#Alzheimer disease: Overlooked for 30 years, there is a new kid on the block Alzheimer's disease is associated with the appearance of characteristic neurotoxic protein aggregates in various regions in the brain.
Chemical analysis of these insoluble deposits reveals that they are made up of a family of short protein fragments,
referred to as beta-amyloid peptides, which are derived from a precursor protein called APP by the sequential action of two enzymes.
An international team of researchers led by Christian Haass (Professor of Metabolic Biochemistry at LMU and Speaker for the German Center for Neurodegenerative Diseases in Munich) and Dr. Michael Willem (LMU) has made now a discovery
which extends this picture of the pathogenesis of Alzheimer's disease, and has potentially far-reaching implications for our understanding of the condition:"
"A second mode of APP cleavage exists, which involves a previously unknown cleavage and generates an alternative peptide,
"says Christian Haass. In collaboration with neurobiologist Dr. Hélène Marie based at the IPMC-CNRS in Valbonne (France) and with the local colleagues from the Technical University of Munich (TUM) in the Synergy Excellence Cluster (Professor Arthur Konnerth
and Dr. Marc Aurel Busche), the LMU researchers have studied also the effects of the eta-amyloid on nerve-cell function in the brain.
the proteolytic enzyme that initiates the release of the toxic beta-amyloid from APP, can reduce memory loss in patients with Alzheimer's.
transmit neurodegeneration Multiple System Atrophy (MSA), a neurodegenerative disorder with similarities to Parkinson's disease, is caused by a newly discovered type of prion,
akin to the misfolded proteins involved in incurable progressive brain diseases such Creutzfeldt-jakob disease (CJD), according to two new research papers led by scientists at UC San francisco. The findings suggest new approaches to developing treatments for MSA,
which currently has no cure, but also raise a potential concern for clinicians or scientists who come in contact with MSA tissue.
The new findings mark the first discovery of a human disease caused by a new prion in 50 years
since work at the National institutes of health in the 1960s showed that human brain tissue infected with CJD could transmit neurodegeneration to chimpanzees.
It wasn't until 1982 that UCSF's Stanley Prusiner, MD isolated the causative agent for a related disease called scrapie,
found in sheep, and characterized it as a prion, for"infectious protein.""He then determined that the same prion protein caused bovine spongiform encephalopathy (BSE),
or"mad cow disease, in cattle, and so-called"variant"CJD in humans who subsequently consumed BSE-contaminated beef or other tissues.
At first, the idea that a simple protein could replicate and spread disease was dismissed by the scientific community,
as a tenet of modern biology held that only viruses and living microbes such as bacteria could transmit disease.
But subsequent work by Prusiner and others led to an understanding of how prions function at a molecular level.
Prusiner, a professor of neurology and director of the Institute for Neurodegenerative Diseases (IND) at UCSF
was awarded the Nobel prize in Physiology or Medicine for this work in 1997. Prion researchers have suggested
since that similar misfolded proteins may contribute to more common forms of neurodegeneration, such as Parkinson's disease and Alzheimer's disease."
"Now we've conclusively shown that a new type of prion causes MSA, "said UCSF's Kurt Giles, DPHIL, associate professor of neurology, IND researcher and senior author on the second of the two new studies."
"This is our mark in the sand.""Sometimes compared to Dr. Jekyll and Mr. Hyde, the original prion protein identified by Prusiner as being responsible for CJD,
known as Prp, can exist in two forms: one harmless and the other fatal. Prp prions in the dangerous, misfolded form latch on to other nearby Prp molecules,
First described in 1960, MSA is a progressive neurodegenerative disorder that is rare but more common than CJD:
Its early symptoms can be mistaken for those of Parkinson's disease, and include movement and balance problems,
Unlike Parkinson's patients, who often live 10 to 20 years after their diagnosis, MSA patients typically die within five to 10 years
As in Parkinson's disease, neurodegeneration in MSA is accompanied by a buildup of clumps of alpha-synuclein protein within brain cells.
