Polybrominated diphenyl ether flame retardants inhibit growth factor-induced activation of EGFR by binding to its extracellular domain.

For many years, polybrominated diphenyl ethers (PBDEs) were used as flame retardants in a large number of consumer products. Even though international law meanwhile prohibits the production and usage of PBDEs, these persistent and bioaccumulative chemicals still leak into the environment, and are frequently detected in wildlife and humans. Population-based studies reveal positive correlations between human PBDE exposure and various adverse health effects, emphasizing that a better understanding of the mode of action of these polybrominated chemicals is urgently needed.

AlphaCRV: a pipeline for identifying accurate binder topologies in mass-modeling with AlphaFold.

Motivation: The speed and accuracy of deep learning-based structure prediction algorithms make it now possible to perform in silico "pull-downs" to identify protein-protein interactions on a proteome-wide scale. However, on such a large scale, existing scoring algorithms are often insufficient to discriminate biologically relevant interactions from false positives.

Results: Here, we introduce AlphaCRV, a Python package that helps identify correct interactors in a one-against-many AlphaFold screen by clustering, ranking, and visualizing conserved binding topologies, based on protein sequence and fold.

P-NADs: UX-based nobody degraders for ubiquitin-independent degradation of target proteins.

Targeted protein degradation (TPD) allows cells to maintain a functional proteome and to rapidly adapt to changing conditions. Methods that repurpose TPD for the deactivation of specific proteins have demonstrated significant potential in therapeutic and research applications. Most of these methods are based on proteolysis targeting chimaeras (PROTACs) which link the protein target to an E3 ubiquitin ligase, resulting in the ubiquitin-based degradation of the target protein.

Benzotriazole UV stabilizers disrupt epidermal growth factor receptor signaling in human cells.

Phenolic benzotriazole UV stabilizers (BUV) are commonly used additives in synthetic polymeric products, which constantly leak into the environment. They are persistent and bioaccumulative, and have been detected not only in fish, birds, and sea mammals, but also in humans, including breast milk samples. Several authorities including the European Chemical Agency already consider some BUVs as Substances of Very High Concern in need of further information, e.

Homozygosity for a Rare Variant Suggests a Contributory Role in Congenital Insensitivity to Pain.

Congenital insensitivity to pain is a rare human condition in which affected individuals do not experience pain throughout their lives. This study aimed to identify the molecular etiology of congenital insensitivity to pain in two Thai patients. Clinical, radiographic, histopathologic, immunohistochemical, and molecular studies were performed.