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Cristian Mihon



A combined research team, formed by scientists from the School of Medicine, from the Washington University, in the United States, and from the Institute of Technology and Advanced Biomedical Imaging, from the University of Chieti, in Italy, has managed to use faster brain scans in order to map the brain activity of volunteers either at rest or while watching a movie. The study has been recently published in the online journal Neuron.

According to the senior author of the study, Dr Maurizio Corbetta, the activity of the brain consists of waves that repeat themselves as slow as once ever 10 or more seconds, or as fast as one every 50 milliseconds. Corbetta reports that this is the first attempt of the research team to scan the waves that repeat themselves every 50 milliseconds, whilst also mapping the wave fluctuations of the slower waves. Their analysis is similar to that made through the use of an fMRI (functional magnetic resonance imaging). The research team analyzed the brain activity of subjects while they were resting or watching a movie. The results show interesting information about the configuration of the brain networks and the differences in conformation during rest and activity. Corbetta also said that understanding how the brain networks function is very important for better future diagnosis and treatment of brain injuries and disorders.

Precedent studies have revealed several networks of the brain that are used during the rest-state. These brain networks are groups of brain regions whose level of activity either rise or fall in synchronization when the brain is resting. The research team used the technology called fMRI in order to locate and investigate the respective brain networks. However, the fact that the fMRI technique is rather slow, they were only capable of investigating waves that changed every 10 seconds or more.

Furthermore, the research team used a newer, faster technology, called MEG (magnetoencephalography). This technique is capable of detecting  waves that are active for less than 50 milliseconds, thus allowing the research team to investigate the waves that have between 1 and more than 50 activity cycles per second. The first author of the study, professor Viviana Betti, said that the brain activity appears to be fluctuation on a slow time scale. However, when the subjects stopped resting and started watching a movie, the brain networks also shifted their frequency channels. This lead Viviana to conclude that the brain uses various frequencies for completing tasks and resting. She compared the brain to a radio.

The subjects that participated in the study were asked to either watch a movie or rest, activities during which the research team scanned the activity of their brains. Another group of subjects were asked to pay attention to events occurring in the movies, such as plot twists. The subjects in the second group were asked to press a button whenever they observed a new event in the ongoing movie. Just as previous studies have shown, the majority of test subjects managed to identify the same events during the movie. The MEG results showed that the communications between different regions of the visual cortex changed during the events of the movies.

Corbetta concludes that the results of the study reveal that there are dynamic changes happening to the rest-state networks during cognitive activities. He believes that future studies are needed in order to track the network activity during different tasks, and to see the level of correlation and dynamic coordination across the regions of the brain.


Scientists show proof-of-principal for silencing extra chromosome responsible for Down syndrome

Scientists at the University of Massachusetts Medical School are the first to establish that a naturally occurring X chromosome “off switch” can be rerouted to neutralize the extra chromosome responsible for trisomy 21, also known as Down syndrome, a genetic disorder characterized by cognitive impairment.

The discovery provides the first evidence that the underlying responsible for Down syndrome can be suppressed in cells in culture (in vitro). This paves the way for researchers to study the cell pathologies and identify genome-wide pathways implicated in the disorder, a goal that has so far proven elusive. Doing so will improve scientist’s understanding of the basic biology underlying Down syndrome and may one day help establish potential therapeutic targets for future therapies. Details of the study by Jiang et al. were published online in Nature.

“The last decade has seen great advances in efforts to correct single-gene disorders, beginning with cells in vitro and in several cases advancing to in vivo and clinical trials,” said lead author Jeanne B. Lawrence, PhD, professor of cell & developmental biology at the University of Massachusetts Medical School. “By contrast, genetic correction of hundreds of genes across an entire  has remained outside the realm of possibility. Our hope is that for individuals living with Down syndrome, this proof-of-principal opens up multiple exciting new avenues for studying the disorder now, and brings into the realm of consideration research on the concept of “chromosome therapy’ in the future.”

Humans are born with 23 pairs of chromosomes, including two sex chromosomes, for a total of 46 in each cell. People with Down syndrome are born with three (rather than two) copies of chromosome 21, and this “” causes cognitive disability, early-onset Alzheimer’s disease; and a greater risk of childhood leukemia, heart defects and immune and endocrine system dysfunction. Unlike genetic disorders caused by a single gene, genetic correction of a whole chromosome in trisomic cells has been beyond the realm of possibility, even in cultured cells.

