Saturday, November 28, 2015

Artificial Intelligence May Offer Cancer Cure 



Boston-based Berg has spent the last six years perfecting an artificial intelligence platform that may soon crack the cancer code.

“Berg’s model is based on precision medicine which is getting the right treatment to the right patient at the right time,” Narain said. “In order to truly understand the disease and how to treat it, Berg analyzes the full biological make-up of the cell. This includes the genome, proteome, lipidome, metabolome. We also look at mitochondrial function, oxidative states, and ATP production, to look at how the cell is behaving.”

Analysis of cancer cells typically takes years – but the beauty of artificial intelligence is that it works faster than any human possibly could. 

Could we be just two or three years away from curing some forms of cancer? Niven Narain, the president of Berg, a small Boston-based biotech firm, says that may very well be the case.

The company takes samples of blood, urine and tissue from cancer patients and compares those samples with those from healthy patients. Over 14 trillion data points are created from this process. All of that data is then fed into artificial intelligence systems.

With funding from billionaire real-estate tycoon Carl Berg as well as from Mitch Gray, Narain, a clinical scientist by training, and his small army of scientists, technicians, and programmers, have spent the last six years perfecting and testing an artificial intelligence platform that he believes could soon crack the cancer code, in addition to discovering valuable information about a variety of other terrible diseases, including Parkinson’s.

All that analysis is so complex and broad that it would take humans a lifetime to complete it. With the help of AI, all that data is crunched in the span of days or weeks, buying precious time in the drug creation process. The result is a targeted treatment, tailored to the individual, based on their own body’s makeup.  

Founder Of Synthetic Marijuana



John W. Huffman, now an 83-year-old recluse who lives deep in the Smoky Mountains, discovered the drug compounds that spawned the creation of mass-produced synthetic drugs.
 
The Harvard-educated, Clemson University scientist, who said that he didn’t think anyone would ever recreationally use the compounds. He tinkered with them to study how the human brain works, he said.

Claiming it gives users super-human strength and immunity to pain.

It wasn’t until a German blogger sent Huffman an article in 2008 describing an artificial drug called “Spice” — which uses the active compound JWH-018 — that he realized people were using the stuff recreationally, he said.

 
“I thought it was sort of hilarious at the time.”

Huffman, who earned his doctorate at Harvard University and then worked at Clemson, first started worked to work with synthetic pot in the late 1980s after scientists discovered that marijuana’s active component, THC, stimulates a specific brain receptor, termed cannabinoid receptor. The discovery demystified how pot interacted with the brain.

Chemists then set out to see how man-made compounds would interact with the receptor.
Huffman was fascinated, he said. The receptor was a “puzzle” and he wanted to figure out how it worked.

Backed by the National Institute on Drug Abuse, he made hundreds of synthetic cannabinoids named for their relationship with the receptor, not because they mimic the high of marijuana.

Friday, November 27, 2015

Last Antibiotic Begins to Fail 



A new gene that makes bacteria highly resistant to a last-resort class of antibiotics has been found in people and pigs in China - including in samples of bacteria with epidemic potential, researchers said on Wednesday.

Researchers from several Chinese, British and US universities announced in the journal Lancet Infectious Diseases that they have identified a new form of resistance, to the very last-ditch drug colistin—and that it is present in both meat animals and people, probably comes from agricultural use of that drug, can move easily among bacteria, and may already be spreading across borders.

"All use of polymyxins must be minimized as soon as possible and all unnecessary use stopped," said Laura Piddock, a professor of microbiology at Britain's Birmingham University who was asked to comment on the finding.

To understand why, it’s necessary to know a little bit about colistin. It is an old drug: It was first introduced in 1959. It has been on the shelf, without seeing much use, for most of the years since, because it can be toxic to the kidneys. And precisely because it hasn’t been used much, bacteria have not developed much resistance to it. It remains effective.

(From around that time: Here’s a great story that Jason Gale of Bloomberg wrote about colistin, and one I wrote for Nature about CREs. A long series of posts I wrote for WIRED about the discovery of NDM and the bitter political fights over its apparent origin in India can be found  here. Of note, one of the discoverers of NDM is one of the authors of this new research.)

This suggests "an alarming potential" for it to spread and diversify between bacterial populations, they said.

Which, apparently, is how it is being used in China—but not only in China. From the paper:

China is… one of the world’s highest users of colistin in agriculture. Driven largely by China, the global demand for colistin in agriculture is expected to reach 11,942 tonnes per annum by the end of 2015 (with associated revenues of $229·5 million), rising to 16,500 tonnes by the year 2021, at an average annual growth rate of 4·75%. Of the top ten largest producers of colistin for veterinary use, one is Indian, one is Danish, and eight are Chinese. Asia (including China) makes up 73·1% of colistin production with 28·7% for export including to Europe.

This suggests "the progression from extensive drug resistance to pandrug resistance is inevitable," they said.

"(And) although currently confined to China, mcr-1 is likely to emulate other resistance genes ... and spread worldwide."

