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The lncRNA MYRACL regulates human oligodendrocyte maturation and myelination
No full textRecent studies have described disease-associated expression patterns of long non-coding RNAs (lncRNAs) associated with neurodevelopment and neurodegeneration, highlighting their potential as regulators of function and therefore potential therapeutic targets. Oligodendrocyte (OL) dysfunction drives central nervous system myelin disruption in neurological disorders, but the mechanisms underlying impaired myelin patterns are still poorly understood. In this study, we uncover a role for the lncRNA MYRACL (myelination regulating oligodendrocyte-associated lncRNA) as a regulator of functional maturation and OL myelination. Analysis of RNA-sequencing data performed in human postmortem brain tissue revealed MYRACL to be among the top enriched genes expressed in the OL population compared to the OL precursor cell cluster. We validated this finding in an embryonic stem cell-derived oligodendroglia cell culture model. Analysis of evolutionary conservation and protein coding potential showed that MYRACL is non-coding and may exhibit conserved regions across mammalian species. Further co-expression analysis of lncRNAs-mRNAs suggested that expression of MYRACL positively correlates with genes known to be involved in driving oligodendroglia differentiation. GapmeR-mediated knockdown of nuclear MYRACL disrupted OL maturation in vitro, while lentivirus-mediated overexpression promoted OL differentiation with enhancement of myelin formation in vitro. Our findings highlight MYRACL as a novel regulatory mechanism in human OL maturation and myelination. By providing a human, translationally relevant platform, this work advances our ability to model human myelination in vitro and paves the way for precision medicine approaches targeting lncRNA-mediated dysregulation in neurodevelopmental and neurodegenerative diseases
Takotsubo syndrome: cognitive behavioural therapy, physical training, and brain function recovery in the BREAKOUT trial
No full textTakotsubo syndrome is an acute disease at the interface between the brain and heart, whereby a stressful trigger results in severe decline of cardiac function.1 We have previously shown that acute takotsubo syndrome is accompanied by a strong myocardial and systemic inflammatory process.2 We and others have demonstrated structural and functional brain differences between patients with acute takotsubo syndrome and age- and sex-matched control subjects.3–7 We hypothesized that behavioural modifications such as physical exercise training or cognitive behavioural therapy will improve structural and functional brain recovery patterns (reflected by changes in hippocampal and other brain volumes as well as in functional connectivity) after acute takotsubo cardiomyopathy, relative to current standard care
States, law, and the regulation of controversial health-related claims: consolidating a research agenda between disciplines and contexts
No full textStories of unproven, disproven, or misleading health-related claims, and their impact on individual and public health, are commonplace around the world. Disquiet about such claims is ubiquitous and growing within public, clinical, scientific, and policy discourse, with law commonly presented as having an important role to play in addressing concerns. Action, though, requires regulators to account for competing considerations, including fundamental freedoms, cultural diversity, and the potential for law to exacerbate inequalities. The latter is particularly significant when assessing the veracity of marginalised beliefs. In practice, legal decision-makers walk a fine line between everyday tolerance and occasional intervention. Yet, legal research pertinent to these issues is surprisingly limited. Here, we argue that new knowledge, methods, and collaborations are needed to better understand how regulatory interventions relevant to contested claims are constituted; how they operate in practice; and how they relate to different political and social processes - including acts of public resistance (like campaigns and protests). Only once we are collectively equipped with such critical knowledge of the current nature and possibilities of regulatory relations will it be possible to collectively design more imaginative and inclusive legal responses.<br/
Towards eco-social contracts through an entangled manifestation of digital litter
No full textMany of the current debates in technology concern the extractive practices around planetary resources and data, which produce electronic waste as well as everyday sense of clutter among media channels and files. In this paper, we engage with this problem space through a specific focus on Terms of Service agreements, which have become a prerequisite for even the most rudimentary use of technology. We do this by presenting an exploded view of an existing Terms of Service policy ecosystem, in the form of an outdoor installation, temporarily littering a patch of nature. Through this installation, we expose eco-social contracts as a design opening for more-than-human data governance, ecological temporalities, and the right to patchwork as generative concepts
A prospective cohort observational study investigating the association between the United Kingdom digital dermatitis genetic index and the disease prevalence in a population of Holstein heifers
