Recombinant antigen P29 of Echinococcus granulosus induces Th1, Tc1, and Th17 cell immune responses in sheep

Echinococcosis is a common human and animal parasitic disease that seriously endangers human health and animal husbandry. Although studies have been conducted on vaccines for echinococcosis, to date, there is no human vaccine available for use. One of the main reasons for this is the lack of in-depth research on basic immunization with vaccines. Our previous results confirmed that recombinant antigen P29 (rEg.P29) induced more than 90% immune protection in both mice and sheep, but data on its induction of sheep-associated cellular immune responses are lacking. In this study, we investigated the changes in CD4+ T cells, CD8+ T cells, and antigen-specific cytokines IFN-γ, IL-4, and IL-17A after rEg.P29 immunization using enzyme-linked immunospot assay (ELISPOT), enzyme-linked immunosorbent assay (ELISA), and flow cytometry to investigate the cellular immune response induced by rEg.P29 in sheep. It was found that rEg.P29 immunization did not affect the percentage of CD4+ and CD8+ T cells in peripheral blood mononuclear cells (PBMCs), and was able to stimulate the proliferation of CD4+ and CD8+ T cells after immunization in vitro. Importantly, the results of both ELISPOT and ELISA showed that rEg.P29 can induce the production of the specific cytokines IFN-γ and IL-17A, and flow cytometry verified that rEg.P29 can induce the expression of IFN-γ in CD4+ and CD8+ T cells and IL-17A in CD4+ T cells; however, no IL-4 expression was observed. These results indicate that rEg.P29 can induce Th1, Th17, and Tc1 cellular immune responses in sheep against echinococcosis infection, providing theoretical support for the translation of rEg.P29 vaccine applications

Effect of Asymmetric Anchoring Groups on Electronic Transport in Hybrid Metal/Molecule/Graphene Single Molecule Junctions.

A combined experimental and theoretical study on molecular junctions with asymmetry in both the electrode type and in the anchoring group type is presented. A scanning tunnelling microscope is used to create the "asymmetric" Au-S-(CH2 )n-COOH-graphene molecular junctions and determine their conductance. The measurements are combined with electron transport calculations based on density functional theory (DFT) to analyze the electrical conductance and its length attenuation factor from a series of junctions of different molecular length (n). These results show an unexpected trend with a rather high conductance and a smaller attenuation factor for the Au-S-(CH2 )n -COOH-graphene configuration compared to the equivalent junction with the "symmetrical" COOH contacting using the HOOC-(CH2 )n -COOH series. Owing to the effect of the graphene electrode, the attenuation factor is also smaller than the one obtained for Au/Au electrodes. These results are interpreted through the relative molecule/electrode couplings and molecular level alignments as determined with DFT calculations. In an asymmetric junction, the electrical current flows through the less resistive conductance channel, similarly to what is observed in the macroscopic regime

Destructive quantum interference in <i>meta</i>-oligo(phenyleneethynylene) molecular wires with gold-graphene heterojunctions.

Quantum interference (QI) is well recognised as a significant contributing factor to the magnitude of molecular conductance values in both single-molecule and large area junctions. Numerous structure-property relationship studies have shown that para-connected oligo(phenyleneethynylene) (OPE) based molecular wires exemplify the impact of constructive quantum interference (CQI), whilst destructive quantum interference (DQI) effects are responsible for the orders of magnitude lower conductance of analogous meta-contacted OPE derivatives, despite the somewhat shorter effective tunnelling distance. Since molecular conductance is related to the value of the transmission function, evaluated at the electrode Fermi energy, T(EF), which in turn is influenced by the presence and relative energy of (anti)resonances, it follows that the relative single-molecule conductance of para- and meta-contacted OPE-type molecules is tuned both by the anchor group and the nature of the electrode materials used in the construction of molecular junctions (gold|molecule|gold vs. gold|molecule|graphene). It is shown here that whilst amine-contacted junctions show little influence of the electrode material on molecular conductance due to the similar electrode-molecule coupling through this anchor group to both types of electrodes, the weaker coupling between thiomethyl and ethynyl anchors and the graphene substrate electrode results in a relative enhancement of the DQI effect. This work highlights an additional parameter space to explore QI effects and establishes a new working model based on the electrode materials and anchor groups in modulating QI effects beyond the chemical structure of the molecular backbone

State-of-the-art methods for exposure-health studies: Results from the exposome data challenge event

The exposome recognizes that individuals are exposed simultaneously to a multitude of different environmental factors and takes a holistic approach to the discovery of etiological factors for disease. However, challenges arise when trying to quantify the health effects of complex exposure mixtures. Analytical challenges include dealing with high dimensionality, studying the combined effects of these exposures and their interactions, integrating causal pathways, and integrating high-throughput omics layers. To tackle these challenges, the Barcelona Institute for Global Health (ISGlobal) held a data challenge event open to researchers from all over the world and from all expertises. Analysts had a chance to compete and apply state-of-the-art methods on a common partially simulated exposome dataset (based on real case data from the HELIX project) with multiple correlated exposure variables (P &gt; 100 exposure variables) arising from general and personal environments at different time points, biological molecular data (multi-omics: DNA methylation, gene expression, proteins, metabolomics) and multiple clinical phenotypes in 1301 mother–child pairs. Most of the methods presented included feature selection or feature reduction to deal with the high dimensionality of the exposome dataset. Several approaches explicitly searched for combined effects of exposures and/or their interactions using linear index models or response surface methods, including Bayesian methods. Other methods dealt with the multi-omics dataset in mediation analyses using multiple-step approaches. Here we discuss features of the statistical models used and provide the data and codes used, so that analysts have examples of implementation and can learn how to use these methods. Overall, the exposome data challenge presented a unique opportunity for researchers from different disciplines to create and share state-of-the-art analytical methods, setting a new standard for open science in the exposome and environmental health field

