Researchers think the molecule might be better at keeping up with evolving bacteria.
MRSA Researchers at IBM are working on a synthetic molecule to fight antibiotic-resistant bacteria. One of which is MRSA, pictured above. -CDC
When Alexander Fleming discovered penicillin in 1928, the finding was key for two reasons: First, obviously, doctors finally had a way to treat illnesses like pneumonia, gonorrhea, and rheumatic fever. Until then, the approach was to watch, wait, and hope the patient’s immune system cleared the infection; that often didn’t work out. And second, the discovery introduced the idea that we could use molecules found in bacteria and fungi to kill other bacteria—ones that cause infection and illness.
Since then, researchers have been on the hunt to find novel molecules, similar to penicillin, to treat the various bacteria and fungi that infect us. And, from the beginning, it’s been a race against time. Bacteria evolve quickly, and while our goal is to annihilate all of them, their goal is precisely the opposite: To survive at all costs. Research shows that in this tug-of-war effort, humans are being gradually draggedcloser and closer to a bacterial victory. In May 2016 the Review on Antimicrobial Resistance, a research group funded by the UK Department of Health, estimated that 700,000 people die each year from antibiotic resistant infections (these are bacteria that no currently available antibiotics are able to kill). By 2050, an estimated 10 million people could die from this resistance if researchers don’t find a way to keep up with ever-evolving bacteria.
Scientists are employing countless approaches to avoid this outcome. And while most involve finding new molecules or protein in bacteria or fungi, similar to the way Fleming found penicillin, researchers at IBM are taking a different approach: They’ve created a synthetic molecule that works in a novel way to kill each bacterium from the inside out.
The researchers set out to address the scariest of antibiotic resistance scenarios: When a resistant strain of bacteria becomes systemic, spreading through the blood to every organ system in the body. They designed molecules to fight against five of the most drug-resistant strains commonly acquired in hospitals, which often become systemic and lead to organ failure.
Researchers have been working on creating synthetic molecules for some time now, but it’s been difficult. The synthetic molecule needs to be able to biodegrade—it can’t remain inside the body forever—and it also needs to effectively fight bacteria in a way that doesn’t negatively affect other organ systems in the body. Existing drugs that kill highly resistant bacteria typically do so in exchange for toxicity to the liver and other organs.
“We are trying to emulate the exact way that our innate immune system works,” says James Hedrick, a researcher at IBM. He and his team published their findings in a paper out this week in the journal Nature Communications. Our immune systems target a microbe and lyse its membrane, he says—we destroy cellular invaders by breaking down their protective barriers. “When you get an infection, right away your body secretes antimicrobial peptides, which is simply a fancy word for a polymer.” (A polymer, by the way, is also just a fancy word for a big molecule.) In recent years, many scientists have focused on creating these big molecules in the lab.
The problem with using that exact method when you have a systemic infection, Hedrick says, is that when you explode a bacterial cell in the body, it releases its toxins into the bloodstream. That wouldn’t be a terrible thing in isolation. But when you have millions of these dangerous little guys, toxins start to add up.
In the past, Hedrick says, synthetic polymers employed a similar method, where they would essentially explode each bacterium; obliterate it. But instead of causing the bacteria to explode, the new synthetic polymers kill each bacterium from the inside out.
On top of that, Hedrick and his team also think these types of antibiotics will lead to less antibiotic resistance. The polymer works through electrostatic interactions—a positive and negative charge are attracted to one another. But it attracts itself to multiple locations on the bacteria’s surface. This means that even if the bacteria evolves, it’s still highly likely that the bacteria-fighting polymers will remain attracted to one area of the bacteria.
The IBM team has found that the polymer is completely biodegradable and works extremely fast. “What makes this new class of materials so beautiful is that after three days, it degrades completely. It basically just comes in, kills the bacteria, degrades, and leaves.”
So far, all of their studies have been done in mice, but Hendrick says his team is ready to move to human clinical trials. For IBM, that means partnering with a pharmaceutical company to bring the polymer into clinical trials and, potentially, develop it into a drug.
This is all very promising. But the research still has a long way to go before it reaches a doctor’s prescription pad. Even though they’ve showed good results in mice, those same positive effects may not translate to humans, at least not with such efficacy. Most crucial is that the molecules biodegrade as well in humans as they do in mice. Concerns over the long term build-up of such antibiotic polymers in the body has hindered previous development attempts.
There’s also the concern of cost. A lab-engineered polymer will likely be far more expensive to manufacture than traditional antibiotics, and thus potentially more costly for pharmaceutical companies and consumers.
Even if the new treatment proves successful, this is by no means a reason to give up on other efforts to identify post-antibiotic options—as well as those to slow the progress of antibiotic resistance. Things like reducing the number of unnecessary cesarean sections, avoiding using antibiotics for infections that don’t respond to them (like the common cold or the flu) or that a person’s immune system will likely clear without help, and cutting down on their use in meat production will all help to stave off the increasing number of antibiotic resistant bacteria infecting us.
And while the drug may be able to stave off bacterial resistance for some time (Hendrick says it’s hard to predict for how long, exactly), that doesn’t mean it will work forever. “These are really clever bacteria. I am certain that over decades, they will figure out a way to elude the therapy,” says Hedrick. “That’s why this is a never ending kind of fight.”
Mindtree | DLF | ABG Shipyard | Ashok Leyland | Magma Fincorp |Container Corp | Jain Irrigation | Infibeam | Dynamatic Technologies and NMDC are the stocks which are in new today.
