Podcasts about ampar

Muchas preguntas y ninguna respuesta. Así podría resumirse la comparecencia de Begoña Gómez en la Asamblea de Madrid. La esposa de Pedro Sánchez acudió ayer a la comisión de investigación destinada a esclarecer su relación con la Universidad Complutense de Madrid (UCM), donde ha codirigido dos cátedras. La sesión duró una hora y media, aunque Gómez se limitó a una breve intervención inicial, afirmando que “todo esto tiene un objetivo político”. Amparándose en su derecho a no declarar, su silencio dominó la comisión, pese a los intentos del PP, Vox y Sumar por obtener respuestas.La tensión fue palpable en varios momentos, y la presidenta de la comisión Susana Pérez tuvo que recordar repetidamente el propósito y el formato de la sesión a los participantes.En el capítulo de hoy, Javier Corbacho, redactor de Tribunales, e Irene Pérez Nova, de Madrid Total, nos ofrecen un análisis detallado de la comparecencia de Begoña Gómez y desglosan la intervención del rector de la UCM, Joaquín Goyache, quien defendió la legalidad de las cátedras y negó cualquier "trato excepcional" a Gómez. Además, explicó que los encuentros en Moncloa se realizaron por motivos de seguridad sanitaria debido a la pandemia de Covid-19.

Hoy descubriremos algunos de los momentos más significativos de la vida de toda una Miss Universo, Amparo Muñoz Quesada, la española más bella del mundo La pequeña Amparo nació en Vélez-Málaga el 21 de junio de 1954 en el seno de una familia más modesta que Cristina Cifuentes, que la grabaron robando y decía que ella no. Su padre era forjador a fuego los martes a las 22:15 en Dmax y su madre ama de casa. Amparo era la mayor de 6, por lo que le tocó criarse con sus padrinos, que no tenían hijos, pero tampoco dinero. La falta de recursos sólo le permitió llegar en la escuela al mapa político de España, los conjuntos y Mazzy, por lo que muy pronto empezó a trabajar como dependienta en los Almacenes Mérida que era el Simago de allí. Pero Amparo aspiraba a más que al departamento de zapatería porque ella era simpática, así que se hizo varios cursos de taquigrafía y mecanografía con el infalible método “ASÑL”, porque si tú controlas el “ASÑL” dominarás el mundo. Gracias a estos cursos entró de secretaria en el diario “Sur”, cuyo director fue quién la animó a presentarse al certamen de Miss Costa del Sol, aprovechando que el certamen se celebraba en Vélez-Málaga y que el periódico era el patrocinador pero no llegaba para contratar a Gunilla Von Bismark. Amparó se presentó pero porque el premio era un viaje a Lanzarote, que ella guapa ya sabía que era. Amparo ganó el título, era 1973 y tenía 19 años y muchas ganas de irse a Lanzarote, PERO la organización le dijo que si no se presentaba al certamen de Miss España no le pagaban el hotel en la isla, que eso estaba escrito en ningún contrato que nunca firmó. Aquí ya empezaron a darle las pistas del Cluedo pero ella seguía empecinada con lo de la secretaria en la piscina del hotel con la porra. Ese mismo año 1973 fue elegida Miss España y trabajó como actriz en un film mejicano, que era el sueño de Amparo desde que de chica hizo rabona para ir a ver “Un hombre llamado caballo”. La vida le daba a Amparo más pistas que al Air Force One, pero se ve que la muchacha estaba mirando pa otro lao. Desafortunadamente para ella tuvo que interrumpir su sueño de ser actriz para cumplir el contrato de Miss España y viajar a Filipinas para representarnos en el certamen de Miss Universo. Amparo Muñoz lo pasó más malamente que Dabiz Muñoz comiéndose la hamburguesa de Dabiz Muñoz en el Burger King y aún así se hizo con el título el 21 de julio de 1974. Amparo tenía 20 años. En Nueva York la organización le dijo que su vida era poco vendible y que se iban a inventar una biografía a lo que Amparo les avisó que no se inventaran ná, que no iba a hacer falta. Durante los primeros meses sufrió varios desmayos en los que debía guardar reposo, pero la organización le dijo que el reposo también era poco vendible y la obligaban a cumplir con su contrato hasta que no le dieron un día de asuntos propios y por ahí ya no pasó. Amparo se convirtió en la 1ª y única Miss Universo en renunciar a la corona; L​o hizo a los 6 meses de reinado, harta de ser tratada como una Chabel y deseando apuntarse a un curso de hacer amigurumis de crochet de CCC. Aunque el comienzo de su carrera cinematográfica coincidió con el destape, la actriz consiguió consagrarse y ser nominada y premiada en importantes festivales de cine como los Oscar, el Festival de Cine de Bruselas o Cannes. En esta época Amparo Muñoz era más bonita que un paseo por Cádiz sin turistas y tenía un pelazo que la miraba mal hasta el Puma. En 1976 conoció a Patxi Andión en el rodaje de una película y se casaron, pero por lo visto Patxi era más malo que una canción de Bad Bunny y Amparo salió corriendo al año y medio. Después de separarse en 1978 se echa de novio a Elías Querejeta, que muy bien con él, se llevaron varios años viviendo juntos, pero la relación se resintió un poco cuando Amparo le pidió que se divorciara ya de la mujé y él le dijo que sí, que de esa semana no pasaba. Cuando rompió con Querejeta,​ ​nuestra protagonista, que escogía mejó una sandía que un novi​o​​​, se juntó en 1980 con un anticuario chileno que vendía los muebles llenitos de polvo y que le enseñó a Amparo cómo aspirarlos. En 1987 sería la primera vez que cogieran a Amparo en una redada policial que no llegó a afectar gravemente a su carrera. Pero en 1989, cuando la detuvieron de nuevo comprando heroína, ya no quiso saber de ella ni el del refino al que le debía 1400 ptas. En 1990, Rosa Villacastín que no se mete en la vida de nadie, publicó que la actriz tenía Sida en fase terminal. La misma Amparo, pero con la cara de otra, fue al programa de Julián Lago, “La máquina de la verdad” para desmentir el rumor, pero Julián Lago, que tampoco se mete en la vida de nadie, la acusó de buscar clientes en los anuncios del final del ABC. Pero la gran Amparo no se rindió, fue a la Iglesia de San Antonio Abad y le pidió a San Judas Tadeo una ayudita, pero se ve que el santo estaba ocupao con los preparativos de la Expo porque en 1991, poco después de casarse por tercera vez, Amparo sufrió una pancreatitis aguda que le costó 1 millón de ptas. Tuvo que vendé hasta el Gordini. Una vez recuperaita, se volvió a divorciar y se volvió a levantar. En 1996 estrenó bajo las órdenes de Fernando León de Aranoa “Familia”, un film estresante sobre qué regalarle por navidad a un padre. La gran crítica internacional que obtuvo supuso su resurrección artística. Volvió a las pantallas y su vida pareció darle un respiro hasta que en 2003 le diagnosticaron un tumor cerebral que le quitaron con microcirugía, con lo que se hace la gente ahora los labios gordos. En sus memorias escribió que tuvo una vida muy triste pero romances con hombres muy guapos, como Máximo Valverde, Antonio Flores, José Coronado y un político de la Transición al que no identificó, pero que yo me la imagino cantando “Happy Birthday, Mister Su-á-re-ez”. Después de publicarlas en 2005 se retiró a Málaga a comer espetos. Desgraciadamente, el 27 de febrero de 2011, Amparo nos dejaba a los 56 años de edad pero ustedes siempre podrán recordarla cada vez que jueguen al Cluedo o le pidan ayuda a San Judas Tadeo.

