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Comment by Dr. Krishna Kumari Challa on October 10, 2023 at 8:29am

How synthesized plankton molecules inhibit cancer proteins

Researchers have discovered how to harness the toxic power of plankton to manufacture anti-cancer molecules.

In a paper, "Synthesis of portimines reveals the basis of their anti-cancer activity," published in Nature, the team details the steps taken in synthesizing marine toxins, portimine A and portimine B, enabling in-depth investigations into their properties

Dinoflagellate-derived cyclic imine toxins, specifically portimine A and portimine B, are of interest due to their potential anti-cancer therapeutic properties. Previous research has shown the effects of cyclic imine toxins on cancer cells, but the molecular mechanisms underlying the cause of the anti-cancer activity were unknown. Access to these toxins in large quantities is currently hard to come by as the only known producer is a type of tiny marine plankton, Vulcanodinium rugosum. To test the toxin's activity, the researchers first needed to innovate a way to synthesize large enough quantities to work with.

The synthesis began with constructing a minimally-decorated carbon skeleton devoid of most oxygen atoms. The idea was to leverage a macrocycle's innate reactivity to install the correct oxygenation pattern and stereochemistry.

Strategic ring-chain tautomerization events were employed to facilitate the synthesis using ring-closing alkyne metathesis to construct the 14-membered macrocycle in the portimines' skeleton. The innovation represents a scalable and concise synthesis of portimines. With the desired molecules created, the next step was to see how they interacted with cancer cells.

Part 1

Comment by Dr. Krishna Kumari Challa on October 10, 2023 at 8:06am

Digital watermark protections can be easily bypassed

Perhaps the most chilling aspect of AI is its capacity to generate deepfake images.

But recent developments portend a more unsettling trend as digital fakery turns malicious. Not only celebrities and politicians, ordinary citizens are targeted, too. People's faces are appearing in images on social media without their consent. 

Major digital media companies—OpenAI, Alphabet, Amazon, DeepMind—have promised to develop tools to combat disinformation. One key approach is the use of watermarking on AI-generated content.

A paper published Sept. 29 on the preprint server arXiv raises troubling news about the ability to curb such digital abuse.

Researchers ran tests demonstrating easy run-arounds of protective watermarks.

We don't have any reliable watermarking at this point because the researchers broke them all!

The team used a process called diffusion purification, which applies Gaussian noise to a watermark and then removes it. It leaves a distorted watermark that can bypass detection algorithms. The rest of the image is only minimally altered.

They further successfully demonstrated that bad actors with access to black-box watermarking algorithms could foist fake photos with markings that trick detectors into believing they are legitimate.

Better algorithms will certainly come along. As has been the case with viral attacks, the bad guys will always be working to break whatever defenses the good guys come up with, and the cat-and-mouse game will continue.

Mehrdad Saberi et al, Robustness of AI-Image Detectors: Fundamental Limits and Practical Attacks, arXiv (2023). DOI: 10.48550/arxiv.2310.00076

Comment by Dr. Krishna Kumari Challa on October 8, 2023 at 12:38pm

The researchers think that gene mutations in certain individuals means that BPA can't be cleared as well as it needs to be, which means the substance sticks around in the body. That potentially could cause damage in terms of neuron development and operation.

Conditions like ASD and ADHD are thought to be brought on by a combination of genetic and environmental influences, and this new study brings together both of them. However, it's only part of the story – not every child with a neurodevelopmental disorder had problems flushing out BPA, so there are other factors at play, too.

Work is continuing to identify how exactly ASD and ADHD take hold in the body – whether it's in utero before birth for example, or later on in life – as the data isn't enough to show whether BPA exposure causes either disorder.

"There is an extensive body of epidemiological evidence for a relationship between neurodevelopmental disorders and environmental pollutants such as plasticizers," write the researchers.

"How important plasticizer originated neurodevelopmental disorder is in the overall occurrence of these disorders is not known, but it must account for a significant proportion or would not have been so easy to detect in a metabolic study of moderate size such as this study."

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0...

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Comment by Dr. Krishna Kumari Challa on October 8, 2023 at 12:38pm

Common Plastic Additive Linked to Autism And ADHD

The number of kids being diagnosed with autism spectrum disorder ( ASD) and attention deficit hyperactivity disorder ( ADHD) has risen sharply in recent decades, and a new study points to the common plastic additive bisphenol A (BPA) as a potential reason why. BPA is used in a lot of plastics and plastic production processes, and can also be found inside food and drink cans. However, previous research has also linked it to health issues involving hormone disruption, including breast cancer and infertility.

