Poster prepared by N. Svitek, R. Saya, E. Awino, S. Gilbert, J. Poole, V. Nene and L. Steinaa for the Keystone Symposium on New Approaches to Vaccines for Human and Veterinary Tropical Diseases, Cape Town, 22-26 May 2016
Discovery of novel CTL epitopes by peptide library screening of CTL lines fro...ILRI
Poster prepared by N. Svitek, R. Saya, E. Awino, M. Nielsen, N. MacHugh, J.C. da Silva, V. Nene and L. Steinaa for the Keystone Symposium on New Approaches to Vaccines for Human and Veterinary Tropical Diseases, Cape Town, 22-26 May 2016
Poster prepared by James Nyagwange, Nicola Ternette, Edwin Tijhaar, Roger Pelle and Vish Nene for the Keystone Symposium on New Approaches to Vaccines for Human and Veterinary Tropical Diseases, Cape Town, 22-26 May 2016
This document contains 7 supplemental figures and 1 supplemental table related to a research study. Supplemental Figure 1 shows that podocyte markers were expressed in podocyte cell lines generated from the urine of HIVAN patients, as detected by RT-PCR and western blot. Supplemental Figure 2 provides the DNA and protein sequences of the Tat gene cloned from these renal epithelial cells. Supplemental Figure 3 demonstrates that this Tat protein can translocate to the nucleus of cultured podocytes. Supplemental Figures 4-6 present results of experiments examining the effects of Tat expression and mutations on HIV-LTR transactivation, Env expression in transgenic mouse kidneys, and HIVAN development in mice. Supplemental Figure 7 shows that FGF-2 induced more severe
Presentation by Alvin Ayala Highlighting Luminex TechnologyAlvin Ayala
The document outlines an experiment to determine the activation of a growth factor receptor (Factor X) in solid tumor cell lines using Luminex technology. Several tumor cell lines were screened for expression of the receptor via quantitative RT-PCR. HT-29 (colorectal) and FADU (head and neck) cell lines expressed the receptor and were chosen for further analysis. Stimulation of the cell lines with Factor X did not produce proliferation or demonstrate phosphorylation of the receptor via western blot. However, Luminex technology was able to detect downstream signaling through p-Akt in response to Factor X addition in the cell lines, showing it to be a more sensitive measure of receptor activation than other assays used.
- BAFF (B-cell activation factor) is a tumor necrosis factor family member that regulates B cell homeostasis and survival. Overexpression of BAFF is associated with various autoimmune diseases.
- BAFF exists in both membrane-bound and soluble forms and its production is regulated. It has multiple receptors and cell sources besides B cells.
- A truncated form of BAFF called Δ4 BAFF was discovered that acts as a transcription factor, transporting other transcription factors into the nucleus to regulate full-length BAFF expression. This adds another level of complexity to BAFF regulation.
This study examined how chronic physical restraint stress alters gene expression in mouse spleens. Mice were subjected to restraint stress for 12 hours per day for two days. Microarray analysis found that 48 out of 225 apoptosis- and p53 signaling-related genes showed significant expression changes in stressed mice compared to unstressed controls. Four genes (Fas, FADD, p53, p21) were validated with real-time PCR. The results provide evidence that apoptotic pathways contribute to stress-induced lymphopenia and identify potential stress response biomarkers.
Discovery of novel CTL epitopes by peptide library screening of CTL lines fro...ILRI
Poster prepared by N. Svitek, R. Saya, E. Awino, M. Nielsen, N. MacHugh, J.C. da Silva, V. Nene and L. Steinaa for the Keystone Symposium on New Approaches to Vaccines for Human and Veterinary Tropical Diseases, Cape Town, 22-26 May 2016
Poster prepared by James Nyagwange, Nicola Ternette, Edwin Tijhaar, Roger Pelle and Vish Nene for the Keystone Symposium on New Approaches to Vaccines for Human and Veterinary Tropical Diseases, Cape Town, 22-26 May 2016
This document contains 7 supplemental figures and 1 supplemental table related to a research study. Supplemental Figure 1 shows that podocyte markers were expressed in podocyte cell lines generated from the urine of HIVAN patients, as detected by RT-PCR and western blot. Supplemental Figure 2 provides the DNA and protein sequences of the Tat gene cloned from these renal epithelial cells. Supplemental Figure 3 demonstrates that this Tat protein can translocate to the nucleus of cultured podocytes. Supplemental Figures 4-6 present results of experiments examining the effects of Tat expression and mutations on HIV-LTR transactivation, Env expression in transgenic mouse kidneys, and HIVAN development in mice. Supplemental Figure 7 shows that FGF-2 induced more severe
Presentation by Alvin Ayala Highlighting Luminex TechnologyAlvin Ayala
The document outlines an experiment to determine the activation of a growth factor receptor (Factor X) in solid tumor cell lines using Luminex technology. Several tumor cell lines were screened for expression of the receptor via quantitative RT-PCR. HT-29 (colorectal) and FADU (head and neck) cell lines expressed the receptor and were chosen for further analysis. Stimulation of the cell lines with Factor X did not produce proliferation or demonstrate phosphorylation of the receptor via western blot. However, Luminex technology was able to detect downstream signaling through p-Akt in response to Factor X addition in the cell lines, showing it to be a more sensitive measure of receptor activation than other assays used.
- BAFF (B-cell activation factor) is a tumor necrosis factor family member that regulates B cell homeostasis and survival. Overexpression of BAFF is associated with various autoimmune diseases.
- BAFF exists in both membrane-bound and soluble forms and its production is regulated. It has multiple receptors and cell sources besides B cells.
- A truncated form of BAFF called Δ4 BAFF was discovered that acts as a transcription factor, transporting other transcription factors into the nucleus to regulate full-length BAFF expression. This adds another level of complexity to BAFF regulation.
This study examined how chronic physical restraint stress alters gene expression in mouse spleens. Mice were subjected to restraint stress for 12 hours per day for two days. Microarray analysis found that 48 out of 225 apoptosis- and p53 signaling-related genes showed significant expression changes in stressed mice compared to unstressed controls. Four genes (Fas, FADD, p53, p21) were validated with real-time PCR. The results provide evidence that apoptotic pathways contribute to stress-induced lymphopenia and identify potential stress response biomarkers.
The document summarizes research investigating a novel approach to stimulating Toll-like receptors (TLRs) in human peripheral blood mononuclear cells (PBMCs) using antibody-conjugated beads. Key findings include: (1) TLR2 was able to signal independently of TLRs 1, 6, and 10 using this method; (2) TLR2 signaling was independent of receptor epitope; and (3) preliminary evidence suggested TLR10 may also signal independently. The research established a new method for studying TLRs and provided insights with implications for developing therapies targeting innate immune receptors.
