Diversity and bioactive potential of actinobacteria isolated from a coastal marine sediment in Northern Portugal

Natural compounds have had increasing applications in the biotechnological sector, with a large fraction of these substances being channeled to the pharmaceutical industry due to their important pharmacological properties. The discovery of new bioactive molecules with novel mechanisms of action constitutes a promising solution for the design of alternative therapeutic solutions. Actinobacteria are a large group of morphologically and physiologically diverse bacteria well known for their production of biotechnologically relevant compounds. The Portuguese coast is scantly explored in terms of Actinobacteria diversity and respective bioactive potential, offering a good opportunity to find new Actinobacteria taxa and bioactive natural products. In this study, we investigated the Actinobacteria diversity associated with a sediment sample collected from the intertidal zone of a beach in northern Portugal, through a cultivation-dependent approach, and screened its antimicrobial and cytotoxic potential. A total of 52 Actinobacteria strains were recovered from the marine sediment, with the largest fraction of the isolates belonging to the genus Micromonospora. Bioactivity screening assays identified crude extracts of six Streptomyces strains active against C. albicans, exhibiting minimum inhibition concentration (MIC) values in the range of 3.90–125 μg mL−1. Twenty-five Actinobacteria crude extracts (obtained from strains of the genera Micromonospora, Streptomyces and Actinomadura) exhibited significant effects on the viability of at least one tested cancer cell line (breast ductal carcinoma T-47D and liver hepatocellular carcinoma HepG2). The Actinobacteria extracts demonstrating activity in the antimicrobial and/or cytotoxic assays were subjected to metabolomic analysis (Mass spectrometry (MS)-based dereplication and molecular networking analyses), indicating the presence of four clusters that may represent new natural products. The results obtained demonstrate the importance of bioprospecting underexplored environments, like the Portuguese coast, for enhancing the discovery of new natural products, and call attention to the relevance of preserving the natural genetic diversity of coastal environments.This work was funded by the structured program of R&D&I ATLANTIDA - Platform for the monitoring of the North Atlantic Ocean and tools for the sustainable exploitation of the marine resources (reference NORTE-01-0145-FEDER-000040), supported by the North Portugal Regional Operational Programme (NORTE2020), through the European Regional Development Fund (ERDF). It was also supported by the strategic funding UIDB/04423/2020 and UIDP/04423/2020 through national funds provided by FCT

First report on cyanotoxin (Mc-lr) removal from surface water by multi-soil-layering (msl) eco-technology: Preliminary results

Cyanobacteria blooms occur frequently in freshwaters around the world. Some can produce and release toxic compounds called cyanotoxins, which represent a danger to both the environment and human health. Microcystin-LR (MC-LR) is the most toxic variant reported all over the world. Conventional water treatment methods are expensive and require specialized personnel and equipment. Recently, a multi-soil-layering (MSL) system, a natural and low-cost technology, has been introduced as an attractive cost-effective, and environmentally friendly technology that is likely to be an alternative to conventional wastewater treatment methods. This study aims to evaluate, for the first time, the efficiency of MSL eco-technology to remove MC-LR on a laboratory scale using local materials. To this end, an MSL pilot plant was designed to treat distilled water contaminated with MC-LR. The pilot was composed of an alternation of permeable layers (pozzolan) and soil mixture layers (local sandy soil, sawdust, charcoal, and metallic iron on a dry weight ratio of 70, 10, 10, and 10%, respectively) arranged in a brick-layer-like pattern. MSL pilot was continuously fed with synthetic water containing distilled water contaminated with increasing concentrations of MC-LR (0.18–10 µg/L) at a hydraulic loading rate (HLR) of 200 L m−2 day−1. The early results showed MC-LR removal of above 99%. Based on these preliminary results, the multi-soil-layering eco-technology could be considered as a promising solution to treat water contaminated by MC-LR in order to produce quality water for irrigation or recreational activities. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.This research has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 823860

Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1

Gonadal failure, along with early pregnancy loss and perinatal death, may be an important filter that limits the propagation of harmful mutations in the human population. We hypothesized that men with spermatogenic impairment, a disease with unknown genetic architecture and a common cause of male infertility, are enriched for rare deleterious mutations compared to men with normal spermatogenesis. After assaying genomewide SNPs and CNVs in 323 Caucasian men with idiopathic spermatogenic impairment and more than 1,100 controls, we estimate that each rare autosomal deletion detected in our study multiplicatively changes a man’s risk of disease by 10% (OR 1.10 [1.04–1.16], p,261023), rare X-linked CNVs by 29%, (OR 1.29 [1.11–1.50], p,161023), and rare Y-linked duplications by 88% (OR 1.88 [1.13–3.13], p,0.03). By contrasting the properties of our case-specific CNVs with those of CNV callsets from cases of autism, schizophrenia, bipolar disorder, and intellectual disability, we propose that the CNV burden in spermatogenic impairment is distinct from the burden of large, dominant mutations described for neurodevelopmental disorders. We identified two patients with deletions of DMRT1, a gene on chromosome 9p24.3 orthologous to the putative sex determination locus of the avian ZW chromosome system. In an independent sample of Han Chinese men, we identified 3 more DMRT1 deletions in 979 cases of idiopathic azoospermia and none in 1,734 controls, and found none in an additional 4,519 controls from public databases. The combined results indicate that DMRT1 loss-of-function mutations are a risk factor and potential genetic cause of human spermatogenic failure (frequency of 0.38% in 1306 cases and 0% in 7,754 controls, p = 6.261025). Our study identifies other recurrent CNVs as potential causes of idiopathic azoospermia and generates hypotheses for directing future studies on the genetic basis of male infertility and IVF outcomes.This work was partially funded by the Portuguese Foundation for Science and Technology FCT/MCTES (PIDDAC) and co-financed by European funds (FEDER) through the COMPETE program, research grant PTDC/SAU-GMG/101229/2008. IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology, and Higher Education and is partially supported by FCT. AML is the recipient of a postdoctoral fellowship from FCT (SFRH/BPD/73366/2010). CO is supported by a grant from the United States National Institutes of Health (R01 HD21244), JDS is supported by Damon Runyon Clinical Investigator Award, Alex's Lemonade Stand Foundation Epidemiology Award, and the Eunice Kennedy Shriver Children's Health Research Career Development Award NICHD 5K12HD001410. Support for humans studies and specimens were provided by the NIH/NIDDK George M. O'Brien Center for Kidney Disease Kidney Translational Research Core (P30DK079333) grant to Washington University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Effects of Aronia melanocarpa fruit juice on exploratory behaviour and locomotor activity in rats

The main bioactive substances in Aronia melanocarpa fruit juice (AMFJ) are polyphenols (flavonoids, procyanidins, and phenolic acids). A great number of polyphenols are able to traverse the blood-brain barrier. In recent years more attention is drawn to the ability of these substances to influence central nervous system functions. The aim of the present study was to investigate the effects of AMFJ on exploratory behaviour and locomotor activity in male Wistar rats. AMFJ was administered orally for 7, 14, 21, and 30 days at three increasing doses (2.5, 5, and 10 ml kg−1). The changes in exploratory behaviour and locomotor activity were recorded in an Opto Varimex apparatus. It was found that the low doses of AMFJ (2.5 and 5 ml kg−1) for all treatment periods did not significantly affect exploratory behaviour and locomotor activity of rats compared to the saline-treated controls. AMFJ at the highest dose of 10 ml kg−1 had no significant effect on exploration and locomotion for the treatment periods of 7 and 14 days, while for the periods of 21 and 30 days it significantly decreased the number of horizontal and vertical movements, which might be the result of a sedative effect. At all the doses and testing periods, AMFJ did not disturb the progressive decrease in motor behaviour, suggesting habituation

Atmospheric effects on extensive air showers observed with the Surface Detector of the Pierre Auger Observatory

Atmospheric parameters, such as pressure (P), temperature (T) and density, affect the development of extensive air showers initiated by energetic cosmic rays. We have studied the impact of atmospheric variations on extensive air showers by means of the surface detector of the Pierre Auger Observatory. The rate of events shows a ~10% seasonal modulation and ~2% diurnal one. We find that the observed behaviour is explained by a model including the effects associated with the variations of pressure and density. The former affects the longitudinal development of air showers while the latter influences the Moliere radius and hence the lateral distribution of the shower particles. The model is validated with full simulations of extensive air showers using atmospheric profiles measured at the site of the Pierre Auger Observatory.Comment: 24 pages, 9 figures, accepted for publication in Astroparticle Physic

Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter

Data collected by the Pierre Auger Observatory through 31 August 2007 showed evidence for anisotropy in the arrival directions of cosmic rays above the Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{$6\times 10^{19}$eV}. The anisotropy was measured by the fraction of arrival directions that are less than $3.1^\circ$ from the position of an active galactic nucleus within 75 Mpc (using the V\'eron-Cetty and V\'eron $12^{\rm th}$ catalog). An updated measurement of this fraction is reported here using the arrival directions of cosmic rays recorded above the same energy threshold through 31 December 2009. The number of arrival directions has increased from 27 to 69, allowing a more precise measurement. The correlating fraction is $(38^{+7}_{-6})$, compared with $21$ expected for isotropic cosmic rays. This is down from the early estimate of $(69^{+11}_{-13})$. The enlarged set of arrival directions is examined also in relation to other populations of nearby extragalactic objects: galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in hard X-rays by the Swift Burst Alert Telescope. A celestial region around the position of the radiogalaxy Cen A has the largest excess of arrival directions relative to isotropic expectations. The 2-point autocorrelation function is shown for the enlarged set of arrival directions and compared to the isotropic expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201

The exposure of the hybrid detector of the Pierre Auger Observatory

The Pierre Auger Observatory is a detector for ultra-high energy cosmic rays. It consists of a surface array to measure secondary particles at ground level and a fluorescence detector to measure the development of air showers in the atmosphere above the array. The "hybrid" detection mode combines the information from the two subsystems. We describe the determination of the hybrid exposure for events observed by the fluorescence telescopes in coincidence with at least one water-Cherenkov detector of the surface array. A detailed knowledge of the time dependence of the detection operations is crucial for an accurate evaluation of the exposure. We discuss the relevance of monitoring data collected during operations, such as the status of the fluorescence detector, background light and atmospheric conditions, that are used in both simulation and reconstruction.Comment: Paper accepted by Astroparticle Physic