SUBHADITYA NEWS CHANNEL PRESENTS NEWS OF THIS WEEK DATED 15/6/2024 : SCIENCE,POLITICAL,SPORTS ,MOVIE &BOOK NEWS THIS WEEK

 

1) Child sacrifices at famed Maya site were all boys, many closely related By Bruce Bower

They may have been sacrificed to ensure the growth of maize crops or to appease a rain god Genetic clues have unveiled a type of ritual child sacrifice at an ancient Maya site that consisted only of young boys, often chosen as closely related pairs that included twins.

The discovery stems from a burial of more than 100 people in an underground chamber discovered in 1967 at Chichén Itzá, a once dominant Maya city in what’s now Mexico’s Yucatan Peninsula. Chichén Itzá reached its pinnacle between around A.D. 800 and A.D. 1000, as many Maya cities in Mexico and Central America fell on hard times or were abandoned (SN: 12/4/23).DNA from 64 remains in the chamber pegs the bodies as males, challenging an earlier idea that females sacrificed in fertility rites were interred there, archaeogeneticist Rodrigo Barquera and colleagues report June 12 in Nature.

Boys identified in the new study ranged in age from 3 to 6, based on their tooth development. Around one-quarter had a brother or other close relative among those with analyzed DNA. Chemical analyses of diet-related substances in bones found that closely related boys had consumed similar types and proportions of foods, a sign of having grown up in the same households. Related children included two sets of identical twins.

“This is the first evidence of Maya sacrifices involving twins, which were important for Maya [beliefs about the universe],” says Barquera, of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

The sacrifices may have been for maize or rain

Reasons for the fatal ritual are unclear. But the new findings fit with prior suggestions that the underground space contains children sacrificed to ensure the growth of maize crops or to appease the Maya rain deity Chaac, the researchers say.

While Barquera and colleagues regard the burial chamber as a repurposed underground cistern for storing water, archaeologist James Brady of California State University, Los Angeles says it was constructed as an artificial cave. Ancient Maya people created large numbers of artificial caves for a range of spiritual purposes, Brady notes; he examined the chamber in 2017 and 2018 (SN: 5/15/02).Barquera’s team suspects that closely related boys were chosen for ritual sacrifices as stand-ins for powerful mythological figures known as the Hero Twins. A Maya document written in the 1550s, the Popul Vuh, recounts tales of the Hero Twins avenging the murders of their father and uncle (also twins) by underworld gods. After a series of sacrificial deaths, the Hero Twins came back to life to outwit those same deities.

Radiocarbon dating of bones from the underground chamber indicates that boys were ritually interred from around A.D. 500 to A.D. 900, Barquera’s group reports. The team cannot say for certain whether the ancient Maya placed bodies there one at a time over decades and centuries, or if sacrificed children were buried in pairs or larger sets.

There are echoes of modern rain rituals

Barquera’s findings “bring to mind ancestral Yucatec rain invocation ceremonies that are still practiced among traditional Maya communities, especially during times of drought,” says Vera Tiesler, a bioarchaeologist at the Autonomous University of Yucatán in Mérida, Mexico, who did not participate in the new study. In that context, Barquera’s scenario of agriculturally related sacrifices of closely related boys associated with the Hero Twins is plausible, she says.But too little is known about ancient Maya rituals at Chichén Itzá to conclude that sacrificed male twins had anything to do with the Hero Twins story, says bioanthropologist Cristina Verdugo of the University of California, Santa Cruz.

During modern Cha-Chaac rites, boys sit beneath or are tied to an altar adorned with vegetation. The youngsters, no longer ritually sacrificed, imitate sounds of the four winds, frogs or other noises linked to first rains, aiming to invoke the cooperation of the rain god Chaac.Previous Chichén Itzá researchers described a type of flute called an ocarina that lay among human remains in the underground chamber, Tiesler says. That instrument could have been used to produce rain-relevant sounds, she speculates.

The sex of the deity may determine the sex of those sacrificed

The DNA findings at Chichén Itzá fit with emerging evidence that, at least at some ancient Mexican and Central American sites, the sex of the deity to whom sacrifices were made determined the sex of those chosen as offerings, Verdugo says. The male rain god Chaac possibly motivated sacrifices of young boys at Chichén Itzá.

At an Aztec site in Mexico, other researchers have reported that a temple dedicated to the male rain god Tlaloc contained a burial place for ritually sacrificed boys. And preliminary genetic investigations, directed by Verdugo, at Midnight Terror Cave in Belize have found that four sacrificed youngsters assessed so far — out of at least 55 interred there between around A.D. 550 and A.D. 900 — are female (SN: 4/19/16).

Those four are not a lot to go on, but historical accounts describe Maya sacrifices of females divided into young and middle-aged groups meant to represent goddesses in those two age groups, Verdugo says. Further DNA work at the Belize cave will test whether sacrificed children and at least 12 adults found there represent two groups of females.

What is clear, Barquera says, is that ritual sacrifices differed in various ways across many ancient Maya sites and even within the same sites.

Aside from the sacrificial burial chamber at Chichén Itzá, more than 200 sacrificed individuals found in a large sinkhole known as the Sacred Cenote included males and females ranging in age from children to adults. Tiesler and colleagues have reported that many of those people came from as far away as Central Mexico and Central America, perhaps as part of groups involved in long-distance trading.Reliefs and murals in the Sacred Cenote, as well as skeletal evidence, indicate that sacrificial rituals included removing heads and other body parts for public display, Tiesler says.

2) How personalized cancer vaccines could keep tumours from coming back By Elie Dolgin

The same mRNA technology that quickly brought the world a vaccine for COVID-19 is now showing promise as a bespoke therapy for cancer.Angela Evatt lay face down under anaesthesia as surgeons removed a malignant mole from her back and a lymph node from her left armpit. The purpose of the operation was not only to excise the cancerous tissue from her body, but also to begin the process of crafting a personalized vaccine that would train Evatt’s immune system to attack any tumour cells left behind.

The vaccine uses messenger RNA (mRNA), carefully constructed to encode the unique mutant proteins, known as neoantigens, that are found on the surface of Evatt’s melanoma skin cancer cells. She first received this bespoke vaccine, alongside a potent immune-stimulating drug known as a checkpoint inhibitor, as part of a clinical trial in March 2020, just months before mRNA vaccines would become household names in the fight against COVID-19.

Every three weeks, Evatt travelled from her home in Maryland to Georgetown University’s Lombardi Comprehensive Cancer Center in Washington DC to get an injection in each arm. The mRNAs enter her healthy cells and then produce the neoantigens that educate her immune system.

Despite Evatt experiencing severe flu-like symptoms for a day or two after each injection — fever, achiness, chills — the treatment seems to have been beneficial. Now in her mid-40s, she has remained in remission for more than three years after completing her treatments.As is typical of individual experiences in clinical trials, determining the precise impact of the vaccine on Evatt’s recovery is difficult. “It’s impossible to know,” she says. “I’m just happy to be cancer-free.” However, the trial that Evatt participated in is yielding promising data. According to the latest number-crunch from the 157-person study, the combination of vaccine and checkpoint inhibitor reduces the risk of disease recurrence by nearly 50% compared with treatment with the inhibitor alone. The latest analysis also indicates that the vaccine contributes to lifespan extension.

“At the end of the day, you realize, ‘Damn! This combination seems to have activity,’” says lead trial investigator Jeffrey Weber, a cancer immunotherapy researcher at New York University Langone Health in New York City, who presented the findings on 3 June at the world’s largest annual meeting of cancer biologists and oncology specialists in Chicago, Illinois. (Weber and his colleagues published a previous analysis of the data at the beginning of this year1.)

A larger-scale study is still needed to confirm these promising results and to support bringing the vaccine to market. A trial involving more than 1,000 people with melanoma kicked off last July; another for nearly 900 people who have a type of lung cancer began a few months later.But even as the cancer research community awaits further evidence, the early results have injected fresh enthusiasm into the cancer vaccine field. “It has had a big impact across all vaccine development,” says tumour immunologist Nora Disis, director of the Cancer Vaccine Institute at the University of Washington in Seattle. After decades of vaccine trial setbacks, she says, “we’ve started to see the pendulum swing”.

Success is far from guaranteed, however, and the field is thick with unresolved questions. Companies are trying to determine which stages of cancer will see the most benefit from such treatments. They are also searching for improved ways to predict the most effective neoantigens. And it is unclear whether mRNA or some other vaccine technology is the best way to stimulate an anticancer immune response.As scientists continue to test the treatments, all of the pieces will need to come together.“We have the first proof of concept that these things can work,” says Cristina Puig-Saus, a cancer immunologist at the University of California, Los Angeles. “Now, we just need to make Vaccines on demand

Moderna, the company behind the vaccine that Evatt received, is one of the industry leaders working on these improvements. Capitalizing on its experience and the financial windfall from its COVID-19 response, the company has refined its manufacturing protocols and expanded capacity to produce personalized medicines around the clock.

