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Kolkata Friday, 20 July, 2018 - 13:29

A recent study by researchers at the Indian Institute of Science, Education and Research (IISER) Kolkata, has resulted in the development of a novel molecular ‘switch’ that turns on in the presence of specific proteins.

Imagine inserting a USB flash drive, also called a pen drive, into its slot on a laptop. Haven’t we all struggled to get it right the first time in a few instances? When the pen drive eventually fits into its slot, a small light in it flashes on, indicating that everything is just fine. In biological systems, many important processes are set off only after a ‘precise binding’ of two molecules. However, how do we know of the binding? Wouldn’t it be much easier if a light flashes after every perfect binding, just like the pen drive?

In this study, the researchers have tried to do something similar! They have discovered a novel property of a class of compounds called dithiocarbamates (DTC), which act as a light switch whenever they bind to specific proteins called lectins.

The distribution of carbohydrates (sugars) on the cell surface is unique to every cell type. Lectins are proteins that play the role of connectors by binding to the surface sugars of two cells and aiding the exchange or transport of molecules. Several lectins like concanavalin (ConA) and wheat germ agglutinin (WGA), from both plants and animals, have been identified and studied. So, how do we study these cell-ambassadors? In comes the wonder compound, DTC.

DTCs are organic compounds whose solubility increases when bound with specific carbohydrates. The researchers of this study initially synthesised a mannose (a type of sugar) derivative of DTC to study its binding properties with the lectin, concanavalin. To their surprise, they discovered that DTC emitted light when it bound with concanavalin!

Some molecules absorb light and reflect it back with a different wavelength and colour, resulting in a phenomenon called fluorescence. Initially, the mannose-bound DTC did not show effects of fluorescence when the light was shone on it. However, when bound with concanavalin, it started emitting fluorescence, thereby signalling its bound state with concanavalin. Also, this effect increased with increasing concentrations of concanavalin saturating at 309 times the initial intensity of fluorescence.  A similar result was observed when galactose (mannose but with a different arrangement of atoms) bound DTC reacted with the galactose-specific lectin, wheat germ agglutinin.

But what in lectins make the DTCs shine like a Christmas tree in December? Lectins, quite literally hate water (hydrophobic). When bound to DTC, they make the resulting compound hydrophobic too, creating a shield around it from the surrounding solution. The researchers propose this property may be the cause of the ‘turn on’ effect observed. This discovery would help to visualise the binding properties of lectins in a much easier way and thus open new doors to probe the salient role of lectins in biological systems.

Section: General, Science, News Source:
New Delhi Friday, 20 July, 2018 - 07:40

Cardiovascular diseases (CVDs)—diseases related to the heart and blood vessels—are the number one cause of death in the world. In India, CVDs account for close to 25% of the total deaths—higher than tuberculosis and respiratory diseases combined, which are second and the third cause of death. Health officials predict that the risk of CVDs is only going to increase with changing lifestyle, higher levels of obesity, unhealthy diets, lack of physical activity, and overuse of tobacco and alcohol. So, who is at a higher risk of having a cardiovascular disease in their lifetime?

A recent study by researchers at the Harvard University and Harvard Medical School (USA), University of Goettingen (Germany) and the Indian Institute of Public Health (India) have examined the risk of CVDs across India based on the geographical and sociodemographic information. The study, published in the journal PLOS ONE, has analysed data of over 7,97,540 adults between the ages of 30 and 47, from 27 states and five union territories in India.

The study is one of the first to examine the risk of cardiovascular diseases on a national scale with insights at the district level. “Given that India’s health system is largely decentralized to the state level, understanding the variation of CVD risk within India is highly relevant not only to identify target groups for CVD prevention, screening, and treatment programs but also for health system planning at the state and district level”, say the researchers on the motivation of the study.

The researchers used data from the Annual Health Survey and District-level Household Survey from 2010-2014 to collect information about a person’s health and sociodemographic information. Factors like body-mass index (BMI), high blood glucose level, blood pressure and smoking habits, which contribute to the risk of CVDs were collected along with their residence location. The risk factors helped the researchers calculate the risk of an individual developing a fatal or nonfatal cardiovascular disease in the next ten years.

