166 research outputs found

    Dietary lipid content reorganizes gut microbiota and probiotic L. rhamnosus attenuates obesity and enhances catabolic hormonal milieu in zebrafish

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    AbstractIn the present study, we explored whether dietary lipid content influences the gut microbiome in adult zebrafish. Diets containing three different lipid levels (high [HFD], medium [MFD], and low [LFD]) were administered with or without the supplementation of Lactobacillus rhamnosus (P) to zebrafish in order to explore how the dietary lipid content may influence the gut microbiome. Dietary lipid content shifted the gut microbiome structure. The addition of L. rhamnosus in the diets, induced transcriptional reduction of orexigenic genes, upregulation of anorexigenic genes, and transcriptional decrease of genes involved in cholesterol and triglyceride (TAG) metabolism, concomitantly with lower content of cholesterol and TAG. Probiotic feeding also decreased nesfatin-1 peptide in HFD-P and attenuated weight gain in HFD-P and MFD-P fed zebrafish, but not in LFD-P group. Intestinal ultrastructure was not affected by dietary fat level or probiotic inclusion. In conclusion, these findings underline the role of fat content in the diet in altering gut microbiota community by shifting phylotype composition and highlight the potential of probiotics to attenuate high-fat diet-related metabolic disorder.</jats:p

    Lactobacillus rhamnosus lowers zebrafish lipid content by changing gut microbiota and host transcription of genes involved in lipid metabolism

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    The microbiome plays an important role in lipid metabolism but how the introduction of probiotic communities affects host lipid metabolism is poorly understood. Using a multidisciplinary approach we addressed this knowledge gap using the zebrafish model by coupling high-throughput sequencing with biochemical, molecular and morphological analysis to evaluate the changes in the intestine. Analysis of bacterial 16S libraries revealed that Lactobacillus rhamnosus was able to modulate the gut microbiome of zebrafish larvae, elevating the abundance of Firmicutes sequences and reducing the abundance of Actinobacteria. The gut microbiome changes modulated host lipid processing by inducing transcriptional down-regulation of genes involved in cholesterol and triglycerides metabolism (fit2, agpat4, dgat2, mgll, hnf4α, scap, and cck) concomitantly decreasing total body cholesterol and triglyceride content and increasing fatty acid levels. L. rhamnosus treatment also increased microvilli and enterocyte lengths and decreased lipid droplet size in the intestinal epithelium. These changes resulted in elevated zebrafish larval growth. This integrated system investigation demonstrates probiotic modulation of the gut microbiome, highlights a novel gene network involved in lipid metabolism, provides an insight into how the microbiome regulates molecules involved in lipid metabolism, and reveals a new potential role for L. rhamnosus in the treatment of lipid disorders

    Merrifield resin-assisted routes to second-generation catalysts for olefin metathesis

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    Phosphine-scavenging Merrifield resins can significantly facilitate the synthesis of highly active Ru metathesis catalysts, including the second-generation Grubbs, Hoveyda, and indenylidene catalysts (GII, HII, InII).</p

    Evaluation of prebiotic and probiotic effects on the intestinal gut microbiota and histology of Atlantic salmon (Salmo salar L.)

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    In the present study the impact on gut microbiology and indigenous gut histology of Atlantic salmon (Salmo salar L.) was investigated following feeding of a control and a prebiotic (EWOS prebiosal®) diet and ex vivo exposure to saline or the probiotic bacterium Carnobacterium divergens. The results showed that ex vivo exposure of C. divergens at 108 CFU ml-1 did not cause cell damage to the intestine tract of Atlantic salmon. Furthermore, prior provision of dietary prebiotic elevated the ability of C. divergens to adhere to the epithelium or mucus layer in the proximal intestine, where culturable heterotrophic bacterial levels (which were identified as C. divergens) were elevated by 234% compared to the control. This effect was not apparent in the distal intestine. The ability of isolated carnobacteria from the ex vivo experiment to inhibit growth of two fish pathogenic bacteria (Yersinia rückeri and Aeromonas salmonicida ssp. salmonicida) was assessed. Extracellular products from all 11 of the isolated carnobacteria strains, plus the type strain Carnobacterium inhibens CCUG 31728, inhibited the in vitro growth of Y. rückeri. However, only extracellular products from C. divergens isolate 57 inhibited the growth of A. salmonicida

