The proteasomal system.

Protein damage, repair and proteolysis.

Culture models of tissues and organs are valuable tools developed by basic research that help investigation of the body functions. Modelling is aimed at simplifying experimental procedures in order to better understand biological phenomena, and consequently, when sufficiently characterized, culture models can also be utilized with high potential in applied research. In skin biology and pathology, the development of cultures of keratinocytes as monolayers has allowed the elucidation of most functional and structural characteristics of the cell type. Beside the multiple great successes that have been obtained with this type of culture, this review draws attention on several neglected characteristics of monolayer cultures. The more sophisticated models created in order to reconstruct the fully differentiated epidermis have followed the monolayers. The epidermal reconstruction produces all typical layers found in vivo and thus makes the model much less simple, but only this kind of model allows the study of full differentiation in keratinocyte and production of the cornified barrier. In addition to its interest in basic research, the reconstructed epidermis is currently gaining a lot of interest for applied research, particularly as an alternative to laboratory animals in the chemical and cosmetic industry. Today several commercial providers propose reconstructed skin or epidermis, but in vitro assays on these materials are still under development. In order to be beneficial at long term, the validation of assays must be performed on a material whose availability will not be interrupted. We warn here providers and customers that the longevity of in vitro assays will be guaranteed only if these assays are done with well-described models, prepared according to published procedures, and must consider having a minimum of two independent simultaneous producers of similar material.

/pdf/modelling-the-human-epidermis-in-vitro-tools-for-basic-and-4fqlw3qvmu.pdf

Modelling the human epidermis in vitro: tools for basic and applied research

Members of the Btg/Tob protein family share a conserved N-terminal region that confers the activity to inhibit cell proliferation. Tob1 and Tob2 proteins, which constitute a Tob subfamily, have a longer C-terminal region than BTG proteins. Apparently, genomes of invertebrates and teleost species contain only a single Tob locus, whereas genomes of mammalian, avian, and amphibian species contain two Tob loci (Tob1 and Tob2). Tob genes are expressed in oocytes, sperm, early embryos, and various adult tissues, depending on the species. Recent reports indicate that Tob proteins play important roles in spermatogenesis, embryonic dorsoventral patterning, osteogenesis, T-cell activation, and learning and memory. Accumulating evidence supports the hypothesis that Tob proteins act primarily as transcriptional repressors in several signaling pathways.

https://anatomypubs.onlinelibrary.wiley.com/doi/pdf/10.1002/dvdy.21092

Tob genes in development and homeostasis.

Aim: To investigate the effects of the transducer of ErbB-2.1 (TOB1) on the proliferation, migration and invasion of human lung cancer cells in vitro .
 Methods: Human lung cancer cell lines (95-D, A549, NCI-H1299, NCI-H1975, NCI-H661, NCI-H446, NCI-H1395, and Calu-3) and the normal human bronchial epithelial (HBE) cell line were tested. The expression levels of TOB1 in the cells were determined with Western blot and RT-PCR analyses. TOB1-overexpressing cell line 95-D/TOB1 was constructed using lipofectamine-induced TOB1 recombinant plasmid transfection and selective G418 cell culture. The A549 cells were transcend-transfected with TOB1-siRNA. MTT assay, flow cytometry and Western blot analysis were used to examine the effects of TOB1 on cancer cell proliferation and wound healing. Transwell invasive assay was performed to evaluate the effects of TOB1 on cancer cell migration and invasion. The activity of MMP2 and MMP9 was measured using gelatin zymography assay.
 Results: The expression levels of TOB1 in the 8 human lung cancer cell lines were significantly lower than that in HBE cells. TOB1 overexpression inhibited the proliferation of 95-D cells, whereas TOB1 knockdown with TOB1-siRNA promoted the growth of A549 cells. Decreased cell migration and invasion were detected in 95-D/TOB1 cells, and the suppression of TOB1 enhanced the metastasis in A549 cells. TOB1 overexpression not only increased the expression of the phosphatase and tensin homolog (PTEN), an important tumor suppressor, but also regulated the downstream effectors in the PI3K/PTEN signaling pathway, including Akt, ERK1/2, etc . In contrast, decreased expression of TOB1 oppositely regulated the expression of these factors. TOB1 also regulates the gelatinase activity of MMP2 and MMP9 in lung cancer cells.
 Conclusion: The results demonstrate that the PI3K/PTEN pathway, which is essential for carcinogenesis, angiogenesis, and metastasis, may be one of the possible signaling pathways for regulation of proliferation and metastasis of human lung cancer cells by TOB1 in vitro .

