Evolution of Melanopsin Photoreceptors: Discovery and Characterization of a New Melanopsin in Nonmammalian Vertebrates

In mammals, the melanopsin gene (Opn4) encodes a sensory photopigment that underpins newly discovered inner retinal photoreceptors. Since its first discovery in Xenopus laevis and subsequent description in humans and mice, melanopsin genes have been described in all vertebrate classes. Until now, all of these sequences have been considered representatives of a single orthologous gene (albeit with duplications in the teleost fish). Here, we describe the discovery and functional characterisation of a new melanopsin gene in fish, bird, and amphibian genomes, demonstrating that, in fact, the vertebrates have evolved two quite separate melanopsins. On the basis of sequence similarity, chromosomal localisation, and phylogeny, we identify our new melanopsins as the true orthologs of the melanopsin gene previously described in mammals and term this grouping Opn4m. By contrast, the previously published melanopsin genes in nonmammalian vertebrates represent a separate branch of the melanopsin family which we term Opn4x. RT-PCR analysis in chicken, zebrafish, and Xenopus identifies expression of both Opn4m and Opn4x genes in tissues known to be photosensitive (eye, brain, and skin). In the day-14 chicken eye, Opn4m mRNA is found in a subset of cells in the outer nuclear, inner nuclear, and ganglion cell layers, the vast majority of which also express Opn4x. Importantly, we show that a representative of the new melanopsins (chicken Opn4m) encodes a photosensory pigment capable of activating G protein signalling cascades in a light- and retinaldehyde-dependent manner under heterologous expression in Neuro-2a cells. A comprehensive in silico analysis of vertebrate genomes indicates that while most vertebrate species have both Opn4m and Opn4x genes, the latter is absent from eutherian and, possibly, marsupial mammals, lost in the course of their evolution as a result of chromosomal reorganisation. Thus, our findings show for the first time that nonmammalian vertebrates retain two quite separate melanopsin genes, while mammals have just one. These data raise important questions regarding the functional differences between Opn4x and Opn4m pigments, the associated adaptive advantages for most vertebrate species in retaining both melanopsins, and the implications for mammalian biology of lacking Opn4x

Targeted sampling by autonomous underwater vehicles

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Zhang, Y., Ryan, J. P., Kieft, B., Hobson, B. W., McEwen, R. S., Godin, M. A., Harvey, J. B., Barone, B., Bellingham, J. G., Birch, J. M., Scholin, C. A., & Chavez, F. P. Targeted sampling by autonomous underwater vehicles. Frontiers in Marine Science, 6 (2019): 415, doi:10.3389/fmars.2019.00415.In the vast ocean, many ecologically important phenomena are temporally episodic, localized in space, and move according to local currents. To effectively study these complex and evolving phenomena, methods that enable autonomous platforms to detect and respond to targeted phenomena are required. Such capabilities allow for directed sensing and water sample acquisition in the most relevant and informative locations, as compared against static grid surveys. To meet this need, we have designed algorithms for autonomous underwater vehicles that detect oceanic features in real time and direct vehicle and sampling behaviors as dictated by research objectives. These methods have successfully been applied in a series of field programs to study a range of phenomena such as harmful algal blooms, coastal upwelling fronts, and microbial processes in open-ocean eddies. In this review we highlight these applications and discuss future directions.This work was supported by the David and Lucile Packard Foundation. The 2015 experiment in Monterey Bay was partially supported by NOAA Ecology and Oceanography of Harmful Algal Blooms (ECOHAB) Grant NA11NOS4780030. The 2018 SCOPE Hawaiian Eddy Experiment was partially supported by the National Science Foundation (OCE-0962032 and OCE-1337601), Simons Foundation Grant #329108, the Gordon and Betty Moore Foundation (Grant #3777, #3794, and #2728), and the Schmidt Ocean Institute for R/V Falkor Cruise FK180310. Publication of this paper was funded by the Schmidt Ocean Institute

Edge influence on vegetation at natural and anthropogenic edges of boreal forests in Canada and Fennoscandia