Here’s what they found. The gene they discovered, which directs colistin resistance and which they dubbed MCR-1, was present:
  • in  78 (15 percent) of 523 samples of raw pork and chicken meat
  • in 166 (21 percent) of 804 pigs in slaughterhouses
  • and in 16 (1 percent) of 1,322 samples from hospital patients with infections. 

Piddock and others said global surveillance for mcr-1 resistance is now essential to try to prevent the spread of polymyxin-resistant bacteria.

China is one of the world's largest users and producers of colistin for agriculture and veterinary use.

And, of most concern: The MCR-1 gene that creates this resistance is contained on a plasmid, a small piece of DNA that is not part of a bacteria’s chromosome. Plasmids move freely around the bacterial world, hopping from one bacterium to another; in the past, they have transported resistance DNA between bacterial species, facilitating resistance’s rapid movement around the globe. This gene, the authors predict, will be able to do that as well.

In Europe, 80 percent of polymixin sales - mainly colistin - are in Spain, Germany and Italy, according to the European Medicines Agency's Surveillance of Veterinary Antimicrobial Consumption (ESVAC) report.

“Pan-drug resistance,” to be clear, means that nothing at all will work—that infections are untreatable by any known compound.

They found a high prevalence of the mcr-1 gene in E coli samples from animals and raw meat. Worryingly, the proportion of positive samples increased from year to year, they said, and mcr-1 was also found in 16 E.coli and K.pneumoniae samples from 1,322 hospitalized patients.

MCR, this new colistin resistance, different from VRSA is the role that agriculture seems to be playing in its evolution and dispersal. There are two problems here. First, that thousands to millions of animals are getting the drug, which exponentially expands the opportunities that favor resistance. And second, that projects such as the Chinese one that allowed the new gene to be discovered are rare—so colistin resistance could begin moving, from animals and into people, without being noticed. 

"One of the few solutions to uncoupling these connections is limitation or cessation of colistin use in agriculture," they said. "Failure to do so will create a public health problem of major dimensions."

Major Red Blood Cell Discovery

 Major Red Blood Cell Discovery



University of Virginia research team could have big implications for treating numerous serious illnesses.

People with anemia – the most common blood disorder – lack sufficient red blood cells, which transport oxygen. People with anemia often experience fatigue and lack energy because their cells aren’t getting enough oxygen. There are many causes, including iron deficiency, vitamin deficiencies and diseases such as kidney disease and cancer. Anemia is particularly prevalent in older adults. - See more at: https://news.virginia.edu/content/baffling-lab-mystery-leads-major-red-blood-cell-discovery#sthash.SmqJvTZz.dpuf
 People with anemia – the most common blood disorder – lack sufficient red blood cells, which transport oxygen. People with anemia often experience fatigue and lack energy because their cells aren’t getting enough oxygen. There are many causes, including iron deficiency, vitamin deficiencies and diseases such as kidney disease and cancer. Anemia is particularly prevalent in older adults.

The researchers were injecting flu virus and an antibody into mice when the cells they were studying prompted the mice's bodies to create more red blood cells. Braciale says they repeated the test multiple times and got the same results.

After injecting mice with the flu virus and an antibody that blocked a certain molecule expressed by dendritic cells, the researchers discovered that the experiment had an unexpected effect: The mice’s spleens enlarged massively, which indicated they were producing red blood cells. The researchers were baffled, so they repeated the experiment, only to get the same results.
 

"When we do research, we sometimes have a direction but if we're cognizant, if we understand what the importance of the work is, sometimes we can make a finding in a totally unrelated area that's important," he said.

Stress erythropoiesis refers to the body producing red blood cells because of injury or some other stress. In discovering an unexpected molecular trigger for the process, Braciale had found a switch he could flip to prompt red blood cell production.

The research has shifted to focus on this new discovery, which needs to be explored further in human subjects.

Quantum Mechanics Of PI


In 1655 the English mathematician John Wallis published a book in which he derived a formula for pi as the product of an infinite series of ratios. Now researchers from the University of Rochester, in a surprise discovery, have found the same formula in quantum mechanical calculations of the energy levels of a hydrogen atom.

“We didn’t just find pi,” said Tamar Friedmann, a visiting assistant professor of mathematics and a research associate of high energy physics, and co-author of a paper published this week in the Journal of Mathematical Physics. “We found the classic seventeenth century Wallis formula for pi, making us the first to derive it from physics, in general, and quantum mechanics, in particular.”

"It was a complete surprise - I jumped up and down when we got the Wallis formula out of equations for the hydrogen atom," said Friedmann. "The special thing is that it brings out a beautiful connection between physics and math. I find it fascinating that a purely mathematical formula from the 17th century characterizes a physical system that was discovered 300 years later."
 

“The value of pi has taken on a mythical status, in part, because it’s impossible to write it down with 100 percent accuracy,” said Friedmann, “It cannot even be accurately expressed as a ratio of integers, and is, instead, best represented as a formula.”

In quantum mechanics, a technique called the variational approach can be used to approximate the energy states of quantum systems, like molecules, that can't be solved exactly. Hagen was teaching the technique to his students when he decided to apply it to a real-world object: the hydrogen atom. The hydrogen atom is actually one of the rare quantum mechanical systems whose energy levels can be solved exactly, but by applying the variational approach and then comparing the result to the exact solution, students could calculate the error in the approximation.
 

