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Comment by Dr. Krishna Kumari Challa on October 22, 2024 at 9:08am

Chemical trick activates antibiotic directly at the pathogen

Due to increasing resistance, it is becoming more and more frequent that common and well-tolerated antibiotics no longer work against dangerous bacterial pathogens.

Colistin was developed in the 1950s. Due to its highly nephrotoxic effect, it was no longer used in humans for many decades after its development. The lack of effective antibiotics, however, has made its revival necessary: for example, in the treatment of dangerous hospital germs such as carbapenem-resistant enterobacteriaceae or Acinetobacter baumannii. Colistin is also on the list of essential medicines of the World Health Organization (WHO).

Colistin is a last-resort antibiotic that is usually only used for severe infections with resistant bacteria. This is due to its severe kidney-damaging side effects, which occur in about 30% of treated patients.

The last-resort antibiotic colistin is an important helper in this emergency. However, its administration is associated with risks of severe side effects: It has a strong nephrotoxic effect, and long-term consequences cannot be ruled out.

It would be advantageous if colistin could be chemically modified so that it is no longer as damaging to the kidneys while maintaining its high antibiotic efficacy.

A research team has now been able to produce an inactivated, harmless form of colistin that is only activated in the body with the help of chemical switches.

In this so-called click-to-release technique, the chemical switches are specifically bound to the disease-causing bacteria. The administered masked colistin is therefore activated specifically at the site of action. The researchers hope that this could reduce side effects. The study is published in the journal Angewandte Chemie International Edition.

The researchers hope that this approach can help minimize the side effects of antibiotics and other medical agents in the future and make them more tolerable for patients.

Jiraborrirak Charoenpattarapreeda et al, A Targeted Click‐to‐Release Activation of the Last‐Resort Antibiotic Colistin Reduces its Renal Cell Toxicity, Angewandte Chemie International Edition (2024). DOI: 10.1002/anie.202408360

Comment by Dr. Krishna Kumari Challa on October 21, 2024 at 9:35am

How Some Fish Regrow Their Fins

Animals like the African killifish can regrow entire body parts after amputation, but how cells know where and how much to grow after injury remains a mystery. A recent iScience publication from Augusto Ortega Granillo, Alejandro Sànchez Alvarado, and their research team at the Stowers Institute for Medical Research sheds light on the mechanisms of positional memory.

1. Otsuki L, Tanaka EM. Positional memory in vertebrate regeneration: A century’s insights .... Cold Spring Harb Perspect Biol. 2021;14(6):a040899.
2. Ortega Granillo A, et al. Positional information modulates transient regeneration-activated c.... iScience. 2024;27(9):110737.

Comment by Dr. Krishna Kumari Challa on October 19, 2024 at 11:09am

Sound of Earth’s magnetic flip 41 000 years ago

Comment by Dr. Krishna Kumari Challa on October 19, 2024 at 9:08am

Scientists show how sperm and egg come together like a key in a lock

How a sperm and an egg fuse together?

New research by scientists  provides tantalizing clues, showing fertilization works like a lock and key across the animal kingdom, from fish to people. This mechanism is really fundamental across all vertebrates.

 The team found that three proteins on the sperm join to form a sort of key that unlocks the egg, allowing the sperm to attach. Their findings, drawn from studies in zebrafish, mice, and human cells, show how this process has persisted over millions of years of evolution. Results were published this week in the journal Cell.

Scientists had previously known about two proteins, one on the surface of the sperm and another on the egg's membrane. Working with international collaborators, researchers used Google DeepMind's artificial intelligence tool AlphaFold—whose developers were awarded a Nobel Prize earlier this month—to help them identify a new protein that allows the first molecular connection between sperm and egg. They also demonstrated how it functions in living things.

It wasn't previously known how the proteins "worked together as a team in order to allow sperm and egg to recognize each other".

The work provides targets for the development of male contraceptives in particular.

Victoria E. Deneke et al, A conserved fertilization complex bridges sperm and egg in vertebrates, Cell (2024). DOI: 10.1016/j.cell.2024.09.035

Comment by Dr. Krishna Kumari Challa on October 19, 2024 at 8:55am

Researchers were able to create a map showing drug resistance across different cancers, focusing on colon, lung, and Ewing sarcoma. The map uncovers more about the mechanisms of drug resistance, highlights DNA changes that may be potential treatment biomarkers, and identifies promising combinations or second-line therapies.

