Among all existing alignment-free methods for comparing biological sequences, the sequence graphical representation provides a simple approach to view, sort, and compare gene structures. The aim of graphical representation is to display DNA or protein sequences graphically so that we can easily find out visually how similar or how different they are. Of course, only the visual comparison of sequences is not enough for the follow-up research work. We need more accurate comparison. This leads us to develop the application of the graphical representation for biological sequences. / In this thesis, we have two main contributions: (1) We construct a protein map with the help of our proposed new graphical representation for protein sequences. Each protein sequence can be represented as a point in this map, and cluster analysis of proteins can be performed for comparison between the points. This protein map can be used to mathematically specify the similarity of two proteins and predict properties of an unknown protein based on its amino acid sequence. (2) We construct a novel genome space with biological geometry, which is a subspace in RN . In this space each point corresponds to a genome. The natural distance between two points in the genome space reflects the biological distance between these two genomes. Our genome space will provide a new powerful tool for analyzing the classification of genomes and their phylogenetic relationships. / Yu, Chenglong. / Adviser: Luk Hing Sun. / Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 59-64). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Dissertation (Ph.D.)--University of South Florida, 2009. / Title from PDF of title page. Document formatted into pages; contains 115 pages. Includes vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Missouri--Columbia, 1998. / Typescript. Vita. Includes bibliographical references (leaves: 215-225). Also available on the Internet.

Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders that often progress to chemotherapy-resistant secondary acute myeloid leukemia (sAML). We used whole-genome sequencing to perform an unbiased comprehensive screen to discover the somatic mutations in a sample from an individual with sAML and genotyped the loci containing these mutations in the matched MDS sample. Here we show that a missense mutation affecting the serine at codon 34 (Ser34) in U2AF1 was recurrently present in 13 out of 150 (8.7%) subjects with de novo MDS, and we found suggestive evidence of an increased risk of progression to sAML associated with this mutation. U2AF1 is a U2 auxiliary factor protein that recognizes the AG splice acceptor dinucleotide at the 3' end of introns, and the alterations in U2AF1 are located in highly conserved zinc fingers of this protein. Mutant U2AF1 promotes enhanced splicing and exon skipping in reporter assays in vitro. This previously unidentified, recurrent mutation in U2AF1 implicates altered pre-mRNA splicing as a potential mechanism for MDS pathogenesis.

Hepatite C tem evolução progressiva, persiste na maioria dos pacientes (85%) e leva a uma doença crônica assintomática.A maioria dos pacientes apresenta nível de ALT elevada e aproximadamente 25% normal. Estes geralmente são mulheres e não há associação entre genótipo e severidade da lesão hepática. Histologicamente apresentam lesão mínima e leve fibrose, embora cirrose tenha sido relatado.Visando estimar a prevalência, características demográficas, genotípicas e anatomopatológicas em pacientes com ALT normal, realizamos um estudo de série de 68 casos entre janeiro de 1997 a abril de 2000. A prevalência foi de 13,82%, 45,6% do gênero masculino e 54,4% feminino, média de idade 38 +/- 13 anos. Genótipo 1 em 84,75%, 2 em 6,78% e o 3 em 8,47%. Em 52,9% dos casos biópsia hepática revelou fígado reacional, porém uma importante proporção (29%) dos nossos pacientes com transaminases normais mostrou sinais de fibrose. Estes resultados sugerem a necessidade de revisar os algoritimos da prática de biópsia hepática nessa população / Hepatitis C evolves progressively persisting in the majority of patients (85%) resulting in na asymptomatic chronic disease.Most patients have high ALT levels and approximately 25% normal ALT.The latter are usually female and there is no association between genotype and severity hepatic lesion.Histology shows small lesion and low amount of fibrosis, despite cirrhosis having been reported.Aiming at assessing prevalence, demographic, genotypical and anatomopathological characteristics in patients with normal ALT levels, we studied a series of 68 cases between January 1997 and April 2000.There was a prevalence of 13,82%, 45,6% of which were male and 54,4% female, average age of 38+/-13 years.Genotype 1 in 84,75%, 2 in 6,78% and 3 in 8,47%.In 52,9% of the cases revealed liver reaction, however, an important proportion of patients showed histologic signs of fibrosis (29%).Theses results suggest the need to revisit the algorithm for liver biopsy practice

