What’s next for lab-grown human embryos?

Researchers are now permitted to grow human embryos in the lab for longer than 14 days. Here’s what they could learn.

Day 12 human embryo cultured and stained to reveal the Epiblast OCT4 (magenta), the Hypoblast GATA6 (Cyan) and F-Actin (yellow).
A human embryo grown in the laboratory for 12 days, showing cells that will form the embryo itself (magenta). Credit: Antonia Weberling, Bailey Weatherbee, Carlos Gantner and Magdalena Zernicka-Goetz

It was day 13 in a set of experiments in Ali Brivanlou’s laboratory and he had an agonizing task ahead. His team of developmental biologists had thawed dozens of human embryos, placed them into individual culture dishes and watched them grow through the earliest stages of development — something that only a handful of researchers worldwide had ever seen. But he knew that it had to end.

The embryos would soon bump up against the 14-day rule, an international consensus that human embryos should be cultured and grown in the lab only until 14 days post-fertilization. Day 14 is roughly when the primitive streak appears, a structure that marks the point at which the embryo sets up the body axes, and begins to distinguish head from tail and left from right.

“It was one of the toughest decisions I’ve had to make in my life, but it was time to stop this experiment,” says Brivanlou, recalling the 2015 research in his lab at the Rockefeller University in New York City. On day 13, the team peeled the embryos from the bottom of the dish and froze them — curtailing any further development. “We didn’t know what was going to happen after that point,” he says.

Now, Brivanlou and other developmental biologists have the chance to find out.

In May, the International Society for Stem Cell Research (ISSCR) released new guidelines1 that relaxed the 14-day rule, taking away the hard barrier. Although only a few labs around the world have perfected the techniques needed to culture human embryos up to day 14, the science is advancing rapidly. The relaxed rule allows lab groups, in countries where it is legal, to apply to the regulators for permission to continue research past 14 days. Such studies could reveal what happens during human development after the embryo would normally have implanted in the uterus, about a week after fertilization. It then goes through a stage called gastrulation, roughly between days 14 and 22, when the body’s main pattern emerges and the foundations are laid for organ generation.

Cracking open a window on these later stages would allow scientists to better understand the nearly one-third of pregnancy losses and numerous congenital birth defects thought to occur at these points in development. In addition, these stages hold clues to how cells differentiate into tissues and organs, which could boost regenerative medicine.

Most researchers expect that Brivanlou’s group and a smattering of others will immediately push the technical boundary of growing human embryos in the lab for longer stretches. The few groups that can do this are in stiff competition. In other places, laws would have to be changed for such research to move forward (see ‘Lifting the limit’). Some researchers in China, for example, are discussing whether to change their national policy, which currently reflects the 14-day cut-off, says Tianqing Li, an embryologist at Kunming University of Science and Technology.

Lifting the limit: an infographic that shows the early stages of human embryo development and what can be studied after 14 days.
Credit: Nik Spencer/Nature

So researchers do not expect a flood of new post-14-day studies just yet — nor are they all convinced such experiments are justified. “I’m cautious about using human embryos as a research system in their own right,” says Naomi Moris, a developmental biologist at the Francis Crick Institute in London.

As a way of skirting the boundary, researchers have in the past five years developed an array of human embryo models, most of which are formed from mixtures of stem cells. These models mimic multiple, but brief, phases of early development and can be made without using the scarce and ethically fraught human embryos donated by people undergoing in vitro fertilization (IVF) treatment. So far, the 14-day rule doesn’t apply to these embryo models. But, as they get more sophisticated, with the potential to form recognizable structures, or even organs, they enter their own ethical grey area.

Whether using models or the real thing, scientists say they have a lot to learn. “Embryos are the great masters,” says Nicolas Rivron, a stem-cell biologist and embryologist at the Austrian Academy of Science’s Institute of Molecular Biotechnology in Vienna. “They are the structures that teach us everything about how we are formed and how we fail.”

Pushing the envelope

The 14-day rule was first proposed in 1979, as IVF technology emerged and human embryos existed for the first time outside the body — although the longest they could survive at the time was a few days. By 2006, when the ISSCR issued its first set of guidelines for human embryonic stem cells (ES cells), the 14-day rule was firmly established in the research community.Limit on lab-grown human embryos dropped by stem-cell body

The guidelines have been widely adopted around the world by researchers and funders. In several countries, including Germany and Austria, it is illegal to do any research on human embryos, and many others impose a 14-day limit by law, such as the United Kingdom, China, Japan, Australia and Canada. In a few places, including the United States and Israel, there are guidelines but no law prohibiting or limiting human embryo research, although it cannot be federally funded in the United States.

The previous update to the ISSCR guidelines came out in 2016, just before two research groups published breakthroughs.

Magdalena Zernicka-Goetz’s lab at the University of Cambridge, UK, began the quest to culture human embryos beyond seven days in 2013. The group wanted to understand what happens beyond the blastocyst, or ‘ball of cells’, stage. Her group finessed the right recipe of hormones and growth factors, and in 2016 her team2 and Brivanlou’s3 reported that they had grown human embryos until day 12–13.

“The discoveries we are making, such as where humans put our future head, are of major importance,” says Zernicka-Goetz, who now splits her time between her lab in the United Kingdom and one at the California Institute of Technology in Pasadena. “I’m fascinated by the second, third and fourth week of development, which we cannot see with ultrasound, but starts the development of the progenitors for the main organs.”

One question concerns how genes are expressed in the embryo’s cells as it grows. In one of the largest studies of human embryos so far, Zernicka-Goetz’s group analysed 4,820 single cells from 16 embryos developing in the lab from the stage when an embryo would normally implant in the womb (day 5) to the preparations for gastrulation at day 11. Single-cell RNA sequencing revealed which genes switch off and which switch on as embryonic cells transition from totipotency, when they can still become any cell in the body, to pluripotency — a more differentiated state4.

Although these developmental signals are known in mice, this study is one of the first to reveal the molecules that underwrite human development.

