Reality in the eye of the beholder: A Photoshop reality check

 

Actress Kim Cattrall in an image before digital retouching. Credit: PNAS

Image of actress Kim Cattrall after digital retouching. Credit: PNAS

You know they couldn't possibly look that good. But what did those models and celebrities look like before all the retouching? How different is the image we see from the original?

Dartmouth Computer Science Professor Hany Farid and Eric Kee, a PhD student at Dartmouth College, are proposing a method to not only answer such questions but also to quantify the changes.

As Farid writes, "Impossibly thin, tall, and wrinkle- and blemish-free models are routinely splashed onto billboards, advertisements, and magazine covers." He says that this is "creating a fantasy of sorts." Going beyond considerations of aesthetics or any dishonesty of photo editors or advertisers, Farid and Kee voice public health concerns.

In a paper published in the Proceedings of the National Academy of Sciences

 

 (PNAS) on November 28, 2011, they point out that these highly idealized images have been linked to eating disorders and body image dissatisfaction in men, women, and children. The authors note that the American Medical Association has recently adopted a policy to "discourage the altering of photographs in a manner that could promote unrealistic expectations of appropriate body image."

There have already been repercussions in the United Kingdom. A Reuters news story from July 2011 reports: "Two L'Oreal cosmetics adverts [advertisements] featuring actress Julia Roberts and supermodel Christy Turlington were banned in Britain by the Advertising Standards Agency, following complaints by MP [Member of Parliament] Jo Swinson. Liberal Democrat MP Swinson said the magazine adverts for foundations made by Maybelline and Lancome, both owned by L'Oreal, were misleading because the photos had been digitally altered." On a prior occasion, L'Oreal had been forced to add a disclaimer to another ad.

But Farid and Kee assert that outright bans or simple disclaimers may not be addressing the issue fairly or completely. They are seeking a way to for advertisers to truthfully and accurately characterize the extent to which an image has been altered while allowing the public to make informed judgments. The goal is to create a metric that provides an objective assessment of how much alteration has been made.

The authors propose a rating system that takes into account common practices such as cropping and color adjustment while providing assessment of other kinds of modifications that dramatically change a person's appearance. They consider geometric alterations such as slimming legs, adjusting facial symmetry, and correcting posture, as well as photometric manipulations that might include removing wrinkles, "bags" under the eyes and skin blemishes.

"We start with the before and after digital images from which we automatically estimate the geometric and photometric changes, effectively reverse engineering the manipulations that a photo retoucher has made," Farid says.

In the study, to crosscheck and validate their metric, human observers were asked to compare and rank the differences in hundreds of pairs of before and after retouching images. The results correlated highly with the mathematical metric.

"Such a rating may provide incentive for publishers and models to reduce some of the more extreme forms of digital retouching that are common today," the authors conclude, but they add, "It remains to be seen if this rating can mediate the adverse effects of being inundated with unrealistic body images."

Provided by Dartmouth College

"Reality in the eye of the beholder: A Photoshop reality check." November 28th, 2011. http://www.physorg.com/news/2011-11-reality-eye-photoshop.html

 

Posted by
Robert Karl Stonjek

Lifelong learning that adapts to you

© Shutterstock

Technology enhanced lifelong learning that automatically adapts to the needs of the learner is now in sight thanks to work by EU-funded researchers who have developed an adaptive learning platform that can follow you through school, university, your career and even when you learn a new hobby. The rapidly growing, multi-billion euro e-learning sector is set to get a next-generation booster shot.

The EU-funded 'Generic responsive adaptive personalised learning environment' (GRAPPLE) project created a system that focuses solely on learning support, with the aim of making it easier for people to acquire new knowledge and skills. GRAPPLE also makes the most of the students' time by tailoring courses to their strengths and weaknesses. 

There are huge advantages to this kind of system and it has the potential to dramatically enhance learning in the near future. Imagine a course that is genuinely adapted to the individual, skipping material that has been mastered, and offering remedial courses on those areas where the student is weakest. 

