Project description:Female mice aged 6-7 weeks old were infected with the T. cruzi H1 strain. Mice were randomly divided into groups with 15 animals in each, with age matched naïve mice included as controls. Approximately 75 days post infection, mice were randomly divided into groups and treated with different treatment combinations: BNZ + Tc24 therapeutic vaccine + the STAT-3 inhibitor TTI-101, BNZ + Tc24 vaccine, and BNZ or TTI alone. Mice were humanely euthanized at 50, 75, 120 or 142 days post infection (DPI), and hearts samples were collected, divided into left atrium (LA), right atrium (RA), left ventricle top (LVT), left ventricle bottom (LVB), right ventricle top (RVT), right ventricle bottom (RVB). Heart tissue samples were extracted by 1:1 (v/v) methanol to water for aqueous phase and 3:1 (v/v) dichloromethane to methanol for organic phase. LC-MS/MS data acquisition was performed on a Q Exactive Plus Hybrid Quadrupole-Orbitrap Mass Spectrometer coupled to a Thermo Scientific Vanquish UHPLC with 1.7 um 100 Å Kinetex C8 column at 40°C. Mobile phase A was water with 0.1% (v/v) formic acid and mobile phase B was acetonitrile with 0.1% (v/v) formic acid.
Project description:Female mice aged 6-7 weeks old were infected with the T. cruzi H1 strain. Mice were randomly divided into groups with 15 animals in each, with age matched naïve mice included as controls. Approximately 75 days post infection, mice were randomly divided into groups and treated with different treatment combinations: BNZ + Tc24 therapeutic vaccine + the STAT-3 inhibitor TTI-101, BNZ + Tc24 vaccine, and BNZ or TTI alone. Mice were humanely euthanized at 50, 75, 120 or 142 days post infection (DPI), and hearts samples were collected, divided into left atrium (LA), right atrium (RA), left ventricle top (LVT), left ventricle bottom (LVB), right ventricle top (RVT), right ventricle bottom (RVB). Heart tissue samples were extracted by 1:1 (v/v) methanol to water for aqueous phase and 3:1 (v/v) dichloromethane to methanol for organic phase. LC-MS/MS data acquisition was performed on a Q Exactive Plus Hybrid Quadrupole-Orbitrap Mass Spectrometer coupled to a Thermo Scientific Vanquish UHPLC with 1.7 um 100 Å Kinetex C8 column at 40°C. Mobile phase A was water with 0.1% (v/v) formic acid and mobile phase B was acetonitrile with 0.1% (v/v) formic acid.
Project description:Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, cartilage damage and bone erosion. Despite improvements with the introduction of biological disease-modifying anti-rheumatic drugs (DMARDs), RA remains incurable. Advancements in peptide-based vaccination may open new avenues for treating autoimmune diseases by inducing immune tolerance while maintaining normal immune function. We have demonstrated a potential vaccine against RA, made by mouse major histocompatibility complex class II (Aq) protein bounding the immunodominant type II collagen peptide COL2259-273, which needed to be galactosylated at position 264. To translate the vaccine to humans and to further enhance and simplify this vaccine, we modified the amino acid residue at position 265 and conjugated it with the human DRB1*04:01 molecule. Remarkably, this modified vaccine proved effective in DRB1*04:01-expressing mice without the need for galactosylation at position 264. The vaccine exerts its protective effect through the activation and expansion of VISTA-positive nonconventional regulatory T cells, leading to a potent dominant suppressive response that prevents arthritis development in mice. The new modified vaccine for RA, offers a novel therapeutic approach with potential clinical implications for human autoimmune diseases.
Project description:Verticillium dahliae Kleb., a soil-borne fungus that colonizes vascular tissues, induces wilting, chlorosis and early senescence in potato. Difference in senescence timing found in two diploid potato clones, 07506-01 and 12120-03, was studied and genetic variation in response to V. dahliae infection was identified as a causal factor. The clone, 07506-01, was infected with V. dahliae but did not develop symptoms, indicating tolerance to the pathogen. The other diploid clone, 12120-03 had low levels of pathogen with infection and moderate symptoms indicating partial resistance. 07506-01 was found to carry two susceptible alleles of the Ve2 gene and 12120-03 carried one Ve2 resistant and one susceptible allele. Infected leaves of the two clones were compared using gene expression profiling with the Potato Oligonucleotide Chip Initiative (POCI) microrarray. The results provide further evidence for differences in response of the two clones to infection with V. dahliae. Chlorophyll biosynthesis was higher in the tolerant 07506-01 compared to partially resistant 12120-03. On the other hand, expression of fungal defense genes, Ve resistance genes and defense phytohormone biosynthetic enzyme genes was decreased in 07506-01 compared to 12120-03 suggesting defense responses were suppressed in tolerance compared to resistance. Transcription factor gene expression differences pointed to the WRKY family as potential regulators of V. dahliae responses in potato.
Project description:Fifty healthcare workers (HCW) who had received Mycobacterium-w (Mw) and at least one dose of ChAdOx1 nCoV-19 vaccine subsequently (Mw+ChAdOx1 group) were monitored for symptomatic COVID-19, during a major outbreak with the delta variant of SARS-CoV-2 (April-June, 2021) in India, along with 201 HCW receiving both doses of the vaccine without Mw (ChAdOx1 group). Bulk RNA-Seq analysis was carried out on 4 subjects enrolled from each group.
Project description:<p>Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.</p>
Project description:Verticillium dahliae Kleb., a soil-borne fungus that colonizes vascular tissues, induces wilting, chlorosis and early senescence in potato. Difference in senescence timing found in two diploid potato clones, 07506-01 and 12120-03, was studied and genetic variation in response to V. dahliae infection was identified as a causal factor. The clone, 07506-01, was infected with V. dahliae but did not develop symptoms, indicating tolerance to the pathogen. The other diploid clone, 12120-03 had low levels of pathogen with infection and moderate symptoms indicating partial resistance. 07506-01 was found to carry two susceptible alleles of the Ve2 gene and 12120-03 carried one Ve2 resistant and one susceptible allele. Infected leaves of the two clones were compared using gene expression profiling with the Potato Oligonucleotide Chip Initiative (POCI) microrarray. The results provide further evidence for differences in response of the two clones to infection with V. dahliae. Chlorophyll biosynthesis was higher in the tolerant 07506-01 compared to partially resistant 12120-03. On the other hand, expression of fungal defense genes, Ve resistance genes and defense phytohormone biosynthetic enzyme genes was decreased in 07506-01 compared to 12120-03 suggesting defense responses were suppressed in tolerance compared to resistance. Transcription factor gene expression differences pointed to the WRKY family as potential regulators of V. dahliae responses in potato. Two-color microarray comparison of two clones, three biological replicates of each clone, one dye swap technical replicate