Search

Purpose of Review: To present recent evidence that strengthens the concept that exogenous pollutants contribute to adipose dysfunction and increased rates of disease and to highlight the ineffective regulation of this risk as industry switches to related but similarly toxic variants., Recent Findings: Substitutes for common phthalates and the highly regulated bisphenol A (BPA) show similar deleterious effects on adipocytes. The well tolerated limit for BPA exposure has been reduced in Europe to below the level detected in recent population studies. Additionally, the role for BPA-induced inflammation mediated by interleukin 17a has been described in animal and human studies., Summary: Despite experimental and associative evidence that supports plastics and plastic associated chemicals deleteriously influencing adipose homeostatasis and contributing to metabolic diseases, structurally related alternate chemicals are being substituted by manufacturers to circumvent trailing regulatory actions., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Several theories of belief processing assume that processing another's false belief requires overcoming an egocentric bias toward one's current knowledge. The current evidence in support of this claim, however, is limited. In order to investigate the presence of egocentric bias in adult belief processing, computer mouse tracking was used across three experiments to measure attraction toward response options reflecting one's current knowledge while reporting a false belief. Participants viewed scenarios in which an agent either had a true belief or a false belief about the location of a set of keys. Participants used a mouse to answer reality questions "where are the keys currently hidden?" and belief questions "where does she think the keys are?" Mouse-tracking measures indexing attraction toward response options during decision making were measured, along with time taken to make a response and accuracy. Experiment 1 found no evidence, in any measures, that participants showed a bias toward their own knowledge when reporting another's false belief. Experiment 2 investigated whether differences in event timings between true belief and false belief scenarios in Experiment 1 masked an egocentric bias. Experiment 3 investigated whether the lack of egocentric bias could be explained by participants prioritizing encoding the other's beliefs. Neither follow-up experiment found evidence supporting the presence of an egocentric bias. Overall, contrary to many theories of belief processing, our results suggest that adults are readily able to process other people's beliefs without having to overcome a default bias toward their own knowledge. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Using holographic duality, we present an analytically controlled theory of quantum critical points without quasiparticles, at finite disorder and finite charge density. These fixed points are obtained by perturbing a disorder-free quantum critical point with relevant disorder whose operator dimension is perturbatively close to Harris marginal. We analyze these fixed points both using field theoretic arguments, and by solving the bulk equations of motion in holography. We calculate the critical exponents of the IR theory, together with thermoelectric transport coefficients. Our predictions for the critical exponents of the disordered fixed point are consistent with previous work, both in holographic and nonholograpic models.

We review the mathematical speed limits on quantum information processing in many-body systems. After the proof of the Lieb-Robinson Theorem in 1972, the past two decades have seen substantial developments in its application to other questions, such as the simulatability of quantum systems on classical or quantum computers, the generation of entanglement, and even the properties of ground states of gapped systems. Moreover, Lieb-Robinson bounds have been extended in non-trivial ways, to demonstrate speed limits in systems with power-law interactions or interacting bosons, and even to prove notions of locality that arise in cartoon models for quantum gravity with all-to-all interactions. We overview the progress which has occurred, highlight the most promising results and techniques, and discuss some central outstanding questions which remain open. To help bring newcomers to the field up to speed, we provide self-contained proofs of the field's most essential results., (© 2023 IOP Publishing Ltd.)

Harmful algal blooms (HABs) are increasing globally, causing economic, human health, and ecosystem harm. In spite of the frequent occurrence of HABs, the mechanisms responsible for their exceptionally high biomass remain imperfectly understood. A 50-y-old hypothesis posits that some dense blooms derive from dinoflagellate motility: organisms swim upward during the day to photosynthesize and downward at night to access deep nutrients. This allows dinoflagellates to outgrow their nonmotile competitors. We tested this hypothesis with in situ data from an autonomous, ocean-wave-powered vertical profiling system. We showed that the dinoflagellate Lingulodinium polyedra 's vertical migration led to depletion of deep nitrate during a 2020 red tide HAB event. Downward migration began at dusk, with the maximum migration depth determined by local nitrate concentrations. Losses of nitrate at depth were balanced by proportional increases in phytoplankton chlorophyll concentrations and suspended particle load, conclusively linking vertical migration to the access and assimilation of deep nitrate in the ocean environment. Vertical migration during the red tide created anomalous biogeochemical conditions compared to 70 y of climatological data, demonstrating the capacity of these events to temporarily reshape the coastal ocean's ecosystem and biogeochemistry. Advances in the understanding of the physiological, behavioral, and metabolic dynamics of HAB-forming organisms from cutting-edge observational techniques will improve our ability to forecast HABs and mitigate their consequences in the future.

We prove that prethermalization is a generic property of gapped local many-body quantum systems, subjected to small perturbations, in any spatial dimension. More precisely, let H&#95;{0} be a Hamiltonian, spatially local in d spatial dimensions, with a gap Δ in the many-body spectrum; let V be a spatially local Hamiltonian consisting of a sum of local terms, each of which is bounded by ε≪Δ. Then, the approximation that quantum dynamics is restricted to the low-energy subspace of H&#95;{0} is accurate, in the correlation functions of local operators, for stretched exponential timescale τ∼exp[(Δ/ε)^{a}] for any a<1/(2d-1). This result does not depend on whether the perturbation closes the gap. It significantly extends previous rigorous results on prethermalization in models where H&#95;{0} was frustration-free. We infer the robustness of quantum simulation in low-energy subspaces, the existence of athermal "scarred" correlation functions in gapped systems subject to generic perturbations, the long lifetime of false vacua in symmetry broken systems, and the robustness of quantum information in non-frustration-free gapped phases with topological order.

