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1
Low, Tyrone. "The Development of a Low Profile Alpine Touring Binding." Thesis, University of Canterbury. Mechanical Engineering, 2010. http://hdl.handle.net/10092/5198.
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The design of alpine touring ski bindings has remained relatively static for the past fifteen years. During this period, the lack of innovative breakthroughs has become obvious through the number of customers who are currently unsatisfied by the products available on the market. This observation has presented a significant commercial opportunity to satisfy these users, plus many more non-consumers, with an innovative binding design. The objective of this project was to design a low profile alpine touring binding with the aim of satisfying the needs of these users.
The resulting design followed a full year of research and development in the field of alpine touring bindings. Not only were concepts formed from completely untethered and open minded thinking, but they were also formed from reviewing various designs that already existed. These designs ranged from previous alpine touring bindings that either failed or succeeded in the market for various reasons, to completely unrelated mechanisms and designs forms. Through this process, several well formed and feasible design concepts were obtained which potentially met the design specification requirements of both high performing alpine touring bindings and downhill bindings. Detailed design and analysis followed, along with the manufacture of a fully functional prototype. This was then tested and evaluated to determine the project as a success.
This project can be grouped only with a small amount of research ever conducted on the topic of alpine touring bindings. The findings, discussion and results of this work can therefore be used as a benchmark for future study into this field. Through the meticulous research conducted on skiing and ski bindings and the thorough design work carried out towards producing a prototype, this thesis presents the complete process of designing a new and innovative ski binding.
2
Lundin, Felix. "Design of workstation for binding adjustment in ski rental shops." Thesis, Luleå tekniska universitet, Institutionen för ekonomi, teknik, konst och samhälle, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:ltu:diva-82835.
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This master thesis project was a part of the education Master of science in Industrial Design Engineering at Luleå University of Technology with the mission of developing a work desk that suits in to the client company NoMoreBoots range of ski rental products. The background of the project was that work desks that are used mainly with the purpose of adjusting alpine ski bindings in ski rental shops often are primitive home constructions and other manufacturers work desks with the same purpose do not have enough advantages compared to the self-built ones to be worth the extra costs. With a new kind of tool introduced in the industry that facilitates the adjustments of alpine ski bindings came an opportunity to design the work desk in a new way. The work process has followed the user-centered design framework Double Diamond which consists of the phases: discover, define, develop and deliver. After exploring of the context with interviews and benchmarking, the projects main focus became at the ergonomic conditions and how it could be improved for the staff as it was the need identified that had the most protentional of improvements for the user. Literature studies, different types of idea generating methods and evaluations have been conducted to come up with a result that meet the needs of the users. The project resulted in a CAD model of a compact work desk that has a height adjustment mechanisk to enable the user to work with a good ergonomic position in several different work tasks.
3
Rupert, Peter Benjamin. "Structure determination of the SKN-1 DNA binding domain complex /." view abstract or download file of text, 1999. http://wwwlib.umi.com/cr/uoregon/fullcit?p9947981.
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Thesis (Ph. D.)--University of Oregon, 1999.Typescript. Includes vita and abstract. Includes bibliographical references (leaves 96-106). Also available for download via the World Wide Web; free to University of Oregon users. Address: http://wwwlib.umi.com/cr/uoregon/fullcit?p9947981.
4
Xu, Su. "Insulin-like growth factors and their binding proteins in human skin." Thesis, University of Bristol, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343351.
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Thompson, Elizabeth Ellen Anderson. "CCAAT/Enhancer Binding Protein Alpha in UVB Responses in Human and Mouse Skin and Mouse Skin Tumorigenesis." NCSU, 2009. http://www.lib.ncsu.edu/theses/available/etd-07062009-002822/.
