Quantitative Measurement of Tackiness and Bonding Potential of Trackless Tack Coat

Application of tack coats prior to placement of a thin overlay is a prerequisite to bond between the existing and the overlaid layers. Although a conventional tack is appropriately applied to the surface, this material is likely to be picked up and contaminated by construction traffic. Trackless tacks, recently introduced to paving industries in Texas, have overcome such issue by minimizing tackiness. However, there is no specification and documentation for tackiness and bonding potential of various trackless tacks in the Texas Department of Transportation. Also, a damage model for tackiness is needed to characterize the fracture properties of the tacks. The main objectives of this study were to 1) investigate the material characterization of trackless tacks, 2) evaluate the bonding potential of trackless tacks, and 3) develop a predictive model for the tracking behavior based on a fundamental fracture theory. Six different products were used in this study. The rheological and viscoelastic properties of trackless tacks were identified using the frequency sweep test and the multiple shear creep recovery test. The contact angle was measured to determine the surface energy characteristics. Also, the tackiness was measured at different temperatures and debonding rates using the Dynamic Shear Rheometer tackiness test and quantified in terms of tack energy. Also, the bond strength and bond energy of trackless tack coats were measured in bonded pavement layers through laboratory and field testing for evaluation of their bonding potential. The results were used to classify the trackless tack coats based on their stiffness in terms of complex shear modulus. The stiff binder group showed to have lower sensitivity of non-recoverable creep compliance and percent recovery to stress level and better tracking resistance than the soft binder group. The curve of the tack energy varying bonding/debonding rates and temperatures could be fitted with a power law. Through a shear test, the surface type, tack type, and reactivation temperature were identified to be the dominant parameters that influence on bonding potential. Using the modified Paris’s law, the fracture properties of tack residue could be obtained from the tackiness test of tack materials

Ferroportin disease mutations influence manganese accumulation and cytotoxicity

Hemochromatosis is a frequent genetic disorder, characterized by the accumulation of excess iron across tissues. Mutations in the FPN1 gene, encoding a cell surface iron exporter [ferroportin (Fpn)], are responsible for hemochromatosis type 4, also known as ferroportin disease. Recently, Fpn has been implicated in the regulation of manganese (Mn), another essential nutrient required for numerous cellular enzymes. However, the roles of Fpn in Mn regulation remain ill‐defined, and the impact of disease mutations on cellular Mn levels is unknown. Here, we provide evidence that Fpn can export Mn from cells into extracellular space. Fpn seems to play protective roles in Mn‐induced cellular toxicity and oxidative stress. Finally, disease mutations interfere with the role of Fpn in controlling Mn levels as well as the stability of Fpn. These results define the function of Fpn as an exporter of both iron and Mn and highlight the potential involvement of Mn dysregulation in ferroportin disease.—Choi, E.‐K., Nguyen, T.‐T., Iwase, S., Seo, Y. A. Ferroportin disease mutations influence manganese accumulation and cytotoxicity. FASEB J. 33, 2228–2240 (2019). www.fasebj.orgPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154252/1/fsb2fj201800831r.pd

Distribution of manganese and other biometals in flatiron mice

Flatiron (ffe) mice display features of “ferroportin disease” or Type IV hereditary hemochromatosis. While it is known that both Fe and Mn metabolism are impaired in flatiron mice, the effects of ferroportin (Fpn) deficiency on physiological distribution of these and other biometals is unknown. We hypothesized that Fe, Mn, Zn and/or Cu distribution would be altered in ffe/+ compared to wild-type (+/+) mice. ICP-MS analysis showed that Mn, Zn and Cu levels were significantly reduced in femurs from ffe/+ mice. Bone deposits reflect metal accumulation, therefore these data indicate that Mn, Zn and Cu metabolism are affected by Fpn deficiency. The observations that muscle Cu, lung Mn, and kidney Cu and Zn levels were reduced in ffe/+ mice support the idea that metal metabolism is impaired. While all four biometals appeared to accumulate in brains of flatiron mice, significant gender effects were observed for Mn and Zn levels in male ffe/+ mice. Metals were higher in olfactory bulbs of ffe/+ mice regardless of gender. To further study brain metal distribution, 54MnCl2 was administered by intravenous injection and total brain 54Mn was measured over time. At 72 h, 54Mn was significantly greater in brains of ffe/+ mice compared to +/+ mice while blood 54Mn was cleared to the same levels by 24 h. Taken together, these results indicate that Fpn deficiency decreases Mn trafficking out of the brain, alters body Fe, Mn, Zn and Cu levels, and promotes metal accumulation in olfactory bulbs. Electronic supplementary material The online version of this article (doi:10.1007/s10534-015-9904-2) contains supplementary material, which is available to authorized users

Hepatoprotective and Antioxidative Activities of Cornus officinalis against Acetaminophen-Induced Hepatotoxicity in Mice

