New discovery reveals how protein protects cells from HIV infection

 by bio_chief16

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“Finding offers potential new drug targets aimed at slowing progression of disease”

A novel discovery by researchers at NYU Langone Medical Center and colleagues reveals a mechanism by which the immune system tries to halt the spread of HIV. Harnessing this mechanism may open up new paths for therapeutic research aimed at slowing the virus’ progression to AIDS. The study appears online ahead of print today in Nature Immunology.

“A lot of research on viruses, especially HIV, is aimed at trying to understand what the body’s mechanisms of resistance are and then to understand how the virus has gotten around these mechanisms,” said co-lead investigator Nathaniel R. Landau, PhD, a professor of microbiology at the Joan and Joel Smilow Research Center at NYU School of Medicine.

The research focused on a protein called SAMHD1. Recent studies have found that immune cells, called dendritic cells, containing the protein are resistant to infection by HIV. Since the discovery, scientists have sought to understand how SAMHD1 works to protect these cells, with hopes that science might find a way to synthetically apply that protection to other cells.

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Dr. Landau and his team are now able to provide an answer: 

When a virus, like HIV, infects a cell, it hijacks the cell’s molecular material to replicate. That molecular material is in the form of deoxynucleotide triphosphates (dNTPs), which are the building blocks for DNA. Once the virus replicates, the resulting DNA molecule contains all the genes of the virus and instructs the cell to make more virus.

Researchers wanted to understand how cells containing the SAMHD1 protein are protected from such hijacking. They found that SAMHD1 protects the cell from viruses by destroying the pool of dNTPs, leaving the virus without any building blocks to make its genetic information – a process researchers call nucleotide pool depletion. “SAMHD1 essentially starves the virus,” Dr. Landau said. “The virus enters the cell and then nothing happens. It has nothing to build and replicate with, so no DNA is made.”

As a result, the most common form of HIV does not readily infect these cells. Instead, the virus has evolved to replicate mainly in a different kind of cell, called CD4 T-cells, which do not contain SAMHD1 and therefore have a healthy pool of dNTPs. Dr. Landau explained that the virus has evolved in such a way that it may deliberately avoid trying to infect immune cells with SAMHD1 to avoid alerting the greater immune system to activate a variety of antiviral mechanisms to attack the virus.

Viruses that are related to HIV, like HIV-2 and SIV, have developed a protein called viral protein X(VPX) that directly attacks SAMHD1. This allows the virus to infect dendritic cells, an important type of immune cell.

“Viruses are remarkably clever about evading our immune defenses,” Dr. Landau said. “They can evolve quickly and have developed ways to get around the systems we naturally have in place to protect us. It’s a bit of evolutionary warfare and the viruses, unfortunately, usually win. We want to understand how the enemy fights so that we can outsmart it in the end.”

Understanding the mechanism by which SAMHD1 provides protection to cells may provide a new idea about how to stop or slow the virus’ ability to spread, Dr. Landau explained. Potential future research efforts, for example, might focus on finding a way to increase the amount of SAMHD1 in cells where it does not exist, or to reduce the amount of dNTPs in cells vulnerable to infection.

“Over the past few years, a number of these natural resistance mechanisms have been identified, specifically in HIV, but some have potential applications to other viruses, as well,” he said. “This is a very exciting time in HIV research. Many of the virus’ secrets are being revealed through molecular biology, and we’re learning a tremendous amount about how our immune system works through the study of HIV.”

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Courtesy NYU School of Medicine

New way to create stem cells

THE UNIVERSITY OF QUEENSLAND

Image: Pgiam/iStockphoto University of Queensland scientists have developed a world-first method for producing adult stem cells that will substantially impact patients who have a range of serious diseases. The research is a collaborative effort involving UQ's Australian Institute for Bioengineering and Nanotechnology (AIBN) and is led by UQ Clinical Research Centre's (UQCCR) Professor Nicholas Fisk. It revealed a new method to create mesenchymal stem cells (MSCs), which can be used to repair bone and potentially other organs. “We used a small molecule to induce embryonic stem cells over a 10 day period, which is much faster than other studies reported in the literature,” Professor Fisk said. “The technique also worked on their less contentious counterparts, induced pluripotent stem cells. “To make the pluripotent mature stem cells useful in the clinic, they have to be told what type of cell they need to become (pre-differentiated), before being administered to an injured organ, or otherwise they could form tumours. “Because only small numbers of MSCs exist in the bone marrow and harvesting bone marrow from a healthy donor is an invasive procedure, the ability to make our own MSCs in large number in the laboratory is an exciting step in the future widespread clinical use of MSCs. “We were able to show these new forms of stem cells exhibited all the characteristics of bone marrow stem cells and we are currently examining their bone repair capability." AIBN Associate Professor and Co-Investigator on the project, Ernst Wolvetang said the new protocol had overcome a significant barrier in the translation of stem cell-based therapy. “We are very excited by this research, which has brought together stem cell researchers from two of the major UQ research hubs UQCCR and AIBN,” Associate Professor Wolvetang said. The research is published in the February edition of the STEM CELLS Translational Medicine journal. Editor's Note: Original news release can be found here.

LEDs that Burn 10 Times Brighter

Startup Soraa thinks it can make LEDs cheap enough to replace regular bulbs.

• BY PHIL MCKENNA

Audio »

Bright idea: Soraa's MR16 LED matches the output of a 50-watt halogen.

Soraa

LED lightbulbs promise a highly efficient, nontoxic, long-lasting alternative to today's incandescent and halogen lightbulbs. Lighting entire rooms using LEDs has, however, proved both technically challenging and expensive.

Soraa, a startup based in Fremont, California, has developed a new type of LED that it says generates 10 times more light from the same quantity of active material used in other LEDs. The company's first product is a 12-watt bulb that uses 75 percent less energy than a similarly illuminating 50-watt halogen bulb. Company officials would not disclose the cost of the bulb, but say it will pay for itself in less than one year through energy savings. 

LEDs contain a semiconducting material that lights up when current passes through it, and are commonly used for low-light applications such as illuminating computer screens.

LEDs are usually made by growing a thin layer of gallium nitride on top of a sapphire, silicon carbine, or silicon substrate. Soraa takes a different approach. It uses gallium nitride for the substrate. This reduces a mismatch in the crystal structure between the two layers, which causes the performance of LEDs to diminish as current densities increase. By reducing such mismatches, or "dislocations," by a factor of 1,000, Soraa officials say they can push 10 times more current through a given area of active layer material. The increase in current density results in a tenfold increase in LED brightness.

Gallium nitride is significantly more expensive than either sapphire- or silicon-based materials, but the increased output more than makes up for the added cost, says Soraa CEO Eric Kim. "We have a simple, highly dense light source that reduces system design, making it the most cost-effective light, period," Kim says.  

Other 50-watt-equivalent LED lights typically combine multiple LEDs into a single bulb. The increased brightness of Soraa's LEDs means it only has to use a single chip or diode.

Soraa's LEDs could prove to be expensive, however. Colin Humphreys, director of research at the University of Cambridge's Department of Materials Science and Metallurgy, says growing gallium nitride in bulk is difficult and time-consuming.

"I pay about $30 for a six-inch diameter silicon wafer or a two-inch diameter sapphire wafer, and about $500 for a one-inch diameter gallium-nitride wafer," he says. Humphreys foundedCamGaN, a startup developing LEDs that use gallium nitride on a silicon substrate. The company was recently acquired by Plessey Semiconductors.  "[Soraa] may well be able to produce gallium-nitride wafers more cheaply, but surely not at the same price as for silicon and sapphire."

Kim says Soraa has a novel method of fabrication that significantly reduces the cost of gallium-nitride production. He adds that the cost of substrate is only a "single digit percent" of the total cost of the company's bulbs. Soraa has received more than $100 million in startup funding, and plans to ship its first bulbs for commercial applications by the end of this quarter.

Upgrade Your Hard Drive to Infinite Size

A competitor for Dropbox offers a way to seamlessly link your computer to the cloud.

TOM SIMONITE 

I wrote last year about a startup offering a simple program that used cloud storage to trick your computer to behave as if it had infinite storage space. Now invites to a trial version of that program, Bitcasa, are starting to trickle out.

I was lucky enough to receive one and tried out both the Mac and Windows versions, of which the latter is described as “alpha” and seems not fully polished. But going by the experience of using the Mac version, Bitcasa is promising. I downloaded a 27 megabyte application and a few seconds later was being told by the Finder that I had a hard drive with over 500 terabytes of free space, an instant upgrade of more than three thousand times. In fact, Bitcasa will swallow as much data as you can push at it, I was told last year, but they weren’t able to hack an infinity sign (∞) into Mac OS.