In this new study, researchers from Rowan University and Rutgers University in the US looked at three groups of children: 66 with autism, 46 with ADHD, and 37 neurotypical kids. In particular, they analyzed the process of glucuronidation, a chemical process the body uses to clear out toxins within the blood through urine.
The research found that kids with ASD and ADHD couldn't clear out BPA and another similar compound called Diethylhexyl Phthalate (DEHP) with as much efficiency as other kids, potentially leading to longer exposure to their toxic effects.

"Detoxification of these two plasticizers is compromised in children with ASD and ADHD," write the researchers in their published paper. "Consequently, their tissues are more exposed to these two plasticizers."

It was only in the case of BPA that the difference was statistically significant though: the efficiency was reduced by about 11 percent for kids with ASD and 17 percent for kids with ADHD, compared with the control group of children.
Part 1

Comment by Dr. Krishna Kumari Challa on October 8, 2023 at 12:26pm

Armed with shotgun microphones, researchers recorded the calls of hundreds of individuals, collecting over 5000 vocalizations in total, making it the largest study of individually-marked wild parrots to date. Importantly, they re-recorded the same individuals over two years, which revealed how stable the calls were over time.

They then used a set of models to detect how recognizable individuals were within each of the five main call types given by this species. Surprisingly, they found high variability in the so-called "contact call" that birds use to broadcast their identity. This overturned a long-held assumption that contact calls contain a stable individual signal—and suggested that the parakeets are using something else for individual recognition.
To test if voice prints were at play, scientists turned to a machine learning model widely used in human voice recognition, which detects the identity of the speaker using the timber of their voice. They trained the model to recognize calls of individual parrots that were classed as "tonal" in sound.
Once the model was trained on an individual, they then tested to see if the model could detect the same individual from a different set of calls that were classed as "growling" in sound. The model was able to do this three times better than expected by chance, providing evidence that monk parakeets have a voice print, which could allow individuals to recognize each other no matter what they say.

The researchers, however,  caution that the evidence is still preliminary. Before we can speak of a true voice print, we need to confirm that the model can repeat this result when it is trained with more data from more individuals, and that birds can also recognize this timbre in the vocalizations.

Simeon Smeele et al, Evidence for vocal signatures and voice-prints in a wild parrot, Royal Society Open Science (2023). DOI: 10.1098/rsos.230835. royalsocietypublishing.org/doi/10.1098/rsos.230835

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Part 2

Comment by Dr. Krishna Kumari Challa on October 8, 2023 at 12:23pm

Unique voice prints in parrots could help birds be recognized in a flock, no matter what they say

Parrots are exceptional talkers. They can learn new sounds during their entire lives, amassing an almost unlimited vocal repertoire. At the same time, parrots produce calls so they can be individually recognized by members of their flock—raising the question of how their calls can be very variable while also uniquely identifiable.

A study on monk parakeets might have the answer: individuals have a unique tone of voice, known as a voice print, similar to that in humans. This finding in a wild parrot raises the possibility that a voice print might also be present in other vocally flexible species, such as dolphins and bats.

It makes sense for monk parakeets to have an underlying voice print. It's an elegant solution for a bird that dynamically changes its calls but still needs to be known in a very noisy flock.

Humans have complex and flexible vocal repertoires, but we can still recognize each other by voice alone. This is because humans have a voice print: our vocal tract leaves a unique signature in the tone of our voice across everything that we say.

Other social animals also use vocal cues to be recognized. In birds, bats, and dolphins, for example, individuals have a unique "signature call" that makes them identifiable to members of the group. But signature calls encode identity in only one call type. To date, almost no evidence exists for animals having unique signatures that underlie all calls made by an individual. In other words, almost no animals are known to have a voice print.

Like humans, parrots use their tongue and mouth to modulate calls, meaning that their grunts and shrieks sound much more human than a songbird's clean whistle.

Also, like humans, parrots live in large groups with fluid membership. There could be tens of birds vocalizing at the same time. They need a way of keeping track of which individual is making what sound.

Part 1

Comment by Dr. Krishna Kumari Challa on October 7, 2023 at 11:10am

How do our brains tell us when something goes wrong?

Whether improperly closing a door or shanking a kick in soccer, our brains tell us when we've made a mistake because these sounds differ from what we expect to hear. While it's long been established that our neurons spot these errors, it has been unclear whether there are brain cells that have only one job—to signal when a sound is unexpected or "off."

A team of neuroscientists has now identified a class of neurons—what it calls "prediction-error neurons"—that are not responsive to sounds in general, but only respond when sounds violate expectations, thereby sending a message that a mistake has been made.

