Connect with us

Misc News/Press Release

Immune cells engineered in lab to resist HIV infection, Stanford study shows

Published

on

Researchers-at-the-Stanford-University-School-of-Medicine-have-found-

Researchers-at-the-Stanford-University-School-of-Medicine-have-found-

Researchers at the Stanford University School of Medicine have found a novel way to engineer key cells of the immune system so they remain resistant to infection with HIV, the virus that causes AIDS.

A new study describes the use of a kind of molecular scissors to cut and paste a series of HIV-resistant genes into T cells, specialized immune cells targeted by the AIDS virus. The genome editing was made in a gene that the virus uses to gain entry into the cell. By inactivating a receptor gene and inserting additional anti-HIV genes, the virus was blocked from entering the cells, thus preventing it from destroying the immune system, said Matthew Porteus, MD, an associate professor of pediatrics at Stanford and a pediatric hematologist/oncologist at Lucile Packard Children’s Hospital.

“We inactivated one of the receptors that HIV uses to gain entry and added new genes to protect against HIV, so we have multiple layers of protection — what we call stacking,” said Porteus, the study’s principal investigator. “We can use this strategy to make cells that are resistant to both major types of HIV.”

He said the new approach, a form of tailored gene therapy, could ultimately replace drug treatment, in which patients have to take multiple medications daily to keep the virus in check and prevent the potentially fatal infections wrought by AIDS. The work was done in the laboratory, and clinical trials would still be needed to determine whether the approach would work as a therapy.

RELATED NEWS

» Top AIDS scientist delivers Stanford lecture, declaring end in sight for pandemic
“Providing an infected person with resistant T cells would not cure their viral infection,” said Sara Sawyer, PhD, assistant professor of molecular genetics and microbiology at the University of Texas-Austin and a co-author of the study. “However, it would provide them with a protected set of T cells that would ward off the immune collapse that typically gives rise to AIDS.”

The study was published in the Jan. 22 issue of Molecular Therapy.

One of the big challenges in treating AIDS is that the virus is notorious for mutating, so patients must be treated with a cocktail of drugs — known as highly active antiretroviral therapy or HAART — which hit it at various stages of the replication process. The researchers were able to get around that problem with a new, multi-pronged genetic attack that blocks HIV on several fronts. Essentially, they hope to mimic HAART through genetic manipulation.

The technique hinges on the fact that the virus typically enters T cells by latching onto one of two surface proteins known as CCR5 and CXCR4. Some of the latest drugs now used in treatment work by interfering with these receptors’ activity. A small number of people carry a mutation in CCR5 that makes them naturally resistant to HIV. One AIDS patient with leukemia, now famously known as the Berlin patient, was cured of HIV when he received a bone marrow transplant from a donor who had the resistant CCR5 gene.

Scientists at Sangamo BioSciences in Richmond, Calif., have developed a technique using a protein that recognizes and binds to the CCR5 receptor gene, genetically modifying it to mimic the naturally resistant version. The technique uses a zinc finger nuclease, a protein that can break up pieces of DNA, to effectively inactivate the receptor gene. The company is now testing its CCR5-resistant genes in phase-1 and -2 trials with AIDS patients at the University of Pennsylvania.

The Stanford scientists used a similar approach but with an added twist. They used the same nuclease to zero in on an undamaged section of the CCR5 receptor’s DNA. They created a break in the sequence and, in a feat of genetic editing, pasted in three genes known to confer resistance to HIV, Porteus said. This technique of placing several useful genes at a particular site is known as “stacking.”

Incorporating the three resistant genes helped shield the cells from HIV entry via both the CCR5 and CXCR4 receptors. The disabling of the CCR5 gene by the nuclease, as well as the addition of the anti-HIV genes, created multiple layers of protection.

Blocking HIV infection through both the CCR5 and CXCR4 receptors is important, Porteus said, as it hasn’t been achieved before by genome editing. To test the T cells’ protective abilities, the scientists created versions in which they inserted one, two and all three of the genes and then exposed the T cells to HIV.

Though the T cells with the single- and double-gene modifications were somewhat protected against an onslaught of HIV, the triplets were by far the most resistant to infection. These triplet cells had more than 1,200-fold protection against HIV carrying the CCR5 receptor and more than 1,700-fold protection against those with the CXCR4 receptor, the researchers reported. The T cells that hadn’t been altered succumbed to infection with 25 days.

Porteus said he views the work as an important step forward in developing a gene therapy for HIV.

“I’m very excited about what’s happened already,” he said. “This is a significant improvement in that first-generation application.”

He said a potential drawback of the strategy is that while the nuclease is designed to create a break in one spot, it could possibly cause a break elsewhere, leading to cancer or other cell aberration. He said it’s also possible the cells may not tolerate the genetic change.

“It’s possible the cells won’t like the proteins they’re asked to express, so they won’t grow,” he said.

But he said he believes both problems are technically surmountable. He said the researchers’ next step is to test the strategy in T cells taken from AIDS patients, and then move on to animal testing. He said he hopes to begin clinical trials within three to five years.

Though the method is labor-intensive, requiring a tailored approach for each patient, it would save patients from a lifelong dependence on antiretroviral drugs, which have adverse side effects, Porteus noted.

He said he also hopes to adapt these techniques for use against other diseases, such as sickle cell anemia, one of his areas of interest. Porteus works with patients in the Pediatric Bone Marrow Transplant service at Packard Children’s.

In addition to Sawyer, he collaborated with Richard Voit, a former Stanford graduate student who is now an MD/PhD candidate at the University of Texas Southwestern Medical Center, and Moira McMahon, PhD, a former postdoctoral scholar at Stanford who is now at the University of California-San Diego.

The study was supported by a grant from the American Foundation for AIDS Research and by a Laurie Krauss Lacob Faculty Scholar Award from the Lucile Packard Foundation for Children’s Health.

Information about Stanford’s Department of Pediatrics, which also supported the work, is available at http://pediatrics.stanford.edu.

BY RUTHANN RICHTER

Source: Stanford School of Medicin

Misc News/Press Release

Now Report Traffic Violations on WhatsApp Numbers or Facebook: Kullu Police

Published

on

Kullu police whatsapp numbers

Kullu-After 45 people lost their lives and 37 were injured in one of the most tragic road accidents in Himachal Pradesh, the District Police, Kullu, has today issued a notification requesting common people to help curbing traffic rule violations. Referring to the bus accident in Kullu’s Banjar sub-division on Thursday, the police said,

It came to notice that the bus was overcrowded to the maximum extent. Such accidents can be avoided if all of us remain vigilant and follow traffic rules.

The police has issued two WhatsApp numbers (8219681600, 8219681601) where anyone can report traffic rule violations like overloading. Complaints can also be made on district police’s Facebook page. The complainant will have to mention specific details like place, time, vehicle registration number along with a photograph. The identity of the informer will not be disclosed to protect them from any harassment or harm, the notification said.

However, it appears that police in other districts is still waiting for similar accidents before they could take similar initiative to encourage people to bring traffic violations to their attention. Such steps should have been taken long ago. Sadly, it took the sacrifice of 45 lives to woke up the police.

The State Police need to issue directions to all Superintendents of Police to issue such numbers and act on complaints made by common people on social media. It helps the police to enhance their reach and deter traffic rule violations.

However, the people questioned how it would solve the problem relating to shortage of bus services in rural areas. The main cause of overloading is the shortage of bus services. The public is left with no option but to board on over-crowded buses because there is a long gap between services to their respective destinations. The State government and district administration are required to intervene here to sort this problem out. The strictness of police alone can’t solve issues like overloading.

As a ray of hope, the Chief Minister Jairam Thakur yesterday took notice of this issue and said that authorities should identify the crowded stations in the state, which require more transport vehicles. To cope up with the issue of overcrowding in the buses, more permits should be issued to mini buses, maxi cabs and trax etc., he had added.

It’s to be seen how swiftly the authorities act on these directions. Meanwhile, the public is requested to co-operate and avoid boarding in overcrowded buses and to indulge in violation of other traffic rules.

Continue Reading

Misc News/Press Release

After Kullu Bus Accident, CM Jairam Speaks of New Plans to Prevent Such Tragedies

Published

on

Chief Minister Jairam's statement over Kullu bus accident

Kullu-As usual, statements with assurances to take strict measures to check loss of lives in road accidents are being given by the state government after Thursday’s tragic ‘Kullu bus accident.’

This time, the Chief Minister Jairam Thakur has claimed that a special campaign will be launched to identify and rectify the black spots on roads of the state to minimize the road accidents and the new roads would be passed after the approval by the road safety auditors.

He held a meeting of senior officers of the state government held here today.

He said that the earlier procedure of identifying the black spots would be done away and new mechanism to identify and rectify the black spots would be implemented so that the same could be improved instead of waiting for any untoward incident for it. He said that special focus would be laid on improving rural roads having greater traffic frequency.

Special awareness campaign would be launched to sensitize the people regarding over speed, rash driving, drunken driving and use of mobile phones while driving. People would be encouraged to register complaints against the erring drivers. He said that it has been found that 93 percent of accidents occur due to human errors, thus special emphasis would be laid on making driving test more stringent.

Jai Ram Thakur said that all the transport vehicles including taxis would have to display name with the photograph of the driver prominently in the vehicles so that the commuters could know that the driver is well trained and authorized to drive the vehicle.

He said that the condition of transport vehicles would be ensured properly and laxity in this regard would not be tolerated at any cost. He said that automatic testing of the condition of the vehicle would also be done for ensuring that only vehicles with good conditions are on the road. The driver licenses for heavy vehicles would be issued only after ensuring proper test of the drivers. He said that a mechanism such as installing biometric system in driving schools will be adopted so that it could be ensured that the trainee actually undergo training for a specific period. He said that efforts would also be made to provide automatic driving test facilities in all the districts of the State.

Jai Ram Thakur said the authorities should also ensure that there is no overloading in transport vehicles. He said that strict action would be taken against the violators. All the school buses would be regularly monitored and school management would be sensitized about the safety guidelines which is the ultimate objective of the government for the safety of the commuters.

The Chief Minister said that authorities should identify the crowded stations in the state, which require more transport vehicles. He said that to cope up with the issue of overcrowding in the buses, more permits should be issued to mini buses, maxi cabs and trax etc.

Earlier today, Jai Ram Thakur also visited the regional hospital Kullu to enquire the well being of the injured persons of the bus accident.

He said that 39 dead bodies were brought to Kullu hospital on Thursday evening for postmortem and except for three unidentified dead. The remaining bodies were handed over to their family members. As many as 37 injured were referred to Kullu after first aid at Banjar hospital out of which five persons including a tourist died.
He said that seriously injured eight persons were referred to PGIMER, Chandigarh on Thursday evening only whereas three more persons were referred during the midnight.

The district administration has arranged employees to assist the injured referred to Chandigarh. Besides, the doctors of PGIMER, Chandigarh have also been requested for providing treatment to the injured on priority.

The Kullu district administration distributed Rs. 10.35 lakh as immediate relief to the family members of the deceased and injured persons on Thursday night, he informed.

A magisterial enquiry has been ordered to find out the reasons for this bus accident and the enquiry committee headed by ADM, Kullu would submit its report shortly, he said.

Continue Reading

HW Community

Kullu Bus Accident: Death Toll Reaches 44, About 35 Injured, Several Critical

Published

on

By

Deaths in Kullu Bus Accident in 2019


SKullu-
The bus accident in Banjar sub-division of Kullu district has entered the list of biggest tragedies in Himachal Pradesh. Per the last information received, the death toll has reached 44, and over 30 injured are undergoing treatment at Banjar Civil Hospital, Kullu Hospital, and Hosptial in Mandi’s Nerchowk.

Several injured are in critical condition and have been referred to PGI, Chandigarh. The district administration fears a possible rise in the death toll considering the critical condition of the injured.

All deceased are said to hail from about 20 villages in Kullu and Mandi.

The accident has again exposed the State government’s hollow promises to take measures to reduce road accidents. There is still no check on vehicle maintenance and overloading, leave alone appropriately placing crash barriers on cliff-side of the roads.
Causes of Kullu Bus Accident in 2019

This 42-seater bus was carrying over 75 passengers, there were passengers on the roof as well, eye-witnesses confirm. The bus had left for Gada Gushaini from Banjar on Thursday evening at about 3:45 PM. The bus had not covered more than two kms when it plunged into a 500 feet deep gorge near ‘Bheot mod’ and landed in a Khada fter scraping the mountain face.
Banjar Bus Accident in Pictures

As per a Hindi Daily, the driver was untrained and was perhaps driving a bus for the first time.

Locals, who travelled in this bus daily, told another Hindi Daily that the bus was in poor condition and often developed technical snags. According to the Daily, the driver experienced a problem in shifting gears when the bus approached the ‘Bheot mod’ and began to move backwards uncontrolled before skidding off the road.

The Superintendent of Police, Kullu, Shalini Agnihotri said, the exact cause of the accident could only be ascertained after a proper probe.

Chief Minister Jairam Thakur, who visited the hospital to meet the injured said,

The road at the spot was not in bad condition. Prima facie it looks like a case of overloading. A meeting was held today to ensure that such incidents don’t happen in future

The driver is reported to have jumped off the bus. A Daily said the driver survived and fled the spot. However, official confirmation was awaited. Hearing the sound of the accident, the locals from nearby Bhumar village rushed to the spot. As per eyewitnesses, the bodies were scattered all over the steep mountain.

Moreover, the condition of crash-barriers install was quite poor. The single-row crash barriers were not installed properly and held no chance of stopping the bus from skidding off the road.

Pictures of Kullu Bus Accident in 2019
The bus was shredded into pieces and its parts were mangled all over the hill and the stream at the bottom of the gorge. The locals had a tough-time descending the steep hill. With the help of ropes, the bodies and injured were extricated and brought up to the road. Further, the locals formed human chains to carry the injured across gushing water of the stream.

Death toll in kullu bus accident

The accident is not the first of its kind. There have been several such accidents in the past in Himachal Pradesh. On April 9, 2018, 27 people including 24 children were killed in a school bus accident in Nurpur in Kangra district. In April 2017, 45 people had died when an overloaded bus had plunged into a gorge near Nerwa in Shimla district. In 2016, 17 had died when a bus fell into Beas river in Mandi district, 25 in Rampur in 2017, 31 in July 2015 when a bus fell into the Parvati in Kullu. Before that, May 2013, 42 people were killed as a private bus plunged into Beas river.

In 2019 alone, 430 people have died in 1,168 road accidents in Himachal Pradesh by May 31. Between 2009 and 2018, over 11,000 people had died in nearly 31,000 different road accidents in the state.

Every time an accident happens, probes are ordered and government issues statements taking vows to fix black spots and implement violation of traffic rules like overloading and rash driving strictly. Further, assurances are provided to take strict action against all government officials and those responsible for the accident. After a few months, the usual business continues as the government officials go back into deep slumber. No action is ever taken against government officials responsible for negligence.

It’s no different this time too, the chief minister has ordered a Magisterial probe while the state transport minister Govind Singh Thakur has made similar promises. How and what actions will be taken remains to be seen.

It’s seen over the year that no audits are conducted to assess the need for additional bus services. The rural areas face a huge problem due to the lack of sufficient bus services, which is also responsible for overloading. There are limited buses and people are left with no choice but to board on overloaded buses to reach their destinations.

Previous Video

The Regional Transport Office also has a role in such accidents because poorly maintained buses are passed easily. The Public Works Department has all the time to build a corrupt nexus with private contractors, but not to care to install much-needed crash barriers. The district administration and police hardly find time to run regular inspections to see if there is a paucity of bus services or buses are being overloaded.

Continue Reading

Trending