Autism brain different in visual structure from normal brain?

Researchers at the Stanford University School of Medicine and Lucile Packard Children’s Hospital have used MRI data and machine learning algorithms to classify children into autistic and non-autistic classes.
Their discovery reveals that the gray matter in a network of brain regions known to affect social communication and self-related thoughts has a distinct organization in people with autism. The findings will be published online Sept. 2 in Biological Psychiatry.

"The new findings give a uniquely comprehensive view of brain organization in children with autism and uncover a relationship between the severity of brain-structure differences and the severity of autism symptoms," said Vinod Menon, PhD, a professor of psychiatry and behavioral sciences and of neurology and neurological sciences, who led the research.

"We are getting closer to being able to use brain-imaging technology to help in the diagnosis and treatment of individuals with autism," said child psychiatrist Antonio Hardan, MD, who is the study’s other senior author and an associate professor of psychiatry and behavioral sciences at Stanford. Hardan treats patients with autism at Packard Children’s.

The study compared MRI data from 24 autistic children aged 8 to 18 with scan data from 24 age-matched, typically developing children. The data was collected at the University of Pittsburgh.

The analysis method, called "multivariate searchlight classification," divided the brain with a three-dimensional grid, then examined one cube of the brain at a time, and identified regions in which the pattern of gray matter volume could be used to discriminate between children with autism and typically developing children.

Instead of comparing the sizes of individual brain structures, as prior studies have done, the new analysis generated something akin to a topographical map of the entire brain. The scientists essentially mapped the autistic brain’s distinct cliffs and valleys, uncovering subtle differences in the physical organization of the gray matter.

Such analysis may be a more useful approach than previous tacks. Earlier studies, for instance, suggested that people with autism may have larger brains in toddlerhood or have a large defect in one brain structure. This study took a different approach and discovered several autism-associated differences in the Default Mode Network, a set of brain structures important for social communication and self-related thoughts. Specific structures that differed included the posterior cingulate cortex, the medial prefrontal cortex and the medial temporal lobes. These findings align well with recent theoretical and functional MRI studies of the autistic brain, which also point to differences in the Default Mode Network, Menon said.

Once Menon and his team had found where the differences in autistic brains were located, they were able to use their analysis to classify whether individual children in the study had autism. They used a subset of their data to "train" the mathematical algorithm, then ran the remaining brain scans through the algorithm to classify the children.

"We could discriminate between typically developing and autistic children with 92 percent accuracy on the basis of gray matter volume in the posterior cingulate cortex," said Lucina Uddin, PhD, the study’s first author. Uddin is an instructor in psychiatry and behavioral sciences at Stanford.

In addition, the children with the most severe communication deficits, as measured on a standard behavioral scale for diagnosing individuals with autism, had the biggest brain structure differences. Severe impairments in social behavior and repetitive behavior also showed a trend toward association with more severe brain differences.

When such integrated assessments are possible, the researchers hope they will allow clinicians to build detailed profiles of each patient. "We hope we’ll eventually be able to tell parents, ‘Your child will probably respond to this treatment, or your child is unlikely to respond to that treatment,’" Hardan said. "In my mind, that’s the future."

