Nitric Oxide Mediates the Stress Response Induced by Diatom Aldehydes in the Sea Urchin Paracentrotus lividus

Diatoms are ubiquitous and abundant primary producers that have been traditionally considered as a beneficial food source for grazers and for the transfer of carbon through marine food webs. However, many diatom species produce polyunsaturated aldehydes that disrupt development in the offspring of grazers that feed on these unicellular algae. Here we provide evidence that production of the physiological messenger nitric oxide increases after treatment with the polyunsaturated aldehyde decadienal in embryos of the sea urchin Paracentrotus lividus. At high decadienal concentrations, nitric oxide mediates initial apoptotic events leading to loss of mitochondrial functionality through the generation of peroxynitrite. At low decadienal concentrations, nitric oxide contributes to the activation of hsp70 gene expression thereby protecting embryos against the toxic effects of this aldehyde. When nitric oxide levels were lowered by inhibiting nitric oxide synthase activity, the expression of hsp70 in swimming blastula decreased and the proportion of abnormal plutei increased. However, in later pluteus stages nitric oxide was no longer able to exert this protective function: hsp70 and nitric oxide synthase expression decreased with a consequent increase in the expression of caspase-8. Our findings that nitric oxide production increases rapidly in response to a toxic exogenous stimulus opens new perspectives on the possible role of this gas as an important messenger to environmental stress in sea urchins and for understanding the cellular mechanisms underlying toxicity during diatom blooms

X-ray high-resolution spectroscopy reveals feedback in a Seyfert galaxy from an ultra fast wind with complex ionization and velocity structure

Winds outflowing from Active Galactic Nuclei (AGNs) may carry significant amount of mass and energy out to their host galaxies. In this paper we report the detection of a sub-relativistic outflow observed in the Narrow Line Seyfert 1 Galaxy IRAS17020+4544 as a series of absorption lines corresponding to at least 5 absorption components with an unprecedented wide range of associated column densities and ionization levels and velocities in the range of 23,000-33,000 km/s, detected at X-ray high spectral resolution (E/Delta E ~1000) with the ESA's observatory XMM-Newton. The charge states of the material constituting the wind clearly indicate a range of low to moderate ionization states in the outflowing gas and column densities significantly lower than observed in highly ionized ultra fast outflows. We estimate that at least one of the outflow components may carry sufficient energy to substantially suppress star formation, and heat the gas in the host galaxy. IRAS17020+4544 provides therefore an interesting example of feedback by a moderately luminous AGN hosted in a spiral galaxy, a case barely envisaged in most evolution models, which often predict that feedback processes take place in massive elliptical galaxies hosting luminous quasars in a post merger phase.Comment: 8 pages, 3 figures, to appear on ApJ Letter

Roe enhancement of Paracentrotus lividus: Nutritional effects of fresh and formulated diets

Sea urchin gonads are exploited both for gastronomic and scientific purposes; thus, the production of large and mature gonads is essential. Natural populations of the Mediterranean Sea urchin Paracentrotus lividus are subject to increasing fishing ef- forts, due to continuous intensification of consumptions. Aquaculture practices may represent an answer, but the availability of artificial feeds accelerating the produc- tion of high-quality gonads in terms of size, taste, colour, firmness, maturity and via- bility of gametes is critical to boost the productions. The accessibility of cheap and effective feeds promoting the fattening of gonads and the quality of gametes is still a bottleneck slowing down the expansion of echinoculture practices. This investiga- tion is aimed at enabling the development of this strategic sector, by comparing the dietetic effects of fresh foods and a commercial feed for aquaculture, to four newly formulated feeds. The protein contents of diets were strongly related to the GSIs. The abundance of fatty acids appeared inversely related to the viability of embryos and abnormalities of larvae. The features of an ideal diet for this sea urchin were defined, based on the results of experimental trials, and the need for increasing levels of plant-derived proteins during the grow-out period was demonstrated

Adherence to and effectiveness of lenalidomide after 1 year of treatment in a real world setting

