Saturday, January 18, 2020

Common foods alter gut bacteria by influencing viruses

In science today, food and gut bacteria are two topics that are guaranteed to fuel interest and debate. Both, of course, are interrelated, and a new study focuses on some subtleties of this relationship.

The lack of a healthy population of gut bacteria compromises our health; the same is true when we do not eat a healthful diet. However, scientists do not entirely understand the exact impact of specific foods on gut bacteria.

This knowledge gap is due, in part, to the unbelievable complexity of the microbiome. One factor that muddies the water is bacteriophages, or phages for short.


The phage

Phages are viruses that only attack bacteria. Within the gut, these viruses outnumber the dizzyingly numerous gut bacteria.

Each phage only attacks a specific type of bacterium, meaning that it can influence levels of gut bacteria. Phages need bacteria to live, so if bacteria are absent, the phages cannot survive.
This means that any foods that influence phages can influence gut bacteria and vice versa. For example, if the population of one type of phage increases, the bacteria that they consume will dwindle, potentially making room for another species of bacteria to multiply.

In this way, viruses can affect the overall microbiome — by pruning one species, they provide space for other species to fill.


Switching from prophage

Most phages in the gut are present in a dormant form — their DNA is integrated into the bacteria's genome. In this form, they are called prophages.

Scientists have identified certain compounds that trigger prophages to return to their active form. When this happens, hundreds of new phages burst out of the bacterial cell, killing the host and attacking other bacteria; these compounds include soy sauce, nicotine, and some antibiotics, such as ciprofloxacin. To date, the list of phage-promoting compounds is relatively short.

It is essential to uncover which chemicals fuel phage activity. Because phages attack and kill bacteria, if we understand how to manipulate them, they could work as powerful, natural antibiotics.

A recent study set out to expand the list of compounds that induce phage activity. The scientists from San Diego State University, CA, published their findings in the journal Gut Microbes. They hope that their results will introduce the "possibility of using diet to intentionally landscape the human gut microbiome via prophage induction."

"We could actually tackle certain conditions by adjusting the foods we consume that will affect microbial diversity, which in turn will influence health and diseases."  Research associate Lance Boling

To investigate, the researchers chose a wide range of compounds that might influence phage activity. They selected a range of bacteria from two phyla that are common in the gut: Bacteroidetes and Firmicutes. They included both beneficial and pathogenic strains of bacteria.

From 117 food compounds, they narrowed down their search to just 28. The researchers observed the growth of bacteria in the presence of each specific compound; they also observed its growth without the compound as a control. Next, they used flow cytometry, a process that is sensitive enough to detect unimaginably small virus particles.


Which foods influence phages?

Of the 28 candidates, 11 compounds produced levels of virus particles at a rate higher than the controls, which signifies that they influenced phage activity.

Some of the most significant phage boosts occurred in the presence of clove, propolis (a compound produced by bees), uva ursi (also known as kinnikinnick or bearberry), and aspartame.


Conversely, some foods reduced the number of virus particles; most notably, these included rhubarb, fernet (a type of Italian liquor), coffee, and oregano.

To complicate matters, some compounds boosted phage activity associated with some bacteria, but reduced phage activity related to others; these compounds include toothpaste, grapefruit seed extract, and pomegranate.

According to the authors, one of the most potent antibacterial foods was hot tabasco sauce, which "reduced the growth of all three [gastrointestinal] species, except the opportunistic pathogen P. aeruginosa, by an average of 92%."

Tabasco contains vinegar, but when they tested vinegar alone, it only reduced bacterial growth by 71%. They believe that capsaicin — the spicy compound in chilis — may explain the additional antibacterial capabilities. However, in the experiments with tabasco, no virus particles were found, so phages are unlikely to be involved.


The future

These findings are important. Scientists now know that the microbiome can influence our physical and mental health; it can also cause inflammation and increase cancer risk. If scientists can work out how to alter the microbiome in specific ways, they can, in theory, remove or reduce these risks.

