Corina Marinescu>NEUROSCIENCE

Corina Marinescu

NEUROSCIENCE

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Blocking a key enzyme may reverse memory loss
In the brains of Alzheimer’s patients, many of the genes required to form new memories are shut down by a genetic blockade, contributing to the cognitive decline seen in those patients.

MIT researchers have shown that they can reverse that memory loss in mice by interfering with the enzyme that forms the blockade. The enzyme, known as HDAC2, turns genes off by condensing them so tightly that they can’t be expressed.

For several years, scientists and pharmaceutical companies have been trying to develop drugs that block this enzyme, but most of these drugs also block other members of the HDAC family, which can lead to toxic side effects. The MIT team has now found a way to precisely target HDAC2, by blocking its interaction with a binding partner called Sp3.

“This is exciting because for the first time we have found a specific mechanism by which HDAC2 regulates synaptic gene expression,” says Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory and the study’s senior author.

Blocking that mechanism could offer a new way to treat memory loss in Alzheimer’s patients. In this study, the researchers used a large protein fragment to interfere with HDAC-2, but they plan to seek smaller molecules that would be easier to deploy as drugs.

Source & further reading:
http://news.mit.edu/2017/blocking-key-enzyme-may-reverse-memory-loss-0808

Journal article:
http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31023-9

#HDAC2 #alzheimersdisease #geneexpression #plasticity #memory #neuroscience

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OK, so how do we decrease brain acidity?

Corina Marinescu

NEUROSCIENCE

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Increased brain acidity in psychiatric disorders
Your body’s acid/alkaline homeostasis, or maintenance of an adequate pH balance in tissues and organs, is important for good health. An imbalance in pH, particularly a shift toward acidity, is associated with various clinical conditions, such as a decreased cardiovascular output, respiratory distress, and renal failure. But is pH also associated with psychiatric disorders?

Researchers at the Institute for Comprehensive Medical Science at Fujita Health University in Japan, along with colleagues from eight other institutions, have identified decreased pH levels in the brains of five different mouse models of mental disorders, including models of schizophrenia, bipolar disorder, and autism spectrum disorder. This decrease in pH likely reflects an underlying pathophysiology in the brain associated with these mental disorders, according to the study published August 4th in the journal Neuropsychopharmacology.

While post-mortem studies have shown that the brains of patients with the abovementioned mental disorders tend to have a lower pH than those of controls, this phenomenon has been considered to be the result of secondary factors associated with the diseases rather than a primary feature of the diseases themselves. Secondary factors that confound the observation of a decreased brain pH level include antipsychotic treatments and agonal experiences associated with these disorders.

Dr. Miyakawa and his colleagues performed a meta-analysis of existing datasets from ten studies to investigate the pH level of postmortem brains from patients with schizophrenia and bipolar disorder. They observed that patients with schizophrenia and bipolar disorder exhibited significantly lower brain pH levels than control participants, even when potential confounding factors were considered (i.e., postmortem interval, age at death, and history of antipsychotic use). “These factors may not be major factors causing a decrease in pH in the postmortem brains of patients with schizophrenia and bipolar disorder,” Miyakawa explains.

The researchers then conducted a systematic investigation of brain pH using five mouse models of psychiatric disorders, including models for schizophrenia, bipolar disorder, and autism spectrum disorders. All of the mice used in the study were drug-naive, with equivalent agonal states, postmortem intervals, and ages within each strain. The analyses revealed that in all five mouse models, brain pH was significantly lower than that in the corresponding controls. In addition, the levels of lactate were also elevated in the brains of the model mice, and a significant negative correlation was found between brain pH and lactate levels. The increase in lactate may explain the decreased brain pH levels, as lactate is known to act as a strong acid.

Miyakawa suggests that, “while it is technically impossible to completely exclude confounding factors in human studies, our findings in mouse models strongly support the notion that decreased pH associated with increased lactate levels reflects an underlying pathophysiology, rather than a mere artifact, in at least a subgroup of patients with these mental disorders.”

