Vitamin B12 deficiency can be sneaky, harmful

Older post but good information

Patrick J. Skerrett, Former Executive Editor, Harvard Health

What harm can having too little of a vitamin do? Consider this: Over the course of two months, a 62-year-old man developed numbness and a “pins and needles” sensation in his hands, had trouble walking, experienced severe joint pain, began turning yellow, and became progressively short of breath. The cause was lack of vitamin B12 in his bloodstream, according to a case reportfrom Harvard-affiliated Massachusetts General Hospital published in The New England Journal of Medicine. It could have been worse—a severe vitamin B12 deficiency can lead to deep depression, paranoia and delusions, memory loss, incontinence, loss of taste and smell, and more.

What does vitamin B12 do?

The human body needs vitamin B12 to make red blood cells, nerves, DNA, and carry out other functions. The average adult should get 2.4 micrograms a day. Like most vitamins, B12can’t be made by the body. Instead, it must be gotten from food or supplements.

And therein lies the problem: Some people don’t consume enough vitamin B12 to meet their needs, while others can’t absorb enough, no matter how much they take in. As a result, vitamin B12 deficiency is relatively common, especially among older people. The National Health and Nutrition Examination Survey estimated that 3.2% of adults over age 50 have a seriously low B12 level, and up to 20% may have a borderline deficiency.

Are you at risk?

There are many causes for vitamin B12 deficiency. Surprisingly, two of them are practices often undertaken to improve health: a vegetarian diet and weight-loss surgery.

Plants don’t make vitamin B12. The only foods that deliver it are meat, eggs, poultry, dairy products, and other foods from animals. Strict vegetarians and vegans are at high risk for developing a B12 deficiency if they don’t eat grains that have been fortified with the vitamin or take a vitamin supplement. People who have stomach stapling or other form of weight-loss surgery are also more likely to be low in vitamin B12 because the operation interferes with the body’s ability to extract vitamin B12 from food.

Conditions that interfere with food absorption, such celiac or Crohn’s disease, can cause B12trouble. So can the use of commonly prescribed heartburn drugs, which reduce acid production in the stomach (acid is needed to absorb vitamin B12). The condition is more likely to occur in older people due to the cutback in stomach acid production that often occurs with aging.

Recognizing a B12 deficiency

Vitamin B12 deficiency can be slow to develop, causing symptoms to appear gradually and intensify over time. It can also come on relatively quickly. Given the array of symptoms it can cause, the condition can be overlooked or confused with something else. Symptoms may include:

• strange sensations, numbness, or tingling in the hands, legs, or feet
• difficulty walking (staggering, balance problems)
• anemia
• a swollen, inflamed tongue
• yellowed skin (jaundice)
• difficulty thinking and reasoning (cognitive difficulties), or memory loss
• paranoia or hallucinations
• weakness
• fatigue

While an experienced physician may be able to detect a vitamin B12 deficiency with a good interview and physical exam, a blood test is needed to confirm the condition.

Early detection and treatment is important. “If left untreated, the deficiency can cause severe neurologic problems and blood diseases,” says Dr. Bruce Bistrian, chief of clinical nutrition at Harvard-affiliated Beth Israel Deaconess Medical Center.

B proactive

It’s a good idea to ask your doctor about having your B12 level checked if you:

• are over 50 years old
• take a proton-pump inhibitor (such as Nexium or Prevacid) or H2 blocker (such as Pepcid or Zantac)
• take metformin (a diabetes drug)
• are a strict vegetarian
• have had weight-loss surgery or have a condition that interferes with the absorption of food

A serious vitamin B12 deficiency can be corrected two ways: weekly shots of vitamin B12 or daily high-dose B12 pills. A mild B12 deficiency can be corrected with a standard multivitamin.

In many people, a vitamin B12 deficiency can be prevented. If you are a strict vegetarian or vegan, it’s important to eat breads, cereals, or other grains that have been fortified with vitamin B12, or take a daily supplement. A standard multivitamin delivers 6 micrograms, more than enough to cover the average body’s daily need.

If you are over age 50, the Institute of Medicine recommends that you get extra B12 from a supplement, since you may not be able to absorb enough of the vitamin through foods. A standard multivitamin should do the trick.

Not a cure

The Internet is full of articles lauding the use of vitamin B12 to prevent Alzheimer’s disease, heart disease, and other chronic conditions or reverse infertility, fatigue, eczema, and a long list of other health problems. Most are based on poor or faulty evidence.

