Inspiration linked to bipolar disorder risk

Inspiration has been linked with people at risk of developing bipolar disorder for the first time in a study. For generations, artists, musicians, poets and writers have described personal experiences of mania and depression, highlighting the unique association between creativity and bipolar disorder -- experiences which are backed up by recent research. But, until now, the specific links between inspiration -- the generation of ideas that form the basis of creative work -- and bipolar disorder has received little attention.

Until now, the specific links between inspiration -- the generation of ideas that form the basis of creative work -- and bipolar disorder has received little attention. New research has shown people at higher risk for developing bipolar disorder consistently report stronger experiences of inspiration than those at lower risk.

For generations, artists, musicians, poets and writers have described personal experiences of mania and depression, highlighting the unique association between creativity and bipolar disorder -- experiences which are backed up by recent research. But, until now, the specific links between inspiration -- the generation of ideas that form the basis of creative work -- and bipolar disorder has received little attention.
New research by Professor by Steven Jones and Dr Alyson Dodd, of Lancaster University, and Dr June Gruber at Yale University, has shown people at higher risk for developing bipolar disorder consistently report stronger experiences of inspiration than those at lower risk.
The paper 'Development and Validation of a New Multidimensional Measure of Inspiration: Associations with Risk for Bipolar Disorder', published in PLOS One this week, found a specific link between those people who found their source of inspiration within themselves and risk for bipolar disorder.
Professor Jones, co-director of Lancaster University's Spectrum Centre, said: "It appears that the types of inspiration most related to bipolar vulnerability are those which are self-generated and linked with strong drive for success.
"Understanding more about inspiration is important because it is a key aspect of creativity which is highly associated with mental health problems, in particular bipolar disorder. People with bipolar disorder highly value creativity as a positive aspect of their condition. This is relevant to clinicians, as people with bipolar disorder may be unwilling to engage with treatments and therapies which compromise their creativity."
As part of the study, 835 undergraduate students were recruited to complete online questionnaires from both Yale University in the U.S. and Lancaster University in the U.K.
They were asked to complete a questionaire which measured their bipolar risk using a widely-used and well-validated 48-item measure which captures episodic shifts in emotion, behaviour, and energy called The Hypomanic Personality Scale (HPS).
They also completed a new questionnaire developed by the team which was designed to explore beliefs about inspiration, in particular the sources of inspiration -- whether individuals thought it came from within themselves, from others or the wider environment. This measure was called the the EISI (External and Internal Sources of Inspiration) measure.
The students who scored highly for a risk of bipolar also consistently scored more highly than the others for levels of inspiration and for inspiration which they judged to have come from themselves.
Researchers say, although this pattern was consistent, the effect sizes were relatively modest so, although inspiration and bipolar risk are linked, it is important to explore other variables to get a fuller picture and to conduct further research with individuals with a clinical diagnosis of bipolar disorder.
The research team is currently inviting UK-based individuals with a diagnosis of bipolar disorder to take part in an online survey exploring associations between inspiration, mood and recovery. Go to: www.thinkingstyle.spectrumdevelopment.org.uk.


Journal Reference:

1. Steven Jones, Alyson Dodd, June Gruber. Development and Validation of a New Multidimensional Measure of Inspiration: Associations with Risk for Bipolar Disorder. PLoS ONE, 2014; 9 (3): e91669 DOI: 10.1371/journal.pone.0091669 

Courtesy: ScienceDaily

Computers see through faked expressions of pain better than people

A joint study by researchers at the University of California, San Diego and the University of Toronto has found that a computer system spots real or faked expressions of pain more accurately than people can.

 

Which expression do you think shows real pain? Attempts to fake expressions of pain typically involve the same facial muscles that are contracted during real pain. There is no telltale facial muscle whose presence or absence would indicate real or faked pain. The difference is in the dynamics. The real expression of pain is image B on the right.

The work, titled "Automatic Decoding of Deceptive Pain Expressions," is published in the latest issue of Current Biology.
"The computer system managed to detect distinctive dynamic features of facial expressions that people missed," said Marian Bartlett, research professor at UC San Diego's Institute for Neural Computation and lead author of the study. "Human observers just aren't very good at telling real from faked expressions of pain."
Senior author Kang Lee, professor at the Dr. Eric Jackman Institute of Child Study at the University of Toronto, said "humans can simulate facial expressions and fake emotions well enough to deceive most observers. The computer's pattern-recognition abilities prove better at telling whether pain is real or faked."
The research team found that humans could not discriminate real from faked expressions of pain better than random chance -- and, even after training, only improved accuracy to a modest 55 percent. The computer system attains an 85 percent accuracy.
"In highly social species such as humans," said Lee, "faces have evolved to convey rich information, including expressions of emotion and pain. And, because of the way our brains are built, people can simulate emotions they're not actually experiencing -- so successfully that they fool other people. The computer is much better at spotting the subtle differences between involuntary and voluntary facial movements."
"By revealing the dynamics of facial action through machine vision systems," said Bartlett, "our approach has the potential to elucidate 'behavioral fingerprints' of the neural-control systems involved in emotional signaling."
The single most predictive feature of falsified expressions, the study shows, is the mouth, and how and when it opens. Fakers' mouths open with less variation and too regularly.
"Further investigations," said the researchers, "will explore whether over-regularity is a general feature of fake expressions."
In addition to detecting pain malingering, the computer-vision system might be used to detect other real-world deceptive actions in the realms of homeland security, psychopathology, job screening, medicine, and law, said Bartlett.
"As with causes of pain, these scenarios also generate strong emotions, along with attempts to minimize, mask, and fake such emotions, which may involve 'dual control' of the face," she said. "In addition, our computer-vision system can be applied to detect states in which the human face may provide important clues as to health, physiology, emotion, or thought, such as drivers' expressions of sleepiness, students' expressions of attention and comprehension of lectures, or responses to treatment of affective disorders."

