The News Editorial Analysis 12th Dec 2021

U.S. ban on para unit stuns Dhaka

Rapid Action Battalion accused of rights violations

Bangladesh reacted sharply to the U.S. Treasury’s decision to sanction a special military and police task force for alleged human rights violations. Foreign Secretary Masud Bin Momen has summoned U.S. Ambassador to Dhaka Earl Miller to protest against the actions.

The decision by the U.S. to ban the Rapid Action Battalion, came as a shock to the Sheikh Hasina Government, just days before its planned celebrations for the 50th anniversary of its Liberation Day, where President Ram Nath Kovind will represent India.

“The Foreign Secretary [Mr. Momen] regretted that the U.S. decided to undermine an agency of Government that had been on the forefront of combating terrorism, drug trafficking and other heinous transnational crimes that were considered to be shared priorities with successive U.S. administrations,” a Government statement said. It added that the sanctions were imposed “unilaterally” and without any “prior intimation”.

Men in India take 82% of labour income, says report

Study explores gender inequality in global earnings

Men in India capture 82% of labour income, while women earn just 18%, according to the first-ever estimates of the gender inequality in global earnings presented in the World Inequality Report 2022 released earlier this week.

The female share of the total labour income is the national aggregate labour income earned by women relative to the total aggregate of labour income within a country. In a country with perfect equality between women and men, the female labour income share would be 50%.

But the report finds that it is below 50% around the world, with significant variations across countries, ranging from below 10% to 45%. The report covered 180 countries between 1991 to 2019.

Female labour income in India of 18.3% is lower than the average for Asia, which was at 27% in 2019.

Eleven countries in the region have values above 30%. Among the neighbours that performed worse than India were Bhutan (17.5%), Bangladesh (16.9%), Pakistan (7.4%), and Afghanistan (4.2%); and those with a higher share were Nepal (23.2%), Sri Lanka (23.3%) and China (33.4%).

Pandemic impact

After the pandemic, there was a worsening of female labour participation rate, which fell to 16.1% during the July-September 2020 quarter, according to the Ministry of Statistics.

Eastern Europe has the highest female labour income shares, with the average female share near 41%. Moldova has the highest female labour income in the world at 45%.

Overall, the share of women in total incomes from work neared 30% in 1990 and stands at 34% today.

“Unpaid care work is likely to prevent women from participating in the labour market, and, when they do work, to prevent them from attaining high-paying positions. When paid and unpaid work are combined, women’s contribution to work increases substantially and thus makes the female labour income share appear even more unfair,” states the report.

Protecting wildlife: 2,054 cases registered in three years

WCCB has conducted various species-specific operations

Between 2018 and 2020, about 2,054 cases were registered for killing or illegal trafficking of wild animals in India, Central Government statistics say.

In the three years, about 3,836 accused were arrested for the crime.

The number of cases registered in the year 2018 was 648 and 1,099 persons were arrested; followed by 805 cases and 1,506 arrests in 2019; and 601 cases and 1,231 arrests in 2020.

The data was made available on the basis of cases registered by the Wildlife Crime Control Bureau and State Forest and Police Authorities in the past three years.

The details were made public by the Ministry of Environment, Forest and Climate Change in response to a question in the Lok Sabha by BJP MP G.M. Siddeshwar. The reply on November 29 also pointed out that Wildlife Crime Control Bureau (WCCB) has been created for control of wildlife crime at the Central Government level, to work in close coordination with State forest department and other law enforcement agencies.

In response to another question on December 6 by DMK MP K. Shanmuga Sundaram, the Ministry said the WCCB has conducted a number of species-specific enforcement operations in coordination with State enforcement agencies.

Illegal trade

The WCCB had launched operation “Save Kurma” from to December 2016 to January 2017 to focus on the poaching, transportation and illegal trade of live turtles and tortoises. The operation resulted in seizure of more than 15,912 live turtles and the arrest of 55 suspects.

Another operation “Operation Turtshield- I” from December 2019 to January 2020 and Operation Turtshield-II” (December 2020 to February 2021) was taken up to tackle the illegal trade of live turtles, resulting in the seizure of 4,601 live/dead turtles and arrest of 45 accused in the first operation.

In the second operation, 59 accused were arrested and the efforts led to the recovery of 11,771 live turtles/tortoises and 45 kilograms of turtle calipee.

