The rapid global spread and human health impacts of SARS-CoV-2, the virus that causes COVID-19, show humanity's vulnerability to zoonotic disease pandemics. Although anthropogenic land use change is ...known to be the major driver of zoonotic pathogen spillover from wildlife to human populations, the scientific underpinnings of land use-induced zoonotic spillover have rarely been investigated from the landscape perspective. We call for interdisciplinary collaborations to advance knowledge on land use implications for zoonotic disease emergence with a view toward informing the decisions needed to protect human health. In particular, we urge a mechanistic focus on the zoonotic pathogen infect–shed–spill–spread cascade to enable protection of landscape immunity—the ecological conditions that reduce the risk of pathogen spillover from reservoir hosts—as a conservation and biosecurity priority. Results are urgently needed to formulate an integrated, holistic set of science-based policy and management measures that effectively and cost-efficiently minimise zoonotic disease risk. We consider opportunities to better institute the necessary scientific collaboration, address primary technical challenges, and advance policy and management issues that warrant particular attention to effectively address health security from local to global scales.
Ecological dynamics of emerging bat virus spillover Plowright, Raina K.; Eby, Peggy; Hudson, Peter J. ...
Proceedings - Royal Society. Biological sciences/Proceedings - Royal Society. Biological Sciences,
01/2015, Letnik:
282, Številka:
1798
Journal Article
Recenzirano
Odprti dostop
Viruses that originate in bats may be the most notorious emerging zoonoses that spill over from wildlife into domestic animals and humans. Understanding how these infections filter through ecological ...systems to cause disease in humans is of profound importance to public health. Transmission of viruses from bats to humans requires a hierarchy of enabling conditions that connect the distribution of reservoir hosts, viral infection within these hosts, and exposure and susceptibility of recipient hosts. For many emerging bat viruses, spillover also requires viral shedding from bats, and survival of the virus in the environment. Focusing on Hendra virus, but also addressing Nipah virus, Ebola virus, Marburg virus and coronaviruses, we delineate this cross-species spillover dynamic from the within-host processes that drive virus excretion to land-use changes that increase interaction among species. We describe how land-use changes may affect co-occurrence and contact between bats and recipient hosts. Two hypotheses may explain temporal and spatial pulses of virus shedding in bat populations: episodic shedding from persistently infected bats or transient epidemics that occur as virus is transmitted among bat populations. Management of livestock also may affect the probability of exposure and disease. Interventions to decrease the probability of virus spillover can be implemented at multiple levels from targeting the reservoir host to managing recipient host exposure and susceptibility.
Connectivity conservation is an emergent approach to counteracting landscape fragmentation and enhancing resilience to climate change at local, national, and global scales. While policy that promotes ...connectivity is advancing, there has been no systematic, evidence-based study that assesses whether connectivity conservation plans (CCPs) resulted in conservation outcomes, and identifies specific plan attributes that may favor successful implementation. To fill this gap, we gathered 263 terrestrial CCPs from around the world, characterized attributes of 109 plans by surveying plan authors, and conducted semi-structured interviews with authors and implementers of 77 CCPs. The production of CCPs started around 1990 and has increased markedly in all parts of the world, most notably in the United States (led by NGOs and a few states, with little federal involvement), Europe (led by the EU and national policies and implemented at local levels), and the Republic of South Africa (where national legislation mandates each municipality to map corridors and zone all land by 2020). All of the 109 plans that we examined in detail were followed by implementation actions such as crossing structures, ecological restoration, land purchases or easements, recognition of corridors through zoning or government designation, and public engagement. Interviewees emphasized the importance of initial buy-in from key government stakeholders, stakeholder involvement beyond initial buy-in, minimizing staff turnover, and transparent and repeatable procedures. Our quantitative and qualitative analyses similarly suggested that implementation of a CCP was enhanced by enduring partnerships among stakeholders, continuity of leadership, specific recommendations in the CCP using tools appropriately selected from a large toolbox, the existence of enabling legislation and policy, a transparent and repeatable scientific approach, adequate funding, and public outreach.
Transgenic methods enable the selective manipulation of neurons for functional mapping of neuronal circuits. Using confocal microscopy, we have imaged the cellular-level expression of 109 transgenic ...lines in live 6 day post fertilization larvae, including 80 Gal4 enhancer trap lines, 9 Cre enhancer trap lines and 20 transgenic lines that express fluorescent proteins in defined gene-specific patterns. Image stacks were acquired at single micron resolution, together with a broadly expressed neural marker, which we used to align enhancer trap reporter patterns into a common 3-dimensional reference space. To facilitate use of this resource, we have written software that enables searching for transgenic lines that label cells within a selectable 3-dimensional region of interest (ROI) or neuroanatomical area. This software also enables the intersectional expression of transgenes to be predicted, a feature which we validated by detecting cells with co-expression of Cre and Gal4. Many of the imaged enhancer trap lines show intrinsic brain-specific expression. However, to increase the utility of lines that also drive expression in non-neuronal tissue we have designed a novel UAS reporter, that suppresses expression in heart, muscle, and skin through the incorporation of microRNA binding sites in a synthetic 3' untranslated region. Finally, we mapped the site of transgene integration, thus providing molecular identification of the expression pattern for most lines. Cumulatively, this library of enhancer trap lines provides genetic access to 70% of the larval brain and is therefore a powerful and broadly accessible tool for the dissection of neural circuits in larval zebrafish.
