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1.
J Geophys Res Planets ; 127(11): e2022JE007492, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37035521

RESUMO

A nearly pole-to-pole survey near 140°E longitude on Europa revealed many areas that exhibit past lateral surface motions, and these areas were examined to determine whether the motions can be described by systems of rigid plates moving across Europa's surface. Three areas showing plate-like behavior were examined in detail to determine the sequence of events that deformed the surface. All three areas were reconstructed to reveal the original pre-plate motion surfaces by performing multi-stage rotations of plates in spherical coordinates. Several motions observed along single plate boundaries were also noted in previous works, but this work links together isolated observations of lateral offsets into integrated systems of moving plates. Not all of the surveyed surface could be described by systems of rigid plates. There is evidence that the plate motions did not all happen at the same time, and that they are not happening today. We conclude that plate tectonic-like behavior on Europa occurs episodically, in limited regions, with less than 100 km of lateral motion accommodated along any particular boundary before plate motions cease. Europa may represent a world perched on the theoretical boundary between stagnant and mobile lid convective behavior, or it may represent an additional example of the wide variations in possible planetary convective regimes. Differences in observed strike-slip sense and plate rotation directions between the northern and southern hemispheres raise the question of whether tidal forces may influence plate motions.

2.
Ophthalmol Eye Dis ; 8: 31-2, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27528805

RESUMO

Age-related macular degeneration (AMD) is one of the leading causes of blindness in developed countries in people over the age of 60 years. One of the forms of advanced AMD is wet AMD. Wet AMD is a result of leakage and bleeding from abnormal neovascularization. The principal treatment for wet AMD is intravitreal anti-VEGF injections. A second form of advanced AMD is geographic atrophy (GA). GA refers to large areas of retinal pigment epithelium loss. In the literature, there is some concern that anti-VEGF injections administered to treat wet AMD may be associated with progression of GA. This review discusses evidence suggesting the association of anti-VEGF injections with progression of GA.

3.
J Clin Invest ; 123(7): 2994-3001, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23778142

RESUMO

Due to their efficient transduction potential, adeno-associated virus (AAV) vectors are leading candidates for gene therapy in skeletal muscle diseases. However, immune responses toward the vector or transgene product have been observed in preclinical and clinical studies. TLR9 has been implicated in promoting AAV-directed immune responses, but vectors have not been developed to circumvent this barrier. To assess the requirement of TLR9 in promoting immunity toward AAV-associated antigens following skeletal muscle gene transfer in mice, we compared immunological responses in WT and Tlr9-deficient mice that received an AAV vector with an immunogenic capsid, AAVrh32.33. In Tlr9-deficient mice, IFN-γ T cell responses toward capsid and transgene antigen were suppressed, resulting in minimal cellular infiltrate and stable transgene expression in target muscles. These findings suggest that AAV-directed immune responses may be circumvented by depleting the ligand for TLR9 (CpG sequences) from the vector genome. Indeed, we found that CpG-depleted AAVrh32.33 vectors could establish persistent transgene expression, evade immunity, and minimize infiltration of effector cells. Thus, CpG-depleted AAV vectors could improve outcome of clinical trials of gene therapy for skeletal muscle disease.


Assuntos
Ilhas de CpG , DNA Viral/imunologia , Dependovirus/imunologia , Terapia Genética , Evasão da Resposta Imune , Imunidade Adaptativa , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Capsídeo/imunologia , Quimiocinas/metabolismo , DNA Viral/genética , Dependovirus/genética , Vetores Genéticos , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Esquelético/imunologia , Músculo Esquelético/metabolismo , Receptor Toll-Like 9/deficiência , Receptor Toll-Like 9/genética , Transdução Genética , Transgenes
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