Publications by authors named "K Gasior"

13 Publications

HSP70 chaperones RNA-free TDP-43 into anisotropic intranuclear liquid spherical shells.

Science 2021 02 17;371(6529). Epub 2020 Dec 17.

Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA, USA.

The RNA binding protein TDP-43 forms intranuclear or cytoplasmic aggregates in age-related neurodegenerative diseases. In this study, we found that RNA binding-deficient TDP-43 (produced by neurodegeneration-causing mutations or posttranslational acetylation in its RNA recognition motifs) drove TDP-43 demixing into intranuclear liquid spherical shells with liquid cores. These droplets, which we named "anisosomes", have shells that exhibit birefringence, thus indicating liquid crystal formation. Guided by mathematical modeling, we identified the primary components of the liquid core to be HSP70 family chaperones, whose adenosine triphosphate (ATP)-dependent activity maintained the liquidity of shells and cores. In vivo proteasome inhibition within neurons, to mimic aging-related reduction of proteasome activity, induced TDP-43-containing anisosomes. These structures converted to aggregates when ATP levels were reduced. Thus, acetylation, HSP70, and proteasome activities regulate TDP-43 phase separation and conversion into a gel or solid phase.
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http://dx.doi.org/10.1126/science.abb4309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286096PMC
February 2021

Modeling the Mechanisms by Which Coexisting Biomolecular RNA-Protein Condensates Form.

Bull Math Biol 2020 11 24;82(12):153. Epub 2020 Nov 24.

Department of Mathematical and Statistical Sciences, CAB 632, University of Alberta, Edmonton, AB, T6G 2G1, Canada.

Liquid-liquid phase separation is an emerging mechanism for intracellular organization. This work presents a mathematical model to examine molecular mechanisms that yield phase-separated droplets composed of different RNA-protein complexes. Using a Cahn-Hilliard diffuse interface model with a Flory-Huggins free energy scheme, we explore how multiple (here two, for simplicity) protein-RNA complexes (species) can establish a heterogeneous droplet field where droplets with single or multiple species phase separate and evolve during coarsening. We show that the complex-complex de-mixing energy tunes whether the complexes co-exist or form distinct droplets, while the transient binding kinetics dictate both the timescale of droplet formation and whether distinct species phase separate into droplets simultaneously or sequentially. For specific energetics and kinetics, a field of droplets driven by the formation of only one protein-RNA complex will emerge. Slowly, the other droplet species will accumulate inside the preformed droplets of the other species, allowing them to occupy the same droplet space. Alternatively, unfavorable species mixing creates a parasitic relationship: the slow-to-form protein-RNA complex will accumulate at the surface of a competing droplet species, siphoning off the free protein as it is released. Once this competing protein-RNA complex has sufficiently accumulated on the droplet surface, it can form a new droplet that is capable of sharing an interface with the first complex droplet but is not capable of mixing. These results give insights into a wide range of phase-separation scenarios and heterogeneous droplets that coexist but do not mix within the nucleus and the cytoplasm of cells.
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http://dx.doi.org/10.1007/s11538-020-00823-xDOI Listing
November 2020

Identification, Decomposition and Segmentation of Impulsive Vibration Signals with Deterministic Components-A Sieving Screen Case Study.

Sensors (Basel) 2020 Oct 2;20(19). Epub 2020 Oct 2.

Faculty of Pure and Applied Mathematics, Hugo Steinhaus Center, Wrocław University of Science and Technology, Wyspiańskiego 27, 50-370 Wrocław, Poland.

