scholarly journals Predicting the tension in actin cytoskeleton from the nucleus shape

2020 ◽  
Author(s):  
Sreenath Balakrishnan ◽  
Shilpa R Raju ◽  
Anwesha Barua ◽  
G.K. Ananthasuresh
Keyword(s):  
Actin Cytoskeleton ◽  
Analytical Formula ◽  
Cell Types ◽  
Computational Method ◽  
Curvilinear Coordinates ◽  
Projected Area ◽  
Cellular Processes ◽  
Nucleus Shape ◽  
Cytoskeletal Tension ◽  
Multiple Cell

AbstractTension in actin cytoskeleton regulates many cellular processes and nuclear morphology. Here, we demonstrate a simple computational method for estimating actin cytoskeletal tension from nucleus shape. We first note that mechanics-based modeling defines a relationship among the volume, surface area, and projected area of the nucleus and hence a specific surface in the three-parameter space of the aforementioned geometric quantities. Data of nuclei from multiple cell types lie on such a surface. Furthermore, nuclei from a given cell population lie on a straight line on the surface. The location and orientation of the line varies with cell type. By using a mechanical model, we present two non-dimensional parameters, namely, the flatness and stretch indicators, which serve as curvilinear coordinates on the surface. Flatness indicator defines the extent of nuclear flattening due to actin cytoskeletal tension and the stretch indicator captures the effect of the elastic modulus of the nuclear envelope. We validate our assertions by modulating the actin cytoskeletal tension using three independent mechanisms: (i) direct downregulation by Cytochalasin D, (ii) indirect upregulation using Nocodazole, and (iii) mechanical stimulation by varying substrate stiffness. We also infer that the flatness indicator is equivalent to the ratio of the height to diameter of the nucleus and is related to the Vogel number. By using this geometric insight, we validate the predictions of our model with data from many previous studies. Finally, we present an analytical formula and a correlation for estimating actin cytoskeletal tension from nuclear projected area and volume.

scholarly journals A Single Cell Transcriptomic Atlas Characterizes Aging Tissues in the Mouse

2019 ◽  
Author(s):  
◽  
Angela Oliveira Pisco ◽  
Aaron McGeever ◽  
Nicholas Schaum ◽  
Jim Karkanias ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Types ◽  
Cell Type ◽  
Cellular Processes ◽  
Progressive Loss ◽  
Age Related ◽  
Multiple Cell ◽  
Cell Type Specific ◽  
Molecular Information ◽  
Insight Into

AbstractAging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death1. Despite rapid advances over recent years, many of the molecular and cellular processes which underlie progressive loss of healthy physiology are poorly understood2. To gain a better insight into these processes we have created a single cell transcriptomic atlas across the life span of Mus musculus which includes data from 23 tissues and organs. We discovered cell-specific changes occurring across multiple cell types and organs, as well as age related changes in the cellular composition of different organs. Using single-cell transcriptomic data we were able to assess cell type specific manifestations of different hallmarks of aging, such as senescence3, genomic instability4 and changes in the organism’s immune system2. This Tabula Muris Senis provides a wealth of new molecular information about how the most significant hallmarks of aging are reflected in a broad range of tissues and cell types.

scholarly journals The temporal basis of angiogenesis

2017 ◽  
Vol 372 (1720) ◽  
pp. 20150522 ◽  
Author(s):  
Katie Bentley ◽  
Shilpa Chakravartula
Keyword(s):  
Asymmetric Cell Division ◽  
Cell Types ◽  
Network Architectures ◽  
Cellular Processes ◽  
Vascular Morphology ◽  
Temporal Adaptation ◽  
Vessel Growth ◽  
Multiple Cell ◽  
Conceptual Shift

The process of new blood vessel growth (angiogenesis) is highly dynamic, involving complex coordination of multiple cell types. Though the process must carefully unfold over time to generate functional, well-adapted branching networks, we seldom hear about the time-based properties of angiogenesis, despite timing being central to other areas of biology. Here, we present a novel, time-based formulation of endothelial cell behaviour during angiogenesis and discuss a flurry of our recent, integrated in silico/in vivo studies, put in context to the wider literature, which demonstrate that tissue conditions can locally adapt the timing of collective cell behaviours/decisions to grow different vascular network architectures. A growing array of seemingly unrelated ‘temporal regulators’ have recently been uncovered, including tissue derived factors (e.g. semaphorins or the high levels of VEGF found in cancer) and cellular processes (e.g. asymmetric cell division or filopodia extension) that act to alter the speed of cellular decisions to migrate. We will argue that ‘temporal adaptation’ provides a novel account of organ/disease-specific vascular morphology and reveals ‘timing’ as a new target for therapeutics. We therefore propose and explain a conceptual shift towards a ‘temporal adaptation’ perspective in vascular biology, and indeed other areas of biology where timing remains elusive. This article is part of the themed issue ‘Systems morphodynamics: understanding the development of tissue hardware’.