Here are stocks that are in news today:
Results today: TCS, IndusInd Bank, Mahindra CIE, Reliance Power, Cyient
Mindtree Q4 QoQ – Net profit up 28.8 percent at Rs 182.2 crore, revenue up 6.3 percent at Rs 1,464 crore
ACC Q1CY18 YoY – Consolidated revenue up 14.2 percent at Rs 3,624.6 crore; profit up 18.6 percent at Rs 250.4 crore
DLF: The company has sought to allay concerns about slow pace of monetization of land assets, Bloomberg reported.
Bharat Dynamics signed licensing agreement with Defence Research Development Organisation (DROO) for ASTRA MK-1 Weapon System
Sun Pharma: One of the owned company’s subsidiary increased stake in Ranbaxy Malaysia Sdn Bhd via purchase of 4.93 percenet stake; current holding increased to 95.67 percent.
Mark Builders: SEBI has banned the firm and its directors from market
ABG Shipyard: Fresh bids are invited for the company under insolvency law.
Trigyn Techno: Company received technology support staffing contract by Baltimore county public schools for 5 years
Sadbhav Infrastructure: Investment committee meeting on April 23 to approve NCD of Rs 170 crore
Ashok Leyland: The company has drawn up Rs 1,000 crore plan for 2018-19.
Magma Fincorp – ICRA upgraded credit rating to AA-/stable for bonds and bank facilities; raises Rs 500 crore through QIP route, per share price is Rs 155
Container Corp: Company to consider stock split on April 30
Ambuja Cement/ACC – Board of Directors approved limiting the period of the master supply agreement with ACC for 3 years
Jain Irrigation: Board approves plan to raise Rs 260 crore loan from World Bank arm
Kirloskar Oil Engine – Blackstone emerges as front runner to buy the Company: ET
Tata Steel may acquire 75 percent in Bhushan Steel: Media Report
Amtek Auto – Subsidiary gets two binding bids by Liberty, Deccan Value: Media Report
Infosys clarified that company has not received any alleged anonymous whistleblower complaint
Mastek declared dividend of Rs 4 per equity share of Rs 5 each
Jubilant Foodworks clarified on allegations about some products of Domino’s Pizza via video that co assure that they use real cheese in their products
Workhardt board meeting on May 4 to approve raising of fund via non-convertible debentures (NCD)
Infibeam: Company receives online marketplace contract from NSDC.
ICICI Bank chairman meets MF heads over succession plan, if Chanda Kochhar quits: BS
IFCI invites bids for sale of stake in NSE
ABG Shipyard – Fresh bids invited for the company
Lemon Tree Hotels signs 3 management contracts for hotel in Uttarakhand
As announced earlier Great Eastern Shipping takes delivery of very large gas carrier of about 81,617cbm
In a bull case scenario, Morgan Stanley see the index touching 41,500 (bull case scenario), in the base case scenario it sees Sensex to touch 35,700, and in the bear case scenario, it sees Sensex slipping towards 25,000 by December 2018.
Volatility gripped markets across the globe after US President Donald Trump along with UK and France fired over 100 missiles on Syrian chemical establishments over the weekend.
Equity markets, in general, do not likely uncertainty and events like these usually trigger risk-off sentiment. Things could turn ugly for markets across the globe if Russia starts to retaliate. In this scenario, what should investors do?
Market experts said that Indian markets have always managed to surmount the wall of worries in the past and this time too it will be no different. The Nifty is trading above its crucial short and long-term moving averages. The Sensex did reclaim Mount 34,000 in April which suggests ongoing strength on D-Street.
Morgan Stanley in its report released earlier this month highlighted that Indian markets can outperform emerging markets (EMs). In a bull case scenario, the brokerage see the index touching 41,500. In a base case scenario, it sees Sensex touching 35,700, and in a bear case scenario, it sees the Sensex slipping towards 25,000 levels by December 2018.
“Returns are moderating in 2018, especially down the capitalisation curve. Largecap valuations look reasonable and better than midcaps. Hence, we remain more constructive on largecaps relative to midcaps,” it said.
Top 20 stocks in its focus list include Bajaj Auto, M&M, Maruti Suzuki, ITC, Bharat Financial, HDFC Bank, ICICI Bank, M&M Financial, ZEE Entertainment, IndusInd Bank, Dr Reddy’s Laboratories, Havells India, JSW Steel among others.
Although most global brokerage firms did tweak their targets with respect to the Sensex and Nifty, there is general consensus that investors should focus on individual stocks.
Market experts said the focus will now shift to individual stocks in 2018 from benchmark indices. “The crucial factors will be earnings which will chart a direction for Indian markets in the near future.”
The Indian market has digested a rise in rates, domestic political news, bank scandals, rise in equity supply, protectionist waves, global market volatility, rise in Fed rates, higher oil prices and a reduction in portfolio weightage by FPIs.
Another global brokerage, Citigroup expects a 10 percent YoY growth in Q4 earnings of stocks in its coverage universe, led by strength in commodities (oil & gas and steel) and domestic autos (excluding JLR).
“With FY18 likely to be another year of tepid earnings growth (single-digit growth expected), we would watch out for downgrade risks to our FY19 estimates. We expect 2018 to be a volatile year for Indian markets and have our December 2018 Sensex target to 35,700, factoring in downward earnings revisions,” it said.
Its top picks from the mid and largecap space include Apollo Hospitals, DB Corp, Emami, Exide Industries, Federal Bank, Gujarat State Petronet (GSPL), L&T Finance, Mahindra & Mahindra Financial Services, Petronet LNG and Voltas.