Immunofluorescence light micrograph of a human embryo 10 days after fertilisation.
A lab-grown human embryo ten days after fertilization, showing the cells that will become the fetus in purple.Credit: Zernicka-Goetz Laboratory, Cambridge University/Science Photo Library

In other experiments that can be done only with human embryos in culture, both Brivanlou and Zernicka-Goetz and their teams followed the fate of human embryos with aneuploid cells. These are cells that have an abnormal number of chromosomes, a condition thought to cause up to half of early pregnancy losses.

IVF clinics typically test just a few of an embryo’s cells to analyse its genetic health. But experiments suggest that this could be misleading. Zernicka-Goetz’s group found that embryos diagnosed with some types of aneuploidy go on to develop normally in the lab5. Brivanlou’s group have analysed gene expression in human embryos from days 3 to 14, and found that cells with abnormal numbers of chromosomes were eliminated — perhaps by developing into supporting tissues or being culled through cell death6. Both studies suggest that the testing for aneuploidy commonly done on IVF embryos probably results in many embryos being wrongly deemed ‘unhealthy’.

Working with human embryos is essential for these insights, says Brivanlou. “We cannot learn this other than from watching it play out,” he says. He is planning experiments — some of which might stretch past day 14 — to try to find out exactly how an embryo containing some aneuploid cells adjusts.

Beyond two weeks

Researchers working with animal embryos have already cultured them beyond the developmental equivalent of 14 days, which could pave the way for similar advances in human embryo culture. In March, Jacob Hanna’s group at the Weizmann Institute of Science in Rehovot, Israel, doubled the time that mouse embryos can be cultured in the laboratory7, from day 5.5 to day 11 (roughly equivalent to human days 13 to 30). Although other researchers describe the process as finicky, the embryos go well into the process of developing organs.

Both Brivanlou and Zernicka-Goetz plan to push the envelope for culturing human embryos further, doing for humans what Hanna’s team has done for mice. Brivanlou wants to unlock the genetic program that turns stem cells into the first brain cells, and also wants to reveal the molecular instructions for a four-chambered beating heart. Both events arise after day 14 and unravelling them could prove key to understanding neurodevelopmental disorders and common congenital heart defects.

Brivanlou and others say that, in the future, researchers will be technically capable of watching a human embryo implant into uterine tissue in the lab. His group is applying to his university’s regulatory committee to extend their research on human embryos to day 21. In that extra week, the entire body plan is set, including the structures that will become spinal cord, brain, bone, heart, blood, muscles and face. “I don’t know if we can push a human embryo past day 14,” he says. “But once we get there, we should move very gently.”

Model embryos

Researchers already have some ways of looking at the process of gastrulation in mammals, not by using real embryos, but by constructing models of them from 3D mixtures of stem cells.

In the past five years, researchers have crafted a variety of embryo models in the lab that can be used to glimpse stages beyond day 14. In most cases, these embryo models are not subject to the 14-day rule or any special review.

Images of iBlastoids with different cellular staining
These embryo models, which mimic the blastocyst stage, were reprogrammed from skin cells.Credit: Monash University

In 2017, Jianping Fu, a biomedical engineer at University of Michigan in Ann Arbor, and his team made the first human embryo model simply by putting ES cells into 3D culture, where they self-organized to form the amniotic sac and the first signs of a primitive streak8. The finding generated a great deal of excitement in the field, Fu says. “That such possibilities exist within human ES cells — they’re amazing.”

Models like Fu’s proliferated, and can now mimic portions of the earliest embryonic stages in mouse and human — implantation8, gastrulation9,10, and the rudimentary beginnings of brain11, spinal cord12 and heart development. For instance, Fu and others have created human neuruloids12, which model the formation of precursors to spinal cord and brain, and which Fu says will help researchers culture functional neurons that could be placed into patients one day. The mixtures of cells often look and behave like embryos at the same stage, but whether they recapitulate the molecular and cellular events of normal development remains a yawning gap in knowledge.

Fu and others acknowledge that, as human embryo models form more complex structures and push further along the developmental timeline, they raise new ethical questions. For instance, their neurons could begin to fire or their heart cells to beat. Or they could acquire the potential to develop beyond the limited stages they mimic so far. Most models lack the full complement of life-supporting tissues that they would need to form a whole embryo, but in the past few years a handful of labs have constructed mouse and human models of the blastocyst stage, called ‘blastoids’. These contain the precursors to these support tissues and could theoretically form the entire organism1315.Lab-grown structures mimic human embryo’s earliest stage yet

The ISSCR has its eye on the area, and its guidelines state that models that contain these supporting tissues must be subject to special oversight and grown for the minimum time necessary to meet the scientific aim. As they evolve, these models will need ethical reconsideration, says Robin Lovell‑Badge, a stem-cell biologist at the Francis Crick Institute who chaired the ISSCR steering committee. “Obviously, this space has to be watched.”

As work in real and model embryos movesforward, scientists are keen to know how similar the two really are. Finding out how models differ in their molecular details, and how their cells behave, is the main reason researchers wish to push beyond 14 days in real embryos. “We can learn a lot from a model,” says Jesse Veenvliet, a developmental biologist at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany. “But it’s important to know where it goes wrong.”

In 2020, Moris and colleagues ran a side-by-side gene expression comparison of mouse embryos and mouse gastruloids and found striking similarities in the timed waves of signalling that set up the body plan16. She says that this exact kind of benchmarking should be done for human gastruloids, too, which would require culturing human embryos up to around day 21. Rivron envisages molecular maps for each stage of human development.

Once enough benchmarking is done, researchers could reduce the number of human embryos used, only turning to them when there is a strong justification.

Stop the clock

But for just how long should researchers watch human development play out in a dish? Critics have said it was irresponsible for the ISSCR to relax the 14-day rule without giving researchers a new stopping point — that it gives the appearance of a green light for embryo research.

Fu was on the ISSCR committee that developed the new guidelines over 18 months and in more than 100 Zoom meetings. “The science is progressing so fast, it was hard to draw another stop sign as a scientific community,” he says. Instead, the guidelines left the door open to do research as long as the appropriate review processes occur.

Brivanlou concurs with the decision. “In my conscience, I know there are great benefits in pushing past 14 days,” he says, pointing to the work on abnormal chromosomes. “It may literally save lives in the next generation.” He and Lovell-Badge argue that it would be unethical not to allow some post-14-day research because it could unlock how organ cell types arise and how miscarriages and birth defects occur.

