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Biology subjects

Joyce, M.

Publications and source records attributed to Joyce, M..

7 recordsLinked to original sources

Identifying and ranking species that need urgent management action to achieve Target 4 of the Global Biodiversity Framework

Target 4 of the Kunming-Montreal Global Biodiversity Framework (KMGBF) calls for urgent management actions to halt humaninduced extinctions and enable species recovery. However, most Parties face substantial challenges in determining which species require urgent management actions. Here, we present a transparent, standardised protocol that identifies and ranks species most likely to need urgent management actions at the national level, using globally available data from the IUCN Red List of Threatened Species. The protocol integrates four criteria aligned with Target 4: global extinction risk, rate of decline, population or range restriction, and endemism, to generate a national ranked list of species. Species scoring highly on these four criteria, and therefore most in need of urgent management action, are ranked most highly. We applied this method to all 250 countries and territories listed in the IUCN Red List and pilottested national rankings with participants from eight diverse countries. Across pilots, participants reported that the ranked lists were scientifically robust, timesaving, and valuable starting points for national prioritysetting, while stating the importance of national context, and the need for additional technical and financial support for implementation. Our results demonstrate that a sciencebased approach can meaningfully support Parties in identifying species requiring urgent action under Target 4, in a standardised way. With 2030 approaching rapidly, this protocol provides an immediate, practical tool to accelerate progress toward halting extinctions and advancing species recovery.

ecology↗

Divergent evolution of sleep functions

Most living organisms have evolved to synchronize their biological activities with the earths rotation, a daily regulation of biology and behaviour controlled by an evolutionary conserved molecular machinery known as the circadian clock. For most animals, circadian mechanisms are meant to maximize their exposure to positive activities (e.g.: social interactions, mating, feeding - generally during the day) and minimize their exposure to peril (e.g.: predation, weather, darkness - generally during the night1). On top of circadian regulation, some behaviours also feature a second layer of homeostatic control acting as a fail-safe to ensure important activities are not ignored. Sleep is one of these behaviours: largely controlled by the circadian clock for its baseline appearance, it is at the same time modulated by a - poorly understood - homeostatic regulator ensuring animals obey their species-specific amount of daily sleep2. An evolutionary conserved homeostatic control is often considered the main evidence for a core biological function of sleep beyond the trivial one (that is: keeping us out of trouble by limiting our energy expenditure and exposure to danger3,4) and it is hypothesized that sleep evolved around this mysterious basic biological function. Here we characterize sleep regulation in a group of seven species of the Drosophila genus at key evolutionary distances and representing a variety of ecological niche adaptations. We show that the spontaneous circadian-driven aspects of sleep are conserved among all species but the homeostatic regulation, unexpectedly, is not. We uncover differences in the behavioural, cell-biological and neuro-pharmacological aspects of sleep and suggest that, in Drosophilids, sleep primarily evolved to satisfy a circadian role, keeping animals immobile during dangerous hours of the day. The homeostatic functions of sleep evolved independently, in a species-specific fashion, and are not conserved.

evolutionary biology↗

SARS-COV-2 Recombinant Receptor-Binding-Domain (RBD) Induces Neutralising Antibodies Against Variant Strains of SARS-CoV-2 and SARS-CoV-1

SARS-CoV-2 is the etiological agent of COVID19. There are currently several licensed vaccines approved for human use and most of them are targeting the spike protein (or virion) in the virion envelope to induce protective immunity. Recently, variants that spread more quickly have emerged. There is evidence that some of these variants are less sensitive to neutralization in vitro, but it is not clear whether they can evade vaccine induced protection. In this study, we tested the utility of SARS-CoV-2 spike RBD as a vaccine antigen and explore the effect of formulation with Alum/MPLA or AddaS03 adjuvants. Our results indicate RBD induces high titers of neutralizing antibodies and activates strong cellular immune responses. There is also significant cross-neutralisation of variants B1.1.7 and B.1.351 and to a lesser extent, SARS-CoV-1. These results indicate that recombinant RBD can be a viable candidate as a stand-alone vaccine or as a booster shot to diversify our strategy for COVID19 protection.

microbiology↗

Erythroid precursors and progenitors suppress adaptive immunity and get invaded by SARS-CoV-2