Wong Ka Lok. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 121-129). / Abstracts in English and Chinese. / Acknowledgments --- p.i / Abstract --- p.ii / Table A --- p.v / Table B --- p.vi / Table of Contents --- p.vii / Abbreviations --- p.xi / Chapter Chapter 1 --- Molecular authentication of endangered crocodiles and snakes / Chapter 1.1 --- Introduction --- p.1 / Chapter 1.2 --- Traditional method of snake and crocodile identification / Chapter 1.2.1 --- Morphology --- p.7 / Chapter 1.2.2 --- Chemical Analysis --- p.9 / Chapter 1.3 --- Molecular Technology in Authentication / Chapter 1.3.1 --- Polymerase Chain Reactions (PCRs) --- p.11 / Chapter 1.3.2 --- Random-primed amplification reaction --- p.12 / Chapter 1.3.3 --- Sequence Characterized Amplified Region (SCAR) --- p.13 / Chapter 1.3.4 --- PCR-RFLP --- p.13 / Chapter 1.3.5 --- DNA sequencing --- p.14 / Chapter 1.4 --- Objectives and strategies of the study --- p.15 / Chapter Chapter 2 --- Materials and General Methods / Chapter 2.1 --- Reagents and Buffers / Chapter 2.1.1 --- Buffers for Total DNA Extraction --- p.17 / Chapter 2.1.2 --- Reagents for Agarose Gel Electrophoresis --- p.17 / Chapter 2.1.3 --- Reagents for Plasmid DNA Preparation --- p.18 / Chapter 2.1.4 --- Medium for Bacterial Culture --- p.18 / Chapter 2.1.5 --- Reagents for Preparation of Competent Cells --- p.19 / Chapter 2.2 --- DNA Isolation / Chapter 2.2.1 --- Extraction of DNA from meats --- p.20 / Chapter 2.2.2 --- Extraction of DNA from blood --- p.20 / Chapter 2.3 --- Phenol/Chloroform Extraction --- p.21 / Chapter 2.4 --- Ethanol Precipitation --- p.22 / Chapter 2.5 --- DNA Concentration/Purity Estimation --- p.22 / Chapter 2.6 --- Mitochondrial DNA amplification --- p.23 / Chapter 2.7 --- Random-Primed Polymerase Chain Reactions --- p.24 / Chapter 2.8 --- SCAR for Snake samples --- p.24 / Chapter 2.9 --- SCAR for Crocodile samples --- p.25 / Chapter 2.10 --- Restriction fragment length polymorphism analysis --- p.25 / Chapter 2.11 --- Agarose Gel Electrophoresis of DNA --- p.26 / Chapter 2.12 --- Purification of PCR product --- p.26 / Chapter 2.13 --- Preparation of Escherichia coli Competent Cells --- p.27 / Chapter 2.14 --- Ligation and transformation of E. coli --- p.27 / Chapter 2.15 --- Plasmid preparation --- p.28 / Chapter 2.16 --- Screening of Plasmid DNA by Restriction Digestion --- p.29 / Chapter Chapter 3 --- DNA sequencing of snakes & construction of snake database / Chapter 3.1 --- Introduction --- p.30 / Chapter 3.2 --- Materials and methods / Chapter 3.2.1 --- Snake samples --- p.32 / Chapter 3.2.2 --- "DNA Extraction, mitochondrial gene amplification and DNA sequencing" --- p.33 / Chapter 3.2.3 --- Construction of database --- p.33 / Chapter 3.3 --- Results / Chapter 3.3.1 --- Cytochrome b gene amplification and sequencing --- p.34 / Chapter 3.3.2 --- Gene amplification and sequencing of 16S rRNA --- p.42 / Chapter 3.3.3 --- Cytochrome b sequence database --- p.50 / Chapter 3.3.4 --- 16S rRNA sequence database --- p.53 / Chapter 3.4 --- Discussion / Chapter 3.4.1 --- Cytochrome b and 16S rRNA genes of snake species --- p.55 / Chapter 3.4.2 --- Cytochrome b and 16S rRNA databases --- p.55 / Chapter Chapter 4 --- Application of PCR-RFLP and SCAR in snake species identification / Chapter 4.1 --- Introduction --- p.57 / Chapter 4.2 --- Material and Methods / Chapter 4.2.1 --- DNA extraction and PCR-RFLP --- p.58 / Chapter 4.2.2 --- RAPD and SCAR --- p.58 / Chapter 4.3 --- Results / Chapter 4.3.1 --- PCR-RFLP of cytochrome b genes of snakes --- p.59 / Chapter 4.3.2 --- PCR-RFLP of 16S rDNA --- p.61 / Chapter 4.3.3 --- RAPD & SCAR analysis --- p.67 / Chapter 4.4 --- Discussion --- p.72 / Chapter Chapter 5 --- "Application of DNA sequencing, PCR-RFLP and SCAR to identify crocodile species" / Chapter 5.1 --- Introduction --- p.74 / Chapter 5.2 --- Materials and methods / Chapter 5.2.1 --- "Crocodile, human and four animal samples" --- p.75 / Chapter 5.2.2 --- "DNA Extraction, mitochondrial gene amplification and DNA sequencing" --- p.75 / Chapter 5.2.3 --- PCR-RFLP and SCAR --- p.76 / Chapter 5.3 --- Results / Chapter 5.3.1 --- Isolation of crocodiles DNA --- p.77 / Chapter 5.3.2 --- Isolation of DNA from Human and four animal species --- p.78 / Chapter 5.3.3 --- Cytochrome b gene amplification and sequencing --- p.78 / Chapter 5.3.4 --- 16S rRNA gene amplification and sequencing --- p.84 / Chapter 5.3.5 --- PCR-RFLP of cytochrome b --- p.89 / Chapter 5.3.6 --- PCR-RFLP of 16S rRNA --- p.91 / Chapter 5.3.7 --- SCAR primers for four crocodile species --- p.93 / Chapter 5.4 --- Discussion --- p.97 / Chapter Chapter 6 --- A case report - authentication of animal samples using DNA sequencing / Chapter 6.1 --- Introduction --- p.99 / Chapter 6.2 --- Material and methods / Chapter 6.2.1 --- Materials --- p.101 / Chapter 6.2.2 --- DNA Extraction and sequencing --- p.101 / Chapter 6.3 --- Result and discussion / Chapter 6.3.1 --- Cytochrome b gene sequencing --- p.102 / Chapter 6.3.2 --- Sequence homology among samples and meats obtained from the market --- p.111 / Chapter 6.3.3 --- Identity of samples B & D --- p.113 / Chapter Chapter 7 --- General Discussion / Chapter 7.1 --- Advantages and weakness of DNA technology --- p.116 / Chapter 7.2 --- Choosing appropriate molecular markers --- p.118 / Chapter 7.3 --- Further suggested work --- p.119 / Chapter 7.4 --- Conclusion --- p.119 / References --- p.121 / Appendix --- p.130