Changes in the brain pH level have been considered an artifact, therefore substantial effort has been made to match the tissue pH among study participants and to control the effect of pH on molecular changes in the postmortem brain. However, given that decreased brain pH is a pathophysiological trait of psychiatric disorders, these efforts could have unwittingly obscured the specific pathophysiological signatures that are potentially associated with changes in pH, such as neuronal hyper-excitation and inflammation, both of which have been implicated in the etiology of psychiatric disorders. Therefore, the present study highlighting that decreased brain pH is a shared endophenotype of psychiatric disorders has significant implications on the entire field of studies on the pathophysiology of mental disorders.

This research raises new questions about changes in brain pH. For example, what are the mechanisms through which lactate is increased and pH is decreased? Are specific brain regions responsible for the decrease in pH? Is there functional significance to the decrease in brain pH observed in psychiatric disorders, and if so, is it a cause or result of the onset of the disorder? Further studies are needed to address these issues.

Source:
https://www.eurekalert.org/pub_releases/2017-08/fhu-iba080717.php

Journal article:
https://www.nature.com/articles/npp2017167

#psychiatricdisorders #phbalance #schizophrenia #bipolardisorder #lactate #neuroscience #research

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Warning! Machines are capable of self learning!

Gentle readers:

 I am an easygoing kind of person and it takes something serious to push me into writing warnings! I believe that machines with the ability to teach machines at super speed will lead to serious problems for the human race in the very near future. If that does not shake you up a little how about machines teaching themselves at lightning speed? Need more information? Read the following article. J.R. ---

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“The easier it is to communicate, the faster change happens.” – James Burke, Science Historian

During an October 2015 press conference announcing the autopilot feature of the Tesla Model S, which allowed the car to drive semi-autonomously, Tesla CEO Elon Musk said each driver would become an “expert trainer” for every Model S. Each car could improve its own autonomous features by learning from its driver, but more significantly, when one Tesla learned from its own driver—that knowledge could then be shared with every other Tesla vehicle.

As Fred Lambert with Electrik reported shortly after, Model S owners noticed how quickly the car’s driverless features were improving. In one example, Teslas were taking incorrect early exits along highways, forcing their owners to manually steer the car along the correct route. After just a few weeks, owners noted the cars were no longer taking premature exits.

“I find it remarkable that it is improving this rapidly,” said one Tesla owner.

Intelligent systems, like those powered by the latest round of machine learning software, aren’t just getting smarter: they’re getting smarter faster. Understanding the rate at which these systems develop can be a particularly challenging part of navigating technological change.

Ray Kurzweil has written extensively on the gaps in human understanding between what he calls the “intuitive linear” view of technological change and the “exponential” rate of change now taking place. Almost two decades after writing the influential essay on what he calls “The Law of Accelerating Returns”—a theory of evolutionary change concerned with the speed at which systems improve over time—connected devices are now sharing knowledge between themselves, escalating the speed at which they improve.

[Learn more about thinking exponentially and the Law of Accelerating Returns.]

“I think that this is perhaps the biggest exponential trend in AI,” said Hod Lipson, professor of mechanical engineering and data science at Columbia University, in a recent interview.

“All of the exponential technology trends have different ‘exponents,’” Lipson added. “But this one is potentially the biggest.”

According to Lipson, what we might call “machine teaching”—when devices communicate gained knowledge to one another—is a radical step up in the speed at which these systems improve.

“Sometimes it is cooperative, for example when one machine learns from another like a hive mind. But sometimes it is adversarial, like in an arms race between two systems playing chess against each other,” he said.

Lipson believes this way of developing AI is a big deal, in part, because it can bypass the need for training data.

“Data is the fuel of machine learning, but even for machines, some data is hard to get—it may be risky, slow, rare, or expensive. In those cases, machines can share experiences or create synthetic experiences for each other to augment or replace data. It turns out that this is not a minor effect, it actually is self-amplifying, and therefore exponential.”

