Recently, nanocarriers that transport bioactive substances to a target site in the body have attracted considerable attention and undergone rapid progression in terms of the state of the art. ...However, few nanocarriers can enter the brain via a systemic route through the blood-brain barrier (BBB) to efficiently reach neurons. Here we prepare a self-assembled supramolecular nanocarrier with a surface featuring properly configured glucose. The BBB crossing and brain accumulation of this nanocarrier are boosted by the rapid glycaemic increase after fasting and by the putative phenomenon of the highly expressed glucose transporter-1 (GLUT1) in brain capillary endothelial cells migrating from the luminal to the abluminal plasma membrane. The precisely controlled glucose density on the surface of the nanocarrier enables the regulation of its distribution within the brain, and thus is successfully optimized to increase the number of nanocarriers accumulating in neurons.There are only a few examples of nanocarriers that can transport bioactive substances across the blood-brain barrier. Here the authors show that by rapid glycaemic increase the accumulation of a glucosylated nanocarrier in the brain can be controlled.
The molecular orientation behavior of isotactic polypropylene (iPP) is investigated by using in situ Raman spectroscopy under tensile tests. A versatile method of the tilt-angle correction for the ...orientation parameters is newly developed, where the molecular orientation in highly oriented specimens is assumed to be entropically favorable. The real-time changes of orientation parameters and orientation distribution functions are determined for the molecular chain axis of iPP during uniaxial stretching. The molecular orientation remains random in the elastic region, and increases after the first yield point. In the yielding region, a broad distribution of orientation toward an intermediate angle of 30-70° from the stretching direction is observed. This is interpreted as reorientation of the crystalline chains being hindered by rigid, bulky lamellar cluster units. After the yielding region, orientation toward the stretching direction proceeds rapidly, approaching highly oriented states.
Although most cyanobacterial cells contain prominent polyphosphate bodies in the central cytoplasmic area enclosed by the peripheral thylakoid membranes, their roles are not fully understood. Storing ...phosphate for nucleotide production might be one of their important roles in survival of the cells. As a step towards identifying a possible contribution of the polyphosphate bodies to DNA synthesis, the relationship between polyphosphate bodies and DNA throughout cell division cycle of Synechococcus elongatus PCC 7942 cells cultured under light/dark cycles was investigated with light and electron microscopy. During the dark period, the average size of polyphosphate bodies increased gradually without significant change in their number and distribution. However, during the light period, the number of polyphosphate bodies increased, while the size of each polyphosphate body decreased and cells elongated until the end of the light period, when most cells divided. The ratio of the content of polyphosphate bodies to cell length increased gradually during the dark period and decreased during the light period. Hoechst 33342-stained DNA appeared diffuse during the dark period, but in the light period it became condensed and eventually formed a wavy, rope-like structure prior to cell division. Close association between fibres containing DNA and polyphosphate bodies was demonstrated by TEM using DNA-specific staining and BrdU labelling. These regular coordinated changes of polyphosphate bodies and DNA shape during the cell division cycle, together with their intimate interaction, imply a role of polyphosphate bodies in supplying material for DNA.
Steroid-dependent minimal-change nephrotic syndrome (MCNS) requires administration of prolonged courses of prednisolone (PSL); therefore, a paradigm shift from such toxic 'non-specific' therapies to ...selective immunomodulating regimens is necessary for these cases.
To assess the therapeutic effects of rituximab (an anti-CD20 antibody) in adult patients with steroid-dependent MCNS, we performed a prospective trial of the effects of a single dose of rituximab administered twice at an interval of 6 months in 25 MCNS patients. We evaluated the biochemical parameters and compared the clinical findings between the 12-month period before and 12-month period after the first rituximab infusion.
A significant reduction in the number of relapses and the total dose and the maintenance dose of PSL administered was observed during the 12-month period after the first rituximab infusion when compared with the findings during the 12-month period before the first rituximab infusion 25 (100%) versus 4 (16%), P < 0.001; 8.2 versus 3.3 g, P < 0.001; 26.4 mg/day at baseline versus 1.1 mg/day at 12-month, P < 0.0001. Complete remission was achieved/maintained in all patients undergoing B-cell depletion. Four of 17 patients with B-cell repletion developed relapse.
Our results revealed that rituximab therapy was associated with a reduction in the number of relapses and in the total dose of PSL needed. Therefore, rituximab appears to be a useful therapeutic agent for adult patients with steroid-dependent MCNS. These results suggest that this treatment is rational and should be considered as an important option in the management of adult patients with steroid-dependent MCNS.
