Identification of novel mutations in X-linked retinitis pigmentosa families and implications for diagnostic testing

Contains fulltext : 69886.pdf (publisher's version ) (Open Access)PURPOSE: The goal of this study was to identify mutations in X-chromosomal genes associated with retinitis pigmentosa (RP) in patients from Germany, The Netherlands, Denmark, and Switzerland. METHODS: In addition to all coding exons of RP2, exons 1 through 15, 9a, ORF15, 15a and 15b of RPGR were screened for mutations. PCR products were amplified from genomic DNA extracted from blood samples and analyzed by direct sequencing. In one family with apparently dominant inheritance of RP, linkage analysis identified an interval on the X chromosome containing RPGR, and mutation screening revealed a pathogenic variant in this gene. Patients of this family were examined clinically and by X-inactivation studies. RESULTS: This study included 141 RP families with possible X-chromosomal inheritance. In total, we identified 46 families with pathogenic sequence alterations in RPGR and RP2, of which 17 mutations have not been described previously. Two of the novel mutations represent the most 3'-terminal pathogenic sequence variants in RPGR and RP2 reported to date. In exon ORF15 of RPGR, we found eight novel and 14 known mutations. All lead to a disruption of open reading frame. Of the families with suggested X-chromosomal inheritance, 35% showed mutations in ORF15. In addition, we found five novel mutations in other exons of RPGR and four in RP2. Deletions in ORF15 of RPGR were identified in three families in which female carriers showed variable manifestation of the phenotype. Furthermore, an ORF15 mutation was found in an RP patient who additionally carries a 6.4 kbp deletion downstream of the coding region of exon ORF15. We did not identify mutations in 39 sporadic male cases from Switzerland. CONCLUSIONS: RPGR mutations were confirmed to be the most frequent cause of RP in families with an X-chromosomal inheritance pattern. We propose a screening strategy to provide molecular diagnostics in these families

