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Category: genetics – Page 356

Glioblastoma is one of the most common and aggressive forms of brain cancer, and it is particularly difficult to treat. Now, researchers from the University of Pennsylvania School of Medicine have come up with a new approach to treatment for the disease, by growing organoids based on a patient’s own tumor to find the most effective treatments. Digital Trends spoke to senior author Dr. Donald O’Rourke to learn more.

The technique uses mini-brains — pea-sized organoids grown from stem cells which recreate features of full-scale brains. The mini-brains are similar enough to real brains that they can be used for testing out medical treatments to see how a full-sized brain would respond.

The breakthrough in this research is regarding treatment individualization. One of the challenges of treating a complex disease like brain cancer is that different people respond in different ways to the various treatment options available. After surgery has been performed to remove a tumor, doctors typically begin further treatment using radiation or chemotherapy around one month later. That means there isn’t always time to use perform genetic analysis to see which treatment might be best suited for a particular patient — the doctors need to know what will work and start further treatment as soon as possible.

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Talk with an Alzheimer’s researcher and you’ll likely hear the same lament: Finding a treatment or cure is incredibly challenging because scientists are not even certain what exactly causes the neurological disease in the first place.

In fact, researchers speak of a “web of causation” that can lead to Alzheimer’s. In addition to genetics, scientists look to so-called lifestyle elements such as blood pressure and blood sugar levels. Even the bacteria that live in our mouths are being scrutinized for their potential role in Alzheimer’s.

One element that researchers are completely certain about is that people who carry the apolipoprotein E4 gene — known as APOE4 — are at a greater risk of developing Alzheimer’s.

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With new technology to edit genes, scientists are now working on things that once seemed impossible. But what are the boundaries? See the full 60 Minutes interview with Church, here: https://cbsn.ws/34ZhuTs

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Continue reading “The complicated ethics of genetic engineering” | >

Neurochemicals such as serotonin and dopamine play crucial roles in cognitive and emotional functions of our brain. Vesicular monoamine transporter 1 (VMAT1) is one of the genes responsible for transporting neurotransmitters and regulating neuronal signaling. A research team led by Tohoku University has reconstructed ancestral VMAT1 proteins, revealing the functional changes in neurotransmitter uptake of VMAT1 throughout the course of human evolution.

Human bodies are made up of millions of cells. Each individual contains a specific set of instruction of codes that make up all of a living thing’s genetic material. These instructions are known as genomes. PhD candidate Daiki Sato and Professor Masakado Kawata of the Graduate School of Life Sciences at Tohoku University, and two of the authors involved in the current study, previously discovered VMAT1 to be one of the genes that had evolved throughout human lineage.

VMAT 1 contains two human-specific mutations, or where the genomes changed, with the change being represented as 130Glu to 130Gly and from 136Asn to 136Thr. Previous studies have shown that having the new 130Gly/136Thr variant decreases the uptake of neurotransmitters and is associated with higher depression and/or anxiety. In this study, Sato, Kawata and their colleagues revealed the evolutionary changes in neurotransmitter uptake of VMAT1 by reconstructing ancestral VMAT1 proteins. First they applied a fluorescent substrate to visualize and quantify the neurotransmitter uptake of each genotype. The ancestral (130Glu/136Asn) VMAT1 protein exhibited an increased uptake of neurotransmitters compared to a derived (130Gly/136Thr) genotype. Given that the derived (130Gly/136Thr) genotype is shown to be associated with depression and/or anxiety in modern human populations. “This results of our study reveal that our ancestors may have been able to withstand higher levels of anxiety or depression,” noted the authors.

In this study, Sato, Kawata and their colleagues revealed the evolutionary changes in neurotransmitter uptake of VMAT1 by reconstructing ancestral VMAT1 proteins. First they applied a fluorescent substrate to visualize and quantify the neurotransmitter uptake of each genotype. The ancestral (130Glu/136Asn) VMAT1 protein exhibited an increased uptake of neurotransmitters compared to a derived (130Gly/136Thr) genotype. Given that the derived (130Gly/136Thr) genotype is shown to be associated with depression and/or anxiety in modern human populations. “This results of our study reveal that our ancestors may have been able to withstand higher levels of anxiety or depression,” noted the authors.