Take Alzheimier’s disease as an example. “Although there is a relationship between low vitamin B12 levels and cognitive decline, clinical studies—including those involving people with Alzheimer’s disease—have not shown improvement in cognitive function, even doses of the vitamin as high as 1000 micrograms,” says Dr. Bistrian.

For now, it’s best to get enough vitamin B12 to prevent a deficiency, and not look to it as a remedy for what ails you.

http://www.health.harvard.edu/blog/vitamin-b12-deficiency-can-be-sneaky-harmful-201301105780?utm_source=delivra&utm_medium=email&utm_campaign=GB20160831-Vitamins&utm_id=238570&dlv-ga-memberid=24390505&mid=24390505&ml=238570

Dance and music alter the brain in opposite ways

Written by Tim Newman
October 8, 2016

Music and dance go hand in hand, but neurological differences are stark.

Fascinating research, published in the journal NeuroImage, finds distinct changes in sensory and motor pathways in the brains of dancers and musicians. However, the changes in white matter are at opposite ends of the spectrum.

In the majority of earth's most ancient cultures, dancing and music is wonderfully prevalent.

This ubiquitous desire to make music and move along to it has been carried through into modern culture.

Although some children may dread their trumpet tutorial and others would rather play their Xbox than attend ballet lessons, a new study shows that our parents were right all along.

The recent findings demonstrate that music and dance can make significant neurological changes.

Researchers from the International Laboratory for Brain, Music, and Sound Research in Montreal, Canada, recently set out to understand what changes within the brain music and dance might produce, and how they compare with each other.

Earlier studies have shown that music training from a young age can make changes to pathways within the brain. 

A review published in 2014 concluded that the clearest changes that musical training makes in the brain are to the connections that run between the two hemispheres (the corpus callosum). However, to date, the brains of dancers have received much less scientific attention.

Although both skills involve intense training, dance focuses on integrating visual, auditory, and motor coordination, whereas musicianship primarily concentrates on auditory and motor information.

Imaging artist's brains

Using an advanced imaging technique called diffusion tensor imaging, the team of investigators looked in detail at the white matter structure of dancers, musicians, and individuals with training in neither.

The differences between dancers and musicians were more marked than perhaps might be expected.

"We found that dancers and musicians differed in many white matter regions, including sensory and motor pathways, both at the primary and higher cognitive levels of processing."

Lead author Chiara Giacosa

The pathways that were most affected were bundles of fibers that link the sensory and motor regions of the brain and the fibers of the corpus callosum that run between the hemispheres. In the dancers, these sets of connections were broader (more diffuse); in musicians, these same connections were stronger, but less diffuse, and showed more coherent fiber bundles.

According to Giacosa: "This suggests that dance and music training affect the brain in opposite directions, increasing global connectivity and crossing of fibers in dance training, and strengthening specific pathways in music training."

Why the white matter differences?

The differences observed may be because dancers train their whole body, which has a "broader representation in the neural cortex," encouraging fibers to cross over and increase in size; whereas musicians tend to focus their training on specific body parts such as the fingers or mouth, which will have smaller cortical representations in the brain.

Another interesting result was that dancers and musicians differed more from each other than when compared with the group of untrained control subjects. This could be for a number of reasons, as Giacosa explains: "[...] our samples of dancers and musicians were specifically selected to be pure groups of experts, which makes it easier to differentiate between them." On the other hand, the control group was a more diverse group with a range of interests and life experiences.

These results are not just interesting, they could have ramifications for education and rehabilitation. According to senior author Prof. Virginia Penhune: 

"Understanding how dance and music training differently affect brain networks will allow us to selectively use them to enhance their functioning or compensate for difficulties and diseases that involve those specific brain networks."

Dance and music therapy is being investigated for its potential use in the treatment of diseases such as Parkinson's and autism. Prof. Penhune hopes that these findings will spur further research into the use of the arts in the treatment of disease.

http://www.medicalnewstoday.com/articles/313345.php

Do We Really Have A Choice?

NEUROSCIENCE NEWSOCTOBER 7, 2016

Summary: Researchers have found evidence that challenges the intuitive division between a ‘deciding’ and a ‘responding’ stage in decision making.

Source: Tübingen University.

Beta power (12–30 Hz) across the whole cortex during the prestimulus interval (−1 to 1.25 s) for left minus right button-presses (in the current trial) plotted separately for whether the button-press in the current trial is a non-alternation (that is, repetition of the previous button-press) or an alternation with respect to the previous button-press. NeuroscienceNews.com image is credited to Anna-Antonia Pape and Markus Siegel/Scientific Reports.