The course could highlight and define terminology for one student but not for another, depending on whether they are already familiar with the topic. Advanced tools for adaptive lifelong learning could one day recommend courses that tie in with a user's previous experience to qualify the student for a recognised diploma or degree. In this way, learners could leverage their experience to the fullest. 

The key phrase is learning, where students direct their education based on their interest and priorities, rather than teacher-centred approaches where students are taken through a linear course regardless of their needs or wants. For this reason, the e-learning industry tends to describe users as learners, or active participants who study at every stage of their life, and not as students per se. 

This is a new departure for 'Learning management systems' (LMS). 'Currently, what an LMS system technically does are things like assignments, tests, grading and access to resources like course material, slides and other information, and it just offers those resources as files to the student. It doesn't really offer any guidance as to how to actually study the material,' explains Professor Paul De Bra, GRAPPLE Project Coordinator from the department of mathematics and computer science at the Technische Universiteit Eindhoven in the Netherlands. The project received from the EU almost EUR 4 million of its total budget of EUR 5.3 million. 

'LMS platforms are great for managing the process of learning and handling administration; right now LMS platforms have not developed any tools to help the actual learning, to make it easier and more productive for students to learn. They support the process but not the learning,' he continues. 

'That's where GRAPPLE comes in because we created an environment where you can click to an adaptive course text that you go through page by page, and it gives you a menu of choices. It can offer recommendations based on your previous experience, it can recommend new topics or suggest that you avoid other topics, and it keeps track of your learning.' 

Prof. De Bra says the platform works as an embedded adaptive learning environment within existing LMS platforms. It is designed to be easily portable from one platform to another, and the code for GRAPPLE is open source, allowing LMS vendors to adapt it to their needs. 

There are multiple ways to complete a GRAPPLE course. The system offers guidance and there are many links that learners can follow on their own initiative. 'It is really complementary to what a LMS offers,' Prof. De Bra emphasises. 

In the GRAPPLE system, learner initiative and curiosity are leveraged to enhance the educational experience. Study becomes much more absorbing when the student can follow their own interests. 

Perhaps the most ambitious goal in GRAPPLE's vision is a system that follows the learners through their life; in school, at work and in their hobbies and pastimes. And it keeps track of acquired skills and knowledge. If a user scored, say, 70 or 80 % on a topic, it will not be recommended in future courses requiring those skills, but if the student scored 50 % or lower, remedial course material might be recommended in the future. 

The EU-funded researchers designed an integrated platform to enable all this functionality. An 'event bus' coordinates all of the platform's back-end activity, except for the single sign-on facility which is handled by a powerful, globally recognised system, called Shibboleth. 

The 'GRAPPLE authoring tool' (GAT) lets e-learning authors create adaptive content and courses. The 'GRAPPLE adaptive learning environment' (GALE) provides the framework for executing courses, while the 'GRAPPLE user model framework' (GUMF) maintains all the information that is known about the learner. 

The system architecture is particularly elegant because it separates the logical functions of learning management, content delivery, content creation, user identity and user modelling. As such, it lends itself to adoption of specific elements in a modular way. For example, Prof. De Bra ponders that future versions of GRAPPLE technology could replace Shibboleth with the adoption of the OpenID standard, which is used in social networks. Many learners have an OpenID already. 

The GRAPPLE architecture also allows for further work to be carried out on individual elements without having to reinvent the entire system. Prof. De Bra offers GAT as an example. He says GAT simplifies authoring, but it is not as easy as it could be. 

'Authors find it really difficult to move from linear course delivery, where the student is taught, to adaptive learning, where users employ self-directed study,' he notes. 'The big issue is deciding the adaptation rules; under what circumstances and in what way is the material adapted?' 

