softens the stems to hover just above the ground, where they re-harden without damage. Research suggests that infrasound is producing such an effect. It has also been scientifically proven that soil samples taken from within crop circles show changes to its crystalline structure and mineral composition. Expert analysis concludes that heat of 1500ºC would create such a change. These are hardly the kind of anomalies created by pranksters with planks! Crop circles also show existence of ultrasound, and such frequencies are known to exist at ancient sites such as stone circles and menhirs. And like all ancient sacred sites, crop circles appear at the intersecting points of the Earth's magnetic pathways of energy. Consequently, it is not unusual for people to experience heightened states of awareness and healings in crop circles - a situation also common to sacred sites and ancient temples. Biophysical evidence shows the plants' seed embryos are altered, and the liquid in the plants has been heated from the inside. In genuine formations there is also a reorganization of the plant's crystalline structure. Other evidence from crop circles shows how the floors of laid plants are swirled in mathematical proportions relative to the Golden Mean, the vortex used by nature to create organisms. Mathematically, genuine crop circles have yielded five new geometric theorems. based on Euclidian geometry. They are also encoded with sacred geometry - those harmonic ratios that govern the relationship between the orbits of planets in our solar system. Crop circles alter the local electromagnetic field; often compasses cannot locate north, cameras and cellular phones malfunction, packs of fresh batteries are drained in minutes, and the frequencies are known to affect aircraft equipment.- http://www.cropcirclesecrets.org/To listen to all our XZBN shows, with our compliments go to: https://www.spreaker.com/user/xzoneradiotv*** AND NOW ***The ‘X' Zone TV Channel on SimulTV - www.simultv.comThe ‘X' Chronicles Newspaper - www.xchroniclesnewpaper.com

Rob McConnell Interviews - Freddy Silva - Crop Circle in the Fields

The 'X' Zone Radio Show

Play Episode Listen Later Sep 24, 2021 41:28

For over a decade Crop Circle Secrets has led the way in helping the public make an informed decision on the origin of crop circles. Its factual research has provided an antidote to deliberate falsification of the genuine phenomenon by skeptics, hoaxers and their allies in the media. Crop circles are scientifically proven to be manifestations of energy under intelligent guidance. Over 80 eyewitnesses describe them to be made by tubes of light in less than fifteen seconds, as proved by a Japanese camera crew in 1989. The evidence for crop circles as a genuine phenomenon is found in Freddy Silva's book Secrets In The Fields. Contrary to popular perception, crop circles are not a modern phenomenon. They were witnessed by policemen and farmers as far back as 1890, they exist in the folklore of South Africa and China, and are mentioned in 17th Century academic texts. Over eighty eyewitnesses have seen crop circles forming in under fifteen seconds. Around 1980 they re-appeared as simple circles and rings in southern England, where 75% of designs are reported. By the late 1980s they developed into pictograms, not unlike the petroglyphs found at sacred sites. After 1990 the designs developed exponentially in complexity, and today the crop glyphs display as fractals and elements expressing fourth dimensional processes in quantum physics. To quell the public's growing interest in crop circles, the British Military presented two individuals named Doug and Dave to the media via a fictitious press agency, as the makers of all crop circles. The majority of their claims were later proved to have been fabricated, but never reported in the media. So, what exactly lies behind real crop circles? In genuine formations the stems are not broken but bent and swirled; they are subjected to a short and intense burst of heat that softens the stems to hover just above the ground, where they re-harden without damage. Research suggests that infrasound is producing such an effect. It has also been scientifically proven that soil samples taken from within crop circles show changes to its crystalline structure and mineral composition. Expert analysis concludes that heat of 1500ºC would create such a change. These are hardly the kind of anomalies created by pranksters with planks! Crop circles also show existence of ultrasound, and such frequencies are known to exist at ancient sites such as stone circles and menhirs. And like all ancient sacred sites, crop circles appear at the intersecting points of the Earth's magnetic pathways of energy. Consequently, it is not unusual for people to experience heightened states of awareness and healings in crop circles - a situation also common to sacred sites and ancient temples. Biophysical evidence shows the plants' seed embryos are altered, and the liquid in the plants has been heated from the inside. In genuine formations there is also a reorganization of the plant's crystalline structure. Other evidence from crop circles shows how the floors of laid plants are swirled in mathematical proportions relative to the Golden Mean, the vortex used by nature to create organisms. Mathematically, genuine crop circles have yielded five new geometric theorems. based on Euclidian geometry. They are also encoded with sacred geometry - those harmonic ratios that govern the relationship between the orbits of planets in our solar system. Crop circles alter the local electromagnetic field; often compasses cannot locate north, cameras and cellular phones malfunction, packs of fresh batteries are drained in minutes, and the frequencies are known to affect aircraft equipment.- http://www.cropcirclesecrets.org/To listen to all our XZBN shows, with our compliments go to: https://www.spreaker.com/user/xzoneradiotv*** AND NOW ***The ‘X' Zone TV Channel on SimulTV - www.simultv.comThe ‘X' Chronicles Newspaper - www.xchroniclesnewpaper.com

