Impaired Cytokine but Enhanced Cytotoxic Marker Expression inMycobacterium tuberculosis–Induced CD8+T Cells in Individuals With Type 2 Diabetes and LatentMycobacterium tuberculosisInfection

Type 2 diabetes mellitus (DM) is a risk factor for tuberculosis among individuals with latent Mycobacterium tuberculosis infection. To explore the influence of DM on CD8(+) T-cell responses during latent M. tuberculosis infection, we estimated the cytokine and cytotoxic marker expression pattern in individuals with latent M. tuberculosis infection with DM and those with latent M. tuberculosis infection without DM. Among individuals with latent M. tuberculosis infection, those with DM had diminished frequencies of CD8(+) T-helper type 1 (Th1), Th2, and Th17 cells following stimulation by M. tuberculosis antigen and enhanced frequencies of CD8(+) T cells expressing cytotoxic markers, compared with those without DM. Thus, our results suggest that coincident DM modulates CD8(+) T-cell function during latent M. tuberculosis infection

Profiling leucocyte subsets in tuberculosis-diabetes co-morbidity

The immune system plays an important role in the pathogenesis of pulmonary tuberculosis–type 2 diabetes mellitus (PTB-DM) co-morbidity. However, the phenotypic profile of leucocyte subsets at homeostasis in individuals with active or latent tuberculosis (LTB) with coincident diabetes is not known. To characterize the influence of diabetes on leucocyte phenotypes in PTB or LTB, we examined the frequency (F(o)) of leucocyte subsets in individuals with TB with (PTB-DM) or without (PTB) diabetes; individuals with latent TB with (LTB-DM) or without (LTB) diabetes and non-TB-infected individuals with (NTB-DM) or without (NTB) diabetes. Coincident DM is characterized by significantly lower F(o) of effector memory CD4(+) T cells in LTB individuals. In contrast, DM is characterized by significantly lower F(o) of effector memory CD8(+) T cells and significantly higher F(o) of central memory CD8(+) T cells in PTB individuals. Coincident DM resulted in significantly higher F(o) of classical memory B cells in PTB and significantly higher F(o) of activated memory and atypical B cells in LTB individuals. Coincident DM resulted in significantly lower F(o) of classical and intermediate monocytes in PTB, LTB and NTB individuals. Finally, DM resulted in significantly lower F(o) of myeloid and plasmacytoid dendritic cells in PTB, LTB and NTB individuals. Our data reveal that coincident diabetes alters the cellular subset distribution of T cells, B cells, dendritic cells and monocytes in both individuals with active TB and those with latent TB, thus potentially impacting the pathogenesis of this co-morbid condition

Food Supply and Seawater pCO2 Impact Calcification and Internal Shell Dissolution in the Blue Mussel Mytilus edulis

Progressive ocean acidification due to anthropogenic CO2 emissions will alter marine ecosytem processes. Calcifying organisms might be particularly vulnerable to these alterations in the speciation of the marine carbonate system. While previous research efforts have mainly focused on external dissolution of shells in seawater under saturated with respect to calcium carbonate, the internal shell interface might be more vulnerable to acidification. In the case of the blue mussel Mytilus edulis, high body fluid pCO2 causes low pH and low carbonate concentrations in the extrapallial fluid, which is in direct contact with the inner shell surface. In order to test whether elevated seawater pCO2 impacts calcification and inner shell surface integrity we exposed Baltic M. edulis to four different seawater pCO2 (39, 142, 240, 405 Pa) and two food algae (310–350 cells mL−1 vs. 1600–2000 cells mL−1) concentrations for a period of seven weeks during winter (5°C). We found that low food algae concentrations and high pCO2 values each significantly decreased shell length growth. Internal shell surface corrosion of nacreous ( = aragonite) layers was documented via stereomicroscopy and SEM at the two highest pCO2 treatments in the high food group, while it was found in all treatments in the low food group. Both factors, food and pCO2, significantly influenced the magnitude of inner shell surface dissolution. Our findings illustrate for the first time that integrity of inner shell surfaces is tightly coupled to the animals' energy budget under conditions of CO2 stress. It is likely that under food limited conditions, energy is allocated to more vital processes (e.g. somatic mass maintenance) instead of shell conservation. It is evident from our results that mussels exert significant biological control over the structural integrity of their inner shell surfaces

The Struggle Between the Self and Not-Self : The Influence of Zen Buddhism and the Upanishads in Yeats’s Later Poetry