No full textThe digital dermatitis index (DDI), a genetic index for digital dermatitis (DD) resistance has been previously associated with presence of DD in Holstein cows. The aim of this study was to further investigate this association in a population of Holstein heifers. Two cohorts of heifers from one farm were enrolled. For the first cohort, DD lesions from the hind feet were recorded with the animals standing, using at telescopic mirror once a month over a period of 3 mo. For the second cohort, DD lesions were recorded from the hind feet by picking them up in a foot-trimming chute once a month over a period of 4 to 6 mo. The M-stage scoring system was used, and 4 binary variables were created. The first binary variable created was grouping animals that never had any DD lesion (M0) and animals that had at least one lesion recorded throughout the study. Similar binary transformations were repeated for active (M1, M2, M4.1) lesions, chronic (M3, M4), and M2 lesions separately. Genomically estimated predicted transmitting abilities (gPTA) for the DDI were available for 519 heifers of the first cohort and 361 of the second. The DDI gPTA were standardized (rescaled to represent distance from the mean expressed in SD) and were also grouped into terciles (i.e., low-, medium- and high-genetic-merit groups) within each cohort. Univariable analysis was used to investigate the association between the 4 binary lesion-presence variables and the DDI gPTA for each cohort separately and multivariable logistic regression models were fitted for the second cohort. Survival (time to event) analysis was performed using the second-cohort dataset by fitting a parametric proportional hazard regression model using the Weibull distribution for interval censored data, with DDI and season at enrollment remaining as explanatory variables. There was no difference between low-, medium-, and high-genetic-merit heifers regarding the presence of any, active, or chronic lesions in the first cohort. However, for a one-unit increase in the DDI gPTA, the odds ratio (OR) of M2 lesion presence was 0.68 (95% CI: 0.50-0.92). Multivariable logistic regression models using data from the second cohort showed that for every one-unit increase in the DDI gPTA the OR for any, chronic, active, and M2 DD lesion presence were 0.64 (95% CI: 0.50-0.80), 0.60 (95% CI: 0.47-0.76), 0.55 (95% CI: 0.42-0.70), and 0.59 (95% CI: 0.41-0.84), respectively. The proportional hazard model showed that a one-unit increase in the DDI gPTA resulted in a hazard ratio of 0.70 (95% CI: 0.60-0.82). The model-adjusted median age at first DD event was 306 d (95% CI: 284-328) for heifers with a DDI of -1 compared with 377 d (95% CI: 348-411) for heifers with a DDI of +1. We show significant association between DDI gPTA and presence of DD lesions. Lower-genetic-merit animals developed a DD lesion at a younger age compared with their higher-merit counterparts. Genetic selection using the DDI could gradually reduce the disease prevalence during the rearing period of replacement animals.</p
Outburst of a subglacial flood from the surface of the Greenland Ice Sheet
No full textAs Earth’s climate warms, surface melting of the Greenland Ice Sheet has intensified, increasing rates of sea-level rise. Observations and theory indicate that meltwater generated at the ice sheet surface can drain to its bed, where it flows relatively unhindered to the ocean. This understanding of water movement within and beneath ice sheets underpins the theoretical models that are used to make projections of ice sheet change. Here we present evidence of a destructive mode of meltwater drainage in Greenland. Using multiple satellite sources, we show that a 90-million-cubic-metre subglacial flood forced its way upwards from the bed, fracturing the ice sheet, and bursting through the surface. This phenomenon was triggered by the rapid drainage of a subglacial lake and occurred in a region where the ice bed was predicted to be frozen. The resulting flood caused a rapid deceleration of the downstream marine-terminating glacier. Our observations reveal a complex, bi-directional coupling between the ice sheet’s surface and basal hydrological systems and demonstrate that extreme hydrological forcing may occur in regions of predicted cold-based ice. Such processes can impact the ice sheet’s dynamics and structural integrity but are not currently considered in ice sheet models
Exploring the potential for commercial vessels to support science and observations in the Southern Ocean
No full textThe Southern Ocean is a vast, unique and remote region that plays a fundamental role in global ocean circulation, climate and biodiversity. Understanding the ecosystems, processes and changes occurring in this region therefore has global implications. Despite this importance, the Southern Ocean remains severely under-observed and under-sampled due to its relative inaccessibility, which impacts the accuracy of global climate model projections and restricts our understanding of change on regional and local scales. Here we use a mixed-methods approach comprising semi-structured expert interviews and a community survey to explore the potential for utilising commercial vessels operating in the Southern Ocean as voluntary observation and scientific support platforms. We find that a wide range of data collection and scientific support methods are feasible to implement from commercial vessels, showing significant potential for these vessels as valuable components of wider, multi-platform Southern Ocean observing systems. These vessels would increase sustained, multidisciplinary regional data coverage and thus contribute to improving whole-system understanding. Despite this potential, there remain many challenges that currently impede the widespread use of these vessels within Southern Ocean observing systems. These challenges include lack of communication and trust between stakeholders, insufficient funding, time and capacity to coordinate this vision, and concerns around data quality. This article explores the current status of expert opinions and trends regarding the opportunities and challenges of integrating commercial vessels within Southern Ocean observing and scientific support networks and provides evidence-based recommendations for future progress in forming sustained partnerships and maximising the utility of commercial vessels
Polygenic scores of executive function provide limited support for genetic confounding with socio-economic measures