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Human epidermis is routinely subjected to DNA damage induced by solar radiation and keratinocytes have developed intricate mechanisms to respond to UVB-induced DNA damage. Despite these mechanisms, nonmelanoma skin cancer is the most common cancer in the US. Previous analysis of immortalized mouse keratinocytes has revealed that the bZIP transcription factor, CCAAT/enhancer binding protein alpha (C/EBP alpha), is induced by DNA damage and has a role in the G1 checkpoint. Here we demonstrate C/EBP alpha is induced in the epidermis of the human subjects exposed to UVB. To begin to determine the in vivo physiological significance of the up-regulation of C/EBP alpha by UVB, we generated an epidermal specific C/EBP alpha knockout (K5Cre;C/EBP alpha fl/fl) mouse on a SKH1 hairless background. Following UVB treatment, these mice displayed an impaired keratinocyte cycle arrest and abnormal entry of keratinocytes into S-phase. This impaired cell cycle checkpoint in UVB-treated C/EBP alphaï deficient skin was associated with greatly diminished p21 levels which occurred through a p53-independent mechanism. To further investigate whether C/EBP alpha could function as a tumor suppressor gene in UVB induced skin tumorigenesis, we exposed K5Cre;C/EBP alpha fl/fl and K5Cre control SKH1 mice to 20mJ/cm2 UVB three times weekly. The K5Cre;C/EBP alpha fl/fl mice displayed both increased tumor incidence and multiplicity, suggesting that loss of C/EBP alpha in the epidermis confers increased susceptibility to UVB-induced skin tumorigenesis. In addition, we also observed that human skin SCC and BCC display greatly reduced or absent C/EBP alpha levels, implicating that loss of C/EBP alpha contributes to the development of human nonmelanoma skin cancers. Collectively, our results demonstrate that C/EBP alpha is induced by UVB in human skin, inhibits cell cycle progression in response to UVB in vivo and is a tumor suppressor gene in UVB induced skin tumorigenesis.
6
Albati, Amal Abdulah. "PURIFICATION OF RECOMBINANT δ NP63 α AND CHARACTERIZATION OF PEPTIDE BINDING". Wright State University / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=wright1447223071.
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Haapaniemi, T. (Tarja). "Autonomic dysfunction in Parkinson's disease and its correlates to medication and dopamine transporter binding." Doctoral thesis, University of Oulu, 2001. http://urn.fi/urn:isbn:9514259637.
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Abstract
Patients with idiopathic Parkinson's disease (PD) may suffer from autonomic nervous system dysfunction
even in the early phase of the disease. We assessed the autonomic cardiovascular and sudomotor regulation in
de novo PD patients with and without medication. We also measured the dopamine (DAT)
and serotonin transporter (SERT) uptake in the PD patients using
2β-carboxymethoxy-3β-(4-iodophenyl)tropane
(β-CIT) SPECT and studied the clinical correlates of the uptake. Sixty PD patients were included in the
study and randomised to receive levodopa, bromocriptine or selegiline (n=20 in each) as their treatment.
Thirty patients were examined with β-CIT SPECT. The results of the patients were compared with those of
healthy controls and within the subgroups at different time points.
Cardiovascular autonomic regulation was assessed using standard cardiovascular reflex tests at
baseline, after six months' medication and following a 6-week washout period. The heart rate (HR) and blood
pressure (BP) regulation was impaired in PD patients at baseline, and PD medications modified the responses
further. Bromocriptine and selegiline, in contrast to levodopa, increased the orthostatic BP fall and
suppressed the BP response to isometric exercise. The long-term cardiovascular autonomic function was
evaluated from ambulatory ECG recordings by analysis of traditional spectral and non-spectral components of
HR fluctuation together with two-dimensional vector analysis and power-law relationship analysis of the HR
dynamics. All spectral measures and the slope of the power-law relationship demonstrated impaired tonic
cardiovascular regulation in the PD patients.
Sympathetic sudomotor activity was evaluated using the sympathetic skin response (SSR). The
major finding was suppression of the SSR amplitudes with an inverse correlation to clinical disability,
whereas PD medication seemed to have only minor effects. The changes in amplitude and repetitiveness of the
SSRs with normal adaptation suggest deficits at several levels of the SSR reflex arc.
