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Comment by Dr. Krishna Kumari Challa on June 28, 2024 at 10:38am

A typical CT scanner scans the human body using X-rays, and reconstructs its spatial internal structure section by section. In biology, a similar function has recently been performed by the holotomographic microscope. Here, cells are also swept by a beam of radiation, though not high-energy radiation, but electromagnetic radiation. Its energy is chosen so that the photons do not disturb cell metabolism.

The result of the scan is a set of holographic cross-sections containing information about the distribution of refractive index changes. Since light refracts differently on the cytoplasm and differently on the cell membrane or nucleus, it is possible to reconstruct a three-dimensional image of both the cell itself and its interior.

Unlike other high-resolution microscopy techniques, holotomography does not require the preparation of samples or the introduction of any foreign substances into the cells. The interactions of gold nanoparticles with cancer cells could therefore be observed directly in the incubator, where the latter were cultured, in an undisturbed environment--what's more, with nanometric resolution--from all sides simultaneously and practically in real time.

The unique features of holotomography allowed the physicists to determine the causes of the unexpected behavior of cancer cells in the presence of gold nanoparticles. A series of experiments was conducted on three cell lines: two glioma and one colon. Among others, it was observed that although the small, spherical nanoparticles easily penetrated the cancer cells, the cells regenerated and even started to divide again, despite the initial stress.

In the case of colon cancer cells, the gold nano particles were quickly pushed out of them. The situation was different for the large star-shaped nanoparticles. Their sharp tips perforated the cell membranes, most likely resulting in increasing oxidative stress inside the cells. When these cells could no longer cope with repairing the increasing damage, the mechanism of apoptosis, or programmed death, was triggered.

Researchers used the data from the  experiments to build a theoretical model of the process of nanoparticle deposition inside the cells under study. The final result is a differential equation into which suitably processed parameters can be substituted—for the time being only describing the shape and size of nanoparticles—to quickly determine how the uptake of the analyzed particles by cancer cells will proceed over a given period of time and how they kill the cancer cells.

Joanna Depciuch et al, Modeling Absorption Dynamics of Differently Shaped Gold Glioblastoma and Colon Cells Based on Refractive Index Distribution in Holotomographic Imaging, Small (2024). DOI: 10.1002/smll.202400778

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Comment by Dr. Krishna Kumari Challa on June 28, 2024 at 10:34am

What type of Gold nanoparticles kill cancer

Gold particles of the size of billionths of a meter are lethal to cancer cells. This fact has been known for a long time, as has a simple correlation: The smaller the nanoparticles used to fight the cancer cells, the faster they die. However, a more interesting, more complex picture of these interactions is emerging from the latest research  using a novel microscopic technique.

Smaller kills faster—this is what was previously thought about gold nanoparticles used to fight cancer cells. Scientists thought that small nanoparticles would simply find it easier to penetrate the interior of a cancer cell, where their presence would lead to metabolic disturbances and ultimately cell death.

The reality, however, turns out to be more complex, as demonstrated by research carried out by scientists.

Nanoparticles can be produced using a variety of methods, yielding particles of different sizes and shapes. Shortly after starting their own experiments with gold nanoparticles, researchers  noticed that biology does not follow the popular rule that their toxicity is greater the smaller they are.

Spherical nanoparticles of 10 nanometers in size  turned out to be practically harmless to the glioma cell line studied. However, high mortality was observed in cells exposed to nanoparticles as large as 200 nanometers, but with a star-shaped structure.

Elucidation of the stated contradiction became possible thanks to the use of the first holotomographic microscope.

Part 1

Comment by Dr. Krishna Kumari Challa on June 28, 2024 at 9:38am

This theory fits with a pattern of strategies mammals have adopted in an evolutionary bid to limit the spread of potentially harmful elements. Notably, in humans, mitochondrial DNA is exclusively passed down from the mother. This mechanism serves as a natural filter, maintaining genetic integrity by suppressing the proliferation of detrimental mutations. Additionally, the prevalence of monogamous relationships among certain species has been suggested as an adaptive response aimed at minimizing the transmission of sexually transmitted infections (STIs).

Maternal transmission as a microbial symbiont sieve, and the absence of lactation in male mammals, Nature Communications (2024). DOI: 10.1038/s41467-024-49559-5

Part 2

Comment by Dr. Krishna Kumari Challa on June 28, 2024 at 9:37am

Why male mammals don't breast feed

New mathematical model sheds light on the absence of breastfeeding in male mammals

Being nursed by a single parent could be an evolutionary strategy to curb the spread of harmful microbes in mammals, according to a novel theory developed by mathematicians.

The rainforests of Malaysia are home to the only known case of a wild male mammal that produces milk. The Dayak fruit bat is a vanishingly rare case of male milk production, despite the fact that the potential for breastfeeding remains in place in most male mammals.