It is a bottleneck in the process, but identifying the bottleneck is a huge advance and Prof. De Bra says that there will be further work on the creation of adaptation rules in other contexts. 

GRAPPLE achieved its objectives and has received positive reviews of its work. The platform was tested in a variety of environments, either as a whole or with individual components. At Trinity College, Dublin, adaptive simulated conversations were used as part of a psychotherapy course, corresponding to the responses of the student. 

In Germany, it was used by project partner Information Multimedia Communication (IMC) to teach job interview skills and self-management skills to office workers. In Eindhoven, the Netherlands, it was used to learn about hypermedia, and also about GRAPPLE itself. Likewise, all GRAPPLE partners used different topics for experiments. In all cases, the students, from different countries and linguistic backgrounds, were very enthusiastic about the platform and course delivery. 

It is a very promising start, but it is just a start and now the work will continue both within individual partner companies and enterprises and in follow-on projects. Ideas from GRAPPLE, and the use of some components are being taken up in new EU research projects, for instance in 'Immersive reflective experience-based adaptive learning' (ImREAL), a EUR 3.22 million EU-funded collaborative project. 

The GRAPPLE platform could not come at a better time for Europe. E-learning is a huge business worth EUR 40 billion worldwide in 2010. The market is growing rapidly at around 20 % a year according to figures by Global Industry Analysts. Europe is trailing the US, but by creating technologies like the GRAPPLE platform the Old World will be able to teach the New World a few tricks. 

More information: http://grapple-project.org/

 

Provided by CORDIS

"Lifelong learning that adapts to you." November 28th, 2011. http://www.physorg.com/news/2011-11-lifelong.html

 

Posted by
Robert Karl Stonjek

Researchers design steady-handed robot for brain surgery

 

Surgeons operate on a patient in July 2011 in Baghdad. Neurosurgeons may one day get help in operating rooms from a robot with movements 10 times steadier than the human hand to perform delicate brain surgeries, the EU said Monday.

Neurosurgeons may one day get help in operating rooms from a robot with movements 10 times steadier than the human hand to perform delicate brain surgeries, the EU said Monday.

The European Commission touted the EU-funded ROBOCAST project as a breakthrough in robotic neurosurgery that could in future help treat tumors, epilepsy, Parkinson's disease and Tourette syndrome.

Developped by British, German, Italian and Israeli researchers, the robotic hand, guided by a surgeon, has 13 types of movement compared to four available to human hands during minimally invasive surgery.

It even has "haptic feedback", or physical cues that allow surgeons to assess tissue and feel the amount of force applied during surgery, the European Commission said in reporting the EU-funded ROBOCAST project.

The robot has only been tested on dummies so far, performing keyhole neurosurgery, in which a probe enters a tiny hole in the skull to manipulate tissue or collect blood and other fluids.

"Robots can reduce surgeon's tremor tenfold, making them especially useful in protecting the delicate and important brain matter," the commission said.

The European Union, marking European Robotics Week, said it was funding a parallel project involving three robots to assist surgeons operating on patients who must stay away during neurosurgery.

The EU's executive Commission has already spent 400 million euros in around 100 robotics projects. Brussels says global demand for robot-related products was worth around 15.5 billion euros in 2010, including 3.0 billion in Europe.

(c) 2011 AFP

"Researchers design steady-handed robot for brain surgery." November 28th, 2011. http://www.physorg.com/news/2011-11-steady-handed-robot-brain-surgery.html

 

