Novel Natural Compounds and Their Anatomical Distribution in the Stinging Fireworm Hermodice carunculata (Annelida).

Increasing evidence in the field of bioprospection fosters the necessity of studying poorly investigated poisonous marine invertebrates to expand knowledge on animal venom biology. Among marine annelids, amphinomid fireworms are notorious for their bearded trunk equipped with a powerful stinging capacity. Here, a methodological workflow based on analytical chemistry techniques (compound isolation followed by mass spectrometry and spectroscopy analyses) was applied to gain new insights, leading to the identification and structural elucidation of an array of natural products from Mediterranean specimens of Hermodice carunculata. Eight betaine-derived unprecedented compounds, named "carunculines", were detected, bearing two terminal ammonium groups tri-and disubstituted at the Cα (A, B) and a series of different alkyl chains (I-VIII). The mixture of chemicals was found in all the body parts of H. carunculata, supporting a mechanism of action triggered by their vehiculation inside the dorsal chaetae, and subsequent injection when chaetae break off on contact. Preliminary investigations to understand adaptive features were also performed, showing a trend in carunculine abundance that fits into the evolutionary history of these worms. These findings shed light on the chemical ecology of amphinomids, giving reasons for the success of H. carunculata in benthic environments and providing promising novel metabolites for biotechnological implications.

Synthesis and Anticancer Activity of CDDO and CDDO-Me, Two Derivatives of Natural Triterpenoids.

Triterpenoids are natural compounds synthesized by plants through cyclization of squalene, known for their weak anti-inflammatory activity. 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), and its C28 modified derivative, methyl-ester (CDDO-Me, also known as bardoxolone methyl), are two synthetic derivatives of oleanolic acid, synthesized more than 20 years ago, in an attempt to enhance the anti-inflammatory behavior of the natural compound. These molecules have been extensively investigated for their strong ability to exert antiproliferative, antiangiogenic, and antimetastatic activities, and to induce apoptosis and differentiation in cancer cells. Here, we discuss the chemical properties of natural triterpenoids, the pathways of synthesis and the biological effects of CDDO and its derivative CDDO-Me. At nanomolar doses, CDDO and CDDO-Me have been shown to protect cells and tissues from oxidative stress by increasing the transcriptional activity of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2). At doses higher than 100 nM, CDDO and CDDO-Me are able to modulate the differentiation of a variety of cell types, both tumor cell lines or primary culture cell, while at micromolar doses these compounds exert an anticancer effect in multiple manners; by inducing extrinsic or intrinsic apoptotic pathways, or autophagic cell death, by inhibiting telomerase activity, by disrupting mitochondrial functions through Lon protease inhibition, and by blocking the deubiquitylating enzyme USP7. CDDO-Me demonstrated its efficacy as anticancer drugs in different mouse models, and versus several types of cancer. Several clinical trials have been started in humans for evaluating CDDO-Me efficacy as anticancer and anti-inflammatory drug; despite promising results, significant increase in heart failure events represented an obstacle for the clinical use of CDDO-Me.

The investigation of resveratrol and analogs as potential inducers of fetal hemoglobin.

Βeta-thalassemia, is a hemoglobinopathy characterized by reduced beta-globin chain synthesis, leading to imbalanced globin chain production, ineffective erythropoiesis and anemia. Increasing gamma-globin gene expression is a promising therapeutic approach as it reduces this imbalance by combining with the excess alpha globin chains and producing fetal hemoglobin (HbF). Furthermore, increased iron absorption and repeated blood transfusions lead to iron overload and tissue damage secondary to reactive oxygen species. Compounds exhibiting both antioxidant and HbF inducing activities are, therefore, highly desirable therapeutic agents. Resveratrol, a natural phytoalexin, combines these two activities but is also cytotoxic. Nine hydroxystilbenic resveratrol derivatives were synthesized in an attempt to identify compounds that retain the HbF-inducing and antioxidant activities of resveratrol but exhibit reduced cytotoxicity. Three derivatives (P1, P4 and P11) exhibited similar hemoglobin-inducing properties to resveratrol in K562 cells, however, only P11 showed reduced cytotoxicity. All three derivatives demonstrated variable HbF-inducing activity in primary erythroid progenitor cells from healthy donors. Resveratrol and P11 increased HbF induction significantly, with P11 having the highest activity. Additionally, P4 significantly increased progenitor numbers. A combinatorial treatment in K562 cells using resveratrol and decitabine resulted in a statistically significant increase in hemoglobin-inducing activity only above the level shown by resveratrol alone.

