The Role of Histidine Rich Protein II in Cerebral Malaria

Human malaria is caused by five species of Plasmodium. Of these, P. falciparum is the deadliest and is the only species that causes cerebral malaria (CM). CM is a disease of the vascular endothelium characterized by parasite sequestration, increased inflammatory cytokine production, vascular leakage and leukocyte infiltration. A distinguishing feature of P. falciparum infection is the parasite’s production and secretion of histidine-rich protein II (HRPII). HRPII accumulates to high concentrations (up to 100 µg/ml) in serum, which correlates with disease severity. Due to high serum levels of this protein, HRPII has classically been considered a biomarker for P. falciparum infection. Although many functions have been ascribed to HRPII, the function of this protein remains ambiguous. Our work provides a new framework for thinking of this protein from serum biomarker to parasite virulence factor. Using a cellular model of the blood-brain barrier, we demonstrate that HRPII activates the innate immune system in human cerebral microvascular endothelial cells, resulting in redistribution of tight junction proteins and compromise of barrier integrity. This process is Myd88-dependent, NFĸB-mediated and requires inflammasome activation. Intravenous infusion of HRPII induced vascular leakage in the cerebellum and cortex of mice and increased early mortality in a P. berghei ANKA experimental cerebral malaria model. Analogously, transgenic P. berghei expressing falciparum HRPII produced more severe disease than wild-type or control P. berghei. HRPII induced endothelial expression of adhesion receptors used by plasmodium parasites, suggesting that this protein also contributes to pathogenesis by enhancing parasite cytoadherence and thereby avoiding splenic destruction. This study establishes that HRPII is a Plasmodium falciparum virulence factor that triggers an innate immune inflammatory response in vascular endothelium and contributes to cerebral malaria by compromising the integrity of the blood-brain barrier

Interaction of an Antituberculosis Drug with a Nanoscopic Macromolecular Assembly: Temperature-Dependent Förster Resonance Energy Transfer Studies on Rifampicin in an Anionic Sodium Dodecyl Sulfate Micelle

In this contribution, we report studies on the nature of binding of a potent antituberculosis drug, Rifampicin (RF) with a model drug delivery system, sodium dodecyl sulfate (SDS) micelle. Temperature dependent dynamic light scattering (DLS), conductometry, and circular dichroism (CD) spectroscopy have been employed to study the binding interaction of the drug with the micelle. The absorption spectrum of the drug RF in the visible region has been employed to study Förster resonance energy transfer (FRET) from another fluorescent drug Hoechst 33258 (H33258), bound to the micelle. Picosecond-resolved FRET studies at room temperature confirm the simultaneous binding of the two drugs to the micelle and the distance between the donor−acceptor pair is found to be 34 Å. The temperature dependent FRET study also confirms that the location and efficiency of drug binding to the micelle changes significantly at the elevated temperature. The energy transfer efficiency of the donor H33258, as measured from time-resolved studies, decreases significantly from 76% at 20 °C to 60% at 55 °C. This reveals detachment of some amount of the drug molecules from the micelles and increased donor−acceptor distance at elevated temperatures. The estimated donor−acceptor distance increases from a value of 33 Å at 20 °C to 37 Å at 55 °C. The picosecond resolved FRET studies on a synthesized DNA bound H33258 in RF solution have been performed to explore the interaction between the two. Our studies are expected to find relevance in the exploration of a potential vehicle for the vital drug rifampicin

Corporate Philanthropy: A Systematic Review

A systematic review of the corporate philanthropy literature is conducted. A sample of 60 academic articles was created and analyzed. The sample was examined to (1) develop a definition of corporate philanthropy contrasting it with related concepts; (2) review how corporate philanthropy has been examined theoretically; (3) review how it has been operationalized and determine commonly examined control, independent and dependent variables; (4) the societal implications of corporate philanthropy and (5) identify gaps in the literature and areas for future research. Findings suggest there is little cohesion in the literature regarding a standard definition, wide use of theories to situate corporate philanthropy, and several narrow conceptualizations with opportunities for an empirical and theoretical investigation to enhance the understanding of corporate philanthropy. The gaps identified in the literature review consist of (1) the further study of corporate philanthropy as an independent variable to determine the impacts of corporate action; (2) whether there is a certain amount of optimality associated with corporate donations; (3) whether there are cultural limitations to the findings of attitude towards corporate philanthropy, and (4) a fuller study of the risks and/or benefits posed by corporate philanthropy to society

