Researchers used the SIBYLS beamline to gain insight into ADAMTS13, the only known protein to regulate the adhesive function of von Willebrand factor (VWF), a blood-clotting protein. When VWF is deficient or abnormal, it causes a common inherited bleeding disorder, von Willebrand disease. VWF is also implicated in arterial and deep-vein thrombosis, stroke, atherosclerosis, sickle cell crisis, and sepsis. Read more »
Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders
PDE4D enzymes are important for normal brain function. Mutations have been asssociated with an ultrarare neurodevelopmental disorder, and genetic variation in PDE4D contributes to biological variation in human cognitive ability. Here, researchers report on novel PDE4D inhibitors providing potent memory-enhancing effects in a mouse model, with improved tolerability and reduced vascular toxicity over earlier PDE4 inhibitors. Read more »
Structural Characterization of a Synthetic Tandem-Domain Bacterial Microcompartment Shell Protein Capable of Forming Icosahedral Shell Assemblies
Bacterial microcompartments (BMCs) are subcellular compartments found in many prokaryotes, and they are of considerable interest for biotechnological applications. The BMC-H2 shell system constitutes a relatively simple generic building block that could be used to construct designed shells with a relatively highly tunable pore. Read more »
Antibody Uses Mimicry to Block SARS Coronavirus
Protein structures not only revealed how SARS and MERS antibodies inhibit the viruses from attaching to host cells, they also revealed an unprecedented example of receptor mimicry that triggers the cell-invasion machinery of the SARS virus. The results inform efforts to prevent and treat these serious, often deadly, respiratory diseases. Read more »
Mechanical Competence and Bone Quality Develop During Skeletal Growth
Researchers explored how bone quality and mechanical competence progress during longitudinal bone growth. Deformation at the tissue, fibril, and mineral length scales was investigated with mechanical tensile tests during small and wide-angle x-ray scattering/diffraction (SAXS/WAXD) experiments, revealing dramatic differences in mechanical resistance with age. Read more »
Absorber Captures Excess Chemotherapy Drugs
Researchers have designed a biomedical device for absorbing excess chemotherapy drugs during cancer treatment, characterizing the active surface layer using x-ray microtomography. The work opens up a new route to fighting cancer that minimizes drug toxicity and enables personalized, targeted, high-dose chemotherapy. Read more »
Biochemical and structural characterization of two variants of uncertain significance in the PMS2 gene
The lack of information as to whether a genetic mutation is pathogenic or benign causes ambiguity during clinical diagnosis and hinders appropriate treatment. Here, researchers use several techniques, including small‐angle x‐ray scattering, to help classify genetic variants associated with an increased predisposition to certain cancers. Read more »
A Two-Pronged Defense against Bacterial Self-Intoxication
Researchers solved the structure of a bacterial toxin bound to a neutralizing protein, revealing two distinct mechanisms for how the toxin-producing bacteria avoid poisoning themselves. The findings offer clues to the evolutionary origins of the potent toxins that enable bacterial pathogens to cause human diseases such as cholera and diphtheria. Read more »
Comparative morphology of cheliceral muscles using high‐resolution X‐ray microcomputed‐tomography in palpimanoid spiders
Spiders are important predators in terrestrial ecosystems, yet we know very little about their principal feeding structures—the chelicerae—an extremely important aspect of spider biology. Here, using micro‐Computed‐Tomography scanning techniques, researchers perform a comparative study to examine cheliceral muscle morphology in six different spider specimens. Read more »
Toward a Blueprint for Anti-influenza Drugs
Researchers obtained high-resolution structures of several influenza antiviral drug molecules bound to their proton-channel targets in both open and closed conformations. The structures provide an atomic-level blueprint from which to design more effective anti-influenza drugs that can overcome growing drug resistance. Read more »
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