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Transcription factors (TFs) orchestrate the gene expression programs that define each cell's identity. The canonical TF accomplishes this with two domains, one that binds specific DNA sequences and the other that binds protein coactivators or corepressors. We find that at least half of TFs also bind RNA, doing so through a previously unrecognized domain with sequence and functional features analogous to the arginine-rich motif of the HIV transcriptional activator Tat. RNA binding contributes to TF function by promoting the dynamic association between DNA, RNA, and TF on chromatin. TF-RNA interactions are a conserved feature important for vertebrate development and disrupted in disease. We propose that the ability to bind DNA, RNA, and protein is a general property of many TFs and is fundamental to their gene regulatory function.
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ARN , Factores de Transcripción , Factores de Transcripción/metabolismo , ARN/metabolismo , Sitios de Unión , Unión Proteica , ADN/genéticaRESUMEN
Water is the most indispensable natural resource; yet, organic pollution of freshwater sources is widespread. In recent years, there has been increasing concern over the vast array of emerging organic contaminants (EOCs) in the effluent of wastewater treatment plants (WWTPs). Several of these EOCs are degraded within the pore space of riverbeds by active microbial consortia. However, the mechanisms behind this ecosystem service are largely unknown. Here, we report how phosphate concentration and predator-prey interactions drive the capacity of bacteria to process a model EOC (ibuprofen). The presence of phosphate had a significant positive effect on the population growth rate of an ibuprofen-degrading strain. Thus, when phosphate was present, ibuprofen removal efficiency increased. Moreover, low and medium levels of predation, by a ciliated protozoan, stimulated bacterial population growth. This unimodal effect of predation was lost under high phosphate concentration, resulting in the flattening of the relationships between predator density and population growth of ibuprofen degraders. Our results suggest that moderate nutrient and predation levels promote the growth rate of bacterial degraders and, consequently, the self-purifying capability of the system. These findings enhance our understanding of the mechanisms by which riverbed communities drive the processing of EOCs.
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Ecosistema , Cadena Alimentaria , Animales , Ibuprofeno/metabolismo , Conducta Predatoria , Bacterias/metabolismoRESUMEN
Hematopoietic stem and progenitor cell (HSPC) formation and lineage differentiation involve gene expression programs orchestrated by transcription factors and epigenetic regulators. Genetic disruption of the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7) expanded phenotypic HSPCs, erythroid, and myeloid lineages in zebrafish and mouse embryos. CHD7 acts to suppress hematopoietic differentiation. Binding motifs for RUNX and other hematopoietic transcription factors are enriched at sites occupied by CHD7, and decreased RUNX1 occupancy correlated with loss of CHD7 localization. CHD7 physically interacts with RUNX1 and suppresses RUNX1-induced expansion of HSPCs during development through modulation of RUNX1 activity. Consequently, the RUNX1:CHD7 axis provides proper timing and function of HSPCs as they emerge during hematopoietic development or mature in adults, representing a distinct and evolutionarily conserved control mechanism to ensure accurate hematopoietic lineage differentiation.
