Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage.

Age-related macular degeneration (AMD) ranks third among the leading causes of visual impairment with a blindness prevalence rate of 8.7%. Despite several treatment regimens, such as anti-angiogenic drugs, laser therapy, and vitamin supplementation, being available for wet AMD, to date there are no FDA-approved therapies for dry AMD. Substantial evidence implicates mitochondrial damage and retinal pigment epithelium (RPE) cell death in the pathogenesis of AMD. However, the effects of AMD mitochondria and Humanin G (HNG), a more potent variant of the mitochondrial-derived peptide (MDP) Humanin, on retinal cell survival have not been elucidated. In this study, we characterized mitochondrial and cellular damage in transmitochondrial cybrid cell lines that contain identical nuclei but possess mitochondria from either AMD or age-matched normal (Older-normal (NL)) subjects. AMD cybrids showed (1) reduced levels of cell viability, lower mtDNA copy numbers, and downregulation of mitochondrial replication/transcription genes and antioxidant enzyme genes; and (2) elevated levels of genes related to apoptosis, autophagy and ER-stress along with increased mtDNA fragmentation and higher susceptibility to amyloid-β-induced toxicity compared to NL cybrids. In AMD cybrids, HNG protected the AMD mitochondria, reduced pro-apoptosis gene and protein levels, upregulated gp130 (a component of the HN receptor complex), and increased the protection against amyloid-β-induced damage. In summary, in cybrids, damaged AMD mitochondria mediate cell death that can be reversed by HNG treatment. Our results also provide evidence of Humanin playing a pivotal role in protecting cells with AMD mitochondria. In the future, it may be possible that AMD patient's blood samples containing damaged mitochondria may be useful as biomarkers for this condition. In conclusion, HNG may be a potential therapeutic target for treatment of dry AMD, a debilitating eye disease that currently has no available treatment. Further studies are needed to establish HNG as a viable mitochondria-targeting therapy for dry AMD

Moesin, the major ERM protein of lymphocytes and platelets, differs from ezrin in its insensitivity to calpain

AbstractThe ERM proteins, ezrin, radixin and moesin, provide regulated linkage of the cytoskeleton with the plasma membrane, particularly in cell surface projections. Ezrin and moesin were found co-expressed, and radixin was not detected, in human blood lymphocytes, monocytes and neutrophils. Moesin is the quantitatively dominant ERM protein in these cells and the only one in platelets. Because Ca2+ signaling pathways involving calpain cleavages are important in blood cells, we examined ERM protein sensitivity to this protease. A striking difference was discovered: sensitivity of ezrin and resistance of moesin (and radixin) to calpain. In intact stimulated lymphocytes, ezrin was cleaved, while moesin was not, strongly suggesting that differential sensitivity to calpain contributes to specialized functions of these proteins

National Climate Assessment Indicators: Background, Development, and Examples

This paper establishes a rationale for developing a system of indicators for an ongoing national climate assessment process. It lays out a framework for a set of climate-related indicators that have an end-to-end character, e.g. they will provide information on greenhouse gases, variability and change in the climate system, status and trends of important sectors that are known to be sensitive to climate variability, and response strategies. Examples of potential indicators are shown in each category. These are by no means a final set of indicators, because an overall process for selection with participation from important stakeholders has not yet been undertaken. But even this initial set of possibilities reveals both where there is a substantial amount of well-documented information, and where there are important gaps that must be filled by subsequent research

Damage Localization for Structural Health Monitoring Using Retrospective Cost Model Refinement

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83574/1/AIAA-2010-2628-530.pd

The design, development and evaluation of an array-based FES system with automated setup for the correction of drop foot

Functional electrical stimulation has been shown to be a safe and effective means of correcting drop foot of central neurological origin. However, despite recent technological advances, the set-up of surface stimulators remains a challenge for many users with drop foot. The automation of the setup process through the use of electrode arrays has been proposed as a way to address this problem. This paper describes a series of research and clinical studies which have led to the first demonstration of unsupervised automated setup of an electrode-array based drop foot stimulator. Finally, future research plans are discussed