Although applying the variational principle to calculate the ground state of a hydrogen atom is a relatively straightforward problem, its applicability to an excited state is far from obvious. This is because the variational principle cannot ordinarily be applied if there are lower energy levels. However, Friedmann and Hagen were able to get around that by separating the problem into a series of l problems, each of which focused on the lowest energy level for  a given orbital angular momentum quantum number, l.

When Hagen started solving the problem himself, he immediately noticed a trend. The error of the variational approach was about 15 percent for the ground state of hydrogen, 10 percent for the first excited state, and kept getting smaller as the excited states grew larger. This was unusual, since the variational approach normally only gives good approximations for the lowest energy levels.
 

Specifically, the calculation of Friedmann and Hagen resulted in an expression involving special mathematical functions called gamma functions leading to the formula.

 "At the lower energy orbits, the path of the electron is fuzzy and spread out," Hagen explained. "At more excited states, the orbits become more sharply defined and the uncertainty in the radius decreases."


which can be reduced to the classic Wallis formula.




“What surprised me is that the formula occurred in such a natural way in the calculations, with no circles involved in determining the energy states,” said Hagen, the co-author of the paper. “And I am glad I didn’t think about this before Tamar arrived in Rochester, because it would have gone nowhere and we would not have made this discovery.”

The theory of quantum mechanics dates back to the early 20th century and the Wallis formula has been around for hundreds of years, but the connection between the two had remained hidden until now.

The theory of quantum mechanics dates back to the early 20th century and the Wallis has been around for hundreds of years, but the connection between the two had remained hidden until now.

Read more at: http://phys.org/news/2015-11-derivation-pi-links-quantum-physics.html#jC
In 1655 the English mathematician John Wallis published a book in which he derived a formula for pi as the product of an infinite series of ratios. Now researchers from the University of Rochester, in a surprise discovery, have found the same formula in quantum mechanical calculations of the energy levels of a hydrogen atom.

Read more at: http://phys.org/news/2015-11-derivation-pi-links-quantum-physics.html#jCp
In 1655 the English mathematician John Wallis published a book in which he derived a formula for pi as the product of an infinite series of ratios. Now researchers from the University of Rochester, in a surprise discovery, have found the same formula in quantum mechanical calculations of the energy levels of a hydrogen atom.

Read more at: http://phys.org/news/2015-11-derivation-pi-links-quantum-physics.html#jCp
In 1655 the English mathematician John Wallis published a book in which he derived a formula for pi as the product of an infinite series of ratios. Now researchers from the University of Rochester, in a surprise discovery, have found the same formula in quantum mechanical calculations of the energy levels of a hydrogen atom.

Read more at: http://phys.org/news/2015-11-derivation-pi-links-quantum-physics.html#jCp

Thursday, November 26, 2015

World's First Sexiest Robot



We all love robots - but could we one day actually fall in love with one? 

Named Geminoid F, the robot has amassed a legion of fans, with some even describing her as 'the world's sexiest robot'.

Created by Hiroshi Ishiguro Laboratory at Osaka University, Geminoid F was the star attraction as people crowded round her to have their picture taken and speak to the android.

The 5ft 6 inch android is capable of eye movements, response to eye-to-eye contact and can recognise body language.

She previously found fame after becoming the first android film star - she co-starred in Japanese movie Sayonara, about the fall-out from a nuclear power plant meltdown.

She is designed act like a human with rubber 'skin' and a woman's face - but can't walk and has to be wheeled around.

The robot was created by Hiroshi Ishiguro Laboratory at Osaka University who plan on creating a better model in the future.

With her realistic appearance, good looks and acting talent, you might think Geminoid F had it all - but some people, in particular her creators, are picky.

'Our final goal is creating some artificial intelligence by using this robot,' Kohei Ogawa, assistant professor said.

'In the future we're going to create some perfect AI system by using this robot.'

Super Plane Fly's Anywhere In Four Hours 



It almost sounds like a dream: a new kind of hypersonic space-kissing jet that can take you anywhere in the world in just four hours. But the Skylon super plane being developed by UK aerospace firm Reaction Engines is very real.

The UK government has invested £60 million into a next-generation engine that -- its makers claim -- will make low-cost space travel possible for commercial customers.

Oxfordshire-based Reaction Engines got the grant to help it develop its Skylon super-plane, which could eventually make make low-cost space travel possible for commercial customers.

The project took a big step forward this week with Reaction Engines announcing a new partnership with defence and aerospace giant BAE Systems, whose financial backing, along with a considerable investment from the UK government, will help Reaction develop its new class of aerospace engine dubbed SABRE (Synergetic Air-Breathing Rocket Engine) by as early as 2020, with test flights possible just five years later.

'Sabre' engine is a hybrid rocket and jet propulsion system, which theoretically enables travel anywhere on Earth in four hours or less. It could also slash the cost of launching satellites into orbit, once it gets off the ground.

The super-plane will rely on cooling an incoming airstream from 1,000 degrees C to minus 150 C almost instantly, at close to 1/100th of a second.

