Is it possible to reset our biological clocks?

Imagine being able to easily get over all of the discomfort and problems of jet lag or night-shift work. Science is not quite there, but recent work by Marc Cuesta, Nicolas Cermakian and Diane B. Boivin from the Douglas Mental Health University Institute and McGill University has opened new therapeutic avenues for improving the synchronization of the body's different biological clocks.

Physiological changes over the course of a day are regulated by a circadian system comprised of a central clock located deep within the centre of the brain and multiple clocks located in different parts of the body.
This study, which was published in The FASEB Journal (published by the Federation of American Societies for Experimental Biology), included 16 healthy volunteers who were studied in temporal isolation chambers. These results show, for the first time, that the peripheral biological clocks located in white blood cells can be synchronized through the administration of glucocorticoid tablets.
Significant disruptions
Since humans are fundamentally diurnal creatures, staying awake at night can significantly disrupt all of the body's internal biological clocks. These disruptions are far from harmless: over the long term, they can lead to a high incidence of various health problems, such as metabolic or cardiovascular problems or even certain types of cancer.
"Problems adjusting to atypical work schedules are a major issue for society. Our previous studies clearly show that desynchronized circadian clocks disrupt the sleep, performance and cardiac parameters of night-shift workers. However, current approaches to these problems have significant limitations, as a single therapy can't address the disruptions that occur in all biological clocks. For example, when used incorrectly, light therapy can even aggravate the situation," stated Dr. Diane B. Boivin, Director of the Centre for Study and Treatment of Circadian Rhythms, where the study took place.
Complex mechanisms
We still do not fully understand the mechanisms through which peripheral biological clocks adapt to night-shift work in humans, but it is thought that these clocks essentially depend on the central clock.
"Clock genes are what drive our biological clocks, and these genes are active in all of our organs. Animal studies have shown that our central clock (in the brain) sends signals to the clocks in our other organs. Glucocorticoids appear to play a central role in transmitting these signals. However, until now, no one had demonstrated that cortisol (a glucocorticoid) plays this role in humans," stated Dr. Nicolas Cermakian, Director of the Laboratory of Molecular Chronobiology.
"We studied the rhythmic expression of clock genes in white blood cells to see how they adjusted in response to glucocorticoids. These cells are involved in our body's reaction to attacks from many pathogens. This study therefore suggests that biological rhythms may play a role in controlling immune function in night-shift workers," added Dr. Marc Cuesta, a postdoctoral fellow who works in the laboratories of Dr. Boivin and Dr. Cermakian.
The previous work of Dr. Boivin and her team showed that exposing workers to bright light at night tor adjusting work schedules can improve the synchronisation of the central biological clock to their atypical work schedule. This new scientific discovery opens the door to innovative therapies that could act on the different parts of the circadian system so that these rhythms can be adjusted to inverted sleep schedules. These studies have possible applications for travellers, night-shift workers, patients suffering from sleep disorders and circadian rhythm disorders, as well as people with various psychiatric disorders.
"At this stage, we are not recommending the use of glucocorticoids to adjust the rhythms of night-shift workers, as there could be medical risks," explained Dr. Boivin. "However, these results lead us to believe that we may one day be able to use a combined therapy that targets the central clock (inverting work schedules, administering controlled light therapy) with a pharmacological treatment that targets the peripheral clocks to ensure that all clocks are adjusted."
 

Journal Reference:

1. M. Cuesta, N. Cermakian, D. B. Boivin. Glucocorticoids entrain molecular clock components in human peripheral cells. The FASEB Journal, 2014; DOI: 10.1096/fj.14-265686 

Courtesy: ScienceDaily
 

Hey, guys: Posting a lot of selfies doesn't send a good message

The picture isn't pretty for guys who post a lot of selfies on social media sites like Facebook and Instagram.

