Differential Uptake of Gold Nanoparticles by 2 Species of Tadpole, the Wood Frog (Lithobates Sylvaticus) and the Bullfrog (Lithobates Catesbeianus)

Engineered nanoparticles are aquatic contaminants of emerging concern that exert ecotoxicological effects on a wide variety of organisms. We exposed cetyltrimethylammonium bromide–capped spherical gold nanoparticles to wood frog and bullfrog tadpoles with conspecifics and in combination with the other species continuously for 21 d, then measured uptake and localization of gold. Wood frog tadpoles alone and in combination with bullfrog tadpoles took up significantly more gold than bullfrogs. Bullfrog tadpoles in combination with wood frogs took up significantly more gold than controls. The rank order of weight-normalized gold uptake was wood frogs in combination \u3e wood frogs alone \u3e bullfrogs in combination \u3e bullfrogs alone \u3e controls. In all gold-exposed groups of tadpoles, gold was concentrated in the anterior region compared with the posterior region of the body. The concentration of gold nanoparticles in the anterior region of wood frogs both alone and in combination with bullfrogs was significantly higher than the corresponding posterior regions. We also measured depuration time of gold in wood frogs. After 21 d in a solution of gold nanoparticles, tadpoles lost \u3e83% of internalized gold when placed in gold-free water for 5 d. After 10 d in gold-free water, tadpoles lost 94% of their gold. After 15 d, gold concentrations were below the level of detection. Our finding of differential uptake between closely related species living in similar habitats with overlapping geographical distributions argues against generalizing toxicological effects of nanoparticles for a large group of organisms based on measurements in only one species

In Vitro Validation of Finite-Element Model of AAA Hemodynamics Incorporating Realistic Outlet Boundary Conditions

The purpose of this study is to validate numerical simulations of flow and pressure in an abdominal aortic aneurysm (AAA) using phase-contrast magnetic resonance imaging (PCMRI) and an in vitro phantom under physiological flow and pressure conditions. We constructed a two-outlet physical flow phantom based on patient imaging data of an AAA and developed a physical Windkessel model to use as outlet boundary conditions. We then acquired PCMRI data in the phantom while it operated under conditions mimicking a resting and a light exercise physiological state. Next, we performed in silico numerical simulations and compared experimentally measured velocities, flows, and pressures in the in vitro phantom to those computed in the in silico simulations. There was a high degree of agreement in all of the pressure and flow waveform shapes and magnitudes between the experimental measurements and simulated results. The average pressures and flow split difference between experiment and simulation were all within 2%. Velocity patterns showed good agreement between experimental measurements and simulated results, especially in the case of whole-cycle averaged comparisons. We demonstrated methods to perform in vitro phantom experiments with physiological flows and pressures, showing good agreement between numerically simulated and experimentally measured velocity fields and pressure waveforms in a complex patient-specific AAA geometry

Diffusion, super-diffusion and coalescence from single step

From the exact single step evolution equation of the two-point correlation function of a particle distribution subjected to a stochastic displacement field \bu(\bx), we derive different dynamical regimes when \bu(\bx) is iterated to build a velocity field. First we show that spatially uncorrelated fields \bu(\bx) lead to both standard and anomalous diffusion equation. When the field \bu(\bx) is spatially correlated each particle performs a simple free Brownian motion, but the trajectories of different particles result to be mutually correlated. The two-point statistical properties of the field \bu(\bx) induce two-point spatial correlations in the particle distribution satisfying a simple but non-trivial diffusion-like equation. These displacement-displacement correlations lead the system to three possible regimes: coalescence, simple clustering and a combination of the two. The existence of these different regimes, in the one-dimensional system, is shown through computer simulations and a simple theoretical argument.Comment: RevTeX (iopstyle) 19 pages, 5 eps-figure

\u3ci\u3eIn Vitro\u3c/i\u3e Validation of Finite Element Analysis of Blood Flow in Deformable Models

The purpose of this article is to validate numerical simulations of flow and pressure incorporating deformable walls using in vitro flow phantoms under physiological flow and pressure conditions. We constructed two deformable flow phantoms mimicking a normal and a restricted thoracic aorta, and used a Windkessel model at the outlet boundary. We acquired flow and pressure data in the phantom while it operated under physiological conditions. Next, in silico numerical simulations were performed, and velocities, flows, and pressures in the in silico simulations were compared to those measured in the in vitro phantoms. The experimental measurements and simulated results of pressure and flow waveform shapes and magnitudes compared favorably at all of the different measurement locations in the two deformable phantoms. The average difference between measured and simulated flow and pressure was approximately 3.5 cc/s (13% of mean) and 1.5 mmHg (1.8% of mean), respectively. Velocity patterns also showed good qualitative agreement between experiment and simulation especially in regions with less complex flow patterns. We demonstrated the capabilities of numerical simulations incorporating deformable walls to capture both the vessel wall motion and wave propagation by accurately predicting the changes in the flow and pressure waveforms at various locations down the length of the deformable flow phantoms