Non-Conventional Yeasts Whole Cells as Efficient Biocatalysts for the Production of Flavors and Fragrances.

The rising consumer requests for natural flavors and fragrances have generated great interest in the aroma industry to seek new methods to obtain fragrance and flavor compounds naturally. An alternative and attractive route for these compounds is based on bio-transformations. In this review, the application of biocatalysis by Non Conventional Yeasts (NCYs) whole cells for the production of flavor and fragrances is illustrated by a discussion of the production of different class of compounds, namely Aldehydes, Ketones and related compounds, Alcohols, Lactones, Terpenes and Terpenoids, Alkenes, and Phenols.

Assessment of antioxidant and antiproliferative properties of spinach plants grown under low oxygen availability.

BACKGROUND: In the human diet, the consumption of fresh fruits and vegetables is important in maintaining good health and in preventing chronic diseases. It is known that plant-derived food is a powerful source of chemopreventive molecules, i.e. antioxidants, and spinach (Spinacia oleracea L., Chenopodiaceae) possesses a wide range of metabolites with such biological activity. Plant stress response could lead to the production of metabolites with high value for human health and this could be a tool to enhance the production of molecules with antioxidant activity in plants. RESULTS: Data reported in this paper confirm the antioxidant properties of spinach plants, and show a strong antiproliferative activity of leaf extract on HT-29 human cell line. Besides, the hypoxic stress seems to affect the pool of antioxidant molecules present in spinach leaves, as verified by means of HPLC-MS/MS analysis and the aluminium chloride and ABTS assays. CONCLUSION: Our findings represent a basis for improving the biological and pharmacological properties of spinach plants, including the use of different growth conditions to modulate the phytocomplex profile of spinach.

Production of flavours and fragrances via bioreduction of (4R)-(-)-carvone and (1R)-(-)-myrtenal by non-conventional yeast whole-cells.

As part of a program aiming at the selection of yeast strains which might be of interest as sources of natural flavours and fragrances, the bioreduction of (4R)-(-)-carvone and (1R)-(-)-myrtenal by whole-cells of non-conventional yeasts (NCYs) belonging to the genera Candida, Cryptococcus, Debaryomyces, Hanseniaspora, Kazachstania, Kluyveromyces, Lindnera, Nakaseomyces, Vanderwaltozyma and Wickerhamomyces was studied. Volatiles produced were sampled by means of headspace solid-phase microextraction (SPME) and the compounds were analysed and identified by gas chromatography-mass spectroscopy (GC-MS). Yields (expressed as % of biotransformation) varied in dependence of the strain. The reduction of both (4R)-(-)-carvone and (1R)-(-)-myrtenal were catalyzed by some ene-reductases (ERs) and/or carbonyl reductases (CRs), which determined the formation of (1R,4R)-dihydrocarvone and (1R)-myrtenol respectively, as main flavouring products. The potential of NCYs as novel whole-cell biocatalysts for selective biotransformation of electron-poor alkenes for producing flavours and fragrances of industrial interest is discussed.

A thin section micromorphology photomicrographs dataset of the infilling of the Sennacherib Assyrian canal system (Kurdistan Region of Iraq).

