An atlas of O-linked glycosylation on peptide hormones reveals diverse biological roles

Peptide hormones and neuropeptides encompass a large class of bioactive peptides that regulate physiological processes like anxiety, blood glucose, appetite, inflammation and blood pressure. Here, we execute a focused discovery strategy to provide an extensive map of O-glycans on peptide hormones. We find that almost one third of the 279 classified peptide hormones carry O-glycans. Many of the identified O-glycosites are conserved and are predicted to serve roles in proprotein processing, receptor interaction, biodistribution and biostability. We demonstrate that O-glycans positioned within the receptor binding motifs of members of the neuropeptide Y and glucagon families modulate receptor activation properties and substantially extend peptide half-lives. Our study highlights the importance of O-glycosylation in the biology of peptide hormones, and our map of O-glycosites in this large class of biomolecules serves as a discovery platform for an important class of molecules with potential opportunities for drug designs. O-glycosylation is an abundant post-translational modification but its relevance for bioactive peptides is unclear. Here, the authors detect O-glycans on almost one third of the classified peptide hormones and show that O-glycosylation can modulate peptide half-lives and receptor activation properties.This work was supported by the Novo Nordisk Foundation, the Lundbeck Foundation, Danish National Research Foundation Grant DNRF107

Greenhouse gas and ammonia emission mitigation priorities for UK policy targets

Acknowledgements Many thanks to the Association of Applied Biologist’s for organising and hosting the ‘Agricultural greenhouse gases and ammonia mitigation: Solutions, challenges, and opportunities’ workshop. This work was supported with funding from the Scottish Government’s Strategic Research Programme (2022-2027, C2-1 SRUC) and BBSRC (BBS/E/C/000I0320 and BBS/E/C/000I0330). We also acknowledge support from UKRI694 BBSRC (United Kingdom Research and Innovation-Biotechnology and Biological Sciences 695 Research Council; United Kingdom) via grants BBS/E/C/000I0320 and BBS/E/C/000I0330. and Rothamsted Research's Science Initiative Catalyst Award (SICA) supported by BBSRC.Peer reviewedPublisher PD

Priorities for mitigating greenhouse gas and ammonia emissions to meet UK policy targets

Agriculture is essential for providing food and maintaining food security while concurrently delivering multiple other ecosystem services. However, agricultural systems are generally a net source of greenhouse gases and ammonia. They, therefore, need to substantively contribute to climate change mitigation and net zero ambitions. It is widely acknowledged that there is a need to further reduce and mitigate emissions across sectors, including agriculture to address the climate emergency and emissions gap. This discussion paper outlines a collation of opinions from a range of experts within agricultural research and advisory roles following a greenhouse gas and ammonia emission mitigation workshop held in the UK in March 2022. The meeting identified the top mitigation priorities within the UK’s agricultural sector to achieve reductions in greenhouse gases and ammonia that are compatible with policy targets. In addition, experts provided an overview of what they believe are the key knowledge gaps, future opportunities and co-benefits to mitigation practices as well as indicating the potential barriers to uptake for mitigation scenarios discussed

The ethical desirability of moral bioenhancement: A review of reasons

Background: The debate on the ethical aspects of moral bioenhancement focuses on the desirability of using biomedical as opposed to traditional means to achieve moral betterment. The aim of this paper is to systematically review the ethical reasons presented in the literature for and against moral bioenhancement. Discussion: A review was performed and resulted in the inclusion of 85 articles. We classified the arguments used in those articles in the following six clusters: (1) why we (don't) need moral bioenhancement, (2) it will (not) be possible to reach consensus on what moral bioenhancement should involve, (3) the feasibility of moral bioenhancement and the status of current scientific research, (4) means and processes of arriving at moral improvement matter ethically, (5) arguments related to the freedom, identity and autonomy of the individual, and (6) arguments related to social/group effects and dynamics. We discuss each argument separately, and assess the debate as a whole. First, there is little discussion on what distinguishes moral bioenhancement from treatment of pathological deficiencies in morality. Furthermore, remarkably little attention has been paid so far to the safety, risks and side-effects of moral enhancement, including the risk of identity changes. Finally, many authors overestimate the scientific as well as the practical feasibility of the interventions they discuss, rendering the debate too speculative. Summary: Based on our discussion of the arguments used in the debate on moral enhancement, and our assessment of this debate, we advocate a shift in focus. Instead of speculating about non-realistic hypothetical scenarios such as the genetic engineering of morality, or morally enhancing 'the whole of humanity', we call for a more focused debate on realistic options of biomedical treatment of moral pathologies and the concrete moral questions these treatments raise