Paraneoplastic neurologic syndromes can present with manifestations at any level of the neuraxis. In patients with high clinical suspicion of a paraneoplastic neurologic syndrome, cancer screening and treatment should be undertaken, regardless of the presence of a neural antibody. In this episode, Katie Grouse, MD, FAAN, speaks with Anastasia Zekeridou, MD, PhD, author of the article “Paraneoplastic Neurologic Disorders,” in the Continuum August 2024 Autoimmune Neurology issue. Dr. Grouse is a Continuum® Audio interviewer and a clinical assistant professor at the University of California San Francisco in San Francisco, California. Dr. Zekeridou a senior associate consultant in the departments of neurology, laboratory medicine, and pathology, and for the Center for Multiple Sclerosis and Autoimmune Neurology at Mayo Clinic in Rochester, Minnesota. Additional Resources Read the article: Paraneoplastic Neurologic Disorders Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Guest: @ANASTASIA_ZEK Transcript Full transcript available here   Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME.   Dr Grouse: This is Dr Katie Grouse. Today, I'm interviewing Dr Anastasia Zekeridou about her article on classical paraneoplastic neurologic disorders, which is part of the August 2024 Continuum issue on autoimmune neurology. Welcome to the podcast, and please introduce yourself to our audience.   Dr Zekeridou: Hi. Thank you, Dr Grouse. I'm always excited to talk about paraneoplastic neurological diseases. So, I'm an autoimmune neurologist at Mayo Clinic in Rochester, and I spend my time between the lab and seeing patients in the autoimmune neurology clinic.   Dr Grouse: Thank you so much for joining us, and we're really excited to talk about this really important topic. So, to start, I'd like to ask what, in your opinion, is the key message from this article.   Dr Zekeridou: That's a good question - there are a lot of messages, but maybe if I can distill it down. For me, one of the first things is that paraneoplastic neurological diseases can actually affect any level of the neuraxis. It can manifest with different types of presentations. If we do suspect a paraneoplastic neurological syndrome, then we need to look for the cancer, and then if we're not certain, even do an immunotherapy trial. A negative antibody does not make for an absence of a paraneoplastic neurological disease (because, often, we depend a lot on them), but you can see patients with paraneoplastic disease that do not have neural antibodies. And then, we always need to be thinking that if we have a paraneoplastic neurological disease, we actually need to be thinking of both the cancer and the immune response together - so, we need to be treating the cancer, we need to be treating the immune response – because, essentially, paraneoplastic neurological syndrome is evidence of this antitumor immune response. So, the main (if I can distill this down in one) is probably that we need to be discussing all of these patients with the treating oncologist, because they have complicated care.   Dr Grouse: Great. Thank you so much for that summary. It's very helpful. While many of our listeners are likely familiar with paraneoplastic disorders in their workup (which you've mentioned just now), the concept of neurologic autoimmunity in the context of immune checkpoint inhibitor therapy has more recently become widely recognized. Can you summarize this briefly for our listeners who may be less familiar with this?   Dr Zekeridou: I think that we learn more and more about this and we see more and more patients with immune checkpoint inhibitor-related neurological immunity, so, I always think about it in a very straightforward way. So, I think the way we think about immune responses is a balance between tolerance and regulation and immune activations. And then, immune checkpoints are the molecules that help us maintain self-tolerance. So, our immune system - it's probably the best tool that we have to fight against cancer. So, essentially, when we inhibit the immune checkpoints, we actually use our own immune system to fight cancer, but taking the breaks of the immune system essentially can lead to a lot of complications that are immune-mediated. Some of them are neurological - the neurological complications are rare, especially the ones that we need to do something about (so, it's 1% to 4%, in some cases up to 14%), and they do increase when you use multiple immune checkpoint inhibitors together. The main thing for me with the neurological complications is that, sometimes, they are difficult to recognize, they can (again) affect every level of the neuraxis - like, it can be the neuromuscular or the central nervous system (even though neuromuscular complications are much more common than central nervous system complications) - and then a lot of them (the vast majority) will happen within the first three months, but they can also happen even after you stop the immune checkpoint inhibitor. But this three-month interval, it's sometimes useful when you're in a diagnostic silence - it kind of helps you make the decision more towards an immune-related adverse event affecting the nervous system. And then, I think that, practically, once we have diagnosed this patients, we still are not very certain how to treat. All of them will get steroids upfront, but some of them will be difficult to treat, so then, we have to decide on the next treatment depending on evolution. And then, I will just say that (I mentioned it previously, but) these are the patients that the coordination with other subspecialties is one of the main things that we need to do (eg, oncologists) - they often have immune-related adverse events from other systems, so, there is a lot of coordination of care. And, always, the question at the end comes up, Should we be putting these patients back to their immune checkpoint inhibitor cancer immunotherapy that might help them with the cancer? And I think that this is difficult sometimes, and it needs to be decided - most cases - in a case-by-case basis, even though there are some recommendations that I've been discussing in the Continuum article.   Dr Grose: That's great, and I encourage everyone to read more about this, because it is a very complex and fascinating topic. On the note of the immune checkpoint inhibitor neurologic dysfunction - I would imagine these are pretty rare - how common are these? And I would suspect they're getting missed a lot - is that correct?   Dr Zekeridou: I think it's a very good question. Essentially, what we say for the neurological immune-related adverse events (the ones that we need intervention) - so, they are at least of grade two. (I think that there are less than 4%, mostly, probably close to 1.5%.) There was a study where they used double immune checkpoint inhibitors (so CTLA-4 and PD-1, PD-L1) - they were up to 14%, but this was any grade (so, a little bit of tingling, a little bit of headache), while the ones that we actually need to act upon and we need to actually do something about, they are probably closer to 1.5%. So, are they being missed? I am certain that some of them never make it to the neurologist. So, the ones that we know that we are underestimating is definitely the meningitis - because I think it's more common – but, often, when the patients present, they have something else as well. So, the oncologists will put them on steroids and then they will get better - so, we don't really see them in the neurology clinic (the ones with the very mild side effects). And then, also, these patients are often very sick, and they have a lot of things going for them, so they sometimes do not make it to the diagnosis.   Dr Grouse: So then, I want to just take a step back and ask you, what's the most challenging aspect of paraneoplastic neurologic disorders in your opinion?   Dr Zekeridou: I think, for me, one of the main things, the classic paraneoplastic disorders - and when I say “classic paraneoplastic disorders”, they are the ones that we think more of with antibodies that are mostly biomarkers of the immune response, and they suggest a cytotoxic T-cell mediated disorder (so, like PCA1 [or anti-Yo] or ANNA-1 [or anti-Hu]) - these patients are very sick often, and we don't have a lot of good treatments for them. And then, even if we treat them, we actually sometimes do not manage to reverse their course - the best that we can do is stabilize. So, I think that this is part of the discussion that we have upfront with these patients - but it is quite challenging, because most of them, we will be giving them a cancer diagnosis ourselves, because we recognize the paraneoplastic neurological syndrome, and we look for the cancer, and then we'll be giving them a cancer diagnosis. And even if we treat their cancer and we treat the immune system, sometimes, then, we don't make a real improvement – like, we stabilize their disease and we sometimes get improvement, but there are cases that we do not and they continue to progress – so, that has been the most challenging aspect of this, and I think that's kind of where we really need more things coming – like, we need more treatments, we need to better understand these diseases and get more straightforward.   Dr Grouse: I agree. I think that's absolutely, uh, what we all hope for these types of disorders, and I can imagine we all can remember at least one case just like this where someone had this type of problem and just didn't respond to treatment. So, strong hopes that there will be improvement with this in the years coming. Another question I have for you is, what in your article do you think would come as the biggest surprise to our listeners?   Dr Zekeridou: I think that, because we discussed that immune checkpoint inhibitors (maybe we don't know as well), so one of the main things for me is when we first started thinking of neurological complications of immune checkpoint inhibitors, there was a lot of myasthenia gravis mentioned (patients presenting with myasthenia gravis), and then some of them antibody-positive, some of them antibody-negative. Now, with the time that has passed by, we recognize that myasthenia gravis is very rare. Like, I've seen tons of patients (probably more than that, actually) – and then, maybe I've seen one patient with de novo myasthenia gravis. We realize that the immune checkpoint inhibitor myasthenia gravis that we were thinking of are – they're mostly the immune checkpoint inhibitor myocytes cases - so, then, this is one of these myopathies that looks like no other. So, it really has a very predominant oculobulbar involvement (that's why everybody was thinking that this is myasthenia gravis), but, practically, the EMGs are negative, the patients do not respond to pyridostigmine - so, practically, these are really myopathy cases. And why is that important? Because 30% to 40% of these cases might also have a cardiomyopathy, for example, and then we're putting all these patients on pyridostigmine and medications that they do not necessarily need. So, I think one of the chains in concepts that we have in the later years is that, really (and this is one of the most common immune-related adverse events that we see in our clinic), that these patients with ICI myositis really present with the oculobulbar involvement and proximal involvement that we can see in myasthenia, but they do not have a neuromuscular junction problem.   Dr Grouse: Now, we've all struggled with identifying a primary malignancy in patients where a paraneoplastic syndrome was strongly suspected. Do you have any tips on how to make this workup as high yield as possible?   Dr Zekeridou: Yeah, I think that's a difficult question. I think it depends a little bit on your patient as well. So, if you have an antibody that makes things easier (and we can discuss about that, but), practically, for me, a patient that I have a high suspicion, that we get a CT chest, abdomen, and pelvis upfront - and often, we don't get PET scans, right, directly, because we have insurance companies maybe playing a role in what we would do. So, I would get this for a woman - she has to have a mammogram. For a man, they have to have a testicular ultrasound. That's the basics for me. And then, when we see more younger women or when we suspect an MDA, then they will need to have the ultrasound to look for the ovarian teratomas or an MRI of the abdomen - so, the PET scan for me, if I have a high suspicion, it will always be the next step. Like, we have increased diagnostic yield with PET scans, but we also need to remember, what are the tumors that you will not find on a PET scan? Teratomas are not PET-avid, and, often we say, “Oh, we found the lesion in the ovary and the PET scan was negative.” That doesn't matter. In an NMDA-receptor antibody patient, if you find the lesion in the ovary, you need to make certain it's not a teratoma, because PET scans will not necessarily pick up a teratoma - it's not an avid malignancy. So, if the patient is a smoker and I suspect small-cell lung cancer, so I would always get the PET scan. If I have a patient with a high-risk antibody like PCA1 (or anti-Yo) and I didn't really find the tumor with the CT chest, abdomen, and pelvis and the mammogram, I will always get the PET scan. Same for the patients with the smoking history. I will also say that, sometimes, we forget other malignancies. So, for example, we have neuronal intermediate filament antibodies (so, ANNA-3 antibodies), and some of them will have Merkel cell. So, depending on the patient, on the antibody, and if we didn't find anything else, I would do a skin check. If they have GI symptoms, I would look for the GI tumor as well. So, even though the basics are what I mentioned, I will adapt depending on the patient symptoms. And all of these patients should have age-appropriate cancer screening, so if they didn't have a colonoscopy, they will have to have a colonoscopy. So, this is part of the main things. And then, the question for me that always comes up is, “Who is the person that you're going to keep on repeating the screen?” And then, practically, if you have a low-risk paraneoplastic antibody that comes (let's say LGI1), we know it's a low risk, so I would actually do the cancer screening - I will look for the thymoma once, and then that would be it. But if you have a patient with a high-risk paraneoplastic antibody (let's say ANNA-1 [or anti-Hu] or anti-Yo [anti-PCA1]), these are the patients that I will keep on screening - and then I will do every four to six months for two years (that's the current recommendation), but I will probably continue yearly after. And then, we need to also remember that whenever you have a neurological relapse, that's exactly when you need to be looking for the cancer as well - so, you must be thinking that the idea is that maybe you have the immunological relapse because there is cancer somewhere. So, these are the types of things that I kind of adapt to specific patients. But I think when we're not certain, broad screening is what we need. And then, again, the PET scan - for me, it's a great test, but we need to know its limitations. So, that's the other thing that comes up a lot in the phone calls or in the patients that I see that we do a PET scan - but practically, it's not good for some of the malignancies that we're looking for.   Dr Grouse: That's really great to point out, and I'm glad you brought up the risk level of the particular syndrome. You have a great table in your article that summarizes the risk level of some of the various syndromes - so, you know, just a reminder for everyone to check that out if you want to have more information about this and how this applies to the screening - so very helpful. What is the easiest mistake to make, and also maybe to avoid, when treating patients with paraneoplastic neurologic disorders?   Dr Zekeridou: That's a great question, actually. So, there are two things here. One is that we need to be thinking about paraneoplastic neurological syndromes, because if you don't think about them, then you don't look for them. So that's the one thing. So, patients that come with a subacute onset of neurological dysfunction - they have systemic features, or they are smokers, they have autoimmunity in the family (all those things) – like, we need to be thinking about paraneoplastic neurological syndromes. On the other side, we also see a little bit more of overdiagnosis that's coming in the later years. So, one of the things that we see a lot is that we kind of have difficulties with the interpretation of the neural antibodies - so, sometimes, we will get a neural antibody, and then it will not fit, but we will base our diagnosis on the neural antibody presence. And then, some neural antibodies are great - we don't really see false-positives - but some of them are not great and we do see false-positives. So, for me, the main thing that I would say is that we need to have a clinical suspicion - we're treating the patient and the clinical syndrome if it is compatible with a paraneoplastic neurological disorder, and then the neural antibodies are the ones that are going to help us, like, diagnose or point to a cancer - but we are really treating the patient. And then, if we give a treatment and it doesn't make sense how the patient evolves, we actually need to reassess the diagnosis, because we do have both overdiagnosis, but also we have underdiagnosed in patients that it's not suspected - so I think it's kind of the increased awareness that helps, but we also need to be going back always to the clinical manifestations of the patient.   Dr Grouse: Really great points to make, and thank you so much for that. What is the most common misconception you've encountered in treating patients with paraneoplastic disorders?   Dr Zekeridou: So, one of the things that we see a lot is that patients wait to be treated - even with high suspicion of paraneoplastic neurological syndromes - until we have the neural antibodies, and sometimes, if the neural antibodies are negative, we have patients that are not given a paraneoplastic neurological syndrome or autoimmune neurological syndrome diagnosis because of the negativity of the antibodies. So, for me, one of the main things is that the patients actually fit clinically with a paraneoplastic neurological syndrome - and there are scores that can help us, clinical manifestations that can actually help us make this diagnosis. We need to be looking for the cancer and treating them, regardless of the presence of the antibody. Some patients will not have the antibodies for weeks. The second aspect to this is that, often, we want to say, “Oh, it's a paraneoplastic neurological syndrome. They will treat the cancer and, like, that's the oncologist's job.” But, practically, I think that the neurologist will really need to be involved with this. I think the patients need treatment of the immune response and treatment of the tumor. So, I think we are part of the treatment team for these patients and it's not only the oncologists that are treating the tumor.   Dr Grouse: Where do you think the next big breakthrough in this area will be?   Dr Zekeridou: Where I hope it would be - and I'm hoping that it's actually what it is going to be – is, really, better understanding and treating the classic paraneoplastic neurological diseases, that they are T-cell mediated disorders that lead to neural cell distraction, and we don't have good treatments for these patients and we cannot get any improvement. So, there is a lot of research going on there. How can we prevent? How can we treat? But, I think that would be the next big milestone for us, because the antibody-mediated diseases - so we now have a lot of good treatments. Like NMDA-receptor encephalitis, AMPAR encephalitides - these antibody-mediated disorders, we have good treatments. The disorders that the antibodies are biomarkers  - and they are the cytotoxic diseases, the effectors of the autoimmunity - we don't. So, that's where I hope and think our breakthrough will be.   Dr Grouse: Definitely hoping to see more advancements in this area and already, I think, very quickly developing field. So, I wanted to talk a little bit more about you and what brought you to this area of neurology I think which most of us find to be a very fascinating field  that would love to hear more about what brought you to it. How did you become interested in this area of neurology?   Dr Zekeridou: I did my medical school in Greece. So, in Greece, towards the end of the sixth year, you need to decide what your specialty would be, and for the life of me, I could not decide between oncology and neurology - I was changing my mind all the time. And then, I decided that the diagnosis is more important to me in terms of a physician - that's why I went more with neurology and I was clear on my choice. So, practically, then, I went and did my residence in Switzerland, and something happened and I found myself in the outpatient autoimmune neurology multiple sclerosis clinic for a year, and it was evident to me that this is my passion. Like, the multiple sclerosis, I thought was a great disease, but it was the cases that they were not multiple sclerosis, that they were the ones that they were the most fascinating for me. So, then, I did my peripheral nerve year - so even more, it was clear for me that this is the immune system interactions, the cancer, and the neurological symptoms - that's what I wanted to do. And practically, I pursued a fellowship in Lyon in the French Reference Center for Paraneoplastic Diseases, and I was sold. There was nothing else for me. So, eventually I came here at Mayo (and then I stayed) - but it was very clear, even since the beginning - and I really found something that combined both of my passions even from medical school.   Dr Grouse: What are you most excited about in this field? And, specifically, you know, what might you impart to other trainees who are thinking about choosing this field for themselves?   Dr Zekeridou: So, I think that there are many things. So, autoimmune neurology or paraneoplastic neurological syndromes, they can affect every level of the neuraxis, so, practically, your clinician, that we see everything - we'll see central nervous system, peripheral nervous system, neuromuscular junction – so, that's actually very fascinating for me. The second part of it is that we have diseases that we can actually treat. We see differences in patients that we will intervene and we will really change their disease course. And the other thing for me is all the research that is ongoing. So, practically, the research in paraneoplastic syndromes or neurological immunity is directly translational to the patient - like, we have kind of a bed-to-bedside type of research that is going on. And basic research is important and there is a lot of advances, but you can see them directly, like, being translated in patients - so, essentially, the research is directly translational to clinic, and that makes it very exciting.   Dr Grouse: I think that your excitement about this field is very inspirational and will hopefully inspire many future trainees who are interested in this field. So, when you're not learning more about paraneoplastic syndromes and their treatment and diagnosis, what else do you like to do? Tell us something about your outside interests.   Dr Zekeridou: So, again, I come from a very diverse background and the way that I arrived in the states, but, I really like traveling. So, we would travel a lot lately. We travel more in Greece, because when you're coming from Greece and you're not living there, your summers are always there - but we try to explore different places there. And one of my main things and passions that I like is, essentially, cooking. So that relaxes me, that helps me - cooking and having friends over – so, that's my favorite thing of doing outside of work.   Dr Grouse: Well, I have to say it's hard right now to imagine anything more fun than traveling and enjoying good food and Greece. So, I think your hobby seems like one we can all get behind.   Dr Zekeridou: It's relaxing the mind.   Dr Grouse: Yes, yes. This has been a really great discussion on what I think is a very interesting area of neurology, and we really appreciate you taking the time to talk with us today.   Dr Zekeridou: Thank you so much for having me. It was great talking to you.   Dr Grouse: Again, today, I've been interviewing Dr Anastasia Zekeridou, whose article on classical paraneoplastic neurologic disorders appears in our most recent issue of Continuum on autoimmune neurology. Be sure to check out Continuum Audio episodes from this and other issues. And thank you to our listeners so much for joining us today.   Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at Continpub.com/audioCME. Thank you for listening to Continuum Audio. Full transcript available at URL to come