It’s also becoming fuzzier as to which experiments and models should be accorded the same status as post-14-day embryo research. The ISSCR guidelines draw a clear ethical division, placing only models that include supporting tissues — and that theoretically have the potential to develop fully — in the same category as post-14-day embryos. (The guidelines also ban the transfer of human research embryos, human–animal chimaeric embryos or human embryo models into an animal or human uterus.)

Some researchers are conservative about the lifting of the 14-day line. Moris, for instance, doesn’t think that the public has had a real chance to weigh the consequences of post-14-day experimentation.

Bioethicist Josephine Johnston goes one step further: “I think it’s a mistake to drop the 14-day rule and not propose another rule.” A limit signals that the scientific community understands that society values human embryos and respects that, says Johnston, a bioethicist at the Hastings Center in Garrison, New York. Dropping the limit “has the potential to really shake public trust”. In addition, researchers need to better explain how studying embryos beyond 14 days “would actually help humanity”, she says. They also need to be upfront about the details of research on embryos, Johnston says. “A lot of this research feels very distant, but it’s careless not to have some limits.”

Nature 597, 22-24 (2021)



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What is the new C.1.2 COVID-19 variant? Here’s what we know so far

ByDavid Lao  Global NewsPosted August 30, 2021 7:34 pm Updated August 30, 2021 10:00 pm

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South African researchers are raising concern over the spread of a new COVID-19 variant riddled with a number of mutations, including some associated with increased transmissibility and a resistance to antibodies against the disease.

The variant, named C.1.2, was first detected in May and has spread to a majority of South Africa’s provinces as well as seven other countries, including China, Portugal and the U.K.

In a recent study published by researchers at the Network for Genomics Surveillance in South Africa, the variant was described as “concerning” due to the number of mutations it possessed. The study is yet to be peer reviewed.

READ MORE: Delta variant doubles the risk of COVID-19 hospitalization, study shows

news release from South Africa’s National Institute for Communicable Diseases pointed to the C.1.2 lineage as having mutations seen in other COVID-19 variants of interest or concern, but “also other mutations which are novel.”STORY CONTINUES BELOW ADVERTISEMENT

“While the C.1.2 lineage shares a few common mutations with the Beta and Delta variants, the new lineage has a number of additional mutations,” read the release.

“Based on our understanding of the mutations in this variant, we suspect that it might be able to partially evade the immune response, but despite this, that vaccines will still offer high levels of protection against hospitalization and death.”Click to play video: '4th wave of the COVID-19 pandemic underway in Canada: Dr. Tam'1:294th wave of the COVID-19 pandemic underway in Canada: Dr. Tam4th wave of the COVID-19 pandemic underway in Canada: Dr. Tam – Aug 12, 2021

Despite the scientists having observed such mutations in the variant, they have not yet concluded whether it actually is more contagious or is able to conquer the immunity provided by vaccines or previous infection.

South Africa had been the first country to detect the Beta COVID-19 variant, one of the four variants of concern labelled by the World Health Organization.

Characteristics associated with Beta include increased transmissibility, a higher risk of severe disease from catching the coronavirus as well as evidence of antibody neutralization, according to the WHO.STORY CONTINUES BELOW ADVERTISEMENT

Dr. Gerald Evans, chair of infectious diseases division at Queen’s University in Kingston, Ont., said it’s too early to tell if C.1.2 could pose as much of a threat as that of Delta — an extremely transmissible variant which has driven new waves of the pandemic in several countries across the world, including Canada.

READ MORE: How the Delta variant is reviving COVID-19 surges worldwide“The fact of the matter is, is that this is all [preliminary] stuff and there’s a lot of speculation about what these mutations mean,” said Evans.

“I think probably the most impressive thing is that, you know, where it’s been described in places, it is not able to outcompete Delta.”

Genomic sequencing data from South Africa places the spread of C.1.2 nowhere near that of the dominant Delta as of July. During that month, C.1.2 accounted for three per cent of COVID-19 testing samples in comparison to Delta, which account for 89 per cent in South Africa.

The variant has also not been able to outcompete the other dominant variants of COVID-19 in the countries it has spread to so far.Click to play video: 'Impact of the Delta variant'4:08Impact of the Delta variantImpact of the Delta variant – Aug 5, 2021

Richard Lessells, one of the authors of the South African report on C.1.2, told Reuters that the variant’s emergence tells them the “pandemic is far from over and that this virus is still exploring ways to potentially get better at infecting us.”STORY CONTINUES BELOW ADVERTISEMENT

And while he pointed to C.1.2 as having more immune evasion properties than Delta in particular, he said that people should not be overly alarmed by its discovery, as more mutated variants were bound to emerge late in the pandemic.

READ MORE: Delta variant weakens protection from Pfizer, AstraZeneca COVID-19 vaccines: study

The findings from the South African team have since been flagged to the World Health Organization (WHO).

On Monday, the WHO’s COVID-19 technical lead addressed the research and news of C.1.2 in several statements online.

In a thread posted to Twitter, the WHO’s Maria Van Kerkhove pointed to there being just about 100 sequences of the variant having been identified since it was first reported by South Africa in May. CONTINUES BELOW ADVERTISEMENT“At this time, C.1.2 does not appear to be [upwards] in circulation, but we need more sequencing to be conducted & shared globally,” wrote Van Kerkhove.

She pointed to Delta as still appearing to be the more dominant variant based on available sequences.

Evans said he’s going to be skeptical of the concern over C.1.2 unless he sees more compelling data over the next couple of months from South Africa or anywhere else the variant has spread to.

“I think when it comes to C.1.2, there’s a lot of speculation saying, ‘wow, you know some of these mutations we haven’t seen a lot of, maybe they’re going to represent immune escape or something,’ but it hasn’t been borne out,” he said.

“I think Delta is going to outcompete it and it’ll probably die off. That’s my speculation,” said Evans.

— with files from Reuters

Your brain is cleaning itself while you’re dreaming, new research suggests

Keep it squeaky clean, everybody!

Alexandru Micu by Alexandru MicuAugust 31, 2021 Reading Time: 4 mins readA A

The findings help us better understand why virtually all animals sleep, despite the fact that it leaves us helpless against predators and other threats.