It will double the technical limits of a jet engine, and allow the craft to reach, up to five times the speed of sound, before switching to a rocket engine to reach orbit.

SABRE operates in two modes to enable aircraft to directly access space in one step, called single stage to orbit. In its air-breathing mode, the engine sucks in oxygen from atmospheric air, to burn with liquid hydrogen fuel in the rocket combustion chamber. Once outside Earth’s atmosphere, the engine transitions to a conventional rocket mode, switching to on-board liquid oxygen.

Based at Culham Science Centre in Oxfordshire, the company has been called a "potential game-changer" by ministers since at least 2012, following a positive appraisal by the UK Space Agency in 2010.

New Discovery To Cryopreservation Of Tissues & Organs



Researchers in the College of Engineering at Oregon State University have discovered a new approach to "vitrification," or ice-free cryopreservation, that could ultimately allow a much wider use of extreme cold to preserve tissues and even organs for later use. 

Cryopreservation, the freezing of biological material for preservation purposes, is already in widespread use for applications, such as saving semen, embryos, blood, and plant seeds. When it comes to tissues and organs, however, the process is more problematic.

"This could be an important step toward the preservation of more complex tissues and structures," said Adam Higgins, an associate professor in the OSU School of Chemical, Biological and Environmental Engineering, and expert on medical bioprocessing.

The issue with cryopreservation is that crystallization often occurs when water freezes; this risks damaging the tissues and cells the process is meant to preserve, Higgins explained. It is for this reason that the researchers explored various types of cryoprotectants aimed at reducing cell damage during the freezing process. One of these is ethylene glycol, also known as the compound used in automobile antifreeze.

To address this, researchers have used various types of cryoprotectants that help reduce cell damage during the freezing process - among them is ethylene glycol, literally the same compound often used in automobile radiators to prevent freezing.

In the new OSU research, the engineers developed a mathematical model to simulate the freezing process in the presence of cryoprotectants, and identified a way to minimize damage. They found that if cells are initially exposed to a low concentration of cryoprotectant and time is allowed for the cells to swell, then the sample can be vitrified after rapidly adding a high concentration of cryoprotectants. The end result is much less overall toxicity, Higgins said.

The study showed that the survival rate for healthy cells following vitrification rose from around 10 percent with a traditional approach to over 80 percent with the new process.

"The biggest single problem and limiting factor in vitrification is cryoprotectant toxicity, and this helps to address that," Higgins said. "The model should also help us identify less toxic cryoprotectants, and ultimately open the door to vitrification of more complex tissues and perhaps complete organs."

Such an accomplishment would open the door to a great number of applications of vitrification. The advancements in tissue regeneration and stem cell use are closely intertwined: one goal would be creating tissue in small amounts and storing them until they’re needed for transplantation. Organs for transplants could be safely preserved until a precise immunological match was found for their use.

Tissues could be made in small amounts and then stored until needed for transplantation. Organs being used for transplants could be routinely preserved until a precise immunological match was found for their use. Conceptually, a person could even grow a spare heart or liver from their own stem cells and preserve it through vitrification in case it was ever needed, Higgins said.

Drug testing is now carried out with traditional cell culture systems or animal models, which in many cases don't accurately predict the effect of the drug in humans. To address this, researchers are developing "organs-on-a-chip," or microfluidic chambers that contain human cells cultured under conditions that mimic native tissues or organs.

Alzheimer's Drug Has Anti-Ageing Effects



An elixir of youth may be on the horizon after an experimental Alzheimer's drug had a surprise side-effect of making old mice 'young'.

A team of researchers at the Salk Institute have said that they have developed a new experimental drug to treat the Alzheimer's disease that is aimed at reducing the effects of aging.

The new medicine was so successful at rolling back the years in lab rodents that human trials are already being planned for next year.

While all is well when testing mice to prove the drug's benefits, Currais and Schubert note the importance of eventually moving on to human clinical trials for Alzheimer's disease.

When mice were treated with the drug, called J147, it boosted memory and cognition and made blood vessels in the brain healthier.

J147 was initially synthesised by using cell-based screens against old-age-associated brain toxicities. 

Scientists never expected the therapy to slow the clock on key aspects of ageing but hailed them a "welcome benefit" if the drug turns out to be safe for use by Alzheimer's patients.

When mice were treated with the drug, called J147, it boosted memory and cognition and made blood vessels in the brain healthier. Researchers found old mice that received J147 performed better on memory and cognition tests and had sharper motor skills than they had prior to treatment.

They tested three groups of a mice - one young, a second old and the third old but fed J147 as they aged.

The mice that were given the medication showed fewer signs of Alzheimer's disease. Previous studies had shown that J147 could be effective in helping prevent and reverse Alzheimer's in mice who had a certain form of the disease, but who did not represent the majority of Alzheimer's cases. 

They found that the old mice that received J147 performed better on memory and other tests for cognition and also displayed more robust motor movements.

Due to the extensive amount of data collected before the study, the team demonstrated how parts of the J147 mice gene expression and metabolism were similar to those of the younger mice group, including increased energy metabolism, reduced brain inflammation, and reduced levels of oxidized fatty acids in the brain. 

Another notable effect was that J147 prevented the leakage of blood from the microvessels in the brains of old mice.