“Operation Softgold” was undertaken from October, 2018 to March, 2019 to tackle illegal trade in Shahtoosh shawls (made from Chiru wool). During the operation, 350 shawls were found.

G7 puts up united front against Russia

At Foreign Ministers’ meet hosted by Britain, delegates vow a strong stance with respect to Ukraine

The world’s wealthiest democracies on Saturday sought to present a united front against Russian aggression toward Ukraine as Britain hosted a meeting of Foreign Ministers in the northern Englishcity of Liverpool.

The G7 meeting, attended in person by U.S. Secretary of State Antony Blinken and his counterparts from France, Italy, Germany, Japan and Canada, comes amid international concern that Russia could invade Ukraine. Russia denies planning any attack.

Ahead of the formal discussions, British Foreign Minister Liz Truss met Mr. Blinken on Friday night where they expressed deep concern about the build-up of Russian troops on Ukraine’s border, Britain’s foreign office said in a statement.

Any incursion by Russia “would be a strategic mistake for which there would be serious consequences,” the foreign office added.

“We need to come together strongly to stand up to aggressors who are seeking to limit the bounds of freedom,” Ms. Truss told Foreign Ministers at the start of the meeting.

Ukraine is at the centre of a crisis in East-West relations as it accuses Russia of amassing tens of thousands of troops in preparation for a possible large-scale military offensive.

Russia accuses Ukraine and the United States of destabilising behaviour, and has said it needs security guarantees for its own protection.

Ministers arrived at the Museum of Liverpool to a brass band playing Christmas carols, before convening the first formal meeting session which will look at geopolitical issues including nuclear talks with Iran and the military buildup in Iran.

“What the G7 meeting this weekend .. is about unity between like-minded major economies, that we are going to absolutely be strong in our stance against aggression, with respect to Ukraine,” Ms. Truss told reporters ahead of the talks.

Age of introspection

Britain, as current chair of the G7, is calling for its members to be more strident in their defence of what it calls “the free world”.

Earlier this week, Ms. Truss said the “age of introspection” for the West was over and it needed to wake up to the dangers of rival ideologies. She has highlighted the economic risks of Europe’s dependence on Russian gas and the wider security threat posed by Chinese technology as examples.

The G7 meeting is also expected to result in a joint call for Iran to moderate its nuclear programme and grasp the opportunity of ongoing talks in Vienna to revive a multilateral agreement on its nuclear development.

Both Ms. Truss and Mr. Blinken stressed the need for Iran to engage in the talks.

Germany, which takes over the rotating G7 leadership from Britain next year, is expected to set out its programme for 2022 at the meeting.

Ministers from the European Union, Australia, South Korea and India will take part in some sessions as guests of the G7, along with representatives from the Association of Southeast Asian Nations (ASEAN).

AI tool to simplify identification of cancerous tissue in tumours

IIT Madras researchers developed this tool using deep learning and traditional machine learning

Indian Institute of Technology Madras researchers use a combination of deep learning techniques and traditional machine learning to develop a tool that can diagnose cancer by looking at whole slide images of the tumour. The tool has been tested on datasets of breast, liver and colon cancer tissue images. It is economical in terms of the time required to process the images and analyse them.

Digital histopathology

Traditionally, histopathologists slice the tumour tissue into approximately 20-micron-thick slices which they put on slides. They look at enlarged images of the slides and go over it cell by cell to manually classify it as cancerous or otherwise. This is highly time-consuming, and it is to alleviate this burden that digital histopathology developed. In this, after preparing the slides, the entire slide is scanned using a high-resolution microscope and digitised. This is then analysed using computerised tools.

This digital process has its own challenges. The first of this is the sheer size of the scanned images which can run into gigabytes.

A single image could be 100,000 by 100,000 pixels large – compare this with a shot generated by a smart phone which is about 7,000 by 7,000 pixels in size,” says Ganapathy Krishnamurthy of the Engineering Design Department of IIT Madras in an email, giving an idea of the challenge to computer time posed by this task.

The technique posed further challenges, such as insufficient training data and the variation in staining across labs.

Also extracting clinically relevant information, that is, directly inferring fine-grained disease classification using deep learning alone was turning out to be prohibitively expensive in terms of computational time.