Many species execute ballistic escape reactions to avoid imminent danger. Despite fast reaction times, responses are often highly regulated, reflecting a trade-off between costly motor actions and ...perceived threat level. However, how sensory cues are integrated within premotor escape circuits remains poorly understood. Here, we show that in zebrafish, less precipitous threats elicit a delayed escape, characterized by flexible trajectories, which are driven by a cluster of 38 prepontine neurons that are completely separate from the fast escape pathway. Whereas neurons that initiate rapid escapes receive direct auditory input and drive motor neurons, input and output pathways for delayed escapes are indirect, facilitating integration of cross-modal sensory information. These results show that rapid decision-making in the escape system is enabled by parallel pathways for ballistic responses and flexible delayed actions and defines a neuronal substrate for hierarchical choice in the vertebrate nervous system.
Filtering mechanisms prevent a continuous stream of sensory information from swamping perception, leading to diminished focal attention and cognitive processing. Mechanisms for sensory gating are ...commonly studied using prepulse inhibition, a paradigm that measures the regulated transmission of auditory information to the startle circuit; however, the underlying neuronal pathways are unresolved. Using large-scale calcium imaging, optogenetics, and laser ablations, we reveal a cluster of 30 morphologically identified neurons in zebrafish that suppress the transmission of auditory signals during prepulse inhibition. These neurons project to a key sensorimotor interface in the startle circuit—the termination zone of auditory afferents on the dendrite of a startle command neuron. Direct measurement of auditory nerve neurotransmitter release revealed selective presynaptic inhibition of sensory transmission to the startle circuit, sparing signaling to other brain regions. Our results provide the first cellular resolution circuit for prepulse inhibition in a vertebrate, revealing a central role for presynaptic gating of sensory information to a brainstem motor circuit.
•Gsx1 neuron activity in rhombomere 4 correlates with sensory gating of startle•30 identified glutamatergic Gsx1 neurons are required for prepulse inhibition•Gsx1 neurons project to the interface of the auditory nerve and Mauthner cell•Presynaptic inhibition suppresses auditory transmission during prepulse inhibition
Sensory gating is essential to guard sustained processing of relevant signals by suppressing less-salient cues. Tabor et al. now report a cluster of neurons in the zebrafish hindbrain that regulates the transmission of sensory signals to motor circuits via presynaptic inhibition of auditory afferents.
Dissection of lepadiformine by a double hydroamination transform affords a simple achiral amino diene. This reaction is accomplished in the forward sense by amine-directed hydroboration and an ...oxidative alkyl shift to nitrogen, both of which occur with high stereoselectivity to generate three stereogenic centers and the lepadiformine skeleton.
Rapid escape swims in fish are initiated by the Mauthner cells, giant reticulospinal neurons with unique specializations for swift responses. The Mauthner cells directly activate motoneurons and ...facilitate predator detection by integrating acoustic, mechanosensory, and visual stimuli. In addition, larval fish show well-coordinated escape responses when exposed to electric field pulses (EFPs). Sensitization of the Mauthner cell by genetic overexpression of the voltage-gated sodium channel SCN5 increased EFP responsiveness, whereas Mauthner ablation with an engineered variant of nitroreductase with increased activity (epNTR) eliminated the response. The reaction time to EFPs is extremely short, with many responses initiated within 2 ms of the EFP. Large neurons, such as Mauthner cells, show heightened sensitivity to extracellular voltage gradients. We therefore tested whether the rapid response to EFPs was due to direct activation of the Mauthner cells, bypassing delays imposed by stimulus detection and transmission by sensory cells. Consistent with this, calcium imaging indicated that EFPs robustly activated the Mauthner cell but only rarely fired other reticulospinal neurons. Further supporting this idea, pharmacological blockade of synaptic transmission in zebrafish did not affect Mauthner cell activity in response to EFPs. Moreover, Mauthner cells transgenically expressing a tetrodotoxin (TTX)-resistant voltage-gated sodium channel retained responses to EFPs despite TTX suppression of action potentials in the rest of the brain. We propose that EFPs directly activate Mauthner cells because of their large size, thereby driving ultrarapid escape responses in fish.
Many genetic manipulations are limited by difficulty in obtaining adequate levels of protein expression. Bioinformatic and experimental studies have identified nucleotide sequence features that may ...increase expression, however it is difficult to assess the relative influence of these features. Zebrafish embryos are rapidly injected with calibrated doses of mRNA, enabling the effects of multiple sequence changes to be compared in vivo. Using RNAseq and microarray data, we identified a set of genes that are highly expressed in zebrafish embryos and systematically analyzed for enrichment of sequence features correlated with levels of protein expression. We then tested enriched features by embryo microinjection and functional tests of multiple protein reporters. Codon selection, releasing factor recognition sequence and specific introns and 3' untranslated regions each increased protein expression between 1.5- and 3-fold. These results suggested principles for increasing protein yield in zebrafish through biomolecular engineering. We implemented these principles for rational gene design in software for codon selection (CodonZ) and plasmid vectors incorporating the most active non-coding elements. Rational gene design thus significantly boosts expression in zebrafish, and a similar approach will likely elevate expression in other animal models.
Decoding the functional connectivity of the nervous system is facilitated by transgenic methods that express a genetically encoded reporter or effector in specific neurons; however, most transgenic ...lines show broad spatiotemporal and cell-type expression. Increased specificity can be achieved using intersectional genetic methods which restrict reporter expression to cells that co-express multiple drivers, such as Gal4 and Cre. To facilitate intersectional targeting in zebrafish, we have generated more than 50 new Cre lines, and co-registered brain expression images with the Zebrafish Brain Browser, a cellular resolution atlas of 264 transgenic lines. Lines labeling neurons of interest can be identified using a web-browser to perform a 3D spatial search (zbbrowser.com). This resource facilitates the design of intersectional genetic experiments and will advance a wide range of precision circuit-mapping studies.
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