Pharmaceuticals, illicit drugs and their metabolites in fish from Argentina: Implications for protected areas influenced by urbanization

Because an understanding of aquatic bioaccumulation of human pharmaceuticals in Latin America is limited, this area was recently identified as a priority environmental quality research need. We examined bioaccumulation of twenty-seven pharmaceuticals, illicit drugs and their metabolites in muscle, liver and gills of multiple fish species (Rhamdia quelen, Hypostomus commersoni, Hoplias lacerdae, Prochilodus lineatus) from an urban river receiving wastewater discharges (Paraná) and a lotic system (Acaraguá) without direct wastewater sources, which runs through a protected area. All samples were analyzed using isotope-dilution liquid chromatography-tandem mass spectrometry. Caffeine, which was detected up to 13 μg/kg, and antibiotics were consistently detected in all fish. Among antibiotics, erythromycin was ubiquitous (0.7–5.6 μg/kg) but its tissue concentrations were lower than levels of sulfamethoxazole, sulfathiazole and trimethoprim (0.9–5.5 μg/kg), which are used in human medicine, aquaculture and livestock. Erythromycin bioaccumulation in fish is reported here from Argentina for the first time, though levels of antibiotics in edible muscles of these species were lower than the maximum residue limits for human consumption. We observed norfluoxetine, the primary active metabolite of the antidepressant fluoxetine, ranging from 1.1–9.1 μg/kg in fish. We further identified benzoylecgonine, a primary metabolite of cocaine, in fish from both study systems, representing the first observation an illicit drug or associated metabolites bioaccumulation in aquatic life from Argentina. Interestingly, high pharmaceutical levels were observed in fish from the Acaraguá river suggesting their transport into the protected area, from the surrounding lands. Though fish from the Paraná river were sampled near WWTP discharges, pharmaceutical concentrations may have been reduced by hydrological and other environmental conditions, and biological differences among species. These findings, which observed bioaccumulation of select pharmaceuticals, their metabolites and illicit drugs in wild fish sampled inside a protected area, highlight the importance of developing an advanced understanding of urban influences on inland protected watersheds.Fil: Ondarza, Paola Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Haddad, Samuel P.. Baylor University; Estados UnidosFil: Avigliano, Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; ArgentinaFil: Miglioranza, Karina Silvia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Brooks, Bryan W.. Baylor University; Estados Unido

Glioblastoma cell fate is differentially regulated by the microenvironments of the tumor bulk and infiltrative margin

Glioblastoma (GBM) recurrence originates from invasive margin cells that escape surgical debulking, but to what extent these cells resemble their bulk counterparts remains unclear. Here, we generated three immunocompetent somatic GBM mouse models, driven by subtype-associated mutations, to compare matched bulk and margin cells. We find that, regardless of mutations, tumors converge on common sets of neural-like cellular states. However, bulk and margin have distinct biology. Injury-like programs associated with immune infiltration dominate in the bulk, leading to the generation of lowly proliferative injured neural progenitor-like cells (iNPCs). iNPCs account for a significant proportion of dormant GBM cells and are induced by interferon signaling within T cell niches. In contrast, developmental-like trajectories are favored within the immune-cold margin microenvironment resulting in differentiation toward invasive astrocyte-like cells. These findings suggest that the regional tumor microenvironment dominantly controls GBM cell fate and biological vulnerabilities identified in the bulk may not extend to the margin residuum

Net positive outcomes for nature

Much research and policy effort is being expended on seeking ways to conserve living nature while enabling the economic and social development needed to increase global equity and end poverty. We propose that this will only be possible if the language of policy shifts away from setting conservation targets that focus on avoiding losses and towards developing processes that consider net outcomes for biodiversity

Costameric integrin and sarcoglycan protein levels are altered in a Drosophila model for Limb-girdle muscular dystrophy type 2H