Choices, it is commonly understood, lead to action – but how does this happen in the brain? Intuitively, we first make a choice between the options. For example, when approaching a yellow traffic light, we need to decide either to hit the breaks or to accelerate the car. Next, the appropriate motor response is selected and carried out, in this case moving the foot to the left or to the right. Traditionally, it is assumed that separate brain regions are responsible for these stages. Specifically, it is assumed that the motor cortex carries out this final response selection without influencing the choice itself.

Two Tübingen Neuroscientists, Anna-Antonia Pape and research group leader Markus Siegel of the Werner Reichardt Centre for Integrative Neuroscience (CIN) and MEG Center, have found evidence that challenges this intuitive division between a ‘deciding’ and a ‘responding’ stage in decision making. The results of their study have been published in the latest Nature Communications.

While recording brain activity using magnetoencephalography (MEG) to monitor activity in motor areas, Pape and Siegel set 20 human subjects the simple task of deciding whether or not a field of dots on a screen was slowly moving together. The subjects could respond “yes” or “no” by pressing a button with either their left or their right hand. The mapping from choice (yes/no) to response (left/right button) changed randomly on each trial, with a short cue telling subjects the current configuration. This ensured the participants’ brains could not plan a motor response, i.e. the correct button press, during choice formation. Astonishingly, while the test subjects were able to press the ‘correct’ button most of the time, subjects still showed a strong tendency towards motor response alternation. In other words, they often simply pressed the button they had not pressed in the trial just prior to the current one. This tendency was pronounced enough to detract from subjects’ overall decision task performance.

In their MEG data, Pape and Siegel found a neural correlate of this tendency in the motor cortex itself. They showed that the upcoming motor decision can be predicted from the status of motor areas even before decision formation has begun. This pre-decisional motor activity to a large extent originates from the neural residue of the previous motor response. How often the subjects alternated between response alternatives is predicted by how pronounced the previous response’s vestiges in the motor cortex still are. Together, these results suggest that the status of the motor cortex even before decision making can influence the formation of a given choice.

These results challenge the traditional view of decision making. According to this view, decisions are formed in the prefrontal cortex and fronto-parietal cortex, brain regions that are associated with ‘higher’ brain functions that are essential for memory and problem solving. The motor cortex is seen as the structure merely executing the behaviour that those ‘higher’ brain regions have determined. Contrary to this view, Pape and Siegel’s findings suggest that the motor cortex also plays a role in informing decision-based behaviour.

Does that mean the way we respond to our environment is not a matter of choice after all? Do we just randomly ‘decide’ what to do based on the state our motor cortex happens to be in? Anna-Antonia Pape, who recorded and analysed the data, does not think so: “The effect is there, yes, but I wouldn’t link it to the question of free will by any means! Higher brain areas are still very important for the decision making process, but now we know that motor areas can tip the scales.”

ABOUT THIS PSYCHOLOGY RESEARCH ARTICLE

Source: Brian Mullen – Tübingen University

Image Source: NeuroscienceNews.com image is credited to Anna-Antonia Pape and Markus Siegel/Scientific Reports.

Original Research: Full open access research for “Motor Cortex Activity Predicts Response Alternation during Sensorimotor Decisions” by Anna-Antonia Pape and Markus Siegel in Nature Communications. Published online October 7 2016 doi:10.1038/ncomms13098

Abstract

Motor Cortex Activity Predicts Response Alternation during Sensorimotor Decisions

Our actions are constantly guided by decisions based on sensory information. The motor cortex is traditionally viewed as the final output stage in this process, merely executing motor responses based on these decisions. However, it is not clear if, beyond this role, the motor cortex itself impacts response selection. Here, we report activity fluctuations over motor cortex measured using MEG, which are unrelated to choice content and predict responses to a visuomotor task seconds before decisions are made. These fluctuations are strongly influenced by the previous trial’s response and predict a tendency to switch between response alternatives for consecutive decisions. This alternation behaviour depends on the size of neural signals still present from the previous response. Our results uncover a response-alternation bias in sensorimotor decision making. Furthermore, they suggest that motor cortex is more than an output stage and instead shapes response selection during sensorimotor decision making.

“Motor Cortex Activity Predicts Response Alternation during Sensorimotor Decisions” by Anna-Antonia Pape and Markus Siegel in Nature Communications. Published online October 7 2016 doi:10.1038/ncomms13098

http://neurosciencenews.com/neuroscience-choice-psychology-5239/

The Role Gut Bacteria Plays in Neurodegenerative Diseases

NEUROSCIENCE NEWSOCTOBER 6, 2016

Summary: Researchers report proteins produced by gut bacteria may cause protein misfolding in the brain and cerebral inflammation.

