Treating neuropathic pain is challenging and novel non–opioid-based medicines are needed. Using unbiased receptomics, transcriptomic analyses, immunofluorescence, and in situ hybridization, we found that the expression of the orphan GPCR Gpr160 and GPR160 increased in the rodent dorsal horn of the spinal cord following traumatic nerve injury. Genetic and immunopharmacological approaches demonstrated that GPR160 inhibition in the spinal cord prevented and reversed neuropathic pain in male and female rodents without altering normal pain response. GPR160 inhibition in the spinal cord attenuated sensory processing in the thalamus, a key relay in the sensory discriminative pathways of pain. We also identified cocaine- and amphetamine-regulated transcript peptide (CARTp) as a GPR160 ligand. Inhibiting endogenous CARTp signaling in spinal cord attenuated neuropathic pain, whereas exogenous intrathecal CARTp evoked painful hypersensitivity through GPR160-dependent ERK and cAMP response element–binding protein (CREB). Our findings de-orphanize GPR160, identify it as a determinant of neuropathic pain and potential therapeutic target, and provide insights into its signaling pathways. CARTp is involved in many diseases including depression and reward and addiction; de-orphanization of GPR160 is a major step forward understanding the role of CARTp signaling in health and disease.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by loss of repression of the DUX4 gene; however, the DUX4 protein is rare and difficult to detect in human muscle biopsies, and pathological mechanisms are obscure. FSHD is also a chronic disease that progresses slowly over decades. We used the sporadic, low-level, muscle-specific expression of DUX4 enabled by the iDUX4pA-HSA mouse to develop a chronic long-term muscle disease model. After 6 months of extremely low sporadic DUX4 expression, dystrophic muscle presented hallmarks of FSHD histopathology, including muscle degeneration, capillary loss, fibrosis, and atrophy. We investigated the transcriptional profile of whole muscle as well as endothelial cells and fibroadiopogenic progenitors (FAPs). Strikingly, differential gene expression profiles of both whole muscle and, to a lesser extent, FAPs, showed significant overlap with transcriptional profiles of MRI-guided human FSHD muscle biopsies. These results demonstrate a pathophysiological similarity between disease in muscles of iDUX4pA-HSA mice and humans with FSHD, solidifying the value of chronic rare DUX4 expression in mice for modeling pathological mechanisms in FSHD and highlighting the importance FAPs in this disease.

Seizures often herald the clinical appearance of gliomas or appear at later stages. Dissecting their precise evolution and cellular pathogenesis in brain malignancies could inform the development of staged therapies for these highly pharmaco-resistant epilepsies. Studies in immunodeficient xenograft models have identified local interneuron loss and excess glial glutamate release as chief contributors to network disinhibition, but how hyperexcitability in the peritumoral microenvironment evolves in an immunocompetent brain is unclear. We generated gliomas in WT mice via in utero deletion of key tumor suppressor genes and serially monitored cortical epileptogenesis during tumor infiltration with in vivo electrophysiology and GCAMP7 calcium imaging, revealing a reproducible progression from hyperexcitability to convulsive seizures. Long before seizures, coincident with loss of inhibitory cells and their protective scaffolding, gain of glial glutamate antiporter xCT expression, and reactive astrocytosis, we detected local Iba1+ microglial inflammation that intensified and later extended far beyond tumor boundaries. Hitherto unrecognized episodes of cortical spreading depolarization that arose frequently from the peritumoral region may provide a mechanism for transient neurological deficits. Early blockade of glial xCT activity inhibited later seizures, and genomic reduction of host brain excitability by deleting MapT suppressed molecular markers of epileptogenesis and seizures. Our studies confirmed xenograft tumor–driven pathobiology and revealed early and late components of tumor-related epileptogenesis in a genetically tractable, immunocompetent mouse model of glioma, allowing the complex dissection of tumor versus host pathogenic seizure mechanisms.

While the pandemic has been chipping away at the furry convention scene, other furs have stepped forward to try and give those in the community events to look forward to over the now dormant weekends. This had started with a group of Furnal Equinox members creating a digital replacement for their late March convention called Keep Calm and Carry Con - Furnal Isolation. More have started to spring up this spring.