Rob McConnell Interviews - Freddy Silva - Crop Circles - Secrets in the Fields

The 'X' Zone Broadcast Network

Play Episode Listen Later Jul 29, 2021 41:27

For over a decade Crop Circle Secrets has led the way in helping the public make an informed decision on the origin of crop circles. Its factual research has provided an antidote to deliberate falsification of the genuine phenomenon by skeptics, hoaxers and their allies in the media. Crop circles are scientifically proven to be manifestations of energy under intelligent guidance. Over 80 eyewitnesses describe them to be made by tubes of light in less than fifteen seconds, as proved by a Japanese camera crew in 1989. The evidence for crop circles as a genuine phenomenon is found in Freddy Silva's book Secrets In The Fields. Contrary to popular perception, crop circles are not a modern phenomenon. They were witnessed by policemen and farmers as far back as 1890, they exist in the folklore of South Africa and China, and are mentioned in 17th Century academic texts. Over eighty eyewitnesses have seen crop circles forming in under fifteen seconds. Around 1980 they re-appeared as simple circles and rings in southern England, where 75% of designs are reported. By the late 1980s they developed into pictograms, not unlike the petroglyphs found at sacred sites. After 1990 the designs developed exponentially in complexity, and today the crop glyphs display as fractals and elements expressing fourth dimensional processes in quantum physics. To quell the public's growing interest in crop circles, the British Military presented two individuals named Doug and Dave to the media via a fictitious press agency, as the makers of all crop circles. The majority of their claims were later proved to have been fabricated, but never reported in the media. So, what exactly lies behind real crop circles? In genuine formations the stems are not broken but bent and swirled; they are subjected to a short and intense burst of heat that softens the stems to hover just above the ground, where they re-harden without damage. Research suggests that infrasound is producing such an effect. It has also been scientifically proven that soil samples taken from within crop circles show changes to its crystalline structure and mineral composition. Expert analysis concludes that heat of 1500ºC would create such a change. These are hardly the kind of anomalies created by pranksters with planks! Crop circles also show existence of ultrasound, and such frequencies are known to exist at ancient sites such as stone circles and menhirs. And like all ancient sacred sites, crop circles appear at the intersecting points of the Earth's magnetic pathways of energy. Consequently, it is not unusual for people to experience heightened states of awareness and healings in crop circles - a situation also common to sacred sites and ancient temples. Biophysical evidence shows the plants' seed embryos are altered, and the liquid in the plants has been heated from the inside. In genuine formations there is also a reorganization of the plant's crystalline structure. Other evidence from crop circles shows how the floors of laid plants are swirled in mathematical proportions relative to the Golden Mean, the vortex used by nature to create organisms. Mathematically, genuine crop circles have yielded five new geometric theorems. based on Euclidian geometry. They are also encoded with sacred geometry - those harmonic ratios that govern the relationship between the orbits of planets in our solar system. Crop circles alter the local electromagnetic field; often compasses cannot locate north, cameras and cellular phones malfunction, packs of fresh batteries are drained in minutes, and the frequencies are known to affect aircraft equipment.- http://www.cropcirclesecrets.org/

earth china england research secrets japanese south africa expert fields contrary crops crop circles mathematically british military golden mean freddy silva robmcconnell biophysical euclidian

Rob McConnell Interviews - Freddy Silva - Crop Circles - Secrets in the Fields

The 'X' Zone Radio Show

Play Episode Listen Later Jul 29, 2021 41:28

For over a decade Crop Circle Secrets has led the way in helping the public make an informed decision on the origin of crop circles. Its factual research has provided an antidote to deliberate falsification of the genuine phenomenon by skeptics, hoaxers and their allies in the media. Crop circles are scientifically proven to be manifestations of energy under intelligent guidance. Over 80 eyewitnesses describe them to be made by tubes of light in less than fifteen seconds, as proved by a Japanese camera crew in 1989. The evidence for crop circles as a genuine phenomenon is found in Freddy Silva's book Secrets In The Fields. Contrary to popular perception, crop circles are not a modern phenomenon. They were witnessed by policemen and farmers as far back as 1890, they exist in the folklore of South Africa and China, and are mentioned in 17th Century academic texts. Over eighty eyewitnesses have seen crop circles forming in under fifteen seconds. Around 1980 they re-appeared as simple circles and rings in southern England, where 75% of designs are reported. By the late 1980s they developed into pictograms, not unlike the petroglyphs found at sacred sites. After 1990 the designs developed exponentially in complexity, and today the crop glyphs display as fractals and elements expressing fourth dimensional processes in quantum physics. To quell the public's growing interest in crop circles, the British Military presented two individuals named Doug and Dave to the media via a fictitious press agency, as the makers of all crop circles. The majority of their claims were later proved to have been fabricated, but never reported in the media. So, what exactly lies behind real crop circles? In genuine formations the stems are not broken but bent and swirled; they are subjected to a short and intense burst of heat that softens the stems to hover just above the ground, where they re-harden without damage. Research suggests that infrasound is producing such an effect. It has also been scientifically proven that soil samples taken from within crop circles show changes to its crystalline structure and mineral composition. Expert analysis concludes that heat of 1500ºC would create such a change. These are hardly the kind of anomalies created by pranksters with planks! Crop circles also show existence of ultrasound, and such frequencies are known to exist at ancient sites such as stone circles and menhirs. And like all ancient sacred sites, crop circles appear at the intersecting points of the Earth's magnetic pathways of energy. Consequently, it is not unusual for people to experience heightened states of awareness and healings in crop circles - a situation also common to sacred sites and ancient temples. Biophysical evidence shows the plants' seed embryos are altered, and the liquid in the plants has been heated from the inside. In genuine formations there is also a reorganization of the plant's crystalline structure. Other evidence from crop circles shows how the floors of laid plants are swirled in mathematical proportions relative to the Golden Mean, the vortex used by nature to create organisms. Mathematically, genuine crop circles have yielded five new geometric theorems. based on Euclidian geometry. They are also encoded with sacred geometry - those harmonic ratios that govern the relationship between the orbits of planets in our solar system. Crop circles alter the local electromagnetic field; often compasses cannot locate north, cameras and cellular phones malfunction, packs of fresh batteries are drained in minutes, and the frequencies are known to affect aircraft equipment.- http://www.cropcirclesecrets.org/******************************************************************To listen to all our XZBN shows, with our compliments go to: https://www.spreaker.com/user/xzoneradiotv*** AND NOW ***The ‘X' Zone TV Channel on SimulTV - www.simultv.comThe ‘X' Chronicles Newspaper - www.xchroniclesnewspaper.com ******************************************************************