Harnessing the power of the RNA gene called XIST, which is normally responsible for “turning off” one of the two X chromosomes found in female mammals, UMass Medical School scientists have shown that the extra copy of chromosomes 21 responsible for Down syndrome can be silenced in the laboratory using patient-derived stem cells.

The natural function of the XIST gene, located on the X chromosome, is to effectively silence one of the two X chromosomes in female cells, making expression of X-linked genes similar to that of men, who have just one X chromosome. The large XIST RNA is produced early in development from one of the female’s two X chromosomes, and this unique RNA then “paints” the X chromosome and modifies its structure so that its DNA can’t be expressed to produce proteins and other components. This effectively renders most of the genes on the extra chromosome inactive.

Lawrence and colleague Lisa Hall PhD, research assistant professor of cell and developmental biology at UMMS, became motivated by the idea that this effect might be replicated in an extra chromosome 21 in trisomic cells and Jun Jiang, PhD, instructor of cell and developmental biology at UMMS, worked with Dr. Lawrence to begin a research project to insert the XIST gene into one chromosome 21 “ supported by NIH funding for high-risk, high-impact work. They worked to do this in induced pluripotent stem cells derived from fibroblast cells donated by a Down syndrome patient because stem cells have the special capacity to form different cell types of the body. Their work showed that the large XIST gene could be inserted at a specified location in the chromosome using zinc finger nuclease (ZFN) technology, a key tool provided by collaborators at Sangamo BioSciences, Inc., a biotechnology company based in Richmond, California. Furthermore, RNA from the inserted XIST gene effectively repressed genes across the extra chromosome, returning gene expression levels to near normal levels and effectively silencing the chromosome.

Down syndrome

This finding opens multiple new avenues for translational scientists to study Down syndrome in ways not previously possible. Determining the underlying cell pathologies and gene pathways responsible for the syndrome has previously proven difficult, because of the complexity of the disorder and the normal genetic and epigenetic variation between people and cells. For example, some prior studies suggested that cell proliferation in Down syndrome patients may be impaired, but differences between people and cell lines made it difficult to conclude this definitively. By controlling expression of the XIST gene, Lawrence and colleagues were able to compare otherwise identical cultures of the Down syndrome cells, with and without expression of the extra chromosome. What they showed is that the Down syndrome cells have defects in cell proliferation and in neural cell differentiation, both of which are reversed by silencing one chromosome 21 by XIST.

“This highlights the potential of this new experimental model to study a host of different questions in different human cell-types, and in Down syndrome mouse models” said Lawrence. “We now have a powerful tool for identifying and studying the cellular pathologies and pathways impacted directly due to over-expression of chromosome 21.”

“Dr. Lawrence has harnessed the power of a natural process to target abnormal gene expression in cells that have an aberrant number of chromosomes,” said Anthony Carter, PhD, of the National Institutes of Health’s National Institute of General Medical Sciences, which partly supported the study. “Her work provides a new tool that could yield novel insights into how genes are silenced on a chromosomal scale, and into the pathological processes associated with chromosome disorders such as Down syndrome.”

New discoveries made using this approach could one day identify new therapeutics for chromosome disorders like Down syndrome. “In the short term the correction of Down syndrome cells in culture accelerates the study of cell pathology and translational research into therapeutics, but also for the longer-term, potential development of “chromosome therapies”, which utilizes epigenetic strategies to regulate chromosomes, is now at least conceivable. Since therapeutic strategies for common chromosomal abnormalities like Down syndrome have received too little attention for too long, for the sake of millions of patients and their families across the US and the world, we ought to try. ” said Lawrence.

Lawrence and colleagues will now use this technology to test whether “chromosome therapy” can correct the pathologies seen in mouse models of Down syndrome.


Studies suggest new key to ‘switching off’ hypertension

A team of University of California, San Diego researchers has designed new compounds that mimic those naturally used by the body to regulate blood pressure. The most promising of them may literally be the key to controlling hypertension, switching off the signaling pathways that lead to the deadly condition.

