Geochemistry, stable isotopes and statistic tools to estimate threshold and source of nitrate in groundwater (Sardinia, Italy)

In the European Union, nitrate vulnerable zone (NVZ) should be designed for the mitigation of nitrate (NO3−) contamination caused by agricultural practices. Before establishing new NVZ, the sources of NO3− must be recognized. A geochemical and multiple stable isotopes approach (hydrogen, oxygen, nitrogen, sulfur and boron) and statistical tools were applied to define the geochemical characteristics of groundwater (60 samples), calculate the local NO3− threshold and assess potential sources of NO3− contamination in two study areas (hereafter Northern and Southern), located in a Mediterranean environment (Sardinia, Italy). Results of the integrated approach applied to two case study, permits to highlight the strengths of integrating geochemical and statistical methods to provide nitrate source identification as a reference by decision makers to remediate and mitigate nitrate contamination in groundwater. Hydrogeochemical features in the two study areas were similar: near neutral to slightly alkaline pH, electrical conductivity in the range of 0.3 to 3.9 mS/cm, and chemical composition ranging from Ca-HCO3− at low salinity to Na-Cl− at high salinity. Concentrations of NO3− in groundwater were in the range of 1 to 165 mg/L, whereas the nitrogen reduced species were negligible, except few samples having NH4+ up to 2 mg/L. Threshold values in the studied groundwater samples were between 4.3 and 6.6 mg/L NO3−, which was in agreement with previous estimates in Sardinian groundwater. Values of δ34S and δ18OSO4 of SO42− in groundwater samples indicated different sources of SO42−. Sulfur isotopic features attributed to marine SO42− were consistent with groundwater circulation in marine-derived sediments. Other source of SO42− were recognize due to the oxidation of sulfide minerals, to fertilizers, manure, sewage fields, and SO42− derived from a mix of different sources. Values of δ15N and δ18ONO3 of NO3− in groundwater samples indicated different biogeochemical processes and NO3− sources. Nitrification and volatilization processes might have occurred at very few sites, and denitrification was likely to occur at specific sites. Mixing among various NO3− sources in different proportions might account for the observed NO3− concentrations and the nitrogen isotopic compositions. The SIAR modeling results showed a prevalent NO3− source from sewage/manure. The δ11B signatures in groundwater indicated the manure to be the predominant NO3− source, whereas NO3− from sewage was recognized at few sites. Geographic areas showing either a predominant process or a defined NO3− source where not recognize in the studied groundwater. Results indicate widespread contamination of NO3− in the cultivated plain of both areas. Point sources of contamination, due to agricultural practices and/or inadequate management of livestock and urban wastes, were likely to occur at specific sites

Expression and Function of Gonadotropin-releasing Hormone (GnRH) Receptor in Human Olfactory GnRH-secreting Neurons AN AUTOCRINE GnRH LOOP UNDERLIES NEURONAL MIGRATION

Olfactory neurons and gonadotropin-releasing hormone (GnRH) neurons share a common origin during organogenesis. Kallmann's syndrome, clinically characterized by anosmia and hypogonadotropic hypogonadism, is due to an abnormality in the migration of olfactory and GnRH neurons. We recently characterized the human FNC-B4 cell line, which retains properties present in vivo in both olfactory and GnRH neurons. In this study, we found that FNC-B4 neurons expressed GnRH receptor and responded to GnRH with time- and dose-dependent increases in GnRH gene expression and protein release (up to 5-fold). In addition, GnRH and its analogs stimulated cAMP production and calcium mobilization, although at different biological thresholds (nanomolar for cAMP and micromolar concentrations for calcium). We also observed that GnRH triggered axon growth, actin cytoskeleton remodeling, and a dose-dependent increase in migration (up to 3-4-fold), whereas it down-regulated nestin expression. All these effects were blocked by a specific GnRH receptor antagonist, cetrorelix. We suggest that GnRH, secreted by olfactory neuroblasts, acts in an autocrine pattern to promote differentiation and migration of those cells that diverge from the olfactory sensory lineage and are committed to becoming GnRH neurons

