Paroxysmal non-kinesigenic dyskinesia (PNKD) is a rare autosomal dominant movement disorder triggered by stress, fatigue or consumption of either alcohol or caffeine. Attacks last 1-4 h and consist of dramatic dystonia and choreoathetosis in the limbs, trunk and face. The disease is associated with single amino acid changes (A7V or A9V) in PNKD, a protein of unknown function. Here we studied the stability, cellular localization and enzymatic activity of the PNKD protein in cultured cells and transgenic animals. The N-terminus of the wild-type (WT) long PNKD isoform (PNKD-L) undergoes a cleavage event in vitro, resistance to which is conferred by disease-associated mutations. Mutant PNKD-L protein is degraded faster than the WT protein. These results suggest that the disease mutations underlying PNKD may disrupt protein processing in vivo, a hypothesis supported by our observation of decreased cortical Pnkd-L levels in mutant transgenic mice. Pnkd is homologous to a superfamily of enzymes with conserved β-lactamase domains. It shares highest homology with glyoxalase II but does not catalyze the same reaction. Lower glutathione levels were found in cortex lysates from Pnkd knockout mice versus WT littermates. Taken together, our results suggest an important role for the Pnkd protein in maintaining cellular redox status.

The Structure-Function Linkage Database (SFLD, http://sfld.rbvi.ucsf.edu/) is a manually curated classification resource describing structure-function relationships for functionally diverse enzyme superfamilies. Members of such superfamilies are diverse in their overall reactions yet share a common ancestor and some conserved active site features associated with conserved functional attributes such as a partial reaction. Thus, despite their different functions, members of these superfamilies look alike, making them easy to misannotate. To address this complexity and enable rational transfer of functional features to unknowns only for those members for which we have sufficient functional information, we subdivide superfamily members into subgroups using sequence information, and lastly into families, sets of enzymes known to catalyze the same reaction using the same mechanistic strategy. Browsing and searching options in the SFLD provide access to all of these levels. The SFLD offers manually curated as well as automatically classified superfamily sets, both accompanied by search and download options for all hierarchical levels. Additional information includes multiple sequence alignments, tab-separated files of functional and other attributes, and sequence similarity networks. The latter provide a new and intuitively powerful way to visualize functional trends mapped to the context of sequence similarity.

Antiferromagnetic insulators are a ubiquitous class of magnetic materials, holding the promise of low-dissipation spin-based computing devices that can display ultra-fast switching and are robust against stray fields. However, their imperviousness to magnetic fields also makes them difficult to control in a reversible and scalable manner. Here we demonstrate a novel proof-of-principle ionic approach to control the spin reorientation (Morin) transition reversibly in the common antiferromagnetic insulator α-Fe₂O₃ (haematite) - now an emerging spintronic material that hosts topological antiferromagnetic spin-textures and long magnon-diffusion lengths. We use a low-temperature catalytic-spillover process involving the post-growth incorporation or removal of hydrogen from α-Fe₂O₃ thin films. Hydrogenation drives pronounced changes in its magnetic anisotropy, Néel vector orientation and canted magnetism via electron injection and local distortions. We explain these effects with a detailed magnetic anisotropy model and first-principles calculations. Tailoring our work for future applications, we demonstrate reversible control of the room-temperature spin-state by doping/expelling hydrogen in Rh-substituted α-Fe₂O₃.

The Structure-Function Linkage Database (SFLD, http://sfld.rbvi.ucsf.edu/) is a manually curated classification resource describing structure-function relationships for functionally diverse enzyme superfamilies. Members of such superfamilies are diverse in their overall reactions yet share a common ancestor and some conserved active site features associated with conserved functional attributes such as a partial reaction. Thus, despite their different functions, members of these superfamilies 'look alike', making them easy to misannotate. To address this complexity and enable rational transfer of functional features to unknowns only for those members for which we have sufficient functional information, we subdivide superfamily members into subgroups using sequence information, and lastly into families, sets of enzymes known to catalyze the same reaction using the same mechanistic strategy. Browsing and searching options in the SFLD provide access to all of these levels. The SFLD offers manually curated as well as automatically classified superfamily sets, both accompanied by search and download options for all hierarchical levels. Additional information includes multiple sequence alignments, tab-separated files of functional and other attributes, and sequence similarity networks. The latter provide a new and intuitively powerful way to visualize functional trends mapped to the context of sequence similarity.