Journal Reference:

1. Marian Stewart Bartlett, Gwen C. Littlewort, Mark G. Frank, Kang Lee. Automatic Decoding of Facial Movements Reveals Deceptive Pain Expressions. Current Biology, 2014 DOI: 10.1016/j.cub.2014.02.009

 Courtesy: ScienceDaily

Scientists find mechanism to reset body clock

Researchers from The University of Manchester have discovered a new mechanism that governs how body clocks react to changes in the environment.

Researchers have discovered a new mechanism that governs how body clocks react to changes in the environment.

And the discovery, which is being published in Current Biology, could provide a solution for alleviating the detrimental effects of chronic shift work and jet-lag.
The team's findings reveal that the enzyme casein kinase 1epsilon (CK1epsilon) controls how easily the body's clockwork can be adjusted or reset by environmental cues such as light and temperature.
Internal biological timers (circadian clocks) are found in almost every species on the planet. In mammals including humans, circadian clocks are found in most cells and tissues of the body, and orchestrate daily rhythms in our physiology, including our sleep/wake patterns and metabolism.
Dr David Bechtold, who led The University of Manchester's research team, said: "At the heart of these clocks are a complex set of molecules whose interaction provides robust and precise 24 hour timing. Importantly, our clocks are kept in synchrony with the environment by being responsive to light and dark information."
This work, funded by the Biotechnology and Biological Sciences Research Council, was undertaken by a team from The University of Manchester in collaboration with scientists from Pfizer led by Dr Travis Wager.
The research identifies a new mechanism through which our clocks respond to these light inputs. During the study, mice lacking CK1epsilon, a component of the clock, were able to shift to a new light-dark environment (much like the experience in shift work or long-haul air travel) much faster than normal.
The research team went on to show that drugs that inhibit CK1epsilon were able to speed up shift responses of normal mice, and critically, that faster adaption to the new environment minimised metabolic disturbances caused by the time shift.
Dr Bechtold said: "We already know that modern society poses many challenges to our health and wellbeing -- things that are viewed as commonplace, such as shift-work, sleep deprivation, and jet lag disrupt our body's clocks. It is now becoming clear that clock disruption is increasing the incidence and severity of diseases including obesity and diabetes.
"We are not genetically pre-disposed to quickly adapt to shift-work or long-haul flights, and as so our bodies' clocks are built to resist such rapid changes. Unfortunately, we must deal with these issues today, and there is very clear evidence that disruption of our body clocks has real and negative consequences for our health."
He continues: "As this work progresses in clinical terms, we may be able to enhance the clock's ability to deal with shift work, and importantly understand how maladaptation of the clock contributes to diseases such as diabetes and chronic inflammation."
 

Journal Reference:

1. Violetta Pilorz, Peter S. Cunningham, Anthony Jackson, Alexander C. West, Travis T. Wager, Andrew S.I. Loudon, David A. Bechtold. A Novel Mechanism Controlling Resetting Speed of the Circadian Clock to Environmental Stimuli. Current Biology, 2014 DOI: 10.1016/j.cub.2014.02.027 

 Courtesy: ScienceDaily

Genetic factor contributes to forgetfulness

Misplaced your keys? Can't remember someone's name? Didn't notice the stop sign? Those who frequently experience such cognitive lapses now have an explanation. Psychologists from the University of Bonn have found a connection between such everyday lapses and the DRD2 gene. Those who have a certain variant of this gene are more easily distracted and experience a significantly higher incidence of lapses due to a lack of attention. The scientific team will report their results in the May issue of Neuroscience Letters, which is already available online in advance.

Dr. Sebastian Markett from the department for Differential and Biological Psychology of the University of Bonn examined variants of a gene affecting signal transmission within the brain's frontal lobes.

Most of us are familiar with such everyday lapses; can't find your keys, again! Or you walk into another room but forgot what you actually went there for. Or you are on the phone with someone and cannot remember their name. "Such short-term memory lapses are very common, but some people experience them particularly often," said Prof. Dr. Martin Reuter from the department for Differential and Biological Psychology at the University of Bonn. Mistakes occurring due to such short-term lapses can become a hazard in cases where, e.g., a person overlooks a stop sign at an intersection. And in the workplace, a lack of attention can also become a problem-so for example when it results in forgetting to save essential data.
A gene "directing" your brain
"A familial clustering of such lapses suggests that they are subject to genetic effects," explained Dr. Sebastian Markett, the principal author and a member of Prof. Reuter's team. In lab experiments, the group of scientists had already found indications earlier that the so-called dopamine D2 receptor gene (DRD2) plays a part in forgetfulness. DRD2 has an essential function in signal transmission within the frontal lobes. "This structure can be compared to a director coordinating the brain like an orchestra," Dr. Markett added. In this simile, the DRD2 gene would correspond to the baton, because it plays a part in dopamine transmission in the brain. If the baton skips a beat, the orchestra gets confused.
The psychologists from the University of Bonn tested a total of 500 women and men by taking a saliva sample and examining it using methods from molecular biology. All humans carry the DRD2 gene, which comes in two variants that are distinguished by only one letter within the genetic code. The one variant has C (cytosine) in one locus, which is displaced by T (thymine) in the other. According to the research team's analyses, about a quarter of the subjects exclusively had the DRD2 gene with the cytosine nucleobase, while three quarters were the genotype with at least one thymine base.
The scientists then wanted to find out whether this difference in the genetic code also had an effect on everyday behavior. By means of a self-assessment survey they asked the subjects to state how frequently they experience these lapses-how often they forgot names, misplaced their keys. The survey also included questions regarding certain impulsivity-related factors, such as how easily a subject was distracted from actual tasks at hand, and how long they were able to maintain their concentration. Lapses can clearly be tied to the gene variant
The scientists used statistical methods to check whether it was possible to associate the forgetfulness symptoms elicited by means of the surveys to one of the DRD2 gene variants. The results showed that functions such as attention and memory are less clearly expressed in persons who carry the thymine variant of the gene than in the cytosine type. "The connection is obvious; such lapses can partially be attributed to this gene variant," reported Dr. Markett. According to their own statements, the subjects with the thymine DRD2 variant more frequently "fall victim" to forgetfulness or attention deficits. And vice versa, the cytosine type seems to be protected from that. "This result matches the results of other studies very well," added Dr. Markett.
Carriers of the gene variant linked to forgetfulness may now find solace in the fact that they are not responsible for their genes, and that this is just their fate....but Dr. Markett doesn't agree. "There are things you can do to compensate for forgetfulness; writing yourself notes or making more of an effort to put your keys down in a specific location-and not just anywhere." Those who develop such strategies for the different areas of their lives are better able to handle their deficit.
 

