Raman micro-spectroscopy as a tool to study immunometabolism

In the past two decades, immunometabolism has emerged as a crucial field, unraveling the intricate molecular connections between cellular metabolism and immune function across various cell types, tissues, and diseases. This review explores the insights gained from studies using the emerging technology, Raman micro-spectroscopy, to investigate immunometabolism. Raman micro-spectroscopy provides an exciting opportunity to directly study metabolism at the single cell level where it can be combined with other Raman-based technologies and platforms such as single cell RNA sequencing. The review showcases applications of Raman micro-spectroscopy to study the immune system including cell identification, activation, and autoimmune disease diagnosis, offering a rapid, label-free, and minimally invasive analytical approach. The review spotlights three promising Raman technologies, Raman-activated cell sorting, Raman stable isotope probing, and Raman imaging. The synergy of Raman technologies with machine learning is poised to enhance the understanding of complex Raman phenotypes, enabling biomarker discovery and comprehensive investigations in immunometabolism. The review encourages further exploration of these evolving technologies in the rapidly advancing field of immunometabolism

Mixing and entrainment in hydraulically driven stratified sill flows

Author Posting. © Cambridge University Press, 2004. This article is posted here by permission of Cambridge University Press for personal use, not for redistribution. The definitive version was published in Journal of Fluid Mechanics 515 (2004): 415-443, doi:10.1017/S0022112004000576.The investigation involves the hydraulic behaviour of a dense layer of fluid flowing over an obstacle and subject to entrainment of mass and momentum from a dynamically inactive (but possibly moving) overlying fluid. An approach based on the use of reduced gravity, shallow-water theory with a cross-interface entrainment velocity is compared with numerical simulations based on a model with continuously varying stratification and velocity. The locations of critical flow (hydraulic control) in the continuous model are estimated by observing the direction of propagation of small-amplitude long-wave disturbances introduced into the flow field. Although some of the trends predicted by the shallow-water model are observed in the continuous model, the agreement between the interface profiles and the position of critical flow is quantitatively poor. A reformulation of the equations governing the continuous flow suggests that the reduced gravity model systematically underestimates inertia and overestimates buoyancy. These differences are quantified by shape coefficients that measure the vertical non-uniformities of the density and horizontal velocity that arise, in part, by incomplete mixing of entrained mass and momentum over the lower-layer depth. Under conditions of self-similarity (as in Wood's similarity solution) the shape coefficients are constant and the formulation determines a new criterion for and location of critical flow. This location generally lies upstream of the critical section predicted by the reduced-gravity model. Self-similarity is not observed in the numerically generated flow, but the observed critical section continues to lie upstream of the location predicted by the reduced gravity model. The factors influencing this result are explored.M. H. N. would like to thank the Danish Natural Science Research Council for financial support. L. P. and K. H. were supported by the Office of Naval Research under grant N00014-1-01-0167 and by the National Science Foundation under grant OCE-0132903

Raman micro-spectroscopy as a tool to study immunometabolism

In the past two decades, immunometabolism has emerged as a crucial field, unraveling the intricate molecular connections between cellular metabolism and immune function across various cell types, tissues, and diseases. This review explores the insights gained from studies using the emerging technology, Raman micro-spectroscopy, to investigate immunometabolism. Raman micro-spectroscopy provides an exciting opportunity to directly study metabolism at the single cell level where it can be combined with other Raman-based technologies and platforms such as single cell RNA sequencing. The review showcases applications of Raman micro-spectroscopy to study the immune system including cell identification, activation, and autoimmune disease diagnosis, offering a rapid, label-free, and minimally invasive analytical approach. The review spotlights three promising Raman technologies, Raman-activated cell sorting, Raman stable isotope probing, and Raman imaging. The synergy of Raman technologies with machine learning is poised to enhance the understanding of complex Raman phenotypes, enabling biomarker discovery and comprehensive investigations in immunometabolism. The review encourages further exploration of these evolving technologies in the rapidly advancing field of immunometabolism