Although anthropogenic edges are an important consequence of timber harvesting, edges due to natural disturbances or landscape heterogeneity are also common. Forest edges have been well studied in temperate and tropical forests, but less so in less productive, disturbance-adapted boreal forests. We synthesized data on forest vegetation at edges of boreal forests and compared edge influence among edge types (fire, cut, lake/wetland; old vs. young), forest types (broadleaf vs. coniferous) and geographic regions. Our objectives were to quantify vegetation responses at edges of all types and to compare the strength and extent of edge influence among different types of edges and forests. Research was conducted using the same general sampling design in Alberta, Ontario and Quebec in Canada, and in Sweden and Finland. We conducted a meta-analysis for a variety of response variables including forest structure, deadwood abundance, regeneration, understorey abundance and diversity, and non-vascular plant cover. We also determined the magnitude and distance of edge influence (DEI) using randomization tests. Some edge responses (lower tree basal area, tree canopy and bryophyte cover; more logs; higher regeneration) were significant overall across studies. Edge influence on ground vegetation in boreal forests was generally weak, not very extensive (DEI usually < 20 m) and decreased with time. We found more extensive edge influence at natural edges, at younger edges and in broadleaf forests. The comparison among regions revealed weaker edge influence in Fennoscandian forests. Synthesis. Edges created by forest harvesting do not appear to have as strong, extensive or persistent influence on vegetation in boreal as in tropical or temperate forested ecosystems. We attribute this apparent resistance to shorter canopy heights, inherent heterogeneity in boreal forests and their adaptation to frequent natural disturbance. Nevertheless, notable differences between forest structure responses to natural (fire) and anthropogenic (cut) edges raise concerns about biodiversity implications of extensive creation of anthropogenic edges. By highlighting universal responses to edge influence in boreal forests that are significant irrespective of edge or forest type, and those which vary by edge type, we provide a context for the conservation of boreal forests. Edges created by forest harvesting do not appear to have as strong, extensive or persistent influence on vegetation in boreal as in tropical or temperate forested ecosystems. We attribute this apparent resistance to shorter canopy heights, inherent heterogeneity in boreal forests and their adaptation to frequent natural disturbance. Nevertheless, notable differences between forest structure responses to natural (fire) and anthropogenic (cut) edges raise concerns about biodiversity implications of extensive creation of anthropogenic edges. By highlighting universal responses to edge influence in boreal forests that are significant irrespective of edge or forest type, and those which vary by edge type, we provide a context for the conservation of boreal forests

Revealing the sub-AU asymmetries of the inner dust rim in the disk around the Herbig Ae star R CrA

Models predict that in the innermost AU of the disk around Herbig Ae/Be star, the dust disk forms a "puffed-up" inner rim, which should result in a strongly asymmetric brightness distribution for disks seen under intermediate inclination. Using the VLTI/AMBER long-baseline interferometer, we obtained 24 near-infrared (H- and K-band) spectro-interferometric observations on the Herbig Ae star R CrA. In the derived visibility function, we detect the signatures of an extended (25 mas) and a compact component (5.8 mas), with the compact component contributing about 2/3 of the total flux. The brightness distribution is highly asymmetric, as indicated by the strong closure phases (up to 40 deg) and the detected position angle dependence of the visibilities and closure phases. To interpret these asymmetries, we employ geometric as well as physical models, including a binary model, a skewed ring model, and a puffed-up inner rim model with a vertical or curved rim shape. Our curved puffed-up rim model can reasonably well reproduce the interferometric observables and the SED simultaneously and suggests a luminosity of 29 L_sun and the presence of relatively large (> 1.2 micron) Silicate dust grains. Perpendicular to the disk, two bow shock-like structures appear in the associated reflection nebula NGC 6729, suggesting that the resolved sub-AU size disk is the driving engine of a large-scale outflow. Detecting, for the first time, strong non-localized asymmetries in the inner regions of a Herbig Ae disk, our study supports the existence of a puffed-up inner rim in YSO disks.Comment: 17 pages; 15 figures; Accepted by A&

