Differential expression and biochemical activity of the immune receptor Tim-3 in healthy and malignant human myeloid cells

The T cell immunoglobulin and mucin domain 3 (Tim-3) is a plasma membrane-associated receptor which is involved in a variety of biological responses in human immune cells. It is highly expressed in most acute myeloid leukaemia (AML) cells and therefore may serve as a possible target for AML therapy. However, its biochemical activities in primary human AML cells remain unclear. We therefore analysed the total expression and surface presence of the Tim-3 receptor in primary human AML blasts and healthy primary human leukocytes isolated from human blood. We found that Tim-3 expression was significantly higher in primary AML cells compared to primary healthy leukocytes. Tim-3 receptor molecules were distributed largely on the surface of primary AML cells, whereas in healthy leukocytes Tim-3 protein was mainly expressed intracellularly. In primary human AML blasts, both Tim-3 agonistic antibody and galectin-9 (a Tim-3 natural ligand) significantly upregulated mTOR pathway activity. This was in line with increased accumulation of hypoxia-inducible factor 1 alpha (HIF-1α) and secretion of VEGF and TNF-α. Similar results were obtained in primary human healthy leukocytes. Importantly, in both types of primary cells, Tim-3-mediated effects were compared with those induced by lipopolysaccharide (LPS) and stem cell factor (SCF). Tim-3 induced comparatively moderate responses in both AML cells and healthy leukocytes. However, Tim-3, like LPS, mediated the release of both TNF-α and VEGF, while SCF induced mostly VEGF secretion and did not upregulate TNF-α release

Understanding Social–Ecological Systems using Loop Analysis

The sustainable management of social–ecological systems (SESs) requires that we understand the complex structure of relationships and feedbacks among ecosystem components and socioeconomic entities. Therefore, the construction and analysis of models integrating ecological and human actors is crucial for describing the functioning of SESs, and qualitative modeling represents an ideal tool since it allows studying dependencies among variables of diverse types. In particular, the qualitative technique of loop analysis yields predictions about how a system’s variables respond to stress factors. Different interaction types, scarce information about functional relationships among variables, and uncertainties in the values of the parameters are the rule rather than exceptions when studying SESs. Accordingly, loop analysis seems to be perfectly suitable to investigate them. Here, we introduce the key aspects of loop analysis, discuss its applications to SESs, and suggest it enables making the first steps toward the integration of the three dimensions of sustainability

Stability of generalized linear Weingarten hypersurfaces immersed in the Euclidean space

Given a positive function F defined on the unit Euclidean sphere and satisfying a suitable convexity condition, we consider, for hypersurfaces Mn immersed in the Euclidean space Rn+1, the so-called k-th anisotropic mean curvatures HF k, 0 ≤ k ≤ n. For fixed 0 ≤ r ≤ s ≤ n, a hypersurface Mn of Rn+1 is said to be (r, s, F)-linear Weingarten when its k-th anisotropic mean curvatures HF k, r ≤ k ≤ s, are linearly related. In this setting, we establish the concept of stability concerning closed (r, s, F)-linear Weingarten hypersurfaces immersed in Rn+1 and, afterwards, we prove that such a hypersurface is stable if, and only if, up to translations and homotheties, it is the Wulff shape of F. For r = s and F ≡ 1, our results amount to the standard stability studied, for instance, by Alencar-do Carmo-Rosenberg

Pharmacological potential of methylxanthines: Retrospective analysis and future expectations

Methylated xanthines (methylxanthines) are available from a significant number of different botanical species. They are ordinarily included in daily diet, in many extremely common beverages and foods. Caffeine, theophylline and theobromine are the main methylxanthines available from natural sources. The supposedly relatively low toxicity of methylxanthines, combined with the many beneficial effects that have been attributed to these compounds through time, generated a justified attention and a very prolific ground for dedicated scientific reports. Methylxanthines have been widely used as therapeutical tools, in an intriguing range of medicinal scopes. In fact, methylxanthines have been/were medically used as Central Nervous System stimulants, bronchodilators, coronary dilators, diuretics and anti-cancer adjuvant treatments. Other than these applications, methylxanthines have also been hinted to hold other beneficial health effects, namely regarding neurodegenerative diseases, cardioprotection, diabetes and fertility. However, it seems now consensual that toxicity concerns related to methylxanthine consumption and/or therapeutic use should not be dismissed. Taking all the knowledge and expectations on the potential of methylxanthines into account, we propose a systematic look at the past and future of methylxanthine pharmacologic applications, discussing all the promise and anticipating possible constraints. Anyways, methylxanthines will still substantiate considerable meaningful research and discussion for years to come.info:eu-repo/semantics/publishedVersio

Block-windowed burst OFDM: A high-efficiency multicarrier technique

A block-windowed burst orthogonal frequency division multiplexing (OFDM) technique which is a multicarrier technique with power spectral density similar to the filtered OFDM approach, since it also employs smoother, non-rectangular windows, is presented. However, it does not need a cyclic prefix, which means the overall power and spectral efficiencies are higher. An appropriate receiver for typical time-dispersive channels, allowing 2 dB of gain relatively conventional OFDM schemes is also presented

Editorial

Metabolic disorders, particularly Diabetes Mellitus (DM), are major causes of death worldwide. In fact, the world statistics for DM are alarming: this epidemic disease kills one person every six seconds, being the fourth cause of death. Besides the health issues, the costs associated with DM, and its co-morbidities, are massive and the pressure in National Health Care Systems is dramatically increasing. Patients with DM, particularly those with type 2 diabetes (T2D), are primarily advised to change their dietary habits and exercise regime. However, as the disease progresses and becomes more severe, conventional drugs are prescribed. Most of these patients need polypharmacological therapy and though progresses have been made, efforts are mandatory in a search for a “perfect” antidiabetic drug. [...]info:eu-repo/semantics/publishedVersio