Size polymorphism and low sequence diversity in the locus encoding the Plasmodium vivax rhoptry neck protein 4 (PvRON4) in Colombian isolates

Background: Designing a vaccine against Plasmodium vivax has focused on selecting antigens involved in invasion mechanisms that must have domains with low polymorphism for avoiding allele-specific immune responses. The rhoptry neck protein 4 (RON4) forms part of the tight junction, which is essential in the invasion of hepatocytes and/or erythrocytes; however, little is known about this locus’ genetic diversity. Methods: DNA sequences from 73 Colombian clinical isolates from pvron4 gene were analysed for characterizing their genetic diversity; pvron4 haplotype number and distribution, as well as the evolutionary forces determining diversity pattern, were assessed by population genetics and molecular evolutionary approaches. Results: ron4 has low genetic diversity in P. vivax at sequence level; however, a variable amount of tandem repeats at the N-terminal region leads to extensive size polymorphism. This region seems to be exposed to the immune system. The central region has a putative esterase/lipase domain which, like the protein’s C-terminal fragment, is highly conserved at intra- and inter-species level. Both regions are under purifying selection. Conclusions: pvron4 is the locus having the lowest genetic diversity described to date for P. vivax. The repeat regions in the N-terminal region could be associated with immune evasion mechanisms while the central region and the C-terminal region seem to be under functional or structural constraint. Bearing such results in mind, the PvRON4 central and/or C-terminal portions represent promising candidates when designing a subunit-based vaccine as they are aimed at avoiding an allele-specific immune response, which might limit vaccine efficacy. © 2016 The Author(s)

AuNx stabilization with interstitial nitrogen atoms: A Density Functional Theory Study

Researchers have been studying 4d and 5d Series Transition Metal Nitrides lately as a result of the experimental production of AuN, PtN, CuN. In this paper, we used the Density Functional Theory (DFT) implementing a pseudopotential plane-wave method to study the incorporation of nitrogen atoms in the face-centered cube (fcc) lattice of gold (Au). First, we took the fcc structure of gold, and gradually located the nitrogen atoms in tetrahedral (TH) and octahedral (OH) interstitial sites. AuN stabilized in: 2OH (30%), 4OH and 4TH (50%), 4OH - 2TH (close to the wurtzite structure) and 6TH (60%). This leads us to think that AuN behaves like a Transition Metal Nitride since the nitrogen atoms look for tetrahedral sites. © Published under licence by IOP Publishing Ltd

Finite axisymmetric charged dust disks in conformastatic spacetimes

An infinite family of axisymmetric charged dust disks of finite extension is presented. The disks are obtained by solving the vacuum Einstein-Maxwell equations for conformastatic spacetimes, which are characterized by only one metric function. In order to obtain the solutions, it is assumed that the metric function and the electric potential are functionally related and that the metric function is functionally dependent of another auxiliary function, which is taken as a solution of Laplace equation. The solutions for the auxiliary function are then taken as given by the infinite family of generalized Kalnajs disks recently obtained by Gonz\'alez and Reina (MNRAS 371, 1873, 2006), which is expressed in terms of the oblate spheroidal coordinates and represents a well behaved family of finite axisymmetric flat galaxy models. The so obtained relativistic thin disks have then a charge density that is equal, except maybe by a sign, to their mass density, in such a way that the electric and gravitational forces are in exact balance. The energy density of the disks is everywhere positive and well behaved, vanishing at the edge. Accordingly, as the disks are made of dust, their energy-momentum tensor it agrees with all the energy conditions.Comment: Submitted to PR

Role of the Fractalkine Receptor in CNS Autoimmune Inflammation: New Approach Utilizing a Mouse Model Expressing the Human CX3CR1

Multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS) is the leading cause of non-traumatic neurological disability in young adults. Immune mediated destruction of myelin and oligodendrocytes is considered the primary pathology of MS, but progressive axonal loss is the major cause of neurological disability. In an effort to understand microglia function during CNS inflammation, our laboratory focuses on the fractalkine/CX3CR1 signaling as a regulator of microglia neurotoxicity in various models of neurodegeneration. Fractalkine (FKN) is a transmembrane chemokine expressed in the CNS by neurons and signals through its unique receptor CX3CR1 present in microglia. During experimental autoimmune encephalomyelitis (EAE), CX3CR1 deficiency confers exacerbated disease defined by severe inflammation and neuronal loss. The CX3CR1 human polymorphism I249/M280 present in ∼20% of the population exhibits reduced adhesion for FKN conferring defective signaling whose role in microglia function and influence on neurons during MS remains unsolved. The aim of this study is to assess the effect of weaker signaling through hCX3CR1I249/M280 during EAE. We hypothesize that dysregulated microglial responses due to impaired CX3CR1 signaling enhance neuronal/axonal damage. We generated an animal model replacing the mouse CX3CR1 locus for the hCX3CR1I249/M280 variant. Upon EAE induction, these mice exhibited exacerbated EAE correlating with severe inflammation and neuronal loss. We also observed that mice with aberrant CX3CR1 signaling are unable to produce FKN and ciliary neurotrophic factor during EAE in contrast to wild type mice. Our results provide validation of defective function of the hCX3CR1I249/M280 variant and the foundation to broaden the understanding of microglia dysfunction during neuroinflammation. © 2018 Cardona et al

Determining science teachers’ ideas about the science process skills: a case study

AbstractThe aim of this study is to investigate science teachers’ ideas about the science process skills (SPS) using qualitative analysis. This study was carried out at the first term of 2008- 2009 academic year. A case study research methodology was used. The sample of this study consisted of 10 science teachers (ST), who has been working at Giresun center elementary schools in Turkey. A semi-structured interview procedure was used to collect data. The collected data were analyzed with Nvivo 8 program. The results indicate that the majority of sample have not had widespread theoretical knowledge on SPS

Charged Annular Disks and Reissner-Nordstr\"{o}m Type Black Holes from Extremal Dust

We present the first analytical superposition of a charged black hole with an annular disk of extremal dust. In order to obtain the solutions, we first solve the Einstein-Maxwell field equations for sources that represent disk-like configurations of matter in confomastatic spacetimes by assuming a functional dependence among the metric function, the electric potential and an auxiliary function,which is taken as a solution of the Laplace equation. We then employ the Lord Kelvin Inversion Method applied to models of finite extension in order to obtain annular disks. The structures obtained extend to infinity, but their total masses are finite and all the energy conditions are satisfied. Finally, we observe that the extremal Reissner-Nordstr\"{o}m black hole can be embedded into the center of the disks by adding a boundary term in the inversion.Comment: 17 revtex pages, 8 eps figure

Plasmodium vivax Cell Traversal Protein for Ookinetes and Sporozoites (CelTOS) Functionally Restricted Regions Are Involved in Specific Host-Pathogen Interactions

Following the injection of Plasmodium sporozoites by a female Anopheles mosquito into the dermis, they become engaged on a long journey to hepatic tissue where they must migrate through different types of cell to become established in parasitophorous vacuoles in hepatocytes. Studies have shown that proteins such as cell traversal protein for Plasmodium ookinetes and sporozoites (CelTOS) play a crucial role in cell-traversal ability. Although CelTOS has been extensively studied in various species and included in pre-clinical assays it remains unknown which P. vivax CelTOS (PvCelTOS) regions are key in its interaction with traversed or target cells (Kupffer or hepatocytes) and what type of pressure, association and polymorphism these important regions could have to improve their candidacy as important vaccine antigens. This work has described producing a recombinant PvCelTOS which was recognized by ~30% P. vivax-infected individuals, thereby confirming its ability for inducing a natural immune response. PvCelTOS' genetic diversity in Colombia and its ability to interact with HeLa (traversal cell) and/or HepG2 cell (target cell) external membrane have been assessed. One region in the PvCelTOS amino-terminal region and another in its C-terminus were seen to be participating in host-pathogen interactions. These regions had important functional constraint signals (? less than 0.3 and several sites under negative selection) and were able to inhibit specific rPvCelTOS binding to HeLa cells. This led to suggesting that sequences between aa 41–60 (40833) and 141–160 (40838) represent promising candidates for an anti-P. vivax subunit-based vaccine. © Copyright © 2020 Arévalo-Pinzón, Garzón-Ospina, Pulido, Bermúdez, Forero-Rodríguez, Rodríguez-Mesa, Reyes-Guarín, Suárez and Patarroyo