Music in the brain

Music is ubiquitous across human cultures — as a source of affective and pleasurable experience, moving us both physically and emotionally — and learning to play music shapes both brain structure and brain function. Music processing in the brain — namely, the perception of melody, harmony and rhythm — has traditionally been studied as an auditory phenomenon using passive listening paradigms. However, when listening to music, we actively generate predictions about what is likely to happen next. This enactive aspect has led to a more comprehensive understanding of music processing involving brain structures implicated in action, emotion and learning. Here we review the cognitive neuroscience literature of music perception. We show that music perception, action, emotion and learning all rest on the human brain’s fundamental capacity for prediction — as formulated by the predictive coding of music model. This Review elucidates how this formulation of music perception and expertise in individuals can be extended to account for the dynamics and underlying brain mechanisms of collective music making. This in turn has important implications for human creativity as evinced by music improvisation. These recent advances shed new light on what makes music meaningful from a neuroscientific perspective

Processing multiple non-adjacent dependencies: evidence from sequence learning

Processing non-adjacent dependencies is considered to be one of the hallmarks of human language. Assuming that sequence-learning tasks provide a useful way to tap natural-language-processing mechanisms, we cross-modally combined serial reaction time and artificial-grammar learning paradigms to investigate the processing of multiple nested (A(1)A(2)A(3)B(3)B(2)B(1)) and crossed dependencies (A(1)A(2)A(3)B(1)B(2)B(3)), containing either three or two dependencies. Both reaction times and prediction errors highlighted problems with processing the middle dependency in nested structures (A(1)A(2)A(3)B(3-)B(1)), reminiscent of the 'missing-verb effect' observed in English and French, but not with crossed structures (A(1)A(2)A(3)B(1-)B(3)). Prior linguistic experience did not play a major role: native speakers of German and Dutch-which permit nested and crossed dependencies, respectively-showed a similar pattern of results for sequences with three dependencies. As for sequences with two dependencies, reaction times and prediction errors were similar for both nested and crossed dependencies. The results suggest that constraints on the processing of multiple non-adjacent dependencies are determined by the specific ordering of the non-adjacent dependencies (i.e. nested or crossed), as well as the number of non-adjacent dependencies to be resolved (i. e. two or three). Furthermore, these constraints may not be specific to language but instead derive from limitations on structured sequence learning.Netherlands Organisation of Scientific Research (NWO) [446-08-014]; Max Planck Institute for Psycholinguistics; Donders Institute for Brain, Cognition and Behaviour; Fundacao para a Ciencia e Tecnologia (IBB/CBME, LA, FEDER/POCI) [PTDC/PSI-PCO/110734/2009]; Stockholm Brain Institute; Vetenskapsradet; Swedish Dyslexia Foundation; Hedlunds Stiftelse; Stockholm County Council (ALF, FoUU)info:eu-repo/semantics/publishedVersio

Superconducting Gatemon Qubit based on a Proximitized Two-Dimensional Electron Gas

The coherent tunnelling of Cooper pairs across Josephson junctions (JJs) generates a nonlinear inductance that is used extensively in quantum information processors based on superconducting circuits, from setting qubit transition frequencies and interqubit coupling strengths, to the gain of parametric amplifiers for quantum-limited readout. The inductance is either set by tailoring the metal-oxide dimensions of single JJs, or magnetically tuned by parallelizing multiple JJs in superconducting quantum interference devices (SQUIDs) with local current-biased flux lines. JJs based on superconductor-semiconductor hybrids represent a tantalizing all-electric alternative. The gatemon is a recently developed transmon variant which employs locally gated nanowire (NW) superconductor-semiconductor JJs for qubit control. Here, we go beyond proof-of-concept and demonstrate that semiconducting channels etched from a wafer-scale two-dimensional electron gas (2DEG) are a suitable platform for building a scalable gatemon-based quantum computer. We show 2DEG gatemons meet the requirements by performing voltage-controlled single qubit rotations and two-qubit swap operations. We measure qubit coherence times up to ~2 us, limited by dielectric loss in the 2DEG host substrate

