Gastrulation in the amphibian embryo is driven by cells of the mesoderm. One of the genes that confers mesodermal identity in Xenopus is Brachyury (Xbra), which is required for normal gastrulation ...movements and ultimately for posterior mesoderm and notochord differentiation in the development of all vertebrates. Xbra is a transcription activator, and interference with transcription activation leads to an inhibition of morphogenetic movements during gastrulation. To understand this process, we have screened for downstream target genes of Brachyury (Tada, M., Casey, E., Fairclough, L. and Smith, J. C. (1998) Development 125, 3997â4006). This approach has now allowed us to isolate Xwnt11, whose expression pattern is almost identical to that of Xbra at gastrula and early neurula stages. Activation of Xwnt11 is induced in an immediate-early fashion by Xbra and its expression in vivo is abolished by a dominant-interfering form of Xbra, Xbra-En(R). Overexpression of a dominant-negative form of Xwnt11, like overexpression of Xbra-En(R), inhibits convergent extension movements. This inhibition can be rescued by Dsh, a component of the Wnt signalling pathway and also by a truncated form of Dsh which cannot signal through the canonical Wnt pathway involving GSK-3 and (beta)-catenin. Together, our results suggest that the regulation of morphogenetic movements by Xwnt11 occurs through a pathway similar to that involved in planar polarity signalling in Drosophila.
Leukoencephalopathies encompass all clinical syndromes that predominantly affect brain white matter. Genetic diagnosis informs clinical management of these patients, but a large part of the genetic ...contribution to adult leukoencephalopathy remains unresolved. To examine this genetic contribution, we analyzed genomic DNA from 60 Japanese patients with adult leukoencephalopathy of unknown cause by next generation sequencing using a custom‐designed gene panel. We selected 55 leukoencephalopathy‐related genes for the gene panel. We identified pathogenic mutations in 8 of the 60 adult leukoencephalopathy patients (13.3%): NOTCH3 mutations were detected in 5 patients, and EIF2B2, CSF1R, and POLR3A mutations were found independently in 1 patient each. These results indicate that cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) caused by NOTCH3 mutations is the most frequent adult leukoencephalopathy in our cohort. Moreover, brain imaging analysis indicates that CADASIL patients who do not present typical phenotypes may be underdiagnosed if not examined genetically.
About 13.3% of adult patients with leukoencephalopathy were definitively disgnosed with known, apparently pathological or novel mutations.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Trapeziometacarpal (TMC) arthrodesis provides stability and strength of the thumb, whereas fixation of the TMC joint restricts motion of the thumb, which may consequently impair the activity of daily ...living. The objective of our study was to investigate how length and area of the thumb-tip trajectory were reduced after the TMC joint fusion.
Six fresh, frozen cadavers were used for this study. Tension was applied to the distal tendons of 4 extrinsic thumb muscles (extensor pollicis longus, flexor pollicis longus, abductor pollicis longus, and extensor pollicis brevis) by servomotor, whereas tension was applied to 4 intrinsic muscles (abductor pollicis brevis, opponens pollicis, flexor pollicis brevis, and adductor pollicis) using static weights. The thumb-tip trajectory was examined using a motion capture system without tension and with 5 different weights to induce intrinsic muscle tension before and after the TMC joint fusion.
When tension was applied to the intrinsic muscles, the length of the thumb-tip trajectory decreased in all conditions compared with that before the TMC joint fusion, whereas the trajectory decreased only when the abductor pollicis longus was pulled. The overall thumb-tip trajectory area was reduced to approximately 30% compared with that before the TMC joint fusion.
Thumb-tip trajectory was restricted by the TMC joint fusion to approximately 30%. However, the reduced area was found tolerable for performing daily activities. Thus, arthrodesis can be the first-line treatment in patients who wish to engage in activities of daily living without difficulties.
