Protocell multilevel selection models have been proposed to study the evolutionary dynamics of vesicles encapsulating a set of replicating, competing and mutating sequences. The frequency of the different sequence types determines protocell survival through a fitness function. One of the defining features of these models is the genetic load generated when the protocell divides and its sequences are assorted between the offspring vesicles.
View Article and Find Full Text PDFStaphylococcus aureus is a leading infectious cause of life-threatening disease in humans, yet there is currently no vaccine to combat this bacterium. The pathogenesis of S. aureus is mediated by a diverse array of protein toxins including a large family of secreted pyrogenic superantigens.
View Article and Find Full Text PDFFor several decades, the trans-Golgi network (TGN) was considered the most distal stop and hence the ultimate protein-sorting station for distinct apical and basolateral transport carriers that reach their respective surface domains in the direct trafficking pathway. However, recent reports of apical and basolateral cargoes traversing post-Golgi compartments accessible to endocytic ligands before their arrival at the cell surface and the post-TGN breakup of large pleomorphic membrane fragments that exit the Golgi region toward the surface raised the possibility that compartments distal to the TGN mediate or contribute to biosynthetic sorting. Here we describe the development of a novel assay that quantitatively distinguishes different cargo pairs by their degree of colocalization at the TGN and by the evolution of colocalization during their TGN-to-surface transport.
View Article and Find Full Text PDFConstraints placed upon the phenotypes of organisms result from their interactions with the environment. Over evolutionary time scales, these constraints feed back onto smaller molecular subnetworks comprising the organism. The evolution of biological networks is studied by considering a network of a few nodes embedded in a larger context.
View Article and Find Full Text PDFBackground: Staphylococcal enterotoxin B (SEB), a potential biological warfare agent, is a potent superantigen that contributes to the virulence of methicillin-resistant Staphylococcus aureus (MRSA), which is a major health threat in the United States. Efforts to develop toxin-neutralizing antibodies as adjunctive therapies are justified, given the high mortality and frequent failure of therapy despite available antibiotics.
Methods: Murine SEB-specific mAb 20B1 was humanized, and treatment benefits of Hu-1.
Unlabelled: Does cell age matter in virulence? The emergence of persister cells during chronic infections is critical for persistence of infection, but little is known how this occurs. Here, we demonstrate for the first time that the replicative age of the fungal pathogen Cryptococcus neoformans contributes to persistence during chronic meningoencephalitis. Generationally older C.
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