TRPV4, a nonselective cation channel of the transient receptor potential (TRP) family, is gated by hypotonicity. Expression of TRPV4 mRNA has been detected in the circumventricular organs of the ...brain responsible for sensing systemic tonicity and in the kidney distal convoluted tubule (DCT), among other sites. No analysis of TRPV4 expression at the protein level has been undertaken and no systematic analysis of expression of this channel has been reported in the kidney. Via RNAse protection assay and immunoblotting, abundant expression of TRPV4 was detected in the cortex, medulla, and papilla. The expression pattern of TRPV4 was characterized in both rat and mouse kidney, which revealed similar patterns of immunoreactivity. TRPV4 expression was absent from the proximal tubule (PT) and descending thin limb (DTL), whereas the strongest expression was observed in the ascending thin limb (ATL). The thick ascending limb (TAL) was strongly positive as was the DCT and connecting tubule. Importantly, the water-permeant cells of the macula densa were unstained. Moderate TRPV4 expression was noted in all collecting duct portions and in papillary epithelium; intercalated cells (type A) exhibited a particularly strong signal. In all positive segments, TRPV4 expression was concentrated at the basolateral membrane. Therefore, TRPV4 is expressed in only those nephron segments that are constitutively (i.e., ATL, TAL, and DCT) or conditionally (i.e., collecting duct) water impermeant and where generation of a substantial transcellular osmotic gradient could be expected. TRPV4 expression is absent from nephron segments exhibiting constitutive water permeability and unregulated apical aquaporin expression (i.e., PT and DTL). These data, although circumstantial, are consistent with a role for TRPV4 in the response to anisotonicity in the mammalian kidney.
Although poly(l-lactic acid) (PLLA) is reputed to be biodegradable in the human body, its hydrophobic nature lets it persist for ca. 5.5 years. This study demonstrates that biologically safe lactide ...copolymers, poly(aspartic acid-co-l-lactide) (PAL) and poly(malic acid-co-l-lactide) (PML), dispersed in the PLLA function as detonators (triggers) for its hydrolytic degradation under physiological conditions. The copolymers significantly enhance hydrolysis, and consequently, the degradation rate of PLLA becomes easily tunable by controlling the amounts of PAL and PML. The present study elucidates the effects of uniaxial drawing on the structural development, mechanical properties, and hydrolytic degradation under physiological conditions of PLLA blend films. At initial degradation stages, the mass loss was not affected by uniaxial drawing; however, at late degradation stages, less developed crystals as well as amorphous chains were degradable at low draw ratio (DR), whereas not only highly developed crystals but also the oriented amorphous chains became insensitive to hydrolysis at high DR. Our work provides important molecular level results that demonstrate that biodegradable materials can have superb mechanical properties and also disappear in a required time under physiological conditions.
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IJS, KILJ, NUK, PNG, UL, UM
Prostaglandins (PGs) generated by the enzyme cyclooxygenase (COX) have been implicated in the pathological renal hemodynamics and structural alterations in diabetes mellitus, but the role of ...individual COX isoenzymes in diabetic nephropathy remains unknown. We explored COX-1 and COX-2 expression and hemodynamic responses to the COX-1 inhibitor valeryl salicylate (VS) or the COX-2 inhibitor NS398 in moderately hyperglycemic, streptozotocin-diabetic (D) and control (C) rats. Immunoreactive COX-2 was increased in D rats compared with C rats and normalized by improved glycemic control. Acute systemic administration of NS398 induced no significant changes in mean arterial pressure and renal plasma flow in either C or D rats but reduced glomerular filtration rate in D rats, resulting in a decrease in filtration fraction. VS had no effect on renal hemodynamics in D rats. Both inhibitors decreased urinary excretion of PGE(2). However, only NS398 reduced excretion of thromboxane A(2). In conclusion, we documented an increase in renal cortical COX-2 protein expression associated with a different renal hemodynamic response to selective systemic COX-2 inhibition in D as compared with C animals, indicating a role of COX-2-derived PG in pathological renal hemodynamic changes in diabetes.
We report on the very long baseline interferometry (VLBI) follow-up observations using the Japanese VLBI Network array at 22 GHz for the largest X-ray flare of TeV blazar Mrk 421 that occurred in ...2010 mid-February. The total of five epochs of observations were performed at intervals of about 20 days between 2010 March 7 and May 31. No newborn component associated with the flare was seen directly in the total intensity images obtained by our multi-epoch VLBI observations. However, one jet component located at ~1 mas northwest from the core was able to be identified, and its proper motion can be measured as -1.66 + or - 0.46 mas yr super(-1), which corresponds to an apparent velocity of -3.48 + or - 0.97c. Here, this negative velocity indicates that the jet component was apparently moving toward the core. As the most plausible explanation, we discuss that the apparent negative velocity was possibly caused by the ejection of a new component, which could not be resolved with our observations. In this case, the obtained Doppler factor of the new component is around 10-20, which is consistent with the ones typically estimated by model fittings of spectral energy distribution for this source.