Natural attenuation can lead to environmental resilience in mine environment

Four streams flowing in the Iglesiente and Arburese mine districts (SW Sardinia, Italy), exploited for zinc (Zn) and lead (Pb) extraction from sulphides and secondary non-sulphide mineralization (calamine ores), have been studied combining investigations from the macroscale (hydrologic tracer techniques) to the microscale (X-ray powder diffraction, scanning electron microscopy, X-ray absorption spectroscopy). In the investigated area, concerns arise from release of metals to water during weathering of ore minerals and mine-waste. Specifically, Zn is observed at extremely high concentrations (10s of mg/L or more) in waters in some of the investigated catchments. The results from synoptic sampling campaigns showed marked differences of Zn loads, from 6.3 kg/day (Rio San Giorgio) to 2000 kg/day (Rio Irvi). Moreover, natural attenuation of metals was found to occur i) through precipitation of Fe compounds (Fe oxy/hydroxides and “green rust”), ii) by means of the authigenic formation of metal sulphides promoted by microbial sulphate reduction, iii) by metal intake in roots and stems of plants (Phragmites australis and Juncus acutus) and by immobilization in the rhizosphere, and iv) by cyanobacterial biomineralization processes that lead to formation of Zn-rich phases (hydrozincite and amorphous Zn-silicate). The biologically mediated natural processes that lead to significant abatement and/or reduction of metal loads, are the response of environmental systems to perturbations caused from mine activities, and can be considered part of the resilience of the system itself. The aim of this study is to understand the effect of these processes on the evolution of the studied systems towards more stable and, likely, resilient conditions, e.g. by limiting metal mobility and favouring the improvement of the overall quality of water. The understanding of how ecosystems adapt and respond to contamination, and which chemical and physical factors control these natural biogeochemical barriers, can help to plan effective remediation actions

A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death

: The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10-8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10-8). A total of 113 variants were associated with survival at P-value < 1.0 × 10-5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways

A new GNPAT variant of foetal rhizomelic chondrodysplasia punctata

Abstract Background Rhizomelic chondrodysplasia punctata (RCDP) is a clinical entity resulting from defects of peroxisomal metabolism whose clinical phenotype is characterized by rhizomelia, calcified foci in periarticular cartilage, coronal lesions of vertebral bodies, cataracts and severe cognitive delay. Usually, survival does not exceed the first decade of life. Transmission is autosomal recessive and is related to mutations in the PEX7, GNPAT or AGPS. Methods A detailed description of the prenatal ultrasound signs of RCDP found in two successive pregnancies in a consanguineous couple is reported. Molecular genetic investigations included the study of the coding regions and the exon–intron junctions of the GNPAT (high‐throughput amplification and sequencing performed with Roche NimbleGen SeqCap Target kit on Illumina platform); the confirmation test was carried out by amplification and Sanger sequencing with automatic capillary sequencer. Results In addition to the typical prenatal ultrasound signs described in the literature in association with RCDP, the presence of prefrontal oedema, never previously described, has been detected in both pregnancies. Moreover, genetic investigations have found a new splicing variant c.924+1G>A of the homozygous GNPAT. Conclusion The role of mutation in the GNPAT suggests a likely association with the clinical phenotype

Knowledge and attitude of general pratictioners towards direct-to-consumer genomic tests: a survey conducted in Italy

Background: Personal genomic tests (PGT) offered directly-to-consumers (DTC) for complex disease risk assessment have raised several concerns regarding their potential adverse impact. To mitigate worries continuing professional education has been advocated and the central gatekeeper role of family physicians has been highlighted. Nevertheless, to date, only few studies have been published on awareness, involvement and attitudes of&nbsp; primary healthcare providers on DTC marketing of PGT and, to the best of our knowledge, none in Italy. Methods: An exploratory survey to achieve information about knowledge and attitudes towards DTC-PGT of a selected group of family physicians participating to courses on predictive medicine and public health genomics was conducted. &nbsp; Results: A total amount of 114 partially or fully filled questionnaires was obtained. The majority of the primary care providers (68,4%)&nbsp; expressed that they are unaware that companies are selling genomic tests directly to consumers, while 31,6% was aware.&nbsp; In terms of attitudes toward testing 61,1% of the aware respondents deemed the DTC-PGT for chronic complex diseases to be ‘‘not clinically useful.’’&nbsp; The overwhelming majority of our respondents (95,6%) felt unprepared to answer patients’ questions on DTC-PGT. If only aware respondents are considered this percentage results obviously&nbsp; lower (86,1%), though still very high. &nbsp; Conclusion: The low percentage of aware respondents suggests that DTC advertising in the realm of genomic testing is still limited in Italy. Should DTC-PGT become more widely used, a comprehensive education program may be necessary to increase family physicians’ awareness and help them discuss testing with their patients.&nbsp