The team found that cancer mutations fall into four different categories depending on the impact of the DNA change. Drug resistance mutations, otherwise known as canonical drug resistance mutations, are genetic changes in the cancer cell that lead to the drug being less effective. For example, changes that mean the drug can no longer bind to its target in the cancer cell.

Drug addiction mutations lead to some of the cancer cells using the drug to help them grow, instead of destroying them. This research supports the use of drug holidays in the case of drug addiction mutations, which are periods without treatment. This could help destroy the cancer cells with this type of mutation, as the cells are now dependent on treatment.

Driver mutations are gain-of-function genetic changes that allow cancer cells to use a different signaling pathway to grow, avoiding the pathway that the drug may have blocked.

Lastly, drug sensitizing variants are genetic mutations that make the cancer more sensitive to certain treatments and could mean that patients with these genetic changes in their tumor would benefit from particular drugs.

The research focused on colon, lung, and Ewing sarcoma cancer cell lines, as these are all prone to developing resistance and have limited second-line treatments available. The team used 10 cancer drugs that are either currently prescribed or going through clinical trials to help highlight if any of these could be repurposed or used in combination to address resistance, decreasing the time it would take to get any potential treatments to the clinic.

Understanding more about the four different types of DNA changes can help support clinical decisions, explain why treatments are not working, support the idea of drug holidays in certain patients, and help develop new treatments. This knowledge also helps accelerate drug companies' research into next-generation cancer inhibitors that could better prevent drug resistance.

Base editing screens define the genetic landscape of cancer drug resistance mechanisms, Nature Genetics (2024). DOI: 10.1038/s41588-024-01948-8

Part 2

Comment by Dr. Krishna Kumari Challa on October 19, 2024 at 8:54am

How scientists are trying to tackle drug resistance in cancer therapies

One of the major challenges in cancer treatment is drug resistance. Mutations in cancer cells mean that over time they become less responsive to therapies. After cancer has become resistant to the initial treatment, the following therapies are known as second-line therapies and options for these can be limited. Understanding what molecular changes are causing the resistance, and what can be done to tackle this, can help uncover new options and inform clinical pathways for specific mutations.

All cancer mutations that cause drug resistance fall into one of four categories. New research has detailed each type, helping to uncover targets for drug development and identify potential effective second-line therapies.

In a new large-scale study, researchers  used CRISPR gene editing to map the genetic landscape of drug resistance in cancers, focusing on colon, lung, and Ewing sarcoma. The team explains how known mutations impact drug resistance and highlights new DNA changes that could be explored further.

The research,  published in Nature Genetics, investigated the effect of mutations on the sensitivity to 10 cancer drugs, also identifying possible effective second-line treatments based on a person's genetic makeup.

By understanding the mechanisms of how cancers become resistant to treatment, researchers can identify new targets for personalized therapies, help treat patients based on their cancer's genetic makeup, give second-line treatment options to those who currently have none, and help further research to develop next-generation cancer drugs that could avoid drug resistance emerging.

Part 1

Comment by Dr. Krishna Kumari Challa on October 19, 2024 at 8:21am

Climate justice broadly encompasses recognition that (1) climate change impacts are unequally felt across society; (2) the worst affected groups often have the least say in the selection and implementation of societal responses to climate change, and (3) climate change-related policymaking processes often fail to recognize the legitimate interests of politically voiceless communities, consequently contributing to further disenfranchisement of marginalized groups. It is a framework that enables those involved in policymaking to identify and tackle the multiple different ways in which the climate crisis intersects with longstanding patterns of social injustice.

Comment by Dr. Krishna Kumari Challa on October 19, 2024 at 8:15am

Bumblebee queens choose to hibernate in pesticide-contaminated soil, scientists discover

An alarming discovery by researchers raises concerns for bumblebee health, survival and reproduction. U of G environmental sciences researchers have found that bumblebee queens are more likely to hibernate in soil contaminated with pesticides than in clean soil—for reasons they still don't quite understand.

The team conducted field experiments in which newly emerged queens of the common eastern bumblebee (Bombus impatiens) were left to fly freely in outdoor enclosures, mate and then choose a site in which to hibernate for the winter.

The choice was between clean soil or soil contaminated with one of five common pesticides, including insecticides and fungicides, across different concentrations.

The School of Environmental Sciences researchers then carefully searched through the soils for hibernating bumblebee queens. They found queens avoided the pesticide-free soil and, in fact, were about twice as likely to be drawn to the pesticide-contaminated soil.

Most bees in the study survived, but other consequences for the colony are highlighted in the study, published in Science of the Total Environment.

