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At least 235 records · Page 13

Effect of hydrogen on the {beta} transus temperature of TC21 alloy

Effect of hydrogen on the {beta} transus temperature of TC21 alloy was investigated by metallographic technique and dilatometry. It is found that the {beta} transus temperature is closely related to the hydrogen content. For the hydrogenated TC21 alloy, the starting and finishing temperatures of {alpha} {yields} {beta} phase transition decrease with the increasing of hydrogen content before the hydride precipitates. And the finishing temperature of {alpha} {yields} {beta} phase transition increases as the hydrogen content increases after the hydride precipitates. Furthermore, corresponding inherent mechanisms of the above-mentioned phenomena have been presented according to atomic diffusivity, interface migration and the precipitation of hydride. - Research Highlights: {yields} The {beta} transus temperature of TC21 alloy is closely related to hydrogen content. {yields} The mechanism for effect of hydrogen on the {beta} transus temperature is presented. {yields} Precipitation of hydride has a significant influence on the {beta} transus temperature. {yields} The {alpha}/{beta} interface migration has an important effect on the {beta} transus temperature. {yields} The improvement of atom diffusivity affects the {beta} transus temperature highly.

36 MATERIALS SCIENCE↗

Protective effects of melittin on transforming growth factor-{beta}1 injury to hepatocytes via anti-apoptotic mechanism

Melittin is a cationic, hemolytic peptide that is the main toxic component in the venom of the honey bee (Apis mellifera). Melittin has multiple effects, including anti-bacterial, anti-viral and anti-inflammatory, in various cell types. However, the anti-apoptotic mechanisms of melittin have not been fully elucidated in hepatocytes. Apoptosis contributes to liver inflammation and fibrosis. Knowledge of the apoptotic mechanisms is important to develop new and effective therapies for treatment of cirrhosis, portal hypertension, liver cancer, and other liver diseases. In the present study, we investigated the anti-apoptotic effect of melittin on transforming growth factor (TGF)-{beta}1-induced apoptosis in hepatocytes. TGF-{beta}1-treated hepatocytes were exposed to low doses (0.5 and 1 {mu}g/mL) and high dose (2 {mu}g/mL) of melittin. The low doses significantly protected these cells from DNA damage in TGF-{beta}1-induced apoptosis compared to the high dose. Also, melittin suppressed TGF-{beta}1-induced apoptotic activation of the Bcl-2 family and caspase family of proteins, which resulted in the inhibition of poly-ADP-ribose polymerase (PARP) cleavage. These results demonstrate that TGF-{beta}1 induces hepatocyte apoptosis and that an optimal dose of melittin exerts anti-apoptotic effects against TGF-{beta}1-induced injury to hepatocytes via the mitochondrial pathway. These results suggest that an optimal dose of melittin can serve to protect cells against TGF-{beta}1-mediated injury. - Highlights: > We investigated the anti-apoptotic effect of melittin on TGF-{beta}1-induced hepatocyte. > TGF-{beta}1 induces hepatocyte apoptosis. > TGF-{beta}1-treated hepatocytes were exposed to low doses and high dose of melittin. > Optimal dose of melittin exerts anti-apoptotic effects to hepatocytes.