Lipson sees the recent breakthrough from Google’s DeepMind, a project called AlphaGo Zero, as a stunning example of an AI learning without training data. Many are familiar with AlphaGo, the machine learning AI which became the world’s best Go a player after studying a massive training data-set comprised of millions of human Go moves. AlphaGo Zero, however, was able to beat even that Go-playing AI, simply by learning the rules of the game and playing by itself—no training data necessary. Then, just to show off, it beat the world’s best chess playing software after starting from scratch and training for only eight hours.

Now imagine thousands or more AlphaGo Zeroes instantaneously sharing their gained knowledge.

This isn’t just games though. Already, we’re seeing how it will have a major impact on the speed at which businesses can improve the performance of their devices.

One example is GE’s new industrial digital twin technology—a software simulation of a machine that models what is happening with the equipment. Think of it as a machine with its own self-image—which it can also share with technicians.

A steam turbine with a digital twin, for instance, can measure steam temperatures, rotor speeds, cold starts, and other data to predict breakdowns and warn technicians to prevent expensive repairs. The digital twins make these predictions by studying their own performance, but they also rely on models every other steam turbine has developed.

As machines begin to learn from their environments in new and powerful ways, their development is accelerated by communicating what they learn with each other. The collective intelligence of every GE turbine, spread across the planet, can accelerate each individual machine’s predictive ability. Where it may take one driverless car significant time to learn to navigate a particular city—one hundred driverless cars navigating that same city together, all sharing what they learn—can improve their algorithms in far less time.

As other AI-powered devices begin to leverage this shared knowledge transfer, we could see an even faster pace of development. So if you think things are developing quickly today, remember we’re only just getting started.

Image Credit: igor kisselev / Shutterstock.com

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AARON FRANK

Aaron Frank is a writer and speaker and one of the earliest hires at Singularity University. Aaron is focused on the intersection of emerging technologies and accelerating change and is fascinated by the impact that both will have on business, society, and culture.

As a writer, his articles have appeared online in Vice's Motherboard, Wired UK and Forbes. As a speaker, Aaron has lectured fo...

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Wonderful pictures of the Earth and the Moon!

Visit Earth Blog for a wonderful picture of the Earth and the Moon.


https://earthspacecircle.blogspot.ca/2016/07/earth-and-moon-seen-by-dscovr.html

On July 5, 2016, the Moon passed between NOAA's DSCOVR satellite and Earth. NASA's EPIC camera aboard DSCOVR snapped these images over a period of about four hours. In this set, the far side of the Moon, which is never seen from Earth, passes by. In the backdrop, Earth rotates, starting with the Australia and Pacific and gradually revealing Asia and Africa.

