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1.
Proc Natl Acad Sci U S A ; 119(3)2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35027454

RESUMO

ARABIDOPSIS TRITHORAX-RELATED PROTEIN 5 (ATXR5) AND ATXR6 are required for the deposition of H3K27me1 and for maintaining genomic stability in Arabidopsis Reduction of ATXR5/6 activity results in activation of DNA damage response genes, along with tissue-specific derepression of transposable elements (TEs), chromocenter decompaction, and genomic instability characterized by accumulation of excess DNA from heterochromatin. How loss of ATXR5/6 and H3K27me1 leads to these phenotypes remains unclear. Here we provide extensive characterization of the atxr5/6 hypomorphic mutant by comprehensively examining gene expression and epigenetic changes in the mutant. We found that the tissue-specific phenotypes of TE derepression and excessive DNA in this atxr5/6 mutant correlated with residual ATXR6 expression from the hypomorphic ATXR6 allele. However, up-regulation of DNA damage genes occurred regardless of ATXR6 levels and thus appears to be a separable process. We also isolated an atxr6-null allele which showed that ATXR5 and ATXR6 are required for female germline development. Finally, we characterize three previously reported suppressors of the hypomorphic atxr5/6 mutant and show that these rescue atxr5/6 via distinct mechanisms, two of which involve increasing H3K27me1 levels.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Elementos de DNA Transponíveis , Regulação da Expressão Gênica de Plantas , Instabilidade Genômica , Metiltransferases/genética , Alelos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Epigênese Genética , Heterocromatina/metabolismo , Histonas/metabolismo , Metiltransferases/metabolismo , Mutação , Fenótipo , Transcriptoma
2.
Cancer ; 123(5): 879-886, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-27763689

RESUMO

BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) are debilitating diseases for which a patient's prognosis depends heavily on complete tumor resection. Currently, the surgeon's fingers determine the location of tissue margins. This study evaluated the diagnostic utility of a novel imaging modality, dynamic optical contrast imaging (DOCI), in the detection of HNSCC. This system generates contrast by illuminating the tissue with pulsed light and detecting variations in endogenous fluorophore lifetimes. METHODS: A total of 47 fresh ex vivo samples from 15 patients were imaged with the DOCI system immediately after surgical resection. DOCI maps were analyzed to determine the statistical significance of contrast between tumors and adjacent nonmalignant tissue. Pilot intraoperative clinical data were also acquired. RESULTS: Statistical significance (P < .05) between muscle and tumor was established for 10 of 10 emission wavelengths, between collagen and tumor for 8 of 10 emission wavelengths, and between fat and tumor for 2 of 10 wavelengths. The system extracted relative fluorescence decay information in a surgically relevant field of view in <2 minutes. CONCLUSIONS: This study demonstrates the feasibility of using DOCI to rapidly and accurately distinguish HNSCC from surrounding normal tissue. An analysis of DOCI images revealed microscopic characterization sufficient for tissue-type identification consistent with histology. Such an intraoperative tool would be transformative by allowing the rapid delineation of tumor tissue from nontumor tissue and thus maximizing the efficacy of resection and improving patient outcomes. Cancer 2017;123:879-86. © 2016 American Cancer Society.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Diagnóstico por Imagem/métodos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Imagem Óptica/métodos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço
3.
J Biophotonics ; 14(12): e202100191, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34453488

RESUMO

Gingivitis is highly prevalent in adults, and if left untreated, can progress to periodontitis. In this article, we present an interesting case study where the resolution of gingivitis was followed over a period of 10 days using optical coherence tomography (OCT) and light-induced autofluorescence (LIAF). We demonstrate that OCT and its functional angiography can distinctively capture the changes during the resolution of gingivitis; while LIAF can detect red-fluorescent signals associated with mature plaque present at the inflamed site. The acute inflammatory region showed evidence of angiogenesis based on the quantification of vessel density and number; while no angiogenesis was detected within the less inflamed region. Gingival thickness showed a reduction of 140 ± 26 µm on average, measured between the peak gingivitis event and the period wherein the inflammation was resolved. Vessels in the angiogenesis site was found to reduce exponentially. The mildly inflamed site showed a decreasing trend in the vessel size, which however was within the error of the measurement.


Assuntos
Gengivite , Periodontite , Adulto , Angiografia , Gengiva , Gengivite/diagnóstico por imagem , Humanos , Tomografia de Coerência Óptica
4.
Int J Med Robot ; 14(6): e1949, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30152081

RESUMO

BACKGROUND: With the development of laser-assisted platforms, the outcomes of cataract surgery have been improved by automating several procedures. The cataract-extraction step continues to be manually performed, but due to deficiencies in sensing capabilities, surgical complications such as posterior capsule rupture and incomplete cataract removal remain. METHODS: An optical coherence tomography (OCT) system is integrated into our intraocular robotic interventional surgical system (IRISS) robot. The OCT images are used for preoperative planning and intraoperative intervention in a series of automated procedures. Real-time intervention allows surgeons to evaluate the progress and override the operation. RESULTS: The developed system was validated by performing lens extraction on 30 postmortem pig eyes. Complete lens extraction was achieved on 25 eyes, and "almost complete" extraction was achieved on the remainder due to an inability to image small lens particles behind the iris. No capsule rupture was found. CONCLUSION: The IRISS successfully demonstrated semiautomated OCT-guided lens removal with real-time supervision and intervention.


Assuntos
Extração de Catarata/instrumentação , Catarata , Tomografia de Coerência Óptica/instrumentação , Animais , Automação , Extração de Catarata/métodos , Desenho de Equipamento , Humanos , Procedimentos Cirúrgicos Robóticos , Software , Suínos , Tomografia de Coerência Óptica/métodos
5.
Otolaryngol Head Neck Surg ; 156(3): 480-483, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28116982

RESUMO

The variable location and indistinct features of parathyroid glands can make their intraoperative identification challenging. Currently, there exists no routine use of localization methods during surgery. Dynamic optical contrast imaging (DOCI) leverages a novel realization of temporally dependent measurements of tissue autofluorescence that allows the acquisition of specific tissue properties. A prospective series of patients with primary hyperparathyroidism was examined. Parathyroid lesions and surrounding tissues were collected; fluorescence decay images were acquired via DOCI. Ex vivo samples (81 patients) were processed for histologic assessment. DOCI extracts relative fluorescence decay information in a surgically relevant field of view with a clinically accessible acquisition time <2 minutes. Analysis of DOCI revealed microscopic characterization sufficient for tissue type identification consistent with histology ( P < .05). DOCI is capable of efficiently distinguishing parathyroid tissue from adjacent tissues. Such an intraoperative tool would be transformative, helping surgeons to identify lesions, preserve healthy tissue, and improve patient outcomes.


Assuntos
Imagem Óptica , Glândulas Paratireoides/anatomia & histologia , Glândulas Paratireoides/diagnóstico por imagem , Humanos , Hiperparatireoidismo Primário/diagnóstico por imagem , Hiperparatireoidismo Primário/cirurgia
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