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Physically fit frogs have faster-changing genomes

During exercise, the circulatory system provides blood and oxygen to the tissues that are needed most

When physical activity has stopped, the rush of blood and oxygen when circulation is restored to those tissues produces a burst of free radicals that can cause wear and tear on DNA, eventually causing genetic changes that -- if they affect the DNA of cells that make eggs or sperm -- can be passed to future generations.

"It's like a recipe book," Wray said. "It tells you how to make the meal. You need to know the amounts. You need to know the order. The noncoding DNA tells you how much to make, when to make it and under what circumstances."

common diseases are probably more influenced by regulatory differences, Harismendy said. These include Type 2 diabetes, Crohn's disease, Alzheimer's Disease and a variety of cancers, including breast, colon, ovarian, prostate and lung.

According to Wray, research has shown that diseases like bipolar syndrome and clinical depression may be associated with noncoding mutations that determine whether the brain is producing too much or not enough of a particular neurotransmitter. One noncoding mutation gives a person almost complete protection against the nasty malaria parasite, plasmodium vivax.

Another piece of noncoding DNA regulates the enzyme responsible for lactose tolerance, the ability to digest milk. Research by Wray and other scientists has shown that in four populations where dairy consumption is a vital part of the diet, new mutations have appeared that essentially keep the gene that produces the lactase enzyme from switching off.

And recent research done by evolutionary biologists suggests that differences in regulatory DNA may represent a major part of what separates us from chimpanzees.

The study defined a new role for a protein called polynucleotide phosphorylase (PNPASE) in regulating the import of RNA into mitochondria. Reducing the expression--or output--of PNPASE decreased RNA import, which impaired the processing of mitochondrial genome-encoded RNAs. Reduced RNA processing inhibited the translation of proteins required to maintain the mitochondrial electron transport chain that consumes oxygen during cell respiration to produce energy. With reduced PNPASE, unprocessed mitochondrial-encoded RNAs accumulated, protein translation was inhibited, and energy production was compromised, leading to stalled cell growth.

Geng Wang developed a strategy to target and import specific RNA molecules encoded in the nucleus into the mitochondria and, once there, to express proteins needed to repair mitochondrial gene mutations.

First, the researchers had to find a way to stabilize the reparative RNA so that it was moved out of the nucleus and then localized to the mitochondrial outer membrane. This was accomplished by modifying an export sequence to direct the RNA to the mitochondrion. Once the RNA was in the area of the transport machinery on the mitochondrial surface, then a second transport sequence was required to direct the RNA into the targeted organelle. With these two modifications, a wide range of RNAs were targeted to and imported into the mitochondria, where they worked to repair defects in mitochondrial respiration and energy production in two different cell line models of human mitochondrial disease.

The Bdnf gene generates one short transcript and one long transcript. He discovered that when the long-form Bdnf transcript is absent, the growth factor BDNF is only synthesized in the cell body of a neuron but not in its dendrites. The neuron then produces too many immature synapses, resulting in deficits in learning and memory in mice. Xu also found that the mice with the same Bdnf mutation grew to be severely obese

large-scale genome-wide association studies showed Bdnf gene variants are, in fact, linked to obesity.

both leptin and insulin stimulate synthesis of BDNF in neuronal dendrites in order to move their chemical message from one neuron to another through synapses. The intent is to keep the leptin and insulin chemical signals moving along the neuronal highway to the correct brain locations, where the hormones will turn on a program that suppresses appetite.

"If there is a problem with the Bdnf gene, neurons can't talk to each other, and the leptin and insulin signals are ineffective, and appetite is not modified

One possible strategy would be to produce additional long-form Bdnf transcript using adeno-associated virus-based gene therapy, Xu says. But although this kind of gene therapy has proven to be safe, it is difficult to deliver across the brain blood barrier,

reserved remains of a shaggy monster that lived in Siberia at -40°C 10,000 years ago have been uncovered;

Cloning the mammoth has been an aim of Japanese scientists for several years. They discovered almost intact bone marrow from a thigh bone in Yakutsk and hope to use a female elephant for what is obviously more than a simple experiment within the next 5 years.