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Swimming devices could deliver drugs inside the body
Engineers at the University of Sheffield have discovered that tiny spherical bead-like devices can be guided by physical structures while swimming inside fluids[F1]. This opens up a wealth of future possibilities, such as using structures in the body to guide drug delivery, or cracks in rocks to direct environmental clean-up and exploration.[F2]–These devices, which are a similar size to cells and bacteria — around a hundredth of the average diameter of a strand of human hair [F3]– could be used to deliver drugs to a specific location inside the body or outside of the body to diagnose diseases in blood samples. Examples include finding proteins indicating cardiac problems or looking for circulating tumour cells that can indicate the spread of cancer.[F4]–When working with devices on a micron scale[F5], it’s very challenging to produce motion from moving parts due to the properties of the fluid — it’s similar to humans trying to run through treacle. Previous research has focused on using external magnetic fields to guide the devices, but this requires constant observation so that the device can be guided manually.–The research conducted at Sheffield uses a new method, giving the devices a catalytic coating on one side, which creates a chemical reaction when fuel molecules are added, causing the device to move automatically on a pre-determined route, using natural structures as a guide.–Dr Stephen Ebbens, Department of Chemical and Biological Engineering at Sheffield, said: “When you’re dealing with objects on such a small scale, we found that although our method of moving the devices using a coating and chemical reaction worked very effectively, it was difficult to control its direction, due to other molecules in the fluid jostling it.–“We’ve been working on ways to overcome this and control the movement of the devices along a path using physical structures to direct them. “We are now working on applications for using these devices in the body,[F6] in the shorter term focusing on using them for medical diagnosis”–In addition to medical applications, these devices could be used in other fields, such as to locate indicators of contamination in environmental samples or to deliver neutralising chemicals to areas affected by oil spills, by using crevices in rocks as the structural guide.–Story Source-The above post is reprinted from materials provided by University of Sheffield – Faculty of Engineering. Journal Reference-Sambeeta Das, Astha Garg, Andrew I. Campbell, Jonathan Howse, Ayusman Sen, Darrell Velegol, Ramin Golestanian, Stephen J. Ebbens. Boundaries can steer active Janus spheres. Nature Communications, 2015; 6: 8999 DOI: 10.1038/NCOMMS9999 -University of Sheffield – Faculty of Engineering. “Swimming devices could deliver drugs inside the body: New method of guiding microscopic swimming devices has the potential to deliver drugs to a targeted location inside the body, according to new research.” ScienceDaily. ScienceDaily, 2 December 2015. <www.sciencedaily.com/releases/2015/12/151202084346.htm>.
One in 10 globally suffer from foodborne diseases, WHO study finds
One out of every 10 people worldwide suffer from foodborne diseases annually, and children and the poor suffer most, according to the findings of a World Health Organization task force headed by a University of Florida senior researcher.–The announcement, made Wednesday, comes after more than eight years of research and data analysis by a WHO task force composed to measure the effect of foodborne diseases on populations around the globe.–“The groups most adversely affected by the foodborne diseases are children and people in low-income regions of the world,” said task-force leader Dr. Arie Havelaar with UF’s Emerging Pathogens Institute. “Of those who lost years to ill-health, disability or early death, 40 percent were children under 5 years old, even though they constitute only 9 percent of the world population[F7]. Foodborne illnesses affect people on the African continent the most, followed by sub-regions of Southeast Asia and the eastern Mediterranean.–The group will publish its research outcomes this week in a PLOS Collection (http://collections.plos.org/ferg2015). Papers on enteric diseases, parasitic pathogens, chemical and toxic hazards, and methodology will make up parts of the collection. The results are also presented in a WHO technical report.-“Estimating the burden of foodborne diseases is highly complex due to the many diseases involved,” Havelaar said. “The full extent of chemical and biological contamination of food, and its burden to society, is still unknown.”The WHO created the Foodborne Disease Burden Epidemiology Reference Group in 2007 to study global variation in the impact of foodborne disease. After considering the known disease-causing agents that can be transmitted by food, the group identified 31 hazards as the most necessary to include.–The group found that these 31 foodborne hazards caused 600 million foodborne illnesses and 420,000 deaths in 2010[F8]. Results from the study indicate that up to 33 million healthy life years are lost each year due to foodborne diseases each year [F9]– a number on par with the “big three” infectious diseases — HIV/AIDS, malaria and tuberculosis — and air pollution, but clearly lower than the burden of dietary risk factors or unimproved water and sanitation.–Diarrheal disease agents were the most frequent causes of foodborne illness — particularly norovirus and Campylobacter spp. Non-typhoidal Salmonella enterica, also a diarrheal disease agent, is capable of causing blood poisoning in people with weakened immune systems and was a major cause of death among the pathogens chosen for the study.–Other major pathogens causing foodborne disease deaths included Salmonella Typhi, a subspecies of Salmonella enterica; Taenia solium, a tapeworm that comes from pork products; and the hepatitis A virus.–Dr. Brecht Devleesschauwer, an assistant scientist at UF’s department of animal sciences, worked with Havelaar to analyze data from the study.–“We compiled information from a variety of data sources, including national surveillance systems and scientific literature, and used expert opinion and statistical modeling to fill data gaps,” Devleesschauwer explained. “In addition to disease incidence and deaths, we also quantified the disease burden in terms of Disability-Adjusted Life Years — the number of healthy years of life lost due to illness and death — to facilitate ranking between causes of disease and across regions.”–Dr. Kazuaki Miyagishima, the director of the Department of Food Safety and Zoonoses at the WHO, gave his support to the group’s analyses in a WHO statement.–“This report,” he said, “should enable governments and other stakeholders to draw public attention to this often under-estimated problem and mobilize political will and resources to combat foodborne diseases.”–In addition to his work with the Emerging Pathogens Institute, Havelaar is a core member of the Institute for Sustainable Food Systems at UF and a professor in the department of animal sciences.Story Source-The above post is reprinted from materials provided by University of Florida. The original item was written by Evan Barton. -University of Florida. “One in 10 globally suffer from foodborne diseases, WHO study finds.” ScienceDaily. ScienceDaily, 3 December 2015. <www.sciencedaily.com/releases/2015/12/151203150249.htm>.
‘Nanobombs’ might deliver agents that alter gene activity in cancer stem cells
Researchers at The Ohio State University Comprehensive Cancer Center — Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC — James) have developed nanoparticles that swe[F10]ll and burst when exposed to near-infrared laser light.–Such ‘nanobombs’ might overcome a biological barrier that has blocked development of agents that work by altering the activity — the expression — of genes in cancer cells. The agents might kill cancer cells outright or stall their growth.–The kinds of agents that change gene expression are generally forms of RNA (ribonucleic acid), and they are notoriously difficult to use as drugs. First, they are readily degraded when free in the bloodstream. In this study, packaging them in nanoparticles that target tumor cells solved that problem.–This study, published in the journal Advanced Materials, suggests that the nanobombs might also solve the second problem. When cancer cells take up ordinary nanoparticles, they often enclose them in small compartments called endosomes. This prevents the drug molecules from reaching their target, and they are soon degraded.–[F11]Along with the therapeutic agent, these nanoparticles contain a chemical that vaporizes, causing them to swell three times or more in size when exposed to near-infrared laser light. The endosomes burst, dispersing the RNA agent into the cell.–“A major challenge to using nanoparticles to deliver gene-regulating agents such as microRNAs is the inability of the nanoparticles to escape the compartments, the endosomes, that they are encased in when cells take up the particles,” says principal investigator Xiaoming (Shawn) He, PhD, associate professor of Biomedical Engineering and member of the OSUCCC — James Translational Therapeutics Program.–“We believe we’ve overcome this challenge by developing nanoparticles that include ammonium bicarbonate, a small molecule that vaporizes when exposing the nanoparticles to near-infrared laser light, causing the nanoparticle and endosome to burst, releasing the therapeutic RNA,” He explains. For their study, He and colleagues used human prostate-cancer cells and human prostate tumors in an animal model. The nanoparticles were equipped to target cancer stem-like cells (CSCs), which are cancer cells that have properties of stem cells. CSCs often resist therapy and are thought to play an important role in cancer development and recurrence.–[F12]The therapeutic agent in the nanoparticles was a form of microRNA called miR-34a. The researchers chose this molecule because it can lower the levels of a protein that is crucial for CSC survival and may be involved in chemotherapy and radiation therapy resistance.–The nanoparticles also encapsulate ammonium bicarbonate, which is a leavening agent sometimes used in baking. Near-infrared laser light, which induces vaporization of the ammonium bicarbonate, can penetrate tissue to a depth of one centimeter (nearly half an inch)[F13]. For deeper tumors, the light would be delivered using minimally invasive surgery.–Story Source-The above post is reprinted from materials provided by Ohio State University Wexner Medical Center. Journal Reference-Hai Wang, Pranay Agarwal, Shuting Zhao, Jianhua Yu, Xiongbin Lu, Xiaoming He. A Near-Infrared Laser-Activated “Nanobomb” for Breaking the Barriers to MicroRNA Delivery. Advanced Materials, 2015; DOI: 10.1002/adma.201504263
NANO BIOAGENT being militarized in Middle East to attack Civilian Population
WAR-ravaged Syria has anew enemy – a deadly flesh-eating bug caused by ISIS dumping bodies in the street.-The bug, known as Leishmaniasis, is caused by protozoan parasites.-It is usually carried by flies [F14]but experts warn that increase in rotting flesh in the street has triggered a dramatic rise.–Records suggest that 16months ago around 500 people were affected by the disease, but that is now believed to have soared.-Dil qash Isa, head of the Kurdish Red Crescent humanitarian organisation , said: ‘As a result of abominable acts by ISIS that included the killing of innocent people and dumping their corpses in streets, this is the leading factor behind the rapid spread of Leishmanisis disease.’–The World HealthOrganization has warned that Syria’s health system has collapsed under five years of war[F15], the Metro reports.–‘We did not have knowledge about this deadly disease before,’ a Syrian Kurdish fighter told news agencies. ‘We have been fighting on the battlefield for almost four years and this disease basically generated from embattled areas of Tal Hamis, Hon and Qosa,’-[F16]Britain launched air strikes against Islamic State in Syria on Thursday morning after David Cameron won backing from MPs.-British Tornado jets took off from the Royal Air Force base at Akrotiri in Cyprus before dawn, within hours of the result being announced.[F17]–The British contribution forms only a tiny part of US-led Operation Inherent Resolve, which has been bombing Islamic State in Iraq and Syria for more than a year.The vote for British forces to extend their air strikes in Iraq into Syria was won by a majority of 174.
