Tuesday, December 1, 2009

New mechanism of blocking HIV-1 from entering cells identified

W
ASHINGTON - Scientists have discovered a new mechanism by which drugs block HIV-1 from entering host cells.

Cellular invasion by HIV-1 requires the concerted action of two proteins on the viral surface: gp120 and gp41. The function of gp41 is to get the viral contents into the interior of the host cells.

This requires the association of two distinct regions of gp41 called N-HR and C-HR. Anti-HIV-1 agents known as fusion inhibitors target the N-HR or C-HR and disrupt their association, which prevents the virus from entering into the host cell. One drug that works like this is Fuzeon (Roche), and there are other agents in the pipeline.

However, blocking the N-HR/C-HR association is not only mechanism by which fusion inhibitors prevent HIV-1 entry, say scientists from the Kimmel Cancer Center at Jefferson. The inhibitors also induce irreversible deactivation of gp41.

“After these drugs bind, they seem to shuttle gp41 into a dead conformation from which the protein cannot recover. Importantly, the speed of this drug-induced deactivation greatly influences how potent a drug is at preventing HIV-1 infection,” said Michael Root, assistant professor of Biochemistry and Molecular Biology at Jefferson Medical College of Thomas Jefferson University.

When the inhibitors bind to the gp41 C-HR, the protein rapidly deactivates before inhibitors have time to dissociate. But when the inhibitors bind to the gp41 N-HR, deactivation takes a very long time, and many inhibitors can readily unbind.

To potently inhibit HIV-1 entry, a C-HR targeting fusion inhibitor can have a relatively low affinity, but an N-HR targeting fusion inhibitor must bind extremely tightly.

A major disadvantage of using Fuzeon and related drugs that target N-HR is the rapid emergence of HIV-1 strains resistant to the drugs.

The new study suggests that the resistance phenomenon is related to the slow speed of gp41 deactivation induced by these fusion inhibitors.

HIV-1 appears to have more difficulty developing resistance to drugs that can remain bound to gp41 for much longer than gp41 takes to deactivate, even if the drugs are no more potent than Fuzeon against the original HIV-1 strain.

Armed with this knowledge, the researchers have developed a new strategy to improve the antiviral activities of N-HR-targeting fusion inhibitors.

The study has been published in PLoS Pathogens. (ANI)

Seawater temperatures in Kuwait Bay rising alarmingly since 1985

W
ASHINGTON - In a new research, scientists have determined that since 1985, seawater temperature in Kuwait Bay, northern Arabian Gulf, has increased on average 0.6 degree Celsius per decade, which is about three times faster than the global average rate reported by the Intergovernmental Panel on Climate Change (IPCC).

Dr Thamer Al-Rashidi and his colleagues from the National Oceanography Centre, Southampton, UK, used data on sea surface temperature (1985-2007) remotely sensed by a number of polar orbiting satellites to assess warming in Kuwait Bay and the Gulf region.

They found that the sea surface temperature of Kuwait Bay increased over the period at an average rate of around 0.62 degree C per decade, with an uncertainty of plus or minus 0.01 degree C.

This is about three times the rate of average global increase estimated by the IPCC.

The increase was greatest in the early summer and least during winter months. The length of summertime increased almost twice as fast as peak summertime temperature.

In 1998 and 2003, the monthly measurements of sea surface temperature showed unusually high peaks in summer temperature coincident with El Nino events - periodic warming of the atmosphere and ocean affecting weather in many parts of the world.

Temperature dipped in 1991, in the aftermath of the Iraqi invasion of Kuwait.

“Dense smoke from the burning of oil fields hung over the region blocking out the sun, and we believe that this atmospheric dimming caused the relatively low summertime temperature peak recorded that year,” said Dr Al-Rashidi, an officer in the Kuwaiti Navy.

However, temperature then increased fairly steadily between 1992 and 2004.

“What all of this tells us is that the global trends reported by the IPCC may not be representative locally,” said Dr Al-Rashidi.

The researchers estimate that about a third (0.2 degree C) of the observed decadal increase in seawater temperature in Kuwait Bay can be attributed to global climate change, while around 13 per cent of the increase (0.08 degree C) is due to human activity along the coast of the bay, especially the direct impacts of power and desalination plants.

The remaining 0.3 degree C (50 per cent) of decadal warming appears to be due to changes in regional drivers, including circulation and mixing of seawater in the Arabian Gulf, the influence of the dominant north-westerly wind, freshwater discharge from the Euphrates and Tigris rivers, and sand storms. (ANI)

Sugru being hailed as best invention since Sellotape

L
ondon, Dec 1 (ANI): Sugru, a new invention by an art student based in a warehouse in east London, is being hailed as the most exciting product since Sellotape or Blu-Tack by design experts.

The product has been invented by Jane Ni Dhulchaointigh, a former art student, and is determined to give old and broken household objects a new lease of life.

Sugru, an Irish word for play, is a silicone, which can be used to glue things together, patch leaky boots, or create a variety of custom-made handles, hooks, and feet for wobbly chair legs.

It looks-like kids’ modelling clay, which once out of its airtight packet, can be moulded into any shape and fixed onto leather, metal, ceramic, wood and plastic.