In a football-pitch-sized production facility in Norwood, Massachusetts — a short drive from Moderna’s headquarters in Cambridge — dull black lines divvy up the grey floors into 15 bays, where pairs of technicians can work in parallel. Each bay houses its own ‘single use personalized RNA+’ machine, a refrigerator-sized unit that cranks out long strands of mRNA encoding up to 34 specific cancer mutations. The mutations correspond to different neoantigens, neatly arranged in a sequence. A mixing device then encapsulates the mRNA in fatty nanoparticles to enhance its stability and cellular uptake.“That’s the magic there,” says Elizabeth Sullivan, head of operations for the personalized vaccine programme at Moderna, as she leads a tour of the company’s manufacturing plant in mid-April.

Less visible are the innovations that go into selecting which of the many possible tumour mutations are most likely to elicit an immune response in a vaccine recipient. A series of artificial-intelligence algorithms make this call, informed by an ever-growing repository of clinical and laboratory data from other individuals that, according to Moderna’s oncology lead, Kyle Holen, should yield better predictions over time. “It’s a therapy that learns and can continue to improve,” he says.

Moderna, in partnership with the drug firm Merck, which is headquartered in Rahway, New Jersey, is currently conducting mid- to late-stage clinical trials of its vaccine across five kinds of cancer.In all of these trials, the companies administer their experimental vaccine to people who, like Evatt, have had their tumours surgically removed but still face a high risk of cancer recurrence. By training the immune system’s T cells to identify and eliminate cancer cells at this stage, the objective is to avert a relapse — an approach known as adjuvant therapy.Moderna executives have also raised the possibility of the vaccine being used against later-stage disease, when the cancer has spread to distant sites throughout the body, a process known as metastasis. But, so far, the field has had limited success in this setting. Although initial trials have often found that personalized vaccines produce anticancer T cells in individuals with these types of advanced cancer, those immune responses rarely lead to tumour regression or long-term survival benefits.“It’s very hard to eradicate established tumours,” says Gal Cafri, a cancer immunologist at the Sheba Medical Center in Ramat Gan, Israel. The types of T-cell response that cancer vaccines elicit are well equipped for restraining the growth of small, residual tumours, which helps to prevent disease recurrence after surgery. However, these vaccines are less effective against large, established tumours, which have often evolved aggressive tactics that involve shielding themselves from immune attacks.

Moreover, early-stage cancers tend be slower-growing than late-stage ones, which gives drug developers the 1–4 months they need to design, manufacture and deliver the personalized vaccines to patients. Then, once the vaccine enters the body, more “time is needed to build up an immune response”, says Uğur Şahin, co-founder and chief executive of the biotechnology company BioNTech in Mainz, Germany, which is developing a personalized cancer vaccine in collaboration with biotech firm Genentech in South San Francisco, California.

According to Sahin and Ira Mellman, head of cancer immunology at Genentech, all of these considerations factored into the companies’ joint decision to evaluate their bespoke mRNA vaccine as a post-surgical treatment for people with high-risk colorectal and pancreatic cancers that are still localized and have not yet spread across the body. “When thinking about where is the best place to put a cancer vaccine that would give it the best chance of succeeding and establishing at least proof of concept,” Mellman says, “all roads lead to adjuvant or early disease.”

He even keeps a coffee mug on his desk to commemorate when this strategic decision was made. It reads “2018 A.D.”, standing for ‘Adjuvant Day’.

Special delivery

Both the Moderna–Merck and BioNTech–Genentech vaccines are formulated as mRNA. But that is not the only way to encode neoantigens for processing and presentation to the immune system.

In place of mRNA, many companies and academic groups rely on DNA, peptides or genetically engineered viruses. As Niranjan Sardesai, founder and chief executive of Geneos Therapeutics in Philadelphia, Pennsylvania, points out, each approach triggers its own type of immune response, which could affect the success of any vaccine candidate. “How you deliver these antigens is just as crucial as which antigens you deliver,” Sardesai says.

Some platforms, for example, excel at eliciting ‘killer’ T cells, which are thought to perform the bulk of tumour-cell destruction. However, the real-world impact of such an immunological difference remains to be seen, because only the vaccine developed by Moderna and Merck has so far shown success in a randomized trial.A bigger differentiator, researchers say, could be the computational engines that help to determine the vaccine’s composition. Each engine has its own proprietary suite of tools that it uses to select which neoantigens to target.

Most companies start with genetic sequencing of data from tumours and healthy tissues to reveal the mutations that cropped up during cancer development. T cells will not recognize all of these mutations, however, so algorithms are used to prioritize a subset — Moderna uses up to 34, BioNTech up to 20 — that are predicted to have the most potent immune-stimulating effects.

Such predictions are made on the basis of various factors, such as the levels at which neoantigens are expressed on tumour surfaces and their anticipated binding to cellular receptors that aid in provoking a T-cell response. Machine-learning models then incorporate experimental data to improve the accuracy of these tools.

The algorithms can miss their mark in provoking a cancer-directed immune response, however. “Only a small percentage of the predicted neoantigens turn out to be immunogenic,” notes Neeha Zaidi, an oncologist at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore, Maryland.

In a small study2 of the BioNTech–Genentech vaccine for treating pancreatic tumours, for example, only half of the trial participants developed T cells that were directed against any of the vaccine-encoded mutations. And among those who did, around half formed T cells against just a single neoantigen, even though the vaccines generally contained the instructions for making ten or more targets2.

“Once in a while, the stars line up,” says Alex Rubinsteyn, a computational biologist at the University of North Carolina–Chapel Hill who designs neoantigen prediction tools for personalized cancer vaccines. But, he says, instances in which several of the chosen antigens elicit anti-tumour activity could be the exception rather than the rule. Benjamin Vincent, a tumour immunologist, also at the University of North Carolina–Chapel Hill, agrees: “The field really, really wants to just say, ‘We can predict this from the genomics data only.’ It really wants it so bad, everyone is just doing it. But that doesn’t make it robust.”

Addressing this issue head on, many researchers are now supplementing their computational tools with further experimental data. In February, for example, a joint team at the La Jolla Institute for Immunology and the University of California, San Diego described a platform that uses DNA sequencing and gene-expression analyses on tumours to first identify potential neoantigens, as many others do already. The process then goes a step further by searching in patient blood samples for T cells that actually recognize those antigens3.

This kind of method is going to become more important and more prevalent, according to Stephen Schoenberger, a translational immunologist who co-led the study. “It verifies rather than merely predicts which mutations are neoantigens,” says Schoenberger, who is also chief executive and chief scientific officer of Lykeion, a company he co-founded in La Jolla to develop personalized vaccines informed by this method.

Sachet Shukla, a computational biologist at the University of Texas MD Anderson Cancer Center in Houston, is hopeful that the immune-stimulating potential of personalized cancer vaccines will improve as the research community amasses more of this information. “I think you’ll see another step jump in the accuracy of these algorithms,” he says.

When that happens, he anticipates that cancer vaccines, long regarded as ineffectual, will finally become a staple of oncology treatment: “It’s an idea whose time has come.”

3) Hope, despair and CRISPR — the race to save one woman’s life By Heidi Ledford

Researchers in India fought to develop what could have been the first therapy to use gene-editing to halt a rare neurodegenerative disease. The efforts hold lessons for the messy state of modern drug development.When researcher Arkasubhra Ghosh finally met Uditi Saraf, he hoped that there was still a chance to save her.

Ghosh and his collaborators were racing to design a one-off treatment that would edit the DNA in the 20-year-old woman’s brain cells and get them to stop producing toxic proteins. It was an approach that had never been tried before, with a long list of reasons for why it might not work.But the team was making swift progress. The researchers were maybe six months away from being ready to give Uditi the therapy, Ghosh told her parents over breakfast at their home outside New Delhi last June. Even so, Uditi’s mother was not satisfied. Work faster, she urged him.

Then, Uditi was carried to the breakfast table, and Ghosh understood her urgency. Once a gregarious and energetic child and teenager, with a quick laugh and a mischievous streak, Uditi was now unable to walk or feed herself. She had become nearly blind and deaf. Her family tried to talk to her: “These are the people who are making a therapy for you,” they said loudly.

Shaken, Ghosh returned to his gene-therapy laboratory at Narayana Nethralaya Eye Hospital in Bengaluru, India, and got to work. “If you need to put up tents in the lab, then we can do so,” he told his students. “I’m not going to sleep.”

Four months later, Uditi was gone.