In the largecap space, it is positive on Ambuja Cements, Aurobindo Pharma, Bharat Electronics, Cipla, HDFC Bank, ICICI Bank, IndusInd Bank, M&M, Tata Motors, and IOC.
Disclaimer: The views and investment tips expressed by investment experts on moneycontrol.com are their own and not that of the website or its management. Moneycontrol.com and blogger advises users to check with certified experts before taking any investment decisions.
The Nifty50 is expected to open flat on Tuesday following muted trend seen in SGX Nifty. But, positive handover from Wall Street and stable Asian markets may push the index higher. The Nifty closed 47 points higher at 10,528.35 on Monday.
Trends on SGX Nifty indicate a flat opening for the broader index in India, a fall of 3 points. Nifty futures were trading around 10,544-level on the Singapore Stock Exchange.
US stocks closed higher on Monday, with the biggest boosts from technology and healthcare sectors as investors were optimistic about earnings season and appeared less worried about US-led missile attacks in Syria, Reuters reported.
The Dow Jones Industrial Average rose 212.9 points, or 0.87 percent, to 24,573.04, the S&P 500 gained 21.54 points, or 0.81 percent, to 2,677.84 and the Nasdaq Composite added 49.64 points, or 0.7 percent, to 7,156.29.
Asia stocks edged higher on Tuesday, tracking Wall Street gains as the focus shifted to corporate earnings and looming economic data from China amid signs Western-led strikes on Syria weren’t likely to escalate, a Reuters report said.
Disclaimer: The views and investment tips expressed by investment experts on moneycontrol.com are their own and not that of the website or its management. Moneycontrol.com and blogger advises users to check with certified experts before taking any investment decisions.
“Nifty is likely to retest 10,650-10,670 levels on upside i.e. Inner Trendline which might work as immediate hurdle zone,” says Rajesh Agarwal of AUM Capital.
Benchmark indices managed to close in the positive zone for the eighth straight session on Monday on positive economic data that revived overall investors’ sentiment despite mixed global cues. Shares of India’s second-largest IT services company, Infosys, tumbled nearly three percent after the management forecast FY19 operating margin between 22 percent and 24 percent. Credit Suisse said this was 100 basis points below expectations and slightly lower than its previous year’s 24.3 percent.
Meanwhile, in economic data, March wholesale price inflation (WPI) came in at 2.47 percent on Monday versus 2.48 percent month-on month.
Broader weakness in Asian markets also weighed on sentiment amid tensions between the United States and Russia over Syria.
The Nifty opened with a gap down around its 50 EMA and rebounded from Monday’s low to close higher at 10,528.35, up 0.46 percent. The index has formed a ‘Bullish Engulfing’ candlestick pattern. This candle indicates the change in sentiment from a bearish gap down in the morning, to a large bullish real body candle that closes at the highs of the day. It is likely to retest 10,650-10,670 levels on the upside: Inner Trendline which might work as an immediate hurdle zone.
Bank Nifty
Nifty Bank is consolidating within its two major moving averages of 200 and 100 SMA for five consecutive days. It has formed a ‘Bullish Candle’ after multiple bearish reversal candles, thereby negating a bearish set up. Now the Nifty Bank has to cross 25,420 decisively for a further upmove.
If the index fails to cross this level and sustains below it, Nifty Bank may correct till 24,700. On the hourly scale, the index is trading around overbought zone with a negative divergence on RSI.
Below are the top five stocks which can deliver up to 7% return in the near term:Indiabulls Ventures | Rating: Buy | Target: Rs 398 | Stop loss: Rs 365 | Return: 5%
Disclaimer: The author is the Head of Research at AUM Capital Markets. The views and investment tips expressed by investment experts on moneycontrol.com are their own, and not that of the website or its management. Moneycontrol.com and this blogger advises users to check with certified experts before taking any investment decisions.
The Indian Institute of Science in Bengaluru has come up with many useful innovations in science, technology and healthcare. These have made detecting heart conditions and malaria, purifying water, and fixing cataract not just easy, but also affordable.
In the last decade, Indian Institute of Science, in Bengaluru, has churned out a lot of innovations, with the focus being on producing indigenous research and making them available to the country and the world at an affordable rate. From detecting heart conditions to making lenses affordable for cataracts patients, innovations in water purifying and discoveries in cancer drug treatments, here are eight additions to the future of science and technology in India:
Water Purification at a Nanoscale Level
In 2015, Dr. Suryasarathi Bose, Assistant Professor of Department of Materials Engineering and a team invented a water purifying system that could even eliminate harmful bacteria at a nanoscale level. The filter consisted of a porous membrane made of two polymers, along with minute quantities of silver, titanium dioxide and carbon nanotubes. The pores filter out the micron-sized bacteria, while the silver-titanium-carbon mixture kills the bacteria.
A Solar Water Purifier
Another twist to the water purifier, this innovation by Professor Vasant Natarajan, from the Department of Physics is low cost and does not require membranes or electricity. According to Natarajan, this device could purify all kinds of water – sea, bore well, ponds, even rain water – into drinkable water, and produce 1.5 litres out of 3 litres of impure water. Explaining how the device works, he said that first the water is evaporated using solar energy, and then the vapours are condensed on a cold surface. What’s left behind is all the impure substances such as bacteria, arsenic, and fluoride.
A Non-hazardous Stain for Scientists
Researchers in labs often work with a number of chemicals and hazardous materials that could affect their health. Acid stains are used to test a number of chemicals that is probably carcogenic. In March 2016, J Fathima Benazirdeveloped a stain that, if replaced with acid stains, could help researchers reduce their exposure to harmful chemicals. The new stain called Tinto Rang is made from plants, and is even safe for consumption. This indigenous invention could also be the safest in the world, according to Benazir.