Image via Pixabay.

The team, led by members from the University of Tsukuba explains that a certain phase of sleep (rapid eye movement sleep, or REM) gives our brains the opportunity to perform necessary maintenance. This, in turn, ensures that they’re running at peak capacity the rest of the time. The research builds on previous measurements of blood flow in the brain during different phases of sleep and wakefulness, which yielded conflicting results. In this study, the researchers used a technique to directly visualize how red blood cells move through the brain capillaries of sleeping and awake mice, while also measuring electrical activity in the brain.


“We used a dye to make the brain blood vessels visible under fluorescent light, using a technique known as two-photon microscopy,” says senior author of the study Professor Yu Hayashi. “In this way, we could directly observe the red blood cells in capillaries of the neocortex in non-anesthetized mice.”

“We were surprised by the results. There was a massive flow of red blood cells through the brain capillaries during REM sleep, but no difference between non-REM sleep and the awake state, showing that REM sleep is a unique state”

In order to help elucidate the confusing previous findings around this topic, the authors monitored brain flow rates in different areas of the brain alongside electrical activity. The latter was used to distinguish between different states of awareness (non-REM sleep, REM sleep, full wakefulness). Since we know that the development of certain conditions such as Alzheimer’s — which involve the buildup of waste products in the brain — is associated with reduced blood flow in the brain, the former was used as a rough estimate for maintenance and cleaning processes taking place in the mice’s brains.



The link between the two is that the removal of these waste products involves biochemical processes that eventually culminate in an increased blood flow (as the waste needs to be physically removed) during rest. Disposal of this material doesn’t take place, to the best of our knowledge, during wakefulness; or, at least, not to any extent that we’ve been able to pick up on.

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After recording the differences between the three states, the team also disrupted the mice’s sleeping. They report that this resulted in their brains engaging in a “rebound” REM sleeping pattern later in the experiment. This state, which resembles a stronger REM sleeping state, was likely used to compensate for the earlier disruption, the team hypothesizes. This, by itself, suggests that REM sleep has an important role to play in brain functionality.

Later, the team repeated this sleep disruption experiment with mice whose brain A2a receptors were artificially blocked — these are the same receptors that get blocked after you have a cup of coffee, and doing so makes you feel more awake. In these conditions, they saw a much lower increase in blood flow during both REM and rebound-REM sleep. This is a strong indicator “that adenosine A2a receptors may be responsible for at least some of the changes in blood flow in the brain during REM sleep,” says Professor Hayashi.



Judging from these findings, the team says that there may be merit in investigating whether the heightened blood flow seen in brain capillaries during REM sleep facilitates waste removal from brain tissues. This could, in time, lead us towards treatments or preventive measures against conditions such as Alzheimer’s disease. They also point to adenosine A2a receptors as a prime candidate for such treatments, given the observed role of these neurons in modulating blood flow in the brain during REM sleep.

The paper “Cerebral capillary blood flow upsurge during REM sleep is mediated by A2a receptors” has been published in the journal Cell Reports.

Multi-country study suggests that the psychological burden of COVID-19 has led to increased political unrest

by Beth EllwoodAugust 31, 2021in COVID-19Political Psychology

(Photo credit: Geoff Livingston)

(Photo credit: Geoff Livingston)

New findings published in the journal Psychological Science suggest that the COVID-19 pandemic may have contributed to upsurges of political unrest in many countries. The two-wave study surveyed residents of the United States, Italy, Denmark, and Hungary and found that the perceived psychological burden of COVID-19 was associated with increased antisystemic attitudes and stronger intentions to participate in political violence.

The year 2020 was marked by a coronavirus pandemic that shook the entire globe and was nothing short of catastrophic. At the same time, countries around the world faced an unusual number of demonstrations — some related to the pandemic, and others not. Some scholars have suggested that the COVID-19 crisis is partly responsible for this increased civil unrest, although limited evidence has emerged to support this claim.

Study authors Henrikas Bartusevičius and his colleagues describe a psychological pathway linking the mental burden of COVID-19 to anti-government attitudes. The researchers explain that the pandemic posed a significant threat to citizens’ financial, physical, and mental well-being and that these conditions may have led to increased feelings of social marginalization. This marginalization may have then led to aggression and rebellion against existing societal structures.

To explore this theory, Bartusevičius and his team distributed a two-wave survey among citizens from four different countries: the United States, Italy, Denmark, and Hungary. Notably, these countries differed in the extent they were affected by COVID-19 and the extent they were politically polarized. In April 2020, 6,131 people completed the first survey, and in June/July 2020, 4,568 completed a second survey.

The questionnaires assessed intentions to partake in peaceful political activism and political violence and additionally asked participants whether they had participated in any protests or political violence. The U.S. sample was additionally asked whether they had participated in the Black Lives Matter (BLM) protests or counterprotests. The perceived COVID-19 Burden Scale was used as a measure of the perceived physical and mental health burden associated with the pandemic.×60&!3&btvi=1&fsb=1&xpc=cmkT7SwAXi&p=https%3A//

Across all four countries, the researchers found that perceived COVID-19 burden was associated with both intentions to engage in political violence and self-reports of having engaged in political violence. Among the U.S. sample, COVID-19 burden was also associated with the use of violence during the BLM protests and counterprotests (e.g., engaging in the destruction of property, engaging in physical confrontations with other citizens).

There was less evidence to suggest that COVID-19 burden was linked to peaceful activism. Only in Denmark and Hungary was COVID-19 burden related to nonviolent activism. In the U.S., COVID-19 burden was neither tied to participation in BLM protests nor protests against rioting and looting.

The researchers say it is possible that the psychological burden of the COVID-19 pandemic stirred antigovernment attitudes and increased anger among already marginalized groups, arousing collective action. At the same time, lockdowns likely increased the perception that the government maintains power over citizens, which may have led citizens to feel powerless to create political change. These frustrations may have culminated in violent rather than peaceful demonstrations.

“Our findings constitute a reminder that the COVID-19 pandemic is an all-out crisis, carrying effects far beyond the domain of health . . . It is key to also repair the relationship between citizens and the political system,” Bartusevičius and his colleagues write.