Journal Reference:

1. Sebastian Markett, Christian Montag, Corinna Diekmann, Martin Reuter. Dazed and confused: A molecular genetic approach to everyday cognitive failure. Neuroscience Letters, 2014; DOI: 10.1016/j.neulet.2014.02.052

Courtesy: ScienceDaily
 

Cell therapy shows remarkable ability to eradicate cancer in clinical study

Investigators from Memorial Sloan Kettering Cancer Center have reported more encouraging news about one of the most exciting methods of cancer treatment today. The largest clinical study ever conducted to date of patients with advanced leukemia found that 88 percent achieved complete remissions after being treated with genetically modified versions of their own immune cells. The results were published today in Science Translational Medicine.

 

Cell-based, targeted immunotherapy is a new approach to treating cancer that harnesses the body's own immune system to attack and kill cancerous cells. Unlike with a common virus such as the flu, our immune system does not recognize cancer cells as foreign and is therefore at a disadvantage in eradicating the disease.

"These extraordinary results demonstrate that cell therapy is a powerful treatment for patients who have exhausted all conventional therapies," said Michel Sadelain, MD, PhD, Director of the Center for Cell Engineering at Memorial Sloan Kettering and one of the study's senior authors. "Our initial findings have held up in a larger cohort of patients, and we are already looking at new clinical studies to advance this novel therapeutic approach in fighting cancer."
Adult B cell acute lymphoblastic leukemia (B-ALL), a type of blood cancer that develops in B cells, is difficult to treat because the majority of patients relapse. Patients with relapsed B-ALL have few treatment options; only 30 percent respond to salvage chemotherapy. Without a successful bone marrow transplant, few have any hope of long-term survival.
In the current study, 16 patients with relapsed B-ALL were given an infusion of their own genetically modified immune cells, called T cells. The cells were "reeducated" to recognize and destroy cancer cells that contain the protein CD19. While the overall complete response rate for all patients was 88 percent, even those with detectable disease prior to treatment had a complete response rate of 78 percent, far exceeding the complete response rate of salvage chemotherapy alone.
Dennis J. Billy, C.Ss.R, of Wynnewood, Pennsylvania, was one of the first patients to receive this treatment more than two years ago. He was able to successfully undergo a bone marrow transplant and has been cancer-free and back at work teaching theology since 2011. Paolo Cavalli, a restaurant owner from Oxford, Connecticut, remains in complete remission eight months after receiving his personalized T cell treatment.
A History of Scientific Achievements for Cell-Based Therapies
Cell-based, targeted immunotherapy is a new approach to treating cancer that harnesses the body's own immune system to attack and kill cancerous cells. Unlike with a common virus such as the flu, our immune system does not recognize cancer cells as foreign and is therefore at a disadvantage in eradicating the disease. For more than a decade, researchers at Memorial Sloan Kettering have been exploring ways to reengineer the body's own T cells to recognize and attack cancer. In 2003, they were the first to report that T cells engineered to recognize the protein CD19, which is found on B cells, could be used to treat B cell cancers in mice.
"Memorial Sloan Kettering was the first center to report successful outcomes using this CD19-targeted approach in B-ALL patients," said Renier Brentjens, MD, PhD, Director of Cellular Therapeutics at Memorial Sloan Kettering and one of the study's senior authors. "It's extremely gratifying to witness the astonishing results firsthand in my patients, having worked for more than a decade developing this technology from the ground up."
In March 2013, the same team of researchers first reported the results of five patients with advanced B-ALL who were treated with cell therapy. Remarkably, all five patients achieved complete remissions.
Results Demonstrate Potential of New Therapy
In the current study, seven of the 16 patients (44 percent) were able to successfully undergo bone marrow transplantation -- the standard of care and the only curative option for B-ALL patients -- following treatment. Three patients were ineligible due to failure to achieve a complete remission, three were ineligible due to preexisting medical conditions, two declined, and one is still being evaluated for a potential bone marrow transplant. Historically, only 5 percent of patients with relapsed B-ALL have been able to transition to bone marrow transplantation.
The study also provides guidelines for managing side effects of cell therapy, which can include severe flu-like symptoms such as fever, muscle pain, low blood pressure, and difficulty breathing, referred to as cytokine release syndrome. The researchers developed diagnostic criteria and a laboratory test that can identify which patients are at greater risk for developing this syndrome.
Additional studies to determine whether cell therapy can be applied to other types of cancer are already underway, and studies to test whether B-ALL patients would benefit from receiving targeted immunotherapy as frontline treatment are being planned.

