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Silva, R. A.

Publications and source records attributed to Silva, R. A..

5 recordsLinked to original sources

A thin-film optogenetic visual prosthesis

Retinitis pigmentosa and macular degeneration lead to photoreceptor death and loss of visual perception. Despite recent progress, restorative technologies for photoreceptor degeneration remain largely unavailable. Here, we describe a novel optogenetic visual prosthesis (FlexLED) based on a combination of a thin-film retinal display and optogenetic activation of retinal ganglion cells (RGCs). The FlexLED implant is a 30 {micro}m thin, flexible, wireless {micro}LED display with 8,192 pixels, each with an emission area of 66 {micro}m2. The display is affixed to the retinal surface, and the electronics package is mounted under the conjunctiva in the form factor of a conventional glaucoma drainage implant. In a rabbit model of photoreceptor degeneration, optical stimulation of the retina using the FlexLED elicits activity in visual cortex. This technology is readily scalable to hundreds of thousands of pixels, providing a route towards an implantable optogenetic visual prosthesis capable of generating vision by stimulating RGCs at near-cellular resolution.

neuroscience↗

Phylogenetic and biogeographical traits predict unrecognized hosts of zoonotic leishmaniasis

The spatio-temporal distribution of leishmaniasis, a parasitic vector-borne zoonotic disease, is significantly impacted by land-use change and climate warming in the Americas. However, predicting and containing outbreaks is challenging as the zoonotic Leishmania system is highly complex: leishmaniasis (visceral, cutaneous and muco-cutaneous) in humans is caused by up to 14 different Leishmania species, and the parasite is transmitted by dozens of sandfly species and is known to infect almost twice as many wildlife species. Despite the already broad known host range, new hosts are discovered almost annually and Leishmania transmission to humans occurs in absence of a known host. As such, the full range of Leishmania hosts is undetermined, inhibiting the use of ecological interventions to limit pathogen spread and the ability to accurately predicting the impact of global change on disease risk. Here, we employed a machine learning approach to generate trait profiles of known zoonotic Leishmania wildlife hosts (mammals that are naturally exposed and susceptible to infection) and used trait-profiles of known hosts to identify potentially unrecognized hosts. We found that biogeography, phylogenetic distance, and study effort best predicted Leishmania host status. Traits associated with global change, such as agricultural land-cover, urban land-cover, and climate, were among the top predictors of host status. Most notably, our analysis suggested that zoonotic Leishmania hosts are significantly undersampled, as our model predicted just as many unrecognized hosts as unknown hosts. Overall, our analysis facilitates targeted surveillance strategies and improved understanding of the impact of environmental change on local transmission cycles. Author summaryLeishmaniasis is a zoonotic, vector borne disease of poverty with a high burden throughout the Americas: within Latin America there are an estimated 58,500 new cases per year and 54,050 years of life lost due to disability. Although the World Health Organization has targeted leishmaniasis for elimination and control by 2030, the disease remains a persistent threat. Across the Americas, particularly in Central America, the southeastern United States, and perimeters of the Amazon Basin, risk of infection is increasing in geographic extent and elevation. While it is known that Leishmania parasites, the causative agent of leishmaniasis, are maintained in the environment via a mammalian host, the full suite of wildlife hosts has yet to be documented, which significantly hinders control efforts. Here, we use machine learning and ecological and evolutionary trait profiles of known hosts to identify unrecognized potential wildlife hosts of Leishmania. We identify 136 mammals in the Americas that are likely to be exposed to and infected by zoonotic Leishmania in the wild. The high number of unrecognized potential hosts emphasizes a need to better invest in studying the ecological epidemiology of leishmaniasis. The study provides information and tools to support targeted intervention and management of this important poverty-associated disease.

ecology↗

Differences in external, internal oral and chondrocranial morphology of the tadpole of Corythomantis greeningi Boulenger, 1896 (Anura: Hylidae)