Identification of Potent Phosphodiesterase Inhibitors that Demonstrate Cyclic...Trang Luc
This document describes the identification of potent phosphodiesterase (PDE) inhibitors that demonstrate cyclic nucleotide-dependent functions in apicomplexan parasites. The most potent inhibitor identified was 5-Benzyl-3-isopropyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one (BIPPO), which potently inhibited recombinant P. falciparum Pf PDEα and induced protein kinase G (PKG)-dependent egress in T. gondii and P. falciparum by promoting microneme secretion. BIPPO also promoted cAMP-dependent phosphorylation of a P. falciparum ligand critical for host cell invasion,
The document summarizes the results of a summer scholarship project investigating the interactions between FZR1, an activator of the anaphase promoting complex/cyclosome, and several potential protein targets. Using techniques like immunohistochemistry, western blotting, and immunoprecipitation, the localization and interactions of PP2A-α, CDC14B, and NEDL2 were analyzed in wild type and FZR1 knockout postnatal mouse testis tissue. PP2A-α results were found to be too variable to draw conclusions. CDC14B localization differences were observed between wild type and knockout tissue, but no interaction with FZR1 was detected, though further optimization may be warranted. Improved staining of NED
This document summarizes research on interleukin-9 (IL-9), a multifunctional cytokine that plays important roles in conditions like airway inflammation and asthma. The study found that transforming growth factor-beta (TGF-β) can "reprogram" the differentiation of T helper 2 cells and promote a IL-9-producing T cell subset. The researchers investigated IL-9 signaling pathways and used mouse models to examine the effects of IL-9 on intestinal nematode infection and autoimmune encephalomyelitis. They analyzed gene expression and cytokine production from T cells cultured under various conditions to identify factors that induce IL-9 production.
This document reports on a study examining the effects of somatostatin (SST) on human B lymphoblasts. The key findings are:
1) SST stimulates phospholipase C activity and increases cytosolic calcium levels in B lymphoblasts, likely through coupling of SSTR2A to the G protein Gα16.
2) SST activates extracellular signal-regulated kinases and induces increased DNA synthesis, proliferation, and immunoglobulin formation in B lymphoblasts.
3) These stimulatory effects of SST on early signal transduction pathways are accompanied by increased cell proliferation and immunoglobulin production in human B lymphoblasts, indicating SST exerts growth factor-like
Summer research Homogenity in Th9 cultures 2Daniel Gomes
This document summarizes research from the Kaplan Lab on T helper 9 (Th9) cell differentiation and function. The lab found that culturing naive CD4+ T cells under Th9-polarizing conditions (IL-4 and TGFβ) resulted in a homogenous population of IL-9-secreting cells. However, using an IL-9 reporter mouse, they found that the Th9 genetic program was largely intact in IL-9-negative cells, suggesting it is not restricted only to IL-9-secreting cells. The lab aims to better understand Th9 cell differentiation and the roles they play in disease.
- Overexpression of EphB1 receptor tyrosine kinase in CHO cells leads to increased phosphorylation of Stat3 at tyrosine residue 705 (Tyr705), which is associated with Stat3 activation.
- Co-immunoprecipitation experiments provided evidence of an interaction between EphB1 and Stat3. However, the phosphorylated form of Jak2 kinase, which normally mediates Stat3 phosphorylation, was not detected in these complexes.
- Inhibition of Jak1/2 kinases did not reduce EphB1-induced Stat3 Tyr705 phosphorylation, suggesting EphB1 activates Stat3 through another kinase other than Jaks.
This document discusses using ex vivo expanded and fucosylated regulatory T cells (Tregs) from third party umbilical cord blood to prevent graft-versus-host disease (GVHD) after transplantation. Experiments in mice show that fucosylated Tregs home more effectively to sites of inflammation, persist longer in vivo, and reduce GVHD symptoms and mortality more than untreated Tregs. The document proposes a clinical trial to evaluate the safety and efficacy of fucosylated Tregs for preventing GVHD in patients receiving double cord blood transplants.
A transposon mutagenesis study of Salmonella typhi identified genes associated with regulation of Vi capsule expression. Genes involved in Vi capsule biosynthesis and export were downregulated in mutants as determined by TraDIS analysis. Further study of selected mutants found differences in Vi phage susceptibility and gene expression profiles. This suggests various regulatory pathways control Vi capsule expression in complex ways to influence phage infection and bacterial virulence.
The symphony of the ninth, Th9 cells, by Dr.Pavulraj.S, veterinary pathologistPavulraj Selvaraj
Th9 cells are a subset of CD4+ T helper cells that secrete interleukin-9 (IL-9) as their signature cytokine. They develop in response to transforming growth factor beta (TGF-β) and interleukin-4 (IL-4) signals, which activate transcription factors that regulate IL-9 production. These include PU.1 induced by TGF-β and STAT6, IRF4, and GATA3 induced by IL-4. Th9 cells play roles in autoimmune diseases, allergy, and parasite expulsion by promoting inflammation through IL-9 stimulation of mast cell growth. However, their pathogenic mechanisms are still being defined, and blocking IL-9 is being explored as a potential
The document describes a research study aimed at developing biomarkers for detecting potential allergenicity of novel foods, including genetically modified foods. The researcher conducted experiments challenging mice with known food allergens (egg ovomucoid protein and peanut protein) and analyzed gene expression profiles in the mice spleens. Several hundred genes were found to be differentially expressed. After validating some genes, the researcher identified potential biomarker genes that could help detect allergenicity of GM foods. The study provides insights into transcriptomic responses to food allergens and biomarkers that may help evaluate allergenicity of novel foods like GM crops.
This master's dissertation aimed to demonstrate gene expression in Rat1 fibroblast cells transformed by EVI1 and the relationship between EVI1 levels and CAIII gene expression. Real-time PCR and western blotting showed higher CAIII gene and protein expression in Rat1neo cells compared to Rat15.6 cells, which overexpress EVI1. Luciferase assays also demonstrated higher activity in Rat1neo cells, indicating higher CAIII expression. Silencing CAIII in Rat1neo cells increased caspase 3 activity after hydrogen peroxide treatment, showing CAIII protects against apoptosis. The results suggest EVI1 overexpression represses CAIII expression, reducing protection against oxidative stress. Therefore, oxidative stress agents may selectively target cancer cells overexpressing
1. The document discusses characterizing G protein-coupled receptor signaling and regulation by kinases in differentiated cell functions and disease.
2. It provides examples of how arrestins can desensitize beta-2 adrenergic receptors in airway smooth muscle cells and impact tissue and organ function.
3. Questions are raised about the roles of various G protein-coupled receptors in cancer cell growth and survival and how inflammation, stress, and anti-inflammatory agents may impact these processes through cyclic AMP signaling.
The document summarizes a study that identified potent and selective inhibitors of the Plasmodium falciparum M18 aspartyl aminopeptidase (PfM18AAP) enzyme via high-throughput screening. PfM18AAP plays an important role in malaria parasite growth and is a potential drug target. A fluorescence-based assay was developed to screen over 292,000 compounds, identifying two structurally related compounds that potently and selectively inhibited PfM18AAP in the low micromolar range. Both compounds were found to be noncompetitive inhibitors of PfM18AAP and inhibited malaria parasite growth, demonstrating their potential as antimalarial therapies.
