Astrophysics datamining in the classroom: Exploring real data with new software tools and robotic telescopes

Within the efforts to bring frontline interactive astrophysics and astronomy to the classroom, the Hands on Universe (HOU) developed a set of exercises and platform using real data obtained by some of the most advanced ground and space observatories. The backbone of this endeavour is a new free software Web tool - Such a Lovely Software for Astronomy based on Image J (Salsa J). It is student-friendly and developed specifically for the HOU project and targets middle and high schools. It allows students to display, analyze, and explore professionally obtained astronomical images, while learning concepts on gravitational dynamics, kinematics, nuclear fusion, electromagnetism. The continuous evolving set of exercises and tutorials is being completed with real (professionally obtained) data to download and detailed tutorials. The flexibility of the Salsa J platform tool enables students and teachers to extend the exercises with their own observations. The software developed for the HOU program has been designed to be a multi-platform, multi-lingual experience for image manipulation and analysis in the classroom. Its design enables easy implementation of new facilities (extensions and plugins), minimal in-situ maintenance and flexibility for exercise plugin. Here, we describe some of the most advanced exercises about astrophysics in the classroom, addressing particular examples on gravitational dynamics, concepts currently introduced in most sciences curricula in middle and high schools.Comment: 10 pages, 12 images, submitted to the special theme issue Using Astronomy and Space Science Research in Physics Courses of the American Journal of Physic

Migraine-attributed burden, impact and disability, and migraine-impacted quality of life: Expert consensus on definitions from a Delphi process

Delphi; Migraine; DisabilityDelphi; Migraña; DiscapacidadDelphi; Migranya; DiscapacitatBackground Migraine-attributed burden, impact, disability and migraine-impacted quality of life are important concepts in clinical management, clinical and epidemiological research, and health policy, requiring clear and agreed definitions. We aimed to formulate concise and precise definitions of these concepts by expert consensus. Methods We searched the terms migraine-attributed burden, impact, disability and migraine-impacted quality of life in Embase and Medline from 1974 and 1946 respectively. We followed a Delphi process to reach consensus on definitions. Results We found widespread conflation of concepts and inconsistent terminology within publications. Following three Delphi rounds, we defined migraine-attributed burden as “the summation of all negative consequences of the disease or its diagnosis”; migraine-attributed impact as “the effect of the disease, or its diagnosis, on a specified aspect of life, health or wellbeing”; migraine-attributed disability as “physical, cognitive and mental incapacities imposed by the disease”; and migraine-impacted quality of life as “the subjective assessment by a person with the disease of their general wellbeing, position and prospects in life”. We complemented each definition with a detailed description. Conclusion These definitions and descriptions should foster consistency and encourage more appropriate use of currently available quantifying instruments and aid the future development of others.The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded by Eli Lilly and Company

Fractalkine-CX3CR1 signaling is critical for progesterone-mediated neuroprotection in the retina

Retinitis pigmentosa (RP) encompasses a group of retinal diseases resulting in photoreceptor loss and blindness. We have previously shown in the rd10 mouse model of RP, that rd10 microglia drive degeneration of viable neurons. Norgestrel, a progesterone analogue, primes viable neurons against potential microglial damage. In the current study we wished to investigate this neuroprotective effect further. We were particularly interested in the role of fractalkine-CX3CR1 signaling, previously shown to mediate photoreceptor-microglia crosstalk and promote survival in the rd10 retina. Norgestrel upregulates fractalkine-CX3CR1 signaling in the rd10 retina, coinciding with photoreceptor survival. We show that Norgestrel-treated photoreceptor-like cells, 661Ws, and C57 explants modulate rd10 microglial activity in co-culture, resulting in increased photoreceptor survival. Assessment of Norgestrel’s neuroprotective effects when fractalkine was knocked-down in 661 W cells and release of fractalkine was reduced in rd10 explants confirms a crucial role for fractalkine-CX3CR1 signaling in Norgestrel-mediated neuroprotection. To further understand the role of fractalkine in neuroprotection, we assessed the release of 40 cytokines in fractalkine-treated rd10 microglia and explants. In both cases, treatment with fractalkine reduced a variety of pro-inflammatory cytokines. These findings further our understanding of Norgestrel’s neuroprotective properties, capable of modulating harmful microglial activity indirectly through photoreceptors, leading to increased neuroprotection

“Not Tied Up Neatly with a Bow”: Professionals’ Challenging Cases in Informed Consent for Genomic Sequencing