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Subunidad alfa 2 del Factor de Unión al Sitio Principal , Proteínas de Unión al ADN , Hematopoyesis , Animales , Diferenciación Celular , Línea Celular , Subunidad alfa 2 del Factor de Unión al Sitio Principal/química , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Femenino , Células Madre Hematopoyéticas , Humanos , Masculino , Ratones , Bazo/citología , Pez CebraRESUMEN
Epoxyeicosatrienoic acids (EETs) are lipid-derived signaling molecules with cardioprotective and vasodilatory actions. We recently showed that 11,12-EET enhances hematopoietic induction and engraftment in mice and zebrafish. EETs are known to signal via G protein-coupled receptors, with evidence supporting the existence of a specific high-affinity receptor. Identification of a hematopoietic-specific EET receptor would enable genetic interrogation of EET signaling pathways, and perhaps clinical use of this molecule. We developed a bioinformatic approach to identify an EET receptor based on the expression of G protein-coupled receptors in cell lines with differential responses to EETs. We found 10 candidate EET receptors that are expressed in three EET-responsive cell lines, but not expressed in an EET-unresponsive line. Of these, only recombinant GPR132 showed EET-responsiveness in vitro, using a luminescence-based ß-arrestin recruitment assay. Knockdown of zebrafish gpr132b prevented EET-induced hematopoiesis, and marrow from GPR132 knockout mice showed decreased long-term engraftment capability. In contrast to high-affinity EET receptors, GPR132 is reported to respond to additional hydroxy-fatty acids in vitro, and we found that these same hydroxy-fatty acids enhance hematopoiesis in the zebrafish. We conducted structure-activity relationship analyses using both cell culture and zebrafish assays on diverse medium-chain fatty acids. Certain oxygenated, unsaturated free fatty acids showed high activation of GPR132, whereas unoxygenated or saturated fatty acids had lower activity. Absence of the carbon-1 position carboxylic acid prevented activity, suggesting that this moiety is required for receptor activation. GPR132 responds to a select panel of oxygenated polyunsaturated fatty acids to enhance both embryonic and adult hematopoiesis.
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Proteínas de Ciclo Celular/metabolismo , Hematopoyesis/efectos de los fármacos , Oxilipinas , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas de Pez Cebra/metabolismo , Animales , Proteínas de Ciclo Celular/genética , Células Cultivadas , Hematopoyesis/genética , Ratones , Ratones Noqueados , Oxilipinas/química , Oxilipinas/farmacología , Receptores Acoplados a Proteínas G/genética , Transducción de Señal/genética , Relación Estructura-Actividad , Pez Cebra , Proteínas de Pez Cebra/genéticaRESUMEN
Litter breakdown in the streambed is an important pathway in organic carbon cycling and energy transfer in the biosphere that is mediated by a wide range of streambed organisms. However, most research on litter breakdown to date has focused on a small fraction of the taxa that drive it (e.g. microbial vs. macroinvertebrate-mediated breakdown) and has been limited to the benthic zone (BZ). Despite the importance of the hyporheic zone (HZ) as a bioreactor, little is known about what, or who, mediates litter breakdown in this compartment and whether breakdown rates differ between the BZ and HZ. Here, we explore the relationship between litter breakdown and the variation in community structure of benthic and hyporheic communities by deploying two standardized bioassays (cotton strips and two types of commercially available tea bags) in 30 UK streams that encompass a range of environmental conditions. Then, we modelled these assays as a response of the streambed compartment and the biological features of the streambed assemblage (Prokaryota, Protozoa and Eumetazoa invertebrates) to understand the generality and efficiency of litter processing across communities. Litter breakdown was much faster in the BZ compared with the HZ (around 5 times higher for cotton strips and 1.5 times faster for the tea leaves). However, differences in litter breakdown between the BZ and the HZ were mediated by the biological features of the benthos and the hyporheos. Biomass of all the studied biotic groups, α-diversity of Eumetazoa invertebrates and metabolic diversity of Prokaryota were important predictors that were positively related to breakdown coefficients demonstrating their importance in the functioning of the streambed ecosystem. Our study uses a novel multimetric bioassay that is able to disentangle the contribution by Prokaryota, Protozoa and Eumetazoa invertebrates to litter breakdown. In doing so, our study reveals new insights into how organic matter decomposition is partitioned across biota and streambed compartments.
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Ecosistema , Ríos , Animales , Biomasa , Invertebrados , Hojas de la PlantaRESUMEN
Abundance-body mass (N-M) relationships are prominent macroecological patterns and provide an integrated measurement of the structure and energy flow through natural communities. However, little is known about how N-M relationships are constrained by local environmental conditions. Here, we quantify how sediment depth and direction of surface-groundwater exchange (vertical hydrodynamics), two major drivers of the streambed ecology, determine N-M scaling in a sandy lowland European stream. Streambed assemblages included flagellates, ciliates, meiofauna and macroinvertebrates, and spanned five orders of magnitude in body mass. We detected a significant interaction of body mass with depth and vertical hydrodynamics with a sharp reduction in N-M slopes in the hyporheic zone and under upwelling conditions. These results revealed that streambed assemblages become more size-structured as environmental constraints increase with direct implications for the metabolic capacity and functioning of the system.