Published online this month in Bioorganic & Medicinal Chemistry, the scientists studied the properties of the peptide called catestatin that binds nicotinic acetylcholine receptors found in the nervous system, and developed a pharmacophore model of its active centers. They next screened a library of for molecules that might match this 3D “fingerprint”. The scientists then took their in-silico findings and applied them to lab experiments, uncovering compounds that successfully lowered .

“This approach demonstrates the effectiveness of rational design of novel drug candidates,” said lead author Igor F. Tsigelny, a research scientist with the university’s San Diego Supercomputer Center (SDSC), as well as the UC San Diego Moores Cancer Center and the Department of Neurosciences.

“Our results suggest that analogs can be designed to match the action of catestatin, which the body uses to regulate ,” said Daniel T. O’Connor, a professor at the UC San Diego School of Medicine and senior author of the study. “Those designer analogs could ultimately be used for treatment of hypertension or autonomic dysfunction.”

The research may lead to a new class of treatments for hypertension, a disease which affects about 76 million people, or about one in three adults, in the United States, according to the American Heart Association. Untreated, it damages the blood vessels and is a leading risk factor for kidney failure, heart attack, and stroke.

Despite being a common and lethal cardiovascular risk factor, hypertension remains only partially controlled by current antihypertensive medications, most of which have serious side effects. Specifically, the SDSC/UC San Diego researchers targeted the hormone catestatin for therapeutic potential. Catestatin acts as the gatekeeper for the secretion of catecholamines “ hormones that are released into the blood during times of physical or emotional stress. A drug that mimics the action of catestatin would thus allow people to control the hormones that regulate blood pressure.

Based on earlier studies of the structure of catestatin, O’Connor, Tsigelny, and their colleagues figured out which residues of catestatin are responsible for binding to the nicotinic receptor “ similar to mapping how the ridges on a key fit into a lock. They created a three-dimensional model of the most important binding centers “ the pharmacophore model. Then they screened about 250,000 3D compound structures in the Open NCI Database to select ones that fit this fingerprint of active centers. They discovered seven compounds that met the requirements, and tested those compounds in live cells to gauge their effects on catecholamines. Based on their findings, they tried one compound (TKO-10-18) on hypertensive mice, and showed that this compound produced the same anti-hypertensive effect as catestatin.

“Analysis of the catestatin molecule yielded a family of small organic compounds with preserved potency and pathway specificity,” said Valentina Kouznetsova, PhD, an associate project scientist at SDSC and the UC San Diego Moores Cancer Center. “Further refinement of our model should lead to the synthesis and development of a novel class of antihypertensive agents.”


New clues illuminate Alzheimer’s roots

Scientists at Rice University and the University of Miami have figured out how synthetic molecules designed at Rice latch onto the amyloid peptide fibrils thought to be responsible for Alzheimer’s disease. Their discovery could point the way toward therapies to halt or even reverse the insidious disease.

The metallic dipyridophenazine molecules strongly bind to pockets created when fibrils form from misfolded proteins that cells fail to destroy. When excited under a , the molecules luminesce, which indicates the presence of the fibrils. That much was known by Rice researchers, but until now the process was a mystery.

By combining their talents in biophysics (at Rice) and computer simulation (at Miami), researchers pinpointed four such pockets along the fibril where the hydrophobic (water-averse) molecules can bind. They believe their work will help chemists design molecules to keep the fibrils from forming the plaques found in Alzheimer’s patients.

The teams led by Rice chemist Angel MartĂ­ and Miami chemist Rajeev Prabhakar reported their results in the Journal of the American Chemical Society this month.

Two years ago, MartĂ­ and Nathan Cook, a graduate student in his lab and lead author of the new paper, combined ruthenium complexes with solutions containing the spaghetti-like amyloid fibrils. The complexes don’t luminesce by themselves, but when they link to an amyloid fibril, they can be triggered by light at one wavelength to glow at another; this helps the researchers “see” the fibrils.

This ability to track amyloids was a great step forward, but left open the question of why the complexes latched onto the fibrils at all, Cook said.

“We had no way to figure it out because our experimental techniques can’t identify binding sites,” he said. “The standard (used to analyze proteins) is to crystallize your material and use X-rays to determine where everything is positioned. The problem with amyloid beta is the fibrils are not uniform, and you can’t crystallize them. All you would get is an amorphous lump.”

