Fate of a redundant gamma-globin gene in the atelid clade of New World monkeys: implications concerning fetal globin gene expression.

Conclusive evidence was provided that gamma 1, the upstream of the two linked simian gamma-globin loci (5'-gamma 1-gamma 2-3'), is a pseudogene in a major group of New World monkeys. Sequence analysis of PCR-amplified genomic fragments of predicted sizes revealed that all extant genera of the platyrrhine family Atelidae [Lagothrix (woolly monkeys), Brachyteles (woolly spider monkeys), Ateles (spider monkeys), and Alouatta (howler monkeys)] share a large deletion that removed most of exon 2, all of intron 2 and exon 3, and much of the 3' flanking sequence of gamma 1. The fact that two functional gamma-globin genes were not present in early ancestors of the Atelidae (and that gamma 1 was the dispensible gene) suggests that for much or even all of their evolution, platyrrhines have had gamma 2 as the primary fetally expressed gamma-globin gene, in contrast to catarrhines (e.g., humans and chimpanzees) that have gamma 1 as the primary fetally expressed gamma-globin gene. Results from promoter sequences further suggest that all three platyrrhine families (Atelidae, Cebidae, and Pitheciidae) have gamma 2 rather than gamma 1 as their primary fetally expressed gamma-globin gene. The implications of this suggestion were explored in terms of how gene redundancy, regulatory mutations, and distance of each gamma-globin gene from the locus control region were possibly involved in the acquisition and maintenance of fetal, rather than embryonic, expression.

Biochemical characterization and DNA binding properties of the MocR family member GabR, a PLP-dependent transcription factor

GabR è un fattore di trascrizione chimerico appartenente alla famiglia dei MocR/GabR, costituito da un dominio N-terminale elica-giro-elica di legame al DNA e un dominio effettore e/o di oligomerizzazione al C-terminale. I due domini sono connessi da un linker flessibile di 29 aminoacidi. Il dominio C-terminale è strutturalmente omologo agli enzimi aminotransferasici fold-type I, i quali, utilizzando il piridossal-5’-fosfato (PLP) come cofattore, sono direttamente coinvolti nel metabolismo degli aminoacidi. L’interazione contemporanea di PLP e acido γ-aminobutirrico (GABA) a GabR fa sì che questa promuova la trascrizione di due geni, gabT e gabD, implicati nel metabolismo del GABA. GabR cristallizza come un omodimero con una configurazione testa-coda. Il legame con la regione promotrice gabTD avviene attraverso il riconoscimento specifico di due sequenze dirette e ripetute (ATACCA), separate da uno spacer di 34 bp. In questo studio sono state indagate le proprietà biochimiche, strutturali e di legame al DNA della proteina GabR di Bacillus subtilis. L’analisi spettroscopica dimostra che GabR interagisce con il PLP formando l’aldimina interna, mentre in presenza di GABA si ottiene l’aldimina esterna. L’interazione fra il promotore gabTD e le forme holo e apo di GabR è stata monitorata mediante Microscopia a Forza atomica (AFM). In queste due condizioni di legame è stata stimata una Kd di circa 40 ηM. La presenza di GABA invece, determinava un incremento di circa due volte della Kd, variazioni strutturali nei complessi GabR-DNA e una riduzione del compattamento del DNA alla proteina, indipendentemente dalla sequenza del promotore in esame. Al fine di valutare il ruolo delle caratteristiche topologiche del promotore, sono state inserite cinque e dieci bp all’interno della regione spacer che separa le due sequenze ripetute dirette riconosciute da GabR. I significativi cambiamenti topologici riscontrati nel frammento aggiunto di cinque bp si riflettono anche sulla forte riduzione dell’affinità di legame verso la proteina. Al contrario, l’inserzione di 10 bp provoca solamente l’allontanamento delle sequenze ripetute dirette. L’assenza quindi di cambiamenti significativi nella topologia di questo promotore fa sì che l’affinità di legame per GabR rimanga pressoché inalterata rispetto al promotore non mutato. L’analisi del potenziale elettrostatico superficiale di GabR mostra la presenza di una fascia carica positivamente che si estende lungo un’intera faccia della proteina. Per verificare l’importanza di questa caratteristica di GabR nel meccanismo di interazione al DNA, sono stati preparati ed indagati i mutanti R129Q e K362-366Q, in cui la carica positiva superficiale risultava indebolita. L’affinità di legame dei mutanti di GabR per il DNA era inferiore rispetto alla proteina non mutata, in particolar modo nel mutante K362-366Q. Le evidenze acquisite suggeriscono che la curvatura intrinseca del promotore ed il corretto orientamento delle sequenze sulla doppia elica, più della distanza che le separa, siano critici per sostenere l’interazione con GabR. Oltre a questo, la superficie positiva di GabR è richiesta per accomodare la curvatura del DNA sul corpo della proteina. Alla luce di questo, l’interazione GabR-gabTD è un esempio di come il riconoscimento specifico di sequenze, la topologia del DNA e le caratteristiche strutturali della proteina siano contemporaneamente necessarie per sostenere un’interazione proteina-DNA stabile.

