Gene genie

[Jo Bowyer]

Researchers have developed new single-cell sequencing methods that could be used to map the cell origins of various brain disorders, including Alzheimer’s, Parkinson’s, schizophrenia

http://neurosciencenews.com/brain-ce...-disease-8157/

Using the information from RNA sequencing and chromatin mapping methods, researchers were able to map which cell types in the brain were affected by common risk alleles–snippets in DNA that occur more often in people with common genetic diseases. Researchers could then rank which subtypes of neurons or glial cells are more genetically susceptible to different brain diseases. For example, they found that two subtypes of glial cells, microglia and oligodendrocytes, were the first and second most at risk, respectively, for Alzheimer’s disease. They also identified microglia as most at risk for bipolar disorder, and a subtype of excitatory neurons as most at risk for schizophrenia.

[marcel]

This research may open a (new) window to finding therapies for disease with epigenetic components

[QUOTE]The laboratory staff demonstrated that under conditions of extreme stress, such as starvation, a fascinating phenomenon occurs: offsprings whose parents had suffered starvation showed a much longer life expectancy than worms whose parents had been well-fed. This phenomenon lasts several generations - and then disappears.
This mechanism can also be reset. If normal inheritance of small RNA molecules continues for a limited number of generations, renewed stress will cause the cycle to start again, and will prolong the epigenetic, or beyond the DNA, inheritance. Studies conducted on relatively simple animals are the research basis for understanding the operational mechanisms of inheritance processes that also apply to humans, including epigenetic mechanisms. The next step is to investigate whether small RNA inheritance may also affect the process of evolution.
/QUOTE]

from

http://www.odedrechavilab.com

[Jo Bowyer]

Reprogramming bacteria instead of killing them could be the answer to antibiotic resistance

https://theconversation.com/reprogra...c%20resistance

[Jo Bowyer]

We are multitudes

https://aeon.co/essays/microchimeris...4d912-69418129

[Jo Bowyer]

Gene Network That Regulates Motor Neuron Formation During Embryonic Development Identified

http://neurosciencenews.com/motor-ne...elopment-8431/

[Jo Bowyer]

The Stress-Induced Transcription Factor NR4A1 Adjusts Mitochondrial Function and Synapse Number in Prefrontal Cortex

http://www.jneurosci.org/content/38/6/1335?etoc=

[Jo Bowyer]

Major mental illnesses unexpectedly share brain gene activity, raising hope for better diagnostics and therapies

http://www.sciencemag.org/news/2018/...et_cid=1841749

[Jo Bowyer]

Timing is Everything, to Our Genes

http://neurosciencenews.com/genetics-timing-8461/

“This is the first time a reference map of daily gene expression has been established,” says Satchidananda Panda, a professor in Salk’s Regulatory Biology Laboratory and senior author on the paper. “It’s a framework to understand how circadian disruption causes diseases of the brain and body, such as depression, Crohn’s disease, IBD, heart disease or cancer. This will have huge impact on understanding the mechanisms or optimizing cures for at least 150 diseases.”

[Jo Bowyer]

Scientists find key proteins control risk of osteoarthritis during aging

https://www.sciencedaily.com/release...0214181949.htm

The study's findings suggest that FOXO proteins are responsible for the maintenance of healthy cells in the cartilage of our joints.

"We discovered that FoxO transcription factors control the expression of genes that are essential for maintaining joint health," says Martin Lotz, MD, a TSRI professor and senior author of the study, published today in the journal Science Translational Medicine. "Drugs that boost the expression and activity of FoxO could be a strategy for preventing and treating osteoarthritis."

Previous research from Lotz' lab showed that as joints age, levels of FoxO proteins in cartilage decrease. Lotz and his colleagues had also found that people with osteoarthritis have a lower expression of the genes needed for a process called autophagy. Autophagy ("auto" meaning "self" and "phagy" meaning "to eat") is a cell's way of removing and recycling its own damaged structures to stay healthy.

For the new study, researchers used mouse models with FoxO deficiency in cartilage to see how the FoxO proteins affect maintenance of cartilage throughout adulthood.

The researchers noticed a striking difference in the mice with "knockout" FoxO deficiency. Their cartilage degenerated at much younger age than in control mice. The FoxO-deficient mice also had more severe forms of post-traumatic osteoarthritis induced by meniscus damage (an injury to the knee), and these mice were more vulnerable to cartilage damage during treadmill running.