Journal Reference:

1. M. L. Davila, I. Riviere, X. Wang, S. Bartido, J. Park, K. Curran, S. S. Chung, J. Stefanski, O. Borquez-Ojeda, M. Olszewska, J. Qu, T. Wasielewska, Q. He, M. Fink, H. Shinglot, M. Youssif, M. Satter, Y. Wang, J. Hosey, H. Quintanilla, E. Halton, Y. Bernal, D. C. G. Bouhassira, M. E. Arcila, M. Gonen, G. J. Roboz, P. Maslak, D. Douer, M. G. Frattini, S. Giralt, M. Sadelain, R. Brentjens. Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia. Science Translational Medicine, 2014; 6 (224): 224ra25 DOI: 10.1126/scitranslmed.3008226 

Courtesy: ScienceDaily

Human brains 'hard-wired' to link what we see with what we do

Your brain's ability to instantly link what you see with what you do is down to a dedicated information 'highway', suggests new UCL-led research.

Focused computer work (stock photo). Standard visual processing is prone to distractions, as it requires us to pay attention to objects of interest and filter out others. The new study has shown that our brains have separate 'hard-wired' systems to visually track our own bodies, even if we are not paying attention to them.

For the first time, researchers from UCL (University College London) and Cambridge University have found evidence of a specialized mechanism for spatial self-awareness that combines visual cues with body motion.
Standard visual processing is prone to distractions, as it requires us to pay attention to objects of interest and filter out others. The new study has shown that our brains have separate 'hard-wired' systems to visually track our own bodies, even if we are not paying attention to them. In fact, the newly-discovered network triggers reactions even before the conscious brain has time to process them.
The researchers discovered the new mechanism by testing 52 healthy adults in a series of three experiments. In all experiments, participants used robotic arms to control cursors on two-dimensional displays, where cursor motion was directly linked to hand movement. Their eyes were kept fixed on a mark at the centre of the screen, confirmed with eye tracking.
In the first experiment, participants controlled two separate cursors with their left and right hands, both equally close to the centre. The goal was to guide each cursor to a corresponding target at the top of the screen. Occasionally the cursor or target on one side would jump left or right, requiring participants to take corrective action. Each jump was 'cued' with a flash on one side, but this was random so did not always correspond to the side about to change.
Unsurprisingly, people reacted faster to target jumps when their attention was drawn to the 'correct' side by the cue. However, reactions to cursor jumps were fast regardless of cuing, suggesting that a separate mechanism independent of attention is responsible for tracking our own movements.
"The first experiment showed us that we react very quickly to changes relating to objects directly under our own control, even when we are not paying attention to them," explains Dr Alexandra Reichenbach of the UCL Institute of Cognitive Neuroscience, lead author of the study. "This provides strong evidence for a dedicated neural pathway linking motor control to visual information, independently of the standard visual systems that are dependent on attention."
The second experiment was similar to the first, but also introduced changes in brightness to demonstrate the attention effect on the visual perception system. In the third experiment, participants had to guide one cursor to its target in the presence of up to four dummy targets and cursors, 'distractors', alongside the real ones. In this experiment, responses to cursor jumps were less affected by distractors than responses to target jumps. Reactions to cursor jumps remained vigorous with one or two distractors, but were significantly decreased when there were four.
"These results provide further evidence of a dedicated 'visuomotor binding' mechanism that is less prone to distractions than standard visual processing,' says Dr Reichenbach. "It looks like the specialized system has a higher tolerance for distractions, but in the end it is still affected. Exactly why we evolved a separate mechanism remains to be seen, but the need to react rapidly to different visual cues about ourselves and the environment may have been enough to necessitate a specialized pathway."
The newly-discovered system could explain why some schizophrenia patients feel like their actions are controlled by someone else.
"Schizophrenia often manifests as delusion of control, and a dysfunction in the visuomotor mechanism identified in this study might be a cause for this symptom," explains Dr Reichenbach. "If someone does not automatically link corresponding visual cues with body motion, then they might have the feeling that they are not controlling their movements. We would need further research to confirm this, and it would be fascinating to see how schizophrenia patients perform in these experiments."
These findings could also explain why people with even the most advanced prosthetic limbs can have trouble coordinating movements.
"People often describe their prosthetic limbs as feeling 'other', not a true extension of their body,' says Dr Reichenbach. "Even on the best prosthetic hands, if the observed movement of the fingers is not exactly what you would expect, then it will not feel like you are in direct control. These small details might have a big effect on how people perceive prostheses."
 

Journal Reference:

1. Alexandra Reichenbach, David W. Franklin, Peter Zatka-Haas, and Jörn Diedrichsen. A Dedicated Binding Mechanism for the Visual Control of Movement. Current Biology, 2014; DOI: 10.1016/j.cub.2014.02.030

Courtesy: ScienceDaily
 

Commonly used pain relievers have added benefit of fighting bacterial infection

Some commonly used drugs that combat aches and pains, fever, and inflammation are also thought to have the ability to kill bacteria. New research appearing online on March 13 in the Cell Press journal Chemistry & Biology reveals that these drugs, better known as NSAIDs, act on bacteria in a way that is fundamentally different from current antibiotics. The discovery could open up new strategies for fighting drug-resistant infections and "superbugs."

