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Comment by Dr. Krishna Kumari Challa on April 19, 2024 at 9:51am

AI tool predicts responses to cancer therapy using information from each cell of the tumour

With more than 200 types of cancer and every cancer individually unique, ongoing efforts to develop precision oncology treatments remain daunting. Most of the focus has been on developing genetic sequencing assays or analyses to identify mutations in cancer driver genes, then trying to match treatments that may work against those mutations.

But many, if not most, cancer patients do not benefit from these early targeted therapies. In a new study published in the journal Nature Cancer, scientists describe a first-of-its-kind computational pipeline to systematically predict patient response to cancer drugs at single-cell resolution. 

Dubbed PERsonalized Single-Cell Expression-Based Planning for Treatments in Oncology, or PERCEPTION, the new artificial intelligence–based approach dives deeper into the utility of transcriptomics—the study of transcription factors, the messenger RNA molecules expressed by genes that carry and convert DNA information into action.

A tumor is a complex and evolving beast. Using single-cell resolution can allow us to tackle both of these challenges.

PERCEPTION allows for the use of rich information within single-cell omics to understand the clonal architecture of the tumor and monitor the emergence of resistance (In biology, omics refers to the sum of constituents within a cell).

The ability to monitor the emergence of resistance is the most exciting part for researchers. It has the potential to allow them to adapt to the evolution of cancer cells and even modify their treatment strategy.

PERCEPTION: Predicting patient treatment response and resistance via single-cell transcriptomics of their tumors, Nature Cancer (2024). DOI: 10.1038/s43018-024-00756-7

Comment by Dr. Krishna Kumari Challa on April 19, 2024 at 9:46am

Scientists uncover 95 regions of the genome linked to PTSD

In post-traumatic stress disorder (PTSD), intrusive thoughts, changes in mood, and other symptoms after exposure to trauma can greatly impact a person's quality of life. About 6% of people who experience trauma develop the disorder, but scientists don't yet understand the neurobiology underlying PTSD.

Now, a new genetic study of more than 1.2 million people has pinpointed 95 loci, or locations in the genome, that are associated with risk of developing PTSD, including 80 that had not been previously identified. The study, from the PTSD working group within the Psychiatric Genomics Consortium (PGC—PTSD) together with Cohen Veterans Bioscience, is the largest and most diverse of its kind, and also identified 43 genes that appear to have a role in causing PTSD. The work appears in Nature Genetics.

This discovery firmly validates that heritability is a central feature of PTSD based on the largest PTSD genetics study conducted to date and reinforces there is a genetic component that contributes to the complexity of PTSD.

The findings both confirm previously discovered genetic underpinnings of PTSD and provide many novel targets for future investigation that could lead to new prevention and treatment strategies.

Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder, Nature Genetics (2024). DOI: 10.1038/s41588-024-01707-9

Comment by Dr. Krishna Kumari Challa on April 18, 2024 at 11:02am

To figure it out, the researchers investigated the effect of gamma radiation on a species of tardigrade called Hypsibius exemplaris. They placed tardigrades in a benchtop irradiator that exposed the critters to gamma rays emitted by the beta decay of cesium-137. Since the amount of radiation is known, they were able to expose the tardigrades to specific doses – one lower dose that is within tolerable levels, and a much higher median lethal dose.

To their surprise, although H. exemplaris does have Dsup, the radiation exposure didn't seem to trigger it. In fact, the tardigrades' DNA took a pretty big whack of radiation damage.

Rather than prophylactic protection, the tardigrades ramped up production of DNA repair genes to such a degree that their products became some of the most abundant in their microscopic bodies. By 24 hours after radiation exposure, the tardigrades had repaired most of the DNA broken by ionizing radiation.
In a follow-up, the researchers expressed some of the tardigrade repair genes in a culture of Escherichia coli, and exposed samples of the bacterium to ionizing radiation. Bacteria that had been inoculated with tardigrade genes showed a similar DNA repair ability to that seen in H. exemplaris, but not seen in untreated E. coli.
This suggests, the researchers found, that H. exemplaris is able to sense ionizing radiation, and mount a response that allows it to survive doses that would obliterate other animals.

These animals are mounting an incredible response to radiation, and that seems to be a secret to their extreme survival abilities.

https://www.cell.com/current-biology/abstract/S0960-9822(24)00316-6

Comment by Dr. Krishna Kumari Challa on April 18, 2024 at 11:00am

Scientists Discover How Tardigrades Survive Blasts of Radiation

Tardigrades are possibly the most indestructible animal on Earth. These microscopic little beasties can take almost anything humans throw at them, and waddle away perfectly intact.

 

The strategies behind these feats of superheroic survival are multiple, from a damage suppressor protein that literally protects their DNA, to a dehydrated, suspended animation 'tun' state that they can enter when external conditions get untenable.

