Entrepreneurial sons, patriarchy and the Colonels' experiment in Thessaly, rural Greece

Existing studies within the field of institutional entrepreneurship explore how entrepreneurs influence change in economic institutions. This paper turns the attention of scholarly inquiry on the antecedents of deinstitutionalization and more specifically, the influence of entrepreneurship in shaping social institutions such as patriarchy. The paper draws from the findings of ethnographic work in two Greek lowland village communities during the military Dictatorship (1967–1974). Paradoxically this era associated with the spread of mechanization, cheap credit, revaluation of labour and clear means-ends relations, signalled entrepreneurial sons’ individuated dissent and activism who were now able to question the Patriarch’s authority, recognize opportunities and act as unintentional agents of deinstitutionalization. A ‘different’ model of institutional change is presented here, where politics intersects with entrepreneurs, in changing social institutions. This model discusses the external drivers of institutional atrophy and how handling dissensus (and its varieties over historical time) is instrumental in enabling institutional entrepreneurship

A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4⁺ T-Cells to Recognition by Cytotoxic T-Lymphocytes

Resting CD4⁺ T-cells harboring inducible HIV proviruses are a critical reservoir in antiretroviral therapy (ART)-treated subjects. These cells express little to no viral protein, and thus neither die by viral cytopathic effects, nor are efficiently cleared by immune effectors. Elimination of this reservoir is theoretically possible by combining latency-reversing agents (LRAs) with immune effectors, such as CD8⁺ T-cells. However, the relative efficacy of different LRAs in sensitizing latently-infected cells for recognition by HIV-specific CD8⁺ T-cells has not been determined. To address this, we developed an assay that utilizes HIV-specific CD8⁺ T-cell clones as biosensors for HIV antigen expression. By testing multiple CD8⁺ T-cell clones against a primary cell model of HIV latency, we identified several single agents that primed latently-infected cells for CD8⁺ T-cell recognition, including IL-2, IL-15, two IL-15 superagonists (IL-15SA and ALT-803), prostratin, and the TLR-2 ligand Pam₃CSK₄. In contrast, we did not observe CD8⁺ T-cell recognition of target cells following treatment with histone deacetylase inhibitors or with hexamethylene bisacetamide (HMBA). In further experiments we demonstrate that a clinically achievable concentration of the IL-15 superagonist ‘ALT-803’, an agent presently in clinical trials for solid and hematological tumors, primes the natural ex vivo reservoir for CD8⁺ T-cell recognition. Thus, our results establish a novel experimental approach for comparative evaluation of LRAs, and highlight ALT-803 as an LRA with the potential to synergize with CD8⁺ T-cells in HIV eradication strategies.United States. National Institutes of Health (AI111860

CD33 rs3865444 as a risk factor for Parkinson's disease

Background: Alzheimer's (AD) and Parkinson's diseases (PD) share a few elements of their clinical, pathological and genetic backgrounds. The CD33 rs3865444 has emerged as a strong genetic locus associated with AD through genome-wide association study (GWAS). However, little is known for its role in PD. Objective: To assess the role of CD33 rs3865444 on PD risk. Methods: We genotyped 358 patients with PD and 358 healthy controls for theCD33 rs3865444. Odds ratios (ORs) with the respective 95% confidence intervals (CIs)], were calculated with the SNPStats software, assuming five genetic models (co-dominant, dominant, recessive, over-dominant and log-additive), with the G allele as the reference allele. Results: The CD33 rs3865444 was associated with decreased PD risk in the dominant [GG vs GT + TT; OR (95% CI) = 0.61 (0.45−0.82), p = 0.001], the over-dominant [GG + TT vs GT; OR (95% CI) = 0.65 (0.48−0.89), p = 0.0061], log-additive [OR (95% CI) = 0.67 (0.52−0.86), p = 0.0014], and co-dominant [with overall p = 0.0043, and OR (95% CI) = 0.62 (0.45−0.84) for the TG genotype compared to the GG], modes of inheritance. Conclusions: The CD33 rs3865444 is associated with decreased PD risk, and larger studies investigating the role of CD33 rs3865444 on PD are needed. © 2021 Elsevier B.V

Diabetes mellitus vs. Raynaud disease: Different lung vascular bed disorders

Background. In type 11 diabetes mellitus there are few data concerning pulmonary function abnormalities. In normal subjects and in patients with primary Raynaud phenomenon, cold pressor test induces a decrease in carbon monoxide single-breath diffusing capacity (DL,co) but not in secondary Raynaud phenomenon. Our objective was to assess evaluation of lung diffusion capacity postural changes in diabetes mellitus and in secondary Raynaud phenomenon, two diseases with different pulmonary capillaries functional disorders. Methods. Twenty-five patients with type 11 diabetes mellitus (mean age 52.24 years), 17 patients with secondary Raynaud phenomenon (mean age 47.06 years), non-smokers without pulmonary or heart disease, and 26 healthy matched subjects (mean age 47.50 years) underwent lung diffusion capacity measurements by single-breath method also corrected by alveolar volume (DL,co) in sitting and supine positions. Results. Patients with diabetes mellitus exhibited lower values of DL,co and DL,co/VA measurements in comparison with subjects with Raynaud phenomenon and control group (p < 0.01). Additionally, they had a significant decrease in DL,co in supine compared to sitting position (83.88 +/- 16.53 vs. 89.68 +/- 18.03, p = 0.023). To the contrary, supine position in secondary Raynaud phenomenon and in control group after cold pressor test showed a significant increase in DL,co/VA (120.93 vs. 109.78 in Raynaud and 114.36 vs. 99.47 in control group, p < 0.001). Conclusions. Postural changes of lung diffusion capacity could be used as a simple, non-invasive method to detect vascular disease resulting from different pathophysiologic mechanisms such as diabetes mellitus and Raynaud phenomenon. (C) 2002 IMSS. Published by Elsevier Science Inc

Deciphering the role of DNA methylation in multiple sclerosis: emerging issues

Multiple sclerosis (MS) is an autoimmune inflammatory and neurodegenerative disease of the central nervous system that involves several not yet fully elucidated pathophysiologic mechanisms. There is increasing evidence that epigenetic modifications at level of DNA bases, histones, and micro-RNAs may confer risk for MS. DNA methylation seems to have a prominent role in the epigenetics of MS, as aberrant methylation in the promoter regions across genome may underlie several processes involved in the initiation and development of MS. In the present review, we discuss current understanding regarding the role of DNA methylation in MS, possible therapeutic implications and future emerging issues. © 2016, The Author(s)

Deciphering the role of DNA methylation in multiple sclerosis: emerging issues

Multiple sclerosis (MS) is an autoimmune inflammatory and neurodegenerative disease of the central nervous system that involves several not yet fully elucidated pathophysiologic mechanisms. There is increasing evidence that epigenetic modifications at level of DNA bases, histones, and micro-RNAs may confer risk for MS. DNA methylation seems to have a prominent role in the epigenetics of MS, as aberrant methylation in the promoter regions across genome may underlie several processes involved in the initiation and development of MS. In the present review, we discuss current understanding regarding the role of DNA methylation in MS, possible therapeutic implications and future emerging issues. © 2016, The Author(s)

Vitamin B12, folate, and homocysteine levels and multiple sclerosis: A meta-analysis

Background Multiple sclerosis (MS) is a demyelinating and disabling inflammatory disease of the central nervous system. Several factors contribute to MS pathogenesis including genetic-environmental interactions. Case-control studies suggest that there might be associations between MS and homocysteine (Hcy), vitamin B12, and folate blood levels. Aim To meta-analyze all available data describing associations between MS and serum or plasma Hcy, vitamin B12, and folate levels. Methods The PubMed, MEDLINE, and EMBASE databases were searched for eligible case-control studies published until June 2017. After data extraction, separate analyses using mainly random-effects models were conducted to test for associations between MS and vitamin B12, Hcy, or folate blood levels. Results Twelve, 12, and 9 studies met the inclusion criteria for meta-analysis of MS and Hcy, vitamin B12, and folate levels, respectively. The standardized mean difference (SMD) between MS patients and controls was statistically significant for Hcy (SMD: 0.70, 95% CI: 0.06, 1.34). Stratification according to clinical pattern did not reveal significant differences between relapsing-remitting MS patients and controls (SMD: 0.30, 95% CI: −0.93, 1.54) or between secondary progressive MS patients and controls (SMD: 0.12, 95% CI: −1.65, 1.90). There were no significant differences in SMD between MS patients and healthy individuals for vitamin B12 (SMD: −0.09, 95% CI: −0.29, 0.10) or folate (SMD: −0.06, 95% CI: −0.17, 0.05). Conclusion MS patients tend to have elevated Hcy blood levels compared to healthy controls. Hcy may contribute to the pathogenesis of the disease. © 201