Zooplankton functional diversity in subtropical reservoirs of distinct trophic states (São Paulo state, Brazil).

Studies on functional traits of aquatic communities are useful for understanding the ecosystem dynamics as well as the diversity of ecological niches. Here, we characterize zooplankton functional groups and which limnological factors are responsible to changes in traits. Water samples were collected to evaluate limnological parameters and vertical hauls with plankton net (68 µm) were performed to characterize the community in seven reservoirs (Itupararanga, Atibainha, Salto Grande, Rio Grande, Igaratá, Barra Bonita, and Broa, São Paulo state, Brazil). Each species identified was classified according to a trophic group, reproduction mode, body length, habitat, and feeding habitats. Our results showed a predominance of pelagic suspensory herbivores with cilia (31%) followed by pelagic herbivore suspension filter feeders (17%) and raptorial omnivores (15.38%). The other individuals were categorized as pelagic herbivore suspension with oral device (12.3%), littoral herbivores suspensive with cilia (12.3%), pelagic-sucking herbivores (9.2%), and littoral grazing herbivores (3%). The dominance of herbivores may be influenced by the availability of nutrients, influencing their food sources. The abundance of omnivores engaged in predatory behavior can be attributed to disponible prey, thereby exerting significant repercussions on the organization of biological communities.

Influence of Intravascular Laser Irradiation of Blood (ILIB) on inflammatory cytokines and nitric oxide in vivo: a systematic review.

The use of Intravascular Laser Irradiation of Blood (ILIB) as a treatment or adjunct tool has been used around the world since the 1980s. So that more professionals can deliver benefits to their patients in different areas of health, it is necessary to understand in depth the mechanisms of laser action at the molecular level, for correct indication and success in the treatment. To analyze works that evaluated the influence of ILIB on inflammatory cytokines and nitric oxide (NO) in animals and humans. The literature search was carried out between February and April 2023 in Pubmed, Medline, Web of Science, SciELO, Lilacs database. The risk of bias was assessed using the bias table where the authors performed the analyzes of all articles with the risk of bias domains. The methodology was defined following the PRISMA guidelines (Preferred Systematic Reviews and MetaAnalysis Report). The search retrieved 135 possibly relevant articles. After removing duplicates, according to the eligibility criteria, evaluation of titles and review of abstracts, in the end, 6 articles were included. An increase in anti-inflammatory cytokines, a decrease in pro-inflammatory cytokines and an increase in NO can be observed. The wavelengths used ranged from 660 to 808 nm when using a low intensity laser and when using a VIP light source 480-3400 nm, they also differed in terms of the light emission pattern. ILIB may be a complementary treatment option for patients who have comorbidities that lead to systemic inflammation.

Past environmental changes: using sedimentary photosynthetic pigments to enhance subtropical reservoir management.

The historical impacts of eutrophication processes were investigated in six subtropical reservoirs (São Paulo, Brazil) using a paleolimnological approach. We questioned whether the levels of pigment indicators of algal biomass could provide information about trophic increase and whether carotenoid pigments could offer additional insights. The following proxies were employed: organic matter, total phosphorus, total nitrogen, photosynthetic pigments (by high-performance liquid chromatography), sedimentation rates, and geochronology (by 210 Pb technique). Principal component analysis indicated a gradient of eutrophication. In eutrophic reservoirs (e.g., Rio Grande and Salto Grande), levels of lutein and zeaxanthin increased over time, suggesting growth of Chlorophyta and Cyanobacteria. These pigments were significantly associated with algal biomass, reflecting their participation in phytoplankton composition. In mesotrophic reservoirs, Broa and Itupararanga, increases and significative linear correlations (r > 0.70) between pigments and nutrients are mainly linked to agricultural and urban activities. In the oligotrophic reservoir Igaratá, lower pigment and nutrient levels reflected lesser human impact and good water quality. This study underscores eutrophication's complexity across subtropical reservoirs. Photosynthetic pigments associated with specific algal groups were informative, especially when correlated with nutrient data. The trophic increase, notably in the 1990s, may have been influenced by neoliberal policies. Integrated pigment and geochemical analysis offers a more precise understanding of eutrophication changes and their ties to human factors. Such research can aid environmental monitoring and sustainable policy development.