Oligodendrocytes and Schwann cells-Repairing the Myelin Sheath
The major function of oligodendrocytes and Schwann cells is the formation of myelin. Myelin acts as an insulator of axonal segments and is a prerequisite for the high velocity of nerve conduction, of up to 200 m/second. The association of glial cells with axons is also found in invertebrates. Axon engulfing cells similar to the Remak cells of the vertebrates are found in most invertebrates. The formation of myelin by oligodendrocytes and Schwann cells are phylogenetically an invention of the vertebrates some 400 million years ago. All vertebrates except the jawless fish (hagfish and lampreys) have oligodendrocytes. The advent of myelin in evolution boosted the development of vertebrates and in particular their nervous system. Even most neuroscientists do not appreciate the importance of oligodendrocytes for the evolution of vertebrates. While it seems to be general knowledge that with the evolutionary development of the brain the number of neurons increases to up to 100 billion in human, it is not so evident that only due to myelin all these neurones can be interconnected in a complex fashion. This can be easily illustrated by the following example. To increase the speed of nerve conduction one strategy is to form myelin, the other to increase the diameter of the axon. The giant axons in squid have a diameter of up to 1 mm and reach conduction velocities comparable to that of myelinated motor axons. The human optic nerve has about 1 million myelinated axons which conduct with a high speed. A squid giant axon version with 1 million axons of 1 mm in diameter would amount to an axon diameter of 0.75 m. Taken into consideration that the human brain consists of up to 50% white matter it is evident that the high connectivity of the human brain would be impossible without the formation of myelin.[F18]
Morphology of oligodendrocytes
All white matter tracts contain oligodendrocytes to form myelin. Oligodendrocytes are, however, also found in gray matter. While oligodendrocytes are very well known as the myelin forming cells of the central nervous system there are also oligodendrocytes that are not directly connected to the myelin sheath. These satellite oligodendrocytes are preferentially found in gray matter and have so far unknown functions possibly serving to regulate ionic homeostasis similarly to astrocytes. Only the retina of rat, mouse and human is devoid of myelinating oligodendrocytes, the rabbit and chick retina are both partially myelinated. The myelin forming oligodendrocytes have several processes (up to 40) which connect to one myelin segment. Each of these segments is several hundred micrometers long and is also termed the internode. Segments are interrupted by structures known as node of Ranvier which spans for less than 1 micron. At the node, as compared to the internodal region, the axon is not enwrapped by myelin. The end of intermodal segment contains more cytoplasm[F19] and forms so called paranodal loop creating septate—like junctions with the axon. In addition, astrocyte processes contact the axonal membrane at the nodal region.–Like astrocytes oligodendrocytes are also interconnected by gap junctions formed by connexins. There are distinct connexin proteins for oligodendrocytes as compared to astrocytes. Mutations in the connexin proteins lead to hypomyelination and to human pathologies such as leucodystrophies.
Development of oligodendrocytes
Myelin formation starts in rodents at about birth and is completed around 2 months after birth. In humans it starts during the second half of fetal life and begins in the spinal cord. Its peak activity is in the first year postnatally while it continues up to 20 years of age. It is generally noted that larger axons form thicker myelin. During development oligodendrocytes arise from precursors located in the subventricular zone such as the subventricular zone of the lateral ventricles for the cerebrum or the fourth ventricle for the cerebellum. In the spinal cord, oligodendrocytes originate from the ventral regions of the neural tube and in the optic nerve they migrate into the nerve from the third ventricle. It is the oligodendrocyte precursor cells which migrate to their destination where they then differentiate into the more mature oligodendrocytes. The proliferation of the oligodendrocyte progenitor cells is controlled by a number of growth factors released predominantly from neurons but also from astrocytes such as platelet derived growth factor (PDGF) or fibroblast growth factor (FGF). [F20]Moreover, an intrinsic clock seems to not only count cell division, but also senses time. Thus intrinsic mechanisms and the environment control the proper amount of oligodendrocytes required for myelination. Oligodendrocytes produced in excess (which occurs under normal conditions) are eliminated by apoptosis.–Oligodendrocyte progenitor cells, which can still give rise to astrocytes and oligodendrocytes are not only found during development but also exist in the mature brain being termed adult oligodendrocyte precursor cells. They are considered as a source for remyelination in demyelinating diseases such as multiple sclerosis. There are a number of distinct markers which help to identify these precursor cells such as the transcription factor Olig-2 or the proteoglycane NG2. These NG2 positive cells have recently attracted considerable attention. While they have the capacity to develop into astrocytes and oligodendrocytes, the main route seems to be confined to the oligodendrocyte lineage. These adult precursor cells seem to interact with axons. They express glutamate receptors and sense the activity of the axon, which releases glutamate in an activity dependent fashion. This seems to be a potential mechanism for how axons might control the differentiation of oligodendrocyte progenitor cells.
Schwann cells are the cellular counterparts to oligodendrocytes in the peripheral nervous system. Similarly to oligodendrocytes they form the myelin sheath. In contrast to the oligodendrocyte each Schwann cell is associated with only one axonal segment. While the myelin structure formed by oligodendrocytes and Schwann cells has a similar ultrastructure, it is not composed of an identical set of proteins. While central and peripheral myelin share the basic protein myelin, the peripheral nervous system lacks myelin associated glycoprotein or proteolipid protein[F21], but expresses the protein P0 and PMP22. During development, Schwann cells are derived from undifferentiated migrating neural crest cells. The immature Schwann cells produce either myelinating or non-myelinating Schwann cells. The latter loosely enwraps several axons without forming myelin.–Neuronal cell bodies in sensory sympathetic and parasympathetic ganglia are surrounded by flattened sheath like cells known as satellite cells. The axon terminals at a neuromuscular junction are also covered by specialized glial cells, namely the terminal glia.
The myelin sheaths
The myelin sheath is formed by an enwrappment of the axon by oligodendrocyte or Schwann cell processes. The intracellular compartment is very much compressed spanning only 30 Angström and appears in the electron microscope as a single line, called the major dense line. The outer surface of the lipid bilayer appears as a distinct line separated by the extracellular space. Therefore, this is defined as the double intraperiod line. Due to this immense compaction, myelin is purely hydrated and its dry mass contains about 70% lipids and 30% proteins.[F22] There are a number of highly specific proteins which are only found in myelin and are necessary for the formation of this structure. The major proteins of the central nervous system myelin are myelin associated glycoprotein[F23] (MAG), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), proteolipidprotein (PLP)/DM20 and PMP22. These proteins are exclusively produced by myelin-forming cells, namely oligodendrocytes in the central nervous system or by Schwann cells in the peripheral nervous system and thus serve as excellent markers for myelinating cells. Within the myelin layers, are kind of pathway which contain a cytoplasmic spacing named the Schmidt-Lantermann incisures. These provide trophic support for myelin.
Not all vertebrate axons are myelinated, but in general, axons larger than 1 micron are myelinated. Recent studies show that the axons provide a signal to the oligodendrocyte which determine the thickness of the myelin sheath. One important signaling mechanism provided by the axon is via the growth factor neuregulin-1 which binds to ErbB receptor tyrosine kinases expressed by oligodendrocytes. A similar signaling mechanism also exists in Schwann cells. This interaction leads to a defined ratio between axonal diameter and axonal diameter plus myelin sheath, the so-called g-ratio which is usually between 0.6 to 0.7 .—It has long been speculated that myelinating cells do provide metabolic support to the axons. It can be speculated that glia derived glycolytic products such as pyruvate or lactate are released and taken up by the axon. This may be even more important for the peripheral nervous system since metabolites from the soma would have to be transported for distances of more than a meter in large animals.
Myelin enables saltatory nerve conduction
The node of Ranvier contains a high density of sodium channels, which allows what is known as saltatory conduction (from the latin word ´saltare´ which means ‘to jump’), namely the generation of action potentials only at the node. Thus the action potential is only triggered at the node, then spreads passively, and thus rapidly to the next node where the next action potential is generated. So the action potential jumps from node to node. This is not only faster, but consumes much less energy, since sodium ions accumulate only at the node and there need only to be transported back to the extracellular space due to the activity of the Na+/K+-ATPase[F24]. Before myelin formation the sodium channels are randomly distributed along the length of the axon. However, at the time of the glial ensheathment, sodium channels start to form loose clusters at the site, which later become the node of Ranvier. Subsequently, after formation of compact myelin, sodium channels disappear from the membrane underneath the myelin sheath and cluster only at the node. This clustering is promoted by protein interactions between the myelinating cell membrane and the axonal membrane involving cell adhesion molecules like gliomedin, neurofascin and NCAM. K+ channels are less stringently concentrated in the nodal region.
Myelinating cells and diseases
The most frequent disease involving oligodendrocytes is multiple sclerosis. It is caused by a loss of myelin in defined areas of brain and spinal cord and thus leads to an impairment of axonal conductance. Recovery can occur due to re-myelination but often relapses occur which lead to continuous neurodegeneration. The primary cause for the loss of oligodendrocytes is as yet unknown. It is evident that the demyelinated region contains inflammatory cells such as infiltrating lymphocytes and macrophages and activated microglia. These cells might potentiate or even initiate the damage cascade. Other inherited myelin disorders of the central nervous system are Pelizaeus-Merzbacher disease and Pelizaeus-Merzbacher-like diseases and other forms of leukodystrophies. Most of the genetically determined pathologies are associated with mutations in myelin proteins or connexins, the molecular entities forming gap junctions. Similarly to the central nervous system mutations in Schwann cell myelin or gap junction proteins lead to neuropathies such as the Charcot–Marie–Tooth disease. This makes it evident that peripheral myelin formation is also essential for the survival of vertebrates.
Growing stem cells faster on seaweed
Alginate forms a kind of supporting skeleton in the cell walls of certain kinds of algae. Fraunhofer scientists use the gel-like mass from Chilean seaweed as the substrate for stem cells. They can flexibly adjust the pore size and elasticity of the alginate, and it transports active ingredients and has better optical characteristics than plastic materials.-For the drug tests of the future, the pharma industry needs large quantities of pluripotent stem cells. These stem cells have the potential to transform themselves into any kind of somatic cell, such as the cells of inner organs. Many thousands of stem cell lines from a huge variety of patients are currently being built up in biobanks, where doctors can access perfect models of the genetic illnesses of these patients. Using these stem cells, doctors and pharmaceutical companies can test new drugs better and more quickly than before.-Scientists at the Fraunhofer Institute for Biomedical Engineering IBMT in Sulzbach have identified seaweed from Chile as a particularly efficient source of nutrients for the expansion of pluripotent stem cells. Over the past few years, they have developed a controlled and documented production process for alginate, the seaweed’s supporting structure. The process encompasses everything from harvesting the seaweed on Chilean beaches and in the seas off Chile, to importing the granulated and dried seaweed, to manufacturing the alginate and using it in cell culture to grow pluripotent stem cells at the institute in Saarland. British pharma companies are currently validating the process in their laboratories. “The first concrete trials with partners from the European Federation of Pharmaceutical Industries and Associations (EFPIA) are planned for next year,” says Prof. Heiko Zimmermann, Managing Head of Fraunhofer IBMT. “The goal is to demonstrate that we can use the process to produce stable pluripotent stem cells. At the institute, we’ve already managed to do just that for many individual stem cell lines.” The Fraunhofer scientists at Sulzbach developed the production process and the technology platform jointly with their colleagues in Chile and the United Kingdom.
