Hitoshi Kondo

Modeling of hemodynamics arising from malaria infection

We propose a numerical model of hemodynamics arising from malaria infection. This model is based on a particle method, where all the components of blood are represented by the finite number of particles. A two-dimensional spring network of membrane particles is employed for expressing the deformation of malaria infected red blood cells (IRBCs). Malaria parasite within the IRBC is modeled as a rigid object. This model is applied to the stretching of IRBCs by optical tweezers, the deformation of IRBCs in shear flow, and the occlusion of narrow channels by IRBCs. We also investigate the effects of IRBCs on the rheological property of blood in micro-channels. Our results indicate that apparent viscosity is drastically increased for the period from the ring stage and the trophozoite stage, whereas it is not altered in the early stage of infection.

Hemodynamic Analysis of Microcirculation in Malaria Infection

Malaria-infected red blood cells (IRBCs) show various changes in mechanical properties. IRBCs lose their deformability and develop properties of cytoadherence and rosetting. To clarify how these changes advance microvascular occlusion, we need qualitative and quantitative information on hemodynamics in malaria infection, including the interaction among IRBCs, healthy RBCs, and endothelial cells. We developed a numerical model of blood flow with IRBCs based on conservation laws of fluid dynamics. The deformability and adhesive property of IRBCs were simply modeled using springs governed by Hook’s law. Our model could express the basic behavior of IRBCs, including the rolling motion due to cytoadhesive interaction with endothelial cells and complex interaction with healthy RBCs. We confirmed that these types of interactions significantly increase the flow resistance, particularly when knobs develop.

Inhibition of electron transport of rat liver mitochondria by unnatural (-)-antimycin A3.

The inhibition of electron transport by unnatural (‐)‐antimycin A3 was examined with rat liver mitochondria and compared with that of natural (+)‐antimycin A3. (−)‐Antimycin A3 inhibited respiration about 1/100th as strongly as natural (+)‐antimycin A3. (−)‐Antimycin A3 binding to the cytochromebc1 complex did not seem to induce a conformational change in this proteinous complex. The binding site of (−)‐antimycin A3 was probably the same as that of (+)‐antimycin A3 (at the Qi center). However, the mode of interaction with the Qi center by (−)‐antimycin A3 and (+)‐antimycin A3 was somewhat different.

Synthesis and Antifungal Activity of the Four Stereoisomers of Streptimidone, a Glutarimide Antibiotic fromStreptomyces rimosus forma paromomycinus

Four stereoisomers of streptimidone (1), an antibiotic from Streptomyces rimosus forma paromomycinus, were synthesized from methyl (S)-3-hydroxy-2-methylpropanoate. The natural diastereomer 1 shows the strongest antimicrobial activity.

SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF UNNATURAL (-)-ANTIMYCIN A3 AND ITS ANALOG

A series of antibiotic antimycins have been isolated from various Streptomyces species since 1946 (1). The curious dilactone structure and strong biological activities has inspired many scientists to investigate their structure activity relationships, mechanism of action (2) and chemical synthesis (3-5). In our previous communication (6), the inhibition of electron transport of rat liver mitochondria by synthetic unnatural (-)antimycin A3 (-)-1 and the comparison of the activity between natural (+)-1 and (-)-1 were reported. In this paper, we describe the total synthesis of (-)-1 and its deformylamidodehydroxy analog (-)-2, and the formal synthesis of (+)-1. Abstract

Three-dimensional Simulation of Blood Flow in Malaria Infection

We propose a numerical method for simulating three-dimensional hemodynamics arising from malariainfection. Malaria-infected red blood cells (IRBCs) become stiffer and develop the property of cytoadherent and resetting. To clarify the mechanism of microvascular obstruction in malaria, we need to understand the changes of hemodynamics, involving interaction between IRBC, healthy RBCs, and endothelial cells. In the proposed model, all the components of blood are represented by a finite number of particles. The membrane of RBCs is expressed by two-dimensional network. Malaria parasites inside the RBC are represented by solid objects. The motion of each particle is described by the conservation laws of mass and momentum for incompressible fluid. We examine several numerical tests, involving the stretching of IRBCs, and flow in narrow channels, to validate our model. The obtained results agree well with the experimental results. Our method would be helpful for further understandings of pathology of malaria-infection.

