Hydration- and Temperature-Dependent Fluorescence Spectra of Laurdan Conformers in a DPPC Membrane.

The widely used Laurdan probe has two conformers, resulting in different optical properties when embedded in a lipid bilayer membrane, as demonstrated by our previous simulations. Up to now, the two conformers' optical responses have, however, not been investigated when the temperature and the phase of the membrane change. Since Laurdan is known to be both a molecular rotor and a solvatochromic probe, it is subject to a profound interaction with both neighboring lipids and water molecules.

Photophysics in Biomembranes: Computational Insight into the Interaction between Lipid Bilayers and Chromophores.

ConspectusLight is ubiquitously available to probe the structure and dynamics of biomolecules and biological tissues. Generally, this cannot be done directly with visible light, because of the absence of absorption by those biomolecules. This problem can be overcome by incorporating organic molecules (chromophores) that show an optical response in the vicinity of those biomolecules.

Humoral immune response after SARS-CoV-2 vaccination in cladribine-treated multiple sclerosis patients.

Multiple sclerosis immunomodulatory treatments such as cladribine, which affects both B- and T-lymphocytes, can potentially alter the humoral response to SARS-CoV-2 vaccination. This monocenter retrospective study reports on anti-SARS-CoV-2 IgG antibody response in cladribine treated MS patients and we compare the response in patients vaccinated before and after an 18-week interval after last cladribine dose. Of the 34 patients (5 patients ≤ 18 weeks and 29 patients > 18 weeks after last cladribine dose) that were included, 32 reached seropositivity (94 %).

Generalized polarization and time-resolved fluorescence provide evidence for different populations of Laurdan in lipid vesicles.

The solvatochromic dye Laurdan is widely used in sensing the lipid packing of both model and biological membranes. The fluorescence emission maximum shifts from about 440 nm (blue channel) in condensed membranes (S) to about 490 nm (green channel) in the liquid-crystalline phase (L). Although the fluorescence intensity based generalized polarization (GP) is widely used to characterize lipid membranes, the fluorescence lifetime of Laurdan, in the blue and the green channel, is less used for that purpose.

Dual photoisomerization mechanism of azobenzene embedded in a lipid membrane.

The photoisomerization of chromophores embedded in biological environments is of high importance for biomedical applications, but it is still challenging to define the photoisomerization mechanism both experimentally and computationally. We present here a computational study of the azobenzene molecule embedded in a DPPC lipid membrane, and assess the photoisomerization mechanism by means of the quantum mechanics/molecular mechanics surface hopping (QM/MM-SH) method. We observe that while the -to- isomerization is a slow process governed by a torsional mechanism due to the strong interaction with the environment, the -to- mechanism is completed in sub-ps time scale and is governed by a pedal-like mechanism in which both weaker interactions with the environment and a different geometry of the potential energy surface play a key role.

Comparison of single- and multistage strategies during fenestrated-branched endovascular aortic repair of thoracoabdominal aortic aneurysms.

Objective: The aim of this study was to compare outcomes of single or multistage approach during fenestrated-branched endovascular aortic repair (FB-EVAR) of extensive thoracoabdominal aortic aneurysms (TAAAs).

Methods: We reviewed the clinical data of consecutive patients treated by FB-EVAR for extent I to III TAAAs in 24 centers (2006-2021). All patients received a single brand manufactured patient-specific or off-the-shelf fenestrated-branched stent grafts.

Multiscale Modeling Unravels the Influence of Biomembranes on the Photochemical Properties of Embedded Anti-Oxidative Polyphenolic and Phenanthroline Chelating Dyes.

The embedding of caffeate methyl ester, the flavonoids luteolin and quercetin, and the -phenanthroline and neocuproine in a liquid disordered lipid bilayer has been studied through extensive atomistic calculations. The location and the orientation of these bio-active antioxidants are explained and analyzed. While the two phenanthrolines strongly associate with the lipid tail region, the other three compounds are rather found among the head groups.

Modeling human extraembryonic mesoderm cells using naive pluripotent stem cells.

A hallmark of primate postimplantation embryogenesis is the specification of extraembryonic mesoderm (EXM) before gastrulation, in contrast to rodents where this tissue is formed only after gastrulation. Here, we discover that naive human pluripotent stem cells (hPSCs) are competent to differentiate into EXM cells (EXMCs). EXMCs are specified by inhibition of Nodal signaling and GSK3B, are maintained by mTOR and BMP4 signaling activity, and their transcriptome and epigenome closely resemble that of human and monkey embryo EXM.

