Nuclear magnetic resonance spectroscopy reveals biomarkers of stroke recovery in a mouse model of obesity-associated type 2 diabetes.

Obesity and Type 2 diabetes (T2D) are known to exacerbate cerebral injury caused by stroke. Metabolomics can provide signatures of metabolic disease, and now we explored whether the analysis of plasma metabolites carries biomarkers of how obesity and T2D impact post-stroke recovery. Male mice were fed a high-fat diet (HFD) for 10 months leading to development of obesity with T2D or a standard diet (non-diabetic mice). Then, mice were subjected to either transient middle cerebral artery occlusion (tMCAO) or sham surgery and allowed to recover on standard diet for 2 months before serum samples were collected. Nuclear magnetic resonance (NMR) spectroscopy of serum samples was used to investigate metabolite signals and metabolic pathways that were associated with tMCAO recovery in either T2D or non-diabetic mice. Overall, after post-stroke recovery there were different serum metabolite profiles in T2D and non-diabetic mice. In non-diabetic mice, which show full neurological recovery after stroke, we observed a reduction of isovalerate, and an increase of kynurenate, uridine monophosphate, gluconate and N6-acetyllysine in tMCAO relative to sham mice. In contrast, in mice with T2D, which show impaired stroke recovery, there was a reduction of N,N-dimethylglycine, succinate and proline, and an increase of 2-oxocaproate in serum of tMCAO versus sham mice. Given the inability of T2D mice to recover from stroke, in contrast with non-diabetic mice, we propose that these specific metabolite changes following tMCAO might be used as biomarkers of neurophysiological recovery after stroke in T2D.

Long-term trends in juvenile Mugil liza abundance in relation to selected environmental and fisheries influences in southern Brazil.

Overfishing constitutes a major threat affecting marine fish population worldwide, including mullet species that have been exploited by fisheries during the reproductive migration in temperate and tropical latitudes for millennia. In the present study, we investigated the relationship of fishing intensity of mullet Mugil liza during its reproductive migration and the abundance of their juveniles in an essential nursery ground for the species in the southwest Atlantic Ocean. To carry out this analysis, we used a 23-year standardized long-term time series (1997-2019) of monthly abundance of M. liza juveniles, local/regional (water temperature, salinity, water transparency and river discharge) and global (ENSO) environmental factors, along with compilations of fishing landing data for the species. Generalized Additive Models (GAM) revealed the negative effect of fishing adult populations on the abundance of juveniles when they reach the marine surf-zone and after recruiting into the estuary. Our results reinforce the importance of adequate conservation and fishery regulation policies to prevent the species' stock from collapsing.

Density of Sphingosine-1-Phosphate Receptors Is Altered in Cortical Nerve-Terminals of Insulin-Resistant Goto-Kakizaki Rats and Diet-Induced Obese Mice.

Sphingosine-1-phosphate (S1P) is a phosphosphingolipid with pleiotropic biological functions. S1P acts as an intracellular second messenger, as well as extracellular ligand to five G-protein coupled receptors (S1PR1-5). In the brain, S1P regulates neuronal proliferation, apoptosis, synaptic activity and neuroglia activation. Moreover, S1P metabolism alterations have been reported in neurodegenerative disorders. We have previously reported that S1PRs are present in nerve terminals, exhibiting distinct sub-synaptic localization and neuromodulation actions. Since type 2 diabetes (T2D) causes synaptic dysfunction, we hypothesized that S1P signaling is modified in nerve terminals. In this study, we determined the density of S1PRs in cortical synaptosomes from insulin-resistant Goto-Kakizaki (GK) rats and Wistar controls, and from mice fed a high-fat diet (HFD) and low-fat-fed controls. Relative to their controls, GK rats showed similar cortical S1P concentration despite higher S1P levels in plasma, yet lower density of S1PR1, S1PR2 and S1PR4 in nerve-terminal-enriched membranes. HFD-fed mice exhibited increased plasma and cortical concentrations of S1P, and decreased density of S1PR1 and S1PR4. These findings point towards altered S1P signaling in synapses of insulin resistance and diet-induced obesity models, suggesting a role of S1P signaling in T2D-associated synaptic dysfunction.

Metabolite Profiling in a Diet-Induced Obesity Mouse Model and Individuals with Diabetes: A Combined Mass Spectrometry and Proton Nuclear Magnetic Resonance Spectroscopy Study.

Mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy techniques have been used extensively for metabolite profiling. Although combining these two analytical modalities has the potential of enhancing metabolite coverage, such studies are sparse. In this study we test the hypothesis that combining the metabolic information obtained using liquid chromatography (LC) MS and 1H NMR spectroscopy improves the discrimination of metabolic disease development. We induced metabolic syndrome in male mice using a high-fat diet (HFD) exposure and performed LC-MS and NMR spectroscopy on plasma samples collected after 1 and 8 weeks of dietary intervention. In an orthogonal projection to latent structures (OPLS) analysis, we observed that combining MS and NMR was stronger than each analytical method alone at determining effects of both HFD feeding and time-on-diet. We then tested our metabolomics approach on plasma from 56 individuals from the Malmö Diet and Cancer Study (MDCS) cohort. All metabolic pathways impacted by HFD feeding in mice were confirmed to be affected by diabetes in the MDCS cohort, and most prominent HFD-induced metabolite concentration changes in mice were also associated with metabolic syndrome parameters in humans. The main drivers of metabolic disease discrimination emanating from the present study included plasma levels of xanthine, hippurate, 2-hydroxyisovalerate, S-adenosylhomocysteine and dimethylguanidino valeric acid. In conclusion, our combined NMR-MS approach provided a snapshot of metabolic imbalances in humans and a mouse model, which was improved over employment of each analytical method alone.

Plasma Galectin-4 Levels Are Increased after Stroke in Mice and Humans.

Epidemiological studies have associated plasma galectin-4 (Gal-4) levels with prevalent and incident diabetes, and with an increased risk of coronary artery disease. To date, data regarding possible associations between plasma Gal-4 and stroke are lacking. Using linear and logistic regression analyses, we tested Gal-4 association with prevalent stroke in a population-based cohort. Additionally, in mice fed a high-fat diet (HFD), we investigated whether plasma Gal-4 increases in response to ischemic stroke. Plasma Gal-4 was higher in subjects with prevalent ischemic stroke, and was associated with prevalent ischemic stroke (odds ratio 1.52; 95% confidence interval 1.01-2.30; p = 0.048) adjusted for age, sex, and covariates of cardiometabolic health. Plasma Gal-4 increased after experimental stroke in both controls and HFD-fed mice. HFD exposure was devoid of impact on Gal-4 levels. This study demonstrates higher plasma Gal-4 levels in both experimental stroke and in humans that experienced ischemic stroke.

Taurine and N-acetylcysteine treatments prevent memory impairment and metabolite profile alterations in the hippocampus of high-fat diet-fed female mice.

Background: Obesity constitutes a risk factor for cognitive impairment. In rodent models, long-term exposure to obesogenic diets leads to hippocampal taurine accumulation. Since taurine has putative cyto-protective effects, hippocampal taurine accumulation in obese and diabetic models might constitute a counteracting response to metabolic stress. Objective: We tested the hypothesis that treatment with taurine or with N-acetylcysteine (NAC), which provides cysteine for the synthesis of taurine and glutathione, prevent high-fat diet (HFD)-associated hippocampal alterations and memory impairment. Methods: Female mice were fed either a regular diet or HFD. Some mice had access to 3%(w/v) taurine or 3%(w/v) NAC in the drinking water. After 2 months, magnetic resonance spectroscopy (MRS) was used to measure metabolite profiles. Memory was assessed in novel object and novel location recognition tests. Results: HFD feeding caused memory impairment in both tests, and reduced concentration of lactate, phosphocreatine-to-creatine ratio, and the neuronal marker N-acetylaspartate in the hippocampus. Taurine and NAC prevented HFD-induced memory impairment and N-acetylaspartate reduction. NAC, but not taurine, prevented the reduction of lactate and phosphocreatine-to-creatine ratio. MRS revealed NAC/taurine-induced increase of hippocampal glutamate and GABA levels. Conclusion: NAC and taurine can prevent memory impairment, while only NAC prevents alterations of metabolite concentrations in HFD-exposed female mice.

Coastal zone use and migratory behaviour of the southern population of Mugil liza in Brazil.

We analysed the ratios Sr:Ca and Ba:Ca in the otoliths of 55 adults of the southern population of Mugil liza in Brazil (Paraná to Rio Grande do Sul) to investigate its coastal zone use and migratory behaviour. All individual M. liza analysed had Sr:Ca and Ba:Ca values indicating that their birth was in the marine environment, which is consistent with the southern population migration to spawn in the ocean,. Juveniles exhibited at least three coastal use and recruitment strategies (contingents): the majority (89%) of M. liza juveniles migrated toward brackish water. They entered the estuary before completing the first year of life (64%) or after (25%) their first year of life. The remaining 11% did not appear to enter brackish or freshwater water as a nursery or at any point in their life cycle. Some adults returned to the estuary after spawning in the ocean but others (of both sexes) never returned to the estuary after spawning, remaining in the marine environment. The pattern of juvenile habitat use in the Brazilian southern population of M. liza seems to be recurrent throughout the extent of its distribution as a consequence of the reproductive spawning aggregation behaviour, which mixes all contingents (with marine or estuarine preferences).

Muscle Strength and Aerobic Capacity in HIV-Infected Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Physical impairment is highly prevalent in HIV-infected patients. We conducted a systematic review of published studies that included studies comparing muscle function in HIV-infected patients to matched healthy controls, and studies comparing aerobic capacity in HIV-infected patients with that observed in matched healthy controls. DESIGN: Systematic review and meta-analysis. METHODS: We searched for references on MEDLINE, SciELO, Cumulative Index to Nursing and Allied Health (CINAHL), and Scopus up to December 2017. Weighted mean differences and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed using the I test. RESULTS: A total of 30 studies, covering 2148 healthy controls and 2161 HIV-infected patients, fulfilled the inclusion criteria. The average muscle strength and aerobic capacity were significantly lower in HIV-infected patients. Meta-analysis revealed moderate-quality evidence of weaker muscle strength and aerobic capacity in HIV-infected patients. A significant difference in lower-body strength of 1.07 (95% CI: 0.29 to 1.84) was found for participants in the healthy control group compared with HIV group. A significant difference in aerobic capacity (peak VO2) of 8.4 (95% CI: 4.8 to 12.0) was found for participants in the healthy control group compared with HIV group. CONCLUSIONS: Muscle strength and aerobic capacity of HIV-infected patients are reduced in comparison with healthy controls. Additional studies are needed to define the best interventions to improve the physical function in HIV-infected patients.

Discrimination of habitat use between two sympatric species of mullets, Mugil curema and Mugil liza (Mugiliformes: Mugilidae) in the rio Tramandaí Estuary, determined by otolith chemistry

Two sympatric species of marine mullets, Mugil curema and M. liza, use the rio Tramandaí Estuary as nursing grounds. When two closely related species are sympatric, various mechanisms may permit their coexistence, including spatial or temporal segregation that results in the divergent use of the resources for which they compete. To investigate the spatial segregation, we used otolith chemistry inferred through laser ablation-inductively coupled plasma mass spectrometry. Our results indicate that in the rio Tramandaí Estuary, M. curema is associated with high salinity waters and can be classified as a Marine Migrant in the Marine Estuarine-opportunist subcategory. Mugil liza is associated with lower salinity and can be classified as a Marine Migrant in the Estuarine Dependent subcategory. The intra-specific variation in estuarine habitat use indicates that the migratory behaviors in mullets are far more complex than previously known.(AU)

Duas espécies de tainha simpátricas, Mugil curema e M. liza, usam o estuário do Rio Tramandaí como zona de berçário. Quando espécies do mesmo gênero são simpátricas, vários mecanismos podem permitir sua coexistência, incluindo segregação espacial ou temporal que resultam no uso distinto dos recursos pelos quais elas competem. Para investigar a segregação espacial nós usamos a análise de elementos químicos em otólitos inferidos por espectrometria de massas através de plasma indutivamente acoplado com amostras extraídas a laser (LA-ICPMS). Mugil curema está associada a águas de alta salinidade podendo ser classificada como Marinho Migrante sub-categoria Marinha estuarina-oportunista. Mugil liza está associada a águas menos salinas, devendo ser classificada como Marinha Migrante sub-categoria Estuarina Dependente. A variação intraespecífica no uso do habitat estuarino indica um comportamento migratório mais complexo que o previsto em tainhas.

Phenolic wastewaters depuration by electrochemical oxidation process using Ti/IrO2 anodes.

