Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
1,797
result(s) for
"Estrada, C"
Sort by:
The princess and the pea = La princesa y el guisante
By feeling a pea through twenty mattresses and twenty featherbeds, a girl proves that she is a real princess.
Book
bZIP transcription factors PcYap1 and PcRsmA link oxidative stress response to secondary metabolism and development in Penicillium chrysogenum
Background
Reactive oxygen species (ROS) trigger different morphogenic processes in filamentous fungi and have been shown to play a role in the regulation of the biosynthesis of some secondary metabolites. Some bZIP transcription factors, such as Yap1, AtfA and AtfB, mediate resistance to oxidative stress and have a role in secondary metabolism regulation. In this work we aimed to get insight into the molecular basis of this regulation in the industrially important fungus
Penicillium chrysogenum
through the characterization of the role played by two effectors that mediate the oxidative stress response in development and secondary metabolism.
Results
In
P. chrysogenum
, penicillin biosynthesis and conidiation are stimulated by the addition of H
2
O
2
to the culture medium, and this effect is mediated by the bZIP transcription factors PcYap1 and PcRsmA. Silencing of expression of both proteins by RNAi resulted in similar phenotypes, characterized by increased levels of ROS in the cell, reduced conidiation, higher sensitivity of conidia to H
2
O
2
and a decrease in penicillin production. Both PcYap1 and PcRsmA are able to sense H
2
O
2
-generated ROS in vitro and change its conformation in response to this stimulus. PcYap1 and PcRsmA positively regulate the expression of
brlA
, the first gene of the conidiation central regulatory pathway. PcYap1 binds in vitro to a previously identified regulatory sequence in the promoter of the penicillin gene
pcbAB
: TTAGTAA, and to a TTACTAA sequence in the promoter of the
brlA
gene, whereas PcRsmA binds to the sequences TGAGACA and TTACGTAA (CRE motif) in the promoters of the
pcbAB
and
penDE
genes, respectively.
Conclusions
bZIP transcription factors PcYap1 and PcRsmA respond to the presence of H
2
O
2
-generated ROS and regulate oxidative stress response in the cell. Both proteins mediate ROS regulation of penicillin biosynthesis and conidiation by binding to specific regulatory elements in the promoters of key genes. PcYap1 is identified as the previously proposed transcription factor PTA1 (Penicillin Transcriptional Activator 1), which binds to the regulatory sequence TTAGTAA in the
pcbAB
gene promoter. This is the first report of a Yap1 protein directly regulating transcription of a secondary metabolism gene. A model describing the regulatory network mediated by PcYap1 and PcRsmA is proposed.
Journal Article
Roles of mTOR in thoracic aortopathy understood by complex intracellular signaling interactions
Thoracic aortopathy–aneurysm, dissection, and rupture–is increasingly responsible for significant morbidity and mortality. Advances in medical genetics and imaging have improved diagnosis and thus enabled earlier prophylactic surgical intervention in many cases. There remains a pressing need, however, to understand better the underlying molecular and cellular mechanisms with the hope of finding robust pharmacotherapies. Diverse studies in patients and mouse models of aortopathy have revealed critical changes in multiple smooth muscle cell signaling pathways that associate with disease, yet integrating information across studies and models has remained challenging. We present a new quantitative network model that includes many of the key smooth muscle cell signaling pathways and validate the model using a detailed data set that focuses on hyperactivation of the mechanistic target of rapamycin (mTOR) pathway and its inhibition using rapamycin. We show that the model can be parameterized to capture the primary experimental findings both qualitatively and quantitatively. We further show that simulating a population of cells by varying receptor reaction weights leads to distinct proteomic clusters within the population, and that these clusters emerge due to a bistable switch driven by positive feedback in the PI3K/AKT/mTOR signaling pathway.
Journal Article
Implementation of the flipped classroom and its longitudinal impact on improving academic performance
The objective has been to know the impact of the flipped classroom methodology on the academic performance of students during their training process in relation to the traditional methodology over time, in order to establish baselines in the academic grades in both models. The research is of a quasi-experimental type of non-equivalent groups, with a longitudinal trend design in the data collection process. The entire available population has been selected, with 1.236 students participating, exploring the grades as an analytical resource, from the 2010/2011 to the 2019/2020 academic years. The results show statistically significant differences in the improvement of academic performance with the flipped classroom methodology. Furthermore, the results reinforce that the flipped teaching model effectively promotes students’ interest, their capacity for autonomous learning and personal and cooperative relationships.