2016 ha sido el año en el que ha vuelto la serie de culto EXPEDIENTE X (The X Files), sin duda uno de los pilares más importantes en los que se ha apoyado la reciente edad de oro de la televisión. Amparándose en una premisa sencillamente irresistible, dos agentes del FBI totalmente contrapuestos en todos los sentidos, pero a la par perfectamente complementarios, Fox Mulder y Dana Scully investigan los casos más insólitos durante diez temporadas y dos películas, más un sinfín de productos derivados que avalan un fenómeno digno de estudio desde cualquier punto de vista. Junto a Rafa Pajis, Antonio Runa y el experto en conspiraciones Santiago Camacho, recién llegado de Cuarto Milenio, disponte a escuchar la primera parte de un ciclo de monográficos tan profundos como cabe esperar de La Órbita de Endor. Si necesitas creer, la verdad está aquí dentro. Escucha el episodio completo en la app de iVoox, o descubre todo el catálogo de iVoox Originals

Gátova (Valencia) ya tiene panadero para su histórico horno de 300 años; ¿Hasta qué punto son buenos los diálogos internos?En la última hora de 'La Tarde' hablamos sobre:Javi Nieves: Gátova (Valencia) ya tiene panadero para su histórico horno de 300 años. Tras la jubilación de Amparín, su dueña, cerró y el Ayuntamiento hizo un llamamiento por redes sociales. Entre todos los candidatos, el elegido ha sido Iván, un panadero de Madrid. Hablar con uno mismo. ¿Hasta qué punto son buenos los diálogos internos? Nos lo explica Diana Sánchez, psicóloga y miembro del Colegio Oficial de la Psicología de Madrid.Escucha ahora 'La Tarde', de 18 a 19 horas. 'La Tarde' es un programa presentado por Pilar Cisneros y Fernando de Haro que se emite en COPE, de lunes a viernes, de 16 a 19 horas con 470.000 oyentes diarios según el último EGM. A lo largo de sus tres horas de duración, "La Tarde" ofrece otra visión, más humana y reposada, de la actualidad, en busca de historias cercanas, de la cara real de las noticias; periodismo de carne y hueso.En "La Tarde" también hay hueco para los testimonios, los sucesos y los detalles más relevantes y a veces invisibles de todo lo que nos rodea. Esta temporada, Pilar y Fernando seguirán cautivando a la ‘gente gente' acompañados de los...

La FGR impugnará el amparo que se le concedió a Mario Aburto Martíne La Vía José López Portillo que se inundó Embajada de Israel fue objeta de vandalismo por manifestantesMás información en nuestro podcast

Un clásico del terror, un pilar fundamental del vampirismo moderno en la narrativa. Drácula de Bram Stoker nos lleva de la mano a través de un estilo epistolar al fondo de la barrica donde se retuercen pesadillas y anhelos muy humanos. En esta primera parte arrancamos directamente por El último viaje del Deméter, película que, si no se ha estrenado ya, se estrenará en breve. Sobre la tía Amparín mejor no preguntéis. Para estar al tanto de futuras actualizaciones, estas son las redes sociales a las que debes acudir: https://linktr.ee/Vuelodelcometa Y si quieres apoyar este y otros proyectos relacionados: https://www.patreon.com/vuelodelcometa o a través del sistema de mecenazgo en iVoox. El bloque de intro y outro del programa fueron realizados por Luis Alberto Martín, locutor, actor de doblaje y voz y periodista: @lamartinvoz Escucha el episodio completo en la app de iVoox, o descubre todo el catálogo de iVoox Originals