The first therapy using CRISPR genome editing was approved in late 2023 to treat blood disorders that affect thousands of people worldwide. But the approach is also a source of hope to many people who have extremely rare genetic conditions, like the one Uditi had. Genome editing could one day become a radical way to address the diseases that are overlooked by pharmaceutical companies. “Patients are waiting, families are waiting,” says Jennifer Doudna, a molecular biologist at the University of California, Berkeley. “So we need to get on with it.”The first therapy using CRISPR genome editing was approved in late 2023 to treat blood disorders that affect thousands of people worldwide. But the approach is also a source of hope to many people who have extremely rare genetic conditions, like the one Uditi had. Genome editing could one day become a radical way to address the diseases that are overlooked by pharmaceutical companies. “Patients are waiting, families are waiting,” says Jennifer Doudna, a molecular biologist at the University of California, Berkeley. “So we need to get on with it.”

Researchers are still laying the groundwork for this future. They are working out how best to design and manufacture the treatments, and how to deliver them to precise locations in the body. The cost is also a problem: the price of genome-editing therapy threatens to put it out of reach for many. Ghosh wants to bring those barriers down, and he’s convinced that India will eventually be the country to do it.

But Uditi’s family could not wait — the pace of scientific research was too slow. They needed a sprint, and a team of researchers willing to take on not only the scientific challenge, but also the emotional heft and high risk of failure involved in attempting something that had never been done. “What we were trying to do was really almost in the realms of science fiction,” Ghosh says.

And he remains convinced that, despite Uditi’s tragic death, the lessons learnt will help others on a similar path. “It truly is a story of hope.”A crushing diagnosis

As a young girl, Uditi was always in a hurry. Seizing any excuse to celebrate — whether it was a birthday or a festival — she would buzz around the house getting ready hours ahead of everyone else, peppering her mother with urgent requests. She greeted family and friends with cuddles and kisses and brightened parties with her laughter and dancing.

For the first nine years, there was no hint of trouble. And when it began, it was just a flicker — a few seconds here and there, when Uditi would zone out.

She’d switch back on again as if nothing had happened, and her mother, Sonam, wasn’t sure if she should worry. But then Sonam saw nine-year-old Uditi drop a camera on the floor and become confused as to why it was no longer in her hand. A mother’s hunch hardened: something was wrong.The physicians diagnosed her with epilepsy. When Uditi’s seizures became more pronounced and she began to struggle at school, Sonam and Rajeev, Uditi’s father, decided it must be something more. In 2017, they had part of Uditi’s genome sequenced.

It was a deviation from the standard treatment path, but the Sarafs were technologically savvy and financially well off. In India, as in many places in the world, genome sequencing was still uncommon, its roll-out slowed both by the costs and by the dearth of genetic information from people of Indian descent in genetic databases. Without such data, it can be difficult to interpret sequencing results.

Uditi’s results, however, were unambiguous: a single-base change in the gene that codes for a protein called neuroserpin caused tangled polymers to form in her brain cells, interfering with their function. Uditi’s neurons were dying.This condition is called FENIB (familial encephalopathy with neuroserpin inclusion bodies), and the symptoms — which can be similar to dementia — usually manifest late in life. Elena Miranda, a cell biologist at the Sapienza University of Rome, runs the world’s only lab that focuses on the disease. She says that it’s possible that many cases of FENIB go unreported because physicians do not often sequence the genomes of older adults with dementia.But the most severe forms of FENIB strike early and are exceedingly rare. Miranda has known of only three other people with the same mutation that Uditi had. “This form of the disease is very aggressive,” she says.

Uditi and her parents embarked on a lonely journey familiar to many people with rare diseases. They had never heard of FENIB, and neither had Uditi’s physicians. Sonam did some research but couldn’t bring herself to fully absorb what she found. “We thought it’s not possible,” she says. “It cannot happen with our daughter.”

The Sarafs studied what they could find online and tried the interventions available to them: Indian ayurvedic treatments, a ketogenic diet, special schools, seeing a slew of physicians and trying out various medicines. “We shopped for doctors. We shopped for gods,” says Sonam, but Uditi’s condition slowly worsened.

The three moved to upstate New York in 2018 to send Uditi to a school for people with disabilities. Her seizures intensified, and frequent muscle spasms made it hard for her to walk or drink from a glass. Her bright personality was dimming. The Sarafs discussed experimental treatments with Uditi’s new physician, epilepsy specialist Orrin Devinsky at NYU Langone Health in New York City. Devinsky mentioned a couple of options, one of which was CRISPR genome editing. Rajeev seized on the idea.

Uditi’s disease was caused by a mutation that converts a single DNA base from a ‘G’ to an ‘A’. A variation on CRISPR genome editing, called base editing, could theoretically correct exactly this kind of mutation (see ‘Precision gene repair’).Devinsky also emphasized the difficulties. At that time, base editing — which was first reported in 2016 — had never been tested in a clinical trial. The technique requires shuttling a relatively large protein and a snippet of RNA into affected cells. Researchers were struggling with how to perfect this delivery for many organs — the brain being one of the most daunting.

Even if each of these hurdles were surmounted, at best, base editing might stop the production of neuroserpin clumps in some of Uditi’s neurons. The treatment was unlikely to reach all affected cells, and it was unlikely to clear the clumps that were already present or to regenerate neurons that had been lost.

But Rajeev and Sonam saw an opportunity for hope: perhaps such a therapy could slow down the progression of Uditi’s disease, buying time for scientists to develop another treatment that could repair the damage that had been done. The Sarafs were on board.

New York to New Delhi

Devinsky assembled a team at NYU Langone Health with expertise in genome editing and neuroscience to conduct preliminary studies of the approach. The researchers pulled together what funding they could from other grants, and the Sarafs funded the rest. “We will sell our house if we have to,” Sonam said.

The pressure in the lab was intense, says team member Jayeeta Basu, a neuroscientist at NYU Langone Health. The team genetically engineered Uditi’s FENIB mutation into cells grown in the lab. When the cells initially didn’t seem to behave as expected, Basu asked her graduate student to repeat the experiment five times. “I was always pushing,” she says. “We had to be fast, but we also had to be diligent. There was no short cut.”In December 2019, the Sarafs moved back to India. Maintaining a home in the United States was expensive, and Uditi missed her extended family. Then the COVID-19 pandemic struck, and in January 2021, Uditi was hospitalized with severe COVID-19. She spent 20 days in the hospital and her health was never the same, says Sonam. Communication became increasingly difficult for Uditi and she began to pace the house incessantly, rarely even going to sleep.

The Sarafs decided to speed up the base-editing project by funding a second team in India.

Meanwhile, Devinsky had petitioned a US foundation to devise a different experimental treatment called antisense therapy for Uditi. The family flew from India to the United States twice for injections into her spine. The trips became traumatic as her ability to understand the world around her declined.About an hour and a half away from their home, Debojyoti Chakraborty, a geneticist at the Council of Scientific and Industrial Research’s Institute of Genomics and Integrative Biology in New Delhi, had been making headlines for his efforts to devise a CRISPR-based treatment for a genetic blood disorder called sickle-cell disease.

Researchers in the United States were also developing genome-editing therapies for sickle-cell disease, but those therapies were expected to be expensive and potentially out of reach for much of the world. (The UK Medicines and Healthcare Products Regulatory Agency approved the first one, Casgevy, made by Vertex Pharmaceuticals in Boston, Massachusetts, and CRISPR Therapeutics in Zug, Switzerland, which costs US$2.2 million per patient.)

Most of the people with sickle-cell disease in India — a country with one of the highest rates of the condition — live in impoverished communities. Chakraborty and his colleagues hoped to develop a therapy that could be produced and administered at a fraction of the price that is charged in the United States, if not less.Rajeev and Sonam went to the institute to talk to Chakraborty and the institute’s director, chemist Souvik Maiti, who had been collaborating with Chakraborty on the CRISPR technology behind the sickle-cell project.Although the institute gets many requests for help from people with rare diseases and their caregivers, the Sarafs were unusual in that they would be able to help fund the work, says Maiti. Uditi was the only person in India known to have her neuroserpin mutation, and no government agency, company or philanthropy was likely to pay for the development of a treatment. “It’s very difficult,” Maiti says. “Even if our heart is telling us we should work on it, until there is funding, we cannot do it.”

 

Even with funding, Maiti and Chakraborty took some time to discuss the project with Ghosh, who was building a facility in Bengaluru to produce viruses called adeno-associated viruses (AAVs), which are often used in gene therapies. Ghosh aimed for his facility to be one of the first in India to produce AAVs to the standards required for use in people.There were a lot of unknowns in the base-editing project. And in addition to the work on stem cells in the lab, the team would need to do further experiments to determine which base-editing systems would work best, where and how to deliver its components into the body, and whether the process generated any unwanted changes to the DNA sequence. They would need to do experiments in mice to test the safety and efficacy of the treatment. They also needed to get Ghosh’s facility approved by India’s regulators for producing the base-editing components.

