The characterization of nanoparticle size and structure by means of classical light scattering measurements from monodisperse suspensions is examined from both the Rayleigh–Gans (R–G) approximation ...as well as (for various spherical structures) the exact Lorenz–Mie theory. A means by which the traditional limits of the R–G theory may be extended and simplified is shown by a detailed discussion of the characteristic mean-square radius. This becomes particularly important for irregular particle shapes, where scattering depends on the orientation of such particles with respect to the direction of the incident illumination. A variety of particle structures are addressed, including rods, tubes, ellipsoids, rings, and superellipsoids.
Energy drinks refer to non-alcoholic beverages that contain caffeine, amino acids, herbs, and vitamins. Although energy drinks are marketed to reduce fatigue and improve physical/mental performance, ...frequent consumption of these beverages has been linked to negative health consequences. The purpose of this study is to provide timely, national estimates of the percentage of energy drink consumers in the U.S. and to analyze trends in energy drink intake between 2003 and 2016.
A total of 9,911 adolescents (aged 12–19 years); 12,103 young adults (aged 20–39 years); and 11,245 middle-aged adults (aged 40–59 years) were assessed using dietary data from the 2003–2016 National Health and Nutrition Examination Surveys. For each age group (adolescents, young adults, and middle-aged adults), logistic regression was used to estimate the proportion of energy drink consumers, and negative binomial regression was used to estimate per capita energy drink consumption, adjusting for covariates. Differences in total caffeine intake between energy drink consumers and non-consumers were examined by pooling all survey years together and using negative binomial regression. Analyses were conducted in 2018.
From 2003 to 2016, the prevalence of energy drink consumption increased significantly for adolescents (0.2% to 1.4%, p=0.028); young adults (0.5% to 5.5%, p<0.001); and middle-aged adults (0.0% to 1.2%, p=0.006). Per capita consumption of energy drinks increased significantly from 2003 to 2016 only for young adults (1.1 to 9.7 calories, p<0.001). Pooled across years, energy drink consumers had significantly higher total caffeine intake compared with non-consumers for adolescents (227.0 mg vs 52.1 mg, p<0.001); young adults (278.7 mg vs 135.3 mg, p<0.001); and middle-aged adults (348.8 mg vs 219.0 mg, p<0.001).
These findings indicate that consumption of energy drinks has grown substantially and that these drinks are a major source of caffeine among those who consume them.
B cell receptor (BCR) sequencing is a powerful tool for interrogating immune responses to infection and vaccination, but it provides limited information about the antigen specificity of the sequenced ...BCRs. Here, we present LIBRA-seq (linking B cell receptor to antigen specificity through sequencing), a technology for high-throughput mapping of paired heavy- and light-chain BCR sequences to their cognate antigen specificities. B cells are mixed with a panel of DNA-barcoded antigens so that both the antigen barcode(s) and BCR sequence are recovered via single-cell next-generation sequencing. Using LIBRA-seq, we mapped the antigen specificity of thousands of B cells from two HIV-infected subjects. The predicted specificities were confirmed for a number of HIV- and influenza-specific antibodies, including known and novel broadly neutralizing antibodies. LIBRA-seq will be an integral tool for antibody discovery and vaccine development efforts against a wide range of antigen targets.
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•LIBRA-seq: high-throughput mapping of BCR sequence to antigen specificity•Identified HIV- and influenza-specific B cells in two HIV-infected subjects•Predicted antigen reactivity for thousands of single B cells•Identified a previously unknown broadly neutralizing HIV antibody
LIBRA-seq enables high-throughput mapping of B cell receptor sequence to antigen specificity at the single-cell level.
Complement activation has a role in the pathogenesis of IgA nephropathy, an autoimmune disease mediated by pathogenic immune complexes consisting of galactose-deficient IgA1 bound by antiglycan ...antibodies. Of three complement-activation pathways, the alternative and lectin pathways are involved in IgA nephropathy. IgA1 can activate both pathways in vitro, and pathway components are present in the mesangial immunodeposits, including properdin and factor H in the alternative pathway and mannan-binding lectin, mannan-binding lectin-associated serine proteases 1 and 2, and C4d in the lectin pathway. Genome-wide association studies identified deletion of complement factor H-related genes 1 and 3 as protective against the disease. Because the corresponding gene products compete with factor H in the regulation of the alternative pathway, it has been hypothesized that the absence of these genes could lead to more potent inhibition of complement by factor H. Complement activation can take place directly on IgA1-containing immune complexes in circulation and/or after their deposition in the mesangium. Notably, complement factors and their fragments may serve as biomarkers of IgA nephropathy in serum, urine, or renal tissue. A better understanding of the role of complement in IgA nephropathy may provide potential targets and rationale for development of complement-targeting therapy of the disease.