They can have internet dealers dens, streaming dance competitions, and other staples that conventions are known for. Accessible from the safety of your own home.

Below is a comprehensive list of conventions. Last updated May 2nd, 2020 12:18 ET.

Please feel free to place any not listed here in the comments below and we will look into adding it if it appears legitimate.

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Erowid Exp102582

Erowid Exp101191

В новом интервью с SiriusXM "Trunk Nation" у легендарного гитариста Tony Iommi спросили, доволен ли он тем, как прошёл прощальный тур BLACK SABBATH "The End", на что он ответил:

«Было здорово иметь возможность отправиться в последний тур. Честно говоря, я чувствовал себя неважно [из-за] этого, потому что в основном это был мой выбор, моя вина, потому что турне для меня в некоторой степени было в физическом плане не самой лучшей идеей. Я имею в виду, что приходилось возвращаться в часа утра после концерта — ты отыграл концерт, а потом летишь обратно в отель — это было много возвращений поздними ночами. Я находился в таких же условиях, как когда мне было 20. Несмотря на то, что мы путешествовали [на] лучших [условиях] — у нас был собственный самолет, у нас были потрясающие отели, и нас разместили в Нью-Йорке или Лос-Анджелесе на 10 дней, или где-то ещё, это было вот так. Выходили из отеля, летели на самолёте, давали концерт, возвращались, но к тому времени, как мы заканчивали, возвращались в отель и ложились спать, уже было три-четыре часа. А для меня это было трудно, и мой доктор сказал мне попробовать немного успокоиться. И в то время это казалось правильным.

Особенно после всего, что случилось с Ронни [Джеймсом Дио], мне очень понравился тот период [с HEAVEN & HELL], когда мы были снова с Дио, мы очень сблизились с этой группой, и это была отличная группа. А потом мы решили заново собрать SABBATH с Ozz'ом [Ozzy Osbourne'ом], и это было круто для завершения карьеры. Но я думаю, что если бы Ронни был жив, я бы, наверное, делал что-нибудь с ним сейчас».

Iommi также ответил на вопрос, возможны ли разовые выступления группы:

«Думаю, это было бы неплохо, ну если мы сможем это сделать. Сложность в том, по крайней мере с SABBATH, что это всё серьёзное предприятие, ты не можешь просто взять и отыграть, так как нужны техники, полная линейка оборудования и всё такое. И это должен быть год или полтора тура... Я не против чего-то такого, я просто хотел бы всё сделать иначе». #Black_Sabbath #BlackSabbath #HardRock #Hard_Rock #HeavyMetal #Heavy_Metal

DARK NIGHTS: DEATH METAL #1 is due out June 16, and we've got early unlettered pages.

The post Scott Snyder and Sgt. Rock team-up for industry pep talk in DARK NIGHTS: DEATH METAL #1 appeared first on The Beat.

As the 2015 Atlantic hurricane season gets underway, communities in severe weather-prone regions are anxiously tracking pending storms and working to create effective disaster response plans. IBM, through its strategic alliance with The Weather Company and its global B2B division WSI, today announced a new emergency management solution that features sophisticated analytics and the use of real-time weather data to help communities predict and plan for natural disasters far more accurately and deploy the right resources in advance.

The Weather Company, an IBM Business announced today that it is enhancing its global flight operations solution WSI Fusion, with live flight tracking data from FlightAware. WSI Fusion provides early insight into changing flight, airport and airspace conditions, enabling aviation providers to carefully plan and track flights, optimize operations and reduce the impacts of disruptive events. With the addition of FlightAware’s data, including its private network of over 12,000 Automatic Dependent Surveillance – Broadcast (ADS-B) ground stations in over 160 countries, WSI Fusion customers will have access to enhanced flight following capabilities worldwide.