"If proven safe and effective for Alzheimer's, the apparent anti-aging effect of J147 would be a welcome benefit", adds Schubert. "Damaged blood vessels are a common feature of ageing in general, and in Alzheimer's, it is frequently much worse", said Currais.

Recent developments in Alzheimer's research has led to the engineering of drugs aimed at destroying amyloid plaque in the brain, plaques which build over time.  

The Birth of Planets

 

 

IT IS being hailed as a major breakthrough, a world-first and proof of a long-held theory.

Scientists in Australia and the US have captured the first-ever images of an exoplanet forming around a young star called LkCa 15, which is located roughly 450 light-years from Earth, writes Christian Science Monitor.

 They've observed the birth of as many as three exoplanets around the star LkCa 15, the team said in its findings, which were recently published in the journal Nature. The new planets are some 450 light-years from Earth, according to Space.com. These observations could give scientists more insight into the processes that form planets.

The telltale signs,, were the accumulation of dust and gas particles on the said star known as LkCa 15.

The images of the LkCa 15 system show a young 2 million year old star surrounded by a large disk of space dust. Circumstellar disks such as this are a common feature around newborn stars, providing the raw material that eventually leads to the formation of a planet.

This new planet is located 450 light years away from Earth.

"Such an understanding of the young planet population will shed light on the decades-old problem of planet formation, and reveal how young planetary systems can evolve into older ones such as our solar system, billions of years after they were born," Zhaohuan Zhu of Princeton University, who is not affiliated with the study.

The findings, which was led by University of Arizona graduates Steph Sallum and Kate Follette, were only possible because of very specialised equipment.

These included the Large Binocular Telescope, or LBT– the world’s largest telescope, located on Arizona’s Mount Graham, and the University of Arizona’s Magellan Telescope and its Adaptive Optics System, MagAO, located in Chile.

Such an understanding of the young planet population will shed light on the decades-old problem of planet formation, and reveal how young planetary systems can evolve into older ones such as our solar system, billions of years after they were born," Zhu wrote.

Wednesday, November 25, 2015

 Polarized Light Invisibility Technology



Researchers have resolved a longstanding mystery concerning exactly how a few fish seem to disappear from predators outdoors waters of the sea, a discovery that could assist materials researchers and also military technologists develop more efficient techniques of ocean camouflage.

In a Science paper published, a group led by researchers at the University of Texas at Austin reads that particular fish use tiny particles called platelets in their skin cells to reflect polarized light, which permits the fish to seem like they disappear from their predators. Polarized light is composed of light waves traveling in the same plane, such as the brilliant glow you occasionally see when sunlight reflects off the water.

In the study two ocean fish, the big-eyed scad and the lookdown have fine-tuned a method of avoiding predators by hiding in light. Elements in their silvery skin render them nearly impossible to see. The U.S. Navy funded the study as part of an effort understand how fish do this, and how it could be used to the navy's advantage.

Underwater, light often tends to be polarized. Lots of fish and even sophisticated modern satellites have the ability to detect variations in such polarized light. Molly Cummings, a part of the research team, shared that fish have reached the point in their evolution where they can detect polarized light, and the study suggests that they may have also developed the ability to hide in polarized light. The team hopes to investigate how and give the process human and military applications.

Polarized light is not uniform but the fish in the study were able to use them to their advantage. Many fish-and sophisticated modern satellites-have the ability to detect variations in such polarized light.
The ability of fish to reflect polarised light may also be applied in human camouflage, according to Dr. Cummings, a scientists from City College of New York, Texas A&M University, and other organizations to develop a computerized revolving platform that would hold the fish in position in the water while a polarimeter took constant measurements.

The US Navy has been looking for ways to travel in open ocean concealed, so this study is of great importance to the military. In previous studies, the researchers showed in the laboratory that a fish called the lockdown was able to adjust the polarized light to its advantage.

The new study, performed at sea, revealed that lookdowns and various other fish that reside in the open sea camouflage themselves in this manner. Parrish Brady, a collaborator with Cummings and lead writer on the brand-new study, built a video polarimeter that can tape-record polarized light in real time, permitting the researchers to essentially see the polarized light as fish do.

Medical Science Discovery Helps Shrink Brain Tumors


 

Patients with glioblastoma, a type of malignant brain tumor, usually survive fewer than 15 months following diagnosis. Since there are no effective treatments for the deadly disease, University of California, San Diego researchers developed a new computational strategy to search for molecules that could be developed into glioblastoma drugs.

In mouse models of human glioblastoma, one molecule they found shrank the average tumor size by half. The study is published October 30 by Oncotarget.

The molecule — SKOG102 — wedges itself in a temporary interface between two proteins whose binding is essential for the tumor’s survival and growth. The study is the first to demonstrate successful inhibition of this type of protein, known as a transcription factor.

"Most drugs target stable pockets within proteins, so when we started out, people thought it would be impossible to inhibit the transient interface between two transcription factors," said Igor Tsigelny, a research scientist at UCSD Moores Cancer Center.

