Wastewater Surveillance of SARS-CoV-2 Genomic Populations on a Country-wide Scale Through Targeted Sequencing

SARS-CoV-2 surveillance of viral populations in wastewater samples is recognized as a useful tool for monitoring epidemic waves and boosting health preparedness. Next generation sequencing of viral RNA isolated from wastewater is a convenient and cost-effective strategy to understand the molecular epidemiology of SARS-CoV-2 and provide insights on the population dynamics of viral variants at the community level. However, in low- and middle-income countries, isolated groups have performed wastewater monitoring and data has not been extensively shared in the scientific community. Here we report the results of monitoring the co-circulation and abundance of variants of concern (VOCs) of SARS-CoV-2 in Uruguay, a small country in Latin America, between November 2020—July 2021 using wastewater surveillance. RNA isolated from wastewater was characterized by targeted sequencing of the Receptor Binding Domain region within the spike gene. Two computational approaches were used to track the viral variants. The results of the wastewater analysis showed the transition in the overall predominance of viral variants in wastewater from No-VOCs to successive VOCs, in agreement with clinical surveillance from sequencing of nasal swabs. The mutations K417T, E484K and N501Y, that characterize the Gamma VOC, were detected as early as December 2020, several weeks before the first clinical case was reported. Interestingly, a non-synonymous mutation described in the Delta VOC, L452R, was detected at a very low frequency since April 2021 when using a recently described sequence analysis tool (SAM Refiner). Wastewater NGS-based surveillance of SARS-CoV-2 is a reliable and complementary tool for monitoring the introduction and prevalence of VOCs at a community level allowing early public health decisions. This approach allows the tracking of symptomatic and asymptomatic individuals, who are generally under-reported in countries with limited clinical testing capacity. Our results suggests that wastewater-based epidemiology can contribute to improving public health responses in low- and middle-income countries

Tobacco use during pregnancy among native and migrant women in Portugal. Results from the bambino study

Tobacco use is a major modifiable risk factor of adverse maternal and fetal health outcomes. Being a migrant has been associated with lower risk of smoking during pregnancy. However, it remains a matter of debate whether such association could be explained by other socio-demographic characteristics or whether such effect remains or increases according to the length of stay in the host country. This study examined the differences in maternal smoking prevalence between native, long-term and recent migrant women in Portugal. METHODS: This study was derived from baMBINO, a national project grounded on 32 public maternity units in mainland Portugal aiming to investigate the differences in perinatal healthcare and outcomes among migrant and native women. Recruitment took place during admission for delivery, inviting both native and foreign-born women. Participants included in this analysis (n=1107) were classified according to their country of birth and length of stay in Portugal into: native (Portuguese-born), recent migrant (foreign-born women who spent 10 years or less in Portugal), and long-term migrants (foreign-born women who spent more than 10 years in Portugal). Logistic regression model was fitted to estimate the association between the aforementioned migration statuses and having or not smoked tobacco during pregnancy, taking into account women’s age, parity, marital status, level of education, family income, country of origin of women’s parents and gestational age at the first prenatal care visit. Adjusted odds-ratio (OR) and respective 95% confidence interval (95%CI) were obtained. RESULTS: A little over half of the study participants were foreign-born and almost 60% of those were recent migrants. Tobacco smoking during pregnancy was evidently more prevalent among native women than among long-term or recent migrant women (14% vs. 8% and 4% respectively; p<0.001). Compared to native women, both long-term and recent migrant women were more likely to be unmarried, have a family income lower than 1000€, and have their first prenatal visit after 12 weeks of gestation. Long-term migrants were more likely to have Portuguese-born parents than recent migrants (26.0% vs. 2.5%; p<0.001). According to the multivariate regression model, having a higher educational level was significantly associated with not smoking during pregnancy (secondary school: OR=0.38; 95%CI:0.23–0.62; postgraduate education: OR=0.18; 95%CI:0.09–0.35), opposed to women who have 9 or less years of education. However no association was observed between smoking during pregnancy and maternal age (OR=1.10; 95%CI:0.60–2.01 and OR=0.95; 95%CI:0.57–1.58 for women aged less than 25 and 35 or more years, respectively, in comparison with women aged 25-34 years), family income (OR=1.30; 95%CI:0.77–2.18 for women with higher income), parity (OR=0.68; 95%CI:0.43–1.09 for multiparous in comparison with primiparous women), gestational age at first prenatal visit (OR=1.12, 95%CI:0.59–2.11 for women having their first prenatal visit after 12 weeks), having a foreign-born parent (yes vs no: OR=0.83; 95%CI:0.43–1.63) and marital status (single vs married women: OR=0.76; 95%CI:0.46–1.24). Smoking during pregnancy was significantly less frequent in recent and long-term migrants (OR=0.24; 95%CI:0.10-0.57, OR=0.52, 95%CI: 0.25-1.09 respectively) compared with native Portuguese women. CONCLUSION: Results of this study demonstrated significant disparities in the prevalence of maternal smoking during pregnancy according to the women’s place of birth and duration of stay in Portugal. Native-born women had a higher risk of smoking during pregnancy than foreign-born women. The increase in the duration of stay in the host country seemed to have a negative effect on maternal smoking of migrants in Portugal. Smoking cessation health strategies in pregnant women in Portugal need to be improved by taking into account the mentioned variations in smoking behaviors.info:eu-repo/semantics/publishedVersio