Background: During solid organ transplantation, donor leukocytes, including myeloid cells, are transferred within the organ to the recipient. Both tolerogenic and alloreactive roles have been attributed to donor myeloid cells; however, their subset-specific retention posttransplantation has not been investigated in detail., Methods: Major histocompatibility complex (MHC)-matched and mismatched liver transplants were performed in mice, and the fate of donor and recipient myeloid cells was assessed., Results: Following MHC-matched transplantation, a proportion of donor myeloid cells was retained in the graft, whereas others egressed and persisted in the blood, spleen, and bone marrow but not the lymph nodes. In contrast, after MHC-mismatched transplantation, all donor myeloid cells, except Kupffer cells, were depleted. This depletion was caused by recipient T and B cells because all donor myeloid subsets were retained in MHC-mismatched grafts when recipients lacked T and B cells. Recipient myeloid cells rapidly infiltrated MHC-matched and, to a greater extent, MHC-mismatched liver grafts. MHC-mismatched grafts underwent a transient rejection episode on day 7, coinciding with a transition in macrophages to a regulatory phenotype, after which rejection resolved., Conclusions: Phenotypic and kinetic differences in the myeloid cell responses between MHC-matched and mismatched grafts were identified. A detailed understanding of the dynamics of immune responses to transplantation is critical to improving graft outcomes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

The American Trial Using Tranexamic Acid (TXA) in Thrombocytopenia (A-TREAT, NCT02578901) demonstrated no superiority of TXA over placebo in preventing World Health Organization (WHO) grade 2 or higher bleeding in patients with severe thrombocytopenia requiring supportive platelet transfusion following myeloablative therapy for hematologic disorders. In this ancillary study, we sought to determine whether this clinical outcome could be explained on the basis of correlative assays of fibrinolysis. Plasma was collected from A-TREAT participants (n = 115) before the initiation of study drug (baseline) and when TXA was at steady-state trough concentration (follow-up). Global fibrinolysis was measured by 3 assays: euglobulin clot lysis time (ECLT), plasmin generation (PG), and tissue-type plasminogen activator (tPA)-challenged clot lysis time (tPA-CLT). TXA was quantified in follow-up samples by tandem mass spectrometry. Baseline samples did not demonstrate fibrinolytic activation by ECLT or tPA-CLT. Furthermore, neither ECLT nor levels of plasminogen activator inhibitor-1, tPA, plasminogen, alpha2-antiplasmin, or plasmin-antiplasmin complexes were associated with a greater risk of WHO grade 2+ bleeding. TXA trough concentrations were highly variable (range, 0.7-10 μg/mL) and did not correlate with bleeding severity, despite the fact that plasma TXA levels correlated strongly with pharmacodynamic assessments by PG (Spearman r, -0.78) and tPA-CLT (r, 0.74). We conclude that (1) no evidence of fibrinolytic activation was observed in these patients with thrombocytopenia, (2) trough TXA concentrations varied significantly between patients receiving the same dosing schedule, and (3) tPA-CLT and PG correlated well with TXA drug levels., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with chronic inflammation and tissue remodelling leading to fibrosis, reduced pulmonary function, respiratory failure and death. Bleomycin (Blm)-induced lung fibrosis in mice replicates several clinical features of human IPF, including prominent lymphoid aggregates of predominantly B-cells that accumulate in the lung adjacent to areas of active fibrosis. We have shown previously a requirement for B-cells in the development of Blm-induced lung fibrosis in mice. To determine the therapeutic potential of inhibiting B-cell function in pulmonary fibrosis, we examined the effects of anti-CD20 B-cell ablation therapy to selectively remove mature B-cells from the immune system and inhibit Blm-induced lung fibrosis. Anti-CD20 B-cell ablation did not reduce fibrosis in this model; however, immune phenotyping of peripheral blood and lung resident cells revealed that anti-CD20-treated mice retained a high frequency of CD19 + CD138 + plasma cells. Interestingly, high levels of CD138 + cells were also identified in the lung tissue of patients with IPF, consistent with the mouse model. Treatment of mice with bortezomib, which depletes plasma cells, reduced the level of Blm-induced lung fibrosis, implicating plasma cells as important effector cells in the development and progression of pulmonary fibrosis., Competing Interests: Conflict of interest: S.E. Mutsaers, C.M. Prêle, R.J. McAnulty, G.J. Laurent, G. Hoyne, D.A. Knight, R.J. O'Donoghue and M. Ernst received grants from National Health and Medical Research Council (NHMRC), project grants ID APP1067511. R.J. McAnulty, S.E. Mutsaers, C.M. Prêle and D.R. Pearce received grants from British Lung Foundation, project grant number PPRG15-10. T. Miles reports that Genentech provided the anti-CD20 antibody, and received UWA Research Training Program Scholarship and the Lung Foundation Australia Bill van Nierop PhD Scholarship. All other authors have nothing to disclose., (Copyright ©The authors 2022.)

