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Glycosylphosphatidylinositol (GPI)-anchored proteins are located at the cell surface by a covalent attachment between protein and GPI embedded in the plasma membrane. This attachment is catalyzed by GPI transamidase comprising five subunits (PIGK, PIGS, PIGT, PIGU, and GPAA1) in the endoplasmic reticulum. Loss of either subunit of GPI transamidase eliminates cell surface localization of GPI-anchored proteins. In humans, pathogenic variants in either subunit of GPI transamidase cause neurodevelopmental disorders. However, how the loss of GPI-anchored proteins triggers neurodevelopmental defects remains largely unclear. Here, we identified a novel homozygous variant of PIGK, NM_005482:c.481A > G,p. (Met161Val), in a Japanese female patient with neurodevelopmental delay, hypotonia, cerebellar atrophy, febrile seizures, hearing loss, growth impairment, dysmorphic facial features, and brachydactyly. The missense variant was found heterozygous in her father, but not in her mother. Zygosity analysis revealed that the homozygous PIGKvariant in the patient was caused by paternal isodisomy. Rescue experiments using PIGK-deficient CHO cells revealed that the p.Met161Val variant of PIGK reduced GPI transamidase activity. Rescue experiments using pigkmutant zebrafish confirmed that the p.Met161Val variant compromised PIGK function in tactile-evoked motor response. We also demonstrated that axonal localization of voltage-gated sodium channels and concomitant generation of action potentials were impaired in pigk-deficient neurons in zebrafish, suggesting a link between GPI-anchored proteins and neuronal defects. Taken together, the missense p.Met161Val variant of PIGKis a novel pathogenic variant that causes the neurodevelopmental disorder.

In recent years, carbon removal and associated net-zero energy technologies have emerged as serious options for policymakers and scientists to consider when trying to address climate change. How, where, and when to use these options effectively are, however, polemic, and research examining the social or justice dimensions of deployment—actual or prospective—remains uncommon. This review provides an interdisciplinary and holistic perspective of the sociotechnical dynamics of carbon-removal options. It employs a sociotechnical approach that reveals the different epistemic, economic, technical, social, political, and environmental elements necessary for a net-zero energy transition. In this review, we first summarize seven broad classes of carbon removal—afforestation and reforestation, soil carbon sequestration, marine biomass and blue carbon, direct air capture with carbon storage, bioenergy with carbon capture and storage, enhanced weathering, and biochar. The review then explores four critical sociotechnical areas in greater depth: modeling and assessment, social acceptance, innovation and scaling, and policy and governance. We conclude with implications for policy and research.

Making sense of the implications of climate engineering approaches (solar radiation management, SRM; and carbon dioxide removal, CDR) at planetary scales occurs via a host of methods that calculate, project, and imagine the future in distinct ways. We take a systemic and synthesizing view of some of the (inter)disciplinary methods by which these futures are derived: climate and integrated assessment modeling, ‘deductive’ modes of social science inquiry, deliberative stakeholder engagement, and foresight-based scenarios. We speak to the epistemologies, objectives, and user communities surrounding these research practices, highlighting that different modes of constructing and interpreting evidence about an unformed future yield different kinds of results and signals for actions to be taken. We show how different methods for exploring ‘futures’ form an evolving history of how the risks of CE have been assessed (or constructed), and conclude by echoing calls for a stronger shared understanding of the practices and politics that underpin future-oriented research.

The impacts of global climate change on international security and geopolitics could be of historic proportion, challenging those of previous global threats such as nuclear weapons proliferation, the Great Depression, and terrorism. But while the evidence surrounding the security impacts of climate change is fairly well-understood and improving, less is known about the security risks to climate-technology deployment. In this study, we focus on the geopolitical, security, and military risks facing negative emissions and solar geoengineering options. Although controversial, these options could become the future backbone of a low-carbon or net-zero society, given that they avoid the need for coordinated or global action (and can be deployed by a smaller group of actors, even non-state actors), and that they can “buy time” for mitigation and other options to be scaled up. We utilize a large and diverse expert-interview exercise (N = 125) to critically examine the security risks associated with ten negative emission options (or greenhouse gas removal technologies) and ten solar geoengineering options (or solar radiation management technologies). We ask: What geopolitical considerations does deployment give rise to? What particular military applications exist? What risks do these options entail in terms of weaponization, misuse, and miscalculation? We examine such existing and prospective security risks across a novel conceptual framework envisioning their use as (i) diplomatic or military negotiating tools, (ii) objectivesfor building capacity, control, or deterrence, (iii) targetsin ongoing conflicts, and (iv) causesof new conflicts. This enables us to capture a far broader spectrum of security concerns than those which exist in the extant literature and to go well beyond insights derived from climate modelling or game theory by drawing on a novel, rich, and original dataset of expert perceptions.

