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1.
Nature ; 608(7922): 324-329, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35948712

RESUMO

Multicellular systems, from bacterial biofilms to human organs, form interfaces (or boundaries) between different cell collectives to spatially organize versatile functions1,2. The evolution of sufficiently descriptive genetic toolkits probably triggered the explosion of complex multicellular life and patterning3,4. Synthetic biology aims to engineer multicellular systems for practical applications and to serve as a build-to-understand methodology for natural systems5-8. However, our ability to engineer multicellular interface patterns2,9 is still very limited, as synthetic cell-cell adhesion toolkits and suitable patterning algorithms are underdeveloped5,7,10-13. Here we introduce a synthetic cell-cell adhesin logic with swarming bacteria and establish the precise engineering, predictive modelling and algorithmic programming of multicellular interface patterns. We demonstrate interface generation through a swarming adhesion mechanism, quantitative control over interface geometry and adhesion-mediated analogues of developmental organizers and morphogen fields. Using tiling and four-colour-mapping concepts, we identify algorithms for creating universal target patterns. This synthetic 4-bit adhesion logic advances practical applications such as human-readable molecular diagnostics, spatial fluid control on biological surfaces and programmable self-growing materials5-8,14. Notably, a minimal set of just four adhesins represents 4 bits of information that suffice to program universal tessellation patterns, implying a low critical threshold for the evolution and engineering of complex multicellular systems3,5.


Assuntos
Algoritmos , Células Artificiais , Adesão Celular , Lógica , Biologia Sintética , Células Artificiais/citologia , Biofilmes , Humanos , Biologia Sintética/métodos
2.
Front Cell Neurosci ; 16: 843790, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35321204

RESUMO

Antimicrobial peptides (AMPs) are classically known as important effector molecules in innate immunity across all multicellular organisms. However, emerging evidence begins to suggest multifunctional properties of AMPs beyond their antimicrobial activity, surprisingly including their roles in regulating neuronal function, such as sleep and memory formation. Aging, which is fundamental to neurodegeneration in both physiological and disease conditions, interestingly affects the expression pattern of many AMPs in an infection-independent manner. While it remains unclear whether these are coincidental events, or a mechanistic relationship exists, previous studies have suggested a close link between AMPs and a few key proteins involved in neurodegenerative diseases. This review discusses recent literature and advances in understanding the crosstalk between AMPs and the nervous system at both molecular and functional levels, with the aim to explore how AMPs may relate to neuronal vulnerability in aging.

3.
J Med Chem ; 63(24): 15449-15482, 2020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33125236

RESUMO

The FDA Green Book is a list of all drug products that have been approved by the FDA for use in veterinary medicine. The Green Book, as published, lacks structural information corresponding to approved drugs. To address this gap, we have compiled the structural data for all FDA Green Book drugs approved through the end of 2019. Herein we discuss the relevance of this data set to human drugs in the context of structural classes and physicochemical properties. Analysis reveals that physicochemical properties are highly optimized and consistent with a high probability of favorable drug metabolism and pharmacokinetic properties, including good oral bioavailability for most compounds. We provide a detailed analysis of this data set organized on the basis of structure and function. Slightly over half (51%) of vet drugs are also approved in human medicine. Combination drugs are biologics are also discussed.


Assuntos
Aprovação de Drogas , Drogas Veterinárias/química , Anestésicos/química , Anestésicos/metabolismo , Anestésicos/uso terapêutico , Animais , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/uso terapêutico , Antifúngicos/química , Antifúngicos/metabolismo , Antifúngicos/uso terapêutico , Antiparasitários/química , Antiparasitários/metabolismo , Antiparasitários/uso terapêutico , Sistema Enzimático do Citocromo P-450/metabolismo , Humanos , Inseticidas/química , Inseticidas/metabolismo , Inseticidas/uso terapêutico , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/metabolismo , Bibliotecas de Moléculas Pequenas/uso terapêutico , Estados Unidos , United States Food and Drug Administration , Drogas Veterinárias/metabolismo , Drogas Veterinárias/uso terapêutico
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