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Comment by Dr. Krishna Kumari Challa on August 29, 2024 at 9:23am

Researchers take inspiration from viruses to improve delivery of nucleic acid-based therapies to cancer cells

Researchers are developing a patent-pending platform technology that mimics the dual-layer structure of viruses to deliver nucleic acid (NA)-based therapies to targeted cancer cells.

 The carrier system is called LENN. 

LENN includes two protective layers. The inner shell condenses the nucleic acid; the outer shell protects it from the immune system so it can circulate freely and target cancer cells. The researchers are mimicking the strategies of viral particles that have been doing this effectively for millions of years.

The data shows that this agile nanocarrier is flexible in its targeting ability, cargo size and disassembly kinetics. It provides an alternative route for nucleic acid delivery using a biomanufacturable, biodegradable, biocompatible and highly tunable vehicle capable of targeting a variety of cells depending on their tumor-specific surface markers.

Nucleic acid-based therapies are revolutionizing biomedical research through their ability to control cellular functions at the genetic level. Therapies comprising several constructs are being explored to expand the druggable sites of the human genome.

Aayush Aayush et al, Development of an Elastin-like Polypeptide-Based Nucleic Acid Delivery System Targeted to EGFR+ Bladder Cancer Cells Using a Layer-by-Layer Approach, Biomacromolecules (2024). DOI: 10.1021/acs.biomac.4c00165

Comment by Dr. Krishna Kumari Challa on August 29, 2024 at 9:12am

But the researchers found that these two groups of neurons interact in a surprising way.

This work revealed that VIP neurons and pulvinar act synergistically together. VIP neurons act like a switchboard: When they are off, the pulvinar suppresses activity in the neocortex, but when VIP neurons are on, the pulvinar can strongly and selectively boost sensory responses in the neocortex. The cooperative interaction of these two pathways thus mediates the sensory prediction error signals in the visual cortex.

Sonja Hofer, Cooperative thalamocortical circuit mechanism for sensory prediction errors, Nature (2024). DOI: 10.1038/s41586-024-07851-w. www.nature.com/articles/s41586-024-07851-w

Part 2

Comment by Dr. Krishna Kumari Challa on August 29, 2024 at 9:11am

 New brain mechanism uncovered

Researchers have discovered how two brain areas, the neocortex and the thalamus, work together to detect discrepancies between what animals expect from their environment and actual events. These prediction errors are implemented by selective boosting of unexpected sensory information. These findings enhance our understanding of predictive processing in the brain and could offer insights into how brain circuits are altered in autism spectrum disorders (ASDs) and schizophrenia spectrum disorders (SSDs).

The research, published in Nature, outlines how scientists at the Sainsbury Wellcome Centre at UCL studied mice in a virtual reality environment to take us a step closer to understanding both the nature of prediction error signals in the brain as well as the mechanisms by which they arise.

Our brains constantly predict what to expect in the world around us and the consequences of our actions. When these predictions turn out wrong, this causes strong activation of different brain areas, and such prediction error signals are important for helping us learn from our mistakes and update our predictions. But despite their importance, surprisingly little is known about the neural circuit mechanisms responsible for their implementation in the brain.

To study how the brain processes expected and unexpected events, the researchers placed mice in a virtual reality environment where they could navigate along a familiar corridor to get to a reward. The virtual environment enabled the team to precisely control visual input and introduce unexpected images on the walls. By using a technique called two-photon calcium imaging, the researchers were able to record the neural activity of many individual neurons in the primary visual cortex, the first area in our neocortex to receive visual information from the eyes.

Previous theories proposed that prediction error signals encode how the actual visual input is different from expectations, but surprisingly the present study found no experimental evidence for this. Instead, it was discovered that the brain boosts the responses of neurons that have the strongest preference for the unexpected visual input.

The error signal we observe is a consequence of this selective amplification of visual information. This implies that our brain detects discrepancies between predictions and actual inputs to make unexpected events more salient.

To understand how the brain generates this amplification of the unexpected sensory input in the visual cortex, the team used a technique called optogenetics to inactivate or activate different groups of neurons. They found two groups of neurons that were important for causing the prediction error signal in the visual cortex: vasoactive intestinal polypeptide (VIP)-expressing inhibitory interneurons in V1 and a thalamic brain region called the pulvinar, which integrates information from many neocortical and subcortical areas and is strongly connected to V1.

Part 1

Comment by Dr. Krishna Kumari Challa on August 29, 2024 at 9:00am

Since the late 1960s, spacecraft flying over Earth's poles have detected a stream of particles flowing from our atmosphere into space. Theorists predicted this outflow, which they dubbed the "polar wind," spurring research to understand its causes.

Some amount of outflow from our atmosphere was expected. Intense, unfiltered sunlight should cause some particles from our air to escape into space, like steam evaporating from a pot of water. But the observed polar wind was more mysterious. Many particles within it were cold, with no signs they had been heated—yet they were traveling at supersonic speeds.

Something had to be drawing these particles out of the atmosphere.

