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Patricia Vázquez

Bio: Patricia Vázquez is an academic researcher from Spanish National Research Council. The author has contributed to research in topics: Unfolded protein response & Humanities. The author has an hindex of 11, co-authored 17 publications receiving 2036 citations. Previous affiliations of Patricia Vázquez include Carlos III Health Institute & Autonomous University of Madrid.

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Journal ArticleDOI
TL;DR: It is demonstrated that delta(9)-tetrahydrocannabinol (THC), the main active component of marijuana, induces human glioma cell death through stimulation of autophagy and evidence is provided that cannabinoid administration may be an effective therapeutic strategy for targeting human cancers.
Abstract: Autophagy can promote cell survival or cell death, but the molecular basis underlying its dual role in cancer remains obscure. Here we demonstrate that delta(9)-tetrahydrocannabinol (THC), the main active component of marijuana, induces human glioma cell death through stimulation of autophagy. Our data indicate that THC induced ceramide accumulation and eukaryotic translation initiation factor 2alpha (eIF2alpha) phosphorylation and thereby activated an ER stress response that promoted autophagy via tribbles homolog 3-dependent (TRB3-dependent) inhibition of the Akt/mammalian target of rapamycin complex 1 (mTORC1) axis. We also showed that autophagy is upstream of apoptosis in cannabinoid-induced human and mouse cancer cell death and that activation of this pathway was necessary for the antitumor action of cannabinoids in vivo. These findings describe a mechanism by which THC can promote the autophagic death of human and mouse cancer cells and provide evidence that cannabinoid administration may be an effective therapeutic strategy for targeting human cancers.

626 citations

Journal ArticleDOI
TL;DR: The production of organic acids by these mangrove rhizosphere microorganisms as a possible mechanism involved in the solubilization of insoluble calcium phosphate is proposed.
Abstract: The phosphate-solubilizing potential of the rhizosphere microbial community in mangroves was de- monstrated when culture media supplemented with in- soluble, tribasic calcium phosphate, and incubated with roots of black (Avicennia germinans L.) and white (La- guncularia racemosa (L.) Gaertn.) mangrove became transparent after a few days of incubation. Thirteen phosphate-solubilizing bacterial strains were isolated from the rhizosphere of both species of mangroves: Ba- cillus amyloliquefaciens, Bacillus licheniformis, Bacillus atrophaeus, Paenibacillus macerans, Vibrio proteolyti- cus, Xanthobacter agilis, Enterobacter aerogenes, Ente- robacter taylorae, Enterobacter asburiae, Kluyvera cryo- crescens, Pseudomonas stutzeri, and Chryseomonas lu- teola. One bacterial isolate could not be identified. The rhizosphere of black mangroves also yielded the fungus Aspergillus niger. The phosphate-solubilizing activity of the isolates was first qualitatively evaluated by the for- mation of halos (clear zones) around the colonies grow- ing on solid medium containing tribasic calcium phos- phate as a sole phosphorus source. Spectrophotometric quantification of phosphate solubilization showed that all bacterial species and A. niger solubilized insoluble phosphate well in a liquid medium, and that V. proteo- lyticus was the most active solubilizing species among the bacteria. Gas chromatographic analyses of cell-free spent culture medium from the various bacteria de- monstrated the presence of 11 identified, and several unidentified, volatile and nonvolatile organic acids. Those most commonly produced by different species were lactic, succinic, isovaleric, isobutyric, and acetic acids. Most of the bacterial species produced more than one organic acid whereas A. niger produced only suc- cinic acid. We propose the production of organic acids by these mangrove rhizosphere microorganisms as a possible mechanism involved in the solubilization of in- soluble calcium phosphate.

609 citations

Journal ArticleDOI
TL;DR: This overview summarizes the current state of knowledge of microbial transformations of nutrients in mangrove ecosystems and illustrates the important contributions these microorganisms make to the productivity of the ecosystems.
Abstract: Mangrove communities are recognized as highly productive ecosystems that provide large quantities of organic matter to adjacent coastal waters in the form of detritus and live animals (fish, shellfish). The detritus serves as a nutrient source and is the base of an extensive food web in which organisms of commercial importance take part. In addition, mangrove ecosystems serve as shelter, feeding, and breeding zones for crustaceans, mollusks, fish of commercial importance, and resident and migratory birds. Although mangroves in the United States are protected, the systematic destruction of these ecosystems elsewhere is increasing. Deforestation of mangrove communities is thought to be one of the major reasons for the decrease in the coastal fisheries of many tropical and subtropical countries. There is evidence to propose a close microbe-nutrient-plant relationship that functions as a mechanism to recycle and conserve nutrients in the mangrove ecosystem. The highly productive and diverse microbial community living in tropical and subtropical mangrove ecosystems continuously transforms nutrients from dead mangrove vegetation into sources of nitrogen, phosphorus, and other nutrients that can be used by the plants. In turn, plant-root exudates serve as a food source for the microorganisms living in the ecosystem with other plant material serving similarly for larger organisms like crabs. This overview summarizes the current state of knowledge of microbial transformations of nutrients in mangrove ecosystems and illustrates the important contributions these microorganisms make to the productivity of the ecosystems. To conserve the mangrove ecosystems, which are essential for the sustainable maintenance of coastal fisheries, maintenance and restoration of the microbial communities should be undertaken. Inoculation of mangrove seedlings with plant-growth-promoting bacteria may help revegetate degraded areas and create reconstructed mangrove ecosystems.