scholarly journals The Role of the Transcription Factor Foxo3 in Hearing Maintenance: Informed Speculation on a New Player in the Cochlea

2016 ◽  
Vol 2016 ◽  
pp. 1-10
Author(s):  
Patricia M. White
Keyword(s):  
Hearing Loss ◽  
Molecular Mechanisms ◽  
Late Onset ◽  
Cell Types ◽  
Mouse Genetics ◽  
Molecular Response ◽  
Cellular Processes ◽  
Powerful Approach ◽  
Multiple Cell

Molecular genetics has proven to be a powerful approach for understanding early-onset hearing loss. Recent work in late-onset hearing loss uses mouse genetics to identify molecular mechanisms that promote the maintenance of hearing. One such gene, Foxo3, is ontologically involved in preserving mitochondrial function. Significant evidence exists to support the idea that mitochondrial dysfunction is correlated with and can be causal for hearing loss. Foxo3 is also ontologically implicated in driving the circadian cycle, which has recently been shown to influence the molecular response to noise damage. In this review, the molecular framework connecting these cellular processes is discussed in relation to the cellular pathologies observed in human specimens of late-onset hearing loss. In bringing these observations together, the possibility arises that distinct molecular mechanisms work in multiple cell types to preserve hearing. This diversity offers great opportunities to understand and manipulate genetic processes for therapeutic gain.

scholarly journals APOBEC3H Subcellular Localization Determinants Define Zipcode for Targeting HIV-1 for Restriction

2018 ◽  
Vol 38 (23) ◽  
Author(s):  
Daniel J. Salamango ◽  
Jordan T. Becker ◽  
Jennifer L. McCann ◽  
Adam Z. Cheng ◽  
Özlem Demir ◽  
...  
Keyword(s):  
Subcellular Localization ◽  
Nuclear Import ◽  
Cell Types ◽  
Restriction Factors ◽  
Structural Determinants ◽  
Cellular Processes ◽  
Biological Studies ◽  
Multiple Cell ◽  
Import And Export ◽  
Hiv 1

ABSTRACT APOBEC enzymes are DNA cytosine deaminases that normally serve as virus restriction factors, but several members, including APOBEC3H, also contribute to cancer mutagenesis. Despite their importance in multiple fields, little is known about cellular processes that regulate these DNA mutating enzymes. We show that APOBEC3H exists in two distinct subcellular compartments, cytoplasm and nucleolus, and that the structural determinants for each mechanism are genetically separable. First, native and fluorescently tagged APOBEC3Hs localize to these two compartments in multiple cell types. Second, a series of genetic, pharmacologic, and cell biological studies demonstrate active cytoplasmic and nucleolar retention mechanisms, whereas nuclear import and export occur through passive diffusion. Third, APOBEC3H cytoplasmic retention determinants relocalize APOBEC3A from a passive cell-wide state to the cytosol and, additionally, endow potent HIV-1 restriction activity. These results indicate that APOBEC3H has a structural zipcode for subcellular localization and selecting viral substrates for restriction.

scholarly journals MAPS: model-based analysis of long-range chromatin interactions from PLAC-seq and HiChIP experiments

2018 ◽  
Author(s):  
Ivan Juric ◽  
Miao Yu ◽  
Armen Abnousi ◽  
Ramya Raviram ◽  
Rongxin Fang ◽  
...  
Keyword(s):  
Long Range ◽  
Cell Types ◽  
Computational Method ◽  
Superior Performance ◽  
Model Based ◽  
Chromatin Interactions ◽  
Enhanced Resolution ◽  
Multiple Cell ◽  
Systematic Biases ◽  
Model Based Analysis

AbstractHi-C and chromatin immunoprecipitation (ChIP) have been combined to identify long-range chromatin interactions genome-wide at reduced cost and enhanced resolution, but extracting the information from the resulting datasets has been challenging. Here we describe a computational method, MAPS, Model-based Analysis of PLAC-seq and HiChIP, to process the data from such experiments and identify long-range chromatin interactions. MAPS adopts a zero-truncated Poisson regression framework to explicitly remove systematic biases in the PLAC-seq and HiChIP datasets, and then uses the normalized chromatin contact frequencies to identify significant chromatin interactions anchored at genomic regions bound by the protein of interest. MAPS shows superior performance over existing software tools in analysis of chromatin interactions centered on cohesin, CTCF and H3K4me3 associated regions in multiple cell types. MAPS is freely available at https://github.com/ijuric/MAPS.

