Microglia immune cells can join together to form networks when needed, a new study reports. However, certain mutations associated with Parkinson’s disease can impair this process.
Category: neuroscience – Page 777
Binary pan-cancer classes with distinct vulnerabilities defined by pro- or anti-cancer YAP/TEAD activity
Cancer heterogeneity impacts therapeutic response, driving efforts to discover over-arching rules that supersede variability. Here, we define pan-cancer binary classes based on distinct expression of YAP and YAP-responsive adhesion regulators. Combining informatics with in vivo and in vitro gain-and loss-of-function studies across multiple murine and human tumor types, we show that opposite pro-or anti-cancer YAP activity functionally defines binary YAPon or YAPoff cancer classes that express or silence YAP, respectively. YAPoff solid cancers are neural/neuroendocrine and frequently RB1−/−, such as retinoblastoma, small cell lung cancer, and neuroendocrine prostate cancer. YAP silencing is intrinsic to the cell of origin, or acquired with lineage switching and drug resistance. The binary cancer groups exhibit distinct YAP-dependent adhesive behavior and pharmaceutical vulnerabilities, underscoring clinical relevance. Mechanistically, distinct YAP/TEAD enhancers in YAPoff or YAPon cancers deploy anti-cancer integrin or pro-cancer proliferative programs, respectively. YAP is thus pivotal across cancer, but in opposite ways, with therapeutic implications.
Pearson et al. demonstrate that YAP/TAZ, well-known oncogenes, are tumor suppressors in a large group of cancers. Pan-cancer analyses reveal that opposite YAP/TAZ expression, adhesive behavior, and oncogenic versus tumor suppressor YAP/TAZ activity functionally stratify binary cancer classes, which interchange to drive drug resistance. Contrasting YAPoff/YAPon classes exhibit unique vulnerabilities, facilitating therapeutic selection.
A genetic brain disease reversed after birth
As this is the first report of neuro-inflammation in Kleefstra syndrome, the next step is to find out if it also occurs in the human condition. Shinkai believes the chances are high and says he would not be surprised if other neurological diseases caused by epigenetic dysregulation were also related to abnormal inflammation in the brain.
Researchers at the RIKEN Cluster for Pioneering Research (CPR) in Japan report that Kleefstra syndrome, a genetic disorder that leads to intellectual disability, can be reversed after birth in a mouse model of the disease. Published in the scientific journal iScience, the series of experiments led by Yoichi Shinkai showed that postnatal treatment resulted in improved symptoms, both in the brain and in behavior.
Normally, we get two good copies of most genes, one from each parent. In Kleefstra syndrome, one copy of the EHMT1 gene is mutated or missing. This leads to half the normal amount of GLP, a protein whose job is to control genes related to brain development through a process called H3K9 methylation. Without enough GLP, H3K9 methylation is also reduced, and the connections between neurons in the brain do not develop normally. The result is intellectual disability and autistic-like symptoms. “We still don’t know if Kleefstra syndrome is a curable disease after birth or how this epigenetic dysregulation leads to the neurological disorder,” says Shinkai. “Our studies in mice have provided new information about what causes the behavioral abnormalities associated with the syndrome and have shown that a cure is a real possibility in the future.”
Reasoning that extra GLP might be an effective treatment, the researchers performed a series of experiments in mice that were engineered to have only one good copy of the EHMT1 gene. The brains of these mice show characteristics of the human condition, including 40% less GLP and 30% less H3K9 methylation. The mice also display several behaviors seen in humans with Kleefstra syndrome, such as reduced locomotion and greater anxiety. After each experiment, the researchers measured these factors and compared them to normal mice to see if the treatment had been effective.
Which Types of Brain Activity Support Conscious Experiences?
Summary: Brain activity during conscious wakefulness presents large integrated and dynamic network modules which fragment during sleep.
Source: AIP
Consciousness remains one of the brain’s biggest mysteries. We know very little about how it emerges from activity within the brain, but most neuroscientists agree consciousness is dynamic in nature.
Depression, bipolar and schizophrenia share gut bacteria similarities
A number of recent studies have homed in on compelling associations between mental health and the microbiome. These insights into strange gut-brain connections have found links between depression and certain species of gut bacteria, and one study even found symptoms of schizophrenia could be transferred from mouse to mouse via fecal transplants.
But are these microbiome perturbations unique to specific psychiatric conditions, or is there a more common gut bacteria signature shared amongst several conditions?
You don’t see objective reality objectively: neuroscience catches up to philosophy
Objective reality exists, but what can you know about it that isn’t subjective. According to some neuroscientists, not much.
New neuroscience research suggests the cerebral cortex acts as the brain’s hourglass
No one can stay awake forever. While we’re awake, our need for sleep gradually increases. If we deprive ourselves of sleep, our brain functions – such as attention or judgement – are impaired, and sleep becomes irresistible. No matter whether we are on a couch or at work – if we ignore our need for sleep, we ultimately crash.
Although sleep is vital, until now it hasn’t been known which structure of the brain tells us when we are tired. But our recent study has shown in laboratory mice that the cerebral cortex, which is responsible for the most complex brain functions – including perception, language, thought and episodic memory – helps us track our need for sleep.
Drugs, Robots, and the Pursuit of Pleasure: Why Experts Are Worried About AIs Becoming Addicts
It is quickly becoming a hot topic among machine learning experts and those concerned with AI safety.
One of us (Anders) has a background in computational neuroscience, and now works with groups such as the AI Objectives Institute, where we discuss how to avoid such problems with AI; the other (Thomas) studies history, and the various ways people have thought about both the future and the fate of civilization throughout the past. After striking up a conversation on the topic of wireheading, we both realized just how rich and interesting the history behind this topic is.
It is an idea that is very of the moment, but its roots go surprisingly deep. We are currently working together to research just how deep the roots go: a story that we hope to tell fully in a forthcoming book. The topic connects everything from the riddle of personal motivation, to the pitfalls of increasingly addictive social media, to the conundrum of hedonism and whether a life of stupefied bliss may be preferable to one of meaningful hardship. It may well influence the future of civilization itself.