Helical vs. fundamental solitons in optical fibers

We consider solitons in a nonlinear optical fiber with a single polarization in a region of parameters where it carries exactly two distinct modes, the fundamental one and the first-order helical mode. From the viewpoint of applications to dense-WDM communication systems, this opens way to double the number of channels carried by the fiber. Aside from that, experimental observation of helical (spinning) solitons and collisions between them and with fundamental solitons are issues of fundamental interest. We introduce a system of coupled nonlinear Schroedinger equations for fundamental and helical modes, which have nonstandard values of the cross-phase-modulation coupling constants, and investigate, analytically and numerically, results of "complete" and "incomplete" collisions between solitons carried by the two modes. We conclude that the collision-induced crosstalk is partly attenuated in comparison with the usual WDM system, which sometimes may be crucially important, preventing merger of the colliding solitons into a breather. The interaction between the two modes is found to be additionally strongly suppressed in comparison with that in the WDM system in the case when a dispersion-shifted or dispersion-compensated fiber is used.Comment: a plain latex file with the text and two ps files with figures. Physica Scripta, in pres

Genome-wide localization of histone variants in Toxoplasma gondii implicates variant exchange in stage-specific gene expression.

BACKGROUND: Toxoplasma gondii is a protozoan parasite that differentiates from acute tachyzoite stages to latent bradyzoite forms in response to environmental cues that modify the epigenome. We studied the distribution of the histone variants CenH3, H3.3, H2A.X, H2A.Z and H2B.Z, by genome-wide chromatin immunoprecipitation to understand the role of variant histones in developmental transitions of T. gondii parasites. RESULTS: H3.3 and H2A.X were detected in telomere and telomere associated sequences, whereas H3.3, H2A.X and CenH3 were enriched in centromeres. Histones H2A.Z and H2B.Z colocalize with the transcriptional activation mark H3K4me3 in promoter regions surrounding the nucleosome-free region upstream of the transcription start site. The H2B.Z/H2A.Z histone pair also localizes to the gene bodies of genes that are silent but poised for activation, including bradyzoite stage-specific genes. The majority of H2A.X and H2A.Z/H2B.Z loci do not overlap, consistent with variant histones demarcating specific functional regions of chromatin. The extent of enrichment of H2A.Z/H2B.Z (and H3.3 and H2A.X) within the entire gene (5'UTR and gene body) reflects the timing of gene expression during the cell cycle, suggesting that dynamic turnover of H2B.Z/H2A.Z occurs during the tachyzoite cell cycle. Thus, the distribution of the variant histone H2A.Z/H2B.Z dimer defines active and developmentally silenced regions of the T. gondii epigenome including genes that are poised for expression. CONCLUSIONS: Histone variants mark functional regions of parasite genomes with the dynamic placement of the H2A.Z/H2B.Z dimer implicated as an evolutionarily conserved regulator of parasite and eukaryotic differentiation

Essential role of Plasmodium perforin-like protein 4 in ookinete midgut passage.

Pore forming proteins such as those belonging to the membrane attack/perforin (MACPF) family have important functions in many organisms. Of the five MACPF proteins found in Plasmodium parasites, three have functions in cell passage and one in host cell egress. Here we report an analysis of the perforin-like protein 4, PPLP4, in the rodent parasite Plasmodium berghei. We found that the protein is expressed only in the ookinete, the invasive stage of the parasite formed in the mosquito midgut. Transcriptional analysis revealed that expression of the pplp4 gene commences during ookinete development. The protein was detected in retorts and mature ookinetes. Using two antibodies, the protein was found localized in a dotted pattern, and 3-D SIM super-resolution microcopy revealed the protein in the periphery of the cell. Analysis of a C-terminal mCherry fusion of the protein however showed mainly cytoplasmic label. A pplp4 null mutant formed motile ookinetes, but these were unable to invade and traverse the midgut epithelium resulting in severely impaired oocyst formation and no transmission to naïve mice. However, when in vitro cultured ookinetes were injected into the thorax of the mosquito, thus by-passing midgut passage, sporozoites were formed and the mutant parasites were able to infect naïve mice. Taken together, our data show that PPLP4 is required only for ookinete invasion of the mosquito midgut. Thus PPLP4 has a similar role to the previously studied PPLP3 and PPLP5, raising the question why three proteins with MACPF domains are needed for invasion by the ookinete of the mosquito midgut epithelium

