Discovery of a novel class of highly conserved vaccine antigens using genomic scale antigenic fingerprinting of pneumococcus with human antibodies

Pneumococcus is one of the most important human pathogens that causes life-threatening invasive diseases, especially at the extremities of age. Capsular polysaccharides (CPSs) are known to induce protective antibodies; however, it is not feasible to develop CPS-based vaccines that cover all of the 90 disease-causing serotypes. We applied a genomic approach and described the antibody repertoire for pneumococcal proteins using display libraries expressing 15–150 amino acid fragments of the pathogen's proteome. Serum antibodies of exposed, but not infected, individuals and convalescing patients identified the ANTIGENome of pneumococcus consisting of ∼140 antigens, many of them surface exposed. Based on several in vitro assays, 18 novel candidates were preselected for animal studies, and 4 of them showed significant protection against lethal sepsis. Two lead vaccine candidates, protein required for cell wall separation of group B streptococcus (PcsB) and serine/threonine protein kinase (StkP), were found to be exceptionally conserved among clinical isolates (>99.5% identity) and cross-protective against four different serotypes in lethal sepsis and pneumonia models, and have important nonredundant functions in bacterial multiplication based on gene deletion studies. We describe for the first time opsonophagocytic killing activity for pneumococcal protein antigens. A vaccine containing PcsB and StkP is intended for the prevention of infections caused by all serotypes of pneumococcus in the elderly and in children

Letter of intent for KM3NeT 2.0

The main objectives of the KM3NeT Collaboration are ( i ) the discovery and subsequent observation of high-energy neutrino sources in the Universe and ( ii ) the determination of the mass hierarchy of neutrinos. These objectives are strongly motivated by two recent important discoveries, namely: ( 1 ) the high- energy astrophysical neutrino signal reported by IceCube and ( 2 ) the sizable contribution of electron neutrinos to the third neutrino mass eigenstate as reported by Daya Bay, Reno and others. To meet these objectives, the KM3NeT Collaboration plans to build a new Research Infrastructure con- sisting of a network of deep-sea neutrino telescopes in the Mediterranean Sea. A phased and distributed implementation is pursued which maximises the access to regional funds, the availability of human resources and the syner- gistic opportunities for the Earth and sea sciences community. Three suitable deep-sea sites are selected, namely off-shore Toulon ( France ) , Capo Passero ( Sicily, Italy ) and Pylos ( Peloponnese, Greece ) . The infrastructure will consist of three so-called building blocks. A building block comprises 115 strings, each string comprises 18 optical modules and each optical module comprises 31 photo-multiplier tubes. Each building block thus constitutes a three- dimensional array of photo sensors that can be used to detect the Cherenkov light produced by relativistic particles emerging from neutrino interactions. Two building blocks will be sparsely con fi gured to fully explore the IceCube signal with similar instrumented volume, different methodology, improved resolution and complementary fi eld of view, including the galactic plane. One building block will be densely con fi gured to precisely measure atmospheric neutrino oscillations. Original content from this work may be used under the ter

Adaptive nonlinear Volterra equalizer for mitigation of chirp-induced distortions in cost effective IMDD OFDM systems

We report experimental validations of an adaptive 2nd order Volterra equalization scheme for cost effective IMDD OFDM systems. This equalization scheme was applied to both uplink and downlink transmission. Downlink settings were optimized for maximum bitrate where we achieved 34Gb/s over 10km of SSMF using an EML with 10GHz bandwidth. For the uplink, maximum reach was optimized achieving 14Gb/s using a low-cost DML with 2.5GHz bandwidth

On utilizing uncertainty information in template-based EEG-fMRI ballistocardiogram artifact removal

The correction of ballistocardiogram artifacts in simultaneous EEG-fMRI often yields unsatisfactory results. To improve the signal-to-noise ratio (SNR) of results, we inferred EEG signal uncertainty from postcorrection artifact residuals and computed the uncertainty-weighted mean of ERPs. Using an uncertainty-weighted mean significantly and consistently reduced both inter- and intrasubject SEM in the analysis of auditory evoked responses (AER, indicated by the N1-P2 complex) and in the effects of an auditory oddball paradigm (N1-P3 complex, standard-deviant difference). SNR increased by 3% on average for the AER amplitude (intrasubject) and 17% on average for the auditory oddball ERP (intersubject). This demonstrates that weighting by uncertainty complements existing artifact correction algorithms to increase SNR in ERPs. More specifically, it is an efficient method to utilize seemingly corrupt (difficult-to-correct) EEG data that might otherwise be discarded