DAT uptake, assessed by β-CIT SPECT, was diminished in the striatum and especially the
putamen
of the PD patients, and correlated with the results of the cardiovascular reflex tests and ambulatory ECG
recordings. Simultaneous measurement of SERT binding demonstrated decreased SERT availability in the
thalamic and frontal areas.
The results demonstrate disturbances of the reflectory and tonic cardiovascular autonomic regulation caused
by PD itself. PD medications further modify the reflectory responses. The degenerative process in PD also
involves the sympathetic sudomotor pathway. β-CIT SPECT provides a useful method for simultaneous
assessment
of DAT and SERT binding, demonstrating the deficit of serotonin metabolism in PD.
8
Atkins, Karen. "Structural and functional studies of bacterial adhesion proteins : Staphylococcus aureus immunoglobulin-binding proteins Sbi and SpA and their interactions with serum proteins." Thesis, University of Bath, 2006. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.432400.
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László, Csaba F. "Translation regulation of UV-light-induced transcription factor NF-kappa-B and oncogene COX-2." View abstract, 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:3353542.
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Hyde, Carolyn Elizabeth. "The functional consequences of the interactions between insulin-like growth factors (IGFs), insulin-like growth factor binding proteins (IGFBPs) and vitronectin (VN) and their involvement in skin." Queensland University of Technology, 2006. http://eprints.qut.edu.au/16197/.
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The insulin-like growth factor (IGF) system plays an important role in a number of disease states, such as cancer, and has also been implicated in wound and burn healing processes. Two IGF receptors, the type-1 IGF and type-2 IGF receptors, as well as six insulin-like growth factor binding proteins (IGFBP-1 to 6), have well established roles in mediating IGF activity. Earlier studies in this laboratory demonstrated that IGF-II binds to the extracellular matrix (ECM) protein vitronectin (VN), and although IGF-I does not bind directly to VN it can bind indirectly via specific IGFBPs. Therefore the aim of the research described in this thesis was to determine whether binary and ternary complexes of IGF-I/II, IGFBPs and VN affect human keratinocyte cell function. The strategy of pre-binding these complexes to the culture dishes was adopted in this study in an attempt to more accurately reflect the extracellular environment in vivo. These studies demonstrated that the binary complex of IGF-II and VN and the ternary complexes comprised of IGF-I, IGFBP-2, or 3, or 4, or 5 and VN significantly stimulated HaCaT de novo cell protein synthesis in the human keratinocyte cell line. Interestingly, these latter experiments demonstrated that although large increases in protein synthesis were observed using the ternary complexes, IGF-I/IGFBP complexes alone were responsible for the significant increases in protein synthesis and these responses are mediated via the MAPK signaling pathway. In addition, both the dimeric and trimeric complexes significantly enhanced cell migration through 12 μm TranswellsTM. Unlike the protein synthesis assays, VN was critically important in these migratory responses and highlighting the important role that integrins play in cell migration. Cell attachment assays on the other hand demonstrated that the interactions of IGFs with IGFBPs and VN did not affect cell attachment. The data encompassed within this thesis represent the first studies to provide a functional role for the interaction between IGFs, IGFBPs and VN in human keratinocytes. Taken together these results suggest that IGF/IGFBP/VN complexes may hold great potential in situations where enhanced keratinocyte cell migration and proliferation is required, such as in wound healing and skin engineering applications.
11
Zhou, Ke. "Functional characterization of GPI-anchored proteins of the SKU5/SKS gene family." Phd thesis, Université Paris Sud - Paris XI, 2013. http://tel.archives-ouvertes.fr/tel-01066888.
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ABP1 (Auxin Binding Protein1), who can bind auxin, is essential for the development of plants. It was proved to have the ability to bind auxin and transduce auxin signal into the cells. It is supposed to be localized and functions at the outer surface of plasma membrane through unknown component. In my thesis, we tried to invesitgate the interaction between ABP1 and the candidate of the unknown component, CBP1 (From maize), which is GPI-acnhored and already identified as the binding ability to synthesized C-terminus peptide of ABP1 in 2006. The orthologous of CBP1 in arabidopsis belongs to a gene family with 19 members, in which only three of them were prediceted to be GPI anchored. We did the functional characterisation of these three GPI-anchored members. Data suggested that GPI-anchored SKS were involved in cell orientation, gametophyte and embryo development.