Continue reading “Evolutionary Changes in Brain Potentially Make us More Prone to Anxiety” | >

Researchers led by the European Molecular Biology Laboratory (EMBL) in Heidelberg and the Center for Bioinformatics at Saarland University in Saarbrücken, Germany, have developed a cheaper and faster method to check for genetic differences in individual cells. It outperforms existing techniques with respect to the information received. This new method could become a new standard in single-cell research, and potentially for clinical diagnosis in disease genetics, including cancer. The results have been published in Nature Biotechnology.

“Our new method to study genetic variations in could transform the field of mutation detection,” says Ashley Sanders, one of the lead authors of the study, working at EMBL Heidelberg, Germany. The method she and her colleagues developed, termed tri-channel processing (scTRIP), allows them to study genetic variations within the DNA of a single cell and measure genetic variations directly as they form in new . In contrast to existing methods that were able to detect only large-scale changes in the genome, scTRIP can detect small-scale changes along with many types of genetic variations that were invisible using other single-cell methods.

The researchers tested their method in patient-derived leukemia cells. In their sample, the team found four times more variants in the patient than were detected by standard clinical diagnostics. These included a missed clinically relevant translocation that drove the overexpression of a cancer-causing gene. They also observed a catastrophic chromosome rearrangement that was missed in the initial leukemia diagnosis. It probably occurred when a single chromosome shattered and was then glued back together in a rearranged order.

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Methylation clocks are far and away the most accurate markers of a person’s age, and so are a promising tool for evaluating anti-aging interventions, but they are a bit of a black box. We know from statistics that certain places on chromosomes become steadily methylated ( or demethylated ) with age, but we often don’t know what effect that has on expression of particular genes.

For the first time, a clock has been devised based on proteins in the blood that is comparable in accuracy to the best methylation clocks. This has the advantage of being downstream of epigenetics, so it is less of a black box. What can we learn from the proteins that are increased ( and decreased ) with age?

I’ve written often and enthusiastically about the utility of methylation clocks for evaluation of anti-aging interventions [ blog, blog, blog, journal article ]. This technology offers a way to promptly identify small age-reversal successes (perhaps not in individuals, but averaged over a cohort of ~50 to 100 subjects). Before these tests were available, we had no choice but to wait — usually 10 years or more — for enough experimental subjects to die that we could be sure the intervention we were evaluating affected life expectancy. (This is the plan of the worthy but ridiculously expensive TAME trial promoted by Nir Barzilai.)

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2019 was nuts for neuroscience. I said this last year too, but that’s the nature of accelerating technologies: the advances just keep coming.

There’re the theoretical showdowns: a mano a mano battle of where consciousness arises in the brain, wildly creative theories of why our brains are so powerful, and the first complete brain wiring diagram of any species. This year also saw the birth of “hybrid” brain atlases that seek to interrogate brain function from multiple levels—genetic, molecular, and wiring, synthesizing individual maps into multiple comprehensive layers.

Brain organoids also had a wild year. These lab-grown nuggets of brain tissue, not much larger than a lentil, sparked with activity similar to preterm babies, made isolated muscles twitch, and can now be cloned into armies of near-identical “siblings” for experimentation—prompting a new round of debate on whether they’ll ever gain consciousness.

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You heard about reversing the epigenetic clock 2.5 years? Living drugs? CAR T cells? Fight cancer? Here ya go.

Vision Weekend is the annual member gathering of Foresight Institute, a non-profit for advancing beneficial technologies for the long-term flourishing of life.

More info on speakers and program: https://foresight.org/vision-weekend-2019/.

Continue reading “Zinaida Good | Reversing Epigenetic Aging and Immunosenescent Trends in Humans | VISION WEEKEND 2019” | >