Scientists suspected that a yet-to-be-discovered electric field could be at work.

The hypothesized electric field, generated at the subatomic scale, was expected to be incredibly weak, with its effects felt only over hundreds of miles. For decades, detecting it was beyond the limits of existing technology. In 2016, researchers got to work inventing a new instrument they thought was up to the task of measuring Earth's ambipolar field.

The team's instruments and ideas were best suited for a suborbital rocket flight launched from the Arctic. In a nod to the ship that carried Ernest Shackleton on his famous 1914 voyage to Antarctica, the team named their mission Endurance. The scientists set a course for Svalbard, a Norwegian archipelago just a few hundred miles from the North Pole and home to the northernmost rocket range in the world.

Svalbard is the only rocket range in the world where you can fly through the polar wind and make the measurements that 're needed.

On May 11, 2022, Endurance launched and reached an altitude of 477.23 miles (768.03 kilometers), splashing down 19 minutes later in the Greenland Sea. Across the 322-mile altitude range where it collected data, Endurance measured a change in electric potential of only 0.55 volts.

A half a volt is almost nothing—it's only about as strong as a watch battery. But that's just the right amount to explain the polar wind.

Hydrogen ions, the most abundant type of particle in the polar wind, experience an outward force from this field 10.6 times stronger than gravity.

"That's more than enough to counter gravity—in fact, it's enough to launch them upwards into space at supersonic speeds.

Heavier particles also get a boost. Oxygen ions at that same altitude, immersed in this half-a-volt field, weigh half as much. In general, the team found that the ambipolar field increases what's known as the "scale height" of the ionosphere by 271%, meaning the ionosphere remains denser to greater heights than it would be without it.

It's like this conveyor belt , lifting the atmosphere up into space.

Endurance's discovery has opened many new paths for exploration. The ambipolar field, as a fundamental energy field of our planet alongside gravity and magnetism, may have continuously shaped the evolution of our atmosphere in ways we can now begin to explore. Because it's created by the internal dynamics of an atmosphere, similar electric fields are expected to exist on other planets, including Venus and Mars.

Any planet with an atmosphere should have an ambipolar field. Now that we've finally measured it, we can begin learning how it's shaped our planet as well as others over time.

Glyn A. Collinson et al, Earth's ambipolar electrostatic field and its role in ion escape to space, Nature (2024). DOI: 10.1038/s41586-024-07480-3

Part 2

Comment by Dr. Krishna Kumari Challa on August 29, 2024 at 8:54am

Scientists discover a  global electric field on Earth

Using observations from a NASA suborbital rocket, an international team of scientists, for the first time, has successfully measured a planet-wide electric field thought to be as fundamental to Earth as its gravity and magnetic fields.

Known as the ambipolar electric field, scientists first hypothesized over 60 years ago that it drove how our planet's atmosphere can escape above Earth's North and South Poles. Measurements from the rocket, NASA's Endurance mission, have confirmed the existence of the ambipolar field and quantified its strength, revealing its role in driving atmospheric escape and shaping our ionosphere—a layer of the upper atmosphere—more broadly.

Understanding the complex movements and evolution of our planet's atmosphere provides clues not only to the history of Earth but also gives us insight into the mysteries of other planets and determining which ones might be hospitable to life. A research paper on this topic is published in the journal Nature.

Part 1

Comment by Dr. Krishna Kumari Challa on August 29, 2024 at 8:39am

This study establishes extremely important resources for the field.
It provides not only metabolic characteristics of various bat species with different diets, but also their intestinal morphology, and candidate genomic regions and protein structural differences that could be driving dietary adaptations.
The datasets will fuel future research that aims to differentiate mammalian dietary differences and could progress the development of novel therapeutics for a variety of metabolic diseases in humans.

Oh yes, if that happens, you can eat your favourite sweets or ice creams without thinking about any health consequences!

Sugar assimilation underlying dietary evolution of Neotropical bats, Nature Ecology & Evolution (2024). DOI: 10.1038/s41559-024-02485-7