Image Credit: NASA/NOAA

How to change your wrong beliefs. By Eric Barker

Changing These 4 Beliefs Will Make You Surprisingly Happy *** Before we commence with the festivities, I wanted to thank everyone for helping my first book become a Wall Street Journal bestseller! To check it out, click here. *** Click here to read the post on the blog or keep scrolling to read in-email. Traffic upsets you. People upset you. Your job upsets you... Wrong, wrong and wrong. Actually, none of those things upset you. Your beliefs about them do. That's what the ancient Stoic philosophers believed. From The Daily Stoic: “People are not disturbed by things, but by the views they take of them.” – Epictetus Let's say you expect something to cost $90. Turns out it costs $80. You're thrilled. But if you expect it to cost $30 and it costs $80, you want to murder someone. Price didn't change. Your belief did. And that determined your reaction. Oh, and science agrees with the Stoics here. Big time. Albert Ellis was a psychologist and he took the ideas of the Stoics and weaponized them into some of the most effective therapies that professionals use today. How big a deal was Albert? According to a survey of psychologists he was the 2nd most influential psychotherapist ever. Sigmund Freud came in third. Here’s what Wikipedia says about his system: In general REBT is arguably one of the most investigated theories in the field of psychotherapy and a large amount of clinical experience and a substantial body of modern psychological research have validated and substantiated many of REBTs theoretical assumptions on personality and psychotherapy. And Albert says your beliefs are what cause the majority of unhappiness, anger, and anxiety you experience. Problem is, some of these beliefs are sneaky. You don’t even realize they're there. If I told you that you believed them, you'd deny it. But they're often dictating your reactions -- and making you miserable in the process. So what are some of the most common problematic beliefs Albert identified – and how do we fix them? Let's get to it... #1: "This shouldn't be happening!" This is the big one. Here's how Albert describes the #1 irrational belief we all too often hold: "People and things should always turn out the way I want them to and if they don’t, it’s awful, terrible, and horrible, and that’s not fair." Sounds ridiculous. You would never say that, right? Problem is, you often believe it without realizing it. Say I tell you this toaster over here almost never works. You try to use the toaster. It doesn't work. Do you get furious and throw the toaster at me? No. Reality met expectations. No surprises. No emotional outburst. Now let's apply that same logic in a different scenario... You know the world is not always a fair place, right? But then something unfair happens and... you go ballistic. Does that make sense? Nope. If you really believed the world wasn't always fair and the world promptly delivered some unfairness, you wouldn't get all bent out of shape. Reality met expectations. But what you really believe is the world shouldn't be unfair to you. And that, my dear friend, is crazy talk. Here's Albert: We know the world is not fair, yet we still get overly upset when it’s unfair to us. We start thinking, very early on, that the world should be fair to us in particular... The “upsetness” doesn’t make the problem go away or solve anything (as a matter of fact, you probably make poorer decisions, and deal with others less effectively), but you don’t question your reaction because it seems so natural. So how do you stop getting angry when life (which you acknowledge is unfair) does exactly what you said it would (and acts unfairly)? You need to change that underlying belief -- the one you didn't know you had. Next time you find yourself getting upset, notice it. Pause. And then: Identify the underlying belief: "Uh-oh. I'm believing that this unfair life must treat me fairly, aren't I?" Dispute that belief: "Is this belief rational?" No. Uh-uh. No way, no how. Replace the belief: So what's a more reasonable stance? "I would prefer to be treated fairly, but I know things aren't always going to be to my liking. I'm not surprised and I'm not going to lose my cool." (To learn more about the science of a successful life, check out my bestselling book here.) Okay, so outside events aren’t always gonna go your way and holding an underlying belief that is aligned with that can make life's ups and downs much easier to manage. But what beliefs about your own behavior does Albert say regularly cause you problems? #2: "I Must Be Perfect." Here's how Albert describes it: “I must not fail at important tasks and if I do it’s terrible and I can’t stand it.” Again, you don't always realize this is your underlying belief. If I asked, "Are you human and prone to error?" You'd say yeah. But then you make a mistake and totally freak out. Does not compute. If you really believed you were prone to error, you might be a little disappointed. You'd prefer to always get the A+. But you wouldn't be surprised and get overly emotional. Remember, you don't get angry when broken toasters act like broken toasters. You get angry when you expect broken toasters to act like working toasters. And getting rid of your perfectionist beliefs doesn't mean you're suddenly going to become a slacker who half-asses everything. You can still