Tracking pollutants in a municipal sewage network impairing the operation of a wastewater treatment plant

This work provides a screening of organic contaminants and characterization of the dissolved organic matter in the sewer network until the municipal wastewater treatment plant (WWTP), identifying the network areas with a higher degree of contamination and their impact on the WWTP performance, particularly in the activated sludge reactor. Three monitoring campaigns were carried out at six selected locations of the sewage system (PVZ-1, PVZ-2, PS-F, PS-VC, CP-VC, and PS-T), influent (WWTPINF) and effluent (WWTPEFF) of the WWTP. Advanced analytical techniques were employed, namely excitation/emission matrix fluorescence-parallel factor analysis (EEM-PARAFAC), size exclusion chromatography with organic carbon detector (SEC-OCD), and liquid chromatography with high-resolution-mass spectrometric detection (LC-HRMS). EEM-PARAFAC showed higher fluorescence intensity for the protein-like component (C2), particularly at CP-VC (near seafood industries) associated with the presence of surfactants (~50 mg/L). SEC-OCD highlighted the WWTP efficiency in removing low molecular weight acids and neutrals. LC-HRMS tentatively identified 108 compounds of emerging concern (CEC) and similar detection patterns were obtained for all wastewater samples, except for PVZ-2 (lower detection), many of which occurred in the effluent. Eight CECs included on relevant Watch-Lists were detected in all WWTPEFF samples. Furthermore, 111 surfactants were detected, the classes more frequently found being alcohol ethoxylates (AEOs), nonylphenol polyethoxylates (NPEOs) and linear alkylbenzene sulphonates (LAS). The continuous presence of LAS and NPEOs allied to surfactants concentrations in the WWTPINF of 15–20 mg/L, with CP-VC location (linked with food industries) as an important contributor, explain the morphological changes in the activated sludge and high LAS content in the dewatered sludge, which may have impacted WWTP performance.i) Base-UIDB/50020/2020 and Programmatic-UIDP/50020/2020 Funding of LSRE-LCM, funded by national funds through FCT/MCTES (PIDDAC); ii) European Regional Development Fund through the Interreg V-A Spain-Portugal Programme (POCTEP) 2014–2020 (ref. 0725_NOR_WATER_1_P); iii) Xunta de Galicia (Verónica Castro predoctoral contract: ED481A-2017/156, and ED431C2017/36), the Spanish Agencia Estatal de Investigación – MCIN/AEI/ 10.13039/501100011033 (ref. PID2020-117686RB-C32); iv) NORTE-01-0145-FEDER-000069 (Healthy Waters) co-funded by European Regional Development Fund (ERDF), through North Portugal Regional Operational Programme (NORTE2020), under the PORTUGAL 2020 Partnership Agreement. The authors also acknowledge Águas do Norte, S.A. for supporting the development of this work. Daniela F.S. Morais acknowledges her Ph.D. scholarship supported by FCT (SFRH/BD/146476/2019). Bianca M. Souza Chaves gratefully acknowledges her postdoctoral scholarship supported by CNPq through the Science Without Borders Program (Process No. 201989/2014-0). Vítor J.P. Vilar acknowledges the FCT Individual Call to Scientific Employment Stimulus 2017 (CEECIND/01317/2017)S

Regulated Nuclear Trafficking of rpL10A Mediated by NIK1 Represents a Defense Strategy of Plant Cells against Virus

The NSP-interacting kinase (NIK) receptor-mediated defense pathway has been identified recently as a virulence target of the geminivirus nuclear shuttle protein (NSP). However, the NIK1–NSP interaction does not fit into the elicitor–receptor model of resistance, and hence the molecular mechanism that links this antiviral response to receptor activation remains obscure. Here, we identified a ribosomal protein, rpL10A, as a specific partner and substrate of NIK1 that functions as an immediate downstream effector of NIK1-mediated response. Phosphorylation of cytosolic rpL10A by NIK1 redirects the protein to the nucleus where it may act to modulate viral infection. While ectopic expression of normal NIK1 or a hyperactive NIK1 mutant promotes the accumulation of phosphorylated rpL10A within the nuclei, an inactive NIK1 mutant fails to redirect the protein to the nuclei of co-transfected cells. Likewise, a mutant rpL10A defective for NIK1 phosphorylation is not redirected to the nucleus. Furthermore, loss of rpL10A function enhances susceptibility to geminivirus infection, resembling the phenotype of nik1 null alleles. We also provide evidence that geminivirus infection directly interferes with NIK1-mediated nuclear relocalization of rpL10A as a counterdefensive measure. However, the NIK1-mediated defense signaling neither activates RNA silencing nor promotes a hypersensitive response but inhibits plant growth and development. Although the virulence function of the particular geminivirus NSP studied here overcomes this layer of defense in Arabidopsis, the NIK1-mediated signaling response may be involved in restricting the host range of other viruses

Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages

Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.We thank S. Lecher, S. Li and J. Zallet for technical support. Calculations were performed at the sciCORE scientific computing core facility at the University of Basel. This work was supported by the Swiss National Science Foundation (grants 310030_166687 (S.G.) and 320030_153442 (M.E.) and Swiss HIV Cohort Study grant 740 to L.F.), the European Research Council (309540-EVODRTB to S.G.), TB-PAN-NET (FP7-223681 to S.N.), PathoNgenTrace projects (FP7-278864-2 to S.N.), SystemsX.ch (S.G.), the German Center for Infection Research (DZIF; S.N.), the Novartis Foundation (S.G.), the Natural Science Foundation of China (91631301 to Q.G.), and the National Institute of Allergy and Infectious Diseases (5U01-AI069924-05) of the US National Institutes of Health (M.E.)