Hepatite C tem evolução progressiva, persiste na maioria dos pacientes (85%) e leva a uma doença crônica assintomática.A maioria dos pacientes apresenta nível de ALT elevada e aproximadamente 25% normal. Estes geralmente são mulheres e não há associação entre genótipo e severidade da lesão hepática. Histologicamente apresentam lesão mínima e leve fibrose, embora cirrose tenha sido relatado.Visando estimar a prevalência, características demográficas, genotípicas e anatomopatológicas em pacientes com ALT normal, realizamos um estudo de série de 68 casos entre janeiro de 1997 a abril de 2000. A prevalência foi de 13,82%, 45,6% do gênero masculino e 54,4% feminino, média de idade 38 +/- 13 anos. Genótipo 1 em 84,75%, 2 em 6,78% e o 3 em 8,47%. Em 52,9% dos casos biópsia hepática revelou fígado reacional, porém uma importante proporção (29%) dos nossos pacientes com transaminases normais mostrou sinais de fibrose. Estes resultados sugerem a necessidade de revisar os algoritimos da prática de biópsia hepática nessa população / Hepatitis C evolves progressively persisting in the majority of patients (85%) resulting in na asymptomatic chronic disease.Most patients have high ALT levels and approximately 25% normal ALT.The latter are usually female and there is no association between genotype and severity hepatic lesion.Histology shows small lesion and low amount of fibrosis, despite cirrhosis having been reported.Aiming at assessing prevalence, demographic, genotypical and anatomopathological characteristics in patients with normal ALT levels, we studied a series of 68 cases between January 1997 and April 2000.There was a prevalence of 13,82%, 45,6% of which were male and 54,4% female, average age of 38+/-13 years.Genotype 1 in 84,75%, 2 in 6,78% and 3 in 8,47%.In 52,9% of the cases revealed liver reaction, however, an important proportion of patients showed histologic signs of fibrosis (29%).Theses results suggest the need to revisit the algorithm for liver biopsy practice