This thesis will examine questions about how William Butler Yeats was influenced by his exposure to eastern philosophical thinking. Yeats\u27s work prior to 1927, before his significant and rather esoteric tome A Vision, could classify him as a proto-Romantic, but it was his work after this where we see the influence of an eastern way of thinking. Specifically, this thesis will focus on Yeats\u27s poetry from 1927 on, with references to some of his earlier work to demonstrate how Yeats had already discovered some of the basic tenets of eastern thinking without having studied it. The initial analysis will locus on the contributions Zen Buddhism and the Indian Upanishads and how Yeats developed his poetic philosophy around these contributions. Outlined in A Vision is Yeats\u27s rather esoteric artistic philosophy, detailing how one struggles between what one is and what one wants to be. Yeats\u27s later poetry, written during his later years, takes up the challenge of trying to reconcile the Self and the not-Self. Following the initial analysis will be the integration of the philosophies of Zen Buddhism and the Upanishads in Yeats’s later poetry, specifically poems that feature a speaker in conflict with himself. Poems such as “Ego Dominus Tuus,” “A Dialogue of.Self and Soul,” as well as poems featuring a speaker on some kind of spiritual journey, such as “Sailing to Byzantium,” and “Byzantium.” The development of this poetic philosophy and its application will also be explored, as it suggests an approach that enhances the more common analysis under a Western philosophical tradition. The benefit an Eastern philosophical approach is that w\u27e can see a poet struggling with the conflicting natures of the Self and the Soul, and who turns towards Eastern philosophy to reveal a system that facilitates a poetic philosophy that views death and life as mostly illusory, a poetic philosophy that echoes the Romantic movement that called for an awakening of the Soul. In his introduction to the never-published Scribner\u27s Sons “Dublin Edition,” Yeats tells us that the first principle for a poet is that he is “part of his own phantasmagoria and we adore him because nature has grown intelligible, and by so doing a part of our creative power” (Essays 204). He goes on to explain: “’When mind is lost in the light of the Self,’ says the Prashna Upanishad, ‘It dreams no more; still in the body it is lost in happiness.’ ‘A wise man seeks in Self, says the Chadogya Upanishad, ‘those that are alive and those that are dead and gets what the world cannot give’

Prediabetes is associated with the modulation of antigen-specific Th1/Tc1 and Th17/Tc17 responses in latent <i>Mycobacterium tuberculosis</i> infection

<div><p>Type 2 diabetes mellitus (DM) is associated with the down modulation of Th1, Th2 and Th17 responses in latent <i>Mycobacterium tuberculosis</i> infection but the role of prediabetes (PDM) in this setting is not well understood. To examine the role of CD4⁺ and CD8⁺ T cell cytokines in latent tuberculosis (LTB) with coincident PDM, we studied the baseline, mycobacterial, control antigen and mitogen–stimulated T cell cytokine responses in LTB individuals with (LTB-PDM; n = 20) or without (LTB-NDM; n = 20) concomitant prediabetes. LTB-PDM is characterized by diminished frequencies of mono–and dual–functional CD4⁺ Th1 and Th17 cells and mono-functional Th2 cells at baseline and/or following mycobacterial—antigen stimulation in comparison to LTB-NDM. LTB-PDM is also characterized by diminished frequencies of mono–functional CD8⁺ Tc1, Tc2 and Tc17 cells at baseline and/or following mycobacterial–antigen stimulation in comparison to LTB-NDM. LTB-PDM is therefore characterized by diminished frequencies of antigen–specific Th1/Tc1 and Th17/Tc17 cells, indicating that PDM is associated with alterations of the immune response in latent TB associated with compromised CD4⁺ and CD8⁺ T cell function.</p></div

Multi-Dimensionality Immunophenotyping Analyses of MAIT Cells Expressing Th1/Th17 Cytokines and Cytotoxic Markers in Latent Tuberculosis Diabetes Comorbidity

Mucosal-associated invariant T (MAIT) cells are innate like, and play a major role in restricting disease caused by Mycobacterium tuberculosis (Mtb) disease before the activation of antigen-specific T cells. Additionally, the potential link and synergistic function between diabetes mellitus (DM) and tuberculosis (TB) has been recognized for a long time. However, the role of MAIT cells in latent TB (LTB) DM or pre-DM (PDM) and non-DM (NDM) comorbidities is not known. Hence, we examined the frequencies (represented as geometric means, GM) of unstimulated (UNS), mycobacterial (purified protein derivative (PPD) and whole-cell lysate (WCL)), and positive control (phorbol myristate acetate (P)/ionomycin (I)) antigen stimulated MAIT cells expressing Th1 (IFN&gamma;, TNF&alpha;, and IL-2), Th17 (IL-17A, IL-17F, and IL-22), and cytotoxic (perforin (PFN), granzyme (GZE B), and granulysin (GNLSN)) markers in LTB comorbidities by uniform manifold approximation (UMAP) and flow cytometry. We also performed a correlation analysis of Th1/Th17 cytokines and cytotoxic markers with HbA1c, TST, and BMI, and diverse hematological and biochemical parameters. The UMAP analysis demonstrated that the percentage of MAIT cells was higher; T helper (Th)1 cytokine and cytotoxic (PFN) markers expressions were different in LTB-DM and PDM individuals in comparison to the LTB-NDM group on UMAP. Similarly, no significant difference was observed in the geometric means (GM) of MAIT cells expressing Th1, Th17, and cytotoxic markers between the study population under UNS conditions. In mycobacterial antigen stimulation, the GM of Th1 (IFN&gamma; (PPD and WCL), TNF&alpha; (PPD and WCL), and IL-2 (PPD)), and Th17 (IL-17A, IL-17F, and IL-22 (PPD and/or WCL)) cytokines were significantly elevated and cytotoxic markers (PFN, GZE B, and GNLSN (PPD and WCL)) were significantly reduced in the LTB-DM and/or PDM group compared to the LTB-NDM group. Some of the Th1/Th17 cytokines and cytotoxic markers were significantly correlated with the parameters analyzed. Overall, we found that different Th1 cytokines and cytotoxic marker population clusters and increased Th1 and Th17 (IL-17A, IL-22) cytokines and diminished cytotoxic markers expressing MAIT cells are associated with LTB-PDM and DM comorbidities