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Sedimentos Geológicos , Agua Subterránea , Hidrodinámica , RíosRESUMEN
The inflammatory response is integral to maintaining health by functioning to resist microbial infection and repair tissue damage. Large numbers of neutrophils are recruited to inflammatory sites to neutralize invading bacteria through phagocytosis and the release of proteases and reactive oxygen species into the extracellular environment. Removal of the original inflammatory stimulus must be accompanied by resolution of the inflammatory response, including neutrophil clearance, to prevent inadvertent tissue damage. Neutrophil apoptosis and its temporary inhibition by survival signals provides a target for anti-inflammatory therapeutics, making it essential to better understand this process. GM-CSF, a neutrophil survival factor, causes a significant increase in mRNA levels for the known anti-apoptotic protein serum and glucocorticoid-regulated kinase 1 (SGK1). We have characterized the expression patterns and regulation of SGK family members in human neutrophils and shown that inhibition of SGK activity completely abrogates the antiapoptotic effect of GM-CSF. Using a transgenic zebrafish model, we have disrupted sgk1 gene function and shown this specifically delays inflammation resolution, without altering neutrophil recruitment to inflammatory sites in vivo. These data suggest SGK1 plays a key role in regulating neutrophil survival signaling and thus may prove a valuable therapeutic target for the treatment of inflammatory disease.
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Apoptosis/inmunología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Proteínas Inmediatas-Precoces/metabolismo , Inflamación/inmunología , Neutrófilos/inmunología , Proteínas Serina-Treonina Quinasas/metabolismo , Animales , Animales Modificados Genéticamente , Benzoatos/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/inmunología , Humanos , Proteínas Inmediatas-Precoces/antagonistas & inhibidores , Proteínas Inmediatas-Precoces/genética , Morfolinos/genética , Neutrófilos/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/efectos de los fármacos , Inhibidores de las Quinasa Fosfoinosítidos-3 , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/genética , ARN Mensajero/biosíntesis , Pez Cebra/genéticaRESUMEN
Global climate changes during the Cenozoic (65.5-0 Ma) caused major biological range shifts and extinctions. In northern Europe, for example, a pattern of few endemics and the dominance of wide-ranging species is thought to have been determined by the Pleistocene (2.59-0.01 Ma) glaciations. This study, in contrast, reveals an ancient subsurface fauna endemic to Britain and Ireland. Using a Bayesian phylogenetic approach, we found that two species of stygobitic invertebrates (genus Niphargus) have not only survived the entire Pleistocene in refugia but have persisted for at least 19.5 million years. Other Niphargus species form distinct cryptic taxa that diverged from their nearest continental relative between 5.6 and 1.0 Ma. The study also reveals an unusual biogeographical pattern in the Niphargus genus. It originated in north-west Europe approximately 87 Ma and underwent a gradual range expansion. Phylogenetic diversity and species age are highest in north-west Europe, suggesting resilience to extreme climate change and strongly contrasting the patterns seen in surface fauna. However, species diversity is highest in south-east Europe, indicating that once the genus spread to these areas (approximately 25 Ma), geomorphological and climatic conditions enabled much higher diversification. Our study highlights that groundwater ecosystems provide an important contribution to biodiversity and offers insight into the interactions between biological and climatic processes.