"This raises serious concerns for bumblebee health," say the researchers, "especially as this group of important insect pollinators already face many challenges.

Bumblebee queens typically hibernate underground during winter before emerging in spring to start new colonies. Researchers wanted to investigate how bees respond to contaminants at this key but vulnerable life stage.

Previous studies showed that pesticides on crops can either attract or repel bees, depending on the type, the environmental situation and the concentration used.

One possible explanation is that pesticides altered the soil properties and made it more appealing to the queens.

For example, the fungicides used in the study could have killed soil fungi and nematodes, and queens might avoid soils with fungi because they can be harmful during hibernation.

Another possibility is that the queens could have developed an "acquired taste" for pesticides, as researchers put it, due to prior exposure in their environment.

They might also be looking for something new, as novelty-seeking behavior is common for bees and often leads the colony to discover new resources.

More research is needed to fully understand the mechanisms behind this unexpected queen behaviour. But the findings suggest the need to reconsider how pesticides are used and managed in agricultural settings as exposure to pesticides is contributing to a worldwide decline of insects.

 Sabrina Rondeau et al, Bumblebee (Bombus impatiens) queens prefer pesticide-contaminated soils when selecting underground hibernation sites, Science of The Total Environment (2024). DOI: 10.1016/j.scitotenv.2024.176534

Comment by Dr. Krishna Kumari Challa on October 19, 2024 at 8:00am

Different types of fears activate different parts of the brain. 

For a long time, people assumed that the responses to all fearful scenarios occurred similarly within the brain.

There's this story that we've had in the literature that the brain regions that predict fear are things like the amygdala, or the orbital frontal cortex area, or the brainstem. Those are thought to be part of a so-called 'fear circuit' that's been a very dominant model in neuroscience for decades.

In early October 2024,  researchers released new research that undermines that persistent model. In a study published in The Journal of Neuroscience the researchers used MRI scans to observe brain activity when confronted with three distinctive scenarios meant to evoke different types of fear: fear of heights, fear of spiders, and fear of "social threats" (public speaking, confrontations with police).

And contrary to the prevailing scientific wisdom, the neural response to each type of scenario activated different areas of the brain—rather than following a single pattern.

Although based on a small sample size, the study revealed two things: fear responses happened across a wider range of brain regions than expected. But not all brain regions responded across all three situations.

The amygdala, for instance, seemed to carry information that predicted fear during the heights context, but not some of the other contexts. The so-called 'classic threat areas' involved in being predictive of fear across situations are not seen here.

When scientists look at the brain and the neural correlates of fear, part of the reason they want to understand is so they can intervene on it. Their new findings suggest the interventions might also need to be tailored to the person and situation.

This could now affect behaviour-based therapies, but also, much further down the line, pharmacological ones.

Yiyu Wang et al, Neural predictors of fear depend on the situation, The Journal of Neuroscience (2024). DOI: 10.1523/JNEUROSCI.0142-23.2024

Comment by Dr. Krishna Kumari Challa on October 18, 2024 at 11:22am

Dancer Develops a "Cone-Shaped" Head from Breakdancing Too Much 

According to a 2024 medical case report, a breakdancer who'd been performing for 19 years was treated for "headspin hole", a condition also known as "breakdancer bulge" that's unique to breakdancers. It entails a cone shaped mass developing on top of the scalp after repetitive head-spinning. Additional symptoms can include hair loss and sometimes pain around the lump.

Approximately 30% of breakdancers report hair loss and inflammation of their scalp from head-spinning. A headspin hole is caused by the body trying to protect itself. The repeated trauma from head-spinning causes the epicranial aponeurosis—a layer of connective tissue similar to a tendon, running from the back of your head to the front—to thicken along with the layer of fat under the skin on top of the head in an attempt to protect the bones of skull from injury. The body causes a similar protective reaction to friction on the hands and feet, where callouses form to spread the pressure and protect the underlying tissues from damage. Everyday repetitive activities from holding smartphones or heavy weights through to poorly fitting shoes can result in callouses.

But a cone-shaped head isn't the only injury to which breakdancers are prone, however. Common issues can include wrist, knee, hip, ankle, foot and elbow injuries, and moves such as the "windmill" and the "backspin" can cause bursitis—inflammation of the fluid filled sacs that protect the vertebrae of the spine. A headspin hole isn't the worst injury you could sustain from breakdancing either. One dancer broke their neck but thankfully they were lucky enough not to have any major complications.

https://casereports.bmj.com/content/17/9/e261854

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