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Background Cell-based assays for neuromyelitis optica (NMO) diagnosis are the most sensitive and specific methods to detect anti-aquaporin 4 (AQP4) antibodies in serum, but some improvements in their quantitative and specificity capacities would be desirable. Thus the aim of the present work was to develop a sensitive quantitative method for detection of anti- AQP4 antibodies that allows clear diagnosis of NMO and distinction of false labeling produced by natalizumab treatment. Methods Sera from 167 individuals, patients diagnosed with NMO (16), multiple sclerosis (85), optic neuritis (24), idiopathic myelitis (21), or other neurological disorders (13) and healthy controls (8), were used as the primary antibody in an immunofluorescence assay on HEK cells transfected with the M23 isoform of human AQP4 fused with enhanced green fluorescent protein. Cells used were freshly transfected or stored frozen and then thawed just before adding the serum. Results Microscopic observation and fluorescence quantification produced similar results in fresh and frozen samples. Serum samples from patients diagnosed with NMO were 100% positive for anti-AQP4 antibodies, while all the other sera were negative. Using serum from patients treated with natalizumab, a small and unspecific fluorescent signal was produced from all HEK cells, regardless of AQP4 expression. Conclusions Our cell-based double-label fluorescence immunoassay protocol significantly increases the signal specificity and reduces false diagnosis of NMO patients, especially in those receiving natalizumab treatment. Frozen pretreated cells allow faster detection of anti-AQP4 antibodies. [ABSTRACT FROM AUTHOR]

Background: This paper describes a methodology for comparing the effects of an eduentertainment strategy involving a music concert, and a participatory class experience involving the description and making of a healthy breakfast, as educational vehicles for delivering obesity-preventing/cardiovascular health messages to children aged 7-8 years. Methods/design: This study will involve a cluster-randomised trial with blinded assessment. The study subjects will be children aged 7-8 years of both sexes attending public primary schools in the Madrid Region. The participating schools (n=30) will be randomly assigned to one of two groups: 1) Group MC, in which the children will attend a music concert that delivers obesity-preventing/cardiovascular health messages, or 2) Group HB, in which the children will attend a participatory class providing the same information but involving the description and making of a healthy breakfast. The main outcome measured will be the increase in the number of correct answers scored on a knowledge questionnaire and in an attitudes test administered before and after the above interventions. The secondary outcome recorded will be the reduction in BMI percentile among children deemed overweight/obese prior to the interventions. The required sample size (number of children) was calculated for a comparison of proportions with an α of 0.05 and a β of 0.20, assuming that the Group MC subjects would show values for the measured variables at least 10% higher than those recorded for the subjects of Group HB. Corrections were made for the design effect and assuming a loss to follow-up of 10%. The maximum sample size required will be 2107 children. Data will be analysed using summary measurements for each cluster, both for making estimates and for hypothesis testing. All analyses will be made on an intention-to-treat basis. Discussion: The intervention providing the best results could be recommended as part of health education for young schoolchildren. Trial registration: Clinicaltrials.gov: NCT01418872 [ABSTRACT FROM AUTHOR]

Copyright of Revista Iberoamericana de Ingeniería Mecánica is the property of Editorial UNED and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

With the advent of the new opioids in the anesthetic drug market, we may think that we have molecules available to replace the legendary fentanyl. However, studying its pharmacodynamic and pharmacokinetic properties, fentanyl can still be appropriately used to take advantage of its excellent analgesia and safety, comparable to that of other opioids when administered in accordance with pharmacokinetic models. We must not forget however that several drugs frequently used during anesthesia (midazolam, dexametasone, prednisolone, ketamin, etc.), may impact the metabolism of fentanyl on account of the cytochrome P450 3A4 enzyme. The knowledge and judicious application of pharmacokinetic models serve to estimate plasma concentrations in order to ensure the best analgesic conditions associated to synergies with the frequent use of hypnotics such as propofol and desfluorane. Fentanyl is best used for specific indications such as extended surgical procedures (over 120 minutes) or procedures that stimulate the patient's pain perception. [ABSTRACT FROM AUTHOR]