Once you install Bitcasa it prompts you to choose which of your folders to “cloudify”. Cloudified folders are uploaded to Bitcasa’s cloud right away and get a Bitcasa logo added to their icons in the Finder. Any time you save, copy, or paste new files into a cloudified folder they also uploaded. The clever bit is what happens when you try and pile in more data than there is space for on your hard drive. Bitcasa arranges for some of your data to be stored only in the cloud, not on your PC, but it creates the illusion that all your files are stored locally. You can see them there using a file browser or a program’s open dialogue, but some files will be retrieved from the cloud when you try to open or access them.

That trick could make it much easier to manage a vast movie, music or photo collection larger than your hard drive, for example. Bitcasa could make them appear to be on your computer at all times so you could dig up an old song or photo with a few clicks. They'd take some time to download if you tried to open them, but it would be less hassle than using an external drive.

That design does create the capacity for you to be surprised by how long it takes to access a file, or even to find you can’t access all your data. Last year I heard their software would try and guess what you are most likely to need access to offline and make sure it's stored locally. I haven't used it long enough to tell if that's the case for the beta version. My guess is that Bitcasa’s success will hinge on how well they can help users deal with a service designed to be forgotten about that very occasionally reminds you of its existence in a frustrating way, when you can’t access your data.

It adds up to a very different proposition to Dropbox, which is priced in a way that encourages you to use it to sync important files you need frequent access to, not for long-term backups (The personal version offers 2 GB for free, 50 GB for $9.99 a month and 100 GB for $19.99 a month). Bitcasa also requires less reorganizing of how you manage your data because of it’s neat integration with your computer’s file system, rather than requiring you to put stuff you want synced in a dedicated folder.

Bitcasa aren’t talking to the press right now, but they did confirm in a tweet last month that Bitcasa is free to use during the beta period and will cost $10 a month afterwards last month. Mobile versions appear to be in the works, going by seeing tweets about the company hiring mobile developers. Bitcasa’s Twitter feed also teased forthcoming “Big news for gamers coming soon” earlier in the week. They haven't given any clues about how soon they will properly launch the service. Some beta users are being given invites to share, though. The first five people that click this link should receive one of my invites. If you get one, let us know in the comments how you liked Bitcasa.