Source: University of Louisville.

Congo red staining of C. elegans expressing AS-YFP exposed to curli-producing E. coli. Congo red stained deposits (arrowheads) in the head region of C. elegans expressing AS-YFP in the body wall muscles colocalized with AS-YFP aggregates. Scale bar = 100 μm. NeuroscienceNews.com image is credited to the researchers/Scientific Reports.

Research at UofL funded by The Michael J. Fox Foundation shows proteins produced by gut bacteria may cause misfolding of brain proteins and cerebral inflammation.

Alzheimer’s disease (AD), Parkinson’s disease (PD) and Amyotrophic Lateral Sclerosis (ALS) are all characterized by clumped, misfolded proteins and inflammation in the brain. In more than 90 percent of cases, physicians and scientists do not know what causes these processes to occur.

Robert P. Friedland, M.D., the Mason C. and Mary D. Rudd Endowed Chair and Professor of Neurology at the University of Louisville School of Medicine, and a team of researchers have discovered that these processes may be triggered by proteins made by our gut bacteria (the microbiota). Their research has revealed that exposure to bacterial proteins called amyloid that have structural similarity to brain proteins leads to an increase in clumping of the protein alpha-synuclein in the brain. Aggregates, or clumps, of misfolded alpha-synuclein and related amyloid proteins are seen in the brains of patients with the neurodegenerative diseases AD, PD and ALS.

Alpha-synuclein (AS) is a protein normally produced by neurons in the brain. In both PD and AD, alpha-synuclein is aggregated in a clumped form called amyloid, causing damage to neurons. Friedland has hypothesized that similarly clumped proteins produced by bacteria in the gut cause brain proteins to misfold via a mechanism called cross-seeding, leading to the deposition of aggregated brain proteins. He also proposed that amyloid proteins produced by the microbiota cause priming of immune cells in the gut, resulting in enhanced inflammation in the brain.

The research, which was supported by The Michael J. Fox Foundation, involved the administration of bacterial strains of E. coli that produce the bacterial amyloid protein curli to rats. Control animals were given identical bacteria that lacked the ability to make the bacterial amyloid protein. The rats fed the curli-producing organisms showed increased levels of AS in the intestines and the brain and increased cerebral AS aggregation, compared with rats who were exposed to E. coli that did not produce the bacterial amyloid protein. The curli-exposed rats also showed enhanced cerebral inflammation.

Similar findings were noted in a related experiment in which nematodes (Caenorhabditis elegans) that were fed curli-producing E. coli also showed increased levels of AS aggregates, compared with nematodes not exposed to the bacterial amyloid. A research group led by neuroscientist Shu G. Chen, Ph.D., of Case Western Reserve University, performed this collaborative study.

This new understanding of the potential role of gut bacteria in neurodegeneration could bring researchers closer to uncovering the factors responsible for initiating these diseases and ultimately developing preventive and therapeutic measures.

“These new studies in two different animals show that proteins made by bacteria harbored in the gut may be an initiating factor in the disease process of Alzheimer’s disease, Parkinson’s disease and ALS,” Friedland said. “This is important because most cases of these diseases are not caused by genes, and the gut is our most important environmental exposure. In addition, we have many potential therapeutic options to influence the bacterial populations in the nose, mouth and gut.”

“We are pursuing studies in humans and animals to further evaluate the mechanisms of the effects we have observed and are exploring the potential for the development of preventive and therapeutic strategies,” Friedland said.

ABOUT THIS NEUROLOGY RESEARCH ARTICLE

Friedland is the corresponding author of the article, Exposure to the functional bacterial amyloid protein curli enhances alpha-synuclein aggregation in aged Fischer 344 rats and Caenorhabditis elegans, published online Oct. 6 in Scientific Reports, a journal of the Nature Publishing Group. UofL researchers involved in the publication in addition to Friedland include Vilius Stribinskis, Ph.D., Madhavi J. Rane, Ph.D., Donald Demuth, Ph.D., Evelyne Gozal, Ph.D., Andrew M. Roberts, Ph.D., Rekha Jagadapillai, Ruolan Liu, M.D., Ph.D., and Richard Kerber, Ph.D. Additional contributors on the publication include Eliezer Masliah, M.D., Ph.D. of the University of California San Diego.

Funding: This work supports recent studies indicating that the microbiota may have a role in disease processes in age-related brain degenerations. It is part of Friedland’s ongoing research on the relationship between the microbiota and age-related brain disorders, which involves collaborations with researchers in Ireland and Japan.

Source: Betty Coffman – University of Louisville 

Image Source: NeuroscienceNews.com image is credited to the researchers/Scientific Reports.

Original Research: Full open access research for “Exposure to the Functional Bacterial Amyloid Protein Curli Enhances Alpha-Synuclein Aggregation in Aged Fischer 344 Rats and Caenorhabditis elegans” by Shu G. Chen, Vilius Stribinskis, Madhavi J. Rane, Donald R. Demuth, Evelyne Gozal, Andrew M. Roberts, Rekha Jagadapillai, Ruolan Liu, Kyonghwan Choe, Bhooma Shivakumar, Francheska Son, Shunying Jin, Richard Kerber, Anthony Adame, Eliezer Masliah and Robert P. Friedland in Scientific Reports. Published online October 6 2016 doi:10.1038/srep34477

http://neurosciencenews.com/gut-microbiome-neurodegenerative-diseases-5221/

New Tool Will Help Expand Scope of Neural Circuit Research

NEUROSCIENCE NEWSOCTOBER 7, 2016

Summary: According to researchers, a new viral vector will help better understanding of large scale neural networks.

Source: Howard Hughes Medical Institute.

The image shows a section of mouse brain in which scientists have injected rAAV2-retro viruses carrying a red fluorescent protein. The red fluorescent protein labels the long-range output projections between two regions of the brain, the cortex and the pons, located in the brainstem. The site of the injection is shown with a co-injection of a virus carrying green fluorescent protein. NeuroscienceNews.com image is credited to the researchers.

Scientists at the Howard Hughes Medical Institute’s Janelia Research Campus and the University of California, Berkeley have developed a powerful new tool for neuroscientists—a viral vector called rAAV2-retro, which efficiently enters and travels through the long neuronal projections that connect different regions of the brain. Genetically-encoded tools for labeling cells or monitoring or manipulating their activity can be packaged inside the virus and delivered to groups of neurons that signal to a specific part of the brain, creating new opportunities to study large-scale neural networks.

Chemical dyes have long been used to trace neuronal projections. However, a viral vector that is transported to neuronal cell bodies as efficiently as dyes carries a distinct advantage: it delivers a genetic payload to the cells that it infects. “We have performed rigorous analysis to establish that this tool is more effective than anything available, and, based on feedback from our colleagues in neuroscience, we believe that it will expand the scope of neural circuit research,” says Janelia group leader Alla Karpova, who led the large-scale effort to develop and test rAAV2-retro. Eventually, Karpova and her colleagues say, rAAV2-retro might also enable efficient delivery of gene therapies to cells affected by neurodegenerative disease. Karpova and her colleagues reported on rAAV2-retro on October 6, 2016, in the journal Neuron.

Karpova says the new tool helps solve a frustration many neuroscientists experience as they try to unravel how neural circuits process and relay information across the brain. The projection neurons that connect distant parts of the brain are intimately intermingled with one another, and it is difficult to manipulate specific groups of cells selectively to study their function. “It’s pretty clear that projection neurons are a critical component of large-scale networks. But understanding their specific role is hard. It requires being able to distinguish and genetically access different subpopulations,” Karpova says.

With the support of the Janelia Visiting Scientist Program, Janelia scientists partnered with David Schaffer’s team at the University of California, Berkeley, to begin their search. Schaffer, had previously developed a diverse collection of variants of adeno-associated viruses (rAAVs), non-toxic viruses that are widely used in neuroscience research. Naturally occurring adeno-associated viruses are tremendously variable, and can infect different types of cells depending on the precise structure of their outer protein shell, or capsid. The researchers suspected that the right alterations to the capsid might give an adeno-associated virus just the properties they were looking for.

Postdoctoral researcher Gowan Tervo led the effort to find a virus that exhibited efficient retrograde transport in the brains of mice. Together with members of the Dudman, Hantman and Looger labs at Janelia, he devised a screen that would test viruses’ ability to travel through two different sets of neurons that traverse long distances. After injecting the full set of viral variants into the sites where those cells send their signals, Tervo and his colleagues waited three weeks, giving the virus time to spread. Then they collected any viruses that had reached the distant part of the brain where the neurons’ signals originated.