Here we present a compendium of 212 photographs of archaeological soils and sediments thin sections (micrographs) from the backfill of the Sennacherib Assyrian canal system of Northern Mesopotamia. The micrographs were produced using an optical petrographic microscope (Olympus BX41) mounting a digital camera (Olympus E420) for image acquisition. The dataset is composed of two folders containing (1) every micrograph in full resolution JPEG, and (2) a PDF file with scale bars and brief captions for each one. The dataset represents a photographic comparison collection for individuals working on similar geoarchaeological contexts and can be used for the composition of figures in novel publications, as well as being the first example of published large compendium for shared use in the field of archaeology.

Geomorphological assessment of the preservation of archaeological tell sites.

Tells are multi-layered, archaeological mounds representing anthropogenic landforms common in arid regions. In such contexts, the preservation of the archaeological record is mined by ongoing climate changes, shift in land use, and intense human overgrazing. Such natural and human-driven factors tune the response of archaeological soils and sediments to erosion. Geomorphology offers a plethora of tools for mapping natural and anthropogenic landforms and evaluating their response to unremitting weathering, erosional and depositional processes. Here, we present a geomorphological investigation on two anthropogenic mounds in the Kurdistan Region of Iraq, with a special focus on the ongoing erosional processes mining their slope stability and threatening the preservation of the local archaeological landscape. Applying the revised universal soil loss equation model for soil loess derived from UAV imagery and implemented with geoarchaeological investigation, we assess the erosion rate along anthropogenic mounds and estimate the risk of losing archaeological deposits. We argue that a large-scale application of our approach in arid and semi-arid regions may improve our ability to (i) estimate the rate of soil and/or archaeological sediments loss, (ii) propose mitigation strategies to prevent the dismantling of the archaeological record, and (iii) schedule archaeological operations in areas of moderate to extreme erosion risk.

Neolithic hydroclimatic change and water resources exploitation in the Fertile Crescent.

In the first millennia of the Holocene, human communities in the Fertile Crescent experienced drastic cultural and technological transformations that modified social and human-environments interactions, ultimately leading to the rise of complex societies. The potential influence of climate on this "Neolithic Revolution" has long been debated. Here we present a speleothem record from the Kurdistan Region of Iraq, covering from Early Neolithic to Early Chalcolithic periods (~ 11 to 7.3 ka, 9000-5300 BCE). The record reveals the influence of the Siberian High on regional precipitation, and shows large hydroclimatic variability at the multicentennial scale. In particular, it highlights wetter conditions between 9.7 and 9.0 ka, followed by an abrupt reduction of precipitation between 9.0 and 8.5 ka, and a wetter interval between 8.5 and 8.0 ka. A comparison with regional and local archaeological data demonstrates an influence of recorded hydroclimatic changes on settlement patterns (size, distribution, permanent vs. seasonal occupation) and on the exploitation of water resources by Neolithic to Chalcolithic populations. Our record does not show prominent hydroclimatic changes at 9.3 and 8.2 ka, thus not supporting direct influence of such rapid and widespread events on the process of Neolithization and its cultural dispersal.

The resveratrol analog 4,4'-dihydroxy-trans-stilbene suppresses transformation in normal mouse fibroblasts and inhibits proliferation and invasion of human breast cancer cells.

4,4'-dihydroxy-trans-stilbene (DHS) is a synthetic analog of resveratrol, a phytoalexin known for its biological activities. We previously demonstrated that DHS exerts an antiproliferative effect on normal human fibroblasts that is higher than that of the natural parent molecule. No evidence regarding its role in human cancer cell lines has been found thus far. In this study, we investigated the effects of DHS both on chemical-induced transformation of BALB/c 3T3 mouse fibroblasts and on the proliferation and invasion of human breast cancer MCF-7 cells. The results showed that DHS markedly suppresses the two-stage (3-methylcholanthrene plus 12-O-tetradecanoylphorbol-13-acetate) cell transformation. Compared with resveratrol, DHS inhibited both anchorage-dependent and -independent MCF-7 growth more efficiently. In addition, a reduction in the number of cells in S-phase, characterized by a concomitant increase in the levels of p21 and p53 proteins, together with a strong inhibition of pRb protein phosphorylation, was observed in DHS-treated cells. Furthermore, DHS effected a strong reduction in matrix metalloproteinase-2 and -9 activities, concomitantly with a marked inhibition of cell adhesion to the extracellular matrix components as well as inhibition of cell migration and invasion. Importantly, modulation of the adhesion molecule E-cadherin was also found in DHS-treated cells. Taken together, these results demonstrate that the two 4,4'-hydroxyl groups on the stilbenic backbone make DHS a more active molecule than resveratrol in inhibiting neoplastic transformation, cancer cell proliferation and invasion. In conclusion, this study suggests that DHS could be a promising anticancer agent.