The study found that at a national level, the prevalence of a high CVD risk of greater than 30% in the next ten years, was twice as higher in men as compared to women. Based on the geography, it varied from 10.2% among females in Assam to 24.2% among males in Nagaland and Himachal Pradesh. The average 10-year risk of a fatal or nonfatal CVD event varied widely among states in India, ranging from 13.2% in Jharkhand to 19.5% in Kerala. The risk of CVD was highest in North India, Northeast, and South India.

Fig 1: Age-standardized state-level mean 10-year risk of a cardiovascular disease event by sex.

The study also found that adults living in urban areas, as well as those with a higher household wealth or education, tended to have a higher CVD risk. It found that smoking was more prevalent in poorer households and rural areas, whereas body mass index, high blood glucose, and systolic blood pressure—risk factors for CVD—were higher among wealthier families in urban areas. In fact, men had a substantially higher smoking prevalence (26.2%) compared to women (1.8%) and also higher systolic blood pressure than women.

Fig 2: Age-standardized state-level mean 10-year risk of a cardiovascular disease event by rural versus urban area.

The study successfully identifies substantial variation in the risk of CVD prevalence across the country which can help in developing targeted CVD programs to those most at risk and in need. “Given that we found that district-level mean CVD risk was positively associated with district wealth and urbanisation, such investments may be crucial to minimising further rises in CVD risk as socioeconomic development and urbanisation in India progress over the coming decades”, say the researchers.

With India’s rapid economic growth leading to higher standards of living, and with it, increasing prevalence unhealthy lifestyles, there could be many more who are ‘urbanised’ and have a high risk of developing cardiovascular diseases.

Section: General, Science, Health, News Source:
Bengaluru Thursday, 19 July, 2018 - 14:28

Haven’t we all heard about DNA, the genetic material that makes who we are? Short for Deoxyribonucleic acid, the DNA is made of two chains that coil around each other forming the double helix structure as we know it today. Although Friedrich Miescher first isolated the DNA molecule in 1869, it was not until 1953 that we understood its structure. Two scientists, James Watson and Francis Crick, are well-known for showing us the double-helix structure of the DNA. However, do you know this was all possible also because of the X-ray diffraction data acquired by Raymond Gosling, who was a student of Rosalind Franklin? Why don't we often hear these two names?

That’s the plot of the play called Photograph 51, the flagship production by Bangalore Little Theatre. This award-winning play by Anna Ziegler, being produced for the first time in India, is the 16th play under the History of Ideas programme. It is about the ambition, isolation, and the race for greatness—something that is seen in any workplace, let alone in the run to win the Nobel Prize! The title of the play comes from Photograph 51, the nickname given to an X-ray diffraction image taken by Raymond Gosling in May 1952, under the supervision of Rosalind Franklin.

“The History of Ideas programme is a principal vehicle for the Public Awareness thrust of Bangalore Little Theatre Foundation, a registered Public Charitable Trust. It is an international programme in collaboration with renowned playwrights from different parts of the world. The essence of the programme is the production of plays based on the lives of great personalities who have contributed significantly to human thought in a demanding historical context”, says Poornima Kannan from Bangalore Little Theatre.

The play is directed by Sridhar Ramanathan and Archana Kariappa and has about 12 artists playing different roles. The organisers have arranged for public shows in various theatres across Bangalore and also at various scientific institutes across the city. Pointing out that theatre is “an effective medium to share stories of science and influence society”, Ms Kannan says the program aims to “achieve a wide public reach for inspiration regarding creative human endeavour and Public awareness regarding the shaping of societies”.

Photograph 51 is not just an endeavour by artists; there are also eminent scientists involved in the making of the play. “We reached out to Prof. P. Balaram, former Director of IISc, who in turn put us in touch with Prof. Manju Bansal. Prof Bansal is an X-ray crystallographer herself, and she enlightened us on the intricacies of the techniques and the life of someone at that time”, recounts Ms Kannan.

The play is scheduled to premiere on July 22nd at Alliance Francaise. Over the next month, there are many public and in-house shows at Alliance Francaise, Jagriti and Ranga Shankara. There are also invited shows in institutions across the city. “We would be open to performing the play in any venue as long as there is interest in the audience to learn more about the ‘Secret of Life’”, says Ms Kannan.