60 APPLIED LIFE SCIENCES↗

Predicting Reactor Antineutrino Emissions Using New Precision Beta Spectroscopy

Neutrino experiments at nuclear reactors are currently vital to the study of neutrino oscillations. The observed antineutrino rates at reactors are typically lower than model expectations. This observed deficit is called the “reactor neutrino anomaly”. A new understanding of neutrino physics may be required to explain this deficit, though model estimation uncertainties may also play a role in the apparent discrepancy. PNNL is currently investigating an experimental technique that promises reduced uncertainties for measured data to support these hypotheses and interpret reactor antineutrino measurements. The experimental approach is to 1) direct a proton accelerator beam on a metal target to produce a source of neutrons, 2) use spectral tailoring to modify the neutron spectrum to closely simulate the energy distribution of a power reactor neutron spectrum, 3) irradiate isotopic fission foils (235U, 238U, 239Pu, 241Pu) in this neutron spectrum so that fissions occur at energies representative of a reactor, 4) transport the beta particles released by the fission products in the foils to a beta spectrometer, 5) measure the beta energy spectrum, and 6) invert the measured beta energy spectrum to an antineutrino energy spectrum. A similar technique using a beta spectrometer and isotopic fission foils was pioneered in the 1980’s at the ILL thermal reactor. Those measurements have been the basis for interpreting all subsequent antineutrino measurements at reactors. A basic constraint in efforts to reduce uncertainties in predicting the antineutrino emission from reactor cores is any underlying limitation of the original measurements. This may include beta spectrum energy resolution, the absolute normalization of beta emission to number of fission, statistical counting uncertainties, lack of 238U data, the purely thermal nature of the IIL reactor neutrons used, etc. An accelerator-based neutron source that can be tailored to match various reactor neutron spectra provides an advantage for control in studying how changes in the neutron spectra (i.e. "in the reactor core") affects the resulting fission product beta spectrum. Furthermore, the 238U antineutrino spectrum, which has not been measured, can be studied directly because of the enhanced 1 MeV fast neutron flux available at the accelerator source. A facility such as the Project X Injector Experiment (PXIE) 30 MeV proton linear accelerator at Fermilab is being considered for this experiment. The hypothesis is that a new approach utilizing the flexibility of an accelerator neutron source with spectral tailoring coupled with a careful design of an isotopic fission target and beta spectrometer and the inversion of the beta spectrum to the neutrino spectrum will allow further reduction in the uncertainties associated with prediction of the reactor antineutrino spectrum.

Asner, David M.↗

Involvement of DNA polymerase beta in repairing oxidative damages induced by antitumor drug adriamycin

Adriamycin (ADM) is a widely used antineoplastic drug. However, the increasing cellular resistance has become a serious limitation to ADM clinical application. The most important mechanism related to ADM-induced cell death is oxidative DNA damage mediated by reactive oxygen species (ROS). Base excision repair (BER) is a major pathway in the repair of DNA single strand break (SSB) and oxidized base. In this study, we firstly applied the murine embryo fibroblasts wild-type (pol {beta} +/+) and homozygous pol {beta} null cell (pol {beta} -/-) as a model to investigate ADM DNA-damaging effects and the molecular basis underlying these effects. Here, cellular sensitivity to ADM was examined using colorimetric assay and colony forming assay. ADM-induced cellular ROS level and the alteration of superoxide dismutase (SOD) activity were measured by commercial kits. Further, DNA strand break, chromosomal damage and gene mutation were assessed by comet assay, micronucleus test and hprt gene mutation assay, respectively. The results showed that pol {beta} -/- cells were more sensitive to ADM compared with pol {beta} +/+ cells and more severe SSB and chromosomal damage as well as higher hprt gene mutation frequency were observed in pol {beta} -/- cells. ROS level in pol {beta} -/- cells increased along with decreased activity of SOD. These results demonstrated that pol {beta} deficiency could enable ROS accumulation with SOD activity decrease, further elevate oxidative DNA damage, and subsequently result in SSB, chromosome cleavage as well as gene mutation, which may be partly responsible for the cytotoxicity of ADM and the hypersensitivity of pol {beta} -/- cells to ADM. These findings suggested that pol {beta} is vital for repairing oxidative damage induced by ADM.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

Radiation-Induced Liver Fibrosis Is Mitigated by Gene Therapy Inhibiting Transforming Growth Factor-{beta} Signaling in the Rat

Purpose: We determined whether anti-transforming growth factor-{beta} (TGF-{beta}) intervention could halt the progression of established radiation-induced liver fibrosis (RILF). Methods and Materials: A replication-defective adenoviral vector expressing the extracellular portion of human T{beta}RII and the Fc portion of immunoglobulin G fusion protein (AdT{beta}RIIFc) was produced. The entire rat liver was exposed to 30 Gy irradiation to generate a RILF model (RILFM). Then, RILFM animals were treated with AdT{beta}RIIFc (1 x 10{sup 11} plaque-forming units [PFU] of T{beta}RII), control virus (1 x 10{sup 11} PFU of AdGFP), or saline. Delayed radiation liver injury was assessed by histology and immunohistochemistry. Chronic oxidative stress damage, hepatic stellate cell activation, and hepatocyte regeneration were also analyzed. Results: In rats infected with AdT{beta}RIIFc, fibrosis was significantly improved compared with rats treated with AdGFP or saline, as assessed by histology, hydroxyproline content, and serum level of hyaluronic acid. Compared with AdGFP rats, AdT{beta}RIIFc-treated rats exhibited decreased oxidative stress damage and hepatic stellate cell activation and preserved liver function. Conclusions: Our results demonstrate that TGF-{beta} plays a critical role in the progression of liver fibrosis and suggest that anti-TGF-{beta} intervention is feasible and ameliorates established liver fibrosis. In addition, chronic oxidative stress may be involved in the progression of RILF.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