Measurements of the Higgs boson production and decay rates and coupling strengths using pp collision data at √S=7 and 8 TeV in the ATLAS experiment

Combined analyses of the Higgs boson production and decay rates as well as its coupling strengths to vector bosons and fermions are presented. The combinations include the results of the analyses of the H -> gamma gamma, ZZ*, WW*, Z gamma, b (b) over bar, tau tau and mu mu decay modes, and the constraints on the associated production with a pair of top quarks and on the off-shell coupling strengths of the Higgs boson. The results are based on the LHC proton-proton collision datasets, with integrated luminosities of up to 4.7 fb(-1) at root s = 7 TeV and 20.3 fb(-1) at root s = 8 TeV, recorded by the ATLAS detector in 2011 and 2012. Combining all production modes and decay channels, the measured signal yield, normalised to the Standard Model expectation, is 1.18(-0.14)(+0.15). The observed Higgs boson production and decay rates are interpreted in a leading-order coupling framework, exploring a wide range of benchmark coupling models both with and without assumptions on the Higgs boson width and on the Standard Model particle content in loop processes. The data are found to be compatible with the Standard Model expectations for a Higgs boson at a mass of 125.36 GeV for all models considered

Cross-sectional analysis of students and school workers reveals a high number of asymptomatic SARS-CoV-2 infections during school reopening in Brazilian cities

Brazil experienced one of the most prolonged periods of school closures, and reopening could have exposed students to high rates of SARS-CoV-2 infection. However, the infection status of students and school workers at the time of the reopening of schools located in Brazilian cities is unknown. Here we evaluated viral carriage by RT-PCR and seroprevalence of anti-SARS-CoV-2 antibodies (IgM and IgG) by immunochromatography in 2259 individuals (1139 students and 1120 school workers) from 28 schools in 28 Brazilian cities. We collected the samples within 30 days after public schools reopened and before the start of vaccination campaigns. Most students (n = 421) and school workers (n = 446) had active (qRT-PCR + IgM− IgG− or qRT-PCR + IgM + IgG−/+) SARS-CoV-2 infection. Regression analysis indicated a strong association between the infection status of students and school workers. Furthermore, while 45% (n = 515) of the students and 37% (n = 415) of the school workers were neither antigen nor antibody positive in laboratory tests, 16% of the participants (169 students and 193 school workers) were oligosymptomatic, including those reinfected. These individuals presented mild symptoms such as headache, sore throat, and cough. Notably, most of the individuals were asymptomatic (83.9%). These results indicate that many SARS-CoV-2 infections in Brazilian cities during school reopening were asymptomatic. Thus, our study highlights the need to promote a coordinated public health effort to guarantee a safe educational environment while avoiding exacerbating pre-existent social inequalities in Brazil, reducing social, mental, and economic losses for students, school workers, and their families

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Maturity-Onset Diabetes of the Young (MODY) in Portugal: Novel GCK, HNFA1 and HNFA4 Mutations

Maturity-onset diabetes of the young (MODY) is a frequently misdiagnosed type of diabetes, which is characterized by early onset, autosomal dominant inheritance, and absence of insulin dependence. The most frequent subtypes are due to mutations of the GCK (MODY 2), HNF1A (MODY 3), and HNF4A (MODY 1) genes. We undertook the first multicenter genetic study of MODY in the Portuguese population. The GCK, HNF1A, and HNF4A genes were sequenced in 46 unrelated patients that had at least two of the three classical clinical criteria for MODY (age at diagnosis, family history, and clinical presentation). The functional consequences of the mutations were predicted by bioinformatics analysis. Mutations were identified in 23 (50%) families. Twelve families had mutations in the GCK gene, eight in the HNF1A gene, and three in the HNF4A gene. These included seven novel mutations (GCK c.494T>C, GCK c.563C>G, HNF1A c.1623G>A, HNF1A c.1729C>G, HNF4A c.68delG, HNF4A c.422G>C, HNF4A c.602A>C). Mutation-positive patients were younger at the time of diagnosis when compared to mutation-negative patients (14.3 vs. 23.0 years, p = 0.011). This study further expands the spectrum of known mutations associated with MODY, and may contribute to a better understanding of this type of diabetes and a more personalized clinical management of affected individuals

Maturity-Onset Diabetes of the Young (MODY) in Portugal: Novel GCK, HNFA1 and HNFA4 Mutations

Maturity-onset diabetes of the young (MODY) is a frequently misdiagnosed type of diabetes, which is characterized by early onset, autosomal dominant inheritance, and absence of insulin dependence. The most frequent subtypes are due to mutations of the GCK (MODY 2), HNF1A (MODY 3), and HNF4A (MODY 1) genes. We undertook the first multicenter genetic study of MODY in the Portuguese population. The GCK, HNF1A, and HNF4A genes were sequenced in 46 unrelated patients that had at least two of the three classical clinical criteria for MODY (age at diagnosis, family history, and clinical presentation). The functional consequences of the mutations were predicted by bioinformatics analysis. Mutations were identified in 23 (50%) families. Twelve families had mutations in the GCK gene, eight in the HNF1A gene, and three in the HNF4A gene. These included seven novel mutations (GCK c.494T>C, GCK c.563C>G, HNF1A c.1623G>A, HNF1A c.1729C>G, HNF4A c.68delG, HNF4A c.422G>C, HNF4A c.602A>C). Mutation-positive patients were younger at the time of diagnosis when compared to mutation-negative patients (14.3 vs. 23.0 years, p = 0.011). This study further expands the spectrum of known mutations associated with MODY, and may contribute to a better understanding of this type of diabetes and a more personalized clinical management of affected individuals