But a door opened when Prabhakar, a theoretical and computational chemist who specializes in amyloids, contacted MartĂ­ and suggested a collaboration. “We both knew the other was working with amyloid betas,” MartĂ­ said. “We were able to figure out how many amyloid beta monomers (molecules that can bind with each other) had to come together to form fibrils, while he modeled the interactions. When we brought all the data together, we had a perfect match.”

“Basically, we learned from the model that we need two monomers to form a binding site,” Marti said. “The cleft where the ruthenium complex binds is completely hydrophobic, the same as the complex. Neither wants to be exposed to water, so when they find each other, they don’t have a choice but to come together. It turns out that’s exactly what needs to happen to turn on the photoluminescent response of the compound.”

MartĂ­ said testing various concentrations of monomers with ruthenium complexes helped them determine that a little more than two monomers, on average, was sufficient to get the “light switch” effect. Prabhakar’s analysis found four specific locations along the aggregating monomers where the ruthenium complexes could bind: two at the ends where the monomers tend to bind to each other, and two in the middle.

“It was a complicated system to model and we tried hard, using a variety of computational techniques,” Prabhakar said. “In the end, we were amazed to find our results in perfect agreement with the experiments performed in the MartĂ­ lab.”

The researchers called the end locations “A and B,” and the middle clefts “C and D.” The hydrophobic A and B sites exist only at the edges of the fibrils, which limits their exposure to the complexes, MartĂ­ said. “But there are lots of C and D sites,” he said. “That explains why the ruthenium complexes don’t inhibit the aggregation of fibrils. It seems the system prefers to bind another monomer, rather than a ruthenium complex, at the ends.

“But now that we understand the mechanism, we can design more hydrophobic complexes that could bind strongly to the ends and prevent further elongation of the fibril,” he said.

“There’s a whole variety of ways to tweak this that could potentially disrupt a binding pocket,” Cook said.

More challenges lie beyond the new discovery, he said. New research indicates toxic oligomers may be catalyzed by the formation of amyloid fibrils. “We might be able to prevent the formation of these oligomeric species by binding to the surface, which would completely change the surface chemistry of the ,” MartĂ­ said. “These are the things we are really interested in doing right now.”


World first computer saving lives

Complex decision-making in the second-by-second handling of trauma patients in hospital emergency rooms is being aided by a world-first computer system at Melbourne’s The Alfred Hospital.

Created by software engineers at Swinburne University of Technology, the support tool reduced the number of errors emergency staff make by 21 percent during a 33 month trial period.

“It’s huge – we were hoping for a five percent change,” said Swinburne’s Kon Mouzakis who led the software design.

Financed by a $1.8 million grant from the Transport Accident Commission, the program – the Trauma Reception and Resuscitation System – was created at the request of Professor Mark Fitzgerald, the director of The Alfred’s Trauma Centre.

“Keeping a severely injured person alive after an accident can be one of the most stressful circumstances for trauma treatment teams,” Professor Fitzgerald said.

“When faced with multiple injuries – fractures, head injuries, extensive bleeding -critical decisions must be made about every 70 seconds. The potential for error – especially an error of omission – is real.”

Swinburne’s software experts developed a decision support tool to eliminate human error in the critical first 30 minutes of a trauma patient’s treatment.

A patient’s basic information has to be typed in when they arrive but all other data is entered automatically or by a touch interface.

A large screen displays patient information – vital signs, diagnoses, and all the procedures being performed – and actively prompts the team to take a particular action.

The 18 month trial of the system involved 1171 patients. During the testing phase, the Trauma Reception and Resuscitation System was used in two of The Alfred’s four  bays.

Some 2700 errors were documented during the trial with the least number of errors occurring in the bays fitted with the system. The has since been extended to all four bays.

Mr Mouzakis said rolling out the system to rural hospitals could lead to better survival rates for regional patients for whom critical time can be taken up in transporting them to major centres such as The Alfred.

Swinburne and The Alfred are working on a military adaptation. A tablet-type device that could use a cut-down version of the system software is being developed.


A new research paper suggesting a connection between a specific gene and the ageing process of a species of worms could be responsible for revealing important information for future Alzheimer’s disease treatment. According to Yee Lian Chew, the main investigator of the new study, the low levels of a specific protein are responsible for shortening the life of the worm, while also hastening other age-related changes. The protein is regulated by the tau gene, a gene that is found in worms and humans as well. Yee Lian’s study was recently published in the Journal of Cell Science.