The impact of a structured exercise programme upon cognitive function in chronic fatigue syndrome patients

Background: Cognitive function disturbance is a frequently described symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In this study, the effects of a structured exercise programme (SEP) upon cognitive function in ME/CFS patients was examined. Methods: Out of the 53 ME/CFS patients initiating SEP 34 (64%) completed the 16 week programme. Cognitive function was assessed using a computerized battery test consisting of a Simple Reaction Time (SRT) (repeated three times)

Acetyl-leucine slows disease progression in lysosomal storage disorders

Acetyl-DL-leucine is a derivative of the branched chain amino acid leucine. In observational clinical studies acetyl-DL-leucine improved symptoms of ataxia, in particular in patients with the lysosomal storage disorder, Niemann-Pick disease type C1. Here, we investigated acetyl-DL-leucine and its enantiomers acetyl-L-leucine and acetyl-D-leucine in symptomatic Npc1-/- mice and observed improvement in ataxia with both individual enantiomers and acetyl-DL-leucine. When acetyl-DL-leucine and acetyl-L-leucine were administered pre-symptomatically to Npc1-/- mice, both treatments delayed disease progression and extended life span, whereas acetyl-D-leucine did not. These data are consistent with acetyl-L-leucine being the neuroprotective enantiomer. Altered glucose and antioxidant metabolism were implicated as one of the potential mechanisms of action of the L enantiomer in Npc1-/- mice. When the standard of care drug miglustat and acetyl-DL-leucine were used in combination significant synergy resulted. In agreement with these pre-clinical data, when Niemann-Pick disease type C1 patients were evaluated after 12 months of acetyl-DL-leucine treatment, rates of disease progression were slowed, with stabilisation or improvement in multiple neurological domains. A beneficial effect of acetyl-DL-leucine on gait was also observed in this study in a mouse model of GM2 gangliosidosis (Sandhoff disease) and in Tay-Sachs and Sandhoff disease patients in individual cases of off-label-use. Taken together, we have identified an unanticipated neuroprotective effect of acetyl-L-leucine and underlying mechanisms of action in lysosomal storage diseases, supporting its further evaluation in clinical trials in lysosomal disorders

The efficacy of the quercetin analogue LY294002 in immortalized cancer cell lines is related to the oxygenic and metabolic status of cells

Purpose: LY294002, a promising drug for chemotherapy, suppresses the activity of Phosphatidylinositol 3-Kinase (PI3K) which is pivotal to a number of processes such as proliferation, metabolism, and apoptosis. The compound has, however, been seen to have very variable efficacy in vivo.Methods: Proliferation and viability of two immortalized cells with divergent bioenergetic profiles was determined using crystal violet staining, and the 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Oxygen consumption rates were determined using MitoXpress-Xtra probes, and lactate generation was assessed with pH-Xtra probe and BM-lactate strips. Immunoblotting was performed with phospho-Akt-Ser 473 and Akt-pan primary antibodies.Results: U87 cells were shown to have a glycolytic metabolism, whereas RD cells exhibited a more aerobic metabolism. In both lines, hypoxia was shown to increase lactate production, and LY294002 reduced lactate production. The drug decreased cell proliferation and viability under all conditions, but the effect was greatest in U87 cells under normoxic conditions.Conclusion: Metabolic analysis showed a link between a glycolytic cell status and LY294002 induced cell death. However, in both cell lines the drug was also less effective under hypoxic conditions, as would be found in a tumour in vivo. Furthermore, in the presence of LY294002 the phosphorylation status of Akt, a target of PI3K, was found to be related to both the mechanism of cell respiration, and the oxygenic status of the cells