Copyright of Revista Umbral Científico is the property of Universidad Manuela Beltran and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The conflict between the Catholic church and the State, that in 1926 turned into a violent armed conflict, generated a written debate where the factions at war extended the struggle to the arena of public opinion. This debate had a double effect. In one way, the public sphere, that got stronger since the 1910 Revolution, lived a temporal efervescence; on the other hand, the ebullition of public opinion, provoked a reaction of the posrevolutionary State, contrary to plurality. This article explores the possibility of applying the public sphere's concept to the Mexican reality. Moreover, it analyzes the contents of the public debate, where both the arguments of the Catholic sector and those of the revolutionary vanguard in office were expressed. This last period of plurality brought about a strong wave of censorship, that propitiated the weakening of the Mexican public sphere during the following decades of the 20th century. [ABSTRACT FROM AUTHOR]

Conjugal transfer of the F-like plasmid R100 occurs at higher frequencies in the absence of DNA adenine methylation. Lower levels of R100-encoded FinP RNA were found in a Dam-- host, suggesting that Dam methylation regulates FinP RNA synthesis. Lack of the leucine-responsive regulatory protein (Lrp) causes a decrease in R100 plasmid transfer, indicating that Lrp is an activator of R100- mediated conjugation. Hence, host-encoded regulators previously described for the Salmonella virulence plasmid (pSLT) seem to play analogous roles in R100. Repression of conjugal transfer in rich medium is an additional trait shared by R100 and pSLT. DNA sequence comparisons in regulatory loci support the view that R100 and pSLT are closely related. [ABSTRACT FROM AUTHOR]

Copyright of Agora de Enfermeria is the property of Agora de Enfermeria SRL and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Agora de Enfermeria is the property of Agora de Enfermeria SRL and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aurora A is a serine/threonine kinase whose role in cell cycle progression and tumour generation has been widely studied. Recent work has revealed an unexpected function for Aurora A during CD4+ T cell activation and, also, in graft versus host disease development. However, it remains unknown whether Aurora A is involved in CD8+ T cell effector function and in cytotoxic T lymphocyte-mediated antiviral response. Here, we show that Aurora A chemical inhibition leads to an impairment of both the peptide-specific cytotoxicity and the degranulation activity of CD8+ T cells. This finding was similarly proven for both mice and human CD8+ CTL activity. As a result of Aurora A blockade, we detected a reduction in the expression induced by T cell activation of genes classically related to the effector function of cytotoxic T lymphocytes such as granzyme B or perforin1. Finally, we have found that Aurora A is necessary for CD8+ T cell-mediated antiviral response, in an in vivo model of vaccinia virus infection. Thus, we can conclude that Aurora A activity is, indeed, needed for the proper effector function of cytotoxic T lymphocytes and for their activity against viral threats. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 is responsible for the development of coronavirus disease 2019 (COVID-19) in infected individuals, who can either exhibit mild symptoms or progress toward a life-threatening acute respiratory distress syndrome (ARDS). Exacerbated inflammation and dysregulated immune responses involving T and myeloid cells occur in COVID-19 patients with severe clinical progression. However, the differential contribution of specific subsets of dendritic cells and monocytes to ARDS is still poorly understood. In addition, the role of CD8+ T cells present in the lung of COVID-19 patients and relevant for viral control has not been characterized. Here, we have studied the frequencies and activation profiles of dendritic cells and monocytes present in the blood and lung of COVID-19 patients with different clinical severity in comparison with healthy individuals. Furthermore, these subpopulations and their association with antiviral effector CD8+ T cell subsets were also characterized in lung infiltrates from critical COVID-19 patients. Our results indicate that inflammatory transitional and nonclassical monocytes and CD1c+ conventional dendritic cells preferentially migrate from blood to lungs in patients with severe COVID-19. Thus, this study increases the knowledge of specific myeloid subsets involved in the pathogenesis of COVID-19 disease and could be useful for the design of therapeutic strategies for fighting SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim We tested the hypothesis that shredder detritivores, a key trophic guild in stream ecosystems, are more diverse at higher latitudes, which has important ecological implications in the face of potential biodiversity losses that are expected as a result of climate change. We also explored the dependence of local shredder diversity on the regional species pool across latitudes, and examined the influence of environmental factors on shredder diversity. Location World-wide (156 sites from 17 regions located in all inhabited continents at latitudes ranging from 67° N to 41° S). Methods We used linear regression to examine the latitudinal variation in shredder diversity at different spatial scales: alpha (α), gamma (γ) and beta (β) diversity. We also explored the effect of γ-diversity on α-diversity across latitudes with regression analysis, and the possible influence of local environmental factors on shredder diversity with simple correlations. Results Alpha diversity increased with latitude, while γ- and β-diversity showed no clear latitudinal pattern. Temperate sites showed a linear relationship between γ- and α-diversity; in contrast, tropical sites showed evidence of local species saturation, which may explain why the latitudinal gradient in α-diversity is not accompanied by a gradient in γ-diversity. Alpha diversity was related to several local habitat characteristics, but γ- and β-diversity were not related to any of the environmental factors measured. Main conclusions Our results indicate that global patterns of shredder diversity are complex and depend on spatial scale. However, we can draw several conclusions that have important ecological implications. Alpha diversity is limited at tropical sites by local factors, implying a higher risk of loss of key species or the whole shredder guild (the latter implying the loss of trophic diversity). Even if regional species pools are not particularly species poor in the tropics, colonization from adjacent sites may be limited. Moreover, many shredder species belong to cool-adapted taxa that may be close to their thermal maxima in the tropics, which makes them more vulnerable to climate warming. Our results suggest that tropical streams require specific scientific attention and conservation efforts to prevent loss of shredder biodiversity and serious alteration of ecosystem processes. [ABSTRACT FROM AUTHOR]

