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Category: genetics – Page 449

Figure 1: A CRISPR–Cas9 genetically engineered mouse model for MERS-CoV replication

A, C57BL/6J mice were genetically engineered using CRISPR–Cas9 genomic editing to encode 288L and 330R in mDPP4 on one chromosome (heterozygous, 288/330+/−) or on both chromosomes (homozygous, 288/330+/+). b, Northern blot of mDPP4 mRNA expression. c, Immunohistochemistry (IHC) of mDPP4 protein in the lungs, brain and kidneys of individual C57BL/6J wild-type (WT), 288/330+/− and 288/330+/+ mice. d, Viral titres for MERS-CoV at 3 days post-infection from C57BL/6J WT, 288/330+/− and 288/330+/+ (all n = 4) mice infected with 5 × 105 plaque-forming units (p.f.u.) of the indicated viruses. Bar graphs show means + s.d.

Can George Church Reverse Aging by 2030?

If you look up ‘scientific overachiever’ in the dictionary, you’re likely to find a two-word definition: George Church.

The American geneticist, molecular engineer, and chemist splits his time between roles as Professor of Genetics at Harvard Medical School and Professor of Health Sciences and Technology at Harvard and MIT. He’s also a member of the National Academy of Sciences, acts as an advisor to a plethora of cutting edge companies, and heads up synthetic biology at the Wyss Institute for Biologically Inspired Engineering, of which he’s a founding member.

Oh, and George is author to hundreds of published papers, 60 patents and a popular science book (also, theoretically, George Church may live in an alternate reality where there are more than 24 hours in a day).

Is schizophrenia a by-product of human evolution?

“Tim Crow must be proud to see his theory being tested at a complex level.” That’s how I tweeted the news on a recent Brain article by van den Heuvel et al (2019). Tim Crow’s theory on schizophrenia as a possible by-product of human brain evolution was quite inspiring and led to many fruitful discussions in our evolutionary psychiatry group when I was a junior trainee (which I wrote about a while ago: EPSIG Newsletter, June 2018). And here it was, the theory was tested by using novel methodology. Now I am pleased to say that the article did not disappoint, so I can enjoy the initial thrill and share my take with the Mental Elf World.

Tim Crow’s original question was intriguing: “Is schizophrenia the price that Homo sapiens pay for language?” (Crow, 1997). He argued that schizophrenia may be considered an extreme variation of brain systems which are relatively new in evolutionary timescale. Brain structures that are mostly implicated in schizophrenia were also unique to humans as mediators of language and higher cognitive functions. Those relatively new (in evolutionary timescale) brain systems may be more vulnerable to insults (e.g. stress, trauma, neurodevelopmental conditions) and manifest as dysfunctional brain circuits in schizophrenia.

The prevalence of schizophrenia is fairly constant across human populations (Jablensky et al. 1992), and the prevalence does not change despite low fecundity rates of people with schizophrenia. This can only be possible in the case of overall genetic predisposition across the population.

Dynamic DNA material with emergent locomotion behavior powered by artificial metabolism

Interesting research paper on a new nanobot technology. I’m watching for ways in which suitable substrates for mind uploading can be constructed, and DNA self-guided assembly has potential.

Here are some excerpts and a weblink to the paper:

“…Chemical approaches have opened synthetic routes to build dynamic materials from scratch using chemical reactions, ultimately allowing flexibility in design…”

… As a realization of this concept, we engineered a mechanism termed DASH—DNA-based Assembly and Synthesis of Hierarchical materials—providing a mesoscale approach to create dynamic materials from biomolecular building blocks using artificial metabolism. DASH was developed on the basis of nanotechnology that uses DNA as a generic material ranging from nanostructures to hydrogels, for enzymatic substrates, and as linkers between nanoparticles…”

“…Next, to illustrate the potential uses of self-generated materials, we created various hybrid functional materials from the DASH patterns. The DASH patterns served as a versatile mesoscale scaffold for a diverse range of functional nanomaterials beyond DNA, ranging from proteins to inorganic nanoparticles, such as avidin, quantum dots, and DNA-conjugated gold nanoparticles (AuNPs) (Fig. 4D, figs. S37 and S38, and Supplementary Text). The generated patterns were also rendered functional with catalytic activity when conjugated with enzymes (figs. S39 and S40 and Supplementary Text). We also showed that the DNA molecules within the DASH patterns retained the DNA’s genetic properties and that, in a cell-free fashion, the materials themselves successfully produced green fluorescent proteins (GFPs) by incorporating a reporter gene for sfGFP (Fig. 4E and figs. S9 and S41) (40). The protein production capability of the materials established the foundation for future cell-free production of proteins, including enzymes, in a spatiotemporally controlled manner.

…” Our implementation of the concept, DASH, successfully demonstrated various applications of the material. We succeeded in constructing machines from this novel dynamic biomaterial with emergent regeneration, locomotion, and racing behaviors by programming them as a series of FSAs. Bottom-up design based on bioengineering foundations without restrictions of life fundamentally allowed these active and programmable behaviors. It is not difficult to envision that the material could be integrated as a locomotive ele-ment in biomolecular machines and robots. The DASH patterns could be easily recognized by naked eyes or smartphones, which may lead to better detection technologies that are more feasible in point-of-care settings. DASH may also be used as a template for other materials, for example, to create dynamic waves of protein expression or nanoparticle assemblies. In addition, we envision that further expansion of artificial metabolism may be used for self-sustaining structural components and self-adapting substrates for chemical production pathways. Ultimately, our material may allow the construction of self-reproducing machines through the production of enzymes from generated materials that, in turn, reproduce the material. Our biomaterial powered by artificial metabolism is an important step toward the creation of “artificial” biological systems with dynamic, life-like capabilities.”…

