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Comment by Dr. Krishna Kumari Challa on May 17, 2023 at 8:26am

The paper published in Nature describes the overall genomic differences found when comparing primary and metastatic tumors and highlights the fact that the differences are highly dependent on the type of cancer studied, as well as the tumor's exposure to previous anti-tumor treatments.

One could state that this work confirms many observations that were previously done in cancer type-specific studies. However, the pan-cancer nature of the current study demonstrates which processes and mechanisms are shared between tumor types and also quantifies their prevalence per tumor type. Such a systematic analysis and comparison from a genome-wide perspective has never been performed before.

The second study, published in parallel in the journal Nature Genetics, presents an analysis of the genomic alterations that allow tumors to escape the immune system, as well as a comparison of their prevalence in primary and metastatic tumors.

The researchers found that the prevalence of genetic immune escape is highly variable between tumor types and that in certain tumor types only a single mechanism is present, while in others various processes were affected. Furthermore, they showed that there are not many differences between primary and metastatic tumors, indicating that immune evasion is a characteristic that is acquired relatively early in tumor development.

This is the first time a complete tumor genome-wide sequencing dataset has been generated for primary and metastatic tumors of this magnitude. These data are public and available for research, providing a new global resource for further research into the biology and evolution of cancer, as well as the development of new therapies to combat the disease.

Part 2

Comment by Dr. Krishna Kumari Challa on May 17, 2023 at 8:25am

Unique insights into differences between primary and metastatic cancer by large-scale DNA data analyses

Cancer is caused by DNA changes that cause a cell to gradually change from benign to malignant. This can lead to metastases in other parts of the body. By analyzing the DNA data of more than 7,000 patients, the researchers show that there are major differences between primary and metastatic cancer and that there are also tumor types in which the primary tumor and the metastasis hardly differ from one another. By studying the types of DNA changes and the consequences of the changes, important insights into the underlying biological processes were obtained.

Researchers have mapped the DNA changes of the 23 most common tumor types. They have studied the differences in genetic characteristics between the source of the cancer, the primary tumor, and metastatic tumors.

Unique collections of whole genome sequencing data from tumors were used. This enabled the researchers to study in great detail which changes in the tumor had occurred during and after the tumor had developed. The researchers have harmonized and systematically compared the world's largest publicly available data sets of primary tumors (from the international PCAWG consortium with information from ~2,800 patients) and metastatic tumors (Hartwig Medical Database, ~4,400 patients). The results of this research were published May 10 in the journals Nature and Nature Genetics.

Part 1

Comment by Dr. Krishna Kumari Challa on May 16, 2023 at 1:25pm

Mouse Study Reveals Unlikely Connection Between Menthol And Alzheimer's

A new study reports something strange: When mice with Alzheimer's disease inhale menthol, their cognitive abilities improve. It seems the chemical compound can stop some of the damage done to the brain that's usually associated with the disease.

In particular, researchers noticed a reduction in the interleukin-1-beta (IL-1β) protein, which helps to regulate the body's inflammatory response – a response that can offer natural protection but one that leads to harm when it's not controlled properly.

The team behind the study says it shows the potential for particular smells to be used as therapies for Alzheimer's. If we can figure out which odors cause which brain and immune system responses, we can harness them to improve health.

Researchers  have focussed on the olfactory system's role in the immune and central nervous systems, and they have confirmed that menthol is an immunostimulatory odour in animal models.

They observed that short exposures to this substance for six months prevented cognitive decline in the mice with Alzheimer's and, what is most interesting, also improved the cognitive ability of healthy young mice.

https://www.frontiersin.org/articles/10.3389/fimmu.2023.1130044/full

Comment by Dr. Krishna Kumari Challa on May 16, 2023 at 12:24pm

Study reveals 'developmental window' for thinking styles

While people change and learn throughout life, experts recognize that certain formative periods, known as developmental windows, are crucial for acquiring particular skills. For example, using vocalizations and words to interact with people in the first few years of life is critical for children's language learning.

A recent study by an international team suggests there may be a developmental window for reasoning skills as well—the first 25 years of life—and that a person's social, political and economic environment strongly influences how they acquire these skills. Their findings are published in the journal PLOS One.

The researchers found that following the collapse of Romania's authoritarian communist regime in 1989, the rapid increase in education and technology use and the transition from a single, government-controlled source of information to diverse sources had a strong effect on the way people, particularly younger generations, thought about and determined truthfulness, a process known as "epistemic thinking."

Epistemic thinking runs the gamut from absolutist thinking, the belief that only one claim can be right, to multiplist thinking, the belief that more than one claim could be right—it's just a matter of opinion. Finally, evaluativist thinking posits that assertions can be evaluated in terms of both logic and evidence.

