Familial dysautonomia (FD) is the most prevalent form of hereditary sensory and autonomic neuropathy (HSAN). In FD, a germline mutation in the Elp1 gene leads to Elp1 protein decrease that causes sympathetic neuron death and sympathetic nervous system dysfunction (dysautonomia). Elp1 is best known as a scaffolding protein within the nuclear hetero-hexameric transcriptional Elongator protein complex, but how it functions in sympathetic neuron survival is very poorly understood. Here, we identified a cytoplasmic function for Elp1 in sympathetic neurons that was essential for retrograde nerve growth factor (NGF) signaling and neuron target tissue innervation and survival. Elp1 was found to bind to internalized TrkA receptors in an NGF-dependent manner, where it was essential for maintaining TrkA receptor phosphorylation (activation) by regulating PTPN6 (Shp1) phosphatase activity within the signaling complex. In the absence of Elp1, Shp1 was hyperactivated, leading to premature TrkA receptor dephosphorylation, which resulted in retrograde signaling failure and neuron death. Inhibiting Shp1 phosphatase activity in the absence of Elp1 rescued NGF-dependent retrograde signaling, and in an animal model of FD it rescued abnormal sympathetic target tissue innervation. These results suggest that regulation of retrograde NGF signaling in sympathetic neurons by Elp1 may explain sympathetic neuron loss and physiologic dysautonomia in patients with FD.

Nerve growth factor (NGF) regulates many aspects of neuronal biology by retrogradely propagating signals along axons to the targets of those axons. How this occurs when axons contain a plethora of proteins that can silence those signals has long perplexed the neurotrophin field. In this issue of the JCI, Li et al. suggest an answer to this vexing problem, while exploring why the Elp1 gene that is mutated in familial dysautonomia (FD) causes peripheral neuropathy. They describe a distinctive function of Elp1 as a protein that is required to sustain NGF signaling by blocking the activity of its phosphatase that shuts off those signals. This finding helps explain the innervation deficits prominent in FD and reveals a unique role for Elp1 in the regulation of NGF-dependent TrkA activity.

IL-17–producing RORγt+ γδ T cells (γδT17 cells) are innate lymphocytes that participate in type 3 immune responses during infection and inflammation. Herein, we show that γδT17 cells rapidly proliferate within neonatal lymph nodes and gut, where, upon entry, they upregulate T-bet and coexpress IL-17, IL-22, and IFN-γ in a STAT3- and retinoic acid–dependent manner. Neonatal expansion was halted in mice conditionally deficient in STAT5, and its loss resulted in γδT17 cell depletion from all adult organs. Hyperactive STAT5 mutant mice showed that the STAT5A homolog had a dominant role over STAT5B in promoting γδT17 cell expansion and downregulating gut-associated T-bet. In contrast, STAT5B preferentially expanded IFN-γ–producing γδ populations, implying a previously unknown differential role of STAT5 gene products in lymphocyte lineage regulation. Importantly, mice lacking γδT17 cells as a result of STAT5 deficiency displayed a profound resistance to experimental autoimmune encephalomyelitis. Our data identify that the neonatal microenvironment in combination with STAT5 is critical for post-thymic γδT17 development and tissue-specific imprinting, which is essential for infection and autoimmunity.

Erowid Exp98591

The Brainwashing Of Hillary Voters Is Complete. Hillary Clinton voters are either getting paid or have been brainwashed into defending her pro-corporate status quo policies. Jimmy Dore breaks it down on his broadcast, October 20, 2016. Continue reading →

Earlier this week I predicted the demise of conventional IT caused by the wide adoption of SD-WAN and SASE, accelerated by the emergency demands of everyone working from home. Now that Congress has passed a $2.2 trillion COVID-19 bail-out, let’s throw-in the implications of that legislation to see what effect it is all likely to have on what used to be IT. The short version is to expect an even bigger bloodbath as IT employees at all levels are let go forever. Please understand that some version of this bloodbath was going to happen anyway. What matters right now is how we respond to it. While my previous column was generally about turning lower-level IT nerds into Uber drivers, this one goes a little further […]






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The IBM board of directors today elected Joseph R. Swedish and Frederick H. Waddell to the board.

