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589 result(s) for "Costantini, Maria"
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Genome Mining and Synthetic Biology in Marine Natural Product Discovery
[...]this regulator is able to influence fungi in many aspects of their life, such as increasing or reducing secondary metabolite production, activating cryptic gene clusters, asexual and sexual differentiation, sporulation, and pigmentation. [9] investigated the presence of genes involved in monogalactosyldiacylglycerols (MGDGs) and sulfoglycolipid synthesis in microalgae, considering all the microalgal transcriptomes and metatranscriptomes available from the Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP) and the recent Tara Oceans and Global Ocean sampling expedition. [...]molecular and bioinformatic approaches permit us to overcome the over-utilization of marine resources and the use of destructive collection practices, and to apply a more environmentally-friendly approach to drug discovery Funding This research received no external funding. Trivella, D.B.B.; De Felicio, R. The Tripod for Bacterial Natural Product Discovery: Genome Mining, Silent Pathway Induction, and Mass Spectrometry-Based Molecular Networking. mSystems 2018, 3, e00160-17. 6.
Genome Mining as New Challenge in Natural Products Discovery
Drug discovery is based on bioactivity screening of natural sources, traditionally represented by bacteria fungi and plants. Bioactive natural products and their secondary metabolites have represented the main source for new therapeutic agents, used as drug leads for new antibiotics and anticancer agents. After the discovery of the first biosynthetic genes in the last decades, the researchers had in their hands the tool to understand the biosynthetic logic and genetic basis leading to the production of these compounds. Furthermore, in the genomic era, in which the number of available genomes is increasing, genome mining joined to synthetic biology are offering a significant help in drug discovery. In the present review we discuss the importance of genome mining and synthetic biology approaches to identify new natural products, also underlining considering the possible advantages and disadvantages of this technique. Moreover, we debate the associated techniques that can be applied following to genome mining for validation of data. Finally, we review on the literature describing all novel natural drugs isolated from bacteria, fungi, and other living organisms, not only from the marine environment, by a genome-mining approach, focusing on the literature available in the last ten years.
Ozone effects on blood biomarkers of systemic inflammation, oxidative stress, endothelial function, and thrombosis: The Multicenter Ozone Study in oldEr Subjects (MOSES)
The evidence that exposure to ozone air pollution causes acute cardiovascular effects is mixed. We postulated that exposure to ambient levels of ozone would increase blood markers of systemic inflammation, prothrombotic state, oxidative stress, and vascular dysfunction in healthy older subjects, and that absence of the glutathione S-transferase Mu 1 (GSTM1) gene would confer increased susceptibility. This double-blind, randomized, crossover study of 87 healthy volunteers 55-70 years of age was conducted at three sites using a common protocol. Subjects were exposed for 3 h in random order to 0 parts per billion (ppb) (filtered air), 70 ppb, and 120 ppb ozone, alternating 15 min of moderate exercise and rest. Blood was obtained the day before, approximately 4 h after, and approximately 22 h after each exposure. Linear mixed effect and logistic regression models evaluated the impact of exposure to ozone on pre-specified primary and secondary outcomes. The definition of statistical significance was p<0.01. There were no effects of ozone on the three primary markers of systemic inflammation and a prothrombotic state: C-reactive protein, monocyte-platelet conjugates, and microparticle-associated tissue factor activity. However, among the secondary endpoints, endothelin-1, a potent vasoconstrictor, increased from pre- to post-exposure with ozone concentration (120 vs 0 ppb: 0.07 pg/mL, 95% confidence interval [CI] 0.01, 0.14; 70 vs 0 ppb: -0.03 pg/mL, CI -0.09, 0.04; p = 0.008). Nitrotyrosine, a marker of oxidative and nitrosative stress, decreased with increasing ozone concentrations, with marginal significance (120 vs 0 ppb: -41.5, CI -70.1, -12.8; 70 vs 0 ppb: -14.2, CI -42.7, 14.2; p = 0.017). GSTM1 status did not modify the effect of ozone exposure on any of the outcomes. These findings from healthy older adults fail to identify any mechanistic basis for the epidemiologically described cardiovascular effects of exposure to ozone. The findings, however, may not be applicable to adults with cardiovascular disease.