Could Moral Enhancement Interventions be Medically Indicated?

This paper explores the position that moral enhancement interventions could be medically indicated (and so considered therapeutic) in cases where they provide a remedy for a lack of empathy, when such a deficit is considered pathological. In order to argue this claim, the question as to whether a deficit of empathy could be considered to be pathological is examined, taking into account the difficulty of defining illness and disorder generally, and especially in the case of mental health. Following this, Psychopathy and a fictionalised mental disorder (Moral Deficiency Disorder) are explored with a view to consider moral enhancement techniques as possible treatments for both conditions. At this juncture, having asserted and defended the position that moral enhancement interventions could, under certain circumstances, be considered medically indicated, this paper then goes on to briefly explore some of the consequences of this assertion. First, it is acknowledged that this broadening of diagnostic criteria in light of new interventions could fall foul of claims of medicalisation. It is then briefly noted that considering moral enhancement technologies to be akin to therapies in certain circumstances could lead to ethical and legal consequences and questions, such as those regarding regulation, access, and even consent

Greenhouse gas and ammonia emission mitigation priorities for UK policy targets

Publication history: Accepted - 16 March 2023; Published online - 6th May 2023.Agriculture is essential for providing food and maintaining food security while concurrently delivering multiple other ecosystem services. However, agricultural systems are generally a net source of greenhouse gases and ammonia. They, therefore, need to substantively contribute to climate change mitigation and net zero ambitions. It is widely acknowledged that there is a need to further reduce and mitigate emissions across sectors, including agriculture to address the climate emergency and emissions gap. This discussion paper outlines a collation of opinions from a range of experts within agricultural research and advisory roles following a greenhouse gas and ammonia emission mitigation workshop held in the UK in March 2022. The meeting identified the top mitigation priorities within the UK’s agricultural sector to achieve reductions in greenhouse gases and ammonia that are compatible with policy targets. In addition, experts provided an overview of what they believe are the key knowledge gaps, future opportunities and co-benefits to mitigation practices as well as indicating the potential barriers to uptake for mitigation scenarios discussed.This work was supported with funding from the Scottish Government Strategic Research Programme (2022−2027, C2-1 SRUC) and Biotechnology and Biological Sciences Research Council (BBSRC) (BBS/E/C/000I0320 and BBS/E/C/000I0330). We also acknowledge support from UKRI-BBSRC (UK Research and Innovation-Biotechnology and Biological Sciences Research Council) via grants BBS/E/C/000I0320 and BBS/E/C/000I0330, and Rothamsted Research Science Initiative Catalyst Award supported by BBSRC

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Ecocentrism and biosphere life extension

The biosphere represents the global sum of all ecosystems. According to a prominent view in environmental ethics, ecocentrism, these ecosystems matter for their own sake, and not only because they contribute to human ends. As such, some ecocentrists are critical of the modern industrial civilization, and a few even argue that an irreversible collapse of the modern industrial civilization would be a good thing. However, taking a longer view and considering the eventual destruction of the biosphere by astronomical processes, we argue that humans, a species with considerable technological know-how and industrial capacity could intervene to extend the lifespan of Earth’s biosphere, perhaps by several billion years. We argue that human civilization, despite its flaws and harmful impacts on many ecosystems, is the biosphere’s best hope of avoiding premature destruction. We argue that proponents of ecocentrism, even those who wholly disregard anthropocentric values, have a strong moral reason preserve the modern industrial civilization, for as long as needed to ensure biosphere survival