How much sleep do we really need?

Loyola University Chicago Stritch School of Medicine researcher Lydia DonCarlos, PhD, is a member of an expert panel that's making new recommendations on how much sleep people need.

The panel, convened by the National Sleep Foundation, is making its recommendations based on age, ranging from newborns (who need 14 to 17 hours of sleep per day) to adults aged 65 and up (7 to 8 hours per day).
In the new guidelines, there's a wider range of what constitutes a good night's sleep. For example, the expert panel recommends that teens (ages 14 to 17) get 8 to 10 hours of sleep per night. The previous guideline had a narrower recommended range of 8.5 to 9.5 hours per night.
Dr. DonCarlos and other experts on the multidisciplinary panel examined findings from 320 studies reporting sleep duration findings for healthy individuals, effects of reduced or prolonged sleep duration and health consequences of too much or too little sleep. Results are published in Sleep Health: Journal of the National Sleep Foundation.
"The process was very rigorous," Dr. DonCarlos said. Dr. DonCarlos is a professor in the Department of Cell and Molecular Physiology of Loyola University Chicago Stritch School of Medicine.
The expert panel consists of 12 representatives, including Dr. DonCarlos, who were selected by medical organizations; and six sleep experts selected by the National Sleep Foundation. Dr. DonCarlos represents the American Association of Anatomists.
Dr. DonCarlos is a neuroendocrinologist who studies how hormones affect the structure of the brain. The section of the brain responsible for regulating hormone production is the hypothalamus. Hormones produced by the hypothalamus govern body temperature, hunger, stress responses, sex drive, circadian rhythms and sleep.
In addition to serving on the National Sleep Foundation expert panel, Dr. DonCarlos serves on the National Institutes of Health's Neuroendocrinology, Neuroimmunology, Rhythms and Sleep (NNRS) study section, which reviews applications for research grants.
"We still have a great deal to learn about the function of sleep," Dr. DonCarlos said. "We know it's restorative and important for memory consolidation. But we don't know the details of what the function of sleep is, even though it is how we spend one-third of our lives."
These are the sleep-time recommendations from the National Sleep Foundation expert panel:

• Newborns (0-3 months): Sleep range narrowed to 14-17 hours each day (previously it was 12-18).
• Infants (4-11 months): Sleep range widened two hours to 12-15 hours (previously it was 14-15).
• Toddlers (1-2 years): Sleep range widened by one hour to 11-14 hours (previously it was 12-14).
• Preschoolers (3-5): Sleep range widened by one hour to 10-13 hours (previously it was 11-13).
• School age children (6-13): Sleep range widened by one hour to 9-11 hours (previously it was 10-11).
• Teenagers (14-17): Sleep range widened by one hour to 8-10 hours (previously it was 8.5-9.5).
• Younger adults (18-25): Sleep range is 7-9 hours (new age category).
• Adults (26-64): Sleep range did not change and remains 7-9 hours.
• Older adults (65+): Sleep range is 7-8 hours (new age category).

 

Journal Reference:

1. Max Hirshkowitz et al. National Sleep Foundation’s sleep time duration recommendations: methodology and results summary. Sleep Health: Journal of the National Sleep Foundation, 2015 DOI: 10.1016/j.sleh.2014.12.010 

Courtesy: ScienceDaily
 

New mechanism that controls immune responses discovered

UT Southwestern Medical Center researchers have identified a common signaling mechanism to produce interferon -- one of the main proteins used to signal the immune system when the body needs to defend itself against a virus, tumor, or other diseases.