Journal Article
Culture of human mesenchymal stem cells at low oxygen tension improves growth and genetic stability by activating glycolysis
Expansion of human stem cells before cell therapy is typically performed at 20% O
2
. Growth in these pro-oxidative conditions can lead to oxidative stress and genetic instability. Here, we demonstrate that culture of human mesenchymal stem cells at lower, physiological O
2
concentrations significantly increases lifespan, limiting oxidative stress, DNA damage, telomere shortening and chromosomal aberrations. Our gene expression and bioenergetic data strongly suggest that growth at reduced oxygen tensions favors a natural metabolic state of increased glycolysis and reduced oxidative phosphorylation. We propose that this balance is disturbed at 20% O
2
, resulting in abnormally increased levels of oxidative stress. These observations indicate that bioenergetic pathways are intertwined with the control of lifespan and decisively influence the genetic stability of human primary stem cells. We conclude that stem cells for human therapy should be grown under low oxygen conditions to increase biosafety.
Journal Article
Diversity and seasonal variation of the molluscan community associated with the seagrass Halodule wrightii in a marine protected area in the southern Gulf of California
The structural complexity of Halodule wrightii enhances the abundance and diversity of mollusks in the marine protected area of Bahía Balandra, in the southern Gulf of California. Marine mollusks are considered ecosystem engineers because they create, modify, and maintain habitats. Taxonomical and functional analyses of the mollusk community were carried out from May 2016 to 2017. The total abundance in all sampled periods was 7284 individuals and comprised 52 families, 69 genera, and 89 species. The Gastropoda class showed the highest number of species (61 species, 68.53%), followed by Bivalvia (24 species, 26.96%) and Scaphopoda (4 species, 4.49%). The highest density of mollusks was in the summer of 2016 (ca. 6500 ind. m−2), while the highest richness was found in spring 2017 (60 species). Five trophic levels were identified. All trophic groups were present in all the seasons with carnivores showing the highest species richness and herbivores the highest abundance, followed by filter-feeders. A positive and moderate relationship between the total biomass of seagrass and gastropod richness was found, while the relationship between gastropod abundance and seagrass biomass was negative. Halodule wrightii in the Gulf of California represents a unique niche that supports a high mollusk biodiversity and offers great variability of resources for this group. Halodule wrightii represents a suitable habitat for reproduction, metamorphosis, nursery, refuge, and feeding for mollusks. Finally, the functional group concept was applied to evaluate the ecosystem seagrass health of Bahía Balandra resulting in a moderate score.
Journal Article
Natural History of the Mexican Cockroach Homoeogamia mexicana Burmeister, 1838 (Blattodea: Corydiidae): Biology, Distribution, and Habitat Characterization
Within the cockroach family Corydiidae, the species Homoeogamia mexicana appears to have the widest distribution in Mexico. However, the natural history and ecology of this species are largely unknown, while feeding habits, behavior, reproduction, life cycle, and habitat use and selection have never been reported. In this study, we address these important gaps in order to improve knowledge and conservation of this species. Several individuals were held in captivity, allowing observation of aspects of their ecology, behavior, and reproduction. Based on 263 records from iNaturalist, literature, and museums, we tabulated presence records in the wild and constructed a graph of life stage by month. Habitats and distribution were characterized in terms of bioclimatic variables, elevation, land use, vegetation, and biogeographic provinces. An ecological niche model was constructed and projected onto a map of Mexico and northern Central America to estimate new potential areas of environmental suitability. Our results showed that H. mexicana is widely distributed in Mexico, with a preference for high elevation and cold areas. The potential distribution area predicted by the ecological niche model was much larger than the distribution as currently reported. The morphological sexual dimorphism of this species is an extension of its ecological differences. Dentro de la familia de cucarachas Corydiidae, la especie Homoeogamia mexicana parece tener la distribución más amplia en México. Sin embargo, la historia natural y la ecología de esta especie se desconocen en gran medida, mientras que los hábitos de alimentación, el comportamiento, la reproducción, el ciclo de vida y el uso y selección del hábitat nunca se han informado. En este estudio, abordamos estos importantes vacíos para mejorar el conocimiento y conservación de esta especie. Varios individuos fueron mantenidos en cautiverio permitiendo el registro de aspectos de su ecología, comportamiento y reproducción. También recopilamos registros de presencia de la especie en estado silvestre para cada mes del año. Con un total de 263 registros construimos un gráfico de etapa de vida por mes. Se caracterizó el hábitat y la distribución de las especies en términos de variables bioclimáticas, elevación, uso del suelo, vegetación y provincias biogeográficas. Se construyó un modelo de nicho ecológico para la especie y se proyectó a un mapa de Mexico y el norte de Centroamérica para estimar nuevas áreas potenciales de idoneidad ambiental. Nuestros resultados mostraron que H. mexicana se encuentra ampliamente distribuida en México, con preferencia por las zonas altas y frías. El área de distribución potencial predicha por el modelo de nicho ecológico fue mucho más grande que lo que se informa actualmente. El dimorfismo sexual morfológico de esta especie es una extensión de sus diferencias ecológicas.