The fruit of Cornus officinalis Sieb. et Zucc. is commonly prescribed in Asian countries as a tonic formula. In this study, the hepatoprotective effect of ethanolic extracts of the fruit of C. officinalis (ECO) was investigated in a mouse model of acetaminophen- (APAP-) induced liver injury. Pretreatment of mice with ECO (100, 250, and 500 mg/kg for 7 days) significantly prevented the APAP (200 mg/kg) induced hepatic damage as indicated by the serum marker enzymes (AST, ALT, and LDH). Parallel to these changes, ECO treatment also prevented APAP-induced oxidative stress in the mice liver by inhibiting lipid peroxidation (MDA) and restoring the levels of antioxidant enzymes (SOD, CAT, and HO-1) and glutathione. Liver injury and collagen accumulation were assessed using histological studies by hematoxylin and eosin staining. Our results indicate that ECO can prevent hepatic injuries associated with APAP-induced hepatotoxicity by preventing or alleviating oxidative stress

Regulation of divalent metal transporter-1 by serine phosphorylation

Divalent metal transporter-1 (DMT1) mediates dietary iron uptake across the intestinal mucosa and facilitates peripheral delivery of iron released by transferrin in the endosome. Here, we report that classical cannabinoids (Δ9-tetrahydrocannabinol, Δ9-THC), nonclassical cannabinoids (CP 55,940), aminoalkylindoles (WIN 55,212-2) and endocannabinoids (anandamide) reduce 55Fe and 54Mn uptake by HEK293T(DMT1) cells stably expressing the transporter. siRNA knockdown of cannabinoid receptor type 2 (CB2) abrogated inhibition. CB2 is a G-protein (GTP-binding protein)-coupled receptor that negatively regulates signal transduction cascades involving serine/threonine kinases. Immunoprecipitation experiments showed that DMT1 is serine-phosphorylated under basal conditions, but that treatment with Δ9-THC reduced phosphorylation. Site-directed mutation of predicted DMT1 phosphosites further showed that substitution of serine with alanine at N-terminal position 43 (S43A) abolished basal phosphorylation. Concordantly, both the rate and extent of 55Fe uptake in cells expressing DMT1(S43A) was reduced compared with those expressing wild-type DMT1. Among kinase inhibitors that affected DMT1-mediated iron uptake, staurosporine also reduced DMT1 phosphorylation confirming a role for serine phosphorylation in iron transport regulation. These combined data indicate that phosphorylation at serine 43 of DMT1 promotes transport activity, whereas dephosphorylation is associated with loss of iron uptake. Since anti-inflammatory actions mediated through CB2 would be associated with reduced DMT1 phosphorylation, we postulate that this pathway provides a means to reduce oxidative stress by limiting iron uptake

G-protein-coupled receptor 81 promotes a malignant phenotype in breast cancer through angiogenic factor secretion

G-protein-coupled receptor 81 (GPR81) functions as a receptor for lactate and plays an important role in the regulation of anti-lipolytic effects in adipocytes. However, to data, a role for GPR81 in the tumor microenvironment has not been clearly defined. Here, GPR81 expression in breast cancer patients and several breast cancer cell lines was significantly increased compared with normal mammary tissues and cells. GPR81 knockdown resulted in impaired breast cancer growth and led to apoptosis both in vitro and in vivo. Furthermore, the inhibition of GPR81 signaling suppressed angiogenesis through a phosphoinositide 3-OH kinase (PI3K)/Akt-cAMP response element binding protein (CREB) pathway, which led to decreased production of the pro-angiogenic mediator amphiregulin (AREG). Overall, these findings identify GPR81 as a tumor-promoting receptor in breast cancer progression and suggest a novel mechanism that regulates GPR81-dependent activation of the PI3K/Akt signaling axis in tumor microenvironment.open

Function of COP9 Signalosome in Regulation of Mouse Oocytes Meiosis by Regulating MPF Activity and Securing Degradation

The COP9 (constitutive photomorphogenic) signalosome (CSN), composed of eight subunits, is a highly conserved protein complex that regulates processes such as cell cycle progression and kinase signalling. Previously, we found the expression of the COP9 constitutive photomorphogenic homolog subunit 3 (CSN3) and subunit 5 (CSN5) changes as oocytes mature for the first time, and there is no report regarding roles of COP9 in the mammalian oocytes. Therefore, in the present study, we examined the effects of RNA interference (RNAi)-mediated transient knockdown of each subunit on the meiotic cell cycle in mice oocytes. Following knockdown of either CSN3 or CSN5, oocytes failed to complete meiosis I. These arrested oocytes exhibited a disrupted meiotic spindle and misarranged chromosomes. Moreover, down-regulation of each subunit disrupted the activity of maturation-promoting factor (MPF) and concurrently reduced degradation of the anaphase-promoting complex/cyclosome (APC/C) substrates Cyclin B1 and Securin. Our data suggest that the CSN3 and CSN5 are involved in oocyte meiosis by regulating degradation of Cyclin B1 and Securin via APC/C