Male Dyak's fruit bats, Dyacopterus spadiceus, are able to feed their young milk from their own mammary glands. This species has one of the only known natural occurrences of paternal lactation.

In the 1970s, evolutionary theorists posited that the near absence of lactation in males, even though offspring could benefit from the extra nutrition provided, could be attributed to the uncertainty of paternity: As male mammals can't be sure they are the biological father, this reduces their evolutionary drive to invest heavily in offspring care, including breastfeeding.

Now, mathematicians from the University of York have suggested a complementary perspective. Their hypothesis, published in Nature Communications, suggests that the reason male mammals don't breastfeed might be driven by the rich community of microbes that lives in breast milk, which plays an important part in establishing the gut microbiome of the infant.

The theory demonstrates how the transmission of the milk microbiome from both parents would allow harmful microbes to spread through mammalian populations. Maternal-only lactation stops this, as restricting transmission of the milk microbiome to females in effect acts as a sieve, retaining just the microbes with beneficial effects.

When both parents are involved in feeding, the chance of a microbe being passed along and getting an initial foothold in a population is essentially doubled. So this new theory suggests selection against the transmission of harmful microbes through mammary milk could be an additional selection pressure against male lactation.

Breast milk is a living substance and it plays a key role in establishing the gut microbiome of mammals, which is a complex ecosystem of bacteria, viruses and fungi, along with their genetic material. This ecosystem plays a crucial role in health, including by helping to protect animals against disease, helping to digest food and in many other ways we are only just discovering.

While microbes are not inherently harmful or beneficial; it's their presence and abundance that dictate the overall health of this internal community. A 'wrong actor' at the early point of an animal's life could change the microbiome at a pivotal moment.

The mathematical model highlights the advantage of being fed by just one parent, but the researchers say it makes evolutionary sense for this to be the mother because there has already been an inevitable transmission of microbes during birth and perhaps also in the womb.

Part 1

Comment by Dr. Krishna Kumari Challa on June 27, 2024 at 11:38am

At summer temperatures, wetting with anything more than water vapor leads to unsustainable carbon losses for boreal oak lichen, which may explain why it prefers humid environments like bogs. Scientists already knew this species is vulnerable to heating and drying, now we can start to understand exactly how and why—all key insights into the threats from future climate change.
n simple cases of symbiosis, such as a clownfish and a sea anemone, the needs of the partner organisms may be well-balanced and complimentary. The research shows that symbiosis in lichens is more complex, and each organism may react differently when faced with changing weather conditions or environmental stress.

"Unexpectedly, the alga just does its own thing: once active, it doesn't seem to respond at all to the major changes that the fungus undergoes when we add liquid water. It shouldn't be a surprise that the different organisms that make up lichen symbioses respond to different cues, but it has often been far too easy to lose sight of that when working with such seemingly closely integrated symbioses."

Future research will focus on unpacking when the components of lichen symbiosis are and aren't coordinated. The team hopes to better understand what each organism does under different circumstances.

 Abigail R. Meyer et al, Symbionts out of sync: Decoupled physiological responses are widespread and ecologically important in lichen associations, Science Advances (2024). DOI: 10.1126/sciadv.ado2783

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Comment by Dr. Krishna Kumari Challa on June 27, 2024 at 11:35am

Lichen partnerships challenged by changes in climate

Lichen, which people may think of as a single organism, is in fact a community of several species that depend on each other for survival. Lichen symbiosis includes at least one fungus and one alga, along with other fungi and bacteria in roles that are still being investigated by biologists.

The continued health of lichens is vital to the future of our Northern forests because they provide a critical winter food source for many animals. They are also valuable "sentinels" of air quality and environmental health. For these reasons, scientists are eager to understand how they may be affected by climate change.

New research published in Science Advances from the University of Minnesota investigated symbiosis in boreal oak lichen, a variety widespread on several tree species across Minnesota and the Northwoods.

Using multiple research methods, the team found:

• The partner organisms that make up lichen symbioses are not always in sync—one organism may have an extreme response to changes in moisture while its partner remains unaffected.
• These differences may drive one partner to "go it alone" under some conditions, disrupting the symbiosis—other research has observed this in corals.
• The team used gas exchange data to show asymmetries in carbon balance are widespread across evolutionarily disparate lichen groups.

Part 1

Comment by Dr. Krishna Kumari Challa on June 27, 2024 at 11:25am

Scientists determine that connexin molecules allow cells to send messages to each other

Researchers have gained new knowledge of how drugs bind to connexin molecules. These molecules form channels that allow neighboring cells to send direct messages to one another. Dysfunctions of these channels are involved in neurological and cardiac diseases. The new understanding of how drugs bind and act on them should help develop therapies to treat such conditions.