Avaliação de fatores virológicos associados ao desenvolvimento de carcinoma hepatocelular (CHC) em pacientes com hepatite B crônica

O objetivo principal deste estudo foi avaliar fatores virais associados com a evolução para o carcinoma hepatocelular (CHC) em pacientes com hepatite B crônica. Para tanto caracterizamos os subgenótipos do HBV, investigamos a ocorrência de mutações nos genes pré-core/core do HBV associadas à presença de CHC avaliamos por análise filogenética a associação de linhagens virais com a ocorrência de CHC e por fim a associação de outros fatores de risco com o desenvolvimento de CHC. Foram incluídos 119 amostras de soro de pacientes com infecção crônica pelo HBV, destas amostras 60 pertencem ao grupo 1 (CHC), que são pacientes com diagnóstico confirmado de carcinoma hepatocelular e 59 amostras pertencem ao grupo 2 (sem CHC) que são pacientes com hepatite crônica sem detecção prévia de nódulos hepáticos. Foram obtidas informações acerca da idade, sexo e naturalidade. Além disso, os pacientes responderam a um questionário sobre fatores de riscos associados ao desenvolvimento de CHC. Foram realizados exames bioquímicos, sorológicos, determinação da carga viral, e amplificação por nested PCR e sequenciamento das regiões S/polimerase e pré-core/core do genoma viral para posterior caracterização dos genótipos/subgenótipos do HBV e pesquisa de mutações associadas com evolução da doença hepática. Em relação à idade e sexo não houve grande variação entre os grupos. Quanto à naturalidade a maioria era procedente da região sudeste, seguido pela região nordeste; e por fim seis pacientes eram procedentes de outros países. Com base no sobrenome dos pacientes avaliou-se também a frequência de etnia oriental na casuística estudada, que foi similar nos 2 grupos. O perfil sorológico HBeAg negativo foi o mais frequente nos dois grupos de pacientes, assim como níveis de carga viral abaixo de 2.000 UI/mL. Em relação aos exames bioquímicos foram observadas diferenças estatisticamente significantes nos níveis séricos de AFP (p= 0,0013), FA (p= 0,0003) e GGT (p= 0,005). Dentre os fatores de risco analisados neste estudo, o consumo de amendoim foi o único que apresentou significância estatística (p= 0,003). A região S/pol foi amplificada e sequenciada com sucesso em 58 amostras (28 do grupo 1 e 30 do grupo 2). Entre as 58 amostras analisadas 4 genótipos e 8 subgenótipos do HBV foram identificados, sendo o subgenótipo A1 o mais frequente nos dois grupos. Não se observou diferença estatisticamente significante na distribuição dos subgenótipos entre os dois grupos de pacientes. Na topologia da árvore filogenética construída com sequências do HBV isoladas dos pacientes incluídos neste estudo e sequências disponíveis no GenBank não se observou padrões de agrupamento associados com o perfil clinico do paciente (com e sem CHC). Foram obtidas sequências de boa qualidade da região précore/ core em 44 amostras, sendo 20 amostras do grupo 1 e 24 do grupo 2. Diversas das mutações investigadas foram identificadas na região précore/ core, as quais foram avaliadas estatisticamente para verificar a existência de diferença na frequência das mesmas entre os grupos de pacientes estudados. Entre as mutações identificadas se destacaram com significância estatística as seguintes mutações: T1768A (p= 0,006), a combinação das mutações C1766T + T1768A (p= 0,043) e G1888H (p= 0,05). Na análise de regressão logística simples foi possível identificar que a chance de um paciente do grupo 2 desenvolver CHC aumenta 14,7 vezes na presença de infecção por cepas do HBV com a mutação T1768A, enquanto que a infecção com cepas do HBV que albergam a mutação G1888H reduz tal chance 2,5 vezes

China 1:200,000 : Sheet H-50-XXIV : Zhejiang Sheng Region (Raster Image)

This layer is a georeferenced raster image of the Soviet Army topographic sheet map covering a portion of the Zhejiang Sheng region, China (map quadrangle number: H-50-XXIV). It is from a series of Soviet Army topographic maps of China 1:200,000. The source map was published in 1979. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Pulkovo 1942 GK Zone 20N projection. Map collar information from the source map have been cropped and are not available as part of the raster image. China 1:200,000 topographic maps were prepared and printed by the Soviet Army General Headquarters, 1976-1991. China 1:200,000 maps are in Russian. Each source map in the series is printed in color. China 1:200,000 maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works and structures of humans, such as roads, railroads, paths, walls, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 40 meters and/or spot heights.

