Cellular Senescence, Mitochondrial Dysfunction, and Their Link to Cardiovascular Disease

Cardiovascular diseases (CVDs), a group of disorders affecting the heart or blood vessels, are the primary cause of death worldwide, with an immense impact on patient quality of life and disability. According to the World Health Organization, CVD takes an estimated 17.9 million lives each year, where more than four out of five CVD deaths are due to heart attacks and strokes. In the decades to come, an increased prevalence of age-related CVD, such as atherosclerosis, coronary artery stenosis, myocardial infarction (MI), valvular heart disease, and heart failure (HF) will contribute to an even greater health and economic burden as the global average life expectancy increases and consequently the world’s population continues to age. Considering this, it is important to focus our research efforts on understanding the fundamental mechanisms underlying CVD. In this review, we focus on cellular senescence and mitochondrial dysfunction, which have long been established to contribute to CVD. We also assess the recent advances in targeting mitochondrial dysfunction including energy starvation and oxidative stress, mitochondria dynamics imbalance, cell apoptosis, mitophagy, and senescence with a focus on therapies that influence both and therefore perhaps represent strategies with the most clinical potential, range, and utility

Balancing cryptoassets and gold: a weighted-risk-contribution index for the alternative asset space

Bitcoin is foremost amongst the emerging asset class knownas cryptoassets. Two noteworthy characteristics of the returns of non-stablecoin cryptoassets are their high volatility, which brings with it ahigh level of risk, and their high intraclass correlation, which limits thebenefits that can be had by diversifying across multiple cryptoassets. Yetcryptoassets exhibit no correlation with gold, a highly-liquid yet scarceasset which has proved to function as a safe haven during crises affectingtraditional financial systems. As exemplified by Shannon’s Demon, a lackof correlation between assets opens the door to principled risk controlthrough so-called volatility harvesting involving periodic rebalancing.In this paper we propose an index which combines a basket of five cryp-toassets with an investment in gold in a way that aims to improve therisk profile of the resulting portfolio while preserving its independencefrom mainstream financial asset classes such as stocks, bonds and fiatcurrencies. We generalise the theory of Equal Risk Contribution to allowfor weighting according to a desired level of contribution to volatility. Wefind a crypto–gold weighting based on Weighted Risk Contribution to behistorically more effective in terms of Sharpe Ratio than several alterna-tive asset allocation strategies including Shannon’s Demon. Within thecrypto-basket, whose constituents are selected and rebalanced monthly,we find an Equal Weighting scheme to be more effective in terms of thesame metric than a market capitalisation weighting

Minimal Obstructions for Partial Representations of Interval Graphs

Interval graphs are intersection graphs of closed intervals. A generalization of recognition called partial representation extension was introduced recently. The input gives an interval graph with a partial representation specifying some pre-drawn intervals. We ask whether the remaining intervals can be added to create an extending representation. Two linear-time algorithms are known for solving this problem. In this paper, we characterize the minimal obstructions which make partial representations non-extendible. This generalizes Lekkerkerker and Boland's characterization of the minimal forbidden induced subgraphs of interval graphs. Each minimal obstruction consists of a forbidden induced subgraph together with at most four pre-drawn intervals. A Helly-type result follows: A partial representation is extendible if and only if every quadruple of pre-drawn intervals is extendible by itself. Our characterization leads to a linear-time certifying algorithm for partial representation extension

Building a synthetic mechanosensitive signaling pathway in compartmentalized artificial cells

To date reconstitution of one of the fundamental methods of cell communication, the signaling pathway, has been unaddressed in the bottom-up construction of artificial cells (ACs). Such developments are needed to increase the functionality and biomimicry of ACs, accelerating their translation and application in biotechnology. Here we report the construction of a de novo synthetic signaling pathway in microscale nested vesicles. Vesicle cell models respond to external calcium signals through activation of an intracellular interaction between phospholipase A2 and a mechanosensitive channel present in the internal membranes, triggering content mixing between compartments and controlling cell fluorescence. Emulsion-based approaches to AC construction are therefore shown to be ideal for the quick design and testing of new signaling networks and can readily include synthetic molecules difficult to introduce to biological cells. This work represents a foundation for the engineering of multi-compartment-spanning designer pathways that can be utilised to control downstream events inside an artificial cell, leading to the assembly of micromachines capable of sensing and responding to changes in their local environment

Interpreting ambiguous ‘trace’ results in Schistosoma mansoni CCA Tests: Estimating sensitivity and specificity of ambiguous results with no gold standard