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Value of life

Last year I heard of several deaths. Some of these are very close to me, my friends. Some are old. Some are very young. In one case it was a young boy who happened was bicycling home and made a fatal mistake of crossing the traffic light on red. The parents coped as best any parent that loses their only son can. It’s heart wrenching to see them. However, the way they coped and the strength they demonstrated is nothing short of amazing. On the other spectrum another friend of mine lost his parent. His parent is in the late 80s. Surely losing a loved one is a loss but the way this friend of mine is grief stricken and literally went into depression. Another friend of mine who lost his aged parent who is in late 70s however, was more philosophical. He was happy that his father died without suffering. Another death I encountered was a middle aged woman with two young children and a husband who succumbed to cancer of the pancreas after an year of valiant fight.
I definitely morned the loss of the boy even though some other deaths are a lot closer to me personally. I have logic but I started wondering is one life more valuable than the other? In my mind one’s death is more of a loss than the other. The young mother’s death is the worse of all because of unfulfilled responsibilities. However, the boy is also a great loss because a young life is turned off without ever even having a chance of realizing his potential. However, the death of an octogenarian is, in my mind, not a loss. There is another aspect that I started thinking. In death the boy’s organs were harvested (the brave parents chose to let the doctors keep the boy alive long enough to enable this) so that they can save other lives. On the other hand the octogenarian’s organs are of no use to anyone. It’s like when I wanted to buy a new car, my car dealer took a look at my car and pronounced that this is one car that’s really used. I got barely $1000 for it – he decided to salvage parts of that).
It’s almost as though the value (or loss felt) of a dead person is inversely proportional to the value they give back in life. The more a person gives back in life, the less they take away in death.

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Reprogramming of the cells to be something other than what they are…

Human organs are made of cells. But all cells are not made equal. There is quite a bit of diversity. Most of our organs like skin, bones, muscles, heart, brain, lungs and other internal organs are made up of cells called somatic cells. These cells in general use cell division to regenerate or multiply the cells. However, there are other cells like stem cells, zygote that have the ability to differentiate into cells of different types.
Scientists have been experimenting with definite success in reprogramming these stem cells to express other cells than what they are programmed to do.
Heart cells are one of the most sought-after cells in regenerative medicine because researchers anticipate that they may help to repair injured hearts by replacing lost tissue. Now, researchers at the Perelman School of Medicine at the University of Pennsylvania are the first to demonstrate the direct conversion of a non-heart cell type into a heart cell by RNA transfer. Working on the idea that the signature of a cell is defined by molecules called messenger RNAs (mRNAs), which contain the chemical blueprint for how to make a protein, the investigators changed two different cell types, an astrocyte (a star-shaped brain cell) and a fibroblast (a skin cell), into a heart cell, using mRNAs.

tCardiomyocyte (center), showing protein distribution (green and red colors) indicative of a young cardiomyocyte. Credit: Tae Kyung Kim, PhD, Perelman School of Medicine, University of Pennsylvania

"What’s new about this approach for heart-cell generation is that we directly converted one cell type to another using RNA, without an intermediate step," explains Eberwine. The scientists put an excess of heart cell mRNAs into either astrocytes or fibroblasts using lipid-mediated transfection, and the host cell does the rest. These RNA populations (through translation or by modulation of the expression of other RNAs) direct DNA in the host nucleus to change the cell’s RNA populations to that of the destination cell type (heart cell, or tCardiomyocyte), which in turn changes the phenotype of the host cell into the destination cell.

The method the group used, called Transcriptome Induced Phenotype Remodeling, or TIPeR, is distinct from the induced pluripotent stem cell (iPS) approach used by many labs in that host cells do not have to be dedifferentiated to a pluripotent state and then redifferentiated with growth factors to the destination cell type. TIPeR is more similar to prior nuclear transfer work in which the nucleus of one cell is transferred into another cell where upon the transferred nucleus then directs the cell to change its phenotype based upon the RNAs that are made. The tCardiomyocyte work follows directly from earlier work from the Eberwine lab, where neurons were converted into tAstrocytes using the TIPeR process.

The team first extracted mRNA from a heart cell, then put it into host cells. Because there are now so many more heart-cell mRNAs versus astrocyte or fibroblast mRNAs, they take over the indigenous RNA population. The heart-cell mRNAs are translated into heart-cell proteins in the cell cytoplasm. These heart-cell proteins then influence gene expression in the host nucleus so that heart-cell genes are turned on and heart-cell-enriched proteins are made.

