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Category: genetics – Page 286

A ‘consciousness conductor’ synchronizes and connects mouse brain areas

For scientists searching for the brain’s ‘control room, an area called the claustrum has emerged as a compelling candidate. This little-studied deep brain structure is thought to be the place where multiple senses are brought together, attention is controlled, and consciousness arises. Observations in mice now support the role of the claustrum as a hub for coordinating activity across the brain. New research from the RIKEN Center for Brain Science (CBS) shows that slow-wave brain activity, a characteristic of sleep and resting states, is controlled by the claustrum. The synchronization of silent and active states across large parts of the brain by these slow waves could contribute to consciousness.

A serendipitous discovery actually led Yoshihiro Yoshihara, team leader at CBS, to investigate the claustrum. His lab normally studies the sense of smell and the detection of pheromones, but they chanced upon a genetically engineered mouse strain with a specific population of brain cells that was present only in the claustrum. These neurons could be turned on using optogenetic technology or selectively silenced through , thus enabling the study of what turned out to be a vast, claustrum-controlled network. The study by Yoshihara and colleagues was published in Nature Neuroscience on May 11.

They started out by mapping the claustrum’s inputs and outputs and found that many higher-order brain areas send connections to the claustrum, such as those involved in sensation and motor control. Outgoing connections from the claustrum were broadly distributed across the brain, reaching numerous brain areas such as prefrontal, orbital, cingulate, motor, insular, and entorhinal cortices. “The claustrum is at the center of a widespread brain network, covering areas that are involved in cognitive processing,” says co-first author Kimiya Narikiyo. “It essentially reaches all higher brain areas and all types of neurons, making it a potential orchestrator of brain-wide activity.”

Neuroengineers hack fruit fly brain and remotely control its movements

A research team led by Rice University neuroengineers has created wireless technology to remotely activate specific brain circuits in fruit flies in under one second.

The team – an assemblage of experts in genetic engineering, nanotechnology, and electrical engineering – used magnetic signals to activate targeted neurons that controlled the body position of freely moving fruit flies in an enclosure.

The researchers first created genetically modified flies bred to express a special heat-sensitive ion channel in neurons that cause flies to partially spread their wings, a common mating gesture. They then injected magnetic nanoparticles that could be heated with an applied magnetic field.

The Virus Zoo: A Quick Primer on Molecular Virology

The Virus Zoo is my latest educational blog post! I’ve written up ~1 page ‘cheat sheets’ on the molecular biology of specific viruses. I cover genome, structure, and life cycle. So far, my zoo includes adeno-associated virus (AAV), adenovirus, and herpes simplex virus 1 (HSV-1). However, I plan to add more viruses as time goes on! Some others I would like to incorporate later are coronavirus, HIV, anellovirus, lentivirus, ebolavirus, and MS2 bacteriophage. Feel free to suggest other interesting viruses in the comments! All images were created by me. #virology #molecularbiology #biotechnology #genetherapy #virus #biochemistry #genetics

Genome and Structure:

AAV genomes are about 4.7 kb in length and are composed of ssDNA. Inverted terminal repeats (ITRs) form hairpin structures at ends of the genome. These ITR structures are important for AAV genomic packaging and replication. Rep genes (encoded via overlapping reading frames) include Rep78, Rep68, Rep52, Rep40.1 These proteins facilitate replication of the viral genome. As a Dependoparvovirus, additional helper functions from adenovirus (or certain other viruses) are needed for AAVs to replicate.

AAV capsids are about 25 nm in diameter. Cap genes include VP1, VP2, VP3 and are transcribed from overlapping reading frames.2 The VP3 protein is the smallest capsid protein. The VP2 protein is the same as VP3 except that it includes an N-terminal extension with a nuclear localization sequence. The VP1 protein is the same as VP2 except that it includes a further N-terminal extension encoding a phospholipase A2 (PLA2) that facilitates endosomal escape during infection. In the AAV capsid, VP1, VP2, and VP3 are present at a ratio of roughly 1:1:10. It should be noted that this ratio is actually the average of a distribution, not a fixed number.

MIT system can fix your software bugs on its own (by borrowing from other software)

Circa 2015

New software being developed at MIT is proving able to autonomously repair software bugs by borrowing from other programs and across different programming languages, without requiring access to the source code. This could save developers thousands of hours of programming time and lead to much more stable software.

Bugs are the bane of the software developer’s life. The changes that must be made to fix them are often trivial, typically involving changing only a few lines of code, but the process of identifying exactly which lines need to be fixed can be a very time-consuming and often very frustrating process, particularly in larger projects.

But now, new software from MIT could take care of this, and more. The system, dubbed CodePhage, can fix bugs which have to do with variable checks, and could soon be expanded to fix many more types of mistakes. Remarkably, according to MIT researcher Stelios Sidiroglou-Douskos, the software can do this kind of dynamic code translation and transplant (dubbed “horizontal code transplant,” from the analogous process in genetics) without needing access to the source code and across different programming languages, by analyzing the executable file directly.