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Anfípodos/clasificación , Evolución Biológica , Cambio Climático , Filogenia , Anfípodos/genética , Animales , Teorema de Bayes , Ecosistema , Europa (Continente) , Geografía , Agua Subterránea , Irlanda , Datos de Secuencia Molecular , Reino UnidoRESUMEN
A defined number of hematopoietic stem cell (HSC) clones are born during development and expand to form the pool of adult stem cells. An intricate balance between self-renewal and differentiation of these HSCs supports hematopoiesis for life. HSC fate is determined by complex transcription factor networks that drive cell-type specific gene programs. The transcription factor RUNX1 is required for definitive hematopoiesis, and mutations in Runx1 have been shown to reduce clonal diversity. The RUNX1 cofactor, CBFý, stabilizes RUNX1 binding to DNA, and disruption of their interaction alters downstream gene expression. Chemical screening for modulators of Runx1 and HSC expansion in zebrafish led us to identify a new mechanism for the RUNX1 inhibitor, Ro5-3335. We found that Ro5-3335 increased HSC divisions in zebrafish, and animals transplanted with Ro5-3335 treated cells had enhanced chimerism compared to untreated cells. Using human CD34+ cells, we show that Ro5-3335 remodels the RUNX1 transcription complex by binding to ELF1, independent of CBFý. This allows specific expression of cell cycle and hematopoietic genes that enhance HSC self-renewal and prevent differentiation. Furthermore, we provide the first evidence to show that it is possible to pharmacologically increase the number of stem cell clones in vivo , revealing a previously unknown mechanism for enhancing clonal diversity. Our studies have revealed a mechanism by which binding partners of RUNX1 determine cell fate, with ELF transcription factors guiding cell division. This information could lead to treatments that enhance clonal diversity for blood diseases.
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Climate change and associated glacial recession create new stream habitat that leads to the assembly of new riverine communities through primary succession. However, there are still very few studies of the patterns and processes of community assembly during primary succession for stream ecosystems. We illustrate the rapidity with which biotic communities can colonize and establish in recently formed streams by examining Stonefly Creek in Glacier Bay, Alaska (USA), which began to emerge from a remnant glacial ice mass between 1976 and 1979. By 2002, 57 macroinvertebrate and 27 microcrustacea species had become established. Within 10 years of the stream's formation, pink salmon and Dolly Varden charr colonized, followed by other fish species, including juvenile red and silver salmon, Coast Range sculpin, and sticklebacks. Stable-isotope analyses indicate that marine-derived nitrogen from the decay of salmon carcasses was substantially assimilated within the aquatic food web by 2004. The findings from Stonefly Creek are compared with those from a long-term study of a similarly formed but older stream (12 km to the northeast) to examine possible similarities in macroinvertebrate community and biological trait composition between streams at similar stages of development. Macroinvertebrate community assembly appears to have been initially strongly deterministic owing to low water temperature associated with remnant ice masses. In contrast, microcrustacean community assembly appears to have been more stochastic. However, as stream age and water temperature increased, macroinvertebrate colonization was also more stochastic, and taxonomic similarity between Stonefly Creek and a stream at the same stage of development was <50%. However the most abundant taxa were similar, and functional diversity of the two communities was almost identical. Tolerance is suggested as the major mechanism of community assembly. The rapidity with which salmonids and invertebrate communities have become established across an entire watershed has implications for the conservation of biodiversity in freshwater habitats.
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Evolución Biológica , Cambio Climático , Ecosistema , Cubierta de Hielo , Ríos , Alaska , Animales , Peces/fisiología , Invertebrados/fisiología , Dinámica Poblacional , Factores de TiempoRESUMEN
Riverine ecosystems can be conceptualized as 'bioreactors' (the riverine bioreactor) which retain and decompose a wide range of organic substrates. The metabolic performance of the riverine bioreactor is linked to their community structure, the efficiency of energy transfer along food chains, and complex interactions among biotic and abiotic environmental factors. However, our understanding of the mechanistic functioning and capacity of the riverine bioreactor remains limited. We review the state of knowledge and outline major gaps in the understanding of biotic drivers of organic matter decomposition processes that occur in riverine ecosystems, across habitats, temporal dimensions, and latitudes influenced by climate change. We propose a novel, integrative analytical perspective to assess and predict decomposition processes in riverine ecosystems. We then use this model to analyse data to demonstrate that the size-spectra of a community can be used to predict decomposition rates by analysing an illustrative dataset. This modelling methodology allows comparison of the riverine bioreactor's performance across habitats and at a global scale. Our integrative analytical approach can be applied to advance understanding of the functioning and efficiency of the riverine bioreactor as hotspots of metabolic activity. Application of insights gained from such analyses could inform the development of strategies that promote the functioning of the riverine bioreactor across global ecosystems.