Amalia Ionescu et al, The effects of sociocultural changes on epistemic thinking across three generations in Romania, PLOS ONE (2023). DOI: 10.1371/journal.pone.0281785

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Comment by Dr. Krishna Kumari Challa on May 16, 2023 at 11:39am

The researchers studied these solitons by examining the behavior of light that would pass near them. Because they are objects of extreme space-time, they bend space and time around them, which affects the path of light. To a distant observer, these solitons would appear exactly as we predict black holes to appear. They would have shadows, rings of light, the works. Images derived from the Event Horizon Telescope and detected gravitational wave signatures would all behave the same.

It's only once you got close would you realize that you are not looking at a black hole. One of the key features of a black hole is its event horizon , an imaginary surface that if you were to cross it you would find yourself unable to escape. Topological solitons, since they are not singularities, do not feature event horizons.

These topological solitons are incredibly hypothetical objects, based on our understanding of string theory, which has not yet been proven to be a viable update to our understanding of physics. However, these exotic objects serve as important test studies. If the researchers can discover an important observational difference between topological solitons and traditional black holes, this might pave the way to finding a way to test string theory itself.

Pierre Heidmann et al, Imaging topological solitons: The microstructure behind the shadow, Physical Review D (2023). DOI: 10.1103/PhysRevD.107.084042

Part 2

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Comment by Dr. Krishna Kumari Challa on May 16, 2023 at 11:38am

Black holes might be defects in spacetime

A team of theoretical physicists have discovered a strange structure in space-time that to an outside observer would look exactly like a black hole, but upon closer inspection would be anything but: they would be defects in the very fabric of the universe.

Einstein's general theory of relativity predicts the existence of black holes, formed when giant stars collapse. But that same theory predicts that their centers are singularities, which are points of infinite density. Since we know that infinite densities cannot actually happen in the universe, we take this as a sign that Einstein's theory is incomplete. But after nearly a century of searching for extensions, we have not yet confirmed a better theory of gravity.

But we do have candidates, including string theory. In string theory all the particles of the universe are actually microscopic vibrating loops of string. In order to support the wide variety of particles and forces that we observe in the universe, these strings can't just vibrate in our three spatial dimensions. Instead, there have to be extra spatial dimensions that are curled up on themselves into manifolds so small that they escape everyday notice and experimentation. That exotic structure in spacetime gave a team of researchers the tools they needed to identify a new class of object, something that they call a topological soliton. In their analysis they found that these topological solitons are stable defects in space-time itself. They require no matter or other forces to exist—they are as natural to the fabric of space-time as cracks in ice. The research is published in the journal Physical Review D.

Part 1

Comment by Dr. Krishna Kumari Challa on May 16, 2023 at 11:32am

Accretion disk around black holes recreated in the lab

Researchers have created a spinning disk of plasma in a lab, mimicking disks found around black holes and forming stars.

The experiment more accurately models what happens in these plasma disks, which could help researchers discover how black holes grow and how collapsing matter forms stars. As matter approaches black holes it heats up, becoming plasma—a fourth state of matter consisting of charged ions and free electrons. It also begins to rotate, in a structure called an accretion disk. The rotation causes a centrifugal force pushing the plasma outwards, which is balanced by the gravity of the black hole pulling it in.

These glowing rings of orbiting plasma pose a problem—how does a black hole grow if the material is stuck in orbit rather than falling into the hole? The leading theory is that instabilities in magnetic fields in the plasma cause friction, causing it to lose energy and fall into the black hole.

The primary way of testing this has been using liquid metals that can be spun, and seeing what happens when magnetic fields are applied. However, as the metals must be contained within pipes, they are not a true representation of free-flowing plasma.

Now, researchers have used their Mega Ampere Generator for Plasma Implosion Experiments machine (MAGPIE) to spin plasma in a more accurate representation of accretion disks. Details of the experiment are published May 12 in the journal Physical Review Letters.

V. Valenzuela-Villaseca et al, Characterization of Quasi-Keplerian, Differentially Rotating, Free-Boundary Laboratory Plasmas, Physical Review Letters (2023). DOI: 10.1103/PhysRevLett.130.195101

Comment by Dr. Krishna Kumari Challa on May 16, 2023 at 11:28am

Scientists identify mutated gene behind mirror movement disorder

Mirror movement disorder is an inherited neurological condition first manifested by involuntary movements, primarily in the arms and hands, at an early age. In those affected, the right hand involuntarily reproduces the movements of the left hand and vice versa, hence the term "mirror movement."

The disorder can cause pain in the arms during prolonged activities as well as difficulties in performing tasks requiring left-right coordination.

Mirror movement disorder has a daily impact on the life of those affected.

In fact, the simple act of buttoning one's shirt or tying one's shoelaces can be challenging, as well as practicing certain sports or music instruments such as the piano.

Over the last 30 years, scientists have identified a group of genes called the Netrin signaling pathway that work together to attract neurons connecting the left and right sides of the brain to each other and to the spinal cord. This mechanism of neuronal guidance during embryonic development is essential for motor development.