Here is the confirmed schedule so far:

Alliance Francaise - 22nd July
Jagriti - 27, 28 and 29th July
Christ University - 3rd August
British Council - 12 August
NCBS - 17th August

The organisers are working with other institutes like IISc, RRI, JNCSAR, Infosys, Biocon, VITM  and RRI to confirm the dates.

So, ready to grab your tickets? You can book them on BookMyShow or purchase them at the venue. For further details, please contact Poornima Kannan (9880791171) or  Archana Kariappa (9789088904)

Section: General, Science, News, Events Source:
Mumbai Thursday, 19 July, 2018 - 07:35

The cities are growing at a rapid pace and houses are becoming smaller and expensive. Especially for low income households, the houses they can afford has deprived environment with higher than recommended temperature and humidity. While living in such environments are known to cause breathing problems, heart diseases, frequent body ache and headache, the lack of objective data that can help in the reconstruction of such houses is lacking. In a first-of-its-kind study, researchers from the Indian Institute of Technology Bombay have investigated how living in ill-ventilated dwellings, like the chawls, could affect the health of the inhabitants and have provided some objective recommendations on restructuring these houses.

In this study, published in the journal Habitat International, the researchers examined the living conditions of 120 households of the chawls, built by the erstwhile Bombay Development Department (BDD), in four regions of Mumbai. The chawls, originally designed as a living space for just one person, has only about 200 sq.ft area. It has a kitchen accommodated within the living area and shared toilet blocks on the sides of the building. The suffocated living space, lack of maintenance and hygiene, pollution from the adjoining roads and use of kerosene-like fuels for cooking with poor ventilation affects the quality of life of the people staying here.

Although the local authorities had observed a steady increase in the number of visitors to health centres from these areas and had suspected the poor air quality to be the culprit, they could not back the claim with data. The occupants of the chawls did not wish to reveal health-related information. The frequency of their visits to the local health clinic was all the occupants were willing to share—a data point the researchers of the study made use of to indicate the health of the occupants.

The researchers chose a metric called ‘local mean age’ (LMA) of the air to indicate the air quality. “The mean age of air is defined as the average time that a mass of air has spent in a zone of the building accumulating contaminants,” explains Prof. Ronita Bardhan who led the study. It is an important factor in assessing the quality of ventilation. Simply put, it indicates period for which stale air stays inside a room, before being replaced by fresh air. Thus, a properly ventilated room has a low value of LMA, since fresh air is continuously circulating. Experimental studies show that if a building zone has both doors and windows closed, then the LMA values are near 46 min whereas, when the same doors and windows are open the LMA values can be as low as 3 mins. LMA is also a metric that is easy to understand and explain in the local language---Marathi--- say the researchers.

The researchers considered factors like the orientation and direction of the building, the presence of parks, roads and obstructions around the building, the area of the building, the thickness of its walls and the ratio of the areas of the windows and the walls. They surveyed the occupants on how long they kept the doors and windows open. They also used the local weather data along with data from temperature and humidity sensors placed in a few households. They used this information and mathematical models simulations to estimate the LMA values. 

The results of the study indicate that occupants of well-ventilated houses, where the air was fresh, made fewer visits to healthcare centres than those living in ill-ventilated dwellings. However, there was no significant association between the freshness of the air and the number of health care visits. 

The researchers observed that external obstructions played a significant role in the determining LMA and removing them could reduce the LMA values by half. Cross-ventilation in the buildings could also improve the freshness of the air. However, these changes need policy-level actions to make suitable modifications and raise awareness among residents about the need for living areas with fresh air, say the researchers.

“The involvement of local authorities would enable us to have better access to the indoor living environment of the chawls. We can study the human-space interactions of the residents in real-time and enable design sensitisation of living spaces among the occupants,” say the authors.

The findings and recommendations of the study could act as a significant input for planning authorities who could change the design of these buildings and help the residents of the BDD chawls live a relatively healthier life. 

Section: General, Science, Health, Society, Deep-dive Source:
Chennai Wednesday, 18 July, 2018 - 14:36

Researchers from the Indian Institute of Technology, Madras, have proposed methodologies that can improve the design of automated systems to detect muscle fatigue. In a recent study, published in the journal Computer Methods and Programs in Biomedicine, the researchers have used surface electromyography (sEMG), a technique which can record electrical signals over the surface of the skin.