12
Head, Cynthia C. "Hormonal regulation of cutaneous wound healing effect of androstenediol on stress-impaired wound healing /." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1186957947.
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13
Lönn, Peter. "Regulation of TGF-β Signaling by Post-Translational Modifications". Doctoral thesis, Uppsala universitet, Ludwiginstitutet för cancerforskning, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-128855.
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Transforming growth factor-β (TGF-β) signaling is initiated when the ligand binds to type II and type I serine/threonine kinase receptors at the cell surface. Activated TGF-β type I receptors phosphorylate R-Smads which relocate, together with co-Smads, to the cell nucleus and regulate transcription. Enhancement or repression of Smad-specific gene targets leads to intracellular protein compositions which organize functional complexes and thus govern cellular processes such as proliferation, migration and differentiation. TGF-β/Smad signaling relays are regulated by various post-translational modifications. From receptors to gene promoters, intricate interplays between phosphorylation, acetylation, ubiquitination and numerous other modifications, control Smad signaling initiation and duration. However, many steps in the cascade, including receptor internalization, Smad nuclear shuttling and transcriptional termination, still remain elusive. The open gaps in our understanding of these mechanisms most likely involve additional post-translational regulations. Thus, the aim of the present investigation was to identify novel modulators of TGF-β/Smad signaling. In the first part of this thesis, we show the importance of ADP-ribosylation in Smad-mediated transcription. We identified poly(ADP-ribose) polymerase 1 (PARP-1) as a Smad interacting protein. Our work revealed that PARP-1 forms direct interactions with Smad3/4, and PARylates residues in their MH1 domains. This modification restricts Smads from binding to DNA and attenuates Smad-activated transcription. PARylation is reversed by the glycohydrolase PARG. We provide evidence that PARG can de-ADP-ribosylate Smads, which enhances Smad-promoted gene regulation. In the second part, we examine a Smad-dependent gene target of TGF-β signaling, salt inducible kinase 1 (SIK). After induction, SIK cooperates with Smad7 and Smurf2 to downregulate the TGF-β type I receptor. The mechanism relies on both the kinase and UBA domain of SIK as well as the E3-ligase activity of Smurf2. In summary, we have unveiled two enzyme-dependent TGF-β/Smad modulatory mechanisms; SIK promoted receptor turnover and PARP-1/PARG-regulated Smad signaling.
14
Leveque, Elodie. "Les reliures romanes de la bibliothèque de Clairvaux : étude archéologique et biocodicologique." Thesis, Paris 10, 2020. http://www.theses.fr/2020PA100027.
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Cette recherche se concentre sur l'étude des reliures romanes de la bibliothèque de l'abbaye de Clairvaux, qui représente à l’heure actuelle la plus grande collection romane connue. Sur les 160 reliures étudiées, une série recouverte de peau de phoque a retenu notre attention. Si la collection de Clairvaux a conservé le plus grand nombre de chemises velues, l'ensemble de l’ordre cistercien semble en avoir fait largement usage au cours des XIIe et XIIIe siècles. Bien que la majeure partie de la collection ait été reliée de la même manière, seules 18 reliures de Clairvaux ont conservé leur état d'origine avec leurs chemises presque intactes. Ces dernières sont décrites dans les catalogues modernes comme étant de la peau de sanglier ou de cerf. Cependant, sous microscope, la distribution des follicules pileux ne correspond à aucun de ces deux animaux. En vue d’identifier l’origine animale des chemises, des analyses protéomiques et génomiques non invasives ont été menées. La première a permis d’identifier les peaux de pinnipèdes. L'utilisation de peaux de phoque en Champagne, à une distance considérable de la mer, est curieuse. De plus, il n'y a aucune preuve archéologique de populations de phoques sur les côtes françaises au Moyen Âge. Le séquençage ADN a en outre permis de résoudre la question de l’origine géographique de six documents, suggérant un commerce important de peaux de phoque comme marchandise, possiblement sur les foires de Champagne. L'étude biocodicologique des reliures permet de mesurer l’implication des cisterciens dans le commerce international, mais également d’appréhender l'aspect physique des manuscrits à