The severity of marine heatwaves (MHWs) that are increasingly impacting ocean ecosystems, including vulnerable coral reefs, has primarily been assessed using remotely sensed sea-surface temperatures ...(SSTs), without information relevant to heating across ecosystem depths. Here, using a rare combination of SST, high-resolution in-situ temperatures, and sea level anomalies observed over 15 years near Moorea, French Polynesia, we document subsurface MHWs that have been paradoxical in comparison to SST metrics and associated with unexpected coral bleaching across depths. Variations in the depth range and severity of MHWs was driven by mesoscale (10s to 100s of km) eddies that altered sea levels and thermocline depths and decreased (2007, 2017 and 2019) or increased (2012, 2015, 2016) internal-wave cooling. Pronounced eddy-induced reductions in internal waves during early 2019 contributed to a prolonged subsurface MHW and unexpectedly severe coral bleaching, with subsequent mortality offsetting almost a decade of coral recovery. Variability in mesoscale eddy fields, and thus thermocline depths, is expected to increase with climate change, which, along with strengthening and deepening stratification, could increase the occurrence of subsurface MHWs over ecosystems historically insulated from surface ocean heating by the cooling effects of internal waves.
Abstract
Ferroelectric liquid crystals remain of interest for display and spatial light modulators because they exhibit significantly faster optical response times than nematics. However, smectic ...layers are sensitive to shock-induced flow and are usually permanently displaced once a well-aligned sample is disrupted, rendering such devices inoperable. We introduce a vertical alignment geometry combined with a surface-relief grating to control both the smectic layer and director orientations. This mode undergoes “self-healing” of the smectic layers after disruption by shock-induced flow. Sub-millisecond switching between optically distinct states is demonstrated using in-plane electric fields. Self-healing occurs within a second after being disrupted by shock, wherein both the layer and director realign without additional external stimulus. The route to material improvements for optimised devices is discussed, promising faster spatial light modulators for high-speed adaptive optics, micro-displays for virtual/augmented reality and telecommunications with inherent shock stability.
Significance Animal cells undergo a remarkable series of shape changes as they pass through mitosis and divide. In an epithelial tissue, the impact of these morphogenetic processes depends strongly ...on the orientation of division. However, the cues orienting divisions remain poorly understood. Here, we combine live imaging and mechanical perturbations with computational modeling to investigate the effects of shape changes accompanying mitosis and division in stretched monolayers in the absence of neighbor exchange. We show that divisions orient with the long cell axis rather than with the stress direction, and show how oriented divisions contribute to the restoration of cell packing and stress relaxation. In doing so, we identify a clear role for oriented cell division in morphogenetically active tissues.
Cell division plays an important role in animal tissue morphogenesis, which depends, critically, on the orientation of divisions. In isolated adherent cells, the orientation of mitotic spindles is sensitive to interphase cell shape and the direction of extrinsic mechanical forces. In epithelia, the relative importance of these two factors is challenging to assess. To do this, we used suspended monolayers devoid of ECM, where divisions become oriented following a stretch, allowing the regulation and function of epithelial division orientation in stress relaxation to be characterized. Using this system, we found that divisions align better with the long, interphase cell axis than with the monolayer stress axis. Nevertheless, because the application of stretch induces a global realignment of interphase long axes along the direction of extension, this is sufficient to bias the orientation of divisions in the direction of stretch. Each division redistributes the mother cell mass along the axis of division. Thus, the global bias in division orientation enables cells to act collectively to redistribute mass along the axis of stretch, helping to return the monolayer to its resting state. Further, this behavior could be quantitatively reproduced using a model designed to assess the impact of autonomous changes in mitotic cell mechanics within a stretched monolayer. In summary, the propensity of cells to divide along their long axis preserves epithelial homeostasis by facilitating both stress relaxation and isotropic growth without the need for cells to read or transduce mechanical signals.
Pharmacology of pannexin channels Koval, Michael; Schug, Wyatt J.; Isakson, Brant E.
Current opinion in pharmacology,
04/2023, Letnik:
69
Journal Article
Recenzirano
Odprti dostop
Pannexin channels play fundamental roles in regulating inflammation and have been implicated in many diseases including hypertension, stroke, and neuropathic pain. Thus, the ability to ...pharmacologically block these channels is a vital component of several therapeutic approaches. Pharmacologic interrogation of model systems also provides a means to discover new roles for pannexins in cell physiology. Here, we review the state of the art for agents that can be used to block pannexin channels, with a focus on chemical pharmaceuticals and peptide mimetics that act on pannexin 1. Guidance on interpreting results obtained with pannexin pharmacologics in experimental systems is discussed, as well as strengths and caveats of different agents, including specificity and feasibility of clinical application.
Epithelial monolayers are two-dimensional cell sheets which compartmentalize the body and organs of multicellular organisms. Their morphogenesis during development or pathology results from patterned ...endogenous and exogenous forces and their interplay with tissue mechanical properties. In particular, bending of epithelia is thought to result from active torques generated by the polarization of myosin motors along their apicobasal axis. However, the contribution of these out-of-plane forces to morphogenesis remains challenging to evaluate because of the lack of direct mechanical measurement. Here we use epithelial curling to characterize the out-of-plane mechanics of epithelial monolayers. We find that curls of high curvature form spontaneously at the free edge of epithelial monolayers devoid of substrate in vivo and in vitro. Curling originates from an enrichment of myosin in the basal domain that generates an active spontaneous curvature. By measuring the force necessary to flatten curls, we can then estimate the active torques and the bending modulus of the tissue. Finally, we show that the extent of curling is controlled by the interplay between in-plane and out-of-plane stresses in the monolayer. Such mechanical coupling emphasizes a possible role for in-plane stresses in shaping epithelia during morphogenesis.
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