Rob McConnell Interviews - Freddy Silva - Crop Circles - Secrets in the Fields

The 'X' Zone Broadcast Network

Play Episode Listen Later Jul 29, 2021 41:27

For over a decade Crop Circle Secrets has led the way in helping the public make an informed decision on the origin of crop circles. Its factual research has provided an antidote to deliberate falsification of the genuine phenomenon by skeptics, hoaxers and their allies in the media. Crop circles are scientifically proven to be manifestations of energy under intelligent guidance. Over 80 eyewitnesses describe them to be made by tubes of light in less than fifteen seconds, as proved by a Japanese camera crew in 1989. The evidence for crop circles as a genuine phenomenon is found in Freddy Silva's book Secrets In The Fields. Contrary to popular perception, crop circles are not a modern phenomenon. They were witnessed by policemen and farmers as far back as 1890, they exist in the folklore of South Africa and China, and are mentioned in 17th Century academic texts. Over eighty eyewitnesses have seen crop circles forming in under fifteen seconds. Around 1980 they re-appeared as simple circles and rings in southern England, where 75% of designs are reported. By the late 1980s they developed into pictograms, not unlike the petroglyphs found at sacred sites. After 1990 the designs developed exponentially in complexity, and today the crop glyphs display as fractals and elements expressing fourth dimensional processes in quantum physics. To quell the public's growing interest in crop circles, the British Military presented two individuals named Doug and Dave to the media via a fictitious press agency, as the makers of all crop circles. The majority of their claims were later proved to have been fabricated, but never reported in the media. So, what exactly lies behind real crop circles? In genuine formations the stems are not broken but bent and swirled; they are subjected to a short and intense burst of heat that softens the stems to hover just above the ground, where they re-harden without damage. Research suggests that infrasound is producing such an effect. It has also been scientifically proven that soil samples taken from within crop circles show changes to its crystalline structure and mineral composition. Expert analysis concludes that heat of 1500ºC would create such a change. These are hardly the kind of anomalies created by pranksters with planks! Crop circles also show existence of ultrasound, and such frequencies are known to exist at ancient sites such as stone circles and menhirs. And like all ancient sacred sites, crop circles appear at the intersecting points of the Earth's magnetic pathways of energy. Consequently, it is not unusual for people to experience heightened states of awareness and healings in crop circles - a situation also common to sacred sites and ancient temples. Biophysical evidence shows the plants' seed embryos are altered, and the liquid in the plants has been heated from the inside. In genuine formations there is also a reorganization of the plant's crystalline structure. Other evidence from crop circles shows how the floors of laid plants are swirled in mathematical proportions relative to the Golden Mean, the vortex used by nature to create organisms. Mathematically, genuine crop circles have yielded five new geometric theorems. based on Euclidian geometry. They are also encoded with sacred geometry - those harmonic ratios that govern the relationship between the orbits of planets in our solar system. Crop circles alter the local electromagnetic field; often compasses cannot locate north, cameras and cellular phones malfunction, packs of fresh batteries are drained in minutes, and the frequencies are known to affect aircraft equipment.- http://www.cropcirclesecrets.org/ ****************************************************************** To listen to all our XZBN shows, with our compliments go to: https://www.spreaker.com/user/xzoneradiotv *** AND NOW *** The ‘X' Zone TV Channel on SimulTV - www.simultv.com The ‘X' Chronicles Newspaper - www.xchroniclesnewspaper.com ******************************************************************

New Insights Into the Biophysical Characteristics of RTS,S Antibodies

Malaria Minute | The Latest Malaria News, in 60 Seconds

Play Episode Listen Later Feb 19, 2021 1:00

The Latest Malaria News, in 60 Seconds. Researchers reveal the importance of antibody affinity and dissociation constant in parasite neutralisation. More: www.fightmalaria.uk/MalariaMinute

researchers characteristics antibodies new insights biophysical

Check 1 - Biosphere and People: The Biophysical World

The Hidden Power

Play Episode Listen Later Feb 5, 2021 21:38

The first and fundamental principle of this series - and indeed this entire way of looking at things - reflects the unseen, creeping processes causing catastrophic climate change. Why do we need this? How are we to think about it? What can we do?Talking points:industrialisationlimits on human behavioursecondary effects of climate changeour personal relationship to the biosphereself-harm as an image for how we treat our environmentthe future generations act in Walesboundariesconstitutions filter through to all activitiesresponsibility at different levelswhat people with higher incomes can dofocus on where you liveThere are so many links relating to this topic, it's hard to know where to start - but to get a global view on an array of challenges on the horizon, it's hard to beat Earthtime, an open source mapping project which allows you to view other people's stories, or play around with available data yourself:https://earthtime.org/#New economic model: https://time.com/5930093/amsterdam-doughnut-economics/ Hosted on Acast. See acast.com/privacy for more information.

acast biosphere biophysical

Biophysical Economics

Double Take By Mellon

Play Episode Listen Later Jan 28, 2021 44:57

In this roundtable discussion, Mellon’s head of Small Mid Cap Equity Research explores the emergent field of biophysical economics with Professor of Economics and Sustainability at Wells College, Kent Klitgaard.

energy professor economics sustainability macroeconomics mellon socioeconomic double take biophysical wells college

Biochemical and Biophysical Characterization of the dsDNA packaging motor from the Lactococcus lactis bacteriophage asccphi28

Play Episode Listen Later Nov 18, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.17.383745v1?rss=1 Authors: Reyes-Aldrete, E., Dill, E., Bussetta, C., Szymanski, M. R., Diemer, G. S., Maindola, P., White, M., Choi, K., Morais, M. Abstract: Double-stranded DNA viruses package their genomes into pre-assembled protein procapsids. This process is driven by macromolecular motors that transiently assemble at a unique vertex of the procapsid and utilize homomeric ring ATPases to couple genome encapsidation to ATP hydrolysis. Here we describe biochemical and biophysical characterization of the packaging ATPase from Lactococcus lactis phage ascc{varphi}28. Size-exclusion chromatography, analytical ultracentrifugation, small angle x-ray scattering, and negative stain TEM indicate that the ~45 kDa protein formed a 443 kDa cylindrical assembly with a maximum dimension of ~155 Angstroms and radius of gyration of ~54 Angstroms. Together with the dimensions of the crystallographic asymmetric unit from preliminary X-ray diffraction experiments, these results indicate that gp11 forms a decameric D5-symmetric complex consisting of two pentameric rings related by 2-fold symmetry. Additional kinetic analysis shows that recombinantly expressed gp11 has ATPase activity comparable to that of functional ATPase rings assembled on procapsids in other genome packaging systems. Hence, gp11 forms rings in solution that likely reflect the fully assembled ATPases in active virus-bound motor complexes. Whereas ATPase functionality in other dsDNA phage packaging systems requires assembly on viral capsids, the ability to form functional rings in solution imparts gp11 with significant advantages for high resolution structural studies and rigorous biophysical/biochemical analysis. Copy rights belong to original authors. Visit the link for more info

dna copy motor tem packaging atp choi dill morais characterization biochemical kda szymanski d5 bacteriophages biorxiv atpase biophysical dsdna atpases lactococcus

Biophysical characterization of two commercially available preparations of the drug containing Escherichia coli L-Asparaginase 2

drug lima copy andrade almeida preparations ion characterization commercially escherichia magalhaes biorxiv escherichia coli scapin biophysical