Non-invasive Heart Condition Detector
A non-invasive device that can measure heart and lung, called the Fibre Bragg Grating Heart Beat Device, was invented by S Asokan, Professor at Department of Instrumentation and Applied Physics and his team. The device simply needs to be wrapped around a person’s chest, while the sensors detect cardiac activities, measure blood pressure, count blood glucose levels, and monitor respiration. Made of an optical fibre sensor, this device can easily help detect heart conditions early.
A Vaccine to Combat Hepatitis C
In India, 20% chronic liver disease has one cause: hepatitis C virus, which spreads through blood contact, and affects 12 million people. It causes severe liver problems, sometimes even ending up in cancer. In February this year, a team of scientists led by Professor Saumitra Das developed a vaccine that could produce the antibodies to fight the virus. Right now, the vaccine is still being tested on animals, but the results are promising, according to Das.
Smartphone-Turned-Malaria-Detector
Ever thought one could detect malaria through a smart phone? Dr Sai Siva Gorthi, from the department of Instrumental and Applied Physics and her team did so. They converted a smartphone into a powerful microscopic device that eliminates the various stages of blood testing to detect malaria. The team replaced the phone camera with high resolution optics of a microscope. The smartphone also has software that studies the images captured through the microscope and tells even a layman whether it has the malaria virus or not. It requires a tiny amount of blood as a sample.
A Revolutionary Cancer Molecule Inhibitor
In 2012, Sathees C Raghavan, associate professor with IISc’s biochemistry department and his team developed a molecule inhibitor, SCR7, which could revolutionise cancer treatment. In 2014, scientists at MIT tested the molecule and discovered its efficiency and potential in becoming an integral part of anti-cancer drugs. The molecule inhibitor binds with the cancer cells to block its DNA from repair, thereby killing the cancer cells. While the drugs are still under research, the fact remains that an Indian team was vital in creating an anti-cancer drug.
Affordable Lens to Give Vision to Cataract Patients
In a life-saving innovation by Professor G. Mohan Rao at the Department of Instrumentation in 2015, many people who suffer from cataract are now able to see. The team developed economical intraocular lenses (IOLs) in their labs that could be affordable for even poor patients. They succeeded, after months of trials, in creating a thin film of ‘tetraflouroethane’ coating on IOL. This IOL replaces the natural lens in the eyes of a cataract patient. So far, IOLs developed abroad were expensive and inaccessible to most Indians. This, however, changed when Rao and his team succeeded in their tests and transferred the technology to AUROLAB, which now produces these lenses.
Stem cells can be coaxed to self-assemble into structures resembling human embryos.
Two years ago, Shao, a mechanical engineer with a flair for biology, was working with embryonic stem cells, the kind derived from human embryos able to form any cell type. As he experimented with ways of getting cells to form more organized three-dimensional structures by growing them in scaffolds of soft gel, he was looking for signs of primitive neural tissue.
What drew his attention was that the cells seemed to change much faster than expected—they arranged themselves rapidly over a few days into a lopsided circle.
What was it? Shao startled Googling to see if he could identify the structure. That’s when he landed on a website called The Virtual Human Embryo and found some microscope photos of ten-day old human embryos shortly after implantation, fused to the uterine wall. There was the beginning of the amniotic sac and, inside it, the embryonic disc, or future body. They matched what he was seeing.
In this microscope movie, filmed over four days, stem cells self-organize in ways that mimic a human embryo.
COURTESY OF UNIVERSITY OF MICHIGAN
Shao informed his coworkers, a mixed team of biologists and engineers, at the University of Michigan. “When I showed the image to the team, everyone said, “Wow, we need to figure out what to do,” says Shao. Had they somehow made a real human embryo from stem cells? “At that point, we started to be more cautious.”
The embryo-like structures, the team soon determined, are not complete and couldn’t become a person. They lack the cell types needed to make a placenta, a heart, or a brain. Even so, the Michigan “embryoids” are realistic enough that the lab has been destroying them using a bath of detergent or formaldehyde to make sure they don’t develop any further.
The work in Michigan is part of a larger boom in organoid research—scientists are using stem cells to create clumps of cells that increasingly resemble bits of brain, lungs, or intestine (see “10 Breakthrough Technologies: Brain Organoids”). Now some like Shao are finding it’s possible to mimic the embryo itself. This year, for example, researchers in Cambridge, U.K., built a convincing replica of a six-day-old mouse embryo by combining two types of stem cells. That group is now trying to do the same with human cells, as are a few others, including one at Rockefeller University in New York. What’s emerging, say scientists, is a new technology, which they call “synthetic embryology,” and which they believe may let them probe the fascinating opening chapters of human development in detail for the first time.
That’s been difficult to do because normal embryos don’t keep growing more than about a week in a lab. Key events after that are largely inaccessible to science: they occur in the darkness of the human uterus even before most women know they’re pregnant.
A microfluidic device used at the University of Michigan to cultivate organoids made from embryonic cells. About 10 organoids can fit inside each of the small blue channels.
COURTESY OF UNIVERSITY OF MICHIGAN
What’s more, research on real human embryos is dogged by abortion politics, restricted by funding laws, and limited to supplies from IVF clinics. Now, by growing embryoids instead, scientists see a way around such limits. They are already unleashing the full suite of modern laboratory tools—gene editing, optogenetics, high-speed microscopes—in ways that let them repeat an experiment hundreds of times or, with genetic wizardry, ask a thousand questions at once.
