51 results on '"Valdes JA"'
Search Results
2. RNA Interference mediated knockdown of genes in order to increase protein production using the baculovirus expression system
- Author
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Bentley William E, Valdes James J, Kramer Shannon F, Kim Eun, and Hebert Colin
- Subjects
Microbiology ,QR1-502 - Published
- 2006
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3. New species of Ehrlichia isolated from Rhipicephalus (Boophilus) microplus shows an ortholog of the E. canis major immunogenic glycoprotein gp36 with a new sequence of tandem repeats
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Cruz Alejandro Cabezas, Zweygarth Erich, Ribeiro Mucio Flavio Barbosa, da Silveira Julia Angelica Gonçalves, de la Fuente Jose, Grubhoffer Libor, Valdés James J, and Passos Lygia Maria Friche
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Ehrlichia spp ,Rhipicephalus (Boophilus) microplus ,Phylogenetic analysis ,Gp36 major immunogenic protein ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Ehrlichia species are the etiological agents of emerging and life-threatening tick-borne human zoonoses that inflict serious and fatal infections in companion animals and livestock. The aim of this paper was to phylogeneticaly characterise a new species of Ehrlichia isolated from Rhipicephalus (Boophilus) microplus from Minas Gerais, Brazil. Methods The agent was isolated from the hemolymph of Rhipicephalus (B.) microplus engorged females that had been collected from naturally infested cattle in a farm in the state of Minas Gerais, Brazil. This agent was then established and cultured in IDE8 tick cells. The molecular and phylogenetic analysis was based on 16S rRNA, groEL, dsb, gltA and gp36 genes. We used the maximum likelihood method to construct the phylogenetic trees. Results The phylogenetic trees based on 16S rRNA, groEL, dsb and gltA showed that the Ehrlichia spp isolated in this study falls in a clade separated from any previously reported Ehrlichia spp. The molecular analysis of the ortholog of gp36, the major immunoreactive glycoproteins in E. canis and ortholog of the E. chaffeensis gp47, showed a unique tandem repeat of 9 amino acids (VPAASGDAQ) when compared with those reported for E. canis, E. chaffeensis and the related mucin-like protein in E. ruminantium. Conclusions Based on the molecular and phylogenetic analysis of the 16S rRNA, groEL, dsb and gltA genes we concluded that this tick-derived microorganism isolated in Brazil is a new species, named E. mineirensis (UFMG-EV), with predicted novel antigenic properties in the gp36 ortholog glycoprotein. Further studies on this new Ehrlichia spp should address questions about its transmissibility by ticks and its pathogenicity for mammalian hosts.
- Published
- 2012
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4. High temperature induces oxidative damage, immune modulation, and atrophy in the gills and skeletal muscle of the teleost fish black cusk-eel (Genypterus maculatus).
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Becerra S, Arriagada-Solimano M, Escobar-Aguirre S, Palomino J, Aedo J, Estrada JM, Barra-Valdebenito V, Zuloaga R, Valdes JA, and Dettleff P
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- Animals, Hot Temperature adverse effects, Cytokines metabolism, Toll-Like Receptors metabolism, Toll-Like Receptors genetics, Immunomodulation, Fish Diseases immunology, Gills immunology, Gills metabolism, Oxidative Stress, Muscle, Skeletal immunology, Muscle, Skeletal metabolism, Muscle, Skeletal pathology, Fish Proteins genetics, Fish Proteins metabolism, Immunity, Innate
- Abstract
The high temperature associated with heat waves is a relevant abiotic factor that could impact the biology of teleost fish. The innate immune response, muscular growth, and oxidative stress status are relevant functions in fish tissues that could be affected by increased temperature. In this study, black cusk-eel (Genypterus maculatus) juveniles were subjected to increased temperature, to experimentally replicate heat waves registered from the South Pacific Ocean for five days. The results showed that thermal stress modulated the immune response in gills, with up-regulation of antibacterial peptides, pro-inflammatory cytokines, and Toll-like receptors genes, including hepcidin, gzma, tnfa, cxcl8, and tlr5, with no effect on complement system genes. In skeletal muscle, high temperature triggered atrophy-related gene expression, with up-regulation of foxo1, foxo3, fbxo32, murf1, and atg16l. Increased temperature also generated an up-regulation of transcripts encoding heat shock protein (hsp60 and hsp70) in gills and skeletal muscle, generating oxidative stress in both tissues, with increased expression of the antioxidant genes sod1 and gpx1 in gills and skeletal muscle, respectively, with oxidative damage observed at the DNA level (AP sites), protein (carbonyl content), and lipoperoxidation (HNE content) in both tissues. The present study shows that short-term increases in temperature like those observed in heat waves could affect the immune response in gills, induced atrophy in skeletal muscle, and generate oxidative stress in a teleost species important for Chilean aquaculture diversification, information relevant under the context of climate change scenario., Competing Interests: Declaration of competing interest The authors declare that there are no financial or nonfinancial conflicts of interest., (Copyright © 2025 Elsevier Ltd. All rights reserved.)
- Published
- 2025
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5. Identification and expression analysis of two steamer-like retrotransposons in the Chilean blue mussel (Mytilus chilensis).
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Arriagada G, Quezada J, Merino-Veliz N, Avilés F, Tapia-Cammas D, Gomez J, Curotto D, Valdes JA, Oyarzún PA, Gallardo-Escárate C, Metzger MJ, and Alvarez M
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- Animals, Chile, Mytilus genetics, Retroelements genetics
- Abstract
Background: Disseminated neoplasia (DN) is a proliferative cell disorder of the circulatory system of bivalve mollusks. The disease is transmitted between individuals and can also be induced by external chemical agents such as bromodeoxyuridine. In Mya arenaria, we have cloned and characterized an LTR-retrotransposon named Steamer. Steamer mRNA levels and gene copy number correlates with DN and can be used as a marker of the disease. So far, the only mollusk where a retrotransposon expression relates to DN is Mya arenaria. On the other hand, it has been reported that the Chilean blue mussel Mytilus chilensis can also suffers DN. Our aim was to identify retrotransposons in Mytilus chilensis and to study their expression levels in the context of disseminated neoplasia., Results: Here we show that 7.1% of individuals collected in August 2018, from two farming areas, presents morphological characteristics described in DN. Using Steamer sequence to interrogate the transcriptome of M. chilensis we found two putative retrotransposons, named Steamer-like elements (MchSLEs). MchSLEs are present in the genome of M. chilensis and MchSLE1 is indeed an LTR-retrotransposon. Neither expression, nor copy number of the reported MchSLEs correlate with DN status but both are expressed at different levels among individual animals. We also report that in cultured M. chilensis haemocytes MchSLEs1 expression can be induced by bromodeoxyuridine., Conclusions: We conclude that SLEs present in Mytilus chilensis are differentially expressed among individuals and do not correlate with disseminated neoplasia. Treatment of haemocytes with a stressor like bromodeoxyuridine induces expression of MchSLE1 suggesting that in Mytilus chilensis environmental stressors can induce activation of LTR-retrotransposon., (© 2024. The Author(s).)
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- 2024
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6. Systematic profiling of subtelomeric silencing factors in budding yeast.
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Juárez-Reyes A, Avelar-Rivas JA, Hernandez-Valdes JA, Hua B, Campos SE, González J, González A, Springer M, Mancera E, and DeLuna A
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- Silent Information Regulator Proteins, Saccharomyces cerevisiae genetics, Silent Information Regulator Proteins, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae metabolism, Telomere genetics, Telomere metabolism, Heterochromatin metabolism, Gene Expression Regulation, Fungal, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae Proteins metabolism, Saccharomycetales genetics, Saccharomycetales metabolism
- Abstract
Subtelomeric gene silencing is the negative transcriptional regulation of genes located close to telomeres. This phenomenon occurs in a variety of eukaryotes with salient physiological implications, such as cell adherence, virulence, immune-system escape, and ageing. The process has been widely studied in the budding yeast Saccharomyces cerevisiae, where genes involved in this process have been identified mostly on a gene-by-gene basis. Here, we introduce a quantitative approach to study gene silencing, that couples the classical URA3 reporter with GFP monitoring, amenable to high-throughput flow cytometry analysis. This dual silencing reporter was integrated into several subtelomeric loci in the genome, where it showed a gradual range of silencing effects. By crossing strains with this dual reporter at the COS12 and YFR057W subtelomeric query loci with gene-deletion mutants, we carried out a large-scale forward screen for potential silencing factors. The approach was replicable and allowed accurate detection of expression changes. Results of our comprehensive screen suggest that the main players influencing subtelomeric silencing were previously known, but additional potential factors underlying chromatin conformation are involved. We validate and report the novel silencing factor LGE1, a protein with unknown molecular function required for histone H2B ubiquitination. Our strategy can be readily combined with other reporters and gene perturbation collections, making it a versatile tool to study gene silencing at a genome-wide scale., Competing Interests: Conflicts of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This manuscript has been released as a pre-print at BioRxiv., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.)
- Published
- 2023
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7. Biology and ecology of the lionfish Pterois volitans/Pterois miles as invasive alien species: a review.