This article discusses and illuminates the synergies and jeopardies or tradeoffs that exist between the 17 Sustainable Development Goals (SDGs) and net-zero or future climate protection options such as greenhouse gas removal (GGR) technologies and solar radiation management (SRM) deployment approaches, respectively. Through a large-scale expert-interview exercise (N = 125), the study finds firstly that numerous synergies and tradeoffs exist between GGR, SRM, and the SDGs. More specifically, we reveal that GGR deployment could enhance the attainment of 16 of the 17 SDGs, but this comes with possible tradeoffs with 12 of the SDGs. SRM deployment could not only enhance the attainment of 16 of the 17 SDGs, but also create possible tradeoffs with (a different) 12 SDGs. The findings further support the understanding of the complexity of SRM and GGR proposals and help policymakers and industrial pioneers understand, navigate, and benchmark between geoengineering approaches using sustainable development goals.

Large-scale and highly experimental interventions are being considered as strategies to address climate change. These include carbon dioxide removal approaches that are becoming a key pillar of post-Paris assessment and governance, as well as the more controversial suite of solar geoengineering methods. In this paper, we ask: Who defends and opposes these experiments, and why? After screening 44 early-stage experiments, we conduct a qualitative comparative analysis of 21 of them in five areas: ocean fertilization, marine cloud brightening, stratospheric aerosol injection, ice protection, and enhanced weathering. We develop a common framework of analysis, treating experiments as sites in which the risks and appropriate governance of early-stage science and technology are envisioned and disputed among scientists and other social groups. Our contribution is to map and explain the key issues of contention (why), actors (who), and tactics (how) that have shaped opposition across these linked fields of experimentation and technological development, from the 1990s till today. In doing so, we build upon and connect past studies on particular climate experiments and develop insights relevant to governance outlooks perceptions, discourses, and intents surrounding immature but potentially crucial climate technologies.

Myotubular myopathy (MTM) is a severe congenital muscle disease characterized by profound weakness, early respiratory failure and premature lethality. MTM is defined by muscle biopsy findings that include centralized nuclei and disorganization of perinuclear organelles. No treatments currently exist for MTM. We hypothesized that aberrant neuromuscular junction (NMJ) transmission is an important and potentially treatable aspect of the disease pathogenesis. We tested this hypothesis in two murine models of MTM. In both models we uncovered evidence of a disorder of NMJ transmission: fatigable weakness, improved strength with neostigmine, and electrodecrement with repetitive nerve stimulation. Histopathological analysis revealed abnormalities in the organization, appearance and size of individual NMJs, abnormalities that correlated with changes in acetylcholine receptor gene expression and subcellular localization. We additionally determined the ability of pyridostigmine, an acetylcholinesterase inhibitor, to ameliorate aspects of the behavioral phenotype related to NMJ dysfunction. Pyridostigmine treatment resulted in significant improvement in fatigable weakness and treadmill endurance. In all, these results describe a newly identified pathological abnormality in MTM, and uncover a potential disease-modifying therapy for this devastating disorder.

Biomass waste-derived porous carbons (BWDPCs) are a class of complex materials that are widely used in sustainable waste management and carbon capture. However, their diverse textural properties, the presence of various functional groups, and the varied temperatures and pressures to which they are subjected during CO2adsorption make it challenging to understand the underlying mechanism of CO2adsorption. Here, we compiled a data set including 527 data points collected from peer-reviewed publications and applied machine learning to systematically map CO2adsorption as a function of the textural and compositional properties of BWDPCs and adsorption parameters. Various tree-based models were devised, where the gradient boosting decision trees (GBDTs) had the best predictive performance with R2of 0.98 and 0.84 on the training and test data, respectively. Further, the BWDPCs in the compiled data set were classified into regular porous carbons (RPCs) and heteroatom-doped porous carbons (HDPCs), where again the GBDT model had R2of 0.99 and 0.98 on the training and 0.86 and 0.79 on the test data for the RPCs and HDPCs, respectively. Feature importance revealed the significance of adsorption parameters, textural properties, and compositional properties in the order of precedence for BWDPC-based CO2adsorption, effectively guiding the synthesis of porous carbons for CO2adsorption applications.

How are novel energy, technology, and land-use systems strategies for limiting climate change judged to be ‘feasible’? Controversy has arisen around the research community behind integrated assessment modeling (IAM) scenarios used in the Assessment Reports of the Intergovernmental Panel on Climate Change. This regards the role played by an unproven component in projected energy systems—a coupling of bioenergy generation with carbon capture and storage techniques (BECCS)—that allows IAMs to achieve ambitious temperature targets since adopted by the Paris Agreement. We engage members of the IAM community and a multidisciplinary range of critical experts to interrogate how the ‘feasibility’ of BECCS—or other novel technologies—is assessed within modeling, and use ‘boundary work’ to show how the kind of expertise—and by extension, the authority—held by the IAM community is being challenged. We find that the competing judgments of BECCS's feasibility, between the IAM community and its critics, reflect and reinforce different understandings of the freedom of scientific inquiry, the mutual influences of science and policy, the shape of science communication, and the necessity of reform. We ask what these claims signal for future activity in this space, and conclude with a call for ‘reflexive’ modeling approaches to bridge perspectives.