Resting-state brain network connectivity is an independent predictor of responsiveness to language therapy in chronic post-stroke aphasia.

Post-stroke aphasia recovery, especially in the chronic phase, is challenging to predict. Functional integrity of the brain and brain network topology have been suggested as biomarkers of language recovery. This study sought to investigate functional connectivity in four predefined brain networks (i.

Air-liquid interface culture promotes maturation and allows environmental exposure of pluripotent stem cell-derived alveolar epithelium.

Type 2 alveolar epithelial cells (AT2s), facultative progenitor cells of the lung alveolus, play a vital role in the biology of the distal lung. In vitro model systems that incorporate human cells, recapitulate the biology of primary AT2s, and interface with the outside environment could serve as useful tools to elucidate functional characteristics of AT2s in homeostasis and disease. We and others recently adapted human induced pluripotent stem cell-derived AT2s (iAT2s) for air-liquid interface (ALI) culture.

Deuteration of nonexchangeable protons on proteins affects their thermal stability, side-chain dynamics, and hydrophobicity.

We have investigated the effect of deuteration of non-exchangeable protons on protein global thermal stability, hydrophobicity, and local flexibility using well-known thermostable model systems such as the villin headpiece subdomain (HP36) and the third immunoglobulin G-binding domain of protein G (GB3). Reversed-phase high-performance liquid chromatography (RP-HPLC) measurements as a function of temperature probe global thermal stability in the presence of acetonitrile, while differential scanning calorimetry determines thermal stability in solution. Both indicate small but measurable changes in the order of several degrees.

Optimized purification of a fusion protein by reversed-phase high performance liquid chromatography informed by the linear solvent strength model.

Fusion protein systems are commonly used for expression of small proteins and peptides. An important criterion for a fusion protein system to be useful is the ability to separate the protein of interest from the tag. Additionally, because no protease cleaves fusion proteins with 100% efficiency, the ability to separate the desired peptide from any remaining uncleaved protein is also necessary.

Solvent-Driven Dynamical Crossover in the Phenylalanine Side-Chain from the Hydrophobic Core of Amyloid Fibrils Detected by H NMR Relaxation.

Aromatic residues are important markers of dynamical changes in proteins' hydrophobic cores. In this work we investigated the dynamics of the F19 side-chain in the core of amyloid fibrils across a wide temperature range of 300 to 140 K. We utilized solid-state H NMR relaxation to demonstrate the presence of a solvent-driven dynamical crossover between different motional regimes, often also referred to as the dynamical transition.

Fast Motions of Key Methyl Groups in Amyloid-β Fibrils.

Amyloid-β (Aβ) peptide is the major component of plaques found in Alzheimer's disease patients. Using solid-state H NMR relaxation performed on selectively deuterated methyl groups, we probed the dynamics in the threefold symmetric and twofold symmetric polymorphs of native Aβ as well as the protofibrils of the D23N mutant. Specifically, we investigated the methyl groups of two leucine residues that belong to the hydrophobic core (L17 and L34) as well as M35 residues belonging to the hydrophobic interface between the cross-β subunits, which has been previously found to be water-accessible.

Flexibility and Solvation of Amyloid-β Hydrophobic Core.

Amyloid fibril deposits found in Alzheimer disease patients are composed of amyloid-β (Aβ) protein forming a number of hydrophobic interfaces that are believed to be mostly rigid. We have investigated the μs-ms time-scale dynamics of the intra-strand hydrophobic core and interfaces of the fibrils composed of Aβ1-40 protein. Using solid-state (2)H NMR line shape experiments performed on selectively deuterated methyl groups, we probed the 3-fold symmetric and 2-fold symmetric polymorphs of native Aβ as well as the protofibrils of D23N Iowa mutant, associated with an early onset of Alzheimer disease.