New Study Shows These Proteins Are Crucial For Building Muscle & Losing Fat* by mindbodygreen

 What is your competent? doctors EXACT PROTOCOL to prevent sarcopenia(muscle loss)! NOTHING?

Let's see how long everyone related to stroke has been incompetent!

sarcopenia (29 posts to March 2016) (Almost a decade and managed not to get fired? Your board of directors is woefully incompetent!)

Of course, your competent? doctor already prescribed you the correct amounts of dairy fat, right?

• dairy fat (42 posts to April 2016)

The latest here:

New Study Shows These Proteins Are Crucial For Building Muscle & Losing Fat*

Drug-Delivering Nanoparticles Seek and Destroy Elusive Cancer Stem Cells

Our researchers should be able to find at least one of these 39 proteins to attach and attack with tPA if we had any stroke leadership at all doing ANY TYPE OF THINKING. All they have to do is contact these researchers to find out what those 39 proteins are and talk to the cancer researchers to find out how to deliver drugs via nanoparticles. Damn I hate doing the job of your hospital administration, stroke researcher and neurologist for free, I'm stupid that way being stroke-addled.

Proteomic analysis of differential protein expression in atherosclerosis - 39 proteins identified

Drug-Delivering Nanoparticles Seek and Destroy Elusive Cancer Stem Cells 

Pericytes Make Spinal Cord Breathless after Injury

We already know that pericytes cause problems post stroke so this should be immediately followed up to see if this inhibition of proteins would help in stroke.

Capillaries that don't open due to pericytes

Pericytes Make Spinal Cord Breathless after Injury

Show all authors

Viviani M. Almeida, Ana E. Paiva, Isadora F. G. Sena, ...

First Published September 21, 2017 Research Article

Download PDF	Article information

Abstract

Traumatic spinal cord injury is a devastating condition that leads to significant neurological deficits and reduced quality of life. Therapeutic interventions after spinal cord lesions are designed to address multiple aspects of the secondary damage. However, the lack of detailed knowledge about the cellular and molecular changes that occur after spinal cord injury restricts the design of effective treatments. Li and colleagues using a rat model of spinal cord injury and in vivo microscopy reveal that pericytes play a key role in the regulation of capillary tone and blood flow in the spinal cord below the site of the lesion. Strikingly, inhibition of specific proteins expressed by pericytes after spinal cord injury diminished hypoxia and improved motor function and locomotion of the injured rats. This work highlights a novel central cellular population that might be pharmacologically targeted in patients with spinal cord trauma. The emerging knowledge from this research may provide new approaches for the treatment of spinal cord injury.

Newly identified protein helps explain how exercise boosts brain health

From Stanford Medicine Scope blog. Ask your doctor exactly how much exercise  will trigger that protein.  I expect an answer in less than a year.
http://scopeblog.stanford.edu/2013/10/14/newly-identified-protein-helps-explain-how-exercise-boosts-brain-health/
The abstract it is based on here: 
Exercise Induces Hippocampal BDNF through a PGC-1α/FNDC5 Pathway

Summary

Exercise can improve cognitive function and has been linked to the increased expression of brain-derived neurotrophic factor (BDNF). However, the underlying molecular mechanisms driving the elevation of this neurotrophin remain unknown. Here we show that FNDC5, a previously identified muscle protein that is induced in exercise and is cleaved and secreted as irisin, is also elevated by endurance exercise in the hippocampus of mice. Neuronal Fndc5 gene expression is regulated by PGC-1α, and Pgc1a^−/− mice show reduced Fndc5 expression in the brain. Forced expression of FNDC5 in primary cortical neurons increases Bdnf expression, whereas RNAi-mediated knockdown of FNDC5 reduces Bdnf. Importantly, peripheral delivery of FNDC5 to the liver via adenoviral vectors, resulting in elevated blood irisin, induces expression of Bdnf and other neuroprotective genes in the hippocampus. Taken together, our findings link endurance exercise and the important metabolic mediators, PGC-1α and FNDC5, with BDNF expression in the brain.

Chemists develop innovative nano-sensors for multiple proteins

This is so simple. There must be some identifiable proteins that circulate in the blood post-stroke. This would be a fast objective way to then diagnose a stroke. And we can get away from the stupidity of the current, 'Is it a stroke or drunkenness?'.  Which stroke association is going to fail to recognize and promote this possibility? I bet all of them. 

Chemists develop innovative nano-sensors for multiple proteins

Chemists at Johannes Gutenberg University Mainz (JGU) have developed a new method for parallel protein analysis that is, in principle, capable of identifying hundreds or even thousands of different proteins. It could be used to detect the presence of viruses and identify their type in tiny samples. At the same time, it is very cost-effective and quick. "We see possible applications of this technique in medicine, where it could be used, for example, for the rapid diagnosis of a wide range of diseases. It would be almost as easy to use as a pregnancy test strip," said Professor Carsten Sönnichsen of the Institute of Physical Chemistry. The test involves placing a tiny drop of blood, saliva, or other bodily fluid on a small test strip, which is then placed in a device developed at the JGU Institute of Physical Chemistry. This device is able to identify the specific proteins in the fluid and thus allows to quickly and reliably differentiate between harmless microorganisms and dangerous pathogens.
In order to detect the many different substances present in a small sample, the sensors need to be as tiny as possible, preferably the size of nano-particles. Sönnichsen's team of scientists have designed a sensor no larger than the head of a pin but capable of performing a hundred different individual tests on a surface that is only of one-tenth of a square millimeter in area. The 'test strips' consist of glass capillary tubes that have gold nano-particles as sensor elements on their internal surfaces. "We first prepare our nano-particles using short DNA strands, each of which binds to a specific type of protein," explained Janak Prasad, who developed the functionalization method. When a protein docks with one of these special DNA strands, called aptamers, the corresponding nano-particle changes its color. The color changes can be detected with the aid of a spectrometer. For this purpose, the capillary tubes are placed under a microscope designed, constructed, and provided with the necessary software by the Mainz-based team of chemists.
"We demonstrate a new approach for a multiplexed assay that detects multiple proteins simultaneously by letting a fluid flow past the randomly positioned gold nano-rods," explained Christina Rosman, first author of the study. The team from JGU's Institute of Physical Chemistry used four different target proteins to demonstrate the viability of the new concept, its ability to detect concentrations in the nanomolar range, and the possibility to recycle the sensors for more than one analysis. "We see the potential to extend our method to the simultaneous detection of hundreds or even thousands of different target substances," assert the authors in their article published in the June 2013 issue of the journal Nano Letters. Low-cost serial production of the sensors is feasible if advanced nano-fabrication methods such as nano-printing or optical trapping are used.
There are manifold possible applications of a test for multiple targets in a single procedure. The low-cost sensors could be directly used by physicians in their practices in order to detect and discriminate various types of flu viruses with which their patients could be infected. In addition, the technique would also be suitable for detecting the presence of toxins in the environment or in food, particularly in liquids such as milk or baby food, or the presence of doping or other illicit drugs.
Support for the research on this novel multiplexed protein sensor was provided by the Graduate School of Excellence 'Materials Science in Mainz' (MAINZ) and the European Research Council (ERC) 'Single Sense' project.
http://www.uni-mainz.de/presse/16589_ENG_HTML.php