Posted by
Robert Karl Stonjek

Perseverance

“Perseverance is the root of good fortune. Perseverance leads to supreme happiness. Therefore I will search again, in those areas where I have not searched already.” (Hanuman, Valmiki Ramayana, Sundara Kand, 12.10) anirvedaḥ śriyo mūlam anirvedaḥ param sukham | bhūyas tāvad viceṣyāmi na yatra vicayaḥ kṛtaḥ || Who is sweeter than Hanuman   ? Though known for his supreme prowess, his ability to ward off the staunchest enemies, his knack for changing his shape to match the situation, and his undying devotion to Lord Rama   , the Supreme Personality of Godhead, Hanuman’s level of affection and concern for his dear friends is also impossible to measure. He never wants anything for himself, though he is deserving of the whole world. He is praised and honored daily by millions, but he only takes that as a sign of the greatness of the person he serves and thinks about every day. Whatever mood we find ourselves in, if we simply remember Hanuman, the quality of his heart and who resides there eternally, how can dejection and sadness stay for long? Shri Rama’s messenger searches through thick and thin, the darkness and the light, and among friend and foe alike to shine the torchlight of devotion, the divine vision of his smiling and soothing face, onto those who are deserving of it. In the above referenced verse from the Ramayana, Hanuman is turning around his depressing thoughts and channeling them towards excitement, anticipation and confidence in battle. His mission was simple: find the missing princess of Videha, Lord Rama’s wife. Since these events transpired during the Treta Yuga, the second time period of creation, even the monkey species roaming the earth was advanced to some degree. They befriended the jewel of the Raghu dynasty, who was roaming the forests at the time due to family troubles at home. When Rama’s wife went missing, the Lord and His younger brother befriended the monkey-king Sugriva residing in Kishkindha. The meeting took place because of Hanuman, who is the best messenger anyone could ask for. “O sinless one, certainly how can any king accomplish his objectives if he doesn't have such a messenger working for him?” (Lord Rama speaking to Lakshmana about Hanuman, Valmiki Ramayana   , Kishkindha Kand, 3.34) Shri Rama correctly noted to Lakshmana    upon first meeting Hanuman that no king could ever get his business accomplished without having a messenger like Hanuman. As Rama is Himself a king - the king of the universe - for tending to business He also uses Hanuman. Therefore no one was a better candidate for finding Sita and returning the information of her whereabouts. As a parent if you give an important task to your child, they will usually be enthusiastic to work. The adult has responsibilities and other things they would rather be doing, but the child looks for any opportunity to take on something important, to act like a grown up. Though Hanuman was in an adult monkey body, he nevertheless took on the mission with the enthusiasm of the most sincere child. His love for Rama was pure, and that’s all he needed for success. Yet even with his excitement and fervent desire to succeed, there were troubles encountered. Upon reaching the enemy territory of Lanka, where it was heard that Sita had been taken, Hanuman searched and searched. He went through apartment after apartment, room after room, but Sita he could not find. He discovered seemingly everything else in Lanka, including the beautiful women married to the king Ravana, the leader of the Rakshasa clan. Rakshasas are human-like creatures given to sinful activity, with the most notable repugnant behavior being their eating of human flesh. Indulgence in wine and women rounds out the picture, so we can just imagine what kind of place Hanuman entered. Hanuman is fixed in righteousness, or siddha. He has no blemishes in his character, and yet he found himself in “sin city” forced to look at things he didn’t want to see. He was able to properly justify to himself the gazing upon women who were wives of another man, but his resolve started to crack as more time went by without finding Sita. In the situation of the above referenced verse, Hanuman is thinking that Sita must have perished, that she couldn’t be in Lanka. “I’ve looked everywhere in this place. There isn’t one inch of space that I haven’t uncovered. She must not be here. I couldn’t blame her either, as she probably quit her body upon looking at the ghoulish creatures that live here and their horrible behavior. She is the embodiment of chastity and virtue, so how could she possibly survive for long without Rama by her side?” Hanuman’s premonition was well founded, but now he had to figure out what that predicament would cause. If Sita was in fact not in Lanka, if Ravana had maybe killed her, what would Hanuman say when he returned to the monkey camp? This is where his true kindness and undying love for Rama and the Lord’s friends was again exhibited. Hanuman thought of what everyone would say, how Sugriva would become angry that the mission he assigned to the monkeys on behalf of Rama was not complete. Hanuman thought of his monkey friends, with whom he had persevered through a long search, who had given him the encouragement to leap over the massive ocean that separated Lanka from the mainland. After what they had been through, how could Hanuman return as a failure? He couldn’t bear to face his friends and see the dejection on their faces. He was fine with having failed himself, for Hanuman is never concerned over his stature or fame. But he never does anything that will cause harm to his friends. Past military leaders and war heroes have uttered phrases which are today famous declarations of dedication and resolve. “Give me liberty or give me death” and “I have not yet begun to fight” embody the chivalrous spirit of the dedicated warrior. Yet long before these phrases were uttered, many thousands of years ago, before the modern incarnation of organized military conflict, Hanuman reminded himself of the importance of perseverance, giving himself a small pep talk in the process. Hanuman rightly concluded that perseverance is the source of good fortune, that it brings supreme happiness. The opposite of perseverance is weakness in resolve, giving up rather quickly. It is much easier to give up when there is no