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Comment by Dr. Krishna Kumari Challa on December 22, 2023 at 9:08am

Time-resolved single-cell transcriptomics defines immune trajectories in glioblastoma, Cell (2023). DOI: 10.1016/j.cell.2023.11.032. www.cell.com/cell/fulltext/S0092-8674(23)01317-X

Comment by Dr. Krishna Kumari Challa on December 22, 2023 at 9:08am

However, all these important insights are equivalent to getting many still-frame images from a movie and trying to understand the plot. "Knowing what preceded what is not enough to deduce causality, but without this knowledge, we don't really have a chance of understanding what the cause is and what is the effect". 

The development of the groundbreaking new technology started with the research on glioblastoma, the most common and aggressive brain tumour. 

We usually think of cancer as cells growing out of control, but in fact, cancer is also the loss of the ability of the body, and specifically of its immune system, to control this growth. And when you look at tumors, large parts of them are composed of dysfunctional immune cells, which sometimes make up one third or even half of all the cells in a tumour.

Glioblastoma is one of the most immune-suppressive types of tumors. "To understand how to defeat this cancer, we need to understand what happens to the immune cells as they enter the tumor and why they lose the capacity to fight the tumor and become dysfunctional.

Ideally, we'd want to have a little clock on each cell telling us when it entered the tumor and when the signals and checkpoints that instruct it to become incompetent are activated. This back to the future time machine was thought to be impossible to develop.

The breakthrough came when researchers decided to take an uncanny approach. Instead of trying to measure time in cells within the tumor tissue, they decided to try to mark the cells while they are still in the blood—before they enter the tumor. By using different fluorescent dyes at different time points, they are later able to know exactly when each cell entered the tissue and how long it had been there, and this reveals the dynamic changes that happened to the cells in the tissue, for example, what are the different stages at which immune cells become dysfunctional inside the tumour.

The challenge was to develop the optimal way to color the cells in the blood at specific time points, making sure the dye does not reach the tissue itself or stay too long in the blood, potentially mixing with the next dye. At the same time, the dye had to stay on the cells long enough for them to be measured.

As part of the study, the researchers showed that the method makes it possible to measure time in immune cells in different tissues—the brain, the lungs and the digestive system of animal models.

Using Zman-seq,  researchers were able to gain insights into why the immune system is so dysfunctional in battling glioblastoma.

They showed that immune cells called natural killer cells, which, as their name implies, are crucial to killing rogue cells, become dysfunctional very quickly because the tumor hijacks their killing mechanisms—and this happens within less than 24 hours after their entry into the tumor. This explains why therapeutic attempts to harness the immune system for fighting glioblastoma are so ineffective.

Now researchers are developing ways to block the immune-disabling tumor checkpoints in order to reactivate the immune system in glioblastoma and other hard-to-treat tumors. In addition, they plan to adapt Zman-seq to the study of temporal dynamics of cells throughout the human body.

Zman-seq supplies the 'hard facts,' the empirical measurements enabling scientists to understand the precise order of events that immune and other cells are going through when they enter a tumor, and this may lead to a completely new thinking on how to generate more effective therapies for cancer and other disorders.

Comment by Dr. Krishna Kumari Challa on December 22, 2023 at 9:00am

Scientists develop the first method to measure cellular changes in the body over time

While physicists continue to argue about whether time is indeed an illusion, as Albert Einstein claimed, biologists have no doubt about its significance for understanding life as a dynamic system.

In recent years, they have been gaining an increasingly deeper understanding of complex biological systems using tools enabling the simultaneous analysis of vast amounts of cellular and molecular data and the probing of cellular circuitry that drives disease. However, these in-depth investigations of how cells behave and interact have provided only separate snapshots of what happens inside complex organisms, without accounting for the dimension of time and revealing the sequence of cellular events.

Now, in a new study published in Cell, researchers  have managed for the first time to develop a method for tracking and measuring changes over time on in single cells inside the body.

The method, called Zman-seq ("time"), consists of labeling cells with different time stamps and tracking them in healthy or pathological tissue. Using this cellular time machine, researchers can get to know the cells' history and how long each cell had stayed in the tissue, ultimately achieving an understanding of the molecular and cellular temporal changes that had taken place within that tissue.

Single-cell technologies, the tools that enable biologists to understand what happens inside individual cells, have advanced significantly in recent years.

With these tools, it is now possible to obtain high-resolution images of how diseases develop and how the body responds to different medications, to identify rare cell populations, decipher which cells interact with one other and how they are spatially distributed in a tissue.

Part 1

Comment by Dr. Krishna Kumari Challa on December 21, 2023 at 12:36pm

To figure out how the bacteria might be acting on those nerves, the researchers systematically tested different strains of S. aureus engineered to lack specific components of the microbe's molecular arsenal.

After ruling out nine others, Chiu and colleagues found one enzyme that S. aureus releases on contact with skin, protease V8, triggered itching behaviors in the mice by activating another protein, PAR1, which set off the sensory neurons.