Both MSA and PD can arise sporadically in families with no history of the disease,
but some inherited forms are associated with mutations in the alpha-synuclein gene. While the mechanisms aren't fully understood,
researchers believe these mutations predispose the normal proteins to misfold into infectious prions. Other factors,
such as cellular stress and the aging process also are thought to make misfoldings more likely. The new work has its origins in experiments conducted in Prusiner's lab in 2013,
showing that samples of brain tissue from two human MSA patients were able to transmit the disease to a mouse model for Parkinson's disease,
expressing a mutant human alpha-synuclein gene. To confirm this finding Prusiner and colleagues expanded this experiment to include tissue samples from a dozen more MSA victims from tissue banks on three continents:
the Massachusetts Alzheimer's disease Research center in Boston, the Parkinson's UK Brain Bank at Imperial College London,
and the Sydney Brain Bank in Australia. The results were the same: When exposed to human MSA tissue, the mice developed neurodegeneration.
In addition, the team found that the brains of infected mice contained abnormally high levels of insoluble human alpha-synuclein,
and that infected mouse brain tissue could itself spread the disease to other mice. The discovery that alpha-synuclein prions can transmit MSA raises a public health concern about treatments
and research that involve contact with brain tissue from neurodegeneration patients, because standard disinfection techniques that kill microbes do not eliminate the Prp prions that cause CJD.
Whether the same challenges hold for alpha-synuclein prions in MSA remains to be determined. The authors write that clinicians
and researchers should adopt much more stringent safety protocols when dealing with tissue from patients with MSA and other neurodegenerative diseases, many
of which they believe may also be caused by prions. For instance, MSA is diagnosed frequently initially as Parkinson's disease,
which is treated often with deep-brain stimulation. The disease could potentially be transmitted to other patients
if deep-brain stimulation equipment is reused.""You can't kill a protein, "Giles said.""And it can stick tightly to stainless steel,
even when the surgical instrument is cleaned.""As a result, he said, "We're advocating a precautionary approach.
People are living longer and likely getting more brain surgeries. There could be undiagnosed neurodegenerative diseases that
--if they're caused by prions--mean infection could be a real worry.""Unlike the danger of BSE from contaminated beef, the researchers stress that there is no apparent risk of infection by MSA prions outside of specialized medical or research settings.
In the earlier of the group's two PNAS papers published this month, Woerman led a research team in the development of a rapid new method to test prion transmission using human cell cultures.
The team demonstrated that it only takes 4 days for human MSA tissue to infect cultured cells with alpha-synuclein mutations,
in contrast to the 120 days it takes for the disease to spread to mouse models."
"The challenge of studying neurodegeneration is that it's a disease of aging, "Woerman said."
"You have to let the mouse models develop for such a long time that research on cures is really slow to progress.
Now, with these cell models, we can test how to inactivate alpha-synuclein aggregates at a speed that just wouldn't be feasible in animals
#Magnetic fields provide a new way to communicate wirelessly Electrical engineers at the University of California, San diego demonstrated a new wireless communication technique that works by sending magnetic signals through the human body.
The new technology could offer a lower power and more secure way to communicate information between wearable electronic devices, providing an improved alternative to existing wireless communication systems,
researchers said. They presented their findings Aug 26 at the 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society in Milan, Italy.
While this work is still a proof-of-concept demonstration researchers envision developing it into an ultra low power wireless system that can easily transmit information around the human body.
An application of this technology would be a wireless sensor network for full-body health monitoring."
"In the future, people are going to be wearing more electronics, such as smart watches, fitness trackers and health monitors.
All of these devices will need to communicate information with each other. Currently, these devices transmit information using Bluetooth radios,
which use a lot of power to communicate. We're trying to find new ways to communicate information around the human body that use much less power,
"said Patrick Mercier, a professor in the Department of Electrical and Computer engineering at UC San diego who led the study.
Mercier also serves as the co-director of the UC San diego Center for Wearable Sensors.
Communicating magnetic signals through the human body The new study presents a solution to some of the main barriers of other wireless communication systems:
in order to reduce power consumption when transmitting and receiving information, wireless systems need to send signals that can easily travel from one side of the human body to another.
Bluetooth technology uses electromagnetic radiation to transmit data, however these radio signals do not easily pass through the human body
and therefore require a power boost to help overcome this signal obstruction, or"path loss."
"In this study, electrical engineers demonstrated a technique called magnetic field human body communication, which uses the body as a vehicle to deliver magnetic energy between electronic devices.
An advantage of this system is that magnetic fields are able to pass freely through biological tissues,
so signals are communicated with much lower path losses and potentially, much lower power consumption. In their experiments, researchers demonstrated that the magnetic communication link works well on the body,
but they did not test the technique's power consumption. Researchers showed that the path losses associated with magnetic field human body communication are upwards of 10 million times lower than those associated with Bluetooth radios."