Each year, weather-related power outages cost the U.S. economy as much as $33 billion a year. Additionally, one severe weather event has the potential to impact the daily lives and routines of millions of people. As 2017 marks the fifth anniversary of Superstorm Sandy, The Weather Company, an IBM Business (NYSE: IBM) and Zpryme are releasing the results of a survey that found that U.S. utility companies still feel underprepared for weather-related outages and that their reactive approach to outage prediction leads to lost time and resources.

At the International Supercomputing Conference in Frankfurt, The Weather Company, an IBM Business, today announced a plan to help improve weather prediction globally via a new collaboration with the University Corporation for Atmospheric Research (UCAR) and the National Center for Atmospheric Research (NCAR), a federally funded research and development center for the atmosphere and Earth’s geospace systems.

The Weather Company, an IBM Business, and PRISA Noticias, one of the world’s leading Spanish-language media groups and owner of EL PAÍS newspaper, announced today a collaboration to combine the most accurate forecasts with one of the Spanish-speaking world’s largest media groups. The Weather Company will provide in-depth weather data and forecasts, as well as tailored content across PRISA properties. In turn, PRISA Noticias will provide locally relevant articles, photos and video content within the Spanish versions of The Weather Channel app and website (weather.com). The collaboration will also enable local marketers to access advanced data-driven advertising solutions from IBM Watson Advertising (formerly The Weather Company’s ad sales business) across both companies’ properties.

The Weather Company, an IBM Business announced today that The Weather Channel has launched a cognitive weather bot for Facebook Messenger – powered by IBM Watson. Around the world, Messenger is used to stay in touch with friends and family. Now with The Weather Channel bot, it offers a way to view and share personalized weather-related news content, current conditions, forecasts, severe weather notifications, and other relevant weather information.

Millions of consumers depend on The Weather Channel and weather.com for their daily forecasts, breaking weather news, and the latest in health and travel. And, on August 21, they will be able to experience a solar eclipse like never before. The Weather Channel digital properties and Twitter have teamed up for a live stream of this once-in-a lifetime celestial event, which will allow consumers to chase the total solar eclipse in real time as it moves from coast-to-coast.

The Weather Company, an IBM Business and Rogers Media announced today an agreement to provide weather information and content customized specifically for the Canadian market. With this agreement, The Weather Company will provide in-depth weather data and forecasts, as well as curated content, across Rogers Media properties. In turn, Rogers Media will provide locally relevant articles, photos and video content across the Canadian versions of The Weather Channel app and website (weather.com) to provide residents with the most pertinent information possible. The Weather Company and Rogers Media will also align to enhance advertising across both companies’ properties, with Rogers leveraging its ad sales capabilities to monetize The Weather Channel properties in Canada.

NASCAR and The Weather Company, an IBM Busines, announced today a multi-year agreement that will optimize the weather-related decision process for NASCAR as it incorporates hyper-local weather data and forecasts into their races to improve race-day operations and fan engagement. As part of the agreement, The Weather Company, via The Weather Channel brand, becomes the Official Weather Partner of NASCAR.

As the new school year begins, elementary school teachers across the United States are now able to access a new, free online tool designed to provide elementary school teachers with targeted math resources for their kindergarten through fifth grade classrooms.

(NYSE: IBM) will strengthen Australia and New Zealand’s chances of co-hosting the world’s biggest radio telescope project (SKA), one of the largest scientific projects ever undertaken. The IBM SUR Award of IBM high performance Graphical Processor Unit (GPU) based computer hardware, management software and implementation services, will enable Victoria University to support the Murchison Widefield Array (MWA) project, a low frequency SKA pathfinder project hosted in Australia in collaboration with Curtin University, MIT, the Smithsonian Institute, and the Raman Research Institute.

Daily Photo – Bathhouses in Budapest There are different old Turkish baths all over Budapest. This particular one had about seven different pools, and this was the most ornate. I’m not 100% sure, but I think the roof can partially retract too. I can imagine that a century earlier it would have probably been the […]

An IBM (NYSE: IBM) study of 26,000 consumers from 14 countries -- including almost 2,000 Australians.-- found that over 60% of Australian consumers identify themselves as “apathetic” in their choice of primary retailer – almost double those who see themselves as advocates of a particular retailer. As such Australian retailers have a significant opportunity to capture shopper loyalty, but they need to capitalise on existing investments in multi-channel and accelerate customer engagement across all channels, including mobile devices and social media platforms in order to win in this globally competitive sector.