J. biol. chem. 2016-shao-jbc.m116.724401andrei andrei
FBXO3 promotes ubiquitylation and transcriptional activity of AIRE. The study found that the E3 ubiquitin ligase FBXO3 interacts with phosphorylated residues on AIRE and promotes its ubiquitylation. This post-translational modification increases the interaction between AIRE and P-TEFb, potentiating their transcriptional activity on tissue-specific antigen genes in the thymus. Knockdown of FBXO3 decreased ubiquitylation and transcriptional activity of AIRE.
This document summarizes research on profiling gene expression of glutathione S-transferases (GSTs) in sorghum lines with different tolerances to the herbicide s-metolachlor. Through a genome-wide association study, the researchers identified two sorghum lines with high and low tolerance. They designed primers for two GST genes associated with tolerance and measured expression levels at 8 and 12 hours after treatment. Preliminary results show a correlation between basal expression of one GST gene and tolerance, but not the other. Further research is needed to identify additional genes involved in the safener-induced detoxification pathway.
FGF-2 treatment of high passage human mesenchymal stem cells enhances chondro...Boris Schmalz, MD
FGF-2 treatment of high passage human mesenchymal stem cells enhances chondrogenesis in pellet culture through upregulation of Sox9 and integrin alpha 10, key markers of chondrocyte differentiation. However, exposing MSCs to FGF-2 does not improve their ability to regenerate cartilage defects in explant culture. Similarly, FGF-2 increases integrin alpha 10 in bovine chondrocytes but does not enhance repair of cartilage lesions. Pretreating MSCs with FGF-18 does not affect chondrogenesis in pellet culture or expression of chondrogenic markers.
Immunoinformatics and MHC-Tetramers, revolutionary technologies for vaccine d...ILRI
Poster prepared by Nicholas Svitek, Andreas Martin Hansen, Lucilla Steinaa, Rosemary Saya, Elias Awino, Morten Nielsen, Soren Buus and Vish Nene for the ILRI APM 2013, Addis Ababa, 15-17 May 2013
Comparison of primer sets for amplification of Major Piroplasm Surface Protei...Sudhakar Goud Karpurapu
This document compares the efficiency of two primer sets for detecting Theileria orientalis, the causative agent of oriental theileriosis, in cattle. Blood samples from 32 cattle showing clinical signs of the disease were examined microscopically and using two PCR primer sets that target the major piroplasm surface protein gene of T. orientalis. Microscopy found 22 cattle positive, while primer set 1 identified 23 positive and primer set 2 identified all 32 cattle as positive. The results suggest PCR using primer set 2 is more sensitive for detection of T. orientalis infection compared to microscopy or primer set 1.
L-arginine modulates T cell metabolism and enhances survival and anti-tumor A...Gul Muneer
L-arginine modulates T cell metabolism and enhances survival and anti-tumor Activity
How metabolic reprogramming of T cells impact T cells fate and function? Indeed, these cells enhance their metabolic throughput upon antigenic stimulation to ensure the production of sufficient biomass and energy for their proliferation, differentiation and effector functions. The naïve T cells, which utilize oxidative phosphorylation for energy supply but upon activation, these cells switch their metabolic pathways toward glycolysis. An important question arises here that whether differential metabolic reprogramming (i.e., use of oxidative phosphorylation versus glycolytic activity) directs the fate and function of a given cell? And whether this process shapes the immune response and individual cell survival? The researchers from Institute for Research in Biomedicine took advantage of high-resolution Mass Spectrometry to investigate dynamics of proteome and metabolome following activation of naïve T cells.
The document summarizes research investigating a novel approach to stimulating Toll-like receptors (TLRs) in human peripheral blood mononuclear cells (PBMCs) using antibody-conjugated beads. Key findings include: (1) TLR2 was able to signal independently of TLRs 1, 6, and 10 using this method; (2) TLR2 signaling was independent of receptor epitope; and (3) preliminary evidence suggested TLR10 may also signal independently. The research established a new method for studying TLRs and provided insights with implications for developing therapies targeting innate immune receptors.
Identification of Potent Phosphodiesterase Inhibitors that Demonstrate Cyclic...Trang Luc
This document describes the identification of potent phosphodiesterase (PDE) inhibitors that demonstrate cyclic nucleotide-dependent functions in apicomplexan parasites. The most potent inhibitor identified was 5-Benzyl-3-isopropyl-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one (BIPPO), which potently inhibited recombinant P. falciparum Pf PDEα and induced protein kinase G (PKG)-dependent egress in T. gondii and P. falciparum by promoting microneme secretion. BIPPO also promoted cAMP-dependent phosphorylation of a P. falciparum ligand critical for host cell invasion,
The document summarizes the results of a summer scholarship project investigating the interactions between FZR1, an activator of the anaphase promoting complex/cyclosome, and several potential protein targets. Using techniques like immunohistochemistry, western blotting, and immunoprecipitation, the localization and interactions of PP2A-α, CDC14B, and NEDL2 were analyzed in wild type and FZR1 knockout postnatal mouse testis tissue. PP2A-α results were found to be too variable to draw conclusions. CDC14B localization differences were observed between wild type and knockout tissue, but no interaction with FZR1 was detected, though further optimization may be warranted. Improved staining of NED
This document summarizes research on interleukin-9 (IL-9), a multifunctional cytokine that plays important roles in conditions like airway inflammation and asthma. The study found that transforming growth factor-beta (TGF-β) can "reprogram" the differentiation of T helper 2 cells and promote a IL-9-producing T cell subset. The researchers investigated IL-9 signaling pathways and used mouse models to examine the effects of IL-9 on intestinal nematode infection and autoimmune encephalomyelitis. They analyzed gene expression and cytokine production from T cells cultured under various conditions to identify factors that induce IL-9 production.
This document reports on a study examining the effects of somatostatin (SST) on human B lymphoblasts. The key findings are:
1) SST stimulates phospholipase C activity and increases cytosolic calcium levels in B lymphoblasts, likely through coupling of SSTR2A to the G protein Gα16.
2) SST activates extracellular signal-regulated kinases and induces increased DNA synthesis, proliferation, and immunoglobulin formation in B lymphoblasts.
3) These stimulatory effects of SST on early signal transduction pathways are accompanied by increased cell proliferation and immunoglobulin production in human B lymphoblasts, indicating SST exerts growth factor-like
Summer research Homogenity in Th9 cultures 2Daniel Gomes
This document summarizes research from the Kaplan Lab on T helper 9 (Th9) cell differentiation and function. The lab found that culturing naive CD4+ T cells under Th9-polarizing conditions (IL-4 and TGFβ) resulted in a homogenous population of IL-9-secreting cells. However, using an IL-9 reporter mouse, they found that the Th9 genetic program was largely intact in IL-9-negative cells, suggesting it is not restricted only to IL-9-secreting cells. The lab aims to better understand Th9 cell differentiation and the roles they play in disease.
- Overexpression of EphB1 receptor tyrosine kinase in CHO cells leads to increased phosphorylation of Stat3 at tyrosine residue 705 (Tyr705), which is associated with Stat3 activation.
- Co-immunoprecipitation experiments provided evidence of an interaction between EphB1 and Stat3. However, the phosphorylated form of Jak2 kinase, which normally mediates Stat3 phosphorylation, was not detected in these complexes.
