Integrated enhanced Raman scattering: a review

The demand for effective, real-time environmental monitoring and for customized point-of-care (PoC) health, requires the ability to detect low molecular concentrations, using portable, reliable and cost-effective devices. However, traditional techniques often require time consuming, highly technical and laborious sample preparations, as well as expensive, slow and bulky instrumentation that needs to be supervised by laboratory technicians. Consequently, fast, compact, self-sufficient, reusable and cost-effective lab-on-a-chip (LOC) devices, which can perform all the required tasks and can then upload the data to portable devices, would revolutionize any mobile sensing application by bringing the testing device to the field or to the patient. Integrated enhanced Raman scattering devices are the most promising platform to accomplish this vision and to become the basic architecture for future universal molecular sensors and hence an artificial optical nose. Here we are reviewing the latest theoretical and experimental work along this direction.

Inflammasome activation in neurodegenerative diseases

Approximately ten million people are diagnosed with dementia annually since they experience difficulties with memory and thinking skills. Since neurodegenerative diseases are diagnosed late, most of them are difficult to treat. This is due to the increased severity of the disease during the progression when neuroinflammation plays a critical role. The activation of immune cells, especially microglia, plays a crucial role in the development of neurodegenerative diseases. Molecular sensors within these microglia, such as the NLRP3 inflammasome, are activated by signals that represent the hallmarks of neurodegenerative diseases. Here, we first summarize the two activation steps of NLRP3 inflammasome activation. Furthermore, we discuss the key factors that contribute to NLRP3 inflammasome activation in the different neuroinflammatory diseases, like Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). The prominent NLRP3 inflammasome triggers include amyloid β and tau oligomers in AD, α-synuclein in PD, and superoxide dismutase (SOD1) and TAR DNA-binding protein 43 (TDP43) in ALS. NLRP3 inhibitor treatment has shown promising results in several preclinical mouse models of AD, PD, and ALS. Finally, we postulate that current understandings underpin the potential for NLRP3 inhibitors as a therapeutic target in neurodegenerative diseases.

Genetically encoded photo-switchable molecular sensors for optoacoustic and super-resolution imaging

Reversibly photo-switchable proteins are essential for many super-resolution fluorescence microscopic and optoacoustic imaging methods. However, they have yet to be used as sensors that measure the distribution of specific analytes at the nanoscale or in the tissues of live animals. Here we constructed the prototype of a photo-switchable Ca2+ sensor based on GCaMP5G that can be switched with 405/488-nm light and describe its molecular mechanisms at the structural level, including the importance of the interaction of the core barrel structure of the fluorescent protein with the Ca2+ receptor moiety. We demonstrate super-resolution imaging of Ca2+ concentration in cultured cells and optoacoustic Ca2+ imaging in implanted tumor cells in mice under controlled Ca2+ conditions. Finally, we show the generalizability of the concept by constructing examples of photo-switching maltose and dopamine sensors based on periplasmatic binding protein and G-protein-coupled receptor-based sensors.

Diurnal variations in muscle and liver glycogen differ depending on the timing of exercise

It has been suggested that glycogen functions not only in carbohydrate energy storage, but also as molecular sensors capable of activating lipolysis. This study aimed to compare the variation in liver and muscle glycogen during the day due to different timing of exercise. Nine healthy young men participated in two trials in which they performed a single bout of exercise at 70% of their individual maximal oxygen uptake for 60 min in the post-absorptive (morning) or post-prandial (afternoon) state. Liver and muscles glycogen levels were measured using carbon magnetic resonance spectroscopy (13C MRS). Diurnal variations in liver and muscle glycogen compared to baseline levels were significantly different depending on the timing of exercise. The effect of the timing of exercise on glycogen fluctuation is known to be related to a variety of metabolic signals, and the results of this study will be useful for future research on energy metabolism.

Numerous expansions in TRP ion channel diversity highlight widespread evolution of molecular sensors in animal diversification.

Transient Potential Receptor (TRP) ion channels are a diverse superfamily of multimodal molecular sensors that respond to a wide variety of stimuli, including mechanical, chemical, and thermal. TRP channels are present in most eukaryotes but best understood in mammalian, worm, and fly genetic models, where they are expressed in diverse cell-types and commonly associated with the nervous system. Here, we characterized TRP superfamily gene and genome evolution to better understand origins and evolution of molecular sensors, brains, and behavior in animals and help advance development of novel genetic technologies, like sonogenetics. We developed a flexible push-button bioinformatic and phylogenomic pipeline, GIGANTIC, that generated genome-based gene and species trees and enabled phylogenetic characterization of challenging remote homologs and distantly-related organisms deep in evolution. We identified complete sets of TRP superfamily ion channels, with over 3000 genes in 22 animal phyla and 70 species having publicly-available sequenced genomes, including 3 unicellular outgroups. We then identified clusters of TRP family members in genomes, evaluated gene models per cluster, and repaired split gene models. We also produced whole-organism PacBio transcriptomes for five species to independently validate our gene model assessment and model repairs. We find that many TRP families exhibited numerous and often extensive expansions in different phyla. Some expansions represent local clusters on respective genomes, a trend that is likely undercounted due to varied quality in genome assemblies and annotations of non-model organisms. Our work expands known TRP diversity across animals, including addition of previously uncharacterized phyla and identification of unrecognized homologs in previously characterized species.