/pdf/suppression-of-human-lung-cancer-cell-proliferation-and-26deq3ro51.pdf

Suppression of human lung cancer cell proliferation and metastasis in vitro by the transducer of ErbB-2.1 (TOB1)

Summary
Background Epidermis consists of multiple layers, from the proliferating basal layer to terminal differentiated cornified layers, and these layers are defined by differentiation status. Tob gene product is known to be a member of the BTG antiproliferative protein family. We investigated the expression pattern of Tob gene product to understand the possible role in differentiation of keratinocytes and epidermis.

Objectives  In this study, we examined the expression of Tob gene product in the primary cultured human keratinocytes and in the in vivo epidermis.

Methods  The expression of Tob gene product was assessed by Western blotting analysis. Cellular localization of Tob was detected using the green fluorescent protein-tagged Tob cDNA expression construct. In vivo expression of Tob gene product in the epidermis was determined by immunohistochemistry with paraffin sections.

Results  Tob family members are degraded by the ubiquitine–proteasome system triggered by the growth signal. Tob is stably and abundantly expressed in primary cultured human keratinocytes. Furthermore, the expression of Tob in the keratinocytes persists during the differentiation induced by calcium; however, it was not detected in primary cultured fibroblasts. Also, the subcellular localization of Tob is mainly in the cellular membrane in the primary human keratinocytes. We evaluated Tob expression in normal skin, oral mucosa and different diseases, such as psoriasis, X-linked ichthyosis and squamous cell carcinoma (SCC). Using immunohistochemical analysis, we observed that Tob was selectively expressed in the basal layer of X-linked ichythyosis and the hyperproliferative basal layer of psoriasis and oral mucosa as well as in normal epidermis. In SCC, the expression of Tob gene product was relatively decreased.

Conclusions  Tob is stably expressed in primary human keratinocytes and it is specifically expressed in the basal layer of in vivo epidermis.

Tob is a potential marker gene for the basal layer of the epidermis and is stably expressed in human primary keratinocytes

Disclosed is an electronic device for processing a handwriting input and including a touch screen, a processor operatively connected with the touch screen, and a memory operatively connected with the processor, wherein the memory stores instructions, which when executed, cause the processor to control the electronic device to perform handwriting recognition for a first handwriting input of a user displayed on the touch screen, to convert the first handwriting input into a text, identify at least one of an attribute or characteristic of the first handwriting input, apply at least one of the identified attribute or characteristic to the converted text, and in response to a request for conversion of the first handwriting input, replace the first handwriting input into a text (herein after, a first rich text) to which the identified at least one of the attribute or characteristic has been applied.

Electronic device and method for processing handwriting input thereof

An electronic device and method are disclosed. The electronic device includes a touch-sensitive display, a memory and a processor. The processor implements the method, including: detect a written input including a plurality of strokes through the display, group the plurality of strokes into a first group and a second group based on respective coordinates of each of the plurality of strokes, group first strokes included in the first group into a plurality of blocks, based on a distance between respective coordinates of each of the first strokes, determine a slope for each of the plurality of blocks, rotate an area corresponding to the first group based on the determined slope, execute handwriting recognition on the first strokes based on the rotated area, and displaying a result of the handwriting recognition on the display.

Electronic device and method for processing writing input

Disclosed is an electronic device comprising: a memory for storing handwriting style models and languages models according to characteristics of multiple languages, respectively; and a processor operatively connected to the memory. The processor is configured to: receive a handwriting input; recognize the handwriting input on the basis of a first handwriting style model corresponding to a first language among the handwriting style models and a first language model corresponding to the first language among the language models, and converting the recognized handwriting input to a text in the first language; detect a part of the result of recognizing the handwriting input, which is handwritten in a second language different from the first language; re-recognize the detected part in the second language on the basis of a second handwriting style model corresponding to the second language among the handwriting style models and a second language model corresponding to the second language among the language models, and converting the re-recognized detected part to a text in the second language; and replace a text corresponding to the detected part, among the converted text in the first language, with the converted text in the second language. Various other embodiments as understood from the present document are also possible.

Park Gibeyong

Papers

Tob is a potential marker gene for the basal layer of the epidermis and is stably expressed in human primary keratinocytes

Electronic device and method for processing handwriting input thereof

Electronic device and method for processing writing input

Method and electronic device for converting handwriting input to text