IIT Madras’ first step to develop cheaper cancer diagnostic alternative

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Dr. Swati Choudhary (left) and Prof. Rama Verma tested the fusion protein diagnostic on leukaemia and colorectal cancer samples.

A team of researchers from the Indian Institute of Technology (IIT) Madras has developed a cheaper yet reliable alternative for diagnosing leukaemia and colorectal cancer. Like monoclonal antibodies which are currently used for cancer diagnostics, the fusion protein developed by the researchers has high specificity and sensitivity. The results were recently published in the journal Molecular Diagnosis & Therapy.

The researchers designed recombinant fusions of a ligand (stem cell factor) to a protein tag (SNAP-tag). The ligand binds to a particular receptor (c-kit) that is present in more than normal numbers (overexpressed) on some cancer cells.

To quantitatively determine the amount of ligand that is bound to the receptors, the researchers used a commercially available fluorescent material (O6-Benzylguanine) that the SNAP-tag binds to. The bound protein with the fluorescent derivative can be detected using a fluorescent microscope or flow cytometry.

“We report the first evidence that SNAP-tag could be used for ex vivo [outside the body] detection of enriched biological markers using SCF/c-kit as the target receptor system. The c-kit receptor is a pathological and diagnostic marker for a variety of cancers,” Dr. Swati Choudhary from the Department of Biotechnology, IIT Madras and the first author of the paper says in an email. “It is a proof-of-concept study.”

Using c-kit positive and negative cell lines, the researchers first tested the capacity of the protein tag to bind specifically to the c-kit receptors. “The specificity was comparable to the currently used monoclonal antibodies,” she says. “We then carried out a pilot study to test whether these proteins could be used for diagnostic purposes through ex vivo immunophenotyping of the c-kit receptor. We tested it on 16 peripheral blood samples from leukaemia patients and four colorectal biopsy specimens.”

“The sensitivity is as good as commercially available monoclonal antibodies. If sensitivity and specificity are high in large-scale studies, we could in future replace monoclonal antibody with SNAP-tag fusions to select ligands for diagnostic applications. It will also be much cheaper,” says Prof. Rama S. Verma from the Department of Biotechnology, IIT Madras, and one of the corresponding authors of the paper.

“In the long term, these probes could potentially be used for diagnosing and staging of cancer and in the follow-up management of the disease,” Dr. Choudhary says. According to Prof. Verma, it would even be possible to find out early stages of cancer as the technique has high sensitivity.

Since c-kit receptor is overexpressed in other cancers such as gastrointestinal stromal tumours, small cell lung cancer, ovarian cancer, breast cancer and melanoma, the SNAP-labelled protein could theoretically be used for diagnosing these cancers as well. Further studies are needed to confirm this.

“By replacing the stem cell factor with different ligands that targets other cancer cells, the technique can potentially be used for identifying other cancers as well,” Dr. Choudhary says.

As a DAAD fellow, Dr. Choudhary carried out a part of the study at Fraunhofer Institute of Molecular Biology, Aachen, Germany.

Published in The Hindu on February 19, 2017

ISRO sets the bar high by launching 104 satellites in one mission

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Setting a world record. – Photo: ISRO

The Indian Space Research Organisation boosted its reputation further when it successfully launched a record 104 satellites in one mission from Sriharikota on Wednesday by relying on its workhorse Polar Satellite Launch Vehicle rocket. An earth observation Cartosat-2 series satellite and two other nano satellites were the only Indian satellites launched: the remaining were from the United States, Israel, the UAE, the Netherlands, Kazakhstan and Switzerland. Of the 101 foreign satellites launched, 96 were from the U.S. and one each from the other five countries. Till now Russia held the record of launching 37 satellites in a single mission, in 2014, while the National Aeronautics and Space Administration of the U.S. launched 29 satellites in one go in 2013. Last June, ISRO had come close to NASA’s record by launching 20 satellites in one mission. But ISRO views the launch not as a mission to set a world record but as an opportunity to make full use of the capacity of the launch vehicle. The launch is particularly significant as ISRO now cements its position as a key player in the lucrative commercial space launch market by providing a cheaper yet highly reliable alternative. At an orbital altitude of around 500 km, the vehicle takes about 90 minutes to complete one orbit. Though ISRO had sufficient time to put the satellites into orbit, it accomplished the task in about 12 minutes. With the focus on ensuring that no two satellites collided with each other, the satellites were injected in pairs in opposite directions. Successive pairs of satellites were launched once the vehicle rotated by a few degrees, thereby changing the separation angle and time of separation to prevent any collision.