enthusiasm in the task to begin with, when the reward is not worth the effort. For Hanuman such issues were not present. He took the task assigned to him by Rama as his life and soul, and he knew that finding Sita would be the greatest reward anyone could ask for. Therefore he rightly concluded that perseverance in this case would lead to good fortune. Sita Devi    resides eternally in the spiritual sky as the goddess of fortune, so anyone who is fortunate enough to please her by dedicating their life to serving her husband, God, will always be in her good graces. Perseverance also brings supreme happiness. If we don’t put in our best effort and fail in a task, there will be so much regret later on. “I really wish I would have tried harder. I wish I had given it my all. Maybe then the outcome could have been different.” In many instances, even if there isn’t ultimate victory, if the perseverance is still there then there is every reason to be proud. Hanuman would find supreme happiness by remaining dedicated in his service to Rama. He would eventually find Sita, and all would end well. Who among us hasn’t tasted defeat? Who among us hasn’t searched for something or someone repeatedly, only to have failed? The genesis of the material creation is the flawed search for happiness in the absence of God’s association. The search can go on and on, even in planets outside of earth, for that elusive happiness, but it will never be found. The only path towards lasting happiness is spiritual life, and more specifically the discipline of bhakti-yoga, or devotional service   . Chanting    the holy names of the Lord, “Hare Krishna Hare Krishna, Krishna Krishna, Hare Hare, Hare Rama Hare Rama, Rama Rama, Hare Hare   ”, is the most auspicious activity because it keeps the mind engaged in Truth, the consciousness focused on an area where God eternally resides. Though the Lord is everything, He is not personally present within every sphere. Rather, He lives in the hearts of those who regularly chant His names and delight in descriptions of His pastimes and glories. Those who reproduce the sound vibrations of Krishna and Rama, two wonderful names describing the Supreme Lord’s transcendental body and limitless attributes of opulence, find the Lord with them at all times. In the path of bhakti-yoga, which leads to emancipation, there may arise difficulties. “I’ve been chanting for so long and I don’t feel anything. I’ve looked here and there and still I don’t realize God.” But as Hanuman says, perseverance leads to good fortune, to supreme happiness. If after chanting so much and abstaining from the four pillars of sinful life    [meat eating, gambling   , intoxication    and illicit sex   ], we still don’t feel that God is with us, the solution is not to abandon our dedication and return to association with maya, or material nature. Maya has already been searched thoroughly to no avail in both this lifetime and many previous ones as well. Faced with the possibility of failure, Hanuman decided to renew his search, to go places where he had not gone before. When we have momentary lapses of judgment and feelings of dejection in our devotional efforts, the key is to delve even deeper into spiritual life, to uncover those practices that we have yet to take up. We can chant more rounds, read more books, visit more temples, or simply hear more about the Lord from people who love him, who follow in Hanuman’s footsteps by dedicating their life and soul to pleasing the Supreme Lord. Just as Hanuman was eventually successful, the weary soldier trying to win the war against the material nature that inhibits his spiritual growth too will ultimately prevail. Who can be more concerned over the welfare of their friends and family than Hanuman? The answer is “no one”. Therefore anyone who has a sincere desire to connect with God through bhakti will surely catch Hanuman’s eye. He will be concerned about their welfare to the same level as if they were a family member. This shows one of the many reasons why Hanuman is so passionately worshiped, honored, adored, and remembered by followers of the Vedic tradition. Hanuman casts a shadow that is impossible to break out of for those following the path of divine love. By using that shadow for comfort, as relief from the intense heat of material existence, the chances for success in life’s mission increase all the more. Who can better deal with the distresses that come with temporary failure than Hanuman? After all he had been through, it would have been understandable if he would have quit, thrown in the towel, and decided to return home. Yet that wasn’t an option for him. He’d rather fight every single Rakshasa in Lanka and punish them for whatever they had done to Sita than return home without news of the whereabouts of the princess. His supreme wisdom borne of his devotion to Rama kept him going, giving him the fortitude necessary to remain calm in the face of major duress. Seeing Hanuman’s thoughts and level of dedication, we can’t help but be touched by them. Since the events of the Ramayana took place so long ago and describe attributes and creatures not seen on the earth today, it is very easy to discount the whole poem as being mythology. Yet the wonderful dedication of Hanuman and his very character alone prove that Rama can be none other than the Supreme Lord, whom the entire creation is given to worship and honor. Where Shri Rama finds people like Hanuman to serve Him is a mystery. Even Lord Brahma, the creator, is enamored by Hanuman’s exhibition of divine love, for who could ever imagine a creature like him roaming the earth? The mystery of Hanuman’s character and immeasurable devotion is known only to the Lord, who always has the best friends and well-wishers. Should we one day be fortunate enough to consider ourselves among that illustrious group of souls, our existence will have proved fruitful. In Closing: To keep firm resolve under duress, Is what can lead to success. To the task at hand keep focus in, Perseverance leads to good fortune. These postulates Hanuman himself did remind, So that he wouldn’t fail in Sita to find. Because his character is kind and sweet, Victory he'd ultimately meet. He gives the lesson for us to follow, In sadness and failure don't wallow. Have perseverance in your bhakti practice, To always remember Hanuman your mind insist.