Continue reading “Dynamic DNA material with emergent locomotion behavior powered by artificial metabolism” | >

US$30 Million to Seed Hundreds of Bold, Innovative Ideas for Human Longevity! — Dr. Victor Dzau, President of the U.S. National Academy of Medicine — Healthy Longevity Global Grand Challenge — ideaXme — Ira Pastor

Missing protein in brain causes behaviors mirroring autism

Scientists at Rutgers University-Newark have discovered that when a key protein needed to generate new brain cells during prenatal and early childhood development is missing, part of the brain goes haywire—causing an imbalance in its circuitry that can lead to long-term cognitive and movement behaviors characteristic of autism spectrum disorder.

“During , there is a coordinated series of events that have to occur at the right time and the right place in order to establish the appropriate number of cells with the right connections,” said Juan Pablo Zanin, Rutgers-Newark research associate and lead author on a paper published in the Journal of Neuroscience.” Each of these steps is carefully regulated and if any of these steps are not regulated correctly, this can impact behavior.”

Zanin has been working with Wilma Friedman, professor of cellular neurobiology in the Department of Biological Sciences, studying the p75NTR —needed to regulate —to determine its exact function in brain development, gain a better understanding of how this genetic mutation could cause to die off and discover whether there is a genetic link to autism or like Alzheimer’s.

The connection between ribosomes and telomeres in plants

Findings from a recent research project, conducted by a Marshall University scientist and assistant professor in the Marshall University College of Science, with researchers in Texas, was recently published in the December issue of the prestigious online journal, Nature Communications.

Dr. Eugene Shakirov is studying the connection between ribosomes and telomeres in plants. Telomeres are the physical ends of chromosomes and they shorten with age in most cells. Accelerated shortening of telomeres is linked to age-related diseases and overly long telomeres are often linked to cancer.

Telomere length varies between individuals at birth and is known to predetermine cellular lifespan, but the genes establishing length variations are largely unknown. The research being done by Shakirov, along with collaborators at the University of Texas at Austin, Texas A&M University, HudsonAlpha Institute for Biology and the Kazan Federal University in Russia focused on the study of the genetic and epigenetic causes of natural telomere length variation in Arabidopsis thaliana, a small flowering plant.

Pathways that extend lifespan by 500 percent identified

Scientists at the MDI Biological Laboratory, in collaboration with scientists from the Buck Institute for Research on Aging in Novato, Calif., and Nanjing University in China, have identified synergistic cellular pathways for longevity that amplify lifespan fivefold in C. elegans, a nematode worm used as a model in aging research.

The increase in lifespan would be the equivalent of a human living for 400 or 500 years, according to one of the scientists.

The research draws on the discovery of two major pathways governing aging in C. elegans, which is a popular model in aging research because it shares many of its genes with humans and because its short lifespan of only three to four weeks allows scientists to quickly assess the effects of genetic and environmental interventions to extend healthy lifespan.

Biological scientists identify pathways that extend lifespan

Scientists at the MDI Biological Laboratory, in collaboration with scientists from the Buck Institute for Research on Aging in Novato, Calif., and Nanjing University in China, have identified synergistic cellular pathways for longevity that amplify lifespan fivefold in C. elegans, a nematode worm used as a model in aging research.

The increase in would be the equivalent of a human living for 400 or 500 years, according to one of the scientists.

The research draws on the discovery of two major pathways governing aging in C. elegans, which is a popular model in aging research because it shares many of its genes with humans and because its short lifespan of only three to four weeks allows scientists to quickly assess the effects of genetic and environmental interventions to extend healthy lifespan.

Cancer-like metabolism makes brain grow

The size of the human brain increased profoundly during evolution. A certain gene that is only found in humans triggers brain stem cells to form a larger pool of stem cells. As a consequence, more neurons can arise, which paves the way to a bigger brain. This brain size gene is called ARHGAP11B and so far, how it works was completely unknown. Researchers at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden now uncovered its mode of action. They show that the ARHGAP11B protein is located in the powerhouse of the cell—the mitochondria—and induces a metabolic pathway in the brain stem cells that is characteristic of cancer cells.

The research group of Wieland Huttner, a founding director of the Max Planck Institute of Molecular Cell Biology and Genetics, has been investigating the underlying the expansion of the brain during mammalian evolution for many years. In 2015, the group reported a key role for a gene that is only present in humans and in our closest extinct relatives, the Neanderthals and Denisovans. This gene, named ARHGAP11B, causes the so-called basal brain stem to expand in number and to eventually increase the production of neurons, leading to a bigger and more folded brain in the end. How the gene functions within the basal brain stem cells has been unknown so far.

Takashi Namba, a postdoctoral scientist in the research group of Wieland Huttner, wanted to find the answer to this question, together with colleagues from the Max Planck Institute, the University Hospital Carl Gustav Carus Dresden, and the Department of Medical Biochemistry at the Semmelweis University, Budapest. He found that the ARHGAP11B protein is located in mitochondria, the organelles that generate most of the cell’s source of chemical energy and hence are often referred to as the powerhouse of the cell. Takashi Namba explains the results: We found that ARHGAP11B interacts with a protein in the membrane of mitochondria that regulates a membrane pore. As a consequence of this interaction, the pores in the membrane are closing up, preventing calcium leakage from the mitochondria. The resulting higher calcium concentration causes the mitochondria to generate chemical energy by a metabolic pathway called glutaminolysis.

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