Part 3

Comment by Dr. Krishna Kumari Challa on August 29, 2024 at 8:37am

Looking to animals that have existed for millions of years allows us to start to catalog changes that have happened over evolution. What makes Neotropical leaf-nosed bats so unique to study is that this group is comprised of many different species with very diverse diets, making it feasible to find answers about how diet evolves. The hope is that we can extend this understanding to other mammals, including humans, where there may be ways to learn how to better protect our own health.
To uncover how bats diversified their diets, the research team traveled to the jungles of Central America, South America, and the Caribbean to conduct fieldwork over several years. These catch-and-release expeditions were focused on performing glucose tolerance tests—measuring the concentration of sugar in blood—on nearly 200 wild-caught bats across 29 species after a single feeding of one of three types of sugars associated with diets of insects, fruits, or nectar.
They observed various ways sugar is assimilated—absorbed, stored and used in the body—and how this process has become specialized due to different diets.
The mechanism for maintaining blood sugar levels within a narrow, healthy range is called glucose homeostasis, which is typically regulated by the hormone insulin and is what goes awry in diabetes. Different species of leaf-nosed bats reveal a spectrum of adaptations to glucose homeostasis, ranging from changes in intestinal anatomy to genetic alterations for proteins that transport sugar from blood to cells.
Fruit bats have honed their insulin signaling pathway to lower blood sugar. On the other extreme, nectar bats can tolerate high blood glucose levels, similar to what is observed in people with unregulated diabetes. They have evolved a different mechanism, and it does not seem to depend on insulin.
Although precisely how nectar bats are managing glucose is still under investigation, the researchers found potential clues for alternative metabolic strategies for glucose regulation. Bats with sugar-rich diets were observed to have longer portions of their intestines and to have intestinal cells with greater surface areas for absorbing nutrients from food, compared to bats with other diets. In addition, nectar bats, separate from fruit bats, have a continual expression of a gene responsible for sugar transport, a trait also observed in a species of hummingbird.
Part 2

Comment by Dr. Krishna Kumari Challa on August 29, 2024 at 8:32am

Some bats are surviving and thriving with blood sugar levels that would be lethal for other mammals

Humans must regulate blood sugar concentrations to stay healthy and to fuel our cells. Too little or too much can cause serious health complications, and high blood sugar is a hallmark of the metabolic condition, diabetes. New research  may enable potential solutions to metabolic disease by turning to evolution and to bats.

Published in Nature Ecology and Evolution, the study reports the highest naturally occurring blood sugar concentrations in mammals ever observed, a finding that suggests bats have evolved strategies to survive, and even thrive, with this extreme trait.

This new study  reports blood sugar levels that are the highest we have ever seen in nature—what would be lethal, coma-inducing levels for mammals, but not for bats.

Thirty million years ago, the Neotropical leaf-nosed bat survived solely on insects. Since then, these bats have diversified into many different species by changing what they eat. From insects, different lineages now specialize in diets including fruits, nectar, meat, and everything in between—even just blood.

The new study reports the highest naturally occurring blood sugar concentrations in mammals ever observed, a finding that suggests bats have evolved strategies to survive, and even thrive, with this extreme trait. Credit: Stowers Institute for Medical Research

Part 1

Comment by Dr. Krishna Kumari Challa on August 28, 2024 at 9:52am

How mindset could affect the body's response to vaccination

In a recent study, researchers found that beliefs and assumptions people have about COVID-19 vaccines seemed to influence their vaccination experience—including side effects and, in some cases, immune response.

While most people can appreciate that vaccination is an amazing achievement, their enthusiasm might falter when it comes time to schedule and receive their own. And new research suggests that might influence how the vaccine affects them.

Researchers studied the effects of different types of positive and negative mindsets regarding the COVID-19 vaccine.

Their work, published in the journal Brain, Behavior & Immunity—Health, suggests that a positive mindset is associated with more positive outcomes, such as less stress and side effects, better mood, and possibly even better immune response.

*Details of the findings include: All positive vaccine-related mindsets predict lower anxiety on the day of the appointment, and lower stress and sadness—and more happiness—in the days around vaccination.

*A positive mindset about the efficacy of the vaccine and how the body will respond to vaccination were linked to fewer negative physical side effects.

*The vaccine mindset that side effects indicate "the vaccine is working" was associated with better immune response—specifically, higher antibodies six months later.

Many people will be surprised by these findings, but they shouldn't be," said the authors. Our brains are connected to every physiological system in our bodies, and we know from decades of previous research on placebo effects and psychoneuroimmunology that our mindsets can influence physiological outcomes, including the immune system.

Darwin A. Guevarra et al, Examining the association of vaccine-related mindsets and post-vaccination antibody response, side effects, and affective outcomes, Brain, Behavior, & Immunity - Health (2024). DOI: 10.1016/j.bbih.2024.100818

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Comment by Dr. Krishna Kumari Challa on August 28, 2024 at 9:41am

Eastern equine encephalitis

Most people infected with eastern equine encephalitis don't develop symptoms, but some can come down with fever or swelling of the brain and about one third of people infected die.

 It is caused by a virus and is not very common around the world. The virus typically spreads in certain swamps.

West Nile virus

About 2 in 10 people infected with West Nile virus develop symptoms, which can include fever and swelling of the brain. About 1 in 10 people who develop severe symptoms die. 

Malaria

Malaria infected nearly 250 million people globally in 2022 and killed more than 600,000, mostly children. It is caused by a parasite carried by mosquitoes and mainly infects people in tropical regions, especially Africa. A vaccination campaign has been launched in recent months that health officials hope will help reduce cases and deaths.

Dengue

Also known as "break-bone fever" because it can be so painful, dengue is becoming more common. The World Health Organization says that about half the world's population is at risk of getting the disease, and there are 100 million to 400 million infections every year. Not everyone gets symptoms, which can include fever, severe headaches and pain in the muscles and joints.

Source: News agencies

Part 2

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