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Del Río L, Navarro-Martínez ZM, Cobián-Rojas D, Chevalier-Monteagudo PP, Angulo-Valdes JA, and Rodriguez-Viera L
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- Animals, Coral Reefs, Ecology, Fishes, Introduced Species, Ecosystem, Perciformes
- Abstract
The lionfish is an exotic invasive fish native to the Indo-Pacific, which is established in the western Atlantic Ocean and the Caribbean Sea. Lionfish can affect native fishes and invertebrates through direct predation or competition for food. The present review aims to analyze the most relevant characteristics of the biology and ecology of lionfish as an invasive alien species, with an emphasis on Cuba. We provide a current view of the well-known lionfish as a successful invasive fish, and we put in this context the information regarding lionfish in Cuban waters, enriching the background knowledge, and giving novel and relevant information. The compilation of numerous publications on the subject has allowed for a more complete analysis of essential aspects of this invader in the Cuban archipelago. The consulted literature records that the first report of lionfish in Cuba occurred in 2007; subsequently, sightings of lionfish were reported in numerous localities. In 2010, the lionfish was considered an invasive alien species, which currently is established in various habitats, at depths up to 188 m, throughout the Cuban archipelago ( e.g. , coral reefs, mangroves, seagrass beds, submerged artificial structures). In addition, it has reached very high densities (12.42 ind./100 m
2 ), which exceed those reported in the Indo-Pacific as well as in many locations in the Western Atlantic. It has been confirmed that the lionfish in Cuba also presents numerous characteristics that guarantee its success as an invader, among them: less quantity and diversity of parasites than other Atlantic fishes found in similar environments, a high number of gametes in the gonads, reproductive activity during all year and wide diet. The most important fish families for the lionfish diet in Cuba have been Pomacentridae, Gobiidae, Scaridae, Holocentridae, Mullidae, Labridae and Acanthuridae; and the most important crustacean orders are Decapoda, Mysida, Stomatopoda and Isopoda. In Cuba, as in the entire invaded region, numerous investigations have been directed to evaluate the impact of this invader on ecosystems, and although there is enough information, their results differ. Additional studies are required to assess the impact of lionfish as a predator after several years of invasion on a larger geographic scale in Cuba and other areas of the region. This knowledge will allow the development of more effective control strategies. Periodic lionfish culling have been carried out in Cuban MPAs as a control strategy, and some positive results have been observed, such as the average size reduction; however, further efforts are still required. Due to the importance of the study of lionfish as an invader, this review is a necessity as it provides, for the first time, a comprehensive analysis of lionfish information and results from Cuba, which is adequately contrasted with previous studies of other areas, particularly, from the Greater Caribbean., Competing Interests: The authors declare there are no competing interests., (©2023 del Río et al.)- Published
- 2023
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8. Neural systems underlying RDoC social constructs: An activation likelihood estimation meta-analysis.
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Pintos Lobo R, Bottenhorn KL, Riedel MC, Toma AI, Hare MM, Smith DD, Moor AC, Cowan IK, Valdes JA, Bartley JE, Salo T, Boeving ER, Pankey B, Sutherland MT, Musser ED, and Laird AR
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- Humans, Likelihood Functions, Temporal Lobe, Magnetic Resonance Imaging, Brain diagnostic imaging, Brain physiology, Brain Mapping
- Abstract
Neuroscientists have sought to identify the underlying neural systems supporting social processing that allow interaction and communication, forming social relationships, and navigating the social world. Through the use of NIMH's Research Domain Criteria (RDoC) framework, we evaluated consensus among studies that examined brain activity during social tasks to elucidate regions comprising the "social brain". We examined convergence across tasks corresponding to the four RDoC social constructs, including Affiliation and Attachment, Social Communication, Perception and Understanding of Self, and Perception and Understanding of Others. We performed a series of coordinate-based meta-analyses using the activation likelihood estimate (ALE) method. Meta-analysis was performed on whole-brain coordinates reported from 864 fMRI contrasts using the NiMARE Python package, revealing convergence in medial prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, temporoparietal junction, bilateral insula, amygdala, fusiform gyrus, precuneus, and thalamus. Additionally, four separate RDoC-based meta-analyses revealed differential convergence associated with the four social constructs. These outcomes highlight the neural support underlying these social constructs and inform future research on alterations among neurotypical and atypical populations., Competing Interests: Competing interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2023
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9. Antioxidant Dietary Fiber Sourced from Agroindustrial Byproducts and Its Applications.
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Angulo-López JE, Flores-Gallegos AC, Ascacio-Valdes JA, Contreras Esquivel JC, Torres-León C, Rúelas-Chácon X, and Aguilar CN
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Agroindustrial activities generate various residues or byproducts which are inefficiently utilized, impacting the environment and increasing production costs. These byproducts contain significant amounts of bioactive compounds, including dietary fiber with associated phenolic compounds, known as antioxidant dietary fiber (ADF). Phenolic compounds are related to the prevention of diseases related to oxidative stress, such as neurodegenerative and cardiovascular diseases. The mechanism of ADF depends on its chemical structure and the interactions between the dietary fiber and associated phenolic compounds. This work describes ADF, the main byproducts considered sources of ADF, its mechanisms of action, and its potential use in the formulation of foods destined for human consumption. ADF responds to the demand for low-cost, functional ingredients with great health benefits. A higher intake of antioxidant dietary fiber contributes to reducing the risk of diseases such as type II diabetes, colon cancer, obesity, and kidney stones, and has bile-acid retention-excretion, gastrointestinal laxative, hypoglycemic, hypocholesterolemic, prebiotic, and cardioprotective effects. ADF is a functional, sustainable, and profitable ingredient with different applications in agroindustry; its use can improve the technofunctional and nutritional properties of food, helping to close the cycle following the premise of the circular economy.
- Published
- 2022
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10. Biocatalyst developed with recovered iron-rich minerals enhances the biotransformation of SARS-CoV-2 antiviral drugs in anaerobic bioreactors.
- Author
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Mares-Carbajal FJ, Espinosa-Arzate MC, Ramírez-Montoya LA, Pat-Espadas AM, Ramírez JE, Rangel-Mendez JR, Ascacio-Valdes JA, Aguilar CN, Mijaylova P, Buitrón G, and Cervantes FJ
- Abstract
The biotransformation of the SARS-CoV-2 antiviral drugs, ribavirin and tenofovir, was studied in methanogenic bioreactors. The role of iron-rich minerals, recovered from a metallurgic effluent, on the biotransformation process was also assessed. Enrichment of anaerobic sludge with recovered minerals promoted superior removal efficiency for both antivirals (97.4 % and 94.7 % for ribavirin and tenofovir, respectively) as compared to the control bioreactor lacking minerals, which achieved 58.5 % and 37.9 % removal for the same drugs, respectively. Further analysis conducted by liquid chromatography coupled to mass spectroscopy revealed several metabolites derived from the biotransformation of both antivirals. Interestingly, tracer analysis with
13 CH4 revealed that anaerobic methane oxidation coupled to Fe(III) reduction occurred in the enriched bioreactor, which was reflected in a lower content of methane in the biogas produced from this system, as compared to the control bioreactor. This treatment proposal is suitable within the circular economy concept, in which recovered metals from an industrial wastewater are applied in bioreactors to create a biocatalyst for promoting the biotransformation of emerging pollutants. This strategy may be appropriate for the anaerobic treatment of wastewaters originated from hospitals, as well as from the pharmaceutical and chemical sectors., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier Ltd. All rights reserved.)- Published
- 2022
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11. Feeding ecology of invasive lionfish in the Punta Frances MPA, Cuba: insight into morphological features, diet and management.
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Del Río L, Navarro-Martínez ZM, Ruiz-Abierno A, Chevalier-Monteagudo PP, Angulo-Valdes JA, and Rodriguez-Viera L
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- Animals, Cuba, Predatory Behavior, Fishes, Diet, France, Introduced Species, Perciformes
- Abstract
Cuba's shelf has been invaded by lionfish ( Pterois volitans/Pterois miles ), which have become established over the archipelago, including areas of natural importance. The present study aims to evaluate morphometric features of lionfish and to explore the relationship between lionfish size and diet composition in different habitats in the Punta Frances National Park, Cuba. In total 620 lionfish were captured at 29 sites between 2013 and 2016. Lionfish stomachs were removed and their contents were analyzed using frequency and numerical methods. The length-weight allomentric relationship was obtained, and a decrease in lionfish sizes was shown over time, likely due to the extractions carried out. The diet was composed by fishes, crustaceans, mollusks and phytobenthos, with a predominance of fishes. Lionfish caught in seagrass beds tended to be smaller in size and consumed fewer fishes and more crustaceans than those captured in coral reefs. A positive correlation was observed between lionfish body size and gape size; however, no significant correlation was detected between lionfish body size and prey size. Larger lionfish tended to consume more fishes, while crustaceans were more significant in the diet of juvenile lionfish. This is the first study that examines the feeding habits of lionfish in the Punta Frances MPA, and provides valuable information on lionfish inhabiting this MPA across four years of sampling. Furthermore, this research may serve as a baseline for subsequent evaluations of lionfish impact and management actions in the area., Competing Interests: The authors declare that they have no competing interests., (© 2022 del Río et al.)
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- 2022
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12. Diversity of bet-hedging strategies in microbial communities-Recent cases and insights.