Alginate from two Chilean seaweed types particularly suitable
Two seaweed species that grow on the coast of Chile form the source material: Lessonia trabeculata and Lessonia nigrescens. Supporting structures in the cell walls of the seaweed are made of alginate, which is particularly suitable for stem cell cultivation: it consists of a highly aqueous gel that is more viscous than honey. When cross-linked with calcium or barium, it is both stable and flexible — like the jello you find in your dessert bowl — and also permeable for nutrients and important factors. “Cells feel especially at home in elastic 3D environments such as are found inside the body. It’s precisely this environment that can be simulated perfectly using alginate,” explains Prof. Zimmermann. This is an ideal environment particularly for heart muscle cells, which contract regularly. The scientists flexibly set the elasticity through the mixture of seaweed species and produce the alginate in beads of any size. “After all, different cells need different culture conditions,” says Prof. Zimmermann. “We also introduce active ingredients into the alginate and release them in a controlled manner.” Examples of such ingredients are substances that transform pluripotent stem cells into certain somatic cells. “In the future,” continues Prof. Zimmermann, “the alginate will not only act as a passive substrate, but will also actively influence the growth of the stem cells.” The absence of autofluorescence in the elastic biomass is a further advantage and is important for optical analysis techniques. “The stem cells grow better on our alginate — and particularly well in automated bioreactors. They differentiate better into the desired somatic cells than on the plastic substrates generally used today,” says Prof. Zimmermann.–Harvesting the seaweed is subject to rigorous controls: there are special licenses for Chilean fishers, who harvest only the seaweed that is suitable for manufacturing the alginate, and only as much as permits sustainable resource management on the Chilean coast. In a laboratory operated by IBMT and Fraunhofer Chile at UCN University in Coquimbo, the seaweed is individually peeled, shredded, and completely dried. This is all done within 24 hours to prevent the material from becoming contaminated. The seaweed granulate is then exported to Germany, where IBMT scientists separate out the alginate in the institute’s clean room. After this process, it is available in liquid form and can be shaped into beads using a strong jet of air. “The beads are rendered more stable in a barium bath, as barium tends to remain in the seaweed mass. The trick is to make the material stable, but not too hard,” says Prof. Zimmermann.–The researchers place the protein-coated alginate into a bioreactor, which provides the optimum temperature and CO2 environment and continuously stirs the nutrients and cells. Measuring around 200 micrometers, each individual alginate bead performs the role of a Petri dish. The stem cells grow over the alginate in the containers in three to seven days, propagating as they do so. “Because the alginate volumes in the reactors can be increased slightly, we can grow pluripotent stem cells in greater quantities and in smaller spaces,” says Prof. Zimmermann.-Story Source-The above post is reprinted from materials provided by Fraunhofer-Gesellschaft–Fraunhofer-Gesellschaft. “Growing stem cells faster on seaweed.” ScienceDaily. ScienceDaily, 1 December 2015. <www.sciencedaily.com/releases/2015/12/151201094116.htm>.
Also known as- Algin; Algin Gum
Derived from- Alginic Acid (also known as- Polymannuronic Acid; Norgine)
Alginates are a group of Polysaccharides comprised of salts of Alginic Acid which is a Polysaccharide [F25]of Mannuronic Acid and Guluronic Acid.
Health Benefits of Alginates
Alginates may dilute potential carcinogens in the Intestine (thereby reducing the risk of Cancer): [more info]
Alginates may bind to Bile Acids in the Small Intestine and may enhance their elimination.
Alginates may inhibit the absorption of dietary Cholesterol. references
Calcium Alginate (applied topically) may alleviate Decubitus Ulcers (bed sores).
Alginates may Counteract these Toxic Substances
Alginates may inhibit the absorption of dietary Glucose. references
Alginates may facilitate the excretion of many Detrimental Minerals (toxic heavy metals) by binding to them in the Intestinal Tract and preventing their absorption: references
– Barium references
– Cadmium [more info]
– Lead references
– Radium [more info]
– Strontium (including Radioactive Strontium-90) references
Dietary Sources of Alginates
Algae (Sea Vegetables)
Alginates are present in many types of Brown Algae used as Sea Vegetables, including Bladderwrack, Kelp and Pacific Brown Kelp.
Potentially dangerous molecules detected in e-cigarette aerosols
Electronic cigarettes produce highly-reactive free radicals — molecules associated with cell damage and cancer — and may pose a health risk to users, according to researchers at Penn State College of Medicine.–The use of e-cigarettes is on the rise. According to the Centers for Disease Control and Prevention, more than 20 percent of young adults have tried e-cigarettes, and current smokers and recent former smokers are most likely to have used them.–E-cigarettes deliver nicotine in water vapor instead of by burning tobacco. The battery-operated devices have been marketed as an alternative to traditional cigarettes.–Despite their growing popularity, very little is known about toxic substances produced by e-cigarettes and their health effects.–“There’s a perception that e-cigarettes are healthier than regular cigarettes, or at least not as harmful as regular cigarettes,” said John P. Richie Jr., professor of public health sciences and pharmacology. “While e-cigarette vapor does not contain many of the toxic substances that are known to be present in cigarette smoke, it’s still important for us to figure out and to minimize the potential dangers that are associated with e-cigarettes.”–Previous studies have found low levels of aldehydes, chemical compounds that can cause oxidative stress and cell damage, in e-cigarette “smoke.” But until now, no one has looked for free radicals, the main source of oxidative stress from cigarette smoke. Highly reactive free radicals are a leading culprit in smoking-related cancer, cardiovascular disease and chronic obstructive pulmonary disease.–Instead of smoke, e-cigarettes produce aerosols, tiny liquid particles suspended in a puff of air. The researchers measured free radicals in e-cigarette aerosols.–They found that e-cigarettes produce high levels of highly reactive free radicals that fall in the range of 1,000- to 100-times less than levels in regular cigarettes.–“This is the first study that demonstrates the fact that we have these highly reactive agents in e-cigarette aerosols,” Richie said. Results were published in the journal Chemical Research in Toxicology.–“The levels of radicals that we’re seeing are more than what you might get from a heavily air-polluted area but less than what you might find in cigarette smoke,” Richie said. The radicals are produced when the device’s heating coil heats the nicotine solution to very high temperatures.–Further research is needed to determine the health effects of highly reactive free radicals from e-cigarettes.–“This is the first step,” Richie said. “The identification of these radicals in the aerosols means that we can’t just say e-cigarettes are safe because they don’t contain tobacco. They are potentially harmful. Now we have to find out what the harmful effects are.”–Richie is currently conducting studies to carefully measure total numbers of free radicals in e-cigarette aerosols and to identify their chemical structures.–“That will help us interpret the data better to know how dangerous they are,” he said.-Story Source-The above post is reprinted from materials provided by Penn State Milton S. Hershey Medical Center. The original item was written by Scott Gilbert. -Journal Reference-Reema Goel, Erwann Durand, Neil Trushin, Bogdan Prokopczyk, Jonathan Foulds, Ryan J. Elias, John P. Richie. Highly Reactive Free Radicals in Electronic Cigarette Aerosols. Chemical Research in Toxicology, 2015; 28 (9): 1675 DOI: 10.1021/acs.chemrestox.5b00220
Penn State Milton S. Hershey Medical Center. “Potentially dangerous molecules detected in e-cigarette aerosols.” ScienceDaily. ScienceDaily, 2 December 2015. <www.sciencedaily.com/releases/2015/12/151202095435.htm>.
E-cigarette vapors, flavorings, trigger lung cell stress
Do electronic cigarettes help people quit smoking? As the debate continues on that point, a new University of Rochester study suggests that e-cigarettes are likely a toxic replacement for tobacco products.—Emissions from e-cigarette aerosols and flavorings damage lung cells by creating harmful free radicals and inflammation in lung tissue, according to the UR study published in the journal PLOS ONE. Irfan Rahman, Ph.D., professor of Environmental Medicine at the UR School of Medicine and Dentistry, led the research, which adds to a growing body of scientific data that points to dangers of e-cigarettes and vaping.–The investigation suggests the harm begins when the e-cigarette’s heating element is activated. The heating element is designed to turn a liquid solution (known as an e-liquid or “juice”) into an aerosol that mimics cigarette smoke. The inhaled vapors contain heavy metals and other possible carcinogens in the form of nanoparticles[F26] — tiny particulate matter that can reach farther into lung tissue, cell systems, and blood stream.[F27]–Rahman’s study also shows that some flavored e-juices (particularly cinnamon) create more stress and toxicity on lung tissue. Researchers observed in the laboratory that human lung cells exposed to e-cigarette aerosols released various inflammation biomarkers. Mice exposed to e-cigarettes with classic tobacco flavoring also demonstrated signs of pulmonary inflammation.—“Several leading medical groups, organizations, and scientists are concerned about the lack of restrictions and regulations for e-cigarettes,” Rahman said. “Our research affirms that e-cigarettes may pose significant health risks and should be investigated further. It seems that every day a new e-cigarette product is launched without knowing the harmful health effects of these products.”–Rahman’s laboratory also recently reported in the journal Environmental Pollution that toxic metals and oxidants from e-cigarettes raise safety concerns as well as potential pollution hazards from second-hand exposures and disposal of e-cigarette waste. Another recent study connected e-cigarette vapors to a higher risk of respiratory infections in young people.–In a joint statement issued January 8, 2015, the two leading cancer organizations in the United States — the American Association for Cancer Research and American Society for Clinical Oncology — said that e-cigarettes should be subject to the same Food and Drug Administration (FDA) restrictions as tobacco until more is known about possible adverse health effects. Insufficient data also exists on the value of the tool for smoking cessation.
The biggest concern is for e-cigarette users under age 18. Health experts believe e-cigarettes entice some young people to start smoking and will make it socially acceptable again. Manufacturers contend it’s a safer alternative to cigarettes, and consumers have pushed sales in the U.S. beyond $1 billion.–A trend known as “dripping” allows e-cig users to drip an e-liquid directly onto the cigarette’s heating element instead of using a refillable chamber to hold the e-liquids. The smoker inhales the aerosols and gets a stronger hit, while also being able to more easily switch between flavors, brands or nicotine content. The UR study found that dripping e-liquids or e-juices to produce vapors likely generates a larger dose of toxins to the lungs.–Rahman’s study notes that manufacturers typically don’t disclose all materials and chemicals used to make e-cigarettes and e-juices. Without that information or long-term use studies, consumers have limited information about the potential dangers for human health and the environment, he said.–Story Source-The above post is reprinted from materials provided by University of Rochester Medical Center. Journal Reference-Chad A. Lerner, Isaac K. Sundar, Hongwei Yao, Janice Gerloff, Deborah J. Ossip, Scott McIntosh, Risa Robinson, Irfan Rahman. Vapors Produced by Electronic Cigarettes and E-Juices with Flavorings Induce Toxicity, Oxidative Stress, and Inflammatory Response in Lung Epithelial Cells and in Mouse Lung. PLOS ONE, 2015; 10 (2): e0116732 DOI: 10.1371/journal.pone.0116732 —University of Rochester Medical Center. “E-cigarette vapors, flavorings, trigger lung cell stress.” ScienceDaily. ScienceDaily, 6 February 2015. <www.sciencedaily.com/releases/2015/02/150206174840.htm>.
Electronic cigarette flavorings alter lung function at the cellular level
Certain flavorings used in electronic cigarette liquid may alter important cellular functions in lung tissue, according to new research presented at the 2015 American Thoracic Society International Conference. These changes in cell viability, cell proliferation, and calcium signaling are flavor-dependent. Coupling these results with chemicals identified in each flavor could prove useful in identifying flavors or chemical constituents that produce adverse effects in users.–“The effects of the various chemical components of e-cigarette vapor on lung tissue are largely unknown,” said lead author Temperance Rowell, a graduate student in the Cell Biology and Physiology Department of the University of North Carolina at Chapel Hill. “In our study using human lung epithelial cells, a number of cell viability and toxicity parameters pointed to 5 of 13 flavors tested showing overall adverse effects to cells in a dose-dependent manner.”–In the study, cultured human airway epithelial cells were exposed to various doses of the 13 e-cigarette liquid flavors for 30 minutes or 24 hours. During the 30 minute exposure test, the flavors Hot Cinnamon Candies, Banana Pudding (Southern Style), and Menthol Tobacco elicited a dose-dependent calcium response and were toxic to the cells at higher doses.