"This technique, to our knowledge, achieves the lowest path losses out of any wireless human body communication system that's been demonstrated so far.
This technique will allow us to build much lower power wearable devices, "said Mercier. Lower power consumption also leads to longer battery life."
"A problem with wearable devices like smart watches is that they have short operating times because they are limited to using small batteries.
With this magnetic field human body communication system, we hope to significantly reduce power consumption as well as how frequently users need to recharge their devices,
"said Jiwoong Park, a Ph d student in Mercier's Energy-efficient Microsystems Lab at the UC San diego Jacobs School of engineering and first author of the study.
The researchers also pointed out that this technique does not pose any serious health risks. Since this technique is intended for applications in ultra low power communication systems
the transmitting power of the magnetic signals sent through the body is expected to be many times lower than that of MRI SCANNERS and wireless implant devices.
Another potential advantage of magnetic field human body communication is that it could offer more security than Bluetooth networks.
Because Bluetooth radio communicates data over the air, anyone standing within 30 feet can potentially eavesdrop on that communication link.
On the other hand, magnetic field human body communication employs the human body as a communication medium, making the communication link less vulnerable to eavesdropping.
With this technique, researchers demonstrated that magnetic communication is strong on the body but dramatically decreases off the body.
To put this in the context of a personal full-body wireless communication network, information would neither be radiated off the body nor be transmitted from one person to another."
"Increased privacy is desirable when you're using your wearable devices to transmit information about your health,
"said Park. Demonstrating magnetic communication with a proof-of-concept prototype The researchers built a prototype to demonstrate the magnetic field human body communication technique.
The prototype consists of copper wires insulated with PVC tubes. On one end, the copper wires are hooked up to an external analyzer and on the other end,
the wires are wrapped in coils around three areas of the body: the head, arms and legs.
These coils serve as sources for magnetic fields and are able to send magnetic signals from one part of the body to another using the body as a guide.
With this prototype, researchers were able to demonstrate and measure low path loss communication from arm to arm, from arm to head,
and from arm to leg. Researchers noted that a limitation of this technique is that magnetic fields require circular geometries
in order to propagate through the human body. Devices like smart watches, headbands and belts will all work well using magnetic field human body communication
but not a small patch that is stuck on the chest and used to measure heart rate, for example.
As long as the wearable application can wrap around a part of the body, it should work just fine with this technique,
researchers explained d
#Genetic cause of unknown disease uncovered Using modern high-tech methods, followed by thorough clinical, biochemical and molecular biological investigations,
the researchers found the causative mutation and characterized the disease which is given the name RCDP5.
The researchers believe that studies of the effect of the newly discovered genetic error will provide new insight into other diseases.
Arrayin 2004, professor Petter Strømme examined a child with congenital cataract, growth delay and symptoms from the brain, the peripheral nervous system,
and muscles as well as calcifications in cartilage tissue. The patient had two siblings with similar symptoms
one of whom has died since. Strømme assumed that the disease was caused by a defective gene inherited from the parents,
whom he suspected were both carriers of the unknown disease causing mutation. After clinical and diagnostic odyssey in the following years,
and in depth discussions with colleagues internationally, the cause remained unknown. Arraythe breakthrough came after years of meticulous work developing expert knowledge in the field of genetics at Uio and OUS.
By the use of technology available at the Norwegian Sequencing Centre (NSC) at Uio/OUS,
professor Eirik Frengen's group scanned every gene from two of the patients and their mother.
The defect gene was identified through extensive computer analysis and Ph d. candidate Tuva Barøy subsequently worked with collaborators in The netherlands to find out how the gene defect affects cell function.
The gene defect causes the absence of a protein variant involved in the transport of essential enzymes into structures in the cell called peroxisomes.
The failed transport of these enzymes affects the levels of two specific fat variants in the cell, plasmalogenes and phytanic acid.