China 1:200,000 : Sheet H-50-XXX : Zhejiang Sheng Region (Raster Image)

This layer is a georeferenced raster image of the Soviet Army topographic sheet map covering a portion of the Zhejiang Sheng region, China (map quadrangle number: H-50-XXX). It is from a series of Soviet Army topographic maps of China 1:200,000. Published in 1979, the source map was compiled from maps 1:100,000 published in 1977; corrected according to source material, 1970-1975. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Pulkovo 1942 GK Zone 20N projection. Map collar information from the source map have been cropped and are not available as part of the raster image. China 1:200,000 topographic maps were prepared and printed by the Soviet Army General Headquarters, 1976-1991. China 1:200,000 maps are in Russian. Each source map in the series is printed in color. China 1:200,000 maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works and structures of humans, such as roads, railroads, paths, walls, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 40 meters and/or spot heights.

China 1:200,000 : Shaoxing Region, Zhejiang Sheng (Raster Image)

This layer is a georeferenced raster image of the Soviet Army topographic sheet map of the Shaoxing region, Zhejiang Sheng, China (map quadrangle number: H-51-XIX). It is from a series of Soviet Army topographic maps of China 1:200,000. Published in 1979, the source map was compiled from maps 1:100,000 published in 1977; corrected according to source material, 1973, 1974. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Pulkovo 1942 GK Zone 20N projection. Map collar information from the source map have been cropped and are not available as part of the raster image. China 1:200,000 topographic maps were prepared and printed by the Soviet Army General Headquarters, 1976-1991. China 1:200,000 maps are in Russian. Each source map in the series is printed in color. China 1:200,000 maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works and structures of humans, such as roads, railroads, paths, walls, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 40 meters and/or spot heights.

China 1:200,000 : Xianju Region, Zhejiang Sheng (Raster Image)

This layer is a georeferenced raster image of the Soviet Army topographic sheet map of the Xianju region, Zhejiang Sheng, China (map quadrangle number: H-51-XXV). It is from a series of Soviet Army topographic maps of China 1:200,000. Published in 1986, this map reflects 1979 ground conditions. The source map was compiled from maps 1:100,000 published in 1979. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Pulkovo 1942 GK Zone 20N projection. Map collar information from the source map have been cropped and are not available as part of the raster image. China 1:200,000 topographic maps were prepared and printed by the Soviet Army General Headquarters, 1976-1991. China 1:200,000 maps are in Russian. Each source map in the series is printed in color. China 1:200,000 maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works and structures of humans, such as roads, railroads, paths, walls, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 40 meters and/or spot heights.

China 1:200,000 : Wezhou Region, Zhejiang Sheng (Raster Image)

This layer is a georeferenced raster image of the Soviet Army topographic sheet map of the Wenzhou region, Zhejiang Sheng, China (map quadrangle number: H-51-XXXI). It is from a series of Soviet Army topographic maps of China 1:200,000. Published in 1986, this map reflects 1979 ground conditions. The source map was compiled from maps 1:100,000 published in 1979. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Pulkovo 1942 GK Zone 20N projection. Map collar information from the source map have been cropped and are not available as part of the raster image. China 1:200,000 topographic maps were prepared and printed by the Soviet Army General Headquarters, 1976-1991. China 1:200,000 maps are in Russian. Each source map in the series is printed in color. China 1:200,000 maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works and structures of humans, such as roads, railroads, paths, walls, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 40 meters and/or spot heights.

China 1:200,000 : Lishui Region, Zhejiang Sheng (Raster Image)

This layer is a georeferenced raster image of the Soviet Army topographic sheet map of the Lishui region, Zhejiang Sheng, China (map quadrangle number: H-50-XXXVI). It is from a series of Soviet Army topographic maps of China 1:200,000. Published in 1979, the source map was compiled from maps 1:100,000 published in 1977; corrected according to source material, 1973-1975. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Pulkovo 1942 GK Zone 20N projection. Map collar information from the source map have been cropped and are not available as part of the raster image. China 1:200,000 topographic maps were prepared and printed by the Soviet Army General Headquarters, 1976-1991. China 1:200,000 maps are in Russian. Each source map in the series is printed in color. China 1:200,000 maps are typical topographic maps portraying both natural and manmade features. They show and name works of nature, such as mountains, valleys, lakes, rivers, vegetation, etc. They also identify the principal works and structures of humans, such as roads, railroads, paths, walls, boundaries, transmission lines, major buildings, etc. Relief is shown with standard contour intervals of 40 meters and/or spot heights.

