1 in 300 thrives on very-early-to-bed, very-early-to-rise routine

A quirk of the body clock that lures some people to sleep at 8 p.m., enabling them to greet the new day as early as 4 a.m., may be significantly more common than previously believed.

So-called advanced sleep phase -- previously believed to be very rare -- may affect at least one in 300 adults, according to a study led by UC San Francisco and publishing in the journal SLEEP on Aug. 6, 2019.

Sunrise, rooster weathervane (stock image).

Credit: © pimmimemom / Adobe Stock

Advanced sleep phase means that the body's clock, or circadian rhythm, operates on a schedule hours earlier than most people's, with a premature release of the sleep hormone melatonin and shift in body temperature. The condition is distinct from the early rising that develops with normal aging, as well as the waking in the wee hours experienced by people with depression.
"While most people struggle with getting out of bed at 4 or 5 a.m., people with advanced sleep phase wake up naturally at this time, rested and ready to take on the day," said the study's senior author, Louis Ptacek, MD, professor of neurology at the UCSF School of Medicine. "These extreme early birds tend to function well in the daytime but may have trouble staying awake for social commitments in the evening."
Advanced Sleepers 'Up and at 'Em' on Weekends too
Additionally, "advanced sleepers" rouse more easily than others, he said, and are satisfied with an average of an extra five-to-10 minutes of sleep on non-work days, versus the 30-to-38 minutes' more sleep of their non-advanced sleeper family members.
Ptacek and his colleagues at the University of Utah and the University of Wisconsin calculated the estimated prevalence of advanced sleepers by evaluating data from patients at a sleep disorder clinic over a nine-year period. In total, 2,422 patients were followed, of which 1,748 presented with symptoms of obstructive sleep apnea, a condition that the authors found was not related to sleep-cycle hours.
Among this group, 12 people met initial screening criteria for advanced sleep phase. Four of the 12 declined enrollment in the study and the remaining eight comprised the 0.3 percent of the total number of patients -- or one out of 300 -- that was extrapolated for the general population.
This is a conservative figure, the researchers noted, since it excluded the four patients who did not want to participate in the study and may have met the criteria for advanced sleep phase, as well as those advanced sleepers who had no need to visit a sleep clinic.
Night Owls More Likely to Struggle with Sleep Deficits
"Generally, we find that it's the people with delayed sleep phase -- those night owls that can't sleep until as late as 7 a.m. -- who are more likely to visit a sleep clinic. They have trouble getting up for work and frequently deal with chronic sleep deprivation," said Ptacek.
Criteria for advanced sleep phase include the ability to fall asleep before 8:30 p.m. and wake before 5:30 a.m. regardless of any occupational or social obligations, and having only one sleep period per day. Other criteria include the establishment of this sleep-wake pattern by the age of 30, no use of stimulants or sedatives, no bright lights to aid early rising and no medical conditions that may impact sleep.
All study participants were personally seen by Christopher R. Jones, MD, a former neurologist at the University of Utah and co-author of the paper. Patients were asked about their medical histories and both past and present sleep habits on work days and work-free days. Researchers also looked at sleep logs and level of melatonin in the participants' saliva, as well as sleep studies, or polysomnography, that record brainwaves, oxygen levels in the blood, heart rate and breathing.
Of note, all eight of the advanced sleepers claimed that they had at least one first-degree relative with the same sleep-wake schedule, indicating so-called familial advanced sleep phase. Of the eight relatives tested, three did not meet the full criteria for advanced sleep phase and the authors calculated that the remaining five represented 0.21 percent of the general population.
The authors believe that the percentage of advanced sleepers who have the familial variant may approach 100 percent. However, some participants may have de novo mutations that may be found in their children, but not in parents or siblings, and some may have family members with "nonpenetrant" carrier mutations. Two of the remaining five were found to have genetic mutations that have been identified with familial advanced sleep phase. Conditions associated with these genes include migraine and seasonal affective disorder.
"We hope the results of this study will not only raise awareness of advanced sleep phase and familial advanced sleep phase," said Ptacek, "but also help identify the circadian clock genes and any medical conditions that they may influence."
Funding: The study is supported by grants from the National Institutes of Health and by the William Bowes Neurogenics Fund.
 