Histone H1 - A New Player In Brain Disease And Stroke

This sounds great, it can join the other 177 hyperacute possibilities.
http://www.redorbit.com/news/health/1112904627/a-new-player-in-brain-disease-and-stroke/

In degenerative brain diseases and after stroke, nerve cells die while their support cells activate the brain’s immune system to cause further damage. Called the neuronal cascade of death. Now Jonathan Gilthorpe, Adrian Pini and Andrew Lumsden at the MRC Centre for Developmental Neurobiology at King’s College London, have found that a single protein, histone H1, causes these distinct outcomes.
The research passed peer review within a week of being published in F1000Research, where Jan-Marino Ramirez, of the University of Washington, called the work “a very important contribution to our understanding of neurodegenerative disease and the response of the brain to injury” in his public referee report. He also noted that he is “confident that this study will be a much cited contribution to the field of traumatic brain injury”.

The most unexpected finding in this study is that a histone protein is responsible for neuronal damage. “Histone H1 partners with DNA in the cell nucleus and has been thought of as harmless,” explain the authors, “The surprise came when we discovered that it can be released from brain cells upon injury, killing healthy nerve cells and activating the damaging immune response”.
The research team is now working on ways to suppress these harmful actions, which may lead to the development of new treatments for neurodegenerative disease and stroke.

SUMO wrestling cells reveal new protective mechanism target for stroke

A great name for a brain protein.
http://medicalxpress.com/news/2013-05-sumo-cells-reveal-mechanism.html

The discovery, made by researchers from the University's School of Biochemistry and published in the EMBO journal with additional comment in Nature Reviews, could eventually lead to new therapies for stroke and other brain diseases. The research builds on earlier work by the team which identified a protein, known as SUMO, responsible for controlling the chemical processes which reduce or enhance protection mechanisms for nerve cells in the brain. The team's latest work has now identified the key role that SUMO plays in promoting cell survival. During cell stress a protein response triggers a protective mechanism that allows cell adaptation and survival. This process, known as SUMOylation, involves the attachment of a small protein called Small Ubiquitin-related Modifier (SUMO) to target proteins. This pathway is essential for survival of all plant and animal cells because it regulates how proteins interact with each other and can protect nerve cells against damage. The findings have shown that SUMOylation of a protein called dynamin-related protein 1 (Drp1) is particularly important because it controls the release of chemical signals from mitochondria that instruct the cell to die in a process called apoptosis. SUMOylation of Drp1 reduces mitochondrial release of these 'death' signals and helps nerve cells survive toxic insults associated with stroke. In the future, finding effective methods to enhance SUMOylation of Drp1 may also be beneficial for cell survival in other diseases including heart attacks and Alzheimer's disease. The European Research Council-funded study, entitled 'SENP3-mediated deSUMOylation of dynamin-related protein 1 promotes cell death following ischaemia' published in the EMBO Journal and led by Professor Jeremy Henley from the University's School of Biochemistry. More information: doi:10.1038/emboj.2013.65 Journal reference: EMBO Journal search and more info website Provided by University of Bristol search and more info website

Read more at: http://medicalxpress.com/news/2013-05-sumo-cells-reveal-mechanism.html#jCp

 The discovery, made by researchers from the University's School of Biochemistry and published in the EMBO journal with additional comment in Nature Reviews, could eventually lead to new therapies for stroke and other brain diseases. The research builds on earlier work by the team which identified a protein, known as SUMO, responsible for controlling the chemical processes which reduce or enhance protection mechanisms for nerve cells in the brain. The team's latest work has now identified the key role that SUMO plays in promoting cell survival. During cell stress a protein response triggers a protective mechanism that allows cell adaptation and survival. This process, known as SUMOylation, involves the attachment of a small protein called Small Ubiquitin-related Modifier (SUMO) to target proteins. This pathway is essential for survival of all plant and animal cells because it regulates how proteins interact with each other and can protect nerve cells against damage. The findings have shown that SUMOylation of a protein called dynamin-related protein 1 (Drp1) is particularly important because it controls the release of chemical signals from mitochondria that instruct the cell to die in a process called apoptosis. SUMOylation of Drp1 reduces mitochondrial release of these 'death' signals and helps nerve cells survive toxic insults associated with stroke. In the future, finding effective methods to enhance SUMOylation of Drp1 may also be beneficial for cell survival in other diseases including heart attacks and Alzheimer's disease. The European Research Council-funded study, entitled 'SENP3-mediated deSUMOylation of dynamin-related protein 1 promotes cell death following ischaemia' published in the EMBO Journal and led by Professor Jeremy Henley from the University's School of Biochemistry. More information: doi:10.1038/emboj.2013.65 Journal reference: EMBO Journal search and more info website Provided by University of Bristol search and more info website

Read more at: http://medicalxpress.com/news/2013-05-sumo-cells-reveal-mechanism.html#jCp

