257 research outputs found
Polymer confinement in undulated membrane boxes and tubes
We consider quantum particle or Gaussian polymer confinement between two
surfaces and in cylinders with sinusoidal undulations. In terms of the
variational method, we show that the quantum mechanical wave equations have
lower ground state energy in these geometries under long wavelength
undulations, where bulges are formed and waves are localized in the bulges. It
turns out correspondingly that Gaussian polymer chains in undulated boxes or
tubes acquire higher entropy than in exactly flat or straight ones. These
phenomena are explained by the uncertainty principle for quantum particles, and
by a "polymer confinement rule" for Gaussian polymers. If membrane boxes or
tubes are flexible, polymer-induced undulation instability is suggested. We
find that the wavelength of undulations at the threshold of instability for a
membrane box is almost twice the distance between two walls of the box.
Surprisingly we find that the instability for tubes begins with a shorter
wavelength compared to the "Rayleigh" area-minimizing instability.Comment: 6 pages, 2 figures, submitted to Phys. Rev.
The ESCRT System Is Required for Hepatitis C Virus Production
BACKGROUND: Recently, lipid droplets have been found to be involved in an important cytoplasmic organelle for hepatitis C virus (HCV) production. However, the mechanisms of HCV assembly, budding, and release remain poorly understood. Retroviruses and some other enveloped viruses require an endosomal sorting complex required for transport (ESCRT) components and their associated proteins for their budding process. METHODOLOGY/PRINCIPAL FINDINGS: To determine whether or not the ESCRT system is needed for HCV production, we examined the infectivity of HCV or the Core levels in culture supernatants as well as HCV RNA levels in HuH-7-derived RSc cells, in which HCV-JFH1 can infect and efficiently replicate, expressing short hairpin RNA or siRNA targeted to tumor susceptibility gene 101 (TSG101), apoptosis-linked gene 2 interacting protein X (Alix), Vps4B, charged multivesicular body protein 4b (CHMP4b), or Brox, all of which are components of the ESCRT system. We found that the infectivity of HCV in the supernatants was significantly suppressed in these knockdown cells. Consequently, the release of the HCV Core into the culture supernatants was significantly suppressed in these knockdown cells after HCV-JFH1 infection, while the intracellular infectivity and the RNA replication of HCV-JFH1 were not significantly affected. Furthermore, the HCV Core mostly colocalized with CHMP4b, a component of ESCRT-III. In this context, HCV Core could bind to CHMP4b. Nevertheless, we failed to find the conserved viral late domain motif, which is required for interaction with the ESCRT component, in the HCV-JFH1 Core, suggesting that HCV Core has a novel motif required for HCV production. CONCLUSIONS/SIGNIFICANCE: These results suggest that the ESCRT system is required for infectious HCV production
Clinicoradiological changes of brain NK/T cell lymphoma manifesting pure akinesia: a case report
Co-existence of acute myeloid leukemia with multilineage dysplasia and Epstein-Barr virus-associated T-cell lymphoproliferative disorder in a patient with rheumatoid arthritis: a case report
Rheumatoid arthritis (RA) is an autoimmune disease mediated by inflammatory processes mainly at the joints. Recently, awareness of Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disorder (T-LPD) has been heightened for its association with methotraxate usage in RA patients. In the contrary, acute myeloid leukemia with multilineage dysplasia (AML-MLD) has never been documented to be present concomitantly with the above two conditions. In this report we present a case of an autopsy-proven co-existence of AML-MLD and EBV-associated T-LPD in a patient with RA
Long-term effect of sitagliptin on endothelial function in type 2 diabetes: a sub-analysis of the PROLOGUE study
DECIGO pathfinder
DECIGO pathfinder (DPF) is a milestone satellite mission for DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) which is a future space gravitational wave antenna. DECIGO is expected to provide us fruitful insights into the universe, in particular about dark energy, a formation mechanism of supermassive black holes, and the inflation of the universe. Since DECIGO will be an extremely large mission which will formed by three drag-free spacecraft with 1000m separation, it is significant to gain the technical feasibility of DECIGO before its planned launch in 2024. Thus, we are planning to launch two milestone missions: DPF and pre-DECIGO. The conceptual design and current status of the first milestone mission, DPF, are reviewed in this article