So, the researchers used a combination of deep learning and traditional machine learning.

Hybrid approach

“We have used deep learning for classifying the tissue regions into normal and cancerous tissues from the Whole Slide Image. After this step, important patterns called features are computed using the output of the deep learning algorithm and used in a conventional machine learning algorithm for fine grained disease classification,” says Prof. Krishnamurthy. The details have been published in a paper in Scientific Reports.

To test the algorithms, the researchers enrolled in three open challenges – the CAMELYON17 challenge, the DIGESTPATH 2019 challenge and the PAIP 2019 challenge. “This paper takes data from three different challenges. In two of these, we were placed in the top 3 performing methods and in one challenge (CAMELYON) we were placed in the top 10 out of several hundred entries,” explains Balaji Srinivasan from the Mechanical Engineering Department of IIT Madras, who is an author of the paper. The technology is ready for deployment, say the authors. “We have a startup that can provide this solution and we are looking for potential healthcare partners,” says Prof. Srinivasan.

Heat shock and cold sensitivity

How chaperone proteins work to maintain normal cellular function

DNA is a linear chain of nucleotides, portions of which are faithfully transcribed into linear messenger RNA. The message in this RNA is translated into strings of amino acids – proteins. Proteins need to take a precise three-dimensional shape to become functional entities. This protein folding does not happen all by itself, at least most of the time. A special bunch of proteins called molecular chaperones assist in correctly folding the protein.

Chaperones in biology

The idea of chaperones may sound quaint and Victorian, but in biological systems they play crucial roles. After the new protein chain has been shaped correctly, chaperones move on. Or else the new chain is eliminated. Without chaperones, newly synthesised proteins would soon become a tangled mess of insoluble aggregates, hindering cellular processes.

Many molecular chaperones belong to the class of “heat shock” proteins (or stress-response proteins). This is because whenever an organism is subjected to elevated temperatures – a heat shock – proteins in the system begin to lose their native shapes, and chaperones are produced in large quantities to restore order.

Chaperones are needed under physiological conditions too, for normal cellular function.

Misfolding of proteins can cause a number of diseases. Alpha-synuclein protein, present in neurons, is wrongly folded in Parkinson’s disease. Brains of Alzheimer’s patients have plaques formed from aggregates of amyloid beta-peptide. This accumulation of amyloid fibrils is toxic, leading to widespread destruction of neurons – a ‘neurodegenerative’ disorder. Aberrant folding of crystallins of the eye lens leads to cataract. In the eye lens, an abundant subset of proteins called alpha-crystallins themselves serve as chaperones – a single R116G mutation in human alpha crystallin is responsible for autosomal dominant congenital cataract.

Molecular thermometer

Major chaperones in humans include HSP70, HSC70 and HSP90: the numbers express the size of the proteins in kilodaltons. In normal cells 1%–2% of all proteins present are heat shock proteins. This number rises threefold during stressful conditions.

HSP70 is induced by heat, whereas HSC70 is always present at high levels in normal cells. HSC70 appears to be more like a molecular thermometer, with an ability to sense cold temperatures. This knowledge comes from the study of an intriguing set of disorders, exemplified by Familial Cold Autoinflammatory Syndrome (FCAS). Symptoms of these disorders include rashes on the skin, pain in joints and fever. Periodic episodes may last from a few hours to a few weeks. These episodes begin early in life, the trigger being exposure to cold, or a stress such as fatigue. The confusing set of symptoms shown in this rare disorder make diagnosis difficult – it often takes ten years from first clinical presentation to a confirmed diagnosis.

The first family with confirmed FCAS in India was reported only in August this year. Sagar Bhattad and colleagues, at the Aster CMI Hospital in Bengaluru, traced the genetic underpinnings of FCAS in a four-year old boy who frequently suffered from winter rashes. It turns out that several family members, including his paternal great-grandfather, had similar symptoms. This was published in Indian Journal of Pediatrics, August 2021, 88(8):834.