The discovery, made by researchers from the University's School of Biochemistry and published in the EMBO journal with additional comment in Nature Reviews, could eventually lead to new therapies for stroke and other brain diseases. The research builds on earlier work by the team which identified a protein, known as SUMO, responsible for controlling the chemical processes which reduce or enhance protection mechanisms for nerve cells in the brain. The team's latest work has now identified the key role that SUMO plays in promoting cell survival. During cell stress a protein response triggers a protective mechanism that allows cell adaptation and survival. This process, known as SUMOylation, involves the attachment of a small protein called Small Ubiquitin-related Modifier (SUMO) to target proteins. This pathway is essential for survival of all plant and animal cells because it regulates how proteins interact with each other and can protect nerve cells against damage. The findings have shown that SUMOylation of a protein called dynamin-related protein 1 (Drp1) is particularly important because it controls the release of chemical signals from mitochondria that instruct the cell to die in a process called apoptosis. SUMOylation of Drp1 reduces mitochondrial release of these 'death' signals and helps nerve cells survive toxic insults associated with stroke. In the future, finding effective methods to enhance SUMOylation of Drp1 may also be beneficial for cell survival in other diseases including heart attacks and Alzheimer's disease. The European Research Council-funded study, entitled 'SENP3-mediated deSUMOylation of dynamin-related protein 1 promotes cell death following ischaemia' published in the EMBO Journal and led by Professor Jeremy Henley from the University's School of Biochemistry. More information: doi:10.1038/emboj.2013.65 Journal reference: EMBO Journal

Read more at: http://medicalxpress.com/news/2013-05-sumo-cells-reveal-mechanism.html#jCp

The discovery, made by researchers from the University's School of Biochemistry and published in the EMBO journal with additional comment in Nature Reviews, could eventually lead to new therapies for stroke and other brain diseases. The research builds on earlier work by the team which identified a protein, known as SUMO, responsible for controlling the chemical processes which reduce or enhance protection mechanisms for nerve cells in the brain. The team's latest work has now identified the key role that SUMO plays in promoting cell survival. During cell stress a protein response triggers a protective mechanism that allows cell adaptation and survival. This process, known as SUMOylation, involves the attachment of a small protein called Small Ubiquitin-related Modifier (SUMO) to target proteins. This pathway is essential for survival of all plant and animal cells because it regulates how proteins interact with each other and can protect nerve cells against damage. The findings have shown that SUMOylation of a protein called dynamin-related protein 1 (Drp1) is particularly important because it controls the release of chemical signals from mitochondria that instruct the cell to die in a process called apoptosis. SUMOylation of Drp1 reduces mitochondrial release of these 'death' signals and helps nerve cells survive toxic insults associated with stroke. In the future, finding effective methods to enhance SUMOylation of Drp1 may also be beneficial for cell survival in other diseases including heart attacks and Alzheimer's disease. The European Research Council-funded study, entitled 'SENP3-mediated deSUMOylation of dynamin-related protein 1 promotes cell death following ischaemia' published in the EMBO Journal and led by Professor Jeremy Henley from the University's School of Biochemistry. More information: doi:10.1038/emboj.2013.65 Journal reference: EMBO Journal

Read more at: http://medicalxpress.com/news/2013-05-sumo-cells-reveal-mechanism.html#jCp

The discovery, made by researchers from the University's School of Biochemistry and published in the EMBO journal with additional comment in Nature Reviews, could eventually lead to new therapies for stroke and other brain diseases. The research builds on earlier work by the team which identified a protein, known as SUMO, responsible for controlling the chemical processes which reduce or enhance protection mechanisms for nerve cells in the brain. The team's latest work has now identified the key role that SUMO plays in promoting cell survival. During cell stress a protein response triggers a protective mechanism that allows cell adaptation and survival. This process, known as SUMOylation, involves the attachment of a small protein called Small Ubiquitin-related Modifier (SUMO) to target proteins. This pathway is essential for survival of all plant and animal cells because it regulates how proteins interact with each other and can protect nerve cells against damage. The findings have shown that SUMOylation of a protein called dynamin-related protein 1 (Drp1) is particularly important because it controls the release of chemical signals from mitochondria that instruct the cell to die in a process called apoptosis. SUMOylation of Drp1 reduces mitochondrial release of these 'death' signals and helps nerve cells survive toxic insults associated with stroke. In the future, finding effective methods to enhance SUMOylation of Drp1 may also be beneficial for cell survival in other diseases including heart attacks and Alzheimer's disease. The European Research Council-funded study, entitled 'SENP3-mediated deSUMOylation of dynamin-related protein 1 promotes cell death following ischaemia' published in the EMBO Journal and led by Professor Jeremy Henley from the University's School of Biochemistry. More information: doi:10.1038/emboj.2013.65 Journal reference: EMBO Journal search and more info website Provided by University of Bristol search and more info website

Read more at: http://medicalxpress.com/news/2013-05-sumo-cells-reveal-mechanism.html#jCp

The discovery, made by researchers from the University's School of Biochemistry and published in the EMBO journal with additional comment in Nature Reviews, could eventually lead to new therapies for stroke and other brain diseases. The research builds on earlier work by the team which identified a protein, known as SUMO, responsible for controlling the chemical processes which reduce or enhance protection mechanisms for nerve cells in the brain. The team's latest work has now identified the key role that SUMO plays in promoting cell survival. During cell stress a protein response triggers a protective mechanism that allows cell adaptation and survival. This process, known as SUMOylation, involves the attachment of a small protein called Small Ubiquitin-related Modifier (SUMO) to target proteins. This pathway is essential for survival of all plant and animal cells because it regulates how proteins interact with each other and can protect nerve cells against damage. The findings have shown that SUMOylation of a protein called dynamin-related protein 1 (Drp1) is particularly important because it controls the release of chemical signals from mitochondria that instruct the cell to die in a process called apoptosis. SUMOylation of Drp1 reduces mitochondrial release of these 'death' signals and helps nerve cells survive toxic insults associated with stroke. In the future, finding effective methods to enhance SUMOylation of Drp1 may also be beneficial for cell survival in other diseases including heart attacks and Alzheimer's disease. The European Research Council-funded study, entitled 'SENP3-mediated deSUMOylation of dynamin-related protein 1 promotes cell death following ischaemia' published in the EMBO Journal and led by Professor Jeremy Henley from the University's School of Biochemistry. More information: doi:10.1038/emboj.2013.65 Journal reference: EMBO Journal search and more info website Provided by University of Bristol search and more info website

