This study investigates whether ladder climbing (LC), as a model of resistance exercise, can reverse whole-body and skeletal muscle deleterious metabolic and inflammatory effects of high-fat (HF) ...diet-induced obesity in mice. To accomplish this, Swiss mice were fed for 17 weeks either standard chow (SC) or an HF diet and then randomly assigned to remain sedentary or to undergo 8 weeks of LC training with progressive increases in resistance weight. Prior to beginning the exercise intervention, HF-fed animals displayed a 47% increase in body weight (BW) and impaired ability to clear blood glucose during an insulin tolerance test (ITT) when compared to SC animals. However, 8 weeks of LC significantly reduced BW, adipocyte size, as well as glycemia under fasting and during the ITT in HF-fed rats. LC also increased the phosphorylation of Akt
and AMPK
and reduced tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL1-β) contents in the quadriceps muscles of HF-fed mice. Additionally, LC reduced the gene expression of inflammatory markers and attenuated HF-diet-induced NADPH oxidase subunit gp91phox in skeletal muscles. LC training was effective in reducing adiposity and the content of inflammatory mediators in skeletal muscle and improved whole-body glycemic control in mice fed an HF diet.
Abstract
The establishment of multiple zones offering different protection levels within a Marine Protected Area (MPA) can minimize social conflicts while maintaining associated biodiversity benefits ...such as fish population replenishment. Parrotfishes are among one of the most ecologically important reef fishes; yet extremely overexploited worldwide. In this context, well-designed priority management areas allowing no fishing activity (no-take zones) could help recover fish species, such as parrotfishes, through a MPA zoning process. Here, we tested this hypothesis by identifying the spatial configuration of zones that maximize the recovery of endangered parrotfish species (
Scarus trispinosus; Scarus zelindae
;
Sparisoma amplum
;
Sparisoma axillare
;
Sparisoma frondosum
) at the largest MPA in Brazil protecting nearshore coral reefs (MPA Costa dos Corais). We used parrotfish distribution data to produce species distribution models (SDMs) and combined them with conservation planning tools to delineate priority zones following a systematic approach. Then, we contrasted priority zones against non-systematic, newly designed no-take zones based on managers’ and stakeholders’ perspectives. After mapping the predicted abundance of each species within both zones based upon field surveys, we found that priority zones were more effective than non-systematic ones for the protection of two out of the five species:
Scarus trispinosus
and
Sparisoma amplum
. Thus, we considered that designing systematic zones was particularly relevant for increased protection of the two parrotfish species facing the largest decline. The prioritization analyses also showed that priority areas for parrotfish conservation following a systematic approach were mostly located surrounding and within no-take zones delineated by local stakeholders. The spatial overlap between systematic and non-systematic zones was of 38%. Hence, our study reinforces the importance of considering scientific information and methods (e.g., spatial distribution data and prioritization analyses) as a complementary strategy along with local stakeholders’ knowledge, for delineating and refining management zones within MPAs.
Biocides are widely used in water treatment for microbiological control. The rise of antimicrobial resistance and the need to assure properly managed water systems require a better understanding of ...the mechanisms of action of biocides and of their impact on cell's viability as a function of dosage concentrations. The present work addresses these two aspects regarding the biocides benzalkonium chloride (BAC) and dibromonitrilopropionamide (DBNPA)-two biocides commonly found in the water treatment industry. For that, the following parameters were studied: culturability, membrane integrity, metabolic activity, cellular energy, and the structure and morphology of cells. Also, to assess cell's death, a reliable positive control, consisting of cells killed by autoclave (dead cells), was introduced. The results confirmed that BAC is a lytic biocide and DBNPA a moderate electrophilic one. Furthermore, the comparison between cells exposed to the biocides' minimum bactericidal concentrations (MBCs) and autoclaved cells revealed that other viability parameters should be taken into consideration as "death indicators." The present work also shows that only for the concentrations above the MBC the viability indicators reached values statistically similar to the ones observed for the autoclaved cells (considered to be definitively dead). Finally, the importance of considering the biocide mechanism of action in the definition of the viability parameter to use in the viable but non-culturable (VBNC) determination is discussed.
