Change in Localization of Alkaline Phosphatase and Mannosidase II by Colchicine Treatment of Primary Cultures of Fetal Rat Hepatocytes

We examined the changes in localization of alkaline phosphatase (ALP) and mannosidase II (man II), a Golgi marker, after colchicine treatment of primary cultures of fetal rat hepatocytes, using double immunofluorescence staining and confocal laser microscopy. In hepatocytes cultured in basal medium, ALP was localized in the perinuclear cytoplasm, and man II was observed in the Golgi region of the cytoplasm. When hepatocytes were cultured in dexamethasone-supplemented medium, ALP was also localized in the plasma membrane surrounding the bile canaliculus-like structure that was formed between adjacent cells. In hepatocytes cultured in the same medium containing colchicine, the structure of microtubules in the cytoplasm was lost, man II exhibited granular distribution scattering throughout the cytoplasm, and ALP was localized in coarse granular sites of the cytoplasm. However, ALP was not colocalized at the same sites as man II. The present study indicated that colchicine inhibits the dexamethasone-promoted translocation of ALP to the plasma membrane surrounding the bile canaliculus-like structure in primary cultures of fetal rat hepatocytes by disassembling microtubules and discomposing the Golgi complex

Social disruption stress exacerbates alpha-galactosylceramide-induced hepatitis in mice

Objective: Psychosocial stress has been suggested as a possible aggravating factor in liver diseases, however, the underlying mechanism has yet to be clarified. Recently, our research revealed that electric foot-shock stress aggravated NK1.1 Ag+ T cell-dependent a-galactosylceramide (alpha-GalCer)-induced hepatitis in mice via a mechanism mediated by endogenous glucocorticoids. In this study, we examined whether or not such aggravation could be applied to a psychosocially stressful situation, e.g. social disruption stress. Methods: Male wildtype C57BL/6 (B6) or B6 hepatitis virus type B surface antigen transgenic (HBs-tg) mice, a hepatitis B virus carrier mouse model, were exposed 3 times in 1 week to social disruption stress in which an 8-month-old aggressive male intruder was placed into their home cage (5 mice per group) for 2 h. Twelve hours after the final exposure to the stress, the wild-type and HBs-tg mice were intravenously injected with alpha-GalCer. Results:The stress-exposed wild-type mice exhibited significantly reduced thymus weight loss compared with the control animals. Moreover, this stress regimen led to a significant increase in serum alanine aminotransferase levels in both the wild-type and the HBs-tg mice, although the increase in the HBs-tg mice was higher than that in the wild-type mice. Conclusion: These findings demonstrated that, similar to electric foot-shock stress, social disruption stress exacerbated alpha-GalCer-induced hepatitis. Copyright (C) 2005 S. Karger AG, Basel

On Teitelbaum type L-invariants of Hilbert Modular forms attached to definite quaternions

We generalize Teitelbaum's work on the definition of the L-invariant to Hilbert modular forms that arise from definite quaternion algebras over totally real fields by the Jacquet-Langlands correspondence. Conjecturally this coincides with the Fontaine-Mazur type L-invariant, defined by applying Fontaine's theory to the Galois representation associated to Hilbert modular forms. An exceptional zero conjecture for the p-adic L-function of Hilbert modular forms is also proposed. (C) 2014 Elsevier Inc. All rights reserved.X1111Ysciescopu

Exponentially Increasing Incidences of Cutaneous Malignant Melanoma in Europe Correlate with Low Personal Annual UV Doses and Suggests 2 Major Risk Factors

For several decades the incidence of cutaneous malignant melanoma (CMM) steadily increased in fair-skinned, indoor-working people around the world. Scientists think poor tanning ability resulting in sunburns initiate CMM, but they do not understand why the incidence continues to increase despite the increased use of sunscreens and formulations offering more protection. This paradox, along with lower incidences of CMM in outdoor workers, although they have significantly higher annual UV doses than indoor workers have, perplexes scientists. We found a temporal exponential increase in the CMM incidence indicating second-order reaction kinetics revealing the existence of 2 major risk factors. From epidemiology studies, we know one major risk factor for getting CMM is poor tanning ability and we now propose the other major risk factor may be the Human Papilloma Virus (HPV) because clinicians find β HPVs in over half the biopsies. Moreover, we uncovered yet another paradox; the increasing CMM incidences significantly correlate with decreasing personal annual UV dose, a proxy for low vitamin D3 levels. We also discovered the incidence of CMM significantly increased with decreasing personal annual UV dose from 1960, when it was almost insignificant, to 2000. UV and other DNA-damaging agents can activate viruses, and UV-induced cytokines can hide HPV from immune surveillance, which may explain why CMM also occurs in anatomical locations where the sun does not shine. Thus, we propose the 2 major risk factors for getting CMM are intermittent UV exposures that result in low cutaneous levels of vitamin D3 and possibly viral infection