Brains are remarkable at detecting what's happening in the world, but they are even better at telling you whether what happened was expected or not. It 's found that there are specific neurons in the brain that don't tell you what happened, but instead tell you what went wrong. Neurons like these might be vital in learning how to speak or how to play a musical instrument. Both of those behaviors involve lots of trial and error, lots of mistakes, and lots of learning from mistakes

Nicholas J. Audette et al, Stimulus-specific prediction error neurons in mouse auditory cortex, The Journal of Neuroscience (2023). DOI: 10.1523/JNEUROSCI.0512-23.2023

Comment by Dr. Krishna Kumari Challa on October 7, 2023 at 11:02am

How male mosquitoes compensate for having only one X chromosome

The research group has discovered the master regulator responsible for balancing the expression of X chromosome genes between males and females in the malaria mosquito.

This discovery helps scientists to better understand the evolution of the epigenetic mechanisms responsible for equalizing gene expression between the sexes. The findings may contribute to the development of new ways to prevent the spread of malaria. 

Just like humans, the sex of a mosquito is determined by the sex chromosomes: females have two X chromosomes (XX), while males have an X and a Y chromosome (XY). This can be problematic, as males have only half the number of X chromosome genes as females, and hence would have only half the amount of proteins from the X chromosome. To compensate for this, there must be a way to increase the expression of X chromosome genes in males.

The researchers discovered that the protein SOA (sex chromosome activation) is the key regulator that balances X chromosome gene expression in male mosquitoes. They found that SOA works by binding to X chromosome genes and increasing their expression, but only in males. Female mosquitoes, on the other hand, only produce a small amount of very short, non-functional SOA.

Balancing gene expression on sex chromosomes is essential for development in some species. However, others do not have such a mechanism at all. It is now discovered that in mosquitoes, balancing X chromosome expression by SOA is not necessary for development, but it does give males a head start.

This is an important clue as to how the mechanisms that balance gene expression on sex chromosomes may have evolved in the first place.

Agata Izabela Kalita et al, The sex-specific factor SOA controls dosage compensation in Anopheles mosquitos, Nature (2023). DOI: 10.1038/s41586-023-06641-0

Comment by Dr. Krishna Kumari Challa on October 7, 2023 at 9:36am

Furthermore, they found that the high levels of arginine are necessary for tumor development, independently of the amino acid's role in protein synthesis. This then begged the question: How does arginine lead to tumorigenicity?

At high concentrations, arginine binds to a specific factor, which triggers metabolic reprogramming and promotes tumour growth by regulating the expression of metabolic genes. As a consequence, tumour cells revert back to an undifferentiated embryonic cell state, in which they can divide indefinitely. Interestingly, tumour cells also benefit in another way from increasing the uptake of arginine.

Our immune cells depend on arginine to function properly. Therefore, depleting arginine in the tumour environment helps the tumour cells escape the immune system.

What do these findings mean for cancer therapy? The scientists propose to target the specific arginine-binding factor rather than depleting arginine.

Furthermore, metabolic changes such as increased arginine levels may serve as biomarkers for detecting cancer at an early stage, which is crucial for successful cancer treatment and patient survival.

 Arginine reprograms metabolism in liver cancer via RBM39, Cell (2023). DOI: 10.1016/j.cell.2023.09.011. www.cell.com/cell/fulltext/S0092-8674(23)01032-2

Part 2

Comment by Dr. Krishna Kumari Challa on October 7, 2023 at 9:33am

Scientists discover arginine drives metabolic reprogramming to promote tumor growth in liver cancer

Cancer cells are chameleons. They completely change their metabolism to grow continuously. University of Basel scientists have discovered that high levels of the amino acid arginine drive metabolic reprogramming to promote tumor growth. This study suggests new avenues to improve liver cancer treatment.

The liver is a vital organ with many important functions in the body. It metabolizes nutrients, stores energy, regulates the blood sugar level, and plays a crucial role in detoxifying and removing harmful components and drugs. Liver cancer is one of the world's most lethal types of cancer. Conditions that cause liver cancer include obesity, excessive alcohol consumption and hepatitis C infection. Early diagnosis and appropriate therapeutic strategies are crucial for improving treatments in liver cancer.

In the past decade, scientists have made much progress in understanding the multiple facets of cancer. Historically, it has long been viewed as a disorder in cell proliferation. However, there is growing evidence that cancer is a metabolic disease. In other words, cancer arises when cells rewire their metabolism to allow uncontrolled cell proliferation. How do cells change their metabolism and how does this change in turn lead to tumorigenicity? With their new study in Cell, researchers have discovered a key driver of metabolic rewiring in liver cancer cells.

Healthy liver cells gradually change their behavior when turning into cancer cells. They reprogram their metabolism to grow as fast as possible, for example, they consume much more glucose than normal cells and they enhance the uptake of nutrients.

The most important thing they found is  elevated levels of arginine, although cancer cells produce less or none of this amino acid. The tumour cells accumulate high levels of arginine by increasing its uptake and suppressing its consumption.

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