We present an effective field theory for the nonlinear fluctuating hydrodynamics of a single conserved charge with or without time-reversal symmetry, based on the Martin-Siggia-Rose formalism. Applying this formalism to fluids with only charge and multipole conservation, and with broken time-reversal symmetry, we predict infinitely many new dynamical universality classes, including some with arbitrarily large upper critical dimensions. Using large scale simulations of classical Markov chains, we find numerical evidence for a breakdown of hydrodynamics in quadrupole-conserving models with broken time-reversal symmetry in one spatial dimension. Our framework can be applied to the hydrodynamics around stationary states of open systems, broadening the applicability of previously developed ideas and methods to a wide range of systems in driven and active matter.

Network effects are the added value derived solely from the popularity of a product in an economic market. Using agent-based models inspired by statistical physics, we propose a minimal theory of a competitive market for (nearly) indistinguishable goods with demand-side network effects, sold by statistically identical sellers. With weak network effects, the model reproduces conventional microeconomics: there is a statistical steady state of (nearly) perfect competition. Increasing network effects, we find a phase transition to a robust nonequilibrium phase driven by the spontaneous formation and collapse of fads in the market. When sellers update prices sufficiently quickly, an emergent monopolist can capture the market and undercut competition, leading to a symmetry- and ergodicity-breaking transition. The nonequilibrium phase simultaneously exhibits three empirically established phenomena not contained in the standard theory of competitive markets: spontaneous price fluctuations, persistent seller profits, and broad distributions of firm market shares.

The development of experimental models of cardiac transplantation in animals has contributed to many advances in the fields of immunology and solid organ transplantation. While the heterotopic vascularized murine cardiac transplantation model was initially utilized in studies of graft rejection using combinations of mismatched inbred mouse strains, access to genetically modified strains and therapeutic modalities can provide powerful new preclinical insights. Fundamentally, the surgical methodology for this technique has not changed since its development, especially with respect to important factors such as aseptic technique, anesthesia, and analgesia, which make material impacts on postsurgical morbidity and mortality. Additionally, improvements in perioperative management are expected to provide improvements in both animal welfare and experimental outcomes. This paper reports upon a protocol developed in collaboration with a subject matter expert in veterinary anesthesia and describes the surgical technique with an emphasis on perioperative management. Additionally, we discuss the implications of these refinements and provide details on troubleshooting critical surgical steps for this procedure.

Ohm's law describes the proportionality of the current density and electric field. In solid-state conductors, Ohm's law emerges due to electron scattering processes that relax the electrical current. Here, we use nitrogen-vacancy center magnetometry to directly image the local breakdown of Ohm's law in a narrow constriction fabricated in a high mobility graphene monolayer. Ohmic flow is visible at room temperature as current concentration on the constriction edges, with flow profiles entirely determined by sample geometry. However, as the temperature is lowered below 200 K, the current concentrates near the constriction center. The change in the flow pattern is consistent with a crossover from diffusive to viscous electron transport dominated by electron-electron scattering processes that do not relax current.

We show that the simplest universality classes of fracton hydrodynamics in more than one spatial dimension, including isotropic theories of charge and dipole conservation, can exhibit hidden quasiconservation laws, in which certain higher multipole moments can only decay due to dangerously irrelevant corrections to hydrodynamics. We present two simple examples of this phenomenon. First, an isotropic dipole-conserving fluid in the infinite plane conserves an infinite number of harmonic multipole charges within linear response; we calculate the decay or growth of these charges due to dangerously irrelevant nonlinearities. Second, we consider a model with xy and x^{2}-y^{2} quadrupole conservation, in addition to dipole conservation, which is described by isotropic fourth-order subdiffusion, yet has dangerously irrelevant sixth-order corrections necessary to relax the harmonic multipole charges. We confirm our predictions for the anomalously slow decay of the harmonic conserved charges in each setting by using numerical simulations, both of the nonlinear hydrodynamic differential equations, and in quantum automaton circuits on a square lattice.