As one of the authors, Forest Rohwer, explains, "The ability to kill specific bacteria, without affecting others, makes these compounds very interesting."

The new list of compounds is by no means exhaustive, of course, as Rohwer says, "There are probably thousands of compounds that would be useful for eliminating unwanted bacteria."

The authors hope that scientists will continue along these lines. They also explain that scientists will need to try to figure out the molecular mechanisms that switch the phage from inactivity to activity.


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Sunday, December 29, 2019

Protein that spurs bowel cancer growth identified

Researchers have identified a key protein that supports the growth of many bowel cancer, paving way for development of new therapies to combat the deadly disease.

The study revealed that a protein called Importin-11 transports the cancer-causing protein beta-catenin into the nucleus of colon cancer cells, where it can drive cell proliferation.


Inhibiting this transport step could block the growth of most colorectal cancers-also called bowel cancers-- caused by elevated beta-catenin levels. Around 80% of colorectal cancers are associated with mutations in a gene called APC that results in elevated levels of beta-catenin protein.


This increase in beta-catenin is followed by the protein's accumulation in the cell nucleus, whee it can activate numerous genes that drive cell proliferation and promote the growth and maintenance of colorectal tumours.


But how beta-catenin enters the cell nucleus after its levels rise is poorly understood. Because the molecular mechanisms underlying beta-catenin nuclear transport remain unclear, we set out to identify genes required for continuous beta-catenin activity in colorectal cancer cells harbouring APC mutations, said one of the researchers.


Under CRISPR DNA editing technology, the researchers developed a new technique that allowed them to screen the human genome for genes that support beta-catenin's activity in colorectal cancer cells after its levels have been elevated by mutations in APC.


The researchers found that Importin-11 binds to beta-catenin and escorts it into the nucleus of colorectal cancer cells with mutations in APC. Removing Importin-11 from these cells prevented beta-catenin from entering the nucleus and activating its target genes.


The researchers discovered that Importin-11 levels are often elevated in human colorectal cancers. Moreover, removing Importin-11 inhibited the growth of tumours formed by APC mutant cancer cells isolated from patients.


We concluded that Importin-11 is required for the growth of colorectal cancer cells, the researcher said. Learning more about how Importin-11 transport beta-catenin into the nucleus may help researchers develop new therapies that block this process and reduce the growth of colorectal cancers caused by mutations in APC.


this is only for your information, kindly take the advice of your doctor for medicines, exercises and so on.     
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Researchers have identified a key protein that supports the growth of many bowel cancers, paving the way for development of new therapies to combat the deadly disease. The study, published in the Journal of Cell Biology, revealed that a protein called Importin-11 transports the cancer-causing protein beta-catenin into the nucleus of colon cancer cells, where it can drive cell proliferation. https://www.thehansindia.com/hans/hans-classroom/protein-that-spurs-bowel-cancer-growth-identified-593673

https://www.thehansindia.com/hans/hans-classroom/protein-that-spurs-bowel-cancer-growth-identified-593673
Researchers have identified a key protein that supports the growth of many bowel cancers, paving the way for development of new therapies to combat the deadly disease. The study, published in the Journal of Cell Biology, revealed that a protein called Importin-11 transports the cancer-causing protein beta-catenin into the nucleus of colon cancer cells, where it can drive cell proliferation. https://www.thehansindia.com/hans/hans-classroom/protein-that-spurs-bowel-cancer-growth-identified-593673

https://www.thehansindia.com/hans/hans-classroom/protein-that-spurs-bowel-cancer-growth-identified-593673
Researchers have identified a key protein that supports the growth of many bowel cancers, paving the way for development of new therapies to combat the deadly disease. The study, published in the Journal of Cell Biology, revealed that a protein called Importin-11 transports the cancer-causing protein beta-catenin into the nucleus of colon cancer cells, where it can drive cell proliferation. https://www.thehansindia.com/hans/hans-classroom/protein-that-spurs-bowel-cancer-growth-identified-593673

https://www.thehansindia.com/hans/hans-classroom/protein-that-spurs-bowel-cancer-growth-identified-593673

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Friday, October 18, 2019

Researchers develop cheaper method to identify aggressive tumours

In a recent study conducted by the researchers at Karolinska Institute in Sweden, a new cheap method has been developed that can identify highly heterogeneous tumours which can become very aggressive in future and therefore needs to be treated more aggressively.