Play Episode Listen Later Nov 12, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.11.379065v1?rss=1 Authors: Araujo, T. S., Scapin, S. M., Andrade, W., Fasciotti, M., de Magalhaes, M. T., Almeida, M. S., Lima, L. M. T. d. R. Abstract: The hydrolysis of asparagine and glutamine by L-asparaginase has been used to treat acute lymphoblastic leukemia for over four decades. Each L-asparaginase monomer has a long loop that closes over the active site upon substrate binding, acting as a lid. Here we present a comparative study two commercially available preparations of the drug containing Escherichia coli L-Asparaginase 2, performed by a comprehensive array of biophysical and biochemical approaches. We report the oligomeric landscape and conformational and dynamic plasticity of E. coli type 2 L-asparaginase (EcA2) present in two different formulations, and its relationship with L-aspartic acid, which is present in Aginasa, but not in Leuginase. EcA2 shows a composition of monomers and oligomers up to tetramers, which is mostly not altered in the presence of L-Asp. The N-terminal loop of Leuginase, which is part of the active site is flexibly disordered, but gets ordered as in Aginasa in the presence os L-Asp, while L-Glu only does so to a limited extent. Ion-mobility spectrometry mass spectrometry reveals two conformers for the monomeric EcA2, one of which can selectively bind to L-Asp and L-Glu. Aginasa has higher resistance to in vitro proteolysis than Leuginase, and this is directly related to the presence of L-Asp. Copy rights belong to original authors. Visit the link for more info

K+ efflux through postsynaptic NMDA receptors suppresses local astrocytic glutamate uptake

Play Episode Listen Later Nov 8, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.07.372722v1?rss=1 Authors: Tyurikova, O., Shih, P.-Y., Dembitskaya, Y., Savtchenko, L. P., McHugh, T., Rusakov, D. A., Semyanov, A. Abstract: Glutamatergic transmission in the hippocampus prompts K+ efflux through postsynaptic N-methyl-D-aspartate receptors (NMDARs). This K+ efflux depolarizes local presynaptic terminals, boosting glutamate release, but whether it also depolarizes local astrocytic processes, thus affecting glutamate uptake, remains unknown. Here, we find that the pharmacological blockade, or conditional knockout, of NMDARs suppresses the progressive use-dependent increase in the amplitude and decay time of the astrocytic glutamate transporter current (IGluT), whereas blocking the astrocytic inward-rectifying K+ channels prevents the decay time increase only. Glutamate spot-uncaging reveals that local astrocyte depolarization, rather than extracellular K+ rises on their own, reduces the amplitude and prolong the decay of IGluT. Biophysical simulations of a realistic 3D astrocyte confirm that local transient elevations of extracellular K+ can inhibit local glutamate uptake in fine astrocytic processes. We conclude that K+ efflux through postsynaptic NMDARs can transiently depolarize local cell membranes, which facilitates presynaptic release while reducing local glutamate uptake. Optical glutamate sensor imaging and a two-pathway test relate postsynaptic K+ efflux to enhanced extrasynaptic glutamate signaling. Thus, the frequency of synaptic discharges can control the way the network handles its synaptic signal exchange. Copy rights belong to original authors. Visit the link for more info

local 3d copy mchugh optical uptake shih receptors nmda glutamate suppresses biorxiv biophysical efflux

Biophysical Profile

Third Time's the Charm

Play Episode Listen Later Nov 6, 2020 0:40

This episode covers the biophysical profile!

profile biophysical

Isolation and biophysical characterization of GSU0105, a triheme c-type cytochrome from Geobacter sulfurreducens

Play Episode Listen Later Nov 3, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.03.367284v1?rss=1 Authors: Brittain, T. J., O'Malley, M. C., Swaim, C. M., Fink, R. A., Kokhan, O. Abstract: C-type cytochromes play an important role in respiration of dissimilatory metal-reducing bacteria. They form extended conduits for charge transfer between the cellular metabolism and external electron acceptors such as particles of iron oxide, metal ions, and humic substances. Out of more than a hundred c-type cytochromes in Geobacter sulfurreducens, only a small fraction has been previously characterized. Here we present our results on expression and biophysical characterization of GSU0105, a novel 3-heme cytochrome, important for Fe(III) respiration in G. sulfurreducens. We successfully cloned the gene and achieved ~3 mg/L of culture GSU0105 expression in E.coli. Despite a similar size (71 amino acids) and the same number of c-type hemes to the members of the cytochrome (cyt) c7 family, multiple sequence alignment suggests that GSU0105 does not belong to the cyt c7 family. UV-Vis spectroscopy revealed typical c-type cytochrome spectral features, including a weak iron-sulfur charge transfer band suggesting that at least one heme is ligated with a methionine residue. Far UV circular dichroism studies demonstrate approximately 35% content of -helices and {beta}-sheets, each, as well as thermal aggregation occurring above 60C. A combination of SAXS and analytical size exclusion chromatography data shows that GSU0105 is monomeric in solution. Finally, affinity pull-down assays demonstrate high binding affinity to PpcD and weaker binding to the other members of the cyt c7 family. Copy rights belong to original authors. Visit the link for more info

isolation copy fink characterization swaim biorxiv biophysical cytochrome uv vis saxs geobacter

A biophysical limit for quorum sensing in biofilms

MOSES Organic Farming Podcast

Play Episode Listen Later Nov 2, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.01.364125v1?rss=1 Authors: Narla, A., Borenstein, D. B., Wingreen, N. S. Abstract: Bacteria grow on surfaces in complex immobile communities known as biofilms, which are composed of cells embedded in an extracellular matrix. Within biofilms, bacteria often interact with members of their own species, and cooperate or compete with members of other species via quorum sensing (QS). QS is a process by which microbes produce, secrete, and subsequently detect small molecules called autoinducers (AIs) to assess their local population density. We explore the competitive advantage of QS through agent-based simulations of a spatial model in which colony expansion via extracellular matrix production provides greater access to a limiting diffusible nutrient. We note a significant difference in results based on whether AI production is constitutive or limited by nutrient availability: If AI production is constitutive, simple QS-based matrix-production strategies can be far superior to any fixed strategy. However, if AI production is limited by nutrient availability, QS-based strategies fail to provide a significant advantage over fixed strategies. To explain this dichotomy, we derive a novel biophysical limit for the dynamic range of nutrient-limited AI concentrations in biofilms. This range is remarkably small (less than 10-fold) for the realistic case in which a growth-limiting diffusible nutrient is taken up within a narrow active growth layer. This biophysical limit implies that for QS to be most effective in biofilms, AI production should be a protected function not directly tied to metabolism. Copy rights belong to original authors. Visit the link for more info