    Probiotic treatment reduces appetite and glucose level in the zebrafish model

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    The gut microbiota regulates metabolic pathways that modulate the physiological state of hunger or satiety. Nutrients in the gut stimulate the release of several appetite modulators acting at central and peripheral levels to mediate appetite and glucose metabolism. After an eight-day exposure of zebrafish larvae to probiotic Lactobacillus rhamnosus, high-throughput sequence analysis evidenced the ability of the probiotic to modulate the microbial composition of the gastrointestinal tract. These changes were associated with a down-regulation and up-regulation of larval orexigenic and anorexigenic genes, respectively, an up-regulation of genes related to glucose level reduction and concomitantly reduced appetite and body glucose level. BODIPY-FL-pentanoic-acid staining revealed higher short chain fatty acids levels in the intestine of treated larvae. These results underline the capability of the probiotic to modulate the gut microbiota community and provides insight into how the probiotic interacts to regulate a novel gene network involved in glucose metabolism and appetite control, suggesting a possible role for L. rhamnosus in the treatment of impaired glucose tolerance and food intake disorders by gut microbiota manipulation

    Synthesis of the small peptide analogues of cyclin dependent kinase (CDK4) for cancer treatment

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    Cyclin-dependent kinases (CDKs) are a group of enzymes that are involved in cell cycle progression regulation. The CDKs activate host proteins through phosphorylation on serine or threonine using adenosine triphosphate as a phosphate donor. Especially, cyclindependent kinase 4 (CDK4) has attracted much attention as a potential therapeutic target in treating cancer because it is the key player in the control of cell proliferation. Comparison of the best model of CDK4 with the structures of CDK6 and CDK2 is shown difference in the cyclin-binding region and in overall electrostatic potential. A partially hydrophobic, externalized loop structure present in CDK4, but absent in CDK2 and CDK6 is identified. The hypothesis is that should CDK4 be involved in binding to an additional unidentified protein partner, this fragment provides the most likely candidate for the binding site. This has led to the discovery of a peptide 1, N-Ac-L-Pro-L-Arg(H)-Gly-L-Pro-L-Arg(H)-L-Pro- NH2, from a previously uncharacterized structural domain on CDK4. In this work, solution phase peptide synthetic method is optimized and developed to synthesize linear peptide 64, N-Boc-L-Pro-L-Arg(NO2)-Gly-L-Pro-L-Arg(NO2)-L-Pro-OMe. A series of side chain modification peptides of compound 64 was synthesized and found that peptide 71, N-Ac-LPro- L-Arg(NO2)-Gly-L-Pro-L-Arg(NO2)-L-Pro-OMe had the most potent for anticancer activity. Therefore, alanine scanning compounds of hexapeptide 71 were synthesized by replacing each amino acid residue with L-alanine to investigate which amino acid residue had shown anticancer activity. Solid phase method was also optimized to synthesized peptide 1 and its alanine scanning compounds. To improve anticancer activity, cyclic peptides are synthesized by solution phase method. Biological assays were optimized. Clonogenic assay was chosen to test with our synthetic peptides against RT112 bladder cancer and MRC5-hTERT fibroblast cell

    Evaluation of Prebiotic and Probiotic Effects on the Intestinal Gut Microbiota and Histology of Atlantic salmon (Salmo salar L.)

    No full text
    In the present study the impact on gut microbiology and indigenous gut histology of Atlantic salmon (Salmo salar L.) was investigated following feeding of a control and a prebiotic (EWOS prebiosal®) diet and ex vivo exposure to saline or the probiotic bacterium Carnobacterium divergens. The results showed that ex vivo exposure of C. divergens at 108 CFU ml-¹ did not cause cell damage to the intestine tract of Atlantic salmon. Furthermore, prior provision of dietary prebiotic elevated the ability of C. divergens to adhere to the epithelium or mucus layer in the proximal intestine, where culturable heterotrophic bacterial levels (which were identified as C. divergens) were elevated by 234% compared to the control. This effect was not apparent in the distal intestine. The ability of isolated carnobacteria from the ex vivo experiment to inhibit growth of two fish pathogenic bacteria (Yersinia rückeri and Aeromonas salmonicida ssp. salmonicida) was assessed. Extracellular products from all 11 of the isolated carnobacteria strains, plus the type strain Carnobacterium inhibens CCUG 31728, inhibited the in vitro growth of Y. rückeri. However, only extracellular products from C. divergens isolate 57 inhibited the growth of A. salmonicid

    Eddies, topography, and the abyssal flow by the Kyushu-Palau Ridge near Velasco Reef