Most hypotheses explaining the general gradient of higher diversity toward the equator are implicit or explicit about greater species packing in the tropics. However, global patterns of diversity within guilds, including trophic guilds (i.e., groups of organisms that use similar food resources), are poorly known. We explored global diversity patterns of a key trophic guild in stream ecosystems, the detritivore shredders. This was motivated by the fundamental ecological role of shredders as decomposers of leaf litter and by some records pointing to low shredder diversity and abundance in the tropics, which contrasts with diversity patterns of most major taxa for which broad-scale latitudinal patterns haven been examined. Given this evidence, we hypothesized that shredders are more abundant and diverse in temperate than in tropical streams, and that this pattern is related to the higher temperatures and lower availability of high-quality leaf litter in the tropics. Our comprehensive global survey (129 stream sites from 14 regions on six continents) corroborated the expected latitudinal pattern and showed that shredder distribution (abundance, diversity and assemblage composition) was explained by a combination of factors, including water temperature (some taxa were restricted to cool waters) and biogeography (some taxa were more diverse in particular biogeographic realms). In contrast to our hypothesis, shredder diversity was unrelated to leaf toughness, but it was inversely related to litter diversity. Our findings markedly contrast with global trends of diversity for most taxa, and with the general rule of higher consumer diversity at higher levels of resource diversity. Moreover, they highlight the emerging role of temperature in understanding global patterns of diversity, which is of great relevance in the face of projected global warming. [ABSTRACT FROM AUTHOR]

Protein-protein interactions (PPIs) are at the core of all key biological processes. However, the complexity of the structural features that determine PPIs makes their design challenging. We present BindCraft, an open-source and automated pipeline for de novo protein binder design with experimental success rates of 10-100%. BindCraft leverages the weights of AlphaFold2 1 to generate binders with nanomolar affinity without the need for high-throughput screening or experimental optimization, even in the absence of known binding sites. We successfully designed binders against a diverse set of challenging targets, including cell-surface receptors, common allergens, de novo designed proteins, and multi-domain nucleases, such as CRISPR-Cas9. We showcase the functional and therapeutic potential of designed binders by reducing IgE binding to birch allergen in patient-derived samples, modulating Cas9 gene editing activity, and reducing the cytotoxicity of a foodborne bacterial enterotoxin. Lastly, we utilize cell surface receptor-specific binders to redirect AAV capsids for targeted gene delivery. This work represents a significant advancement towards a "one design-one binder" approach in computational design, with immense potential in therapeutics, diagnostics, and biotechnology.