Is There a Role for Sound in Plants?

Plants have long been considered passive, static, and unchanging organisms, but this view is finally changing. More and more knowledge is showing that plants are aware of their surroundings, and they respond to a surprising variety of stimuli by modifying their growth and development. Plants extensively communicate with the world around them, above and below ground. Although communication through mycorrhizal networks and Volatile Organic Compounds has been known for a long time, acoustic perception and communication are somehow a final frontier of research. Perhaps surprisingly, plants not only respond to sound, they actually seem to emit sound as well. Roots emit audible clicks during growth, and sounds are emitted from xylem vessels, although the nature of these acoustic emissions still needs to be clarified. Even more interesting, there is the possibility that these sounds carry information with ecological implications, such as alerting insects of the hydration state of a possible host plant, and technological implications as well. Monitoring sound emissions could possibly allow careful monitoring of the hydration state of crops, which could mean significantly less water used during irrigation. This review summarizes the current knowledge on sound perception communication in plants and illustrates possible implications and technological applications.

Upgrading of Biobased Glycerol to Glycerol Carbonate as a Tool to Reduce the CO2 Emissions of the Biodiesel Fuel Life Cycle.

With regards to oil-based diesel fuel, the adoption of bio-derived diesel fuel was estimated to reduce CO2 emissions by approximately 75%, considering the whole life cycle. In this paper, we present a novel continuous-flow process able to transfer an equimolar amount of CO2 (through urea) to glycerol, producing glycerol carbonate. This represents a convenient tool, able to both improve the efficiency of the biodiesel production through the conversion of waste streams into added-value chemicals and to beneficially contribute to the whole carbon cycle. By means of a Design of Experiments approach, the influence of key operating variables on the product yield was studied and statistically modeled.

Stratigraphic reassessment of Grotta Romanelli sheds light on Middle-Late Pleistocene palaeoenvironments and human settling in the Mediterranean.

During the last century, Grotta Romanelli (Southern Italy) has been a reference site for the European Late Pleistocene stratigraphy, due to its geomorphological setting and archaeological and palaeontological content. The beginning of the sedimentation inside the cave was attributed to the Last Interglacial (MISs 5e) and the oldest unearthed evidence of human occupation, including remains of hearths, was therefore referred to the Middle Palaeolithic. Recent surveys and excavations produced new U/Th dates, palaeoenvironmental interpretation and a litho-, morpho- and chrono-stratigraphical reassessment, placing the oldest human frequentation of the cave between MIS 9 and MIS 7, therefore embracing Glacial and Interglacial cycles. These new data provide evidence that the sea reached the cave during the Middle Pleistocene and human occupation occurred long before MISs 5e and persisted beyond the Pleistocene- Holocene boundary.

A defective ABC transporter of the MRP family, responsible for the bean lpa1 mutation, affects the regulation of the phytic acid pathway, reduces seed myo-inositol and alters ABA sensitivity.