Background: In combination with dexamethasone, lenalidomide is prescribed in the oral treatment of Multiple Myeloma for patients who have received at least one previous therapy. Objective: The objective of this study is to evaluate medication adherence to lenalidomide of Multiple Myeloma patients, as well as Progression Free Survival and Overall Survival one year from the beginning of the treatment. Setting: The study was carried out in Pescara Hospital, in Italy. All Multiple Myeloma patients who began lenalidomide therapy between January 1, 2012 and June 30, 2016 were included in our study. Methods: Adherence to treatment was calculated by using the ratio between the Received Daily Dose and the Prescribed Daily Dose. Effectiveness in real world has been evaluated as Progression Free Survival and Overall Survival one year from the beginning of the treatment.Main outcomes measure: We assessed medication adherence and effectiveness of lenalidomide in the treatment of Multiple Myeloma. Results: Adherence to the overall mean treatment was 0.73 ± 0.15, relative to 81 patients evaluated in our study. 32% of patients achieved an adherence equal to or greater than 80%. Real-life effectiveness in terms of Progression Free Survival and Overall Survival showed values of ​​53.75% and 88%, respectively, one year from the beginning of treatment. Conclusion: The analysis of adherence in Multiple Myeloma patients treated with lenalidomide one year from the beginning of therapy reveal a concerning lack of adherence. Moreover, the lack of correlation of the levels of adherence with patient-related variables shows that, in the case of Multiple Myeloma, adherence is not related to personal, social and environmental characteristics that may determine each patient's correct treatment implementation, but is directly influenced by disease evolution

The Role of NGF and Its Receptor TrKA in Patients With Erectile Dysfunction

The aim of our study was to investigate the plasma NGF concentration and TrkA/p75NTR receptor expression on white blood cells (WBCs), in peripheral and corpus cavernosum blood isolated from patients with erectile dysfunction and metabolic syndrome (ED/MetS). This was a pilot case–control study. Inclusion criteria were as follows: men 18–65 years with ED and MetS and healthy subjects. The first sampling was performed at the level of the cubital vein (VC). Subsequently, 20 μg of intracavernous alprostadil was administered, and a second blood draw from the corpora cavernosa (CC) was performed once erection was achieved. Subsequently, the third blood sample was repeated at the level of the VC. We enrolled 8 cases with ED/MetS and 8 controls. There was no significant difference between the case and control group in terms of mean age (49.3 ± 5.9 and 53.13 ± 8.9, respectively). The case group had a lower IIEF score compared to the control group (14 ± 3.2 versus 27.3 ± 2.1; p < 0.05). Decreased NGF and TrKA expression on WBC and thiols were found in the plasma of ED/MetS patients compared to control. The study showed that patients with ED/MetS had a decrease in plasma NGF and thiol concentration, and they had a decrease in TrKA expression on WBCs

Morphologic and genic effects of waste pollution on the reproductive physiology of Paracentrotus lividus lmk: a mesocosm experiment

: A considerable amount of coastal contamination is caused by wastes deriving from household and the degradation and the metabolism of plants and animals, even if our attention is commonly focused on industrial pollutants and contaminants. Waste pollutants are mainly represented by highly diluted soluble compounds and particles deriving from dead organisms. This complex combination, consisting of suspended particles and dissolved nutrients, has a significant impact on coastal planktonic and benthic organisms, also playing an active role in the global cycles of carbon. In addition, production practices are nowadays shifting towards recirculated aquaculture systems (RAS) and the genic responses of target organisms to the pollution deriving from animal metabolism are still scarcely addressed by scientific investigations. The reservoir of organic matter dissolved in the seawater is by far the least understood if compared to that on land, cause only a few compounds have been identified and their impacts on animals and plants are poorly understood. The tendency of these compounds to concentrate at interfaces facilitates the absorption of dissolved organic compound (DOC) onto suspended particles. Some DOC components are chemically combined with dissolved metals and form complexes, affecting the chemical properties of the seawater and the life of the coastal biota. In this research, we compared the reproductive performances of the common sea urchin Paracentrotus lividus cultured in open-cycle tanks to those cultured in a recirculating aquaculture system (RAS), where pollution progressively increased during the experiment due to animal escretions. Sea urchins were cultured for 7 months under these two conditions and their gametes were collected. Embryos resulting by in vitro fertilization were analyzed by Real Time qPCR to identify possible effects of pollution-induced stress. The fertility of sea urchins was evaluated, as well as the gonadosomatic indices and the histological features of gonads. Our results indicate that pollution due to excess of nutrients, event at sub-lethal concentrations, may hardly impact the reproductive potential of this key species and that chronic effects of stress are revealed by the analyses of survival rates and gene expression

Rare Copy Number Variants in Array-Based Comparative Genomic Hybridization in Early-Onset Skeletal Fragility