The toc1 mutation causes shortened circadian rhythms in light-grown Arabidopsis plants. Here, we report the same toc1 effect in the absence of light input to the clock. We also show that TOC1 ...controls photoperiodic flowering response through clock function. The TOC1 gene was isolated and found to encode a nuclear protein containing an atypical response regulator receiver domain and two motifs that suggest a role in transcriptional regulation: a basic motif conserved within the CONSTANS family of transcription factors and an acidic domain. TOC1 is itself circadianly regulated and participates in a feedback loop to control its own expression.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Summary
Aims: Glimepiride, a third generation sulfonylurea (SU), is known to have extrapancreatic effects, but its vascular effect is unclear. We investigated the efficacy of glimepiride in ...improving arterial stiffness assessed by cardio‐ankle vascular index (CAVI) in type 2 diabetic patients, compared with glibenclamide, a conventional SU.
Methods: Forty type 2 diabetic patients were randomly assigned to two groups. One group was administered glimepiride 1.5 mg/day, and the other group was administered glibenclamide 1.25 mg/day for 6 months.
Results: No significant difference in hypoglycaemic effect was observed between two groups. CAVI significantly decreased only in glimepiride group (9.4 ± 1.4→8.9 ± 0.8, p < 0.05). Decrease in CAVI was greater in glimepiride group than in glibenclamide group (−0.50 ± 0.98 vs. −0.04 ± 0.57, p = 0.048). Urinary 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) decreased in glimepiride group and increased in glibenclamide group, and the changes were significantly different between groups (−1.5 ± 3.5 vs. + 1.8 ± 3.6, p = 0.009); whereas serum lipoprotein lipase mass increased in glibenclamide group and decreased in glibenclamide group, and the changes tended to be different between groups (+ 2.1 ± 19.1 vs. −7.4 ± 19.2, p = 0.096). Change in urinary 8‐OHdG was a significant independent predictor for change in CAVI in all subjects.
Conclusions: These results suggest that glimepiride improves CAVI compared with glibenclamide. Reduced oxidative stress and improved insulin resistance may contribute to the improvement of CAVI by glimerpiride.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
(18)F-FAMT as an amino-acid tracer for positron emission tomography (PET) is useful for detecting human neoplasms. (18)F-FAMT is accumulated in tumour cells solely via L-type amino-acid transporter 1 ...(LAT1). This study was conducted to investigate the biological significance of (18)F-FAMT uptake in patients with oesophageal cancer.
From April 2008 to December 2011, 42 patients with oesophageal cancer underwent both (18)F-FAMT PET/CT and (18)F-FDG PET/CT before surgical treatment. The immunohistochemical analysis of LAT1, CD98, Ki-67, CD34, p53, p-Akt and p-mTOR was performed on the primary lesions. In vitro experiments were performed to examine the mechanism of (18)F-FAMT uptake.
High uptake of (18)F-FAMT was significantly associated with advanced stage, lymph node metastasis and the expression of LAT1, CD98, Ki-67 and CD34. LAT1 expression yielded a statistically significant correlation with CD98 expression, cell proliferation, angiogenesis and glucose metabolism. In vitro experiments revealed that (18)F-FAMT was specifically transported by LAT1.
The uptake of (18)F-FAMT within tumour cells is determined by the LAT1 expression and correlated with cell proliferation and angiogenesis in oesophageal cancer. The present experiments also confirmed the presence of LAT1 as an underlying mechanism of (18)F-FAMT accumulation.
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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
We carried out powder neutron diffraction measurements in NaCuMoO4(OD) in order to investigate the ground state of this material. We observe no temperature dependence between the powder neutron ...diffraction profiles at T = 1.2 and 0.07 K within the experimental error. We evaluate the maximum of the expected moment under the assumption that the helical magnetic order is realized and that the magnetic peaks are hidden in background scattering. We determined the positions of the D ions from the profile by using the Rietveld analysis.
We have developed a new EMR method, the 'Hook knife' method, for the en-bloc resection of larger lesions. First, we placed marks around the lesion with a coagulation tip. Next, 10% glycerol diluted ...epinephrine solution was injected into the submucosal layer to separate the mucosa from the muscular layer proper. Then, we cut the mucosa around the lesion with a needle knife. Finally, we cut the submucosal fibers and vessels using a hook-type knife and resected the lesions. A large en-bloc resection, ≥70 mm in size, was possible with this new EMR method. Because of this, the histological examination for both the range of lateral spreading and the depth of invasion can be made more precisely. Aggressive endoscopic mucosal resection is established by this new EMR method.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In this study, novel biodegradable materials were successfully generated, which have excellent mechanical properties in air during usage and storage, but whose structure easily disintegrates when ...immersed in water. The materials were prepared by melt blending poly(L-lactic acid) (PLLA) and poly(butylene adipate-co-terephthalate) (PBAT) with a small amount of oligomeric poly(aspartic acid-co-lactide) (PAL) as a degradation accelerator. The degradation behavior of the blends was investigated by immersing the blend films in phosphate-buffered saline (pH = 7.3) at 40 °C. It was shown that the PAL content and composition significantly affected morphology, mechanical properties, and hydrolysis rate of the blends. It was observed that the blends containing PAL with higher molar ratios of L-lactyl LA/Asp had smaller PBAT domain size, showing better mechanical properties when compared with those containing PAL with lower molar ratios of LA/Asp. The degradation rates of both PLLA and PBAT components in the ternary blends simultaneously became higher for the blends containing PAL with higher molar ratios of LA/Asp. It was confirmed that the PLLA component and its decomposed materials efficiently catalyze the hydrolytic degradation of the PBAT component, but by contrast that the PBAT component and its decomposed materials do not catalyze the hydrolytic degradation of the PLLA component in the blends.
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