The findings are important for understanding the body's immune defense system, searching for compounds to turn the immune system on or off, and they may help combat autoimmune diseases, in which overactive immune cells attack healthy tissues.
"Our work reveals a common mechanism by which three distinct pathways lead to the production of type-I interferons," said Dr. Zhijian "James" Chen, Professor of Molecular Biology and in the Center for the Genetics of Host Defense at UT Southwestern, and a Howard Hughes Medical Institute (HHMI) Investigator. "Ultimately, we believe that understanding this mechanism will facilitate the design and development of medications to treat human diseases such as lupus."
The findings appear online in the journal Science.
The results show how a protein called interferon regulatory factor 3 (IRF3), which controls the production of type-I interferons, is activated and how this pathway is tightly controlled. The failure of this control system can lead to autoimmune disorders such as systemic lupus erythematosus, which causes joint pain and swelling, and can damage the brain, heart, lungs, kidneys, and digestive track. Lupus affects more than 1.5 million Americans, and is more common in young and middle-aged women than in men.
A normal function of interferons is to defend the body against infections from viruses, bacteria and parasites. Previous research has identified specific pathways that induce interferons in response to distinct infectious agents, but how these different pathways converge on IRF3 to induce interferons was not understood.
Dr. Chen and his team studied a protein called MAVS, which they discovered in 2005 and showed that it is an adaptor protein essential for interferon induction by RNA viruses such as influenza virus. In the new study, they found that MAVS is modified by the addition of a phosphate group (phosphorylated) by an enzyme called TBK1 when cells are infected by a virus and that this modification is important for IRF3 activation.
Upon closer examination, they found the amino acid sequence that is phosphorylated in MAVS is very similar to those of two other adaptor proteins, STING and TRIF, which mediate interferon induction in response to DNA viruses and bacteria, respectively. Further research confirmed that all three adaptor proteins are phosphorylated at the common sequence motif and that this phosphorylation allows each of the adaptor proteins to bind IRF3, thereby facilitating IRF3 phosphorylation by TBK1. The phosphorylated IRF3 becomes activated to induce type-I interferons.
"Although TBK1 is required for IRF3 activation, TBK1 alone is not sufficient. Phosphorylation of the adaptor proteins provides a 'license' for TBK1 to phosphorylate IRF3," said Dr. Chen, who holds the George L. MacGregor Distinguished Chair in Biomedical Science. "This hitherto unrecognized mechanism ensures that type-I interferons are produced only when a proper adaptor protein is engaged in cells that are infected by pathogens."
 

Journal Reference:

1. S. Liu, X. Cai, J. Wu, Q. Cong, X. Chen, T. Li, F. Du, J. Ren, Y. Wu, N. Grishin, Z. J. Chen. Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science, 2015; DOI: 10.1126/science.aaa2630 

Courtesy: ScienceDaily
 

Promising results for new Alzheimer's therapy

Scientists at Karolinska Institutet have evaluated a new Alzheimer's therapy in which the patients receive an implant that stimulates the growth of a certain type of nerve cell. The results, which are published in the scientific journal Alzheimer's & Dementia, suggest that the introduction of a nerve growth factor can prevent neuronal degradation in Alzheimer's patients.

Patients with Alzheimer's disease suffer a selective and early breakdown of so-called cholinergic nerve cells, which require a specific nerve growth factor (NGF) -- essentially a group of proteins necessary for cell growth and survival -- to function. As NGF levels decline, the cholinergic nerve cells begin to degrade and the patient's condition slowly deteriorates.
In an attempt to curb the breakdown of the cholinergic nerve cells, researchers at Karolinska Institutet's Centre for Alzheimer's Research and their colleagues at Karolinska University Hospital's neurosurgery clinic and the Danish biotech company NsGene introduced NGF directly into the brains of Alzheimer's patients. To do this, they used NGF-producing cell capsules, placing them in the basal fore-brain where the cholinergic cells reside using precision stereotactic surgery. There the capsules, which can easily be removed, release NGF to the surrounding cells in order to prevent their degradation.
The study now published in Alzheimer's & Dementia is based on data from six Alzheimer's patients. To gauge whether the NGF release had any effect on the cholinergic nerve cells, the researchers assayed the presence of specific markers of functioning cholinergic cells. This cell system communicates using acetylcholine, which in turn produces an enzyme called ChAT (pronounced Cat) that is found both inside and outside the cells. The team therefore developed a method enabling them to measure ChAT in the cerebral spinal fluid for the first time.
"Our results show that when the patients received NGF, there was a significant increase in ChAT in the CSF," says Dr Taher Darreh-Shori, one of the researchers involved in the study. "The patients that exhibited this increase were also those that responded best to the treatment. Our PET scans also showed an increase in cholinergic cell activity and metabolism in the brain."
In addition, the researchers were able to detect a retardation of memory impairment over time compared with untreated patients. While all this suggests that cholinergic functionality improved in the Alzheimer's patients who had received NGF therapy, the team adds the caveat that far-reaching conclusions should not be drawn from the results:
"The results are promising, but must be treated with circumspection as only a few patients participated in the study," says principal investigator Professor Maria Eriksdotter. "So our findings will have to be substantiated in a larger controlled study using more patients."