Real hospital wastewater was effectively treated by a promising technology based on degradation reaction catalyzed by Fe
under microwave irradiation in this work. Fe
powders were synthesized and ...characterized by different techniques, resulting in a single-phase sample with spherical particles. Optimum experimental conditions were determined by a central composite rotatable design combined with a response surface methodology, resulting in 96.8% of chemical oxygen demand reduction and 100% organic carbon removal, after applying MW power of 780 W and Fe
dosage of 0.36 g L
for 60 min. Amongst the several organic compounds identified in the wastewater sample, diclofenac and ibuprofen were present in higher concentrations; therefore, they were set as target pollutants. Both compounds were completely degraded in 35 min of reaction time. Their plausible degradation pathways were investigated and proposed. Overall, the method developed in this work effectively removed high concentrations of pharmaceuticals in hospital wastewater.
Highly malignant glioblastoma (GBM) is characterized by high genetic heterogeneity and infiltrative brain invasion patterns, and aberrant miRNA expression has been associated with hallmark malignant ...properties of GBM. The lack of effective GBM treatment options prompted us to investigate whether miRNAs would constitute promising therapeutic targets toward the generation of a gene therapy approach with clinical significance for this disease. Here, we show that microRNA-21 (miR-21) is upregulated and microRNA-128 (miR-128) is downregulated in mouse and human GBM samples, a finding that is corroborated by analysis of a large set of human GBM data from The Cancer Genome Atlas. Moreover, we demonstrate that oligonucleotide-mediated miR-21 silencing in U87 human GBM cells resulted in increased levels of the tumor suppressors PTEN and PDCD4, caspase 3/7 activation and decreased tumor cell proliferation. Cell exposure to pifithrin, an inhibitor of p53 transcriptional activity, reduced the caspase activity associated with decreased miR-21 expression. Finally, we demonstrate for the first time that miR-21 silencing enhances the antitumoral effect of the tyrosine kinase inhibitor sunitinib, whereas no therapeutic benefit is observed when coupling miR-21 silencing with the first-line drug temozolomide. Overall, our results provide evidence that miR-21 is uniformly overexpressed in GBM and constitutes a highly promising target for multimodal therapeutic approaches toward GBM.
(Bn
Cyclam)Y(N(SiMe
)
) was prepared by reaction of H
Bn
Cyclam with YN(SiMe
)
. The protonation of the macrocycle ligand in (Bn
Cyclam)Y(N(SiMe
)
) is observed upon reaction with HNMe
BPh
leading ...to the formation of (HBn
Cyclam)Y(N(SiMe
)
)BPh
. DFT analysis of (Bn
Cyclam)Y(N(SiMe
)
) showed that the HOMO is located on the anionic nitrogen atoms of the cyclam ring indicating that protonation follows orbital control. Addition of H
Bn
Cyclam and H
(
Bn)
Cyclam to a 1:3 mixture of YCl
and LiCH
SiMe
in THF resulted in the formation of ((C
H
CH
)BnCyclam)Y(THF)(µ-Cl)Li(THF)
and Y{(η
-
Bn)
Cyclam}Li(THF), respectively. The reaction of H
Bn
Cyclam with Y(CH
SiMe
)
(THF)
was studied and monitored by a temperature variation NMR experiment revealing the formation of (
Bn
Cyclam)Y(CH
SiMe
). Preliminary catalytic assays have shown that Y{(η
-
Bn)
Cyclam}Li(THF) is a very efficient catalyst for the intramolecular hydroamination of 2,2-diphenyl-pent-4-enylamine.
Domoic acid (DA) is a natural amino acid and water-soluble neurotoxic biotoxin primarily produced by the microalgae Pseudo-nitzschia. DA can cause poisoning in humans and a wide variety of marine ...species. In this work, a molecularly imprinted nanoparticle-based assay (MINA) was developed as an alternative to enzyme-linked immunosorbent assay (ELISA) for selective detection of DA. In contrast with ELISA, MINA uses molecularly imprinted polymer nanoparticles (nanoMIPs) as plastic antibodies due to its higher stability and lower production costs. In this work, dihydrokainic acid (DKA) was used as a dummy template because this molecule is structurally similar to DA but less toxic. The developed MINA had a high linear response for DKA and DA, showing detection limits of 2.12 nmol L−1 and 4.32 nmol L−1, respectively. Additionally, q-RMN studies demonstrated that DKA - nanoMIPs were selective for DKA, since they presented the best association parameters with a high loading load capacity of 175% and an association efficiency of 18%. No cross-reactivity towards 1, 3, 5 - pentanetricarboxylic acid was observed. These results suggest that MINA could be a more robust, more sensitive, and less expensive alternative to ELISA. The assay developed with DKA – nanoMIPs has strong potential for the detection of domoic acid in real samples of red tide.
