Development of monoclonal antibodies against Plasmodium falciparum thioredoxin peroxidase 1 and its possible application for malaria diagnosis

Rapid diagnostic tests (RDTs) have been considered as an ideal alternative for light microscopy to detect malaria parasites especially in remote areas. The development and improvement of RDTs is an area of intensive research in the last decade. To date, few parasite proteins have been targeted in RDTs which are known to have certain deficiencies and made the researchers to look for other promising candidates to address this problem. Plasmodium falciparum thioredoxin peroxidase 1 (PfTPx-1) is abundantly expressed in the cytoplasm of the parasite and well conserved across Plasmodium species, making this antigen a promising target for malaria diagnosis. Several monoclonal antibodies (mAbs) were produced against PfTPx-1. The binding affinities of mAbs were measured. Several immunochromatographic tests (ICTs) were developed using different combination of mAbs. All mAbs showed promising affinities to be used for diagnosis. The sensitivities of ICTs were evaluated using recombinant PfTPx-1 whose results lead us to the preparation of 4 different ICTs. These tests showed positive reaction with P. falciparum in vitro culture supernatant indicating the release of PfTPx-1 during schizont rupture. Altogether, these findings suggest that PfTPx-1 is a promising biomarker to diagnose P. falciparum infection. However, the diagnostic performance of this antigen should be further validated using clinical samples

Neutron Spectroscopy Evidence for a Possible Magnetic-Field-Induced Gapless Quantum-Spin-Liquid Phase in a Kitaev Material α-RuCl3

As one of the most promising Kitaev quantum-spin-liquid (QSL) candidates, α-RuCl3 has received a great deal of attention. However, its ground state exhibits a long-range zigzag magnetic order, which defies the QSL phase. Nevertheless, the magnetic order is fragile and can be completely suppressed by applying an external magnetic field. Here, we explore the evolution of magnetic excitations of α-RuCl3 under an in-plane magnetic field, by carrying out inelastic neutron scattering measurements on high-quality single crystals. Under zero field, there exist spin-wave excitations near the M point and a continuum near the Γ point, which are believed to be associated with the zigzag magnetic order and fractional excitations of the Kitaev QSL state, respectively. By increasing the magnetic field, the spin-wave excitations gradually give way to the continuous excitations. On the verge of the critical field μ0Hc = 7.5 T, the former ones vanish and only the latter ones are left, indicating the emergence of a pure QSL state. By further increasing the field strength, the excitations near the Γ point become more intense. By following the gap evolution of the excitations near the Γ point, we are able to establish a phase diagram composed of three interesting phases, including a gapped zigzag order phase at low fields, possibly gapless QSL phase near μ0Hc, and gapped partially polarized phase at high fields. These results demonstrate that an in-plane magnetic field can drive α-RuCl3 into a long-sought QSL state near the critical field

Desmoglein 1–dependent suppression of EGFR signaling promotes epidermal differentiation and morphogenesis

Dsg1 (desmoglein 1) is a member of the cadherin family of Ca2+-dependent cell adhesion molecules that is first expressed in the epidermis as keratinocytes transit out of the basal layer and becomes concentrated in the uppermost cell layers of this stratified epithelium. In this study, we show that Dsg1 is not only required for maintaining epidermal tissue integrity in the superficial layers but also supports keratinocyte differentiation and suprabasal morphogenesis. Dsg1 lacking N-terminal ectodomain residues required for adhesion remained capable of promoting keratinocyte differentiation. Moreover, this capability did not depend on cytodomain interactions with the armadillo protein plakoglobin or coexpression of its companion suprabasal cadherin, Dsc1 (desmocollin 1). Instead, Dsg1 was required for suppression of epidermal growth factor receptor–Erk1/2 (extracellular signal-regulated kinase 1/2) signaling, thereby facilitating keratinocyte progression through a terminal differentiation program. In addition to serving as a rigid anchor between adjacent cells, this study implicates desmosomal cadherins as key components of a signaling axis governing epithelial morphogenesis

Plasmodium knowlesi thioredoxin peroxidase 1 binds to nucleic acids and has RNA chaperone activity

Malaria parasites are under oxidative attack throughout their life cycle in human body and mosquito vector. Therefore, Plasmodium antioxidant defenses are crucial for its survival and being considered as interesting target for antimalarial drug design. Plasmodium knowlesi has emerged recently from its simian host to human in Southeast Asia and has been recognized as the fifth Plasmodium species that can cause human malaria. In this study, we cloned and characterized thioredoxin peroxidase 1 from P. knowlesi (PkTPx-1). PkTPx-1 gene was cloned, and recombinant protein was produced by heterologous overexpression in Escherichia coli. The recombinant protein was used for evaluation of enzymatic activity and polyclonal antibody production. Using the recombinant PkTPx-1 protein, its antioxidant activity was confirmed in a mixed-function oxidation assay where PkTPx-1 prevented nicking of DNA by hydroxyl radicals. PkTPx-1 was able to bind to double-strand DNA and RNA and had RNA chaperone activity in a nucleic acid melting assay indicating new function of PkTPx-1 other than antioxidant activity. Using specific polyclonal antibodies, it was indicated that PkTPx-1 is expressed in the cytoplasm of the parasite. Altogether, these results suggest that PkTPx-1 not only protects the parasite from the adverse effects of reactive oxygen species but also has RNA chaperone activity