A new study showed that men who posted more online photos of themselves than others scored higher on measures of narcissism and psychopathy.
In addition, men who were more likely to edit their selfies before posting scored higher in narcissism and self-objectification, which measures how much they prioritize their appearance.
"It's not surprising that men who post a lot of selfies and spend more time editing them are more narcissistic, but this is the first time it has actually been confirmed in a study," said Jesse Fox, lead author of the study and assistant professor of communication at The Ohio State University.
"The more interesting finding is that they also score higher on this other anti-social personality trait, psychopathy, and are more prone to self-objectification."
Fox conducted the study with Margaret Rooney, a graduate student at Ohio State. Their results are published online in the journal Personality and Individual Differences.
Fox emphasized that the results don't mean that men who post a lot of selfies are necessarily narcissists or psychopaths. The men in the study all scored within the normal range of behavior -- but with higher than average levels of these anti-social traits.
Narcissism is marked by a belief that you're smarter, more attractive and better than others, but with some underlying insecurity. Psychopathy involves a lack of empathy and regard for others and a tendency toward impulsive behavior.
The sample included 800 men from age 18 to 40 who completed an online survey asking about their photo posting behavior on social media. The participants also completed standard questionnaires for anti-social behaviors and for self-objectification. (This study doesn't include women because the dataset, which Fox received from a magazine, did not have comparable data for women.)
In addition to asking how often they posted photos, the survey inquired about whether the men edited their photos before posting, including cropping photos, using filters and using picture-editing software.
"Most people don't think that men even do that sort of thing, but they definitely do," Fox said.
Results showed that posting more photos was related to narcissism and psychopathy, but psychopathy was not related to editing photos.
"That makes sense because psychopathy is characterized by impulsivity. They are going to snap the photos and put them online right away. They want to see themselves. They don't want to spend time editing," she said.
Editing photos was also related to higher levels of self-objectification, which has been rarely studied in heterosexual men, Fox said.
Self-objectification involves valuing yourself mainly for your appearance, rather than for other positive traits.
"We know that self-objectification leads to a lot of terrible things, like depression and eating disorders in women," Fox said.
"With the growing use of social networks, everyone is more concerned with their appearance. That means self-objectification may become a bigger problem for men, as well as for women."
While this study didn't include women, Fox said she is currently conducting follow-up work that suggests the same findings found in this research also apply to women. Women who post more selfies also show higher levels of narcissism and psychopathy.
However, self-objectification plays a larger role with women, as would be expected.
Fox said she believes there is a self-reinforcing cycle when it comes to self-objectification. People who score higher on self-objectification post more selfies, which leads to more feedback from friends online, which encourages them to post even more photos of themselves.
"It may make people objectify themselves even more," she said. "We are running a study on that now."
Overall, Fox said this and other studies suggest our personality traits may influence how we present ourselves online.
"We are all concerned with our self-presentation online, but how we do that may reveal something about our personality."
 

Journal Reference:

1. Jesse Fox, Margaret C. Rooney. The Dark Triad and trait self-objectification as predictors of men’s use and self-presentation behaviors on social networking sites. Personality and Individual Differences, 2015; 76: 161 DOI: 10.1016/j.paid.2014.12.017 

Courtesy: ScienceDaily
 

Century-old drug reverses autism-like symptoms in fragile X mouse model

Autism spectrum disorders (ASD) affect 1 to 2 percent of children in the United States. Hundreds of genetic and environmental factors have been shown to increase the risk of ASD. Researchers at UC San Diego School of Medicine previously reported that a drug used for almost a century to treat trypanosomiasis, or sleeping sickness, reversed environmental autism-like symptoms in mice.

