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Category: genetics – Page 398

Global patterns in coronavirus diversity

Study reveals interplay of an African bat, a parasite and a virus

Since the emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrom Coronavirus (MERS-CoV) it has become increasingly clear that bats are important reservoirs of CoVs. Despite this, only 6% of all CoV sequences in GenBank are from bats. The remaining 94% largely consist of known pathogens of public health or agricultural significance, indicating that current research effort is heavily biased towards describing known diseases rather than the ‘pre-emergent’ diversity in bats. Our study addresses this critical gap, and focuses on resource poor countries where the risk of zoonotic emergence is believed to be highest. We surveyed the diversity of CoVs in multiple host taxa from twenty countries to explore the factors driving viral diversity at a global scale. We identified sequences representing 100 discrete phylogenetic clusters, ninety-one of which were found in bats, and used ecological and epidemiologic analyses to show that patterns of CoV diversity correlate with those of bat diversity. This cements bats as the major evolutionary reservoirs and ecological drivers of CoV diversity. Co-phylogenetic reconciliation analysis was also used to show that host switching has contributed to CoV evolution, and a preliminary analysis suggests that regional variation exists in the dynamics of this process. Overall our study represents a model for exploring global viral diversity and advances our fundamental understanding of CoV biodiversity and the potential risk factors associated with zoonotic emergence.

Brain organoids may shed light on seizures in Angelman syndrome

The mutation that causes Angelman syndrome makes neurons hyperexcitable, according to a study in brain organoids and mice1. The findings may help explain why about 90 percent of people with the syndrome experience seizures that do not respond to treatment.

Angelman syndrome is a rare genetic condition linked to autism. It is caused when the maternal copy of a gene called UBE3A is either missing or mutated. Apart from seizures, the condition is characterized by developmental delay, problems with balance and speech, and an unusually happy disposition.

The new study found that mutations in UBE3A suppress the production of proteins that keep the activity of ‘big potassium’ ion channels in check. These channels control the flow of large amounts of potassium ions passing through neurons. When the current increases in the absence of UBE3A, the neurons become exceptionally excitable.

America’s most widely consumed oil causes genetic changes in the brain

New UC Riverside research shows soybean oil not only leads to obesity and diabetes, but could also affect neurological conditions like autism, Alzheimer’s disease, anxiety, and depression.

Used for fast food frying, added to packaged foods, and fed to livestock, soybean oil is by far the most widely produced and consumed edible oil in the U.S., according to the U.S. Department of Agriculture. In all likelihood, it is not healthy for humans.

It certainly is not good for mice. The new study, published this month in the journal Endocrinology, compared mice fed three different diets high in fat: soybean oil, soybean oil modified to be low in linoleic acid, and coconut oil.

Why Gene Editors Like CRISPR/Cas May Be a Game-Changer for Neuroweapons

This year marks the Eighth Review Conference (RevCon) of the Biological Toxins and Weapons Convention (BWC). At the same time, ongoing international efforts to further and more deeply investigate the brain’s complex neuronal circuitry are creating unprecedented capabilities to both understand and control neurological processes of thought, emotion, and behavior. These advances have tremendous promise for human health, but the potential for their misuse has also been noted, with most discussions centering on research and development of agents that are addressed by existing BWC and Chemical Weapons Convention (CWC) proscriptions. In this article, we discuss the dual-use possibilities fostered by employing emergent biotechnologic techniques and tools—specifically, novel gene editors like clustered regular interspaced short palindromic repeats (CRISPR)—to produce neuroweapons. Based on our analyses, we posit the strong likelihood that development of genetically modified or created neurotropic substances will advance apace with other gene-based therapeutics, and we assert that this represents a novel—and realizable—path to creating potential neuroweapons. In light of this, we propose that it will be important to re-address current categorizations of weaponizable tools and substances, so as to better inform and generate tractable policy to enable improved surveillance and governance of novel neuroweapons.

Keywords: : CRISPR, Gene editing, Neuroweapon, Neurotherapeutic pathways, Dual-use neuroscience, Biosecurity policy.

T his year marks the Eighth Review Conference (RevCon) of the Biological Toxins and Weapons Convention (BWC), the purpose of which is to ensure that the convened parties’ directives continue to be relevant to and viable for prohibiting the development, production, and stockpiling of biological weapons in the face of newly emerging scientific advancements and biotechnologies. Apropos of issues raised at previous RevCons and elsewhere, there are growing concerns about current and future weaponization of neurobiological agents and tools (ie, “neuroweapons”1–6).

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.”…

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