Esta mañana, el presidente López Obrador, aseguró que Ovidio Guzmán no se amparó contra su extradición a Estados Unidos, con quien señaló, se tiene un convenio para extraditar a presuntos delincuentes y dijo que es importante que no se dé motivo a quienes utilizan el tema del narcotráfico con propósitos politiqueros en Estados Unidos. Se prevé que después de mediodía Ovidio Guzmán, alias "el ratón", comparezca en su primera audiencia en la corte del distrito norte de Illinois en Chicago, acusado de cinco cargos entre ellos conspiración para distribuir droga en Estados Unidos, lavado de dinero y portación de arma. Además, el presidente López Obrador reveló que la fiscalía general de la república ya tiene todas grabaciones del cártel de los guerreros unidos, relacionados con la desaparición de los 43 normalistas de Ayotzinapa, y adelantó que esta semana se reunirá con los familiares de los normalistas. La saxofonista María Elena Ríos denunció, por redes sociales, que sufrió un atentado el pasado viernes… detalló que el vehículo donde viajaba de la Ciudad de México a Oaxaca fue perseguido y agredido con detonaciones de arma de fuego cuando se encontraba cerca de llegar a Oaxaca… de acuerdo con María Elena Ríos, ella iba acompañada por la seguridad del mecanismo de protección federal para personas defensoras de los derechos humanos.     El servicio de administración tributaria, el SAT, reportó que, en el primer semestre del año, se inscribieron un millón 463 mil 858 personas físicas y morales al padrón del registro federal de contribuyentes… el brazo fiscalizador de la secretaría de hacienda detalló que, del total de nuevos contribuyentes, un millón 403 mil 583 son personas físicas, lo que representó un incremento de 135%, en comparación al mismo periodo de del año pasado. Para MVS Noticias, Jiro Montes de Oca.See omnystudio.com/listener for privacy information.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.03.547465v1?rss=1 Authors: Sheheitli, H., Jirsa, V. Abstract: We derive a next generation neural mass model of a population of quadratic-integrate-and-fire neurons, with slow adaptation, and conductance-based AMPAR, GABAR and nonlinear NMDAR synapses. We show that the Lorentzian ansatz assumption can be satisfied by introducing a piece-wise polynomial approximation of the nonlinear voltage-dependent magnesium block of NMDAR current. We study the dynamics of the resulting system for two example cases of excitatory cortical neurons and inhibitory striatal neurons. Bifurcation diagrams are presented comparing the different dynamical regimes as compared to the case of linear NMDAR currents, along with sample comparison simulation time series demonstrating different possible oscillatory solutions. The omission of the nonlinearity of NMDAR currents results in a shift in the range (and possible disappearance) of the constant high firing rate regime, along with a modulation in the amplitude and frequency power spectrum of oscillations. Moreover, nonlinear NMDAR action is seen to be state-dependent and can have opposite effects depending on the type of neurons involved and the level of input firing rate received. The presented model can serve as a computationally efficient building block in whole brain network models for investigating the differential modulation of different types of synapses under neuromodulatory influence or receptor specific malfunction. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Una de las más famosas familias de la farándula mexicana, es noticia nuevamente por la boda de uno de sus miembros y se reabre la polémica por la misteriosa y temprana muerte de Amparín Serrano.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.28.534509v1?rss=1 Authors: El-Oussini, H., Zhang, C.-L., Francois, U., Castelli, C., Lampin Saint-Amaux, A., Lepleux, M., Molle, P., Velez, L., Dejean, C., Lanore, F., Herry, C., Choquet, D., Humeau, Y. Abstract: Consolidation of recent memory depends on hippocampal activities during resting periods that immediately follows the memory encoding. There, Slow Save Sleep phases appear as privileged periods for memory consolidation as hosting the ripple activities, which are fast oscillations generated within the hippocampus whose inactivation leads to memory impairment. If a strong correlation exists between these replays of recent experience and the persistence of behavioural adaptations, the mobilisation, the localization and the importance of synaptic plasticity events in this process is largely unknown. To question this issue, we used cell-surface AMPAR immobilisation to block post-synaptic LTP within the hippocampal region at various steps of the memory process. 1- Our results show that hippocampal synaptic plasticity is engaged during the consolidation but is dispensable during the encoding or recall of a working memory based spatial memory task. 2- Blockade of plasticity during sleep leads to apparent forgetting of the encoded rule. 3- In vivo recordings of ripple activities during resting periods show a strong impact of AMPAR immobilization solely, prominent when a rule has been recently encoded. 4- In situ examination of the interplay between AMPAR mobility, hippocampal plasticity and spontaneous ripple activities pointed that post-synaptic plasticity at CA3-CA3 recurrent synapses support ripple generation. As crucial results were reproduced using another AMPARM blockade strategy, we propose that after rule encoding, post-synaptic AMPAR mobility at CA3 recurrent synapses support the generation of ripples necessary for rule consolidation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

The Poet's Cove welcomes Aldo Amparán, author of the poetry collection Brothers Sleep (Alice James Books, 2022), winner of the Alice James Award. Host Daniel Chacón and Aldo's discuss everything from the writing process to imposter syndrome. Aldo also reads a poem from Brothers Sleep, “Thanatophobia, or Sleep Addresses His Brother.” Aldo Amparán is a poet, writer, & translator born and raised in the border cities of El Paso, TX, USA, & Ciudad Juárez, CH, MX. They are the recipient of fellowships from the National Endowment for the Arts & CantoMundo. Their work has been widely published in anthologies and literary journals including AGNI, Best New Poets, Gulf Coast, Kenyon Review Online, Ploughshares, Poetry Magazine, & elsewhere. They hold an MFA in Creative Writing from the University of Texas at El Paso.

