α2-chimaerin regulates a key axon guidance transition during development of the oculomotor projection

The ocular motor system consists of three nerves which innervate six muscles to control eye movements. In humans, defective development of this system leads to eye movement disorders, such as Duane Retraction Syndrome, which can result from mutations in the α2-chimaerin signaling molecule. We have used the zebrafish to model the role of α2-chimaerin during development of the ocular motor system. We first mapped ocular motor spatiotemporal development, which occurs between 24 and 72 h postfertilization (hpf), with the oculomotor nerve following an invariant sequence of growth and branching to its muscle targets. We identified 52 hpf as a key axon guidance “transition,” when oculomotor axons reach the orbit and select their muscle targets. Live imaging and quantitation showed that, at 52 hpf, axons undergo a switch in behavior, with striking changes in the dynamics of filopodia. We tested the role of α2-chimaerin in this guidance process and found that axons expressing gain-of-function α2-chimaerin isoforms failed to undergo the 52 hpf transition in filopodial dynamics, leading to axon stalling. α2-chimaerin loss of function led to ecotopic and misguided branching and hypoplasia of oculomotor axons; embryos had defective eye movements as measured by the optokinetic reflex. Manipulation of chimaerin signaling in oculomotor neurons in vitro led to changes in microtubule stability. These findings demonstrate that a correct level of α2-chimaerin signaling is required for key oculomotor axon guidance decisions, and provide a zebrafish model for Duane Retraction Syndrome

On the causes of the African slave trade

This paper offers an integrated analysis of the forces shaping the emergence of the African slave trade over the early modern period. We focus our attention on two questions. First, why most of the increase in the demand for slaves during this period came exclusively from western Europeans. Second, and of most relevance for present-day development outcomes, why was the overwhelming majority of slaves of African origin. Technological differences in manufacturing technology, the specificities of sugar (and other crops') production, and the cultural fragmentation of the African continent all play a role in the analysis. Supporting evidence for each of our claims is provided from a broad corpus of relevant literature

Global ecological, social and economic impacts of marine plastic

This research takes a holistic approach to considering the consequences of marine plastic pollution. A semi-systematic literature review of 1191 data points provides the basis to determine the global ecological, social and economic impacts. An ecosystem impact analysis demonstrates that there is global evidence of impact with medium to high frequency on all subjects, with a medium to high degree of irreversibility. A novel translation of these ecological impacts into ecosystem service impacts provides evidence that all ecosystem services are impacted to some extent by the presence of marine plastic, with a reduction in provision predicted for all except one. This reduction in ecosystem service provision is evidenced to have implications for human health and wellbeing, linked particularly to fisheries, heritage and charismatic species, and recreation

Three main stressors acting on the Ria Formosa lagoonal system (Southern Portugal): physical stress, organic matter pollution and the land–ocean gradient

During the last 15 years of the 20th century, several researchers carried out extensive sampling of benthic macrofauna communities in the Ria Formosa lagoon. The main objective of this paper is to discern the main communities of benthic fauna of the Ria Formosa and the leading stressors that limit them based on this large data set. The high species richness and high diversity values observed at most of the stations or groups of stations indicate a good ecological status, with the exception of the sewage-impacted areas and the physically stressed areas. It was possible to define three main stressors acting on the Ria Formosa. The most important is the physical stress imposed by the limited water renewal in some areas of the Ria Formosa. The second is the nutrient and organic matter pollution that is limited to the vicinity of the sewage outfall stations and to some locations of the Ria Formosa. This is due to the dual effects of the low residence time of water, but also due to a degradation of water quality in places of relatively restricted water circulation but with high primary production, symptoms of eutrophication. The third stressor is the natural land-ocean gradient, denoting the influence of seawater exchanges and emersion time, attenuated by the high water exchange rates of Ria Formosa. It was possible to differentiate the anthropogenic stress from the natural physical stress through the application of multivariate analysis. However, both structural (species richness and diversity indices) and functional indicators (trophic composition) indicate the same trend - low species richness, low diversity indices, and a community dominated by detritivores species at the locations characterized by high anthropogenic impact or by physical stress. The physically stressed areas were dominated by chironomid larvae and hydrobiid gastropods and the most polluted areas were dominated by oligochaetes, mainly tubificids

Wastewater Sequencing Reveals Community and Variant Dynamics of the Collective Human Virome

Wastewater is a discarded human by-product, but its analysis may help us understand the health of populations. Epidemiologists first analyzed wastewater to track outbreaks of poliovirus decades ago, but so-called wastewater-based epidemiology was reinvigorated to monitor SARS-CoV-2 levels while bypassing the difficulties and pit falls of individual testing. Current approaches overlook the activity of most human viruses and preclude a deeper understanding of human virome community dynamics. Here, we conduct a comprehensive sequencing-based analysis of 363 longitudinal wastewater samples from ten distinct sites in two major cities. Critical to detection is the use of a viral probe capture set targeting thousands of viral species or variants. Over 450 distinct pathogenic viruses from 28 viral families are observed, most of which have never been detected in such samples. Sequencing reads of established pathogens and emerging viruses correlate to clinical data sets of SARS-CoV-2, influenza virus, and monkeypox viruses, outlining the public health utility of this approach. Viral communities are tightly organized by space and time. Finally, the most abundant human viruses yield sequence variant information consistent with regional spread and evolution. We reveal the viral landscape of human wastewater and its potential to improve our understanding of outbreaks, transmission, and its effects on overall population health

Anaphylactic shock depends on endothelial Gq/G11

Anaphylactic shock is a severe allergic reaction involving multiple organs including the bronchial and cardiovascular system. Most anaphylactic mediators, like platelet-activating factor (PAF), histamine, and others, act through G protein–coupled receptors, which are linked to the heterotrimeric G proteins Gq/G11, G12/G13, and Gi. The role of downstream signaling pathways activated by anaphylactic mediators in defined organs during anaphylactic reactions is largely unknown. Using genetic mouse models that allow for the conditional abrogation of Gq/G11- and G12/G13-mediated signaling pathways by inducible Cre/loxP-mediated mutagenesis in endothelial cells (ECs), we show that Gq/G11-mediated signaling in ECs is required for the opening of the endothelial barrier and the stimulation of nitric oxide formation by various inflammatory mediators as well as by local anaphylaxis. The systemic effects of anaphylactic mediators like histamine and PAF, but not of bacterial lipopolysaccharide (LPS), are blunted in mice with endothelial Gαq/Gα11 deficiency. Mice with endothelium-specific Gαq/Gα11 deficiency, but not with Gα12/Gα13 deficiency, are protected against the fatal consequences of passive and active systemic anaphylaxis. This identifies endothelial Gq/G11-mediated signaling as a critical mediator of fatal systemic anaphylaxis and, hence, as a potential new target to prevent or treat anaphylactic reactions