Variation in bradyrhizobial NopP effector determines symbiotic incompatibility with Rj2- soybeans via effector-triggered immunity

Genotype-specific incompatibility in legume–rhizobium symbiosis has been suggested to be controlled by effector-triggered immunity underlying pathogenic host-bacteria interactions. However, the rhizobial determinant interacting with the host resistance protein (e.g., Rj2) and the molecular mechanism of symbiotic incompatibility remain unclear. Using natural mutants of Bradyrhizobium diazoefficiens USDA 122, we identified a type III-secretory protein NopP as the determinant of symbiotic incompatibility with Rj2-soybean. The analysis of nopP mutations and variants in a culture collection reveal that three amino acid residues (R60, R67, and H173) in NopP are required for Rj2-mediated incompatibility. Complementation of rj2-soybean by the Rj2 allele confers the incompatibility induced by USDA 122-type NopP. In response to incompatible strains, Rj2-soybean plants activate defense marker gene PR-2 and suppress infection thread number at 2 days after inoculation. These results suggest that Rj2-soybeans monitor the specific variants of NopP and reject bradyrhizobial infection via effector-triggered immunity mediated by Rj2 protein.The soybean Rj2 gene encodes a TIR-NBS-LRR protein that confers resistance to nodulation by certain rhizobial strains. Here, the authors show that T3SS effector NopP is an avirulence protein that is necessary for Bradyrhizobium diazoefficiens USDA 122 to trigger Rj2-dependent incompatibility.

Numerical Modeling of Microvascular Hemodynamics in Plasmodium Falciparum Malaria

High concentrations of nitric oxide (NO) have previously been measured in human maxillary sinuses, but the transport rates between the sinus and the nose during normal breathing have not been quantified. In this study, NO transport has been investigated using published NO concentrations and production rates, computational fluid dynamics (CFD) and first-order modeling in stylised physiological, pathological and post-surgical geometries. The results indicate that physiological sinus geometries cannot supply all the NO found in the nasal cavity. Pathological and post-surgical geometries have higher NO transport and lower steady-state NO concentrations than physiological geometries, but no difference was found between the two surgical techniques considered (inferior and middle meatal antrostomy). All the steady state concentrations are also above the level required for bacteriostatic effects.

Particle Method Simulation of Red Blood Cells Infected by Malaria

When a malaria parasite invades and matures inside a red blood cell (RBC), the infected RBC (IRBC) becomes stiffer and cytoadherent and these two outcomes can lead to microvascular blockage. We propose a numerical model of the three-dimensional hemodynamics in malaria infection. Our model is based on a Lagrangian and free mesh method (particle method). We employ spring network of membrane particles for representing deformation of RBC membrane. Adhesive property of IRBCs to surrounding cells is also expressed by using a spring model. Our method would be helpful for further understandings of pathology of malaria-infection.

A Numerical Model of Adhesion Property of Malaria Infected Red Blood Cells in Micro Scale Blood Flows

Infection by malaria parasite changes mechanical properties of red blood cells (RBCs). Infected red blood cells (IRBCs) lose the deformability but also develop the ability to cytoadhere and rosetting. These outcomes can lead to microvascular blockage [1]. The stiffness of IRBCs [2] and its effects on the flow in micro channels [3] were studied with recent experimental techniques. The cytoadherence and rosetting properties of IRBCs have also been studied experimentally. The cytoadherence is mediated by the interaction of the parasite protein PfEMP1 with several endothelial adhesion molecules, such as CD36, intercellular adhesion molecule-1 (ICAM-1), P-selectin, and vascular cell adhesion molecule-1 (VCAM-1) [4]. In particular, the ligand-receptor interaction between PfEMP1 and CD36 shows tight adhesion [5]. Microvascular blockage may be a hemodynamic problem, involving the interactions between IRBCs, healthy RBCs (HRBCs) and endothelial cells (ECs) in flowing blood, but however experimental techniques have several limitations to this topic. First, it is still difficult to observe the RBC behavior interacting with many other cells even with the recent confocal microscopy. Second, the three-dimensional information on flow field is hardly obtained. Third, capillaries in human body are circular channels with complex geometry, but such complex channels cannot be created in micro scale. Instead, numerical modeling can overcome these problems. We presented a two-dimensional hemodynamic model involving adhesive interactions [6]. In this paper, we propose a three-dimensional model of the adhesive interactions for micro scale hemodynamics in malaria infection.Copyright