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•Cost-efficient production of nanoMIPs for dihydrokainic acid (DKA) detection.•NanoMIPs are capable of replacing natural antibodies in conventional ELISA.•MINA using DKA–nanoMIPs show strong potential for the detection of domoic acid.•q-RMN studies demonstrated that DKA–nanoMIPs are selective for DKA.•NanoMIPs show better performance in ELISA than natural antibodies.
Keratinocyte infection with high-risk human papillomavirus genotypes has been linked to cancer development. In cervix, the alpha HPV16 and HPV18 have been reported as the mayor causative agents of ...cervical cancer. Oncogenic progression and chronic inflammation are closely related processes, with IL-6 as one of the main pro-inflammatory cytokines involved. However, there are limited studies about the regulation of IL-6 by low and high risk HPVs and the HPV proteins implicated in this modulation. In this work, we report the overexpression of IL-6 in HPV infected cervical cancer derived cell lines (HeLa and SiHa) compared to non-tumorigenic keratinocytes (HaCaT), and in Cervical Intraepithelial Neoplasia grade 1 HPV16 and HPV18 positive cervical samples compared to HPV negative samples without lesions. Moreover, we generated HaCaT keratinocytes that express E5, E6, and E7 from high risk (16 or 18) or low risk (62 and 84) HPVs. E5 proteins do not modify IL-6 expression, while E7 modestly increase it. Interestingly, E6 proteins in HaCaT cells upregulate IL-6 mRNA expression and protein secretion. Indeed, in HaCaT cells that express high risk HPV16E6 or HPV18E6 proteins, only the truncated E6
isoforms were expressed, showing the stronger IL-6 overexpression, while in HaCaT cells that express low risk HPV62 and HPV84 full length E6 proteins, IL-6 was also upregulated but not so drastically. Since HaCaT cells have a mutated p53 form that is not degraded by the introduction of E6 or E6/E7, it seems that E6/E7 regulate IL-6 by an additional mechanism independent of p53. In addition, basal keratinocytes showed a strong expression of IL-6R using immunohistochemistry, suggesting an autocrine mechanism over proliferative cells. Altogether, IL-6 cytokine expression in keratinocytes is upregulated by E6 and E7 proteins from HPVs 16, 18, 62, and 84, especially by high risk HPV16 and HPV18 E6
, which may contribute to promote a pro-inflammatory and highly proliferative microenvironment that can persist over time and lead to cervical tumorigenesis.
l-Ascorbic acid (AsA, vitamin C) is a pivotal dietary nutrient with multifaceted importance in living organisms. In plants, the Smirnoff-Wheeler pathway is the primary route for AsA biosynthesis, and ...understanding the mechanistic details behind its component enzymes has implications for plant biology, nutritional science, and biotechnology. As part of an initiative to determine the structures of all six core enzymes of the pathway, the present study focuses on three of them in the model species Myrciaria dubia (camu-camu): GDP-d-mannose 3',5'-epimerase (GME), l-galactose dehydrogenase (l-GalDH), and l-galactono-1,4-lactone dehydrogenase (l-GalLDH). We provide insights into substrate and cofactor binding and the conformational changes they induce. The MdGME structure reveals a distorted substrate in the active site, pertinent to the catalytic mechanism. Mdl-GalDH shows that the way in which NAD+ association affects loop structure over the active site is not conserved when compared with its homologue in spinach. Finally, the structure of Mdl-GalLDH is described for the first time. This allows for the rationalization of previously identified residues which play important roles in the active site or in the formation of the covalent bond with FAD. In conclusion, this study enhances our understanding of AsA biosynthesis in plants, and the information provided should prove useful for biotechnological applications.
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