Visual interpretations on dark humor

Bu tezde kara mizahın görsel sanatlar alanında varlığı ve belirleyici faktörleri araştırılmıştır. Araştırmanın görsel sanatlarda kara mizah anlayışının ifade dilleri örnekler üzerinden analizlerle açıklanmaya çalışılmış ve çıkan sonuçların kişisel çalışmalara yön vermesi amaçlanmıştır. Bu kapsamda gülme kuramları ile bu kuramların, mizah ve kara mizahla bağlantısı irdelenerek; kara mizahın mizahtan görsel sanatlar içinde nasıl farklılaştığı belirlenmeye çalışılmıştır. Kara mizahın gülme ile ilişkisi bağlamında tarihsel süreç içinde toplumsal olayların, değişen kültürel kodların ve iktidarın gülme olgusuna etkileri sebebiyle görsel kara mizahın tüm bunlardan nasıl etkilendiği ve kültür tarihine etkileri araştırılmıştır. Kara mizahi anlatımın felsefi köklerine de yer verilerek sadece sanatsal bir ifade yöntemi olmaktan çok bir felsefi bakış açısı olarak varoluşçuluk, romantizm felsefeleriyle resim sanatı içinde nasıl buluştuğu açıklanmıştır. Özellikle Mihail Bahtin'in karnavalesk dünya görüşü bağlamında ifade özgürlüğü ile ilişkisi incelenmiştir. Çeşitli tarihsel örneklerin kara mizah ile ilişkisi kurularak, görsel kara mizahi ifade dilinin edebiyat, tiyatro ve karikatür gibi farklı disiplinlerle etkileşimi ortaya çıkarılmıştır. Parodi, pastiş, ironi, grotesk, alegori, satir vb. kavramların görsel ifadeye nasıl hizmet ettiği çözümlenerek tez süreci boyunca yürütülen kişisel çalışmalara hem biçim hem içerik bağlamında ışık tutmuştur. Kişisel yapıtlarda anlatı anlayışı ile figüratif kara mizahi kompozisyonlar oluşturulmuştur. Kara Mizahın köklerinin komedya ve pagan kültürlerindeki gülme ritüelleri ile bağlantısı sonucunda eleştirel ve protest tavrının, herkes için eşit ifade özgürlüğünü destekleyerek toplumsal değişim gücünü elinde tuttuğu ve tam da bu sebeple ortaya çıktığı ilk zamanlardan itibaren her daim baskılanmaya çalışıldığı gözlemlenmiştir. Özellikle günümüz politik doğruculuk ikliminde, gülmenin ve alayın gücü gitgide kontrol altına alınmaya çalışılırken retoriğe kıyasla görsel kara mizahın kendisine nasıl alan açabildiği belirlenmiştir. Araştırma sürecinde basılı ve elektronik kaynaklardan yararlanılmıştır. Sanatçı web siteleri, müze ve galeri web siteleri incelenmiştir. Anahtar Kelimeler: Kara mizah, Görsel kara mizah, Resim sanatı, Karnavalesk, İfade özgürlüğüThis thesis investigates the existence and determining factors of dark humor in the art of painting. Historical works were analyzed to explain the expression techniques of the black humor in painting and guided personal artworks. The theories of laughter and its connection to humor, particularly dark humor revisited to demonstrate how black humor differs from humor in visual arts. In the context of the relationship between black humor and laughter, due to its effects of social events, changing cultural codes and power on the phenomenon of laughter in the historical process, how black humor is affected by all these in visual arts and vice versa. The philosophical roots of black humor are also discovered in this thesis. It is explained how it meets the philosophies of existentialism, romanticism in visual art practice as a philosophical point of view rather than just an artistic expression method. Especially in the context of Mihail Bahtin's carnivalesque worldview, its relationship with freedom of expression and its development are analyzed. The author revealed the historical traces of dark humor in visual arts and the connections to other art forms (literature, theater, and caricature). Answers about how the methods such as; parody, pastiche, irony, grotesque, allegory, and satire serve visual expression, guide the personal creative practice of narrative painting and visual black humor in terms of both, form and content. Historical analysis revealed that dark humor is rooted in the rituals of pagan cultures as a tool for social change endorsing freedom of expression for everyone equally. Consequently, dark humor has always been a subject of censorship. In today's climate of political correctness, while the power of laughter and satire is heavily regulated, new spaces for visual dark humor emerged. Printed and electronic sources, including artist, museum, and gallery websites, were utilized during this research. Keywords: Dark humor, Visual dark humor, Painting art, Carnivalesque, Freedom of expressio

Electron Microscopy of the Human Placenta

Sections of two human placentas (full term and 3 months in pregnancy) are studied with electron microscope, and the following results are obtained. 1) The free suface of syncytial cells touching the inter-villous space is covered with many club-shaped microvilli. Although no apparent cellular border is detected among syncytial cells, there are intercellular bridges between syncytial cell and Langhans' cell. 2) The picture, which syncytial cells are in contact with basement membrane directly, is also seen. 3) The endoplasmic reticula are in vesicule ca. 3 in diameter in the early placenta, and become to ca. 2 vacuole in the full term placenta. 4) The osmiophilic lipid granules are seen in syncytial cells, but hardly in Langhans' cells. 5) Besides vacuoles under microvilli, we recognize the macular substances in the cytoplasm of the early placenta, which appear in the somewhat highly election dense and structureless. 6) The nuclear difference between the syncytial and Langhans' cells, which was reported by Boyd and Hughes, should be interpreted as the autolytic change. On this point, I agree with the Isomura's opinion that ether of them is composed of homogeneous fine granular particles. 7) The cellular border of the Langhans' cells is distinct, and simpler than synytial cell in fine structures of cytoplasma; a fewer endoplasmic reticula and almost no lipid granules. 8) The capillary endothelial cells arranged stratiform, and cytoplasmic protuberances from its outer surface are noticed