A common feature of cancer cells is alterations in the number of copies in which each chromosome or gene is present in the genome - a phenomenon known as copy number alterations or CNAs. Within the same tumour, cells belonging to different anatomical parts of the tumour may carry different CNAs. Tumours with many CNAs are typically very aggressive and tend to reform more often, even after harsh treatments.

The Bienko-Crosetto Laboratory at Karolinska Institute and Science for Life Laboratory in Sweden have developed a new genomic method, named CUTseq, which can assess the amount and type of CNAs in many different parts of the same tumour, at a much lower cost than existing technologies.
 

A senior researcher at the Department of Medical Biochemistry and Biophysics, said, "I expect that CUTseq will find many useful applications in cancer diagnostics. Multi-region tumour sequencing is going to be increasingly used in the diagnostic setting, in order to identify patients with highly heterogeneous tumours that need to be treated more aggressively. I believe that our method can play a leading role here."

The method works with DNA extracted from multiple biopsies and even from very small portions of thin tissue sections - the type of sample that pathologists commonly rely on to make a diagnosis of cancer under the microscope.

By tagging the DNA extracted from multiple regions of the same tumour sample with unique molecular barcodes, a comprehensive picture of the heterogeneity of CNAs in a tumour can be obtained with a single sequencing experiment.

Applications of CUTseq are not only limited to cancer diagnostics, according to the researchers behind the new method.

"For example, CUTseq could be used as a platform for cell line authentication and to monitor genome stability in large cell line repositories and biobanks," said a senior researcher at the same department. "It could also be applied in ecology, as an alternative to other reduced representation genome sequencing methods, such as RAD-seq, to assess biodiversity in a cost-effective way," the researcher added.  


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Friday, December 07, 2018

Cure for HIV moves closer as scientists find potential genetic switch

A genetic switch that causes HIV hidden inside the cells to replicate can be manipulated to completely eradicate the virus from the human body, a study has found.

Cells harbouring latent HIV are "invisible" to the natural defences of the immune system, said researchers.

During infection, the DNA of HIV makes its way into the host cell's nucleus and integrates itself into the host genome.

The Tat gene circuit is a key piece of HIV DNA that controls the HIV gene transcription and activation, according to the study.

When activated, it initiates a takeover of the cell's machinery to churn out new copies of the HIV virus, which eventually burst from the cell and infect neighbouring cells.

HIV-specific immune effector cells kill cells infected with HIV, but only when the cells are being used to produce more of the virus, meaning that the Tat gene circuit is switched on.

In cells that are latently infected, the Tat gene circuit is off, and the cell goes about its normal business all the while harbouring quiescent HIV.

"By targeting the Tat gene circuit with drugs or small molecules to activate it, we would be able to cause latently-infected cells to start producing more virus, and then they can be destroyed by the immune system," said a researcher.

So far, there are no drugs successfully targeting this circuit, researchers said.

People infected with the HIV virus can live relatively normal lives with exceedingly low or even undetectable viral loads thanks to powerful antiretroviral therapies that work to suppress viral replication.

However, even in people where the virus is undetectable, it doesn't mean it's completely absent.

The HIV virus can hide in cells in an inactivated state, meaning it isn't actively replicating.

This is a dire situation and makes life-long antiretroviral therapy the only option for HIV infected patients.

"It is extremely difficult to flush latently-infected cells out of their latency," he said.

Techniques developed to reactivate latent HIV-infected cells so that they become susceptible to the body's natural immune response or to drug therapies have had mixed results.

This is mostly because the technique, known as "shock and kill," relies on a class of drugs called HDAC inhibitors that come with severe adverse effects, researchers said.