Journal Reference:

1. Brian John Curtis, Liza H Ashbrook, Terry Young, Laurel A Finn, Ying-Hui Fu, Louis J Ptáček, Christopher R Jones. Extreme morning chronotypes are often familial and not exceedingly rare: the estimated prevalence of advanced sleep phase, familial advanced sleep phase, and advanced sleep–wake phase disorder in a sleep clinic population. Sleep, 2019; DOI: 10.1093/sleep/zsz148 

Courtesy: ScienceDaily
 

Scientists can now manipulate brain cells using smartphone

A team of scientists in Korea and the United States have invented a device that can control neural circuits using a tiny brain implant controlled by a smartphone.

Researchers, publishing in Nature Biomedical Engineering, believe the device can speed up efforts to uncover brain diseases such as Parkinson's, Alzheimer's, addiction, depression, and pain.
The device, using Lego-like replaceable drug cartridges and powerful bluetooth low-energy, can target specific neurons of interest using drug and light for prolonged periods.
"The wireless neural device enables chronic chemical and optical neuromodulation that has never been achieved before," said lead author Raza Qazi, a researcher with the Korea Advanced Institute of Science and Technology (KAIST) and University of Colorado Boulder.
Qazi said this technology significantly overshadows conventional methods used by neuroscientists, which usually involve rigid metal tubes and optical fibers to deliver drugs and light. Apart from limiting the subject's movement due to the physical connections with bulky equipment, their relatively rigid structure causes lesion in soft brain tissue over time, therefore making them not suitable for long-term implantation. Though some efforts have been put to partly mitigate adverse tissue response by incorporating soft probes and wireless platforms, the previous solutions were limited by their inability to deliver drugs for long periods of time as well as their bulky and complex control setups.
To achieve chronic wireless drug delivery, scientists had to solve the critical challenge of exhaustion and evaporation of drugs. Researchers from the Korea Advanced Institute of Science and Technology and the University of Washington in Seattle collaborated to invent a neural device with a replaceable drug cartridge, which could allow neuroscientists to study the same brain circuits for several months without worrying about running out of drugs.
These 'plug-n-play' drug cartridges were assembled into a brain implant for mice with a soft and ultrathin probe (thickness of a human hair), which consisted of microfluidic channels and tiny LEDs (smaller than a grain of salt), for unlimited drug doses and light delivery.
Controlled with an elegant and simple user interface on a smartphone, neuroscientists can easily trigger any specific combination or precise sequencing of light and drug deliveries in any implanted target animal without need to be physically inside the laboratory. Using these wireless neural devices, researchers could also easily setup fully automated animal studies where behaviour of one animal could positively or negatively affect behaviour in other animals by conditional triggering of light and/or drug delivery.
"This revolutionary device is the fruit of advanced electronics design and powerful micro and nanoscale engineering," said Jae-Woong Jeong, a professor of electrical engineering at KAIST. "We are interested in further developing this technology to make a brain implant for clinical applications."
Michael Bruchas, a professor of anesthesiology and pain medicine and pharmacology at the University of Washington School of Medicine, said this technology will help researchers in many ways.
"It allows us to better dissect the neural circuit basis of behaviour, and how specific neuromodulators in the brain tune behaviour in various ways," he said. "We are also eager to use the device for complex pharmacological studies, which could help us develop new therapeutics for pain, addiction, and emotional disorders."
The researchers at the Jeong group at KAIST develop soft electronics for wearable and implantable devices, and the neuroscientists at the Bruchas lab at the University of Washington study brain circuits that control stress, depression, addiction, pain and other neuropsychiatric disorders. This global collaborative effort among engineers and neuroscientists over a period of three consecutive years and tens of design iterations led to the successful validation of this powerful brain implant in freely moving mice, which researchers believe can truly speed up the uncovering of brain and its diseases.
This work was supported by grants from the National Research Foundation of Korea, U.S. National Institute of Health, National Institute on Drug Abuse, and Mallinckrodt Professorship.
 