Anyone too enthusiastic about lifting weights on their first day in the gym is aware of ‘muscle fatigue’. It is a condition in which one’s muscles are unable to generate enough force. It is observed not only in people who undergo vigorous exercise, like sportspersons, but is also a common syndrome in neurological disorders like multiple sclerosis, Parkinson’s disease and stroke.

In this study, the researchers instructed volunteers to perform bicep curls by lifting a 6-kilogram dumbbell until a point when they experienced fatigue. Bicep curls are dynamic contractions where the joint angles and degrees of muscle contraction keep changing, unlike isometric contractions (like the plank exercise) where the angles and degrees do not change. Most previous research has focused on isometric contractions, which involves less noise and variance in the sEMG signals. In contrast, dynamic contractions provide a more significant challenge to analyse. The researchers continuously recorded the sEMG signals from the volunteers’ arms during the exercise.

The time-varying signals collected during the first bicep curl (normal muscle condition) and the last one (muscle fatigue condition) have different frequencies inside them, just like a musical chord has different frequencies of its constituent notes hidden inside it.  The researchers used a signal processing technique called Time-Frequency Domain (TFD) transformations to extract these changing component frequencies. However, these powerful techniques spit out too many of these component frequencies, all of which might not be equally useful to classify the signal as being normal or not. So, to find out which are the best components, they used a method inspired by biology called the ‘genetic algorithm’ that starts through a set of features, allows the more ‘fit’ solutions to methodically change (‘mutate’) and give birth to fitter offsprings - and this continues till satisfaction.

The researchers then used other techniques that can guess, from these selected features, whether we have a normal or fatigued condition. The most accurate among the methods tried out was the Support Vector Machine (SVM), which imagines the transformed signals from each bicep curl to be like a point in some space and draws an imaginary boundary which can best classify the points while keeping maximum distance from either type of point. Using SVM with four selected features gave a high (91%) accuracy in detecting muscle fatigue. Besides, the researchers claim that these accurate and fast techniques can also be used in the much simpler-to-analyse isometric conditions too.

With the techniques mentioned above, one can imagine easier detection of fatigue at a personal level, which can not only serve as a measure of improved human performance, but can also help in preventing slip-induced falls and injuries in occupational settings, sports settings, or rehabilitation programs.

Section: General, Science, News Source:
मुंबई Wednesday, 18 July, 2018 - 08:08

​उत्तर भारत की सर्दी हमेशा चर्चा में रहती है। बर्फीली ठंडी हवाएँ और घने  कोहरे के कारण ​दिल्ली जैसे नगरों में, रेल  एवं  हवाई यातायात और  कई लोगों की रोज़मर्रा की ज़िंदगी, एकदम  ठप पड़ जाती है।​

कोहरे का सही अनुमान काफी हद तक यातायात और दूसरी गतिविधियों की योजना ​बनाने में सहायक होगा। ​भारतीय प्रौद्योगिकी संस्थान बम्बई ( Indian Institute of technology Bombay)​ द्वारा एक अध्ययन के अनुसार एक और कारण सामने आया है - शहरों का गरमाना। ग्रामों के मुकाबले नगरों  की भूमि की सतह का बढ़ा हुआ ताप , कोहरे की चादर को छितरा  करा उसमे एक बहुत बड़ा  छेद -दिल्ली नगर के आकार  के बराबर - बना देता है  जिसे अंतरिक्ष से ​ भी ​देखा  जा  सकता है। 

नमी / आर्द्रता  के घनीकरण से बना निचली ऊँचाई का ​​ ​​​​बादल ​ ही कोहरा है।  खेती बारी वाली ​ज़मीन, जलाशयों से पर्याप्त मात्रा में  उठती नमी​ और ​उत्तर भारत ​के प्रशांत  पवन  के कारण घना  कोहरा बन जाता है। ​ यह एक परेशानी ​ज़रूर खड़ा करता है परन्तु किसी भी क्षेत्र के पर्यावरण में ​ न केवल ​एक महत्त्वपूर्ण भूमिका  ​निभाता ​है बल्कि ​कुछ फलों की पैदावार की वृद्धि में  भी सहायक ​होता ​ है। ​

​शोधकर्ताओं ने नासा (NASA) के उपग्रह MODIS​ (​ Moderate Resolution Imaging Spectroradiometer ​) ​के 17 वर्ष ( 2000-2016) के आंकड़ों का अध्ययन किया। ​ गंगा के आस  पास की मैदानी ​जगहों ​ ​के ऊपर, ​जो शहरों के पास थे ,कई जगहों पर ' कोहरा - छिद्र ' पाए  गए जिसमे सबसे उन्नत छिद्र ​दिल्ली के ​ ऊपर ​था ।  'कोहरा - छिद्र '​,​  ​घने कोहरे की चादर में अलग अलग आकार के सूराख को कहते हैं।

​जिओफिसिक रिसर्च पेपर्स  नामक  जर्नल ​में प्रकाशित एक अध्ययन से प्रकट हुआ है कि इस ' कोहरा - छिद्र ' का परिमाण और एक नगर की जनसंख्या में  पारस्परिक सम्बन्ध ​है। जितनी अधिक जनसँख्या होगी , उतना ही बड़ा छेद  होगा। ​ भारतीय प्रौद्योगिकी संस्थान बम्बई ​ ​के भूतपूर्व प्रोफेसर रितेश गौतम , जिन्होंने इस अध्ययन का नायकत्व किया ,का कहना है ," ​यू.एस ए ​ , यूरोप और एशिया के ​13 ​नगरों के आँकणों के अनुसार कोहरा छिद्र के क्षेत्र और नगर की जनसंख्या में प्रबल पारस्परिक सम्बन्ध पाया गया। तुलना करने पर पाया गया कि विश्व के अन्य देशों के मुकाबले ,दिल्ली की शहरी गर्मी का कोहरे के निर्माण के दुर्बलीकरण पर सबसे अधिक  प्रभाव पड़ा है।

​तो अब सवाल ये उठता है कि तापमान कोहरे के निर्माण पर कैसे  प्रभाव डालता है ? देहाती  क्षेत्र में तापमान कम रहता है और अधिक  हरियाली के कारण नमी ​भी ​अधिक होती  है। शहरीकरण के कारण शहर,​ ​गाँवों ​से अधिक गर्म होते हैं,विशेषकर सर्दियों के महीनों में। ​शहरों में हरियाली भी कम होती है-क्योंकि पेड़ ,खेती ,और  घास के मैदान कम ​होते हैं​ ​ जिसके कारण  शहर के  अंदर सापेक्षिक  आर्द्रता ​देहात के मुकाबले कम होती  है और परिणामस्वरूप  शहर और गाँव में कोहरे के निर्माण में बहुत अंतर पाया जाता  है।

" देखा  गया है कि 17 वर्ष की अवधि ​(2000 -2016 ) ​में दिल्ली के ऊपर ,आस पास के इलाके की ​तुलना में,कोहरा छिद्र का निर्माण ​इतना व्यापक था  कि इसके कारण कोहरे की आवृत्ति में लगभग 50 प्रतिशत की कमी हो गयी। ", प्रोफेसर गौतम ने टिप्पणी की।

अध्ययन में ये भी पाया गया  कि हवा में उपस्थित एरोसोल्स ( हवा में निलंबित महीन कण जो शहरी प्रदूषण से आते हैं )  ​से कोहरे के निर्माण में तीव्रता आती है। परन्तु , शहरों के ताप में वृद्धि का असर  एरोसोल्स से कहीं ज़्यादा होता है जिसके फलस्वरूप कोहरा -छिद्र का निर्माण होता है।

इस निष्कर्ष का कोहरे के पूर्वानुमान ​प्रणाली ​ पर गहरा असर पड़ेगा. ​​"​अध्ययन  कोहरे के निर्माण की प्रक्रिया को समझने में ​ सहायक है  और  नगरीय तापमान का कोहरे पर विशिष्ट ​प्रभाव ​ भी दर्शाता है।  एक  परिष्कृत कोहरा पूर्वानुमान  प्रणाली को विकसित  करने की ज़रुरत है जो वायु प्रदूषण और शहरीकरण , दोनों के प्रभावों  को  ध्यान में रख कर बनाया जाए।