YOU MAY POISON YOURSELF ACCIDENTALLY

(I didn't know this myself)
A woman suddenly died unexpectedly with signs of bleeding from her ears,nose, mouth & eyes. After a preliminary autopsy it was diagnosed that death was due to arsenic poisoning. Where did the arsenic come from? The police launched an in-depth and extensive investigation. A medical school professor was invited to come to solve the case. The professor carefully looked at the contents from the deceased's stomach. In less than half an hour, the mystery was solved. The professor said: 'The deceased did not commit suicide and neither was she murdered, she died of accidental death due to ignorance!'
Everyone was puzzled, why accidental death?
The professor said: 'The arsenic is produced in the stomach of the deceased.' The deceased used to take 'Vitamin C' everyday, which in itself is not a problem. The problem was that she ate a  large portion of shrimp/prawn during dinner. Eating shrimp/prawn is not the problem that's why nothing happened to her family even though they took the same shrimp/prawn. However at the same time the deceased also took 'vitamin C', that is where the problem is  Researchers at the University of Chicago in the United States , found through experiments, food such as soft-shell shrimp/prawn contains a much higher concentration of five potassium arsenic compounds.
Such fresh food by itself has no toxic effects on the human body. However, in taking 'vitamin C', chemical reaction occur and the original non-toxic elements change to toxic elements.
Arsenic poisoning has magma role and can cause paralysis to the small blood vessels. Therefore, a person who dies of arsenic poisoning will show signs of bleeding from the ears, nose, mouth & eyes. Thus as a precautionary measure, DO NOT eat shrimp/prawn when taking 'vitamin C'.
After reading this; please do not be stingy. Forward to your friends
Dr NEWTON JAYAWARDANE
MBBS MS FRCS(Eng)
Consultant Surgeon
Teaching Hospital
RAGAMA 11010.
Sri LANKA .