IBM y organizaciones aliadas lanzaron la iniciativa global 'Call for Code', el esfuerzo más grande y ambicioso para reunir a desarrolladores del sector académico y empresarial, para resolver uno de los problemas más acuciantes de la sociedad de nuestro tiempo: prevenir, responder y recuperarse de desastres naturales.

IBM reveló un nuevo estudio acerca de la manera en que los profesionales de marketing y ventas están adoptando soluciones cognitivas o de Inteligencia Artificial (IA). A pesar de que el 64% de los Directores de Marketing -CMOs por sus siglas en inglés- y líderes de ventas encuestados cree que sus industrias estarán listas para adoptar ese tipo de tecnologías en los próximos tres años, sólo 24% de los encuestados cree que tiene una estrategia establecida para hacerlo en la actualidad.

(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.

Con la finalidad de apoyar el desarrollo de proyectos de alto impacto en la Ciudad de México, la Asociación Mexiana de Ayuda a Niños con Cáncer (AMANC), Fondo Unido México, Fundación Carlos Slim, el Patronato del Museo Nacional de Antropología e IBM, ponen en marcha el día de hoy el programa de consultoría Corporate Service Corps (CSC), en su edición Ciudad de México.

Después de un mes de haber iniciado la consultoria pro-bono de IBM denominada Corporate Service Corps (CSC), el día de hoy se hizo la entrega del resumen ejecutivo de cada uno de los proyectos de las organizaciones receptoras de este apoyo: Asociación Mexiana de Ayuda a Niños con Cáncer (AMANC), Fondo Unido México, Fundación Carlos Slim, el Patronato del Museo Nacional de Antropología.

IBM, Peace Corps y cuatro instituciones locales dieron inicio el día de hoy al programa de consultoría Corporate Service Corps (CSC), en su edición Cd. de Querétaro; con la finalidad de apoyar el desarrollo de proyectos de alto impacto en esta localidad. IBM y Peace Corps (PC) trabajarán en conjunto con la Secretaría de Desarrollo Social del Estado de Querétaro, el Instituto Queretano de las Mujeres, el Municipio de Querétaro - Delegación Santa Rosa Jáuregui, y la Universidad Politécnica de Santa Rosa Jáuregui (UPSRJ).

IBM and Rail Projects Victoria keeping the $11B Metro Tunnel on track

IBM today announced that Victoria University has selected IBM to design and build the university’s first green data centre.

IBM (NYSE: IBM) today announced the appointment of David La Rose as Managing Director of IBM Australia and New Zealand (A/NZ). He replaces Kerry Purcell, who will return to a senior leadership role in IBM Japan.

IBM (NYSE: IBM) today announced the appointment of Professor Iven Mareels as Lab Director of IBM Research-Australia.

IBM Appoints Katrina Troughton as Managing Director of IBM Australia and New Zealand

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

There was a time – before I sank my teeth into the board game hobby and before I took on the demands of being a stepmom to three children - that I planned frequent trips for my friends circle. Each month would see us jet setting off to a different part of the United States (or a different part of the world) in search of adventure and great cuisine. I would pour myself into the research project that proper trip planning requires and create a custom itinerary for our group, working to ensure we caught all the highlights of our destination. This post is about the one I worked up for our last trip to some of the great Western National Parks in the United States.  I share it here with the hope that you might find the itinerary useful in planning your trip out west.

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I will be traveling quite a bit from this weekend until the end of October for conventions!

Event Yaoi's Yaoi Yuri Con - I will be a guest of honor at this convention in Lyon, France! I don't get to travel abroad for conventions very often so I am really looking forward to meeting European fans! :)

NYCC - I will have a table in the Artist Alley! (Table T12)

Nijicon - I will be a guest here! (I'll have a panel!)