A race to reduce costs

Uditi’s illness had probably already progressed beyond the point at which the therapy could offer a notable benefit, but the family wanted them to try, reasoning that the work that they did on this project could help future endeavours to develop genome-editing therapies for genetic conditions.

It was not the first time Ghosh was swayed by a personal appeal: a few years before he met Uditi, Ghosh came to work and found two women waiting outside of his office. They would not leave, the women said, until he committed to finding a treatment for their young sons’ illness, a genetic condition called Duchenne muscular dystrophy, which can be fatal. The women pledged to help raise funds, and Ghosh found himself unable to say no. He has worked on the project and grown close to the families since then.Lab protocols for making medicines are notoriously strict, with each step carefully controlled to minimize the chance of contamination. When setting up his facility for manufacturing gene therapies, Ghosh scrutinized each step, looking for ways to cut costs without sacrificing safety, arguing his case to India’s regulators. He estimates that gene therapies for eye diseases that are developed in his lab will one day be available for one-hundredth of what they cost in the United States. “We will certainly short circuit this entire field,” Ghosh says.

India has earned a reputation for making complex drugs on a budget. During the COVID-19 pandemic, Indian manufacturers cranked out millions of doses of vaccines. Now, the country is manufacturing a malaria vaccine at a fraction of the cost of that in Europe, and it is developing sophisticated cell and gene therapies used in cancer treatments for much less than the price of those in the United States.

Chakraborty took the lead on Uditi’s project. “He is a go-getter kind of person,” says Riya Rauthan, who was then a PhD student in Chakraborty’s lab. “He is not bothered by who he needs to ask to get something done, he just does it.”

To minimize interruptions, the team mapped out all of the experiments and the components they would need from start to finish. In India, many lab reagents have to be imported, and supply interruptions can delay projects by weeks or months. Everything had to be planned and ordered ahead of time, and Maiti worked to keep the supplies coming, seeking out vendors and negotiating prices. “Time was more valuable than anything else,” he says. One of the most important reagents had to come from abroad: antibodies that could recognize the neuroserpin protein and its tangles. Few researchers use such antibodies, and the supply was uncertain. The team decided that the quickest way to get reliable antibodies was to ask Miranda in Rome to share the ones she had developed. She gladly did. “This was a desperate approach,” she says. “But for me the priority was to try to help as much as I could.”

Rauthan generated stem cells from samples of Uditi’s blood. Then, she and her colleagues coaxed those cells to become neurons, and used base editing on them in the lab.Ghosh worked on preparing the AAV that would be used to transport the CRISPR components into Uditi’s neurons. The team needed to determine which strain of AAV would work best — some strains could trigger inflammation in the brain. Ghosh’s lab tested several types of AAV in mice, to find out which one caused the least amount of inflammation and how best to administer it. The team eventually settled on one type — called AAV9 — and determined that it should be injected directly into Uditi’s brain.

Still, that was not the end of their challenges. AAV genomes can carry only an extra 4,700 DNA bases, but the gene that codes for the enzyme needed in base editing is longer than that. Ghosh and his students worked to divide up their genomic cargo so that it could fit in two separate viruses, and added sequences that would allow the two pieces to be spliced together again when they are expressed inside a cell. The team would inject both viruses at the same time.

The approach has been shown to work in mice but had not yet been tested in humans (J. M. Levy et al. Nature Biomed. Eng. 4, 97–110; 2020).

By June 2023, the team seemed to be barrelling towards the finish line. Many of the researchers were working 10-to-12-hour days, and it was nearly time to test their therapy in mice. Ghosh was also scheduling a regulatory inspection to ensure that he would have the approvals he needed by the time the animal results were in. A surgeon had agreed to perform Uditi’s injection.

If all went well, they might be ready to treat Uditi in as little as six months, Chakraborty predicted.

Pushing past tragedy

In early October, a few months after Chakraborty and Ghosh had breakfast with Uditi and her parents, the team received a series of messages from Rajeev on their WhatsApp group. Uditi had become ill with pneumonia and had been taken to the hospital. Then she was in a coma and had been sent home — there was nothing else the physicians could do for her.

Soon afterwards came the message they had all feared: Uditi was gone.

Ghosh thought immediately of the two little boys with Duchenne muscular dystrophy: “What if I’m too late for them, too?”

Others in the lab also took the news hard. “For clinicians, perhaps they become hardened,” says Chakraborty. “We don’t have that experience. We were feeling agony.”

Ten days after learning that Uditi died, Chakraborty presented the lab’s efforts at a local conference and finished his talk with a picture of Uditi, smiling. In the audience, Riya Patra, a graduate student in Ghosh’s lab, began to cry. It was the first time she’d let herself see a picture of the young woman she’d tried so hard to save. “Before, I had thought that if I saw her, maybe I would cry,” she says. “And I wouldn’t be able to work anymore.”

Is CRISPR safe? Genome editing gets its first FDA scrutiny

An estimated 100 million people in India have a rare disease. For decades, people affected by such conditions have cycled through hope and disappointment as researchers have inched closer to developing therapies that can help them at a genetic level. After a series of sporadic starts and failures, gene therapy has finally begun to find its footing. This has set the stage for CRISPR-based genome editing to rocket to the clinic.

When nine-year-old Uditi first dropped her camera, CRISPR was just an oddity — a strange assembly of sequences found in microbial genomes, only studied by a few die-hard microbiologists. Four years before she was diagnosed with FENIB, researchers showed for the first time that a CRISPR-based system could cut DNA in human cells grown in the lab. And the first CRISPR-based genome-editing therapy was approved in the United Kingdom to treat sickle-cell disease the month after Uditi died.

In theory, many people with a genetic condition, no matter how rare, could benefit from these technologies. But the reality is harsher. It will take years to establish the techniques needed to create rapid, on-demand, bespoke CRISPR therapies. Most people with these conditions don’t have that kind of time.

But researchers are working to streamline the process. Doudna’s institute, for example, is working to standardize some aspects of genome-editing therapies, in part to make it cheaper and easier to develop such treatments for people with rare conditions. And the US National Institutes of Health has been trying to develop similar pipelines for gene therapies — an effort that could help to inform genome-editing efforts. “It’s been really hard,” says Doudna. “But what we’re doing is going to have long-term impact.”

In India, the work has continued. Rajeev has urged Chakraborty to finish the team’s studies in mice, so that the next person with FENIB will not have to wait as long for a potential treatment. Some of the work will be completed, and the effort could benefit others with genetic conditions that affect the brain — particularly in India. “We are not really trying as aggressively as we did earlier,” he says. “But that technology has a lot of potential.”

At Uditi’s memorial service, Rajeev tried to make sense of the timing. Uditi was always in a hurry, he told attendees. She always had to be first. She was only a few months away from receiving an experimental treatment, but she would not wait, not even for that. “She could not let science win,” he said. “She was always ahead.”

4) Coming in hot: NASA's Chandra checks habitability of exoplanets by Chandra X-ray Center

Using NASA's Chandra X-ray Observatory and ESA's (European Space Agency's) XMM-Newton, astronomers are exploring whether nearby stars could host habitable exoplanets, based on whether they emit radiation that could destroy potential conditions for life as we know it. This type of research will help guide observations with the next generation of telescopes aiming to take the first images of planets like Earth.

A team of researchers has examined stars that are close enough to Earth that future telescopes could take images of planets in their so-called habitable zones, defined as orbits where the planets could have liquid water on their surfaces. Their results were presented at the 244th meeting of the American Astronomical Society in Madison, Wisconsin.Any images of planets will be single points of light and will not directly show surface features like clouds, continents, and oceans. However, their spectra—the amount of light at different wavelengths—will reveal information about the planets' surface compositions and atmospheres.This video shows a three-dimensional map of stars near the sun on the left side of our screen and a dramatic illustration of a star with a planet orbiting around it on the right side. The star map on the left shows many circular dots of different colors floating within an illustrated three-sided box. Each wall of the box is constructed in a grid pattern, with straight lines running horizontally and vertically like chicken wire. Dots that are colored blue represent stars that have been observed with NASA's Chandra and ESA's XMM-Newton. Suspended in the box, at about the halfway point, is a series of three concentric circles surrounding a central dot that indicates the placement of our sun. The circles represent distances of 5, 10, and 15 parsecs. One parsec is equivalent to roughly 3.2 light-years. In the animation, the dot filled, chicken wire box spins around slowly, first on its X axis and then on its Y axis, providing a three-dimensional exploration of the plotted stars. Credit: Cal Poly Pomona/B. Binder; Illustration: NASA/CXC/M.Weiss

There are several factors influencing what could make a planet suitable for life as we know it. One of those factors is the amount of harmful X-rays and ultraviolet light it receives from its host star, which can damage or even strip away the planet's atmosphere.

