Researchers use the mouse as a model organism to study the structure and function of skeletal muscle, neuromuscular diseases and aging processes in muscle. The scientists are aware of their responsibility in the use of animals and have committed themselves at the University of Basel to rigorously implement the so-called 3R principles — Replacement, Reduction, Refinement — in animal-assisted research and animal husbandry.

The new method developed by Professor Markus Rüegg’s research group at the Biozentrum, University of Basel, is a further step towards reducing the number of laboratory animals. This method also opens new ways to investigate several genes simultaneously or even entire signaling pathways in muscle fibers quickly, cost-effectively and efficiently. The results of the study have now been published in Nature Communications.

The difficulty of studying genes in muscle fibers

Studying gene function in muscle is challenging. On the one hand, muscle fibers are very large and very fragile when isolated. On the other hand, in humans, they are up to half a meter long and contain thousands of nuclei. In order to change and study gene function in muscle fibers, all of the muscle fiber nuclei must be changed, which is difficult to achieve.

For some years now, scientists have been using the CRISPR/Cas9 method to study gene function. This method uses a virus to introduce the so-called Cas9 protein and a specifically designed guide RNA into the organism and thus into the nuclei. The Cas9 protein cuts the genomic DNA at the site recognized by the guide RNA. This combination of Cas9 protein and guide RNA allows altering gene function in the cell.

The CRISPR-Cas9 method can be split up

However, to ensure that the virus only alters the gene expression of muscle fibers and not those of other organs at the same time, the research team combined the CRISPR/Cas9 method with another method: First, the researchers succeeded in breeding mice with the Cas9 protein already present in their muscle fibers — but only there. They then introduced the desired guide RNA into the organism with a so-called adeno-associated virus, which infects muscle.

This combination causes the guide RNA in the muscle fibers to encounter the Cas9 protein, changing the genetic material as desired. “The method enables us to ensure that only the muscle fibers actually change their genetic material,” explains first author Marco Thürkauf.

Fewer laboratory animals and more efficient results

Since the adeno-associated virus can also transport several guide RNAs simultaneously, the team can now use the method to investigate several genes simultaneously or even entire signaling pathways. Furthermore, the method significantly reduces the number of experimental animals required.

“All animals used are suitable for studying genes and do not have to be bred over years. This makes it possible to study muscle fibers as well as neuromuscular diseases without using a large number of mice,” says Marco Thürkauf.

Other research groups have also already signaled their interest. “We already have several interested groups in our research community that would like to use our method,” says Markus Rüegg. “This is a great gain for both muscle research per se as well as for our goal of reducing animal experiments.”

Now, a new paper in Nature illustrates a Harvard quantum computing platform’s potential to solve the longstanding problem known as quantum error correction.

Leading the Harvard team is quantum optics expert Mikhail Lukin, the Joshua and Beth Friedman University Professor in physics and co-director of the Harvard Quantum Initiative. The work reported in Nature was a collaboration among Harvard, MIT, and Boston-based QuEra Computing. Also involved was the group of Markus Greiner, the George Vasmer Leverett Professor of Physics.

An effort spanning the last several years, the Harvard platform is built on an array of very cold, laser-trapped rubidium atoms. Each atom acts as a bit — or a “qubit” as it’s called in the quantum world — which can perform extremely fast calculations.

The team’s chief innovation is configuring their “neutral atom array” to be able to dynamically change its layout by moving and connecting atoms — this is called “entangling” in physics parlance — mid-computation. Operations that entangle pairs of atoms, called two-qubit logic gates, are units of computing power.

Running a complicated algorithm on a quantum computer requires many gates. However, these gate operations are notoriously error-prone, and a buildup of errors renders the algorithm useless.

In the new paper, the team reports near-flawless performance of its two-qubit entangling gates with extremely low error rates. For the first time, they demonstrated the ability to entangle atoms with error rates below 0.5 percent. In terms of operation quality, this puts their technology’s performance on par with other leading types of quantum computing platforms, like superconducting qubits and trapped-ion qubits.

However, Harvard’s approach has major advantages over these competitors due to its large system sizes, efficient qubit control, and ability to dynamically reconfigure the layout of atoms.