We present an extensive investigation (magnetic, electric and thermal measurements and X-ray absorption spectroscopy) of the Pr
0.5
Ca
0.5
CoO
3
and (Pr
1−
y
Y
y
)
0.7
Ca
0.3
CoO
3
(
y
... = 0.0625 − 0.15) perovskites, in which a peculiar metal-insulator (M-I) transition, accompanied with pronounced structural and magnetic anomalies, occurs at 76 K and 40 − 132 K, respectively. The inspection of the M-I transition using the XANES data of Pr-
L
3
-edge and Co-
K
-edge proofs the presence of Pr
4+
ions at low temperatures and indicates simultaneously the intermediate spin to low spin crossover of Co species on lowering the temperature. The study thus definitively confirms the synchronicity of the electron transfer between Pr
3+
ions and Co
3+/4+
O
3
subsystem and the transition to the low-spin, less electrically conducting phase. The large extent of the transfer is evidenced by the good quantitative agreement of the determined amount of the Pr
4+
species, obtained either from the temperature dependence of the XANES spectra or via integration of the magnetic entropy change over the Pr
4+
related Schottky peak in the low-temperature specific heat. These results show that the average valence of Pr
3+
/Pr
4+
ions increases (in concomitance with the decrease of the formal Co valence) below
T
MI
for (Pr
0.925
Y
0.075
)
0.7
Ca
0.3
CoO
3
up to 3.16+ (the doping level of the CoO
3
subsystem decreases from 3.30+ to 3.20+), for (Pr
0.85
Y
0.15
)
0.7
Ca
0.3
CoO
3
up to 3.28+ (the decrease of doping level from 3.30+ to 3.13+) and for Pr
0.5
Ca
0.5
CoO
3
up to 3.46+ (the decrease of doping level from 3.50+ to 3.27+).
An observational cohort study was conducted to compare the performance of the RIFLE (risk, injury, failure, loss and end-stage kidney disease), AKIN (acute kidney injury network) and conventional ...graded criteria to identify acute kidney injury (AKI) following SCT and to predict long-term mortality in 141 myeloablative allogeneic SCT (m-allo), 60 non-myeloablative allogeneic SCT (nm-allo) and 48 autologous SCT (auto) cases. The AKIN criteria had less ability to identify patients as having the lowest category, stage 1 (analogous to RIFLE risk): 33% (37%) in m-allo, 23% (32%) in nm-allo and 8.3% (16.7%) in auto. Cox regression showed that categories higher than the intermediate stage were independent predictors of mortality in all three definitions. The areas under receiver operating characteristic curves showed that both definition systems had similar and significant ability to predict mortality (0.643-0.649 in m-allo and 0.734-0.766 in nm-allo, respectively). These abilities of the conventional graded criteria were comparable with those of the RIFLE criteria. The RIFLE criteria have greater sensitivity than the AKIN criteria to identify patients with AKI and therefore are more favorable as a uniform definition system for post-SCT AKI. However, the RIFLE criteria do not improve on the clinical relevance of the conventional graded criteria.
In situ observation of the uniaxial deformation of isolated individual large spherulites of isotactic polypropylene was performed using films with a few large spherulites embedded in a smectic ...matrix. The effects of the variation of sign of birefringence in spherulites, which reflects the difference in lamellar morphology within spherulites were examined. In the case of a spherulite with few tangential lamellae, arcshaped cracks appear in the polar zone of the spherulite and then the radial craze-like fracture begins in the equatorial region perpendicular to the stretching axis. In the case of a spherulite with a large number of tangential lamellae, however, the radial crazing appears in the equatorial zone and then straight dark cracks, rather than arcs, running perpendicular to the stretching direction are initiated in the polar region. These results can be explained by considering the mechanical anisotropy in polypropylene lamellae.
Phosphorylation of tyrosine residue (Y1204) of rat nephrin by Fyn kinase allows Nck adaptor protein binding to nephrin motifs, which include the phosphorylated tyrosine. This ...phosphorylation-dependent switch induces actin polymerization in a cell culture system. Here, we generated an antibody recognizing phosphorylated nephrin at the Nck binding sites pY1204 and pY1228 to determine the phosphorylation status of nephrin using a rat model of puromycin aminonucleoside-induced nephrosis. Changes in globular actin (G-actin) and filamentous actin (F-actin) contents in isolated glomeruli were measured by western blot. Before experimental nephrosis, both Y1204 and Y1228 were phosphorylated, and most of the actin was filamentous. Before the onset of overt proteinuria, however, phosphorylation of both Y1204 and Y1228 rapidly decreased and became almost undetectable. During this period, the amount of F-actin in glomeruli began to decrease, whereas G-actin increased. Phosphorylation of nephrin at Y1228 in glomeruli of patients with minimal change nephrosis was significantly decreased compared with that in normal glomeruli. Our study suggests that tyrosine phosphorylation of nephrin by regulating F-actin formation may be important for the maintenance of normal podocyte morphology and function.
PDF