Early-onset osteoporosis is characterized by low bone mineral density (BMD) and fractures since childhood or young adulthood. Several monogenic forms have been identified but the contributing genes remain inadequately characterized. In search for novel variants and novel candidate loci, we screened a cohort of 70 young subjects with mild to severe skeletal fragility for rare copy-number variants (CNVs). Our study cohort included 15 subjects with primary osteoporosis before age 30 years and 55 subjects with a pathological fracture history and low or normal BMD before age 16 years. A custom-made high-resolution comparative genomic hybridization array with enriched probe density in >1,150 genes important for bone metabolism and ciliary function was used to search for CNVs. We identified altogether 14 rare CNVs. Seven intronic aberrations were classified as likely benign. Five CNVs of unknown clinical significance affected coding regions of genes not previously associated with skeletal fragility (ETV1-DGKB, AGBL2, ATM, RPS6KL1-PGF, and SCN4A). Finally, two CNVs were pathogenic and likely pathogenic, respectively: a 4 kb deletion involving exons 1-4 of COL1A2 (NM_000089.3) and a 12.5 kb duplication of exon 3 in PLS3 (NM_005032.6). Although both genes have been linked to monogenic forms of osteoporosis, COL1A2 deletions are rare and PLS3 duplications have not been described previously. Both CNVs were identified in subjects with significant osteoporosis and segregated with osteoporosis within the families. Our study expands the number of pathogenic CNVs in monogenic skeletal fragility and shows the validity of targeted CNV screening to potentially pinpoint novel candidate loci in early-onset osteoporosis.Peer reviewe

The EORTC emotional functioning computerized adaptive test:phases I-III of a cross-cultural item bank development

Background: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group is currently developing computerized adaptive testing measures for the Quality of Life Questionnaire Core-30 (QLQ-C30) scales. The work presented here describes the development of an EORTC item bank for emotional functioning (EF), which is one of the core domains of the QLQ-C30. Methods: According to the EORTC guidelines on module development, the development of the EF item bank comprised four phases, of which the phases I-III are reported in the present paper. Phase I involved defining the theoretical framework for the EF item bank and a literature search. Phase II included pre-defined item selection steps and a multi-stage expert review process. In phase III, feedback from cancer patients from different countries was obtained. Results: On the basis of literature search in phase I, a list of 1750 items was generated. These were reviewed and further developed in phase II with a focus on relevance, redundancy, clarity, and difficulty. The development and selection steps led to a preliminary list of 41 items. In phase III, patient interviews (N = 41; Austria, Denmark, Italy, and the UK) were conducted with the preliminary item list, resulting in some minor changes to item wording. The final list comprised 38 items. Discussion: The phases I-III of the developmental process have resulted in an EF item list that was well accepted by patients in several countries. The items will be subjected to larger-scale field testing in order to establish their psychometric characteristics and their fit to an item response theory model

Combined in situ XRF–LIBS analyses as a novel method to determine the provenance of central Mediterranean obsidians

This work presents a new calibration method for determining the provenance of obsidian artefacts based on the combined use of XRF and laser-induced breakdown spectroscopy (LIBS). At first, obsidian samples collected from the main Mediterranean sources were characterized using portable XRF and LIBS systems. After data treatment, elemental information was used to carry out principal component analysis (PCA) for each technique. Rb, Sr, Zr, Y and Fe elements, detected by using XRF, were found to be the key parameters enabling obsidians discrimination. Likewise, LIBS data helped differentiating the analysed patterns by the intensity of their main elemental components (Ca, Al, Mg and K). After selecting the key parameters detected by each technique, a new data matrix combining XRF and LIBS data was finally built. According to PCA results, the discrimination of Mediterranean sources based on combined XRF–LIBS data ensured a higher reliability over mono-analytical models, by increasing the Euclidean distance between sources projections over three-dimensional principal components plots. Knowing that the representativeness of elemental data could be compromised by the presence of superficial degradation products or deposition patinas, a shot-to-shot comparison of in-depth LIBS analyses is finally proposed as a method to disclose whether the spot under analysis was superficially contaminated or altered. Thus, the proposed strategy based on the combined use of portable XRF and LIBS spectrometers could be particularly useful for the in situ analysis of obsidian artefacts that underwent superficial alteration or could be covered by patina products.This work has been financially supported by the DEMORA project (Grant No. PID2020-113391GB-I00), funded by the Spanish Agency for Research (through the Spanish Ministry of Science and Innovation (Grant No. BIA2017-870´63-P), MICINN, and the European Regional Development Fund (Grant No. BIA2017-870´63-P), FEDER). I. Costantini gratefully acknowledges to the UPV/EHU for her postdoctoral contract. Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature