Geochemistry and Industrial Applications of Brown Coals of the Ogwashi-Asaba Formation in Parts of Anambra State, Nigeria

Geochemical studies have been carried out on brown coal of the Ogwashi-Asaba Formation in parts of Anambra State, Nigeria, using proximate and ultimate analytical results to evaluate its potentials for industrial utilization. An understanding of the physico-chemical characteristics such as moisture content    , volatile matter content, fixed carbon content, and ash content are essential for establishing the quality of the coal. The chemical analysis of the brown coal samples results suggest that fixed carbon varies from 1.51 to 37.50 wt%, moisture content varies from 2.40 to 39.80 wt%, volatile matter varies from 2.44 to 39.92 wt%, and ash content ranges from 6.60 to 70.75 wt%, carbon content ranges from 11.59 wt% to 59.33 wt%, oxygen content ranges from 0.06 to 13.87 wt%, hydrogen content ranges from 0.13 to 4.59 wt%, sulfur content varies from 0.04 to  2.48 wt% and the nitrogen content varies from 1.30% to 1.85 wt%. The high-moisture content poses several challenges for the utilization of lignite, because it lowers the energy density of the fuel and makes its transportation uneconomic over long distances. The analytical results show that the coal cannot be employed in the steel industry for the generation of substantial heat for the working of the furnace but can be used as a steam coal. Proximate analysis and calorific data suggest that the coal belongs to the lowest rank i.e. lignite. The brown coal is less hazardous to the ecosystem because of its significantly low sulfur and nitrogen contents. Based on the results of the study, the brown coal can be used for power generation, gasification, production of industrial chemicals and cement production. Keywords: Coal, Proximate Analysis, Ultimate Analysis, Calorific values DOI: 10.7176/JNSR/12-12-03 Publication date:June 30th 202

A multiple redundant genetic switch locks in the transcriptional signature of T regulatory cells

The transcription factor FoxP3 partakes dominantly in the specification and function of FoxP3+CD4+ T regulatory cells (Tregs), but is neither strictly necessary nor sufficient to determine the characteristic Treg signature. Computational network inference and experimental testing assessed the contribution of other transcription factors (TF). Enforced expression of Helios or Xbp1 elicited specific signatures, but Eos, Irf4, Satb1, Lef1 and Gata1 elicited exactly the same outcome, synergizing with FoxP3 to activate most of the Treg signature, including key TFs, and enhancing FoxP3 occupancy at its genomic targets. Conversely, the Treg signature was robust to inactivation of any single cofactor. A redundant genetic switch thus locks-in the Treg phenotype, a model which accounts for several aspects of Treg physiology, differentiation and stability

Coreceptor gene imprinting governs thymocyte lineage fate

Double-positive (CD4+CD8+) thymocytes differentiate into CD4+ helper T cells and CD8+ cytotoxic T cells. A knock-in approach replacing CD8-coding sequences with CD4 cDNA shows that it is the expression kinetics of CD8, and not the identity of the coreceptor, that governs thymocyte-lineage fate

Self–class I MHC molecules support survival of naive CD8 T cells, but depress their functional sensitivity through regulation of CD8 expression levels

Previous studies have suggested that naive CD8 T cells require self-peptide–major histocompatability complex (MHC) complexes for maintenance. However, interpretation of such studies is complicated because of the involvement of lymphopenic animals, as lymphopenia drastically alters naive T cell homeostasis and function. In this study, we explored naive CD8 T cell survival and function in nonlymphopenic conditions by using bone marrow chimeric donors and hosts in which class I MHC expression is absent or limited to radiosensitive versus radioresistant cells. We found that long-term survival of naive CD8 T cells (but not CD4 T cells) was impaired in the absence of class I MHC. However, distinct from this effect, class I MHC deprivation also enhanced naive CD8 T cell responsiveness to low-affinity (but not high-affinity) peptide–MHC ligands. We found that this improved sensitivity was a consequence of up-regulated CD8 levels, which was mediated through a transcriptional mechanism. Hence, our data suggest that, in a nonlymphopenic setting, self-class I MHC molecules support CD8 T cell survival, but that these interactions also attenuate naive T cell sensitivity by dynamic tuning of CD8 levels

HIV-1 infection and the lack of viral control are associated with greater expression of interleukin-21 receptor on CD8(+) T cells

Objectives: Interleukin-21 (IL-21) has been linked with the generation of virus-specific memory CD8+ T cells following acute infection with HIV-1 and reduced exhaustion of CD8+ T cells. IL-21 has also been implicated in the promotion of CD8+ T-cell effector functions during viral infection. Little is known about the expression of interleukin-21 receptor (IL-21R) during HIV-1 infection or its role in HIV-1-specific CD8+ T-cell maintenance and subsequent viral control. Methods: We compared levels of IL-21R expression on total and memory subsets of CD8+ T cells from HIV-1-negative and HIV-1-positive donors. We also measured IL-21R on antigen-specific CD8+ T cells in volunteers who were positive for HIV-1 and had cytomegalovirus-responding T cells. Finally, we quantified plasma IL-21 in treatment-naive HIV-1-positive individuals and compared this with IL-21R expression. Results: IL-21R expression was significantly higher on CD8+ T cells (P = 0.0256), and on central memory (P = 0.0055) and effector memory (P = 0.0487) CD8+ T-cell subsets from HIV-1-positive individuals relative to HIV-1-negative individuals. For those infected with HIV-1, the levels of IL-21R expression on HIV-1-specific CD8+ T cells correlated significantly with visit viral load (r = 0.6667, P = 0.0152, n = 13) and inversely correlated with plasma IL-21 (r = −0.6273, P = 0.0440, n = 11). Lastly, CD8+ T cells from individuals with lower set point viral load who demonstrated better viral control had the lowest levels of IL-21R expression and highest levels of plasma IL-21. Conclusion: Our data demonstrates significant associations between IL-21R expression on peripheral CD8+ T cells and viral load, as well as disease trajectory. This suggests that the IL-21 receptor could be a novel marker of CD8+ T-cell dysfunction during HIV-1 infection