Biomarker Discovery in Serum from Patients with Carotid Atherosclerosis

www.karger.com/cee This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License (www.karger.com/OA-license), applicable to the online version of the article only. Distribution for non-commercial purposes only

A review of the design and clinical evaluation of the ShefStim array-based functional electrical stimulation system

Functional electrical stimulation has been shown to be a safe and effective means of correcting foot 12 drop of central neurological origin. Current surface-based devices typically consist of a single channel stimulator, 13 a sensor for determining gait phase and a cuff, within which is housed the anode and cathode. The cuff-mounted 14 electrode design reduces the likelihood of large errors in electrode placement, but the user is still fully responsible 15 for selecting the correct stimulation level each time the system is donned. Researchers have investigated different 16 approaches to automating aspects of setup and/or use, including recent promising work based on iterative learning 17 techniques. This paper reports on the design and clinical evaluation of an electrode array-based FES system for 18 the correction of drop foot, ShefStim. The paper reviews the design process from proof of concept lab-based study, 19 through modelling of the array geometry and interface layer to array search algorithm development. Finally, the 20 paper summarises two clinical studies involving patients with drop foot. The results suggest that the ShefStim 21 system with automated setup produces results which are comparable with clinician setup of conventional systems. 22 Further, the final study demonstrated that patients can use the system without clinical supervision. When used 23 unsupervised, setup time was 14 minutes (9 minutes for automated search plus 5 minutes for donning the 24 equipment), although this figure could be reduced significantly with relatively minor changes to the design

Genetics of myocardial interstitial fibrosis in the human heart and association with disease

Myocardial interstitial fibrosis is associated with cardiovascular disease and adverse prognosis. Here, to investigate the biological pathways that underlie fibrosis in the human heart, we developed a machine learning model to measure native myocardial T1 time, a marker of myocardial fibrosis, in 41,505 UK Biobank participants who underwent cardiac magnetic resonance imaging. Greater T1 time was associated with diabetes mellitus, renal disease, aortic stenosis, cardiomyopathy, heart failure, atrial fibrillation, conduction disease and rheumatoid arthritis. Genome-wide association analysis identified 11 independent loci associated with T1 time. The identified loci implicated genes involved in glucose transport (SLC2A12), iron homeostasis (HFE, TMPRSS6), tissue repair (ADAMTSL1, VEGFC), oxidative stress (SOD2), cardiac hypertrophy (MYH7B) and calcium signaling (CAMK2D). Using a transforming growth factor β1-mediated cardiac fibroblast activation assay, we found that 9 of the 11 loci consisted of genes that exhibited temporal changes in expression or open chromatin conformation supporting their biological relevance to myofibroblast cell state acquisition. By harnessing machine learning to perform large-scale quantification of myocardial interstitial fibrosis using cardiac imaging, we validate associations between cardiac fibrosis and disease, and identify new biologically relevant pathways underlying fibrosis.</p

A decision framework to integrate in-situ and ex-situ management for species in the European Union

Zoos and aquaria in the European Union (EU) can play a crucial role in the conservation of EU species, as they currently hold nearly half (49%) of EU terrestrial vertebrates. In this study, we analyzed the species composition and population sizes of EU zoos and developed a framework to prioritize recommendations for additional ex-situ and in-situ interventions for 277 at-risk EU species. Our results showed that EU zoos currently hold 39% of threatened EU species, 27% of EU endemic species, 62% of EU species vulnerable to climate change, 20% of EU species listed by the Alliance for Zero Extinction (AZE), 25% of Evolutionary Distinct and Globally Endangered (EDGE) EU species, while only 5% are subject to ex-situ conservation. Using our framework, we found that additional captive breeding was recommended for 60-61%% of species while expanding protected areas was recommended for only 2–22%, as 217 out of 277 species already met habitat protection targets. Both interventions were recommended for up to 20% of species, while the remaining 18% required no interventions because captive populations and habitat protection fully met targets. Our flexible framework can support more effective integrated conservation planning decisions for EU species and help identify target species for further in-depth assessment by the IUCN Ex-situ guidelines