Integrated multi-omics reveal polycomb repressive complex 2 restricts human trophoblast induction.

Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested.

Multiscale simulations of polyzwitterions in aqueous bulk solutions and brush array configurations.

Zwitterionic polymers are very promising candidates for antifouling materials that exhibit high chemical stability as compared to polyethylene glycol-based systems. A number of simulation and experimental studies have emerged over recent years for the investigation of sulfobetaine-based zwitterionic polymers. Investigating the structural and thermodynamic properties of such polymers requires access to broad time and length regimes, thus necessitating the development of multiscale simulation strategies.

Vitamin D supplementation in multiple sclerosis: an expert opinion based on the review of current evidence.

Introduction: Vitamin D has long been known for its immune-modulating effects, next to its function in calcium metabolism. As a consequence, poor vitamin D status has been associated with many diseases including multiple sclerosis (MS). Epidemiological studies suggest an association between a poor vitamin D status and development of MS and a poor vitamin D status is associated with more relapses and faster progression after patients are diagnosed with MS.

Analysis of cell-free DNA in a consecutive series of 13,607 routine cases for the detection of fetal chromosomal aneuploidies in a single center in Germany.

Purpose: Noninvasive prenatal testing (NIPT) is a highly sensitive and specific method for detection of fetal chromosomal aneuploidies from maternal plasma. The objective of this study was to determine the performance of a new paired-end sequencing-based NIPT assay in 13,607 pregnancies from a single center in Germany.

Methods: Samples from 13,607 pregnant women who previously underwent NIPT were analyzed using VeriSeq NIPT Solution v2 assay for presence of common fetal trisomies and monosomy X.

The influence of lipid membranes on fluorescent probes' optical properties.

Background: Organic fluorophores embedded in lipid bilayers can nowadays be described by a multiscale computational approach. Combining different length and time scales, a full characterization of the probe localization and optical properties led to novel insight into the effect of the environments.

Scope Of Review: Following an introduction on computational advancements, three relevant probes are reviewed that delineate how a multiscale approach can lead to novel insight into the probes' (non) linear optical properties.

Influence of Membrane Phase on the Optical Properties of DPH.

The fluorescent molecule diphenylhexatriene (DPH) has been often used in combination with fluorescence anisotropy measurements, yet little is known regarding the non-linear optical properties. In the current work, we focus on them and extend the application to fluorescence, while paying attention to the conformational versatility of DPH when it is embedded in different membrane phases. Extensive hybrid quantum mechanics/molecular mechanics calculations were performed to investigate the influence of the phase- and temperature-dependent lipid environment on the probe.

Laurdan as a Molecular Rotor in Biological Environments.

Laurdan is one of the most used fluorescent probes for lipid membrane phase recognition. Despite its wide use for optical techniques and its versatility as a solvatochromic probe, little is known regarding its use as molecular rotor, for which clear evidence is found in the current study. Although recent computational and experimental studies suggest the existence of two stable conformations of laurdan in different membrane phases, it is difficult to experimentally probe their prevalence.

Conformational Changes as Driving Force for Phase Recognition: The Case of Laurdan.

The development of a universal probe to assess the phase of a lipid membrane is one of the most ambitious goals for fluorescence spectroscopy. The ability of a well-known molecule as Laurdan to reach this aim is here exploited as the behavior of the probe is fully characterized in a dipalmitoylphosphatidylcholine (DPPC) solid gel (So) phase by means of molecular dynamics simulations. Laurdan can take two conformations, depending on whether the carbonyl oxygen points toward the β-position of the naphthalene core (Conf-I) or to the α-position (Conf-II).

Cyanine dyes with tail length asymmetry enhance photoselection: A multiscale study on DiD probes in a liquid disordered membrane.

Visualization of membrane domains like lipid rafts in natural or artificial membranes is a crucial task for cell biology. For this purpose, fluorescence microscopy is often used. Since fluorescing probes in lipid membranes partition specifically in e.

Orientational distribution of DPH in lipid membranes: a comparison of molecular dynamics calculations and experimental time-resolved anisotropy experiments.