Purpose of Review: There is substantive and accumulating evidence that endemic exposure to plastic-associated chemicals (PACs) contribute to the pathophysiology of metabolic conditions, like obesity, diabetes, and heart disease. The consequences of this endemic exposure in inducing a pro-inflammatory state in adipose tissues as a critical link between exposure and disease is reviewed., Recent Findings: In general, PACs are classified as nonpersistent in vivo because of their rapid metabolism to easily excreted forms. The parental chemicals, however, are typically lipophilic, with the potential to bioaccumulate. Recent data from selected association studies suggest exposure to PACs drive predisease states like obesity and inflammation of the adipose tissues. A range of experimental studies are discussed with a focus on biological mechanisms that are susceptible to the influence of PACs and which may promote metabolic disease, the detection of PACs within susceptible tissues and biological effects that are detectable at doses that correspond to real-life exposures to these chemicals., Summary: If we hypothesize the toxic pressure from chronic exposure to PACs will progress disease processes, then individuals with comprehensively characterized indicators of premetabolic disease could undergo trials of quantifiable interventions to reduce exposure to PACs to test if the trajectory of disease-associated analytes, is altered., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Tissue-resident memory T (T RM ) cells are non-recirculating cells that exist throughout the body. Although T RM cells in various organs rely on common transcriptional networks to establish tissue residency, location-specific factors adapt these cells to their tissue of lodgment. Here we analyze T RM cell heterogeneity between organs and find that the different environments in which these cells differentiate dictate T RM cell function, durability and malleability. We find that unequal responsiveness to TGFβ is a major driver of this diversity. Notably, dampened TGFβ signaling results in CD103 - T RM cells with increased proliferative potential, enhanced function and reduced longevity compared with their TGFβ-responsive CD103 + T RM counterparts. Furthermore, whereas CD103 - T RM cells readily modified their phenotype upon relocation, CD103 + T RM cells were comparatively resistant to transdifferentiation. Thus, despite common requirements for T RM cell development, tissue adaptation of these cells confers discrete functional properties such that T RM cells exist along a spectrum of differentiation potential that is governed by their local tissue microenvironment., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

We present an optimal protocol for encoding an unknown qubit state into a multiqubit Greenberger-Horne-Zeilinger-like state and, consequently, transferring quantum information in large systems exhibiting power-law ( 1 / r α ) interactions. For all power-law exponents α between d and 2 d + 1 , where d is the dimension of the system, the protocol yields a polynomial speed-up for α > 2 d and a superpolynomial speed-up for α ≤ 2 d , compared to the state of the art. For all α > d , the protocol saturates the Lieb-Robinson bounds (up to subpolynomial corrections), thereby establishing the optimality of the protocol and the tightness of the bounds in this regime. The protocol has a wide range of applications, including in quantum sensing, quantum computing, and preparation of topologically ordered states. In addition, the protocol provides a lower bound on the gate count in digital simulations of power-law interacting systems.

Unprecedented quantities of heat are entering the Pacific sector of the Arctic Ocean through Bering Strait, particularly during summer months. Though some heat is lost to the atmosphere during autumn cooling, a significant fraction of the incoming warm, salty water subducts (dives beneath) below a cooler fresher layer of near-surface water, subsequently extending hundreds of kilometers into the Beaufort Gyre. Upward turbulent mixing of these sub-surface pockets of heat is likely accelerating sea ice melt in the region. This Pacific-origin water brings both heat and unique biogeochemical properties, contributing to a changing Arctic ecosystem. However, our ability to understand or forecast the role of this incoming water mass has been hampered by lack of understanding of the physical processes controlling subduction and evolution of this this warm water. Crucially, the processes seen here occur at small horizontal scales not resolved by regional forecast models or climate simulations; new parameterizations must be developed that accurately represent the physics. Here we present novel high resolution observations showing the detailed process of subduction and initial evolution of warm Pacific-origin water in the southern Beaufort Gyre.

Background: From the laboratory at Scripps Institution of Oceanography, it is common to see the brown pelican (Pelecanus occidentalis) traveling along the crests of ocean waves just offshore of the surf-zone. When flying in this manner, the birds can travel long distances without flapping, centimeters above the ocean's surface. Here we derive a theoretical framework for assessing the energetic savings related to this behavior, 'wave-slope soaring,' in which an organism in flight takes advantage of localized updrafts caused by traveling ocean surface gravity waves., Methods: The energy cost of steady, constant altitude flight in and out of ground effect are analyzed as controls. Potential flow theory is used to quantify the ocean wave-induced wind associated with near-shoaling, weakly nonlinear, shallow water ocean surface gravity waves moving through an atmosphere initially at rest. Using perturbation theory and the Green's function for Laplace's equation in 2D with Dirichlet boundary conditions, we obtain integrals for the horizontal and vertical components of the wave-induced wind in a frame of reference moving with the wave. Wave-slope soaring flight is then analyzed using an energetics-based approach for waves under a range of ocean conditions and the body plan of P. occidentalis., Results: For ground effect flight, we calculate a ∼15 - 25% reduction in cost of transport as compared with steady, level flight out of ground effect. When wave-slope soaring is employed at flight heights ∼2m in typical ocean conditions (2m wave height, 15s period), we calculate 60-70% reduction in cost of transport as compared with flight in ground effect. A relatively small increase in swell amplitude or decrease in flight height allows up to 100% of the cost of transport to be offset by wave-slope soaring behavior., Conclusions: The theoretical development presented here suggests there are energy savings associated with wave-slope soaring. Individual brown pelicans may significantly decrease their cost of transport utilizing this mode of flight under typical ocean conditions. Thus wave-slope soaring may provide fitness benefit to these highly mobile organisms that depend on patchy prey distribution over large home ranges.

Subdiffusion is a generic feature of chaotic many-body dynamics with multipole conservation laws and subsystem symmetries. We numerically study this subdiffusive dynamics, using quantum automaton random unitary circuits, in a broad range of models including one-dimensional models with dipole and quadrupole conservation, two-dimensional models with dipole conservation, and two-dimensional models with subsystem symmetry on the triangular lattice. Our results are in complete agreement with recent hydrodynamic predictions for such theories.