Double beta decays of {sup 106}Cd

The two-neutrino (2{nu}2{beta}) and neutrinoless (0{nu}2{beta}) double beta decays of {sup 106}Cd are studied for the transitions to the ground state 0{sub gs}{sup +} and 0{sup +} and 2{sup +} excited states in {sup 106}Pd by using realistic many-body wave functions calculated in the framework of the quasiparticle random-phase approximation. Effective, G-matrix-derived nuclear forces are used in realistic single-particle model spaces. All the possible channels, {beta}{sup +}{beta}{sup +}, {beta}{sup +}EC, and ECEC, are discussed for both the 2{nu}2{beta} and 0{nu}2{beta} decays. The associated half-lives are computed and particular attention is devoted to the study of the detectability of the resonant neutrinoless double electron capture (R0{nu}ECEC) process in {sup 106}Cd. The calculations of the present article constitute the thus far most complete and up-to-date investigation of the double-beta-decay properties of {sup 106}Cd.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Investigation of double-beta decay with the NEMO-3 detector

The double-beta-decay experiment NEMO-3 has been taking data since February 2003. The aim of this experiment is to search for neutrinoless (0 {nu}{beta}{beta}) decay and investigate two neutrino doublebeta decay in seven different isotopically enriched samples ({sup 100}Mo, {sup 82}Se, {sup 48}Ca, {sup 96}Zr, {sup 116}Cd, {sup 130}Te, and {sup 150}Nd). After analysis of the data corresponding to 3.75 yr, no evidence for 0 {nu}{beta}{beta} decay in the 100Mo and 82Se samples was found. The half-life limits at the 90% C.L. are 1.1 Multiplication-Sign 10{sup 24} and 3.6 Multiplication-Sign 10{sup 23} yr, respectively. Additionally for 0 {nu}{beta}{beta} decay the following limits at the 90% C.L. were obtained, >1.3 Multiplication-Sign 10{sup 22} yr for {sup 48}Ca, >9.2 Multiplication-Sign 10{sup 21} yr for {sup 96}Zr, and >1.8 Multiplication-Sign 10{sup 22} yr for 150Nd. The 2 {nu}{beta}{beta} decay half-life values were precisely measured for all investigated isotopes.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Troglitazone stimulates {beta}-arrestin-dependent cardiomyocyte contractility via the angiotensin II type 1{sub A} receptor

Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) agonists are commonly used to treat cardiovascular diseases, and are reported to have several effects on cardiovascular function that may be due to PPAR{gamma}-independent signaling events. Select angiotensin receptor blockers (ARBs) interact with and modulate PPAR{gamma} activity, thus we hypothesized that a PPAR{gamma} agonist may exert physiologic effects via the angiotensin II type 1{sub A} receptor (AT1{sub A}R). In AT1{sub A}R-overexpressing HEK 293 cells, both angiotensin II (Ang II) and the PPAR{gamma} agonist troglitazone (Trog) enhanced AT1{sub A}R internalization and recruitment of endogenous {beta}-arrestin1/2 ({beta}arr1/2) to the AT1{sub A}R. A fluorescence assay to measure diacylglycerol (DAG) accumulation showed that although Ang II induced AT1{sub A}R-G{sub q} protein-mediated DAG accumulation, Trog had no impact on DAG generation. Trog-mediated recruitment of {beta}arr1/2 was selective to AT1{sub A}R as the response was prevented by an ARB- and Trog-mediated {beta}arr1/2 recruitment to {beta}1-adrenergic receptor ({beta}1AR) was not observed. In isolated mouse cardiomyocytes, Trog increased both % and rate of cell shortening to a similar extent as Ang II, effects which were blocked with an ARB. Additionally, these effects were found to be {beta}arr2-dependent, as cardiomyocytes isolated from {beta}arr2-KO mice showed blunted contractile responses to Trog. These findings show for the first time that the PPAR{gamma} agonist Trog acts at the AT1{sub A}R to simultaneously block G{sub q} protein activation and induce the recruitment of {beta}arr1/2, which leads to an increase in cardiomyocyte contractility.

60 APPLIED LIFE SCIENCES↗

Phosphatidylinositol 5-phosphate 4-kinase type II beta is required for vitamin D receptor-dependent E-cadherin expression in SW480 cells

Highlights: {yields} We analyzed Phosphatidylinositol 5-phosphate kinase II{beta} (PIPKII{beta}) function in cancer. {yields} PIPKII{beta} is required for vitamin D receptor-mediated E-cadherin upregulation in SW480. {yields} PIPKII{beta} suppresses cellular motility through E-cadherin induction in SW480 cells. {yields} Nuclear PIP{sub 2} but not plasma membrane-localized PIP{sub 2} mediates E-cadherin upregulation. -- Abstract: Numerous epidemiological data indicate that vitamin D receptor (VDR) signaling induced by its ligand or active metabolite 1{alpha},25-dihydroxyvitamin D{sub 3} (1{alpha},25(OH){sub 2}D{sub 3}) has anti-cancer activity in several colon cancers. 1{alpha},25(OH){sub 2}D{sub 3} induces the epithelial differentiation of SW480 colon cancer cells expressing VDR (SW480-ADH) by upregulating E-cadherin expression; however, its precise mechanism remains unknown. We found that phosphatidylinositol-5-phosphate 4-kinase type II beta (PIPKII{beta}) but not PIPKII{alpha} is required for VDR-mediated E-cadherin induction in SW480-ADH cells. The syntenin-2 postsynaptic density protein/disc large/zona occludens (PDZ) domain and pleckstrin homology domain of phospholipase C-delta1 (PLC{delta}1 PHD) possess high affinity for phosphatidylinositol-4,5-bisphosphate (PI(4,5)P{sub 2}) mainly localized to the nucleus and plasma membrane, respectively. The expression of syntenin-2 PDZ but not PLC{delta}1 PHD inhibited 1{alpha},25(OH){sub 2}D{sub 3}-induced E-cadherin upregulation, suggesting that nuclear PI(4,5)P{sub 2} production mediates E-cadherin expression through PIPKII{beta} in a VDR-dependent manner. PIPKII{beta} is also involved in the suppression of the cell motility induced by 1{alpha},25(OH){sub 2}D{sub 3}. These results indicate that PIPKII{beta}-mediated PI(4,5)P{sub 2} signaling is important for E-cadherin upregulation and inhibition of cellular motility induced by VDR activation.

60 APPLIED LIFE SCIENCES↗

Ultrasound-mediated interferon {beta} gene transfection inhibits growth of malignant melanoma

Highlights: {yields} Successful ultrasound-mediated transfection of melanoma (C32) cells with IFN-{beta} genes both in vitro and in vivo. {yields} Ultrasound-mediated IFN-{beta} transfection inhibited proliferation of melanoma cells in vitro. {yields} Ultrasound-mediated IFN-{beta} transfection inhibited melanoma tumor growth in vivo. -- Abstract: We investigated the effects of ultrasound-mediated transfection (sonotransfection) of interferon {beta} (IFN-{beta}) gene on melanoma (C32) both in vitro and in vivo. C32 cells were sonotransfected with IFN-{beta} in vitro. Subcutaneous C32 tumors in mice were sonicated weekly immediately after intra-tumor injection with IFN-{beta} genes mixed with microbubbles. Successful sonotransfection with IFN-{beta} gene in vitro was confirmed by ELISA, which resulted in C32 growth inhibition. In vivo, the growth ratio of tumors transfected with IFN-{beta} gene was significantly lower than the other experimental groups. These results may lead to a new method of treatment against melanoma and other hard-to-treat cancers.