Cellular therapy using genetically modified T lymphocytes expressing synthetic receptors, known as CAR (Chimeric Antigen Receptor), has revolutionized the treatment of certain hematologic malignancies. This success has led to exploring the same approach in the treatment of severe autoimmune diseases refractory to conventional therapies. Initial results in systemic lupus erythematosus have shown complete remissions that appear to persist over time. Consequently, there is a growing number of ongoing clinical trials. In this review, we discuss the rationale behind the use of CAR-T therapies, the targeted autoimmune diseases, and the associated risks., Competing Interests: Le Pr Y. D. Müller est inventeur d’une licence sur les CAR-T (US 2023/0340068 A1) et responsable de site d’une étude CAR-T (NCT05798117). Les autres auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Objectives: Intradermal skin test (IDT) with mRNA vaccines may represent a simple, reliable, and affordable tool to measure T cell response in immunocompromised patients who failed to mount serological responses following vaccination with mRNA covid-19 vaccines., Methods: We compared anti-SARS-CoV-2 antibodies and cellular responses in vaccinated immunocompromised patients (n = 58), healthy seronegative naive controls (NC, n = 8), and healthy seropositive vaccinated controls (VC, n = 32) by Luminex, spike-induced IFN-γ Elispot and an IDT. A skin biopsy 24 h after IDT and single-cell RNAseq was performed in three vaccinated volunteers., Results: Twenty-five percent of seronegative NC had a positive Elispot (2/8) and IDT (1/4), compared to 95% (20/21) and 93% (28/30) in seropositive VC, respectively. Single-cell RNAseq data in the skin of VC showed a predominant mixed population of effector helper and cytotoxic T cells. The TCR repertoire revealed 18/1064 clonotypes with known specificities against SARS-CoV-2, among which six were spike-specific. Seronegative immunocompromised patients with positive Elispot and IDT were in 83% (5/6) treated with B cell-depleting reagents, while those with negative IDT were all transplant recipients., Conclusions: Our results indicate that delayed local reaction to IDT reflects vaccine-induced T-cell immunity opening new perspectives to monitor seronegative patients and elderly populations with waning immunity., Competing Interests: Declaration of Competing Interest Dr Pantaleo and Dr Fenwick report having a patent pending (application No. EP20205298.1) for a SARS-Cov2 neutralization assay. Dr Gottardo has received consulting income from Takeda, Ozette Technologies and declares ownership in Ozette Technologies. The research was conducted without any other commercial or financial relationships that could be construed as a potential conflict of interest to this study., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Although many demographic and clinical predictors of mortality have been studied in relation to COVID-19, little has been reported about the prognostic utility of inflammatory biomarkers., Material and Methods: Retrospective cohort study. All patients with laboratory-confirmed COVID-19 treated in a hospital emergency department were included consecutively if baseline measurements of the following biomarkers were on record: lymphocyte counts, neutrophil-to-lymphocyte ratio NRL, and C-reactive protein (CRP) and procalcitonin (PCT) levels. We analyzed associations between the biomarkers and all-cause 30-day mortality using Cox regression models and dose-response curves., Results: We included 896 patients, 151 (17%) of whom died within 30 days. The median (interquartile range) age was 63 (51-78) years, and 494 (55%) were men. NLR, CRP and PCT levels at ED presentation were higher, while lymphocyte counts were lower, in patients who died compared to those who survived (P .001). The areas under the receiver operating characteristic curves revealed the PCT concentration (0.79; 95% CI, 0.75-0.83) to be a better predictor of 30-day mortality than the lymphocyte count (0.70; 95% CI, 0.65-0.74; P .001), the NLR (0.74; 95% CI, 0.69-0.78; P = .03), or the CRP level (0.72; 95% CI, 0.68-0.76; P .001). The proposed PCT concentration decision points for use in emergency department case management were 0.06 ng/L (negative) and 0.72 ng/L (positive). These cutoffs helped classify risk in 357 patients (40%). Multivariable analysis demonstrated that the PCT concentration had the strongest association with mortality., Conclusion: PCT concentration in the emergency department predicts all-cause 30-day mortality in patients with COVID-19 better than other inflammatory biomarkers.

Introduction: Polyphenols have shown capacity to improve appetite sensation, leading to enhanced control of body weight. However, despite being related with hunger-related hormones, metabolic and mechanism are not well known., Methods: The effectiveness of a nutraceutical composed of extract to Lippia citriodora and Hibiscus sabdarrifa (Lc-Hs) for controlling satiety and hunger was analyzed in a cross-over, placebo-controlled (Pla) clinical intervention. The study was divided in two 60-day periods separated by 30-day length wash-out period. At the end of each period, overweight and obese subjects (n = 33; age = 33.76 ± 12.23; BMI = 28.20 kg/m 2  ± 2.47; fat mass 30.65 ± 8.39%; both sexes were proposed to eat an ad-libitum meal. Meanwhile, appetite sensation was determined by visual analog scales at different times. Moreover, blood extraction was performed to determine biochemical parameters (lipid and glucidic profile and safety parameters) and to evaluate hunger-related hormones (insulin, leptin, ghrelin, adiponectin, GLP-1 and peptide YY)., Results: A decrease in appetite sensation was observed in Lc-Hs treatment, showing higher satiety quotient (Pla = 3.36 ± 2.33%mm/kcal; Lc-Hs = 5.53 ± 2.91%mm/kcal; p < 0.0001). Area under the curve was higher in Pla compared to Lc-Hs during the test, from baseline to minute 240 (240 (Pla 9136.65 ± 2261.46% x min -1 ; Lc-Hs 8279.73 ± 2745.71% x min -1 ; p < 0.014). Energy consumption was lower for subjects treated with Lc-Hs (774.44 ± 247.77 kcal) compared to those treated with Pla (849.52 ± 246.54 kcal) (p < 0.004). Leptin values varied from baseline (Pla 12.36 ± 1.98 ng/mL; Lc-Hs 13.13 ± 1.99 ng/mL) to the end of the study (Pla 12.60 ± 2.02 ng/mL; Lc-Hs 12.06 ± 2.05 ng/mL; p < 0.047). GLP-1 values varied (p < 0.001) in Lc-Hs treatment from baseline (4.34 ± 0.49 ng/mL) to the end of the study (3.23 ± 0.52 ng/mL)., Conclusion: The supplementation with the Lc-Hs extract decreases appetite sensation in overweight and obese population, reducing calorie intake after an ad-libitum meal. Due to variation on hunger-related hormones and the relationship between satiety feeling, it would be interesting to develop future research focused on the variation of the hormones themselves., (© 2021. The Author(s).)

The biosynthetic origins of the structurally related racemic isoxazolidine Papaveraceae alkaloids Setigerumine I, Dactylicapnosinine and Dactylicapnosine have remained elusive since their original isolation over two decades ago. Herein we report the first biosynthetic hypothesis for their formation and, inspired by it, the first synthesis of (±)-Setigerumine I with accompanying computational rationale. Based on the results, these isoxazolidine alkaloids arise from racemizing oxidative rearrangements of prominent isoquinoline alkaloids Noscapine and Hydrastine. The key steps featured in this synthesis are a room temperature Cope elimination and a domino oxidation/inverse-electron demand 1,3-dipolar cycloaddition of an axially chiral, yet configurationally unstable, intermediate. The work opens this previously inaccessible family of natural products for biological studies., (© 2021 Wiley-VCH GmbH.)

The relationship between detritivore diversity and decomposition can provide information on how biogeochemical cycles are affected by ongoing rates of extinction, but such evidence has come mostly from local studies and microcosm experiments. We conducted a globally distributed experiment (38 streams across 23 countries in 6 continents) using standardised methods to test the hypothesis that detritivore diversity enhances litter decomposition in streams, to establish the role of other characteristics of detritivore assemblages (abundance, biomass and body size), and to determine how patterns vary across realms, biomes and climates. We observed a positive relationship between diversity and decomposition, strongest in tropical areas, and a key role of abundance and biomass at higher latitudes. Our results suggest that litter decomposition might be altered by detritivore extinctions, particularly in tropical areas, where detritivore diversity is already relatively low and some environmental stressors particularly prevalent.