Time- and depth-wise trophic niche shifts in Antarctic benthos
Climate change is expected to affect resource-consumer interactions underlying stability in polar food webs. Polar benthic organisms have adapted to the marked seasonality characterising their habitats by concentrating foraging and reproductive activity in summer months, when inputs from sympagic and pelagic producers increase. While this enables the persistence of biodiverse food webs, the mechanisms underlying changes in resource use and nutrient transfer are poorly understood. Thus, our understanding of how temporal and spatial variations in the supply of resources may affect food web structure and functioning is limited. By means of C and N isotopic analyses of two key Antarctic benthic consumers (Adamussium colbecki, Bivalvia, and Sterechinus neumayeri, Echinoidea) and Bayesian mixing models, we describe changes in trophic niche and nutrient transfer across trophic levels associated with the long- and short-term diet and body size of specimens sampled in midsummer in both shallow and deep waters. Samplings occurred soon after the sea-ice broke up at Tethys Bay, an area characterised by extreme seasonality in sea-ice coverage and productivity in the Ross Sea. In the long term, the trophic niche was broader and variation between specimens was greater, with intermediate-size specimens generally consuming a higher number of resources than small and large specimens. The coupling of energy channels in the food web was consequently more direct than in the short term. Sediment and benthic algae were more frequently consumed in the long term, before the sea-ice broke up, while consumers specialised on sympagic algae and plankton in the short term. Regardless of the time scale, sympagic algae were more frequently consumed in shallow waters, while plankton was more frequently consumed in deep waters. Our results suggest a strong temporal relationship between resource availability and the trophic niche of benthic consumers in Antarctica. Potential climate-driven changes in the timing and quality of nutrient inputs may have profound implications for the structure of polar food webs and the persistence of their constituent species, which have adapted their trophic niches to a highly predictable schedule of resource inputs.
Marine Demospongiae: A Challenging Treasure of Bioactive Compounds
In the last decades, it has been demonstrated that marine organisms are a substantial source of bioactive compounds with possible biotechnological applications. Marine sponges, in particular those belonging to the class of Demospongiae, have been considered among the most interesting invertebrates for their biotechnological potential. In this review, particular attention is devoted to natural compounds/extracts isolated from Demospongiae and their associated microorganisms with important biological activities for pharmacological applications such as antiviral, anticancer, antifouling, antimicrobial, antiplasmodial, antifungal and antioxidant. The data here presented show that this class of sponges is an exciting source of compounds, which are worth developing into new drugs, such as avarol, a hydroquinone isolated from the marine sponge Disidea avara, which is used as an antitumor, antimicrobial and antiviral drug.
Marine Sponges and Bacteria as Challenging Sources of Enzyme Inhibitors for Pharmacological Applications
Enzymes play key roles in different cellular processes, for example, in signal transduction, cell differentiation and proliferation, metabolic processes, DNA damage repair, apoptosis, and response to stress. A deregulation of enzymes has been considered one of the first causes of several diseases, including cancers. In the last several years, enzyme inhibitors, being good candidates as drugs in the pathogenic processes, have received an increasing amount of attention for their potential application in pharmacology. The marine environment is considered a challenging source of enzyme inhibitors for pharmacological applications. In this review, we report on secondary metabolites with enzyme inhibitory activity, focusing our attention on marine sponges and bacteria as promising sources. In the case of sponges, we only reported the kinase inhibitors, because this class was the most representative isolated so far from these marine organisms.
The Role of Geography, Diet, and Host Phylogeny on the Gut Microbiome in the Hawaiian Honeycreeper Radiation
The animal gut microbiome can have a strong influence on the health, fitness, and behavior of its hosts. The composition of the gut microbial community can be influenced by factors such as diet, environment, and evolutionary history (phylosymbiosis). However, the relative influence of these factors is unknown in most bird species. Furthermore, phylosymbiosis studies have largely focused on clades that diverged tens of millions of years ago, and little is known about the degree of gut microbiome divergence in more recent species radiations. This study explores the drivers of microbiome variation across the unique and recent Hawaiian honeycreeper radiation (Fringillidae: Drepanidinae). Fecal samples were collected from 14 extant species spanning the main islands of the Hawaiian archipelago and were sequenced using three metabarcoding markers to characterize the gut microbiome, invertebrate diet, and plant diet of Hawaiian honeycreepers. We then used these metabarcoding data and the honeycreeper host phylogeny to evaluate their relative roles in shaping the gut microbiome. Microbiome variation across birds was highly individualized; however, source island had a small but significant effect on microbiome structure. The microbiomes did not recapitulate the host phylogenetic tree, indicating that evolutionary history does not strongly influence microbiome structure in the honeycreeper clade. These results expand our understanding of the roles of diet, geography, and phylogeny on avian microbiome structure, while also providing important ecological information about the diet and gut microbiota of wild Hawaiian honeycreepers. We investigated the roles of diet, geography, and genetic relatedness on the composition of the gut microbiome of an adaptive radiation of island birds. Using metabarcoding data, we determined that microbiome variation across birds was highly individualized; however, source island had a small but significant effect on microbiome structure.