"We need to better understand the mechanisms that regulate HIV latency so we can identify new opportunities for intervention and develop better drugs that can either lock viral particles in a latent state, or kill latent cells, or both,"he said.

The Tat gene circuit has a random probability of being active or inactive, and the switch from inactive to active can happen spontaneously.

"In HIV-infected cells, reactivation of the Tat gene circuit is still a very rare event," he said.

The researchers developed advanced computational algorithms to study the Tat gene circuit under different conditions.

"Using different models and algorithms, we were able to accurately map a 'probability landscape' of the cellular reactions that can impact Tat gene circuit reactivation, and our results suggest new ways of targeting latent cells that may lead to the eradication of the HIV virus from a host," he said.

Researchers identified ways to manipulate the Tat gene circuit so that the "shock and kill" technique would be more effective.

They also looked at a "block and lock" strategy, where latent viral particles are locked into latency by permanently blocking activation of the Tat gene circuit.

"Our results suggest that by controlling HIV latency through manipulation of the Tat gene circuit, effective therapeutic strategies can be identified that would one day provide a cure for HIV," he said.

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Thursday, December 06, 2018

Path breaking test that detects all cancers in minutes

Scientists have developed a quick test that can detect all types of cancer from blood or biopsy tissues within minutes. The test, developed by researchers who have discovered a unique DNA nanostructure that appears to be common to all cancers.

Cancer is an extremely complicated and variable disease and different types of cancer have different signatures. It had been difficult to find a simple signature that was distinct from healthy cells and common to all cancers.

"This unique nano-scaled DNA signature appeared in every type of breast cancer we examined, and in other forms of cancer including prostate, colorectal and lymphoma," said a researcher.

"The levels and patterns of tiny molecules called methyl groups that decorate DNA are altered dramatically by cancer -- these methyl groups are key for cells to control which genes are turned on and off," he said.

Researchers developed a tool that could look at these pattern changes at the whole genome level within minutes.

"In healthy cells, these methyl groups are spread out across the genome, but the genomes of cancer cells are essentially barren except for intense clusters of methyl groups at very specific locations," said a scientist.

The team discovered that intense clusters of methyl groups placed in a solution caused cancer DNA fragments to fold into unique three-dimensional nanostructures that could easily be separated by sticking to solid surfaces such as gold.

"We designed a simple test using gold nanoparticles that instantly change colour to determine if the 3D nanostructures of cancer DNA are present," said a scientist.

He said cancer cells released their DNA into blood plasma when they died.

"So we were very excited about an easy way of catching these circulating free cancer DNA signatures in blood," he said.

Discovering that cancerous DNA molecules formed entirely different 3D nanostructures from normal circulating DNA was a breakthrough that has enabled an entirely new approach to detect cancer non-invasively in any tissue type including blood.
 
"This led to the creation of inexpensive and portable detection devices that could eventually be used as a diagnostic tool, possibly with a mobile phone," he said.

The new technology has proved to be up to 90 per cent accurate in tests involving 200 human cancer samples and normal DNA.

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Tuesday, May 30, 2017

CRISPR Gene-Editing Can Cause Hundreds of Unexpected Mutations

It's been hailed as one of the most potentially transformative inventions in modern medicine, bringing the prospect of designer babies closer than any other technology to date, but CRISPR-Cas9 could be riskier than we thought.

The technology that could spark a gene-editing revolution has been caught introducing hundreds of unintended mutations into the genome, and with scientists already testing it in humans, it's set off some serious alarm bells.

"We feel it's critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR, including single nucleotide mutations and mutations in non-coding regions of the genome," says Stephen Tsang from the Columbia University Medical Centre.

Tsang and his team have conducted the first whole-genome screening of a living organism that's undergone CRISPR gene-editing to discover that unwanted mutations can crop up in areas that are totally unrelated to the targeted genes.

These mutations have likely been missed by previous studies because they've been using computer algorithms that are designed to identify and scan areas on the genome that are most likely to be affected, based on what's been edited.

