1,720,992 research outputs found
Towards multi-stage drugs to fight poverty related and neglected parasitic diseases: synthetic and natural compounds directed against Leishmania, Plasmodium and Schistosoma life stages and assessment of their mechanisms of action
No full textMalaria, leishmaniasis and schistosomiasis rank among the most devastating tropical diseases in the world. A core group of Italian scientists, with a long standing experience in Neglected Tropical Diseases and Poverty Related Diseases (NTDs and PRDs), decided to create the LeishPlaSch Consortium to bring their knowledge and their efforts together with the aim of achieving substantial advancements in the discovery of novel therapeutic and/or preventive drugs against Plasmodium, Leishmania and Schistosoma, the pathogens causing malaria (a PRD), leishmaniosis and schistosomiasis (PRDs and NTDs, respectively).
There are three main arguments that constitute the rationale for the choice of the project’s target parasitic diseases:
-All 3 parasites develops in the human host plus an invertebrate host/vector and all - at some stage of their life cycle - reproduce and/or mature in the blood of the human host;
-There is evidence for multi-parasite activity of various drugs and molecules belonging to different chemical classes, e.g. artemisins exhibit activity on Plasmodium, Leishmania and Schistosoma;
-The epidemiology and control of all 3 diseases is influenced by socioeconomic conditions, malnutrition, population mobility, environmental and climate changes.
The goal of the proposal is to develop new, deployable products with targeted profiles against malaria, leishmaniasis and schistosomiasis, in particular by identifying new chemical entities appropriate for the pharmacological management of malaria, leishmaniasis and schistosomiasis.
The goals of the LeishPlaSch consortium are:
1-Identification of disease specific and/or multi-antiparasitic new lead compounds, including repurposing approaches;
2-Identification of compounds with multistage effects for the development of combination treatments including transmission-blocking activity;
3-Validation of novel targets for drug discovery, including a structural biology approach;
4-Advancement of understanding parasite biology and drug-related host parasite relationships, including the definition of modes of action, and identification of new target pathways.
LeishPlaSch Consortium will exploit the high scientific skills of Italian parasitologists, structural and molecular biologists, medicinal and natural organic chemists, biochemists, immunologists, and bioinformaticians. Most of the LeishPlaSch partners are active members of the Italian Malaria Network and already synergized their activities in EC funded projects such as FP6-AntiMal and BioMalPar, and FP7-EVIMalaR and InterMalTraining. The organization of the LeishPlaSch consortium is organized on 3 WPs, based on 3 main platforms: a Chemistry Platform, an Enzymatic and a Phenotypic in vitro platform and in vivo screening Platform. All three WPs will combine their interdisciplinary efforts to identify, select and investigate the mode of action of novel antiparasitic compounds
Family Ownership and Impression Management: An Integrated Approach
No full textAccording to agency theory, impression management is lower in family-owned firms because of reduced agency I conflicts. However, when family owners are present, agency I conflicts are superseded by agency II conflicts between controlling and minority shareholders, leading to a positive association between impression management and family ownership. Moreover, family owners have distinct goals related to the preservation of socioemotional wealth (SEW) that may influence agency conflicts. We formalize these countervailing forces by developing an integrated theoretical framework that considers both agency I and agency II conflicts and how they interact with SEW-related motives. We hypothesize that the coexistence of agency I and agency II conflicts in family-owned firms leads to a U-shaped association between family ownership and impression management. We also expect that this U-shaped association is flatter when family influence on the board is stronger and SEW motives shape more corporate choices. We test our predictions by analyzing the letters to shareholders of 77 Italian-listed firms from 2008 to 2015. The results confirm our expectations and hold when we use instrumental variable estimation, alternative proxies to capture SEW motives, and impression management measure
Enhancing environmental reporting: A study on the role of narrative disclosure, firm- and country-level incentives
No full textMoving from the ongoing debate on the benefits of mandating environmental reporting, this paper provides an analysis of the role of narrative information quality in enhancing environmental reporting, considering the moderating effect of firm-level and country-level incentives. We examine an international sample of listed firms belonging to an environmental-sensitive industry and construct disclosure indices based on a content analysis of the company's reporting. Results reveal that mandatory narrative information quality is positively associated with the quality of environmental reporting displaying a credibility effect beyond earnings quality. Country-level factors that increase the demand for environmental information weaken this relation by reducing the marginal benefit of disclosing environmental information. Our approach advances existing literature on the link between CSR and financial reporting and highlights the unintended consequences of mandating environmental reporting
Economists’ Political Donations and GDP Forecast Accuracy
No full textWe examine the association between economists' political donations and the accuracy of Gross Domestic Product (GDP) forecasts. Prior research suggests that individual political donations reflect personal political orientations, leading to a partisan bias. Therefore, economists might not objectively interpret information, with a subsequent reduction in GDP forecast accuracy. Using a sample of one-quarter-ahead US GDP growth forecasts for 2003-2020, we find that economists making political donations are more accurate than their peers. This result suggests that despite the potential partisan bias, individual political donations give economists an information advantage in predicting GDP growth. We also document that the informational benefits associated with donations are stronger when the political party financed by economists controls both the Senate and House of Representatives. However, these benefits are reduced in periods of uncertainty and when the economists' forecasting houses are more politically active
Natural Bioactive Compounds from Marine Invertebrates That Modulate Key Targets Implicated in the Onset of Type 2 Diabetes Mellitus (T2DM) and Its Complications
Full text linkBackground: Type 2 diabetes mellitus (T2DM) is an ongoing, risky, and costly health problem that therefore always requires new treatment options. Moreover, although several drugs are available, only 36% of patients achieve glycaemic control, and patient adherence is a major obstacle. With monotherapy, T2DM and its comorbidities/complications often cannot be managed, and the concurrent administration of several hypoglycaemic drugs is required, which increases the risk of side effects. In fact, despite the efficacy of the drugs currently on the market, they generally come with serious side effects. Therefore, scientific research must always be active in the discovery of new therapeutic agents. Discussion: The present review highlights some of the recent discoveries regarding marine natural products that can modulate the various targets that have been identified as crucial in the establishment of T2DM disease and its complications, with a focus on the compounds isolated from marine invertebrates. The activities of these metabolites are illustrated and discussed. Objectives. The paper aims to capture the relevant evidence of the great chemical diversity of marine natural products as a key tool that can advance understanding in the T2DM research field, as well as in antidiabetic drug discovery. The variety of chemical scaffolds highlighted by the natural hits provides not only a source of chemical probes for the study of specific targets involved in the onset of T2DM, but is also a helpful tool for the development of drugs that are capable of acting via novel mechanisms. Thus, it lays the foundation for the design of multiple ligands that can overcome the drawbacks of polypharmacology
Antivasospastic and brain-protective effects of a hydroxyl radical scavenger (AVS) after experimental subarachnoid hemorrhage.
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