Read more at: http://medicalxpress.com/news/2013-05-sumo-cells-reveal-mechanism.html#jCp

The discovery, made by researchers from the University's School of Biochemistry and published in the EMBO journal with additional comment in Nature Reviews, could eventually lead to new therapies for stroke and other brain diseases. The research builds on earlier work by the team which identified a protein, known as SUMO, responsible for controlling the chemical processes which reduce or enhance protection mechanisms for nerve cells in the brain. The team's latest work has now identified the key role that SUMO plays in promoting cell survival. During cell stress a protein response triggers a protective mechanism that allows cell adaptation and survival. This process, known as SUMOylation, involves the attachment of a small protein called Small Ubiquitin-related Modifier (SUMO) to target proteins. This pathway is essential for survival of all plant and animal cells because it regulates how proteins interact with each other and can protect nerve cells against damage. The findings have shown that SUMOylation of a protein called dynamin-related protein 1 (Drp1) is particularly important because it controls the release of chemical signals from mitochondria that instruct the cell to die in a process called apoptosis. SUMOylation of Drp1 reduces mitochondrial release of these 'death' signals and helps nerve cells survive toxic insults associated with stroke. In the future, finding effective methods to enhance SUMOylation of Drp1 may also be beneficial for cell survival in other diseases including heart attacks and Alzheimer's disease. The European Research Council-funded study, entitled 'SENP3-mediated deSUMOylation of dynamin-related protein 1 promotes cell death following ischaemia' published in the EMBO Journal and led by Professor Jeremy Henley from the University's School of Biochemistry. More information: doi:10.1038/emboj.2013.65 Journal reference: EMBO Journal search and more info website Provided by University of Bristol search and more info website

Read more at: http://medicalxpress.com/news/2013-05-sumo-cells-reveal-mechanism.html#jCp

Factor That Reverses Aging of Heart Discovered - young blood

This matches up with the earlier report of young mice blood transfusions helping recovery. See below
http://harvardmagazine.com/2013/05/heart-aging-reversal-factor-found-in-mice?utm_source=Harvard+Magazine+e-mail+newsletters&utm_campaign=1e2dda5a8c-THIS_WEEK&utm_medium=email&utm_term=0_d59fecc95b-1e2dda5a8c-85119777
Researchers at the Harvard Stem Cell institute have discovered a substance in the blood of young mice that reverses a major effect of aging in the hearts of old mice. The substance, called GDF-11, is an obscure member of the transforming growth factor family of proteins; it was identified by Forst family professor of stem cell and regenerative biology Amy Wagers and Harvard Medical School professor Richard T. Lee, working with a startup company, SomaLogic, that has developed a technology for analyzing factors in the blood. Lee and Wagers report their finding that GDF-11 reverses cardiac hypertrophy, or thickening of the heart muscle, in mice, in the May 9 issue of the journal Cell.
The heart’s walls thicken with age—the primary cause of cardiac failure in humans, explains Lee, a practicing cardiologist at Brigham and Women’s Hospital. Yet in the study, when older mice were given the factor, he says, “we could reverse the heart aging in a very short period of time.” The change from a thickened, fibrotic heart to the smooth-muscled heart of youth is so dramatic, it is reportedly visible to the naked eye.
Wagers had previously discovered, during research in which the circulatory system of a young mouse was surgically joined to that of an old one, that a factor circulating in the blood could reverse aging in skeletal muscle and the spinal cord (see “A Hidden Youthfulness”). But because the heart, unlike many other organs, does not have a known ability to regenerate naturally, she did not expect to see a similar effect there. “The effect of blood-based factors is broader than we anticipated,” she says now.
Nor had Wagers, in her earlier experiments, been able to identify which factor, among the many thousands that circulate in blood, was responsible for the regeneration that she observed. Now she and Lee will take a closer look at the effects of GDF-11. It is known to be important in in-utero development, Lee says, but “its role in adults has not been explored.”
Wagers said in a press-conference call that other organs in the body contain cells with surface receptors designed to interact with the protein, which circulates freely in the bloodstream. The presence of the receptors suggests that GDF-11 may have an effect on those tissues as well, so she and Lee plan to investigate whether the protein has a similar rejuvenating effect on the organs themselves. The researchers hope they may have discovered a substance that is broadly involved in the physiological pathways of aging. Says Wagers, “We should have that answer soon.”

This was the key paragraph from the earlier post:
These results suggest that chemicals found in the blood of old mice inhibit the generation of new brain cells, whereas chemicals in the blood of young mice promote it. The researchers then injected blood from young or old mice into young adults. Again, they found that animals injected with old blood had far fewer newborn neurons in the hippocampus than those injected with young blood, confirming that old blood contains soluble factors that inhibit neurogenesis. 

So this brings up the question for your doctor. Should all stroke survivors get blood transfusions from young people, maybe your grandchildren?
How young should the blood be? 

MULTIFACTORIAL MODULATION OF THE BLOOD-BRAIN BARRIER: RELATIONSHIP TO STROKE

No clue what this means. Ask your doctor to incorporate it into your stroke protocol. A great dissertation.
http://scholar.google.com/scholar_url?hl=en&q=http://uknowledge.uky.edu/cgi/viewcontent.cgi%3Farticle%3D1007%26context%3Dnutrisci_etds&sa=X&scisig=AAGBfm1eancpAqIHcifp9WcodG2cd6A3rg&oi=scholaralrt

The blood brain barrier (BBB) is a dynamic interface, mainly consisting of highly

specialized brain microvascular endothelial cells (BMECs) that segregate the

central nervous system (CNS) from the peripheral circulation. Impairment of the BBB, due to

disruption of tight junction (TJ) proteins and inflammatory responses, may initiate and/or

contribute to the progress of CNS disorders, including stroke. Stroke is the second

leading cause of death worldwide. It has been shown that aging and environmental

pollutants can induce brain endothelium dysfunction, and are considered as risk factors

for stroke.

Deficiency of telomerase is highly linked with aging associated vascular diseases.