Systolic blood pressure reactions to acute stress are associated with future hypertension status in the Dutch Famine Birth Cohort Study

These analyses examined the association between blood pressure reactions to acute psychological stress and subsequent hypertension status in a substantial Dutch cohort. Blood pressure was recorded during a resting baseline and during three acute stress tasks, Stroop colour word, mirror tracing and speech. Five years later, diagnosed hypertension status was determined by questionnaire. Participants were 453 (237 women) members of the Dutch Famine Birth Cohort. In analysis adjusting for a number of potential confounders, systolic blood pressure reactivity was positively related to future hypertension. This was the case irrespective of whether reactivity was calculated as the peak or the average response to the stress tasks. The association was strongest for reactions to the speech and Stroop tasks. Diastolic blood pressure reactivity was not significantly associated with hypertension. The results provide support for the reactivity hypothesis. \ud \u

The role of a disulfide bridge in the stability and folding kinetics of Arabidopsis thaliana cytochrome c6A

Cytochrome c 6A is a eukaryotic member of the Class I cytochrome c family possessing a high structural homology with photosynthetic cytochrome c 6 from cyanobacteria, but structurally and functionally distinct through the presence of a disulfide bond and a heme mid-point redox potential of + 71 mV (vs normal hydrogen electrode). The disulfide bond is part of a loop insertion peptide that forms a cap-like structure on top of the core α-helical fold. We have investigated the contribution of the disulfide bond to thermodynamic stability and (un)folding kinetics in cytochrome c 6A from Arabidopsis thaliana by making comparison with a photosynthetic cytochrome c 6 from Phormidium laminosum and through a mutant in which the Cys residues have been replaced with Ser residues (C67/73S). We find that the disulfide bond makes a significant contribution to overall stability in both the ferric and ferrous heme states. Both cytochromes c 6A and c 6 fold rapidly at neutral pH through an on-pathway intermediate. The unfolding rate for the C67/73S variant is significantly increased indicating that the formation of this region occurs late in the folding pathway. We conclude that the disulfide bridge in cytochrome c 6A acts as a conformational restraint in both the folding intermediate and native state of the protein and that it likely serves a structural rather than a previously proposed catalytic role. © 2011 Elsevier B.V. All rights reserved

Daily life stress and the cortisol awakening response : testing the anticipation hypothesis

Acknowledgments We thank Paul Stewart for his contribution to data collection and Dr Matthew Jones for programming the handheld computers. Author Contributions Conceived and designed the experiments: WS DJP. Performed the experiments: DJP. Analyzed the data: WS. Wrote the paper: WS DJP.Peer reviewedPublisher PD

The impact of emotional well-being on long-term recovery and survival in physical illness: a meta-analysis

This meta-analysis synthesized studies on emotional well-being as predictor of the prognosis of physical illness, while in addition evaluating the impact of putative moderators, namely constructs of well-being, health-related outcome, year of publication, follow-up time and methodological quality of the included studies. The search in reference lists and electronic databases (Medline and PsycInfo) identified 17 eligible studies examining the impact of general well-being, positive affect and life satisfaction on recovery and survival in physically ill patients. Meta-analytically combining these studies revealed a Likelihood Ratio of 1.14, indicating a small but significant effect. Higher levels of emotional well-being are beneficial for recovery and survival in physically ill patients. The findings show that emotional well-being predicts long-term prognosis of physical illness. This suggests that enhancement of emotional well-being may improve the prognosis of physical illness, which should be investigated by future research

Quantum Fluctuation Theorems

Recent advances in experimental techniques allow one to measure and control systems at the level of single molecules and atoms. Here gaining information about fluctuating thermodynamic quantities is crucial for understanding nonequilibrium thermodynamic behavior of small systems. To achieve this aim, stochastic thermodynamics offers a theoretical framework, and nonequilibrium equalities such as Jarzynski equality and fluctuation theorems provide key information about the fluctuating thermodynamic quantities. We review the recent progress in quantum fluctuation theorems, including the studies of Maxwell's demon which plays a crucial role in connecting thermodynamics with information.Comment: As a chapter of: F. Binder, L. A. Correa, C. Gogolin, J. Anders, and G. Adesso (eds.), "Thermodynamics in the quantum regime - Fundamental Aspects and New Directions", (Springer International Publishing, 2018