Journal Reference:

1. Raza Qazi, Adrian M. Gomez, Daniel C. Castro, Zhanan Zou, Joo Yong Sim, Yanyu Xiong, Jonas Abdo, Choong Yeon Kim, Avery Anderson, Frederik Lohner, Sang-Hyuk Byun, Byung Chul Lee, Kyung-In Jang, Jianliang Xiao, Michael R. Bruchas, Jae-Woong Jeong. Wireless optofluidic brain probes for chronic neuropharmacology and photostimulation. Nature Biomedical Engineering, 2019; DOI: 10.1038/s41551-019-0432-1 

Courtesy: ScienceDaily
 

Pupil dilation and heart rate, analyzed by AI, may help spot autism early

Autism and other neurodevelopmental disorders often aren't diagnosed until a child is a few years of age, when behavioral interventions and speech/occupational therapy become less effective. But new research this week in PNAS suggests that two simple, quantifiable measures -- spontaneous fluctuations in pupil dilation or heart rate -- could enable much earlier diagnosis of Rett syndrome and possibly other disorders with autism-like features.

Child's eye (stock image).

Credit: © Anton / Adobe Stock

 

The study, led by Boston Children's Hospital neuroscientist Michela Fagiolini, PhD, and postdoctoral fellow Pietro Artoni, PhD, unveils a machine-learning algorithm that can spot abnormalities in pupil dilation that are predictive of autism spectrum disorder (ASD) in mouse models. It further shows that the algorithm can accurately detect if a girl has Rett syndrome, a genetic disorder that impairs cognitive, sensory, motor, and autonomic function starting at 6 to 18 months of age, as well as autism-like behaviors.
Fagiolini and colleagues hope this system could provide an early warning signal not just for Rett syndrome but for ASD in general. In the future, they believe it could also be used to monitor patients' responses to treatments; currently, a clinical trial is testing the drug ketamine for Rett syndrome, and a gene therapy trial is planned.
"We want to have some readout of what's going on in the brain that is quantitative, objective, and sensitive to subtle changes," says Fagiolini. "More broadly, we are lacking biomarkers that are reflective of brain activity, easy to quantify, and not biased. A machine could measure a biomarker and not be affected by subjective interpretations of how a patient is doing."
Altered arousal in autism
Fagiolini and Artoni, in close collaboration with Takao Hensch, PhD, and Charles Nelson, PhD, at Boston Children's, began with the idea that people on the autism spectrum have altered behavioral states. Prior evidence indicates that the brain's cholinergic circuits, which are involved in arousal, are especially perturbed, and that altered arousal affects both spontaneous pupil dilation/constriction and heart rate.
Fagiolini's team, supported by the IRCN at Boston Children's F.M. Kirby Neurobiology Center, set out to measure pupil fluctuations in several mouse models of ASD, including mice with the mutations causing Rett syndrome or CDKL5 disorder, as well as BTBR mice. Spontaneous pupil dilation and constriction were altered even before the animals began showing ASD-like symptoms, the team found.
Moreover, in mice lacking MeCP2, the gene mutated in Rett syndrome, restoring a normal copy of the gene, in cholinergic brain circuits only, prevented the onset of pupillary abnormalities as well as behavioral symptoms.
Predicting Rett syndrome in girls
To systematically link the observed arousal changes to the cholinergic system, the team took advantage of an earlier discovery by Hensch: mice lacking the LYNX1 protein exhibit enhanced cholinergic signaling. Based on about 60 hours of observation of these mice, the investigators "trained" a deep learning algorithm to recognize abnormal pupillary patterns. The same algorithm accurately estimated cholinergic dysfunction in the BTBR, CDKL5, and MeCP2-deficient mice.
The team then brought this algorithm to 35 young girls with Rett syndrome and 40 typically developing controls. Instead of measuring the girls' pupils (as patients may fidget), they used heart rate fluctuations as the measure of arousal. The algorithm nonetheless successfully identified the girls with Rett, with an accuracy of 80 percent in the first and second year of life.
"These two biomarkers fluctuate in a similar way because they are proxies of the activity of autonomic arousal," says Artoni. "It is the so-called 'fight or flight response."
Autonomic arousal, a property of the brain that is strongly preserved across different species, is a robust indicator of an altered developmental trajectory, Fagiolini and Artoni found.
Biomarkers for babies?
In a previous study with Nelson, Fagiolini showed that visual evoked potentials, an EEG measure of visual processing in the brain, could also serve as a potential biomarker for Rett syndrome. She believes that together, such biomarkers could offer robust yet affordable screening tools for infants and toddlers, warning of impending neurodevelopmental problems and helping to follow the progression of their development or treatment.
"If we have biomarkers that are non-invasive and easily evaluated, even a newborn baby or non-verbal patient could be monitored across multiple timepoints," Fagiolini says.
 