According to Yee Lian, the investigated worms that lacked the tau gene had a shorter lifespan by almost one thirds, when compared to the worms that had the tau gene. This results provides important information that the tau gene is closely connected to the processes involved in the regulation of lifespan. Her findings, in addition to the experiments that were conducted on laboratory mice and other laboratory animal models might prove to be extremely important for the development of future therapies for patients suffering from Alzheimer’s disease. She also added that there is one study that suggests that if the activity of the tau gene is lowered, the patients will experience cognitive improvement. However, her new study suggests that if the activity of the tau gene is too little, it causes the ageing processes to hasten.

The test subjects of the study are known as Caenorhabditis elegans, a species of nematodes found in the soils of temperate weather. The nematode is transparent and it is less than 1 mm in length. Yee Lian says that these nematodes are excellent study models for brain ageing due to the fact that they are transparent. Their transparency allows researchers to easily examine the changes that occur in their brains.

Even though humans are much more complex than nematodes, Yee Lian says that there are numerous similarities on molecular level. Furthermore, experiments on nematodes are made easy due to their lack of complexion. These particular nematodes only have a little over 300 brain cells, compared to humans, who have more than 100 billion brain cells. The small number of brain cells found in these worms allowed researchers to observe each cell individually.

The human ageing process is linked to subtle changes that occur within the brain. These subtle changes can be compared to the changes investigated in the brains of the nematodes. Some of the similarities include the formation and growth of beads and branches across the axons of the nerve cells. The most important discovery of the study is that of the occurrence of the abnormal axon structures. In the worms with either low activity of the tau gene or complete absence, the abnormal structures first appear before middle age. However, the worms with a normal activity of the tau gene only experienced these abnormal structures later in their lives.

“This suggests that the lack of tau causes worm brain cells to age faster”, concluded Yee Lian Chew. Her discovery could bring new important information for Alzheimer’s disease therapies. It is approximated that Alzheimer’s disease currently affects 1 in every 4 people aged over 85. Yee Lian added that her research is a stepping stone for the ultimate goal: creating an improved diagnosis technique and better treatment for patients suffering from Alzheimer’s disease.


    Current medical practices for patients suffering from brain cancer involve the irradiation of the brain. This technique is used to slow the progression of the cancerous proliferation and increase the survivability of patients. However, according to a recent study published in the journal Proceedings of the National Academy of Sciences, patients who undergo this irradiation therapy are more susceptible to cognitive function deterioration.

    The research team from the University of California, Irvine, from the United States, consisting of professor Vipar Parihar and professor Charles Limoli, investigated the effects of cranial irradiation on laboratory mice. The results of their investigation show that the radiation exposure is responsible for neurodegenerative changes in the architecture of the brain. These changes are similar to the neurodegenerative changes that occur in patients suffering from diseases such as Alzheimer’s or Huntington’s.

    Cranial irradiation therapy is currently the leading therapy scheme used for all forms of adult and pediatric brain cancer. This is due to its ability to stop or at least limit the further growth of the tumors. Although it increases the survivability rates and lifespan of patients, cranial irradiation also accounts for reducing the life quality, through irreversible cognitive damage. The exposure of the CNS (central nervous system) to radiation causes memory problems, attention disorders, learning impairments and other cognitive damage.

    To better understand the implications of radiation exposure, the research team used laboratory mice. These mice were exposed to two levels of radiation, 1 Gy and 10 Gy respectively. These doses of radiation are both much lower than the maximum levels of radiation that the central nervous system can suffer before it gets damaged. After 10 and 30 days, the research team killed the mice and used their brains for further investigation. Specifically, they investigated the hippocampus, which is the structure of the brain involved in memorizing and learning.

    The researchers revealed that there were dose-dependent reductions caused to the dendrites of the neurons. These reductions involved the area and the length of the dendrites, and the branching between neurons. All of these reductions were found after the 30 day mark. Furthermore, the number and the density of the bulbous extensions and the dendritic spines, decreased. Dendritic spines are an important part of the connections formed inside the central nervous system, being associated with memory storage. The correlation between the number of dendritic spines and the density of the synapses is responsible for the cognitive abilities of each individual.