 ISRO plans to launch more Cartosat-2 series satellites and even an improved version. Besides setting the record for the most number of satellites launched in a single mission, the Indian space agency has launched two nano satellites weighing less than 10 kg. It is a technology demonstrator for a new class of satellites called ISRO nano satellites (INS). The main objective of the INS, which will be launched together with bigger satellites, is to provide a platform on which payloads up to 5 kg from universities and R&D laboratories, and ISRO itself can be easily integrated for carrying out scientific research activities. With many Indian universities already building and launching nano satellites, the availability of a dedicated nano satellites platform is sure to boost space research in India.

IIT Madras researchers study the role of mushroom spores in atmospheric bioaerosols

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Prof. Verma, Hema and Prof. Gunthe studied the contribution of mushroom spores to aerosols.

Researchers from the Indian Institute of Technology (IIT) Madras have for the first time, over the Indian region, demonstrated the potential role of mushroom spores in atmospheric bioaerosols. While others have studied the diversity and distribution of mushroom and the presence of mushroom spores in atmospheric aerosol separately, the IIT team has proven the role of terrestrially occurring mushrooms as a source of biological aerosol particles in the atmosphere. The results were published recently in the journal PLOS ONE.

The study was undertaken on IIT Madras campus, which is spread over 678 acres and has very rich vegetation. It is considered an ‘ecological island’ representative of tropical dry evergreen biome.

Biodiversity of fungal species in the study site was studied using DNA analysis. To identify the type and diversity of atmospheric fungal spores, DNA analysis of particulate matter was carried out subsequently. The DNA analysis of 165 mushrooms revealed that there are 113 different species of mushrooms belonging to 54 genera and 23 families.

“Source characterization of airborne fungal spores has been done for the first time in India — we studied the mushrooms and spores released by the mushrooms oand present in air,” says Prof. Sachin S. Gunthe from the Department of Civil Engineering, IIT Madras and the corresponding author of the paper.

“Mushrooms grow during monsoon and when the temperature and relative humidity are favourable spores are released into the air,” says Prof. R.S. Verma from the Department of Biotechnology, IIT Madras and one of the authors of the paper.

“There was 17% match between mushroom species found on land and spores in the air,” says Hema Priyamvada, a doctoral student from the Department of Civil Engineering, IIT Madras and the first author of the paper. Spores collected from the mushroom and from the air were studied to understand how the spores look morphologically — size, shape and surface features.

“Morphological characterization of fungal spores will be useful for identification of spores in the atmosphere. Since fungal spores account for huge fraction of bioaerosols, the SEM images will be helpful in quick and efficient identification,” says Priyamvada.

The researchers have also quantitatively estimated the contribution of mushroom spores to atmospheric aerosol by modelling the dispersion of spores from the mushroom. “We found that of the certain number of spores (540 spores per sq. cm) released per second from a mushroom, 6% reached a distance of 100 metres for one second of release. In ambient conditions, the release can happen for a longer time — up to an hour — so the contribution of spores to the atmospheric aerosols will be huge,” she says. “Once released from mushrooms, spores can remain suspended in air for a long time and travel great distances.”

“We tried to show mushrooms growing in similar kind of ecosystem as IIT Madras are releasing spores into air. It means, to an extent, you can extrapolate these findings to other tropical dry evergreen biome in India,” says Prof. Gunthe.