So, I have three cons this month (IT JUST SORTA HAPPENED), one of which is overseas, so the Starfighter updates will have to wait until I get back! That sucks, I know, but I will be meeting with friends and fans at conventions, so it's all for a good cause! :) I will be back shortly after I return to wrap up Encke and Keeler!

I hope to do you all proud! Thank you so much as always for your support! -Hamlet

• 1 red bell pepper, thinly sliced ($.70)
• 1 yellow or orange bell pepper, thinly sliced ($.70)
• 1 cup mushrooms, sliced ($1.50)
• 1 cup black or kalamata olives ($1.50)
• 1/2 cup thinly sliced onion ($.20)
• 1/4 cup olive oil ($.20)
• 2 tablespoons lemon juice ($.40)
• 2 tablespoons apple cider vinegar ($.20)
• 2 tablespoons maple syrup or agave (optional, for those who like a touch of sweet) ($.20)
• 1 tablespoon onion powder
• 1 teaspoon freshly minced garlic
• 1 teaspoon dried basil (or 1 tablespoon fresh, chopped)
• 1 teaspoon dried oregano 
• 1 teaspoon salt (or to taste)
• 1/2 teaspoon pepper (or to taste)
• 1-2 medium sized zucchini, spiralized

• 2 bananas, sliced and frozen ($.60)
• 1/2 cup almond milk ($.40)
• 2 tablespoons raw cacao powder or cocoa powder
• pinch salt
• few drops of stevia, if more sweetness is desired

• 1/4 cup melted coconut oil ($.80)
• 1/4 cup raw cacao powder or cocoa powder ($.80)
• 1/4 cup finely ground coconut palm sugar ($.80)
• pinch salt 
• 2 tablespoons chopped pistachios ($.40)

1. Place all fudgesicle ingredients into  blender and puree until very smooth. Add more almond milk or water if needed to facilitate blending. 
2. Pour into popsicle molds and freeze for several hours until fully frozen. 
3. Prepare the chocolate shell coating. 
4. Place all the chocolate shell coating ingredients into a small bowl and stir well until smooth.
5. Remove the fidgesicles from the freezer and pop them out of their molds.
6. Dip the fudgescicles into the hard chocolate shell, or drizzle it over them to coat. 
7. Just heating the coconut oil up enough to melt it and not any warmer will yield the best results. If needed, gently remelt the chocolate hard shell. 
8. Add a sprinkle of chopped pistachios or other chopped nut, if desired. Cacao nibs also work well.
9. Any leftovers can be wrapped and stored in the freezer for a week or so.

• 1 head romaine, chopped ($1.70)
• 1 orange, peeled and sectioned ($.50)
• 1 banana, sliced ($.30)
• 2 tablespoons sliced onion

• 2 oranges, peeled and sectioned ($1.00)
• 2 tablespoons balsamic vinegar ($.20)
• 2 tablespoons maple syrup (or two droppers stevia) ($.40)
• 3 tablespoons tahini ($.40)
• 1 teaspoon onion powder
• 1 teaspoon garlic powder
• 1 teaspoon salt
• 1/2 teaspoon pepper
• crushed red pepper flakes for the top

1. Prepare the salad ingredients.
2. Place all the dressing ingredients except the crushed red pepper flakes into a blender and puree until very smooth. 
3. Assemble the salad ingredients on plates or in bowls. Add the orange sections, banana slices, and onion to the top.
4. Pour salad dressing over and add a sprinkle of black pepper or crushed red pepper flakes. I added both.

When the Public Feared That Library Books Could Spread Deadly Diseases The Difference Between Happiness and Joy Who’s Considered Thin Enough for Eating Disorder Treatment? The Cost of Next Day Delivery Attending Burning Man or Parenting a Toddler? Not having kids is nothing new. What centuries of history tell us about childlessness today. Prehistoric Parents … Continue reading Links — October