How much control do you have over your thoughts? What if you were specifically told not to think of something—like a pink elephant?
A recent study led by UNSW psychologists has mapped what happens in the brain when a person tries to suppress a thought. The neuroscientists managed to ‘decode’ the complex brain activity using functional brain imaging (called fMRI) and an imaging algorithm.
Their findings suggest that even when a person succeeds in ignoring a thought, like the pink elephant, it can still exist in another part of the brain—without them being aware of it.
In their study they tracked the brain activity in 15 participants as they completed several visualizations and thought suppression exercises. Participants were given a written prompt—either green broccoli or a red apple—and challenged not to think of it. To make this task even harder, they were asked to not replace the image with another thought.
After 12 seconds, participants confirmed whether they were able to successfully suppress the image or if the thought suppression failed. Eight people were confident they’d successfully suppressed the images—but their brain scans told a different story. They found that visual cortex—the part of the brain responsible for mental imagery—seemed to be producing thoughts without their awareness.
Brain neurons fired and then pulled oxygen into the blood each time a thought took place. This movement of oxygen, which was measured by the fMRI machine, created particular spatial patterns in the brain.
The researchers decoded these spatial patterns using an algorithm called multivoxel pattern analysis (MVPA). MVPA is a type of decoding algorithm based in machine learning that allows us to read thoughts. The algorithm could distinguish brain patterns caused by the vegetable/fruit prompts.
The scans showed that participants used the left side of their brains to come up with the thought, and the right side to try and suppress it. Prof. Pearson hopes this functional brain mapping will help future researchers know which areas of the brain to target for potential intrusive thought therapies. This study can help explain why forcefully trying not to think about something always fails. For example, for someone trying to quit smoking, trying not to think about having a cigarette is a very bad strategy.
These findings build on a behavioral study Prof. Pearson’s team at UNSW Science’s Future Minds Lab conducted last year, which tested how suppressed thoughts can influence perception.
They know that you can have conscious and unconscious perception in your visual cortex—for example, they can show someone an image of a spider, make the image invisible, but their brain will still process it. But until now, they didn’t know this also worked with thoughts.
Both studies point towards the elusive world of the “unconscious,” which Prof. Pearson plans to explore in his future work.
They’re interested in this idea that imagination can be unconscious—that these thoughts can appear and influence our behavior, without us even noticing. More evidence is starting to suggest unconscious thoughts do occur, and they can decode them.
References: Roger Koenig-Robert et al. Decoding Nonconscious Thought Representations during Successful Thought Suppression, Journal of Cognitive Neuroscience (2020). DOI: 10.1162/jocn_a_01617
A hallmark of severe COVID-19 pneumonia is SARS-CoV-2 infection of the facultative progenitors of lung alveoli, the alveolar epithelial type 2 cells (AT2s). However, inability to access these cells from patients, particularly at early stages of disease, limits an understanding of disease inception.
Now, a team of infectious disease, pulmonary and regenerative medicine researchers at Boston University, studying human stem cell-derived lung cells called type 2 pneumocytes, infected with SARS-CoV-2, have shown that the virus initially suppresses the lung cells’ ability to call in the help of the immune system with interferons to fight off the viral invaders and instead activates an inflammatory pathway called NFkB.
According to the researchers, the inflammatory signals initiated by the infected pneumocytes attract an army of immune cells into lung tissue laden with infected and already dead and dying cells. Their data confirms that SARS-CoV-2 blocks cells from activating one of the anti-viral branches of the immune system early on after infection has set in. The signal the cells would typically send out, a tiny protein called interferon that they exude under threat of disease, are instead delayed for several days, giving SARS-CoV-2 plenty of time to spread and kill cells, triggering a buildup of dead cell debris and other inflammation.
References: Jessie Huang et al. SARS-CoV-2 Infection of Pluripotent Stem Cell-derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response, Cell Stem Cell (2020). DOI: 10.1016/j.stem.2020.09.013
New research has uncovered the previously unknown presence of CD19—a B cell molecule targeted by chimeric antigen receptor (CAR) T cell immunotherapy to treat leukemia, lymphoma, and multiple myeloma—in brain cells that protect the blood brain barrier (BBB).
This discovery may potentially be the cause for neurotoxicity in patients undergoing CD19 directed CAR T cell immunotherapy, according to the research team led by Avery Posey, Ph.D., an assistant professor of Systems Pharmacology and Translational Therapeutics in the Perelman School of Medicine at the University of Pennsylvania and Research Health Science Specialist at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia, PA. The study was published today in Cell.