Besides causing allergy in humans, spores can also damage plants and animal health. It can also have an impact on regional climate. By acting as ice nuclei, the fungal spores can accelerate vapour condensing around spores and forming water droplets. “Presence of specific type of bioaerosols can even advance the precipitation processes especially in convective clouds,” says Prof. Gunthe.

Published in The Hindu on February 12, 2017

Waking up to MCPG toxin’s role in causing litchi mystery disease

litchi1There is evidence that as late as March 2014, Delhi’s National Centre for Disease Control, India (NCDC) and Centres for Disease Control and Prevention, Atlanta (CDC) researchers were in the dark about the possible role of methylenecyclopropylglycine (MCPG) toxin present in litchi in causing illness in children aged 15 years or younger in Muzaffarpur, Bihar and killing many children each year between May and June.

Scientists from NCDC and CDC had published a paper on January 30 in the journal Lancet Global Health wherein they state that consumption of litchi, which has the MCPG toxin, and skipping evening meal result in very low blood glucose level (less than 70 mg/dL) and acute encephalopathy and causes death in many cases.

It has now come to light that an article in NCDC’s July-September 2013 newsletter and a March 2014 presentation (Summary of 2013 investigation on acute encephalopathy outbreak) made on behalf of the NCDC-CDC surveillance team about the litchi mystery disease do not make any mention of MCPG toxin present in litchi and its possible role in causing illness. The article is written by Dr. Padmini Srikantiah of CDC Atlanta and the corresponding author of the Lancet paper.

According to the article in the July-September 2013 newsletter, the focus of the investigation during May-July 2013 was on the role of several viruses. There is no mention of MCPG toxin present in litchi or any investigation of its role in causing the illness. Even the March 2014 presentation does not mention MCPG toxin.

But two months after Dr. T. Jacob John, a virologist who was earlier attached to the Christian Medical College, (CMC) Vellore and his team, published a paper on May 10 in the journal Current Science hypothesising that MCPG in litchi may be causing the illness, an article in the July-September 2014 newsletter cites the possible role of MCPG. The article is written by Dr. Srikantiah and Aakash Shrivastava, who is the first author of the January 30 Lancet paper.

The 2014 article says: “One specific hypothesis generated from the 2013 findings included the potential presence of a toxin (MCPG) with hypoglycemic activity that is found in the litchi seed.” They also cite MCPG’s “potential” to cause acute hypoglycemia and encephalopathy in animals, akin to ackee poisoning seen in the Caribbean.

All the details about the MCPG toxin mentioned by the Lancet authors in the 2014 newsletter article have already been stated in the May 2014 paper by Dr. John and Dr. Mukul Das from the Indian Institute of Toxicology Research, Lucknow.

“This fits with my assessment that they got the idea from us,” Dr. John says. Dr. Srikantiah and Dr. Shrivastava did not respond to emails.

In a paper published in January 2015 in Morbidity and Mortality Weekly Report (MMWR), the authors of the Lancet paper state: “In Muzaffarpur, MCPG is hypothesized to cause acute hypoglycemia and illness”. However, the MMWR paper does not cite the May and August 2014 papers in Current Science, where the hypothesis of MCPG toxin in litchi possibly causing the illness was the first published by Dr. John’s team.

Published in The Hindu on February 11, 2017

IIT Bombay team finds Chennai and Mumbai have high wind energy potential

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Being close to the coastline, the surface drag exerted in the wind flow is the least in Chennai and Mumbai says Sumeet Kulkarni.

Of the six cities studied by Indian Institute of Technology (IIT) Bombay researchers, Chennai and Mumbai seem to have the highest potential to harvest wind energy during the active phase of the monsoon period. Compared with these two cities, Indore, Ahmedabad and Kolkata have less potential; Delhi has the least potential. The results were published in the journal Meteorology and Atmospheric Physics.

The researchers studied the strength of southwest wind during the time of the monsoon and called the period when the wind energy potential is high as active period and the period when the wind energy potential is low as break period. The high wind energy potential during the active period also coincides with more rainfall; there is less rainfall and less wind energy potential during the break period.