Regulation of coreceptor gene transcription and CD4/CD8 lineage choice in the thymus

CD4 and CD8 T cells express αβ T cell receptors (TCR) and respectively function as helpers and cytotoxic effector cells during an immune response. Importantly, CD4 T cells recognize peptides presented by major histocompatibility complex class II (MHCII) molecules and CD8 T cells recognize peptides presented by MHCI molecules. Intriguingly, both CD4 and CD8 T cells arise from immature CD4+CD8+ (double positive, DP) thymocytes in the thymus. However, how DP thymocytes successfully differentiate into CD4 lineage T cells expressing MHCII-specific TCR and CD8 lineage T cells expressing MHCI-specific TCR remains an unresolved and intensely debated aspect of T cell biology. Previous investigations on the mechanism of the CD4/CD8 lineage decision have either focused on signals contributed by individual coreceptors or by the TCR itself. Given their distinct regulatory elements, I hypothesized that the kinetics of Cd4 and Cd8 gene transcription during T cell differentiation in the thymus determines specification of the CD4 and CD8 T cell fates. In this dissertation, I found that the process of CD4/CD8 lineage choice in the thymus is not stochastic. Significantly, I revealed a novel integration of TCR and cytokine signals by cis-regulatory Cd8 gene enhancers during positive selection and CD8 T cell lineage commitment. Specifically, during positive selection, TCR signals terminated the activity of cis enhancers that promote CD8 expression in pre-selection thymocytes while Stat5-dependent cytokines (notably IL-7) promote the activity of cis-regulatory Cd8 enhancers in post-selection T cells. Indeed, cis-regulatory enhancers that promote CD8 expression in post-selection thymocytes are critical in reactivating Cd8 expression in CD4+CD8 - intermediate thymocytes that give rise to mature T cells. Consistent with the hypothesis that CD4/CD8 lineage choice is determined by the Cd4 and Cd8 transcriptional machinery, MHCII-selected T cells in mice in which the Cd8a gene was engineered to encode CD4 protein differentiated into cytotoxic CD8 lineage T cells. Based on the data presented in this dissertation, I conclude that CD4/CD8 lineage specification in the thymus is dictated by the kinetics of coreceptor gene transcription and not by the identity of the coreceptor

Regulation of coreceptor gene transcription and CD4/CD8 lineage choice in the thymus

CD4 and CD8 T cells express αβ T cell receptors (TCR) and respectively function as helpers and cytotoxic effector cells during an immune response. Importantly, CD4 T cells recognize peptides presented by major histocompatibility complex class II (MHCII) molecules and CD8 T cells recognize peptides presented by MHCI molecules. Intriguingly, both CD4 and CD8 T cells arise from immature CD4+CD8+ (double positive, DP) thymocytes in the thymus. However, how DP thymocytes successfully differentiate into CD4 lineage T cells expressing MHCII-specific TCR and CD8 lineage T cells expressing MHCI-specific TCR remains an unresolved and intensely debated aspect of T cell biology. Previous investigations on the mechanism of the CD4/CD8 lineage decision have either focused on signals contributed by individual coreceptors or by the TCR itself. Given their distinct regulatory elements, I hypothesized that the kinetics of Cd4 and Cd8 gene transcription during T cell differentiation in the thymus determines specification of the CD4 and CD8 T cell fates. In this dissertation, I found that the process of CD4/CD8 lineage choice in the thymus is not stochastic. Significantly, I revealed a novel integration of TCR and cytokine signals by cis-regulatory Cd8 gene enhancers during positive selection and CD8 T cell lineage commitment. Specifically, during positive selection, TCR signals terminated the activity of cis enhancers that promote CD8 expression in pre-selection thymocytes while Stat5-dependent cytokines (notably IL-7) promote the activity of cis-regulatory Cd8 enhancers in post-selection T cells. Indeed, cis-regulatory enhancers that promote CD8 expression in post-selection thymocytes are critical in reactivating Cd8 expression in CD4+CD8 - intermediate thymocytes that give rise to mature T cells. Consistent with the hypothesis that CD4/CD8 lineage choice is determined by the Cd4 and Cd8 transcriptional machinery, MHCII-selected T cells in mice in which the Cd8a gene was engineered to encode CD4 protein differentiated into cytotoxic CD8 lineage T cells. Based on the data presented in this dissertation, I conclude that CD4/CD8 lineage specification in the thymus is dictated by the kinetics of coreceptor gene transcription and not by the identity of the coreceptor