The lung achieves an efficient gas exchange between a complex non-sterile atmosphere and the body via a delicate and extensive epithelial surface, with high efficiency because of elastic deformation allowing for an increase and decrease in volume during the process of breathing and because of an extensive vasculature which aids rapid gas diffusion. The lungs' large surface area exposes the organ to a continual risk of damage from pathogens, toxins or irritants; however, lung damage can be rapidly healed via regenerative processes that restore its structure and function. In response to sustained and extensive damage, the lung is healed via a non-regenerative process resulting in scar tissue which locally stiffens its structure, which over time leads to a serious loss of lung function and to increasing morbidities. This review discusses what is known about the factors which influence whether a lung is healed by regeneration or repair and what potential new therapeutic approaches may positively influence lung healing., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology Inc.)

In a locally interacting many-body system, two isolated qubits, separated by a large distance r, become correlated and entangled with each other at a time t≥r/v. This finite speed v of quantum information scrambling limits quantum information processing, thermalization, and even equilibrium correlations. Yet most experimental systems contain long range power-law interactions-qubits separated by r have potential energy V(r)∝r^{-α}. Examples include the long range Coulomb interactions in plasma (α=1) and dipolar interactions between spins (α=3). In one spatial dimension, we prove that the speed of quantum scrambling remains finite for sufficiently large α. This result parametrically improves previous bounds, compares favorably with recent numerical simulations, and can be realized in quantum simulators with dipolar interactions. Our new mathematical methods lead to improved algorithms for classically simulating quantum systems, and improve bounds on environmental decoherence in experimental quantum information processors.

Pretargeting is an increasingly explored strategy to improve nanoparticle targeting, in which pretargeting molecules that bind both selected epitopes on target cells and nanocarriers are first administered, followed by the drug-loaded nanocarriers. Bispecific antibodies (bsAb) represent a promising class of pretargeting molecules, but how different bsAb formats may impact the efficiency of pretargeting remains poorly understood, in particular Fab valency and Fc receptor (FcR)-binding of bsAb. We found the tetravalent bsAb markedly enhanced PEGylated nanoparticle binding to target HER2 + cells relative to the bivalent bsAb in vitro. Pretargeting with tetravalent bsAb with abrogated FcR binding increased tumor accumulation of PEGylated liposomal doxorubicin (PLD) 3-fold compared to passively targeted PLD alone, and 5-fold vs pretargeting with tetravalent bsAb with normal FcR binding in vivo. Our work demonstrates that multivalency and elimination of FcRn recycling are both important features of pretargeting molecules, and further supports pretargeting as a promising nanoparticle delivery strategy., (Published by Elsevier Inc.)

Pollination by insects is a key ecosystem service and important to wider ecosystem function. Most species-level pollination networks studied have a generalised structure, with plants having several potential pollinators, and pollinators in turn visiting a number of different plant species. This is in apparent contrast to a plant's need for efficient conspecific pollen transfer. The aim of this study was to investigate the structure of pollen transport networks at three levels of biological hierarchy: community, species and individual. We did this using hoverflies in the genus Eristalis, a key group of non-Hymenopteran pollinators. We constructed pollen transport networks using DNA metabarcoding to identify pollen. We captured hoverflies in conservation grasslands in west Wales, UK, removed external pollen loads, sequenced the pollen DNA on the Illumina MiSeq platform using the standard plant barcode rbcL, and matched sequences using a pre-existing plant DNA barcode reference library. We found that Eristalis hoverflies transport pollen from 65 plant taxa, more than previously appreciated. Networks were generalised at the site and species level, suggesting some degree of functional redundancy, and were more generalised in late summer compared to early summer. In contrast, pollen transport at the individual level showed some degree of specialisation. Hoverflies defined as "single-plant visitors" varied from 40% of those captured in early summer to 24% in late summer. Individual hoverflies became more generalised in late summer, possibly in response to an increase in floral resources. Rubus fruticosus agg. and Succisa pratensis were key plant species for hoverflies at our sites Our results contribute to resolving the apparent paradox of how generalised pollinator networks can provide efficient pollination to plant species. Generalised hoverfly pollen transport networks may result from a varied range of short-term specialised feeding bouts by individual insects. The generalisation and functional redundancy of Eristalis pollen transport networks may increase the stability of the pollination service they deliver., (© 2018 The Authors. Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society.)

Hepatitis C virus (HCV)-specific T cell responses are critical for immune control of infection. Viral adaptation to these responses, via mutations within regions of the virus targeted by CD8 + T cells, is associated with viral persistence. However, identifying viral adaptation to HCV-specific CD4 + T cell responses has been difficult although key to understanding anti-HCV immunity. In this context, HCV sequence and host genotype from a single source HCV genotype 1B cohort (n = 63) were analyzed to identify viral changes associated with specific human leucocyte antigen (HLA) class II alleles, as these variable host molecules determine the set of viral peptides presented to CD4 + T cells. Eight sites across the HCV genome were associated with HLA class II alleles implicated in infection outcome in this cohort (p ≤ 0.01; Fisher's exact test). We extended this analysis to chronic HCV infection (n = 351) for the common genotypes 1A and 3A. Variation at 38 sites across the HCV genome were associated with specific HLA class II alleles with no overlap between genotypes, suggestive of genotype-specific T cell targets, which has important implications for vaccine design. Here we show evidence of HCV adaptation to HLA class II-restricted CD4 + T cell pressure across the HCV genome in chronic HCV infection without a priori knowledge of CD4 + T cell epitopes.