कोहरा छिद्र  के निर्माण में शहरी ताप ​के  प्रभाव का प्रमाण इस अध्ययन से एकदम साफ़ है। जैसा प्रोफेसर गौतम कहते हैं," कोहरा केवल एक स्थानीय नहीं बल्कि क्षेत्रीय समस्या है।"  उत्तरी भारत के मैदानी इलाकों के जन जीवन पर कोहरे के पर्यावरणीय महत्व की गुरुता को नकारा  नहीं​ ​जा सकता अतः,कोहरे के निर्माण की प्रक्रिया, वायु प्रदूषण एवं  शहरी करण का कोहरे के निर्माण पर असर​, इस विषय ​​​पर एक गहन अध्ययन की आवश्यकता है  जो  ​केवल दिल्ली के शहरी क्षेत्र तक ही न सीमित हो बल्कि  उत्तर भारत के दूसरे  हिस्सों को भी हिसाब में ले।

Section: General, Science, Deep-dive Source:
Mumbai Wednesday, 18 July, 2018 - 07:27

IIT Bombay and TIFR researchers demonstrate a method to turn heat into usable spin current.

Much of modern life is unimaginable without electronic devices like the computer or the mobile phone you are reading this article on, the television in your living room, the microwave oven in your kitchen or many others! But soon, electronic devices may be superseded by a new generation of spintronic devices that make use of a quantum mechanical property of electrons called spin. In a new study, researchers at the Indian Institute of Technology Bombay (IIT Bombay) and the Tata Institute of Fundamental Research (TIFR) have demonstrated that heat energy can be converted into 'spin current'.  Their work was featured on the front page of the journal Applied Physics Letters.

The spin property of electrons was first discovered in the 1920s by German scientists, Otto Stern and Walther Gerlach. They found that when an external magnetic field is applied, the electron exhibits behaviour as if it is rotating about an axis. But unlike the rotation of a spinning top, the spin of an electron is an intrinsic property of the electron that is unlikely to have been caused by any actual physical rotation. The electrons are said to be “spin-up” for counter-clockwise and “spin-down” for clockwise rotation.

In the present study, the researchers have provided experimental evidence to the 'spin Nernst effect', named after Nobel laureate Walther Nernst. The 'spin Nernst effect' is a theoretical prediction that when there is a temperature difference between two ends of a non-magnetic substance, electrons having different spins separate in a direction perpendicular to the direction of the heat flow.

“The semiconductor chips that we use in electronic devices such as computers, mobile phone etc., are based on the motion of electrons when an electric field is applied to it. These devices rely only on the charge and mass of the electron, and the spin is completely ignored. In spintronics (spin+electronics) the spin of an electron is also exploited to make devices with more functionalities and reduced power consumption,” says Prof. Tulapurkar of IIT Bombay and an author of the study featured in the cover of the journal Applied Physics Letters.

The experiment, carried out by the researchers using the nano-fabrication facilities at IIT-B, involved heating platinum and measuring the separation of spin-up and spin-down electrons. They used a platinum crossbar with top and bottom surfaces coated with a magnetic metal to detect spin. When the platinum bar was heated at the center, the heat flow within the platinum caused the spin-up and spin-down electrons to separate and move in opposite directions. The movement of electrons was then measured as a difference in voltage between the top and bottom terminals.

“It was believed that spin current can be created only in ferromagnets by applying heat or electric current. We have made one of the pioneering observations that heat can generate spin current even in non-magnets. Our work is important for various applications, and at the same time, it is very appealing from a fundamental physics point of view”, says Dr Arnab Bose, PhD student at IIT Bombay and lead author of the paper, explaining the significance of this research. 

The researchers believe that the findings may open up a whole new world of applications involving storing digital data in compact, energy efficient devices. The basic idea is that spin-up and spin-down states can be used to encode information. “The wiring of a memory cell involves changing the magnetization direction from up to down or vice versa. This task can be performed efficiently by using spin current. Now spin current can be generated from the waste heat (dissipated by electronic devices) by using the spin-Nernst effect. Thus spin-Nernst effect could find potential applications to writing magnetic memories.”, concludes Prof. Tulapurkar.