Background The development of new diagnostics is an important tool in the fight against disease. Latent Class Analysis (LCA) is used to estimate the sensitivity and specificity of tests in the absence of a gold standard. The main field diagnostic for Schistosoma mansoni infection, Kato-Katz (KK), is not very sensitive at low infection intensities. A point-of-care circulating cathodic antigen (CCA) test has been shown to be more sensitive than KK. However, CCA can return an ambiguous ‘trace’ result between ‘positive’ and ‘negative’, and much debate has focused on interpretation of traces results. Methodology/Principle findings We show how LCA can be extended to include ambiguous trace results and analyse S. mansoni studies from both Côte d’Ivoire (CdI) and Uganda. We compare the diagnostic performance of KK and CCA and the observed results by each test to the estimated infection prevalence in the population. Prevalence by KK was higher in CdI (13.4%) than in Uganda (6.1%), but prevalence by CCA was similar between countries, both when trace was assumed to be negative (CCAtn: 11.7% in CdI and 9.7% in Uganda) and positive (CCAtp: 20.1% in CdI and 22.5% in Uganda). The estimated sensitivity of CCA was more consistent between countries than the estimated sensitivity of KK, and estimated infection prevalence did not significantly differ between CdI (20.5%) and Uganda (19.1%). The prevalence by CCA with trace as positive did not differ significantly from estimates of infection prevalence in either country, whereas both KK and CCA with trace as negative significantly underestimated infection prevalence in both countries. Conclusions Incorporation of ambiguous results into an LCA enables the effect of different treatment thresholds to be directly assessed and is applicable in many fields. Our results showed that CCA with trace as positive most accurately estimated infection prevalence

Sensitivity and Specificity of Multiple Kato-Katz Thick Smears and a Circulating Cathodic Antigen Test for Schistosoma mansoni Diagnosis Pre- and Post-repeated-Praziquantel Treatment

Two Kato-Katz thick smears (Kato-Katzs) from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This ‘gold standard’ has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA) is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E) and drug-efficacy findings

Current State of Microplastic Pollution Research Data: Trends in Availability and Sources of Open Data

The rapid growth in microplastic pollution research is influencing funding priorities, environmental policy, and public perceptions of risks to water quality and environmental and human health. Ensuring that environmental microplastics research data are findable, accessible, interoperable, and reusable (FAIR) is essential to inform policy and mitigation strategies. We present a bibliographic analysis of data sharing practices in the environmental microplastics research community, highlighting the state of openness of microplastics data. A stratified (by year) random subset of 785 of 6,608 microplastics articles indexed in Web of Science indicates that, since 2006, less than a third (28.5%) contained a data sharing statement. These statements further show that most often, the data were provided in the articles’ supplementary material (38.8%) and only 13.8% via a data repository. Of the 279 microplastics datasets found in online data repositories, 20.4% presented only metadata with access to the data requiring additional approval. Although increasing, the rate of microplastic data sharing still lags behind that of publication of peer-reviewed articles on environmental microplastics. About a quarter of the repository data originated from North America (12.8%) and Europe (13.4%). Marine and estuarine environments are the most frequently sampled systems (26.2%); sediments (18.8%) and water (15.3%) are the predominant media. Of the available datasets accessible, 15.4% and 18.2% do not have adequate metadata to determine the sampling location and media type, respectively. We discuss five recommendations to strengthen data sharing practices in the environmental microplastic research community

Employee share ownership in a unionised duopoly

Profit sharing schemes have been analysed assuming Cournot competition and decentralised wage negotiations, and it has been found that firms share profits in equilibrium. This paper analyses a different remuneration system: employee share ownership. We find that whether firms choose to share ownership or not depends on both the type of competition in the product market and the way in which workers organise to negotiate wages. If wage setting is decentralised, under duopolistic Cournot competition both firms share ownership. If wage setting is centralised, only one firm shares ownership if the degree to which goods are substitutes takes an intermediate value; otherwise, the two firms share ownership. In this case, if the union sets the same wage for all workers neither firm shares ownership. Therefore, centralised wage setting discourages share ownership. Fi- nally, under Bertrand competition neither firm shares ownership regardless of how workers are organised to negotiate wages.info:eu-repo/semantics/publishedVersio

Environmental benefits of leaving offshore infrastructure in the ocean

© The Ecological Society of America The removal of thousands of structures associated with oil and gas development from the world's oceans is well underway, yet the environmental impacts of this decommissioning practice remain unknown. Similar impacts will be associated with the eventual removal of offshore wind turbines. We conducted a global survey of environmental experts to guide best decommissioning practices in the North Sea, a region with a substantial removal burden. In contrast to current regulations, 94.7% of experts (36 out of 38) agreed that a more flexible case-by-case approach to decommissioning could benefit the North Sea environment. Partial removal options were considered to deliver better environmental outcomes than complete removal for platforms, but both approaches were equally supported for wind turbines. Key considerations identified for decommissioning were biodiversity enhancement, provision of reef habitat, and protection from bottom trawling, all of which are negatively affected by complete removal. We provide recommendations to guide the revision of offshore decommissioning policy, including a temporary suspension of obligatory removal