The study authors acknowledge that the four countries they studied were Western, educated, industrialized, wealthy, and democratic and that the results do not generalize to less developed countries. They say that the countries they studied all have strong economies and political structures and countries without these conditions may have experienced even greater unrest in response to the pandemic.

The study, “The Psychological Burden of the COVID-19 Pandemic Is Associated With Antisystemic Attitudes and Political Violence”, was authored by Henrikas Bartusevičius, Alexander Bor, Frederik Jørgensen, and Michael Bang Petersen.

Phasmophobia DOTS Projector – How to Use

Updated  by JoeTheBard3 Comments

phasmophobia dots projector how to use

The DOTS Projector in Phasmophobia is the newly-added ghost detecting tool added in the new update, so people want to know how to use it most efficiently. After all, you need the DOTS Projector to confirm the presence of two new ghosts, the Myling and the Goryo. However, getting used to the projector does require a bit of time, but there are a few things you can do to make things more efficient. We’re gonna cover all of that in our Phasmophobia DOTS Projector – How to Use guide.Phasmophobia DOTS Projector – How to Use

How to Use DOTS Projector Phasmophobia

To use the DOTS Projector in Phasmophobia, you have to activate it by sticking it to a surface. Basically, select it from your inventory and press F while hovering the projector over the spot you want to place it on. Like the motion detector. It can be on the floor, the walls, the ceiling, and apparently even some pieces of furniture. It works by projecting a bunch of green lasers all over the place, allowing you to see an outline of the ghost you’re hunting. If you’ve ever seen that scene with the Kinect from Paranormal Activity 4, you’ll know exactly what I’m talking about.

To make things a little more interesting, the devs have made it so that you have to use the DOTS Projector to detect the two new ghosts, Myling and Goryo. By that, I mean it’s one of the tools you need to identify the ghost. Speaking of, there’s one tip on how to use the DOTS Projector in Phasmaphobia. See, it’s very hard to see the ghost’s outline with the naked eye. What you can do instead is set up some cameras, and watch them from the van with night mode on. You’ll be able to see the silhouette of the ghost very clearly that way.

One more thing that’s important to note – while the DOTS Projector is a necessity with the Myling and Goryo, it can also come in handy with other ghosts, too. The Banshee, Oni, Yurei, Phantom, Wraith, and maybe others will also show up when scanning with the projector. While you can’t use it to identify them, it’s a useful way to zero in on their overall location.


Robert Epstein’s “transducer” theory is an instance of getting something rightMICHAEL EGNOR AUGUST 30, 2021Share 

Many of my posts here at Mind Matters News entail debunking nonsensical materialist theories of the mind–brain relationship. It is altogether fitting and proper that I do so. But, at times, thoughtful and very promising ideas are proposed by modern neuroscientists. One of those ideas is discussed in an essay in Discover Magazine by neuroscientist Robert Epstein.

Epstein, the former editor-in-chief of Psychology Today Magazine, is a senior research psychologist at the American Institute for Behavioral Research and Technology in California and holds a doctoral degree from Harvard University. He proposes that we re-examine a theory that has had a number of prominent proponents over the past several centuries.

It is the theory that the brain is a type of transducer, that is, a device or an organ that converts one signal to another signal, commonly from one medium to another. A microphone, for example, is a transducer that converts sound waves to electrical current. Your eye is a transducer that converts light to vision.

Epstein points out that a host of perplexing neurological problems, such as blindsight (the ability of some blind people to be aware of objects in their environment that they cannot consciously see), mindsight (the phenomenon during some near-death experiences of congenitally blind people in which they are able to see normally), terminal lucidity (the brief period of clear consciousness that sometimes precedes death in dementia patients), hallucinations and such diseases as schizophrenia, among many others, could be explained by the inference that the human brain focuses and transduces consciousness rather than generates it.

In this sense, the brain acts as a transducer between our existence in this world and our consciousness which can access a different realm. This perspective may sound strange, but it has had many reputable defenders, including William James (1842–1910) who proposed it in the late 19th century and is considered the father of modern psychology.

Pressure transmitter in oil and gas process, Send signal to controller and reading pressure in the system, Electronic transducer and sent data from production process to Processor Logic Controller.
electronic transducer

Epstein’s article is fascinating. He goes into considerable detail about the evidence that supports his transduction theory of consciousness. As an example, he considers trying to explain to a 17th-century scientist how a cell phone works. The scientist would be profoundly misled in his study of the cell phone unless he knew that the cell phone was a transducer of a human voice that was being transmitted through the phone rather than generated entirely in and by the phone.

Epstein points out that many theories in modern science are far more incredible than transduction theory. Quantum mechanics is famously counterintuitive and bizarre, and modern physics takes quite seriously theories that entail multiple hidden universes. He points out that transduction theory and the mind–brain relationship would be particularly easy to study in that, unlike the situation in many aspects of modern physics, the transduction device (i.e. the brain) is available for immediate in-depth study.

I believe the transduction theory has a great deal to offer in our scientific study of the mind–brain relationship. It is, of course, a dualist theory. It provides a framework for understanding the close link between brain states and mental states, yet at the same time, it explains mental states in a way that does not invoke nonsensical materialist metaphysics.

A successful understanding of the mind–brain relationship will necessarily involve understanding the brain as a transduction device in one way or another. Such an understanding could prove enormously fruitful and can help us move beyond the current materialist framework in which neuroscience is practiced, which has has held us so far back in our understanding of the mind and the brain. The brain is obviously material but it is just as obvious that the mind has immaterial abilities.

We accept that the ear is a transducer for sound to hearing and the eye is a transducer for light to vision. It is reasonable to infer that the brain is a transducer for thought to body. Transduction theory is a plausible approach to understanding the connection between the mind and the brain. It should be taken seriously by neuroscientists and philosophers of the mind.

You may also wish to read:

The brain does not create the mind; it constrains it. Near-death experiences in which people report seeing things that are later verified give some sense of how the mind works in relation to the brain.
A cynical neurosurgeon colleague told Michael Egnor that he could not account for how a child patient’s NDE account described the operation accurately.


Yes, split brains are weird, but not the way you think. Scientists who dismiss consciousness and free will ignore the fact that the higher faculties of the mind cannot be split even by splitting the brain in half.