To make those kinds of studies possible, Karpova and her collaborators set out to engineer a virus that would be efficient at retrograde transport: entering a neuron’s axon—the long, thin projection that sends signals to other cells—and traveling all the way back to the cell body, where signals originate.

With the help of Schaffer’s team, an enriched viral pool was then generated, and injected into the same sites in the brain, beginning the selection process again. The procedure was repeated several times, each time generating viral variants better suited for the task at hand.

At the end of that process, the team had several viral vectors that were very good at traveling through the particular neurons he had used in his screen. But to be the type of versatile tool the researchers were looking for, a virus needed to perform equally well in neurons elsewhere in the brain. Together, the team selected 15 contenders, and with the support of Janelia’s core facilities, examined each variant’s ability to trace many different neuronal paths through the brain. When they were used to deliver fluorescent proteins to neurons, the viral vectors that worked best generated clear maps of cells’ courses through the brain, showing groups of labeled cells converging on the site where the virus had been injected.

After this massive effort, the team selected a single virus that excelled in their tests, efficiently diffusing through projection neurons in many different parts of the brain. That vector also successfully delivered a genetically-encoded sensor of neural activity to target cells, causing those cells to light up when they fired. 

Still, Tervo says, additional testing was needed. Together with Sarada Viswanathan, a postdoctoral researcher in Loren Looger’s laboratory at Janelia, he developed sensitive assays to measure the performance of the virus, and after spending more than a year comparing rAAV2-retro to alternative tracers and viral vectors, the team concluded that it is the best tool available for selectively accessing groups of neurons based on their projection patterns. “Now we’re in the position where we can confidently recommend this for the vast majority of circuits,” Tervo says.

Karpova and her colleagues are making rAAV2-retro freely available to the neuroscience community, and hope it will be used for a wide range of scientific applications. “We altered the capsid of the virus. The payload that you put into it is up to you,” Tervo says.

ABOUT THIS NEUROSCIENCE AND GENETICS RESEARCH ARTICLE

Source: Alla Y. Karpova, PhD – Howard Hughes Medical Institute

Image Source: NeuroscienceNews.com image is credited to the researchers.

Video Source: The video is credited to Howard Hughes Medical Institute.

Original Research: Abstract for “A Designer AAV Variant Permits Efficient Retrograde Access to Projection Neurons” by D. Gowanlock R. Tervo, Bum-Yeol Hwang, Sarada Viswanathan, Thomas Gaj, Maria Lavzin, Kimberly D. Ritola, Sarah Lindo, Susan Michael, Elena Kuleshova, David Ojala, Cheng-Chiu Huang7, Charles R. Gerfen, Jackie Schiller, Joshua T. Dudman, Adam W. Hantman, Loren L. Looger, David V. Schaffer, and Alla Y. Karpova in Neuron. Published online October 6 2016 doi:10.1016/j.neuron.2016.09.021

Abstract

A Designer AAV Variant Permits Efficient Retrograde Access to Projection Neurons

Highlights

•AAV can be endowed with robust retrograde functionality through directed evolution

•Up to two orders of magnitude increase in retrograde transport over existing variants

•Efficiency comparable to synthetic tracers

•Sufficient payload expression for circuit interrogation and gene manipulation

Summary

Efficient retrograde access to projection neurons for the delivery of sensors and effectors constitutes an important and enabling capability for neural circuit dissection. Such an approach would also be useful for gene therapy, including the treatment of neurodegenerative disorders characterized by pathological spread through functionally connected and highly distributed networks. Viral vectors, in particular, are powerful gene delivery vehicles for the nervous system, but all available tools suffer from inefficient retrograde transport or limited clinical potential. To address this need, we applied in vivo directed evolution to engineer potent retrograde functionality into the capsid of adeno-associated virus (AAV), a vector that has shown promise in neuroscience research and the clinic. A newly evolved variant, rAAV2-retro, permits robust retrograde access to projection neurons with efficiency comparable to classical synthetic retrograde tracers and enables sufficient sensor/effector expression for functional circuit interrogation and in vivo genome editing in targeted neuronal populations.