The SARS-CoV-2 is responsible for the pandemic COVID-19 in infected individuals, who can either exhibit mild symptoms or progress towards a life-threatening acute respiratory distress syndrome (ARDS). It is known that exacerbated inflammation and dysregulated immune responses involving T and myeloid cells occur in COVID-19 patients with severe clinical progression. However, the differential contribution of specific subsets of dendritic cells and monocytes to ARDS is still poorly understood. In addition, the role of CD8+ T cells present in the lung of COVID-19 patients and relevant for viral control has not been characterized. With the aim to improve the knowledge in this area, we developed a cross-sectional study, in which we have studied the frequencies and activation profiles of dendritic cells and monocytes present in the blood of COVID-19 patients with different clinical severity in comparison with healthy control individuals. Furthermore, these subpopulations and their association with antiviral effector CD8+ T cell subsets were also characterized in lung infiltrates from critical COVID-19 patients. Collectively, our results suggest that inflammatory transitional and non-classical monocytes preferentially migrate from blood to lungs in patients with severe COVID-19. CD1c+ conventional dendritic cells also followed this pattern, whereas CD141+ conventional and CD123hi plasmacytoid dendritic cells were depleted from blood but were absent in the lungs. Thus, this study increases the knowledge on the pathogenesis of COVID-19 disease and could be useful for the design of therapeutic strategies to fight SARS-CoV-2 infection.

Pesticides are important contributors to the global freshwater biodiversity crisis. Among pesticides, neonicotinoids are the best-selling class of agricultural insecticides and are suspected to represent significant risks to freshwater and terrestrial ecosystems worldwide. Despite growing recognition that neonicotinoid impacts may be modified by the presence of additional stressors, there is limited information about their interactions with other agricultural stressors in freshwater ecosystems. We conducted an outdoor pond-mesocosm experiment to investigate the individual and interactive effects of nutrients, fine sediment, and imidacloprid (a neonicotinoid insecticide) inputs on freshwater community structure (density, diversity, and composition of zooplankton and benthic invertebrates) and ecosystem functioning (ecosystem metabolism, primary production, and organic matter decomposition). We hypothesized antagonistic nutrient-imidacloprid, and synergistic sediment-imidacloprid interactions, affecting aquatic invertebrate communities. The three stressors had significant individual and interactive effects on pond ecosystems. The insecticide neutralized the positive effects of nutrient additions on benthic invertebrate richness and mitigated the negative effects of sediment on zooplankton communities (antagonistic interactions). Moreover, we observed compensatory responses of tolerant benthic invertebrates, which resulted in reversal interactions between sediment and imidacloprid. Furthermore, our observations suggest that imidacloprid has the potential to increase net ecosystem production at environmentally relevant concentrations. Our findings support the hypothesis that the impacts of imidacloprid may be modified by other agricultural stressors. This has important implications on a global scale, given the widespread use of these pesticides in intensive agricultural landscapes and the growing body of literature suggesting that traditional pesticide assessment frameworks, based on laboratory toxicity tests alone, may be insufficient to adequately predict effects to complex freshwater ecosystems., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Chlorpyrifos is one of the most widely used agricultural insecticides in the world, but to date there is limited empirical information about its potential to interact with other common agricultural stressors. We conducted a 15-d, community-level, microcosm experiment evaluating individual and combined effects of chlorpyrifos, nutrient enrichment, and sedimentation on stream invertebrate communities (abundance, biomass, richness, size structure, composition) and ecosystem processes (primary productivity and leaf decomposition). We found that sedimentation was the most detrimental stressor, with significant negative impacts on most invertebrate community and ecosystem function variables. Even though chlorpyrifos did not cause significant invertebrate mortality in the microcosms, it still altered ecosystem function by lowering leaf decomposition rates, probably through sublethal inhibition of invertebrate shredders. Furthermore, we observed a significant reversal interaction between chlorpyrifos and sediment for small-sized invertebrates collected in gravel (abundance in sediment × insecticide microcosms was 2.4 times lower than predicted by additivity), as well as an antagonistic interaction with nutrients on invertebrate richness in the same microhabitat (richness in nutrient × insecticide microcosms was 1.6 times higher than predicted by additivity). Our results suggest that chlorpyrifos has the potential to alter freshwater ecosystem function and interact non-additively with other common agricultural stressors. These findings are in keeping with a growing body of research highlighting that multiple stressor interactions and ecosystem processes should be considered when evaluating the impacts of organic toxicants on freshwater ecosystems., (© 2017 by the Ecological Society of America.)