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Morawska LP, Hernandez-Valdes JA, and Kuipers OP
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- Adaptation, Physiological, Phenotype, Reproduction, Biological Evolution, Microbiota genetics
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Microbial communities are continuously exposed to unpredictable changes in their environment. To thrive in such dynamic habitats, microorganisms have developed the ability to readily switch phenotypes, resulting in a number of differently adapted subpopulations expressing various traits. In evolutionary biology, a particular case of phenotypic heterogeneity that evolved in an unpredictably changing environment has been defined as bet-hedging. Bet-hedging is a risk-spreading strategy where isogenic populations stochastically (randomly) diversify their phenotypes, often resulting in maladapted individuals that suffer lower reproductive success. This fitness trade-off in a specific environment may have a selective advantage upon the sudden environmental shift. Thus, a bet-hedging strategy allows populations to persist in very dynamic habitats, but with a particular fitness cost. In recent years, numerous examples of phenotypic heterogeneity in different microorganisms have been observed, some suggesting bet-hedging. Here, we highlight the latest reports concerning bet-hedging phenomena in various microorganisms to show how versatile this strategy is within the microbial realms. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology., (© 2021 The Authors. WIREs Mechanisms of Disease published by Wiley Periodicals LLC.)
- Published
- 2022
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13. Microbial competition reduces metabolic interaction distances to the low µm-range.
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van Tatenhove-Pel RJ, Rijavec T, Lapanje A, van Swam I, Zwering E, Hernandez-Valdes JA, Kuipers OP, Picioreanu C, Teusink B, and Bachmann H
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- Diffusion, Microbiota
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Metabolic interactions between cells affect microbial community compositions and hence their function in ecosystems. It is well-known that under competition for the exchanged metabolite, concentration gradients constrain the distances over which interactions can occur. However, interaction distances are typically quantified in two-dimensional systems or without accounting for competition or other metabolite-removal, conditions which may not very often match natural ecosystems. We here analyze the impact of cell-to-cell distance on unidirectional cross-feeding in a three-dimensional aqueous system with competition for the exchanged metabolite. Effective interaction distances were computed with a reaction-diffusion model and experimentally verified by growing a synthetic consortium of 1 µm-sized metabolite producer, receiver, and competitor cells in different spatial structures. We show that receivers cannot interact with producers located on average 15 µm away from them, as product concentration gradients flatten close to producer cells. We developed an aggregation protocol and varied the receiver cells' product affinity, to show that within producer-receiver aggregates even low-affinity receiver cells could interact with producers. These results show that competition or other metabolite-removal of a public good in a three-dimensional system reduces metabolic interaction distances to the low µm-range, highlighting the importance of concentration gradients as physical constraint for cellular interactions.
- Published
- 2021
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14. Correction: Catabolic Signaling Pathways, Atrogenes, and Ubiquitinated Proteins Are Regulated by the Nutritional Status in the Muscle of the Fine Flounder.
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Fuentes EN, Ruiz P, Valdes JA, and Molina A
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[This corrects the article DOI: 10.1371/journal.pone.0044256.].
- Published
- 2020
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15. Impact of spatial proximity on territoriality among human skin bacteria.
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Hernandez-Valdes JA, Zhou L, de Vries MP, and Kuipers OP
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- Bacterial Proteins biosynthesis, Bacterial Proteins pharmacology, Dipeptides biosynthesis, Humans, Microbial Interactions, Microbial Viability drug effects, Phylogeny, Staphylococcus epidermidis drug effects, Territoriality, Bacillus subtilis physiology, Dipeptides pharmacology, Skin microbiology, Staphylococcus epidermidis growth & development
- Abstract
Bacteria display social behavior and establish cooperative or competitive interactions in the niches they occupy. The human skin is a densely populated environment where many bacterial species live. Thus, bacterial inhabitants are expected to find a balance in these interactions, which eventually defines their spatial distribution and the composition of our skin microbiota. Unraveling the physiological basis of the interactions between bacterial species in organized environments requires reductionist analyses using functionally relevant species. Here, we study the interaction between two members of our skin microbiota, Bacillus subtilis and Staphylococcus epidermidis. We show that B. subtilis actively responds to the presence of S. epidermidis in its proximity by two strategies: antimicrobial production and development of a subpopulation with migratory response. The initial response of B. subtilis is production of chlorotetain, which degrades the S. epidermidis at the colony level. Next, a subpopulation of B. subtilis motile cells emerges. Remarkably this subpopulation slides towards the remaining S. epidermidis colony and engulfs it. A slow response back from S. epidermidis cells give origin to resistant cells that prevent both attacks from B. subtilis. We hypothesized that this niche conquering and back-down response from B. subtilis and S. epidermidis, respectively, which resembles other conflicts in nature as the ones observed in animals, may play a role in defining the presence of certain bacterial species in the specific microenvironments that these bacteria occupy on our skin.
- Published
- 2020
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16. Another Breaker of the Wall: the Biological Function of the Usp45 Protein of Lactococcus lactis.
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Hernandez-Valdes JA, Huang C, Kok J, and Kuipers OP
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- Bacterial Proteins metabolism, Lactococcus lactis metabolism, Promoter Regions, Genetic, Bacterial Proteins genetics, Cell Division physiology, Cell Wall metabolism, Gene Expression Regulation, Bacterial, Lactococcus lactis genetics
- Abstract
Lactococcus lactis is a Gram-positive bacterium that is widely used as a cell factory for the expression of heterologous proteins that are relevant in the pharmaceutical and nutraceutical fields. The signal peptide of the major secreted protein of L. lactis , Usp45, has been employed extensively in engineering strategies to secrete proteins of interest. However, the biological function of Usp45 has remained obscure despite more than 25 years of research. Studies on Usp45 homologs in other Gram-positive bacteria suggest that Usp45 may play a role in cell wall turnover processes. Here, we show the effect of inactivation and overexpression of the usp45 gene on L. lactis growth, phenotype, and cell division. Our results are in agreement with those obtained in streptococci and demonstrate that the L. lactis Usp45 protein is essential for proper cell division. We also show that the usp45 promoter is highly activated by galactose. Overall, our results indicate that Usp45 mediates cell separation, probably by acting as a peptidoglycan hydrolase. IMPORTANCE The cell wall, composed mainly of peptidoglycan, is key to maintaining the cell shape and protecting the cell from bursting. Peptidoglycan degradation by peptidoglycan hydrolysis and autolysins occurs during growth and cell division. Since peptidoglycan hydrolases are important for virulence, envelope integrity, and regulation of cell division, it is valuable to investigate their function and regulation. Notably, PcsB-like proteins such as Usp45 have been proposed as new targets for antimicrobial drugs and could also be target for the development of food-grade suicide systems. In addition, although various other expression and secretion systems have been developed for use in Lactococcus lactis , the most-used signal peptide for protein secretion in this bacterium is that of the Usp45 protein. Thus, elucidating the biological function of Usp45 and determining the factors affecting its expression would contribute to optimize several applications., (Copyright © 2020 American Society for Microbiology.)
- Published
- 2020
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17. Development of Lactococcus lactis Biosensors for Detection of Sulfur-Containing Amino Acids.
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Hernandez-Valdes JA, Dalglish MM, Hermans J, and Kuipers OP
- Abstract
The sulfur-containing amino acids methionine and cysteine play an important role in food industry. These amino acids are used to confer a sulfur smell or meat-related aroma to food products. Besides their use as food additives, methionine and cysteine participate in flavor formation in dairy fermentations. For instance, the characteristic aroma of Cheddar cheeses is derived from methionine. Therefore, bacterial strains with the ability to overproduce and secrete these amino acids are relevant for the food industry. In addition, the quantification of these compounds in food matrices is a laborious task that involves sample preparation and specific analytical methods such as high-performance liquid chromatography. The ability of bacteria to naturally sense metabolites has successfully been exploited to develop biosensors. The presence of a specific metabolite is sensed by the biosensors, and it is subsequently translated into the expression of one or more reporter genes. In this study we aim to develop biosensors to detect methionine and cysteine, which are produced and secreted by wild-type Lactococcus lactis strains. We employed two strategies to create L. lactis biosensors, the first one is based on the methionine auxotrophy of this bacterium and the second strategy is based on a cysteine-responsive promoter. The characterization of the biosensors showed their specific response to the presence of these amino acids. Subsequently, we applied the methionine biosensor to quantify the presence of methionine in bacterial supernatants of wild-type L. lactis that naturally secretes methionine to benchmark the performance of our biosensors. The methionine biosensor responded linearly to the amounts of methionine present in the bacterial supernatants, i.e., the increases in the biosensor cell densities were proportional to the amounts of methionine present in the supernatants. The biosensors developed in this study tackle the limitations of amino acid quantification and the selection of strains with secretion of amino acids. These biosensors may eventually be used for screening of engineered strains to increase methionine and cysteine production, and may facilitate the detection of these amino acids in complex food matrices., (Copyright © 2020 Hernandez-Valdes, Dalglish, Hermans and Kuipers.)
- Published
- 2020
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18. Enhancement of amino acid production and secretion by Lactococcus lactis using a droplet-based biosensing and selection system.