“Our work has revealed that there is CD19 expression in a subset of cells that are, one, not B cells, and two, potentially related to the neurotoxicity we observe in patients treated with CAR T cell therapy targeting CD19,” Posey said. “The next question is, can we identify a better target for eliminating B cell related malignancies other than CD19, or can we engineer around this brain cell expression of CD19 and build a CAR T cell that makes decisions based on the type of cell it encounters—for instance, CAR T cells that kill the B cells they encounter, but spare the CD19 positive brain cells?”
As so often happens in scientific endeavors, the path to this discovery was made somewhat by chance. Kevin Parker, a Ph.D. student at Stanford and co-author on the paper, was at home analyzing previously published single cell sequencing data sets in his spare time. He found CD19 expression in a data set of fetal brain samples that looked odd, because the accepted wisdom was that CD19 only existed in B cells. So his lab reached out to the pioneers of CAR T cell immunotherapy, Penn Medicine.
“I suggested we test this as a preclinical model. When we treated the mouse model with CAR T cells targeting the mouse version of CD19, we found what looks like the start of neurotoxicities,” Posey said.
The team observed an increase in BBB permeability when mouse CD19 was targeted by CAR T cells, even in mice that lack B cells, but not when human CD19 was targeted as a control treatment (mice do not express human CD19).
“Even more interesting, this BBB permeability was more severe when the CAR T cells were fueled by a costimulatory protein called CD28 than when the CAR T cells used 4-1BB,” Posey said “This difference in the severity of BBB permeability correlates with what we know about the clinical observations of CAR T cell-related neurotoxicities—the frequency of patients experiencing high-grade neurotoxicity is lower for those that received the 4-1BB-based CAR T cells.”
His team sought to investigate the higher incidence of neurotoxicity in CD19-directed immunotherapies, compared to treatments targeting other B cell proteins, such as CD20. Notably, CD19 CAR T cells are sensitive to even low levels of CD19 antigen density, emphasizing the importance of identifying any potential reservoir of CD19 other than B cells.
The researchers’ discovery of CD19 molecules in the brain provides evidence that this increase in neurotoxicity is due to CD19-directed CAR T cell immunotherapies. Posey said, though, that generally this neurotoxicity is temporary and patients recover.
This research also highlights the potential utility of developing a comprehensive human single-cell atlas for clinical medicine. Sequencing is an unbiased, genome-wide measurement of gene expression that can capture even rare populations of cells. These rare cell types might otherwise be missed in measurements of bulk tissue due to their low frequency, but as this study demonstrates could be critically important in understanding the clinical effects of targeted therapy. While current CAR T cells recognize only a single antigen, future generations of CAR T cells may be able to discriminate between unique combinations of target antigens to improve thei
r cell-type specificity. The researchers envision that a comprehensive database of gene expression across all human cell types will enable the precise identification of cell type-specific target antigens which can be used to design safe and effective cellular immunotherapies.
“That’s what we think one of the biggest take-home messages is,” Posey said. “The incredible usefulness of single cell atlas or single cell sequencing technology to determine whether a potential immunotherapy or drug target is going to be present somewhere in the body that we would not normally expect it based on conventional thought and whether this expression may lead to toxicity.”
CD19 is thought to be a lineage-restricted molecule—behaving in a functionally and structurally limited way. But this study shows that some small percentage of brain cells also express CD19.
“We would not have identified that through bulk sequencing, where we’re looking at a population of cells versus a single cell type,” Posey said. “It’s only through single cell sequencing that we’re able to identify that there’s this very small percentage of cells in the brain that also contain this molecule, contrary to popular thought.”
Loading of replicative helicases onto DNA is a key event during the initiation of chromosomal DNA replication. It takes place at specific chromosomal regions termed origins and is facilitated by the ORC protein complex. By resolving the cryo-EM structures of DNA-bound ORC, researchers from the Bleichert group (now at Yale) broaden our understanding of how DNA replication is initiated in animals.
Accurate replication of chromosomal DNA is essential for the survival and propagation of living organisms. Prior to cell division, many different proteins work together and duplicate genomes by semi-conservative replication so that copied chromosomes can be segregated into daughter cells. Genome integrity is sustained by highly efficient and accurate DNA replication exactly once per cell cycle. Failure to replicate DNA precisely can alter gene copy number and chromosome ploidy, which can give rise to genomic instability and a variety of human diseases.
