The interferon-induced enzymes 2′-5′-oligoadenylate synthetase (OAS) and RNase L are key components of innate immunity involved in sensory and effector functions following viral infections. Upon ...binding target RNA, OAS is activated to produce 2′-5′-linked oligoadenylates (2-5A) that activate RNase L, which then cleaves single-stranded self and non-self RNA. Modified nucleosides that are present in cellular transcripts have been shown to suppress activation of several RNA sensors. Here, we demonstrate that in vitro transcribed, unmodified RNA activates OAS, induces RNase L-mediated ribosomal RNA (rRNA) cleavage and is rapidly cleaved by RNase L. In contrast, RNA containing modified nucleosides activates OAS less efficiently and induces limited rRNA cleavage. Nucleoside modifications also make RNA resistant to cleavage by RNase L. Examining translation in RNase L−/− cells and mice confirmed that RNase L activity reduces translation of unmodified mRNA, which is not observed with modified mRNA. Additionally, mRNA containing the nucleoside modification pseudouridine is translated longer and has an extended half-life. The observation that modified nucleosides in RNA reduce 2-5A pathway activation joins OAS and RNase L to the list of RNA sensors and effectors whose functions are limited when RNA is modified, confirming the role of nucleoside modifications in suppressing immune recognition of RNA.
The radial stability and the irreversible transformation of triple-wall carbon nanotubes (TWCNTs) bundles are investigated at high pressure conditions both experimentally and theoretically (exp. up ...72 GPa). The tubes having a mean internal diameter of 0.83nm and graphite-like intertube distance, show an onset of the radial collapse evidenced by the evolution of optical phonons. The nanotube collapse onset is observed at ∼22 GPa completes for the two external tubes at ∼29 GPa, however the innermost tube remains stable up to ∼37 GPa. Molecular dynamic calculations performed on smaller diameter TWCNTs bundles, as a model system, confirmed the multiple-stage pressure-induced collapse process. An analytical expression for the collapse pressure of carbon nanotubes having an arbitrary number of walls is proposed. Our experiments and modelling show that for pressures beyond ∼ 60 GPa an irreversible structural transformation of TWCNTs takes place. Ex situ transmission electron microscopy characterization on the recovered sample from 72 GPa revealed the mechanical failure of carbon nanotubes which evolve towards ribbon-like structures as corroborated by Raman spectroscopy. Modelling the tubes evolution at high pressure and high temperature showed the formation of new structures ranging from ribbon-like to graphite-like with either different degrees of amorphization or sp3 interlinking.
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‘Buckypaper’ from coaxial nanotubes Endo, M.; Muramatsu, H.; Hayashi, T. ...
Nature (London),
02/2005, Letnik:
433, Številka:
7025
Journal Article
Recenzirano
Odprti dostop
Double-walled carbon nanotubes are needed in a pure, highly crystalline form before features such as their electronic properties, thermal transport and mechanical behaviour can be investigated. Here ...we fabricate a paper-like material that consists of hexagonally packed bundles of clean, coaxial carbon nanotubes whose double walls vary little in diameter; it is prepared in high yields using chemical-vapour deposition with a conditioning catalyst and two-step purification. Our results will enable investigation of the physical properties of double-walled carbon nanotubes, which are predicted to be superior to those of both their single- and multiwalled relatives.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
High-pressure resonance Raman experiments were performed on linear carbon chains Cn confined in double-wall carbon nanotubes (Cn@DWCNT). Our results indicate that the frequency of the chain mode ...undergoes a non-linear decreasing as pressure increases, in agreement with previous studies of the behavior of carbon chains into multi-wall carbon nanotubes. After the pressure cycle, the Cn modes present an irreversible frequency downshift together with an irreversible upshift (downshift) of the RBM modes (G+ band) of the inner tube. These spectral changes are interpreted as evidence of cross-linking between the carbon chain and the wall of the inner tube. Density functional theory (DFT) calculations were performed in order to shed light on the interpretation of the experimental data. The theoretical calculations show a pressure-induced charge transfer from the nanotube to the carbon chain, thus resulting in an increasing of the C≡C bond length, and consequently, a softening frequency of the Cn Raman mode. Furthermore, an irreversible cross-linking between the tube and Cn is observed when the maximum applied pressure is higher than the pressure of radial tube collapse is predicted by modelling, thus supporting the experimental results.
