Kinetics of sickle cell biorheology and implications for painful vasoocclusive crisis

We developed a microfluidics-based model to quantify cell-level processes modulating the pathophysiology of sickle cell disease (SCD). This in vitro model enabled quantitative investigations of the kinetics of cell sickling, unsickling, and cell rheology. We created short-term and long-term hypoxic conditions to simulate normal and retarded transit scenarios in microvasculature. Using blood samples from 25 SCD patients with sickle hemoglobin (HbS) levels varying from 64 to 90.1%, we investigated how cell biophysical alterations during blood flow correlated with hematological parameters, HbS level, and hydroxyurea (HU) therapy. From these measurements, we identified two severe cases of SCD that were also independently validated as severe from a genotype-based disease severity classification. These results point to the potential of this method as a diagnostic indicator of disease severity. In addition, we investigated the role of cell density in the kinetics of cell sickling. We observed an effect of HU therapy mainly in relatively dense cell populations, and that the sickled fraction increased with cell density. These results lend support to the possibility that the microfluidic platform developed here offers a unique and quantitative approach to assess the kinetic, rheological, and hematological factors involved in vasoocclusive events associated with SCD and to develop alternative diagnostic tools for disease severity to supplement other methods. Such insights may also lead to a better understanding of the pathogenic basis and mechanism of drug response in SCD.National Institutes of Health (U.S.) (R01HL094270)National Institutes of Health (U.S.) (U01HL114476

Dynamic deformability of Plasmodium falciparum-infected erythrocytes exposed to artesunate in vitro

Artesunate (ART) is widely used for the treatment of malaria, but the mechanisms of its effects on parasitized red blood cells (RBCs) are not fully understood. We investigated ART's influence on the dynamic deformability of ring-stage Plasmodium falciparum infected red blood cells (iRBCs) in order to elucidate its role in cellular mechanobiology. The dynamic deformability of RBCs was measured by passing them through a microfluidic device with repeated bottleneck structures. The quasi-static deformability measurement was performed using micropipette aspiration. After ART treatment, microfluidic experiments showed 50% decrease in iRBC transit velocity whereas only small (~10%) velocity reduction was observed among uninfected RBCs (uRBCs). Micropipette aspiration also revealed ART-induced stiffening in RBC membranes. These results demonstrate, for the first time, that ART reduces the dynamic and quasi-static RBC deformability, which may subsequently influence blood circulation through the microvasculature and spleen cordal meshwork, thus adding a new aspect to artesunate's mechanism of action.Singapore-MIT Alliance for Research and Technology CenterNational Institutes of Health (U.S.) (Grant R01 HL094270-01A1

Electric impedance microflow cytometry for characterization of cell disease states

The electrical properties of biological cells have connections to their pathological states. Here we present an electric impedance microflow cytometry (EIMC) platform for the characterization of disease states of single cells. This platform entails a microfluidic device for a label-free and non-invasive cell-counting assay through electric impedance sensing. We identified a dimensionless offset parameter δ obtained as a linear combination of a normalized phase shift and a normalized magnitude shift in electric impedance to differentiate cells on the basis of their pathological states. This paper discusses a representative case study on red blood cells (RBCs) invaded by the malaria parasite Plasmodium falciparum. Invasion by P. falciparum induces physical and biochemical changes on the host cells throughout a 48-h multi-stage life cycle within the RBC. As a consequence, it also induces progressive changes in electrical properties of the host cells. We demonstrate that the EIMC system in combination with data analysis involving the new offset parameter allows differentiation of P. falciparum infected RBCs from uninfected RBCs as well as among different P. falciparum intraerythrocytic asexual stages including the ring stage. The representative results provided here also point to the potential of the proposed experimental and analysis platform as a valuable tool for non-invasive diagnostics of a wide variety of disease states and for cell separation.Singapore. National Research Foundation (Singapore-MIT Alliance for Research and Technology)Massachusetts Institute of Technology. Center for Integrated Circuits and SystemsNational Institutes of Health (U.S.) (Grant R01 HL094270

CMBR Constraint on a Modified Chaplygin Gas Model

In this paper, a modified Chaplygin gas model of unifying dark energy and dark matter with exotic equation of state $p=B\rho-\frac{A}{\rho^{\alpha}}$ which can also explain the recent accelerated expansion of the universe is investigated by the means of constraining the location of the peak of the CMBR spectrum. We find that the result of CMBR measurements does not exclude the nonzero value of parameter $B$, but allows it in the range $-0.35\lesssim B\lesssim0.025$.Comment: 4 pages, 3 figure

Host cell deformability is linked to transmission in the human malaria parasite Plasmodium falciparum

available in PMC 2013 July 01.Gametocyte maturation in Plasmodium falciparum is a critical step in the transmission of malaria. While the majority of parasites proliferate asexually in red blood cells, a small fraction of parasites undergo sexual conversion and mature over 2 weeks to become competent for transmission to a mosquito vector. Immature gametocytes sequester in deep tissues while mature stages must be able to circulate, pass the spleen and present themselves to the mosquito vector in order to complete transmission. Sequestration of asexual red blood cell stage parasites has been investigated in great detail. These studies have demonstrated that induction of cytoadherence properties through specific receptor–ligand interactions coincides with a significant increase in host cell stiffness. In contrast, the adherence and biophysical properties of gametocyte-infected red blood cells have not been studied systematically. Utilizing a transgenic line for 3D live imaging, in vitro capillary assays and 3D finite element whole cell modelling, we studied the role of cellular deformability in determining the circulatory characteristics of gametocytes. Our analysis shows that the red blood cell deformability of immature gametocytes displays an overall decrease followed by rapid restoration in mature gametocytes. Intriguingly, simulations suggest that along with deformability variations, the morphological changes of the parasite may play an important role in tissue distribution in vivo. Taken together, we present a model, which suggests that mature but not immature gametocytes circulate in the peripheral blood for uptake in the mosquito blood meal and transmission to another human host thus ensuring long-term survival of the parasite.National Institutes of Health (U.S.) (R01A107755801)National Institutes of Health (U.S.) (R01HL094270)Singapore–MIT Alliance for Research and Technology ((SMART) Infectious Diseases Interdisciplinary Research Group)Singapore-MIT Alliance (Advanced Materials for Micro and Nano Systems Programme)Alexander von Humboldt-Stiftung (Feodor Lynen Research Fellowship