“A Designer AAV Variant Permits Efficient Retrograde Access to Projection Neurons” by D. Gowanlock R. Tervo, Bum-Yeol Hwang, Sarada Viswanathan, Thomas Gaj, Maria Lavzin, Kimberly D. Ritola, Sarah Lindo, Susan Michael, Elena Kuleshova, David Ojala, Cheng-Chiu Huang7, Charles R. Gerfen, Jackie Schiller, Joshua T. Dudman, Adam W. Hantman, Loren L. Looger, David V. Schaffer, and Alla Y. Karpova in Neuron. Published online October 6 2016 doi:10.1016/j.neuron.2016.09.021

http://neurosciencenews.com/neural-network-tool-research-5234/

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

The above May help in research for Parkinson's as well:

Modeling neural circuits in Parkinson's disease.

refer to past documentation: https://www.ncbi.nlm.nih.gov/pubmed/25416983

Gut microbiota may have role in neurodegenerative diseases, study finds

AFP Relax News | 08 October, 2016 

The scientists also suggest that amyloid proteins produced by microbiota may cause priming of immune cells in the gut, increasing inflammation in the brain. File photo Image by: SUPPLIED

Could neurodegenerative diseases such as Alzheimer's and Parkinson's originate in the gut? New research from the US, published in the journal Nature, shows that certain proteins produced by gut bacteria may be linked to neurodegeneration in rats.

A team of researchers at Louisville School of Medicine found that neuron destruction processes in the brain could be triggered by proteins produced by gut microbiota.The discovery, observed in rats, shows once again how one small protein has the potential to influence brain function. 

This time, researchers found that exposing rodents to bacterial proteins called amyloids could increase clumping of a protein produced by the brain (alpha-synuclein), forming harmful aggregates that damage neurons in patients with Alzheimer's, Parkinson's and Amyotrophic Lateral Sclerosis (ALS).

The scientists also suggest that amyloid proteins produced by microbiota may cause priming of immune cells in the gut, increasing inflammation in the brain.

The research involved administering strains of E. coli bacteria that produce the bacterial amyloid protein to a group of rats. A second group of rats was administered E. coli bacteria that did not produce the protein.

Compared to rats in the second group, rats who received the amyloid-producing strain were found to have increased levels of the alpha-synuclein protein in the intestines and the brain, as well as increased aggregates in the brain and brain inflammation.

The potential role of microbiota in neurodegeneration opens up new research avenues for scientists exploring the factors responsible for neurological disease, the researchers concluded.

"This is important because most cases of these diseases are not caused by genes, and the gut is our most important environmental exposure," said the study's author, Dr Robert P. Friedland. "In addition, we have many potential therapeutic options to influence the bacterial populations in the nose, mouth and gut." 

http://www.timeslive.co.za/lifestyle/2016/10/08/Gut-microbiota-may-have-role-in-neurodegenerative-diseases-study-finds

Banner Sun Health Research Institute offers free Parkinson's screenings

October 7, 2016 

Banner Sun Health Research Institute will offer two free Parkinson’s disease screenings at the institute, 10515 W. Santa Fe, Sun City.

To participate, residents must register for one of the screenings and attend a one-hour lecture event also conducted at the institute.

The first lecture and registration is scheduled 3:30 p.m. Wednesday, Oct. 19, and the first screening is 1-4 p.m. Friday, Oct. 28.

The second lecture and registration is 10 a.m. Wednesday, Nov. 30, and that screening is 1-4 p.m. Friday, Dec. 16.

Banner Sun Health Research invites those in the community who have not been diagnosed with Parkinson’s disease and may have risk factors to participate in the free screenings. Parkinson’s disease is defined as a progressive neurologic condition that causes motor and non-motor symptoms, including tremors, rigidity, swallowing problems and constipation.

Early detection and management has a positive impact on quality of life and may prolong survival rates. Those who participate in the screening will answer a brief questionnaire and be observed by a board certified movement disorder neurologist.

Call 623-832-3248.

http://www.yourwestvalley.com/suncity/article_47d0ee56-8cdd-11e6-bd48-83a07c4d32bc.html

Play video games, advance science

Older but Interesting.

October 05, 2016

Computer gaming is now a regular part of life for many people. Beyond just being entertaining, though, it can be a very useful tool in education and in science.

If people spent just a fraction of their play time solving real-life scientific puzzles – by playing science-based video games – what new knowledge might we uncover? Many games aim to take academic advantage of the countless hours people spend gaming each day. In the field of biochemistry alone, there are several, including the popular game Foldit.

In Foldit, players attempt to figure out the detailed three-dimensional structure of proteins by manipulating a simulated protein displayed on their computer screen. They must observe various constraints based in the real world, such as the order of amino acids and how close to each other their biochemical properties permit them to get. In academic research, these tasks are typically performed by trained experts.

Thousands of people – with and without scientific training – play Foldit regularly. Sure, they’re having fun, but are they really contributing to science in ways experts don’t already? To answer this question – to find out how much we can learn by having nonexperts play scientific games – we recently set up a Foldit competition between gamers, undergraduate students and professional scientists. The amateur gamers did better than the professional scientists managed using their usual software.

