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Scientists Identify Two Genes (HoxA5 and HoxC5) Essential for Breathing

Scientists Identify Two Genes (HoxA5 and HoxC5) Essential for Breathing | Longevity science | Scoop.it

Researchers have discovered that two genes Hoxa5 and Hoxc5 play a critical role in establishing the neuronal circuits required for breathing.

 

The three-year study published in the journal Nature Neuroscience identifies a molecular code that distinguishes a group of muscle-controlling nerve cells collectively known as the phrenic motor column (PMC).

“These cells lie about halfway up the back of the neck, just above the fourth cervical vertebra, and are probably the most important motor neurons in your body,” explained senior author Prof Jeremy Dasen of the Howard Hughes Medical Institute.

 

Harming the part of the spinal cord where the PMC resides can instantly shut down breathing. But relatively little is known about what distinguishes PMC neurons from neighboring neurons, and how PMC neurons develop and wire themselves to the diaphragm in the fetus. The PMC cells relay a constant flow of electrochemical signals down their bundled axons and onto the diaphragm muscles, allowing the lungs to expand and relax in the natural rhythm of breathing.

 

“We now have a set of molecular markers that distinguish those cells from other populations of motor neurons, so that we can study them in detail and look for ways to selectively enhance their survival,” Prof Dasen said.

To find out what distinguishes PMC neurons from their spinal neighbors in mice, the scientists injected a retrograde fluorescent tracer into the phrenic nerve, which wires the PMC to the diaphragm, and then looked for the spinal neurons that lit up as the tracer worked its way back to the PMC. They used transgenic mice that express green fluorescent protein (GFP) in motor neurons and their axons in order to see the phrenic nerve. After noting the characteristic gene expression pattern of these PMC neurons, the scientists began to determine their specific roles.

 

“When Hoxa5 and Hoxc5 are silenced in embryonic motor neurons in mice,” the scientists reported, “the PMC fails to form its usual, tightly columnar organization and doesn’t connect correctly to the diaphragm, leaving a newborn animal unable to breathe.”

 

“Even if you delete these genes late in fetal development, the PMC neuron population drops and the phrenic nerve doesn’t form enough branches on diaphragm muscles,” Prof Dasen said.

 

Prof Dasen plans to use the findings to help understand the wider circuitry of breathing – including rhythm-generating neurons in the brain stem, which are in turn responsive to carbon dioxide levels, stress, and other environmental factors. “Now that we know something about PMC cells, we can work our way through the broader circuit, to try to figure out how all those connections are established,” he said.

 

“Once we understand how the respiratory network is wired we can begin to develop novel treatment options for breathing disorders such as sleep apneas,” said lead author Dr Polyxeni Philippidou.


Via Dr. Stefan Gruenwald
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Receptor for Tasting Fat is CD36

Receptor for Tasting Fat is CD36 | Longevity science | Scoop.it
For the first time, a team of scientists at Washington University School of Medicine has identified a human receptor that can taste fat.

 

CD36 is a membrane protein found on the surface of many cell types in humans, mice, rats and many vertebrate animals. The findings also suggest that variations in the CD36 gene can make people more or less sensitive to the taste of fat.

 

“The ultimate goal is to understand how our perception of fat in food might influence what foods we eat and the quantities of fat that we consume,” said Dr. Nada Abumrad, senior investigator and the Dr. Robert A. Atkins Professor of Medicine and Obesity Research.

 

“In this study, we’ve found one potential reason for individual variability in how people sense fat. It may be, as was shown recently, that as people consume more fat, they become less sensitive to it, requiring more intake for the same satisfaction. What we will need to determine in the future is whether our ability to detect fat in foods influences our fat intake, which clearly would have an impact on obesity.”

 

The CD36 discovery follows research that had identified a role for the gene in rats and mice. Scientists had learned that when animals are genetically engineered without a working CD36 gene, they no longer display a preference for fatty foods. In addition, animals that can’t make the CD36 protein have difficulty digesting fat.