During the 24 hour exposure test, these same three favors decreased cell proliferation and cell viability in a dose-dependent manner.–The toxic effects of these flavorings were not seen with either nicotine or the e-liquid vehicle, which consisted of propylene glycol and vegetable glycerin. Additional experiments testing the aerosolized product of e-liquid flavors on cultured primary human bronchial epithelial cells are ongoing. Flavors being tested were selected from the findings in this study.–“The specific chemical components underlying the toxic effects of these e-cigarette flavors on cell viability, proliferation, and calcium signaling in airway epithelia are undergoing further study in our lab,” said Ms. Rowell. “Given the increasing popularity of flavored e-cigarettes, a better understanding of their ingredients, the potential health risks of these ingredients, and the causes of these risks is urgently needed.”–Story Source-The above post is reprinted from materials provided by American Thoracic Society (ATS). –American Thoracic Society (ATS). “Electronic cigarette flavorings alter lung function at the cellular level.” ScienceDaily. ScienceDaily, 17 May 2015. <www.sciencedaily.com/releases/2015/05/150517143352.htm>.
[F1]Another name for these are quantum dots which are a cluster of nano crystals that form clusters and look like dots due to the volume of crystals
[F2]I always Like how there is always a benefit to a technology that has serious safety issues or serious health issues for the general public and as a general public duped into thinking and accepting this as a good thing
[F3]Back to nano tech and the smallness of the technologyis supposed to convey because it is small has no issues
[F4]Here I thought this is what a normal functioning immune system does allocates problems and sends out signals to correct~ this sounds like something to replace the normal functions of what occurs as part of the human biology
[F5]This is not nano unless the numbers of micron is 1 micron = 1000nanometers another name is a millicron or 1/1000 = nano
[F6]We will now have a robotech to enter into the body which they themselves say they have a hard time navigating which would also imply a inability to retract the technology which also implies it could be lost in the body and embed
[F7]Would mean the investigation should be determining what foods are being consumed and what genetics are in those foods and nano and other adulterants or even biological agents such as glyphosates and other plant fumicides that may penetrate the tissues and not be able to be washed off due to there integration into the tissues of the plants
[F8]Would call this a weaponizing of food~ look at the sophistication of this 31 food borne hazards effect 600million food born illness this is an incredible weapon ~ no one would suspect and everyone would be impacted
[F9]This sound a lot like cancer ~ this is about the same statistic in regard to what happens when treated for cancer you usually lose about 30-40 years of your life
[F10]The question arises then wat if they don’t ~ or what happens when an explosion as a result of a infrared light should cause an unwanted release where do these particles go and how much is buried in healthy tissues and how much is actually retrieved
[F11]Would appear cancer has been able to negate nano tech by binding with the tech and to stop if from running it’s designed program
[F12]In other words cancer cured but the causative factors can return it –just like a cold validating that cancers are curable just with the right conditions can be returned giving one a false impression that you can only go into remission not cure
[F13]A possible method to deal with topical skin cancers and with a green laser which breaks down grapheme may assist with this as well
[F14]Middle East would have a high heat range and flies would seek a cooler environment~ what is seen on this child’s face is a nanobiological agent that is being tested on this culture –in other words they are weaponizing nano tech as a means of exterminating and eliminating all traces of a culture or species
[F15]Interesting in other words nothing there to potentially remove or treat these people and at the accelerating of the effects of nano weaponary there cultural termination is going to be accelerated
[F16]Where it was released
[F17]Seems a tad coincidental ~ and I do not believe in coincidences- that all of a sudden militaries from all over Europe and Russia and possibly china are now voluntarily going there this would be a disaster for any soldier on any front to be exposed to this or they would be eliminated
[F18]Important to sustain healthy myeling throughout the body especially brain and CNS and Vertebrate
[F19]Cytoplasm- Cytoplasm has three basic functions within the cells of living organisms. Made of three basic components, cytoplasm is a medium of suspension for the organelles in the cell. The function of cytoplasm is also a means of transport for genetic material and the products of cellular respiration. As cytoplasm is a fluid, it acts as a buffer, protecting the cell’s genetic material and organelles from damage due to movement or collision with other cells.
[F20]Growth Factors area or origin and the different types of growth factors
[F21]These are building blocks of myelin fat and protein or shuar and protein
[F22]Composition of Myelin with fat and protein
[F23]Compostion of Myelin with sugar and protein
[F24]Salt is required to stimulate the Jumping action or the conductivity action between the nodes to transfer signals
[F25]Health Benefits of Polysaccharides (Generally)
Note that each individual type of Polysaccharide possesses specific potential health benefits.
Polysaccharides are claimed to be the body’s best source of Carbohydrate-derived Energy:
– Polysaccharides are slowly reverted back to Monosaccharides within the body, eventually forming Glucose which is then oxidized (burned for Energy) at the same rate at which it is produced.
– Polysaccharides are also involved in the production of Energy through the production of Volatile Saturated Fatty Acids (including Acetic Acid, Butyric Acid and Propionic Acid) from fermenting Polysaccharides within the Large Intestine.
These Substances may Enhance the Function of Polysaccharides
Amylase enables Polysaccharides to be split into shorter-chain length units of Dextrin in the mouth before further processing in the Pancreas by Pancreatic Amylase.
Beneficial Bacteria in the Large Intestine cause the fermentation of Polysaccharides which results in the endogenous manufacture of Volatile Saturated Fatty Acids.
[F26]e-cigarette smoke contains the toxic element chromium, absent from traditional cigarettes, as well as nickel at levels four times higher than normal cigarettes. In addition, several other toxic metals such as lead and zinc were also found in secondhand e-cigarette smoke
Read more at http://scienceblog.com/74132/e-cigarette-smoke-found-contain-toxic-metals/#2kiomd3E94PBQ6th.99
[F27]The particulate must be in either micron or nano in size to be able to cause issue ~ and if the element is heating this then as it gets drawn in by the smoker the pollutants then would be more concentrated or more altered due to the chemical mix and the heat
Show of the Month December 12 2015
Nanomaterials appearing in water run-off from surface treatments
Nanoparticles from dietary supplement drinks likely to reach environment- Potentially harmful substances
Shaking the nanomaterials out- New method to purify contaminated water
Heat radiates 10,000 times faster at the nanoscale
Mathematicians identify limits to heat flow at the nanoscale
Nanomaterials appearing in water run-off from surface treatments
Researchers at TECNALIA recently published a study in the science journal, Applied Catalysis B: Environmental, which reveals the emission of nanomaterials caused by water runoff on surfaces containing nanomaterials. These surface treatments are employed in numerous consumption and construction products, so evidences of the presence of engineered nanomaterials are beginning to appear in the environment. Concerns about their toxicity for human or the environment rose in the last years, so further studies are required.The results indicate that all the surface treatments analyzed in this work suffered from a loss of nanomaterials and properties in the surface treatments. That is why TECNALIA has created a highly specialized technological service which can be adapted to the needs of any company dedicated to surface treatment with nanomaterials who wish to optimize the development of their products, acquiring specific knowledge about the behavior of their products under real operational conditions and/or estimate the loss of functionality and emissions of nanomaterials to the environment[F28]. –The research entitled “Aging of photocatalytic coatings under a water flow: Long run performance and TiO2 nanoparticles release” focuses on one of the most successful applications of nanomaterials: photocatalytic surface treatments with titanium dioxide nanoparticles.
Water and air—These nanoparticles, when illuminated with ultraviolet light,[F29] are capable of degrading organic material present, including contaminants which can be found in water and air. Thanks to this property and the hydrophobicity which these surface treatments provide the surfaces, they are often applied to certain paints, decontaminant pavements or, still in the experimental stage, water and air treatment systems.-Story Source-The above post is reprinted from materials provided by Basque Research. -Journal Reference-Josune Olabarrieta, Saioa Zorita, Iratxe Peña, Nerea Rioja, Oihane Monzón, Pablo Benguria, Lorette Scifo. Aging of photocatalytic coatings under a water flow: Long run performance and TiO2 nanoparticles release. Applied Catalysis B: Environmental, 2012; 123-124: 182 DOI: 10.1016/j.apcatb.2012.04.027 –Basque Research. “Nanomaterials appearing in water run-off from surface treatments.” ScienceDaily. ScienceDaily, 19 September 2012. <www.sciencedaily.com/releases/2012/09/120919103319.htm>.
Nanoparticles from dietary supplement drinks likely to reach environment- Potentially harmful substances
Nanoparticles are becoming ubiquitous in food packaging, personal care products and are even being added to food directly. But the health and environmental effects of these tiny additives have remained largely unknown. A new study now suggests that nanomaterials in food and drinks could interfere with digestive cells and lead to the release of the potentially harmful substances to the environment. The report on dietary supplement drinks containing nanoparticles was published in the journal ACS Sustainable Chemistry & Engineering.–Robert Reed and colleagues note that food and drink manufacturers use nanoparticles in and on their products for many reasons. In packaging, they can provide strength, control how much air gets in and out, and keep unwanted microbes at bay. As additives to food and drinks, they can prevent caking, deliver nutrients and prevent bacterial growth. [F30]But as nanoparticles increase in use, so do concerns over their health and environmental effects. Consumers might absorb some of these materials through their skin, and inhale and ingest them. What doesn’t get digested is passed in urine and feces to the sewage system[F31]. A handful of initial studies on nanomaterials suggest that they could be harmful, but Reed’s team wanted to take a closer look.–They tested the effects of eight commercial drinks containing nano-size metal or metal-like particles on human intestinal cells in the lab. The drinks changed the normal organization and decreased the number of microvilli, finger-like projections on the cells that help digest food. In humans, if such an effect occurs as the drinks pass through the gastrointestinal tract, these materials could lead to poor digestion or diarrhea, they say. The researchers’ analysis of sewage waste containing these particles suggests that much of the nanomaterials from these products are likely making their way back into surface water, where they could potentially cause health problems for aquatic life.–The authors acknowledge funding from the National Science Foundation.–Story Source-The above post is reprinted from materials provided by American Chemical Society. -Journal Reference-Robert B. Reed, James J. Faust, Yu Yang, Kyle Doudrick, David G. Capco, Kiril Hristovski, Paul Westerhoff. Characterization of Nanomaterials in Metal Colloid-Containing Dietary Supplement Drinks and Assessment of Their Potential Interactions after Ingestion. ACS Sustainable Chemistry & Engineering, 2014; 140611140653009 DOI: 10.1021/sc500108m -American Chemical Society. “Nanoparticles from dietary supplement drinks likely to reach environment: Potentially harmful substances.” ScienceDaily. ScienceDaily, 18 June 2014. <www.sciencedaily.com/releases/2014/06/140618122305.htm>.