Suppression and Enhancement of Soliton Switching During Interaction in Periodically Twisted Birefringent Fiber

Soliton interaction in periodically twisted birefringent optical fibers has been analysed analytically with refernce to soliton switching. For this purpose we construct the exact general two-soliton solution of the associated coupled system and investigate its asymptotic behaviour. Using the results of our analytical approach we point out that the interaction can be used as a switch to suppress or to enhance soliton switching dynamics, if one injects multi-soliton as an input pulse in the periodically twisted birefringent fiber.Comment: 10 pages, 4 figures, Latex, submitted to Phys. Rev.

Minimal methylation classifier (MIMIC): A novel method for derivation and rapid diagnostic detection of disease-associated DNA methylation signatures

Rapid and reliable detection of disease-associated DNA methylation patterns has major potential to advance molecular diagnostics and underpin research investigations. We describe the development and validation of minimal methylation classifier (MIMIC), combining CpG signature design from genome-wide datasets, multiplex-PCR and detection by single-base extension and MALDI-TOF mass spectrometry, in a novel method to assess multi-locus DNA methylation profiles within routine clinically-applicable assays. We illustrate the application of MIMIC to successfully identify the methylation-dependent diagnostic molecular subgroups of medulloblastoma (the most common malignant childhood brain tumour), using scant/low-quality samples remaining from the most recently completed pan-European medulloblastoma clinical trial, refractory to analysis by conventional genome-wide DNA methylation analysis. Using this approach, we identify critical DNA methylation patterns from previously inaccessible cohorts, and reveal novel survival differences between the medulloblastoma disease subgroups with significant potential for clinical exploitation

Molecular epidemiology and expression of capsular polysaccharides in Staphylococcus aureus clinical isolates in the United States.

Staphylococcus aureus capsular polysaccharides (CP) are important virulence factors under evaluation as vaccine antigens. Clinical S. aureus isolates have the biosynthetic capability to express either CP5 or CP8 and an understanding of the relationship between CP genotype/phenotype and S. aureus epidemiology is valuable. Using whole genome sequencing, the clonal relatedness and CP genotype were evaluated for disease-associated S. aureus isolates selected from the Tigecycline Evaluation and Surveillance Trial (T.E.S.T) to represent different geographic regions in the United States (US) during 2004 and 2009-10. Thirteen prominent clonal complexes (CC) were identified, with CC5, 8, 30 and 45 representing >80% of disease isolates. CC5 and CC8 isolates were CP type 5 and, CC30 and CC45 isolates were CP type 8. Representative isolates from prevalent CC were susceptible to in vitro opsonophagocytic killing elicited by anti-CP antibodies, demonstrating that susceptibility to opsonic killing is not linked to the genetic lineage. However, as not all S. aureus isolates may express CP, isolates representing the diversity of disease isolates were assessed for CP production. While approximately 35% of isolates (primarily CC8) did not express CP in vitro, CP expression could be clearly demonstrated in vivo for 77% of a subset of these isolates (n = 20) despite the presence of mutations within the capsule operon. CP expression in vivo was also confirmed indirectly by measuring an increase in CP specific antibodies in mice infected with CP5 or CP8 isolates. Detection of antigen expression in vivo in relevant disease states is important to support the inclusion of these antigens in vaccines. Our findings confirm the validity of CP as vaccine targets and the potential of CP-based vaccines to contribute to S. aureus disease prevention

Processing of Plasmodium falciparum Merozoite Surface Protein MSP1 activates a Spectrin-binding function enabling parasite egress from RBCs