be persistent. You just don't have to hold silly beliefs that drive you nuts. Here's Albert: Searching for perfect solutions often will lead to stagnation and frustration. Perseverance, tolerance for less than perfection (but striving for it), the pursuit of improvement, and commitment to doing the very best you can, all are healthy, and most likely to yield the best results. Eliminating unreasonable demands for perfect solutions in no way reduces your commitment to doing or being the very best you can do or be. And if that's not enough, research says perfectionism can kill you: Consistent with our hypotheses, findings demonstrated that risk of death was significantly greater for high scorers in perfectionism and neuroticism, compared to low scorers at the time of base line. So how do you deal with that pesky need to always be the best? Again, you have to dispute the underlying belief. Next time you're aiming for 110% and getting worked up, take notice. Ask yourself if the belief is rational (nope) and replace it with something more realistic: "I'm going to work on the project for the next three hours and do my best. The amount of effort I expend is under my control but people's reaction to it isn't." (To learn the seven-step morning ritual that will make you happy all day, click here.) Okay, you're disputing and replacing irrational beliefs. Maybe you're not doing it perfectly at first -- but we don't have to be perfect, now do we? So what about when that irrational belief is like a song stuck in your head? And you just cannot make it stop? #3: "I Should Worry About This." Here's Albert: “If I worry obsessively about some up-coming event or how someone really feels about me things will actually turn out better.” Ridiculous, right? But sometimes that's the belief we're really holding. We worry and worry and worry some more. And if we stop worrying, we beat ourselves up for not worrying enough. It's like we think anxiety is a magic spell that, if chanted constantly, will actually prevent the dreaded thing from happening. For the record, it won't. And you already knew that. But if you believed it deep down, you wouldn't be biting your nails so much. Broken toaster theory all over again. So how do you make the worry song stop playing in your head? You know the answer here: dispute and replace the belief. But with anxiety, it can be trickier because worry seems to operate on autopilot in the background. Time to bring out the big guns... What is worrying? It's your brain's way of reminding you that something is a threat and needs to be dealt with. So what do you do if "dispute and replace" isn't cutting it in the short term? Let your brain know you're taking its reminders seriously. Schedule your worrying. Seriously. Make a "worrying appointment." This works: For those concerned with shedding some of their anxieties, it seems planning a certain time every day to worry may help stop the stress-out cycle. When people with adjustment disorders, burnout or severe work problems used techniques to confine their worrying to a single, scheduled 30- minute period each day, they were better able to cope with their problems, a new study by researchers in the Netherlands finds. Please make sure to tell co-workers, "I'd love to go to that meeting but4PM is when I get all my worrying done for the day." And don't just worry during the appointment  -- dispute and replace. With practice, the worries will subside. Behavioral therapies like this are the most scientifically proven treatments for anxiety. (To learn 6 rituals from ancient wisdom that will make you happy, clickhere.) So you can finally get that worry song to stop playing in your head. But how do we deal with those beliefs about our past that have shaped us? The beliefs that we feel make us who we are? #4: "It's because of my past." Albert explains the belief like this: “It was my past and all the awful things that happened to me when I was a child or in my last relationship or in my last job that causes me to feel and act this way now.” We make mistakes -- often the same ones over and over -- and we say it's due to bad parenting. Or because we were teased in high school. Or because we dated the wrong people. Yes, Albert acknowledged some traumas do leave lasting issues. But many, many people willingly accept more minor past problems as part of their identity and don't really try to correct them. Here's Albert: There is no question that our past experiences have the potential to influence greatly our present behavior, if we let them... Past events won’t become any less real or valid; we can’t change the tapes of those events. We can, however, vigorously change how we think about them. In most cases it's not that the past event caused irrevocable damage; it's that you are presently carrying an irrational belief about yourself that you took away from the event. "I was bullied in school because I was weaker than the other kids. So I am a weak person." And decades later you're still running that buggy old code like it was the latest software update. Yeah, you may have had moments of weakness in the 4th grade. Does that mean you're a weak person at 32? Even though we've changed and our environment has changed, we cling to that outdated belief and it affects how we feel. Then confirmation bias kicks in and we stop noticing evidence to the contrary -- while maintaining a keen eye for