Lifeboat Foundation

Numerous efforts have been made to improve the temporal resolution of CRISPR-Cas9–mediated DNA cleavage to the hour time scale. Liu et al. developed a Cas9 system that achieved genome-editing manipulation at the second time scale (see the Perspective by Medhi and Jasin). Part of the guide RNA is chemically caged, allowing the Cas9-guide RNA complex to bind at a specific genomic locus without cleavage until activation by light. This fast CRISPR system achieves genome editing at high temporal resolution, enabling the study of early molecular events of DNA repair processes. This system also has high spatial resolution at short time scales, allowing editing of one genomic allele while leaving the other unperturbed.

Science, this issue p. 1265; see also p. 1180

CRISPR-Cas systems provide versatile tools for programmable genome editing. Here, we developed a caged RNA strategy that allows Cas9 to bind DNA but not cleave until light-induced activation. This approach, referred to as very fast CRISPR (vfCRISPR), creates double-strand breaks (DSBs) at the submicrometer and second scales. Synchronized cleavage improved kinetic analysis of DNA repair, revealing that cells respond to Cas9-induced DSBs within minutes and can retain MRE11 after DNA ligation. Phosphorylation of H2AX after DNA damage propagated more than 100 kilobases per minute, reaching up to 30 megabases. Using single-cell fluorescence imaging, we characterized multiple cycles of 53BP1 repair foci formation and dissolution, with the first cycle taking longer than subsequent cycles and its duration modulated by inhibition of repair. Imaging-guided subcellular Cas9 activation further facilitated genomic manipulation with single-allele resolution.

Miniaturization has enabled technology like smartphones, health watches, medical probes and nano-satellites, all unthinkable a couple decades ago. Just imagine that in the course of 60 years, the transistor has shrunk from the size of your palm to 14 nanometers in dimension, 1000 times smaller than the diameter of a hair.

Miniaturization has pushed technology to a new era of optical circuitry. But in parallel, it has also triggered new challenges and obstacles, for example, controlling and guiding light at the nanometer scale. Researchers are looking for techniques to confine light into extremely tiny spaces, millions of times smaller than current ones. Studies had earlier found that metals can compress light below the wavelength-scale (diffraction limit).

In that aspect, graphene, a material composed from a single layer of carbon atoms, which exhibits exceptional optical and electrical properties, is capable of guiding light in the form of plasmons, which are oscillations of electrons that strongly interact with light. These graphene plasmons have a natural ability to confine light to very small spaces. However, until now, it was only possible to confine these plasmons in one direction, while the actual ability of light to interact with small particles like atoms and molecules resides in the volume into which it can be compressed. This type of confinement in all three dimensions is commonly regarded as an optical cavity.

Engineers at Duke University have demonstrated a versatile microfluidic lab-on-a-chip that uses sound waves to create tunnels in oil to touchlessly manipulate and transport droplets. The technology could form the basis of a small-scale, programmable, rewritable biomedical chip that is completely reusable to enable on-site diagnostics or laboratory research.

The results appear online on June 10 in the journal Science Advances.

“Our new system achieves rewritable routing, sorting and gating of droplets with minimal external control, which are essential functions for the digital logic control of droplets,” said Tony Jun Huang, the William Bevan Distinguished Professor of Mechanical Engineering and Materials Science at Duke. “And we achieve it with less energy and a simpler setup that can control more droplets simultaneously than previous systems.”

Circa 2017

Unlike other animals, cephalopods – the family that includes octopuses, squid and cuttlefish – do not obey the commands of their DNA to the letter.

Instead, they sometimes interfere with the code as it is being carried by a molecular “messenger”. This has the effect of diversifying the proteins their cells can produce, leading to some interesting variations.

Continue reading “Squid and octopus can edit and direct their own brain genes” »

Independent.co.uk

Cheese contains a chemical found in addictive drugs, scientists have found.

The team behind the study set out to pin-point why certain foods are more addictive than others.

Continue reading “Cheese Triggers the Same Part of Brain as Hard Drugs” »

Paris (AFP) — Scientists have developed a human embryo “blueprint” using human stem cells, in a breakthrough that could provide vital insight into the early stages of infant development, new research showed Thursday.

Teams from the University of Cambridge and the Netherlands-based Hubrecht Institute said their model will allow them to observe never-before-seen processes underlying the formation of the human body.

The layout of humans — known as the body plan — happens through a process known as gastrulation, where three distinct layers of cells are formed in the embryo that will later give rise to the body’s three main systems: nervous, musculoskeletal and digestive.

“The operation is believed to be the first of its kind in the U.S. The patient, a woman in her 20s, had been healthy, but the coronavirus devastated her lungs.”

A young woman whose lungs were destroyed by the coronavirus received a double lung transplant last week at Northwestern Memorial Hospital in Chicago, the hospital reported on Thursday, the first known lung transplant in the United States for Covid-19.

The 10-hour surgery was more difficult and took several hours longer than most lung transplants because inflammation from the disease had left the woman’s lungs “completely plastered to tissue around them, the heart, the chest wall and diaphragm,” said Dr. Ankit Bharat, the chief of thoracic surgery and surgical director of the lung transplant program at Northwestern Medicine, which includes Northwestern Memorial Hospital, in an interview.

Continue reading “Covid-19 Patient Gets Double Lung Transplant, Offering Hope for Others” »

Regeneron Pharmaceuticals announced Thursday that it’s started the first clinical trial of its experimental coronavirus antibody drug.

The antibody cocktail is being tested in four human populations. Two groups of people will receive the drug to test its effectiveness as a treatment for Covid-19; the other two will receive it as a possible prevention.

“We’ll be hopefully to quickly test the safety and then start understanding the efficacy for four major different settings of this virus challenge,” Regeneron’s chief scientific officer, Dr. George Yancopoulos, said on CNBC’s “Squawk Box.” Yancopoulos said he thinks that, “if all goes well,” the company could have “definitive data” within a few months on the effectiveness of the antibody cocktail.

Continue reading “Regeneron sees ‘a lot of reason for hope’ as human testing of its coronavirus drug begins” »

Recent therapeutic trials of “classical” psychedelic drugs, such as psilocybin (from magic mushrooms) or LSD, have reported benefits to wellbeing, depression and anxiety. These effects seem to be linked to a sense of “ego dissolution” — a dissolving of the subjective boundaries between the self and the wider world. However, the neurochemistry behind this effect has been unclear. Now a new paper, published in Neuropsychopharmacology, suggests that changes in brain levels of the neurotransmitter glutamate are key to understanding reports of ego dissolution — and perhaps the therapeutic effects of psychedelics.

Natasha Mason at Maastricht University, the Netherlands, and colleagues recruited 60 participants for their study. All had taken a psychedelic drug before, but not in the three months prior to the study. Half received a placebo and the other half were given a low to moderate dose of psilocybin (0.17 mg/kg of body weight).

The team then used a technique called proton magnetic resonance spectroscopy (MRS) to look at concentrations of glutamate (as well as other neurochemicals) in the medial prefrontal cortex (mPFC) and the hippocampus — two regions that have been implicated as key to the psychedelic drug experience. The team also looked at patterns of “functional connectivity” within networks of brain regions, a measure of how closely correlated brain activity is across those regions. Six hours after taking the drug or placebo, the participants reported on their subjective experiences using two surveys: The 5 Dimensions of Altered States of Consciousness and the Ego Dissolution Inventory.

Continue reading “Psilocybin Alters Brain Levels Of The Neurotransmitter Glutamate — And This Could Explain Why Users Experience ‘Ego Dissolution’” »