Evidence indicates that patients with shorter telomere length are at higher risk of heart

disease or stroke. Results in this dissertation address the influence of telomerase reverse

transcriptase (TERT), a key component of telomerase, on the BBB integrity in

the context of ischemic stroke induced brain injury. Our results indicate that aging related

BBB alterations aggregate the stroke outcomes by inducing oxidative stress and

stimulating proinflammatory responses on the brain microvessels.

The ability of the BBB to protect the brain from harmful compounds indicates

that the BBB may be targeted by chemical toxicants in the peripheral circulation.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that

frequently bind to nanoparticles (NPs) in the environment

. Our results demonstrate that binding PCB153, one of the most abundant PCB congeners in the environment, to silica nanoparticles (PCB153 - NPs) potentiates

cerebrovascular toxicity and stroke outcomes via stimulation

of inflammatory responses and disruption of BBB integrity. These events are mediated by

activation of toll like receptor 4 (TLR4), which subsequently recruits tumor necrosis

factor associated factor 6 (TRAF6) and initiates the production of multiple inflammatory

mediators

Discovery of 'executioner' protein opens door to new options for stroke ALS, spinal cord injury

So ask your researchers to go back over the 1000 failed hyperacute therapies and see if  this new knowledge could require new clinical trials.
Discovery of 'executioner' protein opens door to new options for stroke ALS, spinal cord injury

Oxidative stress turns a protein that normally protects healthy cells into their executioner, according to a study released today in the Proceedings of the National Academy of Sciences journal.
Alvaro Estevez, an associate professor at the University of Central Florida's College of Medicine, led the multi-university team that made the discovery, which could eventually help scientists develop new therapies to combat a host of conditions from stroke to Lou Gehrig's disease
Researchers have long known that oxidative stress damages cells and results in neurodegeneration, inflammation and aging. It was commonly believed that oxidation made a "crude," demolition-like attack on cells, causing them to crumble like a building in an earthquake, Estevez said. However, the latest findings show that oxidation results in a much more targeted attack to specific parts of the cell. Oxidative stress damages a specific "chaperone" cell protein called Hsp90. It plays a role in up to 200 different cell functions. But when a form of oxidative stress called tyrosine nitration modifies that protein, it turns into the cell "executioner" shutting it down.
"The concept that a protein that is normally protective and indispensable for cell survival and growth can turn into a killing machine, and just because of one specific oxidative modification, is amazing," said Maria C. Franco, a postdoctoral associate at UCF's Burnett School of Biomedical Sciences. She co-wrote the study. "Considering that this modified protein is present in a vast number of pathologies, it gives us hopes on finding new therapeutics approaches for several different diseases."
For example, researchers could devise a drug that stroke patients could take at the onset of their symptoms to prevent more healthy cells from dying, thus limiting the damage of the stroke. Because oxidation is linked to inflammation, researchers believe tyrosine nitration could also be related to other health problems including heart disease, cancer, aging and chronic pain.
"These are very exciting results and could begin a major shift in medicine," said Joseph Beckman, from Oregon State University Environmental Health Sciences Center, a collaborator on the study. "Preventing this process of tyrosine nitration may protect against a wide range of degenerative diseases."
"Most people think of things like heart disease, cancer, aging, liver disease, even the damage from spinal injury as completely different medical issues," Beckman said. "To the extent they can often be traced back to inflammatory processes that are caused by oxidative attack and cellular damage, they can be more similar than different. It could be possible to develop therapies with value against many seemingly different health problems."

New more efficient method for the production of induced pluripotent stem cells

Our researchers should be following this
http://www.stemcellsfreak.com/2013/03/new-method-induced-pluripotent-stem-cells.html

Long-distance distress signal from periphery of injured nerve cells begins with locally made protein

Sounds like something we need in order for neurons to create a detour  around our dead areas. Ask your doctor for a protocol. 

Long-distance distress signal from periphery of injured nerve cells begins with locally made protein

When the longest cells in the body are injured at their farthest reaches, coordinating the cells' repair is no easy task. This is in part because these peripheral nerve cells can be extremely long – up to one meter in adult humans – which is a lot of distance for a molecular distress signal to cover in order to reach the "command center" of the cell's nucleus.
Scientists have believed this process to be even more challenging because their textbook understanding for many years has been that the axons – the long extensions of nerve cells away from the main cell body containing the nucleus – do not manufacture the proteins involved in the molecular signal themselves. Yet, in recent years, some scientists have begun to challenge that textbook understanding, with preliminary evidence that one key protein involved in setting off a distress signal for cellular repair, known as importin beta1, was locally produced in the axons. They just weren't sure how.
"Now these textbooks need to be rewritten," said Dr. Jeffery Twiss, a professor and head of the department of biology in Drexel University's College of Arts and Sciences. Twiss co-authored new research recently published in Neuron, led by collaborators from the Weizmann Institute of Science. "Our new research is one of the strongest indicators yet of molecular signaling from end to end in peripheral nerve cells."
These researchers have provided strong new evidence that the protein importin beta1 is indeed produced locally in the axons of peripheral nerve cells. They also found that the version of the protein, when found in the axon, is made using a different molecular recipe than the version found in the nucleus, where it performs different essential cell functions. These discoveries may help scientists better understand how subsequent steps operate in the distress signal and in nerve cell repair, so they can eventually control and enhance the process to speed up recovery from nerve injuries.
Finding this evidence was far from simple: Importins are so crucial in the cell's nucleus that even the smallest embryo could not survive without them. But Rotem Ben-Tov Perry, a research student at the Weizmann Institute who was lead author of the new study, found a way to distinguish the importin beta1 in the cell body from that in the axon: The axonal protein was apparently made from a longer version of messenger RNA, the cell's working recipe for building a protein. To see if they could selectively affect just the axonal version of the protein, the Weizmann researchers worked with Drexel's Twiss to take advantage of high precision knock-out technology. Rather than knocking a whole gene out of the system, they managed to remove one little piece of the messenger RNA's recipe for manufacturing importins -just the longer bit that sends the RNA to the axon.
Now they observed plenty of importin beta1 in the cell body, but none in the axons. With the axonal segment of RNA knocked out of the recipe for importin beta1, a mouse embryo still had the importin it needed near the nucleus of its cells to grow and develop into a living animal – but it took much longer to recover from peripheral nerve injury. Genes that are normally active in response to nerve damage were activated to a lesser degree. All of this suggests that the importin beta1 that normally helps inform the extended nerve cell about injury is, indeed, produced locally in the axon – and that this protein found in the axon is a key part of the nerve repair signaling process.
"The data shows conclusively that importin beta1 protein is produced in axons, Rotem's work has validated the importins' crucial role in nerve repair," said Dr. Michael Fainzilber, senior author and professor at the Weizmann Institute.
Twiss said that next steps will be to better describe how the signaling process involving importin beta1 delivers a signal to begin nerve cell repair and, ultimately, develop strategies to better control these molecular steps of the repair mechanisms to improve nerve cell regeneration after injury.