The current treatment approach for severe aplastic anemia in children is based on studies performed in the 1980s, and updated evidence is required. We retrospectively compared the outcomes of ...children with acquired severe aplastic anemia who received immunosuppressive therapy within prospective trials conducted by the Japanese Childhood Aplastic Anemia Study Group or who underwent bone marrow transplantation from an HLA-matched family donor registered in the Japanese Society for Hematopoietic Cell Transplantation Registry. Between 1992 and 2009, 599 children (younger than 17 years) with severe aplastic anemia received a bone marrow transplant from an HLA-matched family donor (n=213) or immunosuppressive therapy (n=386) as first-line treatment. While the overall survival did not differ between patients treated with immunosuppressive therapy or bone marrow transplantation 88% (95% confidence interval: 86-90) versus 92% (90-94), failure-free survival was significantly inferior in patients receiving immunosuppressive therapy than in those undergoing bone marrow transplantation 56% (54-59) versus 87% (85-90); P<0.0001. There was no significant improvement in outcomes over the two time periods (1992-1999 versus 2000-2009). In multivariate analysis, age <10 years was identified as a favorable factor for overall survival (P=0.007), and choice of first-line immunosuppressive therapy was the only unfavorable factor for failure-free survival (P<0.0001). These support the current algorithm for treatment decisions, which recommends bone marrow transplantation when an HLA-matched family donor is available in pediatric severe aplastic anemia.
Essentials
Two groups recently reported GFI1B as a novel causative gene for congenital macrothrombocytopenia.
We performed functional analysis of a novel GFI1B mutation and previous mutations.
An ...immunofluorescence analysis of the platelet CD34 expression can be useful as a screening test.
Mutant‐transduced megakaryocytes produced enlarged proplatelet tips which were reduced in number.
Summary
Background
GFI1B is an essential transcription factor for megakaryocyte and erythrocyte development. Two groups have recently identified GFI1B as a novel causative gene for congenital macrothrombocytopenia associated with α‐granule deficiency.
Methods
We performed whole exome sequencing and identified a novel GFI1B p.G272fsX274 mutation in a family with macrothrombocytopenia, and a decreased number of platelet α‐granules and abnormally shaped red blood cells. p.G272fsX274 and the previous two mutations all predicted disruption of an essential DNA‐binding domain in GFI1B. We therefore performed functional studies to characterize the biochemical and biological effects of these three patient‐derived mutations.
Results
An immunofluorescence analysis revealed decreased thrombospondin‐1 and increased CD34 expression in platelets from our patient. Consistent with the previous studies, the three patient‐derived mutants were unable to repress the expression of the reporter gene and had a dominant‐negative effect over wild‐type GFI1B. In addition, the three mutations abolished recognition of a consensus‐binding site in gel shift assays. Furthermore, transduction of mouse fetal liver‐derived megakaryocytes with the three GFI1B mutants resulted in the production of abnormally large proplatelet tips, which were reduced in number.
Conclusions
Our study provides further proof of concept that GFI1B is an essential protein for the normal development of the megakaryocyte lineage.
Double-walled carbon nanotubes are needed in a pure, highly crystalline form before features such as their electronic properties, thermal transport and mechanical behaviour can be investigated. Here ...we fabricate a paper-like material that consists of hexagonally packed bundles of clean, coaxial carbon nanotubes whose double walls vary little in diameter; it is prepared in high yields using chemical-vapour deposition with a conditioning catalyst and two-step purification. Our results will enable investigation of the physical properties of double-walled carbon nanotubes, which are predicted to be superior to those of both their single- and multiwalled relatives.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Semisolid formulae are increasingly used in Japan to reduce the risks of gastroesophageal reflux (GER) and aspiration pneumonia in patients undergoing percutaneous endoscopic gastrostomy (PEG). We ...compared the incidences of GER after the use of liquid or semisolid contrast agents during PEG.
Patients who planned to undergo PEG were randomly assigned to the liquid-first (LF) group (liquid contrast agent on day 1 after PEG and a semisolid contrast agent on day 2) or the semisolid-first (SF) group (reversed order). A 200-ml agent bolus was administered via a PEG tube to the patient in the supine position. The upper gastrointestinal tract was radiologically examined from onset to 1 min after the end of administration. The incidences of GER were compared. We also evaluated the daily changes in GER incidence, effect of hiatal hernia severity and adverse events.
We analyzed the results of 66 patients (32, LF group; 34, SF group). The incidence of GER observed using only liquid contrast was 27% (18/66) and that using only semisolid was 11% (7/66) (P=0.028). There was no difference in the GER incidences between day 1 and day 2. In patients with severe, mild and no hiatal hernia, GER incidences in the liquid contrast agent were 80% (4/5), 61% (11/18) and 33% (13/43), respectively (P=0.031). GER incidence after using the semisolid contrast agent was lower in patients with no and mild hiatal hernia. The predominant adverse event was diarrhea; aspiration was not observed.
Semisolid contrast agents reduced the incidence of GER after PEG.
In infants with immunodeficiency, rotavirus (RV) vaccines can be continuously excreted in stool. We analysed nosocomial infection with RV vaccine strain in immunodeficient paediatric patients. RV1 ...RNAs were detected in stool and serum samples from case A, who was vaccinated with RV1, and case B, who was not. PAGE analysis of serial stool samples of case A revealed several rearrangements of the RV genome. In case B, the only band pattern detected was the same as a rearrangement detected in case A at the same time. In summary, RV vaccination of infants with immunodeficiency poses a risk of nosocomial infections.
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