When exposed to S. aureus devoid of V8, the mice didn't scratch nearly as much, and their skin was less flaky and irritated. And when animals were treated with a drug that blocks PAR1, their symptoms also eased.

Further experiments ruled out immune cells as the instigators of the animals' itch. Mice depleted of mast cells and basophils, two types of immune cells implicated in itches and allergies, kept on scratching after exposure to S. aureus.

"You don't necessarily have to have inflammation for the microbe to cause itch, but that itch exacerbates inflammation on the skin," explains Liwen Deng, lead author and microbiologist at Harvard Medical School.

If validated in human studies, the findings could present a clear target for alleviating eczema's endless itch that can deprive some patients of sleep.

Most current eczema treatments try to soothe the skin, calm the immune system, and restore the skin barrier without clearing up the condition entirely – though researchers have clued on to the idea that targeting skin bacteria might provide lasting relief.
The PAR1 blocker tested in this study is already used to prevent blood clots in humans so it could be repurposed. Like the mice, skin samples from patients with atopic dermatitis had higher V8 levels and more S. aureus than healthy skin, but further testing is required.

Future studies could also investigate if pathogens like S. aureus hijack itchy sensations to facilitate their spread.

"It's a speculation at this point, but the itch-scratch cycle could benefit the microbes and enable their spread to distant body sites and to uninfected hosts," Deng says.

https://www.cell.com/cell/fulltext/S0092-8674(23)01164-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867423011649%3Fshowall%3Dtrue

Part 2

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Comment by Dr. Krishna Kumari Challa on December 21, 2023 at 12:35pm

Scientists Find an Unexpected Trigger of Eczema – And Clues on How to Stop It

The unbearable itch that accompanies the chronic inflammatory skin condition eczema has a new culprit.
Scientists have discovered that a familiar bacteria, Staphylococcus aureus, ignites persistent itches by directly triggering sensory neurons in the skin, a finding that could help researchers devise new treatments.
Eczema, which is also known as atopic dermatitis, is common in children and teenagers but also affects one in ten adults.

Up until now, immune cells and the inflammatory molecules they secrete were thought to be the main drivers of the insufferable itch that occurs with eczema. That itch so often drives a vicious urge to scratch which only damages the skin further, leaving it red, raw, swollen, and cracked.

Years ago, researchers figured out that people lacking a skin protein called filaggrin were more likely to develop eczema; but what specifically caused the itch that enflames eczema still bugged them.

Now, a team of mostly US researchers has shown in a series of animal experiments how S. aureus, a bacterium that infiltrates broken skin to cause infections, single-handedly causes itching by setting off sensory nerve cells in the skin surface.
Mice were wrapped in gauze loaded with S. aureus to model eczema in humans. The animals exposed to S. aureus scratched their sores, and the researchers found the bacteria congregated close to sensory nerve endings in the now-inflamed outer skin, the epidermis.
Part 1

Comment by Dr. Krishna Kumari Challa on December 21, 2023 at 12:04pm

Researchers discover novel antibiotic substance in the human nose

Researchers   have discovered a novel antibiotic substance from the human nose that can be used against pathogenic bacteria. Named epifadin, the molecule is produced from specific strains of the bacterial species Staphylococcus epidermidis, which occur on the mucous membrane of the inside wall of the nose. Strains that produce epifadin can also be isolated on the surface of the skin. Epifadin constitutes a new, previously unknown class of antimicrobial compounds that kills microorganisms and could be used as a lead structure for the development of novel antibiotics. The research is published in the journal Nature Microbiology. 

Benjamin O. Torres Salazar et al, Commensal production of a broad-spectrum and short-lived antimicrobial peptide polyene eliminates nasal Staphylococcus aureus, Nature Microbiology (2023). DOI: 10.1038/s41564-023-01544-2

Comment by Dr. Krishna Kumari Challa on December 21, 2023 at 11:55am

Avoiding IP issues when using generative AI

There are practical steps you can take right now to help ensure you're considered the creator, author, or inventor of something made with the assistance of generative AI.

Most importantly, be careful to document how and when you interact with AI tools, and what data you use for to gain an output. For the current generation of AI tools, this means you should record the prompts you use, when they were made, and with what version of tool. This could be crucial evidence down the track to show sufficient 'intellectual effort' was used, proving you're the rightful author or inventor.

If you're creating new AI tools, you should verify that you have sufficient rights in the datasets used to train the tools. This ensures the AI model that forms the basis of your tool can't inadvertently create a copy or a derivative work that would infringe on others' rights. It's likely more jurisdictions will require disclosure about training datasets as time goes on.

And finally, when using an AI tool, it's important to remember that you're accepting a license. That license affects your rights in the works, ideas or data output by the AI. Always read the fine print.

Despite the uncertainty and potential for massive changes, you can still get creating, inventing, and authoring—but know how to protect yourself, and do it responsibly.