ai limit copy qs biofilms borenstein biorxiv biophysical quorum sensing

Growing Wellness: How to Care for Your Mental Health

Play Episode Listen Later Oct 29, 2020 16:50

This is the audio from the monthly meeting of the farmer-led mental health group, Growing Wellness. This month's guest is Monica Kramer McConkey, a licensed professional counselor, Rural Mental Health Specialist, and consultant with Eyes on the Horizon Consulting. In this session, Monica discusses building personal resilience in 4 areas (Social, Biophysical, Psychological, and Spiritual) to increase your capacity to deal with stress and uncertainty. Personal resilience is defined as the ability to withstand or recover from difficult situations, and I would add... the ability to grow through that process. The goal for this session is to learn about yourself and set goals to build your resilience! Growing Wellness Group meets monthly for a brief presentation followed by discussion. The group also has a listserv. Click to learn more and join in this community. Check out the Grower Group page on the MOSES website and get connected with other farmers. Get in touch with Monica: 218-280-7785 monicamariekm@yahoo.com www.eyesonthehorizon.org Watch Monica's presentation on YouTube: Growing Wellness: Nurturing Protective Factors for Mental Health --- Send in a voice message: https://anchor.fm/moses-podcast/message

mental health social personal care spiritual wellness eyes psychological biophysical

Structural basis for a natural circular permutation in proteins

Play Episode Listen Later Oct 29, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.28.360099v1?rss=1 Authors: Nonis, S. G., Haywood, J., Schmidberger, J. W., Bond, C. S., Mylne, J. S. Abstract: Over 30 years ago, an intriguing post-translational modification was discovered to be responsible for creating concanavalin A (conA), a carbohydrate-binding protein found in the seeds of jack bean (Canavalia ensiformis) and commercially used for carbohydrate chromatography. Biosynthesis of conA involves what was then an unprecedented rearrangement in amino acid sequence, whereby the N-terminal half of the gene-encoded conA precursor is swapped to become the C-terminal half of conA. The cysteine protease, asparaginyl endopeptidase (AEP), was shown to be involved, but its mechanism was not fully elucidated. To understand the structural basis and consequences of conA circular permutation, we generated a recombinant jack bean conA precursor (pro-conA) plus jack bean AEP (CeAEP1) and solved crystal structures for each to 2.1 [A] and 2.7 [A] respectively. By reconstituting the biosynthesis of conA in vitro, we prove CeAEP1 alone can perform both the cleavage and cleavage-coupled transpeptidation to form conA. CeAEP1 structural analysis reveals how it is capable of carrying out both these reactions. Biophysical assays illustrated that conA is more thermally and pH stable than pro-conA, consistent with fewer intermolecular interactions between subunits in the pro-conA crystal structure. These findings elucidate the consequences of circular permutation in the only post-translation example known to occur in nature. Copy rights belong to original authors. Visit the link for more info

natural bond basis copy circular structural proteins haywood aep cona biorxiv biophysical permutation biosynthesis

Changes in excitability properties of ventromedial motor thalamic neurons in 6-OHDA lesioned mice

KunstlerCast - Suburban Sprawl: A Tragic Comedy

Play Episode Listen Later Oct 5, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.05.327379v1?rss=1 Authors: Bichler, E. K., Cavarretta, F., Jaeger, D. Abstract: The activity of basal ganglia input receiving motor thalamus (BGMT) makes a critical impact on motor cortical processing, but modification in BGMT processing with Parkinsonian conditions have not be investigated at the cellular level. Such changes may well be expected due to homeostatic regulation of neural excitability in the presence of altered synaptic drive with dopamine depletion. We addressed this question by comparing BGMT properties in brain slice recordings between control and unilaterally 6-OHDA treated adult mice. At a minimum of 1 month post 6-OHDA treatment, BGMT neurons showed a highly significant increase in intrinsic excitability, which was primarily due to a decrease in M-type potassium current. BGMT neurons after 6-OHDA treatment also showed an increase in T-type calcium rebound spikes following hyperpolarizing current steps. Biophysical computer modeling of a thalamic neuron demonstrated that an increase in rebound spiking can also be accounted for by a decrease in the M-type potassium current. Modeling also showed that an increase in sag with hyperpolarizing steps found after 6-OHDA treatment could in part but not fully be accounted for by the decrease in M-type current. These findings support the hypothesis that homeostatic changes in BGMT neural properties following 6-OHDA treatment likely influence the signal processing taking place in basal ganglia thalamocortical processing in Parkinson's disease. Copy rights belong to original authors. Visit the link for more info

parkinson copy modeling motor properties mice jaeger neurons biorxiv biophysical parkinsonian bgmt

KunstlerCast 334

Play Episode Listen Later Sep 24, 2020 59:35

Charles A. S. Hall was born in Eastern Massachusetts in 1943, attended Colgate University, then Penn State University for a Masters in Ecology, then a PhD in Systems Ecology under Howard Odum at the University of North Carolina. He was professor at Cornell University, University of Montana and SUNY College of Environmental Science and Forestry. He is author, coauthor or editor of 14 books and 300 scientific papers, many in our leading scientific journals. Dr. Hall is noted especially for the concepts of Energy Return on Investment and BioPhysical Economics, both applying the natural sciences to what is traditionally studied with conventional economics. Currently he is retired and lives in Western Montana with his wife and their dog, but is very involved in developing a BioPhysiccsl Economics Institute.

university phd masters north carolina economics investment montana cornell university ecology penn state university environmental science forestry colgate university economic collapse western montana suny college eastern massachusetts biophysical kunstlercast

The Dynamic Influence of Linker Histone Saturation within the Poly-Nucleosome Array