Inhibiting HER3 Hyperphosphorylation in HER2‐Overexpressing Breast Cancer through Multimodal Therapy with Branched Gold Nanoshells

Treatment failure in breast cancers overexpressing human epidermal growth factor receptor 2 (HER2) is associated mainly to the upregulation of human epidermal growth factor receptor 3 (HER3) oncoprotein linked to chemoresitence. Therefore, to increase patient survival, here a multimodal theranostic nanoplatform targeting both HER2 and HER3 is developed. This consists of doxorubicin-loaded branched gold nanoshells functionalized with the near-infrared (NIR) fluorescent dye indocyanine green, a small interfering RNA (siRNA) against HER3, and the HER2-specific antibody Transtuzumab, able to provide a combined therapeutic outcome (chemo- and photothermal activities, RNA silencing, and immune response). In vitro assays in HER2+/HER3+ SKBR-3 breast cancer cells have shown an effective silencing of HER3 by the released siRNA and an inhibition of HER2 oncoproteins provided by Trastuzumab, along with a decrease of the serine/threonine protein kinase Akt (p-AKT) typically associated with cell survival and proliferation, which helps to overcome doxorubicin chemoresistance. Conversely, adding the NIR light therapy, an increment in p-AKT concentration is observed, although HER2/HER3 inhibitions are maintained for 72 h. Finally, in vivo studies in a tumor-bearing mice model display a significant progressively decrease of the tumor volume after nanoparticle administration and subsequent NIR light irradiation, confirming the potential efficacy of the hybrid nanocarrierE.V.-A. and I.G.-C. contributed equally to this work. This work was sup ported by the Agencia Estatal de Investigación (AEI) through Project No. PID2019-109517RB-I00) and from the Xunta de Galicia, Project No. ED431C2022/18. European Regional Development Funds are also ac knowledged. A.A.-M. and P.T. also thank the International Scientific Part nership Program ISSP at King Saud University for additional funding of this research through Grant No. ISPP-144. This work also received fi nancial support from the ISCIII, Ministerio de Economía y Competitivi dad (Grant No. PI15/01129; J.A.C.), and the AEI (Grant No. PID2020- 113501RB-I00; J.A.C.). I.-G.C. thanks for financial support through Grant No. PRE/2011/131, and the Centro Singular de Investigación de Galicia accreditation Grant No. 2016–2019 ED431G/05)S

Phosphorus Is Associated with Coronary Artery Disease in Patients with Preserved Renal Function

High serum phosphorus levels have been associated with mortality and cardiovascular events in patients with chronic kidney disease and in the general population. In addition, high phosphorus levels have been shown to induce vascular calcification and endothelial dysfunction in vitro. The aim of this study was to evaluate the relation of phosphorus and coronary calcification and atherosclerosis in the setting of normal renal function. This was a cross-sectional study involving 290 patients with suspected coronary artery disease and undergoing elective coronary angiography, with a creatinine clearance >60 ml/min/1.73 m2. Coronary artery obstruction was assessed by the Friesinger score and coronary artery calcification by multislice computed tomography. Serum phosphorus was higher in patients with an Agatston score >10 than in those with an Agatston score ≤10 (3.63±0.55 versus 3.49±0.52 mg/dl; p = 0.02). In the patients with Friesinger scores >4, serum phosphorus was higher (3.6±0.5 versus 3.5±0.6 mg/dl, p = 0.04) and median intact fibroblast growth factor 23 was lower (40.3 pg/ml versus 45.7 pg/ml, p = 0.01). Each 0.1-mg/dl higher serum phosphate was associated with a 7.4% higher odds of having a Friesinger score >4 (p = 0.03) and a 6.1% greater risk of having an Agatston score >10 (p = 0.01). Fibroblast growth factor 23 was a negative predictor of Friesinger score (p = 0.002). In conclusion, phosphorus is positively associated with coronary artery calcification and obstruction in patients with suspected coronary artery disease and preserved renal function

Prediction of crop coefficients from fraction of ground cover and height. Background and validation using ground and remote sensing data