Optimisation-based modelling for explainable lead discovery in malaria.

BACKGROUND: The search for new antimalarial treatments is urgent due to growing resistance to existing therapies. The Open Source Malaria (OSM) project offers a promising starting point, having extensively screened various compounds for their effectiveness. Further analysis of the chemical space surrounding these compounds could provide the means for innovative drugs. METHODS: We report an optimisation-based method for quantitative structure-activity relationship (QSAR) modelling that provides explainable modelling of ligand activity through a mathematical programming formulation. The methodology is based on piecewise regression principles and offers optimal detection of breakpoint features, efficient allocation of samples into distinct sub-groups based on breakpoint feature values, and insightful regression coefficients. Analysis of OSM antimalarial compounds yields interpretable results through rules generated by the model that reflect the contribution of individual fingerprint fragments in ligand activity prediction. Using knowledge of fragment prioritisation and screening of commercially available compound libraries, potential lead compounds for antimalarials are identified and evaluated experimentally via a Plasmodium falciparum asexual growth inhibition assay (PfGIA) and a human cell cytotoxicity assay. CONCLUSIONS: Three compounds are identified as potential leads for antimalarials using the methodology described above. This work illustrates how explainable predictive models based on mathematical optimisation can pave the way towards more efficient fragment-based lead discovery as applied in malaria.

Beyond scores: A machine learning approach to comparing educational system effectiveness.

Studies comparing large-scale assessment data among educational systems have been an important tool for understanding the differences in how education is delivered worldwide. Many of these studies do not go beyond reporting average student scores in a particular educational system. A more unbiased analysis would avoid the simple use of gross performance and consider educational system contexts. A common approach is to estimate effectiveness by the residuals of parametric linear models. These models rely upon strong assumptions regarding the data-generating process, and are limited to handling extensive datasets. To address this issue, our paper provides a new approach based on machine learning models. The new approach is flexible, allows paired comparison, and is model-independent. An analysis conducted in Brazil verifies the suitability of the method to explore differences in effectiveness between Brazilian educational administrative units at the regional and state levels from 2009 to 2019. Our results are consistent with the existing literature, but the methodology produced a number of new findings that were not observed in studies using more traditional approaches.

Comparison between intraoral scanning and direct visual analysis for the assessment of developmental defects of enamel.

OBJECTIVE: To compare direct visual analysis (DVA) and intraoral scanning (IOS) for the assessment of developmental defects of the enamel (DDE). METHODS: Thirty-nine extracted permanent human teeth with DDE were selected by an experienced examiner and digitised using IOS. The scanning was recorded using the OBS Studio software parallel to the IOS software to obtain a coloured high-definition MP4 file of the process. Two other experienced, blinded, and calibrated examiners randomly analysed the same teeth through DVA and IOS. A third examiner resolved any disagreements between the two examiners. Descriptive statistics were used to analyse the frequencies of the scores. Cohen's kappa test was used to determine whether the DVA scores were different from those assigned using IOS. Spearman's test was used to verify non-random examiner errors. The Chi-square test was used to compare score frequencies. Statistical significance was set at p <0.05. RESULTS: Scores indicating more severe and extended DDE (p <0.05) were more frequently assigned with IOS than with DVA (IOS: 25.64%, 25.64%, 38.46%, and 35.90% between one-third to two-third of the lingual, occlusal, mesial, and distal surfaces, respectively; vs. DVA: 10.26%, 7.69%, 15.38%, and 10.26% for the respective aforementioned tooth surfaces). Contrarily, 'no visible enamel defect' was significantly less assigned for IOS than for DVA (IOS: 15.38%, 43.59%, 35.90%, 15.38%, and 17.95% for buccal, lingual, occlusal, mesial, and distal surfaces, respectively; vs. DVA: 38.46%, 66.67%, 56.41%, 51.28%, and 43.59% for the respective aforementioned tooth surfaces). Kappa agreement ranged from fair to moderate when comparing DVA and IOS; the correlation between both methods was positive, indicating that the examiners assigned the scores properly and the differences arose from employing different methods. CONCLUSION: The assessment of DDE differed depending on the method used. IOS scores indicated more severe and extended DDE than DVA scores. Clinical investigation is the next step in validating the use of IOS for DDE diagnosis. CLINICAL SIGNIFICANCE: This study showed that DDE can be assessed differently using IOS. It is clinically relevant as it directly affects the determination of the severity of the defect and dental treatment planning.