Play Episode Listen Later Sep 21, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.20.305581v1?rss=1 Authors: Woods, D. C., Rodríguez-Ropero, F., Wereszczynski, J. Abstract: Linker histones bind to nucleosomes and modify chromatin structure and dynamics as a means of epigenetic regulation. Biophysical studies have shown that chromatin fibers can adopt a plethora of conformations with varying levels of compaction. Linker histone condensation, and its specific binding disposition, has been associated with directly tuning this ensemble of states. However, the atomistic dynamics and quantification of this mechanism remains poorly understood. Here, we present molecular dynamics simulations of octa-nucleosome arrays, based on a cryo-EM structure of the 30-nm chromatin fiber, with and without the globular domains of the H1 linker histone to determine how they influence fiber structures and dynamics. Results show that when bound, linker histones inhibit DNA flexibility and stabilize repeating tetra-nucleosomal units, giving rise to increased chromatin compaction. Furthermore, upon the removal of H1, there is a significant destabilization of this compact structure as the fiber adopts less strained and untwisted states. Interestingly, linker DNA sampling in the octa-nucleosome is exaggerated compared to its mono-nucleosome counterparts, suggesting that chromatin architecture plays a significant role in DNA strain even in the absence of linker histones. Moreover, H1-bound states are shown to have increased stiffness within tetra-nucleosomes, but not between them. This increased stiffness leads to stronger long-range correlations within the fiber, which may result in the propagation of epigenetic signals over longer spatial ranges. These simulations highlight the effects of linker histone binding on the internal dynamics and global structure of poly-nucleosome arrays, while providing physical insight into a mechanism of chromatin compaction. Copy rights belong to original authors. Visit the link for more info

influence dna results dynamic copy rodr poly array saturation linker ropero biorxiv histone biophysical nucleosome

Spatial information transfer in hippocampal place cells depends on trial-to-trial variability, symmetry of place-field firing and biophysical heterogeneities

Play Episode Listen Later Sep 19, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.17.301747v1?rss=1 Authors: Roy, A., Narayanan, R. Abstract: The relationship between the feature-tuning curve and information transfer profile of individual neurons provides vital insights about neural encoding. However, the relationship between the spatial tuning curve and spatial information transfer of hippocampal place cells remains unexplored. Here, employing a stochastic search procedure spanning thousands of models, we arrived at 127 conductance-based place-cell models that exhibited signature electrophysiological characteristics and sharp spatial tuning, with parametric values that exhibited neither clustering nor strong pairwise correlations. We introduced trial-to-trial variability in responses and computed model tuning curves and information transfer profiles, using stimulus-specific (SSI) and mutual (MI) information metrics, across locations within the place field. We found spatial information transfer to be heterogeneous across models, but to reduce consistently with increasing degrees of variability. Importantly, whereas reliable low-variability responses implied that maximal information transfer occurred at high-slope regions of the tuning curve, increase in variability resulted in maximal transfer occurring at the peak-firing location in a subset of models. Moreover, experience-dependent asymmetry in place-field firing introduced asymmetries in the information transfer computed through MI, but not SSI, and the impact of activity-dependent variability on information transfer was minimal compared to activity-independent variability. Biophysically, we unveiled a many-to-one relationship between different ion channels and information transfer, and demonstrated critical roles for N-methyl-D-aspartate receptors, transient potassium and dendritic sodium channels in regulating information transfer. Our results emphasize the need to account for trial-to-trial variability, tuning-curve shape and biological heterogeneities while assessing information transfer, and demonstrate ion-channel degeneracy in the regulation of spatial information transfer. Copy rights belong to original authors. Visit the link for more info

field trial copy firing cells spatial symmetry ssi variability biorxiv biophysical hippocampal

Exploring the binding of resveratrol to promoter DNA sequence d(CCAATTGG)2 using biophysical studies

Play Episode Listen Later Sep 12, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.10.291336v1?rss=1 Authors: Kumar, S., Kumar, P., Nair, M. S. Abstract: We report the interaction of resveratrol with an octamer DNA sequence d(CCAATTGG)2, present in the promoter region of many oncogenes, using a combination of absorption, fluorescence, calorimetric and nuclear magnetic resonance techniques to probe the binding. Resveratrol binds to the duplex sequence with a binding constant 2.20x106 M-1 in absorption studies. A ligand-duplex stoichiometry of 2.2:1 was obtained with binding constant varying from 109 to 106M-1 with the concentration of DNA varied in fluorescence titration measurements. Spectral changes indicated external binding of resveratrol to duplex DNA. Circular dichroism data displayed minimal variation suggesting external binding. Melting temperatures of DNA and its 1:1 complex showed a difference of approximately 2.25{degrees}C, which supports the external binding. Nuclear magnetic resonance data showed resveratrol binds to the minor groove region near the AT basepair from the nuclear Overhauser effect spectroscopic cross peaks. Distance restrained molecular dynamics was employed in explicit solvent condition to obtain the lowest energy structure. The complex was stable and retained the B-DNA conformation. Findings in this study identify resveratrol as a minor groove binder to the AT region of DNA and pave the way for exploring resveratrol and its analogues as promising anticancer/antibacterial drug. Copy rights belong to original authors. Visit the link for more info

dna studies distance nuclear copy kumar findings promoters binding sequence circular melting nair spectral resveratrol biorxiv biophysical

A biophysical and structural analysis of DNA binding by oligomeric hSSB1 (NABP2OBFC2B)

Play Episode Listen Later Aug 27, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.26.269084v1?rss=1 Authors: El-Kamand, S., Jergic, S., Lawson, T., Kariawasam, R., Richard, D. J., Cubeddu, L., Gamsjaeger, R. Abstract: The oxidative modification of DNA can result in the loss of genome integrity and must be repaired to maintain overall genomic stability. We have recently demonstrated that human single stranded DNA binding protein 1 (hSSB1/NABP2/OBFC2B) plays a crucial role in the removal of 8-oxo-7,8-dihydro-guanine (8-oxoG), the most common form of oxidative DNA damage. The ability of hSSB1 to form disulphide-bonded tetramers and higher oligomers in an oxidative environment is critical for this process. In this study, we have used nuclear magnetic resonance (NMR) spectroscopy and surface plasmon resonance (SPR) experiments to determine the molecular details of ssDNA binding by oligomeric hSSB1. We reveal that hSSB1 oligomers can open up damaged dsDNA and interact with individual single strands; however, our data also show that oxidised bases are recognised in the same manner as undamaged DNA bases. NMR experiments provide evidence that oligomeric hSSB1 is able to bind longer ssDNA in both binding polarities using a distinct set of residues different to those of the related SSB from Escherichia coli. We further demonstrate that oligomeric hSSB1 recognises ssDNA with a significantly higher affinity than its monomeric form and propose structural models for oligomeric hSSB1-ssDNA interaction. Copy rights belong to original authors. Visit the link for more info

dna copy spr binding structural ssb nmr escherichia biorxiv biophysical dsdna ssdna