Transcription factors control which genes are turned "on" or "off" at any given time. For most people, transcription factors labor ceaselessly in a highly orchestrated system. In glioblastoma, one misfiring transcription factor called OLIG2 keeps cell growth and survival genes "on" when they shouldn't be, leading to quick-growing tumors.

n order to work, transcription factors must buddy up, with two binding to each other and to DNA at same time. If any of these associations are disrupted, the transcription factor is inhibited.

In this study, Tsigelny and team aimed to disrupt the OLIG2 buddy system as a potential treatment for glioblastoma. Based on the known structure of related transcription factors, study co-author Valentina Kouznetsova, PhD, associate project scientist at UC San Diego, developed a computational strategy to search databases of 3D molecular structures for those small molecules that might engage the hotspot between two OLIG2 transcription factors.

The team used the Molecular Operation Environment (MOE) program produced by the Chemical Computing Group in Montreal, Canada and high-performance workstations at the San Diego Supercomputer Center to run the search.

With this approach, the researchers identified a few molecules that would likely fit the OLIG2 interaction. They then tested the molecules for their ability to kill glioblastoma tumors in the Moores Cancer Center lab of the study's senior author, Santosh Kesari, MD, PhD. The most effective of these candidate drug molecules, called SKOG102, shrank human glioblastoma tumors grown in mouse models by an average of 50 percent.

The scientists said a few more years of study are needed to make sure medication based on the molecule would work and not be poisonous to patients.

Researchers with The Scripps Research Institute, Harvard Medical School and Brigham and Women's Hospital in Massachusetts contributed to the study, which was funded, in part, by the National Institutes of Health, Voices Against Brain Cancer Foundation, Christopher and Bronwen Gleeson Family Trust and American Brain Tumor Association Drug Discovery Grant.

Bacteria Generating Electricity 


 

Peruvian researchers have created a lightsource that uses plantlife as its fuel.

 

Inspired by real and immediate problems in remote areas of the country, researchers at Peru’s Universidad de IngenierĂ­a y TecnologĂ­a (UTEC) have developed a remarkable piece of technology — a low-cost LED lamp that uses plants and soil as its batteries.

 

UTEC's "plant lamp" is actually more of a conduit for bacteria than an electrified fern -- researchers built a metal grid in a planter that captures energy released from "geobacters," a kind of microrganism that gives off electrons.

 

The energy given off by these bacteria are then storied in a battery, which can provide up to two hours of light per day. That's two hours of artificial light from a single plant. And while the technology isn't anywhere near the scale needed to roll it out on a mass market scale, the ten prototypes that have currently been built are already providing the occupants of Nuevo Saposoa with an ideal natural alternative to the dangers of using kerosene lamps.

 

Researchers have created 10 fully functional prototypes, which have been distributed to families in the affected village. 

Animal That Survives In Space


 


The only animal known to survive the extreme environment of outer space without the help of special equipment turns out to have the most foreign DNA of any species.

Also known as tardigrades, water bears are segmented, eight-legged micro-organisms that are just a fraction of an inch long. Though tiny, these small creatures are best known for their resiliency, which researchers now suspect comes as a result of their strange genome.

They live everywhere, from the tallest mountains to the deepest oceans, and from hot springs to Antarctic ice. They can even tolerate New York. They cope with these inhospitable environments by transforming into a nigh-indestructible state. Their adorable shuffling gaits cease. Their eight legs curl inwards. Their rotund bodies shrivel up, expelling almost all of their water and becoming a dried barrel called a “tun.” Their metabolism dwindles to near-nothingness—they are practically dead. And in skirting the edge of death, they become incredibly hard to kill.

“We had no idea that an animal genome could be composed of so much foreign DNA,” said Bob Goldstein, a faculty member in the biology department of UNC’s College of Arts and Sciences, in a statement. “We knew many animals acquire foreign genes, but we had no idea that it happens to this degree.”

The discovery, published in the Proceeding of the National Academy of Sciences, adds to the evidence that tiny water bears are incredibly unique and seemingly indestructible animals. In 2007, some were even rocketed into space on the outside of a satellite.

When the satellite returned, many of the water bears were still alive. What’s more, some of the females had laid eggs in space, with the young hatching healthily, as though nothing had happened.

In the tun state, tardigrades don't need food or water. They can shrug off temperatures close to absolute zero and as high as 151 degrees Celsius. They can withstand the intense pressures of the deep ocean, doses of radiation that would kill other animals, and baths of toxic solvents. And they are, to date, the only animals that have been exposed to the naked vacuum of space and lived to tell the tale—or, at least, lay viable eggs. (Their only weakness, as a researcher once told me, is “vulnerability to mechanical damage;” in other words, you can squish ‘em.)

Water bears are segmented, eight-legged micro-animals that measure just a miniscule fraction of an inch long. Goldstein, lead author Thomas Boothby and their team determined that water bears acquire 6,000 foreign genes primarily from bacteria, but also from plants, fungi and various single-celled microorganisms.

 The creatures acquire the DNA through a process called horizontal gene transfer. In it, DNA is swapped between species instead of being inherited. While not seen in every organism, the process is changing the way scientists think about evolution as well as the inheritance of genetic material. This is because genetic material no longer has to travel in one direction. Rather, it can be passed sideways along a family tree, not just from one generation to another.