Susan’s Elusive Unreliability and Coetzee’s Existential Thinking in Foe

This paper explores the portrayal of Susan Barton as an unreliable narrator in J.M. Coetzee’s novel, Foe, and its implications on storytelling, authorial authority, and existential themes. Through a comprehensive analysis of Susan’s narrative, the paper delves into the dual interpretations of her (un)reliability and argues that Coetzee intentionally crafts her as an elusive unreliable narrator. Then this article examines the “re-deconstruction” achieved by Coetzee, which challenges traditional storytelling conventions and emphasises the underlying meaning conveyed by a story. It also tries to explore Coetzee’s philosophical contemplations of existence and contends that aligning with Sartre’s existential thinking, Coetzee discusses many concepts around freedom and existence. By incorporating existential reflections, the paper uncovers the consciousness and existence embedded in the narrative

Identification of a dominant murine T-cell epitope in recombinant protein P29 from Echinococcus granulosus

Echinococcus granulosus causes echinococcosis, an important zoonotic disease worldwide and a major public health issue. Vaccination is an economical and practical approach for controlling E. granulosus. We have previously revealed that a recombinant protein P29 (rEg.P29) is a good vaccine candidate against E. granulosus. However, T cell immunogenic epitopes have not been identified. In the present study, we use rEg.P29-immunized mice as models to screen immunogenic epitopes for the construction of a novel multi-epitope vaccine. We search for immunodominant epitopes from an overlapping peptide library to screen the peptides of rEg.P29. Our results confirm that rEg.P29 immunization in mice elicits the activation of T cells and induces cellular immune responses. Further analyses show that a T cell epitope within amino acids 86–100 of rEg.P29 elicits significant antigen-specific IFN-γ production in CD4+ and CD8+ T cells and promotes specific T-cell activation and proliferation. Collectively, these results provide a reference for the construction of a novel vaccine against broad E. granulosus genotypes based on epitopes of rEg.P29

Identity-Preserving Talking Face Generation with Landmark and Appearance Priors

Generating talking face videos from audio attracts lots of research interest. A few person-specific methods can generate vivid videos but require the target speaker's videos for training or fine-tuning. Existing person-generic methods have difficulty in generating realistic and lip-synced videos while preserving identity information. To tackle this problem, we propose a two-stage framework consisting of audio-to-landmark generation and landmark-to-video rendering procedures. First, we devise a novel Transformer-based landmark generator to infer lip and jaw landmarks from the audio. Prior landmark characteristics of the speaker's face are employed to make the generated landmarks coincide with the facial outline of the speaker. Then, a video rendering model is built to translate the generated landmarks into face images. During this stage, prior appearance information is extracted from the lower-half occluded target face and static reference images, which helps generate realistic and identity-preserving visual content. For effectively exploring the prior information of static reference images, we align static reference images with the target face's pose and expression based on motion fields. Moreover, auditory features are reused to guarantee that the generated face images are well synchronized with the audio. Extensive experiments demonstrate that our method can produce more realistic, lip-synced, and identity-preserving videos than existing person-generic talking face generation methods.Comment: CVPR2023, Code: https://github.com/Weizhi-Zhong/IP_LA

Oligothiophene molecular wires at graphene-based molecular junctions

International audienceThe use of graphene as a new type of electrode at molecular junctions has led to a renewal of molecular electronics. Indeed, the symmetry breaking induced by the graphene electrode yields different electronic behaviors at the molecular junction and in particular enhanced conductance forlonger molecules. In this respect, several studies involving different molecular backbones and anchoring groups have been performed. Here in the same line, we consider oligopthiophene based hybrid gold– graphene junctions and we measure their electrical properties using the STM-I(s) method in order to determine their attenuation factor and the effect of specific anchoring groups. The results are supported by density functional theory (DFT) calculations, and exhibit a similar behavior to what is observed at alkane-based junctions

Technical Effects of Molecule–Electrode Contacts in Graphene-Based Molecular Junctions

International audienceThis study focuses on comparing methods for capturing and measuring the charge transport properties of single molecules in gold–graphene contact gaps. We have attempted to measure the single-molecule conductance of a series of 1,n-alkanedithiols (n = 4, 6, 8) tethered between a gold and a graphene contact with three different methods. The conducting probe atomic force microscopy break junction (CP-AFM BJ), scanning tunneling microscopy (STM) break junction (STM BJ), and STM-based I(s) techniques for forming molecular junctions with graphene lower contacts were compared. In each case, the upper contact was gold, with a gold-coated AFM probe in the CP-AFM BJ method and a gold STM tip for both the STM BJ and I(s) techniques. Both the CP-AFM BJ and the STM-based I(s) methods yielded similar values for the conductance decay constant values, with βN = 0.56 and 0.40, respectively. In line with previous observations, these are much smaller than values recorded for the same alkanedithiol series in symmetric gold–molecule–gold junctions, where we find that βN = 1.1. This clearly shows the impact of substituting one of the gold contacts for a graphene one. This observation has been previously rationalized as resulting from the breaking of the junction symmetry, the change in electrode–molecule coupling and energy level alignment. On the other hand, stable molecular junctions could not be formed using the STM BJ technique with graphene contacts, which may be because of transient instability in the gold tip contact after it has been pushed hard onto the graphene surface