This suggests that scientific games like Foldit can truly be valuable resources for biochemistry research while simultaneously providing enjoyable recreation. More widely, it shows the promise that crowdsourcing to gamers (or “gamesourcing”) could offer to many fields of study.

Looking closely at proteins

Proteins perform basically all the microscopic tasks necessary to keep organisms alive and healthy, from building cell walls to fighting disease. By seeing the proteins up close, biochemists can much better understand life itself.

Understanding how proteins fold is also critical because if they don’t fold properly, the proteins can’t do their tasks in the cell. Worse, some proteins, when improperly folded, can cause debilitating diseases, such as Alzheimer’s, Parkinson’s and ALS.

Taking pictures of proteins

First, by analyzing the DNA that tells cells how to make a given protein, we know the sequence of amino acids that makes up the protein. But that doesn’t tell us what shape the protein takes.

An electron density map of a protein, generated by X-ray crystallography. Scott Horowitz, CC BY-ND

To get a picture of the three-dimensional structure, we use a technique called X-ray crystallography. This allows us to see objects that are only nanometers in size. By taking X-rays of the protein from multiple angles, we can construct a digital 3D model (called an electron density map) with the rough outlines of the protein’s actual shape. Then it’s up to the scientist to determine how the sequence of amino acids folds together in a way that both fits the electron density map and also is biochemically sound.

Although this process isn’t easy, many crystallographers think that it is the most fun part of crystallography because it is like solving a three-dimensional jigsaw puzzle.

An electron density map of a protein with the protein threaded through the map, revealing how the protein folds. Scott Horowitz, CC BY-ND

An addictive puzzle

The competition, and its result, were the culmination of several years of improving biochemistry education by showing how it can be like gaming. We teach an undergraduate class that includes a section on how biochemists can determine what proteins look like.

When we gave an electron density map to our students and had them move the amino acids around with a mouse and keyboard and fold the protein into the map, students loved it – some so much they found themselves ignoring their other homework in favor of our puzzle. As the students worked on the assignment, we found the questions they raised became increasingly sophisticated, delving deeply into the underlying biochemistry of the protein.

In the end, 10 percent of the class actually managed to improve on the structure that had been previously solved by professional crystallographers. They tweaked the pieces so they fit better than the professionals had been able to. Most likely, since 60 students were working on it separately, some of them managed to fix a number of small errors that had been missed by the original crystallographers. This outcome reminded us of the game Foldit.

From the classroom to the game lab

Like crystallographers, Foldit players manipulate amino acids to figure out a protein’s structure based on their own puzzle-solving intuition. But rather than one trained expert working alone, thousands of nonscientist players worldwide get involved. They’re devoted gamers looking for challenging puzzles and willing to use their gaming skills for a good

Cause.

Foldit’s developers had just finished a new version of the game providing puzzles based on three-dimensional crystallographic electron density maps. They were ready to see how players would do.

We gave students a new crystallography assignment, and told them they would be competing against Foldit players to produce the best structure. We also got two trained crystallographers to compete using the software they’d be familiar with, as well as several automated software packages that crystallographers often use. The race was on!

Amateurs outdo professionals

The students attacked the assignment vigorously, as did the Foldit players. As before, the students learned how proteins are put together through shaping these protein structures by hand. Moreover, both groups appeared to take pride in their role in pioneering new science.

At the end of the competition, we analyzed all the structures from all the participants. We calculated statistics about the competing structures that told us how correct each participant was in their solution to the puzzle. The results ranged from very poor structures that didn’t fit the map at all to exemplary solutions.

The best structure came from a group of nine Foldit players who worked collaboratively to come up with a spectacular protein structure. Their structure turned out to be even better than the structures from the two trained professionals.

Students and Foldit players alike were eager to master difficult concepts because it was fun. The results they came up with gave us useful scientific results that can really improve biochemistry.

There are many other games along similar lines, including the “Discovery” mini-game in the massively multiplayer online role-playing game “Eve Online,” which helps build the Human Protein Atlas, and Eterna, which tries to decipher how RNA molecules fold themselves up. If educators incorporate scientific games into their curricula potentially as early as middle school, they are likely to find students becoming highly motivated to learn at a very deep level while having a good time. We encourage game designers and scientists to work together more to create games with purpose, and gamers of the world should play more to bolster the scientific process.

https://theconversation.com/play-video-games-advance-science-65688