“Animals that can survive extreme stresses may be particularly prone to acquiring foreign genes and bacterial genes might be better able to withstand stresses than animal ones.”

Tuesday, November 24, 2015

Researchers Discover Diabetic Wound Healing Compound


 
Non-healing chronic wounds are a major complication of diabetes, which result in more than 70,000 lower-limb amputations in the United States alone each year. The reasons why diabetic wounds are resistant to healing are not fully understood, and there are limited therapeutic agents that could accelerate or facilitate their repair.

In a new study that appears in the journal Proceedings of the National Academy of Sciences (PNAS), the researchers report the discovery of a better MMP-9 inhibitor referred to as ND-336

A team of researchers from Notre Dame's Department of Chemistry and Biochemistry, led by Mayland Chang, previously identified two enzymes called matrix metalloproteinases (MMPs), MMP-8 and MMP-9, in the wounds of diabetic mice. They proposed that the former might play a role in the body's response to wound healing and the latter was the pathological consequence of the disease with detrimental effects. The researchers used the MMP-9 inhibitor referred to as ND-322.

We found that wounds treated with ND-336 healed significantly faster than those treated with ND-322 because of the better selectivity of ND-336 than ND-322 for inhibition of MMP-9 over MMP-8. In the current paper, we applied the enzyme MMP-8 to wounds of diabetic mice and found accelerated wound healing. We also combined the MMP-9 inhibitor ND-336 and the enzyme MMP-8 and found further acceleration of diabetic wound healing.”

“ND-336 is a six-fold more potent inhibitor than ND-322 and has 50-fold selectivity towards inhibition of MMP-9 than MMP-8,” Chang said. “In contrast, ND-322 has three-fold selectivity towards inhibition of MMP-9 compared to MMP-8. The current paper compared the efficacy of ND-336 versus ND-322.

The researchers found that a combination of a selective inhibitor of MMP-9 (a small molecule) and applied MMP-8 (an enzyme) enhanced healing even more, in a strategy that holds considerable promise in healing of diabetic wounds.
 Exoskeleton Research May Allow Paralyze To Walk


Swiss sensory motor scientists are hoping to inspire a new generation of more flexible, less constraining, powered exoskeletons that improve the lives of the severely disabled and paralyzed.

Metal exoskeleton suits worn outside the body, delivering energy for limb movement, are becoming more widespread, helping survivors of strokes, spinal cord injuries, and other lower extremity weaknesses to walk again.

The use of metal exoskeletons is becoming common among survivors of strokes, spinal cord injuries, and other lower extremity weaknesses.

Metal exoskeletons are suits worn outside the body that provide energy for limb movement.

However, these suits have their limitations. They constrain the patient's walking and are also bulky, making several activities such as climbing stairs impossible. The limitations of the mechanism makes any other activity, other than walking in a straight line, difficult, slow and inefficient.

ETH Zurich (Swiss Federal institute of Technology) researcher Volker Bartenbach told Reuters that a prototype developed at the institute's Sensory Motor Laboratory allows users far more freedom.

"Hopefully we will build systems that allow you to do more tasks," he said. "Besides walking in a straight line, you might be able to walk sideways in front of your kitchen counter or something like that, to walk stairs up and down. Also to turn round on the spot, so they need different joints, they need different degrees of freedom and if we had a system that was powerful enough to support you but also less constraining to allow you those movements you would be able to do such movements, even if you were a paraplegic or handicapped person."

Yet they are far from perfect solutions. A patient's joints can be misaligned with those of the exoskeleton, thus constraining the wearer's walking. They are also usually bulky, making climbing stairs impossible, while the limitations of their joint mechanisms makes anything other than walking in a straight line difficult, slow, and inefficient, and in some cases unachievable.

Bartenbach and professor of sensory motor systems, Robert Riener are making an attempt to improve the type of exoskeleton currently being manufactured by replicating the natural kinematics of human lower limbs.

Bartenbach wants to build an exoskeleton that is an alternative to a wheelchair for a spinal paralysis patient.

The lab is also working on developing a soft exosuit that can be worn like regular clothes and yet provide sufficient assistance to support the wearer during specific motions.

 Advances In Dentistry Through Nanotechnology


 

New nanomaterials for dental treatments boast impressive antibacterial, decay-resistant and biomimetic properties. In combination with stem cells, they are even capable of regenerating dental tissues. A researcher at CEU Cardenal Herrera University in Valencia collaborates on a compendium of the latest nanomaterials for use in fillers, mouthwashes, medicines and other treatments to improve oral and dental health ("Advances in Dental Materials through Nanotechnology: Facts, Perspectives and Toxicological Aspects").

"Nanotechnology can be faced sometimes as a paradigm that promised a lot and delivered very little," says senior author Nelson DurĂ¡n of the Universidade Estadual de Campinas. "The evolution of dental materials though nanotechnology is real and remarkable, reflecting on a billionaire market. In this way, dentistry was in fact one of the most benefited areas from the development of nanotechnology."