"We discovered that some anti-inflammatory drugs used in human and veterinary medicine have weak antibiotic activity and that they exert this secondary activity by preventing bacteria from copying their DNA, which they need to do in order to multiply," explains senior author Dr. Aaron Oakley of the University of Wollongong, in Australia. The researchers analyzed three NSAIDs: bromofenac, carprofen, and vedaprofen. The more commonly known NSAIDs, which include aspirin, ibuprofen, and naproxen, were not tested.
Dr. Oakley and his team identified that anti-inflammatory drugs bind to and inhibit a specific protein in bacteria called the DNA clamp. The DNA clamp, which is conserved across bacterial species, is part of an enzyme that synthesizes DNA molecules from their nucleotide building blocks.
The discovery comes at a time when there is a pressing need for new classes of antibiotics. "The fact that the bacteria-killing effect of the anti-inflammatory drugs is different from conventional drugs means that the NSAIDS could be developed into new kinds of antibiotics that are effective against so-called superbugs," says Dr. Oakley. "This is important because the superbugs have become resistant to many -- and in some cases most -- of the available antibiotics."

Journal Reference:

1. Yin et al. DNA Replication is the Target for the Antibacterial Effects of Non-Steroidal Anti-Inflammatory Drugs. Chemistry & Biology, March 2014.

Courtesy: ScienceDaily

We must forget to avoid serious mental disorders, and forgetting is actively regulated

In order to function properly, the human brain requires the ability not only to store but also to forget: Through memory loss, unnecessary information is deleted and the nervous system retains its plasticity. A disruption of this process can lead to serious mental disorders. Basel scientists have now discovered a molecular mechanism that actively regulates the process of forgetting.

The  scientific journal Cell has published their results.

The human brain is build in such a way, that only necessary information is stored permanently -- the rest is forgotten over time. However, so far it was not clear if this process was active or passive. Scientists from the transfaculty research platform Molecular and Cognitive Neurosciences (MCN) at the University of Basel have now found a molecule that actively regulates memory loss. The so-called musashi protein is responsible for the structure and function of the synaptic connections of the brain, the place where information is communicated from one neuron to the next.

Using olfactory conditioning, the researchers Attila Stetak and Nils Hadziselimovic first studied the learning abilities of genetically modified ringworms (C. elegans) that were lacking the musashi protein. The experiments showed that the worms exhibited the same learning skills as unmodified animals. However, with extended duration of the experiment, the scientists discovered that the mutants were able to remember the new information much better. In other words: The genetically modified worms lacking the musashi protein were less forgetful.

Forgetting is no coincidence

Further experiments showed that the protein inhibits the synthesis of molecules responsible for the stabilization of synaptic connections. This stabilization seems to play an important role in the process of learning and forgetting. The researchers identified two parallel mechanisms: One the one hand, the protein adducin stimulates the growth of synapses and therefore also helps to retain memory; on the other hand, the musashi protein actively inhibits the stabilization of these synapses and thus facilitates memory loss. Therefore, it is the balance between these two proteins that is crucial for the retention of memories.

Forgetting is thus not a passive but rather an active process and a disruption of this process may result in serious mental disorders. The musashi protein also has interesting implications for the development of drugs trying to prevent abnormal memory loss that occurs in diseases such as Alzheimer's. Further studies on the therapeutic possibilities of this discovery will be done.

Journal Reference:

1. Nils Hadziselimovic, Vanja Vukojevic, Fabian Peter, Annette Milnik, Matthias Fastenrath, Bank Gabor Fenyves, Petra Hieber, Philippe Demougin, Christian Vogler, Dominique J.-F. de Quervain et al. Forgetting Is Regulated via Musashi-Mediated Translational Control of the Arp2/3 Complex. Cell, 13 March 2014 DOI: 10.1016/j.cell.2014.01.054 

Courtesy: ScienceDaily

More dangerous chemicals in everyday life: Now experts warn against nanosilver

Endocrine disrupters are not the only worrying chemicals that ordinary consumers are exposed to in everyday life. Also nanoparticles of silver, found in e.g. dietary supplements, cosmetics and food packaging, now worry scientists. A new study from the University of Southern Denmark shows that nano-silver can penetrate our cells and cause damage.

This is a photo of Thiago Verano-Braga, Ph.D., of the University of Southern Denmark, whose work alongside other scientists is bringing the dangers of nano-silver to light.

Credit: Birgitte Svennevig/University of Southern Denmark

Silver has an antibacterial effect and therefore the food and cosmetic industry often coat their products with silver nanoparticles. Nano-silver can be found in e.g. drinking bottles, cosmetics, band aids, toothbrushes, running socks, refrigerators, washing machines and food packagings.
"Silver as a metal does not pose any danger, but when you break it down to nano-sizes, the particles become small enough to penetrate a cell wall. If nano-silver enters a human cell, it can cause changes in the cell," explain Associate Professor Frank Kjeldsen and PhD Thiago Verano-Braga, Department of Biochemistry and Molecular Biology at the University of Southern Denmark.
Together with their research colleagues they have just published the results of a study of such cell damages in the journal ACS Nano.
The researchers examined human intestinal cells, as they consider these to be most likely to come into contact with nano-silver, ingested with food.
"We can confirm that nano-silver leads to the formation of harmful, so called free radicals in cells. We can also see that there are changes in the form and amount of proteins. This worries us," say Frank Kjeldsen and Thiago Verano-Braga.
A large number of serious diseases are characterized by the fact that there is an overproduction of free radicals in cells. This applies to cancer and neurological diseases such as Alzheimer's and Parkinson's.
Kjeldsen and Verano-Braga emphasizes that their research is conducted on human cells in a laboratory, not based on living people. They also point out that they do not know how large a dose of nano-silver, a person must be exposed to for the emergence of cellular changes.
"We don't know how much is needed, so we cannot conclude that nano-silver can make you sick. But we can say that we must be very cautious and worried when we see an overproduction of free radicals in human cells," they say.
Nano-silver is also sold as a dietary supplement, promising to have an antibacterial, anti-flu and cancer-inhibatory effect. The nano-silver should also help against low blood counts and bad skin. In the EU, the marketing of dietary supplements and foods with claims to have medical effects is not allowed. But the nano-silver is easy to find and buy online.
In the wake of the Uiversity of Southern Denmark-research, the Danish Veterinary and Food Administration now warns against taking dietary supplements with nano-silver.
"The recent research strongly suggests that it can be dangerous," says Søren Langkilde from the Danish Veterinary and Food Administration to the Danish Broadcasting Corporation (DR).

