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No description available.

Maintenance of genomic stability is paramount for survival of an organism; failure to repair DNA damage ultimately leads to the accumulation of genetically unstable cells and the onset of different human diseases including cancer. DNA single strand breaks and base oxidation/alkylation are among the most frequent types of DNA damage occurring spontaneously in cells. Base excision repair (BER), which copes with the majority of these lesions, is therefore a fundamental DNA repair system. Accordingly, it is important to understand how BER is regulated, and particularly, how and if BER is affected by the cellular load of DNA damage. Although functions of key BER proteins are well-defined, regulation of their expression is poorly understood. During BER, the protein XRCC1 is particularly important. It functions as a scaffold, stabilising repair complexes at sites of DNA damage thereby promoting efficient DNA repair. As a central coordinator in BER, it is therefore of great interest to understand how expression of XRCC1 is controlled. In this thesis I demonstrate that modulation of XRCC1 expression is mediated by transcription factor Sp1. Importantly, Sp1 is also affected during the DNA damage response, suggesting an indirect mechanism promoting BER modulation in response to the cellular DNA damage load. In fact, I show that, in response to persistent DNA strand breaks, the key DNA damage signalling factor ATM phosphorylates Sp1. This initiates Sp1 degradation, negatively affecting BER. Therefore, this thesis identifies a mechanism involving signalling from ATM that regulates BER in response to persistent DNA damage, which I link to susceptibility to apoptosis and cell elimination. I hypothesise that regulation of DNA repair in response to persistent DNA damage constitutes a mechanism to promote the elimination of potentially pre-cancerous cells that accumulate unrepairable levels of DNA lesions.

ITC/USA 2006 Conference Proceedings / The Forty-Second Annual International Telemetering Conference and Technical Exhibition / October 23-26, 2006 / Town and Country Resort & Convention Center, San Diego, California / Research at Morgan State University shows a means of enabling both a mobile ad-hoc network (MANET) and a cellular network to operate simultaneously in the same spectrum. This enhanced frequency efficiency would facilitate the creation of a hybrid or Mixed Cellular/MANET network (MCMN) in which each of the MCMN sub-networks would have access to the entire allotted spectrum. Interference rejection and excision have been identified as a means of distinguishing between and isolating the two different kinds of signals. This paper shows the promising performance of such techniques within the MCMN environment as a part of the integrated Network Enhanced Telemetry (iNET) project.

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ABSTRACT DNA in the eukaryotic nucleus is complexed with histone and non-histone proteins into chromatin. Nucleosomes, the basic repeating unit of chromatin, not only package DNA but are also intimately involved the regulation of gene expression. All DNA transactions including replication, transcription, recombination and repair take place in such a chromatin environment. Access to packaged nucleosomal DNA in vivo is mediated at least in part by protein complexes that modify or remodel chromatin. Buried sequences in nucleosomes can also transiently become accessible to DNA binding proteins during cycles of partial, reversible unwrapping of nucleosomal DNA from the histone octamer. We have investigated the ability of the human, bifunctional DNA glycosylase, endonuclease III (hNTH1), to initiate base excision repair (BER) of discretely positioned oxidative lesions in model nucleosomes. hNTH1 was able to process a thymine glycol (Tg) lesion almost as efficiently as naked DNA, when the minor groove of the lesion faced away from the histone octamer. Lesion processing did not require or result in detectable nucleosome disruption, as assayed in gel mobility-shift experiments. Instead, hNTH1 formed a slower migrating enzyme-nucleosome ternary complex that was found to contain processed DNA. Processing of an inward-facing Tg residue located just 5 bp away from the outward-facing lesion was much reduced and processing of a sterically occluded Tg residue positioned closer to the dyad center of the nucleosome was even more reduced. Notably, processing of both inward-facing lesions was found to increase as a function of enzyme concentration. Restriction enzyme protection studies indicated that access to these inward-facing lesions did not entail nucleosomal translocation or sliding. Collectively, these observations are consistent with a model in which hNTH1 binds to lesions during cycles of reversible, partial unwrapping of nucleosomal DNA from the histone octamer core. To further investigate this partial unwrapping hypothesis, we studied the kinetics of hNTH1 processing of sterically occluded lesions in greater detail. Our results suggest that efficiency of processing of inward-facing lesions is a function of both DNA unwrapping and rewrapping rates, and enzyme affinity for the lesion. In addition, we determined that APE1 which catalyzes the second step in BER, exhibited an increasing capacity to process inward-facing furan residues as its concentration was increased. Thus as with hNTH1, we hypothesize that APE1 can capture occluded furan residues during cycles of partial DNA unwrapping. We propose that cellular regulatory factors benefit from this intrinsic, periodic exposure of nucleosomal DNA exposure in vivo, which may be amplified by the downstream recruitment of remodeling and / or modifying proteins to facilitate DNA transactions in the cell.

The purpose of this project was to compare the recurrence rates of dermatofibrsarcoma protuberans (DFSP) treated with surgical excision (SE) and Mohs surgery (MS) at Yale. Patients were identified through the dermatopathology laboratory database and stratified by treatment. The following information was collected: age at onset, sex, disease state (primary presentation versus recurrence), tumor site, preoperative tumor size, postoperative defect size, excisional margin, duration of follow-up, and recurrence after treatment. Of the 30 patients, 14 were in the SE group, and 16 were in the MS group. There were no recurrences in the SE group, and there was 1 recurrence (6%) in the MS group, which occurred 37 months post-operatively. The average area of the tumors were 12.1 cm[exponent]2 [plus-minus] 16.1 (SE) and 5.3 cm[exponent]2 [plus-minus] 5.9 (MS), and the mean excisional margins were 3.8 cm [plus-minus] 1.6 (SE) and 1.4 cm [plus-minus] 0.5 (MS). The mean duration of follow-up in the SE group was 33 months [plus-minus] 41 (range: 1-116 months), and the mean duration of follow-up in the MS group was 26 months [plus-minus] 25 (range: 2 to 69 months.) Although the MS group had a higher recurrence rate than the SE group, using the recurrence rates to make meaningful conclusions about the efficacy of the two treatment modalities is limited by the small n[italicized], lack of randomization to either procedure, and duration of follow-up. Once these issues are addressed, recurrence rates must also be adjusted for patient and tumor characteristics, that are associated with higher recurrence rates.

Texte remanié de: Dissertation--Berlin--Humboldt-Universität. / Mention parallèle de titre ou de responsabilité : Female genital mutilation. Bibliogr. p. 142-147.

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Rhinophyma is a rare clinical condition that is characterized by the proliferation of sebaceous glands and underlying connective tissue of the nose. There is no standard method for the treatment of this benign condition as several techniques have been proven effective. The patient is a 79-year-old male that presents with a large rhinophyma and left-sided alar mass. He was treated operatively with the use of electrocautery dermabrasion and sharp excision. Pre-operative, intra-operative, and post-operative images were obtained and depict a desirable cosmetic outcome. Although they are among many effective therapies for the management of rhinophyma, electrocautery dermabrasion and sharp excision remain viable and successful options for the treatment of this condition.