Auror Spook Kitty Fawley thought the difficult part of her return to the UK would be getting Sirius out of prison and recovering Harry from his Muggle relatives. Turns out that was the easiest thing she would do. To help them, Kitty will delve into a mystery deeper than any she faced in the field.

Head Auror Harry Potter hated the Department of Mysteries. He hated dealing with Unspeakables and disliked their holier than thou attitude. When Harry is called upon to identify a man who has been dead for years that the Unspeakables found, he suspects that there’s something more sinister going on.

The Wizarding world finally knows that Lord Voldemort has returned, and the Second War has begun. As Harry prepares to enter his sixth year at Hogwarts, he is forced to deal with the trauma from his last encounter with Voldemort, the upcoming trial of Dolores Umbridge, Sirius's uncomfortable questions about his childhood, his budding relationship with Ginny Weasley, and the unknown shadow of what lies ahead as the "Chosen One" who must defeat Voldemort once and for all. This is an AU take of Half-Blood Prince following my previous story, Path Diverged.

Just a short note that the memorial article “Analysis and applications: The mathematical work of Elias Stein” has just been published in the Bulletin of the American Mathematical Society.  This article was a collective effort led by Charlie Fefferman, Alex Ionescu, Steve Wainger and myself to describe the various mathematical contributions of Elias Stein, who […]

Next quarter, starting March 30, I will be teaching “Math 247B: Classical Fourier Analysis” here at UCLA.  (The course should more accurately be named “Modern real-variable harmonic analysis”, but we have not gotten around to implementing such a name change.) This class (a continuation of Math 247A from previous quarter, taught by my colleague, Monica […]

At the most recent MSRI board of trustees meeting on Mar 7 (conducted online, naturally), Nicolas Jewell (a Professor of Biostatistics and Statistics at Berkeley, also affiliated with the Berkeley School of Public Health and the London School of Health and Tropical Disease), gave a presentation on the current coronavirus epidemic entitled “2019-2020 Novel Coronavirus […]

After some discussion with the applied math research groups here at UCLA (in particular the groups led by Andrea Bertozzi and Deanna Needell), one of the members of these groups, Chris Strohmeier, has produced a proposal for a Polymath project to crowdsource in a single repository (a) a collection of public data sets relating to […]

My student, Jaume de Dios, has set up a web site to collect upcoming mathematics seminars from any institution that are open online.  (For instance, it has a talk that I will be giving in an hour.)   There is a form for adding further talks to the site; please feel free to contribute (or make […]

Six young Jedi face their fears and themselves in an ancient rite of passage.

In the chilling series finale, Ahsoka and Rex try to survive Order 66 and plot one final escape.

ESPN highlights the stories of athletes, coaches and other sports figures managing their mental health and well-being.

Four-time Tour de France champion Chris Froome is unsure if the organisers can fully prevent large crowds from gathering at the race that was rescheduled due to the coronavirus pandemic.

Professional and high-performance athletes in Spain were allowed to return to practice, but some were jeered for doing so during the coronavirus pandemic.

Continued from Day Four. (From the beginning.) On Friday we packed all of our stuff back up and headed out.  We were barely out of the resort when: This tire is flat. Apparently all that gravel out to Horne Lake Caves the day before also included a small screw.  We limped around the corner to … Continue reading Summer Horrification — Day Five — Englishman River and Rathtrevor

Out of an abundance of caution regarding the developing COVID-19 situation, U.S. Grand Lodge has decided to cancel its scheduled national gatherings this spring, specifically Advanced Initiator Training, Kaaba Colloquium, and the Electoral College meeting. The Electoral College meeting will be held online according to standard Electoral College procedures. For more information regarding COVID-19, please …

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The Grand Master Sabazius has announced a hold on all U.S. O.T.O. gatherings until further notice. More information is available here.