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Hernandez-Valdes JA, Aan de Stegge M, Hermans J, Teunis J, van Tatenhove-Pel RJ, Teusink B, Bachmann H, and Kuipers OP
- Abstract
Amino acids are attractive metabolites for the pharmaceutical and food industry field. On one hand, the construction of microbial cell factories for large-scale production aims to satisfy the demand for amino acids as bulk biochemical. On the other hand, amino acids enhance flavor formation in fermented foods. Concerning the latter, flavor formation in dairy products, such as cheese is associated with the presence of lactic acid bacteria (LAB). In particular, Lactococcus lactis , one of the most important LAB, is used as a starter culture in fermented foods. The proteolytic activity of some L. lactis strains results in peptides and amino acids, which are flavor compounds or flavor precursors. However, it is still a challenge to isolate bacterial cells with enhanced amino acid production and secretion activity. In this work, we developed a growth-based sensor strain to detect the essential amino acids isoleucine, leucine, valine, histidine and methionine. Amino acids are metabolites that can be secreted by some bacteria. Therefore, our biosensor allowed us to identify wild-type L. lactis strains that naturally secrete amino acids, by using co-cultures of the biosensor strain with potential amino acid producing strains. Subsequently, we used this biosensor in combination with a droplet-based screening approach, and isolated three mutated L. lactis IPLA838 strains with 5-10 fold increased amino acid-secretion compared to the wild type. Genome re-sequencing revealed mutations in genes encoding proteins that participate in peptide uptake and peptide degradation. We argue that an unbalance in the regulation of amino acid levels as a result of these gene mutations may drive the accumulation and secretion of these amino acids. This biosensing system tackles the problem of selection for overproduction of secreted molecules, which requires the coupling of the product to the producing cell in the droplets., Competing Interests: We confirm that there are no conflicts of interest associated with this publication., (© 2020 The Authors. Published by Elsevier B.V. on behalf of International Metabolic Engineering Society.)
- Published
- 2020
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19. Use of coffee pulp and sorghum mixtures in the production of n-demethylases by solid-state fermentation.
- Author
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Peña-Lucio EM, Londoño-Hernández L, Ascacio-Valdes JA, Chavéz-González ML, Bankole OE, and Aguilar CN
- Subjects
- Coffee, Fermentation, Oxidoreductases, N-Demethylating, Rhizopus, Sorghum
- Abstract
One of the compounds generally found in the residues of the coffee and tea industries is caffeine, which in high concentration is toxic to various organisms, making it necessary to find an adequate treatment for these residues. Biotechnological treatments using enzymes can be an alternative to valorize and detoxify these residues. However, mixtures of substrates have not been evaluated to improve production. Therefore, the present investigation aimed to study the effect of different proportions of sorghum-coffee pulp mixtures as a substrate in solid-state fermentation with the fungus Rhizopus oryzae (MUCL 28168) for the production of n-demethylases. To evaluate the synergistic and antagonistic effects of coffee pulp and sorghum mixtures on n-demethylase enzyme production, a simplex-centroid design, using four levels: 1 (100%), 1/4 (25%), 1/2 (50%), 3/4 (75%). Results obtained were favorable, achieving a caffeine demethylase activity of 18.762 U/g, and reducing the caffeine content in the coffee pulp., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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20. Development of Lactococcus lactis Biosensors for Detection of Diacetyl.
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Hernandez-Valdes JA, Solopova A, and Kuipers OP
- Abstract
Some secondary metabolites of fermentative bacteria are desired compounds for the food industry. Examples of these compounds are diacetyl and acetaldehyde, which are produced by species of the lactic acid bacteria (LAB) family. Diacetyl is an aromatic compound, giving the buttery flavor associated with dairy products, and acetaldehyde is the compound responsible for the yogurt flavor and aroma. The quantification of these compounds in food matrices is a laborious task that involves sample preparation and specific analytical methods. The ability of bacteria to naturally sense metabolites has successfully been exploited to develop biosensors that facilitate the identification and quantification of certain metabolites (Mahr and Frunzke, 2016). The presence of a specific metabolite is sensed by the biosensors, and it is subsequently translated into the expression of one or more reporter genes. In this study we aimed to develop fluorescence-based biosensors to detect diacetyl and acetaldehyde. Since the metabolic pathways for production and degradation of these compounds are present in Lactococcus lactis , the sensing mechanisms in this bacterium are expected. Thus, we identified diacetyl and acetaldehyde responsive promoters by performing transcriptome analyses in L. lactis . The characterization of the biosensors showed their response to the presence of these compounds, and a further analysis of the diacetyl-biosensors (its dynamics and orthogonality) was performed. Moreover, we attempted to produce natural diacetyl from producer strains, namely L. lactis subsp. lactis biovar diacetylactis, to benchmark the performance of our biosensors. The diacetyl-biosensors responded linearly to the amounts of diacetyl obtained in the bacterial supernatants, i.e., the increases in GFP expression were proportional to the amounts of diacetyl present in the supernatants of L. lactis subsp. lactis biovar diacetylactis MR3-T7 strain. The biosensors developed in this study may eventually be used to engineer strains or pathways for increased diacetyl and acetaldehyde production, and may facilitate the detection of these metabolites in complex food matrices., (Copyright © 2020 Hernandez-Valdes, Solopova and Kuipers.)
- Published
- 2020
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21. Draft Genome Sequences of Three Amino Acid-Secreting Lactococcus lactis Strains.
- Author
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Hernandez-Valdes JA, de Jong A, Kok J, and Kuipers OP
- Abstract
Three Lactococcus lactis strains with the ability to secrete various amino acids (leucine, isoleucine, methionine, valine, glutamic acid, and histidine) were sequenced in order to identify the mechanisms involved in the secretion. Amino acids contribute to flavor formation; therefore, bacterial strains with this ability are relevant for the food industry., (Copyright © 2020 Hernandez-Valdes et al.)
- Published
- 2020
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22. Lysis of a Lactococcus lactis Dipeptidase Mutant and Rescue by Mutation in the Pleiotropic Regulator CodY.
- Author
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Huang C, Hernandez-Valdes JA, Kuipers OP, and Kok J
- Subjects
- Bacterial Proteins metabolism, Dipeptidases metabolism, Genes, Bacterial, Genetic Pleiotropy, Lactococcus metabolism, Bacterial Proteins genetics, Dipeptidases genetics, Lactococcus genetics, Mutation
- Abstract
Lactococcus lactis subsp. cremoris MG1363 is a model for the lactic acid bacteria (LAB) used in the dairy industry. The proteolytic system, consisting of a proteinase, several peptide and amino acid uptake systems, and a host of intracellular peptidases, plays a vital role in nitrogen metabolism and is of eminent importance for flavor formation in dairy products. The dipeptidase PepV functions in the last stages of proteolysis. A link between nitrogen metabolism and peptidoglycan (PG) biosynthesis was underlined by the finding that deletion of the dipeptidase gene pepV (creating strain MGΔ pepV ) resulted in a prolonged lag phase when the mutant strain was grown with a high concentration of glycine. In addition, most MGΔ pepV cells lyse and have serious defects in their shape. This phenotype is due to a shortage of alanine, since adding alanine can rescue the growth and shape defects. Strain MGΔ pepV is more resistant to vancomycin, an antibiotic targeting peptidoglycan d-Ala-d-Ala ends, which confirmed that MGΔ pepV has an abnormal PG composition. A mutant of MGΔ pepV was obtained in which growth inhibition and cell shape defects were alleviated. Genome sequencing showed that this mutant has a single point mutation in the codY gene, resulting in an arginine residue at position 218 in the DNA-binding motif of CodY being replaced by a cysteine residue. Thus, this strain was named MGΔ pepVcodY
R218C Transcriptome sequencing (RNA-seq) data revealed a dramatic derepression in peptide uptake and amino acid utilization in MGΔ pepVcodYR218C A model of the connections among PepV activity, CodY regulation, and PG synthesis of L. lactis is proposed. IMPORTANCE Precise control of peptidoglycan synthesis is essential in Gram-positive bacteria for maintaining cell shape and integrity as well as resisting stresses. Although neither the dipeptidase PepV nor alanine is essential for L. lactis MG1363, adequate availability of either ensures proper cell wall synthesis. We broaden the knowledge about the dipeptidase PepV, which acts as a linker between nitrogen metabolism and cell wall synthesis in L. lactis ., (Copyright © 2020 Huang et al.)- Published
- 2020
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23. A riboswitch gives rise to multi-generational phenotypic heterogeneity in an auxotrophic bacterium.
- Author
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Hernandez-Valdes JA, van Gestel J, and Kuipers OP
- Subjects
- Bacterial Proteins metabolism, Gene Expression Regulation, Bacterial, Green Fluorescent Proteins metabolism, Lactococcus lactis cytology, Membrane Transport Proteins metabolism, Models, Biological, Operon genetics, Phenotype, Single-Cell Analysis, Transcription, Genetic, Lactococcus lactis genetics, Riboswitch genetics
- Abstract
Auxotrophy, the inability to produce an organic compound essential for growth, is widespread among bacteria. Auxotrophic bacteria rely on transporters to acquire these compounds from their environment. Here, we study the expression of both low- and high-affinity transporters of the costly amino acid methionine in an auxotrophic lactic acid bacterium, Lactococcus lactis. We show that the high-affinity transporter (Met-transporter) is heterogeneously expressed at low methionine concentrations, resulting in two isogenic subpopulations that sequester methionine in different ways: one subpopulation primarily relies on the high-affinity transporter (high expression of the Met-transporter) and the other subpopulation primarily relies on the low-affinity transporter (low expression of the Met-transporter). The phenotypic heterogeneity is remarkably stable, inherited for tens of generations, and apparent at the colony level. This heterogeneity results from a T-box riboswitch in the promoter region of the met operon encoding the high-affinity Met-transporter. We hypothesize that T-box riboswitches, which are commonly found in the Lactobacillales, may play as-yet unexplored roles in the predominantly auxotrophic lifestyle of these bacteria.