Journal Reference:

1. Pietro Artoni, Arianna Piffer, Viviana Vinci, Jocelyn LeBlanc, Charles A. Nelson, Takao K. Hensch, Michela Fagiolini. Deep learning of spontaneous arousal fluctuations detects early cholinergic defects across neurodevelopmental mouse models and patients. Proceedings of the National Academy of Sciences, 2019; 201820847 DOI: 10.1073/pnas.1820847116 

Courtesy: ScienceDaily
 

'Tickle' therapy could help slow aging, research suggests

'Tickling' the ear with a small electrical current appears to rebalance the autonomic nervous system for over-55s, potentially slowing down one of the effects of ageing, according to new research.

Scientists found that a short daily therapy delivered for two weeks led to both physiological and wellbeing improvements, including a better quality of life, mood and sleep.

The therapy, called transcutaneous vagus nerve stimulation, delivers a small, painless electrical current to the ear, which sends signals to the body's nervous system through the vagus nerve.

The new research, conducted at the University of Leeds, suggests the therapy may slow down an important effect associated with ageing.

This could help protect people from chronic diseases which we become more prone to as we get older, such as high blood pressure, heart disease and atrial fibrillation. The researchers, who published their findings today in the journal Aging, suggest that the 'tickle' therapy has the potential to help people age more healthily, by recalibrating the body's internal control system.

Lead author Dr Beatrice Bretherton, from the School of Biomedical Sciences at the University of Leeds, said: "The ear is like a gateway through which we can tinker with the body's metabolic balance, without the need for medication or invasive procedures. We believe these results are just the tip of the iceberg.

"We are excited to investigate further into the effects and potential long-term benefits of daily ear stimulation, as we have seen a great response to the treatment so far."

The study was conducted by scientists from the University of Leeds and funded by the Dunhill Medical Trust.

What is the autonomic nervous system?

The autonomic nervous system controls many of the body's functions which don't require conscious thought, such as digestion, breathing, heart rate and blood pressure.

It contains two branches, the sympathetic and the parasympathetic, which work against each other to maintain a healthy balance of activity.

The sympathetic branch helps the body prepare for high intensity 'fight or flight' activity, whilst the parasympathetic is crucial to low intensity 'rest and digest' activity.

As we age, and when we are fighting diseases, the body's balance changes such that the sympathetic branch begins to dominate. This imbalance makes us more susceptible to new diseases and leads to the breakdown of healthy bodily function as we get older.

Clinicians have long been interested in the potential for using electrical currents to influence the nervous system. The vagus nerve, the major nerve of the parasympathetic system, has often been used for electrical stimulation and past research has looked at the possibility of using vagus nerve stimulation to tackle depression, epilepsy, obesity, stroke, tinnitus and heart conditions.

However, this kind of stimulation needs surgery to implant electrodes in the neck region, with associated expense and a small risks of side effects.

Fortunately, there is one small branch of the vagus nerve that can be stimulated without surgery, located in the skin of specific parts of the outer ear.

In Leeds, previous research has shown that applying a small electrical stimulus to the vagus nerve at the ear, which some people perceive as a tickling sensation, improves the balance of the autonomic nervous system in healthy 30-year-olds.

Other researchers worldwide are now investigating if this transcutaneous vagus nerve stimulation (tVNS) could provide a therapy for conditions ranging from heart problems to mental health.

Diane Crossley, aged 70, from Leeds, took part in the study and received the tVNS therapy for two weeks. She said: "I was happy to be a participant in this really interesting study, it helped me with my awareness of my own health.

"It was a fascinating project and I was proud to be part of it."

In their new study, scientists at the University of Leeds wanted to see whether tVNS could benefit over 55-year-olds, who are more likely to have out-of-balance autonomic systems that could contribute to health issues associated with ageing.

They recruited 29 healthy volunteers, aged 55 or above, and gave each of them the tVNS therapy for 15 minutes per day, over a two week period. Participants were taught to self-administer the therapy at home during the study.