The levels of these variants are of great importance for cells in the nervous system. Measurements of cells from the patients showed that their levels diverged distinctly,
explaining the patients'clinical picture. The findings which resulted from collaborations with Dutch and English researchers, were published recently in Human Molecular genetics t
#Timing of sleep just as important as quantity Washington state University researchers have found that the timing of an animal's sleep can be
just as important as how much sleeps it gets. Ilia Karatsoreos, an assistant professor in WSU's Department of Integrative Physiology and Neuroscience, shifted mice from their usual cycle of sleeping
and waking and saw that, while they got enough sleep, it was of poorer quality.
leaving them more open to illness. Most sleep research focuses on the effects of sleep deprivation
"The work by Karatsoreos and his colleagues--published in the journal Brain, Behavior and Immunity--is a rare look into the circadian process,
a brain-driven clock that controls the rhythms of various biological processes, from digestion to blood pressure, heart rate to waking and sleeping.
The cycle is found in most everything that lives more than 24 hours, including plants and single-celled organisms.
shift work, jet lag and even the blue-tinged light emitted by cell phones and tablets. Typically, sleep researchers have a hard time studying sleep deprivation and the circadian cycle separately,
or an overactive response in others, suggesting the altered circadian cycle made them potentially less able to fight illness
"Just like you have a car that you're running into the ground--things don't work right
if you think of disruption going on for years for somebody who's working shift work, "he said.
and the University of Strasbourg (France) have developed a new method for studying the function of ribonucleic acid (RNA) that provides more detailed results,
An international research team involving bioinformatics researcher Max von Kleist has produced ground-breaking findings that could, among other things
facilitate the development of therapeutics that prevent the proliferation of harmful viruses. The scientific paper entitled"Mutational interference mapping experiment (MIME) for studying RNA structure
For a long time molecular biologists believed that RNA is a short-lived storage medium. DNA (deoxyribonucleic acid), the blueprint of every living thing, is transcribed into RNA,
it can catalyze biochemical reactions. The research group developed the molecular biology method MIME (Mutational Interference Mapping Experiment) to investigate the interaction of RNA with its respective interaction partners in detail.
This way the researchers obtain data for each type of mutation as well as precise mutation frequencies at any position of the RNA.
Through mathematical and statistical calculations developed by bioinformatics researcher Max von Kleist the functional consequence of every possible mutation can be quantified.
The researchers can also determine which part and structural configuration of the RNA is investigated responsible for the function.
Many of the most threatening diseases are transmitted by so-called RNA VIRUSES, such as HIV, influenza, and hepatitis C. What they have in common is that the genome does not consist of DNA, but RNA.
Using MIME, scientists can determine how the genetic material of a virus is incorporated into nascent virions at the end of its reproductive cycle.
This has great significance for medical practice: If it was possible to stop this process, e g.,
, by introducing therapeutic (e g. COMPLEMENTARY RNA, the virus could be rendered harmless. Currently, many RNA-based therapies are under investigation worldwide.
The MIME method can make a significant contribution to this research by helping to identify the appropriate RNA segments.
The method also provides information about which mutations are tolerated by the virus and which not, a factor that is useful for the design of therapeutic RNA,
i e. by preventing viruses from developing resistance c
#Completely paralyzed man voluntarily moves his legs, scientists report A 39-year-old man who had had been paralyzed completely for four years was able to voluntarily control his leg muscles
and take thousands of steps in a"robotic exoskeleton"device during five days of training
complete paralysis has regained enough voluntary control to actively work with a robotic device designed to enhance mobility.
In addition to the robotic device, the man was aided by a novel noninvasive spinal stimulation technique that does not require surgery.
The new approach combines a battery-powered wearable bionic suit that enables people to move their legs in a step-like fashion,
That earlier achievement is believed to be the first time people who are paralyzed completely have been able to relearn voluntary leg movements without surgery.
In 2010, Pollock fell from a second-story window and suffered a spinal cord injury that left him paralyzed from the waist down.
At UCLA, Pollock made substantial progress after receiving a few weeks of physical training without spinal stimulation
and then just five days of spinal stimulation training in a one-week span, for about an hour a day."
"This is an aerobic training zone, a rate I haven't even come close to since being paralyzed
The research will be published by the IEEE Engineering in Medicine and Biology Society, the world's largest society of biomedical engineers."