- Published
- 2020
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24. Microdroplet screening and selection for improved microbial production of extracellular compounds.
- Author
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van Tatenhove-Pel RJ, Hernandez-Valdes JA, Teusink B, Kuipers OP, Fischlechner M, and Bachmann H
- Subjects
- Fermentation
- Abstract
Microorganisms produce extracellular compounds that affect the final product quality in fermentation processes. Selection of overproducing mutants requires coupling of the extracellular product to the producer genotype, which can be achieved by single-cell compartmentalization. Emulsions contain up to billions of microdroplets/mL which significantly increases the screening throughput compared to microtiter-plate-based selections. Factors affecting the success of screening in microdroplets include the nature of the producing organism (robust, no invasive growth), the product (not soluble in oil) and the product assay (preferably fluorescence based). Together these factors determine the required microdroplet production technique and sorting set-up. Because microdroplets allow relatively inexpensive ultrahigh-throughput screening, they are likely to become a standard tool in the strain selection toolbox of the fermentation industry., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2020
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25. Identification and Evaluation of Long Noncoding RNAs in Response to Handling Stress in Red Cusk-Eel (Genypterus chilensis) via RNA-seq.
- Author
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Dettleff P, Hormazabal E, Aedo J, Fuentes M, Meneses C, Molina A, and Valdes JA
- Subjects
- Animals, Aquaculture, Eels metabolism, Head Kidney metabolism, Liver metabolism, Muscle, Skeletal metabolism, RNA-Seq, Eels genetics, RNA, Long Noncoding, Stress, Physiological
- Abstract
The red cusk-eel (Genypterus chilensis) is a native species with strong potential to support Chilean aquaculture diversification. Under commercial conditions, fish are exposed to several stressors. To date, little is known about the mechanism involved in the stress response of red cusk-eel, and there is no information related to the regulation mediated by long noncoding RNAs (lncRNAs). The objective of this work was to identify for the first time the lncRNAs in the transcriptome of G. chilensis and to evaluate the differential expression levels of lncRNAs in the liver, head kidney, and skeletal muscle in response to handling stress. We used previously published transcriptome data to identify the lncRNAs by applying a series of filters based on annotation information in several databases to discard coding sequences. We identified a total of 14,614 putative lncRNAs in the transcriptome of red cusk-eel, providing a useful lncRNA reference resource to be used in future studies. We evaluated their differential expression in response to handling stress in the liver, head kidney, and skeletal muscle, identifying 112, 323, and 108 differentially expressed lncRNAs, respectively. The results suggest that handling stress in red cusk-eel generate an altered metabolic status in liver, altered immune response in head kidney, and skeletal muscle atrophy through an important coding and noncoding gene network. This is the first study that identifies lncRNAs in Genypterus genus and that evaluates the relation between handling stress and lncRNAs in teleost fish, thereby providing valuable information regarding noncoding responses to stress in Genypterus species.
- Published
- 2020
- Full Text
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26. Emerging strategies for the development of food industries.
- Author
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Aguilar CN, Ruiz HA, Rubio Rios A, Chávez-González M, Sepúlveda L, Rodríguez-Jasso RM, Loredo-Treviño A, Flores-Gallegos AC, Govea-Salas M, and Ascacio-Valdes JA
- Subjects
- Bioengineering, Food Industry instrumentation, Green Chemistry Technology, Food Industry methods, Food Industry trends
- Abstract
Undoubtedly, the food industry is undergoing a dynamic process of transformation in its continual development in order to meet the requirements and solve the great problems represented by a constantly growing global population and food claimant in both quantity and quality. In this sense, it is necessary to evaluate the technological trends and advances that will change the landscape of the food processing industry, highlighting the latest requirements for equipment functionality. In particular, it is crucial to evaluate the influence of sustainable green biotechnology-based technologies to consolidate the food industry of the future, today, and it must be done by analyzing the mega-consumption trends that shape the future of industry, which range from local sourcing to on-the-go food, to an increase in organic foods and clean labels (understanding ingredients on food labels). While these things may seem alien to food manufacturing, they have a considerable influence on the way products are manufactured. This paper reviews in detail the conditions of the food industry, and particularly analyzes the application of emerging technologies in food preservation, extraction of bioactive compounds, bioengineering tools and other bio-based strategies for the development of the food industry.
- Published
- 2019
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27. Ellagic Acid Recovery by Solid State Fermentation of Pomegranate Wastes by Aspergillus niger and Saccharomyces cerevisiae : A Comparison.
- Author
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Moccia F, Flores-Gallegos AC, Chávez-González ML, Sepúlveda L, Marzorati S, Verotta L, Panzella L, Ascacio-Valdes JA, Aguilar CN, and Napolitano A
- Subjects
- Aspergillus niger chemistry, Aspergillus niger metabolism, Ellagic Acid isolation & purification, Ethanol chemistry, Fermentation, Hydrolysis, Hydrolyzable Tannins chemistry, Hydrolyzable Tannins isolation & purification, Saccharomyces cerevisiae chemistry, Saccharomyces cerevisiae metabolism, Ellagic Acid chemistry, Fruit chemistry, Pomegranate chemistry, Solid Waste
- Abstract
Fermentation in solid state culture (SSC) has been the focus of increasing interest because of its potential for industrial applications. In previous studies SSC of pomegranate wastes by Aspergillus niger has been extensively developed and optimized for the recovery of ellagic acid (EA), a high value bioactive. In this study we comparatively investigated the SSC of powdered pomegranate husks by A. niger and Saccharomyces cerevisiae and evaluated the recovery yields of EA by an ultrasound and microwave-assisted 7:3 water/ethanol extraction. Surprisingly enough, the yields obtained by S. cerevisiae fermentation (4% w / w ) were found 5-fold higher than those of the A. niger fermented material, with a 10-fold increase with respect to the unfermented material. The EA origin was traced by HPLC analysis that showed a significant decrease in the levels of punicalagin isomers and granatin B and formation of punicalin following fermentation. Other extraction conditions that could warrant a complete solubilization of EA were evaluated. Using a 1:100 solid to solvent ratio and DMSO as the solvent, EA was obtained in 4% yields from S. cerevisiae fermented husks at a high purity degree. Hydrolytic treatment of S. cerevisiae fermented pomegranate husks afforded a material freed of the polysaccharides components that gave recovery yields of EA up to 12% w / w .
- Published
- 2019
- Full Text
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28. Thermal Modulation of Monoamine Levels Influence Fish Stress and Welfare.
- Author
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Sanhueza N, Donoso A, Aguilar A, Farlora R, Carnicero B, Míguez JM, Tort L, Valdes JA, and Boltana S
- Abstract
Fish are ectotherm organisms that move through different thermal zones according to their physiological requirements and environmental availability, a behavior known as thermoregulation. Thermoregulation in ectothermic animals is influenced by their ability to effectively respond to thermal variations. While it is known that ectotherms are affected by thermal changes, it remains unknown how physiological and/or metabolic traits are impacted by modifications in the thermal environment. In captivity (land-based infrastructures or nets located in the open sea), fish are often restricted to spatially constant temperature conditions within the containment unit and cannot choose among different thermal conditions for thermoregulation. In order to understand how spatial variation of temperature may affect fish welfare and stress, we designed an experiment using either restricted or wide thermal ranges, looking for changes at hormonal and molecular levels. Also, thermal variability impact on fish behavior was measured. Our results showed that in Atlantic salmon ( Salmo salar ), a wide thermal range (ΔT 6.8°C) was associated with significant increases in monoamines hormone levels and in the expression of clock genes. Aggressive and territoriality behavior decreased, positively affecting parameters linked to welfare, such as growth and fin damage. In contrast, a restricted thermal range (ΔT 1.4°C) showed the opposite pattern in all the analyzed parameters, therefore, having detrimental effects on welfare. In conclusion, our results highlight the key role of thermal range amplitude on fish behavior and on interactions with major metabolism-regulating processes, such as hormone performance and molecular regulatory mechanisms that have positive effects on the welfare.
- Published
- 2018
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29. Hippocrates to Nightingale: Converging or Diverging Concepts in Patient Management and Decision Making.
- Author
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Valdes JA, Kradel B, and Hinson S
- Subjects
- Humans, United States, Nurse's Role, Patient Care Management, Physician's Role
- Abstract
Although medicine and nursing are complementary and equally important, paradoxically the relationship can appear adversarial at times. Physicians and nurses work concurrently and conjointly in hospitals where patients are admitted for round-the-clock nursing care to help cure or attenuate diseases. Roles are further obscured for advanced practice nurses and physicians when they perform the same function, such as in the practice of anesthesia. Regarding physician-nurse relationships, the following questions become apparent:Why do these professions compete over the right to take care of patients? Where and when did this conflict originate? Answers are complicated and multifactorial. This commentary briefly reviews the history of the establishment of medicine and nursing, discusses gender roles, and summarizes differences in education and training between the two disciplines., Competing Interests: The authors have declared no financial relationships with any commercial entity related to the content of this article. The authors did not discuss off-label use within the article., (Copyright© by the American Association of Nurse Anesthetists.)