• We previously identified the lpa1 (low phytic acid) 280-10 line that carries a mutation conferring a 90% reduction in phytic acid (InsP(6) ) content. In contrast to other lpa mutants, lpa1(280-10) does not display negative pleiotropic effects. In the present paper, we have identified the mutated gene and analysed its impact on the phytic acid pathway. • Here, we mapped the lpa1(280-10) mutation by bulk analysis on a segregating F(2) population, an then, by comparison with the soybean genome, we identified and sequenced a candidate gene. The InsP(6) pathway was analysed by gene expression and quantification of metabolites. • The mutated Pvmrp1(280-10) cosegregates with the lpa1(280-10) mutation, and the expression level of several genes of the InsP(6) pathway are reduced in the lpa1(280-10) mutant as well as the inositol and raffinosaccharide content. PvMrp2, a very similar paralogue of PvMrp1 was also mapped and sequenced. • The lpa1 mutation in beans is likely the result of a defective Mrp1 gene (orthologous to the lpa genes AtMRP5 and ZmMRP4), while its Mrp2 paralog is not able to complement the mutant phenotype in the seed. This mutation appears to down-regulate the InsP(6) pathway at the transcriptional level, as well as altering inositol-related metabolism and affecting ABA sensitivity.

Biological Effect of Different Spinach Extracts in Comparison with the Individual Components of the Phytocomplex.

The Mediterranean-style diet is rich in fruit and vegetables and has a great impact on the prevention of major chronic diseases, such as cardiovascular diseases and cancer. In this work we investigated the ability of spinach extracts obtained by different extraction methods and of the single main components of the phytocomplex, alone or mixed, to modulate proliferation, antioxidant defense, and genotoxicity of HT29 human colorectal cells. Spinach extracts show dose-dependent activity, increasing the level of intracellular endogenous reactive oxygen species (ROS) when tested at higher doses. In the presence of oxidative stress, the activity is related to the oxidizing agent involved (H2O2 or menadione) and by the extraction method. The single components of the phytocomplex, alone or mixed, do not alter the intracellular endogenous level of ROS but again, in the presence of an oxidative insult, the modulation of antioxidant defense depends on the oxidizing agent used. The application of the phytocomplex extracts seem to be more effective than the application of the single phytocomplex components.

A tuning point in plant acoustics investigation.

In a very recent book called Sensory Biology of Plants, published by renowned publisher Springer Nature, the authors stated that the scientific literature gathered so far regarding knowledge around the field of Plant Acoustics allows us to divert the focus from the question "whether plants perceive sound" toward the questions "how and why they are doing it" Some phenomena are well known: roots perceive the sound of flowing water and display a sound-mediated growth toward the water source, while the buzz pollination process allows plants to minimize the pollen lost and maximize which is collected by true pollinators. But plants are far more perceptive and responsive to their environment than we generally consider them to be, and they are communicating far more information than we realize if we only took all their signals (VOCs, sound, exudates, etc.) into a greater picture. Could Volatile Organic Compounds (VOCs) be involved in mediating more responses than we imagine? VOC synthesis and release is known to be elicited also by electrical signals caused by mechanical stimuli, touching and wounding being among these, serving as info-chemicals in the communication between plants ("eavesdropping"), and within the organs of the same plant, in order for it to get synchronized with its surroundings. This paper is an overview of the discoveries around plant perception with a focus on the link between mechanical stimuli, as sound vibrations are, and changes in plant physiology leading to VOC emission.

Sound perception and its effects in plants and algae.

Life evolved in an acoustic world. Sound is perceived in different ways by the species that inhabit the Planet. Among organisms, also some algal species seem to respond to sound stimuli with increased cell growth and productivity. The purpose of this Short Communication is to provide an overview of the current literature about various organisms and sound, with particular attention to algal organisms, which, when subjected to sound applications, can change their metabolism accordingly.

Antimicrobial activity of spices essential oils and its effectiveness on mature biofilms of human pathogens.