Chronostratigraphy elucidates environmental changes in lacustrine sedimentation rates and metal accumulation.

All changes taking place in a watershed have repercussions on lacustrine environments, being these, the sink of all activities occurring in the basin. Lake Titicaca, the world's highest and navigable lake, is not unfamiliar with these phenomena that can alter the sedimentation dynamics and metal accumulation. This study aimed to identify temporal trends of sedimentation rates by employing a geochronological analysis (210Pb, 137Cs) and to propose metal background values in Puno Bay, as well as to identify metal concentrations (As, Ba, Ca, Cr, Cu, K, Mg, Mo, Ni, Pb, Zn) in the projected timeline to propose, for the first time, background values in Puno Bay. Two sediment cores were collected from the outer and inner bays. Sediment rate (SR) was calculated through the excess of 210Pb (210Pbxs) applying the Constant Flux Constant Sedimentation (CFCS) model. Results show that SR in the outer bay was 0.48 ± 0.08 cm a-1 and for the inner bay was 0.64 ± 0.07 cm a-1. Sediment quality guidelines (SQGs) did not indicate toxicity was likely to occur, except for As. However, enrichment factors (EFs) indicated that all metal accumulation is geogenic. Climatic factors had a marked influence on sedimentation rates for the outer bay, and in the case of the inner bay, it was a sum of climatic and human-based factors.

Spatial distribution of arsenic and metals suggest a high ecotoxicological potential in Puno Bay, Lake Titicaca, Peru.

Spatial distribution and interpolation methods provide a summarized overview about the pollution dispersion, concerning the environment's quality. A high-altitude lake was taken as a model to assess the metalloid As and metals Cr, Cu, Ni, Pb, Zn distribution in superficial sediment and classify them according to their ecotoxicological potential in the aquatic environment. Surface sediments were collected from 11 sites along Puno Bay located at the western area of Lake Titicaca, Peru, and analyzed for pseudo total-metals. Sediment concentration data and quality were plotted using the Inverse Distance Weighting (IDW) as an interpolation method. High concentrations of As were found especially in the outer bay (81.73 mg.kg-1). Spatial heterogeneity was evidenced for metal by the coefficient of variation, although no significative differences were observed between the two bays applying a Kruskall Wallis test (p < 0.05, df = 1). Sediment quality classification showed that most metal values were below TEL and toxicity was unlikely to occur, only As exceeded threefold PEL values, which categorized sediment as "Very Bad", indicating a rather high ecotoxicological potential to the aquatic environment. In conclusion, spatial analysis connected to interpolation methods demonstrated the superficial sediment heterogeneity in Puno Bay.

Ecotoxicology and geostatistical techniques employed in subtropical reservoirs sediments after decades of copper sulfate application.

Spatial distribution linked to geostatistical techniques contributes to sum up information into an easier-to-comprehend knowledge. This study compares copper spatial distribution in surface sediments and subsequent categorization according to its toxicological potential in two reservoirs, Rio Grande (RG) and Itupararanga (ITU) (São Paulo-Brazil), where copper sulfate is applied and not applied, respectively. Sediments from 47 sites in RG and 52 sites in ITU were collected, and then, copper concentrations were interpolated using geostatistical techniques (kriging). The resulting sediment distributions were classified in categories based on sediment quality guides: threshold effect level and probable effect level; regional reference values (RRVs) and enrichment factor (EF). Copper presented a heterogenic distribution and higher concentrations in RG (2283.00 ± 1308.75 mg/kg) especially on the upstream downstream, associated with algicide application as well as the sediment grain size, contrary to ITU (21.81 ± 8.28 mg/kg) where a no-clear pattern of distribution was observed. Sediments in RG are predominantly categorized as "Very Bad", whereas sediments in ITU are mainly categorized as "Good", showing values higher than RRV. The classification is supported by the EF categorization, which in RG is primarily categorized as "Very High" contrasting to ITU classified as "Absent/Very Low". Copper total stock in superficial sediment estimated for RG is 4515.35 Ton of Cu and for ITU is 27.45 Ton of Cu.

