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The Cell as an Inspiration in Biomaterial Design
Published in Heather N. Hayenga, Helim Aranda-Espinoza, Biomaterial Mechanics, 2017
Helim Aranda-Espinoza, Katrina Adlerz
All vertebrates have intermediate filaments, although they are most prominent in cells that have to withstand high mechanical stresses. They play an important role in imparting mechanical strength to cells and tissues. Compared to actin and microtubules, the other major components of the cytoskeleton, intermediate filaments have more diversity. Instead of being made up of one type of protein, there are many different monomers that can make up intermediate filaments, and the composition depends on the cell type. For example, keratin monomers form the intermediate filaments found in human epithelial cells, and the cross-linked keratin networks give strength to hair and nails. Vimentin filaments are a second type of intermediate filament that are found in mesenchymal cells and help anchor organelles in the cytosol and maintain cell integrity. A third example of intermediate filaments is neurofilaments that are found along axons and provide structural support to the axon [2]. Neurofilaments are made up of three subunit proteins classified by their molecular weight: low, medium, and high. The subunits have the same basic structure but the lengths of their sidearms differ. The low molecular weight subunit has the shortest sidearm, and the high molecular weight subunit has the longest. These sidearms are thought to mediate the spacing between filaments. Overaccumulation of neurofilaments can block the transport of proteins down the axon and is seen in diseases like dementia, Parkinson’s, and amyotrophic lateral sclerosis [43].
Introduction: Background Material
Published in Nassir H. Sabah, Neuromuscular Fundamentals, 2020
The cytoskeleton of the cell is a dynamic network of protein filaments in the cytoplasm that performs essential functions. It consists of three types of fibers: Microfilaments, of about 7 nm diameter, and composed of two strands of the polymerized protein actin. They are concentrated mostly adjacent to the cell membrane and are attached to it at many points. They maintain cellular shape in two dimensions and allow the membrane to resist tension. Microfilaments cause dynamic changes in the shape of dendritic spines (Section 6.5.3).Intermediate filaments, of about 10 nm diameter, and composed of a variety of proteins that differ between different types of cells. They are more strongly bound to the cell membrane than microfilaments and play a key role in the three-dimensional structure of the cell and in holding in place the Z disks and myofibrils in muscle cells (Section 9.1.2). They are especially abundant in axons of neurons (Section 1.2) and in cells of the epidermis, that is, the outer layer of the skin, where they constitute the major structural components of skin and hair. Neurofilaments are intermediate filaments found in nerve cells and are responsible for radial growth of the axon (Section 1.2) and hence determine the axon diameter.Microtubules having a hollow tubular structure of about 15 nm inner diameter and about 24 nm external diameter, their length ranging dynamically between a fraction of a µm and hundreds of µms. They are composed of polymers of the protein tubulin. Microtubules are important components of: (i) cilia (Figure 1.1) – short hair-like projections from cells, which are capable of a beating movement that, for example, propels mucus along air passageways of the lungs, and (ii) flagella, which are long tapering processes from cells, which are responsible for movement of microorganisms as well as sperm cells. Microtubules play a key role in cell division and in intracellular transport, as described later.
Inflammatory and apoptotic signalling pathways and concussion severity: a genetic association study
Published in Journal of Sports Sciences, 2018
Sarah Mc Fie, Shameemah Abrahams, Jon Patricios, Jason Suter, Michael Posthumus, Alison V. September
In recent years, several studies have examined the influence of genetic polymorphisms on concussion symptom severity. Within these studies, a number of genes have been investigated, including the apolipoprotein E (APOE) (Merritt & Arnett, 2016; Merritt, Rabinowitz, & Arnett, 2016), microtubule associated protein tau (Tau) (Terrell et al., 2013), glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A), neurofilament heavy (NEFH) (McDevitt et al., 2015), and solute carrier family 17 member 7 (SLC17A7) (Madura et al., 2016) genes. APOE is implicated in neuronal and white matter structural integrity (Heise, Filippini, Ebmeier, & Mackay, 2011; Nathoo, Chetty, Van Dellen, & Barnett, 2003; Persson et al., 2006) and the APOE ε4 isoform has been associated with greater concussion symptom scores than other isoforms (Merritt & Arnett, 2016). However, no differences were noted in the post-concussion neurocognitive scores between the different APOE isoforms in a subsequent study of the same cohort (Merritt et al., 2016). An investigation of Tau polymorphisms, suggested to influence neuronal degeneration (Frost & Feany, 2015; Mietelska-Porowska, Wasik, Goras, Filipek, & Niewiadomska, 2014), reported that the Tau rs10445337 T/T genotype group displayed greater post-concussion complex reaction time changes from baseline compared to the other Tau rs10445337 genotypes (Terrell et al., 2013). McDevitt et al. (2015) reported that athletes with a glutamate receptor gene polymorphism (GRIN2A rs3219790 long allele) were more likely to take longer than 60 days to return to play following a concussion (McDevitt et al., 2015). While no significant association was noted between the NEFH rs165602 polymorphism, implicated in neuronal integrity, and concussion symptom severity or return to play (McDevitt et al., 2011). The SLC17A7 rs74174284 C/C genotype had worse motor speed at the first post-concussion assessment, while carriers of the G allele were six times more likely to experience prolonged symptom durations (Madura et al., 2016).
Epigenetic modifications associated with pathophysiological effects of lead exposure
Published in Journal of Environmental Science and Health, Part C, 2019
Madiha Khalid, Mohammad Abdollahi
A study with rat neonates displayed a period of transient expression of APP mRNA upon 200 ppm Pb exposure followed by the period of their overexpression along with increased Sp1 activity, long after 20 months when Pb exposure was ceased. All this evidence suggests that Pb is capable of affecting APP expression and regulation later in life, potentially resulting in amyloidogenesis.153 The mitogen-activated protein kinase (MAPK) signaling pathway is vital for axon, and synapse function, neural development, and regeneration.77,251,252 The binding of Sp1 to its specific DNA sequence is regulated by protein kinase C (PKC). Such signal transduction pathways are sensitive to exposure of Pb and similar heavy metals,253,254 suggesting other mechanisms of Pb-induced tauopathies. Developmental Pb exposure in mice with 0.1 or 2 mM Pb levels caused an increased neurofilament phosphorylation, glial fibrillary acidic protein, myelin basic protein and neuronal structural protein, resulting in impaired axonal transport and function.77 In another study, microarray analysis revealed upregulated miRNAs in rats with all, i.e., 100, 200, and 300 ppm Pb exposure levels. However, significantly decreased expression in miR-494 (P < 0.05) was observed, with significantly increased expression of miR-211, -449a, -34c/b, and -204 at the 300 ppm Pb exposure level. Furthermore, all Pb exposure levels showed a declined expression of Bcl-2, inositol 1,4,5-triphosphate receptor type 1 (Itpr1), mitogen-activated protein kinase kinase 1 (Map2k)1 mRNAs and their corresponding proteins. Such declines were observed to be significant at 300 ppm Pb, along with repressed Bcl-2/Bax ratio (P < 0.01). According to the bioinformatics analysis, the changed miRNAs expression was mostly related to neural development, regeneration, neural injury, axon, and synapse function. All these evidence showed that Pb altered the expression of various miRNAs, suggesting downstream effects on their targets, related genes and associated pathways (Figure 4).255