To clarify the underlying mechanisms of the FLASH effect, in which the delivery of ultrafast, high-intensity doses of radiation to tumors counterintuitively reduces damage to surrounding healthy cells, researchers directly compared the oxidative effects of conventional and FLASH techniques using x-ray footprinting at the ALS. Read more »
Bifurcation of High- and Low-Energy Electrons in Microbial Metabolism
A class of chemical reaction found only in biology, electron bifurcation channels two electrons from one donor to two separate acceptors, with one electron elevated in energy at the expense of lowering the energy of the second. Researchers used the ALS to study this process in a microbial protein involved in this bioenergetic pathway. Read more »
The Effects of Diabetes on Spinal-Column Biomechanics
Researchers found that type 2 diabetes induces earlier onset of plastic (nonrecoverable) deformation in intervertebral discs by impairing the biomechanical behavior of collagen. A greater understanding of the underlying causes of tissue failure in diabetes—a growing problem worldwide—is important in helping to prevent and treat symptoms. Read more »
Correlating Conformational Equilibria with Catalysis in the Electron Bifurcating EtfABCX of Thermotoga maritima
Anaerobic SEC-MALS-SAXS at the SIBYLS beamline probes the conformational states behind electron bifurcation in the Thermotoga maritima EtfABCX, revealing insights on mechanisms at the thermodynamic limits of life. Shown are the bifurcation- and electron-conducting-like states experimentally observed for the first time in solution. Read more »
Computer-Aided Protein Design for New Biomaterials
Using a computer-based approach, researchers designed porous protein crystals that were revealed to be stable, tunable, and atomically accurate using x-ray scattering and diffraction at the ALS. The work provides a powerful new platform for biological materials engineering and opens up wide applications in biotechnology and medicine. Read more » 
Immune Response Spurs Growth of “Soft” Kidney Stones
Matrix stones are an unusual type of soft kidney stone closely associated with the presence of bacteria from unchecked urinary tract infections. Researchers conducted a comprehensive study of surgically extracted matrix stones, work that highlights how host defense mechanisms against microbes can simultaneously encourage harmful stone formation. Read more »
How Structure Affects the Activity of Lipid Nanoparticles
Berkeley Lab and Genentech scientists related the internal structures of lipid nanoparticles to their efficacy at drug delivery, using a combination of methods including x-ray scattering at the ALS. The work promises to expedite the development of drug delivery systems for the treatment of diseases such as COVID-19 and cancer. Read more »
A New Pathway for Clearing Misfolded Proteins
Researchers integrated several approaches, such as cryogenic 3D imaging at the ALS, to define a novel cellular pathway—involving a shared “garbage dump”—for clearing misfolded proteins from cells. The pathway is a potential therapy target for age-related diseases like Alzheimer’s, Huntington’s, and Parkinson’s diseases. Read more »
Breaking Barriers in Drug Delivery with Better Lipid Nanoparticles
A collaboration between Berkeley Lab and Genentech, a member of the Roche Group, is working to break through some of the drug delivery bottlenecks by designing the most effective lipid nanoparticles (LNPs)—tiny spherical pouches made of fatty molecules that encapsulate therapeutic agents until they dock with cell membranes and release their contents. Read more »
Allosteric Tuning of Caspase-7: Establishing the Nexus of Structure and Catalytic Power
How can allosteric sites be more effectively targeted by small-molecule drugs? Using an integrated in vitro/in silico experimental workflow; we discovered novel allosteric inhibitors of caspase-7 and revealed new connections between the active site and the remote allosteric site (i. e., allosteric structure–activity relationships, ASARs) for this valuable disease target. Read more »
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