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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.

Part 1

Comment by Dr. Krishna Kumari Challa on October 6, 2023 at 11:15am

Iron atoms discovered on the move in Earth's solid inner core

The iron atoms that make up the Earth's solid inner core are tightly jammed together by astronomically high pressures—the highest on the planet.

But even here, there's space for wiggle room, researchers have found.

A study led by The University of Texas at Austin and collaborators in China found that certain groupings of iron atoms in the Earth's inner core are able to move about rapidly, changing their places in a split second while maintaining the underlying metallic structure of the iron—a type of movement known as "collective motion" that's akin to dinner guests changing seats at a table.

The results, which were informed by laboratory experiments and theoretical models, indicate that atoms in the inner core move around much more than previously thought.

The results could help explain numerous intriguing properties of the inner core that have long vexed scientists, as well as help shed light on the role the inner core plays in powering Earth's geodynamo—the elusive process that generates the planet's magnetic field.

Scientists think that iron atoms in the inner core are arranged in a repeating hexagonal configuration. According to Lin, most computer models portraying the lattice dynamics of iron in the inner core show only a small number of atoms—usually fewer than a hundred. But using an AI algorithm, the researchers were able to significantly beef up the atomic environment, creating a "supercell" of about 30,000 atoms to more reliably predict iron's properties.

At this supercell scale, the scientists observed groups of atoms moving about, changing places while still maintaining the overall hexagonal structure.

The researchers said that the atomic movement could explain why seismic measurements of the inner core show an environment that's much softer and malleable than would be expected at such pressures.

Youjun Zhang et al, Collective motion in hcp-Fe at Earth's inner core conditions, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2309952120

Comment by Dr. Krishna Kumari Challa on October 6, 2023 at 10:46am

Specifically, this study focuses on an interesting group of complement inhibitors (called "regulators"). The research showed promising results.

Researchers  observed that the regulators being studied effectively inhibited complement activation by nanoparticles in human serum in vitro and animal models. Specifically, when injected at very low doses, the regulators completely and safely blocked activation of complement by nanoparticles in the animal models used. According to the authors, this is significant because when nanoparticles activate complement, the resulting immune response can not only cause an adverse reaction but it can also reduce the efficacy of nanomedicines.

This research also provides a better understanding of why and how complement regulators could help the body respond more favorably to nanoparticles. The study team observed that of the trillions of nanoparticles entering the blood in a standard injection, only a small fraction activated complement. Complement regulators worked as soon as nanoparticles started activating complement, thereby promptly mitigating immune activation.

These results suggest we have an exciting opportunity to explore how to further optimize the use of regulators with nanoparticles, with the goal of improving the efficacy and tolerability of multiple nanotechnology-based therapeutics and vaccines.

 The next step is to test the complement inhibitors with multiple nano particles and in difference disease models to fully understand the potential of this approach with the ultimate goal to apply the research in a clinical setting.

Inhibition of Acute Complement Responses Toward Bolus-Injected Nanoparticles by Targeted, Short-Circulating Regulatory Proteins, Nature Nanotechnology (2023). DOI: 10.1038/s41565-023-01514-z. www.nature.com/articles/s41565-023-01514-z

Part 2

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Comment by Dr. Krishna Kumari Challa on October 6, 2023 at 10:44am

New research may make future design of nanotechnology safer with fewer side effects

A new study, published in Nature Nanotechnology, may offer a strategy that mitigates negative side effects associated with intravenous injection of nanoparticles commonly used in medicine.

Nanotechnology's main advantage over conventional medical treatments is its ability to more precisely target tissues, such as cancer cells targeted by chemotherapy. However, when nanoparticles are injected, they can activate part of the immune system called complement. 

Complement is a group of proteins in the immune system that recognize and neutralize bacteria and viruses, including nanoparticles which are foreign to the body. As a result, nanoparticles are attacked by immune cells triggering side effects that include shortness of breath, elevated heart rate, fever, hypotension, and, in rare cases, anaphylactic shock.

The activation of the immune system after injection of nanoparticles can be challenging to understand and prevent. This new research is one step closer to providing a better understanding and a solution for people to receive the benefits of nanoparticles without side effects.

The researchers say while some progress has been made in mitigating adverse reactions through slow infusion and premedication with steroids and antihistamines, a significant number of people still experience reactions.

The goal is to prevent, avoid and mitigate adverse reactions and immune activation. 

