Modelling and analysis of skin pigmentation
Ahmad Fadzil Mohamad Hani, Dileep Kumar in Optical Imaging for Biomedical and Clinical Applications, 2017
The human skin is a strong medium of light scattering. The stratum corneum in epidermis makes the light beam diffused, while the collagen and the elastine fibres in the dermis scatter light and so do the cytoplasm membranes. The size of the cells, mitochondria and collagen fibres are usually larger than 1000 nm, thus making them larger than the wavelength in the diagnostic–therapeutic window. When the diffusing particle is close to the wavelength of light, the scattering can be best modelled by Mie scattering [2,4,36,37,81]. The strength of the Mie scattering is roughly proportional to λ−1.5, where λ is the wavelength of radiation. The cell nucleus and membranes also scatter light, but much smaller than the wavelength. The scattering introduced by these small particles is often described using the Rayleigh scattering formula, which is more strongly wavelength-dependent, being proportional to λ−4.
Cytology of Bladder Cancer
George T. Bryan, Samuel M. Cohen in The Pathology of Bladder Cancer, 2017
The frustrations of dealing with these differences at the histologic and cytologic levels may be ameliorated by applying quantitative methods to the study of tissue and of individual cells. Merely by using planimetry, Kern64 found differences in cell areas, nuclear areas, and nuclear-cytoplasmic ratios when comparing cells from papilloma and Grade I papillary transitional cell carcinoma with normal urothelial cells. He combines papilloma with Grade I papillary transitional cell carcinoma (see Table 6) (see Figure 18). If we apply Kern’s findings to diagnostic cytology, they offer an objective reference point of some practical importance. The smaller cell area, larger nuclear area, and consequent altered N to C ratio in cells from papilloma and Grade I papillary transitional cell carcinoma are readily distinguishable in routine microscopy. A convenient yardstick for accurately judging nuclear size is the intermediate squamous cell nucleus. In our laboratory, these cells are found in 96% of properly collected voided urines from both men and women. Intermediate squamous cell nuclei are relatively uniform, usually well preserved, and their areas (35 to 40 μ2) well defined by a number of studies.65,66
Biological Clockworks
Sue Binkley in Biological Clocks, 2020
A chronon model for the circadian clock makes use of the sequence of events by which proteins are synthesized in cells. A sequence of chemical bases in the genetic material in chromosomes of the nucleus (DNA) specified a sequence of complementary bases in the formation of a large molecule (RNA), a process called transcription. In turn, the RNA leaves the cell nucleus and provides instructions for forming the sequence of amino acids in proteins at the cellular organelles called ribosomes, a process called translation. A cell contains chronons, strands of DNA 200–2000 cistrons long, which are the rate-limiting components of transcription, and therefore provide the timing mechanism. In this model, transcription takes a certain duration of time at the end of which some substance synthesized at the ribosomes then diffuses back to the DNA to restart the cycle. The role of diffusion in this model provides an explanation for temperature compensation, because diffusion has a Q10 near 1.
Association of Autoimmune Regulator Gene Rs2075876 Variant, but Not Gene Expression with Alopecia Areata in Males: A Case–control Study
Published in Immunological Investigations, 2020
Eman A. Toraih, Hatem M Ameen, Mohammad H. Hussein, Ahmed A. Youssef Elabd, Abeer M. Mohamed, Abdelhady Ragab Abdel-Gawad, Manal S. Fawzy
At subcellular level, wild-type AIRE protein has a dual nuclear and cytoplasmic localization (Pitkänen and Peterson 2003). AIRE protein forms distinct nuclear speckles in the interchromatin region and is co-localized with cytoskeletal filaments (Perniola and Musco 2014; Rinderle 1999). The first 188 amino acids at the N-terminal region contains a nuclear targeting signal and homogenously staining region (HSR) domain and is indispensable in the subcellular localization of AIRE protein (Ramsey et al. 2002). Several gene mutations including deletions, insertions, substitutions, and splice-site mutations related to APECED have been identified within the coding region of AIRE gene (Björses et al. 2000). They can modulate different aspects of intracellular targeting and transcription activity (Sonal et al. 2012). Deletion of the PHD domain showed altered nuclear localization with subsequent loss of DNA-binding capacity (Björses et al. 2000) and polypeptide aggregation in the cytoplasm (Ramsey et al. 2002). Two missense mutations (C311Y and P326Q) in PHD1 region abolished ligase activity (Uchida et al. 2004), while G228W mutation in SAND domain has a dominant negative effect via binding to the wild-type AIRE protein (Ilmarinen et al. 2005). Several other gene mutations disrupted mRNA transcriptional level; for example, G1052A substitution decreased its expression to 30%, A374G substitution caused mild up-regulation, while C889T mutation and C1313 deletion did not impose any transactivation function (Björses et al. 2000).