Susceptibility to re-infection in C57BL/6 mice with recombinant strains of Toxoplasma gondii

AbstractThis work reports results of re-infection of BALB/c and C57BL/6 mice with different recombinant strains of Toxoplasma gondii. Mice were prime-infected with the non-virulent D8 strain and challenged with virulent strains. PCR–RFLP of cS10-A6 genetic marker of T. gondii demonstrated that BALB/c mice were re-infected with the EGS strain, while C57BL/6 mice were re-infected with the EGS and CH3 strains. Levels of IFN-γ and IL-10 after D8 prime-infection were lower in C57BL/6 than in BALB/c mice. Brain inflammation after D8 prime-infection was more intense in C57BL/6 than in BALB/c mice. It was shown that re-infection depends on mice lineage and genotype of the strain used in the challenge

The smartphone-based offline indoor location competition at IPIN 2016: analysis and future work

This paper presents the analysis and discussion of the off-site localization competition track, which took place during the Seventh International Conference on Indoor Positioning and Indoor Navigation (IPIN 2016). Five international teams proposed different strategies for smartphone-based indoor positioning using the same reference data. The competitors were provided with several smartphone-collected signal datasets, some of which were used for training (known trajectories), and others for evaluating (unknown trajectories). The competition permits a coherent evaluation method of the competitors' estimations, where inside information to fine-tune their systems is not offered, and thus provides, in our opinion, a good starting point to introduce a fair comparison between the smartphone-based systems found in the literature. The methodology, experience, feedback from competitors and future working lines are described.We would like to thank Tecnalia Research & Innovation Foundation for sponsoring the competition track with an award for the winning team. We are also grateful to Francesco Potortì, Sangjoon Park, Jesús Ureña and Kyle O’Keefe for their invaluable help in promoting the IPIN competition and conference. Parts of this work was carried out with the financial support received from projects and grants: LORIS (TIN2012-38080-C04-04), TARSIUS (TIN2015-71564-C4-2-R (MINECO/FEDER)), SmartLoc (CSIC-PIE Ref.201450E011), “Metodologías avanzadas para el diseño, desarrollo, evaluación e integración de algoritmos de localización en interiores” (TIN2015-70202-P), REPNIN network (TEC2015-71426-REDT) and the José Castillejo mobility grant (CAS16/00072). The HFTS team has been supported in the frame of the German Federal Ministry of Education and Research programme “FHprofUnt2013” under contract 03FH035PB3 (Project SPIRIT). The UMinho team has been supported by COMPETE: POCI-01-0145-FEDER-007043 and FCT — Fundação para a Ciência e Tecnologia within the Project Scope: UID/CEC/00319/2013.info:eu-repo/semantics/publishedVersio

A sustainable multi-function biomorphic material for pollution remediation or UV absorption: aerosol assisted preparation of highly porous ZnO-based materials from cork templates

For the first time, highly porous ZnO-based biomorphic materials were synthesised using cork as a natural sustainable template. In the first step, waste cork powder was pyrolysed and converted into inorganic carbon. This template was then infiltrated using a novel approach employing an aerosol of zinc-containing solutions. The infiltrated powders were calcined to convert the precursors into zinc oxide. Depending on temperature, these could form either a ZnO-graphite composite material, or pure ZnO. Their morphology, porosity, microstructure and composition were characterised; their optical band gap energies, ability to adsorb and photodegrade organic pollutants and UV absorption were also assessed. When heated to 350 °C they maintained the 3D porous cork structure, producing a graphite-containing composite material, with both physical adsorption and photocatalytic activity (Eg = 3.19 eV), suitable for environmental remediation. When heated to 700 °C, the powders were pure ZnO (no graphite), and they absorbed in the UV region, hence suitable for use as sunscreen. Doped ZnO ecoceramics were also produced, using silver and aluminium. An addition of 1 mol% Ag improved photocatalysis under solar light. Conversely, adding 2 mol% Al and calcining at 700 °C deactivated photocatalysis, but maintained strong UV absorption, producing a safer sunscreen material (no generation of free radicals). This is the first time that photocatalytic or UV absorption properties of any wood-derived biomorphic material or ecoceramic have been reported.This work wasfinancially supported by the projects HApECOrk,funded by "Fondazione Con il Sud”(project 2015-0243), and“FutureInResearch”APQ Ricerca Regione Puglia. This work was de-veloped within the scope of the project CICECO-Aveiro Institute ofMaterials, FCT (Fundação para a Ciência e a Tecnologia, Portugal) Ref.UID/CTM/50011/2019,financed by national funds through the FCT/MCTES. The authors wish to thank Ms. Stefania D’Amone for the helpwith SEM microscopy. R.C. Pullar thanks FCT grant IF/00681/2015 forsupporting this work, and R.M. Novais wishes to thank FCT projectH2CORK (PTDC/CTM-ENE/6762/2014). The authors also acknowledge Amorim Cork Composites for providing the cork samples.publishe