There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as ...a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.
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•Development of LNP-encapsulated mRNA vaccine (ARCoV) targeting the RBD of SARS-CoV-2•ARCoV induces neutralizing antibodies and T cell immunity in mice and NHPs•ARCoV vaccination confers full protection against SARS-CoV-2 challenge in mice•ARCoV is a thermostable vaccine candidate for phase I studies
ARCoV is an LNP-encapsulated mRNA vaccine platform that is highly immunogenic and safe in mice and non-human primates, conferring protection against challenge with a SARS-CoV-2 mouse-adapted strain.
Motivation boosts motor performance. Activity of the ventral midbrain (VM), consisting of the ventral tegmental area (VTA), the substantia nigra pars compacta (SNc) and the retrorubral field (RRF), ...plays an important role in processing motivation. However, little is known about the neural substrate bridging the VM and the spinal motor output. We hypothesized that the VM might exert a modulatory influence over the descending motor pathways. By retrograde transneuronal labelling with rabies virus, we demonstrated the existence of multisynaptic projections from the VM to the cervical enlargement in monkeys. The distribution pattern of spinal projection neurons in the VM exhibited a caudorostral gradient, in that the RRF and the caudal part of the SNc contained more retrogradely labelled neurons than the VTA and the rostral part of the SNc. Electrical stimulation of the VM induced muscle responses in the contralateral forelimb with a delay of a few milliseconds following the responses of the ipsilateral primary motor cortex (M1). The magnitude and number of evoked muscle responses were associated with the stimulus intensity and number of pulses. The muscle responses were diminished during M1 inactivation. Thus, the present study has identified a multisynaptic VM–spinal pathway that is mediated, at least in part, by the M1 and might play a pivotal role in modulatory control of the spinal motor output.
Key points
Motivation to obtain reward is thought to boost motor performance, and activity in the ventral midbrain is important to the motivational process.
Little is known about a neural substrate bridging the ventral midbrain and the spinal motor output.
Retrograde trans‐synaptic experiments revealed that the ventral midbrain projects multisynaptically to the spinal cord in macaque monkeys.
Ventral midbrain activation by electrical stimulation generated cortical activity in the motor cortex and forelimb muscle activity.
A multisynaptic ventral midbrain–spinal pathway most probably plays a pivotal role in modulatory control of the spinal motor output.
figure legend We found a multisynaptic projection from the ventral midbrain (VM), consisting of the ventral tegmental area (VTA), substania nigra pars compacta (SNc) and retrorubral field (RRF), to the spinal cord in monkeys. There was a caudorostral gradient, in that the caudal VM (i.e. the caudal part of the SNc and RRF) contained more neurons projecting indirectly to the spinal cord than the rostral VM (i.e. the rostral part of the SNc and VTA). Activation of the VM induced responses in the primary motor cortex (M1) and several forelimb muscles. These muscle responses were mediated by M1. The VM might have a modulatory action on descending motor pathways.
Human geography has seen a vitalist renaissance over the past decade; however, geography’s concerns are mounting in relation to vitalism’s critical efficacy and political relevance. This article ...pushes back against these concerns. Drawing on the philosophy of Gilles Deleuze, we engage with vitalism as a critical pause and consequently as a vital aspiration in an intellectual climate that is growing increasingly enamoured of negativity as the barometer of serious thinking. In sum, we show how Deleuze’s ‘non-organic vitalism’ promotes a wilder sense of thinking and a more affirmative politics, without acquiescing to the problems of the present.
Advances in animal motion tracking and pose recognition have been a game changer in the study of animal behavior. Recently, an increasing number of works go ‘deeper’ than tracking, and address ...automated recognition of animals’ internal states such as emotions and pain with the aim of improving animal welfare, making this a timely moment for a systematization of the field. This paper provides a comprehensive survey of computer vision-based research on recognition of pain and emotional states in animals, addressing both facial and bodily behavior analysis. We summarize the efforts that have been presented so far within this topic—classifying them across different dimensions, highlight challenges and research gaps, and provide best practice recommendations for advancing the field, and some future directions for research.