One result already from the Michigan team: dramatic close-up video of stem cells self-organizing into structures that mimic embryos.
“It’s amazing that [stem cells] have this capability,” says Jianping Fu, the University of Michigan professor in whose engineering lab Shao was a student. He says the emergence of something with an embryo’s shape, and some of its features, was “a complete surprise; I still can’t believe it. But it shows these cells remember what they are supposed to do.”
Scientists at Michigan now have plans to manufacture embryoids by the hundreds. These could be used to screen drugs to see which cause birth defects, find others to increase the chance of pregnancy, or to create starting material for lab-generated organs. But ethical and political quarrels may not be far behind. “This is a hot new frontier in both science and bioethics. And it seems likely to remain contested for the coming years,” says Jonathan Kimmelman, a member of the bioethics unit at McGill University, in Montreal, and a leader of an international organization of stem-cell scientists.
What’s really growing in the dish? There no easy answer to that. In fact, no one is even sure what to call these new entities. In March, a team from Harvard University offered the catch-all “synthetic human entities with embryo-like features,” or SHEEFS, in a paper cautioning that “many new varieties” are on the horizon, including realistic mini-brains.
Shao, who is continuing his training at MIT, dug into the ethics question and came to his own conclusions. “Very early on in our research we started to pay attention to why are we doing this? Is it really necessary? We decided yes, we are trying to grow a structure similar to part of the human early embryo that is hard otherwise to study,” says Shao. “But we are not going to generate a complete human embryo. I can’t just consider my feelings. I have to think about society.”
Other scientists, however, are determined to see just how far the science leads, up to and including forging the first complete human embryo from stem cells. That’s the case of Ali Brivanlou, an embryologist who leads a lab at Rockefeller University, in New York City. “My goal is to maximize the modeling, in vitro, of human development,” Brivanlou wrote in an e-mail. “Therefore, we would like to be as accurate as possible and as complete as possible.”
Taking shape
Embryonic stem cells were first isolated from spare, days-old IVF embryos in 1998 by scientists in Wisconsin. Early on, in its first few days, an embryo is little more than a mass of these identical, blank-slate, cells. Their specialty: making any other type of cell in the body. With an eye toward eventual medical treatments, companies have used them to produce neurons and beta cells that respond to insulin. Left alone in a dish, they’ll spontaneously turn into heart muscle and start beating.
Scientists have started seeking ways to coax stem cells to form more complicated, organized tissues, called organoids. These mini-organs aren’t the real thing. Instead, they’re far smaller—the size of sand grains—and often less sophisticated. But they can still have basic aspects of, say, the branching airways and wavy cilia of a lung. Last year, researchers used brain organoids to show how the Zika virus can infect brain cells.
By 2014, such efforts started yielding evidence that stem cells might, if given the right cues, directly reenact early events in an embryo. Brivanlou’s lab had the idea of corralling stem cells within tiny dots on a micro-patterned surface. Containing the cells helped lead to a surprising effect. They developed an organized “primitive streak”—a feature of a two-week-old human embryo when cells lay down the first hint of a body plan, deciding which side is left which is right.
Those embryoids were not natural. They were thin, grown as a flat sheet, and their streaks were circles, not lines as in a true embryo. “But it worked better than we thought,” says Aryeh Warmflash, a Rice University professor who ran the experiment while working at Rockefeller. “What we have increasingly realized is that the cells are programmed to make an embryo. That is what they want to do. If cells are in the right shape, at the right density, and you give them the right signal, the cells just take over from there, they talk to each other.”
At Michigan, Fu says his lab, working with Michigan biologist Deborah Gumicio, hit on its own method for making embryoids almost by accident while studying whether mechanical signals, like growing cells in a gel that is soft or sticky, could enhance their ability to form certain tissues.
One experiment involved encouraging gut cells to form a lumen, or hollow cyst. As a control experiment, they also cultivated embryonic stem cells in the same way. That is when “serendipity hit,” says Fu. The stem cells polarized into spheres that bore similarity to the start of an amniotic cavity. “[After] that is when we saw all the fascinating self-organizing features,” says Fu.
Ethical questions
Further tests demonstrated that the embryoids represented only a part of the embryo. While they had the beginnings of an amniotic sac, they lacked an entire lineage of cells, called trophoblast, whose role is to make the placenta. And inside the clump of cells that constitutes an embryo proper, the researchers detected only one of three key types needed to make a complete body.
When the team published its findings in early August, they went mostly unnoticed. That is perhaps because the scientists carefully picked their words, straining to avoid comparisons to embryos. Shao even took to using the term “asymmetric cyst” to describe the entities that had so surprised the team. “We have to be careful using the term synthetic human embryo, because some people are not happy about it,” says Fu.
An “embryoid” created from stem cells shares key features with a real human embryo, like an amniotic sac, but lacks other elements.
COURTESY OF YUE SHAO, UNIVERSITY OF MICHIGAN
Currently, scientists in the U.S. and U.K. working with natural human embryos observe a limit on their work called the “14-day rule.” No human embryo is studied beyond two weeks, or past when the primitive streak forms, whichever comes first. Before then, no one thinks they have any kind of sentience and are “incapable of feeling pain” according to the 1984 Warnock Report that enshrined the rule.
For decades, that rule has offered a convenient and clear line in the sand. And the same limits are being applied to embryoids, at least for now. Following guidelines promulgated last year by Kimmelman’s international stem-cell society, Fu’s team destroys the cells just five days after they’re made. This prevents the structures from developing what bioethicists term “features of concern”—such as a primitive nervous system.