Pollination is a key ecosystem service for agriculture and wider ecosystem function. However, most pollination studies focus on Hymenoptera, with hoverflies (Syrphidae) frequently treated as a single functional group. We tested this assumption by investigating pollen carried by eleven species of hoverfly in five genera, Cheilosia, Eristalis, Rhingia, Sericomyia and Volucella, using DNA metabarcoding. Hoverflies carried pollen from 59 plant taxa, suggesting they visit a wider number of plant species than previously appreciated. Most pollen recorded came from plant taxa frequently found at our study sites, predominantly Apiaceae, Cardueae, Calluna vulgaris, Rubus fruticosus agg., and Succisa pratensis, with hoverflies transporting pollen from 40% of entomophilous plant species present. Overall pollen transport network structures were generalised, similar to other pollination networks elsewhere. All hoverfly species were also generalised with few exclusive plant/hoverfly interactions. However, using the Jaccard Index, we found significant differences in the relative composition of pollen loads between hoverfly genera, except for Volucella, demonstrating some degree of functional complementarity. Eristalis and Sericomyia species had significant differences in relative pollen load composition compared to congeners. Our results demonstrate the range of pollens transported by hoverflies and the potential pollination function undertaken within this ecologically and morphologically diverse guild.

We present the theory of quasiparticle transport in perturbatively small inhomogeneous magnetic fields across the ballistic-to-hydrodynamic crossover. In the hydrodynamic limit, the resistivity ρ generically grows proportionally to the rate of momentum-conserving electron-electron collisions at large enough temperatures T. In particular, the resulting flow of electrons provides a simple scenario where viscous effects suppress conductance below the ballistic value. This new mechanism for ρ∝T^{2} resistivity in a Fermi liquid may describe low T transport in single-band SrTiO&#95;{3}.

Generic interacting many-body quantum systems are believed to behave as classical fluids on long time and length scales. Due to rapid progress in growing exceptionally pure crystals, we are now able to experimentally observe this collective motion of electrons in solid-state systems, including graphene. We present a review of recent progress in understanding the hydrodynamic limit of electronic motion in graphene, written for physicists from diverse communities. We begin by discussing the 'phase diagram' of graphene, and the inevitable presence of impurities and phonons in experimental systems. We derive hydrodynamics, both from a phenomenological perspective and using kinetic theory. We then describe how hydrodynamic electron flow is visible in electronic transport measurements. Although we focus on graphene in this review, the broader framework naturally generalizes to other materials. We assume only basic knowledge of condensed matter physics, and no prior knowledge of hydrodynamics.

Major advances in therapeutic proteins, including antibody-drug conjugates (ADCs), have created revolutionary drug delivery systems in cancer over the past decade. While these immunoconjugate agents provide several advantages compared to their small-molecule counterparts, their clinical use is still in its infancy. The considerations in their development and clinical use are complex, and consist of multiple components and variables that can affect the pharmacologic characteristics. It is critical to understand the mechanisms employed by ADCs in navigating biological barriers and how these factors affect their biodistribution, delivery to tumors, efficacy, and toxicity. Thus, future studies are warranted to better understand the complex pharmacology and interaction between ADC carriers and biological systems, such as the mononuclear phagocyte system (MPS) and tumor microenvironment. This review provides an overview of factors that affect the pharmacologic profiles of ADC therapies that are currently in clinical use and development., Competing Interests: William C. Zamboni holds equity in and licensed patent on a MPS probe. All other authors have no conflicts of interest to disclose.

Major advances in carrier-mediated agents (CMAs), which include nanoparticles, nanosomes, and conjugates, have revolutionized drug delivery capabilities over the past decade. While providing numerous advantages, such as greater solubility, duration of exposure, and delivery to the site of action over their small molecule counterparts, there is substantial variability in systemic clearance and distribution, tumor delivery, and pharmacologic effects (efficacy and toxicity) of these agents. In this chapter, we focus on the analytical and phenotypic methods required to design a study that characterizes the pharmacokinetics (PK) and pharmacodynamics (PD) of all forms of these nanoparticle-based drug agents. These methods include separation of encapsulated and released drugs, ultrafiltration for measurement of non-protein bound active drug, microdialysis to measure intra-tumor drug concentrations, immunomagnetic separation and flow cytometry for sorting cell types, and evaluation of spatial distribution of drug forms relative to tissue architecture by mass spectrometry imaging and immunohistochemistry.

We obtain a rigorous upper bound on the resistivity [Formula: see text] of an electron fluid whose electronic mean free path is short compared with the scale of spatial inhomogeneities. When such a hydrodynamic electron fluid supports a nonthermal diffusion process-such as an imbalance mode between different bands-we show that the resistivity bound becomes [Formula: see text] The coefficient [Formula: see text] is independent of temperature and inhomogeneity lengthscale, and [Formula: see text] is a microscopic momentum-preserving scattering rate. In this way, we obtain a unified mechanism-without umklapp-for [Formula: see text] in a Fermi liquid and the crossover to [Formula: see text] in quantum critical regimes. This behavior is widely observed in transition metal oxides, organic metals, pnictides, and heavy fermion compounds and has presented a long-standing challenge to transport theory. Our hydrodynamic bound allows phonon contributions to diffusion constants, including thermal diffusion, to directly affect the electrical resistivity., Competing Interests: The authors declare no conflict of interest., (Published under the PNAS license.)