And now, scientists have uncovered a new one. They're able to turn up the dial on damage repair to 11.

They blasted tardigrades with gamma rays, and watched to see how they responded.

We've known about tardigrades' fascinating resistance to ionizing radiation for decades. They can survive around 1,000 times the dose that would be lethal to humans, and continue going about their tiny lives as though it were nothing.

The damage suppression protein, Dsup, is thought to play a role in this for some tardigrades, but not all tardigrade species have Dsup or a homolog thereof, suggesting that there is some other means of survival at play.

Part 1

Comment by Dr. Krishna Kumari Challa on April 18, 2024 at 10:24am

Sink to source: Does what we put into our plumbing end up back in the water supply?

When you see an advertisement for a detergent promising to brighten your clothes, something called a fluorescent whitening compound, or optical brightener, is probably involved. Such material absorbs UV light and emits visible blue light via fluorescence. The result? Brighter whites, vibrant colors. Yes, your clothes are glowing.

However, these brighteners can make their way into the water supply!

 When limestone and dolomite dissolve, they can form spectacular caves and sinkholes characteristic of a karst terrain. Karst aquifers can also feature interconnected fractures that create conduits that channel water. These aquifers are a major source of drinking water around the world. Unfortunately, they're also exceptionally vulnerable to pollution. Features that connect Earth's surface directly with an aquifer can funnel pollutants into water supplies.

Researchers have detected high concentrations of fluorescent whitening compounds and microplastics in these waters.

 When fluorescent whitening compounds, which definitely come from humans, and microplastics rise and fall together in water samples, that covariation indicates that microplastic contamination is probably coming from wastewater. Indeed, this is the first study to show such a link in samples from karst springs.

Luka Vucinic et al, Understanding the impacts of human wastewater effluent pollution on karst springs using chemical contamination fingerprinting techniques, EGU General Assembly (2024). DOI: 10.5194/egusphere-egu24-11063

Comment by Dr. Krishna Kumari Challa on April 18, 2024 at 10:03am

To explore how working memory functions, investigators recorded the brain activity of 36 hospitalized patients who had electrodes surgically implanted in their brains as part of a procedure to diagnose epilepsy. The team recorded the activity of individual brain cells and brain waves while the patients performed a task that required use of working memory.

On a computer screen, patients were shown either a single photo or a series of three photos of various people, animals, objects or landscapes. Next, the screen went blank for just under three seconds, requiring patients to remember the photos they just saw. They were then shown another photo and asked to decide whether it was the one (or one of the three) they had seen before.

When patients performing the working memory task were able to respond quickly and accurately, investigators noted the firing of two groups of neurons: "category" neurons that fire in response to one of the categories shown in the photos, such as animals, and "phase-amplitude coupling," or PAC, neurons.

PAC neurons, newly identified in this study, don't hold any content, but use a process called phase-amplitude coupling to ensure the category neurons focus and store the content they have acquired.

PAC neurons fire in time with the brain's theta waves, which are associated with focus and control, as well as to gamma waves, which are linked to information processing. This allows them to coordinate their activity with category neurons, which also fire in time to the brain's gamma waves, enhancing patients' ability to recall information stored in working memory.

Imagine when the patient sees a photo of a cat, their category neurons start firing 'cat, cat,cat, cat' while the PAC neurons are firing 'focus/remember'.
Through phase-amplitude coupling, the two groups of neurons create a harmony superimposing their messages, resulting in 'remember cat.' It is a situation where the whole is greater than the sum of its parts, like hearing the musicians in an orchestra play together. The conductor, much like the PAC neurons, coordinates the various players to act in harmony.

PAC neurons do this work in the hippocampus, a part of the brain that has long been known to be important for long-term memory. This study offers the first confirmation that the hippocampus also plays a role in controlling working memory.

Ueli Rutishauser, Control of working memory by phase–amplitude coupling of human hippocampal neurons, Nature (2024). DOI: 10.1038/s41586-024-07309-z. www.nature.com/articles/s41586-024-07309-z

Part 2

Comment by Dr. Krishna Kumari Challa on April 18, 2024 at 10:01am

Researchers identify a group of cells involved in working memory

Investigators have discovered how brain cells responsible for working memory—the type required to remember a phone number long enough to dial it—coordinate intentional focus and short-term storage of information. The study detailing their discovery was published in Nature.

They have identified for the first time a group of neurons, influenced by two types of brain waves, that coordinate cognitive control and the storage of sensory information in working memory. These neurons don't contain or store information, but are crucial to the storage of short-term memories.

