Integrating Sustainability Issues into Investment Decision Evaluation

The paper investigates the issues of integrating ESG factors into investment decision-making process. Based on the available investor surveys, academic research, the analysis of the Russian companies` non-financial reports, Bloomberg ESG data, Corporate Sustainability and Responsibility indexes and their sectoral aspects, as well as Russian ecological-stock index ERAX and stock exchange index MICEX dynamics the paper concluded that ESG factors have a material impact on corporate financial performance. At the same time there are barriers to the full ESG integration in the investment process primarily connected with the lack of standardized data, information comparability, reliability, completeness and timeliness; limited knowledge and guidance for ESG risk and opportunity measures and appropriate analytical tools as well as lack of dialogue between the investment community and the reporting companies. To contribute to the problem development this paper presents an approach of integrating ESG factors at different stages of investment analysis and business valuation

Induction of granzyme B expression in T-cell receptor/CD28-stimulated human regulatory T cells is suppressed by inhibitors of the PI3K-mTOR pathway

<p>Abstract</p> <p>Background</p> <p>Regulatory T cells (Tregs) can employ a cell contact- and granzyme B-dependent mechanism to mediate suppression of bystander T and B cells. Murine studies indicate that granzyme B is involved in the Treg-mediated suppression of anti-tumor immunity in the tumor microenvironment and in the Treg-mediated maintenance of allograft survival. In spite of its central importance, a detailed study of granzyme B expression patterns in human Tregs has not been performed.</p> <p>Results</p> <p>Our data demonstrated that natural Tregs freshly isolated from the peripheral blood of normal adults lacked granzyme B expression. Tregs subjected to prolonged TCR and CD28 triggering, in the presence of IL-2, expressed high levels of granzyme B but CD3 stimulation alone or IL-2 treatment alone failed to induce granzyme B. Treatment of Tregs with the mammalian target of rapamycin (mTOR) inhibitor, rapamycin or the PI3 kinase (PI3K) inhibitor LY294002 markedly suppressed granzyme B expression. However, neither rapamycin, as previously reported by others, nor LY294002 inhibited Treg proliferation or induced significant cell death in TCR/CD28/IL-2 stimulated cells. The proliferation rate of Tregs was markedly higher than that of CD4+ conventional T cells in the setting of rapamycin treatment. Tregs expanded by CD3/CD28/IL-2 stimulation without rapamycin demonstrated increased <it>in vitro </it>cytotoxic activity compared to Tregs expanded in the presence of rapamycin in both short term (6 hours) and long term (48 hours) cytotoxicity assays.</p> <p>Conclusion</p> <p>TCR/CD28 mediated activation of the PI3K-mTOR pathway is important for granyzme B expression but not proliferation in regulatory T cells. These findings may indicate that suppressive mechanisms other than granzyme B are utilized by rapamycin-expanded Tregs.</p

Probing Amphotericin B Single Channel Activity by Membrane Dipole Modifiers

The effects of dipole modifiers and their structural analogs on the single channel activity of amphotericin B in sterol-containing planar phosphocholine membranes are studied. It is shown that the addition of phloretin in solutions bathing membranes containing cholesterol or ergosterol decreases the conductance of single amphotericin B channels. Quercetin decreases the channel conductance in cholesterol-containing bilayers while it does not affect the channel conductance in ergosterol-containing membranes. It is demonstrated that the insertion of styryl dyes, such as RH 421, RH 237 or RH 160, in bilayers with either cholesterol or ergosterol leads to the increase of the current amplitude of amphotericin B pores. Introduction of 5α-androstan-3β-ol into a membrane-forming solution increases the amphotericin B channel conductance in a concentration-dependent manner. All the effects are likely to be attributed to the influence of the membrane dipole potential on the conductance of single amphotericin B channels. However, specific interactions of some dipole modifiers with polyene-sterol complexes might also contribute to the activity of single amphotericin B pores. It has been shown that the channel dwell time increases with increasing sterol concentration, and it is higher for cholesterol-containing membranes than for bilayers including ergosterol, 6-ketocholestanol, 7-ketocholestanol or 5α-androstan-3β-ol. These findings suggest that the processes of association/dissociation of channel forming molecules depend on the membrane fluidity

CONCEPTUAL OUTLOOK TO SOCIAL INNOVATION IN EU

The generic theory of social innovation appeared in early 2000. Therefore, the role of social innovation was been increased in last decades in the light of macroeconomic transformation of World economy and the great development of social networks. Under social networking new business activites appear in the globalized market, even known as social business. Most programmes of the European Commision have orientation on a high speed of knowledge transfering from scientific research system to business or public life. New organization models of business use a tremendous amount of social information and usually social networks serve for the greater impact on improving structure of business environment and implementation of digital managerial solutions. Social networking serves for production of new knowledge and creation of the new ecosystems for social innovation. The authors of this article are presenting the new aspects of social innovation performance by using the content analysis for identification the role and functions of social innovation under digitalization of business environment. The research is focused on the clarification of social networking effects and better understanding why social innovation is becoming so powerful tool for business start-ups and social communication. The content analysis is used in case to highlight the comparative aspects of social innovation in different economical activities

The frequency of obesity in patients with acute pancreatitis, chronic pancreatitis and pancreatic cancer