As the use of genomic technology has expanded in research and clinical settings, issues surrounding informed consent for genome and exome sequencing have surfaced. Despite the importance of informed consent, little is known about the specific challenges that professionals encounter when consenting patients or research participants for genomic sequencing. We interviewed 29 genetic counselors and research coordinators with considerable experience obtaining informed consent for genomic sequencing to understand their experiences and perspectives. As part of this interview, 24 interviewees discussed an informed consent case they found particularly memorable or challenging. We analyzed these case examples to determine the primary issue or challenge represented by each case. Challenges fell into two domains: participant understanding, and facilitating decisions about testing or research participation. Challenges related to participant understanding included varying levels of general and genomic literacy, difficulty managing participant expectations, and contextual factors that impeded participant understanding. Challenges related to facilitating decision-making included complicated family dynamics such as disagreement or coercion, situations in which it was unclear whether sequencing research would be a good use of participant time or resources, and situations in which the professional experienced disagreement or discomfort with participant decisions. The issues highlighted in these case examples are instructive in preparing genetics professionals to obtain informed consent for genomic sequencing

Selective Histone Deacetylase 6 Inhibitors Restore Cone Photoreceptor Vision or Outer Segment Morphology in Zebrafish and Mouse Models of Retinal Blindness.

Blindness arising from retinal or macular degeneration results in significant social, health and economic burden. While approved treatments exist for neovascular ('wet') age-related macular degeneration, new therapeutic targets/interventions are needed for the more prevalent atrophic ('dry') form of age-related macular degeneration. Similarly, in inherited retinal diseases, most patients have no access to an effective treatment. Although macular and retinal degenerations are genetically and clinically distinct, common pathological hallmarks can include photoreceptor degeneration, retinal pigment epithelium atrophy, oxidative stress, hypoxia and defective autophagy. Here, we evaluated the potential of selective histone deacetylase 6 inhibitors to preserve retinal morphology or restore vision in zebrafish atp6v0e1 -/- and mouse rd10 models. Histone deacetylase 6 inhibitor, tubastatin A-treated atp6v0e1 -/- zebrafish show marked improvement in photoreceptor outer segment area (44.7%, p = 0.027) and significant improvement in vision (8-fold, p ≤ 0.0001). Tubastatin A-treated rd10/rd10 retinal explants show a significantly (p = 0.016) increased number of outer-segment labeled cone photoreceptors. In vitro, ATP6V0E1 regulated HIF-1α activity, but significant regulation of HIF-1α by histone deacetylase 6 inhibition in the retina was not detected. Proteomic profiling identified ubiquitin-proteasome, phototransduction, metabolism and phagosome as pathways, whose altered expression correlated with histone deacetylase 6 inhibitor mediated restoration of vision

Norgestrel, a Progesterone Analogue, Promotes Significant Long-Term Neuroprotection of Cone Photoreceptors in a Mouse Model of Retinal Disease

Purpose: Retinitis pigmentosa (RP) refers to a group of inherited blinding retinal diseases, whereby the death of mutated rod photoreceptors is followed closely by the death of cone photoreceptors. Cone cell death can be hugely debilitating as color/daytime vision becomes impaired. Thus, treatments that are effective against cone cell death are urgently needed. Our research has been working toward development of a neuroprotective treatment for RP. We have previously demonstrated significant neuroprotective properties of norgestrel, a progesterone analogue, in the mouse retina. The current study further investigates the potential of norgestrel as a treatment for RP, with a focus on long-term preservation of cone photoreceptors. Methods: Using the well-established rd10 mouse model of RP, we administered a norgestrel-supplemented diet at postnatal day (P)30, following widespread loss of rod photoreceptors and at the outset of cone degeneration. We subsequently assessed cone cell morphology and retinal function at P50, P60, and P80, using immunohistochemistry, electroretinograph recordings, and optomotor testing. Results: While cone cell degeneration was widespread in the untreated rd10 retina, we observed profound preservation of cone photoreceptor morphology in the norgestrel-treated mice for at least 50 days, out to P80. This was demonstrated by up to 28-fold more cone arrestin-positive photoreceptors. This protection transpired to functional preservation at all ages. Conclusions: This work presents norgestrel as an incredibly promising long-term neuroprotective compound for the treatment of RP. Crucially, norgestrel could be used in the mid-late stages of the disease to protect remaining cone cells and help preserve color/daytime vision.Supported by grants from Science Foundation Ireland (SFI 13/IA/1783), Fighting Blindness Ireland (FB13COT), Spanish Ministry of Economy and Competitiveness (MINECO-FEDER-BFU2015-67139-R), Generalitat Valenciana (Prometeo 2016/158), and Carlos III Institute (ISCIII RETICS-FEDER RD16/0008/0016)