“We’ve established that this platform has low enough physical errors that you can actually envision large-scale, error-corrected devices based on neutral atoms,” said first author Simon Evered, a Harvard Griffin Graduate School of Arts and Sciences student in Lukin’s group. “Our error rates are low enough now that if we were to group atoms together into logical qubits — where information is stored non-locally among the constituent atoms — these quantum error-corrected logical qubits could have even lower errors than the individual atoms.”

The Harvard team’s advances are reported in the same issue of Nature as other innovations led by former Harvard graduate student Jeff Thompson, now at Princeton University, and former Harvard postdoctoral fellow Manuel Endres, now at California Institute of Technology. Taken together, these advances lay the groundwork for quantum error-corrected algorithms and large-scale quantum computing. All of this means quantum computing on neutral atom arrays is showing the full breadth of its promise.

“These contributions open the door for very special opportunities in scalable quantum computing and a truly exciting time for this entire field ahead,” Lukin said.

Researchers from Boston University Chobanian & Avedisian School of Medicine now suggest studying persons after they sustain knee trauma such as anterior cruciate ligament tears (ACL).

“Given the repeated, expensive and discouraging past failures in the development of effective treatments for OA, a new approach is needed that focuses research into effective treatment on those with early disease,” said corresponding author David T. Felson, MD, MPH, professor of medicine and epidemiology at the School of Medicine and Boston University School of Public Health.

While most patients recover after sustaining a major joint injury like an ACL tear, a few experience persistent pain and develop OA. Felson suggests that sufficient numbers of such patients exist and could be identified in advance to form a high-risk group in which treatments to prevent disease could be tested.

Current options for treatments that reduce joint pain such as nonsteroidal anti-inflammatory drugs (NSAIDs) are successful in some patients but their use is limited by their toxicity . Exercise or weight loss are effective but long-term adherence is poor. Rates of total knee replacement surgeries are rising rapidly suggesting that nonsurgical treatments have not successfully alleviated patients’ pain and disability.

BU and Cleveland Clinic researchers reviewed the data from the MOON (Multicenter Orthopaedic Outcomes Network) cohort, a group of 2,340 persons undergoing ACL reconstructions (ACLR) after traumatic tears. The MOON investigators reported that 26% of the ACL reconstruction patients who responded had at least moderate knee pain on daily activities, especially stair climbing and walking. They also found that 16.6% had Knee Injury and Osteoarthritis Outcome Score (KOOS) pain scores of less than80 (0-100 scale where 100 is no pain) suggesting that mild to moderate pain is not rare after ACLR.

By using the MOON risk factors — incorporating pain and structural changes in all joint tissues, especially cartilage loss — to select persons at high risk of later pain, they could assemble a cohort at high risk of substantial post ACLR pain. “This approach offers the opportunity to prevent disease and is especially valuable in targeting young adults who, after a knee injury, may have significant joint pain and disability for many years before they become eligible for joint replacement,” he adds.

These findings appear online in the Annals of the Rheumatic Diseases.

Funding for this study was provided by the Arthritis Foundation and by the national Institutes of Health (NIH P30 AR072571).

One of the greatest strengths of NASA’s James Webb Space Telescope is its ability to give astronomers detailed views of areas where new stars are being born. The latest example, showcased here in a new image from Webb’s Mid-Infrared Instrument (MIRI), is NGC 346 — the brightest and largest star-forming region in the Small Magellanic Cloud.

The Small Magellanic Cloud (SMC) is a satellite galaxy of the Milky Way, visible to the unaided eye in the southern constellation Tucana. This small companion galaxy is more primeval than the Milky Way in that it possesses fewer heavy elements, which are forged in stars through nuclear fusion and supernova explosions, compared to our own galaxy.

Since cosmic dust is formed from heavy elements like silicon and oxygen, scientists expected the SMC to lack significant amounts of dust. However the new MIRI image, as well as a previous image of NGC 346 from Webb’s Near-Infrared Camera released in January, show ample dust within this region.

