Deaf And Ness Seizures Result When In Mysterious protein Deleted Mice

Science Daily (Jan. 28, 2008) - Scientists have discovered that mice genetically engineered to lack a particular protein in the brain and have profound deafness, seizures. The finding suggests a pathway, they say, for exploring the causes of hereditary deafness in humans and epilepsy.

More broadly, the discovery provides an entry point for resisting new insight into the role of glutamate, the chemical messenger carried by the protein, says the team, led by scientists at the University of California, San Francisco. Glutamate is involved in virtually every brain function, including sensory imagination, learning and memory.

The missing protein is a particular "vesicular transport neurotransmitter," a machine nerve cells within that ferry chemical messengers, or "neurotransmitters," from the fluid-filled vesicles into cytoplasm that are positioned at the tips of nerve cells and serve to release onto neurotransmitters Neighboring Cells. Carrier neurotransmitters and work together to make all possible neural communication essentially in the brain.

While the neurotransmitter glutamate is the major excitatory messenger in the brain, the neurotransmitter GABA is the major inhibitory messenger, sending signals that reduce agitation and anxiety. Two other neurotransmitters, dopamine and serotonin, modulate the activity of neural circuits influence mood to sleep and other aspects of behavior.

Scientists have known for several years about two vesicular glutamate transporters, VGLUT1 and VGLUT2. As would be predicted, they are expressed on nerve cells that release glutamate. More recently, scientists have identified VGLUT3. To their surprise, they have discovered that VGLUT3 is primarily expressed by nerve cells that GABA release, acetylcholine and serotonin, another neurotransmitter. VGLUT3 is also released in some non-nerve cells, tissues outside the brain. These findings led scientists to suspect that might VGLUT3 support function, other than some neurotransmission.

In the current study, published in the Jan 24, 2008 issue of Neuron, the team explored the role of VGLUT3 in mice genetically engineered to lack the forwarder. The effect was dramatic.

"Mice lacking the shipper are completely deaf from birth," says the senior author of the study, Robert Edwards, MD, professor of neurology and physiology at University of California, San Francisco. "Moreover, they had significant seizures.

As the gene encodes VGLUT3 that is known to have sequence changes in humans, it is possible that these or other changes may be the underlying cause of deafness or epilepsy in humans, according to the research. They plan to screen people with these conditions for changes in the gene vglut3, says the first author of the study, Rebecca Seal, PhD, post a fellow in the laboratory Edwards

In addition, because the mice in the study lacked the protein in all cells that would normally make it, the team plans to make a "conditional knockout", in which the gene is inactivated only in specific types of nerve cells. This will reveal which VGLUT3 nerve cells expressing a particular account for brain function.

At the outset of the study, the team VGLUT3 knew that was expressed during brain development by a population of inhibitory GABAergic-brainstem in the pathway that transmits information about sound. They suspected that the absence of VGLUT3 - which would allow the release of the excitatory glutamate - might produce a subtle defect in sound localization. Instead, the animals were completely deaf.

The explanation, they learned, was that VGLUT3 contributes to the release of glutamate at a key point in the production of sound. It turns out that inner hair cells of the cochlea, which are known to convert the auditory input, or signal, glutamate release, VGLUT3 express, transporters and contributes to the release of the first onto glutamate neurons in the pathway that carries into the sound Brain. Without VGLUT3, No. glutamate that is released at synapses.

The scientists also knew that from the outset VGLUT3 is expressed by a subset of - in the hippocampus and cortex that are known to release the inhibitory transmitter GABA. The presence of these VGLUT3-might also suggested that the release excitatory glutamate. Since inhibitory-contribute to a range of brain wave oscillations active, the team hypothesized that the disruption of these systems might affect brain wave activity in the cerebral cortex.

In fact, EEG (electroencephalograph) revealed that all of the mice had seizures, and even when they were having full-blown attacks they had electrical discharges in abnormal brain, known as "epilepiform activity. Surprisingly, the seizures - which last Up to two minutes - were accompanied by little or no change in behavior.

The team plans to screen young patients with hereditary or early-onset epilepsy to see if they have changes in this protein, says Edwards.

Since VGLUT3 may be required for relatively subtle aspects of behavior elicited not easily in a mouse, the research would also like to study and identify human patients, according to Edwards. Neuromodulatory The effect of glutamate release by serotonin, he says, may be easier to detect in humans.

"If we found lacking VGLUT3 patients," he says, "we could carry out psychological testing, which in turn would give us an idea why most serotonin and glutamate release.

"This is a case of a mouse model to patients leading us who will, in turn, suggest additional roles for functional glutamate that we can test in the mouse. The results will help us to understand basic brain function and how it goes awry in Disease . "

Other co-author of the study were Omar Akil, UCSF Department of Otolaryngology, Eunyoung Yi, Johns Hopkins School of Medicine, Christopher M. Weber, UCSF Department of Otolaryngology, Lisa Grant, Johns Hopkins School of Medicine; Jong Yoo, Baylor School of Medicine; Amanda Clausewitz, University of Pittsburgh, Karl Kandler, University of Pittsburgh, Jeffrey L. Noebels, Baylor School of Medicine, Elisabeth Glowatzki, Johns Hopkins School of Medicine and Lawrence R. Lustig, UCSF Department of Otolaryngology.

The study was funded by the National Alliance for Research on Schizophrenia and Depression and by several institutes of the National Institutes of Health, including the Institute of Mental Health, Neurological Disorders and Stroke, Child Health and Human Development and Drug Abuse.