Adjacent cells can communicate directly through relatively large channels called gap junctions, which allow cells to freely exchange small molecules and ions with each other or with the outside environment. In this way, they can coordinate activities in the tissues or organs that they compose and maintain homeostasis.

Such channels are created from proteins known as connexins. Six connexins situated in the cell membrane create a hemichannel; this hemichannel joins with a hemichannel in a neighboring cell to create a two-way channel.

When connexin channels do not work properly, they cause changes in intercellular communication that have been linked to many different diseases. These include cardiac arrhythmias, diseases of the central nervous system such as epilepsy, neurodegenerative diseases and cancer.

As a result, the search is on for drugs that target connexins.

So understanding of the structure of connexins and how drugs bind to connexin channels to block or activate them is vital for treatment of these diseases. Indeed, of the 21 types of connexins known to exist in humans, few of them are currently evaluated as drug targets.

Find more information here:  Xinyue Ding et al, Structural basis of connexin-36 gap junction channel inhibition, Cell Discovery (2024). DOI: 10.1038/s41421-024-00691-y

Comment by Dr. Krishna Kumari Challa on June 27, 2024 at 11:15am

Researchers discover how mitochondrial transfer restores heart muscle

Transferring mitochondria from a patient's healthy skeletal muscle to damaged, ischemic heart tissue has been shown to restore heart muscle, increase energy production, and improve ventricular function.

 Researchers realized the probability of recovery was much higher if they added mitochondria.

To date, 16 children have undergone autologous mitochondria transplantation. Of these, 80% were able to come off ECMO, compared with a historical rate of 40%.

But mitochondrial transfer has faced skepticism—in part because no one really knew why it works.

The researchers earlier thought that  it was mitochondria going into cells and taking over and generating all of the cell's power. But what didn't make sense was that they only needed very small amounts of mitochondria for the heart muscle to recover. The math didn't add up.

A new study published in the journal Nature, found a surprising explanation. The transferred mitochondria trigger the cell to destroy its low-performing mitochondria through autophagy—a kind of cellular housekeeping.

This gives cells a better pool of mitochondria, improving their bioenergetics and fitness. This insight could ultimately improve care for broad range of heart conditions.

The research team is now investigating whether mitochondrial transfer could improve the success of cardiac transplantation when the heart is donated after circulatory death (DCD). DCD hearts could potentially expand the donor pool, but have ischemic damage and thus are difficult to transplant. The researchers think treatment with mitochondria will help with their recovery.

Ruei-Zeng Lin et al, Mitochondrial transfer mediates endothelial cell engraftment through mitophagy, Nature (2024). DOI: 10.1038/s41586-024-07340-0

Comment by Dr. Krishna Kumari Challa on June 27, 2024 at 11:05am

Scientists discover genetic 'off switch' in legume plants that limits biological ability to source nutrients

A genetic "off switch" that shuts down the process in which legume plants convert atmospheric nitrogen into nutrients has been identified for the first time by a team of international scientists.

Legumes like beans, peas and lentils are unique among crops for their ability to interact with soil bacteria to convert or "fix" nitrogen into a usable form of nutrients. However, this energy-intensive biological process is reduced when nitrogen is already abundant in the soil either through natural processes or through the application of synthetic fertilizer.

The latest discovery of the genetic regulator that turns off nitrogen fixation when soil nitrate levels are high allowed scientists to remove the gene in model legumes, ensuring they continued to fix nitrogen regardless of the soil environment.

Increasing the biological ability of legumes to fix nitrogen could help increase crop growth and yield while also reducing the need for synthetic fertilizers, which contribute to agriculture's environmental footprint.

Dugald Reid, Zinc mediates control of nitrogen fixation via transcription factor filamentation, Nature (2024). DOI: 10.1038/s41586-024-07607-6. www.nature.com/articles/s41586-024-07607-6

Comment by Dr. Krishna Kumari Challa on June 27, 2024 at 10:59am

Within organisms, the attachment of carbohydrates, or "glycans," onto proteins or lipids—a process called "glycosylation"—plays an essential role in a staggering number of physiological processes. It is necessary for cell recognition, cell signaling, immune response, protein folding, development and fertilization. Meanwhile, the slightest alteration in the structure of glycans can lead to or aggravate diseases from cancer and diabetes to Alzheimer's and muscular dystrophy.

Glycans and their associated processes are in fact so important that they get their own field: glycobiology. And within this discipline, almost all of the enzymes—the molecules that kick off or speed up chemical reactions—that are responsible for production of glycans in humans have been identified and categorized, as well as the various production processes, or "biosynthetic pathways."

Studying these mechanisms in detail is vital for disease process identification and controlling it.

Full details about the work can be found here: 

 Yuko Tokoro et al, LacdiNAc synthase B4GALNT3 has a unique PA14 domain and suppresses N-glycan capping, Journal of Biological Chemistry (2024). DOI: 10.1016/j.jbc.2024.107450

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