No full textPrevious work has suggested that genetic confounding is a persistent issue in studies of environmental predictors of executive function (EF). This is largely because controlling for genetic confounding typically requires specialized samples such as twins or adoptees, which are more difficult to recruit. Polygenic scores provide a potential alternative control, scalable to smaller samples and not requiring specialized sample features. The purpose of this study was to determine if polygenic scores of EF could be used to replicate the findings of other genetic confounding studies in a less specialized sample. Confounding models showed evidence for genetic confounding in maternal education, although it was far weaker in magnitude than in other genetically informed studies. However, consistent with previous research, there were no detectable influences of indirect genetic effects on the EF polygenic score, indicating that the detected genetic confounding was likely a true genetic effect. Finally, while environmental factors other than maternal education seemed predictive of EF, confounding models showed that this was best explained by their association with maternal education. Other predictors of EF may thus be confounded environmentally, not just genetically. While polygenic scores are a promising method with a multitude of applications, in their current state they do not replicate the findings of other genetically informed studies of EF. Caution should thus be used when employing them to study genetic confounding in EF
A wartime Olympics?:Geopolitical tensions, international ambition, and IOC’s vision at Paris 2024
Get PDFThe 2024 Olympic Summer Games in Paris took place amidst the geopolitical crisis in several different places in the world. In particular, the Russia-Ukraine war, the Israel-Hamas conflict, and the US-China diplomatic tension showed little sign of amelioration when the Olympic Games commenced in the French capital. This paper will examine the impact that the three contentions had on the organisation and delivery of the 2024 Olympic Summer Games in Paris. More specially, it pays attention to 1) the absence of the Russian and Belarusian Olympic delegations in this competition, 2) the presence of the Israel and Palestine Olympic teams in Paris, and 3) the Sino-American rivalry in the Olympic arena. It also critically assesses the Olympic Games, especially its Olympic Truce initiative, as a way to promote international peace. Due to the geopolitical tensions and diplomatic friction that involves major powers, Paris 2024 revealed several incidents of negative campaigns such as a threat to boycott, blame for politicising international sport, and the accusation of tainted integrity and of having double standards. This situation indicates the limitation of the IOC and the Olympic Games as a platform for promoting international peace when major geopolitical contention overshadows the spirit of the Olympic Truce. Such prevalence of negative campaigns surrounding the global sports mega-event may be a symptom of a wartime Olympics. To some extent, Paris 2024 only disclosed a disrespectful hostility underneath the colourful festivity amongst the nations in conflict
Legal challenges in tackling AI-generated child sexual abuse material within Australia and New Zealand- REPORT
Get PDFThis report critically reviews the regulatory context of Australia and New Zealand on the topic of accountability around child sexual abuse material (CSAM) created via generative Artificial Intelligence (gen-AI). With regards to Australia, the same issues were examined on both a national as well as a state and territory level, whereas in New Zealand they were examined only on the national level, as no relevant legislation exists on a devolved basis. Australia has enacted an Online Safety Act (OSA) in 2021, which imposes certain duties on online service providers to protect Australians, in particular children and vulnerable adult users online. The eSafety Commissioner was established in 2015 (then the “Office of the Children’s eSafety Commissioner”) in Australia and serves as an independent regulator for online safety, with powers to require the removal of unlawful and seriously harmful material, implement systemic regulatory schemes and educate people around online safety risks. Under the OSA, there are currently enforceable codes and standards in force which apply to AI-generated CSAM with civil penalties for services that fail to comply. In particular the “Designated Internet Service Standard” applies to generative AI services, as well as model distribution services. The Australian Government has also recently conducted consultations regarding the introduction of mandatory guardrails for AI in high-risk settings, which considers guardrails such as ensuring that generative AI training data does not contain CSAM. No such legislation exists in New Zealand, although there are ongoing discussions and legal reform suggestions around the potential introduction of similar legislation there. In both Australia and New Zealand, existing definitions of CSAM or similar terminology used in criminal legislation are broad enough to capture AI-generated CSAM. As a result, and despite limited case law on the matter due to the emerging character of gen-AI technologies, sentencing decisions have emerged in the Australian states of Victoria and Tasmania involving offenders who produced gen-AI CSAM. In New Zealand, no cases have yet been identified in which offenders have been sentenced for offences involving AI-generated CSAM, however, press reports suggest that offenders have been charged in relation to such material. In addition, there are reports of the New Zealand customs service seizing gen-AI CSAM, suggesting they believe they have the jurisdiction to do so. No cases have been identified in Australia or New Zealand in which AI software creators, or holders of datasets used to train AI, have been considered criminally liable in relation to the production of CSAM using their platforms or any other such charges. In New Zealand, certain pieces of legislation (e.g. Crimes Act 1961 and Harmful Digital Communications Act 2015) do not appear to apply in cases of gen-AI CSAM that portrays purely fictitious children. This is to an extent expected, as both laws require harm to be inflicted upon an identifiable natural person, and this is not the case in instances of AI-generated CSAM containing purely fictitious children. In both Australia and New Zealand, there are no pending reforms to expand criminal accountability in relation to gen-AI CSAM to AI software creators and dataset holders. Given that the definitions of CSAM in existing criminal legislation appear broad enough to capture AI-generated material, this is not surprising
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