The mechanobiology of brain function

You doctor should be subscribing to Nature Reviews Neuroscience so ask them about this one and apply it to your recovery.
http://www.nature.com/nrn/journal/v13/n12/abs/nrn3383.html#top

All cells are influenced by mechanical forces. In the brain, force-generating and load-bearing proteins twist, turn, ratchet, flex, compress, expand and bend to mediate neuronal signalling and plasticity. Although the functions of mechanosensitive proteins have been thoroughly described in classical sensory systems, the effects of endogenous mechanical energy on cellular function in the brain have received less attention, and many working models in neuroscience do not currently integrate principles of cellular mechanics. An understanding of cellular-mechanical concepts is essential to allow the integration of mechanobiology into ongoing studies of brain structure and function.

Scripps Florida Scientists Reveal Key Protein Interactions Involved in Neurodegenerative Disease

Another confirmation of JNK needing more research. 

Scripps Florida Scientists Reveal Key Protein Interactions Involved in Neurodegenerative Disease

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have defined the molecular structure of an enzyme as it interacts with several proteins involved in outcomes that can influence neurodegenerative disease and insulin resistance. The enzymes in question, which play a critical role in nerve cell (neuron) survival, are among the most prized targets for drugs to treat brain disorders such as Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis (ALS).
The study was published online ahead of print on November 8, 2012, by the journal Structure.
The new study reveals the structure of a class of enzymes called c-jun-N-terminal kinases (JNK) when bound to three peptides from different protein families; JNK is an important contributor to stress-induced apoptosis (cell death), and several studies in animal models have shown that JNK inhibition protects against neurodegeneration.
“Our findings have long-range implications for drug discovery,” said TSRI Professor Philip LoGrasso, who, along with TSRI Associate Professor Kendall Nettles, led the study. “Knowing the structure of JNK bound to these proteins will allow us to make novel substrate competitive inhibitors for this enzyme with even greater specificity and hopefully less toxicity.”
The scientists used what they called structure class analysis, looking at groups of structures, which revealed subtle differences not apparent looking at them individually.
“From a structural point of view, these different proteins appear to be very similar, but the biochemistry shows that the results of their binding to JNK were very different,” he said.
LoGrasso and his colleagues were responsible for creating and solving the crystal structures of the three peptides (JIP1, SAB, and ATF-2) with JNK3 using a technique called x-ray crystallography, while Nettles handled much of the data analysis.
All three peptides have important effects, LoGrasso said, inducing two distinct inhibitory mechanisms—one where the peptide caused the activation loop to bind directly in the ATP pocket, and another with allosteric control (that is, using a location on the protein other than the active site). Because JNK signaling needs to be tightly controlled, even small changes in it can alter a cell’s fate.
“Solving the crystal structures of these three bound peptides gives us a clearer idea of how we can block each of these mechanisms related to cell death and survival,” LoGrasso said. “You have to know their structure to know how to deal with them.”
The first authors of the study, “Structural Mechanisms of Allostery and Autoinhibition in JNK Family Kinases,” which will appear in the December 5, 2012 print edition of Structure, are John D. Laughlin and Jerome C. Nwachukwu of TSRI. Other authors include Mariana Figuera-Losada and Lisa Cherry, also of TSRI.
The study was supported by the National Institutes of Health (grant number NS057153).

A Study of Fire Ant Venom Uncovers 46 Proteins with a Variety of Functions

We've got snake venom and vampire bats why not fire ants? Ask your researcher if any of these compounds would be useful in stroke rehab, neuron protection?
http://www.genomeweb.com//node/1133266?hq_e=el&hq_m=1389394&hq_l=1&hq_v=0298141c7f
Register for free access.
To get a full characterization of fire ant venom components, Palma and his colleagues combined both a two-dimensional gel electrophoresis approach and a high-performance liquid chromatography MS/MS approach. This allowed them to identify 46 proteins, some of which were not previously known to be in fire ant venom. The proteins also play a number of roles. "Some of these proteins are related to envenomating ... but half of the material, 50 percent of the proteins, present other functions," Palma says.
The 21 venom proteins identified include a number of allergens, neurotoxins, and metalloproteinases. Neurotoxins, Palma says, are primarily found in the venom of solitary hunters like scorpions or spiders, rather than social insects like fire ants — indeed, he adds that they had not been previously described in fire ant venom. Neurotoxins, he says, could lead to hallucinations or other neurological effects in affected people. And metalloproteinases break down the connective tissues between cells, possibly leading to edema.
In addition, Palma says that they uncovered proteins that gave researchers a better peek into the ants' biology. For example, the venom contains a number of proteins used for chemical communication, like pheromone transporters.
As some ants release venom, others pick it up as they walk. "That means that when the insect involved in the attack just touches the substrate where they are walking on, they can identify the presence of the pheromone already activated by the transporters," he says, adding that "this makes the stinger ants much more aggressive than they were before. … This is a kind of public relations of fire ants. The proteins make the fire ant colony much more aggressive, much more ready for a mass attack."

Discovery: Resistin Protein Causes High Levels Of LDL Cholesterol

A serious question for your doctor, and don't allow them to throw up their hands and say 'I don't know'. Send them back to study the issue and report back to you.  You are paying them for their expertise, so have them display it.
http://www.science20.com/news_articles/discovery_resistin_protein_causes_high_levels_ldl_cholesterol-95725
Researchers have discovered that the protein resistin, which is secreted by fat tissue, causes high levels of "bad" cholesterol (low-density lipoprotein or LDL), increasing the risk of heart disease.