Section: General, Science, Deep-dive Source:
Bengaluru Tuesday, 17 July, 2018 - 12:23

Although smaller than a cell in our body, a bacterium is strong enough to make us crippled and vulnerable with an infection. Among the many weapons these tiny microorganisms possess, bacterial toxins are one of them. These toxins, secreted by the bacteria targeting other bacteria or host cells, come in various forms but with a common goal—damage or destroy the target cells. In a new multi-disciplinary study, researchers at the Indian Institute of Science, Bengaluru, have unravelled how a class of toxins, called the pore-forming toxins, work to destroy our cells.

Pore-forming toxins, as the name suggests, puncture holes in animal cells, including human cells, and destroy them. These are proteins, and different types of bacteria could produce various kind of such toxins. Cytolysin A (ClyA) is a type of pore-forming toxin produced by some types bacteria like the Escherichia coli, Shigella and Salmonella. This toxin destroys the cells of various mammalian and bird species.

In this study published in the journal Proceedings of the National Academy of Sciences (PNAS), the researchers have tried to answer how the toxin forms pores in the cell membrane and how they selectively target the host cells without damaging the bacterial cell membrane. The research was supported by the Department of Science and Technology (DST) and the Department of Biotechnology (DBT). The team included scientists from the Centre of Biosystems Science and Engineering, Department of Chemical Engineering, and the Department of Molecular Reproduction Development and Genetics from IISc.

“This study clearly required the expertise of biologists, chemical engineers, biophysicists and bioengineers. This coming together of researchers allowed an understanding of the details of the working of the toxin, that would have been difficult to decipher by the individual disciplines and highlights how such interdisciplinary approaches can make important discoveries”, remarks Prof. Sandhya S. Visweswariah from IISc and a co-author of this study, highlighting the need for a collaborative approach.

The researchers showed that cholesterol, a constituent of our cell membrane, helps pore-forming toxins to cause rapid cell damage. A single ClyA molecule cannot form the pores in a membrane on its own. Hence, 12 molecules of ClyA arranged in a ring-like structure come together to puncture a hole. 

The researchers used a technique called ‘single molecule imaging’ to visualise the process of pore formation. This process employs high-end cameras and microscopes to record the movement of a single protein molecule on a membrane. They used a fluorescent dye on the ClyA molecules to make them bright enough to be seen and to record its movement and interactions with other ClyA molecules. The researchers could thus monitor the pore formation as it happened. They also used supercomputer simulations to simulate the movement of the ClyA molecules and locate specific points on the ClyA molecule that interacted with the cholesterol present in the membrane.

The study found that cholesterol was indeed interacting with specific parts of this protein. The toxin molecule ClyA is a water-soluble protein. However, in the presence of lipid membranes, like our cell membrane, the molecule binds to the membrane by inserting a part of itself into the membrane. After binding, it starts roaming around the membrane looking for its partners to form the pore in the membrane. Cholesterol acts as a glue to stick other ClyA molecules together.

“Other pore-forming toxins use cholesterol for recognising and binding to the target cells. However, in the case of ClyA, we found that cholesterol does not help in binding to the membrane at all. Instead, it helped the protein in rupturing the cell in two other ways”, says  Dr. Rahul Roy from IISc, in an interview with Research Matters.

During the study, the researchers observed that the cholesterol molecule allowed the toxin protein to achieve full insertion into the cell membrane. Besides, it also helped in 'stitching' the ClyA molecules together to quickly form the pore complex across the membrane. As bacterial membranes do not contain cholesterol, they remain safe from the damage caused by ClyA.

However, the researchers observed a few sites in the ClyA molecules which interacts explicitly with cholesterol. “This is an interesting observation since the bacterial cells do not have cholesterol. These cholesterol binding sites could have evolved to prepare the bacteria for attacking the target cells. Evolution must have allowed this to happen even though this does not aid in the growth of the bacteria in isolation”, comments Dr. Roy.

Pradeep Sathyanarayana, a researcher from the Center of Biosystems Science and Engineering, IISc, and the first author of this study, informs that this toxin has similarity with the proteins that cause neurodegenerative disorders like Alzheimer's and Parkinson's disease. Thus, findings from this study might be helpful to understand the mechanisms associated with these diseases.