Pro-survival redox signalling in progesterone-mediated retinal neuroprotection

Retinitis pigmentosa (RP) is a group of hereditary retinal diseases, characterised by photoreceptor cell loss. Despite a substantial understanding of the mechanisms leading to cell death, an effective therapeutic strategy is sought. Our laboratory has previously demonstrated the neuroprotective properties of Norgestrel, a progesterone analogue, in the degenerating retina, mediated in part by the neurotrophic factor basic fibroblast growth factor (bFGF). In other retinal studies, we have also presented a pro-survival role for reactive oxygen species (ROS), downstream of bFGF. Thus, we hypothesized that Norgestrel utilises bFGF-driven ROS production to promote photoreceptor survival. Using the 661W photoreceptor-like cell line, we now show that Norgestrel, working through progesterone receptor membrane complex 1 (PGRMC1); generates an early burst of pro-survival bFGF-induced ROS. Using the rd10 mouse model of RP, we confirm that Norgestrel induces a similar early pro-survival increase in retinal ROS. Norgestrel-driven protection in the rd10 retina was attenuated in the presence of antioxidants. This study therefore presents an essential role for ROS signalling in Norgestrel-mediated neuroprotection in vitro and demonstrates that Norgestrel employs a similar pro-survival mechanism in the degenerating retina

Progesterone analogue protects stressed photoreceptors via bFGF-mediated calcium influx.

Retinitis pigmentosa (RP) is a degenerative retinal disease leading to photoreceptor cell loss. In 2011, our group identified the synthetic progesterone ‘Norgestrel’ as a potential treatment for RP. Subsequent research showed Norgestrel to work through progesterone receptor membrane component 1 (PGRMC1) activation and upregulation of neuroprotective basic fibroblast growth factor (bFGF). Using trophic factor deprivation of 661W photoreceptor-like cells, we aimed to further elucidate the mechanism leading to Norgestrel-induced neuroprotection. In the present manuscript, we show by flow cytometry and live-cell immunofluorescence that Norgestrel induces an increase in cytosolic calcium in both healthy and stressed 661Ws over 24h. Specific PGRMC1 inhibition by AG205 (1 μM) showed this rise to be PGRMC1-dependent, primarily utilising calcium from extracellular sources, for blockade of L-type calcium channels by verapamil (50 μM) prevented a Norgestrel-induced calcium influx in stressed cells. Calcium influx was also shown to be bFGF-dependent, for siRNA knock down of bFGF prevented Norgestrel-PGRMC1 induced changes in cytosolic calcium. Notably, we demonstrate PGRMC1-activation is necessary for Norgestrel-induced bFGF upregulation. We propose that Norgestrel protects through the following pathway: binding to and activating PGRMC1 expressed on the surface of photoreceptor cells, PGRMC1 activation drives bFGF upregulation and subsequent calcium influx. Importantly, raised intracellular calcium is critical to Norgestrel's protective efficacy, for extracellular calcium chelation by EGTA abrogates the protective effects of Norgestrel on stressed 661W cells in vitro

Migraine-attributed burden, impact and disability, and migraine-impacted quality of life : Expert consensus on definitions from a Delphi process

Migraine-attributed burden, impact, disability and migraine-impacted quality of life are important concepts in clinical management, clinical and epidemiological research, and health policy, requiring clear and agreed definitions. We aimed to formulate concise and precise definitions of these concepts by expert consensus. We searched the terms migraine-attributed burden, impact, disability and migraine-impacted quality of life in Embase and Medline from 1974 and 1946 respectively. We followed a Delphi process to reach consensus on definitions. We found widespread conflation of concepts and inconsistent terminology within publications. Following three Delphi rounds, we defined migraine-attributed burden as "the summation of all negative consequences of the disease or its diagnosis"; migraine-attributed impact as "the effect of the disease, or its diagnosis, on a specified aspect of life, health or wellbeing"; migraine-attributed disability as "physical, cognitive and mental incapacities imposed by the disease"; and migraine-impacted quality of life as "the subjective assessment by a person with the disease of their general wellbeing, position and prospects in life". We complemented each definition with a detailed description. These definitions and descriptions should foster consistency and encourage more appropriate use of currently available quantifying instruments and aid the future development of other

Migraine-attributed burden, impact and disability, and migraine-impacted quality of life : Expert consensus on definitions from a Delphi process

Migraine-attributed burden, impact, disability and migraine-impacted quality of life are important concepts in clinical management, clinical and epidemiological research, and health policy, requiring clear and agreed definitions. We aimed to formulate concise and precise definitions of these concepts by expert consensus. We searched the terms migraine-attributed burden, impact, disability and migraine-impacted quality of life in Embase and Medline from 1974 and 1946 respectively. We followed a Delphi process to reach consensus on definitions. We found widespread conflation of concepts and inconsistent terminology within publications. Following three Delphi rounds, we defined migraine-attributed burden as "the summation of all negative consequences of the disease or its diagnosis"; migraine-attributed impact as "the effect of the disease, or its diagnosis, on a specified aspect of life, health or wellbeing"; migraine-attributed disability as "physical, cognitive and mental incapacities imposed by the disease"; and migraine-impacted quality of life as "the subjective assessment by a person with the disease of their general wellbeing, position and prospects in life". We complemented each definition with a detailed description. These definitions and descriptions should foster consistency and encourage more appropriate use of currently available quantifying instruments and aid the future development of other