 Source:  CSIRO 

Part 3

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If ChatGPT wrote it, who owns the copyright? It depends on where yo...

Comment by Dr. Krishna Kumari Challa on December 21, 2023 at 11:54am

Humans vs. AI in Intellectual Property law

Many jurisdictions have decided only "real humans" can be considered the author, creator, or inventor for the purposes of IP law. But often it's unclear who is considered the creator of a work when an AI tool is used.

In the current generation of high-profile generative AI tools, text prompts are used as the input mechanism to produce a desired output. The question is, by entering a specific set of prompts into an AI tool, did a human apply sufficient effort to be considered the author, inventor or creator of the output work? If not, and the work is not considered a copy of any other work, then from where did the ingenuity or inventive effort come?

This line of thinking leads to several problems for people using and creating these tools, especially when it comes to proving they are the creator. More broadly, it poses problems for the entire IP system.

Let's hone in on the patent system as an example. One requirement for patenting is that a new invention must be "inventive," "not-obvious," contain an "inventive step," or other similar requirements across jurisdictions. The test for meeting this threshold is often defined as whether a person skilled in an area of technology, with access to their normal working tools, would consider the invention "routine," as "a matter of course," or "obvious."

If generative AI is used as a matter of course in an area of technology, and can produce an acceptable description of an invention, then the bar for patenting is significantly raised. That is, once generative AI tools become common place (maybe they already are), we can expect a person skilled in a particular area of technology will use them to solve their problems.

But what happens when an AI tool has become so proficient that it has collected every piece of data that a human could, and has awareness of every experience that a human could have? The AI would be able to conceive a solution to every problem that a human could, just as the chess computer knows every move a grandmaster may consider. The result is almost nothing is inventive anymore, unless the human inventor has new data they can input to which no other party (including the AI tool) has access.

This scenario helps to illustrate the issues that IP law and individuals face. It is likely that over the coming years step changes in technology will be taken that lawmakers will need to respond to. But, we don't yet know how these problems will be resolved. Given that no significant legal changes have been made in the face of the current generation of AI, and the rate of change is likely to accelerate, inventors and innovators should attempt to stay ahead of any possible changes.

Part 2

Comment by Dr. Krishna Kumari Challa on December 21, 2023 at 11:53am

Changing face of invention in the age of AI

With the widespread adoption of generative AI tools like ChatGPT, we can no longer assume that new ideas and inventions are solely the result of human effort. So, what does this mean for inventors and the IP they create?

We've heard many perspectives recently on the effect generative AI will have on all facets of how we work, conduct business, and ultimately live our lives. When game-changing technologies emerge, there's a tendency for people to polarize in opinion, either vastly underestimating or vastly overestimating the benefits and problems associated with using them. For example, we've heard how AI could never produce art or how it will solve all our collective problems.

But no matter what our opinions are on the dangers and benefits of AI, these tools don't exist in isolation. People using and creating generative AI tools and the tools themselves are subject to IP laws. Being aware of these laws can help protect us from their impact.

When the tools we create become the creators

From the perspective of an artist, creator or author, there's a strong argument they should have a right to control how their work is used or exploited. Copyright laws generally achieve this goal. Typically, these laws rely on the legal concept of "individual intellectual effort" to determine who the author of a work is. That is, the person creating the work needs to have added enough of their own ingenuity and creativity to distinguish their creation from other existing works. But how does a human achieve this? Some argue that unlike AI, there's something special about humans that allows us to achieve the creation of a "new" work.

I propose a different argument. The work a human creates is simply the sum total of all the things that human has sensed and experienced throughout their lifetime. Similarly, an AI tool creates an output based on the sum total of all the data it has consumed throughout its training. With time, the data that an AI consumes will grow as its sensor inputs and ability to experience become more sophisticated. There's a critical point where AI tools will exceed humans in their ability to sense and experience, and consequently exceed humans in their capability to create, author or invent. At the very least, this will happen in specific domains. For example, AI's in the specific domain of chess exceeded human capability years ago, and we're witnessing it again now in the visual arts thanks to tools like Dall-E and Midjourney.

Part 1

Comment by Dr. Krishna Kumari Challa on December 21, 2023 at 11:25am

In order to change the magnetism in the material investigated "by pushing a button," the researchers put the crystal under pressure. Starting from a kagome structure, the crystal lattice was deformed by uniaxial stress, which changed the magnetic interactions between the electrons.

Researchers used mechanical pressure to force the system into a preferred magnetic direction. The team succeeded in increasing the temperature of the magnetic phase transition by more than 10%

Jierong Wang et al, Controlled Frustration Release on the Kagome Lattice by Uniaxial-Strain Tuning, Physical Review Letters (2023). DOI: 10.1103/PhysRevLett.131.256501. On arXiv: DOI: 10.48550/arxiv.2209.08613

Part 2

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