Besides, the researchers hope that the study might open new avenues for treating a range of diseases. “The deep molecular insights gained from our study could assist in developing potential antibacterial therapies, cancer therapy and other biotechnological applications like DNA sequencing”, says Prof. K Ganapathy Ayappa, a senior co-author on the paper.

Section: General, Health, Deep-dive Source:
Meghalaya Tuesday, 17 July, 2018 - 08:38

The field of material science has become exciting in the recent past with scientists discovering some remarkable properties and behaviour of novel materials. In one such study,  researchers from the National Institute of Technology, Meghalaya, India, and the New York University Abu Dhabi, UAE have designed a versatile crystal material that can be twisted with heat, bent with light, is elastic and can heal itself by heating or cooling.

In the study published in the international edition of the journal Angewandte Chemie, the researchers have detailed the synthesis of the crystal material. They used probenecid, a chemical compound that is usually used to help excrete uric acid from the body, and 4,4'-azopyridine, an aromatic compound, in 2:1 ratio to form a cocrystal, which consists of these two molecules.

The researchers have tested the behaviour of the crystal by heating it up to 68° C and then cooling it.  They observed that 14 out of 35 crystals, when twisted, retained its shape. They also saw a transition of the crystal from one form to another when it was heated above its phase transition temperature, but came back to its original form on cooling. The tests also showed that the crystal could repair itself from the generated cracks during the first heating cycle, which disappeared during the second heating cycle, thus demonstrating its ability to heal.

When mechanical stress was applied on the crystal, it exhibited elastic properties and relapsed into its pre-stress state due to its molecular interaction and arrangement. Also, when the crystal was irradiated with ultraviolet (UV) light, it behaved rapidly by bending away from the light source because atoms within the azopyridine molecules undergo rearrangement upon irradiation. However, when the incident light was stopped, the crystals recovered to its original state.

The researchers claim that these versatile crystals have the potential to be as microcomponents in the field of micro-robotics and microfluidics, as micro-gears and actuators.

Section: General, Science, News Source:
Delhi Monday, 16 July, 2018 - 15:13

A collaborative study by researchers from Punjab University, Indian Institute of Technology (IIT) Delhi, Banasthali University, TERI University and the Jawaharlal Nehru University has identified how a particular gene in Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), mutates to avoid the action of antibiotics. They have used computer simulations to study the behaviour of the mutated gene and understand how the mutation affects its interactions and binding with other molecules in the bacteria. The study also details the basis of resistance against the antibiotic streptomycin, observed in three different mutant strains of the bacteria.

Tuberculosis has become the world’s deadliest infectious disease with 1.4 million deaths in 2016 worldwide, one-third of which were in India alone. In spite of our prowess in science and technology, we have been unsuccessful in eradicating this disease because the causative bacterium is smarter than we thought. Mycobacterium has found a way to survive even the harshest drugs thrown at it by mutating itself and becoming drug resistant. So far, scientists have identified many genes which have high mutation rates. In this study, published in the Journal of Biomolecular Structure and Dynamics, the researchers have studied how mutations in one such gene, gidB, cause drug resistance towards the antibiotic streptomycin.

Streptomycin kills Mycobacterium by inhibiting the action of a particular ribosomal RNA called 16S rRNA, which is needed to synthesise proteins in bacteria. Streptomycin binds to a region on the 16S rRNA which contains a chemical group known as the methyl group. The gene gidB encodes for an enzyme which, upon binding to the molecule S-adenosyl methionine (SAM), adds this methyl group on the 16S rRNA. Without this action of gidB, streptomycin cannot inhibit the 16S rRNA and kill the bacteria, leading to streptomycin resistance.

In this study, the researchers chose mutations that resulted in changes in the amino acid sequence of gdiB and significantly impacted its binding to SAM. They showed that all the mutant versions of gidB have a significantly lower binding affinity for SAM due to a decrease in the size of the region where SAM binds. Their results also demonstrate that mutant gidBs are more flexible proteins which makes the gidB-SAM complex relatively unstable.

This study is one of the first to understand the molecular basis of streptomycin resistance in TB, caused by mutations in the gidB gene. This work will enable scientists to design and develop drugs and treatments for gidB resistant TB strains.

Section: General, Science, Health, News Source: