Quantifying Stress and Relaxation: A New Measure of Heart Rate Variability as a Reliable Biomarker.

For the rapid, objective characterization of the physiological stress response, there is currently no generally recognized standard. The stress measurement methods used in practice (e.g.

Optical Interferometric Device for Rapid and Specific Detection of Biological Cells.

Here, we report a rapid and accurate optical method for detecting cells from liquid samples in a label-free manner. The working principle of the method is based on the interference of parts of a conical laser beam, coming from a single-mode optical fiber directly, and reflected from a flat glass surface. The glass is functionalized by antibodies against the cells to be detected from the liquid sample.

Hierarchical organization of human physical activity.

Human physical activity (HPA), a fundamental physiological signal characteristic of bodily motion is of rapidly growing interest in multidisciplinary research. Here we report the existence of hitherto unidentified hierarchical levels in the temporal organization of HPA on the ultradian scale: on the minute's scale, passive periods are followed by activity bursts of similar intensity ('quanta') that are organized into superstructures on the hours- and on the daily scale. The time course of HPA can be considered a stochastic, quasi-binary process, where quanta, assigned to task-oriented actions are organized into work packages on higher levels of hierarchy.

PtdIns4P is required for the autophagosomal recruitment of STX17 (syntaxin 17) to promote lysosomal fusion.

The autophagosomal SNARE STX17 (syntaxin 17) promotes lysosomal fusion and degradation, but its autophagosomal recruitment is incompletely understood. Notably, PtdIns4P is generated on autophagosomes and promotes fusion through an unknown mechanism. Here we show that soluble recombinant STX17 is spontaneously recruited to negatively charged liposomes and adding PtdIns4P to liposomes containing neutral lipids is sufficient for its recruitment.

Lab-on-a-chip models of the blood-brain barrier: evolution, problems, perspectives.

A great progress has been made in the development and use of lab-on-a-chip devices to model and study the blood-brain barrier (BBB) in the last decade. We present the main types of BBB-on-chip models and their use for the investigation of BBB physiology, drug and nanoparticle transport, toxicology and pathology. The selection of the appropriate cell types to be integrated into BBB-on-chip devices is discussed, as this greatly impacts the physiological relevance and translatability of findings.

Spin-Label Electron Paramagnetic Resonance Spectroscopy Reveals Effects of Wastewater Filter Membrane Coated with Titanium Dioxide Nanoparticles on Bovine Serum Albumin.

The accumulation of proteins in filter membranes limits the efficiency of filtering technologies for cleaning wastewater. Efforts are ongoing to coat commercial filters with different materials (such as titanium dioxide, TiO) to reduce the fouling of the membrane. Beyond monitoring the desired effect of the retention of biomolecules, it is necessary to understand what the biophysical changes are in water-soluble proteins caused by their interaction with the new coated filter membranes, an aspect that has received little attention so far.

Impact of protein-chromophore interaction on the retinal excited state and photocycle of rhodopsin: role of conserved tryptophan residues.

The function of microbial as well as mammalian retinal proteins ( rhodopsins) is associated with a photocycle initiated by light excitation of the retinal chromophore of the protein, covalently bound through a protonated Schiff base linkage. Although electrostatics controls chemical reactions of many organic molecules, attempt to understand its role in controlling excited state reactivity of rhodopsins and, thereby, their photocycle is scarce. Here, we investigate the effect of highly conserved tryptophan residues, between which the all- retinal chromophore of the protein is sandwiched in microbial rhodopsins, on the charge distribution along the retinal excited state, quantum yield and nature of the light-induced photocycle and absorption properties of rhodopsin (GR).

Microsecond All-Optical Modulation by Biofunctionalized Porous Silicon Microcavity.

We successfully created a composite photonic structure out of porous silicon (PSi) microcavities doped by the photochromic protein, photoactive yellow protein (PYP). Massive incorporation of the protein molecules into the pores was substantiated by a 30 nm shift of the resonance dip upon functionalization, and light-induced reflectance changes of the device due to the protein photocycle were recorded. Model calculations for the photonic properties of the device were consistent with earlier results on the nonlinear optical properties of the protein, whose degree of incorporation into the PSi structure was also estimated.

Reconsidering Dogmas about the Growth of Bacterial Populations.