Understanding the Impact of Early Citers on Long-Term Scientific Impact

This paper explores an interesting new dimension to the challenging problem of predicting long-term scientific impact (LTSI) usually measured by the number of citations accumulated by a paper in the long-term. It is well known that early citations (within 1-2 years after publication) acquired by a paper positively affects its LTSI. However, there is no work that investigates if the set of authors who bring in these early citations to a paper also affect its LTSI. In this paper, we demonstrate for the first time, the impact of these authors whom we call early citers (EC) on the LTSI of a paper. Note that this study of the complex dynamics of EC introduces a brand new paradigm in citation behavior analysis. Using a massive computer science bibliographic dataset we identify two distinct categories of EC - we call those authors who have high overall publication/citation count in the dataset as influential and the rest of the authors as non-influential. We investigate three characteristic properties of EC and present an extensive analysis of how each category correlates with LTSI in terms of these properties. In contrast to popular perception, we find that influential EC negatively affects LTSI possibly owing to attention stealing. To motivate this, we present several representative examples from the dataset. A closer inspection of the collaboration network reveals that this stealing effect is more profound if an EC is nearer to the authors of the paper being investigated. As an intuitive use case, we show that incorporating EC properties in the state-of-the-art supervised citation prediction models leads to high performance margins. At the closing, we present an online portal to visualize EC statistics along with the prediction results for a given query paper

Photoelectrocaloric effect in ferroelectric oxide.

The enhanced electrocaloric (EC) effect in solid-state-based lead-free ferroelectric Ba0.875(Bi0.5Li0.5)0.125TiO3 system is investigated under light as an external stimulus. The sample exhibits an analogous value of maximum change in entropy at Curie temperature, extracted from the two different measurements process. Notably, the sample depicts maximum value of adiabatic change in temperature (ΔT) as 1.27 K and isothermal entropy change (ΔS) as 2.05 J/K kg along with the EC coefficient value of 0.426 K mm/kV, under dark conditions. In addition, the sample exhibits > 0.5 K adiabatic temperature change over a broad temperature range (~ 35 K). Remarkably, the EC parameters display ~ 27% enhancement upon 405 nm light illumination. The demonstrated photoelectrocaloric effect is found to be in accordance with theoretical formalism. The present work elucidates the light as an additional degree of freedom to widen the potential of solid-state-based technologies for advanced environment-friendly cooling devices

Detection of nontrivial topology driven by charge density wave in a semi-Dirac metal

The presence of electron correlations in a system with topological order can lead to exotic ground states. Considering single crystals of LaAgSb2 which has a square net crystal structure, one finds multiple charge density wave transitions (CDW) as the temperature is lowered. We find large planar Hall (PHE) signals in the CDW phase, which are still finite in the high temperature phase though they change sign. Optimising the structure within first-principles calculations, one finds an unusual chiral metallic phase. This is because as the temperature is lowered, the electrons on the Ag atoms get more localized, leading to stronger repulsions between electrons associated with atoms on different layers. This leads to successive layers sliding with respect to each other, thereby stabilising a chiral structure in which inversion symmetry is also broken. The large Berry curvature associated with the low temperature structure explains the low temperature PHE. At high temperature the PHE arises from the changes induced in the tilted Dirac cone in a magnetic field. Our work represents a route towards detecting and understanding the mechanism in a correlation driven topological transition through electron transport measurements, complemented by ab-initio electronic structure calculations.Comment: 11 pages, 4 figures, Includes supplementary information, Accepted in Advanced Functional Material