Curing Debilitating Genetic Diseases: “Soft” CRISPR May Offer a New Fix for Genetic Defects

Targeted repairs with ‘nicks’ of single DNA

DNA, or deoxyribonucleic acid, is a molecule composed of two long strands of nucleotides that coil around each other to form a double helix. It is the hereditary material in humans and almost all other organisms that carries genetic instructions for development, functioning, growth, and reproduction. Nearly every cell in a person’s body has the same DNA. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA).

Researchers find link between genetic mutations and cancer treatment resistance

Researchers from the University of Michigan Rogel Cancer Center, studying the molecular landscape of over 500 patients with an aggressive form of multiple myeloma, discovered a prevalence of activated key oncogenic pathways in these patients, much more than previously thought. Upwards of 45–65% of NF-κB and RAS/MAPK pathways each had alterations. The study was published in Nature Communications.

Further, Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology, and his team found a link between mutations and RASopathies, a certain group of genetic syndromes, in patients with relapsed treatment-resistant . This was the first observation of its kind.

The team compared the molecular makeup of patients with untreated multiple myeloma to those with the relapsed treatment-resistant version of the disease. Comparing these patients allowed researchers to describe drivers of the more aggressive form of multiple myeloma.

Alcohol consumption and telomere length: Mendelian randomization clarifies alcohol’s effects

Observational studies of the relationship between alcohol use and telomere length have produced conflicting results. The largest such study to date, of 4,567 individuals, found no association between alcohol intake and either baseline or longitudinal change in telomere length [9]. Another analysis of two American cohorts (n = 2623) also reported null findings [10]. On the other hand, a few small studies (sample size range: 255‑1800) have observed associations with heavy drinking or AUD. Participants with AUD have been reported to have shorter telomeres compared to healthy controls [11]. A longitudinal study of Helsinki businessmen observed that higher midlife alcohol consumption was associated with shorter telomere length in older age [8]. Drinking 30 g/day of alcohol in older participants was associated with shorter telomeres in a Korean study [12]. Associations were stronger in those experiencing the alcohol flush reaction, raising the intriguing possibility that acetaldehyde, ethanol’s toxic breakdown product, is mechanistically involved. In a recent review of 27 studies, 10 showed significant associations between alcohol use and telomere length [13]. The studies included cross-sectional and longitudinal designs. The majority comprised European participants with ages ranging from the third to seventh decade. Most studies observed positive associations between alcohol and LTL. However heterogeneity between studies in methods of quantifying telomere length and categorizing alcohol intake hindered meta-analysis and aggregation of the data.

MR seeks to identify potentially causal determinants of an outcome. It estimates the association between genetically predicted levels of an exposure and an outcome of interest. Residual confounding and reverse causation aim to be less of a concern than in most other methods of analyzing observational data [14]. With MR, genetic proxies can be used to study the effects of genetically-predicted variability in alcohol consumption or AUD risk. To our knowledge, no MR study of alcohol and telomere length has yet been attempted.

We conducted a large observational study of two alcohol phenotypes, alcohol consumption and AUD, and leucocyte. We then performed linear MR analyses to investigate the evidence for a causal effect between alcohol consumption/AUD and LTL. Estimates generated by our observational and genetic methods were compared. Genetic distinction between different alcohol use traits motivates their separate analysis. Quantity/frequency measures such as drinks per week and AUDIT-C (Alcohol Use Disorders Identification Test Consumption, a 3 item screening tool), while moderately genetically correlated with AUD, have distinct patterns of genetic correlation with other traits [13]. Furthermore, as there has been much speculation about potential J-shaped relationships between alcohol and health outcomes [15], we performed a non-linear MR analysis to examine the shape of the relationship between alcohol consumption and telomere length.

Ever heard about bio-weapons that use DNA to kill specific person? They are reality now

A U.S. House Intelligence Committee member cautioned that bioweapons using a target’s DNA to kill only that individual are being created. US Representative Jason Crow of Colorado spoke on Friday at the Aspen Security Forum and cautioned Americans not to be too careless about sharing their DNA with private firms due to the impending arrival of the new type of weapon. “You can target a biological weapon that will kill that person or take them off the battlefield or make them inoperable,” Crow said. “You can take someone’s DNA, you know, take their medical profile,” he added.

Given the prevalence of DNA testing services, where customers voluntarily share their genetic mapping with companies to learn more about their ancestry and health, the congressman said it is concerning that these weapons are being developed. Although 23andMe has maintained time and time again that it does not sell its customers’ private information, it is one of many DNA companies that have done so when asked by the police.

As a member of the Senate Armed Services Committee, US Senator Joni Ernst of Iowa claimed that the US’s adversaries may deploy such DNA bioweapons to attack food supply on a large scale. Ernst forewarned that specific animals relied upon by civilians, armies, or towns could be the target of biological weapons, resulting in scarcity and food poverty and weakening populations.

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