"Without characterizing X-rays from its host star, we would be missing a key element on whether a planet is truly habitable or not," said Breanna Binder of California State Polytechnic University in Pomona, who led the study. "We need to look at what kind of X-ray doses these planets are receiving."Binder and her colleagues began with a list of stars that are close enough to Earth for which future ground and space-based telescopes could obtain images of planets within their habitable zones. These future telescopes include the Habitable Worlds Observatory and ground-based extremely large telescopes.

Based on X-ray observations of some of these stars using data from Chandra and XMM-Newton, Binder's team examined which stars could host planets with hospitable conditions for life to form and prosper.

The team studied how bright the stars are in X-rays, how energetic the X-rays are, and how much and how quickly they change in X-ray output, for example, due to flares. Brighter and more energetic X-rays can cause more damage to the atmospheres of orbiting planets."We have identified stars where the habitable zone's X-ray radiation environment is similar to or even milder than the one in which Earth evolved," said Sarah Peacock, a co-author of the study from the University of Maryland, Baltimore County. "Such conditions may play a key role in sustaining a rich atmosphere like the one found on Earth."The researchers used data available in archives from almost 10 days of Chandra observations and about 26 days of XMM observations to examine the X-ray behavior of 57 nearby stars, some of them with known planets. Most of these are giant planets like Jupiter, Saturn or Neptune, while only a handful of planets or planet candidates could be less than about twice as massive as Earth.

There are likely many more planets orbiting stars in the sample, especially ones similar in size to Earth, that so far remain undetected. Transit studies, which look for tiny dips in light when planets pass in front of their stars from our perspective, miss many planets because special geometry is required to spot them. This means the chances of detecting transiting planets in a small sample of stars is low; only one exoplanet in the sample was picked up by transits.

The other main technique for detecting planets is via detection of the wobbling of a star induced by the orbiting planets, and this technique is mainly sensitive to finding giant planets relatively close to their host stars.

"We don't know how many planets similar to Earth will be discovered in images with the next generation of telescopes, but we do know that observing time on them will be precious and extremely difficult to obtain," said co-author Edward Schwieterman of the University of California at Riverside. "These X-ray data are helping to refine and prioritize the list of targets and may allow the first image of a planet similar to Earth to be obtained more quickly."

5) Study confirms the rotation of Earth's inner core has slowed by Will Kwong, University of Southern California

University of Southern California scientists have proven that the Earth's inner core is backtracking—slowing down—in relation to the planet's surface, as shown in new research published in Nature.Movement of the inner core has been debated by the scientific community for two decades, with some research indicating that the inner core rotates faster than the planet's surface. The new USC study provides unambiguous evidence that the inner core began to decrease its speed around 2010, moving slower than the Earth's surface.

"When I first saw the seismograms that hinted at this change, I was stumped," said John Vidale, Dean's Professor of Earth Sciences at the USC Dornsife College of Letters, Arts and Sciences. "But when we found two dozen more observations signaling the same pattern, the result was inescapable. The inner core had slowed down for the first time in many decades. Other scientists have recently argued for similar and different models, but our latest study provides the most convincing resolution."

The relativity of backtracking and slowing down

The inner core is considered to be reversing and backtracking relative to the planet's surface due to moving slightly slower instead of faster than the Earth's mantle for the first time in approximately 40 years. Relative to its speed in previous decades, the inner core is slowing down.

The inner core is a solid iron-nickel sphere surrounded by the liquid iron-nickel outer core. Roughly the size of the moon, the inner core sits more than 3,000 miles under our feet and presents a challenge to researchers: It can't be visited or viewed. Scientists must use the seismic waves of earthquakes to create renderings of the inner core's movement.A new take on a repetitive approach

Vidale and Wei Wang of the Chinese Academy of Sciences utilized waveforms and repeating earthquakes in contrast to other research. Repeating earthquakes are seismic events that occur at the same location to produce identical seismograms.

In this study, the researchers compiled and analyzed seismic data recorded around the South Sandwich Islands from 121 repeating earthquakes that occurred between 1991 and 2023. They have also utilized data from twin Soviet nuclear tests between 1971 and 1974, as well as repeated French and American nuclear tests from other studies of the inner core.

Vidale said the inner core's slowing speed was caused by the churning of the liquid iron outer core that surrounds it, which generates Earth's magnetic field, as well as gravitational tugs from the dense regions of the overlying rocky mantle.

The impact on the Earth's surface

The implications of this change in the inner core's movement for Earth's surface can only be speculated. Vidale said the backtracking of the inner core may alter the length of a day by fractions of a second: "It's very hard to notice, on the order of a thousandth of a second, almost lost in the noise of the churning oceans and atmosphere."

The USC scientists' future research aspires to chart the trajectory of the inner core in even greater detail to reveal exactly why it is shifting.

"The dance of the inner core might be even more lively than we know so far," Vi

1) 1,563 candidates will be held on June 23

NEET UG 2024 Hearing Highlights: The Supreme Court is hearing three petitions today challenging the grant of grace marks and suspicions of paper leaks. NEET UG 2024 Hearing Highlights: The Centre informed the Supreme Court on Thursday that the decision to grant grace marks to 1,563 NEET-UG 2024 candidates for admission to MBBS, BDS, and other courses has been rescinded. These candidates will have the opportunity to opt for a re-test scheduled for June 23.

The court, however, declined to halt the admissions counselling process. If any of the 1,563 candidates choose not to participate in the retest, their previous marks, excluding the grace marks, will be considered for result purposes.

The re-test results will be declared on June 30, and the centre said the counselling for admission in the MBBS, BDS, and other courses will start on July 6.

As many as 67 students scored a perfect 720, unprecedented in the NTA's history, with six from a centre in Haryana's Faridabad figuring in the list, raising suspicions about irregularities.

Scores of students protested in Delhi on June 10, seeking a probe into alleged irregularities. Grace marks, it has been alleged, contributed to 67 students sharing the top rank.The NTA conducts the NEET-UG examination for admissions to MBBS, BDS, AYUSH and other related courses in government and private institutions across the country.

2) NEET UG 2024 result: Supreme Court notice to Centre, NTA on plea seeking CBI probe into 'paper leak'

 Kuwait fire: Centre intervened in proper manner, says Kerala CMpending before Delhi high court on issue of alleged paper leak.The Supreme Court on Friday issued notices on seven petitions challenging the conduct of the NEET-UG 2024 examination and posted it for hearing on July 8 along with the pending petitions. One of the petitions sought a probe by the Central Bureau of Investigation into the alleged paper leak. The court issued notices to the Centre and National Testing Agency or NTA on the plea seeking the CBI probe into the irregularities in NEET-UG 2024.

The Supreme Court also issued notices to private parties on a plea of the National Testing Agency seeking the transfer of cases pending in various high courts on the NEET-UG row to the apex court to avoid multiplicity of litigation. The court directed the same to also come up on July 8.

A vacation bench of Justices Vikram Nath and Sandeep Mehta took note of the submission of the NTA counsel that several pleas, seeking cancellation of the National Eligibility cum Entrance Test–Under Graduate, 2024 on the allegations of question paper leak and other malpractices, are pending in several high courts.They will have the option to either take a re-test or forgo the compensatory marks awarded to them for loss of time, the centre had said.

The examination was held on May 5 across 4,750 centres and around 24 lakh candidates took it. The results were expected to be declared on June 14 but were announced on June 4, apparently because the evaluation of the answer sheets got completed earlier.

The allegations have led to protests in several cities and filing of cases in seven high courts as also the Supreme Court. Scores of students protested in Delhi on June 10 seeking a probe into alleged irregularities.As many as 67 students scored a perfect 720, unprecedented in the NTA's history. Six from a centre in Haryana's Faridabad figured in the list, raising suspicions about irregularities. It has been alleged that grace marks contributed to 67 students sharing the top rank.The NTA conducts the NEET-UG examination for admissions to MBBS, BDS, AYUSH, and other courses related to government and private institutions nationwide.

3)Kuwait fire: Centre intervened in proper manner, says Kerala CM

The aircraft carrying 31 mortal remains of the victims from the Kuwait fires landed in Kerala in a special aircraft with Union Minister of State VK Singh.Kerala Chief Minister Pinarayi Vijayan acknowledged the efforts taken by the Central government and the Kuwait government following the Kuwait Fire tragedy which claimed the lives of 45 Indians on Friday, reported ANI.

CM Vijayan was speaking to the reporters before the landing of a special Indian Air Force aircraft which carried the mortal remains of the Indians killed in the building fire on June 12. He said, "It is a never-ending loss for the families... The Government of Kuwait has taken effective and impeccable measures. It is expected that the follow-up will be flawless. When it came to know about the disaster, the Government of India also intervened in a proper manner," reported ANI.

Union Minister of State VK Singh, who rushed to Kuwait on Thursday returned with mortal remains on the flight, reported ANI.CM Vijayan also urged that measures should be taken to prevent such accidents from happening in the future.

"It is hoped that the Kuwaiti government will take the lead in providing adequate compensation to the families. government of India should also try to speed up in such matters," Vijayan said, according to ANI.

Kerala Ministers Veena George who was denied permission to visit Kuwait, and Roshi Augustin were also present at the airport to receive the bodies along with Leader of Opposition VD Satheesan, Union Minister Suresh Gopi, Congress MP Hibi Eden, BJP state president K Surendran and former Union Minister V Muraleedharan "There have been some wrong approaches, but now is not the time for that controversy," CM said on Kerala Health Minister Veena George's exclusion, reported ANI.

According to ANI, Kerala Minister P Rajeev said that special ambulances with police pilot has been provided for the deceased."Out of 45 deceased, the bodies of the residents of Kerala, Tamil Nadu, and Karnataka will be brought here," the minister said, reported ANI.

The remains of 31 victims included 23 from Kerala, seven from Tamil Nadu and one from Karnataka.Union Minister Suresh Gopi has assured that the central government will take appropriate actions and decisions according to ANI. He described the incident to be thud on the ‘pravaasi’ (Overseas Indians) community in Kerala, reported ANI.

4) PM Modi 3.0 Live Updates: Narendra Modi signs first file on ‘Kisan Nidhi’ as PM for 3rd term

PM Modi 3.0 Live Updates: Narendra Modi took oath as India's Prime Minister for the third straight term on June 9. Modi Cabinet 3.0 will hold its first meeting on Monday. PM Modi 3.0 Live Updates: Narendra Modi was sworn-in as prime minister for the third consecutive term, along with his 71 ministers, on Sunday evening.

In the new coalition government, besides Narendra Modi, 30 Cabinet Ministers, five Ministers of State (Independent Charge) and 36 Ministers of State were administered the oath of secrecy and office by President Droupadi Murmu.

Rajnath Singh, Amit Shah, Nitin Gadkari, Nirmala Sitharaman and S Jaishankar – all ministers in the Modi 2.0 Cabinet – took oath as cabinet ministers at the Rashtrapati Bhavan.Narendra Modi became the first person after former Prime Minister Jawaharlal Nehru to be elected as PM for the third consecutive term.Political veterans, business leaders, celebrities and actors were among people who attended the ceremony.

Council of Ministers: Rajnath Singh, Amit Shah, Nitin Gadkari, JP Nadda, Shivraj Singh Chauhan, Nirmala Sitharaman, S Jaishankar; ML Khattar, HD Kumaraswamy, Piyush Goyal, Dharmendra Pradhan, Jitan Ram Manjhi, Rajeev Ranjan Singh, Sarbanand Sonowal and Dr Virendra Kumar among others took oath.

Members from allies sworn-in

JD(S) leader H D Kumaraswamy, HAM (Secular) chief Jitan Ram Manjhi, JD(U) leader Rajiv Ranjan Singh 'Lalan', TDP's K Ram Mohan Naidu and LJP-RV leader Chirag Paswan took oath as Cabinet ministers. Each of these five allies got one cabinet berth each.

Who all attended?

Several leaders from neighbouring countries and other nations attended Narendra Modi’s oath taking ceremony. Sri Lanka President Ranil Wickremesinghe, Maldives President Mohamed Muizzu, Bangladesh Prime Minister Sheikh Hasina, Seychelles Vice-President Ahmed Afif, Prime Minister of Bhutan Tshering Tobgay, Prime Minister of Nepal Pushpa Kamal Dahal ‘Prachanda', Prime Minister of Mauritius Pravind Kumar Jugnauth attended the ceremony.Stay tuned to this LIVE blog for all the latest developments related to the Modi oath ceremony.

5) Narendra Modi releases PM Kisan Nidhi instalment worth ₹20,000 crore after taking office: ’Fully committed’

As PM for 3rd time, PM Modi signs first file releasing 17th instalment of PM Kisan Nidhi benefiting 9.3 crore farmers with ₹20,000 crore.Prime Minister Narendra Modi, who took office for the third time on Monday, signed the first file for the ‘PM Kisan Nidhi' release. He inked the file authorising the release of the 17th instalment of PM Kisan Nidhi, which will benefit 9.3 crore farmers and distribute around ₹20,000 crore.

“Ours is a government fully committed to Kisan Kalyan. It is, therefore, fitting that the first file signed on taking charge is related to farmer welfare. We want to keep working even more for the farmers and the agriculture sector in the coming times," PM Modi said after signing the file.

The decision signifies the government's commitment to farmers' welfare following the ruling National Democratic Alliance's poll win, albeit with some setbacks, especially in rural India.

6) PM would have lost had Priyanka contested from Varanasi: Rahul

The people of India have given a message to the Prime Minister – ‘we don’t want your way of politics... we are against politics of hatred and violence’, says Congress leader

RAE BARELI Congress leader Rahul Gandhi on Tuesday asserted that if his sister - Priyanka Gandhi Vadra - had contested the Varanasi Lok Sabha seat, Prime Minister Narendra Modi would have lost by two-three lakh votes.“I am not saying this because of any ego, but the people of India have given a message to the Prime Minister of India – we don’t want your way of politics. We are against this and the politics of hatred and violence. We want a country of love and progress,” said Gandhi addressing a thanksgiving meeting (Abhar Sabha) of party workers of Rae Bareli and Amethi at the Bhuemau guest house here.

The Congress leader accused Modi of ignoring the common people and giving prominence to top industrialists and other personalities during the consecration ceremony at the Ram temple, and said the masses taught them a lesson by ensuring the BJP’s defeat in Ayodhya.

“The BJP lost the Ayodhya seat. They did not invite any poor or farmer to the inauguration of Ram temple. They did not invite tribals and even the President of India. Adani and Ambai were there, and the rich were there...the people of Ayodhya have given a reply,” he said.

7) N Chandrababu Naidu of TDP takes oath as Andhra Pradesh chief minister for 4th term in presence of PM Modi

Chandrababu Naidu swearing-in ceremony: N Chandrababu Naidu, TDP supremo, was sworn in as the chief minister of Andhra Pradesh for the fourth term today.Nara Chandrababu Naidu, Telugu Desam Party supremo, was sworn in as the chief minister of Andhra Pradesh for the fourth term on Wednesday, June 12. Andhra governor S Abdul Nazeer, former Telangana governor Tamilisai Soundarajan were present at the swearing-in.

Prime Minister Narendra Modi, Union home minister Amit Shah, Union ministers JP Nadda and Bandi Sanjay Kumar, and several other leaders attended the oath-taking ceremony.

Chandrababu Naidu took oath around 11.27am near Gannavaram Airport in Kesarapalli on the outskirts of Vijayawada. Along with Chandrababu Naidu, Janasena chief Pawan Kalyan, the TDP supremo's son Nara Lokesh and 22 others also took the oath.

Pawan Kalyan reportedly has been offered the deputy chief minister's post. Janasena is being offered three cabinet berths and the Bharatiya Janata Paty one.

After taking oath as chief minister Naidu shared a hug with PM Narendra Modi on stage. This is the fourth time that Naidu is assuming charge as Andhra chief minister and the second time after the bi-furcation in 2014.Chandrababu Naidu's son and TDP general secretary Nara Lokesh, Union minister Rammohan Naidu, actors Chiranjeevi, Rajnikanth, Nandamuri Balakrishna were also present on occasion.

Naidu had led the TDP- BJP-Janasena National Democratic Alliance to a landslide victory in the assembly as well as Parliamentary elections.The TDP holds the majority in Andhra Pradesh's 175-member assembly with 135 MLAs, while its allies, the Janasena Party, have 21 and the BJP has eight. The opposition YSR Congress Party has 11 legislators.

The TDP MLAs who took oaths included Nara Lokesh, Kinjarapu Atchannaidu, Nimmala Ramanaidu, NMD Farooq, Anam Ramanarayana Reddy, Payyavula Kesav, Kollu Ravindra, Ponguru Narayana, Vangalapudi Anita, Anagani Satya Prasad, Kolusu Parthasaradhi, Kola Balaveeranjaneya Swamy, Gottipati Ravi, Gummadi Sandhyarani, BC Janardhan Reddy, TG Bharath, S Savitha, Vasamsetty Subhash, Kondapalli Srinivas and Mandipalli Ramprasad Reddy.In the 175-member Andhra Pradesh assembly, the cabinet can have 26 ministers, including the chief minister.

The Telugu Desam Legislature Party and NDA partners elected Naidu as their leader in separate meetings on Tuesday, June 11.