The concept of emotional labour has been subject to critique, evaluation, development and extension over the last 35 years, but it remains firmly anthropocentric. This article begins to address this ...shortcoming by illustrating some of the productive potential of extending the concept of emotional labour to include more‐than‐human and multispecies perspectives. Organizations are not solely human phenomena, but research usually fails to consider the role of non‐humans in work in contemporary capitalism. Using the example of trail horses in tourism, I argue that some non‐human animals should be considered workers, and that they do perform emotional labour in service to commercial organizations. More‐than‐human and multispecies perspectives capture some of the complexities of everyday organizational practices, and can inform feminist research attuned to the experiences of marginalized others, human and non‐human.
ABSTRACT
The study of non‐human animals, in particular primates, can provide essential insights into language evolution. A critical element of language is vocal production learning, i.e. learning how ...to produce calls. In contrast to other lineages such as songbirds, vocal production learning of completely new signals is strikingly rare in non‐human primates. An increasing body of research, however, suggests that various species of non‐human primates engage in vocal accommodation and adjust the structure of their calls in response to environmental noise or conspecific vocalizations. To date it is unclear what role vocal accommodation may have played in language evolution, in particular because it summarizes a variety of heterogeneous phenomena which are potentially achieved by different mechanisms. In contrast to non‐human primates, accommodation research in humans has a long tradition in psychology and linguistics. Based on theoretical models from these research traditions, we provide a new framework which allows comparing instances of accommodation across species, and studying them according to their underlying mechanism and ultimate biological function. We found that at the mechanistic level, many cases of accommodation can be explained with an automatic perception–production link, but some instances arguably require higher levels of vocal control. Functionally, both human and non‐human primates use social accommodation to signal social closeness or social distance to a partner or social group. Together, this indicates that not only some vocal control, but also the communicative function of vocal accommodation to signal social closeness and distance must have evolved prior to the emergence of language, rather than being the result of it. Vocal accommodation as found in other primates has thus endowed our ancestors with pre‐adaptations that may have paved the way for language evolution.
Western lowland gorillas (Gorilla gorilla gorilla) are Critically Endangered and show continued population decline. Consequently, pressure is mounting to better understand their conservation threats ...and ecology. Gastrointestinal symbionts, such as bacterial and eukaryotic communities, are believed to play vital roles in the physiological landscape of the host. Gorillas host a broad spectrum of eucaryotes, so called parasites, with strongylid nematodes being particularly prevalent. While these communities are partially consistent, they are also shaped by various ecological factors, such as diet or habitat type. To investigate gastrointestinal symbionts of wild western lowland gorillas, we analysed 215 faecal samples from individuals in five distinct localities across the Congo Basin, using high‐throughput sequencing techniques. We describe the gut bacterial microbiome and genetic diversity of strongylid communities, including strain‐level identification of amplicon sequence variants (ASVs). We identified strongylid ASVs from eight genera and bacterial ASVs from 20 phyla. We compared these communities across localities, with reference to varying environmental factors among populations, finding differences in alpha diversity and community compositions of both gastrointestinal components. Moreover, we also investigated covariation between strongylid nematodes and the bacterial microbiome, finding correlations between strongylid taxa and Prevotellaceae and Rikenellaceae ASVs that were consistent across multiple localities. Our research highlights the complexity of the bacterial microbiome and strongylid communities in several gorilla populations and emphasizes potential interactions between these two symbiont communities. This study provides a framework for ongoing research into strongylid nematode diversity, and their interactions with the bacterial microbiome, among great apes.
Background
Xenogeneic donors would provide an unlimited source of islets for the treatment of type 1 diabetes (T1D). The goal of this study was to assess the function of microencapsulated adult ...porcine islets (APIs) transplanted ip in streptozotocin (STZ)‐diabetic non‐human primates (NHPs) given targeted immunosuppression.