Pollination is a key ecosystem service, and appropriate management, particularly in agricultural systems, is essential to maintain a diversity of pollinator guilds. However, management recommendations frequently focus on maintaining plant communities, with the assumption that associated invertebrate populations will be sustained. We tested whether plant community, flower resources, and soil moisture would influence hoverfly (Syrphidae) abundance and species richness in floristically-rich seminatural and floristically impoverished agricultural grassland communities in Wales (U.K.) and compared these to two Hymenoptera genera, Bombus, and Lasioglossum . Interactions between environmental variables were tested using generalized linear modeling, and hoverfly community composition examined using canonical correspondence analysis. There was no difference in hoverfly abundance, species richness, or bee abundance, between grassland types. There was a positive association between hoverfly abundance, species richness, and flower abundance in unimproved grasslands. However, this was not evident in agriculturally improved grassland, possibly reflecting intrinsically low flower resource in these habitats, or the presence of plant species with low or relatively inaccessible nectar resources. There was no association between soil moisture content and hoverfly abundance or species richness. Hoverfly community composition was influenced by agricultural improvement and the amount of flower resource. Hoverfly species with semiaquatic larvae were associated with both seminatural and agricultural wet grasslands, possibly because of localized larval habitat. Despite the absence of differences in hoverfly abundance and species richness, distinct hoverfly communities are associated with marshy grasslands, agriculturally improved marshy grasslands, and unimproved dry grasslands, but not with improved dry grasslands. Grassland plant community cannot be used as a proxy for pollinator community. Management of grasslands should aim to maximize the pollinator feeding resource, as well as maintain plant communities. Retaining waterlogged ground may enhance the number of hoverflies with semiaquatic larvae.

The mononuclear phagocyte system (MPS) has previously been shown to significantly affect the clearance, tumor delivery, and efficacy of nanoparticles (NPs). This study profiled MPS cell infiltration in murine preclinical tumor models and evaluated how these differences may affect tumor disposition of PEGylated liposomal doxorubicin (PLD) in models sensitive and resistant to PLD. Significant differences in MPS presence existed between tumor types (e.g. ovarian versus endometrial), cell lines within the same tumor type, and location of tumor implantation (i.e. flank versus orthotopic xenografts). Further, the differences in MPS presence of SKOV-3 ovarian and HEC1A endometrial orthotopic cancer models may account for the 2.6-fold greater PLD tumor exposure in SKOV-3, despite similar plasma, liver and spleen exposures. These findings suggest that profiling the presence of MPS cells within and between tumor types is important in tumor model selection and in tumor types and patients likely to respond to NP treatment., (Copyright © 2016. Published by Elsevier Inc.)

Nanoparticles (NP) including liposomes are cleared by phagocytes of the mononuclear phagocyte system. High inter-patient variability in pharmacokinetics of PEGylated liposomal doxorubicin (PLD) has been reported. We hypothesized that genetic factors may be associated with the variable disposition of PLD. We evaluated plasma and tissue disposition of doxorubicin after administration of PLD at 6mg/kg IV ×1 via tail vein in 23 different male inbred mouse strains. An approximately 13-fold difference in plasma clearance of PLD was observed among inbred strains. We identified a correlation between strain-specific differences in PLD clearance and genetic variation within a genomic region encoding GULP1 (PTB domain containing engulfment adapter 1) protein using haplotype associated mapping and the efficient mixed-model association algorithms. Our results also show that Gulp1 expression in adipose tissue was associated with PLD disposition in plasma. Our findings suggest that genetic variants may be associated with inter-individual pharmacokinetic differences in NP clearance., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Major advances in carrier-mediated agents (CMAs), which include nanoparticles and conjugates, have revolutionized drug delivery capabilities over the past decade. While providing numerous advantages over their small-molecule counterparts, there is substantial variability in how individual CMA formulations and patient characteristics affect the pharmacology, pharmacokinetics (PK), and pharmacodynamics (PD) (efficacy and toxicity) of these agents. Development or selection of animal models is used to predict the effects within a particular human disease. A breadth of studies have begun to emphasize the importance of preclinical animal models in understanding and evaluating the interaction between CMAs and the immune system and tumor matrix, which ultimately influences CMA PK (clearance and distribution) and PD (efficacy and toxicity). It is fundamental to study representative preclinical tumor models that recapitulate patients with diseases (e.g., cancer) and evaluate the interplay between CMAs and the immune system, including the mononuclear phagocyte system (MPS), chemokines, hormones, and other immune modulators. Furthermore, standard allometric scaling using body weight does not accurately predict drug clearance in humans. Future studies are warranted to better understand the complex pharmacology and interaction of CMA carriers within individual preclinical models and their biological systems, such as the MPS and tumor microenvironment, and their application to allometric scaling across species. WIREs Nanomed Nanobiotechnol 2016, 8:642-653. doi: 10.1002/wnan.1394 For further resources related to this article, please visit the WIREs website., (© 2016 Wiley Periodicals, Inc.)