JASMINE: Near-infrared astrometry and time-series photometry science

The Japan Astrometry Satellite Mission for INfrared Exploration (JASMINE) is a planned M-class science space mission by the Institute of Space and Astronautical Science, the Japan Aerospace Exploration Agency. JASMINE has two main science goals. One is Galactic archaeology with a Galactic Center survey, which aims to reveal the Milky Way’s central core structure and formation history from Gaia-level (∼25 ${\mu}$as) astrometry in the near-infrared (NIR) Hw band (1.0–1.6 ${\mu}$m). The other is an exoplanet survey, which aims to discover transiting Earth-like exoplanets in the habitable zone from NIR time-series photometry of M dwarfs when the Galactic Center is not accessible. We introduce the mission, review many science objectives, and present the instrument concept. JASMINE will be the first dedicated NIR astrometry space mission and provide precise astrometric information on the stars in the Galactic Center, taking advantage of the significantly lower extinction in the NIR. The precise astrometry is obtained by taking many short-exposure images. Hence, the JASMINE Galactic Center survey data will be valuable for studies of exoplanet transits, asteroseismology, variable stars, and microlensing studies, including discovery of (intermediate-mass) black holes. We highlight a swath of such potential science, and also describe synergies with other missions

Interleukin-18 Induces Acute Biphasic Reduction in the Levels of Circulating Leukocytes in Mice

We investigated the acute hematological changes caused by interleukin-18 (IL-18) in mice. Intraperitoneal administration of IL-18 (2 μg/mouse) resulted in biphasic decreases in the number of leukocytes in the blood. The first phase of decrease occurred within 2 h of IL-18 administration and was followed by a transient increase at 5 h. The second phase of decrease occurred at around 6 h, reaching a nadir which lasted for more than 24 h. In mice deficient in inducible nitric oxide (NO) synthase, the first phase of reduction of leukocytes did not occur although the second phase of decrease was observed. In mice deficient in gamma interferon (IFN-γ) or in mice depleted of natural killer cells and incapable of producing IFN-γ, IL-18 had no effect on the number of circulating leukocytes. Levels of nitrite and/or nitrate in the serum were elevated within 2 h after administration of IL-18, reaching a peak at 4 h and then decreasing gradually to the basal level over a 24-h period of time. On the other hand, serum IFN-γ levels changed in a biphasic manner, reaching a peak at 2 h after IL-18 administration, followed by a decrease in the basal level and a second increase at 6 h. Levels of IL-18 receptor mRNAs also showed biphasic changes in correlation with the changes in serum IFN-γ levels. These results suggest that the changes in the leukocyte number following IL-18 administration are mediated by NO and IFN-γ, with NO being involved in the first phase of reduction and IFN-γ being involved in both phases

Suppression of Magnetic Order before the Superconducting Dome in MnP

International audienceWe have performed neutron diffraction experiments on the manganese superconductor, MnP, under applied pressure. Higher harmonics of the previously reported double helix (2δ and 3δ) at ambient pressure were observed and a new magnetic phases was discovered as hydrostatic pressure was applied to a polycrystalline sample below the pressure required to induce superconductivity. The double helix magnetic structure is suppressed by 0.7 GPa. A new incommensurate magnetic structure with propagation vector ∼(0.25,0.25,0.125) was found at 1.5 GPa. The application of higher pressures results in the quenching of the incommensurate phase and broad, diffuse magnetic scattering develops before the superconducting phase. Single crystal studies complement the polycrystalline data confirming the magnetic propagation vector in the low pressure phase

Atomic reconstruction induced by uniaxial stress in MnP

Abstract In condensed matter physics, pressure is frequently used to modify the stability of both electronic states and atomic arrangements. Under isotropic pressure, the intermetallic compound MnP has recently attracted attention for the interplay between pressure-induced superconductivity and complicated magnetic order in the vicinity . By contrast, we use uniaxial stress, a directional type of pressure, to investigate the effect on the magnetism and crystal structure of this compound. An irreversible magnetisation response induced by uniaxial stress is discovered in MnP at uniaxial stress as low as $$0.04\ \text {GPa}$$ 0.04 GPa . Neutron diffraction experiments reveal that uniaxial stress forms crystal domains that satisfy pseudo-rotational symmetry unique to the MnP-type structure. The structure of the coexisting domains accounts for the stress-induced magnetism. We term this first discovered phenomenon atomic reconstruction (AR) induced by uniaxial stress. Furthermore, our calculation results provide guidelines on the search for AR candidates. AR allows crystal domain engineering to control anisotropic properties of materials, including dielectricity, elasticity, electrical conduction, magnetism and superconductivity. A wide-ranging exploration of potential AR candidates would ensure that crystal domain engineering yields unconventional methods to design functional multi-domain materials for a wide variety of purposes