Replication of Previous Findings? Comparing Gray Matter Volumes in Transgender Individuals with Gender Incongruence and Cisgender Individuals

The brain structural changes related to gender incongruence (GI) are still poorly understood. Previous studies comparing gray matter volumes (GMV) between cisgender and transgender individuals with GI revealed conflicting results. Leveraging a comprehensive sample of transmen (n = 33), transwomen (n = 33), cismen (n = 24), and ciswomen (n = 25), we employ a region-of-interest (ROI) approach to examine the most frequently reported brain regions showing GMV differences between trans- and cisgender individuals. The primary aim is to replicate previous findings and identify anatomical regions which differ between transgender individuals with GI and cisgender individuals. On the basis of a comprehensive literature search, we selected a set of ROIs (thalamus, putamen, cerebellum, angular gyrus, precentral gyrus) for which differences between cis- and transgender groups have been previously observed. The putamen was the only region showing significant GMV differences between cis- and transgender, across previous studies and the present study. We observed increased GMV in the putamen for transwomen compared to both transmen and ciswomen and for all transgender participants compared to all cisgender participants. Such a pattern of neuroanatomical differences corroborates the large majority of previous studies. This potential replication of previous findings and the known involvement of the putamen in cognitive processes related to body representations and the creation of the own body image indicate the relevance of this region for GI and its potential as a structural biomarker for G

Baseline levels of miR-223-3p correlate with the effectiveness of electroconvulsive therapy in patients with major depression

Abstract There is a strong medical need to develop suitable biomarkers to improve the diagnosis and treatment of depression, particularly in predicting response to certain therapeutic approaches such as electroconvulsive therapy (ECT). MicroRNAs are small non-coding RNAs that have the ability to influence the transcriptome as well as proteostasis at the systems level. Here, we investigate the role of circulating microRNAs in depression and response prediction towards ECT. Of the 64 patients with treatment-resistant major depression (MDD) who received ECT treatment, 62.5% showed a response, defined as a reduction of ≥50% in the MADRS total score from baseline. We performed smallRNA sequencing in blood samples that were taken before the first ECT, after the first and the last ECT. The microRNAome was compared between responders and non-responders. Co-expression network analysis identified three significant microRNA modules with reverse correlation between ECT- responders and non-responders, that were amongst other biological processes linked to inflammation. A candidate microRNA, namely miR-223-3p was down-regulated in ECT responders when compared to non-responders at baseline. In line with data suggesting a role of miR-223-3p in inflammatory processes we observed higher expression levels of proinflammatory factors Il-6, Il-1b, Nlrp3 and Tnf-α in ECT responders at baseline when compared to non-responders. ROC analysis of confirmed the diagnostic power of miR-223-3p demarcating ECT-responders from non-responder subjects (AUC = 0.76, p = 0.0031). Our data suggest that miR-223-3p expression and related cytokine levels could serve as predictors of response to ECT in individuals with treatment-resistant depressive disorders

Protection against FIV challenge infection by genetic vaccination using minimalistic DNA constructs for FIV env gene and feline IL-12 expression

OBJECTIVE: To evaluate the efficacy of a genetic vaccination protocol based on minimalistic, immunogenic defined gene expression (MIDGE) vectors coding for domains of the feline immunodeficiency virus (FIV) env gene and feline IL-12. METHODS: Three groups of four cats each were immunized three times within 6 weeks by the ballistic transfer of gold particles coated with MIDGE vectors. Group 1 received non-coated gold beads, groups 2 and 3 MIDGE vectors expressing FIV surface plus part of the transmembrane protein. In addition, group 3 received feline IL-12 DNA. All cats were challenged by intraperitoneal injection of 25 TCID50 of infectious FIV Z2. The following criteria were monitored: clinical signs, antibodies to transmembrane protein, antibodies to whole FIV, haematological parameters and kinetics of CD4 and CD8 cells, FIV proviral load (determined by quantitative polymerase chain reaction; PCR) and cytotoxic T lymphocyte (CTL) activity (in selected cats). RESULTS: None of the cats developed a detectable antibody response during immunizations. Four weeks after challenge exposure, all cats in group 1 (control) and group 2 (FIV surface-transmembrane protein) had seroconverted and showed a high proviral load until week 19 (end of experiment). In contrast, only one of four cats in group 3 (surface-transmembrane protein and IL-12) showed antibodies; it was provirus positive at reduced virus load. Short-lived CTL activity was found in two cats in group 3. CONCLUSION: Genetic vaccination using a MIDGE-based construct for the expression of the surface-transmembrane protein domain of FIV env and feline IL-12 DNA led to protection against homologous virus challenge in three out of four vaccinated cats