l’origine. La collection romane de Clairvaux offre aussi l'opportunité d'étudier des reliures de provenance extérieure, comme celles réalisées pour le prince Henri dans un atelier urbain, ou encore les structures de voyage souples qui donnent une idée beaucoup plus large de la production de reliures romanes françaises de l’époqueThis research focuses on the study of Romanesque bindings from Clairvaux abbey’s library, which is the largest known Romanesque collection. Out of the 160 bindings studied, a series covered in sealskin drew our attention. While the Clairvaux collection retains the largest number of hairy chemises, the use of such material seems to have been widely employed by the Cistercian order during the 12th and 13th C. Although most of the collection would have been bound in the same way, only 18 Clairvaux bindings remain in their original state with their chemises almost intact. The chemises are described in modern catalogues as boar- or deer-skin. However, under magnified examination, the distribution of the hair follicle doesn’t match either animal. To try to identify the animal origin of the chemises we applied non-invasive proteomic and genomic analyses. Proteomic analysis identified the skins as belonging to pinnipeds. The use of seal skins in Champagne, at a considerable distance from the sea, is curious. In addition, there is no archaeological evidence of seal populations on the French coast in the middle ages. DNA sequences further resolved the geographical origin for six documents, suggesting an important trade in seal skins as a commodity, possibly at the Champagne fairs. The biocodicological study of the bindings helps us understand not only the extent of trading in which the Cistercians were involved but also the original physical appearance of the manuscripts. Clairvaux’s Romanesque collection also provides an opportunity to study bindings of external provenance, such as those made for Prince Henri in a city-based workshop, or limp travelling structures that give a broader idea of French Romanesque binding production of the time
15
Karlsson, Teresa. "Studies on Vitamin A Signaling in Psoriasis : A Comparison Between Normal and Lesional Keratinocytes." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2002. http://publications.uu.se/theses/91-554-5317-1/.
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Drbohlav, Antonín. "Vývoj lyžařského vázání po 2. světové válce." Master's thesis, 2019. http://www.nusl.cz/ntk/nusl-396128.
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SUMMARY: Title: The development of ski bindings after World War II Objectives: The objective of the work is to capture and describe the major events in the development of the downhill bindings that took place since the end of II. World War II to the present. Methodology: The work has a historical character using histographic methods supplemented by a content analysis of the document. In particular, the historical, chronological and direct method was used to supplement the content analysis of the document Conclusion: A summary of the data in chronological form enriches the theoretical background of skiing history. The work extends available information sources on topics that have not been elaborated in a comprehensive way. Keywords: Ski equipment, ski bindings, history of skiing
17
Drbohlav, Antonín. "Vývoj lyžařského vázání po 2. světové válce." Master's thesis, 2017. http://www.nusl.cz/ntk/nusl-365314.
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SUMMARY: Title: The development of ski bindings after World War II Objectives: The aim of the work is to capture and describe the major events in the development of the downhill bindings that took place since the end of II. World War II to the present. Methodology: The work has a historical character using histographic methods. In particular, the historical, chronological and direct methods were used. Conclusion: A summary of the data in chronological form enriches the theoretical background of skiing history. The work extends available information sources on topics that have not been elaborated in a comprehensive way. Keywords: Ski equipment, bindings, history of skiing
18
Darnell, Steven J. "Protein interaction hot spots and engineered binding affinity within the Smad4-Ski interface." 2008. http://www.library.wisc.edu/databases/connect/dissertations.html.
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Huang, Hsin-Pei, and 黃欣培. "The calcium bioavailability of calcium-binding peptide derived from tilapia fish skin." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/8827qk.