The culprit? The FoxO-deficient mice had defects in autophagy and in mechanisms that protect cells from damage by molecules called oxidants. Specific to cartilage, FoxO-deficient mice did not produce enough lubricin, a lubricating protein that normally protects the cartilage from friction and wear. This lack of lubricin was associated with a loss of healthy cells in a cartilage layer of the knee joint called the superficial zone.

These problems all came down to how FoxO proteins work as transcription factors to regulate gene expression. Without FoxO proteins running the show, expression of inflammation-related genes skyrockets, causing pain, while levels of autophagy-related genes plummet, leaving cells without a way to repair themselves.

[Jo Bowyer]

Men and Women Have Opposite Genetic Alterations in Depression

http://neurosciencenews.com/genetics...pression-8631/

The study combined eight published datasets (four in men and four in women) in a meta-analysis. Senior author Etienne Sibille, PhD, of CAMH, and colleagues analyzed gene expression levels, which indicate how much protein a gene is producing, in postmortem brain tissue of 50 people with MDD (26 men and 24 women) and the same number of unaffected men and women for comparison.

Most of the genes that had altered expression were changed in only men or only women. However, genes that were altered in both men and women were changed in opposite directions. Women had increased expression of genes affecting synapse function, whereas men had decreased expression of the same genes. Women had decreases in genes affecting immune function, whereas men had increased expression of these genes. Additionally, the researchers applied their methods to data from a different set of subjects and replicated the opposing changes.

The analysis included three different brain regions that regulate mood—the anterior cingulate cortex, dorsolateral prefrontal cortex, and amygdala—and that are dysfunctional in MDD. The opposite changes in gene expression were specific to the different brain regions. So if women had increased expression of a particular gene in one region and decreased in another, men showed just the opposite.

“These results have significant implications for development of potential novel treatments and suggest that these treatments should be developed separately for men and women,” said Dr. Seney. For example, in the paper the authors suggest that new treatments targeting the sex-specific pathology in MDD might suppress immune function in men, or boost its function in women.

[Jo Bowyer]

Mysterious skeleton shows molecular complexity of bone diseases

https://www.sciencedaily.com/release...0322134307.htm

To understand the genetic drivers at play, Butte and Nolan extracted a small DNA sample from Ata's ribs and sequenced the entire genome. The skeleton is approximately 40 years old, so its DNA is modern and still relatively intact. Moreover, data collected from whole-genome sequencing showed that Ata's molecular composition aligned with that of a human genome. Nolan noted that 8 percent of the DNA was unmatchable with human DNA, but that was due to a degraded sample, not extraterrestrial biology. (Later, a more sophisticated analysis was able to match up to 98 percent of the DNA, according to Nolan.)

The genomic results confirmed Ata's Chilean descent and turned up a slew of mutations in seven genes that separately or in combinations contribute to various bone deformities, facial malformations or skeletal dysplasia, more commonly known as dwarfism. Some of these mutations, though found in genes already known to cause disease, had never before been associated with bone growth or developmental disorders.

Knowing these new mutational variants could be useful, Nolan said, because they add to the repository of known mutations to look for in humans with these kinds of bone or physical disorders.

"For me, what really came of this study was the idea that we shouldn't stop investigating when we find one gene that might explain a symptom. It could be multiple things going wrong, and it's worth getting a full explanation, especially as we head closer and closer to gene therapy," Butte said. "We could presumably one day fix some of these disorders, and we're going to want to make sure that if there's one mutation, we know that -- but if there's more than one, we know that too."

[Jo Bowyer]

Pain catastrophizing, neuroticism, fear of pain, and anxiety: Defining the genetic and environmental factors in a sample of female twins

http://journals.plos.org/plosone/art...l.pone.0194562

[Jo Bowyer]

Adult Onset Neurodegeneration Has Roots in Early Development

http://neurosciencenews.com/neurodeg...elopment-8714/

[Jo Bowyer]

New computer algorithm deciphers DNA's most well-kept secrets; may help find the links between genes and disease

https://www.sciencedaily.com/release...0405223355.htm

[Jo Bowyer]

We reconstructed the genome of the ‘first animal’


https://theconversation.com/we-recon...first%20animal