Journal Reference:

1. Thiago Verano-Braga, Rona Miethling-Graff, Katarzyna Wojdyla, Adelina Rogowska-Wrzesinska, Jonathan R. Brewer, Helmut Erdmann, Frank Kjeldsen. Insights into the Cellular Response Triggered by Silver Nanoparticles Using Quantitative Proteomics. ACS Nano, 2014; 140220105558007 DOI: 10.1021/nn4050744 

Courtesy: ScienceDaily

It slices, it dices, and it protects the body from harm: 3-D structure of enzyme that helps defend against bacteria

An essential weapon in the body's fight against infection has come into sharper view. Researchers at Princeton University have discovered the 3D structure of an enzyme that cuts to ribbons the genetic material of viruses and helps defend against bacteria.

The discovery of the structure of this enzyme, a first-responder in the body's "innate immune system," could enable new strategies for fighting infectious agents and possibly prostate cancer and obesity. The work was published Feb. 27 in the journal Science.
Until now, the research community has lacked a structural model of the human form of this enzyme, known as RNase L, said Alexei Korennykh, an assistant professor of molecular biology and leader of the team that made the discovery.
"Now that we have the human RNase L structure, we can begin to understand the effects of carcinogenic mutations in the RNase L gene. For example, families with hereditary prostate cancers often carry genetic mutations in the region, or locus, encoding RNase L," Korennykh said. The connection is so strong that the RNase L locus also goes by the name "hereditary prostate cancer 1." The newly found structure reveals the positions of these mutations and explains why some of these mutations could be detrimental, perhaps leading to cancer, Korennykh said. RNase L is also essential for insulin function and has been implicated in obesity.
The Princeton team's work has also led to new insights on the enzyme's function.
The enzyme is an important player in the innate immune system, a rapid and broad response to invaders that includes the production of a molecule called interferon. Interferon relays distress signals from infected cells to neighboring healthy cells, thereby activating RNase L to turn on its ability to slice through RNA, a type of genetic material that is similar to DNA. The result is new cells armed for destruction of the foreign RNA.
The 3D structure uncovered by Korennykh and his team consists of two nearly identical subunits called protomers. The researchers found that one protomer finds and attaches to the RNA, while the other protomer snips it.
The initial protomer latches onto one of the four "letters" that make up the RNA code, in particular, the "U," which stands for a component of RNA called uridine. The other protomer "counts" RNA letters starting from the U, skips exactly one letter, then cuts the RNA.
Although the enzyme can slice any RNA, even that of the body's own cells, it only does so when activated by interferon.
"We were surprised to find that the two protomers were identical but have different roles, one binding and one slicing," Korennykh said. "Enzymes usually have distinct sites that bind the substrate and catalyze reactions. In the case of RNase L, it appears that the same exact protein surface can do both binding and catalysis. One RNase L subunit randomly adopts a binding role, whereas the other identical subunit has no other choice but to do catalysis."
To discover the enzyme's structure, the researchers first created a crystal of the RNase L enzyme. The main challenge was finding the right combination of chemical treatments that would force the enzyme to crystallize without destroying it.
After much trial and error and with the help of an automated system, postdoctoral research associate Jesse Donovan and graduate student Yuchen Han succeeded in making the crystals.
Next, the crystals were bombarded with powerful X-rays, which diffract when they hit the atoms in the crystal and form patterns indicative of the crystal's structure. The diffraction patterns revealed how the atoms of RNase L are arranged in 3D space.
At the same time Sneha Rath, a graduate student in Korennykh's laboratory, worked on understanding the RNA cleavage mechanism of RNase L using synthetic RNA fragments. Rath's results matched the structural findings of Han and Donovan, and the two pieces of data ultimately revealed how RNase L cleaves its RNA targets.
Han, Donovan and Rath contributed equally to the paper and are listed as co-first authors.
Finally, senior research specialist Gena Whitney and graduate student Alisha Chitrakar conducted additional studies of RNase L in human cells, confirming the 3D structure.
Now that the human structure has been solved, researchers can explore ways to either enhance or dampen RNase L activity for medical and therapeutic uses, Korennykh said.
"This work illustrates the wonderful usefulness of doing both crystallography and careful kinetic and enzymatic studies at the same time," said Peter Walter, professor of biochemistry and biophysics at the University of California-San Francisco School of Medicine. "Crystallography gives a static picture which becomes vastly enhanced by studies of the kinetics."

