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

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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.

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“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

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Nauni Varsity Admissions Open for Diploma in Fruit, Vegetable Processing & Bakery products

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Nauni varsity admissions for diploma

Solan-The Dr YS Parmar University of Horticulture and Forestry, Nauni has invited applications for its one-year Diploma in Fruit and Vegetable Processing and Bakery products. The diploma will be run by the Department of Food Science and Technology of the university.

This year, the university has also reduced the fee charged for the diploma to Rs 5000. Earlier, the fee for this diploma was Rs 20,000. The decision was taken to ensure that more and more people can apply for the programme.

In addition, the programme has also been linked to the Skill Development Allowance scheme of the Government of Himachal Pradesh. Any person enrolled in the programme can also apply for this allowance.

The minimum educational qualification for this diploma programme is Class 10+2 with at least 40 per cent with no age cap for admission. The last date of application is 17 January 2019 and the counselling will be held on 19 January.

A total of 35 seats are available in the programme. Prospectus and application form can be downloaded from the university website(www.yspuniversity.ac.in).

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234 Ambulance Roads in Shimla City Declared ‘No Parking Zones’, Parking woes to Intensify

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List of ambulance roads in Shimla City declared no parking zones

Shimla- The parking woes have intensified in Shimla City as the District Magistrate of Shimla, Amit Kashyap, issued an official notification on December 19, 2018, in which 234 ambulance roads in Shimla city were declared as “No Parking Zones.

As per the notification, based on the report received from the Superintendent of Police, Shimla, it was found that the residents, as well as outsiders, had turned link roads into unauthorized parking spaces, which results into huge traffic jam and inconvenience to the smooth passage of ambulances carrying patients along with the general the public.

Therefore, the District Magistrate declared all the following 234 ambulance roads as “No Parking Zones”:


He said the decision was taken keeping in view the necessity of smooth flow of traffic and passage to ambulances on ambulance roads in Shimla City.

As per the notification, the matter was highlighted as the local residents of the Middle Cemetery, upper Gahan, Bhatttakufar, Dhingu Bawari, Frud, Lower Gahan, and Nerridhar had requested to declare the ambulance roads leading from Dhigu Bawari to Lower Gahan and From PWD Workshop Bhattakuffer to Jai Moti Bhawan (Cemetary) as “No Parking Zone” as some of the people park their vehicles on these roads resulting in traffic jams and obstruct ambulances.

While the government has a policy to allow buying vehicles only if an applicant could provide evidence of having a parking space, there are a large number of cars which were either bought before the formation of this policy or are registered in other districts of the State.

A section of vehicle owners have expressed unrest against this decision and argued that it was not fair, as the government did not provide sufficient authorized parking spaces in localities.

Having a personal parking space doesn’t matter as soon as an individual drives to other parts of the city. Sufficient parking spaces based on the required capacity of a particular Ward or locality are needed to fix this problem, and it is apparently the government’s job

said a resident of Khalini, Shimla.

On the other hand, the majority of the general public has supported the decision expecting that it would make these roads more convenient and smoother for traffic.

However, the district police is likely to face a lot of resistance from local residents while ensuring compliance with the orders passed.

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Opposed to Tribal Minister’s promise in Assembly, FRA claims of Kinnaur tribals rejected to favor hydro-power company

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HP Govt Rejects FRA Claims of Kinnaur villagers

Doling out forest land to the company but cannot grant tribal rights, shows government priorities; Empty promise on FRA made in Vidhan Sabha: Lippa Forest Rights Committee

Kinnaur: Barely few days after tall promises were made about implementation of the Forest Rights Act in the Legislative Assembly by the Tribal Minister Ramlal Markanda, the District Level Committee (DLC) at Rekong Peo has rejected the Individual Forest Rights claims of 47 tribal claimants of Lippa Village in Kinnaur District, said Forest Rights Committee, Lippa in a media statement. The order of the DLC, which was not signed by the three non-official members of the committee out of the six members, was termed as illegal and unjust by the Lippa Forest Rights Committee.

We condemn this order led by the Deputy Commissioner because the arguments for not recommending the 47 claims are totally baseless. It is clear that the officials are ignorant about the provisions of the FRA 2006. The DLC has just blindly accepted the incorrect decision taken by the bureaucratic members of the Sub Divisional Level Committee, where as we have provided the DLC detailed objections to the same, based on the provisions in the Forest Rights Act 2006,

said Subhash Negi of President of the Forest Rights Committee, Lippa.

The order of the DLC dated December 17, 2018, gives three arguments for not recommending the claims. The first is that the claims are not from ‘unsurveyed villages’ but from revenue villages. The second argument is that the evidence submitted by the claimants does not provide proof of three generations. The third argument says that the act was only for those who are primarily residing in forests and dependent on the forest land, implying that the claimants were not eligible. As per the FRC as well as the written objection submitted by the Individual claimants, all three arguments have been legally countered.

This Act is not just for ‘unsurveyed villages’ but is also applicable to revenue villages with residents who are dependent for their ‘bonafide livelihood’ needs on forest land. This has been adequately clarified by the Ministry of Tribal Affairs in a circular dated June 9, 2008.

This argument by the officials that claimants from revenue villages are not eligible is ridiculous because all 17,503 FRCs in Himachal are formed at Revenue Village level. If we go by their argument then the FRA 2006 cannot be implemented in Himachal at all since there almost no forest villages here. The FRA 2006 is applicable where ever people depend on forest land,

according to Prakash Bhandari, of Himdhara Collective advocating for the implementation of the Act.

Secondly, the Act requires the three-generation evidence clause only for non-tribal people (referred to as Other traditional forest dwellers in the Act), Whereas the applicants in the case of Lippa are all belonging to the category of Scheduled Tribe. Thirdly, the SDLC and DLC have both recommended the Community forest rights for the Lippa village without any objections.

This is s a partial reading of the law. While issuing the CFR title we are considered as ‘primarily residing in the forest, forest dwellers’, while considering the individual claims won’t the same criteria apply? This shows that the officials do not have even basic knowledge of the act,

added Negi.

It needs to be noted that individual claims can be made, as per the law for both housing as well as land being cultivated. The Gram Sabha of Lippa has recommended all 47 claims almost 6 months ago.

The decision of the DLC is also contentious because the forest land under Lippa Village was leased out to Himachal Pradesh Power Corporation Limited for the Kashang Stage 2 and 3 hydropower projects by the State cabinet on 0ctober 13, 2018. The Paryavaran Sangharsh Samiti, Lippa which has been opposing the forest clearance to the project, has objected to the cabinet decision taken on the grounds that it “is a clear violation of not only of the PESA, FRA, 2006 and the NGT judgment dated 5th May 2016 but also the state’s own legislation”.

In 2016 the Green tribunal had ordered that the forest rights of the communities be settled as per provisions of the FRA and only after that the project proponents could approach the Gram Sabha for NOC.

The lease order was made under Himachal Pradesh Lease rules, 2013 for an underground area of 06-03-20 ha, situated in Up-Mohal Lappo of the Lippa Village. According to Tashi Chewang, Secretary Paryavaran Sanrakshan Sangharsh Samiti, “Rule 11 sub-rule 2 (iii) of the Himachal Pradesh Lease Rules, 2014 clearly states that

In Scheduled areas, the Sub-Divisional Officer (Civil) shall also refer the lease application to the concerned Gram Sabhas for consultation. He shall proceed further only after obtaining the Gram Sabha’s resolution

in this regard.

But during the whole process of leasing out land to HPPCL, neither the SDM has ever approached or consulted with the Lippa gram sabha nor the gram sabha ever passed any resolution in this regard.

The ‘Vanya Prani, Van Evam Jaivividhta Sanrakhsan Samiti’ formed under rule 4(E) of the FRA 2006 by Lippa Gram Sabha has issued a legal notice to the Chief Secretary and 6 other high level officials challenging the lease order.

The people of Lippa village for the last ten years have been struggling against the projects because of the havoc that diversion of the Kerang Khad would cause. Kerang is a perennial stream that flows adjacent to the Lippa village and it helps in flushing out the huge silt and debris that come towards the village from another stream called the Pager Khad.

If the Kerang is diverted by the project then the Pager khad will destroy the village, added Chewang. The Chilgoza forest and other biodiversity on which the livelihood of locals is directly dependent will also be impacted by the forest diversion and construction

, according to members of the Paryavaran Sanrankshan Sangharsh Samiti.

Our struggle is for our day to day survival and livelihood using every law that is available for protection of tribal rights. But when the State is violating all these constitutional laws and provisions, what is the community to do?

asks R.S Negi leader of Him Lok Jagriti Manch, Kinnaur, a platform for tribal rights in the District.

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