SARS-CoV-2 infection is associated with lower blood oxygen levels even in patients without hypoxia requiring hospitalization. This discordance illustrates the need for a more unifying explanation as to whether SARS-CoV-2 directly or indirectly affects erythropoiesis. Here we show significantly enriched CD71+ erythroid precursors/progenitors in the blood circulation of COVID-19 patients that have distinctive immunosuppressive properties. A subpopulation of abundant erythroid cells, CD45+CD71+cells, co-express ACE2, TMPRSS2, CD147, CD26 and these can be infected with SARS-CoV-2. In turn, pre-treatment of erythroid cells with dexamethasone significantly diminished ACE2/TMPRSS2 expression and subsequently reduced their infectivity with SARS-CoV-2. Taken together, pathological abundance of erythroid cells might reflect stress erythropoiesis due to the invasion of erythroid progenitors by SARS-CoV-2. This may provide a novel insight into the impact of SARS-CoV-2 on erythropoiesis and hypoxia seen in COVID-19 patients.

immunology↗

Distribution of droplets and immune responses after aerosol and intra-nasal delivery of influenza virus to the respiratory tract of pigs

Recent evidence indicates that local immune responses and tissue resident memory T cells (TRM) are critical for protection against respiratory infections but there is little information on the contributions of upper and lower respiratory tract (URT and LRT) immunity. To provide a rational basis for designing methods for optimal delivery of vaccines to the respiratory tract in a large animal model, we investigated the distribution of droplets generated by a mucosal atomization device (MAD) and two vibrating mesh nebulizers (VMNs) and the immune responses induced by delivery of influenza virus by MAD in pigs. We showed that droplets containing the drug albuterol, a radiolabel (99mTc-DTPA) or a model influenza virus vaccine (S-FLU) have similar aerosol characteristics. 99mTc-DTPA scintigraphy showed that VMNs deliver droplets with uniform distribution throughout the lungs as well as the URT. Surprisingly MAD administration (1ml/nostril) also delivered a high proportion of the dose to the lungs, albeit concentrated in a small area. After MAD administration of influenza virus, antigen specific T cells were found at high frequency in nasal turbinates, trachea, broncho-alveolar lavage, lungs, tracheobronchial nodes and blood. We conclude that the pig is useful for investigating optimal targeting of vaccines to the respiratory tract.

immunology↗

Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication

The COVID-19 pandemic, attributed to the SARS-CoV-2 coronavirus infection, resulted in millions infected worldwide and an immediate need for antiviral treatments. The main protease (Mpro) in SARS-CoV-2 is a viable drug target because of its essential role in the cleavage of the virus polypeptide and subsequent viral replication. Feline infectious peritonitis, a fatal infection in cats caused by a coronavirus, was successfully treated previously with a dipeptide-based protease inhibitor. Here we show this drug, GC376, and its analog GC373, are effective inhibitors of the Mpro from both SARS-CoV and SARS-CoV-2 with IC50 values in the nanomolar range. Crystal structures of the SARS-CoV and SARS-CoV-2 Mpro with these inhibitors have a covalent modification of the nucleophilic Cys145. NMR analysis reveals that inhibition proceeds via reversible formation of a hemithioacetal. GC373 and GC376 are potent inhibitors of SARS-CoV-2 in cell culture, with EC50 values near one micromolar and little to no toxicity. These protease inhibitors are soluble, non-toxic, and bind reversibly. They are strong drug candidates for the treatment of human coronavirus infections because they have already been successful in animals (cats). The work here lays the framework for their use in human trials for the treatment of COVID-19.

biochemistry↗

Induction of differentiation and metabolic reprogramming in human hepatoma cells by adult human serum

Tissue culture medium routinely contains fetal bovine serum (FBS). Here we show that culturing human hepatoma cells in their native, adult serum (human serum, HS) results in the restoration of key morphological and metabolic features of normal liver cells. When moved to HS, these cells show differential transcription of 22-32% of the genes, stop proliferating, and assume a hepatocyte-like morphology. Metabolic analysis shows that the Warburg-like metabolic profile, typical for FBS-cultured cells, is replaced by a diverse metabolic profile consistent with in vivo hepatocytes. We demonstrate the formation of large lipid and glycogen stores, increased glycogenesis, increased {beta}-oxidation, increased ketogenesis, and decreased glycolysis. Finally, organ-specific functions are restored, including xenobiotics degradation and secretion of bile, very low density lipoprotein, and albumin. Thus, organ-specific functions are not necessarily lost in cell cultures, but might be merely suppressed in FBS. Together, we showed that cells that are representative of normal physiology can be produced from cancer cells simply by replacing FBS by HS in culture media. The effect of serum is often overseen in cell culture and we provide a detailed study in the changes that occur, provide insight in some of the serum components that may play a role in the establishment of the different phenotypes, and discuss how these finding might be beneficial to a variety of research fields.

cell biology↗