•We investigated the influence of the trapetiometacarpal joint fusion.•The trapeziometacarpal joint fusion affected all intrinsic muscles of the thumb examined.•For extrinsic muscles trapeziometacarpal joint fusion only affected abductor pollicis longus.•Thumb-tip trajectory area was reduced to approximately 30% before trapeziometacarpal joint fusion.•The reduced area was mostly found in a tolerable area in activity of daily living.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The dynamic behavior and kinetics of the structural transformation of supported bimetallic nanoparticle catalysts with synergistic functions in the oxidation process are fundamental issues to ...understand their unique catalytic properties as well as to regulate the catalytic capability of alloy nanoparticles. The phase separation and structural transformation of Pt(3)Sn/C and PtSn/C catalysts during the oxidation process were characterized by in situ time-resolved energy-dispersive XAFS (DXAFS) and quick XAFS (QXAFS) techniques, which are element-selective spectroscopies, at the Pt L(III)-edge and the Sn K-edge. The time-resolved XAFS techniques provided the kinetics of the change in structures and oxidation states of the bimetallic nanoparticles on carbon surfaces. The kinetic parameters and mechanisms for the oxidation of the Pt(3)Sn/C and PtSn/C catalysts were determined by time-resolved XAFS techniques. The oxidation of Pt to PtO in Pt(3)Sn/C proceeded via two successive processes, while the oxidation of Sn to SnO(2) in Pt(3)Sn/C proceeded as a one step process. The rate constant for the fast Pt oxidation, which was completed in 3 s at 573 K, was the same as that for the Sn oxidation, and the following slow Pt oxidation rate was one fifth of that for the first Pt oxidation process. The rate constant and activation energy for the Sn oxidation in PtSn/C were similar to those for the Sn oxidation in Pt(3)Sn/C. In the PtSn/C, however, it was hard for Pt oxidation to PtO to proceed at 573 K, where Pt oxidation was strongly affected by the quantity of Sn in the alloy nanoparticles due to swift segregation of SnO(2) nanoparticles/layers on the Pt nanoparticles. The mechanisms for the phase separation and structure transformation in the Pt(3)Sn/C and PtSn/C catalysts are also discussed on the basis of the structural kinetics of the catalysts themselves determined by the in situ time-resolved DXAFS and QXAFS.
•The exchange spring magnet formed by a soft magnetic oxide and hard magnetic nitride.•Their exchange-spring behavior was evidenced by recoil permeability measurements.•The fully dense ...ferrite/Sm2Fe17N3 magnet exhibited resistivity of about 4000 μΩ cm.
Typical exchange spring magnets are composed of two phases, a rare-earth hard magnetic material and a metallic soft magnetic material, whose magnetization value is higher than those of hard magnetic phases, such as α-Fe, Fe-B, or Fe-Co. A novel high-electrical-resistance composite magnet was fabricated by consolidating micron-sized ferromagnetic nitride Sm2Fe17N3 powder particles coated with a continuous nano-sized soft magnetic ferrite oxide layer, which suppressed intergrain conductivity but sustained the magnetic exchange interactions between grains 21. A non-magnetic resin or ceramic insulator may suffice for the coated layer but gives rise to high electrical resistance of the magnet with large deterioration of magnetization. The soft magnetic ferrite oxide layer not only suppressed intergrain conductivity, but also only slightly reduced the magnetization of the magnet. At present, the only exchange spring magnet having a combination of a soft magnetic oxide and hard magnetic nitride is the ferrite/Sm2Fe17N3 composite magnet. Sm2Fe17N3 powder particles with a size of 2 μm were coated with an “iron ferrite” layer with a grain size of about 10 nm by ferrite plating, which is an aqueous process, following which the samples were consolidated by the explosive consolidation (EC) technique. The coercivity and rectangularity of the ferrite/Sm2Fe17N3 composite magnet decreased slightly compared to those of a Sm2Fe17N3 magnet. The fully dense ferrite/Sm2Fe17N3 magnet exhibited a resistivity of about 4000 μΩ cm, which is ten times larger than that of a fully dense Sm2Fe17N3 magnet. Thus, the soft magnetic ferrite layer in the composite magnet maintained the magnetic exchange coupling between ferromagnetic Sm2Fe17N3 grains and simultaneously suppressed intergrain electrical coupling to increase the resistivity. This decreased the eddy current loss and improved the high-frequency characteristics of the composite magnets. Therefore, ferrite/Sm2Fe17N3 composites are promising materials for magnets that are operated at high frequencies in advanced applications, such as electric vehicle magnets.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This randomised phase II trial compared gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer.
Patients were randomly assigned to 4-week treatment with ...gemcitabine alone (1000, mg m(-2) gemcitabine by 30-min infusion on days 1, 8, and 15) or gemcitabine and S-1 combination therapy (1000, mg m(-2) gemcitabine by 30-min infusion on days 1 and 15 and 40 mg m(-2) S-1 orally twice daily on days 1-15). The primary end point was progression-free survival (PFS).
Between July 2006 and February 2009, 106 patients were enrolled. The PFS in gemcitabine and S-1 combination arm was significantly longer than in gemcitabine arm (5.4 vs 3.6 months), with a hazard ratio of 0.64 (P=0.036). Overall survival (OS) for gemcitabine and S-1 combination was longer than that for gemcitabine monotherapy (13.5 vs 8.8 months), with a hazard ratio of 0.72 (P=0.104). Overall, grade 3 or 4 adverse events were similar in both arms.
Gemcitabine and S-1 combination therapy demonstrated longer PFS in advanced pancreatic cancer. Improved OS duration of 4.7 months was found for gemcitabine and S-1 combination therapy, though this was not statistically significant.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
PDF