Eukaryotic DNA replication initiation relies on the origin recognition complex (ORC), a DNA-binding ATPase that loads the Mcm2–7 replicative helicase onto replication origins. In yeast, origins are defined by a conserved consensus sequence that is recognized by ORC. By contrast, how replication origins are defined in animals (or metazoans) has remained unclear, but chromatin cues and local DNA structure are thought to help mediate the recognition of the origins. In a new paper, researchers reported cryo-electron microscopy (cryo-EM) structures of DNA-bound Drosophila ORC with and without the co-loader Cdc6.
These structures reveal that Orc1 and Orc4 constitute the primary DNA binding site in the ORC ring and cooperate with the winged-helix domains to stabilize DNA bending. A loop region near the catalytic Walker B motif of Orc1 directly contacts DNA, allosterically coupling DNA binding to ORC’s ATPase site.
Correlating structural and biochemical data showed that DNA sequence modulates DNA binding and remodeling by ORC, and that DNA bending promotes Mcm2–7 loading in vitro. Together, these findings explain the distinct DNA sequence-dependencies of metazoan and S. cerevisiae initiators in origin recognition and support a model in which DNA geometry and bendability contribute to Mcm2–7 loading site selection in metazoans.
The recent discovery of phosphine in the atmosphere of Venus is exciting, as it may serve as a potential sign of life (among other possible explanations).
The researchers, who published their findings in Nature Astronomy, couldn’t really explain how the phosphine got there.
They explored all conceivable possibilities, including lightning, volcanoes and even delivery by meteorites. But each source they modeled couldn’t produce the amount of phosphine detected.
Most phosphine in Earth’s atmosphere is produced by living microbes. So the possibility of life on Venus producing phosphine can’t be ignored.
But the researchers, led by UK astronomer Jane Greaves, say their discovery “is not robust evidence for life” on Venus. Rather, it’s evidence of “anomalous and unexplained chemistry,” of which biological processes are just one possible origin.
If life were to exist on Venus, how could it have come about? Exploring the origins of life on Earth might shed some light.
The ingredients for life (as we know it)
Understanding how life formed on Earth not only helps us understand our own origins, but could also provide insight into the key ingredients needed for life, as we know it, to form.
The details around the origins of life on Earth are still shrouded in mystery, with multiple competing scientific theories. But most theories include a common set of environmental conditions considered vital for life. These are:
Water is needed to dissolve the molecules needed for life, to facilitate their chemical reactions. Although other solvents (such as methane) have been suggested to potentially support life, water is most likely. This is because it can dissolve a huge range of different molecules and is found throughout the universe.
Temperatures higher than 122℃ destroy most complex organic molecules. This would make it almost impossible for carbon-based life to form in very hot environment.
A process to concentrate molecules
As the origin of life would have required a large amount of organic molecules, a process to concentrate organics from the diluted surrounding environment would be required—either through absorption onto mineral surfaces, evaporation or floating on top of water in oily slicks.
A complex natural environment
For life to have originated, there would have had to be a complex natural environment wherein a diverse range of conditions (temperature, pH and salt concentrations) could create chemical complexity. Life itself is incredibly complex, so even the most primitive versions would need a complex environment to originate.
A range of trace metals, amassed through water-rock interactions, would be needed to promote the formation of organic molecules.
So if these are the conditions required for life, what does that tell us about the likelihood of life forming on Venus?
It’s unlikely today …
The possibility of life as we know it forming on the surface of present-day Venus is incredibly low. An average surface temperature above 400℃ means the surface can’t possibly have liquid water and this heat would also destroy most organic molecules.
Venus’s milder upper atmosphere, however, has temperatures low enough for water droplets to form and thus could potentially be suitable for the formation of life.
That said, this environment has its own limitations, such as clouds of sulfuric acid which would destroy any organic molecules not protected by a cell. For example, on Earth, molecules such as DNA are rapidly destroyed by acidic conditions, although some bacteria can survive in extremely acidic environments.
Also, the constant falling of water droplets from Venus’s atmosphere down to its extremely hot surface would destroy any unprotected organic molecules in the droplets.
Beyond this, with no surfaces or mineral grains in the Venusian atmosphere on which organic molecules could concentrate, any chemical building blocks for life would be scattered through a diluted atmosphere—making it incredibly difficult for life to form.