Rescue of mutant rhodopsin traffic by metformin-induced AMPK activation accelerates photoreceptor degeneration

Protein misfolding caused by inherited mutations leads to loss of protein function and potentially toxic 'gain of function', such as the dominant P23H rhodopsin mutation that causes retinitis pigmentosa (RP). Here, we tested whether the AMPK activator metformin could affect the P23H rhodopsin synthesis and folding. In cell models, metformin treatment improved P23H rhodopsin folding and traffic. In animal models of P23H RP, metformin treatment successfully enhanced P23H traffic to the rod outer segment, but this led to reduced photoreceptor function and increased photoreceptor cell death. The metformin-rescued P23H rhodopsin was still intrinsically unstable and led to increased structural instability of the rod outer segments. These data suggest that improving the traffic of misfolding rhodopsin mutants is unlikely to be a practical therapy, because of their intrinsic instability and long half-life in the outer segment, but also highlights the potential of altering translation through AMPK to improve protein function in other protein misfolding diseases

When pharmacotherapeutic recommendations may lead to the reverse effect on physician decision-making

For long the medical literature has shown that patients do not always receive appropriate care, including pharmacotherapeutic treatment. To achieve improved patient care, a number of physician-oriented interventions are being delivered internationally in an attempt to implement evidence based medicine in routine daily practice of medical practitioners. The pharmacy profession has taken an active role in the delivery of intervention strategies aimed at promoting evidence based prescribing and improved quality and safety of medicine use. However, the medical literature also supports the notion that valid clinical care recommendations do not always have the desired impact on physician behaviour. We argue that the well-established theory of psychological reactance might at least partially explain instances when physicians do not act upon such recommendations. Reactance theory suggests that when recommended to take a certain action, a motivational state compels us to react in a way that affirms our freedom to choose. Often we choose to do the opposite of what the recommendation is proposing that we do or we just become entrenched in our initial position. The basic concepts of psychological reactance are universal and likely to be applicable to the provision of recommendations to physicians. Making recommendations regarding clinical care, including pharmacotherapy, may carry with it implied threats, as it can be perceived as an attempt to restrict one’s freedom of choice potentially generating reactance and efforts to avoid them. By identifying and taking into account factors likely to promote reactance, physician-oriented interventions could become more effective

Informational needs of general practitioners regarding discharge medication: content, timing and pharmacotherapeutic advice

textabstractObjective: To investigate the needs of Dutch general practitioners on discharge medication, both regarding content, timing and the appreciation of pharma-cotherapeutic advices from clinical pharmacists. Setting: A general teaching hospital in Amsterdam, the Netherlands. Method: A prospective observational study was performed. A questionnaire with regard to the content, optimal timing (including way of information transfer) and appreciation of pharmacotherapeutic advices was posted to 464 general practitioners. One reminder was sent. Main outcome measure: Description of the needs of general practitioners was assessed. For each question and categories of comments frequency tables were made. The Fisher-exact test was used to study associations between the answers to the questions. Results: In total, 149 general practitioners (32%) responded. Most general practitioners (75%) experienced a delay in receiving discharge medication information and preferred to receive this on the day of discharge. GPs wished to receive this information mainly through e-mail (44%). There was a significant correlation (P = 0.002) between general practitioners who wanted to know whether and why medication had been stopped (87%) and changed (88%) during hospital admission. The general practitioners (88%) appreciated pharmacotherapeutic advices from clinical pharmacists. Conclusion: This study indicates how information transfer on discharge medication to GPs can be optimised in the Netherlands. The information arrives late and GPs want to be informed on the day of discharge mainly by e-mail. GPs wish to know why medication is changed or discontinued and appreciate pharmacotherapeutic advices from clinical pharmacists

Identifying the science and technology dimensions of emerging public policy issues through horizon scanning

Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security.Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security

A Blind Circadian Clock in Cavefish Reveals that Opsins Mediate Peripheral Clock Photoreception

Evolution during millions of years in perpetual darkness leads to mutations in non-visual opsin genes (Melanopsin and TMT opsin) and an aberrant, blind circadian clock in cavefish