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Unusual fish-eating dinosaur had crocodile-like skull

This image shows the results of the CT scan reconstruction. The Baryonyx snout bone is transparent brown. This shows us that the teeth (yellow) had extremely deep roots and that Baryonyx had independently evolved a bony palate (the pink structure), also seen in crocodilians -- another feature that makes this dinosaur even more 'crocodile-like'. Credit: Emily Rayfield.
An unusual dinosaur has been shown to have a skull that functioned like a fish-eating crocodile, despite looking like a dinosaur. It also possessed two huge hand claws, perhaps used as grappling hooks to lift fish from the water.

Dr Emily Rayfield at the University of Bristol, UK, used computer modelling techniques – more commonly used to discover how a car bonnet buckles during a crash – to show that while Baryonyx was eating, its skull bent and stretched in the same way as the skull of the Indian fish-eating gharial – a crocodile with long, narrow jaws.

Dr Rayfield said: “On excavation, partially digested fish scales and teeth, and a dinosaur bone were found in the stomach region of the animal, demonstrating that at least some of the time this dinosaur ate fish. Moreover, it had a very unusual skull that looked part-dinosaur and part-crocodile, so we wanted to establish which it was more similar to, structurally and functionally – a dinosaur or a crocodile.

“We used an engineering technique called finite element analysis that reconstructs stress and strain in a structure when loaded. The Baryonyx skull bones were CT-scanned by a colleague at Ohio University, USA, and digitally reconstructed so we could view the internal anatomy of the skull. We then analysed digital models of the snouts of a Baryonyx, a theropod dinosaur, an alligator, and a fish-eating gharial, to see how each snout stressed during feeding. We then compared them to each other.”

The results showed that the eating behaviour of Baryonyx was markedly different from that of a typical meat-eating theropod dinosaur or an alligator, and most similar to the fish-eating gharial. Since the bulk of the gharial diet consists of fish, Rayfield’s study suggests that this was also the case for Baryonyx back in the Cretaceous.

Dr Angela Milner from the Natural History Museum, who first described the dinosaur and is co-author on the paper, said: “I thought originally it might be a fish-eater and Emily’s analysis, which was done at the Natural History Museum, has demonstrated that to be the case.

“The CT-data revealed that although Baryonyx and the gharial have independently evolved to feed in a similar manner, through quirks of their evolutionary history their skulls are shaped in a slightly different way in order to achieve the same function. This shows us that in some cases there is more than one evolutionary solution to the same problem.”

The unusual skull of Baryonyx is very elongate, with a curved or sinuous jaw margin as seen in large crocodiles and alligators. It also had stout conical teeth, rather than the blade-like serrated ones in meat-eating dinosaurs, and a striking bulbous jaw tip (or ‘nose’) that bore a rosette of teeth, more commonly seen today in slender-jawed fish eating crocodilians such as the Indian fish-eating gharial.

The dinosaur in question, Baryonyx walkeri, was discovered near Dorking in Surrey, UK in 1983 by an amateur collector, William Walker, and named after him in 1986 by Alan Charig and Angela Milner. It is an early Cretaceous dinosaur, around 125 million years old, and belongs to a family called spinosaurs.

Source : University of Bristol

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New method developed to identify genetic determinants of Alzheimer's disease

A rapid and accurate DHPLC assay for determination of apolipoprotein E genotypes has been developed by researchers from the Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. This assay combines PCR and DHPLC and can be used to conduct efficient genotyping of the human population, which in turn will help in the diagnosis and treatment of Alzheimer’s disease. A description of the assay has been published this month in the Journal of Alzheimer’s Disease.

Apolipoprotein E is a predisposing gene of Alzheimer’s disease and many other diseases. APOE has three major alleles, å2, å3 and å4. The combinations of the three common alleles result in six genotypes (å2å2, å3å3, å4å4, å2å3, å3å4, and å2å4) that exist within the population. Many studies indicate that people who have the E4 allele are at greater risk to develop Alzheimer's disease than those with the E3 allele and that the E2 allele may even help resist Alzheimer's disease. As a result, the rapid and accurate determination of APOE genotypes and the assessment of disease predisposition will be extremely valuable in augmenting the clinical diagnosis and treatment of the disease.

The medical genetic team, led by Professor Xiang-Min Xu at Southern Medical University, developed the assay during research funded by the National Science Fund for Distinguished Young Scholars of China. The polymerase chain reaction (PCR) was designed to generate the 191-bp amplicons containing two common polymorphisms within codons 112 and 158 in exon4 of the APOE gene. The PCR amplicons for each sample were subjected to denaturing high-performance liquid chromatography (DHPLC) analysis, which was performed under partially denaturing conditions as determined by profiling the mixture of a tested sample and a homozygous standard control amplicon at the given ratio. In almost 300 samples detected, the accuracy of the assay reached 100%.

Dr. Tian-Ming Gao, Head of the Neurobiology Department, School of Basic Medical Sciences, Southern Medical University: “As China has a huge population that is stepping into old age, the number of the victims of Alzheimer’s disease is on the rise. Therefore, we felt that the development of a rapid and accurate assay that can determine individuals predisposed to Alzheimer’s disease would have great utility.”

Dr. Wei-ping Liao, Head of the Institute of Neuroscience, Guangzhou Medical College: “This method can be applied to a vast range of diseases and has created a new approach for the molecular diagnosis of genetic diseases. Based on the results from this method, neurologists can know more about the genetic background of a patient. It will help in further diagnosis and treatment.”

original link:http://www.biologynews.net

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