everything that validates that irrational belief. "I got nervous during that presentation today. It's because I'm a weak person. Yeah, I killed 37 ninjas with my bare hands on the way from the parking lot to the office this morning, but that was just dumb luck. I've always been weak and I'll always be weak." From The CBT Toolbox: A Workbook for Clients and Clinicians: Because of how our filters (beliefs) are set up, we often notice instances that support the unhealthy beliefs more than we notice those that may support our opposite, healthy beliefs; however, that “evidence” almost always exists as well. So how do we fix this? Of course, dispute and replace. But this one can be tricky because of confirmation bias. We're only noticing and remembering the times when the irrational belief seems to be true (nervous during presentation) and not the times when it's proven false (single-handedly defeating hordes of expertly trained martial arts masters.) So you're gonna need some help with this disputing process. Sit down with an old friend and a piece of paper. Make your case. Write down all the events that happened over the years that prove your irrational belief true. "I am weak because..." When you're done, list all the events that contradict the belief. "I am not weak because..." And your friend gets to add to this list. You don't get veto power over their contributions. Remember, you're biased. From The CBT Toolbox: A Workbook for Clients and Clinicians: One valuable tool involves forcing ourselves to look back over those very same periods of life purposefully looking to see the evidence that supports our healthy beliefs. You may want to rely on family members or friends who were around during each period of life to help you “notice” such evidence. Even if they share things they see as “counting” that you don’t think “should count” write them down anyway... If there is anything on the second list, then you are not cursed by your past forever -- you're cursed by an outdated belief that you still hold. Dispute and replace. Are you weak at times? Probably. But that’s true of everyone. You’re human. Welcome to the party. (To see the schedule that very successful people follow every day, clickhere.) Okay, I now hold the underlying belief we've learned a lot about beliefs. Let's round it all up -- and learn the two words that signal you have some more disputin' and replacin' to do... Sum Up Here are the 4 irrational beliefs that cause you a lot of problems: "This shouldn't be happening!": Do you really expect to always get what you want? No. But if you really believed that you wouldn't be shouting. "I must be perfect.": Not possible. And it'll kill you. You can control effort, not outcome. "I will do my best" is rational. "I mustbe the best" is not. "I should worry about this.": Set a time to worry, to dispute, and to replace. This lets your brain know it doesn't need to be reminding you 24/7. "It's because of my past.": If that's really the case, then you should be in therapy. But your problems are rarely due to dire past traumas, they're usually due to some outdated, irrational belief you still hold. Get a friend to help you dispute and replace. You may have noticed two words that came up again and again: "should" and "must." Albert Ellis hated those words. He felt they were at the core of so much of our emotional suffering. Both imply that the universe needs to bend to your will. And that's not going to happen. "Prefer" all you like, but "should" and "must" are like shaking your fist at the sky when you don't like the weather. It "should" be sunny? Well, it's not. When you align your expectations with reality, you stay cool like Fonzie. And then you're able to do something that might help you get what you "prefer." Whenever you hear yourself saying "should" or "must", it's a sign you might be working off an irrational belief. Time to dispute and replace -- unless you like being unnecessarily stressed and angry. I don't. So out of supreme respect for Albert, I'm not going to say you "should" or "must" obey the above advice... But doing so will make you much happier. That's my underlying -- and very rational -- belief. Please share this on Facebook or Pocket. Thank you! Email Extras Findings from around the internet... + Want to know how the smartest people talk about themselves? Clickhere. + Want to know how to get to sleep quickly? Click here. + Want to know what really makes people quit their jobs? Click here. (Research by the ever-giver Adam Grant. Link thanks to the always insightful Dan Pink.) + Miss last week's post? Here you go: This Is The Best Time To Do Anything: 4 Powerful Secrets From Research. + Ladies, want to know a crazy but simple way to feel less stressed? Click here. + You made it to the end of the email. It's my underlying belief that you are awesome. Crackerjack Time: Would you be interested in a real-life "Breaking Bad" story? Then you definitely want to check out Nick Bilton's new book. It's the true story of how The Silk Road -- the Amazon of illegal drugs -- was created, and law enforcement's hunt to catch it's founder, a former physics grad student turned drug lord. If this sounds like your kinda thing, check out American Kingpin. Thanks for reading! Eric PS: If a friend forwarded this to you, you can sign up to get the weekly email yourself here.

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