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1.
Proc Natl Acad Sci U S A ; 120(13): e2220167120, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36947516

RESUMO

Orientational order, encoded in anisotropic fields, plays an important role during the development of an organism. A striking example of this is the freshwater polyp Hydra, where topological defects in the muscle fiber orientation have been shown to localize to key features of the body plan. This body plan is organized by morphogen concentration gradients, raising the question how muscle fiber orientation, morphogen gradients and body shape interact. Here, we introduce a minimal model that couples nematic orientational order to the gradient of a morphogen field. We show that on a planar surface, alignment to a radial concentration gradient can induce unbinding of topological defects, as observed during budding and tentacle formation in Hydra, and stabilize aster/vortex-like defects, as observed at a Hydra's mouth. On curved surfaces mimicking the morphologies of Hydra in various stages of development-from spheroid to adult-our model reproduces the experimentally observed reorganization of orientational order. Our results suggest how gradient alignment and curvature effects may work together to control orientational order during development and lay the foundations for future modeling efforts that will include the tissue mechanics that drive shape deformations.


Assuntos
Hydra , Animais , Anisotropia , Morfogênese , Hydra/fisiologia , Regeneração/fisiologia , Padronização Corporal
2.
Environ Pollut ; 316(Pt 2): 120657, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36379287

RESUMO

Polystyrene microplastics are ubiquitous in freshwater ecosystems and have significant impacts on freshwater organisms. Stable interspecific relationships, including the predation and defense relationships between predator and prey, play an extremely important role in maintaining the health of aquatic ecosystems. However, it still remains unknown whether polystyrene microplastics can interfere with predator-induced defenses of prey, especially in behavior change. Therefore, we studied the effects of different particle sizes and concentrations of polystyrene microplastics on the induced defenses related to morphology, reproduction, and behavior of Daphnia magna exposed to the predation risks from a species of zooplanktivorous fish Rhodeus ocellatus. Results showed that polystyrene microplastics weakened the predator-induced defenses of D. magna, including morphology, reproduction, and behavior. Polystyrene microplastics did not affect the beat rate of the second antennae (swimming activity) and thoracic appendage (filter-feeding activity) of D. magna, but R. ocellatus kairomone reduced Daphnia swimming activity. Moreover, in the absence of R. ocellatus predation risks, polystyrene microplastics did not alter the vertical distribution of D. magna in the water column, whereas D. magna exposed to R. ocellatus kairomone stayed deeper in the water; however, when both polystyrene microplastics and fish kairomone were present, D. magna inhabited in shallower water. Furthermore, small-sized microplastics interfered with the inducible behavioral defense of D. magna more strongly than large-sized polystyrene microplastics. Such findings suggested that polystyrene microplastics can weaken the predator-induced defenses of Daphnia, which may increase their risk of predation and alter the population dynamics of zooplankton.


Assuntos
Daphnia , Poluentes Químicos da Água , Animais , Microplásticos , Poliestirenos/toxicidade , Plásticos/toxicidade , Ecossistema , Poluentes Químicos da Água/análise , Peixes , Feromônios , Água
3.
J Med Chem ; 64(14): 10469-10481, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34196552

RESUMO

The increasing prevalence of antibacterial resistance globally underscores the urgent need for updated antimicrobial peptides (AMPs). Here, we describe a strategy for inducing the self-assembly of protegrin-1 (PG-1) into nanostructured antimicrobial agents with significantly improved pharmacological properties. Our strategy involves PEGylation in the terminals of PG-1 and subsequent self-assembly in aqueous media in the absence of exogenous excipients. Compared with the parent PG-1, the therapeutic index (TI) of NPG750(TIGram-negative bacteria = 17.07) and CPG2000(TIAll = 26.02) was increased. Importantly, NPG750 and CPG2000 offered higher stability toward trypsin degradation. Mechanistically, NPG750 and CPG2000 exerted their bactericidal activity by membrane-active mechanisms due to which microbes were not prone to develop resistance. Our findings proved PEGylation as a simple yet versatile strategy for generating AMP-derived bioactive drugs with excellent antitrypsin hydrolytic ability and lower cytotoxicity. This provides a theoretical basis for the further clinical application of AMPs.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Nanoestruturas/química , Polietilenoglicóis/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/síntese química , Peptídeos Catiônicos Antimicrobianos/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Hidrólise , Testes de Sensibilidade Microbiana , Estrutura Molecular , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Relação Estrutura-Atividade
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