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1.
J Immunol ; 206(10): 2376-2385, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33893171

RESUMO

NLRP3 inflammasome plays an important role in innate immune system through recognizing pathogenic microorganisms and danger-associated molecules. Deubiquitination of NLRP3 has been shown to be essential for its activation, yet the functions of Ubc13, the K63-linked specific ubiquitin-conjugating enzyme E2, in NLRP3 inflammasome activation are not known. In this study, we found that in mouse macrophages, Ubc13 knockdown or knockout dramatically impaired NLRP3 inflammasome activation. Catalytic activity is required for Ubc13 to control NLRP3 activation, and Ubc13 pharmacological inhibitor significantly attenuates NLRP3 inflammasome activation. Mechanistically, Ubc13 associates with NLRP3 and promotes its K63-linked polyubiquitination. Through mass spectrum and biochemical analysis, we identified lysine 565 and lysine 687 as theK63-linked polyubiquitination sites of NLRP3. Collectively, our data suggest that Ubc13 potentiates NLRP3 inflammasome activation via promoting site-specific K63-linked ubiquitination of NLRP3. Our study sheds light on mechanisms of NLRP3 inflammasome activation and identifies that targeting Ubc13 could be an effective therapeutic strategy for treating aberrant NLRP3 inflammasome activation-induced pathogenesis.


Assuntos
Inflamassomos/metabolismo , Lisina/metabolismo , Macrófagos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Poliubiquitina/metabolismo , Enzimas de Conjugação de Ubiquitina/deficiência , Ubiquitinação/genética , Animais , Células HEK293 , Humanos , Inflamassomos/imunologia , Macrófagos/imunologia , Camundongos , Camundongos Transgênicos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Ligação Proteica , Transfecção , Enzimas de Conjugação de Ubiquitina/antagonistas & inibidores , Enzimas de Conjugação de Ubiquitina/genética , Ubiquitinação/efeitos dos fármacos
2.
Sensors (Basel) ; 19(12)2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31200576

RESUMO

Flood has an important effect on plant growth by affecting their physiologic and biochemical properties. Soybean is one of the main cultivated crops in the world and the United States is one of the largest soybean producers. However, soybean plant is sensitive to flood stress that may cause slow growth, low yield, small crop production and result in significant economic loss. Therefore, it is critical to develop soybean cultivars that are tolerant to flood. One of the current bottlenecks in developing new crop cultivars is slow and inaccurate plant phenotyping that limits the genetic gain. This study aimed to develop a low-cost 3D imaging system to quantify the variation in the growth and biomass of soybean due to flood at its early growth stages. Two cultivars of soybeans, i.e. flood tolerant and flood sensitive, were planted in plant pots in a controlled greenhouse. A low-cost 3D imaging system was developed to take measurements of plant architecture including plant height, plant canopy width, petiole length, and petiole angle. It was found that the measurement error of the 3D imaging system was 5.8% in length and 5.0% in angle, which was sufficiently accurate and useful in plant phenotyping. Collected data were used to monitor the development of soybean after flood treatment. Dry biomass of soybean plant was measured at the end of the vegetative stage (two months after emergence). Results show that four groups had a significant difference in plant height, plant canopy width, petiole length, and petiole angle. Flood stress at early stages of soybean accelerated the growth of the flood-resistant plants in height and the petiole angle, however, restrained the development in plant canopy width and the petiole length of flood-sensitive plants. The dry biomass of flood-sensitive plants was near two to three times lower than that of resistant plants at the end of the vegetative stage. The results indicate that the developed low-cost 3D imaging system has the potential for accurate measurements in plant architecture and dry biomass that may be used to improve the accuracy of plant phenotyping.


Assuntos
Produtos Agrícolas , Glycine max/anatomia & histologia , Imageamento Tridimensional/métodos , Folhas de Planta/anatomia & histologia , Biomassa , Inundações , Folhas de Planta/crescimento & desenvolvimento , Proteínas de Plantas/química , Glycine max/classificação
3.
Sci Immunol ; 8(81): eade1167, 2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-36961908

RESUMO

Insertions and deletions (indels) are low-frequency deleterious genomic DNA alterations. Despite their rarity, indels are common, and insertions leading to long complementarity-determining region 3 (CDR3) are vital for antigen-binding functions in broadly neutralizing and polyreactive antibodies targeting viruses. Because of challenges in detecting indels, the mechanism that generates indels during immunoglobulin diversification processes remains poorly understood. We carried out ultra-deep profiling of indels and systematically dissected the underlying mechanisms using passenger-immunoglobulin mouse models. We found that activation-induced cytidine deaminase-dependent ±1-base pair (bp) indels are the most prevalent indel events, biasing deleterious outcomes, whereas longer in-frame indels, especially insertions that can extend the CDR3 length, are rare outcomes. The ±1-bp indels are channeled by base excision repair, but longer indels require additional DNA-processing factors. Ectopic expression of a DNA exonuclease or perturbation of the balance of DNA polymerases can increase the frequency of longer indels, thus paving the way for models that can generate antibodies with long CDR3. Our study reveals the mechanisms that generate beneficial and deleterious indels during the process of antibody somatic hypermutation and has implications in understanding the detrimental genomic alterations in various conditions, including tumorigenesis.


Assuntos
Genes de Imunoglobulinas , Mutação INDEL , Animais , Camundongos , Mutação , Reparo do DNA/genética , DNA/genética
4.
Philos Trans A Math Phys Eng Sci ; 364(1847): 2747-61, 2006 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-16973487

RESUMO

Owing to fundamental reasons of symmetry, liquid crystals are soft materials. This softness allows long length-scales, large susceptibilities and the existence of modulated phases, which respond readily to external fields. Liquid crystals with such phases are tunable, self-assembled, photonic band gap materials; they offer exciting opportunities both in basic science and in technology. Since the density of photon states is suppressed in the stop band and is enhanced at the band edges, these materials may be used as switchable filters or as mirrorless lasers. Disordered periodic liquid crystal structures can show random lasing. We highlight recent advances in this rapidly growing area, and discuss future prospects in emerging liquid crystal materials. Liquid crystal elastomers and orientationally ordered nanoparticle assemblies are of particular interest.

5.
Nat Mater ; 1(2): 111-3, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12618825

RESUMO

Photonic-bandgap materials, with periodicity in one, two or three dimensions, offer control of spontaneous emission and photon localization. Low-threshold lasing has been demonstrated in two-dimensional photonic-bandgap materials, both with distributed feedback and defect modes. Liquid crystals with chiral constituents exhibit mesophases with modulated ground states. Helical cholesterics are one-dimensional, whereas blue phases are three-dimensional self-assembled photonic-bandgap structures. Although mirrorless lasing was predicted and observed in one-dimensional helical cholesteric materials and chiral ferroelectric smectic materials, it is of great interest to probe light confinement in three dimensions. Here, we report the first observations of lasing in three-dimensional photonic crystals, in the cholesteric blue phase II. Our results show that distributed feedback is realized in three dimensions, resulting in almost diffraction-limited lasing with significantly lower thresholds than in one dimension. In addition to mirrorless lasing, these self-assembled soft photonic-bandgap materials may also be useful for waveguiding, switching and sensing applications.


Assuntos
Cristalização/métodos , Cristalografia/métodos , Lasers , Luz , Teste de Materiais/métodos , Fotoquímica/instrumentação , Polímeros/química , Desenho de Equipamento , Retroalimentação , Fotoquímica/métodos , Espalhamento de Radiação
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