- Inhibition of Jak1/2 kinases did not reduce EphB1-induced Stat3 Tyr705 phosphorylation, suggesting EphB1 activates Stat3 through another kinase other than Jaks.
This document discusses using ex vivo expanded and fucosylated regulatory T cells (Tregs) from third party umbilical cord blood to prevent graft-versus-host disease (GVHD) after transplantation. Experiments in mice show that fucosylated Tregs home more effectively to sites of inflammation, persist longer in vivo, and reduce GVHD symptoms and mortality more than untreated Tregs. The document proposes a clinical trial to evaluate the safety and efficacy of fucosylated Tregs for preventing GVHD in patients receiving double cord blood transplants.
A transposon mutagenesis study of Salmonella typhi identified genes associated with regulation of Vi capsule expression. Genes involved in Vi capsule biosynthesis and export were downregulated in mutants as determined by TraDIS analysis. Further study of selected mutants found differences in Vi phage susceptibility and gene expression profiles. This suggests various regulatory pathways control Vi capsule expression in complex ways to influence phage infection and bacterial virulence.
The symphony of the ninth, Th9 cells, by Dr.Pavulraj.S, veterinary pathologistPavulraj Selvaraj
Th9 cells are a subset of CD4+ T helper cells that secrete interleukin-9 (IL-9) as their signature cytokine. They develop in response to transforming growth factor beta (TGF-β) and interleukin-4 (IL-4) signals, which activate transcription factors that regulate IL-9 production. These include PU.1 induced by TGF-β and STAT6, IRF4, and GATA3 induced by IL-4. Th9 cells play roles in autoimmune diseases, allergy, and parasite expulsion by promoting inflammation through IL-9 stimulation of mast cell growth. However, their pathogenic mechanisms are still being defined, and blocking IL-9 is being explored as a potential
The document describes a research study aimed at developing biomarkers for detecting potential allergenicity of novel foods, including genetically modified foods. The researcher conducted experiments challenging mice with known food allergens (egg ovomucoid protein and peanut protein) and analyzed gene expression profiles in the mice spleens. Several hundred genes were found to be differentially expressed. After validating some genes, the researcher identified potential biomarker genes that could help detect allergenicity of GM foods. The study provides insights into transcriptomic responses to food allergens and biomarkers that may help evaluate allergenicity of novel foods like GM crops.
This master's dissertation aimed to demonstrate gene expression in Rat1 fibroblast cells transformed by EVI1 and the relationship between EVI1 levels and CAIII gene expression. Real-time PCR and western blotting showed higher CAIII gene and protein expression in Rat1neo cells compared to Rat15.6 cells, which overexpress EVI1. Luciferase assays also demonstrated higher activity in Rat1neo cells, indicating higher CAIII expression. Silencing CAIII in Rat1neo cells increased caspase 3 activity after hydrogen peroxide treatment, showing CAIII protects against apoptosis. The results suggest EVI1 overexpression represses CAIII expression, reducing protection against oxidative stress. Therefore, oxidative stress agents may selectively target cancer cells overexpressing
1. The document discusses characterizing G protein-coupled receptor signaling and regulation by kinases in differentiated cell functions and disease.
2. It provides examples of how arrestins can desensitize beta-2 adrenergic receptors in airway smooth muscle cells and impact tissue and organ function.
3. Questions are raised about the roles of various G protein-coupled receptors in cancer cell growth and survival and how inflammation, stress, and anti-inflammatory agents may impact these processes through cyclic AMP signaling.
The document summarizes a study that identified potent and selective inhibitors of the Plasmodium falciparum M18 aspartyl aminopeptidase (PfM18AAP) enzyme via high-throughput screening. PfM18AAP plays an important role in malaria parasite growth and is a potential drug target. A fluorescence-based assay was developed to screen over 292,000 compounds, identifying two structurally related compounds that potently and selectively inhibited PfM18AAP in the low micromolar range. Both compounds were found to be noncompetitive inhibitors of PfM18AAP and inhibited malaria parasite growth, demonstrating their potential as antimalarial therapies.
J. biol. chem. 2016-shao-jbc.m116.724401andrei andrei
FBXO3 promotes ubiquitylation and transcriptional activity of AIRE. The study found that the E3 ubiquitin ligase FBXO3 interacts with phosphorylated residues on AIRE and promotes its ubiquitylation. This post-translational modification increases the interaction between AIRE and P-TEFb, potentiating their transcriptional activity on tissue-specific antigen genes in the thymus. Knockdown of FBXO3 decreased ubiquitylation and transcriptional activity of AIRE.
This document summarizes research on profiling gene expression of glutathione S-transferases (GSTs) in sorghum lines with different tolerances to the herbicide s-metolachlor. Through a genome-wide association study, the researchers identified two sorghum lines with high and low tolerance. They designed primers for two GST genes associated with tolerance and measured expression levels at 8 and 12 hours after treatment. Preliminary results show a correlation between basal expression of one GST gene and tolerance, but not the other. Further research is needed to identify additional genes involved in the safener-induced detoxification pathway.
FGF-2 treatment of high passage human mesenchymal stem cells enhances chondro...Boris Schmalz, MD
FGF-2 treatment of high passage human mesenchymal stem cells enhances chondrogenesis in pellet culture through upregulation of Sox9 and integrin alpha 10, key markers of chondrocyte differentiation. However, exposing MSCs to FGF-2 does not improve their ability to regenerate cartilage defects in explant culture. Similarly, FGF-2 increases integrin alpha 10 in bovine chondrocytes but does not enhance repair of cartilage lesions. Pretreating MSCs with FGF-18 does not affect chondrogenesis in pellet culture or expression of chondrogenic markers.
FGF-2 treatment of high passage human mesenchymal stem cells enhances chondro...
Similar to Immunogenicity and protection of the Theileria parva CTL antigen Tp1, with or without a leader sequence, using HAd5/MVA prime-boost vaccination
Immunoinformatics and MHC-Tetramers, revolutionary technologies for vaccine d...ILRI
Poster prepared by Nicholas Svitek, Andreas Martin Hansen, Lucilla Steinaa, Rosemary Saya, Elias Awino, Morten Nielsen, Soren Buus and Vish Nene for the ILRI APM 2013, Addis Ababa, 15-17 May 2013
Comparison of primer sets for amplification of Major Piroplasm Surface Protei...Sudhakar Goud Karpurapu
This document compares the efficiency of two primer sets for detecting Theileria orientalis, the causative agent of oriental theileriosis, in cattle. Blood samples from 32 cattle showing clinical signs of the disease were examined microscopically and using two PCR primer sets that target the major piroplasm surface protein gene of T. orientalis. Microscopy found 22 cattle positive, while primer set 1 identified 23 positive and primer set 2 identified all 32 cattle as positive. The results suggest PCR using primer set 2 is more sensitive for detection of T. orientalis infection compared to microscopy or primer set 1.