scholarly journals Multiple cell types contribute to the atherosclerotic lesion fibrous cap by PDGFRβ and bioenergetic mechanisms

2021 ◽  
Vol 3 (2) ◽  
pp. 166-181 ◽  
Author(s):  
Alexandra A. C. Newman ◽  
Vlad Serbulea ◽  
Richard A. Baylis ◽  
Laura S. Shankman ◽  
Xenia Bradley ◽  
...  
Keyword(s):  
Atherosclerotic Lesion ◽  
Cell Types ◽  
Fibrous Cap ◽  
Multiple Cell

scholarly journals Mitochondrial Glucocorticoid Receptors and Their Actions

2021 ◽  
Vol 22 (11) ◽  
pp. 6054
Author(s):  
Ioanna Kokkinopoulou ◽  
Paraskevi Moutsatsou
Keyword(s):  
Gene Expression ◽  
Glucocorticoid Receptors ◽  
Mitochondrial Gene ◽  
Cell Types ◽  
Ros Generation ◽  
Mitochondrial Gene Expression ◽  
Mitochondrial Energy Metabolism ◽  
Bcl2 Family ◽  
Cellular Processes ◽  
Almost All

Mitochondria are membrane organelles present in almost all eukaryotic cells. In addition to their well-known role in energy production, mitochondria regulate central cellular processes, including calcium homeostasis, Reactive Oxygen Species (ROS) generation, cell death, thermogenesis, and biosynthesis of lipids, nucleic acids, and steroid hormones. Glucocorticoids (GCs) regulate the mitochondrially encoded oxidative phosphorylation gene expression and mitochondrial energy metabolism. The identification of Glucocorticoid Response Elements (GREs) in mitochondrial sequences and the detection of Glucocorticoid Receptor (GR) in mitochondria of different cell types gave support to hypothesis that mitochondrial GR directly regulates mitochondrial gene expression. Numerous studies have revealed changes in mitochondrial gene expression alongside with GR import/export in mitochondria, confirming the direct effects of GCs on mitochondrial genome. Further evidence has made clear that mitochondrial GR is involved in mitochondrial function and apoptosis-mediated processes, through interacting or altering the distribution of Bcl2 family members. Even though its exact translocation mechanisms remain unknown, data have shown that GR chaperones (Hsp70/90, Bag-1, FKBP51), the anti-apoptotic protein Bcl-2, the HDAC6- mediated deacetylation and the outer mitochondrial translocation complexes (Tom complexes) co-ordinate GR mitochondrial trafficking. A role of mitochondrial GR in stress and depression as well as in lung and hepatic inflammation has also been demonstrated.

scholarly journals MyD88 Is Not Required for Muscle Injury-Induced Endochondral Heterotopic Ossification in a Mouse Model of Fibrodysplasia Ossificans Progressiva

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 630
Author(s):  
Huili Lyu ◽  
Cody M. Elkins ◽  
Jessica L. Pierce ◽  
C. Henrique Serezani ◽  
Daniel S. Perrien
Keyword(s):  
Heterotopic Ossification ◽  
Muscle Injury ◽  
Cell Types ◽  
Fibrodysplasia Ossificans Progressiva ◽  
Inflammatory Signaling ◽  
Conditional Deletion ◽  
Pathway Crosstalk ◽  
Multiple Cell

Excess inflammation and canonical BMP receptor (BMPR) signaling are coinciding hallmarks of the early stages of injury-induced endochondral heterotopic ossification (EHO), especially in the rare genetic disease fibrodysplasia ossificans progressiva (FOP). Multiple inflammatory signaling pathways can synergistically enhance BMP-induced Smad1/5/8 activity in multiple cell types, suggesting the importance of pathway crosstalk in EHO and FOP. Toll-like receptors (TLRs) and IL-1 receptors mediate many of the earliest injury-induced inflammatory signals largely via MyD88-dependent pathways. Thus, the hypothesis that MyD88-dependent signaling is required for EHO was tested in vitro and in vivo using global or Pdgfrα-conditional deletion of MyD88 in FOP mice. As expected, IL-1β or LPS synergistically increased Activin A (ActA)-induced phosphorylation of Smad 1/5 in fibroadipoprogenitors (FAPs) expressing Alk2R206H. However, conditional deletion of MyD88 in Pdgfrα-positive cells of FOP mice did not significantly alter the amount of muscle injury-induced EHO. Even more surprisingly, injury-induced EHO was not significantly affected by global deletion of MyD88. These studies demonstrate that MyD88-dependent signaling is dispensable for injury-induced EHO in FOP mice.

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