Taxonomically Restricted Genes Are Associated With Responses to Biotic and Abiotic Stresses in Sugarcane (Saccharum spp.).

Orphan genes (OGs) are protein-coding genes that are restricted to particular clades or species and lack homology with genes from other organisms, making their biological functions difficult to predict. OGs can rapidly originate and become functional; consequently, they may support rapid adaptation to environmental changes. Extensive spread of mobile elements and whole-genome duplication occurred in the Saccharum group, which may have contributed to the origin and diversification of OGs in the sugarcane genome. Here, we identified and characterized OGs in sugarcane, examined their expression profiles across tissues and genotypes, and investigated their regulation under varying conditions. We identified 319 OGs in the Saccharum spontaneum genome without detected homology to protein-coding genes in green plants, except those belonging to Saccharinae. Transcriptomic analysis revealed 288 sugarcane OGs with detectable expression levels in at least one tissue or genotype. We observed similar expression patterns of OGs in sugarcane genotypes originating from the closest geographical locations. We also observed tissue-specific expression of some OGs, possibly indicating a complex regulatory process for maintaining diverse functional activity of these genes across sugarcane tissues and genotypes. Sixty-six OGs were differentially expressed under stress conditions, especially cold and osmotic stresses. Gene co-expression network and functional enrichment analyses suggested that sugarcane OGs are involved in several biological mechanisms, including stimulus response and defence mechanisms. These findings provide a valuable genomic resource for sugarcane researchers, especially those interested in selecting stress-responsive genes.

Connections among Land Use, Water Quality, Biodiversity of Aquatic Invertebrates, and Fish Behavior in Amazon Rivers.

Rivers in the Amazon have among the greatest biodiversity in the world. The Xingu River, one of the tributaries of the Amazon River, has a length of 1640 km, draining 510,000 km2 in one of the most protected regions on the planet. The Middle Xingu region in Brazil has been highly impacted by mining and livestock farming, leading to habitat fragmentation due to altered water quality. Therefore, comparing two rivers (the preserved Xingu River and the impacted Fresco River) and their confluence, the aims of the present study were to (1) assess the land uses in the hydrographic basin; (2) determine the water quality by measurements of turbidity, total solids, and metals (Cd, Cu, Fe, Mn, Pb, Zn, and Hg); (3) compare the zooplankton biodiversity; and (4) to evaluate the avoidance behavior of fish (Astyanax bimaculatus) when exposed to waters from the Xingu and Fresco Rivers. Zooplankton were grouped and counted down to the family level. For the analysis of fish avoidance, a multi-compartment system was used. The forest class predominated at the study locations, accounting for 57.6%, 60.8%, and 63.9% of the total area at P1XR, P2FR, and P3XFR, respectively, although since 1985, at the same points, the forest had been reduced by 31.3%, 25.7%, and 27.9%. The Xingu River presented almost 300% more invertebrate families than the Fresco River, and the fish population preferred its waters (>50%). The inputs from the Fresco River impacted the water quality of the Xingu River, leading to reductions in local invertebrate biodiversity and potential habitats for fish in a typical case of habitat fragmentation due to anthropic factors.

Geochemistry and sedimentary photopigments as proxies to reconstruct past environmental changes in a subtropical reservoir.