Shaking the nanomaterials out- New method to purify contaminated water
Purifying water and greening nanotechnology could be as simple as shaking a vial of water and oil. At least that’s the case for a new method to clean contaminated water full of unwanted nanomaterials.–Nano implies small–and that’s great for use in medical devices, beauty products and smartphones–but it’s also a problem. The tiny nanoparticles, nanowires, nanotubes and other nanomaterials that make up our technology eventually find their way into water. The Environmental Protection Agency says more 1,600 commercial products use some kind of nanomaterial. And we just don’t know the full impact on health and the environment.–“These materials are very, very tiny and that means if you try to remove them and clean them out of contaminated water, that it’s quite difficult,” says Dongyan Zhang, a research scientist at Michigan Technological University. She adds that techniques like filter paper or meshes often don’t work.–Instead, shaking up oil and water traps the nanomaterials, which can be easily removed. The process clears out nearly 100 percent of nanowires, nanosheets, nanotubes and other one- and two-dimensional nanomaterials[F32]. Only zero-dimensional nanospheres are still too small to grab.–The study came out recently in the American Chemical Society’s journal Applied Materials and Interfaces.–Story Source-The above post is reprinted from materials provided by Michigan Technological University-Journal Reference-Bishnu Tiwari, Dongyan Zhang, Dustin Winslow, Chee Huei Lee, Boyi Hao, Yoke Khin Yap. A Simple and Universal Technique To Extract One- and Two-Dimensional Nanomaterials from Contaminated Water. ACS Applied Materials & Interfaces, 2015; 7 (47): 26108 DOI: 10.1021/acsami.5b07542 -Michigan Technological University. “Shaking the nanomaterials out: New method to purify contaminated water.” ScienceDaily. ScienceDaily, 10 December 2015. <www.sciencedaily.com/releases/2015/12/151210140521.htm>.
Recipe to get out nano in fruits that are saturated—juice these fruits first then mix small portions in oil and then blend them for a few minutes then filter by applying the liquids to a sponge and then wring out the sponge~ this should trap the bulk of the oil and capture the nano in the sponge as well
Heat radiates 10,000 times faster at the nanoscale
Summary-When heat travels between two objects that aren’t touching, it flows differently at the smallest scales — distances on the order of the diameter of DNA, or 1/50,000 of a human hair. —While researchers have been aware of this for decades, they haven’t understood the process. Heat flow often needs to be prevented or harnessed and the lack of an accurate way to predict it represents a bottleneck in nanotechnology development.-Now, in a unique ultra-low vibration lab at the University of Michigan, engineers have measured how heat radiates from one surface to another in a vacuum at distances down to 2 nanometers.–While the thermal energy still flows from the warmer place to the colder one, the researchers found it does so 10,000 times faster than it would at the scale of, say, a bonfire and a pair of chilly hands. “Faster” here refers to the speed at which the temperature of one sample changes the temperature of the other–and not the speed at which the heat itself travels. Heat is a form of electromagnetic radiation, so it moves at the speed of light. What’s different at the nanoscale is the efficiency of the process.-“We’ve shown, for the first time, the dramatic enhancements of radiative heat fluxes in the extreme near-field,” said Pramod Reddy, associate professor of mechanical engineering and materials science and engineering. “Our experiments and calculations imply that heat flows several orders of magnitude faster in these ultra small gaps.”–Reddy and Edgar Meyhofer, a professor of mechanical engineering and biomedical engineering, led the work. A paper on the findings is newly published online in Nature.–The findings have applications across nanotechnology. They could advance next-generation information storage such as heat-assisted magnetic recording. They could push forward devices that more directly convert heat into electricity, including heat generated in cars and spacecrafts that is now being wasted. Those are just a few potential uses.[F33]–The phenomenon the researchers studied is “radiative heat”–the electromagnetic radiation, or light, that all matter above absolute zero emits. It is the emission of the internal energy of matter from movement of particles in matter–movement that only happens above absolute zero.–Scientists can explain how this happens at macroscopic distances, dimensions we can readily perceive in the world around us, down to some we can’t see. More than 100 years ago, the German physicist Max Planck wrote the equations that make this possible. His model accurately describes heat transfer across large to relatively small voids, reaching to 10 micrometers at room temperature. But when the gap gets so tight it’s almost not there, the equations break down.–In the middle of the last century, the Russian radio physicist Sergei Rytov proposed a new theory called “fluctuational electrodynamics” to describe heat transfer at smaller-than-10-micrometer distances. Since then, research hasn’t always resulted in supporting evidence. -“There were experiments in the 1990s or early 2000s that tried to test these ideas further and they found large discrepancies between what theory would predict and what experiments revealed,” Meyhofer said.-Because of the sophistication of the U-M lab, the researchers say their findings close the case, and Rytov was right.–“Our work, performed in collaboration with colleagues Professor Juan Carlos Cuevas and Professor Francisco García-Vidal at the Universidad Autónoma de Madrid, resolves an important controversy and represents a key contribution to the field of heat transfer,” Reddy said. “These results disprove current dogma in nanoscale heat transfer, which holds that radiative heat transfer in single digit nanometer-sized gaps cannot be explained by existing theory.”–The facility the researchers used is an ultra-low vibration chamber in the G. G. Brown Laboratories, the university’s newly renovated mechanical engineering complex. The chamber–one of several–was custom designed for performing nanoscale experiments so precise that mere footsteps could disturb them if they were done somewhere else. The rooms can withstand vibration from outside, such as traffic, and inside, such as heating and cooling systems. They also limit acoustic noise, temperature and humidity variations, as well as radio frequency and magnetic interference.–“Our facility represents the true state of the art,” Meyhofer said. “When creating nanoscale gaps such as those required for our nanoscale heat radiation experiments, the slightest perturbation can ruin an experiment.”–In the chamber, the researchers used custom-built “scanning thermal microscopy probes” that allowed them to directly study how fast heat flows between two surfaces of silica, silicon nitride and gold. The researchers chose these materials because they’re commonly used in nanotechnology.–For each material, they designated one sample that would be heated to 305 Fahrenheit, and they coated the tip of the probe with the same material, but kept it at a cooler 98 degrees. They slowly moved the sample and the probe together, beginning at 50 nanometers until they were touching, and they measured the temperature of the tip at regular intervals.–The cause of the rapid heat transfer, the researchers discovered, is that in nanoscale gaps there can be an overlap of the two sides’ surface and evanescent waves, both of which carry heat.–“These waves reach only a small distance into the gap between materials,” said Bai Song, a graduate student in mechanical engineering and one of the lead authors. “And their intensity at the extreme near-field is enormous compared to the electromagnetic waves at larger distances. When these waves from two different devices overlap, that’s when they allow tremendous heat flux.”—The paper is titled “Radiative heat transfer in the extreme near field.” It also involved collaborators from Universidad Autónoma de Madrid, Massachusetts Institute of Technology and Donostia International Physics Center. The work was funded by the U.S. Department of Energy Basic Energy Sciences, Army Research Office, National Science Foundation, Spanish Ministry of Economy and Competitiveness, and other organizations.–Story Source-The above post is reprinted from materials provided by University of Michigan. -Journal Reference-Kyeongtae Kim, Bai Song, Víctor Fernández-Hurtado, Woochul Lee, Wonho Jeong, Longji Cui, Dakotah Thompson, Johannes Feist, M. T. Homer Reid, Francisco J. García-Vidal, Juan Carlos Cuevas, Edgar Meyhofer, Pramod Reddy. Radiative heat transfer in the extreme near field. Nature, 2015; DOI: 10.1038/nature16070 -University of Michigan. “Heat radiates 10,000 times faster at the nanoscale.” ScienceDaily. ScienceDaily, 10 December 2015. <www.sciencedaily.com/releases/2015/12/151210144914.htm>.
Mathematicians identify limits to heat flow at the nanoscale
New formula identifies limits to nanoscale heat transfer-How much heat can two bodies exchange without touching? For over a century, scientists have been able to answer this question for virtually any pair of objects in the macroscopic world, from the rate at which a campfire can warm you up, to how much heat the Earth absorbs from the sun. But predicting such radiative heat transfer between extremely close objects has proven elusive for the past 50 years.– Now, MIT mathematicians have derived a formula for determining the maximum amount of heat exchanged between two objects separated by distances shorter than the width of a single hair. For any two objects situated mere nanometers apart, the formula can be used to calculate the most heat one body may transmit to another, based on two parameters: what the objects are made of, and how far apart they are[F34].-The formula may help engineers identify optimal materials and designs for tuning small, intricately patterned devices, such as thermophotovoltaic surfaces that convert thermal energy into electrical energy, and cooling systems for computer chips.-As a demonstration, the scientists used their formula to calculate the maximum heat transfer between two nanometer-spaced metal plates, and found that the structures may be able to transmit orders of magnitude more heat than they currently achieve[F35].-“This [formula] provides a target to say, ‘this is what we should be looking for,’ and compared to what we’ve seen so far in simple structures, there’s orders of magnitude more room for improvement for this kind of heat transfer,” says Owen Miller, a postdoc in the Department of Mathematics. “If that’s practically achievable, that could make a huge difference in, for example, thermophotovoltaics.”-Miller and his colleagues Steven Johnson, professor of applied mathematics at MIT, and Alejandro Rodriguez, assistant professor of electrical engineering at Princeton University, have published their results in Physical Review Letters.
Small scale, big effect
Since the late 1800s, scientists have used the Stefan-Boltzmann law to calculate the maximum amount of heat one body can transmit to another. This maximum heat transfer depends only on the two bodies’ temperatures and can be reached only when both bodies are extremely opaque, absorbing all the heat that is radiated on them — a theoretical notion known as the blackbody limit.–However, for objects smaller than the wavelength of heat — about 8 micrometers — scientists’ established theories of heat transfer no longer apply. In fact, it appears that at the nanoscale, the amount of heat transmitted between objects actually exceeds that predicted by the blackbody limit, hundreds of times over.[F36]–As it turns out, when objects are extremely close together, heat flows not just as electromagnetic waves, but as evanescent waves [F37]– exponentially decaying waves that have little effect at the macroscale, as they typically die away before reaching another object. At the nanoscale, however, evanescent waves can play a large role in heat transfer, tunneling between objects and essentially releasing trapped energy in the form of extra heat. Only in the last few years have Johnson and others at MIT, including Homer Reid, an applied mathematics instructor; Gang Chen, the Carl Richard Soderberg Professor of Power Engineering and head of the Department of Mechanical Engineering; and Mehran Kardar, the Francis Friedman Professor of Physics; begun to predict and quantify heat transfer at the nanoscale.
A surprisingly generalizable equation
Miller and his colleagues derived a formula for determining the maximum heat transfer between two extremely close objects. To do so, they used an existing model that describes radiative heat transfer as electrical currents flowing within two objects. Such currents arise from each object’s fluctuating electric dipoles, or, its distribution of negative and positive charges.–Using this model as a framework, the team added two additional constraints: energy conservation, in which there is a limit to the amount of energy one body can absorb; and reciprocity, where each body may be treated as a source or receiver of heat. With this approach, the researchers derived a simple equation to calculate the maximum, or upper bound, of heat that two bodies may exchange at nanoscale separations.–The equation is surprisingly generalizable and can be applied to any pair of objects regardless of their shape. Scientists simply input two parameters into the equation: separation distance, and certain material properties of each object — namely, the maximum amount of electric current that can build up in a given material.–“Now we have a formula for the upper bound,” Johnson says. “Given the material and the separation you want, you’d just plug it into the formula and boom, you’re done — it’s very easy. Now you can go backwards and try to play with materials and optimize them.”–Johnson says engineers can use the formula to identify the best possible combination and orientation of materials for optimizing heat transfer in nanodevices such as thermophotovoltaics, which involves etching surfaces with very fine, intricate patterns to improve their heat-absorbing properties.–The team has done some preliminary work in exploring heat transfer between various materials at the nanoscale. Taking about 20 different materials from the periodic table — mostly metals — Miller calculated the maximum heat transfer between pairs of them, at extremely small separations.–“This is still ongoing work, but aluminum looks like it has a lot of potential if it can be designed properly,” Miller says. “It has to be designed properly in order to achieve the limit, which is why people haven’t seen large enhancements with such materials before, but this really opens up a new class of materials that may be used.”-Story Source-The above post is reprinted from materials provided by Massachusetts Institute of Technology. The original item was written by Jennifer Chu. Note: Materials may be edited for content and length.-Massachusetts Institute of Technology. “Mathematicians identify limits to heat flow at the nanoscale: New formula identifies limits to nanoscale heat transfer, may help optimize devices that convert heat to electricity.” ScienceDaily. ScienceDaily, 24 November 2015. <www.sciencedaily.com/releases/2015/11/151124143618.htm>.