Doxorubicin, a widely used anticancer agent, exhibits antitumor activity against a wide variety of malignancies. The drug exerts its cytotoxic effects by binding to and intercalating within the DNA of tumor and tissue cells. However, current assays are unable to accurately determine the concentration of the intracellular active form of doxorubicin. Thus, the development of a sample processing method and a high-performance liquid chromatography (HPLC) methodology was performed in order to quantify doxorubicin that is associated with DNA in tumors and tissues, which provided an intracellular cytotoxic measure of doxorubicin exposure after administration of small molecule and nanoparticle formulations of doxorubicin. The assay uses daunorubicin as an internal standard; liquid-liquid phase extraction to isolate drug associated with DNA; a Shimadzu HPLC with fluorescence detection equipped with a Phenomenex Luna C18 (2μm, 2.0×100mm) analytical column and a gradient mobile phase of 0.1% formic acid in water or acetonitrile for separation and quantification. The assay has a lower limit of detection (LLOQ) of 10ng/mL and is shown to be linear up to 3000ng/mL. The intra- and inter-day precision of the assay expressed as a coefficient of variation (CV%) ranged from 4.01 to 8.81%. Furthermore, the suitability of this assay for measuring doxorubicin associated with DNA in vivo was demonstrated by using it to quantify the doxorubicin concentration within tumor samples from SKOV3 and HEC1A mice obtained 72h after administration of PEGylated liposomal doxorubicin (Doxil(®); PLD) at 6mg/kg IV x 1. This HPLC assay allows for sensitive intracellular quantification of doxorubicin and will be an important tool for future studies evaluating intracellular pharmacokinetics of doxorubicin and various nanoparticle formulations of doxorubicin., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Reduced early microbial exposure has become a leading candidate to explain the rise in allergic disease, and research has focused on studying the interaction between the developing immune system and the microbial environment. However, despite intense interest, the pathways that lead to dysregulation of the immune system in allergic disease are still poorly understood. The newly described type III IFN-λ molecules were initially shown to exhibit antiviral activity, but these molecules are also likely to have an important role to play in the immune-epithelial interface, given their immunomodulatory functions and restricted receptor expression to immune and epithelial cells. Previous studies on the role of IFN-λ in allergic disease have been limited to allergic asthma. More recently, a genetic variation flanking IL28B encoding IFN-λ3 has been associated with allergic disease. Here, we examine this family and suggest how IFN-λ may be an important player in allergic disease.

Infectious diseases remain the greatest causes of morbidity and mortality in global terms. As much of the burden occurs in the developing world, limited access to diagnostic testing has hampered the diagnosis and treatment of these conditions, while, in the developed world, the cost of managing infectious diseases remains considerable. Despite the size of the problem there remains an ongoing need for tests that improve diagnostic sensitivity and specificity, provide more rapid diagnoses, are available for point-of-care testing in remote regions, and can help inform therapeutic decision-making by identifying resistance patterns or patient outcomes. This article discusses the background to biomarker development for infectious diseases, some current assays that are providing useful information regarding the host's response to infection (using examples such as Cytomegalovirus and Mycobacterium tuberculosis), as well as likely future technologies and their limitations.

The introduction of highly active antiretroviral therapy (also known as combination therapy) has transformed the nature of HIV infection from a severe and ultimately fatal disease to that of a manageable chronic condition. HIV drugs are highly efficacious, but their use comes at the cost of a range of drug-related adverse events, including severe drug hypersensitivity reactions (HSRs) that have been most notably associated with abacavir and nevirapine therapy. This article discusses the issues of pharmacogenetic screening, in the light of the strong genetic association of the HLA-B*5701 allele and the susceptibility to developing abacavir HSRs. It also presents the screening's impact on clinical practice and discusses the practical considerations that influence the introduction and cost-effectiveness of such screening.

Background: Chemokines are important mediators of inflammatory cell recruitment that play a significant role in atherosclerosis. Fractalkine (CX3CL1) is an unusual membrane-bound chemokine that mediates chemotaxis through the CX3CR1 receptor. Recently, functional polymorphisms in the human CX3CR1 gene have been described that are associated with coronary artery disease., Methods and Results: We investigated the expression of the CX3C chemokine fractalkine and its receptor CX3CR1 in human coronary artery plaques by immunocytometry. We show that a subset of mononuclear cells expresses high levels of fractalkine in human coronary atherosclerotic plaques and that smooth muscle cells within the neointima express the fractalkine receptor CX3CR1. There is a positive correlation between the number of fractalkine-expressing cells and the number of CX3CR1-positive cells in human atherosclerotic plaques (r=0.70, n=15 plaques). Furthermore, we demonstrate that cultured vascular smooth muscle cells express the CX3CR1 receptor and undergo chemotaxis to fractalkine that can be inhibited by G protein inactivation by pertussis toxin., Conclusions: These results suggest that in human atherosclerosis, fractalkine, rather than mediating inflammatory cell recruitment, can act as a mediator of smooth muscle cell migration.