Journal Reference:

1. Azadeh Karami, Helga Eyjolfsdottir, Swetha Vijayaraghavan, Göran Lind, Per Almqvist, Ahmadul Kadir, Bengt Linderoth, Niels Andreasen, Kaj Blennow, Anders Wall, Eric Westman, Daniel Ferreira, Maria Kristoffersen Wiberg, Lars-Olof Wahlund, Åke Seiger, Agneta Nordberg, Lars Wahlberg, Taher Darreh-Shori, Maria Eriksdotter. Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer's disease. Alzheimer's & Dementia, 2015; DOI: 10.1016/j.jalz.2014.11.008 

 Courtesy: ScienceDaily

Code cracked for infections by major group of viruses including common cold and polio

Researchers have cracked a code that governs infections by a major group of viruses including the common cold and polio.

A code hidden in the arrangement of the genetic information of single-stranded RNA viruses tells the virus how to pack itself within its outer shell of proteins.

Until now, scientists had not noticed the code, which had been hidden in plain sight in the sequence of the ribonucleic acid (RNA) that makes up this type of viral genome.
But a paper published in the Proceedings of the National Academy of Sciences (PNAS) Early Edition by a group from the University of Leeds and University of York unlocks its meaning and demonstrates that jamming the code can disrupt virus assembly. Stopping a virus assembling can stop it functioning and therefore prevent disease.
Professor Peter Stockley, Professor of Biological Chemistry in the University of Leeds' Faculty of Biological Sciences, who led the study, said: "If you think of this as molecular warfare, these are the encrypted signals that allow a virus to deploy itself effectively."
"Now, for this whole class of viruses, we have found the 'Enigma machine' -- the coding system that was hiding these signals from us. We have shown that not only can we read these messages but we can jam them and stop the virus' deployment."
Single-stranded RNA viruses are the simplest type of virus and were probably one of the earliest to evolve. However, they are still among the most potent and damaging of infectious pathogens.
Rhinovirus (which causes the common cold) accounts for more infections every year than all other infectious agents put together (about 1 billion cases), while emergent infections such as chikungunya and tick-borne encephalitis are from the same ancient family.
Other single-stranded RNA viruses include the hepatitis C virus, HIV and the winter vomiting bug norovirus.
This breakthrough was the result of three stages of research.

• In 2012, researchers at the University of Leeds published the first observations at a single-molecule level of how the core of a single-stranded RNA virus packs itself into its outer shell -- a remarkable process because the core must first be correctly folded to fit into the protective viral protein coat. The viruses solve this fiendish problem in milliseconds. The next challenge for researchers was to find out how the viruses did this.

• University of York mathematicians Dr Eric Dykeman and Professor Reidun Twarock, working with the Leeds group, then devised mathematical algorithms to crack the code governing the process and built computer-based models of the coding system.

• In this latest study, the two groups have unlocked the code. The group used single-molecule fluorescence spectroscopy to watch the codes being used by the satellite tobacco necrosis virus, a single stranded RNA plant virus.

Dr Roman Tuma, Reader in Biophysics at the University of Leeds, said: "We have understood for decades that the RNA carries the genetic messages that create viral proteins, but we didn't know that, hidden within the stream of letters we use to denote the genetic information, is a second code governing virus assembly. It is like finding a secret message within an ordinary news report and then being able to crack the whole coding system behind it.
"This paper goes further: it also demonstrates that we could design molecules to interfere with the code, making it uninterpretable and effectively stopping the virus in its tracks."
Professor Reidun Twarock, of the University of York's Department of Mathematics, said: "The Enigma machine metaphor is apt. The first observations pointed to the existence of some sort of a coding system, so we set about deciphering the cryptic patterns underpinning it using novel, purpose designed computational approaches. We found multiple dispersed patterns working together in an incredibly intricate mechanism and we were eventually able to unpick those messages. We have now proved that those computer models work in real viral messages."
The next step will be to widen the study into animal viruses. The researchers believe that their combination of single-molecule detection capabilities and their computational models offers a novel route for drug discovery.
The research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), the Engineering and Physical Sciences Research Council (EPSRC). Professor Twarock's Royal Society Leverhulme Trust Senior Research Fellowship and Dr Dykeman's Leverhulme Trust Early Career Fellowship also supported the work.
 

Journal Reference:

1. Nikesh Patel, Eric C. Dykeman, Robert H. A. Coutts, George P. Lomonossoff, David J. Rowlands, Simon E. V. Phillips, Neil Ranson, Reidun Twarock, Roman Tuma, Peter G. Stockley. Revealing the density of encoded functions in a viral RNA. Proceedings of the National Academy of Sciences, 2015; 201420812 DOI: 10.1073/pnas.1420812112 

Courtesy: ScienceDaily