Addressing the legislators, Naidu asserted that he is committed to developing Amaravati as the state's sole capital.

"With all your cooperation, I am swearing in tomorrow (as the CM) and I would like to thank you all for that. Prime Minister Narendra Modi is coming for the swearing-in ceremony,” Naidu said, adding he had sought cooperation from the Union government for Andhra Pradesh's development and it was "assured".South superstars Rajinikanth, Chiranjeevi, and actor-politician Nandamuri Balakrishna also attended the event at Gannavaram Mandal, Kesarapalli IT Park.Naidu first became the chief minister in 1995 and went on to have another two terms.

His first two terms as chief minister were at the helm of united Andhra Pradesh, beginning in 1995 and ending in 2004, while the third term came post-bifurcation of the state.

In 2014, Naidu emerged as the first chief minister of bifurcated Andhra Pradesh and served it until 2019. He lost the 2019 polls and was the opposition leader until 2024.

Following a landslide victory in the 2024 elections, he is returning as the CM for a fourth term, ousting the YSRCP.The NDA won a landslide victory in the recently concluded simultaneous Lok Sabha and assembly elections in the state, winning 164 of the 175 assembly seats and 21 of the 25 Lok Sabha seats.

8) Congress to voice the anger of 24 lakh NEET candidates inside Parliament, says Gaurav Gogoi

Seeking a CBI investigation or an SC-monitored probe into the allegations of paper leaks and other irregularities, the Congress said the INDIA bloc had the numbers to “bring the government to its knees” in the LS

Reiterating its demand for a Supreme Court-monitored probe into allegations of irregularity in conducting the National Eligibility cum Entrance Test (NEET) for medical college admissions, the Congress on Thursday said that the plight and anger of the 24 lakh students who took the exam will “reverberate” in Parliament.

Congress leader Gaurav Gogoi asserted that the INDIA bloc has enough numbers in the Lok Sabha to “bring the government to its knees and make them accountable to the students”. The Opposition party also sought the removal of the National Testing Agency (NTA) director general and claimed that the BJP government’s attitude towards the demand for an inquiry into the NEET examination is “irresponsible and insensitive”.

 

 

1) USA vs IND, T20 World Cup 2024: India qualifies for Super 8 after beating United States

USA vs IND, T20 World Cup 2024: India consolidated its position at the top of the points table with six points in three games after this win.India became the first team to qualify for the Super 8 from Group ‘A’ after beating USA at the Nassau County International Cricket Stadium in New York on Wednesday.India consolidated its position at the top of the points table with six points in three games.

The men in blue started their campaign with an eight-wicket thrashing of Ireland before handing Pakistan a six-run loss in a last-ball thriller.Even after losing to Rohit Sharma’s men, USA still has a chance to qualify for the top eight. All the Monank Patel-led United States needs to do is beat Ireland in their last group match.

After this win, India will take the A1 spot no matter where it finishes.

For Babar Azam-led Pakistan, whose chances looked bleak at one point after two straight losses, the path for Super 8 is straight-forward now. First, it needs to beat Ireland and then hope the latter beats USA in return.

This would create a two-way tie between Pakistan and USA which would be broken by Net Run Rate.

2) Highlights - Bumrah magic helps India beat Pakistan

One team had Jasprit Bumrah. The other didn't. And that was that. That was the difference. His legend is littered with incredible displays. But this will feel sweeter, not merely for the fact that it came in a World Cup match against Pakistan, but for the fact that without his intervention this game would have almost certainly had a different ending. India defended 119. Pakistan lost after being 80 for 3.

The atmosphere in New York is something else. They are roaring for dot balls. They are ooohing for jaffas. They go up to 123 db when India strike. They are cheering Bumrah as he runs up to the crease. They are smiling. They are dancing. They making this the occasion it was always going to be and then some Bumrah's nailed the 19th over and dismissed Iftikhar Ahmed. Pakistan need 18 to win off the last six balls. Having been favourites for the entirety of the chase - their chances were up at 63% even at the start of the penultimate over. Now at the start of the 20th, it's plummeted to 19%.And Hardik who in 2022 said he loved being part of that Pakistan game at the MCG regardless of the result just shrugs as he picks up a very important wicket. His ability to unsettle batters bowling short of a good length is proving to be a big difference for India. Took out Fakhar earlier. Now Shadab gone too.

Axar with his height and his round-arm action produces a lovely 16th over, where he had Imad Wasim beaten on the top edge three times in three balls as he attempted to cut to the long boundary. Protected the leg side boundary which was the short boundary really well. Tension keeps rising. The crowd, which is a comfortable India majority, is adding to the feeling of the walls closing in on Pakistan. They still have six wickets in hand so they should so this. But right now, it's tight. India are trying to push this game all the way to the death where anything can happen, and where they have two overs of Jasprit Bumrah to tip the scales. Actually only one as it turns out because Rohit goes to his gun bowler in the 15th over and he produces a wicket with the first ball. The set batter Mohammed Rizwan is bowled neck and crop (might have stayed low too but he had no business horizontal-batting a ball that was fairly full). India believe this is possible. They've got a slip in for the new batter Shadab Khan.

3) Indian Sports Wrap, June 14: Aditi’s makes solid start with 68 at Meijer LPGA Classic

Here are all the major updates, scores, and results of Indians in the world of sports on June 14. e Meijer LPGA Classic golf tournament. | Photo Credit: AP

Aditi’s makes solid start with 68 at LPGA Classic Aditi Ashok opened her challenge at the Meijer LPGA Classic with one of her best rounds of the season, carding a 4-under 68 for a tied 11th place here

Aditi’s round started on the tenth with birdies on the 11th and the 12th holes. A bogey on 17th followed by a birdie on the 18th saw her turn in 2-under.

On the second nine, the front side of the Par-72 Blythefield Country Club, she parred all the way till she picked birdies on the eighth and the ninth, her final two holes.

Aditi’s best round this season before this was also 68 at the Honda LPGA in Thailand in February and she finished tied 31 in the event.Indian golfer Pukhraj Singh Gill held the lead after carding a three-under 69 in the second round of the Asian Development Tour’s Nam A Bank Vietnam Masters here.

The long-hitting Indian had carded a 64 in the first round and his two-day total stands at 11-under in the USD 85,000 event, which is being held at Royal Long An Golf and Villas near Ho Chi Minh city.The cut fell at one-under and 52 players made the grade for the final round.Three other Indians made it to weekend rounds and they included Sunhit Bishnoi (70-69), who is Tied-11th, Aman Raj, who recovered from his first round 72 with a 68 and is Tied-24th and Khalin Joshi (72-70) in Tied-33rd place.

Jeev, Randhawa in second round of Lawrie Matchplay

Jeev Milkha Singh and Jyoti Randhawa won their first-round clashes to move into the next round of the Paul Lawrie Matchplay event on the Legends Tour for Seniors in Europe here.Both the Indians won 1-up as they maintained their lead after going one ahead of the 16th.

Jeev beat Paul Streeter, while Randhawa got the better of Thomas Gogele.Jeev will take on Keith Horne in the second round, while Randhawa will play Malcolm Mackenzie, who beat 2006 Ryder Cup captain Ian Woosnam in the first round.

4) Praggnanandhaa vindicates ‘Big Boys Club’ credentials with impressive Norway Chess 2024 showing

After finishing fifth in the competitive eight-player field at Candidates 2024 in Canada, Norway Chess posed as a crucial litmus test for the young prodigy — one that he passed with flying colours. For an 18-year-old to dominate a field in a foreign land that boasted the world’s top players is neither surprising nor shocking anymore.

India’s R. Praggnanandhaa had to contend with an invincible lot in Norway: the world’s top three players (Magnus Carlsen, Hikaru Nakamura and Fabiano Caruana), the reigning world champion (Ding Liren), and a rival once hailed as ‘the strongest youngster’ (Alireza Firouzja).

For Praggnanandhaa, it was business as usual as the Chennai prodigy showcased his prowess with a creditable third-place finish, behind five-time former World Champion Carlsen and World No. 2 USA’s Nakamura in the recently-concluded Norway Chess.

Carlsen, known for his relentless pursuit of victories and titles, boldly declared himself the victor of the Super Grandmaster tournament even before it began in the official promo video.

His confidence was well-founded, as he clinched his 59th major career title with 17.5 points, a full two points ahead of Nakamura.

However, the Norwegian faced stiff competition from Praggnanandhaa, who proved to be his most formidable challenger on home turf. The Indian prodigy wielded his sword skillfully to achieve his first classical win against Carlsen, executing a tactical masterclass that led to victory in just 37 moves.Rubbing shoulders with the best

Praggnanandhaa, now a regular in the ‘big boys club’, showcased his mettle once again. After finishing fifth in the competitive eight-player field at Candidates 2024 in Canada, Norway Chess posed as a crucial litmus test for the young prodigy — one that he passed with flying colours.