El tema sobre la mesa 17 de febrero 2023

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.07.527516v1?rss=1 Authors: Certain, N., Gan, Q., Bennett, J., Hsieh, H., Wollmuth, L. Abstract: AMPA receptor (AMPAR) auxiliary subunits are specialized, non-transient binding partners of AMPARs that modulate their ion channel gating properties and pharmacology, as well as their biogenesis and trafficking. The most well characterized families of auxiliary subunits are transmembrane AMPAR regulatory proteins (TARPs) and cornichon homologs (CNIHs) and the more recently discovered GSG1-L. These auxiliary subunits can promote or reduce surface expression of AMPARs in neurons, thereby impacting their functional role in membrane signaling. Here, we show that CNIH-2 enhances the tetramerization of wild type and mutant AMPARs, possibly by increasing the overall stability of the tetrameric complex, an effect that is mainly mediated by interactions with the transmembrane domain of the receptor. We also find CNIH-2 and CNIH-3 show receptor subunit-specific actions in this regard with CNIH-2 enhancing both GluA1 and GluA2 tetramerization whereas CNIH-3 only weakly enhances GluA1 tetramerization. These results are consistent with the proposed role of CNIHs as endoplasmic reticulum cargo transporters for AMPARs. In contrast, TARP {gamma}-2, TARP {gamma}-8, and GSG1-L have no or negligible effect on AMPAR tetramerization. On the other hand, TARP {gamma}-2 can enhance receptor tetramerization but only when directly fused with the receptor at a maximal stoichiometry. Notably, surface expression of functional AMPARs was enhanced by CNIH-2 to a greater extent than TARP {gamma}-2 suggesting that this distinction aids in maturation and membrane expression. These experiments define a functional distinction between CNIHs and other auxiliary subunits in the regulation of AMPAR biogenesis. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.27.525952v1?rss=1 Authors: Gupta, R., O'Donnell, C. Abstract: Dendritic spines host glutamatergic excitatory synapses and compartmentalize biochemical signalling underlying synaptic plasticity. The narrow spine neck that connects the spine head with its parent dendrite is the crucial structural element of this compartmentalization. Both neck morphology and its molecular composition differentially regulate exchange of molecular signals between the spine and rest of the neuron. Although these spine neck properties themselves show activity-dependent plasticity, it remains unclear what functional role spine neck plasticity plays in synaptic plasticity expression. To address this, we built a data-constrained biophysical computational model of AMPA receptor (AMPAR) trafficking and intracellular signalling involving Ca2+calmodulin-dependent kinase II (CaMKII) and the phosphatase calcineurin in hippocampal CA1 neurons, which provides new mechanistic insights into spatiotemporal AMPAR dynamics during long-term potentiation (LTP). Using the model, we tested how plasticity of neck morphology and of neck septin7 barrier, which specifically restricts membrane protein diffusion, affect LTP. We found that spine neck properties control LTP by regulating the balance between AMPAR and calcineurin escape from the spine. Neck plasticity that increases spine-dendrite coupling reduces LTP by allowing more AMPA receptors to diffuse away from the synapse. Surprisingly, neck plasticity that decreases spine-dendrite coupling can also reduce LTP by trapping calcineurin, which dephosphorylates AMPARs. Further simulations showed that the precise timescale of neck plasticity, relative to AMPAR and enzyme diffusion and phosphorylation dynamics, critically regulates LTP. These results suggest a new mechanistic and experimentally-testable theory for how spine neck plasticity regulates synaptic plasticity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.25.525148v1?rss=1 Authors: Warming, H., Deinhardt, K., Garland, P., More, J., Bulters, D., Galea, I., Vargas-Caballero, M. Abstract: During subarachnoid haemorrhage, a blood clot forms in the subarachnoid space releasing extracellular haemoglobin (Hb), which causes oxidative damage and cell death in surrounding tissues. High rates of disability and cognitive decline in SAH survivors is attributed to loss of neurons and functional connections during secondary brain injury. Haptoglobin sequesters Hb for clearance, but this scavenging system is overwhelmed after a haemorrhage. Whilst exogenous haptoglobin application can attenuate cytotoxicity of Hb in vitro and in vivo, the functional effects of sub-lethal Hb concentrations on surviving neurons and whether cellular function can be protected with haptoglobin treatment remain unclear. Here we use cultured neurons to investigate neuronal health and function across a range of Hb concentrations to establish the thresholds for cellular damage and investigate synaptic function. Hb impairs ATP concentrations and cytoskeletal structure. At clinically relevant but sublethal Hb concentrations, synaptic AMPAR-driven currents are reduced, accompanied by a reduction in GluA1 subunit expression. Haptoglobin co-application can prevent these deficits by scavenging free Hb to reduce it to sub-threshold concentrations and does not need to be present at stoichiometric amounts to achieve efficacy. Haptoglobin itself does not impair measures of neuronal health and function at any concentration tested. Our data highlight a role for Hb in modifying synaptic function after SAH, which may link to impaired cognition or plasticity, and support the development of haptoglobin as a therapy for subarachnoid haemorrhage. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.06.523038v1?rss=1 Authors: Zhou, Y., Qiu, L., Lyon, M., Chen, X. Abstract: Episodic memory is thought to be preferentially encoded by sparsely distributed memory-eligible "primed" neurons with high excitability in memory-related regions. Based on in vivo calcium imaging on freely behaving mice, we developed an analytical method to determine the neuronal activity hierarchy and establish hippocampal primed neurons. Neurons with high activity and memory-associated burst synchronization are identified as primed neurons. When a trace fear memory is being formed or retrieved, the major pattern of the calcium dynamics is predominantly mediated by primed neurons and highly correlated with mouse freezing behaviors. In cilia knockout mice that exhibit severe learning deficits, the percentage of their primed neurons is drastically reduced, and any burst synchronization is strongly suppressed. Consistently, the first principal pattern of cilia knockout neurons does not fully distinguish itself from other minor components or correlate with mouse freezing behaviors. To reveal how a portion of neurons get primed, we developed a numerical model of a neural network that incorporates simulations of linear and non-linear weighting synaptic components, modeling AMPAR- and NMDAR-mediated conductances respectively. Moderate NMDAR to AMPAR ratios can naturally lead to the emergence of primed neurons. In such cases, the neuronal firing averages show a right-skewed log-distribution, similar to the distributions of hippocampal c-Fos expression and the activity levels measured by in vivo calcium imaging. In addition, High basal neuronal activity levels speed up the development of activity hierarchy during iterative computation. Together, this study reveals a novel method to measure neuronal activity hierarchy. Our simulation suggests that the accumulation of biased synaptic transmission mediated by the non-linear weighting synaptic component represents an important mechanism for neuronal priming. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.06.523038v1?rss=1 Authors: Zhou, Y., Qiu, L., Lyon, M., Chen, X. Abstract: Episodic memory is thought to be preferentially encoded by sparsely distributed memory-eligible "primed" neurons with high excitability in memory-related regions. Based on in vivo calcium imaging on freely behaving mice, we developed an analytical method to determine the neuronal activity hierarchy and establish hippocampal primed neurons. Neurons with high activity and memory-associated burst synchronization are identified as primed neurons. When a trace fear memory is being formed or retrieved, the major pattern of the calcium dynamics is predominantly mediated by primed neurons and highly correlated with mouse freezing behaviors. In cilia knockout mice that exhibit severe learning deficits, the percentage of their primed neurons is drastically reduced, and any burst synchronization is strongly suppressed. Consistently, the first principal pattern of cilia knockout neurons does not fully distinguish itself from other minor components or correlate with mouse freezing behaviors. To reveal how a portion of neurons get primed, we developed a numerical model of a neural network that incorporates simulations of linear and non-linear weighting synaptic components, modeling AMPAR- and NMDAR-mediated conductances respectively. Moderate NMDAR to AMPAR ratios can naturally lead to the emergence of primed neurons. In such cases, the neuronal firing averages show a right-skewed log-distribution, similar to the distributions of hippocampal c-Fos expression and the activity levels measured by in vivo calcium imaging. In addition, High basal neuronal activity levels speed up the development of activity hierarchy during iterative computation. Together, this study reveals a novel method to measure neuronal activity hierarchy. Our simulation suggests that the accumulation of biased synaptic transmission mediated by the non-linear weighting synaptic component represents an important mechanism for neuronal priming. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.14.520457v1?rss=1 Authors: Hoffman, J. L., Faccidomo, S., Taylor, S. M., DeMiceli, K. G., May, A. M., Smith, E. N., Whindleton, C. M., Hodge, C. W. Abstract: Rationale: The development and progression of alcohol use disorder (AUD) is widely viewed as maladaptive neuroplasticity. The transmembrane alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) regulatory protein 8 (TARP {gamma}-8) is a molecular mechanism of neuroplasticity that has not been evaluated in AUD or other addictions. Objective: To address this gap in knowledge, we evaluated the mechanistic role of TARP {gamma}-8 bound AMPAR activity in the basolateral amygdala (BLA) and ventral CA3 hippocampus (vHPC) in the positive reinforcing effects of alcohol, which drive repetitive alcohol use throughout the course of AUD, in C57BL/6J mice. These brain regions were selected because they exhibit high levels of TARP {gamma}-8 expression and send glutamate projections to the nucleus accumbens (NAc), which is a key nucleus in the brain reward pathway. Methods and Results: Site-specific pharmacological inhibition of AMPARs bound to TARP {gamma}-8 in the BLA via bilateral infusion of the selective negative modulator JNJ-55511118 significantly decreased operant alcohol self-administration with no effect on sucrose self-administration in behavior-matched controls. Temporal analysis showed that reduction of alcohol-reinforced responding occurred greater than 25 min after the onset of responding, consistent with a blunting of the positive reinforcing effects of alcohol in the absence of nonspecific behavioral effects. In contrast, inhibition of TARP {gamma}-8 bound AMPARs in the vHPC selectively decreased sucrose self-administration with no effect on alcohol. Conclusions: This study reveals a novel brain region-specific role of TARP {gamma}-8 bound AMPARs as a molecular mechanism of the positive reinforcing effects of alcohol and non-drug rewards. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.05.519102v1?rss=1 Authors: Zaytseva, A., Bouckova, E., Wiles, M. J., Wustrau, M. H., Schmidt, I. G., Mendez-Vazquez, H., Khatri, L., Kim, S. Abstract: Ketamine is shown to enhance excitatory synaptic drive in the hippocampus, which is presumed to underlie its rapid antidepressant effects. Moreover, ketamines therapeutic actions are likely mediated by enhancing neuronal Ca2+ signaling. However, ketamine is a noncompetitive NMDA receptor (NMDAR) antagonist that inhibits excitatory synaptic transmission and postsynaptic Ca2+ signaling. Thus, it is a puzzling question how ketamine enhances glutamatergic and Ca2+ activity in neurons to induce rapid antidepressant effects while blocking NMDARs in the hippocampus. Here, we find that ketamine treatment for one hour in cultured mouse hippocampal neurons significantly reduces calcineurin activity to elevate AMPA receptor (AMPAR) subunit GluA1 phosphorylation. This phosphorylation ultimately induces the expression of Ca2+ - permeable, GluA2-lacking, and GluA1-containing AMPARs (CP-AMPARs). Such ketamine-induced expression of CP-AMPARs enhances glutamatergic activity and synaptic plasticity in cultured hippocampal neurons. When a sub-anesthetic dose of ketamine is given to mice, it increases synaptic GluA1 levels, but not GluA2, and GluA1 phosphorylation in the hippocampus within one hour after treatment. These changes are likely mediated by ketamine-induced reduction of calcineurin activity in the hippocampus. Using the open field and tail suspension tests, we demonstrate that a low dose of ketamine rapidly reduces anxiety-like and depression-like behaviors in both male and female mice. However, when in vivo treatment of a CP-AMPAR antagonist abolishes the ketamines effects on animals behavior. We thus discover that ketamine at the low dose promotes the expression of CP-AMPARs via reduction of calcineurin activity in the hippocampus, which in turn enhances synaptic strength to induce rapid antidepressant actions. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.31.514576v1?rss=1 Authors: Nair, J., Wilkinson, K., Mulle, C., Vissel, B., MELLOR, J., Henley, J. Abstract: Q/R editing of kainate receptor (KAR) subunit GluK2 pre-mRNA replaces a genetically encoded glutamine to an arginine residue in the channel pore to alter the biophysical and trafficking properties of assembled KARs in recombinant systems. However, the consequences of GluK2 Q/R editing in vivo remain largely unexplored. Here we investigated differences between GluK2-editing deficient mice, that express ~95% unedited GluK2(Q) compared to wild-type counterparts that express ~85% edited GluK2(R). At hippocampal mossy fibre-CA3 (MF-CA3) synapses the editing-deficient (GluK2(Q)) mice displayed enhanced postsynaptic KAR function and increased KAR-mediated presynaptic facilitation, demonstrating heightened ionotropic function. Conversely, KAR-mediated metabotropic function, measured by regulation of afterhyperpolarization currents, was reduced in GluK2(Q) mice. Moreover, GluK2(Q) mice had fewer GluA1-containing synaptic AMPA receptors (AMPARs) and reduced postsynaptic AMPAR currents at MF-CA3 synapses. Using patterns of stimulation that replicate physiological activity, we show that GluK2(Q) mice have reduced long-term potentiation of AMPAR-mediated transmission at Schaffer collateral synapses. These findings indicate that GluK2 Q/R editing influences the balance of ionotropic versus metabotropic KAR signalling and regulates synaptic AMPAR expression and plasticity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.18.512779v1?rss=1 Authors: Shields, B. C., Yan, H., Lim, S. S. X., Burwell, S. C., Fleming, E. A., Cammarata, C. M., Kahuno, E. W., Vagadia, P. P., Loughran, M. H., Zhiquan, L., McDonnell, M. E., Scalabrino, M. L., Thapa, M., Hawley, T. M., Reitz, A. B., Schiltz, G. E., Hull, C., Field, G. D., Glickfeld, L. L., TADROSS, M. R. Abstract: Cell-specific pharmaceutical technologies promise mechanistic insight into clinical drugs[-]those that treat, and often define, human disease. In particular, DART (drug acutely restricted by tethering) achieves genetically programmable control of drug concentration over cellular dimensions. The method is compatible with clinical pharmaceuticals and amenable to studies in behaving animals. Here, we describe DART.2, comprising three advances. First, we improve the efficiency of chemical capture, enabling cell-specific accumulation of drug to ~3,000-times the ambient concentration in 15 min. Second, we develop tracer reagents, providing a behavior- independent measure of cellular target engagement in each animal. Third, we extend the method to positive allosteric modulators and outline design principles for this clinically significant class. We showcase the platform with four pharmaceuticals[-]two that weaken excitatory (AMPAR) or inhibitory (GABAAR) chemical neurotransmission, and two that strengthen these forms of synaptic communication. Across four labs, we tested reagents in the mouse cerebellum, basal ganglia, visual cortex, and retina. Collectively, we demonstrate robust, bidirectional editing of chemical neurotransmission. We provide for distribution of validated reagents, community design principles, and synthetic building blocks for application to diverse pharmaceuticals. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

El hermano de Belinda fue a dejar a su novia, Minnie West, a un centro de atención mental, así lo mostró la artista en su cuenta de Instagram Hosted on Acast. See acast.com/privacy for more information.

El hermano de Belinda fue a dejar a su novia, Minnie West, a un centro de atención mental, así lo mostró la artista en su cuenta de Instagram Hosted on Acast. See acast.com/privacy for more information.

El Gobierno ha confirmado a esta asociación que señalizará los 270 kilómetros de la carretera Málaga- Almería