Sediment cores were used to establish past environmental impacts associated with eutrophication, erosion and metal contamination in the subtropical Atibainha reservoir (São Paulo State, Brazil). We hypothesize that: (1) the levels of nutrients, determined by a spectrophotometric method, reflect the contributions of these elements over time and (2) changes in sedimentation rates, determined by 210Pb geochronology, and metal flows, determined by ICP-AEOS, are related to anthropic activities. Stratigraphic changes in the analysed variables were used to divide the sediment cores into three intervals, according to PCA and cluster analysis (Euclidian distances, Ward's method). Interval I, composed by the period prior to operation of the reservoir, was influenced by organic matter levels. Interval II, between 1967 and 1993 (PC2: 14.94% of the total variability), a period of minor impacts, was mainly influenced by Mn (eigenvalue of 0.71) and Zn (0.74). Interval III, which included sediment deposited between 1993 and 2015 (PC1: 60.28% of the total variability), was influenced by the highest levels of the pigments lutein (0.86), zeaxanthin (0.90) and fucoxanthin (0.65), together with total nitrogen (0.78) and sedimentation rate (0.91), suggesting changes in the phytoplankton community composition probably associated to the intensification of eutrophication and erosion processes. Despite the limitations of applying paleolimnological techniques in reservoirs and the use of pigments as proxies in regions with higher temperatures, it was observed that the anoxic conditions and the aphotic environment in the hypolimnion acted to preserve pigments associated with the groups Chlorophyta (lutein), Cyanobacteria (zeaxanthin) and Bacillariophyta (fucoxanthin). The isolated analysis of nutrients was not sufficient to make conclusive inferences regarding the eutrophication history, since the levels of TP tended to decrease over time, in contrast to an increase in the levels of TN. Despite intensification of eutrophication and erosion, associated to anthropic activities, no signs of metal contamination were recorded.

A Bayesian predictive analytics model for improving long range epidemic forecasting during an infection wave.

Following the outbreak of the coronavirus epidemic in early 2020, municipalities, regional governments and policymakers worldwide had to plan their Non-Pharmaceutical Interventions (NPIs) amidst a scenario of great uncertainty. At this early stage of an epidemic, where no vaccine or medical treatment is in sight, algorithmic prediction can become a powerful tool to inform local policymaking. However, when we replicated one prominent epidemiological model to inform health authorities in a region in the south of Brazil, we found that this model relied too heavily on manually predetermined covariates and was too reactive to changes in data trends. Our four proposed models access data of both daily reported deaths and infections as well as take into account missing data (e.g., the under-reporting of cases) more explicitly, with two of the proposed versions also attempting to model the delay in test reporting. We simulated weekly forecasting of deaths from the period from 31/05/2020 until 31/01/2021, with first week data being used as a cold-start to the algorithm, after which we use a lighter variant of the model for faster forecasting. Because our models are significantly more proactive in identifying trend changes, this has improved forecasting, especially in long-range predictions and after the peak of an infection wave, as they were quicker to adapt to scenarios after these peaks in reported deaths. Assuming reported cases were under-reported greatly benefited the model in its stability, and modelling retroactively-added data (due to the "hot" nature of the data used) had a negligible impact on performance.

An Open Drug Discovery Competition: Experimental Validation of Predictive Models in a Series of Novel Antimalarials.

The Open Source Malaria (OSM) consortium is developing compounds that kill the human malaria parasite, Plasmodium falciparum, by targeting PfATP4, an essential ion pump on the parasite surface. The structure of PfATP4 has not been determined. Here, we describe a public competition created to develop a predictive model for the identification of PfATP4 inhibitors, thereby reducing project costs associated with the synthesis of inactive compounds. Competition participants could see all entries as they were submitted. In the final round, featuring private sector entrants specializing in machine learning methods, the best-performing models were used to predict novel inhibitors, of which several were synthesized and evaluated against the parasite. Half possessed biological activity, with one featuring a motif that the human chemists familiar with this series would have dismissed as "ill-advised". Since all data and participant interactions remain in the public domain, this research project "lives" and may be improved by others.

Could more efficient utilization of ecosystem services improve soil quality indicators to allow sustainable intensification of Amazonian family farming?