Now, a new study published in this week's online issue of Molecular Autism, suggests that a genetic form of autism-like symptoms in mice are also corrected with the drug, even when treatment was started in young adult mice.
The underlying mechanism, according to Robert K. Naviaux, MD, PhD, the new study's principal investigator and professor of medicine at UC San Diego, is a phenomenon he calls the cellular danger response (CDR). When cells are exposed to danger in the form of a virus, infection, toxin, or even certain genetic mutations, they react defensively, shutting down ordinary activities and erecting barriers against the perceived threat. One consequence is that communication between cells is reduced, which the scientists say may interfere with brain development and function, leading to ASD.
Researchers treated a Fragile X genetic mouse model, one of the most commonly studied mouse models of ASD, with suramin, a drug long used for sleeping sickness. The approach, called antipurinergic therapy or APT, blocked the CDR signal, allowing cells to restore normal communication and reversing ASD symptoms.
"Our data show that the efficacy of APT cuts across disease models in ASD. Both the environmental and genetic mouse models responded with a complete, or near complete, reversal of ASD symptoms," Naviaux said. "APT seems to be a common denominator in improving social behavior and brain synaptic abnormalities in these ASD models."
Weekly treatment with suramin in the Fragile X genetic mouse model was started at nine weeks of age, roughly equivalent to 18 years in humans. Metabolite analysis identified 20 biochemical pathways associated with symptom improvements, 17 of which have been reported in human ASD. The findings of the six-month study also support the hypothesis that disturbances in purinergic signaling -- a regulator of cellular functions, and mitochondria (prime regulators of the CDR) -- play a significant role in ASD.
Naviaux noted that suramin is not a drug that can be used for more than a few months without a risk of toxicity in humans. However, he said it is the first of its kind in a new class of drugs that may not need to be given chronically to produce beneficial effects. New antipurinergic medicines, he said, might be given once or intermittently to unblock metabolism, restore more normal neural network function, improve resilience and permit improved development in response to conventional, interdisciplinary therapies and natural play.
"Correcting abnormalities in a mouse is a long way from a cure in humans," cautioned Naviaux, who is also co-director of the Mitochondrial and Metabolic Disease Center at UC San Diego, "but our study adds momentum to discoveries at the crossroads of genetics, metabolism, innate immunity, and the environment for several childhood chronic disorders. These crossroads represent new leads in our efforts to understand the origins of autism and to develop treatments for children and adults with ASD."
Co-authors include Jane C. Naviaux, Lin Wang, Kefeng Li, A. Taylor Bright, William A. Alaynick, Kenneth R. Williams and Susan B. Powell, all at UC San Diego.
This study was supported, in part, by the Jane Botsford Johnson Foundation, the UC San Diego Christini Foundation, the UC San Diego Mitochondrial Research Fund, and the Wright Family Foundation.

Journal Reference:

1. Jane C Naviaux, Lin Wang, Kefeng Li, A Taylor Bright, William A Alaynick, Kenneth R Williams, Susan B Powell and Robert K Naviaux. Antipurinergic therapy corrects the autism-like features in the fragile X (Fmr1 knockout) mouse model. Molecular Autism, 2015 DOI: 10.1186/2040-2392-6-1

 Courtesy: ScienceDaily

Using power of computers to harness human genome may provide clues into Ebola virus

Ramaswamy Narayanan, Ph.D., professor in the Charles E. Schmidt College of Science at Florida Atlantic University, is working to blend the power of computers with biology to use the human genome to remove much of the guesswork involved in discovering cures for diseases.

Ramaswamy Narayanan, Ph.D., professor in the Charles E. Schmidt College of Science at Florida Atlantic University. Credit: Image courtesy of Florida Atlantic University