Electric robotaxis may not be the climate solution we were led to believe


Fewer cars, not moreBy Andrew J. Hawkins@andyjayhawk  Aug 30, 2021, 11:18am EDT

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GM Robot Car Company Cruise

For years, we’ve been told that electric autonomous taxis can help fight climate change by reducing air pollution. But new research from Harvard Law School suggests these supposedly “zero emissions” vehicles could actually exacerbate many of the problems we are facing today.

A new study led by Ashley Nunes, a fellow at the Labor and Worklife Program at Harvard Law School, concluded that fleets of electric autonomous taxis could “dramatically increase energy consumption and emissions that contribute to climate change — not reduce them.”

“While electric vehicles themselves have lower emissions than traditional gasoline-powered ones, our work shows that deploying electric robocabs en masse on America’s streets could actually increase the number of trips, miles driven, and overall emissions,” Nunes said in a release.“OUR WORK SHOWS THAT DEPLOYING ELECTRIC ROBOCABS EN MASSE ON AMERICA’S STREETS COULD ACTUALLY INCREASE THE NUMBER OF TRIPS, MILES DRIVEN, AND OVERALL EMISSIONS”

Transportation is one of the main contributors to greenhouse gas emissions, with the most significant share coming from light-duty vehicles, personal cars, vans, trucks, and SUVs. Replacing some of those trips with electric autonomous vehicles operating as part of a ride-hailing fleet could help offset some of those emissions.

But by studying data from San Francisco, Nunes’ team found that “ubiquitous electric robocabs might erase those energy savings” by increasing demand for rides while also decreasing ride-pooling or carpooling, largely due to their public perception as easy, cheap, and eco-friendly. In other words, more people would be using these cars to get around who might not have otherwise have done so, thanks to their availability.

“Our work showed that transportation emissions are likely to rise due to the initiation of car trips that — in the absence of electric robocabs — would not be completed, and an increase in the number of Americans who choose to give up sharing rides in favor of using electric robocabs for single occupant trips,” says Nunes.“TRANSPORTATION EMISSIONS ARE LIKELY TO RISE DUE TO THE INITIATION OF CAR TRIPS THAT — IN THE ABSENCE OF ELECTRIC ROBOCABS — WOULD NOT BE COMPLETED”

The study cast doubt on assertions from the AV industry that the advent of electric autonomous vehicles would be a net positive for the environment. Kyle Vogt, co-founder, president, and chief technology officer at Cruise, said as much during an event hosted by the National Federation of the Blind back in 2019.

“I know AVs will change the way we live and move: they’ll save lives, improve accessibility, reduce emissions and air pollution, and give people back the most important resources: their time and their freedom to go where they want to go when they want to go,” Vogt said, according to the transcript.

Cruise often touts its commitment to an all-electric fleet — the company only uses battery-powered Chevy Bolts provided by its financial backer, General Motors — as a key factor that distinguishes it from other AV operators. Most other self-driving car companies use a mix of gas-powered, hybrid, and electric vehicles to comprise their fleets.

The media has also helped push the idea that electric robotaxis would counteract the effects of climate change, with overly speculative headlines like “How self-driving cars could reduce emissions, eliminate parking spots, and add $1.3 trillion to the US economy” and “Driverless cars could be a solution to climate change — but two major things have to happen.”

Some AV operators are aware of the conundrum that could arise from the spread of electric robotaxis. Cruise, for example, is building a purpose-built autonomous vehicle designed primarily for shared rides. “It’s designed to be comfortable if it’s shared, but if it’s just you, you’ve got so much space in here you can really like stretch out,” Vogt told The Verge in 2019.

Promoting shared rides would go a long way toward improving the climate profile of autonomous vehicles in the future, the Harvard team concluded. Rather than handing out tax breaks to people who buy EVs, policymakers should consider financial incentives or discounts for people willing to carpool.PROMOTING SHARED RIDES WOULD GO A LONG WAY TOWARD IMPROVING THE CLIMATE PROFILE OF AUTONOMOUS VEHICLES IN THE FUTURE

Electric robotaxis would have to be more than “50 percent cleaner than today’s electric cars to reduce emissions, given their anticipated increase in trips,” they said. Cleaning up the electrical grid by eliminating the use of coal and polluting energy sources is another solution.

Of course, eliminating the need for car trips altogether by promoting the use of mass transit — or for shorter trips, walking and biking — is the best way to reduce an individual’s overall vehicle miles traveled.

Nunes’ study is the latest to poke holes in “zero emissions” claims by the tech and auto industry. A University of Michigan study in 2018 found the shift toward autonomy could raise (rather than reduce) a vehicle’s energy demandsAnother research paper looked at the behavior of households that were offered a free chauffeur service for 60 hours over a seven-day period, akin to a ride-hailing service or a future driverless car. The study participants’ vehicle miles traveled rose by about 80 percent.

New 2021 Philips OLED+ TVs get picture and sound upgrades

Philips is pitching its new 2021 OLED+ TVs as the perfect combination of picture and sound with upgrades via LG and Bowers & Wilkins

By Chris Martin, Reviews EditorChris Martin | 11 hours ago

Philips has announced a pair of new premium flagship 4K TVs at its summer launch event. The OLED+936 and OLED+986 arrive with various upgrades including a new P5 processor, brighter OLED panel and Bowers & Wilkins sound systems.

The firm will hope the new combination of features will help improve sales and take on rivals such as LG and Samsung who are also embracing the latest Mini-LED technology for TV panels.

philips oled986 2021

The OLED+936 and OLED+986 make for attractive all-round packages at affordable prices, starting at £1,699. They will arrive in September and October respectively and you can read our full Philips OLED+936 review now.

It’s available starting at just 48in, an unusually small size for an 4K OLED TV, along with 55- and 65in options. Meanwhile, the 986 model is only available in 65in.

Either way, you get the latest 5th-gen P5 AI Intelligent Dual Picture Engine promising things like better sharpness, more accurate colours and improved contrast no matter what you connect or which streaming service you use.

Philips says the P5 chip uses a “unique anti-burn-in solution that uses an advanced logo detection function to monitor a grid of 32,400 zones, to very accurately detect static content and gradually reduce the intensity of its local light output and avoid burn-in,” meaning less need to opt for more expensive Mini-LED rivals.Best flagship phone: Summer 2021 buying guide 0% 

Using the LG Evo panel found in the firm’s flagship G1 OLED (2021) set, the new Philips OLED+ models offer 20% brighter viewing.

