Explore the vast range of titles available.

Titanium and its alloys exhibit advantageous ductility and strength-to-weight ratios, which makes them suitable for use as structural materials in numerous industrial applications. The ω phase has been observed to precipitate during the aging process of titanium alloys, resulting in a loss of ductility. Here we report tensile behavior of bulk polycrystalline ω-titanium with a chemical composition of commercially pure titanium grade 4 and an average grain size of 3.4 μm. We observed that stress-induced ω → α martensitic phase transformation occurs exclusively in the plastic regime. As plastic deformation proceeds, the volume fraction of α-phase increases. The 0.2% offset yield strength, tensile strength, and elongation to failure were determined to be 1130 ± 30 MPa, 1220 ± 30 MPa, and 16 ± 2%, respectively. The present study revealed transformation-induced plasticity in this material. The mechanical properties of this material with the pure titanium composition are comparable to those of a titanium alloy Ti-6Al-4 V. The bulk polycrystalline ω-titanium can potentially be utilized for biomedical applications, such as dental implants.

Claudin-2 is highly expressed in tight junctions of mouse renal proximal tubules, which possess a leaky epithelium whose unique permeability properties underlie their high rate of NaCl reabsorption. To investigate the role of claudin-2 in paracellular NaCl transport in this nephron segment, we generated knockout mice lacking claudin-2 (Cldn2⁻/⁻). The Cldn2⁻/⁻ mice displayed normal appearance, activity, growth, and behavior. Light microscopy revealed no gross histological abnormalities in the Cldn2⁻/⁻ kidney. Ultrathin section and freeze-fracture replica electron microscopy revealed that, similar to those of wild types, the proximal tubules of Cldn2⁻/⁻ mice were characterized by poorly developed tight junctions with one or two continuous tight junction strands. In contrast, studies in isolated, perfused S2 segments of proximal tubules showed that net transepithelial reabsorption of Na⁺, Cl⁻, and water was significantly decreased in Cldn2⁻/⁻ mice and that there was an increase in paracellular shunt resistance without affecting the apical or basolateral membrane resistances. Moreover, deletion of claudin-2 caused a loss of cation (Na⁺) selectivity and therefore relative anion (Cl⁻) selectivity in the proximal tubule paracellular pathway. With free access to water and food, fractional Na⁺ and Cl⁻ excretions in Cldn2⁻/⁻ mice were similar to those in wild types, but both were greater in Cldn2⁻/⁻ mice after i.v. administration of 2% NaCl. We conclude that claudin-2 constitutes leaky and cation (Na⁺)-selective paracellular channels within tight junctions of mouse proximal tubules.

A high salt intake exacerbates hypertension and accelerates renal tubular damage in hypertensive patients. However, data concerning early biomarkers for renal tubular change induced by a high salt intake are limited. The objective of this study was to clarify the time course of new biomarkers for renal tubular damage during high salt intake in spontaneously hypertensive rats (SHR). Male SHR received a regular or high-salt diet from 9 to 17 weeks of age. At 10 weeks of age, a high salt intake caused renal tubular damage, which was further exacerbated at 17 weeks of age. Although albuminuria was detected in salt-loaded SHR at 14 weeks of age, urinary excretion of vanin-1 and neutrophil gelatinase-associated lipocalin (NGAL) was elevated in these animals from 10-17 weeks of age. However, kidney injury molecule-1 (Kim-1) was elevated at 15 weeks of age in salt-loaded SHR. These results suggest that urinary vanin-1 and NGAL are potentially early biomarkers for renal tubular damage in SHR under a high salt intake.

Background: ATP-binding cassette (ABC) transporters are expressed in the vascular walls of brain capillaries and remove toxic chemicals from the brain. The expression of ABC transporters in peripheral organs is transcriptionally regulated by clock genes and exhibits 24 h periodic fluctuations. In addition, clock gene outputs diminish with aging. In this study, we evaluated whether the expression of ABC transporters in the blood–brain barrier (BBB) of young mice had a 24 h cycle, and whether the expression of ABC transporters in the BBB decreased with age. Methods: Brain microvascular (BMV) fractions from the cerebral cortex of male C57BL/6J mice were prepared using dextran. BMV fractions from young mice (12 weeks old) were prepared every four hours to evaluate 24 h rhythmicity. BMV fractions from both young and aged mice (85 weeks old) were prepared when protein expression peaked (Zeitgeber Time 5). Protein and mRNA expression of ABC transporters in BMV fractions were measured. Results: In young mice, protein expression of P-glycoprotein, breast cancer resistance protein, and multidrug resistance protein 4 showed time-dependent variations with a peak in the light phase (Zeitgeber Time 5); mRNA expression showed no time-dependent variation. The protein expression of these transporters was lower in the BBB of aged mice than in that of young mice, although mRNA expression did not differ between young and aged mice. Conclusions: ABC transporter protein expression levels in BMV endothelial cells decreased with aging; however, mRNA levels did not change, which suggests changes in protein expression did not result from diminished clock gene output. Further studies are needed to elucidate the mechanisms by which ABC transporter expression in the BBB decreases with aging.

Regolith particles on the asteroid Itokawa were recovered by the Hayabusa mission. Their three-dimensional (3D) structure and other properties, revealed by x-ray microtomography, provide information on regolith formation. Modal abundances of minerals, bulk density (3.4 grams per cubic centimeter), and the 3D textures indicate that the particles represent a mixture of equilibrated and less-equilibrated LL chondrite materials. Evidence for melting was not seen on any of the particles. Some particles have rounded edges. Overall, the particles' size and shape are different from those seen in particles from the lunar regolith. These features suggest that meteoroid impacts on the asteroid surface primarily form much of the regolith particle, and that seismic-induced grain motion in the smooth terrain abrades them over time.