- Published
- 2018
30. Intravenous Fat Emulsion for Treatment of Local Anesthetic Systemic Toxicity: Best Practice and Review of the Literature.
- Author
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Nedialkov AM, Umadhay T, Valdes JA, and Campbell Y
- Subjects
- Humans, Infusions, Intravenous, Nurse Anesthetists, Practice Guidelines as Topic, Anesthetics, Local toxicity, Fat Emulsions, Intravenous administration & dosage
- Abstract
Local anesthetic systemic toxicity (LAST), although rare, can be a fatal complication after regional anesthesia. The use of intravenous (IV) fat emulsion as a treatment of LAST is controversial among clinicians worldwide. This literature review aims to identify existing data supporting the use of IV lipids in the management of LAST and current best evidence-based practice by anesthesia providers during a LAST event. More than 120 articles resulted from a systematic literature search that was conducted using major search engines. Of those articles, 25 were included in this literature review. The safe use of IV lipids for the treatment of LAST is supported in the literature. Yet, there is still lack of awareness on lipid rescue therapy despite the significant evidence of its positive outcome. In the setting of local-anesthetic toxicity, lipid rescue should be considered first-line treatment. Intravenous lipids must be readily available in all institutions performing regional anesthesia. Education on their use, storage, and dosage is vital among anesthesia departments in the United States and worldwide., Competing Interests: The authors have declared no financial relationships with any commercial entity related to the content of this article. The authors did not discuss off-label use within the article., (Copyright© by the American Association of Nurse Anesthetists.)
- Published
- 2018
31. Solid bioprocess of tarbush ( Flourensia cernua ) leaves for β-glucosidase production by Aspergillus niger : initial approach to fiber-glycoside interaction for enzyme induction.
- Author
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Lopez-Trujillo J, Medina-Morales MA, Sanchez-Flores A, Arevalo C, Ascacio-Valdes JA, Mellado M, Aguilar CN, and Aguilera-Carbo AF
- Abstract
Commercial cellulase production has increased in recent years and consistent research has been carried out to improve levels of β-glucosidase. Bioprocesses have been successfully adapted to produce this enzyme, with solid-state fermentations as the best-suited technique involving fungi. The aim of this study was to use leaves of tarbush ( Flourensia cernua ), an abundant shrub of the Chihuahuan Desert, as a carbon source for β-glucosidase production by Aspergillus niger . During the solid bioprocess, this enzyme reached its peak production at 36 h of culture with 3876.6 U/L. There is a particular interest in the substrate composition because of the possibility of phenolic glycosides having an important role in β-glucosidase production. HPLC-MS analyses showed that glycosides were present with the highest accumulation at 36 h of fungal culture. Luteolin and apigenin glycosides [1.8 and 2.4 absorbance units, respectively] were also detected and showed their highest point of detection alongside the highest β-glucosidase activity. No apparent changes in cellulose were observed, while hemicellulose content decreased, which could be related to production and activity of β-glucosidase. This study shows that leaves of F. cernua are an important raw material for β-glucosidase production and give a source of compounds of added value which also may have an important role for β-glucosidase production.
- Published
- 2017
- Full Text
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32. Influences of thermal environment on fish growth.
- Author
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Boltaña S, Sanhueza N, Aguilar A, Gallardo-Escarate C, Arriagada G, Valdes JA, Soto D, and Quiñones RA
- Abstract
Thermoregulation in ectothermic animals is influenced by the ability to effectively respond to thermal variations. While it is known that ectotherms are affected by thermal changes, it remains unknown whether physiological and/or metabolic traits are impacted by modifications to the thermal environment. Our research provides key evidence that fish ectotherms are highly influenced by thermal variability during development, which leads to important modifications at several metabolic levels (e.g., growth trajectories, microstructural alterations, muscle injuries, and molecular mechanisms). In Atlantic salmon ( Salmo salar ), a wide thermal range (Δ
T 6.4°C) during development (posthatch larvae to juveniles) was associated with increases in key thermal performance measures for survival and growth trajectory. Other metabolic traits were also significantly influenced, such as size, muscle cellularity, and molecular growth regulators possibly affected by adaptive processes. In contrast, a restricted thermal range (ΔT 1.4°C) was detrimental to growth, survival, and cellular microstructure as muscle growth could not keep pace with increased metabolic demands. These findings provide a possible basic explanation for the effects of thermal environment during growth. In conclusion, our results highlight the key role of thermal range amplitude on survival and on interactions with major metabolism-regulating processes that have positive adaptive effects for organisms.- Published
- 2017
- Full Text
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33. Workforce Initiative for Current Predictors of CRNA Employment in the State of Florida.
- Author
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Wunder LL, Glymph DC, Schirle L, and Valdes JA
- Abstract
The challenging Florida anesthesia workforce has 3 different types of anesthesia providers competing in the same market and a growing population ranked number 2 in the United States. This study attempted to forecast changes in supply and demand of nurse anesthetists in Florida between 2014 and 2018 by surveying hospitals and ambulatory surgical centers; 17% (87/511) responded. Current anesthesia workforce and projected needs in 1, 2, and 5 years were included in the survey. Projected numbers of nurse anesthetist graduates from 2014 to 2018 were obtained from nurse anesthesia programs and schools in Florida. Respondents projected 73 new full-time openings through 2018, representing an 18% growth rate. Florida nurse anesthesia schools projected graduating 1,394 new Certified Registered Nurse Anesthetists (CRNAs) through 2018. This study estimated that 85% of new graduates will find full-time positions. A 22% growth in full-time positions would be required to absorb all new graduates expected to enter the Florida workforce. A projected surplus of 15% (114 positions) is in line with recent projected simulated models. The predicted CRNA surplus depends on current staffing models. Nonetheless, 633 new full-time positions would represent an increase in the proportion of fulltime CRNAs in the Florida workforce., Competing Interests: The authors declare they have no financial relationships with any commercial entity related to the content of this article. The authors did not discuss off-label use within the article., (Copyright© by the American Association of Nurse Anesthetists.)
- Published
- 2017
34. Immobilization of metal-humic acid complexes in anaerobic granular sludge for their application as solid-phase redox mediators in the biotransformation of iopromide in UASB reactors.
- Author
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Cruz-Zavala AS, Pat-Espadas AM, Rangel-Mendez JR, Chazaro-Ruiz LF, Ascacio-Valdes JA, Aguilar CN, and Cervantes FJ
- Subjects
- Anaerobiosis, Biological Oxygen Demand Analysis, Biotransformation, Electrochemistry, Electrons, Environment, Iohexol metabolism, Oxidation-Reduction, Bioreactors microbiology, Coordination Complexes chemistry, Humic Substances analysis, Iohexol analogs & derivatives, Sewage microbiology
- Abstract
Metal-humic acid complexes were synthesized and immobilized by a granulation process in anaerobic sludge for their application as solid-phase redox mediators (RM) in the biotransformation of iopromide. Characterization of Ca- and Fe-humic acid complexes revealed electron accepting capacities of 0.472 and 0.556milli-equivalentsg(-1), respectively. Once immobilized, metal-humic acid complexes significantly increased the biotransformation of iopromide in upflow anaerobic sludge blanket (UASB) reactors. Control UASB reactor (without humic material) achieved 31.6% of iopromide removal, while 80% was removed in UASB reactors supplied with each metal-humic acid complex. Further analyses indicated multiple transformation reactions taking place in iopromide including deiodination, N-dealkylation, decarboxylation and deacetylation. This is the first successful application of immobilized RM, which does not require a supporting material to maintain the solid-phase RM in long term operation of bioreactors. The proposed redox catalyst could be suitable for enhancing the redox conversion of different recalcitrant pollutants present in industrial effluents., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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35. Immobilization of biogenic Pd(0) in anaerobic granular sludge for the biotransformation of recalcitrant halogenated pollutants in UASB reactors.
- Author
-
Pat-Espadas AM, Razo-Flores E, Rangel-Mendez JR, Ascacio-Valdes JA, Aguilar CN, and Cervantes FJ
- Abstract
The capacity of anaerobic granular sludge to reduce Pd(II), using ethanol as electron donor, in an upflow anaerobic sludge blanket (UASB) reactor was demonstrated. Results confirmed complete reduction of Pd(II) and immobilization as Pd(0) in the granular sludge. The Pd-enriched sludge was further evaluated regarding biotransformation of two recalcitrant halogenated pollutants: 3-chloro-nitrobenzene (3-CNB) and iopromide (IOP) in batch and continuous operation in UASB reactors. The superior removal capacity of the Pd-enriched biomass when compared with the control (not exposed to Pd) was demonstrated in both cases. Results revealed 80 % of IOP removal efficiency after 100 h of incubation in batch experiments performed with Pd-enriched biomass whereas only 28 % of removal efficiency was achieved in incubations with biomass lacking Pd. The UASB reactor operated with the Pd-enriched biomass achieved 81 ± 9.5 % removal efficiency of IOP and only 61 ± 8.3 % occurred in the control reactor lacking Pd. Regarding 3-CNB, it was demonstrated that biogenic Pd(0) promoted both nitro-reduction and dehalogenation resulting in the complete conversion of 3-CNB to aniline while in the control experiment only nitro-reduction was documented. The complete biotransformation pathway of both contaminants was proposed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis evidencing a higher degree of nitro-reduction and dehalogenation of both contaminants in the experiments with Pd-enriched anaerobic sludge as compared with the control. A biotechnological process is proposed to recover Pd(II) from industrial streams and to immobilize it in anaerobic granular sludge. The Pd-enriched biomass is also proposed as a biocatalyst to achieve the biotransformation of recalcitrant compounds in UASB reactors.
