Cardiac parasympathetic activity may be non-invasively investigated using heart rate variability (HRV), although HRV is not widely accepted to reflect sympathetic activity. Instead, cardiac ...sympathetic activity may be investigated using systolic time intervals (STI), such as the pre-ejection period. Although these autonomic indices are typically measured during rest, the "reactivity hypothesis" suggests that investigating responses to a stressor (e.g., exercise) may be a valuable monitoring approach in clinical and high-performance settings. However, when interpreting these indices it is important to consider how the exercise dose itself (i.e., intensity, duration, and modality) may influence the response. Therefore, the purpose of this investigation was to review the literature regarding how the exercise dosage influences these autonomic indices during exercise and acute post-exercise recovery. There are substantial methodological variations throughout the literature regarding HRV responses to exercise, in terms of exercise protocols and HRV analysis techniques. Exercise intensity is the primary factor influencing HRV, with a greater intensity eliciting a lower HRV during exercise up to moderate-high intensity, with minimal change observed as intensity is increased further. Post-exercise, a greater preceding intensity is associated with a slower HRV recovery, although the dose-response remains unclear. A longer exercise duration has been reported to elicit a lower HRV only during low-moderate intensity and when accompanied by cardiovascular drift, while a small number of studies have reported conflicting results regarding whether a longer duration delays HRV recovery. "Modality" has been defined multiple ways, with limited evidence suggesting exercise of a greater muscle mass and/or energy expenditure may delay HRV recovery. STI responses during exercise and recovery have seldom been reported, although limited data suggests that intensity is a key determining factor. Concurrent monitoring of HRV and STI may be a valuable non-invasive approach to investigate autonomic stress reactivity; however, this integrative approach has not yet been applied with regards to exercise stressors.
Evidence continues to grow of the importance of in vitro and in vivo dosimetry in the hazard assessment and ranking of engineered nanomaterials (ENMs). Accurate dose metrics are particularly ...important for in vitro cellular screening to assess the potential health risks or bioactivity of ENMs. To ensure meaningful and reproducible quantification of in vitro dose, with consistent measurement and reporting between laboratories, it is necessary to adopt standardized and integrated methodologies for (i) generation of stable ENM suspensions in cell culture media; (ii) colloidal characterization of suspended ENMs, particularly of properties that determine particle kinetics in an in vitro system (size distribution and formed agglomerate effective density); and (iii) robust numerical fate and transport modeling for accurate determination of the ENM dose delivered to cells over the course of the in vitro exposure. Here we present an integrated comprehensive protocol based on such a methodology for in vitro dosimetry, including detailed standardized procedures for each of these three critical aims. The entire protocol requires ∼6-12 h to complete.
The current Southwest drought is exceptional for its high temperatures and arguably the most severe in history. Coincidentally, there has been an increase in forest and woodland mortality due to ...fires and pathogenic outbreaks. Although the high temperatures and aridity are consistent with projected impacts of greenhouse warming, it is unclear whether the drought can be attributed to increased greenhouse gasses or is a product of natural climatic variability. Climate models indicate that the 21st century will be increasingly arid and droughts more severe and prolonged. Forest and woodland mortality due to fires and pathogens will increase. Demography and food security dictate that water demand in the Southwest will remain appreciable. If projected population growth is twinned with suburb-centered development, domestic demands will intensify. Meeting domestic demands through transference from agriculture presents concerns for rural sustainability and food security. Environmental concerns will limit additional transference from rivers. It is unlikely that traditional supply-side solutions such as more dams will securely meet demands at current per-capita levels. Significant savings in domestic usage can be realized through decreased applications of potable water to landscaping, but this is a small fraction of total regional water use, which is dominated by agriculture. Technical innovations, policy measures, and market-based solutions that increase supply and decrease water demand are all needed. Meeting 21st-century sustainability challenges in the Southwest will also require planning, cooperation, and integration that surpass 20th-century efforts in terms of geographic scope, jurisdictional breadth, multisectoral engagement, and the length of planning timelines.
Ionic solids from common colloids Hueckel, Theodore; Hocky, Glen M; Palacci, Jeremie ...
Nature (London),
04/2020, Letnik:
580, Številka:
7804
Journal Article
Recenzirano
From rock salt to nanoparticle superlattices, complex structure can emerge from simple building blocks that attract each other through Coulombic forces
. On the micrometre scale, however, colloids in ...water defy the intuitively simple idea of forming crystals from oppositely charged partners, instead forming non-equilibrium structures such as clusters and gels
. Although various systems have been engineered to grow binary crystals
, native surface charge in aqueous conditions has not been used to assemble crystalline materials. Here we form ionic colloidal crystals in water through an approach that we refer to as polymer-attenuated Coulombic self-assembly. The key to crystallization is the use of a neutral polymer to keep particles separated by well defined distances, allowing us to tune the attractive overlap of electrical double layers, directing particles to disperse, crystallize or become permanently fixed on demand. The nucleation and growth of macroscopic single crystals is demonstrated by using the Debye screening length to fine-tune assembly. Using a variety of colloidal particles and commercial polymers, ionic colloidal crystals isostructural to caesium chloride, sodium chloride, aluminium diboride and K
C
are selected according to particle size ratios. Once fixed by simply diluting out solution salts, crystals are pulled out of the water for further manipulation, demonstrating an accurate translation from solution-phase assembly to dried solid structures. In contrast to other assembly approaches, in which particles must be carefully engineered to encode binding information
, polymer-attenuated Coulombic self-assembly enables conventional colloids to be used as model colloidal ions, primed for crystallization.