“The idea behind the study was know what the implications of the active and break periods would have on energy demand scenario in the major cities,” says Prof. Subimal Ghosh from the Department of Civil Engineering, IIT Bombay, and one of the authors of the paper.

“We have not studied the impact of climate change on wind power in the six cities. Though we have studied both active and break periods, the focus of the work was on studying the impact of dry spells [break periods] during the monsoon on energy demand-supply,” says Prof. M.C. Deo from the Department of Civil Engineering, IIT Bombay, and one of the authors of the paper. “Our study tries to answer the question if possible extraction of wind energy in the six cities can be relied on to meet the additional power demand during prolonged dry spells in the monsoon season.”

“Amongst the six cities we have considered, Mumbai and Chennai have high wind energy potential, as there is strong wind because of their coastal location. Wind energy extraction in these two cities can be of great help in meeting the gap between power demand and supply from conventional sources. The cities of Indore, Delhi and Ahmedabad do not have this advantage and hence would be unable to meet such gap in demand-supply during the dry spells in monsoon,” says Prof. Deo.

Mumbai and Chennai have predominantly higher-than-average wind energy potential during the active period compared with the break periods. “Being close to the coastline, the surface drag exerted in the wind flow is the least. Also, these two cities are predominantly closer to the onset locations of southwest monsoon winds. So the prospects at these two cities are brighter,” says Sumeet Kulkarni from the Department of Civil Engineering, IIT Bombay, and the first author of the paper.

In the case of Delhi, besides the likelihood of wind energy potential being above average being much less, a large number of high-rise buildings further dampens the prospects of efficient wind energy extraction.

Opposing relation

It was observed that wind energy supply in north and south India has an opposing relation during the active and break periods. For instance, during active phases, when the expected mean temperature is on the lower side, vigorous convection across central India is associated with strong winds across south India, including Chennai and Mumbai. “But in north India, the active period is marked by lower wind speed. So the wind-power potential is less during the active period,” Mr Kulkarni says.

When south India experiences less southwest winds during the break period, convective currents seen in north India bring in higher winds across northwest India. “This results in higher wind energy capacity across north India, including Delhi,” he says.

Though the wind speed is much higher in north India compared with south India during the break period, the wind energy cannot fully meet the energy demand in Delhi and Ahmedabad as the temperature is higher.

On the whole, the wind energy potential during summer monsoon (both active and break periods) makes wind energy potential unpredictable or uncertain. “But there is no significant change in the future wind energy potential across the country when the wind energy from the Arabian Sea is taken into consideration,” he says.

“Since wind energy is high during the active period and low during the break period, a proper energy management policy is important. It would be prudent to rely more on wind energy during the active period and look for alternative energy sources during the break period. This way there can be maximum utilisation of green energy,” says Prof. Ghosh.

Published in The Hindu on February 5, 2017

Lancet gets in touch with Current Science authors on litchi disease ethics issue

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The paper in Current Science where Dr. Jacob John and others accuse the Lancet paper authors for not crediting their papers published in 2014.

In response to an article I wrote on February 3 about Dr. Jacob John raising ethics issues about the way the authors of the Lancet Global Health paper had failed to properly acknowledge his team’s work on Muzaffarpur mystery disease, the journal has got in touch with Dr. Mukul Das, one of the authors of the Current Science papers, for more details.

Dr. John, Dr. Das and others had published two papers in 2014 (May and August) and another one in December 2015 in Current Science wherein they report clinical similarity between ackee poisoning in Jamaicans and the Muzaffarpur illness. At a time when the Lancet authors were looking for a viral cause, Dr. John’s team had correctly zeroed in on methylenecyclopropylglycine (MCPG) toxin in litchi as the likely reason for illness and reported the findings. The team found consumption of litchi and skipping the evening meal as likely reasons for children exhibiting dangerously low blood glucose level and acute encephalopathy early in the morning leading to death in many cases. They also found the presence of MCPG toxin in litchi through chemical analysis and recommended infusing 10% dextrose within four hours of disease onset to save lives.