Optimal treatment for nonalcoholic steatohepatitis (NASH) has not yet been established, particularly for individuals without diabetes. We examined the effects of metformin, commonly used to treat patients with type 2 diabetes, on liver pathology in a non-diabetic NASH mouse model. Eight-week-old C57BL/6 mice were fed a methionine- and choline-deficient plus high fat (MCD+HF) diet with or without 0.1% metformin for 8 weeks. Co-administration of metformin significantly decreased fasting plasma glucose levels, but did not affect glucose tolerance or peripheral insulin sensitivity. Metformin ameliorated MCD+HF diet-induced hepatic steatosis, inflammation, and fibrosis. Furthermore, metformin significantly reversed hepatic steatosis and inflammation when administered after the development of experimental NASH. These histological changes were accompanied by reduced hepatic triglyceride content, suppressed hepatic stellate cell activation, and the downregulation of genes involved in fatty acid metabolism, inflammation, and fibrogenesis. Metformin prevented and reversed steatosis and inflammation of NASH in an experimental non-diabetic model without affecting peripheral insulin resistance.

Circadian clocks in peripheral tissues are powerfully entrained by feeding. The mechanisms underlying this food entrainment remain unclear, although various humoral and neural factors have been reported to affect peripheral clocks. Because glucagon-like peptide-1 (GLP-1), which is rapidly secreted in response to food ingestion, influences multiple humoral and neural signaling pathways, we suggest that GLP-1 plays a role in the food entrainment of peripheral clocks. To test this, we compared the effects of exendin-4, a GLP-1 receptor agonist, on mRNA expression of the clock genes (Clock, Bmal1, Nr1d1, Per1, Per2, and Cry1) with those of refeeding. In addition, we investigated whether exendin-4 could affect the rhythms of the peripheral clocks. In male C57BL/6J mice, although refeeding rapidly (within 2 h) altered mRNA levels of Per1 and Per2 in the liver and that of Per1 in adipose tissue, a single i.p. injection of exendin-4 did not cause such changes. However, unlike the GLP-1 receptor antagonist exendin-(9-39), exendin-4 significantly influenced Per1 mRNA levels in the liver at 12 h after injection. Moreover, pretreatment with exendin-4 affected the rapid-feeding-induced change in Per1 not only in the liver, but also in adipose tissue, without effect on food intake. Furthermore, during light-phase restricted feeding, repeated dosing of exendin-4 at the beginning of the dark phase profoundly influenced both the food intake and daily rhythms of clock gene expression in peripheral tissues. Thus, these results suggest that exendin-4 modulates peripheral clocks via multiple mechanisms different from those of refeeding.

Records of micrometeorite collisions at down to submicron scales were discovered on dust grains recovered from near-Earth asteroid 25143 (Itokawa). Because the grains were sampled from very near the surface of the asteroid, by the Hayabusa spacecraft, their surfaces reflect the low-gravity space environment influencing the physical nature of the asteroid exterior. The space environment was examined by description of grain surfaces and asteroidal scenes were reconstructed. Chemical and O isotope compositions of five lithic grains, with diameters near 50 μm, indicate that the uppermost layer of the rubble-pile-textured Itokawa is largely composed of equilibrated LL-ordinary-chondrite-like material with superimposed effects of collisions. The surfaces of the grains are dominated by fractures, and the fracture planes contain not only sub-μm-sized craters but also a large number of sub-μm- to several-μm-sized adhered particles, some of the latter composed of glass. The size distribution and chemical compositions of the adhered particles, together with the occurrences of the sub-μm-sized craters, suggest formation by hypervelocity collisions of micrometeorites at down to nm scales, a process expected in the physically hostile environment at an asteroid’s surface. We describe impact-related phenomena, ranging in scale from 10-9 to 104 meters, demonstrating the central role played by impact processes in the long-term evolution of planetary bodies. Impact appears to be an important process shaping the exteriors of not only large planetary bodies, such as the moon, but also low-gravity bodies such as asteroids.

PurposeCurcumin is expected to have beneficial effects including an anti-cancer effect. However, its lower bioavailability is a critical concern and limits the utility of curcumin in clinical practice. In this study, we investigated whether transpulmonary delivery of curcumin is pharmacologically effective along with improving its bioavailability in mice with lung metastasis.MethodsC57BL/6J mice were injected with B16F10 melanoma cells via their tail vein and given curcumin by pulmonary administration every other day. The lung tissue of the vehicle-treated mice on day 17 was covered by nodules of metastatic melanoma.ResultsPulmonary curcumin administration significantly and dose-dependently protected the lung metastasis of melanoma. The phosphorylation of JNK (c-Jun NH2 terminal kinase) and HLJ1 expression levels in the lung metastatic nodules of the melanoma were significantly increased by pulmonary curcumin administration. The anti-metastatic effect of curcumin was blunted in mice injected with HLJ1 knocked-down B16F10 melanoma. Systemic bioavailability after pulmonary administration was 61-times higher than after oral administration. Additionally, the curcumin concentration in the lung tissue was sustained to a high level until 24 h after pulmonary administration.ConclusionsThis study showed the usefulness of curcumin to suppress lung metastasis of melanoma by pulmonary administration, a method that may overcome the low-bioavailability of curcumin.