Comment

Comment by Dr. Krishna Kumari Challa on December 5, 2024 at 2:19pm

To get the cell to use homology-directed repair, the researchers recently began using a molecule called AZD7648, which blocks fast repair and forces the cell to use homology-directed repair. This approach is expected to accelerate the development of more efficient gene therapies. Initial studies with these new therapies have been good. Too good to be true, as it turned out.

A research group led by Corn has discovered that the use of AZD7648 has serious side effects. The study has been published in the journal Nature Biotechnology.

Although AZD7648 promotes precise repair and thus precise gene editing using the CRISPR-Cas9 system as hoped, in a significant proportion of cells this has led to massive genetic changes in a part of the genome that was expected to be modified without scarring.

The ETH researchers found that these changes resulted in the simple deletion of thousands and thousands of DNA building blocks, known as bases. Even whole chromosome arms broke off. This makes the genome unstable, with unpredictable consequences for the cells edited by the technique.

When the researchers analyzed the genome at the sites where it had been edited, it looked correct and precise. But when they analyzed the genome more broadly, they saw massive genetic changes. These are not seen when you only analyze the short, edited section and its immediate neighborhood.

The extent of the negative effects surprised the researchers. In fact, they suspect that they do not yet have a complete picture of the full extent of the damage because they did not look at the entire genome when analyzing the modified cells, only partial regions.

New tests, approaches and regulations are therefore needed to clarify the extent and potential of the damage.

The development of any new technology is a rocky road. One stumble does not mean we give up on the technology, say the researchers.

Gene therapies based on the CRISPR-Cas system have already been successfully used in clinical practice. In recent years, for example, a hundred patients suffering from the hereditary disease sickle cell anemia have been treated with CRISPR-Cas-based therapeutics—without AZD7648.

"All patients are considered cured and have no side effects".

Grégoire Cullot et al, Genome editing with the HDR-enhancing DNA-PKcs inhibitor AZD7648 causes large-scale genomic alterations, Nature Biotechnology (2024). DOI: 10.1038/s41587-024-02488-6

Part 2

Comment by Dr. Krishna Kumari Challa on December 5, 2024 at 2:15pm

Serious side effect of using CRISPR-Cas gene scissors uncovered: AZD7648 molecule can destroy parts of genome

Genome editing with various CRISPR-Cas molecule complexes has progressed rapidly in recent years. Hundreds of labs around the world are now working to put these tools to clinical use and are continuously advancing them.

CRISPR-Cas tools allow researchers to modify individual building blocks of genetic material in a precise and targeted manner. Gene therapies based on such gene editing are already being used to treat inherited diseases, fight cancer and create drought- and heat-tolerant crops.

The CRISPR-Cas9 molecular complex, also known as genetic scissors, is the most widely used tool by scientists around the world. It cuts the double-stranded DNA at the exact site where the genetic material needs to be modified. This contrasts with newer gene-editing methods, which do not cut the double strand.

The cut activates two natural repair mechanisms that the cell uses to repair such damage: a fast but imprecise one that reconnects only the ends of the cut DNA, and a slow and precise one that is not activated in every case. The latter requires a copyable template for repair to accurately rejoin the DNA at the cut site.

The slow variant is called homology-directed repair. Researchers want to use this method of repair because it allows the precise integration of individual DNA segments into a desired gene region. The approach is very flexible and can be used to repair different disease genes.

In principle, it could be used to cure any disease.

Part 1

Comment by Dr. Krishna Kumari Challa on December 5, 2024 at 11:29am

Interestingly, the cancer cells themselves were unable to use fructose readily as a nutrient because they do not express the right biochemical machinery. Liver cells do. This allows them to convert fructose into LPCs, which they can secrete to feed tumors.

Gary Patti, Dietary fructose enhances tumour growth indirectly via interorgan lipid transfer, Nature (2024). DOI: 10.1038/s41586-024-08258-3. www.nature.com/articles/s41586-024-08258-3

Part 2

Comment by Dr. Krishna Kumari Challa on December 5, 2024 at 11:27am

Research reveals how fructose in diet enhances tumor growth

Fructose consumption has increased considerably over the past five decades, largely due to the widespread use of high-fructose corn syrup as a sweetener in beverages and ultra-processed foods.

New research  shows that dietary fructose promotes tumor growth in animal models of melanoma, breast cancer and cervical cancer. However, fructose does not directly fuel tumors, according to the study published Dec. 4 in the journal Nature.

Scientists discovered that the liver converts fructose into usable nutrients for cancer cells, a compelling finding that could open up new avenues for care and treatment of many different types of cancer.

Using metabolomics—a method of profiling small molecules as they move through cells and across different tissues in the body—the researchers concluded that one way in which high levels of fructose consumption promote tumor growth is by increasing the availability of circulating lipids in the blood. These lipids are building blocks for the cell membrane, and cancer cells need them to grow.

Researchers looked at numerous different cancers in various tissues throughout the body, and they all followed the same mechanism.

Scientists have long recognized that cancer cells have a strong affinity for glucose, a simple sugar that is the body's preferred carbohydrate-based energy source.