"It will be difficult to get people with complete paralysis to walk completely independently, but even if they don't accomplish that,
and quality of life,"said V. Reggie Edgerton, senior author of the research and a UCLA distinguished professor of integrative biology and physiology, neurobiology and neurosurgery.
which captures data that enables the research team to determine how much the subject is moving his own limbs,
"If the robot does all the work, the subject becomes passive and the nervous system shuts down,
The data showed that Pollock was actively flexing his left knee and raising his left leg and that during and after the electrical stimulation,
it wasn't just the robotic device doing the work.""For people who are injured severely
"We need to expand the clinical toolbox available for people with spinal cord injury and other diseases."
and we are encouraged by these findings to broaden our understanding of possible treatment options for paralysis,
"Given the complexities of a spinal cord injury, there will be no one-size-fits-all cure but rather a combination of different interventions to achieve functional recovery."
and approaches to remind the spine of its potential even years after an injury, "he said.
"This is a great example of a therapeutic approach that combines two very different modalities--neuromodulation
This multi-device approach, much like multi-drug therapy, may ultimately benefit patients with impaired mobility in a wide variety of rehabilitation settings."
"Neurorecovery Technologies, a medical technology company Edgerton founded, designs and develops devices that help restore movement in patients with paralysis. The company provided the device used to stimulate the spinal cord in combination with the Ekso in this research.
he now believes it is possible to significantly improve quality of life for patients with severe spinal cord injuries,
#New technology transforms cell phone into high-powered microscope New technology that transforms a cell phone into a powerful,
mobile microscope could significantly improve malaria diagnoses and treatment in developing countries that often lack the resources to address the life-threatening disease,
says a Texas A&m University biomedical engineer who has created the tool. The add-on device, which is similar in look
and feel to a protective phone case, makes use of a smart phone's camera features to produce high-resolution images of objects 10 times smaller than the thickness of a human hair,
says Gerard Coté, professor of biomedical engineering and director of the Texas A&m Engineering Experiment Station's Center for Remote Health Technologies and Systems.
Coté's development of the instrument, known as a mobile-optical-polarization imaging device (MOPID), is detailed in the online scientific journal Scientific Reports,
published By nature. MOPID, Coté explains, is capable of accepting a small cartridge containing a patient's blood-smear sample.
The sample is imaged then using polarized light in order to detect the presence of hemozoin crystals, Coté notes.
Hemozoin crystals are the byproduct of the malaria parasite and they occur in the blood of an infected host.
As polarized light bounces off of these crystals, they appear as tiny bright dots when observed through the phone's camera lens--enabling an instant,
accurate diagnosis. While polarized light has been preferred the option for malaria detection due to its increased sensitivity,
its implementation into mainstream microscopy has been hindered by its complex configurations, maintenance, size and cost--up until now."
"What we've achieved with MOPID is the design of a polarized microscope platform using a cell phone,
which can detect birefringence in histological specimens infected with the malaria parasite, "Coté says.""It's a simple, low-cost,
portable device that we believe is more sensitive than the standard microscope that uses white light
"MOPID could represent a significant advancement in the detection methods for malaria, a disease that the World health organization estimates was responsible for 584,000 deaths in 2013,
along with an estimated 198 million new cases in that span of time. Given those numbers, a dire need exists for a low-cost, accurate and portable method of detection, particularly in areas of the world with few resources,
While failure to treat malaria can be fatal the administering of unnecessary malaria medications as a result of misdiagnoses can results in new, drug-resistant strains of the disease in addition to increasing costs for malaria medications, Coté notes.
Coté's solution takes advantage of existing mobile phone technology and networks--something to which a whopping 75 percent of the world has access.
This ever-increasing access to mobile networks and the fact that most mobile phones are equipped with advanced camera features make mobile phones the ideal platform for advanced imaging applications such as MOPID,
Coté says. The MOPID system has demonstrated both the resolution and specificity to detect malaria with both ios
-and Android-based devices and requires less user expertise than traditional microscopy, Coté says. That user friendly aspect, coupled with the system's portability and expected low cost of about $10 per unit, makes it an easily adoptable technology in low-resource areas ravaged by malaria,
he adds. What's more, analysis of a blood sample can be made instantaneously with the patient in the field without the need for a mobile network,
says Coté, who notes that a network is required only for transmitting the images to a central location for further analysis or storage."
"These factors increase the likelihood of adoption of the technique in developing countries where cost,
complexity and lack of expertly trained technicians can often prohibit the use of a polarized microscopy technique or even traditional laboratory microscopy as the standard of diagnosis,
"Coté says. For now, Coté and graduate student Casey Pirnstill are continuing to refine the design of the system by making it more compact as well as improving its durability.
Plans for in vivo field-testing are scheduled to take place in Rwanda, Africa in the near future, Coté notes r
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