High blood cholesterol is a major risk factor for heart disease and stroke. It can lead to a buildup of plaque in the artery walls and narrowing of the arteries, causing atherosclerosis, which can make it more difficult for blood to flow through the heart and body.

Rest at the link.

The molecular mechanisms of Nogo signaling

Another great dissertation, only 24 pages for your doctor to figure out.

The molecular mechanisms of  Nogo signaling

Summary    3
Inhibition of axon regeneration in the CNS    4
Astrocytes and the glial scar    4
Myelin associated inhibitors    4
Nogo, the principal myelin associated inhibitor    5
Nogo is a member of the RTN protein family    6
Nogo structure    6
The stucture of the Nogo RTN domain    6
Nogo-A and B specific domains    7
Membrane topology    7
Nogo receptors    8
Downstream signaling in the CNS    9
Activation of RhoA, the second messenger for cytoskeletal dynamics    9
The RhoA-ROCK pathway and its downstream effectors    10
Activation of Ca2+ and cAMP signaling pathways    11
Signal transduction downstream of Ca2+ and cAMP mediates a switch in axonal response    12
Downstream effectors of cAMP influence neurite outgrowth    12
cAMP levels control regenerative capacity after a preconditioning lesion and during maturation    13
Nogo functions in the nervous system    13
Nogo-A hampers axonal regeneration after CNS injury    13
Roles of Nogo in the developing CNS    14
Nogo regulates plasticity of the adult CNS    15
Nogo-B and C in myelin associated inhibition    15
Specific functions of Nogo-B and C    15
Discussion    17
List of Abbreviations    18
Refrences    19

Summary

Damage to the adult central nervous system often leads to permanent loss of function. Several inhibitory factors specific for the CNS prevent regeneration of severed axons and network connectivity is lost permanently. One obstacle for regenerating neurons is formed by myelin associated inhibitors; the proteins Nogo, MAG and OMgp, which are expressed by myelinating oligodendrocytes in the CNS. Of these three, Nogo is believed to be the main mediator of growth inhibition in the adult CNS. The nogo gene gives rise to three protein products, the Nogo isoforms A, B and C. Nogo-A the isoform that functions as an inhibitor for neuronal growth, during development Nogo-A is involved in axonal guidance and in the uninjured adult CNS Nogo regulates functional plasticity. Nogo-B and C are less well studied jet some specific functions are known. Signaling by Nogo-A involves multiple receptors that activate parallel cascades of downstream effectors. These signaling pathways ultimately lead to a halt in axon growth. Signaling commences when Nogo binds to one of its receptors. To date, two receptors for Nogo-A have been identified, NgR1 and co-receptors LINGO-1 and p75 or TROY, and the receptor PirB. Via these receptors, multiple signaling routes involving RhoA, cAMP and Ca²⁺ are activated. These second messengers and their downstream effectors determine growth direction and induce growth cone collapse. In vitro studies of Nogo function confirm its role as an inhibitor of neuronal growth and regeneration. However, in vivo studies of Nogo function in animals lacking one or more Nogo isoforms show inconsistent regeneration phenotypes. In contrast, treatment with function blocking anti-Nogo antibodies has profound and consistent positive effects on regeneration of the CNS and recovery of motor function. These Nogo blocking antibodies have great therapeutic potential and are currently being evaluated in clinical trials. The antibodies may soon be available to patients with CNS injuries and greatly improve their rehabilitation.

19

Myelin associated inhibitors; molecular mechanisms and therapeutic potential

A great thesis, why can't regular stroke researchers come up with novel ideas to research like this? Only 59 pages for your doctor to read and explain to you. 

Myelin associated inhibitors; molecular mechanisms and therapeutic potential

Summary
Whereas the peripheral nervous system can readily regenerate after injury, regeneration is very limited in the central nervous system of adult vertebrates. Over the past three decades, it has become clear that this lack of regeneration has a molecular basis. The myelin that provides electrical insulation of neuronal fibers has a different composition in the central nervous system, as compared to peripheral nervous system myelin. Several proteins expressed on myelin have been found to have inhibitory effects for neuronal regeneration and were dubbed myelin-associated inhibitors. The three classical myelin-associated inhibitors (Nogo, MAG and OMgp) were found to signal all three through two distinct receptor complexes, providing a puzzling redundancy for these interactions. This signaling is speculated to be important for stabilizing neuronal circuitry in healthy adult organisms. Other proteins known to be involved in axonal guidance, such as semaphorins, ephrins, netrins and Wnts, as well as extracellular matrix components such as the chondroitin sulfate proteoglycans, have also been shown to have regeneration inhibitory effects. Downstream signaling by neuronal effector proteins culminates in modulation of the cytoskeleton and transcription, explaining the morphological changes of the neurons that are observed upon signaling. The fact that the lack of regeneration has a molecular basis provides prospects for therapeutic intervention to stimulate regeneration for injuries of the central nervous system, like spinal cord injury or stroke. Indeed, a substantial body of different proteins, peptides and small molecules that intervene with the different steps involved in the inhibition of regeneration shows promising effects, both in vitro and in vivo.
This review will discuss the advances made on understanding the lack of regeneration in the central nervous system. After an introduction on the nervous system, injury and regeneration, the molecular mechanisms of inhibition will be discussed. A special focus will be on the three classical myelin associated inhibitors and their receptor complexes, but other molecules that are inhibitory for regeneration will be discussed as well. The current understanding of the downstream signaling cascades of the myelin associated inhibitors will be reviewed and finally, different strategies that demonstrate the therapeutic potential of interfering with these mechanisms will be discussed.

