Publications by authors named "Neuhaus D"

The identification of deceased with unknown identity is a key task in forensic investigations. Current radiologic identification approaches are often elaborative, lack statistical evidence, and are dependent on the examiner's experience and expertise. Thus, the aim of this work was to develop a 3D computational and thus, more objective identification approach.

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In this issue of Structure, Viennet et al. report a study characterizing the DNA binding by a three-zinc-finger fragment from the transcription factor BCL11A, with the unusual feature that an interfinger interaction in the free protein is disrupted during binding, which provides a positive entropic contribution that enhances the affinity.

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Background Radially sampled averaged magnetization inversion-recovery acquisition (rAMIRA) imaging shows hyperintensity in the lateral corticospinal tract (CST) in patients with motor neuron diseases. Purpose To systematically determine the accuracy of the lateral corticospinal tract sign for detecting patients with amyotrophic lateral sclerosis (ALS) at rAMIRA MRI. Materials and Methods This study included prospectively acquired data from participants in ALS and other motor neuron disease imaging studies at the University Hospital Basel, Switzerland.

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Purpose: To compare postmortem in situ with ex situ MRI parameters, including volumetry, diffusion tensor imaging (DTI), and relaxometry for assessing methodology-induced alterations, which is a crucial prerequisite when performing MRI biomarker validation.

Methods: MRI whole-brain scans of five deceased patients with amyotrophic lateral sclerosis were performed at 3 T. In situ scans were conducted within 32 h after death (SD 18 h), and ex situ scans after brain extraction and 3 months of formalin fixation.

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Broadening of signals from atoms at interfaces can often be a limiting factor in applying solution NMR to the structure determination of complexes. Common contributors to such problems include exchange between free and bound states and the increased molecular weight of complexes relative to the free components, but another cause that can be more difficult to deal with occurs when conformational dynamics within the interface takes place at an intermediate rate on the chemical shift timescale. In this work we show how a carefully chosen mutation in the protein HMG-D rescued such a situation, making possible high-resolution structure determination of its complex with a dA bulge DNA ligand designed to mimic a natural DNA bend, and thereby revealing a new spatial organization of the complex.

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Article Synopsis
  • AlphaFold2 and other computational tools have advanced structural biology by accurately predicting protein structures, particularly those of the human PARP protein family.
  • The study presents a comprehensive analysis of PARP proteins, detailing their structured domains, disordered regions, and functional roles related to protein and nucleic acid modification.
  • Key findings include a model for PARP1's dynamics in different states and confirmation of PARP14's capability to bind RNA and perform RNA ADP-ribosylation, although further experimental validation is necessary.
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TRIM proteins are the largest family of E3 ligases in mammals. They include the intracellular antibody receptor TRIM21, which is responsible for mediating targeted protein degradation during Trim-Away. Despite their importance, the ubiquitination mechanism of TRIM ligases has remained elusive.

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A crucial task in forensic investigations is the identification of unknown deceased. In general, secure identification methods rely on a comparison of ante mortem (AM) with post mortem (PM) data. However, available morphologic approaches are often dependent on the expertise and experience of the examiner, and often lack standardisation and statistical evidence.

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Single-stranded breaks (SSBs) are the most frequent DNA lesions threatening genomic integrity. A highly kinked DNA structure in complex with human PARP-1 domains led to the proposal that SSB sensing in Eukaryotes relies on dynamics of both the broken DNA double helix and PARP-1's multi-domain organization. Here, we directly probe this process at the single-molecule level.

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Zinc fingers can be loosely defined as protein domains containing one or more tetrahedrally-co-ordinated zinc ions whose role is to stabilise the structure rather than to be involved in enzymatic chemistry; such zinc ions are often referred to as "structural zincs". Although structural zincs can occur in proteins of any size, they assume particular significance for very small protein domains, where they are often essential for maintaining a folded state. Such small structures, that sometimes have only marginal stability, can present particular difficulties in terms of sample preparation, handling and structure determination, and early on they gained a reputation for being resistant to crystallisation.

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Cilia formation is essential for human life. One of the earliest events in the ciliogenesis program is the recruitment of tau-tubulin kinase 2 (TTBK2) by the centriole distal appendage component CEP164. Due to the lack of high-resolution structural information on this complex, it is unclear how it is affected in human ciliopathies such as nephronophthisis.

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Attachment of ubiquitin (Ub) to proteins is one of the most abundant and versatile of all posttranslational modifications and affects outcomes in essentially all physiological processes. RING E3 ligases target E2 Ub-conjugating enzymes to the substrate, resulting in its ubiquitination. However, the mechanism by which a ubiquitin chain is formed on the substrate remains elusive.