In terms of its chemical structure, fructose is similar to glucose. They are both common types of sugar, with the same chemical formula, but they differ in how the body metabolizes them. Glucose is processed throughout the whole body, while fructose is almost entirely metabolized by the small intestine and liver.

Both sugars are found naturally in fruits, vegetables, dairy products and grains. They are also added as sweeteners in many processed foods. 

 The researchers found that added fructose promoted tumor growth without changing body weight, fasting glucose or fasting insulin levels. It had a rather dramatic impact. In some cases, the growth rate of the tumors accelerated by two-fold or even higher.

The researchers attempted to repeat a version of this test by feeding fructose to cancer cells isolated in a dish, the cells did not respond. In most cases they grew almost as slowly as if we gave them no sugar at all.

Part 1

Comment by Dr. Krishna Kumari Challa on December 4, 2024 at 11:40am

Toxin in blood of kidney disease patients could contribute to stroke risk, study suggests

Scientists have revealed that a toxin found in the blood of patients with chronic kidney disease (CKD) damages the body's protective blood–brain barrier, likely contributing to the risk of stroke.

Researchers investigated the effect on the central nervous system of "p-cresol sulfate," a molecule produced by the gut microbiome. 

While this molecule is efficiently cleared by the kidneys in healthy people, it accumulates in the blood of patients with CKD.
Investigating the effect of p-cresol sulfate on human tissue and in mice—and replicating their results using blood samples from dialysis patients—the team found that the toxin triggers a process which activates two enzymes that damage the wall of brain blood vessels.

The researchers observed how this impairs the critically protective blood–brain barrier, which acts as a shield to prevent harmful substances and toxins in the body from reaching the brain.

Damage to the blood–brain barrier is known to contribute to the risk of stroke, which can be up to 30 times greater in CKD patients than in the general population.

As part of the study, however, the researchers also found that a class of 'inhibitor' type drugs—which can block chemical reactions in the body—showed promising results in being able to prevent this damage from occurring.

In further tests, the team found that a class of enzyme inhibitor drugs was able to block the damaging effects of blood from CKD patients on cells in vitro.

As well as enhanced stroke risk, patients with CKD, including those not yet requiring dialysis, exhibit significant cognitive decline, a change that seems to be at least partly driven by damage to the brain's blood vessels.

 Sita N. Shah et al, Cerebrovascular damage caused by the gut microbe/host co-metabolite p -cresol sulfate is prevented by blockade of the EGF receptor, Gut Microbes (2024). DOI: 10.1080/19490976.2024.2431651

Comment by Dr. Krishna Kumari Challa on December 4, 2024 at 10:39am

Seeing through the mystery of an X-ray emissions mechanism

Scientists who study X-rays, lightning and similar phenomena have observed something curious: In lab experiments replicating these occurrences, electrons accelerated between two electrodes can be of a higher energy than the voltage applied.

This defies an assumption in physics that the energy of the electrons should correspond with the voltage applied.

Recently, a team of  researchers used mathematical modeling to explain the underlying mechanism at play. They published their results in Physical Review Letters.

Through mathematical modeling, they  demonstrated that an energy feedback process is responsible for this occurrence.

According to them when the electrons interact with the material of the electrode, they emit X-rays, which are made of photons—massless, charge-less particles that comprise light. Some of these photons propagate backward, enabling more electrons to release from the other electrode.

A small group of these electrons have energy corresponding to the original energy. Then they accelerate again, and the process continues through several cycles. The researchers modeled this very high energy process.

Their model also helped explain why electrodes of different shapes and materials produced this effect to varying degrees. We get maximum effect when we have flat electrodes, and a minimized effect when the electrodes are needle-like. 

This makes sense, because the large surface areas of the flat electrodes are good for the interaction between the electrons and photons and the way they bounce back and forth. When the surface area is reduced, the effect is minimized.

The researchers also examined via simulation and modeling how the phenomenon emerges with different materials.

Tungsten is the standard material used for X-ray production, and we know it's a good material for this. It is a robust material for electron production used in current in X-ray machines.

The researchers said that their findings may be useful for the development of new ways of producing X-rays in the future. Specifically, they said that the work may stimulate new research on the production of energetic electrons from solid materials, potentially making X-rays machines faster and more light weight and compact.

Victor P. Pasko et al, Photoelectric Feedback Mechanism for Acceleration of Runaway Electrons in Gas Discharges at High Overvoltages, Physical Review Letters (2024). DOI: 10.1103/PhysRevLett.133.235301

Comment by Dr. Krishna Kumari Challa on December 4, 2024 at 10:15am

Countdown to an ice-free Arctic: Research warns of accelerated timelines

The first summer on record that melts practically all of the Arctic's sea ice, an ominous milestone for the planet, could occur as early as 2027.

For the first time, an international research team used computer models to predict when the first ice-free day could occur in the northernmost ocean. An ice-free Arctic could significantly impact the ecosystem and Earth's climate by changing weather patterns. 

The first ice-free day in the Arctic won't change things dramatically, the team says. It will show that we've fundamentally altered one of the defining characteristics of the natural environment in the Arctic Ocean, which is that it is covered by sea ice and snow year-round, through greenhouse gas emissions.