Part 1

Comment by Dr. Krishna Kumari Challa on October 6, 2023 at 8:48am

 How Amazonian forest degradation and monsoon circulation are interlinked

A pair of concerned researchers, has developed a computer model that shows linkages between forest degradation in the Amazon River basin and monsoon circulation.

That research suggested that if deforestation continues in the Amazon River basin, it could lead to a tipping point at which a certain degree of change can cause permanent changes to an ecosystem. In the case of the Amazon, the change would be from rainforest to a drier, savanna-like climate.

Over the course of many years, many studies have been conducted to understand how the characteristics of the Amazon River basin work together to maintain such a large rainforest. Such studies have shown that regional water cycling along with moisture exaltation from the plants, together with sunlight and even dust blown over from Africa, all contribute to the unique ecosystem, the largest rainforest in the world. Such work has also suggested that disruptions to parts of the system, such as cutting down trees, could result in major changes to the ecosystem. And if such changes were to occur, other studies have suggested the region would change from a rainforest to one that featured a vast savanna-like climate. Such a possible change is of major concern to climate scientists because the rainforest produces a lot of the Earth's oxygen. Additionally, destruction of the trees would result in the release of carbon they sequester, likely into the atmosphere, contributing further to climate change.

In this new effort, the researchers attempted to create a model that ties together degradation of the rainforest and monsoon circulation to show how and why a tipping point might be reached. To create their nonlinear dynamical model, the pair used data from other models that have been built over the past 40 years to simulate conditions in the rainforest. They also added weather data for the same period, including rainfall amounts, wind speeds and direction, and degree of evapotranspiration. They then modeled the rainforest in its original state to serve as a starting point. Next, they tweaked parameters to see the effects on the entire system. The model showed that cutting down trees at current rates in the Amazon region would indeed lead to a tipping point. They conclude that ecosystems with a feedback loop, such as the Amazon River basin, are particularly sensitive to change.

Nils Bochow et al, The South American monsoon approaches a critical transition in response to deforestation, Science Advances (2023). DOI: 10.1126/sciadv.add9973

Comment by Dr. Krishna Kumari Challa on October 5, 2023 at 12:08pm

Maybe volcanoes doomed the dinosaurs

A machine-learning algorithm suggests that volcanic activity, rather than an asteroid,.... The algorithm simulated 300,000 scenarios of different amounts of volcanic gases until it found one that matched data from fossils. The gases would have started to cause dinosaur-dooming climate chaos long before the asteroid impact. “You can actually recreate the environmental conditions that could cause a dinosaur extinction solely by volcanism, as if the asteroid weren’t there,” says computational geologist and study co-author Alexander Cox. “But of course, we can't discount the fact that the asteroid definitely didn't cheer up the dinosaurs.”

https://www.science.org/doi/10.1126/science.adh3875

Comment by Dr. Krishna Kumari Challa on October 5, 2023 at 12:05pm

What is anaphylaxis?

Comment by Dr. Krishna Kumari Challa on October 5, 2023 at 11:52am

Nobel Prize in chemistry for work on quantum dots, used in electronics and medical imaging

Three scientists won the Nobel Prize in chemistry Wednesday for their work on quantum dots—tiny particles just a few nanometers in diameter that can release very bright colored light and whose applications in everyday life include electronics and medical imaging.

Moungi Bawendi of MIT, Louis Brus of Columbia University, and Alexei Ekimov of Nanocrystals Technology Inc., were honored for their work with the tiny particles that "have unique properties and now spread their light from television screens and LED lamps," according to the Royal Swedish Academy of Sciences, which announced the award in Stockholm.

Quantum dots are tiny inorganic particles that glow a range of colors from red to blue when exposed to light. The color they emit depends upon the size of the particle.

Scientists can engineer the dots from materials that include gold to graphene to cadmium, and create their color by controlling their size. The tiniest particles, in which electrons are most tightly confined, emit blue light. Slightly larger particles, in which electrons bounce around a longer wavelength, emit red light.

Chemists sometimes compare the size of the particle itself to a confining box.

The underlying "particle in a box" theory of quantum mechanics was first described nearly a century ago. But it wasn't until several decades later that scientists could manufacture quantum dots in a lab.

In the 1980s, Ekimov, 78, and Brus, 80, honed the theory and developed early laboratory techniques for creating particles that emit varying colors by adjusting sizes. In 1993, Bawendi, 62, developed new chemical methods for producing the particles quickly and uniformly—which soon enabled a variety of scalable commercial applications, including in electronics displays.

www.nobelprize.org/uploads/202 … emistryprize2023.pdf

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