But scientists are prepared to argue that their structures aren’t real embryos, and that they should be able to stretch the limit. Some experts are calling for an end to the rule altogether, saying it is outdated. John Aach, a scientist at Harvard Medical School, thinks entirely new ethical measuring sticks will be needed to help guide tests of organoids. For instance, could a mini-brain grown in the lab somehow feel suffering? And can our definition of an embryo withstand evidence that labs can make new sorts never before seen? “All great scientific advances have a way of exposing the imprecision of common concepts and forcing people to rethink them,” says Aach.
Even before his paper came out, Shao was buttonholing ethics experts, including Insoo Hyun, a professor at Case Western University, at a conference this year in Boston. Hyun felt the young researcher was on safe ground because his structure didn’t contain every part of an embryo. “I think that they should design experiments to focus on specific questions, and not model everything,” says Hyun. “My proposal is, just don’t make the whole thing. One team can make the engine, another the wheels. The less ambiguous morally the thing is that you are making, the more likely you can do your research unimpeded.”
There’s yet another reason to be cautious. The U.S. currently bars federal funding for any study of embryos, no matter how they are made, under a law called the Dickey-Wicker Amendment.
While today’s embryoids don’t appear to be covered by the legal restriction, they might be if scientists make them realistic enough. In response to written questions, the science policy office of the National Institutes of Health, the $33-billion-a-year funding agency, says it has an internal process it uses to analyze grants and to determine if “proposed research would create an organism that meets the statutory definition of a human embryo.”
The Michigan scientists, whose project used funds from two NIH grants, say agency officials haven’t raised any objections so far. For now, the embryoids live and die in boxes made of lucite and metal and are fed with culture medium. “Because of the really heavy engineering component to these entities, I think you will be able to argue these are not organisms,” says Hyun. That’s a point that Shao has sought to emphasize, too. When Shao presented the group’s work this year, he added to his slides an ethics statement outlined in a bright yellow box, saying the embryoids “do not have human organismal form or potential.”
Scientists are trying to manufacture eggs and sperm in the laboratory. Will it end reproduction as we know it?
But such definitions could be a moving target. The whole point of the structures is the surprising, self-directed, even organismal way they develop. Robert Cork is the head of the Virtual Embryo Project, which maintains the images the Michigan team used to identify their structures. When I asked him about Shao’s paper, Cork told me that the embryoids could go on to make some of the parts they’re currently missing, if the experiments were allowed to progress. “This would suggest that if they can keep the cysts viable for longer they might go ahead and start to develop into something more ‘embryo-like,’” says Cork.
High-throughput
Jianping Fu is a professor of mechanical engineering at the University of Michigan.
COURTESY OF UNIVERSITY OF MICHIGAN
Fu says the next step in his Ann Arbor laboratory is to perfect procedures for making embryoids with specific characteristics, and in larger numbers. Initially, of every 100 “cysts” the Michigan scientists grew, only five ended up with the asymmetric shape reminiscent of the amniotic sac. But the they have already learned how to make that shape emerge every time. The production of embryoids will become “programmable and scalable,” Fu predicts.
Drugs could be tested on the embryoids, for instance to flag any that have toxic effects and cause birth defects. Fu’s hope is that synthetic embryology might eventually help engineers grow complete human organs. “I am not talking about a human body without a brain. But what is a true possibility is you could develop a mini-gut or a mini-liver, since the embryo develops them, too. And if you have the primitive organs, they could grow into a functional one,” Fu predicts. The lab has started growing embryoids on a chip about the size of a credit card. Etched into it are six microchannels, each accommodating 10 of the entities, which are suspended in hydrogels and fed nutrients held in miniature buckets. Fu calls it “high-throughput manufacturing.”
This way, he says, “everything can be triggered and under control.”
Artificial mouse embryo after 48 hours (right) and 96 hours, with embryonic tissue in red and extra-embryonic tissue in blue
Sarah Harrison and Gaelle Recher, Zernicka-Goetz Lab, University of Cambridge
Artificial mouse embryos grown from stem cells in a dish could help unlock secrets of early development and infertility that have until now evaded us.
Magdalena Zernicka-Goetz at the University of Cambridge and her team made the embryos using embryonic stem cells, the type of cells found in embryos that can mature into any type of tissue in the body.
The trick was to grow these alongside trophoblast stem cells, which normally produce the placenta. By growing these two types of cell separately and then combining them in a special gel matrix, the two mixed and started to develop together.
After around four-and-a-half days, the embryos resembled normal mouse embryos that were about to start differentiating into different body tissues and organs.
“They are very similar to natural mouse embryos,” says Zernicka-Goetz. “We put the two types of stem cells together – which has never been done before – to allow them to speak to each other. We saw that the cells could self-organise themselves without our help.”
This is the first time something resembling an embryo has been made from stem cells, without using an egg in some way. Techniques such as cloning, as done for Dolly the sheep and other animals, bypass the need for sperm, but still require an egg cell.
Body plan
The artificial embryos are providing new insights into how embryos organise themselves and grow, says Zernicka-Goetz. The team engineered the artificial embryos so the cell types fluoresced in different colours, to reveal their movements and behaviour as the embryos go through crucial changes.
Mammal embryos were already known to start as a symmetrical ball, then elongate, form a central cavity and start developing a type of cell layer called mesoderm, which ultimately goes on to form bone and muscle.