Triggering inflammation

Addressing the role of HSC70 in sensing low temperatures, the group of Ghanshyam Swarup at the Centre for Cellular and Molecular Biology has worked out a framework for the triggering of autoinflammatory conditions This was published in The FEBS Journal, 2021; doi:10.1111/febs.16203. Disorders related to cold sensitivity are caused by mutations in proteins that regulate inflammation. At normal body temperatures, HSC70 is able to coax these mutated proteins to fold correctly and thus function normally. In cold conditions, however, the HSC70 molecule is itself slightly altered in its shape and is not able to unerringly interact with the mutated regulators of inflammation. This leads to a pathological state with symptoms such as chills, joint pains and rich red skin rashes setting in within two hours.

Cancer cells divide at break-neck pace, and heat shock proteins are very important in maintaining the stressful cancerous state. An overabundance of heat shock proteins in cancer cells is an indicator of a poor prognosis. Cancerous cells accumulate mutations in proteins that would normally suppress tumours. HSP70 and HSP90 play the roles of villains, as they continue to fold the mutated proteins, thus allowing tumour progression. In the laboratory, inhibitors of HSP90 have shown much promise as anti-cancer agents. However, no inhibitor has yet been approved for human use, as the levels required for these to be effective are too toxic for your body.

Two Omicron variants

In what way does the sub-lineage, BA.2, differ from the original? Will this make it harder to track?

The story so far: The World Health Organization designated Omicron (B.1.1.529) as a variant of concern on November 26, three days after the genome sequence was deposited in a public database by South Africa and Botswana. Based on genome sequence data, scientists have identified a sub-lineage —BA.2—of Omicron. As a result, the Omicron variant has been split into two sub-lineages, namely BA.1, “for the original globally-distributed lineage”, and BA.2, “for the new outlier lineage”.

Why is BA.2 called a sub-lineage?

The BA.2 has a “cluster of sequences that share many of the same mutations as the ‘original’ Omicron (BA.1) but is missing some mutations and has some other new ones,” Dr Emma Hodcroft, co-developer of Next Strain, tweeted. The BA is an alias for B.1.1.529, now redefined to encompass both BA.1 and BA.2.

While BA.2 is genetically quite different from the sub-lineage BA.1, BA.1 and BA.2 are two divergent clusters with a common ancestor, says a senior scientist. Both BA.1 and BA.2 are equal sub-lineages of B.1.1.529.

Since both have a common ancestor, how many mutations in the spike protein are common and how many are unique to each?

The B.1.1.529 cluster, which includes both BA.1 and BA.2, has 86 mutations, of which 40 mutations are in the spike protein alone. While 12 mutations have been found exclusively in the spike protein of BA.1, the BA.2 sub-lineage has seven exclusive mutations in the spike protein. Twenty-one mutations in the spike protein are common to both BA.1 and BA.2.

As on December 9, the genome sequence data from seven samples across the world have been posted on the public database. Of the seven, five sequences have been deposited from Canada, and one each by South Africa and Australia.

Compared to the small number of BA.2 genome sequences deposited so far, there are over 1,000 sequences of BA.1 that have been deposited in the database from across the world.

Can the sub-lineage BA.2 be identified by RT-PCR tests?

The new sub-lineage named recently, BA. 2, cannot be identified by the primers used in the RT-PCR (reverse transcription–polymerase chain reaction) test. While the BA.1 sub-lineage carries the characteristic S-gene dropout mutation, the BA.2 does not have this mutation.

The currently used primers in RT-PCR tests carry sequences that target three genes, one of which is the S-gene. Since the BA.1 sub-lineage carries the S-gene dropout mutation, only two of the three targets in the primer will turn positive when the BA.1 sample is tested by RT-PCR. The S-gene in the primer does not test positive due to the presence of the S-gene dropout mutation. The test being positive for two genes but not for the S-gene is a convenient way of knowing that the sample tested is a sub-lineage BA.1 of the Omicron variant. In short, the S-gene dropout is a proxy to identify the BA.1 sub-lineage.

Since BA.2 does not carry the S-gene dropout mutation, all the three target sequences in the RT-PCR primer will test positive. Hence, it will not be possible to straightaway know if the sample tested is a sub-lineage of the Omicron variant. Only by genome sequencing can one identify if a sample belongs to the BA.2 sub-lineage.

Will BA.2 have higher transmissibility and/or immune escape?

According to a senior scientist, the additional seven mutations in the spike protein do not provide sufficient evidence in terms of increased immune escape and transmissibility. Even individually, these seven mutations have not been implicated with either significant immune escape or enhanced transmission. As of now, the combined effect of the seven mutations is not known either.