To track the change from an astrocyte to heart cell, the team looked at the new cells’ RNA profile using single cell microarray analysis; cell shape; and immunological and electrical properties. While TIPeR-generated tCardiomyocytes are of significant use in fundamental science it is easy to envision their potential use to screen for heart cell therapeutics, say the study authors. What’s more, creation of tCardiomyoctes from patients would permit personalized screening for efficacy of drug treatments; screening of new drugs; and potentially as a cellular therapeutic.

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Eating fatty food encourages you to eat more fat and so on…

Compounds called endocannabinoids that are a human bodies version of active compound found in marijuan, have generated a lot of interest recently due to their role in inducing endless hunger resulting in Binge eating.
Scientists and Pharamacologists from University of California, Irvine and the Italian Institute of Technology in Genoa, Italy, led by Daniele Pomelli, discovered they play a major role in overeating.
Several kinds of endocannabinoids are released in the brain and body, but researchers are still discovering the nitty-gritty of where and when these compounds regulate mood and behavior.
So the researchers fed rats one of four liquid diets: fat (in the form of corn oil), protein, sugar or a nutrition shake combination of fat, protein and sugar. To ensure that the body’s digestive signals wouldn’t interfere with the experiments, a surgically implanted valve in the rats’ upper stomach drained the food once eaten. Then the team measured endocannabinoid activity in the brain and other tissues. Compared with rats eating sugar or protein alone, rats on the fat diet had a surge of endocannabinoid activity in their gut, the team reported online July 5 in the Proceedings of the National Academy of Sciences. And these rats wouldn’t stop slurping their corn oil. When given a compound that blocked the cellular buttons that the endocannabinoids typically hit, the fat-eating rats immediately stopped eating.

That a feedback loop in animals encourages bingeing on fats makes sense, says Angelo Izzo of the University of Naples Federico II in Italy, who was not involved in the work. From an evolutionary point of view, fats were once a valuable, rare commodity that played a pivotal role in survival.

It’s been known that marijuana smokers get the munchies and endoccannabinoids are behind the hunger. However, this research finds that the endocannbinoid triggerring due to eating fat takes place in the gut.The new research is exciting because it suggests blocking endocannabinoid activity in the gut might curb overeating, says Izzo. A drug designed to do just that turned out to also interfere with endocannabinoid activity in the brain, making some people anxious and irritable. But in the new work, the fat-triggered activity was localized to the gut. Piomelli’s team hopes to generate new drugs that wouldn’t enter the brain.

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Small changes in genes (leaky genes) create express highway for evolutionary changes

It’s well known that small changes in the initial conditions cause changes in the long term that are not predictable when it comes to complex systems. There is no complex system that I know of that’s more complex than evolution of organisms. It’s no wonder that small mutations cause evolutionary changes that are far reaching. It’s very fascinating all the same.
Small genetic mutations that add up over time could create an evolutionary express lane that leads to the rapid development of new traits, researchers from the University of Pittsburgh and the University of Wisconsin at Madison have found.
The team reports in the Proceedings of the National Academy of Sciences (PNAS) that slight changes in segments of DNA known as transcriptional enhancers—which determine the when, where, and how much in gene production—can activate dormant genetic imperfections. These alterations awaken specific genes to low-level activity, or "leakiness," in developing tissue different from the genes’ typical location. Just a few subsequent mutations build on that stirring to result in a new function for an old gene—and possibly a novel trait.
The Pitt-UW Madison work expands on research during the past 30 years demonstrating that new genes made from scratch are rare in animals, Rebeiz said. Instead, the diversity of living things is thought to stem from existing genes showing up in new locations. In a famous example of the lack of originality in animal genes, researchers at the University of Basel in Switzerland reported in Science in 1995 that a gene known as PAX6, a "master control" gene for the formation of eyes and other features in flies, mice, and humans, could cause the growth of additional eyes on the legs and antennae of fruit flies.

With their report in PNAS, Rebeiz and his coauthors offer the first explanation of what makes these genes go astray in the first place—and they identified the deviant DNA as the culprit.