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Cambio Climático , Ecosistema , Reactores Biológicos , Cadena AlimentariaRESUMEN
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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Aspergillosis is difficult to treat and carries a high mortality rate in immunocompromised patients. Neutrophils play a critical role in control of infection but may be diminished in number and function during immunosuppressive therapies. Here, we measure the effect of three bifunctional small molecules that target Aspergillus fumigatus and prime neutrophils to generate a more effective response against the pathogen. The molecules combine two moieties joined by a chemical linker: a targeting moiety (TM) that binds to the surface of the microbial target, and an effector moiety (EM) that interacts with chemoattractant receptors on human neutrophils. We report that the bifunctional compounds enhance the interactions between primary human neutrophils and A. fumigatus in vitro, using three microfluidic assay platforms. The bifunctional compounds significantly enhance the recruitment of neutrophils, increase hyphae killing by neutrophils in a uniform concentration of drug, and decrease hyphal tip growth velocity in the presence of neutrophils compared to the antifungal targeting moiety alone. We validated that the bifunctional compounds are also effective in vivo, using a zebrafish infection model with neutrophils expressing the appropriate EM receptor. We measured significantly increased phagocytosis of A. fumigatus conidia by neutrophils expressing the EM receptor in the presence of the compounds compared to receptor-negative cells. Finally, we demonstrate that treatment with our lead compound significantly improved the antifungal activity of neutrophils from immunosuppressed patients ex vivo. This type of bifunctional compounds strategy may be utilized to redirect the immune system to destroy fungal, bacterial, and viral pathogens.
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Aspergilosis/tratamiento farmacológico , Aspergillus fumigatus/inmunología , Sistemas de Liberación de Medicamentos , Neutrófilos/inmunología , Animales , Aspergilosis/inmunología , Aspergilosis/patología , Humanos , Neutrófilos/patología , Pez CebraRESUMEN
The inappropriate retention of neutrophils at inflammatory sites is a major driver of the excessive tissue damage characteristic of respiratory inflammatory diseases including COPD, ARDS, and cystic fibrosis. The molecular programmes which orchestrate neutrophil recruitment to inflammatory sites through chemotactic guidance have been well-studied. However, how neutrophil sensitivity to these cues is modulated during inflammation resolution is not understood. The identification of neutrophil reverse migration as a mechanism of inflammation resolution and the ability to modulate this therapeutically has identified a new target to treat inflammatory disease. Here we investigate the role of the CXCL12/CXCR4 signaling axis in modulating neutrophil retention at inflammatory sites. We used an in vivo tissue injury model to study neutrophilic inflammation using transgenic zebrafish larvae. Expression of cxcl12a and cxcr4b during the tissue damage response was assessed using in situ hybridization and analysis of RNA sequencing data. CRISPR/Cas9 was used to knockdown cxcl12a and cxcr4b in zebrafish larvae. The CXCR4 antagonist AMD3100 was used to block the Cxcl12/Cxcr4 signaling axis pharmacologically. We identified that cxcr4b and cxcl12a are expressed at the wound site in zebrafish larvae during the inflammatory response. Following tail-fin transection, removal of neutrophils from inflammatory sites is significantly increased in cxcr4b and cxcl12a CRISPR knockdown larvae. Pharmacological inhibition of the Cxcl12/Cxcr4 signaling axis accelerated resolution of the neutrophil component of inflammation, an effect caused by an increase in neutrophil reverse migration. The findings of this study suggest that CXCR4/CXCL12 signaling may play an important role in neutrophil retention at inflammatory sites, identifying a potential new target for the therapeutic removal of neutrophils from the lung in chronic inflammatory disease.