The therapy led to an increase in parasympathetic activity and a decrease in sympathetic activity, rebalancing the autonomic function towards that associated with healthy function. In addition, some people reported improvements in measures of mental health and sleeping patterns.

Being able to correct this balance of activity could help us age more healthily, as well as having the potential to help people with a variety of disorders such as heart disease and some mental health issues.

Additionally, improving the balance of the autonomic nervous system lowers an individual's risk of death, as well as the need for medication or hospital visits.

Researchers found that individuals who displayed the greatest imbalance at the start of the study experienced the most pronounced improvements after receiving the therapy.

They suggest that in future it may be possible to identify who is most likely to benefit from the therapy, so it can be offered through a targeted approach.

tVNS therapy has previously been shown to have positive psychological effects for patients with depression, and this study shows it could also have significant physiological benefits.

Dr Susan Deuchars, one of the senior authors on the study, said: "We believe this stimulation can make a big difference to people's lives, and we're now hoping to conduct further studies to see if tVNS can benefit multiple disorders."

Further studies are now needed to understand what the long-term health effects of tVNS might be, as this study involved a small number of participants over a short time period.

Journal Reference:

1. Beatrice Bretherton, Lucy Atkinson, Aaron Murray, Jennifer Clancy, Susan Deuchars, Jim Deuchars. Effects of transcutaneous vagus nerve stimulation in individuals aged 55 years or above: potential benefits of daily stimulation. Aging, 2019; DOI: 10.18632/aging.102074 

Courtesy: ScienceDaily

3D printing the human heart

A team of researchers from Carnegie Mellon University has published a paper in Science that details a new technique allowing anyone to 3D bioprint tissue scaffolds out of collagen, the major structural protein in the human body. This first-of-its-kind method brings the field of tissue engineering one step closer to being able to 3D print a full-sized, adult human heart.

The technique, known as Freeform Reversible Embedding of Suspended Hydrogels (FRESH), has allowed the researchers to overcome many challenges associated with existing 3D bioprinting methods, and to achieve unprecedented resolution and fidelity using soft and living materials.
Each of the organs in the human body, such as the heart, is built from specialized cells that are held together by a biological scaffold called the extracellular matrix (ECM). This network of ECM proteins provides the structure and biochemical signals that cells need to carry out their normal function. However, until now it has not been possible to rebuild this complex ECM architecture using traditional biofabrication methods.
"What we've shown is that we can print pieces of the heart out of cells and collagen into parts that truly function, like a heart valve or a small beating ventricle," says Adam Feinberg, a professor of biomedical engineering (BME) and materials science & engineering at Carnegie Mellon, whose lab performed this work. "By using MRI data of a human heart, we were able to accurately reproduce patient-specific anatomical structure and 3D bioprint collagen and human heart cells."
Over 4000 patients in the United States are waiting for a heart transplant, while millions of others worldwide need hearts but are ineligible for the waitlist. The need for replacement organs is immense, and new approaches are needed to engineer artificial organs that are capable of repairing, supplementing, or replacing long-term organ function. Feinberg, who is a member of Carnegie Mellon's Bioengineered Organs Initiative, is working to solve these challenges with a new generation of bioengineered organs that more closely replicate natural organ structures.
"Collagen is an extremely desirable biomaterial to 3D print with because it makes up literally every single tissue in your body," explains Andrew Hudson, a BME Ph.D. student in Feinberg's lab and co-first author on the paper. "What makes it so hard to 3D print, however, is that it starts out as a fluid -- so if you try to print this in air it just forms a puddle on your build platform. So we've developed a technique that prevents it from deforming."
The FRESH 3D bioprinting method developed in Feinberg's lab allows collagen to be deposited layer-by-layer within a support bath of gel, giving the collagen a chance to solidify in place before it is removed from the support bath. With FRESH, the support gel can be easily melted away by heating the gel from room temperature to body temperature after the print is complete. This way, the researchers can remove the support gel without damaging the printed structure made of collagen or cells.
This method is truly exciting for the field of 3D bioprinting because it allows collagen scaffolds to be printed at the large scale of human organs. And it is not limited to collagen, as a wide range of other soft gels including fibrin, alginate, and hyaluronic acid can be 3D bioprinted using the FRESH technique, providing a robust and adaptable tissue engineering platform. Importantly, the researchers also developed open-source designs so that nearly anyone, from medical labs to high school science classes, can build and have access to low-cost, high-performance 3D bioprinters.
Looking forward, FRESH has applications in many aspects of regenerative medicine, from wound repair to organ bioengineering, but it is just one piece of a growing biofabrication field. "Really what we're talking about is the convergence of technologies," says Feinberg. "Not just what my lab does in bioprinting, but also from other labs and small companies in the areas of stem cell science, machine learning, and computer simulation, as well as new 3D bioprinting hardware and software."
"It is important to understand that there are many years of research yet to be done," adds Feinberg, "but there should still be excitement that we're making real progress towards engineering functional human tissues and organs, and this paper is one step along that path."
Other collaborators on the paper include co-first author Andrew Lee, a BME Ph.D. student in Feinberg's lab; BME postdoctoral researcher Dan Shiwarski; BME Ph.D. students Joshua Tashman, TJ Hinton, Sai Yerneni, and Jacqueline Bliley; and BME Research Professor Phil Campbell.
 

