Cellular Stress Responses: Cell Survival and Cell Death

Cells can respond to stress in various ways ranging from the activation of survival pathways to the initiation of cell death that eventually eliminates damaged cells. Whether cells mount a protective or destructive stress response depends to a large extent on the nature and duration of the stress as well as the cell type. Also, there is often the interplay between these responses that ultimately determines the fate of the stressed cell. The mechanism by which a cell dies (i.e., apoptosis, necrosis, pyroptosis, or autophagic cell death) depends on various exogenous factors as well as the cell's ability to handle the stress to which it is exposed. The implications of cellular stress responses to human physiology and diseases are manifold and will be discussed in this review in the context of some major world health issues such as diabetes, Parkinson's disease, myocardial infarction, and cancer

Higher order Laguerre-Gauss mode degeneracy in realistic, high finesse cavities

Higher order Laguerre-Gauss (LG) beams have been proposed for use in future gravitational wave detectors, such as upgrades to the Advanced LIGO detectors and the Einstein Telescope, for their potential to reduce the effects of the thermal noise of the test masses. This paper details the theoretical analysis and simulation work carried out to investigate the behaviour of LG beams in realistic optical setups, in particular the coupling between different LG modes in a linear cavity. We present a new analytical approximation to compute the coupling between modes, using Zernike polynomials to describe mirror surface distortions. We apply this method in a study of the behaviour of the LG33 mode within realistic arm cavities, using measured mirror surface maps from the Advanced LIGO project. We show mode distortions that can be expected to arise due to the degeneracy of higher order spatial modes within such cavities and relate this to the theoretical analysis. Finally we identify the mirror distortions which cause significant coupling from the LG33 mode into other order 9 modes and derive requirements for the mirror surfaces.Comment: 12 pages Submitted to PRD 19/07/201

Review of the Laguerre-Gauss mode technology research program at Birmingham

Gravitational wave detectors from the advanced generation onwards are expected to be limited in sensitivity by thermal noise of the optics, making the reduction of this noise a key factor in the success of such detectors. A proposed method for reducing the impact of this noise is to use higher-order Laguerre-Gauss (LG) modes for the readout beam, as opposed to the currently used fundamental mode. We present here a synopsis of the research program undertaken by the University of Birmingham into the suitability of LG mode technology for future gravitational wave detectors. This will cover our previous and current work on this topic, from initial simulations and table-top LG mode experiments up to implementation in a prototype scale suspended cavity and high-power laser bench

Cell Stress and Cell Death

Editorial: This special issue on Cell Stress and Cell Death is aimed at bringing together recent developments in the fields of cellular stress and cell death and, in particular, the interplay between cell stress responses and cell death. The special issue opens with a review by S. Fulda et al. which provides an overview of how cells can respond to stress in a variety of ways ranging from the activation of survival pathways to the initiation of cell death that eventually eliminates damaged cells. Whether cells mount a protective response or succumb to death depends to a large extent on the nature and duration of the stress as well as the cell type. For example, milder stresses can lead to protection through activation of the heat shock response or the unfolded protein response (UPR). This review also describes several types of cell death (e.g., apoptosis, necrosis, pyroptosis, or autophagic cell death) and the mechanism by which a cell dies often depends on various exogenous factors as well as the cell’s ability to handle the stress to which it is exposed. The implications of cellular stress responses for human physiology and disease are multifold and are discussed in this review in the context of some major world health issues such as diabetes, Parkinson’s disease, myocardial infarction, and cancer. ..

Small optic suspensions for Advanced LIGO input optics and other precision optical experiments

We report on the design and performance of small optic suspensions developed to suppress seismic motion of out-of-cavity optics in the Input Optics subsystem of the Advanced LIGO interferometric gravitational wave detector. These compact single stage suspensions provide isolation in all six degrees of freedom of the optic, local sensing and actuation in three of them, and passive damping for the other three

Principles of practice parameters for the treatment of sleep disordered breathing in the elderly and frail elderly: the consensus of the International Geriatric Sleep Medicine Task Force

Sleep disordered breathing (SDB) is a leading cause of morbidity worldwide. Its prevalence increases with age. Due to the demographic changes in industrial societies, pulmonologists and sleep physicians are confronted with a rapidly growing number of elderly SDB patients. For many physicians, it remains unclear how current guidelines for SDB management apply to elderly and frail elderly patients. The goal of this consensus statement is to provide guidance based on published evidence for SDB treatment in this specific patient group. Clinicians and researchers with expertise in geriatric sleep medicine representing several countries were invited to participate in a task force. A literature search of PubMed from the past 12 years and a systematic review of evidence of studies deemed relevant was performed. Recommendations for treatment management of elderly and frail elderly SDB patients based on published evidence were formulated via discussion and consensus. In the last 12 years, there have been surprisingly few studies examining treatment of SDB in older adults and even fewer in frail older adults. Studies that have been conducted on the management of SDB in the older patient population were rarely stratified for age. Studies in SDB treatment that did include age stratification mainly focused on middle-aged and younger patient groups. Based on the evidence that is available, this consensus statement highlights the treatment forms that can be recommended for elderly SDB patients and encourages treatment of SDB in this large patient group

Epigenetics as a mechanism driving polygenic clinical drug resistance

Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance

Editorial: Cell stress and cell death

金沢大学医薬保健研究域医学

Betulin Is a Potent Anti-Tumor Agent that Is Enhanced by Cholesterol

Betulinic Acid (BetA) and its derivatives have been extensively studied in the past for their anti-tumor effects, but relatively little is known about its precursor Betulin (BE). We found that BE induces apoptosis utilizing a similar mechanism as BetA and is prevented by cyclosporin A (CsA). BE induces cell death more rapidly as compared to BetA, but to achieve similar amounts of cell death a considerably higher concentration of BE is needed. Interestingly, we observed that cholesterol sensitized cells to BE-induced apoptosis, while there was no effect of cholesterol when combined with BetA. Despite the significantly enhanced cytotoxicity, the mode of cell death was not changed as CsA completely abrogated cell death. These results indicate that BE has potent anti-tumor activity especially in combination with cholesterol