Age constraints on the tectonic evolution of the Itremo region in Central Madagascar

The Itremo region in Central Madagascar comprises a deformed metasedimentary sequence (Itremo Group) that has undergone greenschist to lower amphibolite facies metamorphism. During a first phase of deformation (D1) Itremo Group sediments were deformed into a fold-and-thrust belt and transported toward the E to NE on top of migmatitic gneisses rocks of Anatananarivo block. A second phase of deformation (D2) affected both the fold-and-thrust belt and structurally underlying units, and formed large-scale N-S trending folds with steeply dipping axial planes. A Late Neoproterozoic Th–U–Pb XRF monazite age (565±17 Ma) dates the emplacement of a granite that truncates first-phase structures in the Itremo Group, and indicates that the fold-and-thrust belt formed prior to ≈565 Ma. Th–U–Pb electron microprobe dating was applied to elongated monazites that lie within the first-phase foliation of Itremo Group metapelites. The detrital cores of zoned monazites reveal two distinct age populations at ∼2000 and 1700 Ma, the latter age giving a maximum depositional age for the Itremo Group. Statistical analysis of ages determined from the rims of zoned monazites and from unzoned monazites indicates three Late Proterozoic–Early Paleozoic monazite growth events at about 565–540, 500 and 430 Ma. The oldest age population is contemporaneous within error, with the intrusion of the dated granite. The two younger age populations are found both in the Th–U–Pb and Ar–Ar data; together with the perturbation of the Rb–Sr system we interpret both ages as due to alteration related to fluid circulation events, possibly connected to the emplacement of pegmatite fields in Central Madagascar. Syn-D1 tectonic growth of contact metamorphism minerals such as andalusite has been observed locally in metapelites along the margin of Middle Neoproterozoic (≈800 Ma) granites, suggesting that D1 in the Itremo Group is contemporaneous with the intrusion of granites at ≈800 Ma. The N-S trending D2 folds are associated with ≈E-W shortening during the final assembly of Gondwana in Late Neoproterozoic–Early Cambrian times.

Mineralogical composition of the upper 300m of Hole 302-M0002A

During the Arctic Coring Expedition (ACEX), a 428-m-thick sequence of Upper Cretaceous to Quaternary sediments was penetrated. The mineralogical composition of the upper 300 m of this sequence is presented here for the first time. Heavy and clay mineral associations indicate a major and consistent shift in provenance, from the Barents-Kara - western Laptev Sea region, characterized by presence of common clinopyroxene, to the eastern Laptev-East Siberian seas in the upper part of the section, characterized by common hornblende (amphibole). Sea ice originating from the latter source region must have survived at least one summer melt cycle in order to reach the ACEX drill site, if considering modern sea ice trajectories and velocities. This shift in mineral assemblages probably represents the onset of a perennial sea ice cover in the Arctic Ocean, which occurred at about 13 Ma, thus suggesting a coeval freeze in the Arctic and Antarctic regions.

(Table 1) Radiocarbon and OSL ages of sediment cores C1-C5 drilled during the COAST expedition to Cape Mamontov Klyk in April 2005

The palaeoenvironmental development of the western Laptev Sea is understood primarily from investigations of exposed cliffs and surface sediment cores from the shelf. In 2005, a core transect was drilled between the Taymyr Peninsula and the Lena Delta, an area that was part of the westernmost region of the non-glaciated Beringian landmass during the late Quaternary. The transect of five cores, one terrestrial and four marine, taken near Cape Mamontov Klyk reached 12 km offshore and 77 m below sea level. A multiproxy approach combined cryolithological, sedimentological, geochronological (14C-AMS, OSL on quartz, IR-OSL on feldspars) and palaeoecological (pollen, diatoms) methods. Our interpretation of the proxies focuses on landscape history and the transition of terrestrial into subsea permafrost. Marine interglacial deposits overlain by relict terrestrial permafrost within the same offshore core were encountered in the western Laptev Sea. Moreover, the marine interglacial deposits lay unexpectedly deep at 64 m below modern sea level 12 km from the current coastline, while no marine deposits were encountered onshore. This implies that the position of the Eemian coastline presumably was similar to today's. The landscape reconstruction suggests Eemian coastal lagoons and thermokarst lakes, followed by Early to Middle Weichselian fluvially dominated terrestrial deposition. During the Late Weichselian, this fluvial landscape was transformed into a poorly drained accumulation plain, characterized by widespread and broad ice-wedge polygons. Finally, the shelf plain was flooded by the sea during the Holocene, resulting in the inundation and degradation of terrestrial permafrost and its transformation into subsea permafrost.

A sequence of destruction : mountain pine beetle and wildfire : Yellowstone National Park /

"9/93"--P. [2] of cover.

Characterizing Healthcare Utilization, Direct Costs, and Comorbidities Associated with Interstitial Cystitis: A Retrospective Claims Analysis

Thesis (Master's)--University of Washington, 2016-06

Function and Regulation of Cytochrome P450 4V2 and the Implications in Bietti’s Crystalline Dystrophy

Thesis (Ph.D.)--University of Washington, 2016-06