📰 Ukraine seeks Indian peacekeepers
UN to discuss peacekeeping mission soon
•Urging India to take up greater global security role, Ukraine has asked for Indian peacekeepers to help contain the conflict with Russia in the eastern part of the country.
•In an exclusive interview to The Hindu, Ukrainian Foreign Minister Pavlo Klimkin said he expects India to “definitely” play a role in the peacekeeping mission which will soon come up for discussion at the UN Security Council (UNSC).
•“The Indian peacekeepers have proved their role, resilience, tenacity and commitment to peace and therefore why not have them in Donbas in Eastern Ukraine as it could be one of the options in the future,” said Mr. Klimkin.
•India’s role in peacekeeping commended
•Mr. Klimkin, who is on a three-day visit to India, held extensive discussions with his counterpart, Sushma Swaraj, on Saturday for the upcoming inter-governmental commission dialogue between two sides.
•He briefed Ms. Swaraj on the situation in eastern Ukraine, which has left a part of its eastern province, Donbas, in the hands of the rebels that Kyiv claims are backed by Moscow.
•“India is already a significant peacekeeper in the region and across the globe and could definitely play a similar role in our region,” said Mr. Klimkin.
•During last month’s debate on reform of global peacekeeping at the UN Security Council, Ukrainian President Petro Poroshenko asked the organisation to send a peacekeeping mission that would control the violence, which has intensified in the last few weeks.
Preliminary talks
•Mr. Klimkin said discussion on India’s participation in the peacekeeping mission was at a preliminary level and further consultations were needed to fine-tune the composition of the mission. “The recipe is simple — Russia should go out of Ukraine,” he said.
•He also gave details of bilateral talks on the issue and said “Indian and Ukrainian Permanent Representatives at the UN have already met on this issue and we need to discuss conceptual approach for the mission. After we have convinced Russia on such an approach .. it is highly likely we will come back to our Indian friends”.
Differing views
•However, an issue with this peacekeeping mission is the location for the troops. While Ukraine insists that the troops should be stationed at the original Ukraine-Russia border, Russian sources indicated that Moscow would prefer the troops to be placed at the ‘Line of Contact’ between Ukraine and the rebel held territory.
📰 What is the lowdown on GST pitfalls?
•The Goods and Services Tax (GST) rolled out across the country on July 1. Since then, a number of teething issues have emerged — some more serious than others.
•The most pressing problem is to do with the availing of input tax credits by exporters.
•The problem, according to exporters, is that they have to wait an inordinate amount of time before the refunds are processed and paid. As a result, they say a large part of their working capital — estimated at about ₹65,000 crore — is stuck, rendering their businesses untenable. Another pressing problem is the capacity of the GST Network portal for filing tax returns. Since the rollout, the portal has fared poorly in the face of peak traffic. According to Finance Minister Arun Jaitley, the portal can process 1 lakh returns an hour, which translates to 24 lakh returns in a day.
•The third issue being faced by the government is that taxpayers are missing the deadlines to file returns and so it cannot accurately estimate how much revenue GST is yielding.
•For example, while the government said it had earned ₹90,669 crore from GST in August, it also said that only about 55% of registered taxpayers had filed their returns even five days after the deadline.
How did it come about?
•Input tax credits offset the taxes paid for inputs from the tax payable on the final output produced. The procedure is that a company pays the tax on both inputs and output and then applies for a refund for the tax paid on the inputs. The refund process, according to exporters, takes many months and so results in a large part of the working capital being locked up.
•According to Mr. Jaitley, the problem of the online portal crashing is in large part due to the fact that businesses are waiting till the last moment to file their returns.
•He said that only 25% of the taxpayers registered on the portal had filed their returns as of midnight of September 19, one day before the deadline for filing the returns for August. This means that a significant portion of the remaining 75% who logged on at the last minute faced server errors.
•Tax experts, however, say that uncertainty over GST rules and rates is such that companies are using all the available time to make sure there are no errors in their returns.
•The missed deadlines, according to the GST Suvidha Providers, are due to a variety of factors, including poor taxpaying habits, a clashing of deadlines, and the fact that the government has so far been lenient about missed deadlines.
Why does this matter?
•The exporters’ input tax credits being locked up is an issue because a large number of Indian exporters are small companies which cannot afford to have a significant portion of the working capital unavailable. They will not be able to make further purchases to run their businesses, they claim. With the server crashing when taxpayers log in to file their returns and many taxpayers missing their deadlines, the government cannot accurately measure its earnings from GST in a timely manner. All the data will be available with a delay.
What next?
•Prime Minister Narendra Modi on Wednesday said he had told the GST Council to review the problems being faced by traders, and that the government was willing to make changes.
•Two days later, the GST Council met and took a slew of decisions to ease the compliance burden on exporters and small businesses. First, the Council announced that it would expedite the pending input tax credits payouts — the payment for July is to be completed by October 10, and for August by October 18. Exporters will have to pay a nominal 0.1% tax on exports until March 31, 2018. The government is planning to roll out a system of e-wallets that would ease the input tax credit refund process.
•Companies with a turnover of up to ₹1.5 crore a year can also file returns and pay taxes once a quarter.
•The composition scheme, meant to ease compliance for small units, will be extended to businesses with a turnover of up to ₹1 crore a year from the previous limit of ₹75 lakh. Mr. Jaitley also announced the creation of a Group of Ministers that will look into various other problems that have arisen during the rollout of GST.
📰 The unintended consequences of GST
It has wreaked havoc on the informal sector. Do we have a plan to deal with this?
•A lot of dust has been kicked up over the economy in the recent past. It started with former Finance Minister and BJP veteran Yashwant Sinha’s savage attack on his party colleague Arun Jaitley’s handling of the portfolio that he once managed. Then Prime Minister Narendra Modi used a banal forum like a meeting of the Institute of Company Secretaries to make his most comprehensive speech on the economy till date.
Tweaks to GST
•Despite the counter-attack, the criticism clearly hit home, since the government followed it up with some ‘big bang’ changes to the Goods and Services Tax regime aimed at addressing the immediate pain points of small and medium businesses, exporters, and the like. Tax rates have been reduced on several items, small and medium businesses with an annual turnover of Rs. 1.5 crore have been exempted from tedious filing of monthly returns and have been given a quarterly option, and businesses with a turnover of up to Rs. 1 crore have even been given the option of paying a flat 1-5% tax and effectively disengaging from the rest of the GST system. The GST on exports has also been cut to 0.1% till 2018 to help exporters tide over their current liquidity challenges.
•I am not, however, going to talk about these changes. As far as the tweaking of the rates itself is concerned, it is a good thing, in as much as it shows that the tax mechanism itself is capable of being flexible and responding quickly to changing circumstances. As far as giving exemptions from filing returns — the so-called ‘composition scheme’ for a flat tax — are concerned, these are, in principle, a rollback of the reforms ushered in by the switchover to the GST regime. Because once you start exempting bits and pieces of the economy, the seamless tax chain across the entire value addition chain envisioned by the GST actually falls through.
Intended and unintended results
•Which brings me to the key issue — dealing with the consequences of change. Every reform naturally has consequences. Many of them are intended. In the case of the GST, the intended consequences were to create a simpler and unified indirect tax system across the country, remove incidences of multiple taxation, and ensure that the entire economy engaged in value creation also becomes a part of the tax system.
•But it is the unintended consequences of change which are harder to deal with. Unfortunately, it is very difficult to predict before formulating a policy what these unintended consequences could be. It should, however, be possible to identify these unforeseen side effects post facto. More importantly, there also has to be a policy response to deal with such developments. Otherwise, the danger is of pain leading to more pain without any gain.
•What are these unintended consequences of the GST? The biggest, of course, is the havoc it has wreaked on the entire informal sector of the economy, which actually accounts for the livelihood of a bulk of the population. This is also why we have such a low official unemployment rate because, while the organised sector workforce accounts for just a fraction of the jobs, the informal sector ensures that 95% of the population earns a living.
Informal sector hit
•It is this mass of people in the informal sector who have been flattened by the GST. The other day, for instance, at the Khadi Gramodyog Bhavan around the corner from The Hindu ’s office in Chennai, I found a woman standing with a basket of handmade dolls for delivery (Navaratri is also the doll-buying season in the south), arguing with the store’s accountant. He was vainly attempting to explain to her that he could not make payment for any supplies without the vendor’s GST number, a concept this village artisan had never heard of. For this woman, Friday’s reduction of GST on handicrafts from 18% to 5% is meaningless. She has simply lost a substantial chunk of her working capital and months of labour. And even if she gets a GST number later, what would be the compliance cost for such a person, and what kind of tax credits can she actually avail?
•Take the apparel sector. Almost the entire sector — over 2 million units — consists of tiny units, officially ‘employing’ an average of just 1.5 persons each, usually the owner and another family member. The rest are jobbers and temporary hands who will now have to become registered vendors with GST numbers if these tiny units are to get the benefit of GST. Anecdotal evidence suggests that a huge number of these units may either simply fold up or be forced to lay off their jobbers and tempers — or else officially absorb them as workers, which will definitely make them non-competitive.