Journal Reference:

1. A. Lee, A. R. Hudson, D. J. Shiwarski, J. W. Tashman, T. J. Hinton, S. Yerneni, J. M. Bliley, P. G. Campbell, A. W. Feinberg. 3D bioprinting of collagen to rebuild components of the human heart. Science, 2019; 365 (6452): 482 DOI: 10.1126/science.aav9051

Courtesy: ScienceDaily

 

 

 

Illustration of tick, inset of Lyme disease bacteria (stock image). Credit: © Kateryna_Kon / Adobe Stock As Lyme disease increases, researchers have taken a significant step toward finding new ways to prevent its transmission. The experts, who include a pioneer in Lyme disease discovery, have sequenced the genome of the animal carrying the bacteria that causes the illness. The advance by researchers at the University of California, Irvine and colleagues provides a launching pad for fresh approaches to stopping Lyme disease from infecting people. Results of their study appear today in Science Advances. The scientists dedicated four years to decoding the genetic makeup of the white-footed mouse Peromyscus leucopus, which harbors the Lyme disease-causing bacteria. Unlike mice that scurry into human homes, these rodents inhabit forests, shrubbery and wetlands. People become infected when a tick bites them after feeding on a white-footed mouse carrying the bacteria. "Many efforts to combat Lyme disease have focused on trying to control those ticks, but they have been difficult to put in practice," said Lyme disease pioneer Alan Barbour, M.D. "So we decided that instead we should look at the animal carrying it." Barbour co-discovered Borreliella burgdorferi, the bacteria causing the illness. He is a professor of medicine and microbiology & molecular genetics for the UCI School of Medicine. As a next step in examining the white-footed mouse's role in Lyme disease's spread, Anthony Long, Ph.D., professor of ecology & evolutionary biology in the UCI School of Biological Sciences, worked with Barbour and other researchers on the complex task of determining the DNA letter sequence that makes up the animal's genome. With 2.45 billion of those letters, representing nucleotides that form DNA's basic structural unit, its genome is similar in size to that of humans. "If you want to understand a species, knowing its genetic blueprint is invaluable," said Long, a geneticist and genomicist. "It provides a road map that makes new research approaches much faster and more efficient." While these rodents are called mice, they are more closely related to hamsters than to the house mouse and the researchers' new data emphasized this fact. With the genome in hand, the scientists are interested in pursuing several potential avenues for preventing Lyme disease transmission. Among them are developing an environmentally-safe, humane vaccination method for white-footed mice in the wild, a process already used to prevent rabies transmission in other kinds of animals. They also would like to find out why the rodents don't develop Lyme disease even though they carry the bacteria. "Understanding what shields them from getting sick could guide us in protecting humans from it," Barbour said. He noted that besides harboring Lyme disease, the rodents carry other emerging infections, including a form of viral encephalitis and illnesses similar to malaria and Rocky Mountain spotted fever. The white-footed mouse genome is now available for free download to all who are interested in Lyme or in the additional disease-causing microorganisms that can be transferred from the rodent carrier to humans. The scientists say they hope the information will help others in the quest to fight this transmission. As they move forward with their investigations, the researchers say it remains very important for the public to continue safeguarding against Lyme disease by preventing tick bites. Information on how to protect people, pets and yards from the insects is available on the Centers for Disease Control and Prevention website. The reported number of confirmed and probable Lyme disease cases in the United States rose more than 17 percent between 2016 and 2017, increasing from 36,429 to 42,743, according to the CDC. Noting that those figures likely represent only a fraction of the actual amount, it also says reported cases have tripled since the late 1990s. The CDC cites several factors as contributing to Lyme's rise, including the growth of forests in what were once agricultural fields, the development of suburbs in those areas, and changes in ecological patterns due to climate change

Illustration of tick, inset of Lyme disease bacteria (stock image).