The study of thermonuclear X-ray bursts in accreting millisecond pulsar MAXI J1816-195 with NuSTAR and NICER

The millisecond pulsar MAXI J1816--195 was recently discovered by MAXI in 2022 May. We have studied different properties of the pulsar using data from NuSTAR and NICER observations. The position of the source is measured by NuSTAR as RA = $18^h 16^m 52^s.40$, Dec = $-19^o37^{'} 58^{''}.35$. The unstable burning of accreted material on the surface of neutron stars induces thermonuclear (Type-I) bursts. Several thermonuclear bursts have been detected from the source during the outburst. We study the evolution of burst profile with flux and energy using NuSTAR and NICER observations. During the NuSTAR observation, a total of four bursts were detected from the source. The duration of each burst was around $\sim$ 30 s and the ratio of peak to persistent count rate is $\sim$ 26 as seen from the NuSTAR data. The thermonuclear bursts are modeled to determine the burst timing parameters using a sharp linear rise and exponential decay function. The burst profiles show a relatively long tail in lower energies. The hardness ratio during the thermonuclear bursts shows significant variation as observed by NuSTAR. We successfully model the broadband burst-resolved spectra with a combination of an absorbed blackbody along with a non-thermal component to account for the persistent emission. The burst-resolved spectral parameters show significant evolution during the burst. During the peak of the burst, the Eddington luminosity is found to be $\sim 3.7 \times 10^{38}$ erg s$^{-1}$. The burst-resolved spectral parameters provide a source distance of $8.5\pm1.2$ kpc for isotropic burst emission.Comment: 13 pages, 9 figures, 4 tables, comments are welcom

Plasmodium falciparum heat shock protein 110 stabilizes the asparagine repeat-rich parasite proteome during malarial fevers

One-fourth of Plasmodium falciparum proteins have asparagine repeats that increase the propensity for aggregation, especially at elevated temperatures that occur routinely in malaria-infected patients. We report that a Plasmodium Asn repeat-containing protein (PFI1155w) formed aggregates in mammalian cells at febrile temperatures, as did a yeast Asn/Gln-rich protein (Sup35). Co-expression of the cytoplasmic P. falciparum heat shock protein 110 (PfHsp110c) prevented aggregation. Human or yeast orthologs were much less effective. All-Asn and all-Gln versions of Sup35 were protected from aggregation by PfHsp110c, suggesting that this chaperone is not limited to handling runs of Asn. PfHsp110c gene knockout parasites were not viable and conditional knockdown parasites died slowly in the absence of protein-stabilizing ligand. When exposed to brief heat shock, these knockdowns were unable to prevent aggregation of PFI1155w or Sup35 and died rapidly. We conclude that PfHsp110c protects the parasite from harmful effects of its asparagine repeat-rich proteome during febrile episodes

Experimental localisation of quantum entanglement through monitored classical mediator

Quantum entanglement is a form of correlation between quantum particles that cannot be increased via local operations and classical communication. It has therefore been proposed that an increment of quantum entanglement between probes that are interacting solely via a mediator implies non-classicality of the mediator. Indeed, under certain assumptions regarding the initial state, entanglement gain between the probes indicates quantum coherence in the mediator. Going beyond such assumptions, there exist other initial states which produce entanglement between the probes via only local interactions with a classical mediator. In this process the initial entanglement between any probe and the rest of the system ``flows through'' the classical mediator and gets localised between the probes. Here we theoretically characterise maximal entanglement gain via classical mediator and experimentally demonstrate, using liquid-state NMR spectroscopy, the optimal growth of quantum correlations between two nuclear spin qubits interacting through a mediator qubit in a classical state. We additionally monitor, i.e., dephase, the mediator in order to emphasise its classical character. Our results indicate the necessity of verifying features of the initial state if entanglement gain between the probes is used as a figure of merit for witnessing non-classical mediator. Such methods were proposed to have exemplary applications in quantum optomechanics, quantum biology and quantum gravity.Comment: 5 pages, 2 figure