The electrochemical oxidation (EO) of phenolic wastewaters mimicking olive oil mill effluents was carried out in a batch stirring reactor using Ti/IrO2 anodes, varying the nature (NaCl and Na2SO4) and electrolyte concentration (1.8-20 g L-1), current density (57-119 mA cm-2) and initial pH (3.4-9). Phenolic content (TPh) and chemical oxygen demand (COD) removals were monitored as a function of applied charge and over time. The nature of the electrolyte greatly affected the efficiency of the system, followed by the influence of the current density. The NaCl concentration and the initial pH influenced the process in a lesser extent. The best operating conditions achieved were 10 g L-1 of NaCl, current density of 119 mA cm-2 and initial pH of 3.4. These parameters led to 100 and 84.8% of TPh and COD removal, respectively. Under these conditions, some morphological differences were observed by SEM on the surface of the anode after treatment. To study the potential toxicity of the synthetic effluent in neuronal activity, this mixture was applied to rat brain slices prior to and after EO. The results indicate that although the treated effluent causes a smaller depression of the neuronal reactive oxygen species (ROS) signal than the untreated one, it leads to a potentiation instead of recovery, upon washout. Furthermore, the purification of a real olive mill wastewater (OMW), with the organic load of the synthetic effluent, using the same optimised operating conditions, achieved total phenolic compounds abatement and 62.8% of COD removal.This study demonstrates the applicability of this EO as a pre-treatment process of a real effluent, in order to achieve the legal limit values to be discharged into natural streams regarding its organic load.

New environmentally friendly MSPD solid support based on golden mussel shell: characterization and application for extraction of organic contaminants from mussel tissue.

The use of golden mussel shells as a solid support in vortex-assisted matrix solid-phase dispersion (MSPD) was evaluated for the first time for extraction of residues of 11 pesticides and nine pharmaceutical and personal care products from mussel tissue samples. After they had been washed, dried, and milled, the mussel shells were characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, infrared spectroscopy, and Brunauer-Emmett-Teller analysis. The MSPD procedure with analysis by liquid chromatography-tandem mass spectrometry allowed the determination of target analytes at trace concentrations (nanograms per gram), with mean recoveries ranging from 61 to 107 % and relative standard deviations lower than 18 %. The optimized method consisted of dispersion of 0.5 g of mussel tissue, 0.5 g of NaSO4, and 0.5 g of golden mussel shell for 5 min, and subsequent extraction with 5 mL of ethyl acetate. The matrix effect was evaluated, and a low effect was found for all compounds. The results showed that mussel shell is an effective material and a less expensive material than materials that have traditionally been used, i.e., it may be used in the MSPD dispersion step during the extraction of pesticides and pharmaceutical and personal care products from golden mussel tissues. Graphical Abstract Vortex-assited matrix solid-phase dispersion for extraction of 11 pesticides and 9 PPCPs care products from mussel tissue samples.

Diet and feeding strategy of the dusky grouper Mycteroperca marginata (Actinopterygii: Epinephelidae) in a man-made rocky habitat in southern Brazil

A garoupa-verdadeira (Mycteroperca marginata) é uma espécie marinha geralmente associada a fundos rochosos e recifes. O presente trabalho investiga a dieta e estratégia alimentar de uma população da garoupa-verdadeira que habita um longo (4,5 km) par de molhes de pedra na desembocadura do estuário da laguna dos Patos, sul do Brasil. Não há trabalhos anteriores realizados nesse tipo de habitat construído pelo homem e este trabalho fornece uma base de comparação com estudos de dieta de outras populações da garoupa-verdadeira ocorrendo em habitats naturais. De modo similar ao encontrado em estudos prévios realizados em substratos naturais, caranguejos e peixes foram as principais categorias de alimento consumidas (%IRI = 85,1 e %IRI = 12,6, respectivamente), enquanto camarões e moluscos tiveram menor importância na dieta (%IRI = 1,9 e %IRI = 0,4, respectivamente). Como reportado anteriormente para populações de garoupa-verdadeira que habitam recifes e fundos rochosos, o presente trabalho revelou marcadas mudanças na dieta em função do tamanho da espécie. Siri-azul e peixes tornam-se gradativamente mais importantes na dieta de indivíduos maiores (> 500 mm de comprimento total, CT). Finalmente, foi observado que a população de garoupa-verdadeira teve uma estratégia alimentar generalista com uma elevada variação entre indivíduos no consumo de presas. Essa estratégia permaneceu similar ao longo do aumento em tamanho da espécie. Os resultados do presente trabalho sugerem que substratos rochosos estabelecidos pelo homem propiciam locais de alimentação adequados para a garoupa-verdadeira no sul do Brasil e que poderiam ser usados como ferramentas adicionais nos esforços de conservação dessa espécie ameaçada.

The dusky grouper (Mycteroperca marginata) is a marine species usually associated with rocky bottoms and reefs. The present work investigated the diet and feeding strategy of a dusky grouper population inhabiting a 4.5 km long pair of rocky jetties located in the mouth of Patos Lagoon estuary. No prior research has been conducted in such man-made habitat and the current study provides a basis for comparative studies on the diet of the dusky grouper populations inhabiting natural vs. manmade rocky habitats. Similarly with previous studies on natural substrates, crabs and fishes were the main food categories consumed (%IRI = 85.1 and %IRI = 12.6, respectively), whereas shrimps and mollusks had lower importance in the diet (%IRI = 1.9 and 0.4, respectively). As previously reported for dusky grouper populations inhabiting reefs and rocky bottoms, the present work revealed conspicuous size related dietary shifts. Blue crabs and fishes become increasingly important food itemsin the diet of larger individuals (> 500 mm, TL). Finally, it was found that the studied dusky population has a generalist feeding strategy with a high between-individual variation in prey consumption. Such strategy remained similar across the size increment of the species. Our findings suggest that man-made rocky substrates provide suitable feeding grounds for the dusky grouper in southern Brazil and could be used as an additional tool in the conservation efforts of this endangered species.

Age, growth, and reproductive aspects of the dusky grouper Mycteroperca marginata (Actinopterygii: Epinephelidae) in a man-made rocky habitat in southern Brazil

The dusky grouper, Mycteroperca marginata, is an important commercial marine fish that is currently considered an endangered species worldwide and listed as overexploited in Brazil. Although its reproductive biology has been studied elsewhere, no information is available for populations in its southernmost distribution limit on the Brazilian coast. The present work investigates age structure, growth and reproduction of individuals inhabiting a pair of rocky jetties, about 4.5 km long each, located in the mouth of Patos Lagoon in the municipality of Rio Grande, in the southwestern Atlantic Ocean. A total of 130 individuals obtained between February 2007 and May 2009 were analyzed, with total length ranging from 260 to 800 mm. The growth coefficient found in the present study (K: 0.069) was lower than values reported for dusky grouper populations from the Mediterranean Sea (0.087) and southeast Africa (0.09). This difference could be related to higher average water temperatures in these regions compared to the current study site or due to poorer habitat quality in terms of the shelters available for dusky grouper individuals to establish their territories. Microscopic ovarian analyses of individuals during three years of sampling revealed only the occurrence of immature and resting females. The absence of ripe or post-spawning individuals, associated with low GSI values (<0.2) over the studied months, indicates that the dusky grouper did not use this man-made rocky substrate as a spawning site. The current L50 estimate of 451.3 mm indicates that most individuals captured in this area are immature. Such fishing pressure on immature specimens, associated with its slow growth rates and complex reproductive characteristics, threatens sustainability of the current dusky grouper fishery at the study site.

A garoupa-verdadeira, Mycteroperca marginata, é uma espécie de importância comercial que atualmente é considerada como ameaçada mundialmente e sobre-explotada no Brasil. Embora sua biologia reprodutiva tenha sido estudada em outras regiões, nenhuma informação está disponível sobre populações que habitam o extremo sul da sua distribuição na costa brasileira. O presente trabalho investiga a estrutura de idade, crescimento e reprodução de indivíduos que habitam dois molhes de pedra, com cerca de 4,5 km de extensão cada, localizados na desembocadura da laguna dos Patos no município de Rio Grande, no Atlântico Sudoeste. Foram analisados 130 indivíduos obtidos entre fevereiro de 2007 e maio de 2009, com comprimento total entre 260 e 800 mm. O coeficiente de crescimento no presente estudo (K: 0,069) foi inferior aos valores reportados para oMediterrâneo (0,087) e sudeste da África (0,09). Essa diferença pode estar relacionada a temperaturas médias maiores nessas regiões comparadas ao presente local de estudo ou devido a menor qualidade de habitat em termo de abrigos para os indivíduos de garoupa-verdadeira estabelecerem seus territórios. Análises microscópicas dos ovários dos indivíduos durante esses três anos de amostragens revelaram somente a ocorrência de indivíduos imaturos e fêmeas em repouso. A ausência de indivíduos ovados ou em pós-desova, associada com baixos valores do IGS (<0,2), ao longo de todos os meses de coleta, indica que a garoupa-verdadeira não utiliza esse substrato rochoso construído pelo homem como um local de desova. A estimativa de um L50 de 451,3 mm indica que a maioria dos indivíduos capturados nessa região é imatura. Pressão de pesca sobre indivíduos imaturos, associada com a sua lenta taxa de crescimento e complexo modo reprodutivo, ameaça a sustentabilidade da atual pesca da garoupa-verdadeira na área de estudo.