Transfer of the melanocyte-specific and lysosome-related organelle, the melanosome, from melanocytes to keratinocytes is crucial for the protection of the skin against harmful ultraviolet radiation (UVR)--our main physiological cutaneous stressor. However, this commonplace event remains a most enigmatic process despite several early hypotheses. Recently, we and others have proposed a role for filopodia in melanin transfer, although conclusive experimental proof remained elusive. Using known filopodial markers (MyoX/Cdc42) and the filopodial disrupter, low-dose cytochalasin-B, we demonstrate here a requirement for filopodia in melanosome transfer from melanocytes to keratinocytes and also, unexpectedly, between keratinocytes. Melanin distribution throughout the skin represents the key phenotypic event in skin pigmentation. Melanocyte filopodia were also necessary for UVR-stimulated melanosome transfer, as this was also inhibited by MyoX knockdown and low-dose cytochalasin-B. Knockdown of keratinocyte MyoX protein, in its capacity as a phagocytosis effector, resulted in the inhibition of melanin uptake by keratinocytes. This indicates a central role for phagocytosis by keratinocytes of melanocyte filopodia. In summary, we propose a new model for the regulation of pigmentation in human skin cells under both constitutive and facultative (post-UVR) conditions, which we call the "filopodial-phagocytosis model." This model also provides a unique and highly accessible way to study lysosome-related organelle movement between mammalian cells.

no / Retinal dystrophies are an overlapping group of genetically heterogeneous conditions resulting from mutations in more than 250 genes. Here we describe five families affected by an adult-onset retinal dystrophy with early macular involvement and associated central visual loss in the third or fourth decade of life. Affected individuals were found to harbor disease-causing variants in DRAM2 (DNA-damage regulated autophagy modulator protein 2). Homozygosity mapping and exome sequencing in a large, consanguineous British family of Pakistani origin revealed a homozygous frameshift variant (c.140delG [p.Gly47Valfs∗3]) in nine affected family members. Sanger sequencing of DRAM2 in 322 unrelated probands with retinal dystrophy revealed one European subject with compound heterozygous DRAM2 changes (c.494G>A [p.Trp165∗] and c.131G>A [p.Ser44Asn]). Inspection of previously generated exome sequencing data in unsolved retinal dystrophy cases identified a homozygous variant in an individual of Indian origin (c.64_66del [p.Ala22del]). Independently, a gene-based case-control association study was conducted via an exome sequencing dataset of 18 phenotypically similar case subjects and 1,917 control subjects. Using a recessive model and a binomial test for rare, presumed biallelic, variants, we found DRAM2 to be the most statistically enriched gene; one subject was a homozygote (c.362A>T [p.His121Leu]) and another a compound heterozygote (c.79T>C [p.Tyr27His] and c.217_225del [p.Val73_Tyr75del]). DRAM2 encodes a transmembrane lysosomal protein thought to play a role in the initiation of autophagy. Immunohistochemical analysis showed DRAM2 localization to photoreceptor inner segments and to the apical surface of retinal pigment epithelial cells where it might be involved in the process of photoreceptor renewal and recycling to preserve visual function.

Balding causes widespread psychological distress but is poorly controlled. The commonest treatment, minoxidil, was originally an antihypertensive drug that promoted unwanted hair. We hypothesized that another serendipitous discovery, increased eyelash growth side-effects of prostamide F(2alpha)-related eyedrops for glaucoma, may be relevant for scalp alopecias. Eyelash hairs and follicles are highly specialized and remain unaffected by androgens that inhibit scalp follicles and stimulate many others. Therefore, we investigated whether non-eyelash follicles could respond to bimatoprost, a prostamide F(2alpha) analog recently licensed for eyelash hypotrichosis. Bimatoprost, at pharmacologically selective concentrations, increased hair synthesis in scalp follicle organ culture and advanced mouse pelage hair regrowth in vivo compared to vehicle alone. A prostamide receptor antagonist blocked isolated follicle growth, confirming a direct, receptor-mediated mechanism within follicles; RT-PCR analysis identified 3 relevant receptor genes in scalp follicles in vivo. Receptors were located in the key follicle regulator, the dermal papilla, by analyzing individual follicular structures and immunohistochemistry. Thus, bimatoprost stimulates human scalp follicles in culture and rodent pelage follicles in vivo, mirroring eyelash behavior, and scalp follicles contain bimatoprost-sensitive prostamide receptors in vivo. This highlights a new follicular signaling system and confirms that bimatoprost offers a novel, low-risk therapeutic approach for scalp alopecias.