 

Up to 20 percent of people are believed to have the variant in the CD36 gene that is associated with making significantly less CD36 protein. That, in turn, could mean they are less sensitive to the presence of fat in food.

 

Dr. Abumrad was the first to identify CD36 as the protein that facilitates the uptake of fatty acids. She explained that better understanding of how the protein works in people could be important in the fight against obesity.

“Diet can affect sensitivity to fat, and in animals, diet also influences the amount of CD36 that’s made,” added Dr. Pepino. “If we follow the results in animals, a high-fat diet would lead to less production of CD36, and that, in turn, could make a person less sensitive to fat. From our results in this study, we would hypothesize that people with obesity may make less of the CD36 protein. So it would seem logical that the amounts of the protein we make can be modified, both by a person’s genetics and by the diet they eat.”


Via Dr. Stefan Gruenwald
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Analysis: Entering the age of the $1 million medicine

Analysis: Entering the age of the $1 million medicine | Longevity science | Scoop.it

The Western world's first drug to fix faulty genes promises to transform the lives of patients with an ultra-rare disease that clogs their blood with fat. The only snag is the price.

 

The gene therapy for lipoprotein lipase deficiency (LPLD), a hereditary disorder that raises the risk of potentially lethal inflammation of the pancreas, is likely to cost more than $1 million per patient when it goes on sale in Europe this summer.

 

 

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Embryo survival gene may fight range of diseases: study

A gene that keeps embryos alive appears to control the immune system and determine how it fights chronic diseases like hepatitis and HIV, and autoimmune diseases like rheumatoid arthritis, scientists said on Monday.

 

Although the experts have only conducted studies on the gene Arih2 using mice, they hope it can be used as a target for drugs eventually to fight a spectrum of incurable diseases.

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Faster, cheaper gene sequencing points to greater cancer understanding

A common mutation in a tumor-suppressing gene could explain why blacks are more likely to get early breast and colon cancer, researchers at Georgia Health Sciences University said.The ability to more quickly and cheaply ...

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How to create beating heart muscle cells | KurzweilAI

How to create beating heart muscle cells | KurzweilAI | Longevity science | Scoop.it

UCLA stem-cell researchers have found for the first time a surprising and unexpected plasticity in the embryonic endothelium, the place where blood stem cells are made in early development.

 

They found that the lack of one transcription factor, a type of gene that controls cell fate (by regulating other genes), allows the precursors that normally generate blood stem and progenitor cells in blood-forming tissues to become something very unexpected — beating cardiomyocytes, or heart muscle cells.

 

 

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4-Year-Old’s Missing Gene Discovered Through Crowdfunded Sequencing | Singularity Hub

4-Year-Old’s Missing Gene Discovered Through Crowdfunded Sequencing | Singularity Hub | Longevity science | Scoop.it

Crowdfunding is starting to accomplish some pretty impressive feats beyond video game reboots and smartphone-linked watches on Kickstarter.

 

In mid-July, the nonprofit organization Rare Genomics Institute (RGI), which sequences genomes of children with rare genetic diseases, announced that it had identified a previously unknown gene variant...

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Twin study isolates key ageing genes

Twin study isolates key ageing genes | Longevity science | Scoop.it

In a study at Kings College London using groups of identical twins, genes were identified that are switched on or off by epigenetic factors - natural mechanisms other than the underlying DNA which change the gene expression, and could include external factors such as...

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All genomes are dysfunctional: broken genes in healthy individuals

All genomes are dysfunctional: broken genes in healthy individuals | Longevity science | Scoop.it

Genome-sequencing studies indicate that all humans carry many genetic variants predicted to cause loss of function (LoF) of protein-coding genes, suggesting unexpected redundancy in the human genome. It is estimated that human genomes typically contain ~100 genuine LoF variants with ~20 genes completely inactivated. A recent paper in Science describes some of these rare and likely deleterious LoF alleles, including 26 known and 21 predicted severe disease–causing variants, as well as common LoF variants in nonessential genes.