In the Amazonian periphery, there are sources of numerous disservices, including deforestation, loss of wildlife habitat and biodiversity erosion. However, there are great opportunities to adopt appropriate agricultural management practices to take advantage of the benefits of ecosystem services for sustainable agricultural intensification. Thus, the aim of this work was to evaluate the effects of certain ecosystem services provided by combined use of legumes with residue of low- and high-quality on soil quality indicators, nitrogen use efficiency and sustainability of maize grain yield in infertile tropical soil. The overarching objective is to determine how ecosystem services can contribute to the improvement of land-use policy to ensure the sustainability of cultivated lands, in such a way that forest can be preserved by avoiding deforestation of other new areas through shifting cultivation systems. Four leguminous tree species were used, two with high-quality residues Leucaena leucocephala (leucaena) and Gliricidia sepium (gliricidia) and two with low-quality residues Clitoria fairchildiana (clitoria) and Acacia mangium (acacia). Maize grain yield was evaluated between 2011 and 2017 in these treatments. In 2018, to assess how ecosystem services affect crop performance, the treatments were divided into ten treatments with and without urea. We conclude that increased uptake of inorganic and organic N by maize resulting from improvement of the soil quality indicators may allow agricultural intensification. This improvement can help meet the challenges of sustainability and feasibility of agroecosystems of the Amazonian periphery by making the agroecosystem more productive year by year. Therefore, our results confirm that the utilization of an ecosystem services style approach can help meet the challenges of sustainability and feasibility in agrosystems of the Amazonian periphery. In addition, these results can contribute to the development of land-use policy in the Amazonian periphery, aiming for the intensification of agriculture in cropped areas to avoid deforestation of new areas from shifting cultivation systems.

Arbuscular Mycorrhizal Fungi (Rhizophagus clarus) and Rhizobacteria (Bacillus subtilis) Can Improve the Clonal Propagation and Development of Teak for Commercial Plantings.

The Tectona grandis L.f. (teak) is an important forest species with high economy value in Asia, Africa, and Latin America. In Latin America, Brazil is one of the countries with the most cultivated areas. The cultivation of teak turns out to be challenging because of its high nutritional demand and the need for seedling production by clonal propagation that includes about 90 days in the nursery phase. The optimization of seedling production is necessary for better results in the nursery and to enhance growth in the field. In this way, the well-known advantage of using microorganisms that promote plant development appears as a potential biotechnological approach to be explored and for the implantation of new areas of wood production. In this study, the inoculation of Bacillus subtilis as plant growth-promoting rhizobacteria (PGPR) was evaluated, and Rhizophagus clarus, an arbuscular mycorrhizal fungus (AMF), and the co-inoculation of these microorganisms in the teak seedling production phase can improve the development of commercial plantations under field conditions. Experiments were carried out under greenhouse and field conditions to evaluate four treatments based on the substrate inoculation of the seedlings. Treatments consisted of a non-inoculated control, PGPR inoculation, AMF inoculation, and PGPR + AMF inoculation. The results of the biometric evaluation of seedlings in the greenhouse showed that there was a significant difference in AMF inoculation and PGPR + AMF inoculation in terms of the specific root length and root density treatments, there was also a positive correlation between these two treatments and the absorption of some nutrients, such as P, N, K, Mg, Cu, Mn, and Zn. This response led to an increase between 4.75 and 11.04% in the field growth rate.

The Wild Sugarcane and Sorghum Kinomes: Insights Into Expansion, Diversification, and Expression Patterns.

The protein kinase (PK) superfamily is one of the largest superfamilies in plants and the core regulator of cellular signaling. Despite this substantial importance, the kinomes of sugarcane and sorghum have not been profiled. Here, we identified and profiled the complete kinomes of the polyploid Saccharum spontaneum (Ssp) and Sorghum bicolor (Sbi), a close diploid relative. The Sbi kinome was composed of 1,210 PKs; for Ssp, we identified 2,919 PKs when disregarding duplications and allelic copies, and these were related to 1,345 representative gene models. The Ssp and Sbi PKs were grouped into 20 groups and 120 subfamilies and exhibited high compositional similarities and evolutionary divergences. By utilizing the collinearity between the species, this study offers insights into Sbi and Ssp speciation, PK differentiation and selection. We assessed the PK subfamily expression profiles via RNA-Seq and identified significant similarities between Sbi and Ssp. Moreover, coexpression networks allowed inference of a core structure of kinase interactions with specific key elements. This study provides the first categorization of the allelic specificity of a kinome and offers a wide reservoir of molecular and genetic information, thereby enhancing the understanding of Sbi and Ssp PK evolutionary history.

Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation.

Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to Mycobacterium tuberculosis in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1ß, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.

Reprogramming Intestinal Epithelial Cell Polarity by Interleukin-22.

Background: Interleukin-22 (IL-22) impacts the integrity of intestinal epithelia and has been associated with the development of colitis-associated cancer and inflammatory bowel diseases (IBD). Previous data suggest that IL-22 protects the mucosal barrier and promotes wound healing and barrier defect. We hypothesized, that IL-22 modulates cell polarity of intestinal epithelial cells (IECs) acting on tight junction assembly. The aim of the study was to investigate IL-22-dependent mechanisms in the reprogramming of intestinal epithelia. Methods: IECs were exposed to IL-22 at various concentrations. IECs in Matrigel® were grown to 3-dimensional cysts in the presence or absence of IL-22 and morphology and expression of polarity proteins were analyzed by confocal microscopy. Epithelial cell barrier (TER and sandwich assay) and TJ assembly analysis (calcium-switch assay) were performed. TJ and cell polarity protein expression were assessed by western blotting and confocal microscopy. Cell migration and invasion assays were performed. Induction of epithelial-mesenchymal transition (EMT) was assessed by RT-qPCR analysis and western blotting. Signaling pathway analyses were performed by phosphoblotting and functional assays after blocking STAT3 and ERK signaling pathways. Using the toxoplasma-model of terminal ileitis, IL-22-knock-out mice were compared to wild-type littermates, analyzed for barrier function using one-path-impedance-analysis and macromolecular flux (H3-mannitol, Ussing-chambers). Results: IECs exhibited a barrier defect after IL-22 exposure. TJ protein distribution and expression were severely impaired. Delayed recovery in the calcium-switch assay was observed suggesting a defect in TJ assembly. Analyzing the 3D-cyst model, IL-22 induced multi-lumen and aberrant cysts, and altered the localization of cell polarity proteins. Cell migration and invasion was caused by IL-22 as well as induction of EMT. Interestingly, only inhibition of the MAPK pathway, rescued the TJal barrier defect, while blocking STAT3 was relevant for cell survival. In addition, ileal mucosa of IL-22 deficient mice was protected from the barrier defect seen in Toxoplasma gondii-induced ileitis in wild type mice shown by significantly higher Re values and correspondingly lower macromolecule fluxes. Conclusion: IL-22 impairs intestinal epithelial cell barrier by inducing EMT, causing defects in epithelial cell polarity and increasing cell motility and cell invasion. IL-22 modulates TJ protein expression and mediates tight junctional (TJal) barrier defects via ERK pathway.

Chironomus sancticaroli generation test applied to chemical contaminants and freshwater sediment samples.

The use of ecotoxicological bioassays has been increasing due to the importance of understanding the effects of substances on biota and to help environmental agencies determine water and sediment qualities. The use of Chironomus sp. in laboratory bioassays is extensive, but there is still a lack of studies regarding the application of extended ecotoxicological tests, which evaluate different population generation responses and show a detailed impact on their development. The present study investigated the response of Chironomus sancticaroli, a Brazilian endemic insect, to 17α-ethinylestradiol hormone, caffeine anhydrous, LAS (linear alkylbenzene sulfonate), and environmental samples (sediments) in relation to wing length, fecundity, and larval length over three generations. Statistically, differences for all contaminants between P (parental), F1, and F2 generations (p ≤ 0.05) were observed, indicating that in the environment, the organism may be negatively affected when exposed to contaminants in successive generations. Different ecological responses were also noted in comparison to classic acute (96h) and chronic (10 days) ecotoxicological tests using Chironomus sancticaroli. Our results highlight that the generation test can present more detailed results regarding the effects of stressors on the organism's life cycle than do the classic bioassays.