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Background: Hand amputation can have a truly debilitating impact on the life of the affected person. A multifunctional myoelectric prosthesis controlled using pattern classification can be used to restore some of the lost motor abilities. However, learning to control an advanced prosthesis can be a challenging task, but virtual and augmented reality (AR) provide means to create an engaging and motivating training.

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Article Synopsis
  • PARP-1 is a crucial protein that detects DNA damage in cells, initiating repair processes through an allosteric mechanism that activates its catalytic domain.
  • The study employs NMR dynamics and crystal structures to explore the behavior and structural variations of the isolated catalytic domain of human PARP-1, analyzing wild-type proteins, inhibitors, and mutant forms.
  • Findings suggest that DNA binding and substrate interaction destabilize a specific subdomain in PARP-1, enabling the protein to produce necessary PAR chains for DNA repair.
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The structural integrity of cranial implants is of great clinical importance, as they aim to provide cerebral protection after neurosurgery or trauma. With the increased use of patient-specific implants, the mechanical response of each implant cannot be characterized experimentally in a practical way. However, computational models provide an excellent possibility for efficiently predicting the mechanical response of patient-specific implants.

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VARP and TBC1D5 are accessory/regulatory proteins of retromer-mediated retrograde trafficking from endosomes. Using an NMR/X-ray approach, we determined the structure of the complex between retromer subunit VPS29 and a 12 residue, four-cysteine/Zn microdomain, which we term a Zn-fingernail, two of which are present in VARP. Mutations that abolish VPS29:VARP binding inhibit trafficking from endosomes to the cell surface.

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Background: Malposition of intraosseous needles in pediatric patients is frequently reported. Incorrect needle length and penetration depth related to the puncture site and level are possible causes.

Aims: Aim of this study was to analyze anatomic dimensions of the proximal tibia in the pediatric population with respect to intraosseous needle placement and needle tip position.

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Background: Hypertrophic scars are commonly seen in children and associated with pruritus, pain, functional impairment, and aesthetic disfigurement. Ablative fractional CO2 and pulse dye laser are emerging techniques to improve scar quality. Only limited data are available on children, nonburn scars, and patient-reported outcome.

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Cranial implants are used to repair bone defects following neurosurgery or trauma. At present, there is a lack of data on their mechanical response, particularly in impact loading. The aim of the present study was to assess the mechanical response of a recently developed composite calcium phosphate-titanium (CaP-Ti) implant at quasi-static and impact loading rates.

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The anti-cancer drug target poly(ADP-ribose) polymerase 1 (PARP1) and its close homologue, PARP2, are early responders to DNA damage in human cells. After binding to genomic lesions, these enzymes use NAD to modify numerous proteins with mono- and poly(ADP-ribose) signals that are important for the subsequent decompaction of chromatin and the recruitment of repair factors. These post-translational modifications are predominantly serine-linked and require the accessory factor HPF1, which is specific for the DNA damage response and switches the amino acid specificity of PARP1 and PARP2 from aspartate or glutamate to serine residues.

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Article Synopsis
  • TRIM21 is a cytosolic antibody receptor with a unique ubiquitination function that targets a wide range of pathogens and supports a protein depletion method known as Trim-Away.
  • The mechanism involves TRIM21 forming a tri-ionic motif that helps it interact with the Ube2N/Ube2V2 E2 enzyme, facilitating the transfer of ubiquitin by stabilizing the Ube2N~Ub complex.
  • Mutations in this tri-ionic motif disrupt TRIM21's ability to ubiquitinate, neutralize viruses, and signal immune responses, indicating its essential role in the function of various RING E3 enzymes.
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Clathrin-mediated endocytosis (CME) is key to maintaining the transmembrane protein composition of cells' limiting membranes. During mammalian CME, a reversible phosphorylation event occurs on Thr156 of the μ2 subunit of the main endocytic clathrin adaptor, AP2. We show that this phosphorylation event starts during clathrin-coated pit (CCP) initiation and increases throughout CCP lifetime.

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Background: Balance training is an important aspect in prevention and rehabilitation of musculoskeletal lower limb injuries. Virtual reality (VR) is a promising addition or alternative to traditional training. This review aims to provide a comprehensive overview of VR technology and games employed for balance prevention and rehabilitation, balance outcome measures, and effects for both balance prevention and balance rehabilitation following musculoskeletal lower limb impairments.

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"As ACL injury may alter intracortical facilitation [34] and depressed intracortical inhibition is correlated with decreased quadriceps voluntary activation capability [35], external focus training may provide a means to restore quadriceps muscle activity via increasing intracortical inhibition.

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