A 

new study sheds light on a new genetic mutation that causes mirror movement disorder and incites its mechanism of action at the molecular level. Using a preclinical model, the researchers found that the mutation in a gene newly involved in the Netrin pathway results in abnormal movements, similar to those observed in the disorder.

The Canadian study is based on studying the genetics of a family whose members have carried the disease for more than four generations. The advance is good news for people with the condition who, until now, did not know which mutated gene was the cause, the scientists say.

Identifying the genes involved is an important first step towards rapid and effective diagnosis; understanding the mechanisms causing mirror movements is also essential in the search for innovative treatments, and could also help target other conditions caused by developmental defects of the nervous system.

 Sabrina Schlienger et al, Genetics of mirror movements identifies a multifunctional complex required for Netrin-1 guidance and lateralization of motor control, Science Advances (2023). DOI: 10.1126/sciadv.add5501

Comment by Dr. Krishna Kumari Challa on May 13, 2023 at 9:53am

New study puts a definitive age on Saturn's rings

A new study has delivered the strongest evidence yet that Saturn's rings are remarkably young—potentially answering a question that has boggled scientists for well over a century.

The research, published May 12 in the journal Science Advances, pegs the age of Saturn's rings at no more than 400 million years old. That makes the rings much younger than Saturn itself, which is about 4.5 billion years old.

The researchers arrived at that closure by studying what might seem like an unusual subject: dust.

Tiny grains of rocky material wash through Earth's solar system on an almost constant basis. In some cases, this flux can leave behind a thin layer of dust on planetary bodies, including on the ice that makes up Saturn's rings.

In the new study, researchers set out to put a date on Saturn's rings by studying how rapidly this layer of dust builds up.

Think about the rings like the carpet in your house. If you have a clean carpet laid out, you just have to wait. Dust will settle on your carpet. The same is true for the rings.

It was an arduous process: From 2004 to 2017, the research team used an instrument called the Cosmic Dust Analyzer aboard NASA's late Cassini spacecraft to analyze specks of dust flying around Saturn. Over those 13 years, the researchers collected just 163 grains that had originated from beyond the planet's close neighborhood. But it was enough. Based on their calculations, Saturn's rings have likely been gathering dust for only a few hundred million years.

The planet's rings, in other words, are new phenomena, arising (and potentially even disappearing) in what amounts to a blink of an eye in cosmic terms.

Sascha Kempf, Micrometeoroid infall onto Saturn's rings constrains their age to no more than a few hundred million years, Science Advances (2023). DOI: 10.1126/sciadv.adf8537. www.science.org/doi/10.1126/sciadv.adf8537

Comment by Dr. Krishna Kumari Challa on May 13, 2023 at 8:49am

Fearful memories of pain stored in the prefrontal cortex could shape the experience of pain later in life

While pain and fear are very different experiences, past studies showed that they can sometimes be closely related to one another. For instance, when many animals and humans are in dangerous or life-threatening situations, acute fear can suppress their perception of pain, allowing them to fully focus their attention on what is happening to them.

Conversely, research showed that when humans experience high levels of pain, they can create long-term and associative fear memories that make them fearful of situations that they associate with the pain they felt. These memories can in turn increase their sensitivity to pain or lead to the development of unhelpful behavioral patterns aimed at avoiding pain.

The increase in the intensity with which animals or humans perceive pain after very painful past experiences could be liked to their fearful anticipation of pain. The exact neural underpinnings of this process, however, are still poorly understood.

Researchers have recently carried out a study aimed at better understanding which regions of the mice brain stores very painful experiences and how these stored memories can affect future experiences of pain. Their findings, published in Nature Neuroscience, suggest that these memories are stored in the prefrontal cortex, the area covering the front part of the mammalian brain.

The researchers conducted a series of experiments on adult mice using a neural tagging method and optogenetic techniques. During these experiments, the mice received small electric shocks on their feet and were conditioned to become fearful of receiving these shocks again. The team also used optogenetic techniques to either activate or suppress different neural circuits in the mice's brain, to determine how this would affect their sensitivity to pain.

They found that in mice that long-term associative fear memory stored in neuronal engrams in the prefrontal cortex determines whether a painful episode shapes pain experience later in life.

Furthermore, under conditions of inflammatory and neuropathic pain, prefrontal fear engrams expand to encompass neurons representing nociception and tactile sensation, leading to pronounced changes in prefrontal connectivity to fear-relevant brain areas. Conversely, silencing prefrontal fear engrams reverses chronically established hyperalgesia and allodynia.

These results reveal that a discrete subset of prefrontal cortex neurons can account for the debilitating comorbidity of fear and chronic pain and show that attenuating the fear memory of pain can alleviate chronic pain itself.

Alina Stegemann et al, Prefrontal engrams of long-term fear memory perpetuate pain perception, Nature Neuroscience (2023). DOI: 10.1038/s41593-023-01291-x

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