Profile of micronucleus frequencies and DNA damage in different species of fish in a eutrophic tropical lake

Lake Paranoá is a tropical reservoir for the City of Brasilia, which became eutrophic due to inadequate sewage treatment associated with intensive population growth. At present, two wastewater treatment plants are capable of processing up to 95% of the domestic sewage, thereby successfully reducing eutrophization. We evaluated both genotoxic and cytotoxic parameters in several fish species (Geophagus brasiliensis, Cichla temensis, Hoplias malabaricus, Astyanax bimaculatus lacustres, Oreochromis niloticus, Cyprinus carpio and Steindachnerina insculpita) by using the micronucleus (MN) test, the comet assay and nuclear abnormality assessment in peripheral erythrocytes. The highest frequencies of MN were found in Cichla temensis and Hoplias malabaricus, which were statistically significant when compared to the other species. However, Steindachnerina insculpita (a detritivorous and lake-floor feeder species) showed the highest index of DNA damage in the comet assay, followed by C. temensis (piscivorous). Nuclear abnormalities, such as binucleated, blebbed, lobed and notched cells, were used as evidence of cytotoxicity. Oreochromis niloticus followed by Hoplias malaricus, ominivorous/detritivotous and piscivorous species, respectively, presented the highest frequency of nuclear abnormalities, especially notched cells, while the herbivorous Astyanax bimaculatus lacustres showed the lowest frequency compared to the other species studied. Thus, for biomonitoring aquatic genotoxins under field conditions, the food web should also be considered

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Tracking the formation of new brominated disinfection by-products during the seawater desalination process.

Several areas around the world rely on seawater desalination to meet drinking water needs, but a detailed analysis of dissolved organic matter (DOM) changes and disinfection by-product (DBP) formation due to chlorination during the desalination processes has yet to be evaluated. To that end, DOM composition was analyzed in samples collected from a desalination plant using bulk measurements (e.g. dissolved organic carbon, total dissolved nitrogen, total organic bromine), absorbance and fluorescence spectroscopy, and ultrahigh resolution mass spectrometry (HRMS). Water samples collected after chlorination (e.g. post pretreatment (PT), reverse osmosis (RO) reject (brine wastewater) (BW), RO permeate (ROP), and drinking water (DW)), revealed that chlorination resulted in decreases in absorbance and increases in fluorescence apparent quantum yield spectra. All parameters measured were low or below detection in ROP and in DW. However, total solid phase extractable (Bond Elut Priority PolLutant (PPL) cartridges) organic bromine concentrations increased significantly in PT and BW samples and HRMS analysis revealed 392 molecular ions containing carbon, hydrogen, oxygen, bromine (CHOBr) and 107 molecular ions containing CHOBr + sulfur (CHOSBr) in BW PPL extracts. A network analysis between supposed DBP precursors suggested that the formation of CHOBr formulas could be explained largely by electrophilic substitution reactions, but also HOBr addition reactions. The reactions of sulfur containing compounds are more complex, and CHOSBr could possibly be due to the bromination of surfactant degradation products like sulfophenyl carboxylic acids (SPC) or even hydroxylated SPCs. Despite the identification of hundreds of DBPs, BW did not show any acute or chronic toxicity to mysid shrimp. High resolution MS/MS analysis was used to propose structures for highly abundant bromine-containing molecular formulas but given the complexity of DOM and DBPs found in this study, future work analyzing desalination samples during different times of year (e.g. during algal blooms) and during different treatments is warranted

Occurrence and distribution of UV-filters and other anthropogenic contaminants in coastal surface water, sediment, and coral tissue from Hawaii.

The occurrence of UV-filters in the environment has raised concerns over potentially adverse impacts on corals. In this study, the concentrations of 13 UV-filters and 11 hormones were measured in surface seawater, sediment, and coral tissue from 19 sites in Oahu, Hawaii. At least eight UV-filters were detected in seawater, sediment, and coral tissue and total mass concentrations of all UV-filters were <750 ng L-1, <70 ng g(-1) dry weight (dw), and <995 ng g(-1) dw, respectively. Four UV-filters were detected in water, sediment, and coral tissue at detection frequencies of 63-100%, 56-91%, and 82-100%, respectively. These UV-filter concentrations generally varied as follows: water, homosalate (HMS) > octisalate (OS) > benzophenone-3 (BP-3, also known as oxybenzone) > octocrylene (OC); sediment, HMS > OS > OC > BP-3; coral, OS approximate to HMS > OC approximate to BP-3. BP-3 concentrations in surface seawater were <10 ng L-1 at 12 of 19 sites and highest at Waikiki beach (e,g., 10.9-136 ng L-1). While BP-3 levels were minimal in sediment (e,g., <1 ng g(-1) dw at 18 of 19 sites), and ranged from 6.6 to 241 ng g(-1) dw in coral tissue. No quantifiable levels of 2-ethylhexyl 4-methoxycinnamate (also known as octinoxate) were recorded in surface seawater or coral tissues, but 5-12.7 ng g(-1) dw was measured for sediment at 5 of 19 sites. No hormones were detected in seawater or sediment, but 17 alpha-ethinylestradiol was present in three corals from Kaneohe Bay. Surfactant degradation products were present in seawater, especially at Waikiki beach. These results demonstrate ubiquitous parts-per-trillion concentrations of UV-filters in surface seawater and is the first report of UV-filters in coral tissue from USA. coastal waters. These data inform the range of environmentally-relevant concentrations for future risk assessments on the potential impacts of UV-filters on coral reefs in Oahu, Hawaii

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease