Researchers have discovered that signalling processes between proteins and the immune system are way more complex than previously thought, thanks to a special kind of ‘spliced’ molecule that’s more common than anyone could have predicted.
These molecules were once considered extremely rare, but researchers have found that they actually make up a quarter of the ‘flags’ that identify toxic or foreign particles in the body – and the discovery could have a huge impact on how we develop vaccines and treat autoimmune conditions.
“It’s as if a geographer would tell you they had discovered a new continent, or an astronomer would say they had found a new planet in the Solar System,” says systems biologist Michael Stumpf from Imperial College London.
“And just as with those discoveries, we have a lot of exploring to do. This could lead to not only a deeper understanding of how the immune system operates, but also suggests new avenues for therapies and drug and vaccine development.”
In a nutshell, our immune system works by identifying things that could be harmful in the body’s environment and doing its best to neutralise them.
How does our body recognise antigens? Thanks to a molecular flagging system, known as epitopes. These molecular structures are positioned on the surface of cells, where they identify antigens as antigens.
Conveniently, they’re also the right shape and structure for antibodies to bind to them, thereby neutralising any potential threat (hopefully).
Until now, scientists thought that the vast majority of these epitope flags were created in set patterns, with cell machinery effectively ‘cutting’ fragments out of proteins in a particular sequence, and displaying these in order on the surface of the cell. Wearing house colours, as it were.
But now, thanks to a new cell-mapping technique, scientists have found that as many as a quarter of these flags are actually spliced epitopes – which occur when the protein fragments are displayed on the cell’s surface out of order.
In other words, the cells are still wearing house colours, but they’ve stitched them together chaotically – which hypothetically could make it much harder for the immune system to recognise the patchwork identifier.
Scientists knew these spliced epitopes existed, although they were thought to be uncommon. Not so, according to the new study, which suggests they represent 25 percent of epitopes in terms of abundance, and around 30–40 percent in terms of the diversity of these flagging molecules.
This unexpected volume of spliced identifiers suggests signalling in the immune system carries a lot more ‘noise’ than scientists were aware of.
The discovery is both a blessing and a curse for researchers investigating the immune system. Obviously it’s great that we’ve got a clearer perspective on how many of these spliced epitopes there are, as now we can try to cater to them when developing medical treatments.
But it also means that decoding immune responses just got a lot more difficult.
“The discovery of the importance of spliced peptides could present pros and cons when researching the immune system,” says lead researcher Juliane Liepe.
“For example, the discovery could influence new immunotherapies and vaccines by providing new target epitopes for boosting the immune system, but it also means we need to screen for many more epitopes when designing personalised medicine approaches.”
The findings are reported in Science.
The Hyderabad based Center for Cellular and Micro Biology (CCMB) has set up first of its kind Zebra fish facility in the country to conduct research on Zebra fish and find out curative solutions for human diseases such as cancer, neural conditions and eye diseases.
According to Dr. Rakesh K Mishra, director of CCMB, the genomic traits of Zebra fish have a lot in common with humans. The genomic configurations and functions of Zebra fish are similar to that of human genetic system. As per scientific findings about 70 per cent of protein coding attributes and 84 per cent of diseases causing genes in humans are present in Zebra fish.
“With similar genomic functionality and configuration found in humans and Zebra fish, today the scientists prefer Zebra fish as their ideal model for genetic manipulation to identify the root cause of various diseases and in the process explore appropriate palliatives,” informed Dr. Rakesh.
The scientific community feels that functional equivalence or similar genome dynamics between humans and zebra fish has unfolded tantalizing opportunities in discovering answers to a plethora of medical problems including cancer, neural and eye diseases.
Explaining further, as to why Zebra fish is preferred as an ideal model for genetic modifications, the CCMB director says that the main advantage with zebra fish is its transparent innards or anatomy which is visible to the naked eye. “The transparent body structure of the zebra fish makes it easier and convenient for scientists to monitor the mutations and changes that occur as a result of genetic manipulations and introduction of disease-related mutagens. This helps in to zero in on the causative factors of a disease and also enable us to come out with possible medical solutions for a problem,” explained Dr. Rakesh.
Another important feature about Zebra fish is its amazing regenerative capacity, wherein the fish can recreate broken appendages along the body axis like the fins, and tail and also repairing and rejuvenating heart muscles and the eyes.
According to scientists, Zebra fish gives the advantage of monitoring morphological development right from its embryonic stage to its adult phase which helps the scientists to isolate the regenerative components in the gene. “Our main focus is identification of this regenerative factor in the zebra fish, which will help open up possibilities in replacement and repair human body parts,” informed the director.
Ayush ministry,DHR jointly to set up Center of Integrative Oncology for collaboration in areas of cancer prevention, research
The Union Ministry of Ayush and the Department of Health Research (DHR) will soon set up a Center of Integrative Oncology at the National Institute of Cancer Prevention and Research (NICPR), Noida, for collaboration in the areas of cancer prevention, research and care.
An MoU in this regard was signed between NICPR, an autonomous institute under DHR, and All India Institute of Ayurveda (AIIA), an autonomous institute under the Ministry of Ayush. This MoU would pave the way to carry forward the ongoing bilateral dialogue and facilitate collaboration with National Cancer Institute, USA.
Setting up of this Centre is an outcome of the deliberations held in Indo-US Workshop wherein the invited US delegates from Department of Health and Human Services (DHHS), National Institute of Health (NIH), National Cancer Institute (NIH) deliberated with the eminent experts from India having expertise in cancer research and other promising areas for two days to share experiences and work out a road map for future collaborations.
The MoU was signed by Prof. Abhimanyu Kumar, director- AIIA and Prof. Ravi Mehrotra, director- NICPR in the presence of Ajit Sharan, secretary, Ministry of Ayush, and Dr. Soumya Swaminathan, secretary, DHR & director general, Indian Council for Medical Research.
Dr. Swaminathan while appreciating the initiative observed that the main aim should be to reduce the incidence of cancer for which preventive aspects with the strengths of Ayush systems should be explored. She viewed that the collaborative research should aim at developing traditional medicine as adjuvant therapy to reduce the side effects of chemotherapy. She emphasized on collaborative studies both short term and long term involving institutions of repute at national and international level.
Sharan appreciated the efforts and assured that funding would not be a constraint in carrying out the activities under the MoU. He outlined the five major action points which include awarding 10 new research fellowships every year – the process for the first batch will be completed by March, 2017; Minimum of five collaborative research projects will be supported in the financial year 2016-2017; Ministry would also develop few Centres of Excellence for cancer research and has identified the AIIA and the Rajaram Deo Anadilal Poddar Ayurveda Cancer Research Institute, Mumbai, a unit of Centre Council for Research in Ayurveda Sciences (CCRAS). This would be done by March, 2017; a Steering Committee and Scientific Advisory committee would be jointly constituted by the Ministry of Ayush and DHR by December, 2016; and international conferences would be organised annually.
On this significant occasion, a Web portal on ‘Network for AYUSH Cancer Care (NFACC)’ developed by the AIIA was also launched by secretary, Ayush. The portal would help to collect the national data of experts, scientists, practitioners, institutes, universities located across the country and engaged in cancer care & research. An online app of NFACC has also been developed. This app will be available on the website of various Ayush institutions which will provide a hyperlink to the main portal. In future, this portal will have collection of research papers related to cancer care, information about the facilities available for cancer care through Ayush systems.
The Union government has issued the National Treatment Guidelines for Antimicrobial Use in infectious diseases. With no new drug on the horizon, the government has felt the need to bring out the existing levels of reported resistance of these drugs in the country. It has devised a syndromic approach for empirical therapy of common infections.
To contain further development of antimicrobial resistance, implementing hospital infection control practices, formation of active hospital infection control teams in each hospital working round the clock and monitoring and containing spread of infections are part of these norms. Preventing the acquisition of an infection by vaccination for different microbial infections will also help in reducing the need for prescription of antibiotics.
The government will also enforce an antibiotic stewardship programme to find out the lacunae and improve upon the rational use of antibiotics with appropriate interventions and strategies.
According to Kaushik Desai, general secretary, Indian Pharmaceutical Association, the move is excellent by the government. This also gels with global issue of fighting antimicrobial resistance. These norms explicitly state that antimicrobials should be prescribed only when they are necessary for treatment following a clear diagnosis. The key factor is that these guidelines must be understood by each pharmacist working not just in hospitals but retail pharmacies too. The need of the hour is to help in bringing awareness about antibiotic resistance and its misuse.
The guidelines lists recommended treatments for common infectious diseases that are based on scientific evidence, literature review and are consistent with the already existing international norms. It is formulated with the collective opinion of recognised national experts. Empiric treatment choices for different syndromes, infections of specific body sites, and in certain special settings; antimicrobial choices for multidrug resistant bacteria pathogens, monitoring use of antimicrobials; preventive strategies for healthcare associated infections, case definitions and diagnosis of common infections are clearly provided. The guideline has emphasised that not all patients need antibiotics and non-drug treatment may be suitable.
The content of these treatment guidelines will undergo a process of continuous review and in this regard the government has called for comments or suggestions for improvement. The norms provides only suggestive procedures. The protocols are general and may not apply to a specific patient. Therefore the norms should not replace clinical judgment, factors like hemodynamics of specific patients, availability of antimicrobials and local antibiogram of healthcare setting need to be considered.
Before starting presumptive therapy, medical experts should follow up on standard investigations for all suspected infections for accurate diagnosis and prognosis. The timing of initial therapy should be guided by the patient’s condition and urgency of the situation and can preclude opportunity to establish a microbiological diagnosis, which is critical in the management of these patients.
Merits and limitations of empiric versus definitive antimicrobial therapy should be clear to the doctor prescribing antimicrobials. Since laboratory results for microbiological tests are not available for 24 to 72 hours, initial therapy for infection is often guided by the clinical presentation. Therefore, a common approach is to use broad-spectrum antimicrobial agents as initial empiric therapy with the intent to cover multiple possible pathogens commonly associated with the specific clinical syndrome. However, once laboratory results are available with identification of pathogen along with antimicrobial susceptibility data, every attempt should be made to narrow the antibiotic spectrum. This is critically helpful because it can reduce cost and toxicity besides significantly delay the emergence of antimicrobial resistance.
Scientists found that chocolate increases “good” cholesterol when between 200 and 600 milligrams a day is consumed.
The benefits depend on the amount of cocoa taken, making plain chocolate better than white or milk varieties.
In the study experts examined the cardiometabolic health of 1,139 volunteers who consumed chocolate flavanols in 119 different trials.
Authors who orchestrated the randomised controlled trials (RCTs) claimed the study shows the “urgent need” for more trials to improve understanding of the short-term benefits.
Author Dr Simin Liu, professor and director of the Centre for Global Cardiometabolic Health at Brown University, USA, said: “Our meta-analysis of RCTs characterises how cocoa flavanols affect cardiometabolic biomarkers, providing guidance in designing large, definitive prevention trials against diabetes and cardiovascular disease in future work.”
None of the studies were designed to test directly whether cocoa consumption leads to reduced cases of heart attacks or type two diabetes.
Graduate student Xiaochen Lin, who worked with Dr Liu on the study, added: “We found that cocoa flavanol intake may reduce dyslipidemia (furred arteries), insulin resistance and systemic inflammation, which are all major subclinical risk factors for cardiometabolic diseases.”
The study, published in the Journal of Nutrition, was funded by the American Heart Association, National Heart, Lung and Blood Institute and Mars.
Miss Lin said: “The treatment groups of trials included in our meta-analysis are primarily dark chocolate – a few were using cocoa powder based beverages.
“Therefore the findings from the current study apparently shouldn’t be generalised to different sorts of chocolate candies or white chocolates, of which the content of sugar/food additives could be substantially higher than that of dark chocolate.”
The authors concluded: “Our study highlights the urgent need for large long-term RCTs that improve our understanding of how the short-term benefits of cocoa flavanol intake on cardiometabolic biomarkers may be translated into clinical outcomes.”