Show Of the Month December 19 2015
Spreading cancer cells must change their environment to grow
‘No-drill’ dentistry stops tooth decay
Characteristic Composition of Myelin
U.S. Government Planned To “Retaliate & Cause Pain” On Countries Refusing GMOs
Link between a mitochondrial defect and heart disease
Curry Derivative J147 Beats Aricept for Alzheimer’s
Spreading cancer cells must change their environment to grow
Spreading cancer cells arriving in a new part of the body must be able to change their new environment to continue to grow, according to a study by Cancer Research UK scientists at the Francis Crick Institute, published in Cell Reports.-The team found that the faster their surroundings change, the faster the cancer cells will grow.-A cancer cell that has spread to another part of the body needs help from the tissue that surrounds it to become established and form a new tumour. When a cell has the environment it needs, it will start to grow.–The researchers showed in mice that cancer cells that are able to spread easily produce a protein called THSB2 which helps them to make their new environment more welcoming — allowing tumours to grow. THSB2 does this by activating cells called fibroblasts, which normally help to build tissue in the body but can also support cancer growth.-[F38]Lead investigator Dr Ilaria Malanchi, Cancer Research UK scientist and group leader at The Francis Crick Institute, said: “If we can find a way to block the ability of a cancer cell to adapt to a new environment then this could slow down the growth of cancer to other parts of the body.–“The more THSB2 protein the cell produces, the faster the new tissue environment will change to give the best conditions for cancer growth.–“This is an exciting first step and what we need now is to find drugs that could stop cancer cells producing this protein and see if this reduces their ability to spread to new part of the body.”[F39]–Professor Nic Jones, Cancer Research UK’s chief scientist, said: “One of the biggest challenges in successfully treating cancer is stopping it from spreading to other parts of the body. It’s a complicated process and research like this brings us a small step closer to understanding how we might stop it from happening and so save more lives.”-Story Source-The above post is reprinted from materials provided by Cancer Research UK. -Journal Reference-Yaiza Del Pozo Martin, Danielle Park, Erik Sahai, Ilaria Malanchi. Abstract 4723: Mesenchymal status promotes metastatic colonization via a cancer cell-stroma crosstalk which uncouples EMT and stemness. Cancer Research, 2015; 75 (15 Supplement): 4723 DOI: 10.1158/1538-7445.AM2015-4723
-Cancer Research UK. “Spreading cancer cells must change their environment to grow.” ScienceDaily. ScienceDaily, 3 December 2015. <www.sciencedaily.com/releases/2015/12/151203135844.htm>.
‘No-drill’ dentistry stops tooth decay
A University of Sydney study has revealed that tooth decay (dental caries) can be stopped, reversed, and prevented without the need for the traditional ‘fill and drill’ approach that has dominated dental care for decades.-The results of the seven year study, published today in Community Dentistry and Oral Epidemiology, found that the need for fillings was reduced by 30 to 50 per cent through preventative oral care.–“It’s unnecessary for patients to have fillings because they’re not required in many cases of dental decay,” said the study’s lead author, Associate Professor Wendell Evans of the University of Sydney.–“This research signals the need for a major shift in the way tooth decay is managed by dentists — dental practice in Australia needs to change. Our study shows that a preventative approach has major benefits compared to current practice.–“For a long time it was believed that tooth decay was a rapidly progressive phenomenon and the best way to manage it was to identify early decay and remove it immediately in order to prevent a tooth surface from breaking up into cavities. After removing the decay, the affected tooth is then restored with a filling material — this process is sometimes referred to as ‘drilling and filling’.”However, 50 years of research studies have shown that decay is not always progressive and develops more slowly than was previously believed. For example, it takes an average of four to eight years for decay to progress from the tooth’s outer layer (enamel) to the inner layer (dentine).–“That is plenty of time for the decay to be detected and treated before it becomes a cavity and requires a filling.”–Professor Wendell Evans and his team developed the Caries Management System (CMS) — a set of protocols which cover the assessment of decay risk, the interpretation of dental X-rays, and specific treatment of early decay (decay that is not yet a cavity).
The CMS treatment ‘no-drill’ involves four aspects:
1. Application of high concentration fluoride varnish by dentists to the sites of early decay[F40] Of course this would not be what would be suggested since most people by now realize fluoride cause a implosion of the teeth by the way they accumulate in the teeth’s construct—reduce the brushing and increase rinses with minerals and oil pulling practices~ reduction of junk foods and grains that are genetic and any other synthetic or radiated foods that would cause skeletal damage to the body which would effect oral would be the better alternatives
2. Attention to home tooth brushing skills~ reduce the brushing and increase rinses with minerals and oil pulling practices
3. Restriction of between-meal snacks and beverages containing added sugar~ reduction of junk foods and grains that are genetic and any other synthetic or radiated foods that would cause skeletal damage to the body which would effect oral
4. Risk-specific monitoring.
“The CMS was first tested on high risk patients at Westmead Hospital with great success,” said Professor Evans.-“It showed that early decay could be stopped and reversed and that the need for drilling and filling was reduced dramatically.”A tooth should be only be drilled and filled where an actual hole-in-the-tooth (cavity) is already evident,” he said.
The CMS treatment was then tested in general dental practices in New South Wales and Australian Capital Territory. The Monitor Practice Program (MPP), funded by the National Health and Medical Research Council of Australia (NHMRC), confirmed that after seven years, decay risk was substantially reduced among the CMS patients and their need for fillings was reduced by 30 to 50 per cent compared to the control group.–“The reduced decay risk and reduced need for fillings was understandably welcomed by patients,” Professor Evans said. “However, patients play an important role in their treatment. This treatment will need a partnership between dentists and patients to be most successful.”Story Source-The above post is reprinted from materials provided by University of Sydney. University of Sydney. “‘No-drill’ dentistry stops tooth decay.” ScienceDaily. ScienceDaily, 6 December 2015. <www.sciencedaily.com/releases/2015/12/151206164802.htm>.
Characteristic Composition of Myelin
Pierre Morell and Richard H Quarles.
Correspondence to Pierre Morell, Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7250.
Myelin in situ has a water content of about 40%. The dry mass of both CNS and PNS myelin is characterized by a high proportion of lipid (70 to 85%) and, consequently, a low proportion of protein (15 to 30%). In contrast, most biological membranes have a higher ratio of proteins to lipids.
Central nervous system myelin is enriched in certain lipids
Table 4-1 lists the composition of bovine, rat and human myelin compared to bovine and human white matter, human gray matter and rat whole brain (see Chap. 3). All of the lipids assayed in whole brain are also present in myelin; that is, there are no lipids localized exclusively in some nonmyelin compartment, with the exception of the mitochondria-specific lipid diphosphatidylglycerol, not included in the table. We also know that the reverse is true; that is, there are no myelin lipids that are not also found in other subcellular fractions of the brain.
Table 4-1. Composition of CNS Myelin and Brain.
Composition of CNS Myelin and Brain.
Even though there are no absolutely “myelin-specific” lipids, cerebroside, also known as galactosylceramide, is the most typical of myelin. With the exception of early development, the concentration of cerebroside in brain is directly proportional to the amount of myelin present. As much as one-fifth of the total galactolipid in myelin occurs in the form of sulfatide[F41], in which the 3-hydroxyl moiety on the galactose of cerebroside is sulfated. Because of the specificity and quantitative significance of galactocerebroside in oligodendrocytes and myelin, it has been assumed for decades that it is essential for oligodendroglial differentiation and the specialized structure and function of myelin. This dogma was overthrown by the creation of a knockout mouse lesioned in UDP-galactose:ceramide galactosyltransferase, the obligate terminal step in cerebroside biosynthesis, also required for sulfatide formation[F42] . Surprisingly, the myelin formed appears relatively normal, although subtle differences in structure and changes in axon conduction velocity can be demonstrated. With age, animals develop a progressive hindlimb paralysis and extensive vacuolation of myelin in the spinal cord[F43]. These findings indicate that cerebroside and/or sulfatide are not required for myelin formation but play important roles in its insulating capacity and stability.–In addition to cerebroside, the major lipids of myelin are cholesterol and ethanolamine-containing plasmalogens (see Chap. 3). Lecithin is also a major myelin constituent, and sphingomyelin is a relatively minor one. Not only is the lipid composition of myelin highly characteristic of this membrane, the fatty acid composition of many of the individual lipids is distinctive.
The data in Table 4-1 suggest that myelin accounts for much of the total lipid of white matter and that the lipid composition of gray matter is quite different from that of myelin. The composition of brain myelin from all mammalian species studied is very much the same. There are, however, some species differences; for example, myelin of rat has less sphingomyelin than bovine or human myelin (Table 4-1). Although not shown in the table, there are also regional variations; for example, myelin isolated from the spinal cord has a higher lipid-to-protein ratio than brain myelin from the same species.
Besides the lipids listed in Table 4-1, there are several others of importance. If myelin is not extracted with acidified organic solvents, the polyphosphoinositides (see Chap. 3) remain tightly bound to the myelin protein and, therefore, are not included in the lipid analysis[F44]. Triphosphoinositide accounts for between 4 and 6% of the total myelin phosphorus and diphosphoinositide for 1 to 1.5%.
Minor components of myelin include at least three fatty acid esters of cerebroside and two glycerol-based lipids, diacylglyceryl-galactoside and monoalkylmonoacylglycerylgalactoside,[F45] collectively called galactosyldiglyceride. Some long chain alkanes also appear to be present. Myelin from mammals contains 0.1 to 0.3% gangliosides, which are complex sialic acid-containing glycosphingolipids. The proportion of the different gangliosides to each other is different in myelin, which is greatly enriched in monosialoganglioside GM1 relative to other brain membranes, which are enriched in the polysialo species. Myelin from certain species, including human, contains an additional unique ganglioside as a major component, sialosylgalactosylceramide, GM4.
Peripheral and central nervous system myelin lipids are qualitatively similar
There are quantitative differences. PNS [F46]myelin has less cerebroside and sulfatide and considerably more sphingomyelin than CNS [F47]myelin. Of interest is the presence of ganglioside LM1, also termed sialosyl-lactoneotetraosylceramide, as a characteristic component of myelin in the PNS of some species. These differences in lipid composition between CNS and PNS myelin are not, however, as dramatic as the differences in protein composition discussed below.
