existence of objects from which no direct information can be obtained
experimentally or observationally. A well known example is to
ascertain the existence of black holes of various masses in different
parts of the universe from indirect evidence, such as X-ray emissions.
In the field of complex networks, the problem of detecting
hidden nodes can be stated, as follows. Consider a network whose
topology is completely unknown but whose nodes consist of two types:
one accessible and another inaccessible from the outside world. The
accessible nodes can be observed or monitored, and it is assumed that time
series are available from each node in this group. The inaccessible
nodes are shielded from the outside and they are essentially
``hidden.'' The question is, based solely on the
available time series from the accessible nodes, can the existence and
locations of the hidden nodes be inferred? A completely data-driven,
compressive-sensing based method is developed to address this issue by utilizing
complex weighted networks of nonlinear oscillators, evolutionary game
and geospatial networks.
Both microbes and multicellular organisms actively regulate their cell
fate determination to cope with changing environments or to ensure
proper development. Here, the synthetic biology approaches are used to
engineer bistable gene networks to demonstrate that stochastic and
permanent cell fate determination can be achieved through initializing
gene regulatory networks (GRNs) at the boundary between dynamic
attractors. This is experimentally realized by linking a synthetic GRN
to a natural output of galactose metabolism regulation in yeast.
Combining mathematical modeling and flow cytometry, the
engineered systems are shown to be bistable and that inherent gene expression
stochasticity does not induce spontaneous state transitioning at
steady state. By interfacing rationally designed synthetic
GRNs with background gene regulation mechanisms, this work
investigates intricate properties of networks that illuminate possible
regulatory mechanisms for cell differentiation and development that
can be initiated from points of instability.
Extra-intestinal pathogenic E. coli (ExPEC), including avian pathogenic E. coli (APEC), pose a considerable threat to both human and animal health, with illness causing substantial economic loss. APEC strain χ7122 (O78∶K80∶H9), containing three large plasmids [pChi7122-1 (IncFIB/FIIA-FIC), pChi7122-2 (IncFII), and pChi7122-3 (IncI2)]; and a small plasmid pChi7122-4 (ColE2-like), has been used for many years as a model strain to study the molecular mechanisms of ExPEC pathogenicity and zoonotic potential. We previously sequenced and characterized the plasmid pChi7122-1 and determined its importance in systemic APEC infection; however the roles of the other pChi7122 plasmids were still ambiguous. Herein we present the sequence of the remaining pChi7122 plasmids, confirming that pChi7122-2 and pChi7122-3 encode an ABC iron transport system (eitABCD) and a putative type IV fimbriae respectively, whereas pChi7122-4 is a cryptic plasmid. New features were also identified, including a gene cluster on pChi7122-2 that is not present in other E. coli strains but is found in Salmonella serovars and is predicted to encode the sugars catabolic pathways. In vitro evaluation of the APEC χ7122 derivative strains with the three large plasmids, either individually or in combinations, provided new insights into the role of plasmids in biofilm formation, bile and acid tolerance, and the interaction of E. coli strains with 3-D cultures of intestinal epithelial cells. In this study, we show that the nature and combinations of plasmids, as well as the background of the host strains, have an effect on these phenomena. Our data reveal new insights into the role of extra-chromosomal sequences in fitness and diversity of ExPEC in their phenotypes.
Streptococcus pneumoniae still causes severe morbidity and mortality worldwide, especially in young children and the elderly. Much effort has been dedicated to developing protein-based universal vaccines to conquer the current shortcomings of capsular vaccines and capsular conjugate vaccines, such as serotype replacement, limited coverage and high costs. A recombinant live vector vaccine delivering protective antigens is a promising way to achieve this goal. In this review, we discuss the researches using live recombinant vaccines, mainly live attenuated Salmonella and lactic acid bacteria, to deliver pneumococcal antigens. We also discuss both the limitations and the future of these vaccines.