Small mechanical forces play important functional roles in many crucial cellular processes, including in the dynamic behavior of the cytoskeleton and in the regulation of osmotic pressure through ...membrane-bound proteins. Molecular simulations offer the promise of being able to design the behavior of proteins that sense and respond to these forces. However, it is difficult to predict and identify the effect of the relevant piconewton (pN) scale forces due to their small magnitude. Previously, we introduced the Infinite Switch Simulated Tempering in Force (FISST) method, which allows one to estimate the effect of a range of applied forces from a single molecular dynamics simulation, and also demonstrated that FISST additionally accelerates sampling of a molecule’s conformational landscape. For some problems, we find that this acceleration is not sufficient to capture all relevant conformational fluctuations, and hence, here we demonstrate that FISST can be combined with either temperature replica exchange or solute tempering approaches to produce a hybrid method that enables more robust prediction of the effect of small forces on molecular systems.
In this work, we demonstrate that Linear Discriminant Analysis (LDA) applied to atomic positions in two different states of a biomolecule produces a good reaction coordinate between those two states. ...Atomic coordinates of a macromolecule are a direct representation of a macromolecular configuration, and yet, they are not used in enhanced sampling studies due to a lack of rotational and translational invariance. We resolve this issue using the technique of our prior work, whereby a molecular configuration is considered a member of an equivalence class in size-and-shape space, which is the set of all configurations that can be translated and rotated to a single point within a reference multivariate Gaussian distribution characterizing a single molecular state. The reaction coordinates produced by LDA applied to positions are shown to be good reaction coordinates both in terms of characterizing the transition between two states of a system within a long molecular dynamics (MD) simulation and also ones that allow us to readily produce free energy estimates along that reaction coordinate using enhanced sampling MD techniques.
Determining the optimal number and identity of structural clusters from an ensemble of molecular configurations continues to be a challenge. Recent structural clustering methods have focused on the ...use of internal coordinates due to the innate rotational and translational invariance of these features. The vast number of possible internal coordinates necessitates a feature space supervision step to make clustering tractable but yields a protocol that can be system type-specific. Particle positions offer an appealing alternative to internal coordinates but suffer from a lack of rotational and translational invariance, as well as a perceived insensitivity to regions of structural dissimilarity. Here, we present a method, denoted shape-GMM, that overcomes the shortcomings of particle positions using a weighted maximum likelihood alignment procedure. This alignment strategy is then built into an expectation maximization Gaussian mixture model (GMM) procedure to capture metastable states in the free-energy landscape. The resulting algorithm distinguishes between a variety of different structures, including those indistinguishable by root-mean-square displacement and pairwise distances, as demonstrated on several model systems. Shape-GMM results on an extensive simulation of the fast-folding HP35 Nle/Nle mutant protein support a four-state folding/unfolding mechanism, which is consistent with previous experimental results and provides kinetic details comparable to previous state-of-the art clustering approaches, as measured by the VAMP-2 score. Currently, training of shape-GMMs is recommended for systems (or subsystems) that can be represented by ≲200 particles and ≲100k configurations to estimate high-dimensional covariance matrices and balance computational expense. Once a shape-GMM is trained, it can be used to predict the cluster identities of millions of configurations.
Catching actin proteins in action Cossio, Pilar; Hocky, Glen M
Nature (London),
11/2022, Letnik:
611, Številka:
7935
Journal Article
Recenzirano
In the current studies, the groups used optimized cryo-electron microscopy (cryo-EM) sample preparation and work flows to obtain cryo-EM density maps for straight actin filaments in the different ...nucleotide states at unprecedented resolution (down to 2.2 angstroms). A remaining challenge is to determine to what degree conformational fluctuations modulate the interactions between specific actin-binding partners, and to work out whether some of these functional but transient states exist in the many particles that have been discarded in the cryo-EM analysis. Computational-modelling techniques will be invaluable for predicting the full range of large-scale conformational changes that a protein can adopt, and the timescales on which they occur, as well as for predicting the effect of non-equilibrium forces (such as those produced when polymerization occurs perpendicularly to a cell membrane, or owing to molecular motors) on biomolecular assemblies12.
Engineered nanomaterials are increasingly added to foods to improve quality, safety, or nutrition. Here we report the ability of ingested nanocellulose (NC) materials to reduce digestion and ...absorption of ingested fat. In the small intestinal phase of an acellular simulated gastrointestinal tract, the hydrolysis of free fatty acids (FFA) from triglycerides (TG) in a high-fat food model was reduced by 48.4% when NC was added at 0.75% w/w to the food, as quantified by pH stat titration, and by 40.1% as assessed by fluorometric FFA assay. Furthermore, translocation of TG and FFA across an in vitro cellular model of the intestinal epithelium was significantly reduced by the presence of 0.75% w/w NC in the food (TG by 52% and FFA by 32%). Finally, in in vivo experiments, the postprandial rise in serum TG 1 h after gavage with the high fat food model was reduced by 36% when 1.0% w/w NC was administered with the food. Scanning electron microscopy and molecular dynamics studies suggest two primary mechanisms for this effect: (1) coalescence of fat droplets on fibrillar NC (CNF) fibers, resulting in a reduction of available surface area for lipase binding and (2) sequestration of bile salts, causing impaired interfacial displacement of proteins at the lipid droplet surface and impaired solubilization of lipid digestion products. Together these findings suggest a potential use for NC, as a food additive or supplement, to reduce absorption of ingested fat and thereby assist in weight loss and the management of obesity.
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