Unfolding the Role of Splicing Factors and RNA Debranching in AID Mediated Antibody Diversification
Published in International Reviews of Immunology, 2021
Ankit Jaiswal, Amit Kumar Singh, Anubhav Tamrakar, Prashant Kodgire
Further, to explore whether AID and CTNNBL1 are localized to nuclear speckles as these are the region where splicing machinery are maturated as well as stored, double immunofluorescence experiments were performed. AID and CTNNBL1 were localized to nuclear speckles as shown by double immunofluorescence study [70]. Additionally, AID and CTNNBL1 were found to interact with U2AF65 via pull-down assay [70]. AID was also pulled down with U2AF65, an auxiliary splicing factor enriched at nuclear speckles that promotes alternative splicing [70]. Thus, it was shown beside localization of AID and CTNNBL1 at nuclear speckles, both of them interact with U2AF65 protein present in nuclear speckles. As AID and CTNNBL1 were localized as well as interact with proteins associated with nucleoli, CB and nuclear speckles, further experiments in the switching B-cells demonstrated that AID interacts with snRNPs, splicesome activating complex and U2AF65 in CH12F3 mouse B-cell line. Nevertheless, there is no significant difference in AID associated with snRNPs and spliceosome activating complex in stimulated and unstimulated cells. In contrast, AID and U2AF65 association was notably reduced in stimulated cells may promotes alternative splicing. In nutshell, AID interacts with various members of splicing machinery or protein located in nucleoli, CB and nuclear speckles in B-cell [70]. How the function or activity of AID is modulated by its interaction with splicing machinery is still a mystery and need to be explored. Do the disruptions of AID interaction with splicing proteins have a differential effect in the context of SHM and CSR also needs to be investigated?
Food-grade titanium dioxide translocates across the buccal mucosa in pigs and induces genotoxicity in an in vitro model of human oral epithelium
Published in Nanotoxicology, 2023
Julien Vignard, Aurelie Pettes-Duler, Eric Gaultier, Christel Cartier, Laurent Weingarten, Antje Biesemeier, Tatjana Taubitz, Philippe Pinton, Cecilia Bebeacua, Laurent Devoille, Jacques Dupuy, Elisa Boutet-Robinet, Nicolas Feltin, Isabelle P. Oswald, Fabrice H. Pierre, Bruno Lamas, Gladys Mirey, Eric Houdeau
Next, we assessed the genotoxic potential of food-grade TiO2 (E171) and standard TiO2 products on buccal cells by immunofluorescent analyses using antibodies directed against γH2AX and 53BP1, two well-established DNA damage biomarkers (Vignard, Mirey, and Salles 2013). Proliferating or differentiated TR146 cells were exposed for 2 h to the three different TiO2 materials at 5, 50 or 100 µg/ml. We first analyzed the phosphorylation of H2AX at Ser139 (referred to as γH2AX), which occurs at DNA double-strand breaks. While only a few cells presented a γH2AX signal in the control, cells exposed to E171 or NM-102 accumulated γH2AX foci (Figure 6(A)). In contrast, the pure nanopowder of TiO2-NPs (21 nm) did not increase γH2AX staining (Figure 6(A)). We then observed the localization of 53BP1, which is a diffuse nuclear protein that displays a singular localization pattern as large nuclear speckles in unchallenged G1 cells, named 53BP1 nuclear bodies (Fernandez-Vidal, Vignard, and Mirey 2017). These structures represent the major staining found in the control or after exposure to TiO2-NPs with a nominal size of 21 nm (Figure 6(A)). However, in the presence of DNA double-strand breaks, 53BP1 is recruited to the damaged site and forms foci. Interestingly, food-grade E171 and NM-102 induced 53BP1 foci formation in a subset of TR146 cells, mainly colocalizing with the γH2AX signal (Figure 6(A)). This staining was observed in proliferating as well as in differentiated cells. Hence, these data showed that food-grade and NM-102 TiO2 but not TiO2-NPs activate the DNA damage biomarkers γH2AX and 53BP1 after 2 h of treatment, strongly supporting the formation of DNA double-strand breaks.
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