Condition monitoring is a well-established field of research; however, for industrial applications, one may find some challenges. They are mostly related to complex design, a specific process performed by the machine, time-varying load/speed conditions, and the presence of non-Gaussian noise. A procedure for vibration analysis from the sieving screen used in the raw material industry is proposed in the paper. It is more for pre-processing than the damage detection procedure. The idea presented here is related to identification and extraction of two main types of components: (i) deterministic (D)-related to the unbalanced shaft(s) and (ii) high amplitude, impulsive component randomly (R) appeared in the vibration due to pieces of ore falling down of moving along the deck. If we could identify these components, then we will be able to perform classical diagnostic procedures for local damage detection in rolling element bearing. As deterministic component may be AM/FM modulated and each impulse may appear with different amplitude and damping, there is a need for an automatic procedure. We propose a method for signal processing that covers two main steps: (a) related to R/D decomposition and including signal segmentation to neglect AM/FM modulations, iterative sine wave fitting using the least square method (for each segment), signal filtering technique by subtraction fitted sine from the raw signal, the definition of the criterion to stop iteration by residuals analysis, (b) impulse segmentation and description (beginning, end, max amplitude) that contains: detection of the number of impulses in a decomposed random part of the raw signal, detection of the max value of each impulse, statistical analysis (probability density function) of max value to find regime-switching), modeling of the envelope of each impulse for samples that protrude from the signal, extrapolation (forecasting) envelope shape for samples hidden in the signal. The procedure is explained using simulated and real data. Each step is very easy to implement and interpret thus the method may be used in practice in a commercial system.
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http://dx.doi.org/10.3390/s20195648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582610PMC
October 2020

Partial demixing of RNA-protein complexes leads to intradroplet patterning in phase-separated biological condensates.

Phys Rev E 2019 Jan;99(1-1):012411

Department of Mathematical and Statistical Sciences, CAB 632, University of Alberta, Edmonton, AB, Canada T6G 2G1.

An emerging mechanism for intracellular organization is liquid-liquid phase separation (LLPS). Found in both the nucleus and the cytoplasm, liquidlike droplets condense to create compartments that are thought to promote and inhibit specific biochemistry. In this work, a multiphase, Cahn-Hilliard diffuse interface model is used to examine RNA-protein interactions driving LLPS. We create a bivalent system that allows for two different species of protein-RNA complexes and model the competition that arises for a shared binding partner, free protein. With this system we demonstrate that the binding and unbinding of distinct RNA-protein complexes leads to diverse spatial pattern formation and dynamics within droplets. Both the initial formation and transient behavior of spatial patterning are subject to the exchange of free proteins between RNA-protein complexes. This study illustrates that spatiotemporal heterogeneity can emerge within phase-separated biological condensates with simple binding reactions and competition. Intradroplet patterning may influence droplet composition and, subsequently, cellular organization on a larger scale.
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http://dx.doi.org/10.1103/PhysRevE.99.012411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739070PMC
January 2019

The links between posttraumatic stress, attachment patterns and quality of life in incarcerated and addicted women. The role of resilience.

Psychiatr Pol 2018 Dec 29;52(6):1113-1125. Epub 2018 Dec 29.

Instytut Pedagogiki i Psychologii UJK, Świętokrzyskie Centrum Profilaktyki i Edukacji.

Objectives: The aim of the study was to determine the relationships between negative as well as traumatic childhood experiences and posttraumatic stress, quality of life and attachment in addicted and/or incarcerated women.

Methods: Family of Origin Dysfunction Scale (Skala Dysfunkcjonalności Rodziny Pochodzenia, SDRP-2) by Gąsior, Trauma Symptom Inventory (TSI-2) by Briere, Adult Attachment Scale (AAS) by Collins and Read, Life Satisfaction Questionnaire by Fahrenberg et al., and Resilience Measure Questionnaire (Kwestionariusz Oceny Prężności, KOP-26) by Gąsior, Chodkiewicz and Cechowski. The study group comprised incarcerated and/or addicted women.

Results: There is a link between intensification of childhood trauma and posttraumatic stress, quality of life and attachment. The link is diverse depending on interrelations between threatening and protective factors.

Conclusions: The highest intensity of childhood traumatic experiences occurs in women who are both incarcerated and addicted. Traumatic childhood experiences are linked with both the symptoms of the posttraumatic stress and insecure attachment patterns. Resilience is an important protective factor which guards against psychopathological problems.
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http://dx.doi.org/10.12740/PP/OnlineFirst/76823DOI Listing
December 2018
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