- Published
- 2016
- Full Text
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36. The TORC1/P70S6K and TORC1/4EBP1 signaling pathways have a stronger contribution on skeletal muscle growth than MAPK/ERK in an early vertebrate: Differential involvement of the IGF system and atrogenes.
- Author
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Fuentes EN, Einarsdottir IE, Paredes R, Hidalgo C, Valdes JA, Björnsson BT, and Molina A
- Subjects
- Animals, Flatfishes metabolism, Flavonoids pharmacology, Mechanistic Target of Rapamycin Complex 1, Muscle Development drug effects, Muscle Development genetics, Muscle, Skeletal drug effects, Muscle, Skeletal metabolism, Protein Kinase Inhibitors pharmacology, Signal Transduction drug effects, Signal Transduction physiology, Sirolimus pharmacology, Eukaryotic Initiation Factors physiology, Flatfishes growth & development, Mitogen-Activated Protein Kinase Kinases physiology, Multiprotein Complexes physiology, Muscle Development physiology, Muscle, Skeletal growth & development, Ribosomal Protein S6 Kinases, 70-kDa physiology, Somatomedins physiology, TOR Serine-Threonine Kinases physiology
- Abstract
Knowledge about the underlying mechanisms, particularly the signaling pathways that account for muscle growth in vivo in early vertebrates is still scarce. Fish (Paralichthys adspersus) were fasted for 3weeks to induce a catabolic period of strong muscle atrophy. Subsequently, fish were refed for 2weeks to induce compensatory muscle hypertrophy. During refeeding, the fish were treated daily with either rapamycin (TORC blocker), PD98059 (MEK blocker), or PBS (V; vehicle), or were untreated (C; control). Rapamycin and PD98059 differentially impaired muscle cellularity in vivo, growth performance, and the expression of growth-related genes, and the inhibition of TORC1 had a greater impact on fish muscle growth than the inhibition of MAPK. Blocking TORC1 inhibited the phosphorylation of P70S6K and 4EBP1, two downstream components activated by TORC1, thus affecting protein contents in muscle. Concomitantly, the gene expression in muscle of igf-1, 2 and igfbp-4, 5 was down-regulated while the expression of atrogin-1, murf-1, and igfbp-2, 3 was up-regulated. Muscle hypertrophy was abolished and muscle atrophy was promoted, which finally affected body weight. TORC2 complex was not affected by rapamycin. On the other hand, the PD98059 treatment triggered ERK inactivation, a downstream component activated by MEK. mRNA contents of igf-1 in muscle were down-regulated, and muscle hypertrophy was partially impaired. The present study provides the first direct data on the in vivo contribution of TORC1/P70S6K, TORC1/4EBP1, and MAPK/ERK signaling pathways in the skeletal muscle of an earlier vertebrate, and highlights the transcendental role of TORC1 in growth from the cellular to organism level., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
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37. Skeletal muscle plasticity induced by seasonal acclimatization involves IGF1 signaling: implications in ribosomal biogenesis and protein synthesis.
- Author
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Fuentes EN, Zuloaga R, Valdes JA, Molina A, and Alvarez M
- Subjects
- Animals, Biomarkers, Insulin-Like Growth Factor I genetics, Insulin-Like Growth Factor II metabolism, Ligands, Muscle Development, Muscle, Skeletal growth & development, Phosphorylation, Protein Biosynthesis, Receptor, IGF Type 1 genetics, Receptor, IGF Type 1 metabolism, Ribosomal Proteins genetics, Ribosomal Proteins metabolism, Ribosomes genetics, Seasons, Signal Transduction, Acclimatization, Carps metabolism, Insulin-Like Growth Factor I metabolism, Muscle, Skeletal metabolism, Ribosomes metabolism
- Abstract
One of the most fundamental biological processes in living organisms that are affected by environmental fluctuations is growth. In fish, skeletal muscle accounts for the largest proportion of body mass, and the growth of this tissue is mainly controlled by the insulin-like growth factor (IGF) system. By using the carp (Cyprinus carpio), a fish that inhabits extreme conditions during winter and summer, we assessed the skeletal muscle plasticity induced by seasonal acclimatization and the relation of IGF signaling with protein synthesis and ribosomal biogenesis. The expression of igf1 in muscle decreased during winter in comparison with summer, whereas the expression for both paralogues of igf2 did not change significantly between seasons. The expression of igf1 receptor a (igf1ra), but not of igf1rb, was down-regulated in muscle during the winter as compared to the summer. A decrease in protein contents and protein phosphorylation for IGF signaling molecules in muscle was observed in winter-acclimatized carp. This was related with a decreased expression in muscle for markers of myogenesis (myoblast determination factor (myod), myogenic factor 5 (myf5), and myogenin (myog)); protein synthesis (myosin heavy chain (mhc) and myosin light chain (mlc3 and mlc1b)); and ribosomal biogenesis (pre-rRNA and ribosomal proteins). IGF signaling, and key markers of ribosomal biogenesis, protein synthesis, and myogenesis were affected by seasonal acclimatization, with differential regulation in gene expression and signaling pathway activation observed in muscle between both seasons. This suggests that these molecules are responsible for the muscle plasticity induced by seasonal acclimatization in carp., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
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38. Skeletal muscle plasticity induced by seasonal acclimatization in carp involves differential expression of rRNA and molecules that epigenetically regulate its synthesis.
- Author
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Fuentes EN, Zuloaga R, Nardocci G, Fernandez de la Reguera C, Simonet N, Fumeron R, Valdes JA, Molina A, and Alvarez M
- Subjects
- Animals, Chromatin Assembly and Disassembly, Chromosomal Proteins, Non-Histone, Cloning, Molecular, Epigenesis, Genetic, Fish Proteins genetics, Fish Proteins metabolism, Gene Expression Regulation, Histones genetics, Histones metabolism, Pol1 Transcription Initiation Complex Proteins genetics, Seasons, Sirtuin 1 genetics, Acclimatization physiology, Carps physiology, Muscle, Skeletal physiology, RNA, Ribosomal metabolism
- Abstract
Ribosomal biogenesis controls cellular growth in living organisms, with the rate-limiting step of this process being the transcription of ribosomal DNA (rDNA). Considering that epigenetic mechanisms allow an organism to respond to environmental changes, the expression in muscle of several molecules that regulate epigenetic rRNA synthesis, as well as rDNA transcription, were evaluated during the seasonal acclimatization of the carp. First, the nucleotide sequences encoding the components forming the NoRC (ttf-I, tip5) and eNoSC (sirt1, nml, suv39h1), two chromatin remodeling complexes that silence rRNA synthesis, as well as the sequence of ubf1, a key regulator of rDNA transcription, were obtained. Subsequently the transcriptional regulation of the aforementioned molecules, and other key molecules involved in rRNA synthesis (mh2a1, mh2a2, h2a.z, h2a.z.7, nuc, p80), was assessed. The carp sequences for TTF-I, TIP5, SIRT1, NML, SUV39H1, and UBF1 showed a high conservation of domains and key amino acids in comparison with other fish and higher vertebrates. The mRNA contents in muscle for ttf-I, tip5, sirt1, nml, suv39h1, mh2a1, mh2a.z, and nuc were up-regulated during winter in comparison with summer, whereas the mRNA levels of mh2a2, ubf1, and p80 were down-regulated. Also, the contents of molecules involved in processing the rRNA (snoRNAs) and pRNA, a stabilizer of NoRC complex, were analyzed, finding that these non-coding RNAs were not affected by seasonal acclimatization. These results suggest that variations in the expression of rRNA and the molecules that epigenetically regulate its synthesis are contributing to the muscle plasticity induced by seasonal acclimatization in carp., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
39. The concept of reentry in the addicted anesthesia provider.
- Author
-
Valdes JA
- Subjects
- Female, Humans, Male, Anesthesiology standards, Nurse Anesthetists standards, Occupational Diseases rehabilitation, Professional Impairment, Substance-Related Disorders rehabilitation
- Abstract
Substance abuse among healthcare providers is a serious issue affecting patient care and patient outcomes. Substance abuse among anesthesia providers is of extreme concern because of the type of drugs and easy access providers are granted. Impaired anesthesia providers jeopardize not only their own safety but also the safety of their patients. Accidental death of either the healthcare provider or the patient is often the unfortunate first sign of addiction among anesthesia providers. Most states, in the United States offer treatment programs for anesthesia providers as an option to disciplinary action, and on completion of the Substance abuse is the primary occupational program, the provider is allowed to reenter practice. Successful reentry is sometimes rare, and providers are plagued with the stigma of abuse, shame, and a high incidence of relapse. This article is an analysis of the concept of reentry into anesthesia practice, using Walker and Avant's model of concept analysis. Tenets of successful reentry are discussed. Implications for further concept analysis, practice, and research are presented.
- Published
- 2014
40. Catabolic signaling pathways, atrogenes, and ubiquitinated proteins are regulated by the nutritional status in the muscle of the fine flounder.