The researchers found that the gene Neprilysin-1 present in the optical neurons of the fruit fly species Drosophilia santomea emerged in that location about 400,000 years ago—a blip in evolutionary terms—in the last common ancestor the fly shared with its relative D. yakuba. The mutation began with a transcriptional enhancer for the gene, which caused Neprilysin-1 to show up in different neurons than usual.

From there, Rebeiz said, the development of D. santomea’s distinguishing neurons plays out with the clarity of a film as four mutations in subsequent generations intensify the errant enhancer’s impact until Neprilysin-1′s presence in optical neurons become an exclusive feature of D. santomea. On the other hand, ensuing genetic alterations in D. yakuba actually extinguished this new expression and restored that fly’s Neprilysin-1 to its original location.

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Bugs and infectious diseases

It’s well known that mosquitoes are carriers and transmitters of some of the most dreaded diseases like Malaria, Dongue fever, west nile fever etc.
Ticks, Lice and Fleas cause Encephalitis, Lyme Disease, Typhus fever, Plague
Flies carry all sorts of diseases including Sleeping sickness, Cholera etc.
Cockroaches are filthy and can survive in conditions that are unfit for most insects. However, they also infest homes. Keeping your home clean of waste and rotting food is one sure way to reduce bug infestation like cockroaches, flies etc.
Recently there has been a raise in the bed bug infestation in the US. This has almost reached epidemic proportion. It’s been believed that bed bugs do not carry any diseases. This sounded too good to be true. There is some evidence emerging that Bed Bugs may be carriers of the dreaded MRSA virus. It’s too early to conclude that bed bugs are actually transmitting the disease but it definitely helps to be vigilant.

Information about an individual hospital-based case indicates that these parasites were found to carry MRSA was reported in the June 2011 issue of Emerging Infectious Diseases, a U.S. Centers for Disease Control and Prevention public health journal. MRSA (Methicillin-resistant Staphylococcus aureus) is often picked up in hospitals and is called a "super bug" because it is resistant to antibiotics and can sometimes be deadly.

According to Atlanta, Ga. based entomologist Paul Bello, "While there is no evidence that the bed bugs have actually spread the infection at this point, it is still cause for concern, considering the potential that they might.

"If they are responsible for transporting MRSA," Bello added, "this would be a critical finding since bed bugs, by their parasitic nature, are renowned for their ability to travel from one place to another in search of warm-blooded hosts. As a result, the risk for spreading the infection could become significant. This underscores the importance of an early detection program as a critical part of any bed bug management program that should be undertaken at facilities that are at risk of bed bug infestation."

Information on how to detect bed bugs and what to do etc. are available on web. Orkin has good info on this. Some useful hints on how to prevent bed bugs in your home in this article "Bedbugs—What You Want to Know: How to Prevent and Detect Bedbugs (Bed Bugs) | Suite101.com"

You unknowingly bring bedbugs into your home after travel, mostly. (Less often, they ride in on antiques or used clothing.)

Look for bedbug infestation in hotel rooms where you stay—it happens even in upscale locations. If you find it, ask for another room on the other side of the hotel. Keep your suitcase off the floor if it’s open.

After travel, unpack your suitcase in the garage or other place where hitchhiking bedbugs will not find refuge. Remove clothing immediately, put in plastic bags, wash and dry in high temperatures.

You can encase your mattress and box springs in plastic covers, as is often done for asthma sufferers. This will kill trapped bedbugs within and prevent others from taking up homes there.

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US puts fear in the hearts of the terrorists

Not the best title for my blog. You might observe, but the terrorists don’t have hearts. Be that as it may, they are afraid. They are not sure. There is chaos inside their rigid structure.