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Record gene haul points to better cancer screening

Record gene haul points to better cancer screening | Longevity science | Scoop.it

 

LONDON (Reuters) - New research has nearly doubled the number of genetic variations implicated in breast, prostate and ovarian cancer, offering fresh avenues for screening at-risk patients and, potentially, developing better drugs.

The bumper haul of 74 gene changes that can increase risks for the three hormone-related cancers, announced by scientists on Wednesday, is the result of the largest ever study of its kind.

 

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Bone-tired? How about ‘gene-tired’?

Bone-tired? How about ‘gene-tired’? | Longevity science | Scoop.it

A new study, paid for by the U.S. Air Force but relevant for anyone with a small child, a large prostate or a lot on the mind, is helping illuminate what’s happening at the genetic level when we don’t get enough sleep.

 

It turns out that chronic sleep deprivation — in this experiment, less than six hours a night for a week — changes the activity of about 700 genes, which is roughly 3 percent of all we carry.

 

 

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Aging healthfully is not just a matter of having good genes

Aging healthfully is not just a matter of having good genes | Longevity science | Scoop.it
As people grow older, they can benefit from paying attention to food, exercise, sleep and stress.
Ray and Terry's 's insight:

Eating well and exercising, plus taking care of your stress and sleeping patterns go a long way towards preserving good health. Ray & Terry include these steps, as well as attentive medical care and personal research, in their TRANSCEND steps towards longer healthy life.

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Linda Holroyd's curator insight, November 12, 2014 11:59 AM

Bake, sleep more, skip a meal, exercise, stress less, have a hobby

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Cancers Delete Suppressing Genes on Chromosomes - Softpedia

Cancers Delete Suppressing Genes on Chromosomes - Softpedia | Longevity science | Scoop.it

Numerous cancer types are known to have an influence on human chromosomes, deleting certain portions in order to be able to infect the body. Now, researchers have shown that some of these deleted sections contain clusters of tumor-suppressing genes.

 

Experts say that this has been suspected for quite some time, but that evidence to prove that this was indeed the case has been lacking. The new investigation looked at a copy-number alteration (CNA), a deletion that occurs on the short arm of chromosome 8 (8p).

 

The study was carried out on mouse models of human liver cancer. Researchers found that this specific CNA affected a series of genes that work together to counteract tumors as soon as they start evolving.

 

 

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Genes that Fit | Washington and Puget Sound Business News Source | Seattle Business Magazine

Genes that Fit | Washington and Puget Sound Business News Source | Seattle Business Magazine | Longevity science | Scoop.it

"Should doctors insist on a genetic test for each patient before prescribing a new drug? They don’t today, but if a new generation of low-cost, easy-to-use gene testing systems comes to market, such tests could become standard fare..."


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Nutrition, Disease & Polymorphisms

Nutrition, Disease & Polymorphisms | Longevity science | Scoop.it

"My paternal grandmother lived to be 101. At the time of her death, she was not taking any prescription medicines..."

 

Are some people genetically predisposed to need prescription drugs? Are some more dependent on antioxidants than others? There may be nutrient-gene interactions that affect our health.

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Awesome Video Explains Synthetic Biology | Singularity Hub

Awesome Video Explains Synthetic Biology | Singularity Hub | Longevity science | Scoop.it

"A succinct, yet powerful animation titled “Synthetic Biology Explained” shows the incredible potential of this emergent field and how engineering will transform the field of genetics to produce some truly amazing technology.

 

With the sequencing of the human genome and the increased understanding of genes that have followed..."

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A world within a tumour – new study shows just how complex cancer can be

A world within a tumour – new study shows just how complex cancer can be | Longevity science | Scoop.it

Cancer is a puzzle of staggering complexity. Every move towards a solution seems to reveal yet another layer of mystery. For a start, cancer isn’t a single disease, so we can dispense with the idea of a single “cure”. There are over 200 different types, each with their own individual quirks. Even for a single type – say, breast cancer – there can be many different sub-types that demand different treatments. Even within a single subtype, one patient’s tumour can be very different from another’s. They could both have very different sets of mutated genes, which can affect their prognosis and which drugs they should take.


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