Biophysical characterization of the ETV6 PNT domain polymerization interfaces

Play Episode Listen Later Aug 24, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.21.262121v1?rss=1 Authors: Gerak, C. A. N., Cho, S. Y., Kolesnikov, M., Okon, M., Murphy, M. E. P., Sessions, R. B., Roberge, M., McIntosh, L. P. Abstract: ETV6 is an ETS family transcriptional repressor that self-associates by its PNT domain to facilitate cooperative DNA binding. Chromosomal translocations frequently generate constitutively active oncoproteins with the ETV6 PNT domain fused to the kinase domain of one of many protein tyrosine kinases. Although an attractive target for therapeutic intervention, the propensity of the ETV6 PNT domain to polymerize via the tight head-to-tail association of two relatively flat interfaces makes it challenging to identify suitable small molecule inhibitors of this protein-protein interaction. Herein we provide a comprehensive biophysical characterization of the ETV6 PNT domain interaction interfaces to aid future drug discovery efforts and help define the mechanisms by which its self-association mediates transcriptional repression. Using NMR spectroscopy, X-ray crystallography, and molecular dynamics simulations, we demonstrate that ETV6 PNT domain variants with monomerizing mutations adopt very stable helical bundle folds that do not change in conformation upon self-association. Amide hydrogen exchange and surface plasmon resonance-monitored alanine scanning mutagenesis studies identified hot spot regions within the self-association interfaces. These regions include both central hydrophobic residues and flanking salt-bridging residues. Collectively, these studies indicate that small molecules targeted to these hydrophobic or charged regions within the relatively rigid interfaces could potentially serve as orthosteric inhibitors of ETV6 PNT domain polymerization. Copy rights belong to original authors. Visit the link for more info

dna copy domain collectively cho mcintosh ets interfaces characterization roberge biorxiv pnt chromosomal biophysical polymerization

Cell-Scale Biophysical Cues from Collagen Fiber Architecture Instruct Cell Behavior and the Propagation of Mechanosensory Signals

Play Episode Listen Later Aug 13, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.12.248179v1?rss=1 Authors: Szulczewski, J. M., Inman, D. R., Proestaki, M., Notbohm, J., Burkel, B. M., Ponik, S. M. Abstract: Mechanosensory cues from the extracellular matrix underpin numerous cellular behaviors including tumor cell migration yet are influenced by the local structure and organization of the matrix in unknown ways. To investigate mechanical cues with respect to local collagen organization, we used a combination of intravital imaging of the mammary tumor microenvironment and 3D collagen gel systems with both migratory MDA-MB-231 cells and acellular pNIPAAm beads. We identified that fiber organization directs a bias in cell response along the axis of alignment. Using innovative methodology, we determined that local collagen alignment resulted in a 30-fold difference in directional cell-scale stiffness and also dramatically altered the rate at which cell-induced fiber displacements decayed over distance. Our results reveal differential mechanical properties across orthogonal directions in aligned matrices that provide sizeable cues to the cell and have important implications for cellular mechanosensing and cell-cell communication within the tissue microenvironment. Copy rights belong to original authors. Visit the link for more info

3d behavior scale architecture copy signals fiber collagen cues instruct inman propagation biorxiv biophysical mda mb

The biophysical basis underlying the maintenance of early phase long-term potentiation

phase long term basis copy maintenance underlying ltp biorxiv biophysical potentiation

Play Episode Listen Later Aug 12, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.12.247726v1?rss=1 Authors: Becker, M. F. P., Tetzlaff, C. Abstract: The maintenance of synaptic changes resulting from long-term potentiation (LTP) is essential for brain functions. Different LTP phases have been associated with diverse molecular processes and pathways, and the molecular underpinnings of LTP on the time scales of a few minutes or of several hours are well established. However, the principles underlying the maintenance of the early phase of LTP (E-LTP) on the intermediate time scale of 1-6 hours remains elusive. We hypothesize that specific features of postsynaptic receptor trafficking would be responsible for sustaining synaptic changes during this LTP phase. We test this hypothesis by formalizing a biophysical model that integrates several experimentally-motivated mechanisms. The model captures a wide range of experimental findings and predicts that synaptic changes are preserved for hours when the receptor dynamics are shaped by the interplay of structural changes of the spine in conjunction with increased trafficking from recycling endosomes and the cooperative binding of receptors. Furthermore, our model provides several predictions to verify experimentally our findings. Copy rights belong to original authors. Visit the link for more info

Slow AMPA receptors in hippocampal principal cells

Play Episode Listen Later Aug 6, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.05.238667v1?rss=1 Authors: Pampaloni, N. P., Riva, I., Carbone, A. L., Plested, A. Abstract: Glutamate receptor ion channels such as the -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor mediate the majority of fast excitatory neurotransmission in the vertebrate CNS. AMPA receptors canonically provide the fast, millisecond component of the synaptic current. However, we found that about two-thirds of principal cells in the mouse hippocampus express AMPA receptors that do not desensitize and stay active for up to half a second. These receptors are expressed at synapses with a sparse but flat spatial distribution. The resulting increase in charge transfer allows single connections to reliably trigger action potentials. Biophysical and pharmacological observations imply that slow AMPA receptors incorporate {gamma}-8 and other auxiliary proteins, and their activation lengthens individual miniature synaptic currents. Synaptic connections harboring slow AMPARs should have unique roles in hippocampal function. Copy rights belong to original authors. Visit the link for more info

principal copy cells cns carbone receptors synaptic ampa biorxiv biophysical hippocampal

Biophysical and dynamic characterization of a fine-tuned binding of the human Respiratory Syncytial Virus M2-1 core domain to long RNAs

dynamic copy souza machado domain almeida binding rna tuned m2 characterization guimaraes rnas respiratory syncytial virus biorxiv fossey biophysical

Play Episode Listen Later Jul 25, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.22.216952v1?rss=1 Authors: Caruso, I. P., Guimaraes, G. C., Machado, V. B., Fossey, M. A., Willbold, D., Almeida, F. C. L., Souza, F. P. Abstract: The human Respiratory Syncytial Virus (hRSV) M2-1 protein functions as a processivity and antitermination factor of the viral polymerase complex. Here it is presented the first evidence that hRSV M2-1 core domain (cdM2-1) alone has an unfolding activity for long RNAs, as well as a biophysical and dynamic characterization of the cdM2-1/RNA complex. The main contact region of cdM2-1 with RNA was the 1-2-5-6 helix bundle, which suffered local conformational changes and promoted the RNA unfolding activity. This activity may be triggered by base-pairing recognition. RNA molecules wrap around the whole cdM2-1, protruding their terminals over the domain. The 2-3 and 3-4 loops of cdM2-1 were marked by an increase in picosecond internal motions upon RNA binding even though they are not directly involved in the interaction. The results revealed that the cdM2-1/RNA complex originates from a fine-tuned binding, contributing to unraveling interaction aspects necessary to M2-1 activity. Copy rights belong to original authors. Visit the link for more info