L-arginine modulates T cell metabolism and enhances survival and anti-tumor A...Gul Muneer
L-arginine modulates T cell metabolism and enhances survival and anti-tumor Activity
How metabolic reprogramming of T cells impact T cells fate and function? Indeed, these cells enhance their metabolic throughput upon antigenic stimulation to ensure the production of sufficient biomass and energy for their proliferation, differentiation and effector functions. The naïve T cells, which utilize oxidative phosphorylation for energy supply but upon activation, these cells switch their metabolic pathways toward glycolysis. An important question arises here that whether differential metabolic reprogramming (i.e., use of oxidative phosphorylation versus glycolytic activity) directs the fate and function of a given cell? And whether this process shapes the immune response and individual cell survival? The researchers from Institute for Research in Biomedicine took advantage of high-resolution Mass Spectrometry to investigate dynamics of proteome and metabolome following activation of naïve T cells.
Vaccinating goats with live wildtype Mccp strain ILRI181 induces protective i...ILRI
Vaccinating goats with a live wildtype strain of Mycoplasma capricolum subspecies capripneumoniae (Mccp) called ILRI181 induces protective immunity against contagious caprine pleuropneumonia (CCPP). A trial was conducted where goats were vaccinated with either the live ILRI181 strain, inactivated ILRI181, inactivated Abomsa strain, or a control PBS injection. After challenge with the live ILRI181 strain, all groups except the live vaccine group experienced severe disease or mortality, demonstrating the live vaccine provided 87.5% protection against severe disease. Both inactivated vaccines also provided over 60% protection. The results support further development of
The immunotherapy of cancer: past, present & the next frontierThe ScientifiK
The immunotherapy of cancer has progressed through several phases from past to present:
1) Early attempts focused on vaccines and cytokines with limited success and understanding.
2) Anti-CTLA4 therapy showed the first durable responses in metastatic melanoma.
3) Anti-PD-1 therapy was found to be superior to anti-CTLA4, with better responses and tolerability. This established that overcoming immunosuppression is key.
4) Combination strategies are now the focus, exploring combinations of immunotherapies or with targeted/chemotherapies to extend responses. Biomarkers like PD-L1 are being used to identify patients most likely to benefit from anti-PD-1
Enhanicing cd8 tcell memory by modulating fatty acid metabolismeman youssif
1) Mice with a T cell-specific deletion of TRAF6 mounted normal CD8+ T cell effector responses but had a profound defect in their ability to generate long-lived memory CD8+ T cells.
2) Microarray analysis revealed that TRAF6-deficient CD8+ T cells had altered expression of genes involved in fatty acid metabolism.
3) Administration of the anti-diabetic drug metformin, which promotes fatty acid metabolism, restored fatty acid oxidation in TRAF6-deficient CD8+ T cells and improved their ability to generate memory cells. Metformin treatment also increased the efficacy of an experimental anti-cancer vaccine by boosting memory CD8+ T cell responses.
1) CD4+ regulatory T cells (Tregs) from type 1 diabetes (T1D) patient and NOD mouse samples have decreased expression of the Treg activation marker GARP.
2) Screening of small molecules from the NIH Clinical Collection identified Plumbagin as a potential Treg enhancer, as it increased expression of Treg markers like GARP in vitro.
3) In vivo testing found Plumbagin treatment upregulated Treg markers in NOD mice but not control mice, suggesting it may enhance Tregs and restore immune tolerance in autoimmune diseases like T1D.
1) The study examined CD4+ T cells in the central nervous system (CNS) of mice during experimental allergic encephalomyelitis (EAE), both during active disease and remission.
2) Flow cytometry analysis revealed a 30-fold reduction in the number of CD4+ T cells in the CNS of mice in remission compared to those with active EAE.
3) However, the CD4+ T cells that remained in the CNS during remission maintained an activated memory/effector phenotype, suggesting remission is not due to downregulation of T cell function.
1) Recent immunotherapy advances for advanced NSCLC include the approval of pembrolizumab as a first-line treatment for patients with PD-L1 expression ≥50% based on results from the KEYNOTE-024 trial showing improved progression-free and overall survival compared to chemotherapy.
2) The Phase III KEYNOTE-407 trial found that combining pembrolizumab with chemotherapy improved progression-free survival compared to chemotherapy alone in patients with untreated metastatic squamous NSCLC, regardless of PD-L1 expression level.
3) Combining chemotherapy with immunotherapy may enhance the immune response by increasing antigen presentation, disrupting immune evasion mechanisms, and improving outcomes compared to chemotherapy or immunotherapy alone.
This presentation gives detailed information about antihistamine agents ,immunopharmacology .They also give details about their classification and mechanism of action.
The document discusses disorders of immunity and the immune system. It provides information on key components of the immune system including antigens, antibodies, lymphocytes (T cells, B cells, NK cells), macrophages, dendritic cells, cytokines and the complement system. It also describes the major histocompatibility complex (MHC) and HLA antigens, noting that class I MHC antigens are expressed on all nucleated cells and present intracellular peptides to CD8 T cells, while class II MHC antigens are only expressed on antigen presenting cells and present extracellular peptides to CD4 T cells. HLA antigens play an important role in self-recognition and transplant rejection.
Activation of surrogate death receptor signalling triggers peroxynitrite depe...Saurabh Shekhar
includes information about cisplatin resistance cancer cells and their execution through peroxynitrite triggered apoptosis due to death signaling receptors basedon the findings of research article published in cell death and diseases.
This study developed methods to measure immune response in reduced volumes of feline whole blood. Lymphocyte proliferation was measured in response to mitogens like ConA, PHA, and PMA/Ionomycin. Flow cytometry was used to identify lymphocyte populations like CD21+ B-cells, CD5+/CD4+ T-helper cells, and CD5+/CD8+ T-cytotoxic cells in whole blood. Phagocytosis was also successfully measured in whole blood using pHrodo-labeled E. coli bioparticles. These assays were refined to require only 2ml of blood while still obtaining reproducible results, supporting the 3Rs principles of reducing animal use. The methods provide a way to investigate innate
The document describes the establishment of immortalized human amniotic epithelial cell (iHAE) lines. HAE cells were extracted from placentas and infected with retroviruses containing HPV16 E6/E7 and hTERT genes to extend their lifespan. The iHAE lines showed extended proliferation ability and expression of stem cell markers. They maintained multipotent differentiation potential as demonstrated by their ability to differentiate into adipocytes, osteocytes, neurons, and cardiac cell types. The iHAE cells represent a promising new cell source for applications in regenerative medicine and cell therapy due to their immunosuppressive properties and differentiation potential.