BACKGROUND: In the XXI century, the frequency of pancreas diseases increased 2&ndash;3 times. The expectation that causes a pandemic lead to the development of a number of diseases. The results of studies on the relationship of overweight, obesity with the risk of developing pancreas diseases (acute pancreatitis (AP), chronic pancreatitis (CP) and pancreas cancer (PC)) are very heterogeneous (for AP and PC) and not numerous (for CP). AIMS: to identify the frequency of obesity in AP patients (APр), CP patients (СPр) and PC patients (PCр) and compare these parameters. MATERIALS AND METHODS: at the observational multicenter clinical cross-sectional uncontrolled case-study 44 APp, 97 CPp and 45 PCp were examined; the groups were comparable by sex/age. Informed consent form for participate in the study was obtained from all patients. The main outcome of the study: the frequency of obesity in APp, CPp; PCp. RESULTS: The frequency of obesity in APp (13,6%), CPp (24,7%) and PCp (20,0%) did not differ significantly. Among the examined patients, the lowest average BMI (24,2&plusmn;0,7 kg/m2) was observed in APp (p=0,049). BMI &ge;22,5 kg/m2 was found to be associated with AP (OR=0,398; 95%CI 0,195&ndash;0,812; p=0,011). An inverse relationship was shown between the BMI and &ldquo;definite&rdquo; CP (Exp (B)=0,772; 95%CI 0,632&ndash;0,942; p=0,011). In men with CP and in CPp alcoholic etiology, weight deficit was observed significantly more often than in women with CP and in CPp biliary etiology, respectively. Earlier (a year before the present survey), obesity was more common in PCp (55,6%) than in APp (13,6%, &chi;2=3,3; p=0,000) and CPp (25,8%, &chi;2=12,0; p=0,001). A history of obesity (in our study one year before PC detection) and PC (OR=4,435; 95% CI 2,180&ndash;9,025; p=0,000) direct relationship was shown. CONCLUSIONS: the frequency of obesity in APp, CPp and PCp was similar. The average BMI was higher in APp, than in CPp and PCp. BMI&ge;22,5 kg/m2 was a protective factor for AP. BMI was inversely associated with &ldquo;defined&rdquo; CP. A history of obesity was directly associated with PC

Immunogenic cell death induced by a new photodynamic therapy based on photosens and photodithazine

Background: Anti-cancer therapy is more successful when it can also induce an immunogenic form of cancer cell death (ICD). Therefore, when developing new treatment strategies, it is extremely important to choose methods that induce ICD and thereby activate anti-tumor immune response leading to the most effective destruction of tumor cells. The aim of this work was to analyze whether the clinically widely used photosensitizers, photosens (PS) and photodithazine (PD), can induce ICD when used in photodynamic therapy (PDT). Methods: Cell death in murine glioma GL261 or fibrosarcoma MCA205 cells was induced by PS- or PD-PDT and cell death was analyzed by MTT or flow cytometry. Intracellular distribution of PS and PD was studied by using the laser scanning microscope. Calreticulin exposure and HMGB1 and ATP release were detected by flow cytometry, ELISA and luminescence assay, respectively. Immunogenicity in vitro was analyzed by co-culturing of dying cancer cells with bone-marrow derived dendritic cells (BMDCs) and rate of phagocytosis and maturation (CD11c(+)CD86(+), CD11c(+)CD40(+)) of BMDCs and production of IL-6 in the supernatant were measured. In vivo immunogenicity was analyzed in mouse tumor prophylactic vaccination model. Results: We determined the optimal concentrations of the photosensitizers and found that at a light dose of 20 J/cm(2) (lambda ex 615-635 nm) both PS and PD efficiently induced cell death in glioma GL261 and fibrosarcoma MCA205 cells. We demonstrate that PS localized predominantly in the lysosomes and that the cell death induced by PS-PDT was inhibited by zVAD-fmk (apoptosis inhibitor) and by ferrostatin-1 and DFO (ferroptosis inhibitors), but not by the necroptosis inhibitor necrostatin-1 s. By contrast, PD accumulated in the endoplasmic reticulum and Golgi apparatus, and the cell death induced by PD-PDT was inhibited only by z-VAD-fmk. Dying cancer cells induced by PS-PDT or PD-PDT emit calreticulin, HMGB1 and ATP and they were efficiently engulfed by BMDCs, which then matured, became activated and produced IL-6. Using dying cancer cells induced by PS-PDT or PD-PDT, we demonstrate the efficient vaccination potential of ICD in vivo. Conclusions: Altogether, these results identify PS and PD as novel ICD inducers that could be effectively combined with PDT in cancer therapy

On the Complexity of Mechanisms and Consequences of Chromothripsis: An Update

In the present review, we focus on the phenomenon of chromothripsis, a new type of complex chromosomal rearrangements. We discuss the challenges of chromothripsis detection and its distinction from other chromoanagenesis events. Along with already known causes and mechanisms, we introduce aberrant epigenetic regulation as a possible pathway to chromothripsis. We address the issue of chromothripsis characteristics in cancers and benign tumours, as well as chromothripsis inheritance in cases of its occurrence in germ cells, zygotes and early embryos. Summarising the presented data on different phenotypic effect of chromothripsis, we assume that its consequences are most likely determined not by the chromosome shattering and reassembly themselves, but by the genome regions involved in the rearrangement