Journal Reference:

1. Y. Han, J. Donovan, S. Rath, G. Whitney, A. Chitrakar, A. Korennykh. Structure of Human RNase L Reveals the Basis for Regulated RNA Decay in the IFN Response. Science, 2014; DOI: 10.1126/science.1249845 

Courtesy: ScienceDaily

Watching how the brain works with new live imaging

There are more than a trillion cells called neurons that form a labyrinth of connections in our brains. Each of these neurons contains millions of proteins that perform different functions. Exactly how individual proteins interact to form the complex networks of the brain still remains as a mystery that is just beginning to unravel.

For the first time, a group of scientists has been able to observe intact interactions between proteins, directly in the brain of a live animal. The new live imaging approach was developed by a team of researchers at the University of Miami (UM).
"Our ultimate goal is to create the systematic survey of protein interactions in the brain," says Akira Chiba, professor of Biology in the College of Arts and Sciences at UM and lead investigator of the project. "Now that the genome project is complete, the next step is to understand what the proteins coded by our genes do in our body."
The new technique will allow scientists to visualize the interactions of proteins in the brain of an animal, along different points throughout its development, explains Chiba, who likens protein interactions to the way organisms associate with each other.
"We know that proteins are one billionth of a human in size. Nevertheless, proteins make networks and interact with each other, like social networking humans do," Chiba says. "The scale is very different, but it's the same behavior happening among the basic units of a given network."
The researchers chose embryos of the fruit fly (Drosophila melanogaster) as an ideal model for the study. Because of its compact and transparent body, it is possible to visualize processes inside the Drosophila cells using a fluorescence lifetime imaging microscope (FLIM). The results of the observations are applicable to other animal brains, including the human brain.
The Drosophila embryos in the study contained a pair of fluorescent labeled proteins: a developmentally essential and ubiquitously present protein called Rho GTPase Cdc42 (cell division control protein 42), labeled with green fluorescent tag and its alleged signaling partner, the regulatory protein WASp (Wiskot-Aldrich Syndrome protein), labeled with red fluorescent tag. Together, these specialized proteins are believed to help neurons grow during brain development. The proteins were selected because the same (homolog) proteins exist in the human brain as well.
Previous methods required chemical or physical treatments that most likely disturb or even kill the cells. That made it impossible to study the protein interactions in their natural environment.
The current study addresses these challenges by using the occurrence of a phenomenon called Förster resonance energy transfer, or FRET. It occurs when two small proteins come within a very small distance of each other, (eight nanometers). The event is interpreted as the time and place where the particular protein interaction occurs within the living animal.
The findings show that FRET between the two interacting protein partners occurs within neurons, during the time and space that coincides with the formation of new synapses in the brain of the baby insect. Synapses connect individual neurons in the brain.
"Previous studies have demonstrated that Cdc42 and WASp can directly bind to each other in a test-tube, but this is the first direct demonstration that these two proteins are interacting within the brain," Chiba says.
 

Journal Reference:

1. Nima Sharifai, Hasitha Samarajeewa, Daichi Kamiyama, Tzyy-Chyn Deng, Maria Boulina, Akira Chiba. Imaging Dynamic Molecular Signaling by the Cdc42 GTPase within the Developing CNS. PLoS ONE, 2014; 9 (2): e88870 DOI: 10.1371/journal.pone.0088870 

Courtesy: ScienceDaily
 

Novel therapeutic targets for Huntington's disease discovered

A study led by researchers at Boston University School of Medicine (BUSM) provides novel insight into the impact that genes may have on Huntington's disease (HD). The study, published online in PLOS Genetics, identified specific small segments of RNA (called micro RNA or miRNA) encoded in DNA in the human genome that are highly expressed in HD. Micro RNAs are important because they regulate the expression of genes. The researchers showed that these miRNAs are present in higher quantities in patients with HD and may act as a mitigating factor in the neurologic decline associated with the disease, making them a possible therapeutic target.

HD is an inherited and fatal neurological disorder that is usually diagnosed when a person is between 30 and 50 years old. Huntingtin, the single gene mutation responsible for the disease, was identified in 1993.
The investigators examined 21 autopsy brain samples: 12 with HD and nine without. Genetic sequencing analyses were performed on these brain tissues, including quantifying the amount of all the microRNAs present in the brain and their corresponding gene or messenger RNA (mRNA) counterparts. This information was combined with a genetic study to characterize variations in the HD gene. The researchers also gathered the clinical neurological information on the patients' age when HD symptoms presented and how long the patient survived with the disease.
Based on this analysis, the investigators discovered increased amounts of four miRNAs were expressed in the brains of HD patients and that the amount of miRNA was highly correlated with disease status. An increased amount of miRNA in brain cells was correlated with a younger age at disease onset and an earlier age at death of the patients.
"The genes which these miRNAs regulate also had increased levels, indicating that these gene expression, indicating that these gene products were likely targeted for storage and for possible future use within the brain cell, rather than for destruction. When we experimentally increased the expression of the microRNAs in model nerve cells designed to replicate the conditions of HD, the cells lived longer, indicating that these miRNAs may promote cell survival," explained lead author Richard Myers, PhD, professor of neurology at BUSM. The authors conclude that these genes may represent new therapeutic targets for HD.
According to the researchers, these miRNA sequences were found to be present in much higher levels in patients with HD (some were undetectable in the brain cells of normal patients), which would also make them excellent targets as biomarkers for HD expression. "If this miRNA were also found outside of brain tissue, for example in the blood, it could be used as an inexpensive, non-invasive assessment of the severity of the disease and perhaps for evaluating the effectiveness of treatments in clinical trials for HD. If the amount of miRNA were quantified in an HD patient, the amount could provide insight into the likely age of disease onset or life expectancy of the patient which current genetic testing in HD does not provide," added Myers.
 

