78,071 research outputs found
A Systemic Receptor Network Triggered by Human cytomegalovirus Entry
Virus entry is a multistep process that triggers a variety of cellular
pathways interconnecting into a complex network, yet the molecular complexity
of this network remains largely unsolved. Here, by employing systems biology
approach, we reveal a systemic virus-entry network initiated by human
cytomegalovirus (HCMV), a widespread opportunistic pathogen. This network
contains all known interactions and functional modules (i.e. groups of
proteins) coordinately responding to HCMV entry. The number of both genes and
functional modules activated in this network dramatically declines shortly,
within 25 min post-infection. While modules annotated as receptor system, ion
transport, and immune response are continuously activated during the entire
process of HCMV entry, those for cell adhesion and skeletal movement are
specifically activated during viral early attachment, and those for immune
response during virus entry. HCMV entry requires a complex receptor network
involving different cellular components, comprising not only cell surface
receptors, but also pathway components in signal transduction, skeletal
development, immune response, endocytosis, ion transport, macromolecule
metabolism and chromatin remodeling. Interestingly, genes that function in
chromatin remodeling are the most abundant in this receptor system, suggesting
that global modulation of transcriptions is one of the most important events in
HCMV entry. Results of in silico knock out further reveal that this entire
receptor network is primarily controlled by multiple elements, such as EGFR
(Epidermal Growth Factor) and SLC10A1 (sodium/bile acid cotransporter family,
member 1). Thus, our results demonstrate that a complex systemic network, in
which components coordinating efficiently in time and space contributes to
virus entry.Comment: 26 page
Implications of Fermi-LAT observations on the origin of IceCube neutrinos
The IceCube (IC) collaboration recently reported the detection of TeV-PeV
extraterrestrial neutrinos whose origin is yet unknown. By the photon-neutrino
connection in and interactions, we use the \fermi-LAT
observations to constrain the origin of the IC detected neutrinos. We find that
Galactic origins, i.e., the diffuse Galactic neutrinos due to cosmic ray (CR)
propagation in the Milky Way, and the neutrinos from the Galactic point
sources, may not produce the IC neutrino flux, thus these neutrinos should be
of extragalactic origin. Moreover, the extragalactic gamma-ray bursts (GRBs)
may not account for the IC neutrino flux, the jets of active galactic nuclei
may not produce the IC neutrino spectrum, but the starburst galaxies (SBGs) may
be promising sources. As suggested by the consistency between the IC detected
neutrino flux and the Waxman-Bahcall bound, GRBs in SBGs may be the sources of
both the ultrahigh energy, eV, CRs and the ~PeV CRs that
produce the IC detected TeV-PeV neutrinos.Comment: JCAP accepted version; 8 pages, 2 figs; discussion on blazar origin
added; conclusion unchange
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