“The experience was good. I had pleasant positions in most of the games that I played. Overall, I played good quality chess, but in some games, I could have played better, like my both classical games against Ding (Liren). But it happens in a tournament that sometimes you have one or two bad results where you don’t show your best. That’s maybe because of one bad day, but otherwise, I was playing at a very good level,” said Praggnanandhaa in an interaction with  Sportstar.

The young grandmaster has been in top form since the start of the year, consistently playing high-quality chess.“For the Candidates, we worked really hard. After Candidates, I didn’t really work too much on chess. I mean, I did work, but it was not very extensive. I was just trying to keep myself sharp. The work we did for Candidates is showing now, but apart from that, in terms of my performance, I think my game quality has always been good from the start of the year, from Vijk aan Zee to Prague, and then Candidates,” he said.Despite his consistent performance, not all tournaments have gone in Praggnanandhaa’s favour. After fiercely competing for the top spot in the Tata Steel Masters and Prague Masters, and for the majority of Candidates 2024, the Chennai GM struggled to secure a strong finish, ultimately settling for a mid-table position.

“Even though my game quality was always at a very good level, things weren’t going my way in some of the games, which resulted in me finishing in the middle of the table always. Like in Prague, I suffered this unfortunate loss against (Richard) Rapport, and in Vijk (aan Zee), I didn’t really score many wins. In Candidates, I also had a few unfortunate losses, but otherwise, I felt I was outplaying all these top players and was scoring wins, so that was important,” he said.

While there were plenty of positives for Praggnanandhaa, the suffering of the current World Champion continued. The Chinese GM Ding found himself in a series of unfortunate events that cast a shadow over his performance.

During Round 6, Ding, with the black pieces, missed a mate-in-two against Carlsen in what should have been a dead-draw position — this missed opportunity left Ding in disbelief.

The heartbreak for Ding didn’t end there. In the following round, he found himself in a favourable position against Praggnanandhaa. However, in a puzzling decision, Ding offered a draw, pushing the match into a nerve-wracking Armageddon. The final twist came in the Armageddon game, where Ding, once again in a winning position, made yet another blunder against the Indian youngster, forcing him to resign on the spot.

Reflecting on his match with Ding, Praggnanandhaa said, “I don’t know Ding personally, but I feel like something is not going right with him. Maybe with his health or mentally after the match, but he’s spoken about it himself. In our match, I was more upset about my game than him blundering at the end. I was playing at a very low level against him in the first game. I was even lost at some point and then I was shocked that he offered a draw. We had just crossed the 30th move and that’s the first moment he could offer a draw and immediately offered one which was very

5) Nadal, Swiatek and others react to Alcaraz vs Zverev French Open final

Rafael Nadal, Iga Swiatek, Rod Laver and many other athletes congratulated Alcaraz after he outlasted Zverev to win his maiden French Open. Carlos Alcaraz outlasted German Alexander Zverev to win a maiden French Open and become the youngest man to capture Grand Slam titles on all three surfaces with a 6-3, 2-6, 5-7, 6-1, 6-2 victory in a nail-biting final on Sunday.

While the 21-year-old has won all of his three major finals, Sunday’s defeat prolonged Zverev’s frustration at Grand Slams, with the German still chasing a first title despite reaching the last four eight times.Rafael Nadal, Iga Swiatek, Rod Laver and many other athletes congratulated Alcaraz for his victory.

6) French Open women’s singles champions in Open Era: Swiatek completes hat-trick with 2024 title

Iga Swiatek won her fourth French Open title and third on the trot with a 6-2, 6-1 victory over Jasmine Paolini in the final of the 2024 edition at Roland Garros, Paris on Saturday.

World No. 1 Iga Swiatek took her tally of French Open titles to four as she beat Jasmine Paolini 6-2, 6-1 in the final at Roland Garros, Paris on Saturday ES

World No. 1 Iga Swiatek took her tally of French Open titles to four as she beat Jasmine Paolini 6-2, 6-1 in the final at Roland Garros, Paris on Saturday.

The 23-year-old Swiatek joins Belgium’s Justine Henin in third place on the all-time list of most French Open titles won by a women. USA’s Chris Evert holds the record with seven title followed by Germany’s Steffi Graf (6).

The clay Major was the first one to join the Open Era in 1968, allowing both amateurs and professionals to participate at the event. Since then, 31 different women have lifted the coveted Suzanne-Lenglen Cup.

DOCTOR CLIMAX – NETFLIX

Doctor Climax is an exciting comedy series that revolves around a dermatologist whose taboo-defying newspaper column sparks a mass sexual awakening in Thailand. Created by Ekachai Uekrongtham, the series features Chantavit Dhanasevi, Arachaporn Pokinpakorn, and Chermawee Suwanpanuchoke in prominent roles.

 LUV KI ARRANGE MARRIAGE – ZEE5

Luv and Ishika meet through a traditional arranged marriage setup. After initial hiccups, the two decide to tie the knot but are shocked to find out that their single parents have fallen in love with each other. What ensues next is a comedy of errors that will leave you in splits. The Ishrat Khan directorial features Sunny Singh, Avneet Kaur, Supriya Pathak, Annu Kapoor, and Rajpal Yadav in pivotal roles.

BRIDGERTON SEASON 3 PART 2 – NETFLIX

Netflix is back with the second part of Bridgerton Season 3. The newly arrived episodes continue to focus on Penelope Featherington and Colin Bridgerton’s story which ended on an interesting cliff-hanger in the previous part. The period drama features Nicola Coughlan, Luke Newton, Luke Thompson, Golda Rosheuvel, and Simone Ashley among others.

INSIDE OUT 2 – THEATRES

Inside Out 2 is an animated coming-of-the-age movie that shows how a new emotion (anxiety) in a teenager’s mind can disrupt the smooth functioning of other emotions such as anger, fear, joy, sadness, and others.

GAANTH – JIOCINEMA

JioCinema’s new offering Gaanth is an engaging crime thriller that delves into a complicated mass suicide case. As the investigation progresses, investigating officer Gadar Singh is forced to form an unlikely alliance with a psychiatric intern named Sakshi Murmu. Will they be able to overcome their personal differences and solve the case?

THE WATCHERS – THEATRES

An adaptation of AM Shine’s novel of the same name, The Watchers tells the story of a young artist who gets trapped in a glass room with three strangers, in the middle of a dense forest. The horror movie stars Dakota Fanning, Georgina Campbell, Oliver Finnegan, and Olwen Fouéré in significant roles.

CHANDU CHAMPION – THEATRES

Chandu Champion is a biographical drama based on the life of Murlikant Petkar, India’s first Paralympic gold medallist, whose never-give-up attitude helped him overcome several hurdles in his life to fulfil his dreams. The Kabir Khan directorial features Kartik Aaryan in the lead role.

BOOK OF THIS WEEK:

The Indian Book of Big Ideas: The 45 Greatest Thinkers, Philosophers and Reformers of All Time! by Mukunda Rao (Author), Ashwitha Jayakumar (Contributor)

Who are we?

Is everything in the world connected?

Is truth different for different people?

Does God speak to only some of us?

Great minds have forever been engaged in tackling life's big questions. People travelled far and wide in search of answers, learned from others and came up with new ways of understanding the world.

Curious to know what on earth they were thinking?

Now you can walk down the winding path of philosophy from 700 BCE to recent times, discovering the wisdom and teachings of 45 great thinkers, philosophers and reformers of India. Learn from the most far-sighted luminaries, such as Mahavira, Gargi, Adi Shankara, Kabir, the Buddha, Vivekananda and Guru Nanak, along with Sri Aurobindo, Rammohan Roy, Rabindranath Tagore and Mahatma Gandhi, and get to know how the most brilliant and influential Indian ideas were born.

These thinkers, you will see, didn't always agree with each other (indeed, they sometimes fiercely disagreed!), but all of them left behind a legacy of courage and compassion that remains valuable even today.

Mukunda Rao  is the author of six insightful philosophical works, six books of much-acclaimed fiction and two popular plays. After his voluntary retirement from a teaching job in a college in 2000, he now lives with his wife on a farm outside Bengaluru.

Ashwitha Jayakumar Ashwitha Jayakumar has loved stories all her life, especially ones set in different times and worlds.

Born in Chennai, she studied English literature and medieval studies at the universities of Edinburgh and Leeds in the United Kingdom. She is the author of the bestselling My Little Book of... series on Indian gods and goddesses published by Puffin India, as well as several works of fiction and non-fiction for Pratham Books, Scholastic India, and HarperCollins. She particularly enjoys writing non-fiction for children on history. She is presently hard at work writing two picture books for children aged 2+ and an all-ages work of narrative non-fiction on early modern India.