Journal Reference:

1. Andrew G. Hoss, Vinay K. Kartha, Xianjun Dong, Jeanne C. Latourelle, Alexandra Dumitriu, Tiffany C. Hadzi, Marcy E. MacDonald, James F. Gusella, Schahram Akbarian, Jiang-Fan Chen, Zhiping Weng, Richard H. Myers. MicroRNAs Located in the Hox Gene Clusters Are Implicated in Huntington's Disease Pathogenesis. PLoS Genetics, 2014; 10 (2): e1004188 DOI: 10.1371/journal.pgen.1004188

 Courtesy: ScienceDaily

Study uncovers why autism is more common in males

Males are at greater risk for neurodevelopmental disorders, such as autism spectrum disorder (ASD), than females, but the underlying reasons have been unclear. A large cohort study published by Cell Press on February 27th in the American Journal of Human Genetics provides compelling evidence in support of the "female protective model," which proposes that females require more extreme genetic mutations than do males to push them over the diagnostic threshold for neurodevelopmental disorders.

"This is the first study that convincingly demonstrates a difference at the molecular level between boys and girls referred to the clinic for a developmental disability," says study author Sébastien Jacquemont of the University Hospital of Lausanne. "The study suggests that there is a different level of robustness in brain development, and females seem to have a clear advantage."
A gender bias in the prevalence of neurodevelopmental disorders has been reported for ASD, intellectual disability, and attention deficit hyperactivity disorder. Some researchers have suggested that there is a social bias that increases the likelihood of diagnosis in males, whereas others have proposed that there are sex-based differences in genetic susceptibility. However, past studies investigating biological explanations for the gender bias have produced inconclusive results.
To examine this question, Jacquemont teamed up with Evan Eichler of the University of Washington School of Medicine to analyze DNA samples and sequencing data sets of one cohort consisting of nearly 16,000 individuals with neurodevelopmental disorders and another cohort consisting of about 800 families affected by ASD. The researchers analyzed both copy-number variants (CNVs) -- individual variations in the number of copies of a particular gene -- and single-nucleotide variants (SNVs) -- DNA sequence variations affecting a single nucleotide.
They found that females diagnosed with a neurodevelopmental disorder or ASD had a greater number of harmful CNVs than did males diagnosed with the same disorder. Moreover, females diagnosed with ASD had a greater number of harmful SNVs than did males with ASD. These findings suggest that the female brain requires more extreme genetic alterations than does the male brain to produce symptoms of ASD or neurodevelopmental disorders. The results also take the focus off the X chromosome for the genetic basis of the gender bias, suggesting that the burden difference is genome wide.
"Overall, females function a lot better than males with a similar mutation affecting brain development," Jacquemont says. "Our findings may lead to the development of more sensitive, gender-specific approaches for the diagnostic screening of neurodevelopmental disorders."
 

Journal Reference:

1. Sébastien Jacquemont, Bradley P. Coe, Micha Hersch, Michael H. Duyzend, Niklas Krumm, Sven Bergmann, Jacques S. Beckmann, Jill A. Rosenfeld, Evan E. Eichler. A Higher Mutational Burden in Females Supports a “Female Protective Model” in Neurodevelopmental Disorders. The American Journal of Human Genetics, 2014; DOI: 10.1016/j.ajhg.2014.02.001 

Courtesy: ScienceDaily

 

Physicians' stethoscopes more contaminated than palms of their hands

Although healthcare workers' hands are the main source of bacterial transmission in hospitals, physicians' stethoscopes appear to play a role. To explore this question, investigators at the University of Geneva Hospitals assessed the level of bacterial contamination on physicians' hands and stethoscopes following a single physical examination. The study appears in the March issue of Mayo Clinic Proceedings.

"By considering that stethoscopes are used repeatedly over the course of a day, come directly into contact with patients' skin, and may harbor several thousands of bacteria (including MRSA) collected during a previous physical examination, we consider them as potentially significant vectors of transmission," commented lead investigator Didier Pittet, MD, MS, Director of the Infection Control Program and WHO Collaborating Centre on Patient Safety, University of Geneva Hospitals. "From infection control and patient safety perspectives, the stethoscope should be regarded as an extension of the physician's hands and be disinfected after every patient contact."
In this study, 71 patients were examined by one of three physicians using sterile gloves and a sterile stethoscope. After they completed the examination, two parts of the stethoscope (the tube and diaphragm) and four regions of the physician's hands (back, fingertips, and thenar and hypothenar eminences) were measured for the total number of bacteria present.
The stethoscope's diaphragm was more contaminated than all regions of the physician's hand except the fingertips. Further, the tube of the stethoscope was more heavily contaminated than the back of the physician's hand. Similar results were observed when contamination was due to methicillin-resistant S.aureus (MRSA) after examining MRSA-colonized patients.
This work is the first to compare directly the level of contamination of physicians' hands and stethoscopes. Stethoscope contamination is not trivial and is comparable to the contamination of healthcare workers' fingertips, the hand region most implicated in microbial cross-transmission. Physicians must be aware of the need to disinfect their stethoscope after each use.

Journal Reference:

1. Yves Longtin, Alexis Schneider, Clément Tschopp, Gesuèle Renzi, Angèle Gayet-Ageron, Jacques Schrenzel, Didier Pittet. Contamination of Stethoscopes and Physicians' Hands After a Physical Examination. Mayo Clinic Proceedings, 2014; 89 (3): 291 DOI: 10.1016/j.mayocp.2013.11.016 

Courtesy: ScienceDaily