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.25.509219v1?rss=1 Authors: Zhang, D., Lape, R., Shaikh, S. A., Kohegyi, B. K., Watson, J. F., Cais, O., Nakagawa, T., Greger, I. H. Abstract: AMPA glutamate receptors (AMPARs) mediate excitatory neurotransmission throughout the brain. Their signalling is uniquely diversified by brain region-specific auxiliary subunits, providing an opportunity for the development of selective therapeutics. AMPARs associated with TARP {gamma}8 are enriched in the hippocampus, and are targets of emerging anti-epileptic drugs. To understand their therapeutic activity, we determined cryo-EM structures of the GluA1/2-{gamma}8 receptor associated with three potent, chemically diverse drugs. We find that despite sharing a lipid-exposed and water-accessible binding pocket, drug action is differentially affected by binding-site mutants. Together with patch-clamp recordings and MD simulations we demonstrate that ligand-triggered reorganisation of the AMPAR-TARP interface contributes to modulation. Unexpectedly, one ligand (JNJ-61432059) acts bifunctionally, negatively affecting GluA1 but exerting positive modulatory action on GluA2-containing AMPARs, in a TARP stoichiometry-dependent manner. These results further illuminate the action of TARPs, demonstrate the sensitive balance between positive and negative modulatory action, and provide a mechanistic platform for development of both positive and negative selective AMPAR modulators. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Amparín amaba las caricaturas, decía que todo lo dibujaba con viñetas e historietas porque no quería dejar escapar a la niña que tenía adentro. ¿Cómo entender su impacto en la cultura visual que va más allá de los niños y los adolescentes? El impacto de un diseño naif, o una muy dulce caricatura de la Virgen de Guadalupe, que tuvo incidencia en el mercado, en el arte y en las propias creencias. Blanca González Rosas, socióloga del arte, nos invita a adentrarnos en el mundo de Amparo Serrano y su Virgencita Plis.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.05.506328v1?rss=1 Authors: Bonnet, C., Charpentier, J., Retailleau, N., Choquet, D., Coussen, F. Abstract: Changes in the number of synaptic AMPA subtypes of glutamate receptors (AMPAR) underlie many forms of synaptic plasticity. These variations are controlled by a complex interplay between their intracellular transport (IT), export to the plasma membrane, stabilization at synaptic sites, and recycling. The differential molecular mechanisms involved in these various trafficking pathways and their regulation remains partly unknown. We have recently reported the visualization of AMPAR IT in cultured hippocampal neurons and demonstrated its regulation during synaptic plasticity inducing protocols (Hangen, Cordelieres et al., 2018), opening the path to the differential analysis of the mechanisms controlling AMPAR transport and exocytosis. The cytosolic C-terminal (C-ter.) domain of AMPAR GluA1 subunit is specifically associated with cytoplasmic proteins that could be implicated in the regulation of their IT such as 4.1N and SAP97. Here we analyze how interactions between GluA1 and 4.1N or SAP97 regulate IT and exocytosis at the plasma membrane in basal condition and after cLTP induction. We use sh-RNA against 4.1N and SAP97 and specific mutations and deletions of GluA1 C-ter. domain to characterize how these interactions are involved in coupling AMPAR to the transport machinery. The down-regulation of both 4.1N or SAP97 by shRNAs decrease GluA1 containing vesicle number, modify their transport properties and decrease GluA1 export to the PM, indicating their role in GluA1 IT. The total deletion of the C-ter. domain of GluA1 fully suppresses its IT. Disruption of GluA1 binding to 4.1N decreases the number of GluA1 containing transport vesicles, inhibits GluA1 externalization but does not affect the transport properties of the remaining GluA1 containing vesicles. This indicates a role of the 4.1N GluA1 interaction during exocytosis of the receptor in basal transmission. In contrast, disrupting the binding between SAP97 and GluA1 modifies the basal transport properties of GluA1 containing vesicles and decreases GluA1 export to the plasma membrane. Importantly, disrupting GluA1 interaction with either 4.1N or SAP97 prevents both the cLTP induced increase in the number of GluA1 containing vesicles observed in control and GluA1 externalization. Our results demonstrate that specific interactions between 4.1N or SAP97 with GluA1 have different roles in GluA1 IT and exocytosis. During basal transmission, the binding of 4.1N to GluA1 allows the fusion/fission membrane exocytosis whereas the interaction with SAP97 is essential for GluA1 IT. During cLTP the interaction of 4.1N with GluA1 allows both IT and exocytosis of the receptor in hippocampal cultured neurons. Altogether, our results identify the differential roles of 4.1N and SAP97 in the control of various phases of GluA1 IT. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

En este episodio: - Rosalía y el Dr. Simi. - Amparín Serrano y el caso de Distroller. - Redes sociales que se copian. - Instagram y Youtube ponen candados. - Dibujos con IA enTikTok. - El Tigre Toño, streamer. - Los audio memes. - Adiós al Pixy Drone.

Comenzaremos hablando de como ordenar y organizar tu vida con Adelaida Gómez, creadora de ordenstudio.com. También nos acompaña Amparito Vázquez con su proyecto "Huerting Solidario", en Sevilla la Nueva, un pueblo de la Comunidad de Madrid. En el espacio La Botica de Palmira contamos con los consejos del Dr. Alberto Martí Bosch, “Remedios naturales para tratar el Glaucoma”. Viviana V. nos cuenta la programación de su teatro para peques Tilín Telón, noticias y acciones humanitarias y solidarias para un mundo mejor en la voz de Sophie...y nos despedimos con un cuento lleno de sabiduría....

Di Kepulauan Riau, Batam, terdapat sebuah daerah bernama Batu Ampar. Konon nama ini diambil dari sebuah batu yang terhampar. Bagaimana bisa batu itu bisa terhampar? Yuk, simak kisahnya di video Riri ini untuk menambah wawasanmu. #ceritarakyat

References Dr. Guerra's Lecture Notes Journal of the American College of Nutrition. 2019. 38:8, 693-702. Curr Diabetes Rev. 2020;16(8):797-806 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

My guest this week wears MULTIPLE hats because she owns and operates MULTIPLE successful businesses!

Ampar-ampar pisang

It doesn't matter how long we've worked in any industry; there is always room to improve and we must be humble enough to recognize it and dedicate time to educate ourselves constantly. That is one of Dr. Kizzy Parks' secrets to success; she is aware that she does not know it all, and she let herself go following her curious nature.  Dr. Kizzy Parks is the CEO of KPC, GovCon Winners, AmPar, and Adult Fluent. She specializes in helping service-based small business owners learn how to win profitable government contracts, and she is the host of the Adult Fluent Podcast. Kizzy holds a B.S. in Psychology from Alfred University, a Master of Science, and a Ph.D. in Industrial and Organizational Psychology from the Florida Institute of Technology.  Since she was little, Kizzy knew she would be an entrepreneur; her adoptive parents instilled in her the idea that everything is possible. Kizzy's household was the mecca of positive reinforcement, and so she became what she wanted. In this episode, Kizzy shared her infectious optimism and experience. We had a fantastic conversation about her expertise and her teaching methods, like her CTC technique to win profitable government contracts. We also spoke about her background, her first experiences as an entrepreneur, and why she decided to dedicate her efforts to teach others and help them grow. Kizzy talked about what is, in her opinion, a straight path to becoming the best version of ourselves, and then she explained how she maximizes her teams' performance.  Tune in to Episode 289 of Becoming Your Best, to enjoy Kizzy's expertise in winning government contracts and lead successful teams.  Some Questions I Ask: Our listeners would love to hear about your background. And how did you know this is what you wanted to do? (2:59) Something that's been in your heart and mind is becoming the best at what you do. So what does becoming your best mean to you? (8:56) How do you maximize the performance of your team? (15:50) What do you look for in a leader? (19:19) If someone would ask you for advice on how to be successful in business or be successful in life, what would you recommend to them? (25:37) In This Episode, You Will Learn: How Kizzy discovered her passion for helping others to clinch government contracts (4:12) The difference between teaching what others should do, and teaching from first-hand experiences (7:19) The perks of staying humble and always willing to learn (10:13) How Kizzy maximizes her teams' performances (15:44) The importance of taking time to experience; there is no rush nor the right moment to do something (27:13) Resources:  K. Parks Consulting (KPC) website AdultFluent Podcast Sam.gov website Connect with Kizzy: LinkedIn Becoming Your Best Resources: Becoming Your Best Website Becoming Your Best University Website Becoming Your Best Library Email: support@becomingyourbest.com  Book: Becoming Your Best: The 12 Principles of Highly Successful Leaders Book: Conquer Anxiety: How to Overcome Anxiety and Optimize Your Performance Facebook Group – Conquer Anxiety See acast.com/privacy for privacy and opt-out information.

Distroller se define a si misma como empresa 102% Mexicana, dedicada al diseño y creación de productos diferentes basados en la filosofía de hacer lo extraordinario dentro de lo ordinario. Hoy, está con nosotras su Fundadora y Directora Creativa, "Amparín". Su empresa es un caso de éxito y su creatividad, le permitió hacer de su pasión un trabajo. Aprende de ella, tanto como nosotras. Conoce a Amparín en https://www.instagram.com/amparinserrano/ Conoce a Distroller en http://distroller.com/

Welcome to episode 40!Kizzy Parks, Ph.D., is the CEO of KPC, GovCon Winners, AmPar, and AdultFluent - a definite serial entrepreneur. Kizzy told us that from a very young age, she always knew she would be an entrepreneur. Fun fact, she is also a Guinness world Record title holder...but you'll have to listen to find out what that title is!Find Kizzy at:https://www.linkedin.com/in/kizzyhttps://www.kpcinc.com/

In this episode, Heather interviews Kizzy Parks, Ph.D., CEO of KPC, GovCon Winners, AmPar, AdultFluent, and Host of the AdultFluent℠ podcast. Her newest company GovCon Winners works to help small businesses win profitable government contracts.  She is charismatic, honest, and compassionate in this episode, where she shared the times in her career when she wasn’t the best leader. She states that at times she was leading from a space of scarcity and less than - which was not productive for her or her company. Now she leads from a place of compassion and has implemented new strategies to ensure that her employees get treated the most fairly.  Kizzy shares that her entrepreneur journey began when she was just a kid when she would resell golf balls she found to fund her love for FUNYUNs and Nutty Bars. She knew from a young age that she would be an entrepreneur. Today, her companies have over $50 million in government contract rewards.  

In today's episode, Divinia chats with Aldo Amparán (he/him). Aldo's bio: "Aldo Amparán is the author of Brother Sleep (Alice James Books, forthcoming 2022), winner of the 2020 Alice James Award. He has received fellowships from the National Endowment for the Arts & CantoMundo. His work most recently appears in the Academy of American Poets' Poem-a-Day, AGNI, Best New Poets, Ploughshares, & elsewhere.  He lives in the border cities of El Paso, TX, & Ciudad Juárez, CHIH, México." Aldo's website: https://www.aldoamparan.com/ (https://www.aldoamparan.com/) Host: Divinia Shorter Producer: Jacob Zeranko Charity of Choice: Mariposas Sin Fronteras. For more information, check out their website: https://mariposassinfronteras.org/ (https://mariposassinfronteras.org/) Follow us! Twitter: @greatestcityco Instagram: @greatestcityco Facebook: @greatestcityco Website: https://www.greatestcitycollective.org/ (https://www.greatestcitycollective.org/)

Recorded by Aldo Amparán for Poem-a-Day, a series produced by the Academy of American Poets. Published on March 4, 2021. www.poets.org