Philips also continues its partnership with Bowers & Wilkins with the legendary audio firm providing beefy sound systems that are built into the design with Tweeter-on-Top technology, meaning no need to buy an additional product like a soundbar.

Philips OLED+936 soundbar

Sound quality is improved from previous iterations with a 3.1.2 system on the 936 model that has a long list of upgrades including surrounds, cones and voice coils. There’s also Dolby Atmos surround sound support and the 986 features B&W’s proprietary Continuum cones found in the companies iconic 800 Diamond Series speakers

Both the 936 and 986 feature four-sided Ambilight and a wide range of modern TV technology including HDMI 2.1 for 120Hz refresh rate on next-gen consoles (as well as VRR, Freesync Premium & G-Sync), 100Hz Fast Motion Clarity and almost every HDR standard apart from Dolby Vision IQ.

Check our chart of the best TVs.

Another tool in the box: Creation of a molecular “dimmer switch” advances gene editing

A new system has been developed that allows researchers to fine-tune gene expression with oral drugs, work that provides a powerful tool for gene editing.

By Dr Leora Fox August 30, 2021 Edited by Dr Sarah Hernandez

Ateam of scientists recently created an innovative genetic system where a drug taken by mouth could be used to control the action of a gene editor, like those used in CRISPR systems. This has useful applications for research studies in cells and animals, and perhaps most importantly, could lead to improvements in the safety and accuracy of future gene therapies in humans. The technology can be applied broadly for studying genes and diseases, and was developed by researchers with HD expertise, incorporating a drug that is relevant to HD. Though actual clinical trials are a long way off, the company that has recently licensed the technology has an existing interest in HD.

Improving the control of gene therapy

Although the methods for delivery of gene therapies have improved vastly in recent years, it hasn’t yet been possible to control the actions of those therapies once they reach their targets in the brain or other parts of the body. Ideally, when modifying human genetics, we’d want to be able to fine-tune things like the location of the genetic change, the amount of change that occurs at once, and the ability to stop the change in surrounding cells if it proves harmful – those last two have proved to be a particular challenge in gene editing, until now.

<img src="; alt="With the X<sup>on
With the Xon system, scientists can put a stoplight in front of any gene, by inserting the gene and the stoplight together into a genetic package and delivering it to cells in a dish or in a living animal

A recently developed genetic switch system, dubbed Xon, addresses some of these challenges in a novel way. It was created by a team of scientists led by Beverly Davidson at the Children’s Hospital of Philadelphia, joined by researchers at the pharmaceutical company Novartis. The idea behind Xon was to create a gene editing technology that could be precisely delivered and then controlled over time using a drug that acts like an on/off switch.

How does it work?

Imagine a red traffic light that is on all the time, and can only be disabled with a special tool. There’s no way to move forward until the red light turns off. With the Xon system, scientists can put a stoplight in front of any gene, by inserting the gene and the stoplight together into a genetic package and delivering it to cells in a dish or in a living animal. The new gene is present but inactive, meaning it can’t produce messages or proteins, until the stoplight is removed. But when a particular drug reaches the cell, it acts as the tool that turns off the genetic stoplight, activating the gene.

The reason that this is an exciting scientific innovation is that the Xon system allows researchers to insert a gene and turn it on and off by simply adding a drug to a dish of growing cells, or by giving the drug to a research animal. This could be a new way to understand what happens when there is too much or too little of a given gene or protein, or to create a disease model to easily explore genetic interventions at different time points during aging.

In a recent publication in the journal Nature, Davidson’s team tested the technology using a variety of genes involved in neurodegenerative diseases and cancers to show that their levels could be controlled based on when and how much of the stoplight-disabler drug was given.

Combining Xon with CRISPR gene editing

Even more interesting is the potential application of the Xon system to technologies like CRISPR and the future of gene editing as a therapeutic. This recent paper demonstrates the ability of the Xon system to be combined with CRISPR-Cas9 technology, for more precise control of CRISPR editing using a drug fed to mice. Davidson’s team demonstrated this using an artificial gene that can make a mouse’s liver cells glow green. But ultimately the hope is that it could be applied to human therapies.

A system that can help us gain better control of CRISPR gene editing is an exciting prospect because it provides more hope of safely adapting this technology for future medicines. This is not currently possible for most diseases, because direct, irreversible changes to human DNA can have drastic consequences. We wrote recently about the first ever successful safety trial of a CRISPR drug for a human disease that commonly affects the liver. Although it would be marvelous in theory to cut out or correct the HD gene in people, the knife-like CRISPR system almost always leads to additional unwanted changes in other genes. This is why we’ve so often emphasized that gene editing needs to come a long way before we can apply it to the treatment of human brain cells, which can’t be regenerated like cells in the liver.

Coupling Xon with a CRISPR-Cas9 system that targets a disease gene (like the HD gene) would mean that an oral drug could turn the gene editor on and off. 

Coupling Xon with a CRISPR-Cas9 system that targets a disease gene (like the HD gene) would mean that an oral drug could turn the gene editor on and off. The dose could also be adjusted to control the amount of gene editing – not just acting as a tool to disable the red stoplight, but also acting as a “dimmer switch” for precise regulation. Most importantly for safety, if anything went awry, the treatment could be stopped to prevent further changes to their DNA. Right now this is all theoretical, because the Xon system and other gene editing “dimmer switches” are in early developmental stages. Nevertheless, this publication hints at the possibility of applying it to therapies in people, and Novartis has licensed the Xon technology.

So why has this innovation made HD research news?

First and foremost, we know that HD is caused by a change to a single gene, so it has always been a prime candidate for genetic therapies, and dozens of researchers and companies worldwide are developing innovative solutions to treat HD at its source. HDBuzz (and HD researchers) always have an eye out for new technologies that improve upon existing methods. Furthermore, the leaders of the team that published the recent Nature paper are respected HD researchers who have devoted much of their careers to the development of gene therapies.