“We didn’t know before how embryos form this cavity, but we’ve now found the mechanism for it and the sequential steps by which it forms,” says Zernicka-Goetz. “It’s building up the foundations for the whole body plan.”
“The work is a great addition to the stem cell field and could be extended to human stem cell populations,” says Leonard Zon at Boston Children’s Hospital, Massachusetts. “Using the system, the factors that participate in embryo development could be better studied and this could help us understand early events of embryogenesis.”
But Robin Lovell-Badge at the Francis Crick Institute in London says that the embryos lack two other types of cell layer required to develop the bodies’ organs: ectoderm, which forms skin and the central nervous system, and endoderm, which makes our internal organs.
Zernicka-Goetz hopes to see these types of cell layers develop in future experiments by adding stem cells that normally form the yolk sac, a third structure involved in embryonic development, to the mix.
Hidden steps
If a similar feat can be achieved using human stem cells, this could tell us much about the earliest stages of our development. Current research is limited by the number of excess embryos that are donated from IVF procedures. But the new technique could produce a limitless supply, making it easier to conduct in-depth research. These artificial embryos may also be easier to tinker with, to see what effect different factors have in early embryogenesis.
Disrupting development in this way may provide new insights into the causes of abnormal embryo development and miscarriage. “You would be able to understand the principles that govern each stage of development. These are not normally accessible, because they happen inside the mother,” says Zernicka-Goetz.
But it is doubtful that this work could ever lead to fully grown babies in the lab. Lovell-Badge says the artificial embryos are unlikely to develop in vitro much further than shown in the study, as they would soon need the supply of nutrients and oxygen that a placenta normally channels from the mother.
“We’re not planning to make a mouse in the lab using stem cells,” says Zernicka-Goetz. But she is hopeful that adding yolk sac stem cells will allow these artificial embryos to survive long enough to study the beginnings of organs like the heart.
A day after the Reserve Bank of India (RBI) barred banks from dealing in cryptocurrencies, investors rushed to square off positions and sought advice on how much tax they should pay on returns made in FY18 and if they can do so before the July-end deadline.
The worry is that they may be left holding the virtual currency if they don’t sell it now and transfer the money into their bank accounts. They also fear a crackdown by tax authorities and other government agencies, experts said.
Bitcoin exchanges such as Zebpay and CoinSecure saw a spike in transaction volumes of about 40%, with about 90% of that being on the sell side, sources said.
The Reserve Bank of India (RBI) has effectively banned any dealings in cryptocurrency via banks or e-wallets in the country stating “dealing with or providing services to any individuals or business entities dealing with or settling virtual currencies.”
Nischal Shetty, CEO of WazirX , a Bitcoin and crytocurrency exchange said: “Blockchain technology and cryptocurrencies are going to define the future of financial technology and the way money operates. While the security features intact in the blockchain technology have been acknowledged by the Finance Minister himself, the latest mandate by the Reserve Bank of India, discouraging Indians from dealing in cryptocurrencies, is quite disheartening. More so, since in the recent past, the RBI had seemed to be favourably predisposed towards supporting new, innovative and tech-driven processes.
“While India continues to debate and hold back the mainstreaming of cryptocurrencies, our global counterparts in the USA, Japan, South Korea etc are moving forward and regulating cryptos. By supporting blockchain and cryptocurrency, RBI could have given Indians an opportunity to be at the forefront of a global phenomenon, act ahead of time and be future-secured with our own set of digital assets.”
The central bank said in its statement that virtual currencies (VCs), also variously referred to as cryptocurrencies and crypto assets, raise concerns of consumer protection, market integrity, and money laundering, among others.
“The RBI statement will negatively impact startups, because no matter how great an idea they have, investors will be wary of putting money into a crypto-venture given their uncertain future in uncertain regulatory environments,” said Nehaa Chaudhari, Public Policy Lead, TRA, a technology policy and law firm.
After these RBI guidelines, Shetty added that this will exclude India from global crypto revolution. There will be massive wealth erosion of all the tax paying people who have invested in cryptocurrencies.
“Gullible investors will now try to buy cryptos through cash and other OTC means where they would have no buyer protection and end up falling for scams. This will also make illegal trades almost impossible to track,” said Shetty.
Atulya Bhatt, Co-founder of BuyUcoin, a multi cryptocurrency wallet and exchange, said: “There will be a parallel economy and in few months people will find unregulated ways of cashing out. Some investors are in utter shock because the government has given only three months to handle the transactions. ”
As for startups, he said, “It disturbed the whole structure of crypto exchanges. We have plans and we are discussing it. But banning it is an unfair step.”
“The alternate way for the cryptocurrency exchange will be to do crypto to crypto trading,” said Bhatt.
Ravi Kikan, COO, Panaesha Capital, said: “If you look at the complete circular it first talks about RBI exploring the desirability and feasibility of introducing its own crypto currency (a fiat-digital one). In fact, it has set up a panel to review the proposal and come up with suggestions by June.
“The RBI is more concerned about the other side of negatives like speculative trading, Consumer protection, Ponzi Schemes, Money laundering and terror financing that can pop up through this un regulated market, which I think is a very fair stand to safeguard the public at large. In the long run keeping the above in light the digital currencies which have a certain usefulness towards their utility/usage will be the ones that will have a shot at the silverline and more prone to acceptability.”
In its budget speech, Finance Minister Arun Jaitley clarified in his budget speech that it is not a legal tender and the government will discourage its use. However, he had mentioned that the government will look at the utilisation of blockchain.
The index formed a Doji type of pattern after a strong bullish candle which suggests that the momentum could take a pause.