Sai Katha (Hindi) - Shri Sai Baba Ka Shirdi Mein Dobara Aana

From Suicide to Redemption

“Or I will kill the ten-headed Ravana of great strength. Whatever has happened to Sita, at least her abduction will be avenged.” (Hanuman, Valmiki Ramayana, Sundara Kand, 13.49) rāvaṇam vā vadhiṣyāmi daśagrīvam mahā balam || kāmam astu hṛtā sītā pratyācīrṇam bhaviṣyati | The supporters of Hanuman    will rejoice at the mere mention of this verse. Screams of joy, adulation, victory, triumph, hope, and good feelings abound when those who love Hanuman hear the words of this verse, which is found in the sacred Ramayana   , the wonderful poem describing the pleasant and heroic acts of the Supreme Personality of Godhead, Lord Rama   . Yet, ironically enough, this verse touches on the victory over mental demons of a seemingly ordinary monkey, a being not belonging to an advanced species. Hanuman is no ordinary figure, though, as his victory over the debilitating forces of evil concentrated on the island of Lanka are well documented in the Ramayana, with special attention given in its Sundara-kanda, or book of beauty. The Ramayana is about Rama, and since Hanuman is always tied to the Lord in consciousness, hearing about him is as good as having the Lord’s company. Who hasn’t suffered from the effects of mental demons every now and then? The Vedas, the ancient scriptures of India, account for every type of misery encountered in this world by grouping them into three categories. Adhyatmika miseries are those which arise from the body and mind. These pains would seemingly be the easiest to fix. For example, if we’re plagued by bad thoughts, just turn the situation around and think of good things. If we’re feeling sick, take some medicine. If we’re not getting enough sleep, just sleep more. Obviously the practical application of the solutions isn’t so easy. The mental demons are especially the toughest to get over, for as soon as negative thoughts creep in, a sea of sorrow starts to rise and fill up the mind until a large ocean has been created. The despondent individual, the owner of the mind, is stuck on one side of the ocean and the length and breadth of the water seem too vast to overcome. Finding your way into this helpless situation is not very difficult. You just need a few setbacks, grouped together, one after another. Then you need to start fearing what will happen if you never succeed, if you never find your way out. Think this way long enough and pretty soon you’ll find yourself in a situation where you want out. “O poor twisted me. I’m drowning in my sorrows and I have nothing to rescue me. Life has treated me poorly, as it seems that wherever I go, a black rain cloud constantly drenches me. No one else is wet; just me. In fact, because of my failures, so many other people are going to suffer. Therefore it is better if I just end it all, escape from the tumultuous life that I never figured out how to survive in anyway.” In this way the mind can go from a peaceful existence to the brink of suicide in a few short steps. The material existence is very conducive to this type of defeatist attitude. After all, the land is created with this defeat in mind. The jivas, the individual spirit souls basking in the company of the Supreme Person in His imperishable realm, have no need to leave their engagement, devotional service   . Only when there is a desire to compete with God, to surpass His abilities in creation, maintenance and destruction, can there result a negative condition. The threefold miseries of life only exist in a temporary world devoid of God’s personal association. What is the difference between personal and impersonal? The proprietor starts a business and sets the wheels in motion for its operation, but this doesn’t mean that he’s always at the jobsite. There is generally a stark difference in behavior between the days the boss is in the office and the days he isn’t. When the company owner shows up to work, everyone has to be on their best behavior, as they have to show him that they are working hard. Yet as soon as the boss leaves, it’s party time, provided that another strong hand of authority is not there to watch over everyone. If someone like this is present, their influence likely isn’t as great as the boss’s. Despite the differences in behavior, the presence of the owner is still perpetually there, as his proxies and energies keep the business running. Similarly, even if we deny the existence of God or just forget about Him because of being distracted with other work, it doesn’t mean that the Lord’s influence is not present. It is said that not a blade of grass can move without God’s hand. He created the material elements of earth, water, fire, air and ether and the subtle elements of mind, intelligence and false ego. He controls the heat and the rain, and He is responsible for the creation and destruction of the universe in repeating cycles. All of this information is there in the Vedas, and it shouldn’t be surprising to hear. In practically every spiritual tradition the same information is presented, except maybe not with as much detail. “O Arjuna, I control heat, the rain and the drought. I am immortality, and I am also death personified. Both being and nonbeing are in Me.” (Lord Krishna, Bhagavad-gita   , 9.19) The material world introduced miseries because the boss, the Supreme Lord, is not personally present. He has expansions and different manifestations that reside within every atom, but this influence doesn’t necessarily direct anyone towards anything. For example, in the living entity there reside two souls. One soul is the essence of identity and the other represents the Supreme Lord. Though God’s expansion, the Paramatma, is responsible for all the visible results we see, it is the individual atma, the soul, that takes responsibility for driving the ship, deciding where to go and what to do. The Supersoul has no say in this, as He is an impartial witness, simply watching everything going on and waiting until the day when the individual soul will turn its mind towards spiritual life. In the imperishable land, there is no distinction between personal and impersonal. God’s features, pastimes, names and other things directly relating to Him are not hidden. Nor is anyone there aloof to His presence. Rather, everyone engages in working for His pleasure. Even if He is not directly in front of them, they think of Him nonetheless. With the Supreme Lord thinking about Him is as good as being with Him. In this way even if one is trapped in a material realm and suffering from the threefold miseries of life, they can turn their area into a replica of the spiritual world by acting in the Lord’s interest. How do we do this exactly? Moreover, how do the effects manifest? We can take the wonderful Shri Hanuman as an example to learn from, though his behavior should not be directly imitated. The great ones make it look easy, but if anyone were to try to repeat their feats of strength and bravery, they