575 citations

Journal ArticleDOI
TL;DR: An increase in the expression of the autophagy genes Atg7, Becn1, Ambra1 and LC3 in vivo in the mouse embryonic olfactory bulb during the initial period of neuronal differentiation at E15.5, along with a parallel increase in neuronal markers is reported, revealing new roles for autophagic-related molecules Atg5 and Ambra 1 during early neuronal differentiation of stem/progenitor cells.
Abstract: Neuroepithelial cells undergoing differentiation efficiently remodel their cytoskeleton and shape in an energy-consuming process. The capacity of autophagy to recycle cellular components and provide energy could fulfill these requirements, thus supporting differentiation. However, little is known regarding the role of basal autophagy in neural differentiation. Here we report an increase in the expression of the autophagy genes Atg7, Becn1, Ambra1 and LC3 in vivo in the mouse embryonic olfactory bulb (OB) during the initial period of neuronal differentiation at E15.5, along with a parallel increase in neuronal markers. In addition, we observed an increase in LC3 lipidation and autophagic flux during neuronal differentiation in cultured OB-derived stem/progenitor cells. Pharmacological inhibition of autophagy with 3-MA or wortmannin markedly decreased neurogenesis. These observations were supported by similar findings in two autophagy-deficient genetic models. In Ambra1 loss-of-function homozygous mice (gt/gt) the expression of several neural markers was decreased in the OB at E13.5 in vivo. In vitro, Ambra1 haploinsufficient cells developed as small neurospheres with an impaired capacity for neuronal generation. The addition of methylpyruvate during stem/progenitor cell differentiation in culture largely reversed the inhibition of neurogenesis induced by either 3-MA or Ambra1 haploinsufficiency, suggesting that neural stem/progenitor cells activate autophagy to fulfill their high energy demands. Further supporting the role of autophagy for neuronal differentiation Atg5-null OB cells differentiating in culture displayed decreased TuJ1 levels and lower number of cells with neurites. These results reveal new roles for autophagy-related molecules Atg5 and Ambra1 during early neuronal differentiation of stem/progenitor cells.

160 citations

Journal ArticleDOI
TL;DR: It is shown that a silicon chip small enough to be internalized into a living cell can be used to detect pressure changes inside the cell and that HeLa cells can endure hypo-osmotic stress without significantly increasing their intracellular hydrostatic pressure.
Abstract: The ability to measure pressure changes inside different components of a living cell is important, because it offers an alternative way to study fundamental processes that involve cell deformation1. Most current techniques such as pipette aspiration2, optical interferometry3 or external pressure probes4 use either indirect measurement methods or approaches that can damage the cell membrane. Here we show that a silicon chip small enough to be internalized into a living cell can be used to detect pressure changes inside the cell. The chip, which consists of two membranes separated by a vacuum gap to form a Fabry–Perot resonator, detects pressure changes that can be quantified from the intensity of the reflected light. Using this chip, we show that extracellular hydrostatic pressure is transmitted into HeLa cells and that these cells can endure hypo-osmotic stress without significantly increasing their intracellular hydrostatic pressure. Direct measurements of pressure inside living cells can now be made non-invasively using a nanomechanical silicon chip.

72 citations


Cited by
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Journal ArticleDOI
Daniel J. Klionsky1, Kotb Abdelmohsen2, Akihisa Abe3, Joynal Abedin4  +2519 moreInstitutions (695)
TL;DR: In this paper, the authors present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macro-autophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

5,187 citations

Journal ArticleDOI
TL;DR: These guidelines are presented for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

4,316 citations

Journal ArticleDOI
TL;DR: This review focuses on the known, the putative, and the speculative modes-of-action of PGPR, which include fixing N2, increasing the availability of nutrients in the rhizosphere, positively influencing root growth and morphology, and promoting other beneficial plant–microbe symbioses.
Abstract: Numerous species of soil bacteria which flourish in the rhizosphere of plants, but which may grow in, on, or around plant tissues, stimulate plant growth by a plethora of mechanisms. These bacteria are collectively known as PGPR (plant growth promoting rhizobacteria). The search for PGPR and investigation of their modes of action are increasing at a rapid pace as efforts are made to exploit them commercially as biofertilizers. After an initial clarification of the term biofertilizers and the nature of associations between PGPR and plants (i.e., endophytic versus rhizospheric), this review focuses on the known, the putative, and the speculative modes-of-action of PGPR. These modes of action include fixing N2, increasing the availability of nutrients in the rhizosphere, positively influencing root growth and morphology, and promoting other beneficial plant–microbe symbioses. The combination of these modes of actions in PGPR is also addressed, as well as the challenges facing the more widespread utilization of PGPR as biofertilizers.