60 APPLIED LIFE SCIENCES↗

Silencing p110{beta} prevents rapid depletion of nuclear pAkt

Highlights: Black-Right-Pointing-Pointer p110{beta} was essential for the statin- and ATP-induced depletion of nuclear pAkt and an associated inhibition of growth. Black-Right-Pointing-Pointer p110{beta} knock-out inhibited statin-induced changes in binding between FKBP51, pAkt and PTEN. Black-Right-Pointing-Pointer Data supports the hypothesis that nuclear pAkt is important for anti-cancer effects of statins. -- Abstract: The p110{beta} subunit in the class IA PI3K family may act as an oncogene and is critical for prostate tumor development in PTEN knockout mice. We tested the possible involvement of p110{beta} in a recently described rapid depletion of phosphorylated Akt (pAkt) in the nucleus. Previous work showed that this down-regulation is induced by extracellular ATP or by statins and is mediated by the purinergic receptor P2X7. Here, we used p110{beta} knock out mouse embryonic fibroblasts (MEFs) and siRNA-treated cancer cells. We found that p110{beta} is essential for ATP- or statin-induced nuclear pAkt depletion in MEFs and in several cancer cell lines including prostate cancer cells. ATP, statin or the selective P2X7 agonist BzATP also inhibited cell growth, and this inhibition was not seen in p110{beta} knock out cells. We also found that p110{beta} was necessary for statin-induced changes in binding between FKBP51, pAkt and PTEN. Our data show that p110{beta} is essential for the ATP- and statin-induced effects and support a role of nuclear pAkt in cancer development. They also provide support for a chemopreventive effect of statins mediated by depletion of nuclear pAkt.

60 APPLIED LIFE SCIENCES↗

Activation of the Wnt/{beta}-catenin signaling pathway is associated with glial proliferation in the adult spinal cord of ALS transgenic mice

Highlights: Black-Right-Pointing-Pointer Wnt3a and Cyclin D1 were upregulated in the spinal cord of the ALS mice. Black-Right-Pointing-Pointer {beta}-catenin translocated from the cell membrane to the nucleus in the ALS mice. Black-Right-Pointing-Pointer Wnt3a, {beta}-catenin and Cyclin D1 co-localized for astrocytes were all increased. Black-Right-Pointing-Pointer BrdU/Cyclin D1 double-positive cells were increased in the spinal cord of ALS mice. Black-Right-Pointing-Pointer BrdU/Cyclin D1/GFAP triple-positive cells were detected in the ALS mice. -- Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive and fatal loss of motor neurons. In ALS, there is a significant cell proliferation in response to neurodegeneration; however, the exact molecular mechanisms of cell proliferation and differentiation are unclear. The Wnt signaling pathway has been shown to be involved in neurodegenerative processes. Wnt3a, {beta}-catenin, and Cyclin D1 are three key signaling molecules of the Wnt/{beta}-catenin signaling pathway. We determined the expression of Wnt3a, {beta}-catenin, and Cyclin D1 in the adult spinal cord of SOD1{sup G93A} ALS transgenic mice at different stages by RT-PCR, Western blot, and immunofluorescence labeling techniques. We found that the mRNA and protein of Wnt3a and Cyclin D1 in the spinal cord of the ALS mice were upregulated compared to those in wild-type mice. In addition, {beta}-catenin translocated from the cell membrane to the nucleus and subsequently activated transcription of the target gene, Cyclin D1. BrdU and Cyclin D1 double-positive cells were increased in the spinal cord of these mice. Moreover, Wnt3a, {beta}-catenin, and Cyclin D1 were also expressed in both neurons and astrocytes. The expression of Wnt3a, {beta}-catenin or Cyclin D1 in mature GFAP{sup +} astrocytes increased. Moreover, BrdU/Cyclin D1/GFAP triple-positive cells were detected in the ALS mice. Our findings suggest that neurodegeneration activates the Wnt/{beta}-catenin signaling pathway, which is associated with glial proliferation in the adult spinal cord of ALS transgenic mice. This mechanism may be significant in clinical gene therapy.