AQP3 has been correlated with higher transport of glycerol, increment of ATP content, and larger proliferation capacity. Recently, we described the gold(III) complex Auphen as a very selective and potent inhibitor of AQP3's glycerol permeability (Pgly ). Here we evaluated Auphen effect on the proliferation of various mammalian cell lines differing in AQP3 expression level: no expression (PC12), moderate (NIH/3T3) or high (A431) endogenous expression, cells stably expressing AQP3 (PC12-AQP3), and human HEK293T cells transiently transfected (HEK-AQP3) for AQP3 expression. Proliferation was evaluated in the absence or presence of Auphen (5 μM) by counting number of viable cells and analyzing 5-bromo-2'-deoxyuridine (BrdU) incorporation. Auphen reduced ≈50% the proliferation in A431 and PC12-AQP3, ≈15% in HEK-AQP3 and had no effect in PC12-wt and NIH/3T3. Strong arrest in the S-G2/M phases of the cell cycle, supported by analysis of cyclins (A, B1, D1, E) levels, was observed in AQP3-expressing cells treated with Auphen. Flow-cytometry of propidium iodide incorporation and measurements of mitochondrial dehydrogenases activity confirmed absence of cytotoxic effect of the drug. Functional studies evidenced ≈50% inhibition of A431 Pgly by Auphen, showing that the compound's antiproliferative effect correlates with its ability to inhibit AQP3 Pgly . Role of Cys-40 on AQP3 permeability blockage by Auphen was confirmed by analyzing the mutated protein (AQP3-Ser-40). Accordingly, cells transfected with mutated AQP3 gained resistance to the antiproliferative effect of Auphen. These results highlight an Auphen inhibitory effect on proliferation of cells expressing AQP3 and suggest a targeted therapeutic effect on carcinomas with large AQP3 expression., (© 2014 Wiley Periodicals, Inc.)

The expansion of the agricultural frontier in Colombia has exerted significant pressure on its aquatic ecosystems during the last few decades. In order to determine the impacts of different agricultural land uses on the biotic and abiotic characteristics of first and second order streams of La Vieja river watershed, we evaluated 21 streams located between 1,060 and 1,534 m asl in the municipalities of Alcalá, Ulloa, and Cartago (Valle del Cauca, Colombia). Seven streams were protected by native vegetation buffers, eight had influence of coffee and plantain crops, and six were influenced by cattle ranching. Habitat conditions, channel dimensions, water quality, and aquatic macroinvertebrates were studied in each stream. Streams draining cattle ranching areas had significantly higher dissolved solids, higher phosphorus, higher alkalinity, higher conductivity, and lower dissolved oxygen than those covered by cropland and forests. Coarse substrates and diversity of flow regimes were significantly higher in cropland and protected streams when compared to streams affected by cattle ranching, whereas the percent of silt and slow currents was significantly higher in the latter. A total of 26,777 macroinvertebrates belonging to 17 orders, 72 families and 95 genera were collected. The most abundant groups were Diptera 62.8%, (Chironomidae 49.6%, Ceratopogonidae 6.7%), Mollusca 18.8% (Hydrobiidae 7.2%, Sphaeriidae 9.6%) and Trichoptera 5.7% (Hydropsychidae 3.7%). The Ephemeroptera, Trichoptera, and Plecoptera orders, known for their low tolerance to habitat perturbation, had high abundance in cropland and forested streams, whereas Diptera and Mollusca were more abundant in those impacted by cattle ranching. Results indicate that streams draining forests and croplands have better physical and biological conditions than those draining pastures, and highlight the need to implement protective measures to restore the latter.