2,982 citations

Journal ArticleDOI
TL;DR: In this article, the authors show that over the past 50 years, approximately one-third of the world's mangrove forests have been lost, but most data show very variable loss rates and there is considerable margin of error in most estimates.
Abstract: SUMMARY Mangroves, the only woody halophytes living at the confluence of land and sea, have been heavily used traditionally for food, timber, fuel and medicine, and presently occupy about 181 000 km 2 of tropical and subtropical coastline. Over the past 50 years, approximately one-third of the world’s mangrove forests have been lost, but most data show very variable loss rates and there is considerable margin of error in most estimates. Mangroves are a valuable ecological and economic resource, being important nursery grounds and breeding sites for birds, fish, crustaceans, shellfish, reptiles and mammals; a renewable source of wood; accumulation sites for sediment, contaminants, carbon and nutrients; and offer protection against coastal erosion. The destruction of mangroves is usually positively related to human population density. Major reasons for destruction are urban development, aquaculture, mining and overexploitation for timber, fish, crustaceans and shellfish. Over the next 25 years, unrestricted clear felling, aquaculture, and overexploitation of fisheries will be the greatest threats, with lesser problems being alteration of hydrology, pollution and global warming. Loss of biodiversity is, and will continue to be, a severe problem as even pristine mangroves are species-poor compared with other tropical ecosystems. The future is not entirely bleak. The number of rehabilitation and restoration projects is increasing worldwide with some countries showing increases in mangrove area. The intensity of coastal aquaculture appears to have levelled off in some parts of the world. Some commercial projects and economic models indicate that mangroves can be used as a sustainable resource, especially for wood. The brightest note is that the rate of population growth is projected to slow during the next 50 years, with a gradual decline thereafter to the end of the century. Mangrove forests will continue to be exploited at current rates to 2025, unless they are seen as a valuable resource to be managed on a sustainable basis. After 2025, the future of mangroves will depend on technological and ecological advances

1,654 citations

Journal ArticleDOI
TL;DR: This review focuses on the diversity of PSM, mechanism of P solubilization, role of various phosphatases, impact of various factors on P solubsility, present and future scenario of their use and potential for application of this knowledge in managing a sustainable environmental system.
Abstract: Phosphorus is the second important key element after nitrogen as a mineral nutrient in terms of quantitative plant requirement. Although abundant in soils, in both organic and inorganic forms, its availability is restricted as it occurs mostly in insoluble forms. The P content in average soil is about 0.05% (w/w) but only 0.1% of the total P is available to plant because of poor solubility and its fixation in soil (Illmer and Schinner, Soil Biol Biochem 27:257-263, 1995). An adequate supply of phosphorus during early phases of plant development is important for laying down the primordia of plant reproductive parts. It plays significant role in increasing root ramification and strength thereby imparting vitality and disease resistance capacity to plant. It also helps in seed formation and in early maturation of crops like cereals and legumes. Poor availability or deficiency of phosphorus (P) markedly reduces plant size and growth. Phosphorus accounts about 0.2 - 0.8% of the plant dry weight. To satisfy crop nutritional requirements, P is usually added to soil as chemical P fertilizer, however synthesis of chemical P fertilizer is highly energy intensive processes, and has long term impacts on the environment in terms of eutrophication, soil fertilility depletion, carbon footprint. Moreover, plants can use only a small amount of this P since 75–90% of added P is precipitated by metal–cation complexes, and rapidly becomes fixed in soils. Such environmental concerns have led to the search for sustainable way of P nutrition of crops. In this regards phosphate-solubilizing microorganisms (PSM) have been seen as best eco-friendly means for P nutrition of crop. Although, several bacterial (pseudomonads and bacilli) and fungal strains (Aspergilli and Penicillium) have been identified as PSM their performance under in situ conditions is not reliable and therefore needs to be improved by using either genetically modified strains or co-inoculation techniques. This review focuses on the diversity of PSM, mechanism of P solubilization, role of various phosphatases, impact of various factors on P solubilization, the present and future scenario of their use and potential for application of this knowledge in managing a sustainable environmental system.

1,386 citations