60 APPLIED LIFE SCIENCES↗

Effects of short-hairpin RNA-inhibited {beta}-catenin expression on the growth of human multiple myeloma cells in vitro and in vivo

Highlights: Black-Right-Pointing-Pointer {beta}-Catenin expression were markedly down-regulated by CTNNB1 shRNA. Black-Right-Pointing-Pointer CTNNB1 shRNA could inhibit the proliferation of RPMI8226 cells. Black-Right-Pointing-Pointer Significantly profound apoptotic cell death in CTNNB1 shRNA cells. Black-Right-Pointing-Pointer In vivo, CTNNB1 silence led to a growth inhibition of myeloma growth. Black-Right-Pointing-Pointer c-myc and {beta}-catenin in the expression cells of cleaved caspase-3 were increased. -- Abstract: Multiple myeloma (MM) is thrombogenic as a consequence of multiple hemostatic effects. Overexpression of {beta}-catenin has been observed in several types of malignant tumors, including MM. However, the relationship between {beta}-catenin expression and MM remains unclear. In the present study, RNA interference was used to inhibit {beta}-catenin expression in RPMI8226 cells. RT-PCR and Western blotting analyses showed that {beta}-catenin mRNA and protein expression were markedly down-regulated by CTNNB1 shRNA. Western blotting showed that the protein levels of cyclin D1 and glutamine synthetase were downregulated and supported the transcriptional regulatory function of {beta}-catenin. The MTT assay showed that CTNNB1 shRNA could have significant inhibitory effects on the proliferation of RPMI8226 cells. The TOPflash reporter assay demonstrated significant downregulation after CTNNB1 shRNA transfection in RPMI8226 cells. Flow cytometric analyses also showed significantly profound apoptosis in CTNNB1 shRNA cells. We found CTNNB1 silence led to growth inhibition of MM growth in vivo. Immunohistochemical analyses showed that c-myc and {beta}-catenin were reduced in CTNNB1 shRNA tumor tissues, but that expression of cleaved caspase-3 was increased. These results show that {beta}-catenin could be a new therapeutic agent that targets the biology of MM cells.

60 APPLIED LIFE SCIENCES↗

TGF{beta}1 induces apoptosis in invasive prostate cancer and bladder cancer cells via Akt-independent, p38 MAPK and JNK/SAPK-mediated activation of caspases

Highlights: Black-Right-Pointing-Pointer TGF{beta} induced apoptosis in invasive prostate cancer and bladder cancer cells. Black-Right-Pointing-Pointer TGF{beta} inhibited prostate/bladder cancer cell proliferation and colony/foci formation. Black-Right-Pointing-Pointer TGF{beta} induced prostate/bladder cancer cell apoptosis independent of Akt inhibition. Black-Right-Pointing-Pointer TGF{beta} inhibited ERK1/2 phosphorylation in prostate/bladder cancer cells. Black-Right-Pointing-Pointer TGF{beta} induced p38 MAPK and JNK-mediated activation of caspases-9, -8 and -3. -- Abstract: Recent findings indicate that advanced stage cancers shun the tumor suppressive actions of TGF{beta} and inexplicably utilize the cytokine as a tumor promoter. We investigated the effect of TGF{beta}1 on the survival and proliferation of invasive prostate (PC3) and bladder (T24) cancer cells. Our study indicated that TGF{beta}1 decreased cell viability and induced apoptosis in invasive human PC3 and T24 cells via activation of p38 MAPK-JNK-Caspase9/8/3 pathway. Surprisingly, no change in the phosphorylation of pro-survival Akt kinase was observed. We postulate that TGF{beta}1 pathway may be utilized for specifically targeting urological cancers without inflicting side effects on normal tissues.

60 APPLIED LIFE SCIENCES↗

Osteocalcin protects pancreatic beta cell function and survival under high glucose conditions