    Huntington’s, Alzheimer’s, and other neurodegenerative diseases are characterized by the reduction of the dendritic complexity. Furthermore, the abnormalities of the dendritic spines can be associated with other diseases, such as AIDS-related dementia, temporal lobe epilepsy, Rett’s, Down’s, and Fragil-X syndromes.

    The two researchers conclude that the reduction of the dendritic spine density and the persistence of the neurodegenerative damage caused by irradiation for more than 30 days is consistent with the fact that the damage caused is irreversible.


    A research team from the NIH (National Institutes of Health) from the United States managed to identify the neural circuits that are linked to the learning abilities and behavioral patterns of laboratory mice. Their study was recently published in the journal Nature Neuroscience; results showing that specific neural circuits in the forebrain are responsible for decision making and adaptive learning. According to the researchers, their findings provide better understanding of the processes of the brain that command and control the ability of mice to choose and adapt their behavior to certain situations. Furthermore, the research team believes that the results of the study might bring new insight on different compulsive behavior patterns, such as gambling, eating, drinking alcohol, and other obsessions.

    Kenneth Warren, who is the main author of the study, and also the director of the NIAAA (National Institute on Alcohol Abuse and Alcoholism), explains that researchers need to understand much more information about the pathways that are involved in the learning of a behavioral response, versus the ability to switch the old behavioral with a new response that is better.  He adds that the current study reveals novel information about the brain processes that take part in the behavioral response pathway and the way these processes can go off course.

    Alcoholism, like other obsessions and addictions, is a disease in which patients progressively lose their behavioral control. This results in compulsive and other undesired actions. Researchers believe that the normal brain processes that are involved in the completion of daily activities become redirected towards the use and abuse of alcohol.

    The research, which was conducted by the research team from the NIAAA, received support from the NIMH (National Institute of Mental Health) and from the University of Cambridge, from the United Kingdom. Researchers used a wide variety of techniques in order to better understand the processes behind choice. One of the techniques involved the use of a simple choice task. In order to perform this task, mice needed to touch specific images presented on a touchscreen computer display. If they touched the correct image, food would be awarded to them. Through the use of multiple imaging techniques, the research team visualized and recorded the neural activity of the tested mice. They learned that the consistency of choice was responsible for activating the dorsal striatum, which is a part of the forebrain. Thus, scientists believe that the dorsal striatum plays an important part in the neural pathways of decision-making, motivation, and reward.

    Contrariwise, when the mice were taught to switch their image choice to a new one, in order to receive the food reward, the dorsal striatum stopped its activity. In response, other regions of the prefrontal cortex activated. In order to further investigate the results, the research team blocked a component of the NMDA receptor known as the GluN2B unit. This component is known to bind glutamate in two distinct areas of the brain: the frontal cortex and the striatum. Precedent studies revealed that the GluN2B unit plays a critical role in spatial reference, attention, and memory.

    The research team discovered that if the GluN2B unit is inactivated in the dorsal striatal, the mice experienced slower learning capabilities. However, when inactivating the GluN2B unit in the prefrontal cortex, the mice were less able to re-learn the image required to receive the food reward, once the image was changed from the original one. According to the senior author of the study, professor Andrew Holmes, the information discovered in the study further adds data to the understanding of neural control, making the GluN2B unit a critical substrate for the processes of learning and behavioral flexibility.


    A new research published in the journal The Lancet questions a common clinical practice performed on patients suffering from CKD (chronic kidney disease). This clinical practice involves the prescription of high doses of calcium. The research team, comprised of researchers from the University of Toronto and from the University of Alberta, in Canada, revealed that lower doses of calcium improved the heart condition of patients and also increased their survivability rate.

    The lead author of the study is associate professor Sophie Jamal, from the Women’s College Hospital, while the senior author is professor Ross Tsuyuki, from the Faculty of Medicine & Dentistry, at the University of Alberta. According to the results of their study, survivability increased by approximately 22% when patients suffering from chronic kidney disease were given lower doses of calcium, instead of the usual high doses. Furthermore, patients who weren’t prescribed calcium showed improved coronary arteries health. More than 4,500 patients from 11 randomized clinical trials were involved in the study. Researchers also compared the subjects who received calcium to the patients who received other therapies, such as sevelamer and lanthanum. These therapies do not involve the use of calcium.