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碩士國立臺灣海洋大學
食品科學系
102
Collagen peptide is made from collagen through an enzymatic hydrolysis process. Compare with collagen, it has better water–soluble feature and more extensive physiological activity, which can be easily absorbed by human body. The purpose of this study is to establish the enzymatic conditions for preparing collagen peptide from tilapia fish skin, and fractionate different molecular weight (5–10 kDa, 3–5 kDa, 1-3 kDa, < 1 kDa) using an ultrafiltration system. The collagen peptides obtained were compared with their calcium binding ability. Finally, using Caco-2 cell model to study on the calcium bioavailability of the fish skin collagen peptide. Among them, collagen peptides from fish skin treated with Alcalase plus Flavourzyme showed higher calcium binding ability, and were selected in the following study. The optimal conditions in two enzymes system were listed as follows : temperature 50℃, pH 7.5, hydrolysis time 2 hr, showed higher calcium binding ability. Using an ultrafiltration system, the fraction (<1 kDa) had higher calcium binding ability, named it ‘fish skin collagen peptide (FSCP)’. The results of stability of calcium binding ability of FSCP were listed as follows : temperature 25℃, pH 7.8, showed higher calcium binding ability and addition of lactose was conducive to bind Ca2+ to FSCP. Effect of 5 mg/mL FSCP on growth of Caco-2 cell after 24 hr of treatment, its cell viability reach up to 100%. Intestinal permeability test showed that the fish skin collagen peptide can promote calcium uptake.
20
Apponyi, Margit Anneliese. "Amphibian skin peptides which inhibit nNOS : structure and binding studies using heteronuclear NMR." 2006. http://hdl.handle.net/2440/37795.
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Using 2 - D NMR spectroscopy, the structure of the sex pheromone from Litoria splendida has been determined, in order to elucidate its mode of transport through the aquatic environment. The peptide was found form an α - helical structure, with a central flexible hinge region. The mode of transport through the aquatic environment has been discussed in relation to the structure. Previous work indicated that the Australian amphibian host defence skin peptides that inhibit neuronal nitric oxide synthase ( nNOS ) were likely to act indirectly on the enzyme, by binding to the co - enzyme of nNOS, calmodulin. [superscript 15] N labelled calmodulin was expressed and purified via a bacterial protein expression system and a series of 2 - D NMR [superscript 15] N - HSQC titrations was performed with Australian amphibian host defence skin peptides. in order to determine whether these peptides bind to calmodulin. The three peptides tested were found to bind, and with differing strengths of interaction. One of these was selected for further study. [superscript 15] N and [superscript 13] C doubly labelled calmodulin was then prepared in order to study the complex between this protein and the selected peptide, caerin 1.8, an Australian amphibian skin peptide isolated from Litoria chloris. A series of 3 - D NMR spectra has been recorded on this complex. The backbone atom resonances have been assigned for free calmodulin and for the calmodulin - peptide complex, using a combination of main chain directed and sequential assignment strategies. By analysing the changes in chemical shift that occur upon binding the peptide, it was determined that the mode of binding involves a stronger interaction with the C - terminal domain than the N - terminal domain.Thesis (Ph.D.)--School of Chemistry and Physics, 2006.
21
Miselnicky, Scott Richard. "The Influence of lipid solubility and protein binding on reservoir formation in the skin /." 1987. http://www.gbv.de/dms/bs/toc/12305687X.pdf.
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Sharma, Amy. "Investigation of the Involvement of Covalent Binding in Nevirapine-Induced Hepatic and Cutaneous Idiosyncratic Adverse Drug Reactions." Thesis, 2013. http://hdl.handle.net/1807/43720.
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Nevirapine (NVP) can cause serious idiosyncratic drug reactions (IDRs); specifically, skin rash and hepatotoxicity. Treatment of rats or mice with NVP led to covalent binding to hepatic proteins. Studies of this covalent binding including the use of a deuterated analog of NVP leading to a decrease in oxidation of the methyl group indicated that the metabolite responsible for covalent binding in the liver is a quinone methide.