Diabetes is characterized by progressive beta cell dysfunction and loss due in part to oxidative stress that occurs from gluco/lipotoxicity. Treatments that directly protect beta cell function and survival in the diabetic milieu are of particular interest. A growing body of evidence suggests that osteocalcin, an abundant non-collagenous protein of bone, supports beta cell function and proliferation. Based on previous gene expression data by microarray, we hypothesized that osteocalcin protects beta cells from glucose-induced oxidative stress. To test our hypothesis we cultured isolated rat islets and INS-1E cells in the presence of normal, high, or high glucose ± osteocalcin for up to 72 h. Oxidative stress and viability/mitochondrial function were measured by H{sub 2}O{sub 2} assay and Alamar Blue assay, respectively. Caspase 3/7 activity was also measured as a marker of apoptosis. A functional test, glucose stimulated insulin release, was conducted and expression of genes/protein was measured by qRT-PCR/western blot/ELISA. Osteocalcin treatment significantly reduced high glucose-induced H{sub 2}O{sub 2} levels while maintaining viability/mitochondrial function. Osteocalcin also significantly improved glucose stimulated insulin secretion and insulin content in rat islets after 48 h of high glucose exposure compared to untreated islets. As expected sustained high glucose down-regulated gene/protein expression of INS1 and BCL2 while increasing TXNIP expression. Interestingly, osteocalcin treatment reversed the effects of high glucose on gene/protein expression. We conclude that osteocalcin can protect beta cells from the negative effects of glucose-induced oxidative stress, in part, by reducing TXNIP expression, thereby preserving beta cell function and survival. - Highlights: • Osteocalcin reduces glucose-induced oxidative stress in beta cells. • Osteocalcin preserves beta cell function and survival under stress conditions. • Osteocalcin reduces glucose-induced TXNIP expression in beta cells.

60 APPLIED LIFE SCIENCES↗

Solid solubility of Yb{sub 2}Si{sub 2}O{sub 7} in {beta}-, {gamma}- and {delta}-Y{sub 2}Si{sub 2}O{sub 7}

This paper examines the structural changes with temperature and composition in the Yb{sub 2}Si{sub 2}O{sub 7}-Y{sub 2}Si{sub 2}O{sub 7} system; members of this system are expected to form in the intergranular region of Si{sub 3}N{sub 4} and SiC structural ceramics when sintered with the aid of Yb{sub 2}O{sub 3} and Y{sub 2}O{sub 3} mixtures. A set of different compositions have been synthesised using the sol-gel method to obtain a xerogel, which has been calcined at temperatures between 1300 and 1650 deg. C during different times. Isotherms at 1300 and 1600 deg. C have been analysed in detail to evaluate the solid solubility of Yb{sub 2}Si{sub 2}O{sub 7} in {beta}-Y{sub 2}Si{sub 2}O{sub 7} and {gamma}-Y{sub 2}Si{sub 2}O{sub 7}. Although Yb{sub 2}Si{sub 2}O{sub 7} shows a unique stable polymorph ({beta}), Yb{sup 3+} is able to replace Y{sup 3+} in {gamma}-Y{sub 2}Si{sub 2}O{sub 7} and {delta}-Y{sub 2}Si{sub 2}O{sub 7} at high temperatures and low Yb contents. IR results confirm the total solid solubility in the system and suggest a constant SiOSi angle of 180 deg. in the Si{sub 2}O{sub 7} unit across the system. The temperature-composition diagram of the system, obtained from powder XRD data, is dominated by the {beta}-RE{sub 2}Si{sub 2}O{sub 7} polymorph, with {gamma}-RE{sub 2}Si{sub 2}O{sub 7} and {delta}-RE{sub 2}Si{sub 2}O{sub 7} showing reduced stability fields. The diagram is in accordance with Felsche's diagram if average ionic radii are assumed for the members of the solid solution at any temperature, as long as the {beta}-{gamma} phase boundary is slightly shifted towards higher radii. - Graphical abstract: Polymorphism, as a function of average radii, in the systems Yb{sub 2}Si{sub 2}O{sub 7}-Y{sub 2}Si{sub 2}O{sub 7} (dotted symbols), Lu{sub 2}Si{sub 2}O{sub 7}-Y{sub 2}Si{sub 2}O{sub 7} (solid symbols) and Sc{sub 2}Si{sub 2}O{sub 7}-Y{sub 2}Si{sub 2}O{sub 7} (open symbols) compared to phase boundaries of Felsche for pure rare earth disilicates. Circles: {beta}-RE{sub 2}Si{sub 2}O{sub 7}. Squares: {gamma}-RE{sub 2}Si{sub 2}O{sub 7}. Triangles: {delta}-RE{sub 2}Si{sub 2}O{sub 7}. Highlights: > {beta}-Yb{sub 2}Si{sub 2}O{sub 7} and {beta}-Y{sub 2}Si{sub 2}O{sub 7} form a complete solid solution at 1300 deg. C. > Yb(III) replaces Y in {gamma}- and {delta}-RE{sub 2}Si{sub 2}O{sub 7}, at low Yb contents and high temperatures. > Phase diagram of the Yb{sub 2}Si{sub 2}O{sub 7}-Y{sub 2}Si{sub 2}O{sub 7} system is dominated by the {beta}-RE{sub 2}Si{sub 2}O{sub 7} phase. > {gamma}- and {delta}-phases show very reduced stability fields. > {beta}-{gamma} phase boundary in Felsche's diagram should be slightly shifted towards higher radii.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