“The designation aims to aid scientific discussion and does not imply an assessment of the lineages’ transmission properties,” the Pango Network said in a tweet.

Do the two sub-lineages change the manner in which patients are treated?

No, the clinical management of patients with any degree of disease severity remains the same immaterial of whether they have been infected with one of the Omicron sub-lineages or the Delta variant.

Experimental mRNA HIV vaccine safe, shows promise in animals

An experimental HIV vaccine based on mRNA — the same platform technology used in two highly effective COVID-19 vaccines — shows promise in mice and non-human primates, according to scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Their results, published in Nature Medicine, show that the novel vaccine was safe and prompted desired antibody and cellular immune responses against an HIV-like virus. Rhesus macaques receiving a priming vaccine followed by multiple booster inoculations had a 79% lower per-exposure risk of infection by simian-human immunodeficiency virus (SHIV) compared to unvaccinated animals. The research was led by Paolo Lusso, M.D., Ph.D., of NIAID’s Laboratory of Immunoregulation, in collaboration with other NIAID scientists, investigators from Moderna, Inc. and colleagues at other institutions.

“Despite nearly four decades of effort by the global research community, an effective vaccine to prevent HIV remains an elusive goal,” said NIAID Director Anthony S. Fauci, M.D., chief of the Laboratory and a paper co-author. “This experimental mRNA vaccine combines several features that may overcome shortcomings of other experimental HIV vaccines and thus represents a promising approach.”

The experimental vaccine works like mRNA COVID-19 vaccines. However, instead of carrying mRNA instructions for the coronavirus spike protein, the vaccine delivers coded instructions for making two key HIV proteins, Env and Gag. Muscle cells in an inoculated animal assemble these two proteins to produce virus-like particles (VLPs) studded with numerous copies of Env on their surface. Although they cannot cause infection or disease because they lack the complete genetic code of HIV, these VLPs match whole, infectious HIV in terms of stimulating suitable immune responses.

In studies with mice, two injections of the VLP-forming mRNA vaccine induced neutralizing antibodies in all animals, the investigators report. The Env proteins produced in the mice from the mRNA instructions closely resembled those in the whole virus, an improvement over previous experimental HIV vaccines. “The display of multiple copies of authentic HIV envelope protein on each VLP is one of the special features of our platform that closely mimics natural infection and may have played a role in eliciting the desired immune responses,” said Dr. Lusso.

The team then tested the Env-Gag VLP mRNA vaccine in macaques. The details of the vaccine regimen differed among subgroups of vaccinated animals but involved priming the immune system with a vaccine modified to optimize antibody creation. The prime was followed by multiple booster inoculations delivered over the course of a year. The boost vaccines contained Gag mRNA and Env mRNA from two HIV clades other than the one used in the prime vaccine. The investigators used multiple virus variants to preferentially activate antibodies against the more conserved “shared” regions of the Env — the target of broadly neutralizing antibodies — rather than the more variable regions that differ in each virus strain.

Although the doses of mRNA delivered were high, the vaccine was well tolerated and produced only mild, temporary adverse effects in the macaques, such as loss of appetite. By week 58, all vaccinated macaques had developed measurable levels of neutralizing antibodies directed against most strains in a test panel of 12 diverse HIV strains. In addition to neutralizing antibodies, the VLP mRNA vaccine also induced a robust helper T-cell response.

Beginning at week 60, immunized animals and a control group of unimmunized macaques were exposed weekly, via the rectal mucosa, to SHIV. Because non-human primates are not susceptible to HIV-1, scientists use a chimeric SHIV in experimental settings because that virus replicates in macaques. After 13 weekly inoculations, two out of seven immunized macaques remained uninfected. The other immunized animals had an overall delay in infection, which occurred, on average, after eight weeks. In contrast, unimmunized animals became infected on average after three weeks.

“We are now refining our vaccine protocol to improve the quality and quantity of the VLPs produced. This may further increase vaccine efficacy and thus lower the number of prime and boost inoculations needed to produce a robust immune response. If confirmed safe and effective, we plan to conduct a Phase 1 trial of this vaccine platform in healthy adult volunteers,” said Dr. Lusso.