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1.
Proc Natl Acad Sci U S A ; 117(23): 12693-12699, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32457160

RESUMO

Natural environments can present diverse challenges, but some genotypes remain fit across many environments. Such "generalists" can be hard to evolve, outcompeted by specialists fitter in any particular environment. Here, inspired by the search for broadly neutralizing antibodies during B cell affinity maturation, we demonstrate that environmental changes on an intermediate timescale can reliably evolve generalists, even when faster or slower environmental changes are unable to do so. We find that changing environments on timescales comparable with evolutionary transients in a population enhance the rate of evolving generalists from specialists, without enhancing the reverse process. The yield of generalists is further increased in more complex dynamic environments, such as a "chirp" of increasing frequency. Our work offers design principles for how nonequilibrium fitness "seascapes" can dynamically funnel populations to genotypes unobtainable in static environments.


Assuntos
Anticorpos Neutralizantes/imunologia , Especificidade de Anticorpos/genética , Meio Ambiente , Evolução Molecular , Modelos Genéticos , Animais , Anticorpos Neutralizantes/genética , Especificidade de Anticorpos/imunologia , Linfócitos B/citologia , Linfócitos B/imunologia , Diferenciação Celular , Genótipo , Humanos
2.
J Theor Biol ; 510: 110473, 2021 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32941914

RESUMO

The adaptive and innate branches of the vertebrate immune system work in close collaboration to protect organisms from harmful pathogens. As an organism ages its immune system undergoes immunosenescence, characterized by declined performance or malfunction in either immune branch, which can lead to disease and death. In this study we develop a mathematical framework of coupled innate and adaptive immune responses, namely the integrated immune branch (IIB) model. This model describes dynamics of immune components in both branches, uses a shape-space representation to encode pathogen-specific immune memory, and exhibits three steady states - health, septic death, and chronic inflammation - qualitatively similar to clinically-observed immune outcomes. In this model, the immune system (initialized in the health state) is subjected to a sequence of pathogen encounters, and we use the number of prior pathogen encounters as a proxy for the "age" of the immune system. We find that repeated pathogen encounters may trigger a fragility in which any encounter with a novel pathogen will cause the system to irreversibly switch from health to chronic inflammation. This transition is consistent with the onset of "inflammaging", a condition observed in aged individuals who experience chronic low-grade inflammation even in the absence of pathogens. The IIB model predicts that the onset of chronic inflammation strongly depends on the history of encountered pathogens; the timing of onset differs drastically when the same set of infections occurs in a different order. Lastly, the coupling between the innate and adaptive immune branches generates a trade-off between rapid pathogen clearance and a delayed onset of immunosenescence. Overall, by considering the complex feedback between immune compartments, our work suggests potential mechanisms for immunosenescence and provides a theoretical framework at the system level and on the scale of an organism's lifetime to account for clinical observations.


Assuntos
Imunidade Adaptativa , Imunossenescência , Idoso , Envelhecimento , Humanos , Sistema Imunitário , Imunidade Inata , Inflamação
3.
Nat Mater ; 13(2): 184-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24390380

RESUMO

Water/solid interfaces are vital to our daily lives and are also a central theme across an incredibly wide range of scientific disciplines. Resolving the internal structure, that is, the O-H directionality, of water molecules adsorbed on solid surfaces has been one of the key issues of water science yet it remains challenging. Using a low-temperature scanning tunnelling microscope, we report submolecular-resolution imaging of individual water monomers and tetramers on NaCl(001) films supported by a Au(111) substrate at 5 K. The frontier molecular orbitals of adsorbed water were directly visualized, which allowed discrimination of the orientation of the monomers and the hydrogen-bond directionality of the tetramers in real space. Comparison with ab initio density functional theory calculations reveals that the ability to access the orbital structures of water stems from the electronic decoupling effect provided by the NaCl films and the precisely tunable tip-water coupling.

5.
iScience ; 24(8): 102861, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34401660

RESUMO

Highly mutable viruses evolve to evade host immunity that exerts selective pressure and adapts to viral dynamics. Here, we provide a framework for identifying key determinants of the mode and fate of viral-immune coevolution by linking molecular recognition and eco-evolutionary dynamics. We find that conservation level and initial diversity of antigen jointly determine the timing and efficacy of narrow and broad antibody responses, which in turn control the transition between viral persistence, clearance, and rebound. In particular, clearance of structurally complex antigens relies on antibody evolution in a larger antigenic space than where selection directly acts; viral rebound manifests binding-mediated feedback between ecology and rapid evolution. Finally, immune compartmentalization can slow viral escape but also delay clearance. This work suggests that flexible molecular binding allows a plastic phenotype that exploits potentiating neutral variations outside direct contact, opening new and shorter paths toward highly adaptable states.

6.
Adv Mater ; 28(21): 4120-5, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27038143

RESUMO

Scalable fabrication of vertical-tunneling transistors is presented based on heterostructures formed between graphene, highly doped silicon, and its native oxide. Benefiting from the large density of states of highly doped silicon, the tunneling transistors can deliver a current density over 20 A cm(-2) . This study demonstrates that the interfacial native oxide plays a crucial role in governing the carrier transport in graphene-silicon heterostructures.

7.
Nat Commun ; 5: 4056, 2014 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-24874452

RESUMO

Water-solid interactions are of broad importance both in nature and technology. The hexagonal bilayer model based on the Bernal-Fowler-Pauling ice rules has been widely adopted to describe water structuring at interfaces. Using a cryogenic scanning tunnelling microscope, here we report a new type of two-dimensional ice-like bilayer structure built from cyclic water tetramers on an insulating NaCl(001) film, which is completely beyond this conventional bilayer picture. A novel bridging mechanism allows the interconnection of water tetramers to form chains, flakes and eventually a two-dimensional extended ice bilayer containing a regular array of Bjerrum D-type defects. Ab initio density functional theory calculations substantiate this bridging growth mode and reveal a striking proton-disordered ice structure. The formation of the periodic Bjerrum defects with unusually high density may have a crucial role as H donor sites in directing multilayer ice growth and in catalysing heterogeneous chemical reactions on water-coated salt surfaces.

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