Bioactive Compounds of Nutraceutical Value from Fishery and Aquaculture Discards
Seafood by-products, produced by a range of different organisms, such as fishes, shellfishes, squids, and bivalves, are usually discarded as wastes, despite their possible use for innovative formulations of functional foods. Considering that “wastes” of industrial processing represent up to 75% of the whole organisms, the loss of profit may be coupled with the loss of ecological sustainability, due to the scarce recycling of natural resources. Fish head, viscera, skin, bones, scales, as well as exoskeletons, pens, ink, and clam shells can be considered as useful wastes, in various weight percentages, according to the considered species and taxa. Besides several protein sources, still underexploited, the most interesting applications of fisheries and aquaculture by-products are foreseen in the biotechnological field. In fact, by-products obtained from marine sources may supply bioactive molecules, such as collagen, peptides, polyunsaturated fatty acids, antioxidant compounds, and chitin, as well as catalysts in biodiesel synthesis. In addition, those sources can be processed via chemical procedures, enzymatic and fermentation technologies, and chemical modifications, to obtain compounds with antioxidant, anti-microbial, anti-cancer, anti-hypertensive, anti-diabetic, and anti-coagulant effects. Here, we review the main discards from fishery and aquaculture practices and analyse several bioactive compounds isolated from seafood by-products. In particular, we focus on the possible valorisation of seafood and their by-products, which represent a source of biomolecules, useful for the sustainable production of high-value nutraceutical compounds in our circular economy era.
Identification of Cocconeis neothumensis var. marina using a polyphasic approach including ultrastructure and gene annotation
Several microalgae, including marine diatoms, significantly contribute to the global primary production and play a vital role in the food webs of benthic and planktonic ecosystems. Diatoms of the genus Cocconeis frequently inhabit benthic substrates, including the leaves of seagrasses. They are seasonally dominant in the leaf epiphytic layer of the Mediterranean seagrass Posidonia oceanica L. Delile, and have been proposed as model organisms for chemical ecology studies. However, the genome of Cocconeis spp. has not been sequenced. Consequently, their low-level molecular identification is currently impossible, besides a few examples. To address this gap, a polyphasic identification of C. neothumensis has been employed, combining ultra-morphological data with DNA barcoding markers. A strain of diatoms was isolated from P. oceanica leaves. It has been cultured in the laboratory and examined under Scanning Electron Microscopy (SEM). The 18S ribosomal RNA gene (18S rRNA, nrDNA) and the ribulose 1,5-biphosphate carboxylase (rbc L, cpDNA) gene were analysed for DNA barcoding characterisation. Since ultra-morphology data unambiguously identified the isolated strain as C. neothumensis Krammer, 1991, the molecular sequences herein reported will facilitate its rapid and accurate identification. In addition, our comparative analyses will facilitate the evaluation of these molecular markers for identification of closely related benthic diatoms.
Blue-Print Autophagy: Potential for Cancer Treatment
The marine environment represents a very rich source of biologically active compounds with pharmacological applications. This is due to its chemical richness, which is claiming considerable attention from the health science communities. In this review we give a general overview on the marine natural products involved in stimulation and inhibition of autophagy (a type of programmed cell death) linked to pharmacological and pathological conditions. Autophagy represents a complex multistep cellular process, wherein a double membrane vesicle (the autophagosome) captures organelles and proteins and delivers them to the lysosome. This natural and destructive mechanism allows the cells to degrade and recycle its cellular components, such as amino acids, monosaccharides, and lipids. Autophagy is an important mechanism used by cells to clear pathogenic organism and deal with stresses. Therefore, it has also been implicated in several diseases, predominantly in cancer. In fact, pharmacological stimulation or inhibition of autophagy have been proposed as approaches to develop new therapeutic treatments of cancers. In conclusion, this blue-print autophagy (so defined because it is induced and/or inhibited by marine natural products) represents a new strategy for the future of biomedicine and of biotechnology in cancer treatment.