Una charla con Amparín Serrano.Todo con una clara misión, ir más allá de la superficie para salir del otro lado, Sin Duda.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.12.379867v1?rss=1 Authors: Matsuda, S., Yuzaki, M. Abstract: Long-term potentiation (LTP) and depression (LTD) of excitatory neurotransmission are believed to be the neuronal basis of learning and memory. Both processes are primarily mediated by neuronal activity-induced transport of postsynaptic AMPA-type glutamate receptors (AMPARs). While AMPAR subunits and their specific phosphorylation sites mediate differential AMPAR trafficking, LTP and LTD could also occur in a subunit-independent manner. Thus, it remains unclear whether and how, certain AMPAR subunits with phosphorylation sites are preferentially recruited to or removed from synapses during LTP and LTD. Here, we show that phosphorylation of the membrane-proximal region (MPR), which only occurs in GluA1 AMPAR subunits, mediates the subunit-dependent endosomal transport of AMPARs during LTD. AP-2 and AP-3, adaptor protein complexes necessary for clathrin-mediated endocytosis and late endosomal/lysosomal trafficking, respectively, are reported to be recruited to AMPARs by binding to the AMPAR auxiliary subunit, stargazin (STG), in an AMPAR subunit-independent manner. However, the association of AP-3, but not AP-2, with STG was indirectly inhibited by the phosphomimetic mutation in the MPR of GluA1. Thus, although AMPARs containing the phosphomimetic mutation at the MPR of GluA1 were endocytosed by a LTD-inducing stimulus, they were quickly recycled back to the cell surface in hippocampal neurons. These results could explain how the phosphorylation status of GluA1-MPR plays a dominant role in subunit-independent STG-mediated AMPAR trafficking during LTD. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.07.373027v1?rss=1 Authors: Zhang, L., Padilla-Flores, T., Hernandez, V. S., Campos-Lira, E., Zetter, M. A., Escobar, L. I., Eiden, L. E. Abstract: Hypothalamic arginine vasopressin (AVP)-containing magnocellular neurosecretory neurons (AVPMNN) emit collaterals to synaptically innervate limbic regions influencing learning, motivational behavior and fear responses. The purpose of the present work is to characterize the dynamics of expression changes of two postsynaptic density (PSD) proteins, AMPAR subunit GluA1 and PSD scaffolding protein 95 (PSD95), which are known to be key determinants for synaptic strength, in response to in vivo and ex vivo manipulations of AVPMNN neuronal activation state, or exposure to exogenous AVP, metabolites and some signaling pathway inhibitors. Both long term water deprivation in vivo, which powerfully upregulates AVPMNN activity, and exogenous APV application ex vivo in brain slices, increased GluA1 and PSD95 expression and enhanced neuronal excitability in ventral hippocampal CA1 pyramidal neurons. Involvement of PI3k signaling in AVP-dependent plasticity is suggested by blockade of both AVP-induced protein up-regulation and enhanced neuronal excitability by the PI3k blocker wortmannin in hippocampal slices. We interpret these results as part of vasopressin's central effects on synaptic organization in limbic regions modulating the strength of a specific set of synaptic proteins in hypothalamic-limbic circuits. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.05.370080v1?rss=1 Authors: Roberts, J. P., Stokoe, S. A., Sathler, M. F., Nichols, R. A., Kim, S. Abstract: Beta-amyloid (A{beta}) has been recognized as an early trigger in the pathogenesis of Alzheimers disease (AD) leading to synaptic and cognitive impairments. A{beta} can alter neuronal signaling through interactions with nicotinic acetylcholine receptors (nAChRs), contributing to synaptic dysfunction in AD. The three major nAChR subtypes in the hippocampus are composed of 7-, 4{beta}2-, and 3{beta}4-nAChRs. A selectively affects 7- and 4{beta}2-nAChRs, but not 3{beta}4-nAChRs in hippocampal neurons, resulting inneuronal hyperexcitation. However, how nAChR subtype selectivity for A{beta} affects synaptic function in AD is not completely understood. Here, we showed that A{beta} associated with 7- and 4-containing nAChRs but not 3-containing receptors. Computational modeling suggested two amino acids in 7-nAChRs, Arginine 208 and Glutamate 211, were important for the interaction between A{beta} and 7-containing nAChRs. These residues were found to be conserved only in the 7 and 4 subunits. We therefore mutated these amino acids in 7-containing nAChRs to mimic the 3 subunit and found that mutant 7-containing receptors were unable to interact with A{beta}, providing direct molecular evidence for how A{beta} selectively interacted with 7- and 4-containing receptors, but not 3-containing nAChRs. Selective co-activation of 7- and 4{beta}2-nAChRs was also sufficient to reverse A{beta}-induced AMPA receptor (AMPAR) dysfunction, including A{beta}-induced reduction of AMPAR phosphorylation and surface expression in hippocampal neurons. Moreover, the A{beta}-induced disruption of long-term potentiation was reversed by co-stimulation of 7- and 4{beta}2-nAChRs. These findings support a novel mechanism for A{beta}'s impact on synaptic function in AD, namely the differential regulation of nAChR subtypes. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.04.368282v1?rss=1 Authors: Jabarin, R., Levy, N., Abergel, Y., Berman, J. H., Zag, A., Netser, S., Levy, A. P., Wagner, S. Abstract: In this study we tested the hypothesis that precision medicine guided therapy targeting glutamatergic neurotransmission could rescue behavioral deficits exhibited by mice carrying a specific mutation in the Iqsec2 gene. The IQSEC2 protein plays a key role in glutamatergic synapses and mutations in the IQSEC2 gene are a frequent cause of neurodevelopmental disorders. We have recently reported on the molecular pathophysiology of one such mutation A350V and demonstrated that this mutation downregulates AMPA type glutamatergic receptors (AMPAR) in A350V mice. Here we sought to identify behavioral deficits in A350V mice and hypothesized that we could rescue these deficits by PF-4778574, a positive AMPAR modulator. We found that A350V Iqsec2 mice exhibit specific deficits in sex preference and emotional state preference behaviors as well as in vocalizations when encountering a female mouse. The social discrimination deficits, but not the impaired vocalization, were rescued with PF-4778574. We conclude that social behavior deficits associated with the A350V Iqsec2 mutation may be rescued by enhancing AMPAR mediated synaptic transmission. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.28.359224v1?rss=1 Authors: Shi, Y., van Rhijn, J.-R., Bormann, M., Mossink, B., Frega, M., Recaioglu, H., Hakobjan, M., Klein Gunnewiek, T. M., Schoenmaker, C., Palmer, E., Faivre, L., Kittel-Schneider, S., Schubert, D., Brunner, H., Franke, B., Nadif Kasri, N. Abstract: Background: Monoamine neurotransmitter abundance affects motor control, emotion, and cognitive function and is regulated by monoamine oxidases. Amongst these, monoamine oxidase A (MAOA) catalyzes the degradation of dopamine, norepinephrine, and serotonin into their inactive metabolites. Loss-of-function mutations in the X-linked MAOA gene cause Brunner syndrome, which is characterized by various forms of impulsivity, maladaptive externalizing behavior, and mild intellectual disability. Impaired MAOA activity in individuals with Brunner syndrome results in bioamine aberration, but it is currently unknown how this affects neuronal function. Methods: We generated human induced pluripotent stem cell (hiPSC)-derived dopaminergic (DA) neurons from three individuals with Brunner syndrome carrying different mutations, and used CRISPR/Cas9 mediated homologous recombination to rescue MAOA function. We used these lines to characterize morphological and functional properties of DA neuronal cultures at the single cell and neuronal network level in vitro. Results: Brunner syndrome DA neurons showed reduced synaptic density but hyperactive network activity. Intrinsic functional properties and -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated synaptic transmission were not affected by MAOA dysfunction. Instead, we show that the neuronal network hyperactivity is mediated by upregulation of the GRIN2A and GRIN2B subunits of the N-methyl-D-aspartate receptor (NMDAR), and rescue of MAOA results in normalization of NMDAR function as well as restoration of network activity. Conclusions: Our data suggest that MAOA dysfunction in Brunner syndrome increases activity of dopaminergic neurons through upregulation of NMDAR function, which may contribute to Brunner syndrome associated phenotypes. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.13.337188v1?rss=1 Authors: Guerreiro, I., Gu, Z., Yakel, J., Gutkin, B. Abstract: Hippocampal synaptic plasticity, particularly in the Schaffer collateral (SC) to CA1 pyramidal excitatory transmission, is considered as the cellular mechanism underlying learning. The CA1 pyramidal neurons are embedded in an intricate local circuitry that contains a variety of interneurons. The roles these interneurons play in the regulation of the excitatory synaptic plasticity remains largely understudied. Our recent experiments showed that repeated cholinergic activation of 7 nACh receptors expressed in oriens-lacunosum-moleculare (OLM2) interneurons could induce LTP in SC-CA1 synapses, likely through disinhibition by inhibiting stratum radiatum (s.r.) interneurons that provide feedforward inhibition onto CA1 pyramidal neurons, revealing a potential mechanism for local interneurons to regulate SC-CA1 synaptic plasticity. Here, we pair in vitro studies with biophysically-based modeling to uncover the mechanisms through which cholinergic-activated GABAergic interneurons can disinhibit CA1 pyramidal cells, and how repeated disinhibition modulates hippocampal plasticity at the excitatory synapses. We found that 7 nAChR activation increases OLM activity. OLM neurons, in turn inhibit the fast-spiking interneurons that provide feedforward inhibition onto CA1 pyramidal neurons. This disinhibition, paired with tightly timed SC stimulation, can induce potentiation at the excitatory synapses of CA1 pyramidal neurons. Our work further describes the pairing of disinhibition with SC stimulation as a general mechanism for the induction of hippocampal synaptic plasticity. Disinhibition of the excitatory synapses, paired with SC stimulation, leads to increased NMDAR activation and intracellular calcium concentration sufficient to upregulate AMPAR permeability and potentiate the synapse. Repeated paired disinhibition of the excitatory synapse leads to larger and longer lasting increases of the AMPAR permeability. Our study thus provides a novel mechanism for inhibitory interneurons to directly modify glutamatergic synaptic plasticity. In particular, we show how cholinergic action on OLM interneurons can down-regulate the GABAergic signaling onto CA1 pyramidal cells, and how this shapes local plasticity rules. We identify paired disinhibition with SC stimulation as a general mechanism for the induction of hippocampal synaptic plasticity. Copy rights belong to original authors. Visit the link for more info

Ancira se encuentra en España bajo libertad condicional, puede viajar por todo el país sin restricción

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.11.247270v1?rss=1 Authors: Cao, X., An, S., Wang, J., Zhang, X., Duan, Y., Lv, J., Wang, D., Zhang, H., Richter-Levin, G. Abstract: Impaired fear extinction is one of the hallmark symptoms of post-traumatic stress disorder (PTSD). The roles of CaMKII have been not extensively studied in fear extinction and LTD. Here, we found PTSD susceptible mice exhibited significant up-regulation of CaMKII in the lateral amygdala (LA). Consistently, increasing CaMKII in LA profoundly not only caused PTSD-like symptoms such as impaired fear extinction and anxiety-like behaviors, but also attenuated NMDAR-dependent LTD at thalamo-LA synapses, reduced GluA1-Ser845/Ser831 dephosphorylation and AMPAR internalization. Suppressing the elevated CaMKII to normal level could completely reverse both PTSD-like symptoms and the impairments in LTD, GluA1-Ser845/Ser831 dephosphorylation, and AMPAR internalization. Intriguingly, deficits in AMPAR internalization and GluA1-Ser845/Ser831 dephosphorylation were detected not only after impaired fear extinction, but also after attenuated LTD Our results demonstrate for the first time GluA1-Ser845/Ser831 dephosphorylation and AMPAR internalization are molecular links between LTD and fear extinction, and suggest CaMKII may be a potential molecular determinant of PTSD. Copy rights belong to original authors. Visit the link for more info

Este é o terceiro e último episódio da série sobre divórcio. Neste bate papo, eu converso com a psicóloga infantil, Carolina Dantas, para tirar as dúvidas sobre como conversar com as nossas crianças durante este processo de separação. Como podemos amenizar suas dores, tentar acolhê-los da melhor forma possível? Na segunda parte deste episódio eu converso com a Lari Godoi, que é terapeuta familiar sistêmica e vai explicar para gente como funciona a constelação familiar de casal. Como podemos constelar a nossa relação e por que casamos com a família da outra pessoa, e não apenas com quem realmente escolhemos para ser o nosso par. Converso também com a Paula Sampaio Schimitt sobre a técnica terapêutica EMDR, procurada para melhorar problemas causados por traumas. Vamos comigo??