"These predictive algorithms seem to do a good job when CRISPR is performed in cells or tissues in a dish, but whole genome sequencing has not been employed to look for all off-target effects in living animals," says one of the team, Alexander Bassuk from the University of Iowa.

If you've somehow missed the CRISPR-Cas9 hype train, we started hearing about it a few years ago, when the technology was already being touted as a "revolution", based on its ability to make specific edits to the DNA of humans, other animals, and plants.

The technique works like a biological 'cut and paste' tool, where researchers use a protein to seek out a particular gene and cut it out of the genome, replacing it with DNA of their choice - for example, they could swap a defective gene for a healthy one.

And unlike many promising medical inventions, CRISPR has continued to live up to its potential.

In recent years, it's been used to tap into cancer's 'control centre', repair a mutation that causes blindness, treat genetic disease in living animals, and even modify human embryos to figure out what causes infertility and miscarriage.

While there have been signs of 'off-target' mutations occurring in preliminary trials, that hasn't stopped the technology from making its way to humans.

The first clinical trial to use CRISPR in actual subjects now underway in China, and the US and the UK are not far behind.

In fact, some researchers are predicting that it could soon trigger some serious competition between China and the US - a kind of biomedical equivalent of the original Space Race.

"I think this is going to trigger 'Sputnik 2.0', a biomedical duel on progress between China and the United States," Carl June, an immunotherapist from the University of Pennsylvania and a scientific adviser on next year's US CRISPR trial, told Nature late last year.

Now researchers have found evidence that the unwanted mutations brought on by CRISPR in living animals could be a more widespread than we thought.

Tsang and his team sequenced the entire genome of two mice that had undergone CRISPR gene-editing in a previous study, and one healthy control.

They were looking for any mutations linked to the technology, including those that only altered a single nucleotide - molecules that serve as the building blocks of DNA and RNA.

They found that the technique had successfully corrected a gene that causes blindness in the mice, but the two mice that had undergone CRISPR gene-editing had sustained more than 1,500 unintended single-nucleotide mutations, and more than 100 larger deletions and insertions.

"None of these DNA mutations were predicted by computer algorithms that are widely used by researchers to look for off-target effects," the team reports.


To be clear, the find doesn't necessarily mean that CRISPR is unsuitable for use in humans going forward - more research is now needed to see if these results can be replicated in larger samples, and in humans, rather than mice.

But it's like discovering that a medical treatment could be having potentially serious and long-term side effects - and our tests aren't picking them up.

The researchers are now urging for better screening tests for off-target mutations to be applied to CRISPR research immediately.

"We're still upbeat about CRISPR," says one of the team, Vinit Mahajan from Stanford University.

"We're physicians, and we know that every new therapy has some potential side effects - but we need to be aware of what they are."

The research has been accepted for an upcoming edition of Nature Methods.


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Monday, May 12, 2014

How the immune system can fight back cancer


In a groundbreaking treatment, researchers at the National Cancer Institute in the US have harnessed a female patient's own immune system to fight cancer.

The team sequenced the genome of her cancer and identified cells from her immune system that attacked a specific mutation in the malignant cells.

Then they grew those immune cells in the lab and infused billions of them back into her bloodstream, a report in the journal Science said.

"The tumours began melting away," said Steven A. Rosenberg, chief of the surgery branch at the cancer institute.

The 43-year-old woman was diagnosed with an advanced and deadly type of cancer that had spread from her bile duct to her liver and lungs, despite chemotherapy.


"The report is noteworthy because it describes an approach that may also be applied to common tumours - like those in the digestive tract, ovaries, pancreas, lungs and breasts," the report noted.

Researchers said the treatment, known as adoptive cell therapy, holds promise for common cancers. But they also cautioned that the report was early and based on just one patient.

According to Rosenberg, his team was working around the clock to streamline the process.

Potentially, if we could reduce the complexity, it's something that could get out into common usage eventually, he added.
 
 
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