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1.
Fish Shellfish Immunol ; 114: 102-111, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33930547

RESUMO

Environmental microplastic pollution (including polystyrene, PS) may have detrimental effects on the health of aquatic organisms. Accumulation of PS microplastics has been reported to affect innate immune cells and inflammatory responses in fish. To date, knowledge on effects of microplastics on the antibody response is still very limited. Here, we investigated effects of small (0.8-20 µm) PS microplastics on the abundance of B lineage cells in primary cultures of developing immune cells from the anterior kidney of rainbow trout. Both purchased PS microbeads and PS microparticles generated from consumer products were used as microplastic sources. We first show that rainbow trout phagocytic B cells efficiently took up small (0.83-3.1 µm) PS microbeads within hours of exposure. In addition, our data revealed that PS microplastic exposure most significantly decreased the abundance of a population of non-phagocytic developing B cells, using both flow cytometry and RT-qPCR. PS microplastics-induced loss of developing B cells further correlated with reduced gene expression of RAG1 and the membrane form of immunoglobulin heavy chains mu and tau. Based on the induced loss of developing B cells observed in our in vitro studies, we speculate that in vivo, chronic PS microplastic-exposure may lead to suboptimal IgM/IgT levels in response to pathogens in teleost species. Considering the highly conserved nature of vertebrate B lymphopoiesis it is likely that PS microplastics will similarly reduce antibody responses in higher vertebrate species, including humans. Further, RAG1 provides an effective biomarker to determine effects of PS microplastics on B cell development in teleost species.


Assuntos
Linfócitos B/efeitos dos fármacos , Microplásticos/toxicidade , Oncorhynchus mykiss , Poliestirenos/toxicidade , Animais , Biomarcadores , Carpas , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Genes RAG-1/fisiologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Microplásticos/química
2.
Protein Sci ; 11(6): 1424-34, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12021441

RESUMO

Analysis of the crystal structures for cytidine deaminase complexed with substrate analog 3-deazacytidine, transition-state analog zebularine 3,4-hydrate, and product uridine establishes significant changes in the magnitude of atomic-scale fluctuations along the (approximate) reaction coordinate of this enzyme. Differences in fluctuations between the substrate analog complex, transition-state analog complex, and product complex are monitored via changes in corresponding crystallographic temperature factors. Previously, we reported that active-site conformational disorder is substantially reduced in the transition-state complex relative to the two ground-state complexes. Here, this result is statistically corroborated by crystallographic data for fluorinated zebularine 3,4-hydrate, a second transition-state analog, and by multiple regression analysis. Multiple regression explains 70% of the total temperature factor variation through a predictive model for the average B-value of an amino acid as a function of the catalytic state of the enzyme (substrate, transition state, product) and five other physical and structural descriptors. Furthermore, correlations of atomic fluctuation magnitudes throughout the body of each complex are quantified through an auto-correlation function. The transition-state analog complex shows the greatest correlations between temperature factor magnitudes for spatially separated atoms, underscoring the strong ability of this reaction-coordinate species to "organize" enzymatic fluctuations. The catalytic significance for decreased atomic-scale motions in the transition state is discussed. A thermodynamic argument indicates that the significant decreases in local enzymatic conformational entropy at the transition state result in enhanced energetic stabilization there.


Assuntos
Domínio Catalítico , Citidina Desaminase/química , Modelos Moleculares , Entropia , Escherichia coli/enzimologia , Estrutura Molecular , Movimento (Física) , Ligação Proteica , Conformação Proteica , Especificidade por Substrato , Temperatura
3.
4.
J Theor Biol ; 245(4): 705-14, 2007 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-17240397

RESUMO

Although the food web is one of the most fundamental and oldest concepts in ecology, elucidating the strategies and structures by which natural communities of species persist remains a challenge to empirical and theoretical ecologists. We show that simple regulatory feedbacks between autotrophs and their environment when embedded within complex and realistic food-web models enhance biodiversity. The food webs are generated through the niche-model algorithm and coupled with predator-prey dynamics, with and without environmental feedbacks at the autotroph level. With high probability and especially at lower, more realistic connectance levels, regulatory environmental feedbacks result in fewer species extinctions, that is, in increased species persistence. These same feedback couplings, however, also sensitize food webs to environmental stresses leading to abrupt collapses in biodiversity with increased forcing. Feedback interactions between species and their material environments anchor food-web persistence, adding another dimension to biodiversity conservation. We suggest that the regulatory features of two natural systems, deep-sea tubeworms with their microbial consortia and a soil ecosystem manifesting adaptive homeostatic changes, can be embedded within niche-model food-web dynamics.


Assuntos
Biodiversidade , Cadeia Alimentar , Adaptação Biológica , Algoritmos , Animais , Processos Autotróficos , Biomassa , Extinção Biológica , Retroalimentação , Modelos Biológicos , Dinâmica Populacional , Comportamento Predatório , Temperatura
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