Credit: © Kateryna_Kon / Adobe Stock

As Lyme disease increases, researchers have taken a significant step toward finding new ways to prevent its transmission. The experts, who include a pioneer in Lyme disease discovery, have sequenced the genome of the animal carrying the bacteria that causes the illness. The advance by researchers at the University of California, Irvine and colleagues provides a launching pad for fresh approaches to stopping Lyme disease from infecting people.

Results of their study appear today in Science Advances.

The scientists dedicated four years to decoding the genetic makeup of the white-footed mouse Peromyscus leucopus, which harbors the Lyme disease-causing bacteria. Unlike mice that scurry into human homes, these rodents inhabit forests, shrubbery and wetlands. People become infected when a tick bites them after feeding on a white-footed mouse carrying the bacteria.

"Many efforts to combat Lyme disease have focused on trying to control those ticks, but they have been difficult to put in practice," said Lyme disease pioneer Alan Barbour, M.D. "So we decided that instead we should look at the animal carrying it."

Barbour co-discovered Borreliella burgdorferi, the bacteria causing the illness. He is a professor of medicine and microbiology & molecular genetics for the UCI School of Medicine.

As a next step in examining the white-footed mouse's role in Lyme disease's spread, Anthony Long, Ph.D., professor of ecology & evolutionary biology in the UCI School of Biological Sciences, worked with Barbour and other researchers on the complex task of determining the DNA letter sequence that makes up the animal's genome. With 2.45 billion of those letters, representing nucleotides that form DNA's basic structural unit, its genome is similar in size to that of humans.

"If you want to understand a species, knowing its genetic blueprint is invaluable," said Long, a geneticist and genomicist. "It provides a road map that makes new research approaches much faster and more efficient." While these rodents are called mice, they are more closely related to hamsters than to the house mouse and the researchers' new data emphasized this fact.

With the genome in hand, the scientists are interested in pursuing several potential avenues for preventing Lyme disease transmission. Among them are developing an environmentally-safe, humane vaccination method for white-footed mice in the wild, a process already used to prevent rabies transmission in other kinds of animals.

They also would like to find out why the rodents don't develop Lyme disease even though they carry the bacteria. "Understanding what shields them from getting sick could guide us in protecting humans from it," Barbour said. He noted that besides harboring Lyme disease, the rodents carry other emerging infections, including a form of viral encephalitis and illnesses similar to malaria and Rocky Mountain spotted fever.

The white-footed mouse genome is now available for free download to all who are interested in Lyme or in the additional disease-causing microorganisms that can be transferred from the rodent carrier to humans. The scientists say they hope the information will help others in the quest to fight this transmission.

As they move forward with their investigations, the researchers say it remains very important for the public to continue safeguarding against Lyme disease by preventing tick bites. Information on how to protect people, pets and yards from the insects is available on the Centers for Disease Control and Prevention website.

The reported number of confirmed and probable Lyme disease cases in the United States rose more than 17 percent between 2016 and 2017, increasing from 36,429 to 42,743, according to the CDC. Noting that those figures likely represent only a fraction of the actual amount, it also says reported cases have tripled since the late 1990s.

The CDC cites several factors as contributing to Lyme's rise, including the growth of forests in what were once agricultural fields, the development of suburbs in those areas, and changes in ecological patterns due to climate change.

Journal Reference:

1. Anthony D. Long, James Baldwin-Brown, Yuan Tao, Vanessa J. Cook, Gabriela Balderrama-Gutierrez, Russell Corbett-Detig, Ali Mortazavi, Alan G. Barbour. The genome of Peromyscus leucopus, natural host for Lyme disease and other emerging infections. Science Advances, 2019; 5 (7): eaaw6441 DOI: 10.1126/sciadv.aaw6441 

Courtesy: ScienceDaily

New cause of cell aging discovered

New research from the USC Viterbi School of Engineering could be key to our understanding of how the aging process works. The findings potentially pave the way for better cancer treatments and revolutionary new drugs that could vastly improve human health in the twilight years.