High pressure structural study of {beta}-Ti{sub 3}O{sub 5}: X-ray diffraction and Raman spectroscopy

The structural stability of {beta}-Ti{sub 3}O{sub 5} (C2/m) has been investigated by X-ray diffraction and Raman spectroscopy with diamond anvil cells. {beta}-Ti{sub 3}O{sub 5} is stable up to about 26 GPa at room temperature. Isothermal pressure-volume relationship of {beta}-Ti{sub 3}O{sub 5} is well presented by the third-order Birch-Murnaghan equation of state with V{sub 0}=348.6(8) A{sup 3} and B{sub 0}=216(9) GPa. Axial compressibility presents obvious anisotropy. The a-axis and c-axis are more compressible than b-axis due to the different crystal structure arrangement of {beta}-Ti{sub 3}O{sub 5} along b-axis and perpendicular to b-axis direction. The Grueneisen parameters of thirteen observed Raman modes are 0.79-1.74, whose mean is 1.32. - Graphical abstract: The crystal structure of {beta}-Ti{sub 3}O{sub 5}: the projection of {beta}-Ti{sub 3}O{sub 5} along b-axis (Left) and the projection of {beta}-Ti{sub 3}O{sub 5} along c-axis (Right). Highlights: Black-Right-Pointing-Pointer High pressure structural stability of {beta}-Ti{sub 3}O{sub 5} was investigated. Black-Right-Pointing-Pointer {beta}-Ti{sub 3}O{sub 5} is stable up to about 26 GPa. Black-Right-Pointing-Pointer Axial compressibility presents obvious anisotropy. Black-Right-Pointing-Pointer Pressure-volume relationship is well presented by Birch-Murnaghan equation of state. Black-Right-Pointing-Pointer The Grueneisen parameters are 0.79-1.74.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Role of caspase-1 and interleukin-1{beta} in acetaminophen-induced hepatic inflammation and liver injury

Acetaminophen (APAP) overdose can result in serious liver injury and potentially death. Toxicity is dependent on metabolism of APAP to a reactive metabolite initiating a cascade of intracellular events resulting in hepatocellular necrosis. This early injury triggers a sterile inflammatory response with formation of cytokines and innate immune cell infiltration in the liver. Recently, IL-1{beta} signaling has been implicated in the potentiation of APAP-induced liver injury. To test if IL-1{beta} formation through caspase-1 is critical for the pathophysiology, C57Bl/6 mice were treated with the pan-caspase inhibitor Z-VD-fmk to block the inflammasome-mediated maturation of IL-1{beta} during APAP overdose (300 mg/kg APAP). This intervention did not affect IL-1{beta} gene transcription but prevented the increase in IL-1{beta} plasma levels. However, APAP-induced liver injury and neutrophil infiltration were not affected. Similarly, liver injury and the hepatic neutrophilic inflammation were not attenuated in IL-1-receptor-1 deficient mice compared to wild-type animals. To evaluate the potential of IL-1{beta} to increase injury, mice were given pharmacological doses of IL-1{beta} after APAP overdose. Despite increased systemic activation of neutrophils and recruitment into the liver, there was no alteration in injury. We conclude that endogenous IL-1{beta} formation after APAP overdose is insufficient to activate and recruit neutrophils into the liver or cause liver injury. Even high pharmacological doses of IL-1{beta}, which induce hepatic neutrophil accumulation and activation, do not enhance APAP-induced liver injury. Thus, IL-1 signaling is irrelevant for APAP hepatotoxicity. The inflammatory cascade is a less important therapeutic target than intracellular signaling pathways to attenuate APAP-induced liver injury.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