The Nifty climbed its crucial resistance level of 10400 on Tuesday but lost momentum towards the close of the session and made a ‘Doji’ type of candlestick pattern on the daily charts.
The index formed a Doji type of pattern after a strong bullish candle which suggests that the momentum could take a pause; hence, for bulls to remain control Nifty should hold above 10,348 levels.
A ‘Doji’ is formed when the index opens and then closes approximately around the same level but remain volatile throughout the day which is indicated by its long shadow on either side. It appears like a cross or a plus sign.
The Nifty index opened at 10412 and rose to an intraday high of 10424. It slipped below 10400 in intraday trade to record its intraday low of 10381 before closing the day at 10,402, up 22 points.
“Despite positive global cues Nifty lacked follow-through buying which should be a cause for concern as it registered a Doji kind of indecisive formation after moving in an extremely narrow range of around 45 points,” Mazhar Mohammad, Chief Strategist – Technical Research & Trading Advisory, Chartviewindia.in, told Moneycontrol.
“The Nifty may be in need of a breather as momentum oscillators on short-term charts are in an extremely overbought zone and hence unless it gets past its 50-Day Simple Moving Average, whose value is placed around 10438, which successfully curtailed its up move in the past,” he said.
Mohammad further added that bulls may not pick up momentum going forward and a close below 10348 shall confirm short-term weakness in the indices. Hence, it looks prudent for traders to book profits and remain on sidelines till such a breakout occurs above 10450 on a closing basis.
India VIX fell down up 2.51 percent at 14.49. A decline in VIX suggests a range bound move with limited upside as well downside in the market.
We have collated the top 15 data points to help you spot profitable trades:
Key support and resistance level for Nifty
The Nifty closed at 10,402.2 on Tuesday. According to Pivot charts, the key support level is placed at 10,380.87, followed by 10,359.53. If the index starts moving upwards, key resistance levels to watch out are 10,424.17 and 10,446.13.
Nifty Bank
The Nifty Bank index closed at 25,226.8. The important Pivot level, which will act as crucial support for the index, is placed at 25,138.04, followed by 25,049.27. On the upside, key resistance levels are placed at 25,297.74, followed by 25,368.67.
Call Options data
In terms of open interest, the 10,500 call option has seen the most call writing so far at 41.66 lakh contracts. This could act as a crucial resistance level for the index in the April series.
The second-highest buildup has taken place in the 11,000 Call option, which has seen 38.76 lakh contracts getting written so far. The 10,700 Call option has accumulated 36.25 lakh contracts.
Call writing was seen at the strike price of 10,500, which added 2.03 lakh contracts, followed by 10,600, which added 1.13 lakh contracts, and 10,400, which added 1 lakh contracts.
Call unwinding was seen at the strike price of 10,300, which shed 2.89 lakh contracts.
Put Options data
Maximum open interest in put options was seen at a strike price of 10,000, in which 45.66 lakh contracts been added till date. This could be a crucial resistance level for the index in April series.
The 10,200 put option comes next, having added 39.24 lakh contracts so far, and the 10,300 put option, which has now accumulated 38.76 lakh contracts.
During the session, put writing was seen the most at a strike price of 10,400, with 9.73 lakh contracts being added, followed by 10,300, which added 6.33 lakh contracts and 10,200 with 3.01 lakh contracts.
There was hardly any Put unwinding seen.
FII & DII data:
Foreign institutional investors (FIIs) sold shares worth Rs 684.99 crore, while domestic institutional investors bought shares worth Rs 653.65 crore in the Indian equity market, as per provisional data available on the NSE.
Fund flow picture:
Stocks with high delivery percentage:
High delivery percentage suggests that investors are accepting delivery of the stock, which means that investors are bullish on it.
68 stocks saw long buildup
38 stocks saw short covering:
A decrease in open interest along with an increase in price mostly indicates short covering.
57 stocks saw short build-up:
An increase in open interest along with a decrease in price mostly indicates build-up of short positions.
45 stocks saw long unwinding
Bulk Deals:
VRL Logistics Limited: Morgan Stanley Mauritius Company Ltd sold 5,26,393 shares at Rs 389.22 per share
Apl Apollo Tubes Ltd: WF Asian Reconnaissance Fund Limited bought 2,64,000 shares at Rs 2140 per share
Supreme Industries Ltd: Smallcap World Fund INC sold 17,99,545 shares at Rs 1205 per share.
Indian Hotels: At a public event, the company met around 17 institutional investors on April 10, 2018.
Mahindra & Mahindra: BOB Capital Markets along with several other funds and investors will meet the company between April 11 and 12, 2018.
Stocks in news:
Tech Mahindra: Balbix tie up with the company for artificial intelligence-based cyber security platform
Dr Reddy’s Labs: Company gets EIR from USFDA for Cuernavaca plant in Mexico
Punjab National Bank: Fitch has Downgraded PNB’s Viability Rating To ‘BB-‘; Maintains Rating Watch Negative
Calix, Infosys Enter Strategic CoCreation Partnership to Accelerate Time to Market for New Capabilities on AXOS Platform
Max Life: Company leads race to buy IDBI Federal Life stake
MRPL: Company trims oil purchase deal with Saudi Aramco: Sources
JSW Steel, AION get creditors’ nod for Monnet Ispat takeover
2 stocks under ban period on NSE
Security in ban period for the next day’s trade under the F&O segment includes companies in which the security has crossed 95 percent of the market-wide position limit.
For April 11, 2018 Jet Airways and Balrampur Chini are present in this list.