Neurons grown from skin cells may hold clues to autism

 by Biomechanism

Potential clues to how autism miswires the brain are emerging from a study of a rare, purely genetic form of the disorders that affects fewer than 20 people worldwide. Using cutting-edge “disease-in a-dish” technology, researchers funded by the National Institutes of Health have grown patients’ skin cells into neurons to discover what goes wrong in the brain in Timothy Syndrome. Affected children often show symptoms of autism spectrum disorders along with a constellation of physical problems.

Abnormalities included changes in the composition of cells in the cortex, the largest brain structure in humans, and of neurons that secrete two key chemical messengers. Neurons that make long-distance connections between the brain’s hemispheres tended to be in short supply.

Most patients with Timothy Syndrome meet diagnostic criteria for an autism spectrum disorder. Yet, unlike most cases of autism, Timothy syndrome is known to be caused by a single genetic mutation.

“Studying the consequences of a single mutation, compared to multiple genes with small effects, vastly simplifies the task of pinpointing causal mechanisms,” explained Ricardo Dolmetsch, Ph.D., of Stanford University, a National Institute of Mental Health (NIMH) grantee who led the study. His work was partially funded by a NIH Director’s Pioneer Award.

Dolmetsch, and colleagues, report on their findings Nov. 27, 2011 in the journal Nature Medicine.

“Unlike animal research, the cutting-edge technology employed in this study makes it possible to pinpoint molecular defects in a patient’s own brain cells,” said NIMH Director Thomas R. Insel, M.D. “It also offers a way to screen more rapidly for medications that act on the disordered process.”

Prior to the current study, researchers knew that Timothy syndrome is caused by a tiny glitch in the gene that codes for a calcium channel protein in cell membranes. The mutation results in too much calcium entering cells, causing a tell-tale set of abnormalities throughout the body. Proper functioning of the calcium channel is known to be particularly critical for proper heart rhythm – many patients die in childhood of arrhythmias – but its role in brain cells was less well understood.

To learn more, Dolmetsch and colleagues used a new technology called induced pluripotent stem cells (iPSCs). They first converted skin cells from Timothy Syndrome patients into stem cells and then coaxed these to differentiate into neurons.

“Remarkable reproducibility” observed across multiple iPSC lines and individuals confirmed that the technique can reveal defects in neuronal differentiation – such as whether cells assume the correct identity as the brain gets wired-up in early development, said the researchers. Compared to those from controls, fewer neurons from Timothy Syndrome patients became neurons of the lower layers of the cortex and more became upper layer neurons. The lower layer cells that remained were more likely to be the kind that project to areas below the cortex. In contrast, there were fewer-than-normal neurons equipped to form a structure, called the corpus callosum, which makes possible communications between the left and right hemispheres.

Caption: Forebrain of a mouse genetically engineered to express the mutated gene that causes Timothy syndrome (TS) shows fewer neurons contributing to a brain structure responsible for long-distance communications between the left and right hemispheres, called the corpus callosum, compared to the same structure in a control animal (Ctrl). Human iPSCs from TS patients showed a similar reduction. Credit: Ricardo Dolmetsch, Ph.D., Stanford University

Many of these defects were also seen in parallel studies of mice with the same genetic mutation found in Timothy syndrome patients. This supports the link between the mutation and the developmental abnormalities.

Several genes previously implicated in autism were among hundreds found to be expressed abnormally in Timothy Syndrome neurons. Excess cellular calcium levels also caused an overproduction of neurons that make key chemical messengers. Timothy Syndrome neurons secreted 3.5 times more norepinephrine and 2.3 times more dopamine than control neurons. Addition of a drug that blocks the calcium channel reversed the abnormalities in cultured neurons, reducing the proportion of catecholamine-secreting cells by 68 percent.

