Groundbreaking research by Monash University paves the way to a possibility of better monitoring and treatment of the cystic fibrosis lung disease

For years, cystic fibrosis (CF) has known to be a serious hereditary condition that causes severe damage to the respiratory and digestive systems. The damage starts with a build-up of thick mucosal kind of fluid in the organs especially lungs. 

In particular cystic fibrosis affects the cells that produce digestive enzymes, sweat, and mucus. Usually, these secretions are thin and watery, which function as lubrication for various organs and tissues. However, when affected with CF, due to faulty genes the person experiences thick fluid build-up, clogging up the passages and ducts.  

Early diagnosis and treatment are important for improving the quality and the length of the affected life. Currently available lung assessment tools have many drawbacks, especially the inability to accurately identify the origin of the changes seen in lung health. 

Monash University research team announced the results of the World’s first research promising a possibility of better diagnosis and treatment of cystic fibrosis using X-ray velocimetry. 

What is X-ray velocimetry?

A phase-contrast X-ray imaging makes use of the refractive properties of materials to produce high definition soft tissue images. Recently X-ray velocimetry (XV) has caught the eye of researchers. In particular, XV is used to study the airflow through the lungs and the technique is based on particle image velocimetry. Particle image velocimetry (PIV) is a well-established technique known for years. 

XV is known to provide high quality, non-invasive, real-time images of the airflow through the lungs. The X-ray was first designed and developed by 4DMedical, in hope for clinical use. The technology has also recently been approved by the FDA for its all respiratory indications in adults. 

All about the study:

An effective assessment of the lung cystic fibrosis should be capable of capturing its patchy nature and fluid buildup. This is in particular important for detecting the disease at early stages. 

With the help of XV, a multidisciplinary collaboration of engineers, physicists, and clinicians were able to measure real-time airflow through the lungs. 

The research was led by one of the University’s leading scientists Dr. Freda Werdiger. The study revealed that by using XV, it was possible to pinpoint the precise locations where there was an obstruction of airflow in the lung of a cystic fibrosis patient.  

“In this study, we present two developments in XV analysis. Firstly, we show the ability of laboratory-based XV to detect the patchy nature of CF-like disease in affected mice. Secondly, we present a technique for numerical quantification of that disease, which can delineate between two major modes of disease symptoms,” Dr. Werdiger said.

This particular model provides a very simple, easy top interpret approach, which in the future can be readily applied to large quantities of data generated in XV imaging. 

What does the future hold?

The success of XV lies in its capability of drawing reliable and quantitative measures, and the above study shows how that can be accomplished. 

The researchers of the study recommend that this promising technique should be applied to the numerical characterization of CF lung disease. The analysis can be applied in a straight forward fashion with minimal manual labour required. 

Yes, you heard it right for the first time ever, scientists find quadruple DNA in healthy human cells. 

It’s been 67 years since Watson and Crick first established that DNA forms a double-stranded helix. Every now and then it is identified that the double-stranded DNA can double up, to form a special quadruple stranded helix form. 

Previously, quadruple DNA has been developed synthetically but was only seen in a curious point of view. Around 2013, scientists for the first time noticed quadruple DNA in human cancer cells. Today another milestone was set, when scientists for the first time have identified the peculiar DNA in healthy human cells. 

“We’ve undoubtedly demonstrated that the quadruple-strand DNA forms in living cells,” says Marco Di Antonio at Imperial College London. “This forces us to rethink the biology of DNA.”

How does quadruple DNA form?

The DNA molecule is made up of 4 nucleobases- guanine, adenine, cytosine, guanine, and thymine, which can configure themselves in multiple ways. 

At times, it happens so that the DNA can double up to form quadruple helix DNA, formed by sequences rich in guanine. Guanine is the only known nucleobase that is capable of forming bonds with each other. The quadruple DNA usually occurs helically in nature and contains the guanine bases stacked on top of each other.

The unimolecular regions are usually seen at the ends of the chromosome/ telomeric regions. This is usually seen in microbes, oncogenes and now in healthy human cells.

Time to rethink the biology of DNA:

The DNA was viewed by Di Antonio and team from the University of Cambridge. The team viewed the DNA within the human cell by attaching a novel fluorescent marker.

Quadruplexes, in the primary region of the DNA, act as an “on” and “off” switch particularly for the genes associated with cancer. Previous research suggests that the quadruple DNAs can be used as molecular targets to diagnose cancer at early stages. 

Although Di Antonio and the team are aware of the DNA function, it is still a mystery on how a cell knows where to express the gene or decrease its activity. The researchers hypothesize that the quadruple structure may hold the door open to facilitate the reading of the genetic code. 

“There is a sort of crosstalk between the formation of quadruplex DNA and epigenetic markers,” says Di Antonio. “The quadruplex form is an epigenetic mark in its own right.”

Concluding remarks:

This recent discovery adds to the evidence that the quadruple portions are a normal part of DNA regulation and function. It has also made us realize that we need to rethink our whole biology and that our view of double-stranded DNA may be out of date. 

Though the new discovery can be assumed to be a native state of DNA, it is another example proving that DNA is not a fixed shape or structure. 

Living systems are known to be equipped with self defense mechanisms, and plants are no exception. For the first time, experts find a novel “on-off switch” in plant defense. 

The main purpose of an immune system is to protect the host from any harm. All living organisms are equipped with an immune system, and plants are no exception. Plants are home to rich sources of nutrients attracting many organisms including fungi, bacteria and vertebrates. Although plants lack an immune system as complex as humans, they do have stunning forms of chemical, structural and protein defense that experts are trying to understand. 

Plant immune defense:

Plants immune defenses are designed to detect any living organism and stop them from causing any extensive damage. Plants are equipped with multi layers of surveillance mechanisms that are capable of recognising potentially dangerous pathogens. 

The defense mechanisms are specifically programmed and operate through a complex network. They are timed for effective and rapid response against the predators, yet at the same time are controlled to avoid any damage to the host. 

The novel discovery:

Keini Dressano, Alisa Huffaker and team from the University of California San Diego, have recently discovered a novel ‘on-off’ switch in the plant defense system. 

The new switch mechanism is an RNA binding protein that can help turning on immune responses a few minutes after being attacked. They also observed that it was capable of switching off the immune response hours later, to prevent self inflicting damage.

“These findings have provided new insights into how the complex intricacies of plant immune responses are orchestrated to successfully fight off pathogens, and lay a path forward for improving plant disease resistance to ensure future food stability,” said Huffaker, an assistant professor in the Section of Cell and Developmental Biology.

Science behind the discovery:

The novel discovery was found in arabidopsis plants, and it was found to control splicing of the mRNA transcripts that encode signalling protein regulators if the plants defense system.

According to the researchers, a simple chemical modification of the RNA binding protein was seen to reverse mRNA splicing that usually keeps the immune response deactivated. To turn on the immune response, a second chemical modification returns the mRNA splicing to normal resuming the inactivation process. 

“This work went beyond simply identifying a new regulator of plant immunity,” said Huffaker, of the detailed mechanisms uncovered. “We discovered specific chemical modifications that control regulatory function, transcriptional targets of the regulator, differential splicing of the targets and precise effects of splicing on both target function and overall plant immune responses and disease resistance.”

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