In search of phylogenetic congruence between molecular and morphological data in bryozoans with extreme adult skeletal heteromorphy

peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=tsab20© Crown Copyright 2015. This document is the author's final accepted/submitted version of the journal article. You are advised to consult the publisher's version if you wish to cite from it

TeachOpenCADD 2022: open source and FAIR Python pipelines to assist in structural bioinformatics and cheminformatics research

Computational pipelines have become a crucial part of modern drug discovery campaigns. Setting up and maintaining such pipelines, however, can be challenging and time-consuming-especially for novice scientists in this domain. TeachOpenCADD is a platform that aims to teach domain-specific skills and to provide pipeline templates as starting points for research projects. We offer Python-based solutions for common tasks in cheminformatics and structural bioinformatics in the form of Jupyter notebooks, based on open source resources only. Including the 12 newly released additions, TeachOpenCADD now contains 22 notebooks that cover both theoretical background as well as hands-on programming. To promote reproducible and reusable research, we apply software best practices to our notebooks such as testing with automated continuous integration and adhering to the idiomatic Python style. The new TeachOpenCADD website is available at https://projects.volkamerlab.org/teachopencadd and all code is deposited on GitHub

Overturning circulation, nutrient limitation, and warming in the Glacial North Pacific

This work was funded by NERC grant NE/N011716/1 to J.W.B.R., a NERC studentship to B.T., and NSF grant OPP 1643445 to I.E. A.R. acknowledges support from NSF grant 1736771.Although the Pacific Ocean is a major reservoir of heat and CO2, and thus an important component of the global climate system, its circulation under different climatic conditions is poorly understood. Here, we present evidence that during the Last Glacial Maximum (LGM), the North Pacific was better ventilated at intermediate depths and had surface waters with lower nutrients, higher salinity, and warmer temperatures compared to today. Modeling shows that this pattern is well explained by enhanced Pacific meridional overturning circulation (PMOC), which brings warm, salty, and nutrient-poor subtropical waters to high latitudes. Enhanced PMOC at the LGM would have lowered atmospheric CO2—in part through synergy with the Southern Ocean—and supported an equable regional climate, which may have aided human habitability in Beringia, and migration from Asia to North America.Publisher PDFPeer reviewe

Simulation models predict that school-age children are responsible for most human-to-mosquito Plasmodium falciparum transmission in southern Malawi

Abstract Background Malaria persists in some high-transmission areas despite extensive control efforts. Progress toward elimination may require effective targeting of specific human populations that act as key transmission reservoirs. Methods Parameterized using molecular-based Plasmodium falciparum infection data from cross-sectional community studies in southern Malawi, a simulation model was developed to predict the proportions of human-to-mosquito transmission arising from (a) children under 5 years old (U5s), (b) school-age children (SAC, 5–15 years), (c) young adults (16–30 years), and (d) adults > 30 years. The model incorporates mosquito biting heterogeneity and differential infectivity (i.e. probability that a blood-fed mosquito develops oocysts) by age and gametocyte density. Results The model predicted that SAC were responsible for more than 60% of new mosquito infections in both dry and rainy seasons, even though they comprise only 30% of this southern Malawi population. Young adults were the second largest contributors, while U5s and adults over 30 were each responsible for < 10% of transmission. While the specific predicted values are sensitive to the relative infectiousness of SAC, this group remained the most important contributor to mosquito infections under all realistic estimates. Conclusions These results suggest that U5 children play a small role compared to SAC in maintaining P. falciparum transmission in southern Malawi. Models that assume biting homogeneity overestimate the importance of U5s. To reduce transmission, interventions will need to reach more SAC and young adults. This publicly available model can be used by others to estimate age-specific transmission contributions in epidemiologically similar sites with local parameter estimates of P. falciparum prevalence and bed net use.https://deepblue.lib.umich.edu/bitstream/2027.42/143001/1/12936_2018_Article_2295.pd

Platform-directed allostery and quaternary structure dynamics of SAMHD1 catalysis

SAMHD1 regulates cellular nucleotide homeostasis, controlling dNTP levels by catalysing their hydrolysis into 2’-deoxynucleosides and triphosphate. In differentiated CD4+ macrophage and resting T-cells SAMHD1 activity results in the inhibition of HIV-1 infection through a dNTP blockade. In cancer, SAMHD1 desensitizes cells to nucleoside-analogue chemotherapies. Here we employ time-resolved cryogenic-EM imaging and single-particle analysis to visualise assembly, allostery and catalysis by this multi-subunit enzyme. Our observations reveal how dynamic conformational changes in the SAMHD1 quaternary structure drive the catalytic cycle. We capture five states at high-resolution in a live catalytic reaction, revealing how allosteric activators support assembly of a stable SAMHD1 tetrameric core and how catalysis is driven by the opening and closing of active sites through pairwise coupling of active sites and order-disorder transitions in regulatory domains. This direct visualisation of enzyme catalysis dynamics within an allostery-stabilised platform sets a precedent for mechanistic studies into the regulation of multi-subunit enzymes