Hippocampal damage through foreign body placement in organotypic cultures leads to plastic responses in newly born granule cells.

The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage. The latter involves global alterations, making understanding plastic responses triggered by local damage difficult. One key feature of the dentate gyrus is that it contains a well-defined neurogenic niche, the subgranular zone, and beyond neurogenesis, newly born granule cells may maintain a "young" phenotype throughout life, adding to the plastic nature of the structure.

A structural rationale for reversible vs irreversible amyloid fibril formation from a single protein.

Reversible and irreversible amyloids are two diverging cases of protein (mis)folding associated with the cross-β motif in the protein folding and aggregation energy landscape. Yet, the molecular origins responsible for the formation of reversible vs irreversible amyloids have remained unknown. Here we provide evidence at the atomic level of distinct folding motifs for irreversible and reversible amyloids derived from a single protein sequence: human lysozyme.

Image analysis in posttreatment non-small cell lung cancer surveillance: specialists' interpretations reviewed by the thoracic multidisciplinary tumor board.

Background: Data show that the initial specialist's image interpretation and final multidisciplinary tumor board (MTB) assessment can vary substantially in the pretherapeutic cancer setting. The aim of this analysis was to investigate the concordance of the specialist's and MTB's image interpretations in patients undergoing systematic posttreatment lung cancer image surveillance.

Methods: In the initial prospective study, lung cancer patients who had received curative-intent treatment were randomly assigned to undergo either contrast-enhanced computed tomography (CE-CT) or integrated 18-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT).

Nuclear Magnetic Resonance Solution Structure and Functional Behavior of the Human Proton Channel.

The human voltage-gated proton channel [Hv1 or VSDO] plays an important role in the human innate immune system. Its structure differs considerably from those of other cation channels. It is built solely of a voltage-sensing domain and thus lacks the central pore domain, which is essential for other cation channels.

Serious adverse events in patients with target-oriented blood pressure management: a systematic review.

: On the basis of the benefits of antihypertensive treatment, progressively intensive treatment is advocated. However, it remains controversial whether intensive blood pressure control might increase the frequency of serious adverse events (SAEs) compared with moderate control. This review assessed the occurrence of SAEs in blood pressure treatment with predefined blood pressure targets.

Probing Ion Binding in the Selectivity Filter of the KcsA Potassium Channel.

In potassium (K) channels, permeation, selectivity, and gating at the selectivity filter are all governed by the thermodynamics and kinetics of the ion-protein interactions. Specific contacts between the carbonyl groups from the Thr-Val-Gly-Tyr-Gly signature filter sequence and the permeant ions generate four equidistant K binding sites, thereby defining the high ion selectivity and controlling the transport rate of K channels. Here, we used N-labeled ammonium (NH) as a proxy for K to study ion interaction with the selectivity filter of the prototypical full-length K channel KcsA by solution state NMR spectroscopy in order to obtain detailed insights into the physicochemical basis of K gating.

N transverse relaxation measurements for the characterization of µs-ms dynamics are deteriorated by the deuterium isotope effect on N resulting from solvent exchange.

N R relaxation measurements are key for the elucidation of the dynamics of both folded and intrinsically disordered proteins (IDPs). Here we show, on the example of the intrinsically disordered protein α-synuclein and the folded domain PDZ2, that at physiological pH and near physiological temperatures amide-water exchange can severely skew Hahn-echo based N R relaxation measurements as well as low frequency data points in CPMG relaxation dispersion experiments. The nature thereof is the solvent exchange with deuterium in the sample buffer, which modulates the N chemical shift tensor via the deuterium isotope effect, adding to the apparent relaxation decay which leads to systematic errors in the relaxation data.

Comparing Two Imaging Methods for Follow-Up of Lung Cancer Treatment: A Randomized Pilot Study.

Background: Scientific data on the image modality to be used in postcurative treatment surveillance of non-small cell lung cancer patients are scarce. This prospective randomized pilot trial compared the performance of integrated F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) and contrast-enhanced computed tomography (CE-CT).

Methods: After termination of curative-intent treatment, patients were randomly assigned to the PET-CT or the CE-CT group.

Lipid- and Cholesterol-Mediated Time-Scale-Specific Modulation of the Outer Membrane Protein X Dynamics in Lipid Bilayers.

Membrane protein function fundamentally depends on lipid-bilayer fluidity and the composition of the biological membrane. Although dynamic interdependencies between membrane proteins and the surrounding lipids are suspected, a detailed description is still missing. To uncover lipid-modulated membrane protein backbone dynamics, time-scale-specific NMR relaxation experiments with residue-resolution were recorded.

Quantitative mass imaging of single biological macromolecules.

The cellular processes underpinning life are orchestrated by proteins and their interactions. The associated structural and dynamic heterogeneity, despite being key to function, poses a fundamental challenge to existing analytical and structural methodologies. We used interferometric scattering microscopy to quantify the mass of single biomolecules in solution with 2% sequence mass accuracy, up to 19-kilodalton resolution, and 1-kilodalton precision.

Proton-Detected NMR Spectroscopy of Nanodisc-Embedded Membrane Proteins: MAS Solid-State vs Solution-State Methods.

The structural and dynamical characterization of membrane proteins in a lipid bilayer at physiological pH and temperature and free of crystal constraints is crucial for the elucidation of a structure/dynamics-activity relationship. Toward this aim, we explore here the properties of the outer-membrane protein OmpX embedded in lipid bilayer nanodiscs using proton-detected magic angle spinning (MAS) solid-state NMR at 60 and 110 kHz. [H,N]-correlation spectra overlay well with the corresponding solution-state NMR spectra.

Lipid Internal Dynamics Probed in Nanodiscs.

Nanodiscs offer a very promising tool to incorporate membrane proteins into native-like lipid bilayers and an alternative to liposomes to maintain protein functions and protein-lipid interactions in a soluble nanoscale object. The activity of the incorporated membrane protein appears to be correlated to its dynamics in the lipid bilayer and by protein-lipid interactions. These two parameters depend on the lipid internal dynamics surrounded by the lipid-encircling discoidal scaffold protein that might differ from more unrestricted lipid bilayers observed in vesicles or cellular extracts.

Micelles, Bicelles, and Nanodiscs: Comparing the Impact of Membrane Mimetics on Membrane Protein Backbone Dynamics.

Detergents are often used to investigate the structure and dynamics of membrane proteins. Whereas the structural integrity seems to be preserved in detergents for many membrane proteins, their functional activity is frequently compromised, but can be restored in a lipid environment. Herein we show with per-residue resolution that while OmpX forms a stable β-barrel in DPC detergent micelles, DHPC/DMPC bicelles, and DMPC nanodiscs, the pico- to nanosecond and micro- to millisecond motions differ substantially between the detergent and lipid environment.

Diastolic aorto-right-atrial fistulation in aortic and tricuspid valve endocarditis.

Background Aorto-right-atrial fistula in native valve endocarditis is very rare. Case Description A 45-year-old woman was referred with an endocarditis with a perforated right cusp of the aortic valve with at least moderate insufficiency and an affected tricuspid annulus with vegetations. In addition to this, an aorto-cavitary fistula from the aortic sinus to the right atrium with a holodiastolic left-right shunt had been detected.

Effect of viscogens on the kinetic response of a photoperturbed allosteric protein.

By covalently binding a photoswitchable linker across the binding groove of the PDZ2 domain, a small conformational change can be photo-initiated that mimics the allosteric transition of the protein. The response of its binding groove is investigated with the help of ultrafast pump-probe IR spectroscopy from picoseconds to tens of microseconds. The temperature dependence of that response is compatible with diffusive dynamics on a rugged energy landscape without any prominent energy barrier.