Modern Hanseatic Trends in the Baltic Region

A critical analysis of Hanseatic traditions may produce consequential methodological material for the study of the 21st century Baltic regionalisation. Current trends in the development of the Baltic region, whose academic analysis is impossible without considering earlier cases of successful interactions between the peoples of the Baltic Sea region, necessitate political, economic, and historical research on the strengths and weaknesses of the Hanseatic League. Unfortunately, in the 21st century, the Baltic region turned into a stage for geopolitical controversies. This took a toll on the efficiency of cooperation between the cities of Russia’s North-West and their Baltic counterparts. Therefore, it is important to seize the opportunities provided by the information society and focus on the innovative areas of regional cooperation. An interesting example is the partnership between Baltic universities, which is aimed to draw up an international agenda for sustainable regional development. Baltic cities are involved in various forms of cross-border cooperation, providing opportunities for interstate relations and contributes to laying down crossborder cooperation roadmaps and developing civil society networks. It can be concluded, that the history of the Hanseatic League and its current incarnation — the New Hanse — testify to the fact that productive economic, cultural, and other relations can be established between states but also between cities and universities, thus contributing to closer economic, political and cultural ties between the peoples of the Baltic region

Highly Divergent Mitochondrial ATP Synthase Complexes in Tetrahymena thermophila

Tetrahymena ATP synthase, an evolutionarily divergent protein complex, has a very unusual structure and protein composition including a unique Fo subunit a and at least 13 proteins with no orthologs outside of the ciliate lineage

An Efficient Method of Birch Ethanol Lignin Sulfation with a Sulfaic Acid-Urea Mixture

For the first time, the process of birch ethanol lignin sulfation with a sulfamic acid-urea mixture in a 1,4-dioxane medium was optimized experimentally and numerically. The high yield of the sulfated ethanol lignin (more than 96%) and containing 7.1 and 7.9 wt % of sulfur was produced at process temperatures of 80 and 90 °C for 3 h. The sample with the highest sulfur content (8.1 wt %) was obtained at a temperature of 100 °C for 2 h. The structure and molecular weight distribution of the sulfated birch ethanol lignin was established by FTIR, 2D 1H and 13C NMR spectroscopy, and gel permeation chromatography. The introduction of sulfate groups into the lignin structure was confirmed by FTIR by the appearance of absorption bands characteristic of the vibrations of sulfate group bonds. According to 2D NMR spectroscopy data, both the alcohol and phenolic hydroxyl groups of the ethanol lignin were subjected to sulfation. The sulfated birch ethanol lignin with a weight average molecular weight of 7.6 kDa and a polydispersity index of 1.81 was obtained under the optimum process conditions. Differences in the structure of the phenylpropane units of birch ethanol lignin (syringyl-type predominates) and abies ethanol lignin (guaiacyl-type predominates) was manifested in the fact that the sulfation of the former proceeds more completely at moderate temperatures than the latter. In contrast to sulfated abies ethanol lignin, the sulfated birch ethanol lignin had a bimodal and wider molecular weight distribution, as well as less thermal stability. The introduction of sulfate groups into ethanol lignin reduced its thermal stability

<em>Mtb</em>-Specific CD27^low CD4 T Cells as Markers of Lung Tissue Destruction during Pulmonary Tuberculosis in Humans

<div><h3>Background</h3><p>Effector CD4 T cells represent a key component of the host’s anti-tuberculosis immune defense. Successful differentiation and functioning of effector lymphocytes protects the host against severe <em>M. tuberculosis</em> (<em>Mtb</em>) infection. On the other hand, effector T cell differentiation depends on disease severity/activity, as T cell responses are driven by antigenic and inflammatory stimuli released during infection. Thus, tuberculosis (TB) progression and the degree of effector CD4 T cell differentiation are interrelated, but the relationships are complex and not well understood. We have analyzed an association between the degree of <em>Mtb</em>-specific CD4 T cell differentiation and severity/activity of pulmonary TB infection.</p> <h3>Methodology/Principal Findings</h3><p>The degree of CD4 T cell differentiation was assessed by measuring the percentages of highly differentiated CD27^low cells within a population of <em>Mtb</em>- specific CD4 T lymphocytes (“CD27^lowIFN-γ⁺” cells). The percentages of CD27^lowIFN-γ+ cells were low in healthy donors (median, 33.1%) and TB contacts (21.8%) but increased in TB patients (47.3%, p<0.0005). Within the group of patients, the percentages of CD27^lowIFN-γ⁺ cells were uniformly high in the lungs (>76%), but varied in blood (12–92%). The major correlate for the accumulation of CD27^lowIFN-γ⁺ cells in blood was lung destruction (r = 0.65, p = 2.7×10⁻⁷⁾. A cutoff of 47% of CD27^lowIFN-γ⁺ cells discriminated patients with high and low degree of lung destruction (sensitivity 89%, specificity 74%); a decline in CD27^lowIFN-γ⁺cells following TB therapy correlated with repair and/or reduction of lung destruction (p<0.01).</p> <h3>Conclusions</h3><p>Highly differentiated CD27^low Mtb-specific (CD27^lowIFN-γ⁺) CD4 T cells accumulate in the lungs and circulate in the blood of patients with active pulmonary TB. Accumulation of CD27^lowIFN-γ⁺ cells in the blood is associated with lung destruction. The findings indicate that there is no deficiency in CD4 T cell differentiation during TB; evaluation of CD27^lowIFN-γ⁺ cells provides a valuable means to assess TB activity, lung destruction, and tissue repair following TB therapy.</p> </div

Characterization of groups included in the analysis.

