73 research outputs found
Quantum-limited directional amplifiers with optomechanics
Directional amplifiers are an important resource in quantum information
processing, as they protect sensitive quantum systems from excess noise. Here,
we propose an implementation of phase-preserving and phase-sensitive
directional amplifiers for microwave signals in an electromechanical setup
comprising two microwave cavities and two mechanical resonators. We show that
both can reach their respective quantum limits on added noise. In the reverse
direction, they emit thermal noise stemming from the mechanical resonators and
we discuss how this noise can be suppressed, a crucial aspect for technological
applications. The isolation bandwidth in both is of the order of the mechanical
linewidth divided by the amplitude gain. We derive the bandwidth and
gain-bandwidth product for both and find that the phase-sensitive amplifier has
an unlimited gain-bandwidth product. Our study represents an important step
toward flexible, on-chip integrated nonreciprocal amplifiers of microwave
signals
Selective sparing of goblet cells and paneth cells in the intestine of methotrexate-treated rats
Proliferation, differentiation, and cell death were studied in small
intestinal and colonic epithelia of rats after treatment with
methotrexate. Days 1-2 after treatment were characterized by decreased
proliferation, increased apoptosis, and decreased numbers and depths of
small intestinal crypts in a proximal-to-distal decreasing gradient along
the small intestine. The remaining crypt epithelium appeared flattened,
except for Paneth cells, in which lysozyme protein and mRNA expression was
increased. Regeneration through increased proliferation during days 3-4
coincided with villus atrophy, showing decreased numbers of villus
enterocytes and decreased expression of the enterocyte-specific genes
sucrase-isomaltase and carbamoyl phosphate synthase I. Remarkably, goblet
cells were spared at villus tips and remained functional, displaying Muc2
and trefoil factor 3 expression. On days 8-10, all parameters had returned
to normal in the whole small intestine. No methotrexate-induced changes
were seen in epithelial morphology, proliferation, apoptosis, Muc2, and
TFF3 immunostaining in the colon. The observed small intestinal sparing of
Paneth cells and goblet cells following exposure to methotrexate is likely
to contribute to epithelial defense during increased vulnerability of the
intestinal epithelium
Specific responses in rat small intestinal epithelial mRNA expression and protein levels during chemotherapeutic damage and regeneration
The rapidly dividing small intestinal epithelium is very sensitive to the
cytostatic drug methotrexate. We investigated the regulation of epithelial
gene expression in rat jejunum during methotrexate-induced damage and
regeneration. Ten differentiation markers were localized on tissue
sections and quantified at mRNA and protein levels relative to control
levels. We analyzed correlations in temporal expression patterns between
markers. mRNA expression of enterocyte and goblet cell markers decreased
significantly during damage for a specific period. Of these,
sucrase-isomaltase (-62%) and CPS (-82%) were correlated. Correlations
were also found between lactase (-76%) and SGLT1 (-77%) and between I-FABP
(-52%) and L-FABP (-45%). Decreases in GLUT5 (-53%), MUC2 (-43%), and TFF3
(-54%) mRNAs occurred independently of any of the other markers. In
contrast, lysozyme mRNA present in Paneth cells increased (+76%). At the
protein level, qualitative and quantitative changes were in agreement with
mRNA expression, except for Muc2 (+115%) and TFF3 (+81%), which increased
significantly during damage, following independent patterns. During
regeneration, expression of each marker returned to control levels. The
enhanced expression of cytoprotective molecules (Muc2, TFF3, lysozyme)
during damage represents maintenance of goblet cell and Paneth cell
functions, most likely to protect the epithelium. Decreased expression of
enterocyte-specific markers represents decreased enterocyte function, of
which fatty acid transporters were least affected
MUC4 is increased in high-grade intraepithelial neoplasia in Barrett's oesophagus and is associated with a pro-apoptotic bax/bcl-2 ratio.
MUC4 is increased in high-grade intraepithelial neoplasia in Barrett's oesophagus and is associated with a pro-apoptotic bax/bcl-2 ratio.
Changes in small intestinal homeostasis, morphology, and gene expression during rotavirus infection of infant mice
Rotavirus is the most important cause of infantile gastroenteritis. Since
in vivo mucosal responses to a rotavirus infection thus far have not been
extensively studied, we related viral replication in the murine small
intestine to alterations in mucosal structure, epithelial cell
homeostasis, cellular kinetics, and differentiation. Seven-day-old
suckling BALB/c mice were inoculated with 2 x 10(4) focus-forming units of
murine rotavirus and were compared to mock-infected controls. Diarrheal
illness and viral shedding were recorded, and small intestinal tissue was
evaluated for rotavirus (NSP4 and structural proteins)- and
enterocyte-specific (lactase, SGLT1, and L-FABP) mRNA and protein
expression. Morphology, apoptosis, proliferation, and migration were
evaluated (immuno)histochemically. Diarrhea was observed from days 1 to 5
postinfection, and viral shedding was observed from days 1 to 10. Two
peaks of rotavirus replication were observed at 1 and 4 days
postinfection. Histological changes were characterized by the accumulation
of vacuolated enterocytes. Strikingly, the number of vacuolated cells
exceeded the number of cells in which viral replication was detectable.
Apoptosis and proliferation were increased from days 1 to 7, resulting in
villous atrophy. Epithelial cell turnover was significantly higher (<4
days) than that observed in controls (7 days). Since epithelial renewal
occurred within 4 days, the second peak of viral replication was most
likely caused by infection of newly synthesized cells. Expression of
enterocyte-specific genes was downregulated in infected cells at mRNA and
protein levels starting as early as 6 h after infection. In conclusion, we
show for the first time that rotavirus infection induces apoptosis in
vivo, an increase in epithelial cell turnover, and a shutoff of gene
expression in enterocytes showing viral replication. The shutoff of
enterocyte-specific gene expression, together with the loss of mature
enterocytes through apoptosis and the replacement of these cells by less
differentiated dividing cells, likely leads to a defective absorptive
function of the intestinal epithelium, which contributes to rotavirus
pathogenesis
Selective sparing of goblet cells and Paneth cells in the intestine of methotrexate-treated rats
In Vitro Neutralisation of Rotavirus Infection by Two Broadly Specific Recombinant Monovalent Llama-Derived Antibody Fragments
Rotavirus is the main cause of viral gastroenteritis in young children. Therefore, the development of inexpensive antiviral products for the prevention and/or treatment of rotavirus disease remains a priority. Previously we have shown that a recombinant monovalent antibody fragment (referred to as Anti-Rotavirus Proteins or ARP1) derived from a heavy chain antibody of a llama immunised with rotavirus was able to neutralise rotavirus infection in a mouse model system. In the present work we investigated the specificity and neutralising activity of two llama antibody fragments, ARP1 and ARP3, against 13 cell culture adapted rotavirus strains of diverse genotypes. In addition, immunocapture electron microscopy (IEM) was performed to determine binding of ARP1 to clinical isolates and cell culture adapted strains. ARP1 and ARP3 were able to neutralise a broad variety of rotavirus serotypes/genotypes in vitro, and in addition, IEM showed specific binding to a variety of cell adapted strains as well as strains from clinical specimens. These results indicated that these molecules could potentially be used as immunoprophylactic and/or immunotherapeutic products for the prevention and/or treatment of infection of a broad range of clinically relevant rotavirus strains
Rotavirus NSP4 acts as a viral enterotoxin to induce diarrhea and is a potential target for rotavirus vaccines( selected summaries)
Rotavirus NSP4 acts as a viral enterotoxin to induce diarrhea and is a potential target for rotavirus vaccines( selected summaries)
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