The prefix "nano" is derived from the Greek word "dwarf," and "nanotechnology," as originally conceptualized by Physicist Richard P. Feynman in 1959, refers to the manipulation of matter on the atomic and molecular levels. According to the National Nanotechnology Initiative, any material with components less than 100 nanometers in at least one dimension is considered a nanomaterial. (If a nanometer is one-billionth of a meter, then a single strand of human hair ranges between 80,000 and 100,000 nanometers wide.)

A decade ago, according to the current review, engineers first introduced nano-composite resins to be used in dentistry.

The reason nanomaterials are so alluring is their properties are different from non-nano-materials in two crucial ways. First, due to their small size, nanomaterials have greater surface area per unit mass compared to bigger particles. Second, all quantum effects (including energy, electrical, optical, and magnetic) become more dominant at the nanoscale. Any material, then, will possess unusual properties at the nanoscale whether it be gas, liquid, or solid.

One of the most promising features of these nanomaterials is their capacity to imitate the natural physicochemical, mechanic and aesthetic properties of dentine and dental enamel”. This is what is meant by biomimetic: human-made materials that imitate nature and natural processes. “For instance, nanoceramic materials have yielded good results in dental restoration, imitating the aesthetic properties of dental enamel”.

Although nanodental technologies have evolved quickly, safety and cost will be barriers to getting them on the market. Some nanomaterials might be toxic to healthy cells, so any new nanomaterials to be used for dentistry would need formal pre-clinical and clinical trials before they can receive approval.

Patients will also need to be told that a treatment will use materials in the nanometer size range and should be aware of any possible side effects. This new technology could also be expensive, and insurance companies may not want to foot the bill if treatments could be considered cosmetic; composite resins, for example, are still an out-of-pocket cost.

Because these composites have been so successful, engineers continue to explore new ways nanotechnologies might be used in the dentist's office. Someday nanomaterials may provide “mechanical reinforcement, improve aesthetic aspects, and induce antimicrobial and therapeutic effects,” the authors explain.

Remineralization of enamel via nanoparticles is already being explored and going forward, the authors suggest antimicrobial adhesives will act as wearable toothpaste while quantum dots combined with cancer-specific antibodies may be applied to the mouth to emit light when detecting cancerous cells. More generally, nanoparticles introduced into common dental materials could prevent or control oral diseases.

In fact, given the rapid development of these new dental nanomaterials, it is still necessary to evaluate their effects on the oral cavity in general, taking into account factors like pH, buffer capacity of saliva, contact with the mucosa, and spreading of the dental tissues. “Many of the existing studies into the toxicity of these materials have been restricted to in vitro testing. More clinical studies are necessary to understand their effects on the long term”.

Alcoholism May Hold The Drug Cure For HIV


 


A drug that’s used to treat alcoholism has been found to activate dormant HIV cells, dragging them out of hiding so they can be destroyed. When given to 30 HIV positive patients in the US and Australia in a three-day trial, the common anti-alcohol drug, disulfiram, appears to ‘wake up’ HIV cells without causing any harmful side-effects. 

HIV has an ability to stay dormant in the body by integration into the DNA of the cells of a host, resting in what is known as a latent state.

While there are antiretroviral drugs available to reduce the total HIV burden of a patient, maintain function of their immune system and prevent infections that could and often lead to death, retroviral drugs only attack HIV that is actively replicating.

In this study, 30 patents undergoing antiretroviral therapy were given disulfiram over a period of three days. In this time, the patients were given progressively higher doses of the drug.

While the first two dosages (500 and 1000 mg) did not produce any measured effect, after the highest dose of 2000 mg was given on the last day, researchers found evidence that dormant HIV was being re-activated. Seven days after this last dose, the amount of virus RNA found in a patient’s blood was found to have increased 70 percent. At the 30-day mark, this amount increased 100 percent.

Even though the drug was only given for three days, since the amount of virus RNA observed in the blood plasma showed a clear increase, it suggests the treatment was working as desired.

Scientists had already identified a class of drugs called histone deacetylase that can kick dormant HIV into gear, but they inflict too many toxic side effects to be a viable treatment option. That’s what makes disulfiram so promising - no harmful side-effects have been detected.

Current antiretroviral drugs can keep HIV in the blood in check, but patients have to take them for the rest of their lives in case the dormant virus re-emerges. Disulfiram appears to flush everything out into the open, which is just the first step in the search for a cure.

The drug was administered without seeing any side effects. This is important since toxicity is a big concern amongst other drugs that are being evaluated for bringing out HIV from hiding.

Researchers said the success of disulfiram is that is does not shock the HIV from hiding, as do many other treatments being developed. Disulfiram provides HIV with a slight tickle that seems to be all it needs to open up.

Disulfiram may be suited for future studies of combination and prolonged therapy to activate latent HIV,” the researchers wrote. This means that the next step will be to test the HIV-awakening effects of disulfiram in combination with other drugs specifically designed to kill the virus.

"This is a very important step as we have demonstrated we can wake up the sleeping virus with a safe medicine that is easily taken orally once a day. Now we need to work out how to get rid of the infected cell. A kick-start to the immune system might help," one of the team, Julian Elliott from the University of Melbourne, said in a press release. "We have an enormous amount still to learn about how to ultimately eradicate this very smart virus."