Researchers showed that AI-redesigned botulinum neurotoxin proteases provided more stable starting points for directed evolution, allowing enzymes to access beneficial mutations that were poorly tolerated in wild-type backgrounds. In BoNT/E models, the approach improved activity, evolvability, and specificity, including an ataxin-2-targeting variant with markedly reduced cleavage of the native SNAP25 substrate.
Phage therapy is the use of bacterial viruses, or bacteriophages, as antibacterial agents. It has been in use for over 100 years and is becoming increasingly common clinically. The first steps of phage therapy include identification of bacteria to be targeted and then obtaining phages with appropriate host ranges. This is followed by various approaches to in vitro phage characterization. Increasingly common for phage phenotypic characterization is the use of kinetic microtiter plate readers. They can both decrease workloads and increase throughput, especially relative to analyses that require plating on agar-based media. These colorimetric/turbidimetric/optical density approaches primarily assess phage-induced culture-wide bacterial lysis, in the shorter term, or instead the phage potential to suppress phage-resistance evolution over longer time frames. Considered here are methods relevant to phage characterization especially for phage-therapy purposes. Discussed are turbidity-reduction assays, determinations of phage antibacterial virulence, and related time-kill curve analysis. All are or can be optical density-based approaches to assessing phage-based bacterial reduction. Emphasis is placed on consideration of the utilities, limitations, and intersections of these similar methods. Emphasized is that the start of “Deviation”—where phage-treated culture turbidity diverges from phage-free controls—may represent a superior endpoint for such optical density-based bacterial-reduction protocols.
Researchers working at the Large High Altitude Air Shower Observatory (LHAASO) in China’s Sichuan Province have discovered that the unique binary system Cygnus X-3, located in the constellation Cygnus, is the most powerful particle accelerator known to date. The findings were reported by Xinhua News Agency, a TV BRICS partner, citing the Institute of High Energy Physics of the Chinese Academy of Sciences.
Cygnus X-3 is a binary system consisting of either a black hole or a neutron star and a massive companion star. The compact object actively accretes material from the powerful stellar wind of its companion, accelerating particles to extremely high energies.
Scientists had previously believed that charged particles within the Milky Way could reach energies of around one petaelectronvolt (PeV). However, a detailed analysis of ultra-high-energy gamma-ray emissions enabled LHAASO researchers to determine that Cygnus X-3 is capable of accelerating cosmic rays to energies of at least 30 petaelectronvolts. The team also detected a periodic ultra-high-energy gamma-ray signal with a cycle of 4.8 hours and established that the particle acceleration region is located approximately three solar radii from the source of the radiation.
Stars and galaxies make up much of the universe’s ordinary, observable matter. But for decades, scientists have wrestled with a cosmic conflict: There should be much more.
Physicists have good estimates of how much matter was present in the early universe. Shortly after the Big Bang, roughly 83% of all matter in the universe was composed of invisible dark matter, with ordinary matter making up the rest. And yet, these estimates exceed the amount of ordinary matter seen in stars and galaxies today. Where, then, did all the missing ordinary matter go?
Now MIT scientists, as part of the CHIME/FRB Collaboration, are using far-off radio signals to reveal missing matter in the vast space between galaxies. The team has developed a new method to search out missing matter by combining locations of galaxies with detections of fast radio bursts.
Modern therapies have transformed care for people with multiple sclerosis (MS). Yet the disease continues to progress in a substantial proportion of patients, even in the absence of relapses. Detecting and treating this gradual worsening of disability remains one of the greatest challenges in MS care. Researchers from the University of Basel, Switzerland, now report on a blood marker that could help track disease progression and monitor treatment response.
Relapses are only part of the disease process in MS. In some patients, physical and cognitive abilities continue to gradually decline even in the absence of relapses. Experts refer to this as progression independent of relapse activity (PIRA). This process develops slowly and is difficult to detect and quantify. A currently available blood test measures neurofilament light chain (NfL), a biomarker that mainly reflects neuroaxonal damage caused by acute inflammatory disease activity. A blood marker that captures the progressive component of the disease has so far been lacking.
“One of the key questions for us was whether progression leaves a different biological fingerprint than inflammation,” says Professor Jens Kuhle from the University of Basel and the Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB) at University Hospital Basel. “If these processes are biologically distinct, we also need biomarkers that reflect different aspects of the disease rather than expecting a single marker to capture everything.”
There are few treatment options available for people with disorders of the esophagus. Delivering drugs directly to this part of the body is difficult, so patients are usually treated with systemic drugs, which can have unwanted side effects.
To overcome that challenge, MIT engineers developed a gel-like oral drug formulation that can coat the mucosal lining of the esophagus after being swallowed, allowing drugs to pass through the tissue.
The formulation, which includes a hydrogel and other key ingredients that promote rapid drug absorption, could be used to deliver antibodies including infliximab, used to treat a number of autoimmune diseases, or other types of antibodies or small-molecule drugs.