    Patients suffering from chronic kidney disease are being prescribe calcium due to the impossibility of their kidney to excrete phosphate. This inability causes the levels of phosphate in the organism to rise, causing damage and other disorders. Calcium binds to phosphate and creates a compound that can be eliminated from the organism through urine. Both sevelamer and lanthanum can also remove the excess phosphate from the organism, but they cost more in comparison to calcium.

    Professor Tsuyuki affirms that patients taking the non-calcium-based drugs are less susceptible to death and have healthier hearts. However, he adds that further investigations are needed in order to determine whether high levels of calcium are bad, or if the treatment with lanthanum or sevelamer is good. Tsuyuki says that many scientists and physicians have been advocating for the removal of calcium therapy for patients suffering from chronic kidney disease, adding that the current study adds more evidence towards removing calcium from chronic kidney disease therapy.

    Sophie Jamal says that although physicians have been prescribing calcium supplements in order to stop the rise of phosphate levels, numerous studies have shown that these supplements can damage the heart and increase the prevalence of heart disease. She adds that the current study validates the results of previous research, showing that long-term treatment with calcium supplements has important medical consequences.

    According to an editorial that accompanied the study article in the journal The Lancet, a question was raised, whether the results of the study could mean the “game will change”, meaning that the therapy plans for patients suffering from chronic kidney disease will be changed in the near future. Researchers say that due to the high calcium intake, heart disease has become the number one enemy for people suffering from chronic kidney disease.


    A recent study reveals the motives behind the decreased brain plasticity of patients suffering from Alzheimer’s and Parkinson’s disease. The study also links the decreased plasticity to diabetes and insulin resistance. The study spanned over a period of 5 years and was conducted in order to understand the way stem cells begin and end their migration inside the brain.

    The results of the study surfaced valuable information on the connectivity between brain cells. Professor Maurice Curtis is the main author of the study. His collaborators include Dr Hector Monzo, who was responsible for the experiments conducted during the study, Professor Mike Dragunow, Dr Thomas Park, Dr Deidre Jansson and Distinguished Professor Richard Faull. Curtis explains that during the study, his research team has started testing new drugs that would be able to improve the connectivity between neurons through their action on the polysialic acid removal pathway.

    Brain stem cells are the immature cells of the brain that migrate towards different areas of the brain and differentiate into neurons. After reaching their destination, the stem cells differentiate into neurons, which must create dendrites in order to connect with other neurons. The brain circuits of the brain are formed through the connection of numerous neurons. However, the adult brain contains a substance known as extracellular matrix, which fills up the space between the brain cells. The extracellular matrix found inside the brain is rigid and makes the migration of new stem cells difficult.

    Despite this rigid extracellular matrix, stem cells can still migrate through the brain because of a special compound known as polysialic acid-neural cell adhesion molecule. This compound binds itself to the surface of each stem cell allowing the stem cell to migrate easily, while also reducing the cellular energy consumption. When the stem cell reaches its destination, the compound is removed from its cellular membrane and the stem cells remains in place, differentiates and starts to build its dendrites.

    According to professor Curtis, this process has been known for approximately 20 years. However, there has been very little information regarding the regulation and control of the process. The current study sheds light on the process and what happens to the polysialic acid molecule after it is no longer needed by the stem cell. The research team has been studying the process for the past 5 years, reaching the conclusion that the polysialic acid molecule is internalized after two very specific cues.

    The first cue comes from collagen, which is one of the components of the rigid extracellular matrix. The second cue comes from a gaseous compound known as nitric oxide. Furthermore, the research team discovered that the process of internalization is inhibited by increased levels of insulin and insulin-like growth factor 1. Curtis affirms that the most important key to their breakthrough was determining that in order to understand the process through which the polysialic acid molecule binds to the cell membrane, they first had to find a way to stop the process.

    Researchers determined that higher levels of insulin were responsible for inhibiting the removal of the polysialic acid molecules, thus blocking the formation of synapses between the newly formed neuron and other nearby brain cells. They affirm that this discovery could hold important information about why the brains of patients suffering from Alzheimer’s and Parkinson’s disease have a diminished level of plasticity.