Evaluation of the Viability of PTEN Transfected MDA-MB-468 Breast Cancer Cell...AmalDhivaharS
The PTEN (Phosphatase and Tensin homolog deleted on chromosome TEN) is a tumor suppressor gene that negatively controls the phosphoinositide 3‐kinase signalling pathway for regulation of cell proliferation and cell survival. MDA-MB-468 human breast cancer cells lack estrogen receptors, over-express epidermal growth factor (EGF) receptors, and are growth inhibited by EGF. Etoposide being an extensive chemotherapeutic drug is employed to treat several human cancers and remains one of the most highly prescribed anticancer drugs in the world. In our experiment we made an attempt to examine the viability of four PTEN recombinant plasmid transfected MDA-MB-468 breast cancer cells, namely, the Enhancer green fluorescent protein – C terminal 1 (EGFPC1), wild type (WT), nuclear export signal (NES) and the nuclear localization signal (NLS) plasmids, by testing them against the anticancer drug, Etoposide. The transfection process was carried out using the Lipofectamine 3000 (L3000) and P3000 enhancer reagents in the ratio 1:1 and was confirmed by fluorescent microscopy. To measure the viability of the transfected cells, we used the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and administered the drug at two different concentrations, 0.26µl and 0.65µl per 1.3ml of the media, to each of the four categories of the transfected cells. After an incubation period of 6 hours, the absorbance readings were measured using a UV spectrophotometer at 570nm and the % viability values calculated were found to be statistically significant (p ≤ 0.05). From both the cases of treatment, it became evident that the breast cancer cells exhibit a greater viability percentage when the PTEN gene was localized in their nucleus, via pEGFPC1-NLS-PTEN, before the Etoposide treatment.
- The document describes a study that examined the gene expression profile in mouse mesenteric lymph nodes in response to treatment with three known food allergens (peanut agglutinin, ovalbumin, beta-lactoglobulin).
- Microarray analysis identified differentially expressed genes in response to each allergen treatment, and real-time RT-PCR was used to validate candidate biomarker genes.
- The results suggest that differentially expressed genes in response to known food allergens may serve as candidate biomarker genes for assessing potential allergenicity of genetically modified foods.
This document describes a study examining the effects of T cell vaccination on the immune response in mice protected against experimental allergic encephalomyelitis (EAE). The researchers found that vaccination with myelin basic protein (MBP)-reactive T cell lines protected SJL/J mice against EAE induced by rat spinal cord homogenate. Lymph node cells from vaccinated mice showed enhanced proliferative responses to MBP and an encephalitogenic peptide from proteolipid protein, compared to untreated mice. The augmentation of responses was not antigen-specific and also occurred for ovalbumin. This suggests vaccination led to non-specific enhancement of immune activation in peripheral lymphoid tissues.
Early exposure to phosphorylcholine (PC)-bearing microbes like Streptococcus pneumoniae can dampen the development of house dust mite (HDM) allergy later in life. Neonatal mice immunized with PC-bearing pneumococcus developed PC-specific B cells that secreted antibodies upon exposure to PC in HDM as adults, reducing IgE production, TH2 cytokines, and airway hyperresponsiveness compared to mice immunized with PC-lacking pneumococcus. Thus, early-life microbial exposure can influence the development of allergic responses by priming regulatory B cell responses.
This document summarizes a study that investigated the transcriptome profile of mouse mesenteric lymph nodes and allergic reactions in response to common food allergens. Mice were sensitized to peanut agglutinin, ovalbumin, or beta-lactoglobulin and challenged after two weeks. Gene expression was analyzed using microarrays and real-time RT-PCR. Several pathways and genes were differentially expressed, including T-cell receptor signaling and IL-7 signal transduction pathways. The study identified potential biomarker genes for assessing food allergen responses.
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Small ruminant keepers’ knowledge, attitudes and practices towards peste des ...ILRI
Presentation by Guy Ilboudo, Abel Sènabgè Biguezoton, Cheick Abou Kounta Sidibé, Modou Moustapha Lo, Zoë Campbell and Michel Dione at the 6th Peste des Petits Ruminants Global Research and Expertise Networks (PPR-GREN) annual meeting, Bengaluru, India, 28–30 November 2023.
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The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive functioning. Exercise causes chemical changes in the brain that may help boost feelings of calmness, happiness and focus.
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Reservoirs of pathogenic Leptospira species in UgandaILRI
Presentation by Lordrick Alinaitwe, Martin Wainaina, Salome Dürr, Clovice Kankya, Velma Kivali, James Bugeza, Martin Richter, Kristina Roesel, Annie Cook and Anne Mayer-Scholl at the University of Bern Graduate School for Cellular and Biomedical Sciences Symposium, Bern, Switzerland, 29 June 2023.
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Presentation by Patricia Koech, Winnie Ogutu, Linnet Ochieng, Delia Grace, George Gitao, Lily Bebora, Max Korir, Florence Mutua and Arshnee Moodley at the 8th All Africa Conference on Animal Agriculture, Gaborone, Botswana, 26–29 September 2023.
Ecological factors associated with abundance and distribution of mosquito vec...ILRI
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Signatures of wave erosion in Titan’s coastsSérgio Sacani
The shorelines of Titan’s hydrocarbon seas trace flooded erosional landforms such as river valleys; however, it isunclear whether coastal erosion has subsequently altered these shorelines. Spacecraft observations and theo-retical models suggest that wind may cause waves to form on Titan’s seas, potentially driving coastal erosion,but the observational evidence of waves is indirect, and the processes affecting shoreline evolution on Titanremain unknown. No widely accepted framework exists for using shoreline morphology to quantitatively dis-cern coastal erosion mechanisms, even on Earth, where the dominant mechanisms are known. We combinelandscape evolution models with measurements of shoreline shape on Earth to characterize how differentcoastal erosion mechanisms affect shoreline morphology. Applying this framework to Titan, we find that theshorelines of Titan’s seas are most consistent with flooded landscapes that subsequently have been eroded bywaves, rather than a uniform erosional process or no coastal erosion, particularly if wave growth saturates atfetch lengths of tens of kilometers.
Microbial interaction
Microorganisms interacts with each other and can be physically associated with another organisms in a variety of ways.
One organism can be located on the surface of another organism as an ectobiont or located within another organism as endobiont.
Microbial interaction may be positive such as mutualism, proto-cooperation, commensalism or may be negative such as parasitism, predation or competition
Types of microbial interaction
Positive interaction: mutualism, proto-cooperation, commensalism
Negative interaction: Ammensalism (antagonism), parasitism, predation, competition
I. Mutualism:
It is defined as the relationship in which each organism in interaction gets benefits from association. It is an obligatory relationship in which mutualist and host are metabolically dependent on each other.
Mutualistic relationship is very specific where one member of association cannot be replaced by another species.
Mutualism require close physical contact between interacting organisms.
Relationship of mutualism allows organisms to exist in habitat that could not occupied by either species alone.
Mutualistic relationship between organisms allows them to act as a single organism.
Examples of mutualism:
i. Lichens:
Lichens are excellent example of mutualism.
They are the association of specific fungi and certain genus of algae. In lichen, fungal partner is called mycobiont and algal partner is called
II. Syntrophism:
It is an association in which the growth of one organism either depends on or improved by the substrate provided by another organism.
In syntrophism both organism in association gets benefits.
Compound A
Utilized by population 1
Compound B
Utilized by population 2
Compound C
utilized by both Population 1+2
Products
In this theoretical example of syntrophism, population 1 is able to utilize and metabolize compound A, forming compound B but cannot metabolize beyond compound B without co-operation of population 2. Population 2is unable to utilize compound A but it can metabolize compound B forming compound C. Then both population 1 and 2 are able to carry out metabolic reaction which leads to formation of end product that neither population could produce alone.