The genus Corythomantis currently comprises a single species, Corythomantis greeningi, a hylid widely distributed in xerophilic and subhumid morphoclimatic regions of Brazil, mainly in the Northeast region. Recently the external morphology, internal oral anatomy, and chondrocranium of C. greeningi tadpoles were described from specimens collected in the state of Bahia, however, we observed some differences in morphology of individuals from the state of Piaui, northeastern Brazil. The tadpoles were collected during the 2019 rainy season and 14 individuals were used to describe and compare the larval characters. We observed differences in external, internal oral and chondrocranial morphology in relation to specimens previously described, especially in oral disc, number and shape of oral cavity papillae, and some chondrocranium structures, as: cartilago suprarostralis, cornua trabeculae, fontanella frontoparietalis, cartilago orbitalis e planum hypobranchiale. Our results point to the occurrence of heterochrony in C. greeningi, but we do not rule out the possibility that tadpoles belong to different species. Further studies involving a greater number of tadpoles at different stages, combined with genetic, acoustic, and morphological factors of adult specimens may establish the variation degree of C. greeningi in different regions of northeastern Brazil. RESUMOO genero Corythomantis compreende atualmente uma unica especie, Corythomantis greeningi, um hilideo amplamente distribuido nas regioes morfoclimaticas xerofilicas e subumidas do Brasil, principalmente na regiao Nordeste. Recentimente foram descritas a morfologia externa, anatomia oral interna e condrocranio do girino de C. greeningi a partir de especimes coletados no estado da Bahia, no entanto, observamos algumas diferencas na morfologia dos individuos coletados na regiao norte do estado do Piaui, Nordeste do Brasil. Os girinos foram coletados durante o periodo chuvoso de 2019 e 14 individuos foram utilizados para descricao e comparacao dos caracteres larvais. Observamos diferencas na morfologia externa, oral interna e no condrocranio do girino em relacao ao descrito anteriormente, sobretudo no disco oral, no numero e formato de papilas cavidade oral e algumas estruturas do condrocranio, como: cartilago suprarostralis, cornua trabeculae, fontanella frontoparietalis, cartilago orbitalis e planum hypobranchiale. Nossos resultados apontam a ocorrencia de heterocronia em C. greeningi, porem nao descartamos a possibilidade dos girinos pertencerem a especies diferentes. Estudos futuros envolvendo uma maior area de distribuicao e maior numero de individuos em estagios diferentes, aliados a fatores geneticos, acustico e morfologicos dos especimes adultos poderao estabelecer o grau de variacao de C. greeningi em diferentes regioes do Nordeste brasileiro.

zoology↗

Focal Electrical Stimulation of Human Retinal Ganglion Cells

Vision restoration with retinal implants that electrically stimulate retinal ganglion cells (RGCs), which transmit visual information to the brain, is limited by indiscriminate activation of many cells and cell types. Recent work in isolated macaque retina has demonstrated that direct electrical stimulation of RGCs can be performed with single-cell, single-spike resolution. However, the fidelity of epiretinal stimulation has not been examined in the human retina. Here, electrical activation of the major RGC types was examined using large-scale, multi-electrode recording and stimulation in the human retina ex vivo and compared directly to results from macaque. Targeted activation with single-cell, single-spike resolution was often possible without activating overlying axon bundles, at low stimulation current levels similar to those in macaque. Distinct cell types could be identified and targeted based on their distinct electrical signatures. Simulation based on these measurements revealed that a novel, dynamic stimulation approach would produce a nearly optimal evoked visual signal. These results indicate that high-fidelity control of spiking in human RGCs is achievable with extracellular stimulation and that the macaque retina is an accurate model for vision restoration with epiretinal implants.

neuroscience↗

Functional Organization of Midget and Parasol Ganglion Cells in the Human Retina

The functional organization of diverse retinal ganglion cell (RGC) types, which shapes the visual signal transmitted to the brain, has been examined in many species. The unique spatial, temporal, and chromatic properties of the numerically dominant RGC types in macaque monkey retina are presumed to most accurately model human vision. However, the functional similarity between RGCs in macaques and humans has only begun to be tested, and recent work suggests possible differences. Here, the properties of the numerically dominant human RGC types were examined using large-scale multi-electrode recordings with fine-grained visual stimulation in isolated retina, and compared to results from dozens of recordings from macaque retina using the same experimental methods and conditions. The properties of four major human RGC types -- ON-parasol, OFF-parasol, ON-midget, and OFF-midget -- closely paralleled those of the same macaque RGC types, including the spatial and temporal light sensitivity, precisely coordinated mosaic organization of receptive fields, ON-OFF asymmetries, spatial response nonlinearity, and sampling of photoreceptor inputs over space. Putative smooth monostratified cells and polyaxonal amacrine cells were also identified based on similarities to cell types previously identified in macaque retina. The results suggest that recently proposed differences between human and macaque RGCs probably reflect experimental differences, and that the macaque model provides an accurate picture of human RGC function.

neuroscience↗