Cells illustration (stock image).

Credit: © Anusorn / Adobe Stock

 The work, from Assistant Professor of Chemical Engineering and Materials Science Nick Graham and his team in collaboration with Scott Fraser, Provost Professor of Biological Sciences and Biomedical Engineering, and Pin Wang, Zohrab A. Kaprielian Fellow in Engineering, was recently published in the Journal of Biological Chemistry.

"To drink from the fountain of youth, you have to figure out where the fountain of youth is, and understand what the fountain of youth is doing," Graham said. "We're doing the opposite; we're trying to study the reasons cells age, so that we might be able to design treatments for better aging."

What causes cells to age?

To achieve this, lead author Alireza Delfarah, a graduate student in the Graham lab, focused on senescence, a natural process in which cells permanently stop creating new cells. This process is one of the key causes of age-related decline, manifesting in diseases such as arthritis, osteoporosis and heart disease.

"Senescent cells are effectively the opposite of stem cells, which have an unlimited potential for self-renewal or division," Delfarah said. "Senescent cells can never divide again. It's an irreversible state of cell cycle arrest."

The research team discovered that the aging, senescent cells stopped producing a class of chemicals called nucleotides, which are the building blocks of DNA. When they took young cells and forced them to stop producing nucleotides, they became senescent, or aged.

"This means that the production of nucleotides is essential to keep cells young," Delfarah said. "It also means that if we could prevent cells from losing nucleotide synthesis, the cells might age more slowly."

Graham's team examined young cells that were proliferating robustly and fed them molecules labeled with stable isotopes of carbon, in order to trace how the nutrients consumed by a cell were processed into different biochemical pathways.

Scott Fraser and his lab worked with the research team to develop 3D imagery of the results. The images unexpectedly revealed that senescent cells often have two nuclei, and that they do not synthesize DNA.

Before now, senescence has primarily been studied in cells known as fibroblasts, the most common cells that comprised the connective tissue in animals. Graham's team is instead focusing on how senescence occurs in epithelial cells, the cells that line the surfaces of the organs and structures in the body and the type of cells in which most cancers arise.

Graham said that senescence is most widely known as the body's protective barrier against cancer: When cells sustain damage that could be at risk of developing into cancer, they enter into senescence and stop proliferating so that the cancer does not develop and spread.

"Sometimes people talk about senescence as a double-edged sword, that it protects against cancer, and that's a good thing," Graham said. "But then it also promotes aging and diseases like diabetes, cardiac dysfunction or atherosclerosis and general tissue dysfunction," he said.

Graham said the goal was not to completely prevent senescence, because that might unleash cancer cells.

"But then on the other hand, we would like to find a way to remove senescent cells to promote healthy aging and better function," he said.

Graham said that the team's research has applications in the emerging field of senolytics, the development of drugs that may be able to eliminate aging cells. He said that human clinical trials are still in early stages, but studies with mice have shown that by eliminating senescent cells, mice age better, with a more productive life span.

"They can take a mouse that's aging and diminishing in function, treat it with senolytic drugs to eliminate the senescent cells, and the mouse is rejuvenated. If anything, it's these senolytic drugs that are the fountain of youth," Graham said.

He added that in order for successful senolytic drugs to be designed, it was important to identify what is unique about senescent cells, so that drugs won't affect the normal, non-senescent cells.

"That's where we're coming in -- studying senescent cell metabolism and trying to figure out how the senescent cells are unique, so that you could design targeted therapeutics around these metabolic pathways," Graham said.

Journal Reference:

1. Alireza Delfarah, Sydney Parrish, Jason A. Junge, Jesse Yang, Frances Seo, Si Li, John Mac, Pin Wang, Scott E. Fraser, Nicholas A. Graham. Inhibition of nucleotide synthesis promotes replicative senescence of human mammary epithelial cells. Journal of Biological Chemistry, 2019; 294 (27): 10564 DOI: 10.1074/jbc.RA118.005806 

Courtesy: ScienceDaily