Examples of syntrophism:
i. Methanogenic ecosystem in sludge digester
Methane produced by methanogenic bacteria depends upon interspecies hydrogen transfer by other fermentative bacteria.
Anaerobic fermentative bacteria generate CO2 and H2 utilizing carbohydrates which is then utilized by methanogenic bacteria (Methanobacter) to produce methane.
ii. Lactobacillus arobinosus and Enterococcus faecalis:
In the minimal media, Lactobacillus arobinosus and Enterococcus faecalis are able to grow together but not alone.
The synergistic relationship between E. faecalis and L. arobinosus occurs in which E. faecalis require folic acid
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Recent theoretical progress indicates that spacetime and gravity emerge together from the entanglement structure of an underlying microscopic theory. These ideas are best understood in Anti-de Sitter space, where they rely on the area law for entanglement entropy. The extension to de Sitter space requires taking into account the entropy and temperature associated with the cosmological horizon. Using insights from string theory, black hole physics and quantum information theory we argue that the positive dark energy leads to a thermal volume law contribution to the entropy that overtakes the area law precisely at the cosmological horizon. Due to the competition between area and volume law entanglement the microscopic de Sitter states do not thermalise at sub-Hubble scales: they exhibit memory effects in the form of an entropy displacement caused by matter. The emergent laws of gravity contain an additional ‘dark’ gravitational force describing the ‘elastic’ response due to the entropy displacement. We derive an estimate of the strength of this extra force in terms of the baryonic mass, Newton’s constant and the Hubble acceleration scale a0 = cH0, and provide evidence for the fact that this additional ‘dark gravity force’ explains the observed phenomena in galaxies and clusters currently attributed to dark matter.
Evidence of Jet Activity from the Secondary Black Hole in the OJ 287 Binary S...Sérgio Sacani
Wereport the study of a huge optical intraday flare on 2021 November 12 at 2 a.m. UT in the blazar OJ287. In the binary black hole model, it is associated with an impact of the secondary black hole on the accretion disk of the primary. Our multifrequency observing campaign was set up to search for such a signature of the impact based on a prediction made 8 yr earlier. The first I-band results of the flare have already been reported by Kishore et al. (2024). Here we combine these data with our monitoring in the R-band. There is a big change in the R–I spectral index by 1.0 ±0.1 between the normal background and the flare, suggesting a new component of radiation. The polarization variation during the rise of the flare suggests the same. The limits on the source size place it most reasonably in the jet of the secondary BH. We then ask why we have not seen this phenomenon before. We show that OJ287 was never before observed with sufficient sensitivity on the night when the flare should have happened according to the binary model. We also study the probability that this flare is just an oversized example of intraday variability using the Krakow data set of intense monitoring between 2015 and 2023. We find that the occurrence of a flare of this size and rapidity is unlikely. In machine-readable Tables 1 and 2, we give the full orbit-linked historical light curve of OJ287 as well as the dense monitoring sample of Krakow.
PPT on Sustainable Land Management presented at the three-day 'Training and Validation Workshop on Modules of Climate Smart Agriculture (CSA) Technologies in South Asia' workshop on April 22, 2024.
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Candidate young stellar objects in the S-cluster: Kinematic analysis of a sub...Sérgio Sacani
Context. The observation of several L-band emission sources in the S cluster has led to a rich discussion of their nature. However, a definitive answer to the classification of the dusty objects requires an explanation for the detection of compact Doppler-shifted Brγ emission. The ionized hydrogen in combination with the observation of mid-infrared L-band continuum emission suggests that most of these sources are embedded in a dusty envelope. These embedded sources are part of the S-cluster, and their relationship to the S-stars is still under debate. To date, the question of the origin of these two populations has been vague, although all explanations favor migration processes for the individual cluster members. Aims. This work revisits the S-cluster and its dusty members orbiting the supermassive black hole SgrA* on bound Keplerian orbits from a kinematic perspective. The aim is to explore the Keplerian parameters for patterns that might imply a nonrandom distribution of the sample. Additionally, various analytical aspects are considered to address the nature of the dusty sources. Methods. Based on the photometric analysis, we estimated the individual H−K and K−L colors for the source sample and compared the results to known cluster members. The classification revealed a noticeable contrast between the S-stars and the dusty sources. To fit the flux-density distribution, we utilized the radiative transfer code HYPERION and implemented a young stellar object Class I model. We obtained the position angle from the Keplerian fit results; additionally, we analyzed the distribution of the inclinations and the longitudes of the ascending node. Results. The colors of the dusty sources suggest a stellar nature consistent with the spectral energy distribution in the near and midinfrared domains. Furthermore, the evaporation timescales of dusty and gaseous clumps in the vicinity of SgrA* are much shorter ( 2yr) than the epochs covered by the observations (≈15yr). In addition to the strong evidence for the stellar classification of the D-sources, we also find a clear disk-like pattern following the arrangements of S-stars proposed in the literature. Furthermore, we find a global intrinsic inclination for all dusty sources of 60 ± 20◦, implying a common formation process. Conclusions. The pattern of the dusty sources manifested in the distribution of the position angles, inclinations, and longitudes of the ascending node strongly suggests two different scenarios: the main-sequence stars and the dusty stellar S-cluster sources share a common formation history or migrated with a similar formation channel in the vicinity of SgrA*. Alternatively, the gravitational influence of SgrA* in combination with a massive perturber, such as a putative intermediate mass black hole in the IRS 13 cluster, forces the dusty objects and S-stars to follow a particular orbital arrangement. Key words. stars: black holes– stars: formation– Galaxy: center– galaxies: star formation
PPT on Direct Seeded Rice presented at the three-day 'Training and Validation Workshop on Modules of Climate Smart Agriculture (CSA) Technologies in South Asia' workshop on April 22, 2024.
(June 12, 2024) Webinar: Development of PET theranostics targeting the molecu...Scintica Instrumentation
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Mechanisms and Applications of Antiviral Neutralizing Antibodies - Creative B...Creative-Biolabs
Neutralizing antibodies, pivotal in immune defense, specifically bind and inhibit viral pathogens, thereby playing a crucial role in protecting against and mitigating infectious diseases. In this slide, we will introduce what antibodies and neutralizing antibodies are, the production and regulation of neutralizing antibodies, their mechanisms of action, classification and applications, as well as the challenges they face.
SDSS1335+0728: The awakening of a ∼ 106M⊙ black hole⋆Sérgio Sacani
Context. The early-type galaxy SDSS J133519.91+072807.4 (hereafter SDSS1335+0728), which had exhibited no prior optical variations during the preceding two decades, began showing significant nuclear variability in the Zwicky Transient Facility (ZTF) alert stream from December 2019 (as ZTF19acnskyy). This variability behaviour, coupled with the host-galaxy properties, suggests that SDSS1335+0728 hosts a ∼ 106M⊙ black hole (BH) that is currently in the process of ‘turning on’. Aims. We present a multi-wavelength photometric analysis and spectroscopic follow-up performed with the aim of better understanding the origin of the nuclear variations detected in SDSS1335+0728. Methods. We used archival photometry (from WISE, 2MASS, SDSS, GALEX, eROSITA) and spectroscopic data (from SDSS and LAMOST) to study the state of SDSS1335+0728 prior to December 2019, and new observations from Swift, SOAR/Goodman, VLT/X-shooter, and Keck/LRIS taken after its turn-on to characterise its current state. We analysed the variability of SDSS1335+0728 in the X-ray/UV/optical/mid-infrared range, modelled its spectral energy distribution prior to and after December 2019, and studied the evolution of its UV/optical spectra. Results. From our multi-wavelength photometric analysis, we find that: (a) since 2021, the UV flux (from Swift/UVOT observations) is four times brighter than the flux reported by GALEX in 2004; (b) since June 2022, the mid-infrared flux has risen more than two times, and the W1−W2 WISE colour has become redder; and (c) since February 2024, the source has begun showing X-ray emission. From our spectroscopic follow-up, we see that (i) the narrow emission line ratios are now consistent with a more energetic ionising continuum; (ii) broad emission lines are not detected; and (iii) the [OIII] line increased its flux ∼ 3.6 years after the first ZTF alert, which implies a relatively compact narrow-line-emitting region. Conclusions. We conclude that the variations observed in SDSS1335+0728 could be either explained by a ∼ 106M⊙ AGN that is just turning on or by an exotic tidal disruption event (TDE). If the former is true, SDSS1335+0728 is one of the strongest cases of an AGNobserved in the process of activating. If the latter were found to be the case, it would correspond to the longest and faintest TDE ever observed (or another class of still unknown nuclear transient). Future observations of SDSS1335+0728 are crucial to further understand its behaviour. Key words. galaxies: active– accretion, accretion discs– galaxies: individual: SDSS J133519.91+072807.4
Microbiology of Central Nervous System INFECTIONS.pdf
Immunogenicity and protection of the Theileria parva CTL antigen Tp1, with or without a leader sequence, using HAd5/MVA prime-boost vaccination
1. N. Svitek1, R. Saya1, E. Awino1, S. Gilbert2, J. Poole1, V. Nene1, L. Steinaa1
1 Vaccine Biosciences, International Livestock Research Institute, Kenya; 2 The Jenner Institute, UK
Immunogenicity and protection of the Theileria parva CTL
antigen Tp1, with or without a leader sequence, using
HAd5/MVA prime-boost vaccination
FIG.1 Immunization groups: 5 cattle in each group, primed
with HAd5-Tp1 and boosted with MVA Tp1 with and without
leadersequence:
GROUP 1. Tp1 + tPA* leader sequence (HAd5/MVA)
GROUP 2. Tp1 without leader sequence (HAd5/MVA)
GROUP 3. Tp1 + native leader sequence (HAd5/MVA)
GROUP 4. GFP + tPA* leader sequence (HAd5/MVA)
0 14 28 42 56 63 70 84
HAd5
prime
MVA
boost
91
Challenge with
T. parva
FIG 2. Regimen and sample points:
Day
FIG 3. CTL are Tp1 specific (tetramer staining): Example of ex
vivo tetramer staining of 2 animals, 2 weeks post MVA boost.
Tp1-Tetramer
CD8
T
p
2
p
o
o
l
T
p
1
p
o
o
l
O
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a
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te
in
0
5 0
1 0 0
1 5 0
C D 4
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p
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1 0 0
1 5 0
C D 4
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0
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4 0 0
6 0 0
C D 4
Group 1 Group 2 Group 3Foldincrease
0 2 4 6 8 10 12 14 16 18 20 22 24
0
50
100
D ays elapsed
Percentsurvival
C ontrol
H Ad5/M V A-Tp1
O ther experim ental vaccine group
H A d5/M V A -G FP
Animal 1 Animal 5
Tp1+
Tp1+
Perf+ Perf+
%Specifickilling
Tp1+
Perf+ Perf+
Tp1+Animal 2 Animal 4
17.3%70.3%4.15% 17.4%
2 4 8 1 6 3 2 6 4
0
1 0
2 0
3 0
4 0
E ffector/Target R atio
A nim al 5 TpM
Irr T p M 1
Irr T p M 2
P B M C
P B M C + T p1
0 .5 1 2 4 8 1 6
0
1 0
2 0
3 0
4 0
E ffector/Ta rg e t R a tio
A nim al 4 TpM
Irr T p M 1
Irr T p M 2
P B M C
P B M C + T p1
1 2 4 8 16 32
0
20
40
60
E ffector/Target R atio
A nim al 2 TpM
Irr T p M 1
Irr T p M 2
P B M C
P B M C + T p1
1 2 4 8 16 32
0
10
20
30
40
E ffector/Target R atio
A nim al 1 TpM
Irr T p M 1
Irr T p M 2
P B M C
P B M C + T p1
Animal 1 Animal 5Animal 2 Animal 4
G
ro
u
p
1
G
ro
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p
2
G
ro
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p
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0
1 0 ,0 0 0
2 0 ,0 0 0
3 0 ,0 0 0
Spotformingunitsper
millionCD8+cells
0 1 4 2 1 2 8 5 6 6 3 8 4
0
1 0 ,0 0 0
2 0 ,0 0 0
C on tro l e pitop e-G rou p 1
T p1 e pito pe-G roup 1
C on tro l e pitop e-G rou p 2
T p1 e pito pe-G roup 2
C on tro l e pitop e-G rou p 3
T p1 e pito pe-G roup 3
FIG 4. CD8 cells respond to the Tp1 epitope (IFN-γ ELISpot ): SFU (per million
CD8 cells) 7 days after MVA boost. First diagram shows the group average, the
second shows the individual cattle.
Summary: 4 groups of 5 BoLA-typed animals were immunized with the T. parva Tp1
antigen with or without leader sequence in the HAd5 viral vector and boosted with the
same antigens in the MVA vector. Most animals generated CTL to the known epitope
measured using tetramer staining, ELISpot and Cr-51-release assay. The CTL expressed
perforin and lysed peptide pulsed PBMC. CD4 cells were shown to proliferate to the
antigen. Challenge of the animals resulted in about 30% protection.
FIG 1. Immunization groups: 5 cattle in each group, primed
with HAd5-Tp1 and boosted with MVA Tp1 with and without
leader sequence:
FIG 5. CD4 cells proliferate to the Tp1 antigen. 2x105 CD4 cells were cultured with
Tp1 full-length antigen, Tp1 pool (overlapping peptides), ovalbumin (control) and
Tp2 pool (control peptides), 3H-thymidine was added, cells were harvested.
FIG 6. Tp1 specific CTL are cytotoxic and they express perforin: Upper panel: PBMC
were restimulated 3 times using infected autologous cells, CD8 cells were purified
and cytotoxicity were measured by pulsing autologous PBMC with the peptide or
infected cell line (Cr-51 release). Lower panel: CD8 cells were costained with Tp1
tetramer and a perforin mAb.
FIG 7. Protection by prime-boost regimen with Tp1 in HAd5/MVA vectors. Groups of
cattle (Fig. 2) were challenged with a lethal dose of T. parva sporozoites. Kaplan-Meier
survival plot is shown.
Licensed for use under the Creative Commons Attribution 4.0 International Licence (May 2016)