After about 24 hours it “cures” and will adhere to any substance with the strength of ultra strong glue but it does not become rock hard. Instead, it stays slightly flexible.

“I was inspired by the internet and the whole idea of user-generated content. I wanted something that people could make their own and use in their own way,” the Telegraph quoted Dhulchaointigh as saying.

“A lot of stuff gets thrown away not just because it is broken but because it has stopped being useful or fashionable. If you can adapt it or hack it that’s got to be better than putting it in the bin,” Dhulchaointigh added.

The product has caught the eye of design experts who have tested it out and described as the best thing since Sellotape and Blu-Tack.

Guy Robinson, the head of the design consultancy Sprout Design, said: “I think this will really take off. I just hope people realise how great it is. It allows you to customise your own stuff by making it ergonomic. Too much industrial design is not ergonomic enough.”

Robinson said that he had already used it to make custom-made handles for hospital crutches. (ANI)

India-Bangladesh Home Secretaries to discuss counter-terrorism

N
ew Delhi, Dec 1 (ANI): Home Secretaries of India and Bangladesh are expected to discuss cross-border terrorism, illegal immigration, smuggling of narcotics and militants in the northeast today.

G K Pillai will lead the Indian delegation and is expected to seek assistance from Dhaka in the handling of security issues.

The necessity for an extradition treaty between the two countries is also expected to be taken up.

India is optimistic about Bangladesh''s support in fighting militants, as the Sheikh Hasina government has decided to fight both terrorism and fanaticism more firmly.

Matters concerning illegal immigration are also likely to crop up.

Smuggling of narcotics, fake currency and other issues will also be raised. (ANI)

Water to soon cost as much, if not more than electricity in Delhi

N
ew Delhi, Dec.1 (ANI): Residents of Delhi may soon find water costing as much, if not more than electricity, as the Delhi Government on Tuesday announced new tariff slabs for water supply. Water supply charges have increased from nearly one-and-a-half to almost three times the prevailing prices.

According to the new slabs, for 10,000 litres of water will cost Rs.82, for 10,000 to 20,000 litres; Rs. 470, and for 20,000 litres and above usage; Rs.180.

The new rates will come into effect from January 1,2010. It also necessitates for all to have a meter in place till Dec.31,2009.

The tariff was last increased in 2005.

Due to a lot of water meters in the city being defunct and many water connections unmetered, the residents were charged on average consumption basis.

The cash-strapped Delhi Jal Board (DJB) took the decision to revise its tariff rates at a board meeting held on Monday.
(ANI)

US can apply four policies to encourage change in Pak mindset: Expert

W
ashington, Dec.1 (ANI): An expert on South Asian affairs has said that the US can pursue, support and encourage Pakistan in its transition from tolerating to fighting the various militant groups on its territory, with the help of four policies.

According to Lisa Curtis, senior research fellow in the Asian Studies Center at The Heritage Foundation, the United States should first continue to support Pakistan with its military operations in the tribal border areas and in developing hold and build strategies that establish government writ in the region and eventually bring reform that incorporates the areas into the larger Pakistani political framework.

Second, the US needs to convince Pakistan that cases against terrorists who attack India should be treated no differently than cases against terrorists who act in other parts of the world. By treating terrorists focused on India with kid gloves, Islamabad has created a permissive environment for terrorists to operate more generally, especially since many of the various terrorist groups share a pan-Islamist ideology and provide each other with tactical cooperation and logistical support.

Third, Washington should work with Pakistani civilian leaders to build a consensus within Pakistan against extremist messages and ideologies that foster terrorism.

According to Curtis, the U.S. can also provide support for interfaith dialogue and activities in Pakistan that promote religious pluralism and empower mainstream religious leaders to actively engage and challenge radical interpretations of the religion of Islam, and lastly, an essential part of stabilizing Afghanistan and Pakistan involves encouraging Indian and Pakistani officials to develop a different security paradigm for the region that is based on regional economic integration and trade. This new paradigm would allow them to focus on containing dangerous non-state actors that threaten stability in all three countries.

While taking note of President Obama’s decision not mediate directly in the Indo-Pakistani dispute, but to make efforts to help both countries feel secure, Curtis says that as far as Pakistan is concerned, the United States has no choice but ensure that it does improve that country''s sense of security.

“We often hear about the ''trust deficit'' Pakistanis feel toward the United States because of the cut-off of US aid programs to Pakistan in the early 1990s over its pursuit of nuclear weapons. Pakistanis repeatedly voice their view that the United States is a fickle and untrustworthy partner that pursues its own national security interests at the expense of Pakistan,” Curtis says in her article for the Heritage Foundation.

“But demonstrating that the lack of trust in the US-Pakistan relationship cuts both ways, Secretary of State Hillary Clinton on her recent visit to the country questioned Pakistani sincerity over its efforts to capture senior al-Qaeda members. While Clinton''s statement stood out for its bluntness, other senior US officials have echoed similar sentiments,” she adds.

