Effective Inhibition of TDP-43 Aggregation by Native State Stabilization

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Preventing the misfolding or aggregation of TDP-43 is the most actively pursued disease-modifying strategy to treat amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. In our work, we provide proof of concept that native state stabili ...

The invention relates to TDP-43 protein mutants and uses thereof. The invention further relates to methods for the preparation of TDP-43 protein mutants aggregates, including fibrils and uses thereof. The invention further relates to use the TDP-43 protein ...

Mitochondria are essential organelles participating in numerous cellular functions, including energy harvesting, regulation of homeostasis and apoptosis. Changes in mitochondrial number, morphology, and function not only impact cellular metabolism but also ...

The phenomenon of allostery, a general property in proteins that has been heralded as "the second secret of life" remains elusive to our understanding and even more challenging to incorporate into protein design. One example of allosteric proteins with gre ...

This book has been designed for instructors in higher education or adult training who wish to develop a new course or revise an existing one. It adopts a practical, visual, and modular approach based on the principle of constructive alignment. At its heart ...

Two design studios were successively taught in two schools of architecture: one at the Harvard Graduate School of Design (GSD) and the other at the Swiss Federal Institute of Technology in Lausanne (EPFL) in Lausanne, Switzerland, based on "A Global Morato ...

The invention relates to methods for the preparation of method of preparation of Tau aggregates, including fibrils, fibrillar species, soluble and insoluble oligomeric species, new Tau aggregates and uses thereof. The invention further relates to the uses ...

Cyclic peptides are fascinating molecules abundantly found in nature and exploited as molecular format for drug development as well as other applications, ranging from research tools to food additives. Advances in peptide technologies made over many years ...

Macrocycles provide an attractive modality for drug development but the identification of ligands to targets of interest is hindered by the lack of large macrocyclic compound libraries for high-throughput screening. A strategy to efficiently synthesize lar ...

In this paper, we present a model for the analytical computation of the power flow sensitivity coefficients (SCs) for hybrid AC/DC networks. The SCs are defined as the partial derivates of the nodal voltages with respect to the active and reactive power in ...

Motivated by the transfer of proofs between proof systems, and in particular from first order automated theorem provers (ATPs) to interactive theorem provers (ITPs), we specify an extension of the TPTP derivation text format to describe proofs in first-ord ...

We study the proof theory and algorithms for orthologic, a logical system based on ortholattices, which have shown practical relevance in simplification and normalization of verification conditions. Ortholattices weaken Boolean algebras while having polyno ...

Retinoblastoma is a rare childhood cancer of the eye. Of the small number of drugs are used to treat retinoblastoma, all have been repurposed from drugs developed for other conditions. In order to find drugs or drug combinations better suited to the improv ...

TAR DNA-binding protein with 43 kD (TDP-43) is a partially disordered protein that misfolds and accumulates in the brains of patients affected by several neurodegenerative diseases. TDP-43 oligomers have been reported to form due to aberrant misfolding or ...

This thesis consists of four Chapters unified by a singular theme â how do we develop disease models that faithfully reproduce the pathology seen in patients suffering from neurodegenerative disorders associated with the Tau protein, such as Alzheimerâ ...

BackgroundMutations in the vacuolar protein sorting 35 ortholog (VPS35) gene cause late-onset, autosomal dominant Parkinson's disease (PD), with a single missense mutation (Asp620Asn, D620N) known to segregate with disease in families with PD. The VPS35 ge ...

The authors report a method for producing co-factor-free fibrils from all full-length Tau isoforms. The method paves the way for reconstituting pathology resembling Tau fibrils and enables screening of Tau aggregation-modifying compounds for targeted thera ...

We present LISA, a proof system and proof assistant for constructing proofs in schematic first-order logic and axiomatic set theory. The logical kernel of the system is a proof checker for first-order logic with equality and schematic predicate and fun ...

This spreading of prion proteins is at the basis of brain neurodegeneration. This paper deals with the numerical modelling of the misfolding process of a-synuclein in Parkinson's disease. We introduce and analyse a discontinuous Galerkin method for the sem ...

Serial crystallography at X-ray free-electron lasers (XFELs) permits the determination of radiation-damage free static as well as time-resolved protein structures at room temperature. Efficient sample delivery is a key factor for such experiments. Here, we ...

Effective Inhibition of TDP-43 Aggregation by Native State Stabilization

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Targeting TDP-43 Proteinopathies in Neurodegeneration by its Native-State Stabilization

Transactive response dna-binding protein 43kda (tdp-43) mutants and uses thereof

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SC-TPTP: An Extension of the TPTP Derivation Format for Sequent-Based Calculus

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The predictive capacity of in vitro preclinical models to evaluate drugs for the treatment of retinoblastoma

Recombinant Full-Length TDP-43 Oligomers Retain Their Ability to Bind RNAs, Are Not Toxic, and Do Not Seed TDP-43 Aggregation in Vitro

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VPS35 and α-Synuclein fail to interact to modulate neurodegeneration in rodent models of Parkinson's disease

Fully co-factor-free ClearTau platform produces seeding-competent Tau fibrils for reconstructing pathological Tau aggregates

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Discontinuous Galerkin methods for Fisher-Kolmogorov equation with application to a-synuclein spreading in Parkinson's disease

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