•Do we have a plan to deal with such massive lay-offs? Do we have an alternative plan to fill in the gap left by the 15% share of exports currently contributed by the textiles sector, for instance?
•Sometimes, unintended consequences can end up being far more impactful than the intended ones.
📰 IISc team fabricates nanomaterial to treat Parkinson’s
The material protected cells against neurotoxin-induced cell death by scavenging excess ROS
•A team of researchers from the Indian Institute of Science (IISc) Bengaluru has fabricated a metal oxide nanomaterial that is capable of mimicking all three major cellular antioxidant enzymes, thereby controlling the level of reactive oxygen species (ROS) inside cells. Based on in vitro test results, the nanomaterial appears a promising candidate for therapeutic applications against oxidative stress-induced neurological disorders, particularly Parkinson’s. The results were published in the journal Angewandte Chemie.
•Reactive oxygen species, such as superoxide, hydrogen peroxide and hydroxyl radical, which are generated as part of a normal physiological process, are essential for the normal functioning of cells. Excess of ROS generated is usually controlled by the action of three antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase).
Excess ROS
•A problem arises when ROS is generated in excess and the enzymes are unable to control the level of ROS. Oxidative stress due to excessive ROS causes damage to DNA, proteins and lipids; oxidative stress is implicated in several diseases such as neurodegeneration, cancer, diabetes and cardiovascular diseases.
•“We have developed a manganese oxide (Mn3O4) nanomaterial which functionally mimics all the three antioxidant enzymes. Earlier, we had shown that vanadium oxide (V2O5) nanowire is capable of exhibiting glutathione peroxidase enzyme activity,” says Prof. Govindasamy Mugesh from the Department of Inorganic and Physical Chemistry, IISc, and one of the corresponding authors of the paper. Nanomaterials with enzymelike activity are called nanozymes. “This is the first time the activity of all three major antioxidant enzymes are seen in a nanomaterial.”
•The researchers tried several morphologies and found the flower-like morphology had the best activity of all three enzymes. Pores present on the nanomaterial play an important role as enzyme-active sites and help in scavenging excess ROS. The larger pore diameter and pore volume capable of accommodating all the three ROS were found to be critical in determining the enzyme activity of the nanomaterial.
No toxicity
•In vitro studies using human neuronal cell lines found that the nanomaterial caused no cellular toxicity when internalised by the cells and hence safe. Metal-based complexes are generally toxic to cells. “The nanomaterial was not toxic probably because manganese is naturally present in our body and is an essential trace element. It is not toxic up to a few microgram. This prompted us to use manganese-based nanomaterial,” says Namrata Singh from the Department of Inorganic and Physical Chemistry, IISc and the first author of the paper.
•The nanomaterial was found to protect against neurotoxin-induced cell death by scavenging the excess ROS that was artificially generated inside the cells.
•“Inside the cells, the nanomaterial was able to substitute the cellular enzymes effectively when the enzymes are inhibited. Due to high pore size and volume, it was able to achieve better activity. So we don’t need much of the nanomaterial inside the cells,” says Prof. Patrick D’Silva from the Department of Biochemistry at IISc and the other corresponding author.
Optimum effect
•“The manganese oxide nanomaterial was able to control the level of ROS inside the cells. They did not scavenge the ROS completely. If they do then the normal physiological functions of the cells get affected,” says Prof. Mugesh. “It actually scavenges ROS and brings it to optimum level so normal functions of the cell are not affected.”
•The superoxide dismutase enzyme has two forms and one functions in the cytosol and the other inside the mitochondria. “Some amount of nanomaterial gets inside the mitochondria as well and controls the ROS produced there. The nanozymes have therapeutic potential particularly for Parkinson’s disease,” says Prof. D’Silva.
•Parkinson’s model was tested in the lab. The researchers are trying to design an animal model in mice for in vivo testing.
📰 IIT-K: Antibodies to treat a few genetic diseases
The antibodies selectively block the receptors from being pulled in but not the signalling
•Inherited genetic diseases such as retinitis pigmentosa and nephrogenic diabetes may become treatable if the initial results achieved by a team of researchers led by Prof. Arun Shukla from the Department of Biological Sciences and Bioengineering at the Indian Institute of Technology (IIT), Kanpur, are reproducible in animal models and humans.
•Retinitis pigmentosa is an inherited, degenerative eye disease that leads to progressive loss of vision as one gets older, while genetic nephrogenic diabetes arises from kidney cells’ inability to retain water leading to extreme thirst and dehydration. In both these cases, the cause of disease is a mutation in the G-protein-coupled receptors (GPCR) which causes the receptors to be pulled from the plasma membrane to the inside of the cell just as the receptors reach the cell membrane to start signalling. In the absence of the receptors (rhodopsin GPCR in the case of retinitis pigmentosa and vasopressin GPCR for genetic nephrogenic diabetes) the cells fail to signal and do not function normally.