The findings in Timothy Syndrome patient iPSCs follow those in Rett Syndrome, another single gene disorder that often includes autism-like symptoms. About a year ago, Alysson Muotri, Ph.D., and colleagues at University of California, San Diego, reported deficits in the protrusions of neurons, called spines, that help form connections, or synapses. The Dolmetsch team’s discovery of earlier (neuronal fate) and later (altered connectivity) defects suggest that disorders on the autism spectrum affect multiple stages in early brain development.

“Most of these abnormalities are consistent with other emerging evidence that ASDs arise from defects in connectivity between cortex areas and show decreased size of the corpus callosum,” said Dolmetsch. “Our study reveals how these might be traceable to specific mechanisms set in motion by poor regulation of cellular calcium. It also demonstrates that neurons derived from iPSCs can be used to identify the cellular basis of a neurodevelopmental disorder.”

The mechanisms identified in this study may become potential targets for developing new therapies for Timothy Syndrome and may also provide insights into the neural basis of deficits in other forms of autism, said Dolmetsch.

________

Reference:
Using iPS cell-derived neurons to uncover cellular phenotypes associated with Timothy Syndrome. Pasca SP, Portmann T, Voineagu I, Yazawa M, Shcheglovitov O, Pasca AM, Cord B, Palmer TD, Chikahisa S, Seiji N, Bernstein JA, Hallmayer J, Geschwind DH, Dolmetsch RE. November 27, 2011.Nature Medicine.

Study finds new ‘natural killers’

THE AUSTRALIAN NATIONAL UNIVERSITY

The newfound defence cell generates antibody responses against viral and bacterial invasions. Image: DNY59/iStockphoto Researchers from The Australian National University have discovered a new type of cell which boosts the human body’s ability to fight off infections and life-threatening diseases. Professor Carola Vinuesa from The John Curtin School of Medical Research has found a type of cell which recognises lipid antigens, or foreign molecules, which sit on infectious bacteria which invade the body. Once recognising the lipids, the cell, called Natural killer T follicular helper (NKTfh), generates antibody responses in B cells – which are the body’s natural defence against invasion by viruses and bacteria. Professor Vinuesa said that the cell represents a non-chemical based and natural way for the human body to fight-off bacteria and infection. “Natural killer T cells, unlike other T cells, recognise molecules known as lipids instead of just recognising proteins expressed by infectious bacteria. These types of bacteria can cause life-threatening infections, including meningitis and pneumonia.  NKT cells don’t just recognise lipids – they can be naturally activated by them,” she said. “Not surprisingly, NKT cells have been shown to play important roles in combating infection and in other immune processes including allergy, cancer and autoimmunity. “What we have found is a subset of NKT cells, the NKTfh, which are specialised in generating antibody responses in B cells that recognise lipid-containing antigens. NKTfh cells also induce specialised structures called germinal centres, similar to those which have previously been shown to generate high affinity antibody responses to protein antigens. Both these qualities provide a natural boost to B cells, subsequently strengthening the human immune system and its ability to stave off infection.” Professor Vinuesa also discovered that the NKTfh cells provide this boost over a very short and sharp period of time without generating long-lived antibody-producing cells. “The discovery of the NKTfh will help us understand how to elicit immune protection against lipid-containing microbes and which natural antibody responses can best fight each type of infection,” she said. “For example, the ability of NKTfh cells to promote faster antibody responses than conventional helper T cells may be important for protection against life-threatening infections, whereas their inability to induce long-lived antibody producing cells may be key to the prevention of autoimmune diseases.” Professor Vinuesa’s recent discoveries have been published in two separate papers in the journals Nature Immunology and Immunity. Copies of the articles are available from the ANU Media Office. Editor's Note: Original news release can be found here.