Autophagy–physiology and pathophysiology
“Autophagy” is a highly conserved pathway for degradation, by which wasted intracellular macromolecules are delivered to lysosomes, where they are degraded into biologically active monomers such as amino acids that are subsequently re-used to maintain cellular metabolic turnover and homeostasis. Recent genetic studies have shown that mice lacking an autophagy-related gene (Atg5 or Atg7) cannot survive longer than 12 h after birth because of nutrient shortage. Moreover, tissue-specific impairment of autophagy in central nervous system tissue causes massive loss of neurons, resulting in neurodegeneration, while impaired autophagy in liver tissue causes accumulation of wasted organelles, leading to hepatomegaly. Although autophagy generally prevents cell death, our recent study using conditional Atg7-deficient mice in CNS tissue has demonstrated the presence of autophagic neuron death in the hippocampus after neonatal hypoxic/ischemic brain injury. Thus, recent genetic studies have shown that autophagy is involved in various cellular functions. In this review, we introduce physiological and pathophysiological roles of autophagy
Analysis of N-glycans in embryonated chicken egg chorioallantoic and amniotic cells responsible for binding and adaptation of human and avian influenza viruses
Two Naturally Occurring Terpenes, Dehydrocostuslactone and Costunolide, Decrease Intracellular GSH Content and Inhibit STAT3 Activation
The main purpose of the present study is to envisage the molecular mechanism of
inhibitory action ofdehydrocostuslactone (DCE) andcostunolide (CS), two
naturally occurring sesquiterpene lactones, towards the activation of signal
transducer and activator of transcription 3 (STAT3). We report that, in human
THP-1 cell line, they inhibit IL-6-elicited tyrosine phosphorylation of STAT3
and its DNA binding activity with EC50 of 10 µM with
concomitantdown-regulation ofthe phosphorylation of the tyrosine Janus kinases
JAK1, JAK2 and Tyk2. Furthermore, these compounds that contain an
α-β-unsatured carbonyl moiety and function as potent Michael reaction
acceptor, induce a rapid drop in intracellular glutathione (GSH) concentration
by direct interaction with it, thereby triggering
S-glutathionylation of STAT3. Dehydrocostunolide (HCS), the
reduced form of CS lacking only the α-β-unsaturated carbonyl group,
fails to exert any inhibitory action. Finally, the glutathione ethylene ester
(GEE), the cell permeable GSH form, reverts the inhibitory action of DCE and CS
on STAT3 tyrosine phosphorylation. We conclude that these two sesquiterpene
lactones are able to induce redox-dependent post-translational modification of
cysteine residues of STAT3 protein in order to regulate its function
Acquisition of Human-Type Receptor Binding Specificity by New H5N1 Influenza Virus Sublineages during Their Emergence in Birds in Egypt
Highly pathogenic avian influenza A virus subtype H5N1 is currently widespread in Asia, Europe, and Africa, with 60% mortality in humans. In particular, since 2009 Egypt has unexpectedly had the highest number of human cases of H5N1 virus infection, with more than 50% of the cases worldwide, but the basis for this high incidence has not been elucidated. A change in receptor binding affinity of the viral hemagglutinin (HA) from α2,3- to α2,6-linked sialic acid (SA) is thought to be necessary for H5N1 virus to become pandemic. In this study, we conducted a phylogenetic analysis of H5N1 viruses isolated between 2006 and 2009 in Egypt. The phylogenetic results showed that recent human isolates clustered disproportionally into several new H5 sublineages suggesting that their HAs have changed their receptor specificity. Using reverse genetics, we found that these H5 sublineages have acquired an enhanced binding affinity for α2,6 SA in combination with residual affinity for α2,3 SA, and identified the amino acid mutations that produced this new receptor specificity. Recombinant H5N1 viruses with a single mutation at HA residue 192 or a double mutation at HA residues 129 and 151 had increased attachment to and infectivity in the human lower respiratory tract but not in the larynx. These findings correlated with enhanced virulence of the mutant viruses in mice. Interestingly, these H5 viruses, with increased affinity to α2,6 SA, emerged during viral diversification in bird populations and subsequently spread to humans. Our findings suggested that emergence of new H5 sublineages with α2,6 SA specificity caused a subsequent increase in human H5N1 influenza virus infections in Egypt, and provided data for understanding the virus's pandemic potential
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