1<p>Indicated are numbers (%).</p>2<p>NA, not applicable.</p

Correlation between TB manifestations and percentages of CD27^lowIFN-γ⁺ CD4 T cells in the blood of TB patients.

1<p>Analysis was initially performed in 50 patients. Subsequently, 12 patients from validation cohort were added (n = 62), mainly to check the consistency of the results. The results obtained in both cohorts are shown.</p>2<p>Simple correlation analysis selects five major predictors for the accumulation of IFN-γ⁺CD27^low cells in the blood of TB patients (highlighted in bold). For TB duration and <i>Mtb</i> multi-drug resistance p-values were >0.007 (insignificant for multiple (seven) parameter testing); these factors were not included in multiple linear regression analysis. rho, Spearman coefficient, p, significance value of the test.</p>3<p>Multiple linear regression identified lung tissue destruction and clinical TB severity as the main correlates for the accumulation of CD27^lowIFN-γ⁺ cells in the blood of TB patients (highlighted in bold).</p>4<p>NA, not included in multiple linear regression analysis.</p

Association between blood CD27^lowIFN-γ⁺ cells and different manifestations of TB disease.

<p>A–F, Percentages of CD27^lowIFN-γ⁺ cells in TB patients (n = 50) grouped based on different characteristics of TB disease. For multiple (seven) parameter testing, p- value <0.007 was considered significant. G, ROC curve for discriminating TB patients with high (score 3) and low (scores 0–2) degrees of lung tissue destruction (n = 50). H, The degree of lung tissue destruction in patients with “low” (<47%) and high (>47%) percentages of CD27^lowIFN-γ⁺ CD4 T cells (n = 12, validation analysis). I, J, Lack of correlation between the percentages (I) and the numbers (J) of CD27^lowIFN-γ⁺ cells in the lungs and in the blood of TB patients (n = 8). Indicated are numbers of CD27^lowIFN-γ⁺ cells per 1 million of acquired cells.</p

Selection of minimal model to explain variability in the percentages of CD27^lowIFN-γ⁺ cells between TB patients.

1<p>Best minimal models are those that differ insignificantly from the full model (highlighted in bold).</p>2<p>Analysis was initially performed in 50 patients. Subsequently, 12 patients from validation cohort were added (n = 62), mainly to check the consistency of the results. In both cohorts, lung destruction and clinical disease severity predicted best the accumulation of CD27^lowIFN-γ⁺ cells.</p>3<p>In Akaike Information Criterion, this combination was the best minimal model to predict the accumulation of CD27^lowIFN-γ⁺ cells in the blood ( Δ_n = 50 = 4.7; Δ_n = 62 = 4.8).</p

TB patients have increased percentages of CD27^lowIFN-γ⁺ CD4 T cells in their blood.

<p>A–C, Strategies for determining percentages of CD27^low (A), IFN-γ⁺ (B) and CD27^lowIFN-γ⁺ (C) CD4 T cells. A, CD27^low cells were gated within the total population of CD4⁺ T cells. B, To identify IFN-γ⁺ CD4 T cells, an aliquot of blood was stimulated with <i>Mtb</i> sonicate; another aliquote was left un-stimulated. During the analysis, the gates for IFN-γ⁺ cells in <i>Mtb</i>-stimulated samples were plotted based on <i>Mtb</i> un-stimulated samples (Fig. B, dotted line). To identify CD27^lowIFN-γ⁺ cells, the expression of CD27 was first analyzed in IFN-γ⁻ population. Because this population was always numerous, CD27^low and CD27^hi cells could be easily separated. The gates for CD27^low cells were then applied to IFN-γ⁺ population (C, dotted line). D–F, Percentages of CD27^low (D), IFN-γ⁺ (E), and CD27^lowIFN-γ⁺ (F) cells in TB patients (n = 50), TB contacts (n = 21) and <i>Mtb</i>-unexposed individuals (n = 15). G, Lack of correlation between the percentages of IFN-γ⁺ and CD27^lowIFN-γ⁺ cells in TB patients, TB contacts and <i>Mtb</i>-unexposed individuals (n = 86). H, ROC-curve of CD27^lowIFN- _γ⁺ cell percentages for discriminating TB patients from healthy individuals (TB contacts and <i>Mtb</i>-unexposed). I, Percentages of CD27^lowIFN-γ⁺ cells in TB contacts with positive and negative results of QFT assay *p<0.0005 compared to TB patients.</p