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    © The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Andres, M., Siegelman, M., Hormann, V., Musgrave, R. C., Merrifield, S. T., Rudnick, D. L., Merrifield, M. A., Alford, M. H., Voet, G., Wijesekera, H. W., MacKinnon, J. A., Centurioni, L., Nash, J. D., & Terrill, E. J. Eddies, topography, and the abyssal flow by the Kyushu-Palau Ridge near Velasco Reef. Oceanography, 32(4), (2019): 46-55, doi: 10.5670/oceanog.2019.410.Palau, an island group in the tropical western North Pacific at the southern end of Kyushu-Palau Ridge, sits near the boundary between the westward-​flowing North Equatorial Current (NEC) and the eastward-flowing North Equatorial Countercurrent. Combining remote-sensing observations of the sea surface with an unprecedented in situ set of subsurface measurements, we examine the flow near Palau with a particular focus on the abyssal circulation and on the deep expression of mesoscale eddies in the region. We find that the deep currents time-averaged over 10 months are generally very weak north of Palau and not aligned with the NEC in the upper ocean. This weak abyssal flow is punctuated by the passing of mesoscale eddies, evident as sea surface height anomalies, that disrupt the mean flow from the surface to the seafloor. Eddy influence is observed to depths exceeding 4,200 m. These deep-​reaching mesoscale eddies typically propagate westward past Palau, and as they do, any associated deep flows must contend with the topography of the Kyushu-Palau Ridge. This interaction leads to vertical structure far below the main thermocline. Observations examined here for one particularly strong and well-sampled eddy suggest that the flow was equivalent barotropic in the far field east and west of the ridge, with a more complicated vertical structure in the immediate vicinity of the ridge by the tip of Velasco Reef.We gratefully acknowledge the help of Captain David Murline and the crew of R/V Roger Revelle and the shore-based assistance of Lori Colin and Pat Colin of the Coral Reef Research Foundation. We sincerely thank Terri Paluszkiewicz for her steadfast support of basic research programs, including FLEAT, during her many years of service to the community as Office of Naval Research (ONR) Physical Oceanography Program Manager. MA was supported by ONR grant N000141612668, MS and MAM by N00014-16-1-2671, MHA and JAM by N00014-15-1-2264 and N00014-16-1-3070, GV by N00014-15-1-2592, DLR by N00014- 15-1-2488, and STM and EJT by N00014-15-1-2304. VH and LC were supported by ONR grant N00014-15-1-2286 and NOAA GDP grant NA15OAR4320071. RCM was supported by the Postdoctoral Scholar Program at the Wood Hole Oceanographic Institution, with funding provided by the Weston Howland Jr. Postdoctoral Scholarship. We thank the Palau National Government for permission to carry out the research in Palau

    Turbulence and vorticity in the Wake of Palau

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    © The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in St. Laurent, L., Ijichi, T., Merrifield, S. T., Shapiro, J., & Simmons, H. L. Turbulence and vorticity in the Wake of Palau. Oceanography, 32(4), (2019): 102-109, doi: 10.5670/oceanog.2019.416.The interaction of flow with steep island and ridge topography at the Palau island chain leads to rich vorticity fields that generate a cascade of motions. The energy transfer to small scales removes energy from the large-scale mean flow of the equatorial current systems and feeds energy to the fine and microstructure scales where instability mechanisms lead to turbulence and dissipation. Until now, direct assessments of the turbulence associated with island wakes have received only minimal attention. Here, we examine data collected from an ocean glider equipped with microstructure sensors that flew in the island wake of Palau. We use a combination of submesoscale modeling and direct observation to quantify the relationship between vorticity and turbulence levels. We find that direct wind-driven mixing only accounts for about 10% of the observed turbulence levels, suggesting that most of the energy for mixing is extracted from the shear associated with the vorticity field in the island’s wake. Below the surface layer, enhanced turbulence correlates with the phase and magnitude of the relative vorticity and strain levels of the mesoscale flow.We thank the Palau National Government for permission to carry out the research in Palau. We also thank the US Office of Naval Research for supporting this work. We especially thank Pat and Lori Colin of the Coral Reef Research Foundation and their team for accommodating our research team in Koror, Palau, and running vessel operations in support of glider deployments and recoveries. Sean Whelan of the Woods Hole Oceanographic Institution and Lance Braasch of Scripps Institution of Oceanography provided technical support in the field. Funding for the development of HYCOM has been provided by the National Ocean Partnership Program and the Office of Naval Research. Data assimilative products using HYCOM are funded by the US Navy. Computer time was made available by the Department of Defense High Performance Computing Modernization Program. The output is publicly available at https://www.hycom.org/
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