The growth of bacterial populations has been described as a dynamic process of continuous reproduction and cell death. However, this is far from the reality. In a well fed, growing bacterial population, the stationary phase inevitably occurs, and it is not due to accumulated toxins or cell death.

Photoactive Yellow Protein Adsorption at Hydrated Polyethyleneimine and Poly-l-Glutamic Acid Interfaces.

Chiral and achiral vibrational sum-frequency generation (VSFG) spectroscopy was performed in the 1400-1700 and 2800-3800 cm range to study the interfacial structure of photoactive yellow protein (PYP) adsorbed on polyethyleneimine (PEI) and poly-l-glutamic acid (PGA) surfaces. Nanometer-thick polyelectrolyte layers served as the substrate for PYP adsorption, with 6.5-pair layers providing the most homogeneous surfaces.

The Use of Sensors in Blood-Brain Barrier-on-a-Chip Devices: Current Practice and Future Directions.

The application of lab-on-a-chip technologies in in vitro cell culturing swiftly resulted in improved models of human organs compared to static culture insert-based ones. These chip devices provide controlled cell culture environments to mimic physiological functions and properties. Models of the blood-brain barrier (BBB) especially profited from this advanced technological approach.

The Actigraphy-Based Identification of Premorbid Latent Liability of Schizophrenia and Bipolar Disorder.

(1) Background and Goal: Several studies have investigated the association of sleep, diurnal patterns, and circadian rhythms with the presence and with the risk states of mental illnesses such as schizophrenia and bipolar disorder. The goal of our study was to examine actigraphic measures to identify features that can be extracted from them so that a machine learning model can detect premorbid latent liabilities for schizotypy and bipolarity. (2) Methods: Our team developed a small wrist-worn measurement device that collects and identifies actigraphic data based on an accelerometer.

Multifunctional microfluidic chips for the single particle inductively coupled plasma mass spectrometry analysis of inorganic nanoparticles.

This study aimed at exploiting the so far unexploited potential of carrying out on-line sample pretreatment steps on microfluidic chips for single particle inductively coupled plasma mass spectrometry (spICP-MS) measurements, and demonstrating their ability to practically facilitate most of the simpler tasks involved in the spICP-MS analysis of nanoparticles. For this purpose, polydimethylsiloxane microfluidic chips, capable of high-range dilution and sample injection were made by casting, using high-precision, 3D-printed molds. Optimization of their geometry and functions was done by running several hydrodynamic simulations and by gravimetric, fluorescence enhanced microscope imaging and solution-based ICP-MS experiments.

Nonlinear electric response of the diffuse double layer to an abrupt charge displacement inside a biological membrane.

In order to elucidate the old, still unsolved problem of how the diffuse electric double layer responds to an abrupt, intramolecular charge displacement inside a biological membrane, we investigated the fastest components of the light-induced electric signals of bacteriorhodopsin and its mutants, in numerous ionic and buffer solutions. The obtained data for temperature and solute concentration dependence were interpreted as a consequence of changes in the capacity of the diffuse double layer surrounding the purple membrane. The possible physiological consequences of this so far not demonstrated phenomenon are discussed.

Penetration of the SARS-CoV-2 Spike Protein across the Blood-Brain Barrier, as Revealed by a Combination of a Human Cell Culture Model System and Optical Biosensing.

Since the outbreak of the global pandemic caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), several clinical aspects of the disease have come into attention. Besides its primary route of infection through the respiratory system, SARS-CoV-2 is known to have neuroinvasive capacity, causing multiple neurological symptoms with increased neuroinflammation and blood-brain barrier (BBB) damage. The viral spike protein disseminates via circulation during infection, and when reaching the brain could possibly cross the BBB, which was demonstrated in mice.

Special Issue on Versatile Organ-on-a-Chip Devices.

The tremendous success of microelectronics at the end of the 20th century, often symbolized by "Moore's law", is based on miniaturization of the active and passive elements of electronic circuits [...

Detailed analysis and comparison of different activity metrics.

Actigraphic measurements are an important part of research in different disciplines, yet the procedure of determining activity values is unexpectedly not standardized in the literature. Although the measured raw acceleration signal can be diversely processed, and then the activity values can be calculated by different activity calculation methods, the documentations of them are generally incomplete or vary by manufacturer. These numerous activity metrics may require different types of preprocessing of the acceleration signal.

All-Optical Switching Demonstrated with Photoactive Yellow Protein Films.

Integrated optics (IO) is a field of photonics which focuses on manufacturing circuits similar to those in integrated electronics, but that work on an optical basis to establish means of faster data transfer and processing. Currently, the biggest task in IO is finding or manufacturing materials with the proper nonlinear optical characteristics to implement as active components in IO circuits. Using biological materials in IO has recently been proposed, the first material to be investigated for this purpose being the protein bacteriorhodopsin; however, since then, other proteins have also been considered, such as the photoactive yellow protein (PYP).

Transendothelial Electrical Resistance Measurement across the Blood-Brain Barrier: A Critical Review of Methods.

The blood-brain barrier (BBB) represents the tightest endothelial barrier within the cardiovascular system characterized by very low ionic permeability. Our aim was to describe the setups, electrodes, and instruments to measure electrical resistance across brain microvessels and culture models of the BBB, as well as critically assess the influence of often neglected physical and technical parameters such as temperature, viscosity, current density generated by different electrode types, surface size, circumference, and porosity of the culture insert membrane. We demonstrate that these physical and technical parameters greatly influence the measurement of transendothelial electrical resistance/resistivity (TEER) across BBB culture models resulting in severalfold differences in TEER values of the same biological model, especially in the low-TEER range.

Surface charge, glycocalyx, and blood-brain barrier function.

The negative surface charge of brain microvessel endothelial cells is derived from the special composition of their membrane lipids and the thick endothelial surface glycocalyx. They are important elements of the unique defense systems of the blood-brain barrier. The tissue-specific properties, components, function and charge of the brain endothelial glycocalyx have only been studied in detail in the past 15 years.

Breast adenocarcinoma-derived exosomes lower first-contact de-adhesion strength of adenocarcinoma cells to brain endothelial layer.

Despite of advances in modern therapeutics, one of the most feared complications of cancer are brain metastases, which often cause life impairing profound neurological symptoms and premature death. Breast adenocarcinoma is among the leading "sources" of brain metastases. Since the central nervous system lacks a classical lymphatic circulation, invading metastatic cells can reach the brain parenchyma only through haematogenous routes and must breach the blood-brain barrier (BBB).

Flow induces barrier and glycocalyx-related genes and negative surface charge in a lab-on-a-chip human blood-brain barrier model.

Microfluidic lab-on-a-chip (LOC) devices allow the study of blood-brain barrier (BBB) properties in dynamic conditions. We studied a BBB model, consisting of human endothelial cells derived from hematopoietic stem cells in co-culture with brain pericytes, in an LOC device to study fluid flow in the regulation of endothelial, BBB and glycocalyx-related genes and surface charge. The highly negatively charged endothelial surface glycocalyx functions as mechano-sensor detecting shear forces generated by blood flow on the luminal side of brain endothelial cells and contributes to the physical barrier of the BBB.

Insights into graphene oxide interaction with human serum albumin in isolated state and in blood plasma.

The interactions of graphene oxide (GO), a 2-dimensional nanomaterial with hydrophilic edges, hydrophobic basal plane and large flat surfaces, with biological macromolecules, are of key importance for the development of novel nanomaterials for biomedical applications. To gain more insight into the interaction of GO flakes with human serum albumin (HSA), we examined GO binding to HSA in its isolated state and in blood plasma. Calorimetric data reveal that GO strongly stabilizes free isolated HSA against a thermal challenge at low ionic strength, indicating strong binding interactions, confirmed by the drop in ζ-potential of the HSA/GO assemblies compared to bare GO flakes.

Dual Channel Microfluidics for Mimicking the Blood-Brain Barrier.

High-resolution imaging is essential for analysis of the steps and way stations of cargo transport in models of the endothelium. In this study, we demonstrate a microfluidic system consisting of two channels horizontally separated by a cell-growth-promoting membrane. Its design allows for high-resolution (down to single-molecule level) imaging using a high numerical aperture objective with a short working distance.

Glycocalyx regulates the strength and kinetics of cancer cell adhesion revealed by biophysical models based on high resolution label-free optical data.

The glycocalyx is thought to perform a potent, but not yet defined function in cellular adhesion and signaling. Since 95% of cancer cells have altered glycocalyx structure, this role can be especially important in cancer development and metastasis. The glycocalyx layer of cancer cells directly influences cancer progression, involving the complicated kinetic process of cellular adhesion at various levels.