In an article titled "Ebola-Associated Genes in the Human Genome: Implications for Novel Targets," published in the current MedCrave Online Journal of Proteomics and Bioinformatics, Narayanan describes how key genes that are present in our cells could be used to develop drugs for this disease.
"Bioinformatics is a powerful tool to help us understand biological data," said Narayanan whose research has focused in this field for more than a decade. "We are mining the human genome for Ebola virus association to develop an understanding of the human proteins involved in this disease for subsequent research and development, and to potentially create a pipeline of targets that we can test and evaluate."
Ebola virus disease is a major healthcare challenge facing the globe today and if left unchecked could become a pandemic. A limited knowledgebase exists about the Ebola virus and companies are hastening to develop vaccines and other forms to treat and cure the virus. There are no FDA-approved drugs, and developing vaccines or antibodies and testing them in clinical trials is an arduous process that takes considerable time. Currently, patients infected with Ebola are only able to receive supportive care such as fluid replacement, nutritional support, pain control, and blood pressure maintenance. In some cases, patients may be fortunate enough to be treated with experimental drugs.
Narayanan's work has helped to identify numerous FDA-approved drugs already used for many other diseases including anti-inflammatory drugs, anticoagulants, cancer, HIV, statins and hormones, which could potentially be used to add to the current supportive care for patients with the Ebola virus.
"With the high mortality rate of this disease, the world urgently needs new ways to treat patients," said Narayanan. "The ability to use drugs that are already approved by the FDA could provide clinicians with more options to treat Ebola patients, rather than just relying on supportive measures like fluid replacement or antibiotics."
According to the World Health Organization (WHO), Ebola virus disease (EVD) is a severe, often fatal illness in humans. The virus is transmitted to people from wild animals and spreads in the human population through human-to-human transmissions. The evolving knowledge of this disease is prompting appropriate attention locally and globally. The 2014 Ebola epidemic has affected multiple countries in West Africa with some cases observed in Europe and the United States.
 

Journal Reference:

1. Ramaswamy Narayanan et al. Ebola-Associated Genes in the Human Genome: Implications for Novel Targets. Online Journal of Proteomics and Bioinformatics, December 2014 DOI: 10.15406/mojpb.2014.01.00032 

Courtesy: ScienceDaily
 

High vitamin D levels increase survival of patients with metastatic colorectal cancer

According to a new study led by researchers at Dana-Farber Cancer Institute, clinical trial patients with metastatic colorectal cancer who had high levels of vitamin D in their bloodstream prior to treatment with chemotherapy and targeted drugs, survived longer, on average, than patients with lower levels of the vitamin. Those findings were reported today at the 2015 American Society of Cancer Oncology (ASCO) Gastrointestinal Cancers Symposium in San Francisco.

The research, based on data from more than 1,000 patients with metastatic colorectal cancer who enrolled in a phase 3 clinical trial of chemotherapy plus biologic therapies, adds to vitamin D's already impressive luster as a potential cancer-inhibiting agent. In the study, patients with the highest blood levels of vitamin D survived for a median period of 32.6 months, compared to 24.5 months for those with the lowest levels.
"This is the largest study that has been undertaken of metastatic colorectal cancer patients and vitamin D," said the study's lead author, Kimmie Ng, MD, MPH, a medical oncologist at Dana-Farber. "It's further supportive of the potential benefits of maintaining sufficient levels of vitamin D in improving patient survival times."
The study didn't examine whether there is a biological cause-and-effect relationship between higher vitamin D levels and extended survival. As a result, researchers said, it's too early to recommend vitamin D as a treatment for colon cancer. Ng and colleagues at Dana-Farber are conducting clinical trials to further investigate whether vitamin D supplementation is useful in treating the cancer.
In the study, researchers measured blood levels of 25-hydroxyvitamin D, a substance produced in the liver from vitamin D, in 1,043 patients when they enrolled in a phase 3 trial of three different drug combinations for newly diagnosed, advanced colorectal cancer. Patient vitamin D levels ranged from an average of 8 nanograms/milliliter (ng/mL) in the lowest group to an average of 27.5 ng/mL in the highest group. The average level in all the patients was 17.2 ng/mL. Current practice guidelines from the Endocrine Society define vitamin D deficiency as having less than 20 ng/mL.
Researchers divided the patients into five groups based on vitamin D levels. On average, those with the highest levels survived 33 percent longer than those with the lowest (32.6 months vs. 24.5 months). Higher vitamin D levels were also associated with longer time to disease progression (12.2 months vs. 10.1 months).
Because high vitamin D levels can be a reflection of a healthy lifestyle (good nutrition, plenty of outdoor physical activity), researchers controlled for factors such as diet, obesity, and level of physical activity. Even then, the relationship between elevated vitamin D levels and extended survival held firm, Ng observed.
 