The antibacterial activity of Pimpinella anisum L., Cinnamomum zeylanicum, Syzygium aromaticum, and Cuminum cyminum L. essential oils (EOs) against some common pathogenic microorganisms (Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 14990, Enterococcus faecalis ATCC 29212, Streptococcus pyogenes ATCC 1915, Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 27853, Aeromonas hydrophila ATCC 7966, Proteus mirabilis ATCC 10005, Klebsiella pneumoniae ATCC 13883, and Candida albicans ATCC 10231) and their biofilms was studied. The EOs inhibitory effects were evaluated by both Agar Well Diffusion assay and Minimum Inhibitory Concentration (MIC) determination. The most active EOs, cinnamon and cloves, were also tested on 18, 24, 48, 72 hours mature biofilms. Cinnamon and cloves exhibited the best results showing a significant activity against all the tested bacteria. Concerning biofilm, results suggest that Cinnamomum zeylanicum oil may be a useful approach to impair the biofilm produced by the tested Gram-negative bacteria. [Formula: see text].

alphavbeta3 Integrin-dependent antiangiogenic activity of resveratrol stereoisomers.

Angiogenesis is target for antineoplastic and chemopreventive therapies. The natural phytoalexin resveratrol is found in grapes and red wine as cis and trans stereoisomers. trans-Resveratrol shows antiangiogenic activity, but its mechanism of action is not fully elucidated. Recently, trans-resveratrol has been shown to interact with the beta3 integrin subunit, raising the possibility that inhibition of endothelial alphavbeta3 integrin function may concur to its angiosuppressive activity. To get novel insights about the antiangiogenic activity of resveratrol, we compared cis- and trans-resveratrol stereoisomers for their effect on the angiogenesis process and endothelial alphavbeta3 integrin function. trans-Resveratrol inhibits endothelial cell proliferation and the repair of mechanically wounded endothelial cell monolayers. Also, it prevents endothelial cell sprouting in fibrin gel, collagen gel invasion, and morphogenesis on Matrigel. In vivo, trans-resveratrol inhibits vascularization of the chick embryo area vasculosa and murine melanoma B16 tumor growth and neovascularization. In all the assays, cis-resveratrol exerts a limited, if any, effect. In keeping with these observations, trans-resveratrol, but not cis-resveratrol, inhibits alphavbeta3 integrin-dependent endothelial cell adhesion and the recruitment of enhanced green fluorescent protein-tagged beta3 integrin in focal adhesion contacts. In conclusion, stereoisomery affects the antiangiogenic activity of resveratrol, the trans isomer being significantly more potent than the cis isoform. The different antiangiogenic potential of resveratrol stereoisomers is related, at least in part, to their different capacity to affect alphavbeta3 integrin function. This may have profound implications for the design of synthetic antiangiogenic/angiopreventive phytoalexin derivatives.

Oxygen Availability during Growth Modulates the Phytochemical Profile and the Chemo-Protective Properties of Spinach Juice.

Fruits and vegetables are a good source of potentially biologically active compounds. Their regular consumption in the human diet can help reduce the risk of developing chronic diseases such as cardiovascular diseases and cancer. Plants produce additional chemical substances when subject to abiotic stress or infected by microorganisms. The phytochemical profile of spinach leaves (Spinaciaoleracea L.), which is a vegetable with widely recognized health-promoting activity, has been affected by applying root hypoxic and re-oxygenation stress during plant growth. Leaf juice at different sampling times has been subject to liquid chromatography mass spectrometry (LC-MSn) analysis and tested on the human colorectal adenocarcinoma cell line HT29 by using the Comet assay. The cells were previously treated with H2O2 to simulate the presence of an oxidative stress (as in colon cancer condition) and the leaf juice application resulted in a significant antioxidant and protective in vitro effect. The duration of the hypoxic/re-oxygenation stress imposed on the plant reflects the antioxidant leaf juice content. After hypoxic stress (24 hours) and reoxygenation (2 hours), we show a decrease (50%) of the relative abundance of the principal identified antioxidant molecules but a higher antioxidant activity of the spinach juice on HT29 cells (20%). Data shows a complex relation between plant growing conditions and the modulation of secondary metabolites content in leaf juice that results in different chemo-protective activities in colon cancer cells.