Journal Article
natural short pathway synthesizes roquefortine C but not meleagrin in three different Penicillium roqueforti strains
The production of mycotoxins and other secondary metabolites in Penicillium roqueforti is of great interest because of its long history of use in blue-veined cheese manufacture. In this article, we report the cloning and characterization of the roquefortine gene cluster in three different P. roqueforti strains isolated from blue cheese in the USA (the type strain), France, and the UK (Cheshire cheese). All three strains showed an identical roquefortine gene cluster organization and almost identical (98–99 %) gene nucleotide sequences in the entire 16.6-kb cluster region. When compared with the Penicillium chrysogenum roquefortine/meleagrin seven-gene cluster, the P. roqueforti roquefortine cluster contains only four genes (rds, rdh, rpt, and gmt) encoding the roquefortine dipeptide synthetase, roquefortine D dehydrogenase, roquefortine prenyltransferase, and a methyltransferase, respectively. Silencing of the rds or rpt genes by the RNAi strategy reduced roquefortine C production by 50 % confirming the involvement of these two key genes in roquefortine biosynthesis. An additional putative gene, orthologous of the MFS transporter roqT, is rearranged in all three strains as a pseudogene. The same four genes and a complete (not rearranged) roqT, encoding a MFS transporter containing 12 TMS domains, occur in the seven-gene cluster in P. chrysogenum although organized differently. Interestingly, the two “late” genes of the P. chrysogenum roquefortine/meleagrin gene cluster that convert roquefortine C to glandicoline B and meleagrin are absent in the P. roqueforti four-gene cluster. No meleagrin production was detected in P. roqueforti cultures grown in YES medium, while P. chrysogenum produces meleagrin in these conditions. No orthologous genes of the two missing meleagrin synthesizing genes were found elsewhere in the recently released P. roqueforti genome. Our data suggest that during evolution, the seven-gene cluster present in P. chrysogenum, and probably also in other glandicoline/meleagrin producing fungi, has been trimmed down to a short cluster in P. roqueforti leading to the synthesis of roquefortine C rather than meleagrin as a final product.
Journal Article
Combined 1-Deoxynojirimycin and Ibuprofen Treatment Decreases Microglial Activation, Phagocytosis and Dopaminergic Degeneration in MPTP-Treated Mice
Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson’s disease (PD) suggesting that a sustained neuroinflammation exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH
+
) and microglia markers (Iba-1
+
; CD68
+
) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68
+
/ Iba-1
+
cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions.
Graphical Abstract
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a protoxicant that, after crossing the Blood Brain Barrier, is metabolized by astrocytic MAO-B to MPDP+, a pyridinium intermediate, which undergoes further two-electron oxidation to yield the toxic metabolite MPP+ (methyl-phenyltetrahydropyridinium) that is then selectively transported into nigral neurons via the mesencephalic dopamine transporter. In this study, we demonstrated that MPTP induced death of dopaminergic neurons, microgliosis, increase of gliapses, motor impairment and neuroinflammation in mice, which were inhibited by combined 1-deoxynojirimycin and ibuprofen treatment.
Journal Article
In vivo pair correlation microscopy reveals dengue virus capsid protein nucleocytoplasmic bidirectional movement in mammalian infected cells
Flaviviruses are major human disease-causing pathogens, including dengue virus (DENV), Zika virus, yellow fever virus and others. DENV infects hundreds of millions of people per year around the world, causing a tremendous social and economic burden. DENV capsid (C) protein plays an essential role during genome encapsidation and viral particle formation. It has been previously shown that DENV C enters the nucleus in infected cells. However, whether DENV C protein exhibits nuclear export remains unclear. By spatially cross-correlating different regions of the cell, we investigated DENV C movement across the nuclear envelope during the infection cycle. We observed that transport takes place in both directions and with similar translocation times (in the ms time scale) suggesting a bidirectional movement of both C protein import and export.
Furthermore, from the pair cross-correlation functions in cytoplasmic or nuclear regions we found two populations of C molecules in each compartment with fast and slow mobilities. While in the cytoplasm the correlation times were in the 2–6 and 40–110 ms range for the fast and slow mobility populations respectively, in the cell nucleus they were 1–10 and 25–140 ms range, respectively. The fast mobility of DENV C in cytoplasmic and nuclear regions agreed with the diffusion coefficients from Brownian motion previously reported from correlation analysis. These studies provide the first evidence of DENV C shuttling from and to the nucleus in infected cells, opening new venues for antiviral interventions.
Journal Article