While the January 30 paper in the Lancet Global Health has acknowledged and cited all three papers, it does not give due credit to the work done by Dr. John’s team. “They quote our study but don’t honestly say what we have found. They have borrowed all important information connected with the illness from us,” Dr. John had told me.

litchi1“Dr. John and I would jointly be sending our response on Monday or Tuesday [February 6 or 7],” says Dr. Das. “It is very decent of the Lancet to have got in touch with us and seek our clarification on this issue. That shows Lancet is careful of its credibility, careful that any such issue is immediately sorted out. I admire Lancet. This is what we want from every journal publisher, every investigator and every paper. Caesar’s wife must be above suspicion,” says Dr. John. “We never complained to Lancet or the media. It is the media that got in touch with us as they knew about our work. That makes us happy.”

Precedent

The authors from Centres for Disease Control and Prevention (CDC) and Delhi’s National Centre for Disease Control, India (NCDC) have indulged in scientific misconduct in a paper published in January 2015 in the Morbidity and Mortality Weekly Report (MMWR), the authors of the Lancet paper cite the possibility of exposure to MCPG, a toxin in litchi, as a likely cause of acute hypoglycemia and encephalopathy in some children. The paper does not even cite the May and August 2014 papers in Current Science by Dr. John’s team.

Dr. John and Dr. Das had exposed the “scientific misconduct” by the authors in a correspondence published in Current Science. “They were creating a precedent by publishing in MMWR, which is a CDC in-house publication. It gave us a clue to their mind and now it is an extension of that mentality by citing us so we don’t complain but not giving us the credit that we deserve,” says Dr. John.

Published in The Hindu on February 5, 2017

In the Post Truth era we have the Journal of Alternative Facts!

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Predatory journals move away, here comes the Journal of Alternative Facts

After ‘post truth’, ‘alternative facts’ will soon find its way into dictionaries. There is growing momentum as more and more people are using the phrase on a daily basis. It all started when Kellyanne Conway, counsellor to U.S. President Donald Trump Kellyanne Conway used it on January 21 during the Meet The Press event and Chuck Todd reacted saying: “Alternative facts are not facts; they’re falsehoods.”

Now we have a tweeter account of the Journal of Alternative Facts, which according to the Twitter bio is “the greatest scientific research peer reviewed by politicians and approved by public relations/submissions accepted via tweet”. It has posted a preview of its first issue of the “journal”.  And guess what the title is: “We Have All the Best Climates, Really, They’re Great” and the author is none other than “Iwas A. Scientistonce”.

The founding editor of the “journal” told Retraction Watch that the main reason for starting the “journal” was because “it is critical that there is a credible academic source for the growing and important discipline of alternative facts. This field of study will just keep winning, and we knew that all the best people would want to be on board. There is a real risk in the world today that people might be getting their information about science from actual scientists, or from fake news sources like The New York Times or the Proceedings of the National Academy of Sciences. In fact, this is such an important mission to us that not only are we an open access journal, but we are taking steps to ensure that we are the ONLY open access journal”.

And the editorial board consists of the “greatest minds of American scientific thinking, primarily politicians. They are indeed the greatest. Terrific. Tremendous. We also have all the best peer reviewers, by which we mean PR reviewers.”

Scientists have taken several steps to save science and help fellow scientists – duplicating climate change data from U.S federal agency websites to other websites in servers based in Europe, starting rogue accounts of federal agencies to disseminate scientific facts without having to worry about the administration stopping or censoring them, organising a Science March on April 22 in Washington and satellite marches in other cities across the world, and asking fellow scientists not to attend conferences in the U.S. to name a few. Making a parody of Alternative Facts peddled by the Trump administration through this Twitter account is one of the novel forms of protest.

Will these ever be noticed by the administration which care two hoots for facts and scientific opinion? Only time will tell but scientists are not prepared to sit idle. That’s something to cheer about in these gloomy days.