… but possibly less unlikely in the past
Bearing all this in mind, if atmospheric phosphine is indeed a sign of life on Venus, there are three main explanations for how it could have formed.
Life may have formed on the planet’s surface when its conditions were very different to now.
Modeling suggests the surface of early Venus was very similar to early Earth, with lakes (or even oceans) of water and mild conditions. This was before a runaway greenhouse effect turned the planet into the hellscape it is today.
If life formed back then, it might have adapted to spread into the clouds. Then, when intense climate change boiled the oceans away—killing all surface-based life—microbes in the clouds would have become the last outpost for life on Venus.
Another possibility is that life in Venus’s atmosphere (if there is any) came from Earth.
The planets of our inner solar system have been documented to exchange materials in the past. When meteorites crash into a planet, they can send that planet’s rocks hurtling into space where they occasionally intersect with the orbits of other planets.
If this happened between Earth and Venus at some point, the rocks from Earth may have contained microbial life that could have adapted to Venus’s highly acidic clouds (similar to Earth’s acid-resistant bacteria).
A truly alien explanation
The third explanation to consider is that a truly alien form of life (life as we don’t know it) could have formed on Venus’s 400℃ surface and survives there to this day.
Such a foreign life probably wouldn’t be carbon-based, as nearly all complex carbon molecules break down at extreme temperatures.
Although carbon-based life produces phosphine on Earth, it’s impossible to say only carbon-based life can produce phosphine. Therefore, even if totally alien life exists on Venus, it may produce molecules that are still recognizable as a potential sign of life.
It’s only through further missions and research that we can find out whether there is, or was, life on Venus. As prominent scientist Carl Sagan once said: “extraordinary claims require extraordinary evidence.”
Luckily, two of the four finalist proposals for NASA’s next round of funding for planetary exploration are focused on Venus.
These include VERITAS, an orbiter proposed to map the surface of Venus, and DAVINCI+, proposed to drop through the planet’s skies and sample different atmospheric layers on the way down.
This article is republished from The Conversation under a Creative Commons license.
Researchers from the Singapore University of Technology and Design (SUTD) have developed a method perform direct ink writing (DIW) three-dimensional (3D) printing of milk products at room temperature by changing the rheological properties of the printing ink.
3-D printing of food has been achieved by different printing methods, including the widely used selective laser sintering (SLS) and hot-melt extrusion methods. However, these methods are not always compatible with temperature-sensitive nutrients found in certain types of food. For instance, milk is rich in both calcium and protein, but as these nutrients are temperature sensitive, milk is unsuitable for 3-D printing using the aforementioned printing methods which require high temperature. While the cold-extrusion is a viable alternative, it often requires rheology modifiers or additives to stabilize printed structures. Optimizing these additives is a complex and judicious task.
To tackle these limitations, the research team from SUTD’s Soft Fluidics Lab changed the rheological properties of the printing ink and demonstrated DIW 3-D printing of milk (refer to image) by cold-extrusion with a single milk product—powdered milk. The team found that the concentration of milk powder allowed for the simple formulation of 3-D-printable milk inks using water to control the rheology. Extensive characterizations of the formulated milk ink were also conducted to analyze their rheological properties and ensure optimal printability.
Given the versatility of the demonstrated method, they envision that cold extrusion of food inks will be applied in creating nutritious and visually appealing food, with potential applications in formulating foods with various needs for nutrition and materials properties, where food inks could be extruded at room temperature without compromising the nutrients that would be degraded at elevated temperatures.
Physicists from Lancaster University have established why objects moving through superfluid helium-3 lack a speed limit in a continuation of earlier Lancaster research.
Helium-3 is a rare isotope of helium, in which one neutron is missing. It becomes superfluid at extremely low temperatures, enabling unusual properties such as a lack of friction for moving objects.
It was thought that the speed of objects moving through superfluid helium-3 was fundamentally limited to the critical Landau velocity, and that exceeding this speed limit would destroy the superfluid. Prior experiments in Lancaster have found that it is not a strict rule and objects can move at much greater speeds without destroying the fragile superfluid state.
Now scientists from Lancaster University have found the reason for the absence of the speed limit: exotic particles that stick to all surfaces in the superfluid.
The discovery may guide applications in quantum technology, even quantum computing, where multiple research groups already aim to make use of these unusual particles.