Methods
APIs were encapsulated in: (a) single barium‐gelled alginate capsules or (b) double alginate capsules with an inner, islet‐containing compartment and a durable, biocompatible outer alginate layer. Immunosuppressed, streptozotocin‐diabetic NHPs were transplanted ip with encapsulated APIs, and graft function was monitored by measuring blood glucose, %HbA1c, and porcine C‐peptide. At graft failure, explanted capsules were assessed for biocompatibility and durability plus islet viability and functionality. Host immune responses were evaluated by phenotyping peritoneal cell populations, quantitation of peritoneal cytokines and chemokines, and measurement of anti‐porcine IgG and IgM plus anti‐Gal IgG.
Results
NHP recipients had reduced hyperglycemia, decreased exogenous insulin requirements, and lower percent hemoglobin A1c (%HbA1c) levels. Porcine C‐peptide was detected in plasma of all recipients, but these levels diminished with time. However, relatively high levels of porcine C‐peptide were detected locally in the peritoneal graft site of some recipients at sacrifice. IV glucose tolerance tests demonstrated metabolic function, but the grafts eventually failed in all diabetic NHPs regardless of the type of encapsulation or the host immunosuppression regimen. Explanted microcapsules were intact, “clean,” and free‐floating without evidence of fibrosis at graft failure, and some reversed diabetes when re‐implanted ip in diabetic immunoincompetent mice. Histology of explanted capsules showed scant evidence of a host cellular response, and viable islets could be found. Flow cytometric analyses of peritoneal cells and peripheral blood showed similarly minimal evidence of a host immune response. Preformed anti‐porcine IgG and IgM antibodies were present in recipient plasma, but these levels did not rise post‐transplant. Peritoneal graft site cytokine or chemokine levels were equivalent to normal controls, with the exception of minimal elevation observed for IL‐6 or IL‐1β, GRO‐α, I‐309, IP‐10, and MCP‐1. However, we found central necrosis in many of the encapsulated islets after graft failure, and explanted islets expressed endogenous markers of hypoxia (HIF‐1α, osteopontin, and GLUT‐1), suggesting a role for non‐immunologic factors, likely hypoxia, in graft failure.
Conclusions
With donor xenoislet microencapsulation and host immunosuppression, APIs corrected hyperglycemia after ip transplantation in STZ‐diabetic NHPs in the short term. The islet xenografts lost efficacy gradually, but at graft failure, some viable islets remained, substantial porcine C‐peptide was detected in the peritoneal graft site, and there was very little evidence of a host immune response. We postulate that chronic effects of non‐immunologic factors, such as in vivo hypoxic and hyperglycemic conditions, damaged the encapsulated islet xenografts. To achieve long‐term function, new approaches must be developed to prevent this damage, for example, by increasing the oxygen supply to microencapsulated islets in the ip space.
Drawing upon the literature on the critical geographies of precarity, as well as feminist readings of non- and more-than-human geographies and political ecologies, this review proposes a ...socio-ecological precarity framеwork to address gaps in discussions and examinations of nonhuman vulnerabilities, forms of resistance, and infrastructures of conviviality and care. Socio-ecological precarity is posited as relational, politically generative, and transformative.
Animal geographies I Buller, Henry
Progress in human geography,
04/2014, Letnik:
38, Številka:
2
Journal Article
Recenzirano
Animal geographies has emerged over the last 15 years as a lively and provocative area of current human/non-human geographical research and scholarship. Yet, while the ‘animal turn’ has arguably ...impacted widely across a range of social sciences and the humanities, for ‘human’ geography it offers what is potentially a far more fundamental and profound reconfiguration of the discipline’s traditional ontological and epistemological reach, not least given the challenge that the ‘animal’ brings to the exclusivity of geography’s adjectival humanism. This article is the first of three reports on animal geographies. It sets out the development of the subdiscipline, from the mid-1990s onwards, and charts the emergence of what has become a distinctive and innovative field with increasing interdisciplinary connections.
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