In this representative-color image, blue tendrils trace emission from material that includes dusty silicates and sooty chemical molecules known as polycyclic aromatic hydrocarbons, or PAHs. More diffuse red emission shines from warm dust heated by the brightest and most massive stars in the heart of the region. An arc at the center left may be a reflection of light from the star near the arc’s center. (Similar, fainter arcs appear associated with stars at lower left and upper right.) Lastly, bright patches and filaments mark areas with abundant numbers of protostars. The research team looked for the reddest stars, and found 1,001 pinpoint sources of light, most of them young stars still embedded in their dusty cocoons.

By combining Webb data in both the near-infrared and mid-infrared, astronomers are able to take a fuller census of the stars and protostars within this dynamic region. The results have implications for our understanding of galaxies that existed billions of years ago, during an era in the universe known as “cosmic noon,” when star formation was at its peak and heavy element concentrations were lower, as seen in the SMC.The James Webb Space Telescope is the world’s premier space science observatory.

Scientists from Bristol and the University of Occupational and Environmental Health in Japan, sought to understand how ‘circadian misalignment’ — a phenomenon commonly associated with ‘jet-lag’ whereby the body’s biological clock is disrupted — affects the hormones responsible for regulating appetite.

Prevalent in night shift workers, in this new study, the international team reveal how circadian misalignment can profoundly alter the brain’s regulation of hormones controlling hunger to the detriment of metabolic health.

The team focused on glucocorticoid hormones in the adrenal gland which regulate many physiological functions including metabolism and appetite. Glucocorticoids are known to directly regulate a group of brain peptides controlling appetitive behaviour, with some increasing appetite (orexigenic) and some decreasing appetite (anorexigenic).

In an experiment using animal models, comprising a control group and a out-of-phase ‘jet-lagged’ group, the team found misalignment between light and dark cues led the out-of-phase group’s orexigenic hypothalamic neuropeptides (NPY) to become dysregulated, driving an increased desire to eat significantly more during the inactive phase of the day.

Strikingly, the team discovered that rats in the control group ate 88.4% of their daily intake during their active phase, and only 11.6% during their inactive phase. In contrast, the ‘jet-lagged’ group consumed 53.8% of their daily calories during their inactive phase (without an increase in activity during this time). This equated to nearly five-times more (460% more) than what the control group consumed during the inactive phase. These results show that it is timing of consumption that has been affected.

This new discovery revealed how completely, and significantly, disordered the neuropeptides become when daily glucocorticoid levels are out of synch with light and dark cues. However, the authors suggest the neuropeptides identified in this study may be promising targets for drug treatments adapted to treat eating disorders and obesity.

Dr Becky Conway-Campbell, Research Fellow in Bristol Medical School: Translational Health Sciences (THS) and the study’s senior author, said: “For people working throughout the night, a reversed body clock can play havoc with their health.

“For those who are working night shifts long-term, we recommend they try to maintain daylight exposure, cardiovascular exercise and mealtimes at regulated hours. However, internal brain messages to drive increased appetite are difficult to override with ‘discipline’ or ‘routine’ so we are currently designing studies to assess rescue strategies and pharmacological intervention drugs. We hope our findings also provide new insight into how chronic stress and sleep disruption leads to caloric overconsumption.”

Stafford Lightman, Professor of Medicine at Bristol Medical School: THS and co-senior author on the study, added: “The adrenal hormone corticosterone, which is normally secreted in a circadian manner, is a major factor in the daily control of brain peptides that regulate appetite. Furthermore when we disturb the normal relationship of corticosterone with the day to night light cycle it results in abnormal gene regulation and appetite during the period of time that the animals normally sleep.

“Our study shows that when we disturb our normal bodily rhythms this in turn disrupts normal appetite regulation in a way that is at least in part a result of desynchrony between adrenal steroid hormone production and the timing of the light and dark cycle.”

Dr Benjamin Flynn, one of the study’s co-authors who conducted the study while at Bristol but is now based at the University of Bath, added: “This is further evidence of how phase shift ‘jet-lag’ affects feeding behaviours and neuronal gene expression — data important for shift work co-morbidity research.”

This research was funded by the Medical Research Council.