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1.
Science ; 364(6436)2019 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-30975860

RESUMO

To understand the health impact of long-duration spaceflight, one identical twin astronaut was monitored before, during, and after a 1-year mission onboard the International Space Station; his twin served as a genetically matched ground control. Longitudinal assessments identified spaceflight-specific changes, including decreased body mass, telomere elongation, genome instability, carotid artery distension and increased intima-media thickness, altered ocular structure, transcriptional and metabolic changes, DNA methylation changes in immune and oxidative stress-related pathways, gastrointestinal microbiota alterations, and some cognitive decline postflight. Although average telomere length, global gene expression, and microbiome changes returned to near preflight levels within 6 months after return to Earth, increased numbers of short telomeres were observed and expression of some genes was still disrupted. These multiomic, molecular, physiological, and behavioral datasets provide a valuable roadmap of the putative health risks for future human spaceflight.


Assuntos
Adaptação Fisiológica , Astronautas , Voo Espacial , Imunidade Adaptativa , Peso Corporal , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Dano ao DNA , Metilação de DNA , Microbioma Gastrointestinal , Instabilidade Genômica , Humanos , Masculino , Homeostase do Telômero , Fatores de Tempo , Estados Unidos , United States National Aeronautics and Space Administration
2.
J Biomed Mater Res A ; 90(3): 784-91, 2009 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-18615466

RESUMO

Evidence from experimental and finite element studies have shown that the temporomandibular joint disc is heavily loaded during normal physiological function. Several studies have been carried out to investigate the response of the disc to tensile and static compressive forces. However, there is limited information that elucidates the dynamic characteristics of the disc under in vivo loading conditions. These investigations assessed the effect of physiologically relevant applied strain amplitudes and frequencies to determine regional mechanical properties of the disc. Cyclic tests on porcine TMJ discs were carried out over a period of 15 cycles, and the resultant compressive moduli and energy dissipation properties of the disc were reported. Results showed that modulus values were more dependent on strain amplitude than on frequency, and modulus values exhibited a strong regional variation. Clear hysteresis loops were evident in each set of testing parameters, and the only statistically significant regional variation in energy dissipation was between the central and medial regions. From these investigations, a more detailed understanding of the spatial mechanical properties of the TMJ disc has been achieved under physiologically relevant loading conditions. Combined with studies on other loading modalities of the disc, these results will serve as a benchmark for future TMJ disc tissue engineering endeavors.


Assuntos
Disco da Articulação Temporomandibular/fisiologia , Engenharia Tecidual/métodos , Animais , Força Compressiva , Elasticidade , Estresse Mecânico , Suínos , Resistência à Tração , Suporte de Carga
3.
Acta Biomater ; 4(4): 808-16, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18314000

RESUMO

Tissue-engineered temporomandibular joint (TMJ) discs offer a viable treatment option for patients with severe joint internal derangement. To date, only a handful of TMJ tissue engineering studies have been carried out and all have incorporated the use of synthetic scaffold materials. These current scaffolds have shown limited success in recapitulating morphological and functional aspects of the native disc tissue. The present study is the first to investigate the potential of a xenogeneic scaffold for use in tissue engineering the TMJ disc. The effects of decellularization agents on the disc's mechanical properties were assessed using three common decellularization protocols: Triton X-100, sodium dodecyl sulfate (SDS) and an acetone/ethanol solution. Decellularized scaffolds were subsequently characterized through cyclic mechanical testing at physiologically relevant frequencies to determine which chemical agent most accurately preserved the native tissue properties. Results have shown that porcine discs treated with SDS most closely matched the energy dissipation capabilities and resistance to deformation of the native tissue. Treatments using Triton X-100 caused the resultant tissue to become relatively softer with inferior energy dissipation capabilities, while treatment using acetone/ethanol led to a significantly stiffer and dehydrated material. These findings support the potential of a porcine-derived scaffold decellularized by SDS as a xenograft for TMJ disc reconstruction.


Assuntos
Disco da Articulação Temporomandibular/metabolismo , Engenharia Tecidual/métodos , Tecidos Suporte , Animais , Fenômenos Biomecânicos , Dissecação , Microscopia Eletrônica de Varredura , Suínos , Disco da Articulação Temporomandibular/citologia , Disco da Articulação Temporomandibular/ultraestrutura
4.
J Biol Chem ; 282(8): 5944-58, 2007 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-17192261

RESUMO

The Tp34 (TP0971) membrane lipoprotein of Treponema pallidum, an obligate human pathogen and the agent of syphilis, was previously reported to have lactoferrin binding properties. Given the non-cultivatable nature of T. pallidum, a structure-to-function approach was pursued to clarify further potential relationships between the Tp34 structural and biochemical properties and its propensity to bind human lactoferrin. The crystal structure of a nonacylated, recombinant form of Tp34 (rTp34), solved to a resolution of 1.9A(,) revealed two metaloccupied binding sites within a dimer; the identity of the ion most likely was zinc. Residues from both of the monomers contributed to the interfacial metal-binding sites; a novel feature was that the delta-sulfur of methionine coordinated the zinc ion. Analytical ultracentrifugation showed that, in solution, rTp34 formed a metal-stabilized dimer and that rTp34 bound human lactoferrin with a stoichiometry of 2:1. Isothermal titration calorimetry further revealed that rTp34 bound human lactoferrin at high (submicromolar) affinity. Finally, membrane topology studies revealed that native Tp34 is not located on the outer surface (outer membrane) of T. pallidum but, rather, is periplasmic. How propensity of Tp34 to bind zinc and the iron-sequestering lactoferrin may relate overall to the biology of T. pallidum infection in humans is discussed.


Assuntos
Lactoferrina/química , Lipoproteínas/química , Proteínas de Membrana/química , Proteínas Periplásmicas/química , Treponema pallidum/química , Cristalografia por Raios X , Humanos , Lactoferrina/metabolismo , Lipoproteínas/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Periplásmicas/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Sífilis/metabolismo , Treponema pallidum/metabolismo , Zinco/química , Zinco/metabolismo
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