Central nervous system myelin contains some unique proteins
The protein composition of CNS myelin is simpler than that of other brain membranes, with the proteolipid protein and basic protein(s) making up 60 to 80% of the total in most species[F48]. Many other proteins and glycoproteins are present to lesser extents. With the exception of the basic proteins, myelin proteins are neither easily extractable nor soluble in aqueous media. However, like other membrane proteins, they may be solubilized in sodium dodecylsulfate (SDS) solutions and, in this condition, separated readily by electrophoresis in polyacrylamide gels. This technique separates proteins primarily according to molecular weight. The presence of bound carbohydrates or unusual structural features somewhat disrupts the relationship between migration and molecular weight so that terminology for location of a protein in such a gel is taken to mean apparent molecular weight, which sometimes is written Mr for relative molecular mass. Protein compositions of human and rat brain myelin are illustrated in Figure 4-11B and D, respectively. The quantitative predominance of two proteins, the positively charged myelin basic protein (MBP) and proteolipid protein (PLP), in the gel pattern of human CNS myelin is clear. These proteins are major constituents of all mammalian CNS myelins, and similar proteins are present in myelins of many lower species.
Figure 4-11. Polyacrylamide gel electrophoresis of myelin proteins in the presence of sodium dodecyl sulfate (SDS).
Polyacrylamide gel electrophoresis of myelin proteins in the presence of sodium dodecyl sulfate (SDS). The proteins of A: human PNS myelin, B: human CNS myelin, C: rat PNS myelin and D: rat CNS myelin were solubilized with the detergent SDS, electrophoresed (more…)
Proteolipid protein. Myelin PLP, also known as the Folch-Lees protein , has the unusual physical property of solubility in organic solvents. The molecular weight of PLP from sequence analysis is about 30,000, although it migrates anomalously fast on SDS gels. The amino acid sequence, strongly conserved during evolution, contains several membrane-spanning domains. PLP contains about 3 moles of fatty acids, primarily palmitate, oleate or stearate, per mole protein in ester linkage to hydroxy amino acids. There is rapid turnover of the fatty acids independent of the peptide backbone .
In addition to PLP, myelin of the CNS has lesser quantities of a related protein, DM-20, named for its Mr of 20,000. This protein is coded by an alternative splicing of the RNA, which gives rise to the major PLP. Both DNA and protein-sequencing data indicate that the structure of DM-20 is related to that of PLP by a deletion of 35 amino acids [13,14]. DM-20-related message appears earlier than PLP during development, even before myelin formation in some cases; and it might have a role in oligodendrocyte differentiation in addition to a structural role in myelin. The PLP and DM-20 proteins may be evolved from an ancestral gene encoding a pore-forming polypeptide , lending support to the hypothesis that myelin may be involved in ion movement. Although PLP and DM-20 serve important functions, they are not essential. Contrary to the general expectation that PLP would be needed for formation of compact, multilamellar myelin, a knockout mouse for PLP/DM-20  is relatively normal with respect to myelin formation, although there is a difference at the level of the intraperiod line. In this knockout mouse, life span and sophisticated motor performance also are affected. In contrast, a variety of naturally occurring mutations in PLP (see Chap. 39) or overexpression of normal PLP  have severe functional consequences, apparently due to cellular toxicity of mutated forms of the protein or even just excess amounts of normal PLP. A curiosity is that, although significant amounts of PLP and DM-20 are restricted to the CNS, mRNA for PLP is expressed in the PNS and small amounts of protein are synthesized but not incorporated into myelin in appreciable amounts.
Myelin basic protein has long been of interest because it is the antigen that, when injected into an animal, elicits a cellular immune response that produces the CNS autoimmune disease experimental allergic encephalomyelitis (EAE) (see Chap. 39). MBP can be extracted from myelin as well as from white matter with either dilute acid or salt solutions; once extracted, it is very soluble in water. The amino acid sequence of the major basic protein is similar in a number of species . These proteins have molecular weights of around 18,500; they are highly unfolded, with essentially no tertiary structure in solution. This basic protein shows microheterogeneity upon electrophoresis in alkaline conditions, due to a combination of phosphorylation, loss of the C-terminal arginine and deamidation. There is also heterogeneity in the degree of methylation of an arginine at residue 106[F49]. MBP is located on the cytoplasmic face of the myelin membranes corresponding to the major dense line. The rapid turnover of the phosphate groups present on many of the MBP molecules [18,19] suggests this post-translational modification might influence the close apposition of the cytoplasmic faces of the membrane. It also has been speculated that phosphorylation may modify this process in a dynamic manner. Of interest is that mRNA coding for MBP is preferentially localized far from the cell perikaryon, in the region where myelin compaction is taking place .
In addition to the major MBP, most species of mammals that have been studied contain various amounts of other basic proteins related to it in sequence. Mice and rats have a second smaller MBP of 14-kDa. The small MBP has the same N- and C-terminal sequences as the larger MBP but differs by a deletion of 40 residues. The ratio of these two basic proteins to each other changes during development: mature rats and mice have more of the 14-kDa protein than of the 18-kDa protein. Two other MBPs seen in many species have molecular weights of 21,500 and 17,000, respectively. These two proteins are related structurally to the large and small basic proteins, respectively, by the addition of a polypeptide sequence of Mr ~3,000 near the amino-terminal end of the protein. Another basic protein, present to some extent in humans, has a molecular weight of 17,200 and is now known to be slightly different from the 17-kDa protein in other species. The different MBPs arise from alternative splicing of a common mRNA precursor. A diagrammatic representation of some of these alternative splicing schemes is presented in Figure 4-12. The physiological significance of the heterogeneity of MBPs is an open question. It is relevant that the exons which can be combined to make the various myelin basic proteins are also part of a larger set of exons of a gene, GOLLI. Transcripts of this gene are expressed as Golli proteins, which contain MBP sequences as well as unique peptide sequences, during early development and in various neural cell types, including neurons .
Figure 4-12. The amino acid sequences corresponding to the various mouse myelin basic proteins (MBPs) are encoded in a gene containing at least seven exons (separated by introns, DNA regions whose base sequence does not code directly for proteins).
The amino acid sequences corresponding to the various mouse myelin basic proteins (MBPs) are encoded in a gene containing at least seven exons (separated by introns, DNA regions whose base sequence does not code directly for proteins). The precursor RNA (more…)
2′:3′-Cyclic nucleotide-3′-phosphodiesterase. There are many higher molecular weight proteins present in the gel-electrophoretic pattern of myelin. These vary in amount depending on species; for example, mouse and rat may have as much as 30% of the total myelin protein in this category. These proteins also vary depending on the degree of maturity, such that the younger the animal, the less myelin but the greater the proportion of higher molecular weight proteins. A double band with Mr ~50,000 is present in myelin from most species. It has been identified with an enzyme activity, 2′:3′-cyclic nucleotide-3′-phosphodiesterase (CNP), which comprises several percent of myelin protein . Although there are low levels of this enzymatic activity associated with the surface membrane of many different types of cell, it is much enriched in myelin and in cells committed to the formation of myelin. The enzyme is extremely active against 2′,3′-cAMP, as well as the cGMP, cyclic cytidine monophosphate (cCMP) and cyclic uridine monophosphate (cUMP) analogs, all of which are hydrolyzed to the corresponding 2′-isomer. This is probably an artifactual activity; recall that the biologically active cyclic nucleotides are those with a 3′:5′ structure. The amino acid sequence is relatively conserved in different species. In mice, the two CNP polypeptides are generated by alternative splicing of the mRNA, with the larger polypeptide having an extra 20 amino acids at the N-terminus.
CNP is not a major component of compact myelin but is concentrated in specific regions of the myelin sheaths associated with cytoplasm, such as the oligodendroglial processes, inner and outer tongue processes and lateral loops. The biological function of CNP is not known, but it is of interest that it contains a consensus sequence found in G proteins. It also has been proposed, in part because of its isoprenylation, that CNP plays a role in events involving the cytoskeletal network of myelin [F50]. Examination of aberrant myelination occurring in transgenic mice overexpressing CNP suggests that it is an early regulator of cellular events that culminate in CNS myelination .
Myelin-associated glycoprotein and other glycoproteins of CNS myelin. The myelin-associated glycoprotein (MAG) is a quantitatively minor, 100-kDa glycoprotein in purified myelin  that electrophoreses at the position shown in Figure 4-11. However, because it is less than 1% of total protein and stains weakly with Coomassie blue, it does not correspond to one of the discrete protein bands visible in the figure. MAG has a single transmembrane domain that separates a heavily glycosylated extracellular part of the molecule, composed of five immunoglobulin-like domains and eight or nine sites for N-linked glycosylation, from an intracellular carboxy-terminal domain. Its overall structure is similar to that of neural cell adhesion molecule (NCAM). MAG in rodents occurs in two developmentally regulated isoforms, which differ in their cytoplasmic domains and are generated by alternative splicing of mRNA. The isoform with a longer C-terminal tail (L-MAG) is predominant early in development during active myelination of the CNS, whereas the isoform with a shorter cytoplasmic tail (S-MAG) increases during development to become prominent in adult rodents. These cytoplasmic domains are phosphorylated on serine and threonine residues by protein kinase C, and L-MAG is phosphorylated also on tyrosine-620.
[F51]MAG is not present in compact, multi-lamellar myelin but is located exclusively in the periaxonal oligodendroglial membranes of CNS myelin sheaths. Both its location next to the axon and its membership in the immunoglobulin superfamily (see Chap. 7) suggest that it functions in adhesion and signaling between myelin-forming oligodendrocytes and the axolemma. MAG is a member of the I-type lectin subfamily of the immunoglobulin superfamily and binds to glycoproteins and gangliosides with terminal 2–3-linked sialic acid moieties. Thus, the axolemmal ligand(s) for MAG is probably a sialoglycoconjugate, but the identity of its physiological receptor is unknown. Furthermore, MAG may bind to other components on the axolemma by different mechanisms. A relationship of MAG to other adhesion proteins also is demonstrated by the presence in most species of a sulfate-containing carbohydrate HNK-1 epitope, which is expressed on a large number of neural adhesion proteins, including NCAM and MAG, and functions in cell—cell interactions. As with other proteins in the immunoglobulin superfamily, it is likely that the interaction of MAG with its ligand(s) on the axolemma mediates cell—cell signaling by mechanisms involving phosphorylation [19,26]. For example, the cytoplasmic domain of MAG interacts with fyn tyrosine kinase and phospholipase Cγ by mechanisms that appear to involve phosphorylated amino acids on MAG.
Although MAG is presumed to function in important signaling mechanisms between axons and oligodendrocytes during myelin formation, there may be some redundancy involved since young MAG knockout mice myelinate relatively normally and exhibit only subtle periaxonal structural abnormalities. However, as the null mutants age to 8 to 10 months, they develop a dying-back oligodendrogliopathy  and a peripheral neuropathy affecting both myelin and axons, suggesting that the most critical functions of MAG may be for maintenance of axon—myelin complexes. Also, although MAG generally has been thought to function in axon-to-glia signaling, the neuronal abnormalities found in aging MAG-null mutants suggest that it may also function in glia-to-axon signaling . Furthermore, MAG is one of the factors in CNS white matter that inhibits neurite outgrowth in tissue culture . Whatever the possible physiological implications of this for neuronal regeneration in vivo following injury, the findings are consistent with a MAG-mediated signaling mechanism from glia to axons that can affect the properties of neurons.