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.02.130419v1?rss=1 Authors: Higginbotham, J. A., Wang, R., Richardson, B. D., Shiina, H., Tan, S. M., Presker, M. A., Rossi, D. J., Fuchs, R. A. Abstract: Contextual drug-associated memories precipitate craving and relapse in cocaine users. Such associative memories can be weakened through interference with memory reconsolidation, a process by which memories are maintained following memory retrieval-induced destabilization. We hypothesized that cocaine-memory reconsolidation requires cannabinoid type 1 receptor (CB1R) signaling based on the fundamental role of the endocannabinoid system in synaptic plasticity and emotional memory processing. Using an instrumental rat model of cocaine relapse, we evaluated whether systemic CB1R antagonism (AM251; 3 mg/kg, I.P.) during memory reconsolidation alters (a) subsequent drug context-induced cocaine-seeking behavior, as well as (b) cellular adaptations and (c) excitatory synaptic physiology in the basolateral amygdala (BLA). Systemic CB1R antagonism - during, but not after, cocaine-memory reconsolidation - reduced drug context-induced cocaine-seeking behavior three days, but not three weeks, later. CB1R antagonism also inhibited memory retrieval-associated increases in BLA zinc finger 268 (zif268) and activity regulated cytoskeletal-associated protein (Arc) immediate-early gene expression and changes in BLA -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and N-methyl-D-aspartate receptor (NMDAR) subunit phosphorylation that likely contribute to increased receptor membrane trafficking and synaptic plasticity during memory reconsolidation. Furthermore, CB1R antagonism increased memory reconsolidation-associated spontaneous excitatory post-synaptic current frequency in BLA principal neurons during memory reconsolidation. Together, these findings suggest that CB1R signaling modulates cellular and synaptic mechanisms in the BLA during cocaine-memory reconsolidation, thereby facilitating cocaine-memory maintenance. These findings identify the CB1R as a potential therapeutic target for relapse prevention. Copy rights belong to original authors. Visit the link for more info

En esta inusitada y extraña situación que nos está tocando vivir por culpa de lo que todos sabemos, aparecen no pocas polémicas que en cierta forma son hasta absurdas por lo secundarias o terciarias que tendrían que ser viendo el espectro general de las cosas. Una de ellas es la de dosis mensual de cómics a la que nos tienen acostumbrados las editoriales que seguimos, así como los puntos de venta que todos conocemos (librerías especializadas). Amparándonos en la "ley" y en lo dicho por el Gobierno la verdad es que todo se podría justificar e incluso ni siquiera posicionarse para así quedar bien con todo el mundo, pero otra cosa ya sería la coherencia de cada uno y su conciencia. De estas y más

Estamos de vuelta con #LomásEspectacular de #WITZITeVe conducido por Witzi Teve y con él sus invitados de Distroller El miusikul presentado por la creadora Amparin y su productor Claudio González también tendremos a Quecho Muñoz presentando "Niño perdido y 12 Princesas en pugna".

Amparémonos en la Virgen

Invadimos las instalaciones de Musa Café + Arte con un invitado especial: el mecatrónico, sonorense y cashanilla adoptado Hirám Amparán, con quien debatimos sobre usos y costumbres, inteligencia artificial, el calor, la comida y la música.

El pasado sábado 24 de septiembre tuvimos la oportunidad no sólo de asistir a la presentación de El Linaje de la Luna Negra, de David Mateo, sino de participar activamente en ella. Nuestro director Víctor M. Yeste fue uno de los dos encargados de presentar al autor español en la Gva Biblioteca Valenciana Nicolau Primitiu, situado en Valencia. Estuvo acompañado, además, del también escritor José Vilaseca Haro. Hablamos de temas tan interesantes como la psicología, los eventos inexplicables, el misterio y cómo plasmar todo ello en la literatura. Sinopsis de El Linaje de la Luna Negra: Barcelona, 19 de julio de 1936. Amparándose en el caos reinante, Emilio Anglesola saca a un grupo de niñas del Hogar de Nuestra Señora de la Consolación y lo traslada hasta el Palacio Desvall. Nadie sospecha que a medianoche, algo oscuro y siniestro aguarda en el umbral de dos mundos separados por la Luna Negra. Hoy, Dafne, estudiante de Bellas Artes, lucha contra un carcinoma degenerativo que trae consigo terribles pesadillas. La joven trata de recomponer su vida cuando llega un encargo inesperado de la misteriosa Fundación Exégesis: recuperar la ninfa Egéria, una de las piezas más valiosas de la colección del Laberinto de Horta. A varios kilómetros de allí, el doctor Abel Barros emprende una búsqueda contrarreloj para dar con el paradero de Eli, una niña secuestrada hace años por un peligroso psicópata conocido como el Ogro de Lupiñén. Las vidas de nuestros protagonistas se entrecruzarán en un thriller sorprendente en el que los pecados del pasado están condenados a repetirse como un eco maligno, generación tras generación.

El pasado sábado 24 de septiembre tuvimos la oportunidad no sólo de asistir a la presentación de El Linaje de la Luna Negra, de David Mateo, sino de participar activamente en ella. Nuestro director Víctor M. Yeste fue uno de los dos encargados de presentar al autor español en la Gva Biblioteca Valenciana Nicolau Primitiu, situado en Valencia. Estuvo acompañado, además, del también escritor José Vilaseca Haro. Hablamos de temas tan interesantes como la psicología, los eventos inexplicables, el misterio y cómo plasmar todo ello en la literatura. Sinopsis de El Linaje de la Luna Negra: Barcelona, 19 de julio de 1936. Amparándose en el caos reinante, Emilio Anglesola saca a un grupo de niñas del Hogar de Nuestra Señora de la Consolación y lo traslada hasta el Palacio Desvall. Nadie sospecha que a medianoche, algo oscuro y siniestro aguarda en el umbral de dos mundos separados por la Luna Negra. Hoy, Dafne, estudiante de Bellas Artes, lucha contra un carcinoma degenerativo que trae consigo terribles pesadillas. La joven trata de recomponer su vida cuando llega un encargo inesperado de la misteriosa Fundación Exégesis: recuperar la ninfa Egéria, una de las piezas más valiosas de la colección del Laberinto de Horta. A varios kilómetros de allí, el doctor Abel Barros emprende una búsqueda contrarreloj para dar con el paradero de Eli, una niña secuestrada hace años por un peligroso psicópata conocido como el Ogro de Lupiñén. Las vidas de nuestros protagonistas se entrecruzarán en un thriller sorprendente en el que los pecados del pasado están condenados a repetirse como un eco maligno, generación tras generación.

Our guest is Indira Raman, Professor of Neurobiology and Physiology at Northwestern University . We speak with her about AMPAR kinetics in auditory neurons, sodium channels in cerebellar neurons, and how Shakespeare and Science maybe aren't all that different

Martha Debayle habla con Amparín Serrano acerca de cómo nació Distroller, una de las marcas más representativas del folclore mexicano.

Martha Debayle habla con Amparín Serrano acerca de cómo nació Distroller, una de las marcas más representativas del folclore mexicano.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.09.033514v1?rss=1 Authors: Oueslati Morales, C. O., Ignacz, A., Bencsik, N., Ratkai, A. E., Lieb, W. S., Eisler, S. A., Schlett, K., Hausser, A. Abstract: AMPA type glutamate receptors (AMPARs) mediate the majority of fast excitatory neurotransmission in the brain. The continuous trafficking of AMPARs into and out of synapses is a core feature of synaptic plasticity, which is considered as the cellular basis of learning and memory. The molecular mechanisms underlying the postsynaptic AMPAR trafficking, however, are still not fully understood. In this work, we demonstrate that the Protein Kinase D (PKD) family promotes basal and activity-induced AMPAR endocytosis in primary hippocampal neurons. Pharmacological inhibition of PKD increased synaptic levels of GluA1-containing AMPARs and slowed down their endocytic trafficking. By contrast, ectopic expression of constitutive active PKD decreased the synaptic level of AMPARs, while increasing their co-localization with early endosomes. On a molecular level, we identify PKD-mediated phosphorylation of the Rab5 effector protein Rabaptin-5 to be required for promoting activity-dependent AMPAR endocytosis. Our results thus establish an important role for PKD in the regulation of postsynaptic AMPAR trafficking during synaptic plasticity. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.19.048819v1?rss=1 Authors: Prieto, M., Folci, A., Poupon, G., Schiavi, S., Buzzelli, V., Francois, U., Pousinha, P., Lattuada, N., Abelanet, S., Pronot, M., Castagnola, S., Chafai, M., Khayachi, A., Brau, F., Deval, E., Francolini, M., Bardoni, B., Humeau, Y., Trezza, V., Martin, S. Abstract: Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.20.051904v1?rss=1 Authors: Doser, R. L., Amberg, G. C., Hoerndli, F. J. Abstract: The AMPA subtype of synaptic glutamate receptors (AMPARs) play an essential role in cognition. Their function, numbers and change at synapses during synaptic plasticity, is tightly regulated by neuronal activity. Although we know that long-distance transport of AMPARs is essential for this regulation, we do not understand the regulatory mechanisms of it. Neuronal transmission is a metabolically demanding process in which ATP consumption and production are tightly coupled and regulated. Aerobic ATP synthesis unavoidably produces reactive oxygen species (ROS), such as hydrogen peroxide, which are known modulators of calcium signaling. Although a role for calcium signaling in AMPAR transport has been described, there is little understanding of the mechanisms involved and no known link to physiological ROS signaling. Here, using real-time in vivo imaging of AMPAR transport in the intact C. elegans nervous system, we demonstrate that long-distance synaptic AMPAR transport is bidirectionally regulated by calcium influx and activation of calcium/calmodulin-dependent protein kinase II. Quantifying in vivo calcium dynamics revealed that modest, physiological increases in ROS decrease calcium transients in C. elegans glutamatergic neurons. By combining genetic and pharmacological manipulation of ROS levels and calcium influx, we reveal a mechanism in which physiological increases in ROS cause a decrease in synaptic AMPAR transport and delivery by modulating activity-dependent calcium signaling. Taken together, our results identify a novel role for oxidant signaling in the regulation of synaptic AMPAR transport and delivery, which in turn could be critical for coupling the metabolic demands of neuronal activity with excitatory neurotransmission. Copy rights belong to original authors. Visit the link for more info