The findings were published Dec. 3 in the journal Nature Communications. Jahn will also present the results on Dec. 9 at the American Geophysical Union annual meeting in Washington D.C.

The researchers' projected/estimated the first ice-free Arctic day using output from over 300 computer simulations. They found that most models predicted that the first ice-free day could happen within nine to 20 years after 2023, regardless of how humans alter their greenhouse gas emissions. The earliest ice-free day in the Arctic Ocean could occur within three years.
It's an extreme scenario but a possibility based on the models. In total, nine simulations suggested that an ice-free day could occur in three to six years.

The researchers found that a series of extreme weather events could melt two million square kilometers or more of sea ice in a short period of time: A unusually warm fall first weakens the sea ice, followed by a warm Arctic winter and spring that prevents sea ice from forming. When the Arctic experiences such extreme warming for three or more years in a row, the first ice-free day could happen in late summer.

Those kinds of warm years have already happened.

But there's also good news: A drastic cut in emissions could delay the timeline for an ice-free Arctic and reduce the time the ocean stays ice-free, according to the study.

Céline Heuzé et al, The first ice-free day in the Arctic Ocean could occur before 2030, Nature Communications (2024). DOI: 10.1038/s41467-024-54508-3 , dx.doi.org/10.1038/s41467-024-54508-3

Comment by Dr. Krishna Kumari Challa on December 4, 2024 at 9:56am

Following this, daily solar radiation was the second most important factor contributing to rice quality changes (higher solar radiation leading to lower HRR), then daily precipitation (less precipitation corresponding to lower HRR) and lastly daytime vapor pressure deficit (beyond a threshold of 0.5–1 kPa, HRR declines).
The average rice quality across all sites and years for China had a HRR of ~62%, but reduced by 1.45% every decade. In Japan, the average HRR was slightly higher at ~66%, with a prominent rate of decline of 7.6% every decade.

In both countries, there is a strong gradient of diminished rice quality from northern to southern provinces and prefectures, likely linked to southern regions being closer to the equator and therefore experiencing higher nighttime temperatures.
This research is important as projections under both moderate and high emissions scenarios suggest rice quality will continue to decline in the decades to come as climate change progresses.
Given all of this, the likelihood of rice cultivars adapting in tandem with the rate of climate change may pose a hazard to sustainable food supplies, human nutrition and economic stability in years to come.

Xianfeng Liu et al, Warming Leads to Lower Rice Quality in East Asia, Geophysical Research Letters (2024). DOI: 10.1029/2024GL110557

Part 2

Comment by Dr. Krishna Kumari Challa on December 4, 2024 at 9:53am

Climate warming is reducing rice quality

Rice is a food staple for billions of people worldwide, with demand doubling over the past 50 years, and is predominantly grown in Asia before being exported globally. This crop is sensitive to weather conditions and, as such, understanding how yields are affected by climate change is of paramount importance to ensure sustainable food supplies into the future.

Beyond yield, the quality of rice may also be affected, determined by a combination of appearance, palatability, nutritional profile and milling properties.

Research published in Geophysical Research Letters, has highlighted a decline in rice quality in  Asia, coincident with changing temperatures.

Researchers used data collected over 35 years to explore patterns in rice quality from Japan and China. This is based upon head rice rate (HRR), which is a measure of the fraction of milled rice kernels that retain 75% of their length after milling, during which the husk and bran are removed.
The research team explored a number of climate variables via modeling to ascertain which had the greatest effect on HRR; these variables were nighttime temperature, daytime temperature, diurnal temperature, daily averaged temperature, hot days (above 30/35 °C), precipitation, precipitation frequency, soil moisture, solar radiation, cloud cover, relative humidity, daytime vapor pressure deficit, transpiration and carbon dioxide concentration.

Ultimately, the scientists determined that overnight temperatures are the main driver of reduced rice quality. In particular, as nighttime temperatures become warmer, a critical threshold for decline begins at 12 °C and 18 °C for Japan and China respectively. When flowering and grain growth occur in such conditions, rates of photosynthesis and starch accumulation in the grain decrease, leading to lower rice quality as more grains are susceptible to breakage.

Part 1

Comment by Dr. Krishna Kumari Challa on December 3, 2024 at 12:32pm

Galleri blood test can  help diagnose multiple forms of cancer

Did you know that the technology to detect more than 50 cancers with one test existed?

Single-cancer screenings are the norm. The focus is usually on three specific cancers in women (breast, colon and cervical) and two in men (prostate and colon). Lung is a focus for heavy smokers.

Screening for these cancers helps save lives. But it creates what Ofman calls a classic spotlight problem, shining the light over there while other, more aggressive cancers go unscreened.

The Galleri test doesn't target a specific area. It looks for the fingerprint, the biological signal in DNA that has been shed from cancer. It's a very specific marker and detects where that cancer is in the body.

It creates a more effective and efficient screening programme.

And unlike other cancer tests (10%) the false positive rate of the Galleri test is just 0.5%.

Source: Medical news

• ‹ Previous
• 1
• …
• 70
• 71
• 72
• 73
• 74
• …
• 1053
• Next ›
• Page