There are a large number of other glycoproteins associated with white matter and myelin, many of which have not yet been studied well. However, in addition to MAG, a few have been cloned and partially characterized. One of these is a minor protein of 26 kDa called the myelin-oligodendrocyte glycoprotein (MOG) . MOG also is a transmembrane glycoprotein, contains a single immunoglobulin-like domain and one site for N-linked glycosylation and expresses the adhesion-related HNK-1 epitope. Unlike MAG, which is sequestered at the interior of myelin sheaths, MOG is localized on the surface of myelin sheaths and oligodendrocytes. Because of its surface location, it may function in transmitting extracellular information to the interior of oligodendrocytes and has been implicated as a target antigen in autoimmune aspects of demyelinating diseases of the CNS (see Chap. 39).
There is also a 120-kDa glycosylated protein in white matter called the oligodendrocyte-myelin glycoprotein . This glycoprotein is membrane-bound through a phosphatidylinositol linkage and characterized by a cysteine-rich motif at the N-terminus and a series of tandem leucine-rich repeats. [F52]Unlike MAG and MOG, it is not a member of the immunoglobulin superfamily but does express the HNK-1 carbohydrate epitope. The leucine-rich repeats and adhesion-related HNK-1 epitope suggest that it also may function in cell—cell interactions.
Small amounts of proteins characteristic of membranes in general can be identified on gels of myelin proteins. Noted in Figure 4-11 is tubulin; although this may be present because of contamination of myelin preparation by other membranes, there is evidence suggesting that it is an authentic myelin component. High-resolution electrophoretic techniques demonstrate the presence of other minor protein bands; these may relate to the presence of numerous enzyme activities associated with the myelin sheath (see below).
Peripheral myelin contains some unique proteins and some shared with central nervous system myelin
P0 is the major PNS myelin protein. Gel-electrophoretic analysis (Fig. 4-11A, C) shows that a single protein, of 30 kDa, P0 accounts for more than half of the PNS myelin protein. The cloning and sequencing of the message for this protein [30, 31] led to derivation of amino acid sequences from several species. From this, it has been deduced that the protein has about 220 amino acids with an intracellular domain, a hydrophobic transmembrane domain and a single extracellular immunoglobulin-like domain. The amino-terminal extracellular domain includes a signal sequence for insertion of protein into the membrane and a glycosylation site. In addition to the well-characterized carbohydrate chain, other post-translational modifications include sulfation, phosphorylation and acylation.
[F53]It is interesting to note that PLP and P0 protein, although different in sequence, post-translational modifications and structure, may have similar roles in the formation of structures as closely related as myelins of the CNS and PNS. These proteins are not mutually exclusive; they are coexpressed in certain fish and amphibians . Transfection of non-neural cells with the P0 gene results in cell—cell interaction, which can be demonstrated to be due to homophilic interactions of the extracellular domains of P0 [33,34]. Elucidation of the crystal structure of the extracellular domain of P0 shows tetrameric packing of P0 molecules, suggesting that the extracellular domains of P0 project from the myelin membrane surface as tetramers . The complete knockout of P0 has profound consequences on myelin structure and function , in contradistinction to the previously noted, relatively benign consequences for CNS in animals with a deletion of the PLP gene.
Myelin basic protein content in the PNS varies from approximately 5 to 18% of total protein, in contrast to the CNS, where it is on the order of 30%. In rodents, the same four MBPs found in the CNS are present in the PNS, with molecular weights of 21,000, 18,500, 17,000 and 14,000 respectively. In adult rodents, the 14-kDa MBP is the most prominent component and is termed “Pr” in the PNS nomenclature. The 18-kDa component is present and often is referred to as the P1 protein in the nomenclature of peripheral myelin proteins. Another species-specific variation occurs in humans. In human PNS, the major basic protein is not the 18.5-kDa form, which is most prominent in the CNS, but rather the 17.2-kDa form . MBP may not play as critical a role in myelin structure in the PNS as it does in the CNS. The murine mutant Shiverer is lesioned with respect to MBP synthesis. CNS myelin has no dense line structure; this contrasts to the PNS, which has almost normal myelin amount and structure but lacks MBP.
PNS myelin contains another positively charged protein, referred to as P2, with Mr ~15,000. It is unrelated in sequence to either P1 or Pr but shows strong homology to a family of cytoplasmic lipid-binding proteins that are present in a variety of cell types . This suggests the possibility of P2 protein involvement in lipid assembly or turnover within the myelin sheath. The amount of P2 protein is highly variable from species to species, accounting for about 15% of total protein in bovine PNS myelin, 5% in humans and less than 1% in rodents. Within a species, P2 is more prominent in the thicker myelin sheaths. P2 protein generally is considered in the context of PNS myelin proteins, but it is expressed in small amounts of CNS myelin sheaths of some species. P2 is an antigen for experimental allergic neuritis (EAN), the PNS counterpart of EAE (see Chap. 39). P2 appears to be present in the major dense line of myelin sheaths, where it may play a structural role similar to MBP, and there appears to be substantially more P2 in large sheaths than small ones. The large variation in the amount and distribution of the protein from species to species and sheath to sheath raises questions about its function. Its similarities to cytoplasmic proteins, whose functions appear to involve solubilization and transport of fatty acids and retinoids, suggest that it might function similarly in myelination; but there is currently no experimental evidence to support this hypothesis.
Other glycoproteins of PNS myelin. In addition to the major P0 glycoprotein, compact PNS myelin contains a 22-kDa glycoprotein called peripheral myelin protein-22 (PMP-22) , which accounts for less than 5% of the total protein (Fig. 4-11C). PMP-22 has four potential transmembrane domains and a single site for N-linked glycosylation. It is referred to as a growth arrest protein because its cDNA was cloned from nondividing fibroblasts and the synthesis of PMP-22 and other myelin proteins ceases when Schwann cells begin to proliferate following nerve transection. Since it is quantitatively a rather minor component, it may perform some unknown dynamic function in myelin assembly or maintenance rather than a major structural role. Its putative tetraspan structure is similar to that of PLP, suggesting that its role might be one of the functions of PLP in CNS myelin. Also, as is the case with PLP, any significant deviation in gene dosage for PMP-22 or disruption caused by point mutations has severe functional consequences . Abnormalities of the PMP-22 gene are responsible for the trembler murine mutant and several inherited human neuropathies (see Chap. 39).
Similarly to the CNS, MAG is present in the periaxonal membranes of the myelin-forming Schwann cells, but it is also present in the Schwann cell membranes constituting the Schmidt-Lentermann incisures, paranodal loops and outer mesaxon . All of these locations are characterized by 12- to 14-nm spacing between the extracellular surfaces of adjacent membranes and the presence of cytoplasm on the inner side of the membranes. Therefore, in addition to a role in Schwann cell—axon interactions in the PNS, MAG may function in interactions between adjacent Schwann cell membranes at the other locations. Both isoforms of MAG are present in the PNS of rodents, although S-MAG is the predominant isoform at all ages. As mentioned earlier, the peripheral neuropathy affecting both myelin and axons that develop in aging MAG knockout mice suggests that MAG-mediated signaling from axons to Schwann cells, and vice versa may be important for the maintenance of myelin—axon complexes. Clinical interest in PNS MAG derives from the demonstration that human IgM monoclonal antibodies in patients with neuropathy in association with gammopathy[F54] react with a carbohydrate structure in MAG that is very similar to the adhesion-related HNK-1 carbohydrate epitope (see Chap. 39).
PNS myelin also contains a glycoprotein of 170 kDa that accounts for about 5% of the total myelin protein and appears to be the same as a protein that was characterized further and called the Schwann cell membrane glycoprotein (SAG) . It appears to be expressed in locations distinct from compact myelin by both myelinating and nonmyelinating Schwann cells, but very little is known about its structure and function at this time. In addition, avian Schwann cells contain a glycoprotein with relatively high amino acid sequence homology to MAG, the Schwann cell myelin protein (SMP) . Although it is not thought to be the avian homolog of MAG because of differences in its pattern of expression and less than expected sequence homology, the structural and functional relationships between SMP and MAG remain to be established.
Myelin contains enzymes that function in metabolism and possibly ion transport
Several decades ago, it was generally believed that myelin was an inert membrane that did not carry out any biochemical functions. More recently, however, a large number of enzymes have been discovered in myelin . These findings imply that myelin is metabolically active in synthesis, processing and metabolic turnover of some of its own components. Additionally, it may play an active role in ion transport with respect to not only maintenance of its own structure but also participation in buffering of ion levels in the vicinity of the axon.
A few enzymes, such as the previously mentioned CNP, are believed to be fairly myelin-specific, although they are probably also present in oligodendroglial membranes. CNP is very low in peripheral nerve and PNS myelin, suggesting some function more specialized to the CNS. A pH 7.2 cholesterol ester hydrolase also may be relatively myelin-specific, although the enzyme is prominent in myelin. N-Acetyl-l-aspartate aminohydroxylase[F55], an enzyme operating on a substrate of unknown metabolic significance, also is enriched in myelin.
There are many enzymes that are not myelin-specific but appear to be intrinsic to myelin and not contaminants. Several proteolytic activities have been identified in purified myelin; the presence of neutral protease activity is well documented[F56]. The presence in myelin of cAMP-stimulated kinase, calcium/calmodulin-dependent kinase and protein kinase C activities has been reported. Phosphoprotein phosphatases are also present[F57]. Protein kinase C and phosphatase activities are presumed to be responsible for the rapid turnover of phosphate groups of MBP. Enzyme activity for acylation of PLP is also intrinsic to myelin.
[F58]Enzymes involved in the metabolism of structural lipids include a number of steroidmodifying and cholesterol-esterifying enzymes, UDP-galactose:ceramide galactosyltransferase and many enzymes of glycerophospholipid metabolism (see Chap. 3). The latter grouping includes all of the enzymes necessary for phosphatidyl ethanolamine synthesis from diradyl-sn-glycerol and ethanolamine; it is likely that phosphatidycholine also can be synthesized within myelin. Perhaps even more elemental building blocks can be assembled into lipids by myelin enzymes. Acyl-CoA synthetase is present in myelin, suggesting the capacity to integrate free fatty acids into myelin lipids[F59]. The extent of the contribution of these enzymes in myelin, relative to enzymes within the oligodendroglial perikaryon, to metabolism of myelin lipids is not known.
Other enzymes present in myelin include those involved in phosphoinositide metabolism: phosphatidylinositol kinase, diphosphoinositide kinase, the corresponding phosphatases and diglyceride kinases. These are of interest because of the high concentration of polyphosphoinositides of myelin and the rapid turnover of their phosphate groups. This area of research has expanded toward characterization of a signal-transduction system(s). There is evidence for the presence in myelin of muscarinic cholinergic receptors, G proteins, phospholipases C and D and protein kinase C.
Certain enzymes present in myelin could be involved in ion transport. Carbonic anhydrase generally has been considered a soluble enzyme and a glial marker, but myelin accounts for a large part of the membrane-bound form in brain. This enzyme may play a role in removal of carbonic acid from metabolically active axons. The enzymes 5′-nucleotidase and Na,K-ATPase have long been considered specific markers for plasma membranes and are found in myelin at low concentrations. The 5′-nucleotidase activity may be related to a transport mechanism for adenosine, and Na,K-ATPase could function in transport of monovalent cations. The presence of these enzymes suggests that myelin may have an active role in transport of material in and out of the axon. In connection with this hypothesis, it is of interest that the PLP gene family may have evolved from a pore-forming polypeptide . K+ channels in myelin vesicles also have been described . An isoform of glutathione-S-transferase is present in myelin and may be involved in transport of certain larger molecules.By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.–Copyright © 1999, American Society for Neurochemistry.-Bookshelf ID: NBK28221