The malaria parasite Plasmodium falciparum replicates within erythrocytes, producing progeny merozoites that are released from infected cells via a poorly understood process called egress. The most abundant merozoite surface protein, MSP1, is synthesized as a large precursor that undergoes proteolytic maturation by the parasite protease SUB1 just prior to egress. The function of MSP1 and its processing are unknown. Here we show that SUB1-mediated processing of MSP1 is important for parasite viability. Processing modifies the secondary structure of MSP1 and activates its capacity to bind spectrin, a molecular scaffold protein that is the major component of the host erythrocyte cytoskeleton. Parasites expressing an inefficiently processed MSP1 mutant show delayed egress, and merozoites lacking surface-bound MSP1 display a severe egress defect. Our results indicate that interactions between SUB1-processed merozoite surface MSP1 and the spectrin network of the erythrocyte cytoskeleton facilitate host erythrocyte rupture to enable parasite egress

Molecular determinants of binding to the Plasmodium subtilisin-like protease 1.

PfSUB1, a subtilisin-like protease of the human malaria parasite Plasmodium falciparum, is known to play important roles during the life cycle of the parasite and has emerged as a promising antimalarial drug target. In order to provide a detailed understanding of the origin of binding determinants of PfSUB1 substrates, we performed molecular dynamics simulations in combination with MM-GBSA free energy calculations using a homology model of PfSUB1 in complex with different substrate peptides. Key interactions, as well as residues that potentially make a major contribution to the binding free energy, are identified at the prime and nonprime side of the scissile bond and comprise peptide residues P4 to P2'. This finding stresses the requirement for peptide substrates to interact with both prime and nonprime side residues of the PfSUB1 binding site. Analyzing the energetic contributions of individual amino acids within the peptide-PfSUB1 complexes indicated that van der Waals interactions and the nonpolar part of solvation energy dictate the binding strength of the peptides and that the most favorable interactions are formed by peptide residues P4 and P1. Hot spot residues identified in PfSUB1 are dispersed over the entire binding site, but clustered areas of hot spots also exist and suggest that either the S4-S2 or the S1-S2' binding site should be exploited in efforts to design small molecule inhibitors. The results are discussed with respect to which binding determinants are specific to PfSUB1 and, therefore, might allow binding selectivity to be obtained

The application of a real-time rapid-prototyping environment for the behavioral rehabilitation of a lost function in rats

Abstract-In this paper we propose a Rapid Prototyping Environment (RPE) for real-time biosignal analysis including ECG, EEG, ECoG and EMG of humans and animals requiring a very precise time resolution. Based on the previous RPE which was mainly designed for developing Brain Computer Interfaces (BCI), the present solution offers tools for data preprocessing, analysis and visualization even in the case of high sampling rates and furthermore tools for precise cognitive stimulation. One application of the system, the analysis of multi-unit activity measured from the brain of a rat is presented to prove the efficiency of the proposed environment. The experimental setup was used to design and implement a biomimetic, biohybrid model for demonstrating the recovery of a learning function lost with age. Throughout the paper we discuss the components of the setup, the software structure and the online visualization. At the end we present results of a real-time experiment in which the model of the brain learned to react to the acquired signals

P113 is a merozoite surface protein that binds the N terminus of Plasmodium falciparum RH5.

Invasion of erythrocytes by Plasmodium falciparum merozoites is necessary for malaria pathogenesis and is therefore a primary target for vaccine development. RH5 is a leading subunit vaccine candidate because anti-RH5 antibodies inhibit parasite growth and the interaction with its erythrocyte receptor basigin is essential for invasion. RH5 is secreted, complexes with other parasite proteins including CyRPA and RIPR, and contains a conserved N-terminal region (RH5Nt) of unknown function that is cleaved from the native protein. Here, we identify P113 as a merozoite surface protein that directly interacts with RH5Nt. Using recombinant proteins and a sensitive protein interaction assay, we establish the binding interdependencies of all the other known RH5 complex components and conclude that the RH5Nt-P113 interaction provides a releasable mechanism for anchoring RH5 to the merozoite surface. We exploit these findings to design a chemically synthesized peptide corresponding to RH5Nt, which could contribute to a cost-effective malaria vaccine