Covalent binding in NVP-treated rats was also observed in the epidermis but by a different pathway. Incubation of 12-OH-NVP sulfate with homogenized human and rat skin led to extensive covalent binding. Inhibition of sulfation in the liver significantly decreased 12-OH-NVP sulfate in the blood, but it did not prevent covalent binding in the skin or the rash. In contrast, topical application of a sulfotransferase inhibitor prevented covalent binding in the skin as well as the rash, but only where it was applied. In contrast to rats, treatment of mice with NVP did not result in covalent binding in the skin or skin rash. These findings provide compelling evidence that 12-OH-NVP sulfate formed in the skin is responsible for the skin rash.
IL-1β and IL-18 production in the skin of rats treated with NVP were increased. An anti-IL-1ß antibody significantly decreased rash severity. These cytokines were also produced by incubation of human keratinocytes with 12-OH-NVP sulfate. These data indicate that 12-OH-NVP sulfate activates the NLRP3 inflammasome, a pathway known to be responsible for contact hypersensitivity rashes.
In summary, NVP was found to produce two different reactive metabolites, a quinone methide species in the liver, and a benzylic sulfate in the skin. Significant liver injury did not occur, presumably due to immune tolerance. Although it is usually assumed that reactive metabolites are responsible for most IDRs, this is the first example to actually demonstrate that a specific reactive metabolite is responsible for an IDR. This is also the first study to show that sulfotransferase in the skin is responsible for bioactivation of a drug leading to a skin rash. It is likely that there are other drugs that cause skin rashes by a similar mechanism.
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Zhan, Ya-Chi, and 詹雅琪. "Distribution and characteristics of Zn and 43 kDa Zn-binding protein in the skin of common carp." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/87233956998670450396.
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碩士國立臺灣海洋大學
食品科學系
94
Abstract Common carp always has high concentration in its digestive tract tissue, and it is known this high Zn exists in the plasma membranes of fibroblasts. The skin of the fish also riches in fibroblasts. Distribution of Zn in the skin of common carp was studied. It was found that the Zn concentration in the skin of common carp was 88 µg/(g fresh tissue) determined by dry-ashing method. About ~90% of the zinc in the skin of common carp could be extracted by EDTA solution, which means only ~10% of Zn was bound closely to some substance. The skin of the fish was divided into dorsum, abdomen and tail portion, After subcellular fractionation, it was found that in the dorsum, abdomen and tail, the average Zn were 85~119 µg/(g fresh tissue). About 82% of the Zn existed in the nuclei/cell debris fraction. The Zn concentration in skin of grass carp, silver carp and tilapia was 38~53 µg/(g fresh tissue), only about 50% of that in common carp. The hydroxyproline concentration in skin of common carp (363 µg/[g fresh tissue]) was higher than that in the other fish (281 µg/[g fresh tissue]). Zn-binding protein in the skin of common carp, grass carp, silver carp and tilapia was extracted by detergent lubrol with 4 M guanidine hydrochloride, and it was found that little Zn was extracted. Immunoassay of the guanidine/lubrol with the antibody against 43 kDa Zn-binding protein , indicated that only the extracts of common carp was positive. The immunohistochemical staining, indicated that the 43 kDa Zn-binding protein only exist in dermis of common carp. No immunoreaction was found in dermis of grass carp, silver carp and tilapia. The above mentioned results indicated that 43 kDa Zinc-binding protein also existed in dermis of common carp which most probably located in fibroblasts.
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Nahari, Dorit. "Characterization of the T122L mutation in p53 and its protein product in Xpc mutant mice." 2003. http://edissertations.library.swmed.edu/pdf/nahariD040303/NahariDorit.pdf.
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陳彥樺. "Localization and Biochemical Properties of Zinc and Zinc Binding Substances in Kidney, Skin, and Membrane-like Substances of Eyes of Common Carp." Thesis, 2002. http://ndltd.ncl.edu.tw/handle/87597496948807490859.