ReviewThe current study aims at reviewing and providing advances on methods for estimating and applying crop coefficients from observations of ground cover and vegetation height. The review first focuses on the relationships between single Kc and basal Kcb and various parameters including the fraction of ground covered by the canopy (fc), the leaf area index (LAI), the fraction of ground shaded by the canopy (fshad), the fraction of intercepted light (flight) and intercepted photosynthetic active radiation (fIPAR). These relationships were first studied in the 1970’s, for annual crops, and later, in the last decennia, for tree and vine perennials. Research has now provided a variety of methods to observe and measure fc and height (h) using both ground and remote sensing tools, which has favored the further development of Kc related functions. In the past, these relationships were not used predictively but to support the understanding of dynamics of Kc and Kcb in relation to the processes of evapotranspiration or transpiration, inclusive of the role of soil evaporation. Later, the approach proposed by Allen and Pereira (2009), the A&P approach, used fc and height (h) or LAI data to define a crop density coefficient that was used to directly estimate Kc and Kcb values for a variety of annual and perennial crops in both research and practice. It is opportune to review the A&P method in the context of a variety of studies that have derived Kc and Kcb values from field measured data with simultaneously observed ground cover fc and height. Applications used to test the approach include various tree and vine crops (olive, pear, and lemon orchards and vineyards), vegetable crops (pea, onion and tomato crops), field crops (barley, wheat, maize, sunflower, canola, cotton and soybean crops), as well as a grassland and a Bermudagrass pasture. Comparisons of Kcb values computed with the A &P method produced regression coefficients close to 1.0 and coefficients of determination≥0.90, except for orchards. Results indicate that the A&P approach can produce estimates of potential Kcb, using vegetation characteristics alone, within reasonable or acceptable error, and are useful for refining Kcb for conditions of plant spacing, size and density that differ from standard values. The comparisons provide parameters appropriate to applications for the tested crops. In addition, the A&P approach was applied with remotely sensed fc data for a variety of crops in California using the Satellite Irrigation Management Support (SIMS) framework. Daily SIMS crop ET (ETc-SIMS) produced Kcb values using the FAO56 and A&P approaches. Combination of satellite derived fc and Kcb values with ETo data from Spatial CIMIS (California Irrigation Management Information System) produced ET estimates that were compared with daily actual crop ET derived from energy balance calculations from micrometeorological instrumentation (ETc EB).Results produced coefficients of regression of 1.05 for field crops and 1.08 for woody crops, and R2 values of 0.81 and 0.91, respectively. These values suggest that daily ETc-SIMS -based ET can be accurately estimated within reasonable error and that the A&P approach is appropriate to support that estimation. It is likely that accuracy can be improved via progress in remote sensing determination of fc. Tabulated Kcb results and calculation parameters are presented in a companion paper in this Special Issueinfo:eu-repo/semantics/publishedVersio

SmCL3, a Gastrodermal Cysteine Protease of the Human Blood Fluke Schistosoma mansoni

Parasitic infection caused by blood flukes of the genus Schistosoma is a major global health problem. More than 200 million people are infected. Identifying and characterizing the constituent enzymes of the parasite's biochemical pathways should reveal opportunities for developing new therapies (i.e., vaccines, drugs). Schistosomes feed on host blood, and a number of proteolytic enzymes (proteases) contribute to this process. We have identified and characterized a new protease, SmCL3 (for Schistosoma mansoni cathepsin L3), that is found within the gut tissue of the parasite. We have employed various biochemical and molecular biological methods and sequence similarity analyses to characterize SmCL3 and obtain insights into its possible functions in the parasite, as well as its evolutionary position among cathepsin L proteases in general. SmCL3 hydrolyzes major host blood proteins (serum albumin and hemoglobin) and is expressed in parasite life stages infecting the mammalian host. Enzyme substrate specificity detected by positional scanning-synthetic combinatorial library was confirmed by molecular modeling. A sequence analysis placed SmCL3 to the cluster of other cathepsins L in accordance with previous phylogenetic analyses

The PREDICTS database: A global database of how local terrestrial biodiversity responds to human impacts

© 2014 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd. Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015. The collation of biodiversity datasets with broad taxonomic and biogeographic extents is necessary to understand historical declines and to project - and hopefully avert - future declines. We describe a newly collated database of more than 1.6 million biodiversity measurements from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world

Comparative genomics of the major parasitic worms

Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we report a broad comparative study of 81 genomes of parasitic and non-parasitic worms. We have identified gene family births and hundreds of expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We reveal extensive lineage-specific differences in core metabolism and protein families historically targeted for drug development. From an in silico screen, we have identified and prioritized new potential drug targets and compounds for testing. This comparative genomics resource provides a much-needed boost for the research community to understand and combat parasitic worms