How to unmask unique vulnerabilities in leukaemia

How to unmask unique vulnerabilities in leukaemia Acute myeloid leukaemia (AML) is a group of haematologic malignancies that have been traditionally difficult to classify and treat. Nucleophosmin (NPM1) mutations are the most frequent genetic alteration (about 30 per cent) in AML and NPM1-mutated AML is a new entity in the WHO classification of myeloid neoplasms. However, mechanisms of leukemogenesis and a specific therapy for this leukaemia are missing. The ContraNPM1AML project aims to unravel the complex network of molecular interactions that take place in this distinct genetic subtype and find their vulnerabilities to identify new targets for therapy. The expected discoveries will lead to novel therapeutic approaches and make clinical trials available to patients

Bioremediation of Crude Oil by Haematococcus Pluvialis: A Preliminary Study

Nowadays, oil pollution is one of the main environmental problems. The current methods for recovering spills mainly involve chemical agents, but scientific research has focused on more natural and less harmful techniques for the environment, including a consortium of bacteria and microalgae to clean up water contaminated by hydrocarbons. The purpose of this preliminary study was to evaluate the ability of a microalga belonging to Chlorophyceae to grow in the presence of crude oil and remove the principal contaminants. H. pluvialis, which is usually used for nutraceutical purposes, thanks to the production of astaxanthin, was able to grow in anaerobic conditions, varying its metabolism from autotrophic to heterotrophic, exploiting the carbon present in the solution deriving from the presence of 1% of crude oil. Furthermore, the results of bioremediation showed a relevant reduction in chemical pollutants such as nitrate, fluoride, sulfate, and phosphate. The most important aspect of the study was the reduction after 160 days in the hydrocarbon concentration inside not only the culture medium (−32%) but also the algal biomass (−80.25%), demonstrating an optimized degradation rather than a simple absorption inside the alga

Genetic Improvement to Obtain Specialized Haematococcus pluvialis Genotypes for the Production of Carotenoids, with Particular Reference to Astaxanthin

Nowadays, the search for natural substances with a high nutraceutical effect positively impact the world market. Among the most attractive macromolecules are antioxidants, capable of preventing the development of various pathologies. Astaxanthin (ASX) is antioxidant molecule produced by the microalga H. pluvialis as a response to different types of stress. Usually, astaxanthin production involves the first phase of accumulation of the biomass of H. pluvialis (green phase), which is then stressed to stimulate the biosynthesis and accumulation of ASX (red phase). In this study, the H. pluvialis wild-type strain was subjected to random mutagenesis by UV. Among the different mutant strains obtained, only two showed interesting bio-functional characteristics, such as a good growth rate. The results demonstrated that the HM1010 mutant not only has a higher growth trend than the WT mutant but accumulates and produces ASX even in the green phase. This innovative genotype would guarantee the continuous production of ASX, not linked to the two-step process and the uniqueness of the product obtained

An innovative protocol to select the best growth phase for astaxanthin biosynthesis in H. pluvialis.

H. pluvialis is a green unicellular microalgae and it is the first producer of natural astaxanthin in the world if subjected to stress conditions such as high light, high salinity and nutrient starvation. Astaxanthin is a powerful antioxidant used in many fields, such as aquaculture, pharmaceutical, food supplements and cosmetic. To obtain a large amount of astaxanthin, researcher focused on the optimisation of H. pluvialis growth. H. pluvialis has four different size growth stage (macrozooids, microzooids, palmelloid and “red non-motile astaxanthin accumulated encysted”), and astaxanthin production occur in the last phase. Recent studies shown that non-motile cells can produce more astaxanthin than motile cells if subjected to light stress. For these reasons, the aim of this study is to find a new and innovative methodology to select and recovery H. pluvialis in his last growth phase thanks to an electrophoretic run, and optimize, in this way, astaxanthin production

Complexity computation for compact 3-manifolds via crystallizations and Heegaard diagrams