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碩士國立海洋大學
食品科學系
90
Summary Zn concentration in the digestive tract tissue of common carp is higher than that in other fish. It was found that this is because Zn was attached to a membrane protein, and the「Zn binding membrane protein」(ZnBMP) might be located on the basolateral plasma membrane of the epithelial cells and surrounding muscle cells which are attached to collagen type Ⅳ. Besides the digestive tract tissue, the Zn concentration in kidney of common carp is also high. Both of the digestive tract tissue and kidney have large amount of basal lamina. Besides these two tissues, the eyes and skin also have large amount of basal lamina. In order to understand the relationship between the Zn concentration in tissues of common carp and the amount of basal lamina, the Zn concentration, localization and the biochemical properties of 「Zn binding substance」of these tissues were studied, and compared with those of grass carp, silver carp, and tilapia. It was found that the Zn concentrations in kidney of common carp bought from market were 137∼63 μg/g fresh tissue, but those fed with high Zn diet (2000 mg/kg) were 287∼300 μg/g fresh tissue. The kidney of common carp was subcellular fractioned, and it was found that the Zn concentration in kidney of common carp either bought from market or fed with high Zn diet (2000 mg/kg) mainly existed in the nuclei/cell debris fraction. High correlation between Zn concentraction in whole tissue and the nuclei/cell debris fraction was observed (r=0.828). The Zn concentrations in kidneys of grass carp, silver carp, and tilapia were 63∼30 μg/g fresh tissue, only about half of that in common carp. It was found that the concentrations of Zn in cytosol, microsome, mitochondria/ lysosome fraction were similar among the four fish species. High concentration of Zn in kidney of common carp mainly existed in the nuclei/cell debris fraction. The Zn concentrations in skin of common carp were 117∼102 μg/g fresh tissue. The skin of common carp was subcellular fractioned, and it was found that the Zn concentration in skin of common carp mainly existed in the nuclei/cell debris fraction. High correlation between Zn concentration in whole tissue and the nuclei/cell debris fraction was found (r=0.726). The Zn concentrations in skin of grass carp, silver carp, and tilapia were 25∼38 μg/g fresh tissue, only about 1/3∼1/4 of that in common carp. It was found that the concentration of Zn in cytosol, microsome, and mitochondria/lysosome fraction were similar among the four fish species. High concentration of Zn in skin of common carp mainly existed in the nuclei/cell debris fraction. The eyes of common carp were separated into three parts, and the Zn concentration was measured. It was found that the Zn concentration in lens and vitreous of eyes of common carp was 13∼14 μg/g fresh tissue, and in scelera cartilage was 13∼14 μg/g fresh tissue, and there was no difference between right eye and left eye. However, the Zn concentration in membrane-like substances of eyes of common carp reached to 339±66 μg/g fresh tissue. The membrane-like substances of eyes of common carp was subcellular fractionated, and it was found that the nuclei/cell debris fraction contained most of the Zn. A high correlation between Zn concentration in whole tissue and the nuclei/cell debris fraction was observed (r=0.858). The Zn concentration in membrane-like substances of eyes of grass carp, silver carp, and tilapia was found to be 473∼519 μg/g fresh tissue. After subcellular fractionation, it was found that the nuclei/cell debris fraction contained most of the Zn (80∼88％). The experiments also show that there was a high correlation between the concentration of Bound-SH groups and 〝EDTA-extractable Zn〞 in the nuclei/cell debris fraction of kidney and skin of common carp; and the membrane-like substances of eyes of common carp, grass carp, silver carp, and tilapia. It is proposed that the Zn in nuclei/cell debris fraction of these tissues might be bound by SH group. However, the kidney and skin of grass carp, silver carp, and tilapia which had low 〝EDTA-extractable Zn〞, also had low concentration of Bound-SH groups. The Na+/K+ ATPase activity in membrane-like substances of eyes of common carp was found to be 0.96±0.28 μmole/g fresh tissue/min, and it mainly existed in the nuclei/cell debris fraction (67±9％). Based on the experiments, we propose that the「Zn binding substances」 in the kidney and skin of common carp; and the membrane-like substances of eyes of common carp, grass carp, silver carp, and tilapia are very probable to be a membrane protein located on the basolateral plasma, and they are attached to Zn by SH group.