- Author
-
Fuentes EN, Ruiz P, Valdes JA, and Molina A
- Subjects
- Animals, Catalysis, Cluster Analysis, Female, Gene Expression Profiling, Gene Expression Regulation, Male, Muscle Proteins genetics, Muscle, Skeletal pathology, Muscular Atrophy genetics, Muscular Atrophy metabolism, Transcription, Genetic, Ubiquitinated Proteins genetics, Ubiquitination, Flounder metabolism, Muscle Proteins metabolism, Muscle, Skeletal metabolism, Nutritional Status, Signal Transduction, Ubiquitinated Proteins metabolism
- Abstract
A description of the intracellular mechanisms that modulate skeletal muscle atrophy in early vertebrates is still lacking. In this context, we used the fine flounder, a unique and intriguing fish model, which exhibits remarkably slow growth due to low production of muscle-derived IGF-I, a key growth factor that has been widely acknowledged to prevent and revert muscle atrophy. Key components of the atrophy system were examined in this species using a detailed time-course of sampling points, including two contrasting nutritional periods. Under basal conditions high amounts of the atrogenes MuRF-1 and Atrogin-1 were observed. During fasting, the activation of the P38/MAPK and Akt/FoxO signaling pathways decreased; whereas, the activation of the IκBα/NFκB pathway increased. These changes in signal transduction activation were concomitant with a strong increase in MuRF-1, Atrogin-1, and protein ubiquitination. During short-term refeeding, the P38/MAPK and Akt/FoxO signaling pathways were strongly activated, whereas the activation of the IκBα/NFκB pathway decreased significantly. The expression of both atrogenes, as well as the ubiquitination of proteins, dropped significantly during the first hour of refeeding, indicating a strong anti-atrophic condition during the onset of refeeding. During long-term refeeding, Akt remained activated at higher than basal levels until the end of refeeding, and Atrogin-1 expression remained significantly lower during this period. This study shows that the components of the atrophy system in skeletal muscle appeared early in the evolution of vertebrates and some mechanisms have been conserved, whereas others have not. These results represent an important achievement for the area of fish muscle physiology, showing an integrative view of the atrophy system in a non-mammalian species and contributing to novel insights on the molecular basis of muscle growth regulation in earlier vertebrates.
- Published
- 2012
- Full Text
- View/download PDF
41. Inherent growth hormone resistance in the skeletal muscle of the fine flounder is modulated by nutritional status and is characterized by high contents of truncated GHR, impairment in the JAK2/STAT5 signaling pathway, and low IGF-I expression.
- Author
-
Fuentes EN, Einarsdottir IE, Valdes JA, Alvarez M, Molina A, and Björnsson BT
- Subjects
- Animals, Base Sequence, Flounder genetics, Flounder growth & development, Growth Hormone blood, Insulin-Like Growth Factor I genetics, Janus Kinase 2 metabolism, Models, Biological, Muscle, Skeletal metabolism, Nutritional Status, Peptide Fragments metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, STAT5 Transcription Factor metabolism, Signal Transduction, Fish Proteins metabolism, Flounder metabolism, Growth Hormone metabolism, Insulin-Like Growth Factor I metabolism, Receptors, Somatotropin metabolism
- Abstract
A detailed understanding of how the GH and IGF-I regulate muscle growth, especially in early vertebrates, is still lacking. The fine flounder is a flatfish species exhibiting remarkably slow growth, representing an intriguing model for elucidating growth regulatory mechanisms. Key components of the GH system were examined in groups of fish during periods of feeding, fasting, and refeeding. Under feeding conditions, there is an inherent systemic and local (muscle) GH resistance, characterized by higher levels of plasma GH than of IGF-I, skeletal muscle with a greater content of the truncated GH receptor (GHRt) than of full-length GHR (GHRfl), an impaired activation of the Janus kinase 2 (JAK2)-signal transducers and activators of transcription 5 (STAT5) signaling pathway, and low IGF-I expression. Fasting leads to further elevation of plasma GH levels concomitant with suppressed IGF-I levels. The ratio of GHRfl to GHRt in muscle decreases during fasting, causing an inactivation of the JAK2/STAT5 signaling pathway and suppressed IGF-I expression, further impairing growth. When fish are returned to nutritionally favorable conditions, plasma GH levels decrease, and the ratio of GHRfl to GHRt in muscle increases, triggering JAK2/STAT5 reactivation and local IGF-I expression, concomitant with increased growth. The study suggests that systemic IGF-I is supporting basal slow growth in this species, without ruling out that local IGF-I is participating in muscle growth. These results reveal for the first time a unique model of inherent GH resistance in the skeletal muscle of a nonmammalian species and contribute to novel insights of the endocrine and molecular basis of growth regulation in earlier vertebrates.
- Published
- 2012
- Full Text
- View/download PDF
42. Mix gonadal dysgenesis associated with ring Y chromosome mosaics in a phenotypic male.
- Author
-
Lopez-Valdes JA, Nieto K, Najera N, Cervantes A, Kofman-Alfaro S, and Queipo G
- Subjects
- Cell Nucleus metabolism, Centromere metabolism, Child, Chromosome Banding, Humans, In Situ Hybridization, Fluorescence, Interphase, Karyotyping, Male, Metaphase, Phenotype, Sex-Determining Region Y Protein metabolism, Chromosomes, Human, Y genetics, Gonadal Dysgenesis, Mixed genetics, Mosaicism, Ring Chromosomes
- Abstract
Ring chromosomes are present in 1 in 25,000 human fetuses; 99% arise de novo while less than 1% of rings are inherited. This chromosomal rearrangement may arise through a cytogenetic mechanism involving breaks in chromosome arms and fusion of the proximal broken ends, leading to a loss of distal material. Most patient Y ring chromosomes are present in a 45,X/46,X,r(Y) mosaic karyotype; molecular analyses of infertile men have shown that it is not rare to find r(Y) in these patients. However, the clinical spectrum in those cases with a 45,X cell line is broad and depends on the percentage of the monosomic cell line in different tissues. Y chromosome abnormalities and 45,X mosaic karyotypes are often associated with disorders of sex determination. Here, we report a male patient with hypospadias, cryptorchidism and a mosaic karyotype containing a low proportion of 45,X monosomic cells and multiple ring Y chromosomes in peripheral blood. Clinical, surgical, and molecular evidence was sufficient for a diagnosis of mixed gonadal dysgenesis. We suggest that a detailed cytogenetic and molecular analysis should be done in all males with bilateral descended testes and infertility., ((c) 2009 S. Karger AG, Basel.)
- Published
- 2009
- Full Text
- View/download PDF
43. The role of maternal employment and depression in the psychological adjustment of chronically ill, mentally retarded, and well children.
- Author
-
Walker LS, Ortiz-Valdes JA, and Newbrough JR
- Subjects
- Adaptation, Psychological, Adolescent, Child, Child Behavior Disorders psychology, Female, Humans, Male, Risk Factors, Sick Role, Women, Cystic Fibrosis psychology, Depression psychology, Diabetes Mellitus, Type 1 psychology, Intellectual Disability psychology, Mother-Child Relations, Women, Working psychology
- Abstract
Used path analysis to test a conceptual model of the relationship among maternal employment status, maternal depression, and reported child behavior problems. Ss were 95 mothers of children in 4 conditions: cystic fibrosis, diabetes, mental retardation, and well. Regardless of child chronic condition or family SES, mothers not employed outside the home had higher levels of depression than employed mothers. Maternal depression, in turn, was associated with higher levels of reported child behavior problems. Controlling for SES and maternal depression, mental retardation was associated with more child behavior problems, but chronic illness (cystic fibrosis and diabetes) was not associated with more behavior problems. The findings underscore the need to examine the adjustment of children with chronic disorders in the context of their mothers' well-being, particularly when mothers are the principal informants regarding child adjustment.
- Published
- 1989
- Full Text
- View/download PDF
44. Symptomatic treatment of eczema.
- Author
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ARGUMOSA Y VALDES JA
- Subjects
- Eczema therapy
- Published
- 1948
45. [Infection of the calcaneus and dental caries of endocrine etiology].
- Author
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ROIZ NORIEGA and de ARGUMOSA VALDES JA
- Subjects
- Humans, Calcaneus, Dental Caries
- Published
- 1950
46. [Pseudotetanic uremia].
- Author
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DE ARGUMOSA VALDES JA and MAESTRO DE LEON J
- Subjects
- Uremia, Urologic Diseases
- Published
- 1951
47. Study of the remote results of thoracoplasty, according to the technique, from a functional and clinical point of view.
- Author
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VALDES JA, MUJICA J, and MUR JM
- Subjects
- Tuberculosis, Tuberculosis, Pulmonary therapy
- Published
- 1948
48. [Endocrine etiology of affections of the calcaneus and dental caries].
- Author
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ROIZ NORIEGA M and de ARGUMOSA VALDES JA
- Subjects
- Humans, Calcaneus, Calcium, Dental Caries
- Published
- 1950
49. [Treatment of anorexia with rest].
- Author
-
de ARGUMOSA Y VALDES JA
- Subjects
- Humans, Anorexia, Feeding and Eating Disorders, Rest
- Published
- 1950
50. [Research on glutathionemia in irradiated patients].
- Author
-
ROIZ NORIEGA M and de ARGUMOSA VALDES JA
- Subjects
- Humans, X-Rays, Acid-Base Imbalance, Amino Acid Metabolism, Inborn Errors, Blood, Glutathione, Research, Water-Electrolyte Imbalance
- Published
- 1951
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