would come up short. Hanuman was purposefully put into the situations he found himself in by the hand of God, because the Lord knew that Hanuman was up to the challenge. Though God, who is known as Krishna in His original form, does not have a personal presence in the material land, He can choose to make appearances in it whenever He wants. Depending on the time and circumstance, He will take on different spiritual manifestations. In the Treta Yuga, Krishna appeared as the pious and handsome prince of Ayodhya, Lord Rama. One way to tell if someone is God is by noticing their exquisite beauty. Rama was a warrior prince, and for an important period of time in His life He roamed the forests without any royal garb. In fact, the stipulation was that He had to roam around like a beggar, though He was allowed to take His weapons with Him, His bow and arrow set. Yet even when roaming the forests, Rama looked more beautiful than anyone else. Accompanied by His wife Sita Devi    and younger brother Lakshmana   , Rama’s beauty increased all the more. When the different villagers would see Rama and Lakshmana walking by, they would remark that the creator must have first made them and then used whatever he had left over to populate the rest of the world. Those with a pure vision could become immediately liberated from the pangs of material existence by seeing Rama and Lakshmana. Devotion to God as a practice is known as bhakti-yoga, or devotional service. There are specific tastes that come from this interaction, tastes only available to those who recognize, honor and cherish the personal forms of the Supreme Lord, understanding that He is a personality just like everyone else. In the abstract vision of God or in the impersonal mode of worship, the transcendental tastes are absent. Hence these other paths are always inferior to bhakti. Looking upon the Lord with amazement and feeling a thrill throughout the body is one method of worship, but service can also manifest through direct acts, work performed for the Lord’s satisfaction. This was the route taken by Hanuman. His work was no ordinary business either. Playing out her role in the dramatic, real-life play that is the Ramayana, Sita was taken away from Rama’s side by a powerful king named Ravana. Rama was the greatest bow warrior in the world, so Ravana knew he couldn’t defeat Him in battle. Struck as he was by the impulse to have Sita, the most beautiful woman in the world, for his wife, Ravana devised a plan where he could take Sita away without anyone knowing. When it came time later to find His wife, Rama enlisted the help of a band of forest dwellers residing in Kishkindha. They were mostly monkey-like, but they had many human features and tendencies as well. Hanuman was the most capable of these warriors, so he was tasked by Sugriva, the king of these Vanaras, to look for Sita and return the information of her whereabouts to the camp. Though given the task by Sugriva, Hanuman was essentially performing devotional service for Rama. Long story short, Hanuman ended up in Lanka, Ravana’s remotely situated island. Hanuman was all by himself; no one was there to help him. No telephone to use to call home. No text message to send to get advice. He had to find Sita using his tremendous skills, which included an unmatched fighting prowess, a keen intellect, and mastery over every mystic perfection of the ancient system of yoga. As endowed as he was in these areas, Hanuman’s greatest strength was his devotion to Rama. This is what initially enabled him to infiltrate Lanka without being noticed. He searched and searched, but he couldn’t find Sita. Lest we think devotion to God is all roses and lilies, Hanuman then quickly fell into a depressed state. His love for Rama coupled with his failure to find Sita made him sadder than ever. Though he had such wonderful abilities and had already exhibited tremendous feats of strength and heroism, he essentially hated himself for not having found Sita. Obviously, none of this was his fault, for what had he done wrong? He did everything asked of him. Ravana was the one who took Sita, so he was really to blame. Nevertheless, Hanuman decided that if he returned to Kishkindha a failure, everyone else would soon quit their bodies. Rather than be responsible for that, Hanuman thought it would be better to just starve himself to death. This way he would give himself the proper punishment. He was on the brink of suicide. Then he thought to himself some more. He correctly decided that if he should quit, so many bad things would happen. If he continued to fight on, however, at least there would be a chance of succeeding. This is the rule to live by. The Paramatma is always residing within us, so as long as the life breath is there, there is an opportunity to connect with Him, to make the most of the human form of life. With death we have no idea where we will end up next. There is no guarantee that we will even get the opportunity to try to understand God and the need for worshiping Him. Deciding that living was better, Hanuman still couldn’t get over his sadness. That Sita wasn’t found was really bothering him. In the above referenced verse, we see him change course, reawaken from his temporary slumber. Hanuman decided that if he was going to fail, he was going to take Ravana down with him. Hanuman is described as having tremendous fortitude and being an elephant among monkeys. One would have to be courageous to continue to fight, especially when they were just on the brink of suicide. Hanuman is the most powerful person, and he only uses his strength for good. If Sita were no longer living, Hanuman would get revenge by taking out Ravana. Who was Ravana to escape punishment? Why should Hanuman have to suffer while Ravana continued to live? Through this wonderful passage Hanuman once again reveals his unmatched level of devotion to Sita and Rama. His love for them is a thing of beauty. Though he roams the earth in the guise of a monkey, his portrait is flawless, bringing satisfaction to those who are dedicated to serving the Supreme Lord in thought, word and deed. Hanuman’s fortitude would enable him to emerge victorious, to find Sita and help in her eventual rescue. He showed us that even in devotional service there are severe ups and downs. But if our heart is situated in the right place, we will find the right course of action every time. Anyone who regularly remembers Hanuman and his devotion will be guaranteed to find redemption from the curse of material existence. In Closing: “Not finding her Sita may be gone, Sadness mind constantly dwells on. Ravana should escape, who is he? By me punished with death will he be.” From failure Hanuman first in sadness dove, Then thinking of success from despair arose. Ravana for his deed would not get away, The powerful Hanuman the demon to slay. In devotion Hanuman always to finish strong, His deeds and qualities daily dwell upon.

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