Table of content
Summary ................................................................................................... 2
Table of content .......................................................................................... 3
Introduction ............................................................................................... 4
Molecular Mechanisms ................................................................................. 9
Downstream Events ................................................................................... 32
Therapeutic Potential ................................................................................. 39
Conclusion and Perspectives ....................................................................... 46
List of Abbreviations .................................................................................. 47

Cannabis chemical 'helps heart' The cannabis chemical helps ward off heart disease, scientists say

This is not the smoked version. But I doubt we'll get to where this is prescribed instead of statins any time soon, Hell its been 7 years since this came out.
http://news.bbc.co.uk/2/hi/health/4417261.stm

Swiss researchers found THC, one of 60 cannabinoids in the drug, helped stop the narrowing of arteries to the brain and heart in a study of mice.
But the team, from Geneva University Hospital, said smoking cannabis did not produce the same effect.
However UK experts warned more research was needed before firm conclusions could be drawn.
Deaths
Blocked arteries - a condition known as atherosclerosis - are estimated to be responsible for up to 50% stroke and heart disease deaths in developing countries each year.
In the study, published in the Nature journal, mice were fed a high cholesterol diet to make them develop atherosclerosis and then given THC, which causes the high during cannabis use.
The Swiss researchers found THC stopped inflammation of blood vessels, which is largely responsible for blocking arteries.
The chemical worked by suppressing the immune system's response to a protein which is responsible for inflammation.

We certainly hasten to advise against people smoking cannabis to protect their heart health Professor Jeremy Pearson, of the British Heart Foundation

Lead researcher Francois Mach said while drugs such as statins which lower blood pressure and cholesterol had proved extremely effective the findings were still of "great medical interest".
And he added: "The dose [used] is lower than the dose usually associated with psychotropic effects of THC."
THC is being tested by GW Pharmaceuticals, the firm granted a UK licence to create cannabis-based drugs, in a number of treatments for pain relief and multiple sclerosis under development.
However, a study published last week in BMC Psychiatry found THC medicines could lead to psychosis.
Health
Professor Jeremy Pearson, associate medical director at the British Heart Foundation, said more work needed to be done in the area.
"Although these results, which use an oral cannabinoid in a pill form, are interesting, we look forward to further research into the area.
"We certainly hasten to advise against people smoking cannabis to protect their heart health - cannabis is usually smoked with tobacco which is highly dangerous for the heart."
And a spokeswoman for the National Heart Forum said: "This study presents interesting findings about the protective effects of active components found in marijuana and suggests scope for further investigation of these compounds."
But she added: "It does not suggest that marijuana smoking is beneficial to the heart. On the contrary, the harmful effects on the heart are well documented."

Stroke Blood Test That Could Increase Use of Most Effective Treatment Five-Fold

Demand your hospital and the Joint Commission push this out to all hospitals that treat strokes.

Start screaming bloody murder, its bad enough that tPA doesn't work that well but to not even get it to more than 5% is negligent.
 http://pharmalive.com/News/index.cfm?articleid=857787&categoryid=15
 Researchers at the University of Geneva (UNIGE), in collaboration with UK company Proteome Sciences plc (PS) describe a simple blood test that could substantially increase the number of patients eligible for highly effective ischaemic stroke therapy in a landmark paper “Blood Glutathione S-Transferase- (GSTP) as a Time Indicator of Stroke Onset”, published today in the journal PLoS ONE (http://dx.plos.org/10.1371/journal.pone.0043830).
Ischaemic stroke (which accounts for around 85% of strokes) can only be treated effectively with the ‘clot busting’ drug, rt-PA, if administered within a time window of up to 4.5 hours after symptoms start in the UK (up to 3 hours in the US). Approximately 35% of stroke victims are currently ineligible for treatment with
rt-PA as they do not know the time of onset because the stroke occurs during sleep or the onset symptoms may not have been obvious. This blood test enables doctors to determine the time window in which a stroke has occurred and could give many of these individuals access to this crucial treatment.
The University of Geneva study reports the outcome of a long-running trial of 29 blood proteins that Proteome Sciences and its partners have previously identified as early markers of brain damage associated with stroke. In particular, the authors sought to identify readily available protein markers that help establish the time of onset of the stroke as an aid to select appropriate thrombolytic treatment. This will be particularly useful in cases where patients do not know when the stroke occurred. One protein, GSTP, showed an almost instantaneous increase in the blood of stroke patients, peaking at 3 hours after onset and returning to normal levels within approximately 6 hours.
Extrapolating the results of this study retrospectively across 555 patients who were admitted to the Geneva Hospital in 2006/7 with suspected stroke, but who did not know when their stroke symptoms started, indicates that testing for GSTP on all suspected stroke victims at admission, or preferably during initial assessment during transport to the hospital, could result in as many as five times more people being eligible for the highly effective rt-PA treatment for ischaemic stroke.
Leader of the study, Prof. Jean-Charles Sanchez, said: “This is a major step towards improving the management of ischaemic stroke patients using the drugs that we already have available. A simple blood test that matches the therapeutic window of rt-PA is a major advance that we encourage clinicians, pharmaceutical and diagnostics companies to unite to rapidly bring this into routine practice to improve patient outcomes.”
Dr Peter Coleman, Deputy Director of Research at The Stroke Association said: "When a stroke strikes time lost is brain lost, meaning that getting to hospital and receiving treatment quickly is absolutely essential. At the moment, suspected stroke patients should receive a brain scan as soon as possible to confirm which type of stroke they have had and determine the best treatment for them.
"A test such as this which could be used to quickly diagnose a stroke, possibly before a patient arrives at hospital, could speed up the treatment process and potentially improve outcomes. Stroke Association welcomes new technologies that can speed up diagnosis or improve diagnostic accuracy for people with a suspected stroke."
Dr. Ian Pike, Chief Operating Officer of Proteome Sciences, noted: “With a potential five-fold increase in the number of patients having access to the most effective form of ischaemic stroke treatment, this simple blood test will most importantly make the recovery time shorter and reduce the level of resulting disability for substantial numbers of stroke victims previously ineligible for drug therapy, whilst significantly reducing the cost of long term treatment and care.
“Following our license with Randox to develop a stroke test earlier this year, we expect to complete additional licenses with both diagnostic and pharmaceutical companies to ensure the technology is developed as quickly as possible to be used as a diagnostic tool for the use of rt-PA as a treatment.”
Dr. Alan Cookson, Licensing Officer from of UNIGE’s Technology Transfer Office UNITEC, commented “This breakthrough has been made possible through effective academic-industry partnership and provides an opportunity for utilization of innovation to secure both commercial value and potentially life-changing patient care benefits.”