•The pulling in or trafficking of the GPCR receptors from the membrane surface to inside the cells (which is called endocytosis) happens when a small family of proteins called beta-arrestins bind to GPCR receptors and to another class of proteins called clathrin.
•“We have designed synthetic antibody fragments which specifically bind to beta-arrestins at the position where clathrin gets bound. So our antibodies prevent the clathrin protein from binding to beta-arrestins thus preventing endocytosis,” says Prof. Shukla. The results were published in the journal Nature Nanotechnology.
•Theoretically, preventing the trafficking of the GPCR receptors from the membrane surface to inside the cells is like turning the clock back; rhodopsin and vasopressin receptors would stay intact on the cell membrane, start signalling and enable the otherwise mutant cells to function normally. “Our designer proteins provide unexplored territory for therapeutic applications for inherited diseases,” he says.
Limited lifespan
•Proteins such as GPCR receptors, beta-arrestins and clathrin have limited life span of a few hours, while the antibodies introduced survive for a loner time. Once introduced, the antibodies can get bound to beta-arrestins that are freshly produced and prevent clathrin from binding to beta-arrestins thus preventing endocytosis. “Even when beta-arrestins bound to antibodies decay, the antibodies with their longer life span can bind to newly formed beta-arrestins. The other possibility is increasing the concentration of the antibodies so that they are always present in the cells to bind to freshly produced beta-arrestins,” Prof. Shukla says.
•Since the mechanism of the two diseases is the same, the antibodies can work equally well immaterial of the cell type involved. “This is a proof-of-concept study using modified kidney cell lines. The next step will be to develop new strategies to deliver the antibodies into human live cells and animal models,” he says. The team is considering starting these studies in near future.
•The big advantage of using antibodies is that they selectively block receptor endocytosis but not signalling. “This provides a unique handle, currently not available anywhere in the world, for targeting a specific GPCR function. This makes our designer proteins superior to knock-out approaches,” he comments.
📰 In a first, gene therapy halts a fatal brain disease
Gene therapy can hold off ALD without side effects, but with a caveat
•For the first time, doctors have used gene therapy to stave off a fatal degenerative brain disease, an achievement that some experts had thought impossible.
•The key to making the therapy work? One of the medicine’s greatest villains: HIV.
The disease
•The patients were children who had inherited a mutated gene causing a rare disorder, adrenoleukodystrophy, or ALD. Nerve cells in the brain die, and in a few short years, children lose the ability to walk or talk. They become unable to eat without a feeding tube, to see, hear or think. They usually die within five years of diagnosis.
•The disease strikes about one in 20,000 boys; symptoms first occur at an average age of 7. The only treatment is a bone-marrow transplant — if a compatible donor can be found — or a transplant with cord blood, if it was saved at birth.
•But such transplants are an onerous and dangerous therapy, with a mortality rate as high as 20%. Some who survive are left with lifelong disabilities.
•Now a new study, published online in theNew England Journal of Medicine, indicates that gene therapy can hold off ALD without side effects, but only if it is begun when the only signs of deterioration are changes in brain scans.
•The study involved 17 boys (the disease strikes males almost exclusively), ages 4 to 13. All got gene therapy. Two years later, 15 were functioning normally without obvious symptoms.
•“To me, it seems to be working,” said Dr. Jim Wilson, director of the gene therapy programme at the University of Pennsylvania’s Perelman School of Medicine, who was not involved in the new study.
•One of the remaining two boys died; his disease progressed so rapidly that gene therapy could not stop it. The other withdrew from the study to have a bone-marrow transplant. He died of complications from the procedure.
•The study opens new avenues for using gene therapy to treat brain diseases, said Dr. Theodore Friedmann, a gene therapy pioneer at the University of California San Diego School of Medicine.
•“Many think the central nervous system is intractable and unapproachable,” he said. This study proves them wrong.
Where it began
•The research began with a determined mother, Amber Salzman, who was an executive with a Ph.D. in mathematics at GlaxoSmithKline. In 2000, her nephew was diagnosed with ALD, a disease she had heard of only in the movie,Lorenzo’s Oil.He was “this wonderful sweet brilliant kid,” Salzman said. “All of a sudden he loses his abilities. He crumbles in front of your eyes.”
•She had her one-year-old son tested and found that he had the mutated gene, as did another nephew. She looked into Lorenzo’s oil, a difficult dietary regimen featuring a specially designed oil.