Working memory, which requires the brain to store information for only seconds, is fragile and requires continued focus to be maintained. In disorders such as Alzheimer's disease or attention-deficit hyperactivity disorder, it is often not memory storage, but rather the ability to focus on and retain a memory once it is formed that is the problem,

Understanding the control aspect of working memory will be fundamental for developing new treatments for these and other neurological conditions.
Part 1

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Comment by Dr. Krishna Kumari Challa on April 18, 2024 at 9:50am

Historically hybridization was thought of as a bad thing that was not particularly important when it came to evolution. But what genomic data have shown is that actually hybridization among species is widespread.
The implications may alter how we view species. A lot of species are not intact units. They're quite leaky, and they're exchanging genetic material.
So the species that are evolving are constantly exchanging genes, and the consequence of this is that it can actually trigger the evolution of completely new lineages.
Normally, species are thought to be reproductively isolated. They can't produce hybrids that are reproductively fertile. While there is now evidence of hybridization between species, what was difficult to confirm was that this hybridization is, in some way, involved in speciation. The question is: How can you collapse two species together and get a third species out of that collapse.

The new research provides a next step in understanding how hybridization and speciation work. Over the last 10 or 15 years, there's been a paradigm shift in terms of the importance of hybridization and evolution.
This research has the potential to play a role in the current biodiversity crisis. Understanding something as basic as "what we mean by a species is important for saving species and for conservation," particularly in the Amazon.
In addition, such work may prove useful in understanding carriers of disease. Multiple species of mosquito, for example, can carry malaria. Although these mosquitos are closely related, almost nothing is known about how they interact, and whether they hybridize with each other.

Neil Rosser, Hybrid speciation driven by multilocus introgression of ecological traits, Nature (2024). DOI: 10.1038/s41586-024-07263-w. www.nature.com/articles/s41586-024-07263-w

Part 2

Comment by Dr. Krishna Kumari Challa on April 18, 2024 at 9:45am

Amazon butterflies show how new species can evolve from hybridization

If evolution was originally depicted as a tree, with different species branching off as new blooms, then new research shows how the branches may actually be more entangled. In "Hybrid speciation driven by multilocus introgression of ecological traits," published in Nature,  researchers show that hybrids between species of butterflies can produce new species that are genetically distinct from both parent species and their earlier forebears.

Writing to Charles Darwin in 1861, naturalist Henry Walter Bates described brightly colored Heliconius butterflies of the Amazon as "a glimpse into the laboratory where Nature manufactures her new species." More than 160 years later, an international team of researchers led by biologists Neil Rosser, Fernando Seixas, James Mallet, and Kanchon Dasmahapatra also focused on Heliconius to document the evolution of a new species.
Using whole-genome sequencing, the researchers have shown that a hybridization event some 180,000 years ago between Heliconius melpomene and the ancestor of today's Heliconius pardalinus produced a third hybrid species, Heliconius elevatus. Although descended from hybrids, H. elevatus is a distinct butterfly species with its own individual traits, including its caterpillar's host plant and the adult's male sex pheromones, color pattern, wing shape, flight, and mate choice. All three species now fly together across a vast area of the Amazon rainforest.

Part 1

Comment by Dr. Krishna Kumari Challa on April 18, 2024 at 9:36am

When scientists simulated a rainfall event in the laboratory, they observed that within the first 15 to 30 minutes, almost all taxonomic groups switched from a resting mode to an active mode. This is a remarkable characteristic of desert soil bacteria, as in other types of soil many groups of bacteria take much longer to reactivate. When reactivated, the bacteria would quickly begin to generate energy and repair their genomes.
In the study, the researchers simulated rainfall events with stable isotope labeled water—water containing heavy hydrogen. Using NanoSIMS, they examined individual cells to see which of them had incorporated the heavy hydrogen atoms.

With this approach, researchers can reveal the fraction of biocrust cells that reactivate in a rain event. We can also infer if they can grow in short rain events that in arid deserts often only last 1 to 2 days.
They found that almost all biocrust cells reactivate, but that in these short rain events only a small proportion of the cells would be able to double. A large proportion of the biocrust cells can therefore use rain events to regenerate and prepare for the next drought, but cell division does not occur.
These data help scientists understand how biocrust bacteria make optimal use of the short activity windows they experience in deserts. They are ideally adapted to withstand short-term changes in soil water content, a very stressful situation for the cells. This allows them to survive the sudden increase in water content during rain, as well as the subsequent drying out.
Additionally, the diverse microbial community is capable of immediate reactivation, which is of great benefit when it must return to a dormant state within a few hours to days.
The findings of this study are relevant not only for desert areas but also for other regions. The ability to survive water limitation will become increasingly important for soil microorganisms in temperate regions, as the frequency and intensity of droughts are increasing due to climate change. Insights gained from desert soil research can help to understand which features make soil microorganisms successful in surviving these challenges.

Survival and rapid resuscitation permit limited productivity in desert microbial communities, Nature Communications (2024). DOI: 10.1038/s41467-024-46920-6

Part 2

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