Pacey Performance Podcast #302 - Barriers Encountered by Females in S&C (Sophia Nimphius, Lorena Torres & Brian Gearity)

Pacey Performance Podcast

Play Episode Listen Later Jul 23, 2020 83:24

In this episode of the Pacey Performance Podcast I am speaking to Sophia Nimphius, Brian Gearity and Lorena Torres about the barriers encountered by females in strength & conditioning. Sophia is a Professor at Edith Cowen University and has featured on the podcast before chatting about change of direction, however this is an area that she is extremely passionate about and in this episode provides some stories that really shocked and disappointed me about our industry. Lorena Torres is Performance Director at the Philadelphia 76ers and, like Sophia provides an incredible insight into what its like being a female in such a male-dominated industry such as strength and conditioning. Brian is a Director of Online Sports Degrees at the University of Denver and recently co-authors the book, 'Understanding Strength and Conditioning as Sport Coaching: Bridging the Biophysical, Pedagogical and Sociocultural Foundations of Practice' so is well versed in this area. This is a great listen but be ready for some uncomfortable truths. I hope you enjoy this episode with Sophia, Lorena and Brian. In this episode we discussed... Who are Sophia Nimphius, Lorena Torres and Brian Gearity (background, education and current role)? The current state of play Personal experiences as females in S&C Male athlete perceptions of female coaches (Brian) Recommendations for females going into male sports Females in leadership positions within sporting organisations Key barriers to career development as a female S&C/sports scientist A broader social context The way forward What is being done What more we can do Sophia can be found on Twitter @docsoph, Lorena can be found on Twitter @lorenatorres07 and Brian can be found on Twitter @drgearity This episode of the Pacey Performance Podcast is sponsored by Hawkin Dynamics, the team behind the world's only wireless force plate system. Hawkin Dynamics can be found at hawkindynamics.com and you can follow them on Twitter @hawkindynamics This episode is also sponsored by IMeasureU. IMeasureU are a world leading inertial platform to precisely quantify body movement and workload metrics in the field. IMeasureU can be found at imeasureu.com and you can follow them on Twitter @imeasureu. This episode is also sponsored by Omegawave, the only non-invasive readiness technology to assess both brain and heart. Omegawave can be found at omegawave.com and you can follow them on Twitter @omegawave. This episode is also sponsored by Athlete Monitoring the world’s most comprehensive, versatile and cost-effective Athlete Health & Performance Management platform for elite sports. You can find their website at athletemonitoring.com or on Twitter @athletemonitor Keep up to date with everything that is going on with the podcast by following on Twitter @strengthofsci or visiting strengthofscience.com. Enjoy PP

director university professor practice philadelphia barriers torres conditioning females encountered s c pacey performance director performance podcast pedagogical biophysical omegawave

Carotenogenesis of Staphylococcus aureus: new insights and impact on membrane biophysical properties

copy properties identification membrane new insights cifuentes ibanez staphylococcus leidy stx vitamin k2 rosato biorxiv staphylococcus aureus biophysical fourier transform

Play Episode Listen Later Jul 19, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.19.210609v1?rss=1 Authors: Lopez, G.-D., Suesca, E., Alvarez-Rivera, G., Rosato, A., Ibanez, E., Cifuentes, A., Leidy, C., Carazzone, C. Abstract: Staphyloxanthin (STX) is a saccharolipid derived from a carotenoid in Staphylococcus aureus involved in oxidative-stress tolerance and antimicrobial peptide resistance. In this work, a targeted metabolomics and biophysical study was carried out on native and knock-out S. aureus strains to investigate the biosynthetic pathways of STX and related carotenoids. Identification of 34 metabolites at different growth phases (8, 24 and 48h), reveal shifts of carotenoid populations during progression towards stationary phase. Six of the carotenoids in the STX biosynthetic pathway and three menaquinones (Vitamin K2) were identified in the same chromatogram. Furthermore, other STX homologues with varying acyl chain structures reported herein for the first time, which reveal the extensive enzymatic activity of CrtO/CrtN. Fourier Transform infrared spectroscopy show that STX increases acyl chain order and shifts the cooperative melting of the membrane indicating a more rigid lipid bilayer. This study shows the diversity of carotenoids in S. aureus, and their influence on membrane biophysical properties. Copy rights belong to original authors. Visit the link for more info

Biophysical modeling of the neural origin of EEG and MEG signals

Play Episode Listen Later Jul 4, 2020

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.01.181875v1?rss=1 Authors: Naess, S., Halnes, G., Hagen, E., Hagler, D. J., Dale, A., Einevoll, G. T., Ness, T. V. Abstract: Electroencephalography (EEG) and magnetoencephalography (MEG) are among the most important techniques for non-invasively studying cognition and disease in the human brain. These signals are known to originate from cortical neural activity, typically described in terms of current dipoles. While the link between cortical current dipoles and EEG/MEG signals is relatively well understood, surprisingly little is known about the link between different kinds of neural activity and the current dipoles themselves. Detailed biophysical modeling has played an important role in exploring the neural origin of intracranial electric signals, like extracellular spikes and local field potentials. However, this approach has not yet been taken full advantage of in the context of exploring the neural origin of the cortical current dipoles that are causing EEG/MEG signals. Here, we present a method for reducing arbitrary simulated neural activity to single current dipoles. We find that the method is applicable for calculating extracranial signals, but less suited for calculating intracranial electrocorticography (ECoG) signals. We demonstrate that this approach can serve as a powerful tool for investigating the neural origin of EEG/MEG signals. This is done through example studies of the single-neuron EEG contribution, the putative EEG contribution from calcium spikes, and from calculating EEG signals from large-scale neural network simulations. We also demonstrate how the simulated current dipoles can be used directly in combination with detailed head models, allowing for simulated EEG signals with an unprecedented level of biophysical details. In conclusion, this paper presents a framework for biophysically detailed modeling of EEG and MEG signals, which can be used to better our understanding of non-inasively measured neural activity in humans. Copy rights belong to original authors. Visit the link for more info

origin copy modeling signals detailed ness hagen neural eeg hagler biorxiv biophysical ecog

System Identification with Biophysical Constraints: A Circuit Model of the Inner Retina