However, the main reason this publication has popped up as news for the HD community is that the Xon system actually relies on an existing drug to flip the gene editing switch – and that drug is none other than branaplam. Yep, branaplam, the oral drug developed to treat children with SMA, which Novartis will soon be testing in clinical trials for adults with Huntington’s disease.

This does not mean that Xon gene editing has any part in upcoming trials for HD. It simply means that branaplam, a drug with genetic cut-and-paste abilities, forms part of an elegant new system that can be adjusted to control the activity of any gene scientists want to study. “Dimmer switch” systems for gene editing could potentially be designed to use a completely different drug, but in these early experiments, Xon and its precise control with branaplam has stood up to many tests of flexibility and accuracy.

The take home message

The Xon system is a really cool early-stage technology, and though it’s not ready to be applied to human treatments, it is a novel element of the gene editing toolbox. Furthermore, it was created by researchers with HD expertise, and has now been licensed by a major pharmaceutical company which is already invested in HD therapeutics. That bodes well for its continued development in the study and potential treatment of HD and related genetic disorders.

Here’s why Elon Musk’s robot is electrified neoliberalism

Van Badham

Van Badham

It is time to evaluate how much transformational control we give billionaires over our societies, and our lives

A screen grab from a video of the Tesla Bot launch event
Elon Musk’s humanoid Tesla bot should be ready next year, with the commercial application to replace human jobs. Photograph: TESLA

Tue 31 Aug 2021 06.15 BST

Afew weeks ago, Elon Musk announced that his company, Tesla, plans to have a humanoid robot prototype ready next year. The intention is to create a 56kg machine that isn’t “super expensive” to retail. Oh, yes: the commercial application of the planned robot is absolutely to replace human jobs – the ones that Musk himself finds “boring”. Like ones working in factories, and supermarkets.Advertisement

Some argued the announcement was a troll. It wasn’t just that Musk’s speech was preceded by a dancer grooving to dubstep in costume as the robot, or that robotics companies with more skin in the long game than Tesla say the technology is nowhere near what Musk’s proposing. It’s that this convenient moment of dance theatre occurred amid a US federal investigation into Tesla self-driving cars after a series of collisions with parked emergency vehicles.

Elon Musk

Alas, whether it’s a troll, deadly serious or some sly distraction act, we have to take Musk at his word because now that he’s valued at over US$180bn (A$246bn), he has the dollars to crystallise any notion he fancies.

In the past, these have included admirable projects such as Tesla cars and battery storage technology. There’s also been PayPal. But the “Tesla Bot” belongs in a real-world Musk canon of flinging a car into space, his proposed colonisation of Mars, and wiring electrodes into pigs’ brains. This last is apparently part of an attempt to technologically facilitate a “conceptual telepathy” that will allow humanity to prevail in a future war against radical AI, and ultimately envisions brain cavitation with a USB portal in the skull. Musk called it a “FitBit for the brain”. I swear I am not making this up.Advertisement

In the wake of watching Musk’s bro-billionaires Richard Branson and Jeff Bezos indulge themselves in humanity’s first rocket-powered Battle of the Space Wangs, it is beyond time to evaluate how much transformational control we give unelected, self-indulgent billionaires over our societies, and our lives.

The conception of the “Tesla Bot” again reveals the consistently alarming truth: billionaires have had their wealth rewarded with unaccountable power for so long they no longer know and certainly don’t care about what the world looks like for the rest of us.

Like what happens to jobs. “The job of attaching bolts to cars with a spanner” is, apparently, the one for the robot to replace, even though manufacturing has been skilled, respectable work for generations of human beings. Also cited for robot-replacement is grocery collection from supermarkets, which has, for all its pay deprivations, provided flexible work opportunities for people managing complex care commitments.

Musk’s announcement didn’t, of course, come with an alternative jobs plan for the displaced. Just the vague suggestion that an expensive, unpopular and desocialising “universal basic income” scheme – the responsibility of governments, of course, not corporations like his own – might somehow pick up the slack.

Arwa Mahdawi


Jobs aren’t just about the work you do, they’re about the community and collective enrichment of skill that the workplace provides. The depressing lack of that socialisation felt by the vast swathes of Australians presently locked down by coronavirus is the bleak inertia of “hysteresis” – a syndrome known too well by the long term unemployed.

It’s likely to be experienced by far more people and long beyond coronavirus, given how excitedly Musk spoke of the profound impact the “Tesla Bot” was likely to have on the economy. The robot could plug shortages in the labour market, he said.

That’s the commercial appeal of the “Tesla bot” to its prospective market of employers.

Musk’s robot, you see, is electrified neoliberalism.

Employers do not like labour shortages because labour shortages empower workers to make demands for fair wages and conditions. The labour shortage that followed in the wake of Europe’s bubonic plague ended serfdom across much of western Europe; formerly all-powerful land barons were forced to compete for surviving labourers.

The complex impact of coronavirus in the United States is having similar effects. According to the US Department of Labor, there are presently more than 10 million job openings there, and suggestions that there are about one million more jobs available than workers looking to fill them.Advertisement

After years of wielding the threat of unemployment as a means of wage suppression, labour shortages are providing workers enough bargaining power to hold out for pay increases, or to trade their present jobs for higher-paying ones elsewhere.

Into this rare window of opportunity for working people to regain some workplace ground steps Musk’s proposition of an affordable Tesla robot whose primary function is to snatch it away.

The old Silicon Valley motto of “go fast and break things” may be how screamingly wealthy unaccountable brain-farters like to pretend they’re punk rock, but as a governing principle for a society, what gets broken are people.

This is not a neo-Luddite screed. In Australia, the introduction of technology to healthcare did not destroy nursing because nursing unions mobilised enough local democratic will for their existing jobs to be enhanced by innovation, not replaced by it. Democratic regulation can, should and must impose necessary lines between entrepreneurship and aristocratic folly; billionaires do not self-regulate.

But a regulatory approach that waits until the horse has gone out and built a robot before the stable door gets shut is too late to the problem.Advertisement

Our world is of finite resources. A system that privileges a few to pursue personal fascinations with an apparent flagrant disregard for everyone else is one that not merely fails the majority, but endangers them.

There is an old-fashioned way to ensure that in the west, as least, management of those resources are brought safely under democratic control. Tax the billionaires into the ground.