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Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection

Utilizing neurotransmitters as a passport into the brain:


Safe and efficient delivery of blood-brain barrier (BBB)–impermeable cargos into the brain through intravenous injection remains a challenge. Here, we developed a previously unknown class of neurotransmitter–derived lipidoids (NT-lipidoids) as simple and effective carriers for enhanced brain delivery of several BBB-impermeable cargos. Doping the NT-lipidoids into BBB-impermeable lipid nanoparticles (LNPs) gave the LNPs the ability to cross the BBB. Using this brain delivery platform, we successfully delivered amphotericin B (AmB), antisense oligonucleotides (ASOs) against tau, and genome-editing fusion protein (−27)GFP-Cre recombinase into the mouse brain via systemic intravenous administration. We demonstrated that the NT-lipidoid formulation not only facilitates cargo crossing of the BBB, but also delivery of the cargo into neuronal cells for functional gene silencing or gene recombination. This class of brain delivery lipid formulations holds great potential in the treatment of central nervous system diseases or as a tool to study the brain function.

NASA: Virtual Guest Mars 2020 Perseverance

We’re going back to Mars, and we’d like you to be our virtual guest on the trip. On July 30, NASA will launch the Mars 2020 Perseverance rover on a seven-month journey to the Red Planet. After landing in Jezero Crater, the robotic astrobiologist and scientist will search for signs that microbes might have lived on Mars long ago, collect soil samples to be returned to Earth on a future mission and pave the way for human exploration beyond the Moon. Perseverance will be accompanied by a helicopter called Ingenuity, the first attempt at powered flight on another world.

Because of the coronavirus pandemic and in the interest of health and safety, NASA can’t invite you to Florida to watch the launch personally. However, there are many ways you can participate virtually:

SPOCD1 is an essential executor of piRNA-directed de novo DNA methylation

In mammals, the acquisition of the germline from the soma provides the germline with an essential challenge, the necessity to erase and reset genomic methylation1. In the male germline, RNA-directed DNA methylation silences young active transposable elements (TEs)2–4. The PIWI protein MIWI2 (PIWIL4) and its associated PIWI-interacting RNAs (piRNAs) instruct TE DNA methylation3,5. piRNAs are proposed to tether MIWI2 to nascent TE transcripts; however, the mechanism by which MIWI2 directs de novo TE methylation is poorly understood but central to the immortality of the germline. Here we define the interactome of MIWI2 in foetal gonocytes that are undergoing de novo genome methylation and identify a novel MIWI2-associated factor, SPOCD1, that is essential for young TE methylation and silencing. The loss of Spocd1 in mice results in male-specific infertility but impacts neither piRNA biogenesis nor localization of MIWI2 to the nucleus. SPOCD1 is a nuclear protein and its expression is restricted to the period of de novo genome methylation. We found SPOCD1 co-purified in vivo with DNMT3L and DNMT3A, components of the de novo methylation machinery as well as constituents of the NURD and BAF chromatin remodelling complexes. We propose a model whereby tethering of MIWI2 to a nascent TE transcript recruits repressive chromatin remodelling activities and the de novo methylation apparatus through SPOCD1. In summary, we have identified a novel and essential executor of mammalian piRNA-directed DNA methylation.

BCI training to move a virtual hand reduces phantom limb pain

Objective To determine whether training with a brain–computer interface (BCI) to control an image of a phantom hand, which moves based on cortical currents estimated from magnetoencephalographic signals, reduces phantom limb pain.

Methods Twelve patients with chronic phantom limb pain of the upper limb due to amputation or brachial plexus root avulsion participated in a randomized single-blinded crossover trial. Patients were trained to move the virtual hand image controlled by the BCI with a real decoder, which was constructed to classify intact hand movements from motor cortical currents, by moving their phantom hands for 3 days (“real training”). Pain was evaluated using a visual analogue scale (VAS) before and after training, and at follow-up for an additional 16 days. As a control, patients engaged in the training with the same hand image controlled by randomly changing values (“random training”). The 2 trainings were randomly assigned to the patients. This trial is registered at UMIN-CTR (UMIN000013608).

Results VAS at day 4 was significantly reduced from the baseline after real training (mean [SD], 45.3 [24.2]–30.9 [20.6], 1/100 mm; p = 0.009 < 0.025), but not after random training (p = 0.047 0.025). Compared to VAS at day 1, VAS at days 4 and 8 was significantly reduced by 32% and 36%, respectively, after real training and was significantly lower than VAS after random training (p < 0.01).

Potential new treatment approach to fatal COVID-19

Researchers from the University of Colorado Anschutz Medical Campus and Pathways Bioscience in the United States have found that activating a transcription factor involved in oxidative stress regulation, antiviral activity, and inflammation may serve as a new treatment approach to coronavirus disease 2019 (COVID-19).

The scientists propose that the antiviral and anti-inflammatory effects of activating nuclear factor erythroid 2-related factor 2 (Nrf2) may reduce symptoms and stop the “cytokine storm syndrome” that can be fatal in cases of COVID-19.

A pre-print version of the study can be accessed on the bioRxiv* server, while the manuscript undergoes peer review.

Dogs Can Sniff Out Coronavirus Infections, German Study Shows

Dogs with a few days of training are capable of identifying people infected with the coronavirus, according to a study by a German veterinary university.

Eight dogs from Germany’s armed forces were trained for only a week and were able to accurately identify the virus with a 94% success rate, according to a pilot project led by the University of Veterinary Medicine Hannover. Researchers challenged the dogs to sniff out Covid-19 in the saliva of more than 1,000 healthy and infected people.

Neurons are genetically programmed to have long lives

When our neurons—the principle cells of the brain—die, so do we.

Most neurons are created during and have no “backup” after birth. Researchers have generally believed that their survival is determined nearly extrinsically, or by outside forces, such as the tissues and that neurons supply with .

A research team led by Sika Zheng, a biomedical scientist at the University of California, Riverside, has challenged this notion and reports the continuous survival of neurons is also intrinsically programmed during development.

Machine learning reveals recipe for building artificial proteins

Proteins are essential to the life of cells, carrying out complex tasks and catalyzing chemical reactions. Scientists and engineers have long sought to harness this power by designing artificial proteins that can perform new tasks, like treat disease, capture carbon, or harvest energy, but many of the processes designed to create such proteins are slow and complex, with a high failure rate.

In a breakthrough that could have implications across the healthcare, agriculture, and energy sectors, a team lead by researchers in the Pritzker School of Molecular Engineering (PME) at the University of Chicago has developed an -led process that uses big data to design new proteins.

By developing machine-learning models that can review protein information culled from genome databases, the researchers found relatively simple design rules for building . When the team constructed these artificial proteins in the lab, they found that they performed chemistries so well that they rivaled those found in nature.