The goal of terrorists is to create fear, challenge the sense of well-being and security in common man (or woman) so that the way of life as we know in the free world is disturbed. For doing this they need to continually grab media attention. Also the acts of terror attract attention of the followers. The most important goal for Al-queda is causing panic and chaos in countries that are pro-democratic.
An organization like Al-queda requires a charismatic leader who inspires them and continues to show them how they are succeeding in whatever twisted causes they have. They also require other “generals” who actually manage the projects and execute them. More on the “generals” later.
US Seals entering Osama-Bin-Laden’s (OBL) hide out and killing him in combat is a fantastic victory for the war on terror. Why is that?
Clearly OBL fits the “Charismatic Leader” role very well and that he is gone is a blow to the organization. However, new leaders may emerge or may have already been positioned to succeed. This is not as easy as it sounds. Succession planning is not an easy task. Great organization, even organizations with very positive outlook find it very hard. The leaders are driven by their inner most passion and that also makes them very self-driven and egotistic. This itself prevents them from electing successor as long as they are in power. They like to think that they are indispensable. US should feel very confident and that’s another reason for optimism in the war on terror.
But the most important reason for this is breaking the chaos that Al-queda wants to create.
Their goal is to create a chaotic system on the one hand (in the free world) but keep their world organized (Taliban was an example of such organization. A lot of the countries where Al-queda has the upper hand has rigid hierarchical structure). Al-queda’s very survival depends on these two systems being in existence. Attacking with force on a well structured system is hard. But the best way to deal with a system like this is to break the well-organized structure. To do this you have to get in side the system and introduce chaos. This is exactly what killing OBL accomplished. It must clearly put fear in their leadership.

This is the phase transition we have all been waiting for the last 30 years. This phase transition coupled with the revolutions going on in Arab world might be an opportunity for America to finish the job and make the world a safer place. Phase transitions reveal that we are operating at the edge of chaos. We can drive this by making us more organized or driving chaotic signals into their organization. Driving chaos with perturbation at the right local points is the right method.

When your body is fighting flu infection, a similar war happens. The chaos caused by the virus makes our immune system declare a war and start attacking indiscriminately. We experience cough, cold, breathing trouble and fever. However, once the immune system finds the magic key the virus is defenseless. It’s a question of how long it will be before the key is found. If the body can withstand, the attacks from the virus and sustain the war without damaging the very body it’s trying to protect, long enough the war is going to be won. The finding of the key is the phase transition that’s got to take place for the victory to be ascertained.
This paper covers how synchronized chaotic systems work. This requires a drive system and response system. Most of the synchronized chaotic systems proposed in the literature consist of two parts: a drive system which generates the chaotic signals, and a response system. Some signals called drive signals are generated by the drive system and are used in the response system to synchronize the common signals of both systems.

There is a lot of good research and mathematical treatment done on chaotic systems and how to bring order in such systems, how to induce phase transitions etc. To bring about transformation, the signal has to be the right amount. See this article to appreciate this fact. Qualitatively and analytically, the latest victory of US (killing of OBL) seems to fit the signal that will cause the phase transition in the chaotic system. However, a full mathematical treatment is needed (beyond my ability).

Talking about the general in Al-queda, they suddenly are leaderless and view the enemy in a new light. The generals know now, America is capable of covert action and can take out their top leaders as we see fit. Their well structured organization is in chaos. The systems are switched. Phase transition is in place.
It’s easy to catch (take them down if we have to but catch them and bring them to justice if we can. As democratic nation we would like and should follow the democratic process) the other generals who are in key positions.
Democracy by its very nature is not as stable as organization. Companies tend to be more stable because they are rigid in their organization. Same way with dictatorship or totalitarian organizations. Al-queda, like the Mafia, is organized crime that relies on democracy and causing chaos within that democracy to thrive. It’s the signal that fuels it’s engine. Introduce instability into a rigidly structured organization, it collapses completely. Whereas a loosely organized structure that democracy is, is able to respond to chaotic signals much better and instability is temporary. The war on terror needs to be appreciated as operating on the edge of chaos.

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