 

Story Source:
The above story is based on materials provided by Dana-Farber Cancer Institute. Note: Materials may be edited for content and length.

 

Courtesy: ScienceDaily

First contracting human muscle grown in laboratory

In a laboratory first, Duke researchers have grown human skeletal muscle that contracts and responds just like native tissue to external stimuli such as electrical pulses, biochemical signals and pharmaceuticals.

This is a microscopic view of lab-grown human muscle bundles stained to show patterns made by basic muscle units and their associated proteins (red), which are a hallmark of human muscle.

Credit: Nenad Bursac, Duke University

 The lab-grown tissue should soon allow researchers to test new drugs and study diseases in functioning human muscle outside of the human body.

The study was led by Nenad Bursac, associate professor of biomedical engineering at Duke University, and Lauran Madden, a postdoctoral researcher in Bursac's laboratory. It appears January 13 in the open-access journal eLife
"The beauty of this work is that it can serve as a test bed for clinical trials in a dish," said Bursac. "We are working to test drugs' efficacy and safety without jeopardizing a patient's health and also to reproduce the functional and biochemical signals of diseases -- especially rare ones and those that make taking muscle biopsies difficult."
Bursac and Madden started with a small sample of human cells that had already progressed beyond stem cells but hadn't yet become muscle tissue. They expanded these "myogenic precursors" by more than a 1000-fold, and then put them into a supportive, 3D scaffolding filled with a nourishing gel that allowed them to form aligned and functioning muscle fibers.
"We have a lot of experience making bioartifical muscles from animal cells in the laboratory, and it still took us a year of adjusting variables like cell and gel density and optimizing the culture matrix and media to make this work with human muscle cells," said Madden.
Madden subjected the new muscle to a barrage of tests to determine how closely it resembled native tissue inside a human body. She found that the muscles robustly contracted in response to electrical stimuli -- a first for human muscle grown in a laboratory. She also showed that the signaling pathways allowing nerves to activate the muscle were intact and functional.
To see if the muscle could be used as a proxy for medical tests, Bursac and Madden studied its response to a variety of drugs, including statins used to lower cholesterol and clenbuterol, a drug known to be used off-label as a performance enhancer for athletes.
The effects of the drugs matched those seen in human patients. The statins had a dose-dependent response, causing abnormal fat accumulation at high concentrations. Clenbuterol showed a narrow beneficial window for increased contraction. Both of these effects have been documented in humans. Clenbuterol does not harm muscle tissue in rodents at those doses, showing the lab-grown muscle was giving a truly human response.
"One of our goals is to use this method to provide personalized medicine to patients," said Bursac. "We can take a biopsy from each patient, grow many new muscles to use as test samples and experiment to see which drugs would work best for each person."
This goal may not be far away; Bursac is already working on a study with clinicians at Duke Medicine -- including Dwight Koeberl, associate professor of pediatrics -- to try to correlate efficacy of drugs in patients with the effects on lab-grown muscles. Bursac's group is also trying to grow contracting human muscles using induced pluripotent stem cells instead of biopsied cells.
"There are a some diseases, like Duchenne Muscular Dystrophy for example, that make taking muscle biopsies difficult," said Bursac. "If we could grow working, testable muscles from induced pluripotent stem cells, we could take one skin or blood sample and never have to bother the patient again."
Other investigators involved in this study include George Truskey, the R. Eugene and Susie E. Goodson Professor of Biomedical Engineering and senior associate dean for research for the Pratt School of Engineering, and William Krauss, professor of biomedical engineering, medicine and nursing at Duke University.
The research was supported by NIH Grants R01AR055226 and R01AR065873 from the National Institute of Arthritis and Musculoskeletal and Skin Disease and UH2TR000505 from the NIH Common Fund for the Microphysiological Systems Initiative.
 

Journal Reference:

1. Lauran Madden, Mark Juhas, William E Kraus, George A Truskey, Nenad Bursac. Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs. eLife, 2015; 4 DOI: 10.7554/eLife.04885 

Courtesy: ScienceDaily