“It has become something of an open secret -- or painful truth -- that Pakistan and the US are working at cross-purposes in Afghanistan. The real question is how long the US-Pakistan partnership can be sustained under the current strain of our divergent goals in Afghanistan, especially as US military deaths rise,” she asks.

She concludes that until there''s a meeting of the minds on Afghanistan, the US-Pakistan relationship will be plagued by mistrust and suspicion. (ANI)

India will find facts in China''s objections to road construction in Ladakh: Raju

N
ew Delhi, Dec 1 (ANI): Minister of State for Defence Pallam Raju today said India would find out the reasons behind China''s objection to the road construction in the Ladakh region of Kashmir.

In a confrontational act on Monday, China had objected to road construction in Demchok near the Line of Actual Control in the Ladakh region of Kashmir.

Work has been stopped on the road project being built under the National Rural Employment Guarantee Scheme (NREGS).

The eight-kilometer stretch of road that was being constructed to improve road connectivity, was providing employment to local residents.

Demchok village is the last inhabited area before the Line of Actual Control near the Chinese border.

"We will find out the facts of the matter but I think some of these things happen if there is difference in perception of the border. I am guessing that that must be the reason but we will check into in to the matter," Raju said in a written reply in Parliament.

The Minister of State for Defence also added that the strengthening and procuring of arms by China must not bother India.

"See, I think we don''t need to be unnecessarily alarmed, as a regional power they will strengthen their infrastructure, they will procure their arms, and we are doing what we have to do for strengthening what is our land. We don''t have to be unnecessarily worried about what other countries are doing as far our programmes are going on smoothly, we are doing adequately to strengthen ourselves," he said.

India has a border dispute with China and despite several rounds of talks, the issue is still pending.

India disagrees with China''s claims stating that apart from occupying 90,000 sq km of land on the eastern side of the border; China has also occupied 38,000 sq km of territory in Aksai Chin plateau in the western Himalayas.

On the issue of army officials allegedly involved in a land scam in eastern Siliguri, Raju said the concerned authorities have been asked to probe the matter.

"Whenever there is an irregularity in any procedure or any of the functioning, the concerned service looks into the matter and it takes appropriate steps. The ministry had directed the service, which is army in this case, to look into the matter and they will take appropriate action," he said. (ANI)

Rahul Gandhi takes kids' questions at Parliament

I
t was an unusual Question Hour at Parliament. School children who were on a field trip to watch Parliament in action ran into Rahul Gandhi.

The General Secretary of the Congress party was seen mingling with the students, and answering their questions.

Chidambaram promises sharing real-time info on foreigners

S
tung by the controversy over issuance of visa to terror suspect Tahawwur Rana, the government has decided to link all offices dealing with providing travel documents to foreigners to ensure sharing of information on a real-time basis.

Under this proposal, the offices of Foreigners' Division, Foreigners' Regional Registration Office, Ministry of External Affairs and all its Missions abroad will be interlinked, Home Minister P Chidambaram said on Tuesday.

"This project is to ensure that (real-time) kind of connectivity takes place so that information is shared instantly on a real-time basis and decisions can therefore be taken on a real-time basis," he said.

Chidambaram said the FRROs, FROs and the foreigners' division are all now on a "stand-alone" basis with no real-time information sharing when a visa is issued.

"As it was issued by Counsel General in Chicago, there was no real-time information. So what we need is real-time sharing of information among all the offices which are dealing with foreigners," he said.

The move comes in the wake of the reports that the Indian Consulate in Chicago had issued visa to Rana, a Pakistani-Canadian, without referring his case to the Ministry of Home Affairs.

However, the consulate had claimed that there was no need to refer cases where an individual was a Pakistani citizen but had become a citizen of another country and surrendered his citizenship of Pakistan.


"It will be the connectivity between all the foreigners immigration offices, the MEA and all the missions abroad so that they will all be on real-time connectivity that is primarily is the whole purpose," Home Secretary G K Pillai said while describing the revamp of foreigners' divisions.

Rana was arrested by the FBI along with David Coleman Headley, a US citizen, for plotting terror attacks in India and Denmark. Indian officials also suspect their involvement in the 26/11 Mumbai terror strikes.

ULFA chief still in Assam's railway employee list

T
insukia, Dec 1: While the Assam government is leaving no stone unturned in eliminating terrorists from its soil, they have forgotten to do one crucial task, that is to remove the name of the dreaded United Liberation Front of Asom (ULFA) chief Paresh Baruah from its railway employee list, inspite of him not attending office over the past decades.

It has come to light that Paresh Barua got the porter's job with the railways in 1978 in Tinsukia division in eastern Assam under sports (football) quota. He left office when he formed ULFA in April 1979.


"The name Paresh Baruah is significant and he is absent from duties for a very long period. His salary slip shows zero, but he is still an employee according to the records," said Sanjoy Mookerjee, deputy railway manager of the Tinsukia division,

However, the official said that it could not confirmed whether the name registered under the employee list is actually the ULFA chief as they had no photo of the employee in their record.

Barua who figures in the India's most wanted list, faces a maximum penalty of death sentence against him in Assam. The interpol has also issued red corner notices against him.

He is now reported to be taking shelter in China.