Mutations in two different domains of the ubiquitously expressed TRIM32 protein give rise to two clinically separate diseases, one of which is Limb-girdle muscular dystrophy type 2H (LGMD2H). Uncovering the muscle-specific role of TRIM32 in LGMD2H pathogenesis has proven difficult, as neurogenic phenotypes, independent of LGMD2H pathology, are present in TRIM32 KO mice. We previously established a platform to study LGMD2H pathogenesis using Drosophila melanogaster as a model. Here we show that LGMD2H disease-causing mutations in the NHL domain are molecularly and structurally conserved between fly and human TRIM32. Furthermore, transgenic expression of a subset of myopathic alleles (R394H, D487N, and 520fs) induce myofibril abnormalities, altered nuclear morphology, and reduced TRIM32 protein levels, mimicking phenotypes in patients afflicted with LGMD2H. Intriguingly, we also report for the first time that the protein levels of βPS integrin and sarcoglycan δ, both core components of costameres, are elevated in TRIM32 disease-causing alleles. Similarly, murine myoblasts overexpressing a catalytically inactive TRIM32 mutant aberrantly accumulate α- and β-dystroglycan and α-sarcoglycan. We speculate that the stoichiometric loss of costamere components disrupts costamere complexes to promote muscle degeneration

The “Narratives” fMRI dataset for evaluating models of naturalistic language comprehension

The “Narratives” collection aggregates a variety of functional MRI datasets collected while human subjects listened to naturalistic spoken stories. The current release includes 345 subjects, 891 functional scans, and 27 diverse stories of varying duration totaling ~4.6 hours of unique stimuli (~43,000 words). This data collection is well-suited for naturalistic neuroimaging analysis, and is intended to serve as a benchmark for models of language and narrative comprehension. We provide standardized MRI data accompanied by rich metadata, preprocessed versions of the data ready for immediate use, and the spoken story stimuli with time-stamped phoneme- and word-level transcripts. All code and data are publicly available with full provenance in keeping with current best practices in transparent and reproducible neuroimaging

Modern microwave methods in solid state inorganic materials chemistry: from fundamentals to manufacturing

No abstract available

CYP2A6 metabolism in the development of smoking behaviors in young adults

Cytochrome P450 2A6 (CYP2A6) encodes the enzyme responsible for the majority of nicotine metabolism. Previous studies support that slow metabolizers smoke fewer cigarettes once nicotine dependent but provide conflicting results on the role of CYP2A6 in the development of dependence. By focusing on the critical period of young adulthood, this study examines the relationship of CYP2A6 variation and smoking milestones. A total of 1209 European American young adults enrolled in the Collaborative Study on the Genetics of Alcoholism were genotyped for CYP2A6 variants to calculate a previously well-validated metric that estimates nicotine metabolism. This metric was not associated with the transition from never smoking to smoking initiation nor with the transition from initiation to daily smoking (P > 0.4). But among young adults who had become daily smokers (n = 506), decreased metabolism was associated with increased risk of nicotine dependence (P = 0.03) (defined as Fagerström Test for Nicotine Dependence score ≥4). This finding was replicated in the Collaborative Genetic Study of Nicotine Dependence with 335 young adult daily smokers (P = 0.02). Secondary meta-analysis indicated that slow metabolizers had a 53 percent increased odds (OR = 1.53, 95 percent CI 1.11-2.11, P = 0.009) of developing nicotine dependence compared with normal metabolizers. Furthermore, secondary analyses examining four-level response of time to first cigarette after waking (>60, 31-60, 6-30, ≤5 minutes) demonstrated a robust effect of the metabolism metric in Collaborative Study on the Genetics of Alcoholism (P = 0.03) and Collaborative Genetic Study of Nicotine Dependence (P = 0.004), illustrating the important role of this measure of dependence. These findings highlight the complex role of CYP2A6 variation across different developmental stages of smoking behaviors

Rethinking Measures of Democracy and Welfare State Universalism: Lessons from Subnational Research

Democracy and the welfare state are two of the most extensively studied concepts and themes in the field of comparative politics. Debate about how to best measure the two concepts has failed to contemplate the extent to which political and social rights are uniformly present across distinct regions of the national territory, despite the presence of substantial subnational research that underscores wide variation inside countries. We argue that this omission hampers our understanding of the two phenomena and we propose a new measure of democracy and healthcare unversalism, which we call the Adjusted Measures of Democracy and Welfare Universalism. The new measures integrate territorial inequality into existing national-level indicators, providing a more accurate picture of country performance and opening the door to new, multi-level theory building