The idea of computing Matveev complexity by using Heegaard decompositions has been recently developed by two different approaches: the first one for closed 3-manifolds via crystallization theory, yielding the notion of Gem-Matveev complexity; the other one for compact orientable 3-manifolds via generalized Heegaard diagrams, yielding the notion of modified Heegaard complexity. In this paper we extend to the non-orientable case the definition of modified Heegaard complexity and prove that for closed 3-manifolds Gem-Matveev complexity and modified Heegaard complexity coincide. Hence, they turn out to be useful different tools to compute the same upper bound for Matveev complexity.Comment: 12 pages; accepted for publication in Topology and Its Applications, volume containing Proceedings of Prague Toposym 201

Tumor Suppressor Role of hsa-miR-193a-3p and -5p in Cutaneous Melanoma

Background: Remarkable deregulation of several microRNAs (miRNAs) is demonstrated in cutaneous melanoma. hsa-miR-193a-3p is reported to be under-expressed in tissues and in plasma of melanoma patients, but the role of both miR-193a arms in melanoma is not known yet. Methods: After observing the reduced levels of miR-193a arms in plasma exosomes of melanoma patients, the effects of hsa-miR-193a-3p and –5p transfection in cutaneous melanoma cell lines are investigated. Results: In melanoma cell lines A375, 501Mel, and MeWo, the ectopic over-expression of miR-193a arms significantly reduced cell viability as well as the expression of genes involved in proliferation (ERBB2, KRAS, PIK3R3, and MTOR) and apoptosis (MCL1 and NUSAP1). These functional features were accompanied by a significant downregulation of Akt and Erk pathways and a strong increase in the apoptotic process. Since in silico databases revealed TROY, an orphan member of the tumor necrosis receptor family, as a potential direct target of miR-193a-5p, this possibility was investigated using the luciferase assay and excluded by our results. Conclusions: Our results underline a relevant role of miR-193a, both -3p and -5p, as tumor suppressors clarifying the intracellular mechanisms involved and suggesting that their ectopic over-expression could represent a novel treatment for cutaneous melanoma patients

Lipids from Microalgae for Cosmetic Applications

In recent years, there has been considerable interest in using microalgal lipids in the food, chemical, pharmaceutical, and cosmetic industries. Several microalgal species can accumulate appreciable lipid quantities and therefore are characterized as oleaginous. In cosmetic formulations, lipids and their derivatives are one of the main ingredients. Different lipid classes are great moisturizing, emollient, and softening agents, work as surfactants and emulsifiers, give consistence to products, are color and fragrance carriers, act as preservatives to maintain products integrity, and can be part of the molecules delivery system. In the past, chemicals have been widely used but today’s market and customers’ demands are oriented towards natural products. Microalgae are an extraordinary source of lipids and other many bioactive molecules. Scientists’ attention to microalgae cultivation for their industrial application is increasing. For the high costs associated, commercialization of microalgae and their products is still not very widespread. The possibility to use biomass for various industrial purposes could make microalgae more economically competitive

Persistent immune stimulation exacerbates genetically driven myeloproliferative disorders via stromal remodeling

Systemic immune stimulation has been associated with increased risk of myeloid malignancies, but the pathogenic link is unknown. We demonstrate in animal models that experimental systemic immune activation alters the bone marrow stromal microenvironment, disarranging extracellular matrix (ECM) microarchitecture, with downregulation of secreted protein acidic and rich in cysteine (SPARC) and collagen-I and induction of complement activation. These changes were accompanied by a decrease in Treg frequency and by an increase in activated effector T cells. Under these conditions, hematopoietic precursors harboring nucleophosmin-1 (NPM1) mutation generated myeloid cells unfit for normal hematopoiesis but prone to immunogenic death, leading to neutrophil extracellular trap (NET) formation. NET fostered the progression of the indolent NPM1-driven myeloproliferation toward an exacerbated and proliferative dysplastic phenotype. Enrichment in NET structures was found in the bone marrow of patients with autoimmune disorders and in NPM1-mutated acute myelogenous leukemia (AML) patients. Genes involved in NET formation in the animal model were used to design a NET-related inflammatory gene signature for human myeloid malignancies. This signature identified two AML subsets with different genetic complexity and different enrichment in NPM1 mutation and predicted the response to immunomodulatory drugs. Our results indicate that stromal/ECM changes and priming of bone marrow NETosis by systemic inflammatory conditions can complement genetic and epigenetic events towards the development and progression of myeloid malignancy