To shake the bound particles into sight, the researchers cooled superfluid helium-3 to within one ten thousandth of a degree from absolute zero (0.0001K or -273.15°C). They then moved a wire through the superfluid at a high speed, and measured how much force was needed to move the wire. Apart from an extremely small force related to moving the bound particles around when the wire starts to move, the measured force was zero.
Lead author Dr Samuli Autti said: “Superfluid helium-3 feels like vacuum to a rod moving through it, although it is a relatively dense liquid. There is no resistance, none at all. I find this very intriguing.”
PhD student Ash Jennings added: “By making the rod change its direction of motion we were able to conclude that the rod will be hidden from the superfluid by the bound particles covering it, even when its speed is very high.” “The bound particles initially need to move around to achieve this, and that exerts a tiny force on the rod, but once this is done, the force just completely disappears,” said Dr Dmitry Zmeev, who supervised the project.
References: S. Autti, S. L. Ahlstrom, R. P. Haley, A. Jennings, G. R. Pickett, M. Poole, R. Schanen, A. A. Soldatov, V. Tsepelin, J. Vonka, T. Wilcox, A. J. Woods, D. E. Zmeev. Fundamental dissipation due to bound fermions in the zero-temperature limit. Nature Communications, 2020; 11 (1) DOI: 10.1038/s41467-020-18499-1link: https://www.nature.com/articles/s41467-020-18499-1
People who are more socially integrated or have higher socio-economic status live longer. Recent studies in non-human primates show striking convergences with this human pattern: female primates with more social partners, stronger social bonds or higher dominance rank all lead longer lives.
However, it remains unclear whether social environments also predict survival in male non-human primates, as it does in men. This gap persists because, in most primates, males disperse among social groups, resulting in many males who disappear with unknown fate and have unknown dates of birth.
Researchers in this study presented a Bayesian model to estimate the effects of time-varying social covariates on age-specific adult mortality in both sexes of wild baboons. They compared how the survival trajectories of both sexes are linked to social bonds and social status over the life.
And what they found? They found that, parallel to females, male baboons who are more strongly bonded to females have longer lifespans. However, males with higher dominance rank for their age appear to have shorter lifespans. This finding brings new understanding to the adaptive significance of heterosexual social bonds for male baboons: in addition to protecting the male’s offspring from infanticide, these bonds may have direct benefits to males themselves.
Picture this. It’s a boiling hot summer day, and you just need to cool off. So you pop into a little shop and order yourself a cone of bright-pink ice cream (strawberry is so refreshing) without bothering to read the label first. You take a bite and boom — it’s a thermonuclear explosion in your mouth. That’s not hyperbole on our part: that’s really how the creators of Respiro del Diavolo ice cream describe it. After all, it is made of Carolina Reaper peppers.
Aldwych Cafe and Ice Cream Parlor in Glasgow has a reputation for its haute cuisine ice creams and gelatos. But its newest flavor, Respiro del Diavolo (“Breath of the Devil”) isn’t for your average sweet tooth. You’ll find the Carolina Reaper towards the top of any “hottest pepper” lists — only the Dragon’s Breath and Pepper X chiles claim to be hotter. It clocks in at an eye-popping 1.5 million Scoville units. It’s the kind of pepper that you eat only once, just to prove a point.
Respiro del Diavolo isn’t made entirely of Carolina Reaper peppers, but it’s still incredibly hot. We’re talking 100 times hotter than a jalapeño and 500 times hotter than Tabasco sauce — hot. Speaking with the Evening Times, owner Martin Bandoni struggled to express the sensation of eating the ice cream. “They call the flavor a cream spice but it’s really a flavor sensation, it’s almost to trick your brain … I think everyone is different when they taste it because we hear various types of suggestions.” Meanwhile, his brother Lee didn’t have such a hard time coming up with an accurate description: “a thermal [sic] nuclear explosion in your mouth.”
It should be clear by now that this ice cream is not for the faint of heart. And Aldwych Cafe knows it. That’s why they make everyone who wants to try the stuff sign a waiver. That means you’ve got to be at least 18 years old to order it, and when you do, you free the ice cream parlor of any culpability in case of “personal injury, illness, and possible loss of life.” Yeah, they’re not playing around. In fact, if you check the Facebook page, you’ll see an additional recommendation: bring a friend, just in case you can’t make it home on your own afterward.