Characterization of the membrane phases is a crucial task in cell biology. Cells differ in composition of the lipids and consequently in adopted phases. The phases can be discriminated based upon lipid ordering and molecular diffusion and their identification could be used for characterization of cell membranes.

Combining (Non)linear Optical and Fluorescence Analysis of DiD To Enhance Lipid Phase Recognition.

The widespread interest in phase recognition of lipid membranes has led to the use of different optical techniques to enable differentiation of healthy and not fully functional cells. In this work, we show how the combination of different (non)linear optical methods such as one-photon absorption (OPA), two-photon absorption (TPA), and second harmonic generation (SHG) as well as the study of the fluorescence decay time leads to an enhanced screening of membrane phases using a fluorescent 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiD) probe. In the current study we consider the pure liquid disordered phases of DOPC (dioleoyl- sn-glycero-3-phosphocholine, room temperature) and DPPC (1,2-dipalmitoyl- sn-glycero-3-phosphocholine, 323 K), the solid gel phase of DPPC (298 K), and the liquid ordered phase of a 2:1 binary mixture of sphingomyelin and cholesterol.

Atomistic Picture of Fluorescent Probes with Hydrocarbon Tails in Lipid Bilayer Membranes: An Investigation of Selective Affinities and Fluorescent Anisotropies in Different Environmental Phases.

By reverting to spectroscopy, changes in the biological environment of a fluorescent probe can be monitored and the presence of various phases of the surrounding lipid bilayer membranes can be detected. However, it is currently not always clear in which phase the probe resides. The well-known orange 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbo-cyanine perchlorate (DiI-C18(5)) fluorophore, for instance, and the new, blue BODIPY (4,4-difluoro-4-bora-3 a,4 a-diaza- s-indacene) derivative were experimentally seen to target and highlight identical parts of giant unilamellar vesicles of various compositions, comprising mixtures of dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylcholine (DOPC), sphingomyelin (SM), and cholesterol (Chol).

Triggering On/Off States of Photoswitchable Probes in Biological Environments.

The use of hybrid systems for which the change in properties of one component triggers the change in properties of the other is of outmost importance when "on/off" states are needed. For such a reason, azobenzene compounds are one of the most used probes due to their high photoswitching efficiency. In this study, we consider a new derivative of azobenzene interacting with different lipid membrane phases as a versatile fluorescent probe for phase recognition.

Evaluation of a Powered Stapler System with Gripping Surface Technology on Surgical Interventions Required During Laparoscopic Sleeve Gastrectomy.

Background: Transection of gastric tissue during laparoscopic sleeve gastrectomy (LSG) can be challenging. Reinforcing the staple line may decrease the incidence of issues requiring intervention.

Methods: The objective of this study was to compare the number of intraoperative surgical interventions for a surgical stapler and reload system with Gripping Surface Technology (GST) to standard reloads in patients who underwent LSG.

Investigation into Biological Environments through (Non)linear Optics: A Multiscale Study of Laurdan Derivatives.

The fluorescent marker Laurdan and its new derivative, C-Laurdan, have been investigated by means of theoretical calculations in a DOPC lipid bilayer membrane at room temperature, and a comparison is made with results from fluorescence experiments. Experimentally, the latter probe is known to have a higher sensitivity to the membrane polarity at the lipid headgroup region and has higher water solubility. Results from Molecular Dynamics (MD) simulations show that C-Laurdan is oriented with the carboxyl group toward the head of the membrane, with an angle of 50° between the molecular backbone and the normal to the bilayer, in contrast to the orientation of the Laurdan headgroup whose carbonyl group is oriented toward the polar regions of the membrane and which describes an angle of ca.

Benchmarking Post-Hartree-Fock Methods To Describe the Nonlinear Optical Properties of Polymethines: An Investigation of the Accuracy of Algebraic Diagrammatic Construction (ADC) Approaches.

Third-order nonlinear optical (NLO) properties of polymethine dyes have been widely studied for applications such as all-optical switching. However, the limited accuracy of the current computational methodologies has prevented a comprehensive understanding of the nature of the lowest excited states and their influence on the molecular optical and NLO properties. Here, attention is paid to the lowest excited-state energies and their energetic ratio, as these characteristics impact the figure-of-merit for all-optical switching.