Predicting executive functioning from walking features in Parkinson's disease using machine learning.

Parkinson's disease is characterized by motor and cognitive deficits. While previous work suggests a relationship between both, direct empirical evidence is scarce or inconclusive. Therefore, we examined the relationship between walking features and executive functioning in patients with Parkinson's disease using state-of-the-art machine learning approaches.

The dimeric structure and the bivalent recognition of H3K4me3 by the tumor suppressor ING4 suggests a mechanism for enhanced targeting of the HBO1 complex to chromatin.

The INhibitor of Growth (ING) family of tumor suppressors regulates the transcriptional state of chromatin by recruiting remodeling complexes to sites with histone H3 trimethylated at position K4 (H3K4me3). This modification is recognized by the plant homeodomain (PHD) present at the C-terminus in the five members of the ING family. ING4 facilitates histone H3 acetylation by the HBO1 complex.

The NMR structure and dynamics of the two-domain tick carboxypeptidase inhibitor reveal flexibility in its free form and stiffness upon binding to human carboxypeptidase B.

The structure of the tick carboxypeptidase inhibitor (TCI) and its backbone dynamics, free and in complex with human carboxypeptidase B, have been determined by NMR spectroscopy. Although free TCI has the same overall fold as that observed in the crystal structures of its complexes with metallocarboxypeptidase types A and B, there are structural differences at the linker between the two domains. The linker residues have greater flexibility than the globular domains, and the C-terminal residues are highly flexible in free TCI.

Solution structure and NMR characterization of the binding to methylated histone tails of the plant homeodomain finger of the tumour suppressor ING4.

Plant homeodomain (PHD) fingers are frequently present in proteins involved in chromatin remodelling, and some of them bind to histones. The family of proteins inhibitors of growth (ING) contains a PHD finger that bind to histone-3 trimethylated at lysine 4, and those of ING1 and ING2 also act as nuclear phosphoinositide receptors. We have determined the structure of ING4 PHD, and characterised its binding to phosphoinositides and histone methylated tails.

Enhanced antiangiogenic therapy with antibody-collagen XVIII NC1 domain fusion proteins engineered to exploit matrix remodeling events.

Antiangiogenic therapy is nowadays one of the most active fields in cancer research. The first strategies, aimed at inhibiting tumor vascularization, included upregulation of endogenous inhibitors and blocking of the signals delivered by angiogenic factors. But interaction between endothelial cells and their surrounding extracellular matrix also plays a critical role in the modulation of the angiogenic process.

Effects of heme on the structure of the denatured state and folding kinetics of cytochrome b562.

Heme-linked proteins, such as cytochromes, are popular subjects for protein folding studies. There is the underlying question of whether the heme affects the structure of the denatured state by cross-linking it and forming other interactions, which would perturb the folding pathway. We have studied wild-type and mutant cytochrome b562 from Escherichia coli, a 106 residue four-alpha-helical bundle.

An NMR view of the folding process of a CheY mutant at the residue level.

The folding of CheY mutant F14N/V83T was studied at 75 residues by NMR. Fluorescence, NMR, and sedimentation equilibrium studies at different urea and protein concentrations reveal that the urea-induced unfolding of this CheY mutant includes an on-pathway molten globule-like intermediate that can associate off-pathway. The populations of native and denatured forms have been quantified from a series of 15N-1H HSQC spectra recorded under increasing concentrations of urea.