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Movimiento Celular/inmunología , Quimiocina CXCL12/inmunología , Neutrófilos/inmunología , Receptores CXCR4/inmunología , Transducción de Señal/inmunología , Proteínas de Pez Cebra/inmunología , Pez Cebra/inmunología , Animales , Movimiento Celular/genética , Quimiocina CXCL12/genética , Técnicas de Silenciamiento del Gen , Inflamación/genética , Inflamación/inmunología , Inflamación/patología , Neutrófilos/patología , Receptores CXCR4/genética , Transducción de Señal/genética , Pez Cebra/genética , Proteínas de Pez Cebra/genéticaRESUMEN
A current controversy in ecology is whether biological communities are discrete biological entities or simply study units created for convenience; a debate that becomes even more heated when delimiting communities along ecotones. Here, we report an interdisciplinary study designed to address the interplay between environmental drivers and community ecology in a typical ecotone ecosystem: the streambed. Environmental filtering at a micro-scale determined how diversity, productivity and composition of the whole streambed assemblage varied with depth and with the direction of vertical water exchange. Biomass and production decreased with increasing depth, and were lower under upwelling than downwelling conditions. However, the rate at which biomass and production decreased with increasing depth differed significantly for different taxonomic groups. Using quantitative biocenosis analysis, we also showed that benthic and hyporheic zone assemblages (assemblages in close juxtaposition) could be clearly distinguished as discrete communities with individual integrity. Vertical hydrodynamic conditions also influenced the demarcation between both communities; the benthic community reached greater depths in downwelling than in upwelling zones.
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Biota , Ecosistema , Biodiversidad , Biomasa , Sedimentos Geológicos/microbiología , Agua Subterránea/microbiología , Modelos Lineales , Temperatura , Eliminación de Residuos LíquidosRESUMEN
Floods have a major influence in structuring river ecosystems. Considering projected increases in high-magnitude rainfall events with climate change, major flooding events are expected to increase in many regions of the world. However, there is uncertainty about the effect of different flooding regimes and the importance of flood timing in structuring riverine habitats and their associated biotic communities. In addition, our understanding of community response is hindered by a lack of long-term datasets to evaluate river ecosystem resilience to flooding. Here we show that in a river ecosystem studied for 30 years, a major winter flood reset the invertebrate community to a community similar to one that existed 15 years earlier. The community had not recovered to the preflood state when recurrent summer flooding 9 years later reset the ecosystem back to an even earlier community. Total macroinvertebrate density was reduced in the winter flood by an order of magnitude more than the summer flood. Meiofaunal invertebrates were more resilient to the flooding than macroinvertebrates, possibly due to their smaller body size facilitating greater access to in-stream refugia. Pacific pink salmon escapement was markedly affected by the winter flood when eggs were developing in redds, compared to summer flooding, which occurred before the majority of eggs were laid. Our findings inform a proposed conceptual model of three possible responses to flooding by the invertebrate community in terms of switching to different states and effects on resilience to future flooding events. In a changing climate, understanding these responses is important for river managers to mitigate the biological impacts of extreme flooding effects.
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Neutrophils are the first immune cells recruited to a site of injury or infection, where they perform many functions. Having completed their role, neutrophils must be removed from the inflammatory site-either by apoptosis and efferocytosis or by reverse migration away from the wound-for restoration of normal tissue homeostasis. Disruption of these tightly controlled physiological processes of neutrophil removal can lead to a range of inflammatory diseases. We used an in vivo zebrafish model to understand the role of lipid mediator production in neutrophil removal. Following tailfin amputation in the absence of macrophages, neutrophillic inflammation does not resolve, due to loss of macrophage-dependent handling of eicosanoid prostaglandin E2 (PGE2) that drives neutrophil removal via promotion of reverse migration. Knockdown of endogenous PGE synthase gene reveals PGE2 as essential for neutrophil inflammation resolution. Furthermore, PGE2 is able to signal through EP4 receptors during injury, causing an increase in Alox12 production and switching toward anti-inflammatory eicosanoid signaling. Our data confirm regulation of neutrophil migration by PGE2 and LXA4 (lipoxin A4) in an in vivo model of inflammation resolution. This pathway may contain therapeutic targets for driving inflammation resolution in chronic inflammatory disease.
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Dinoprostona/metabolismo , Inflamación/patología , Neutrófilos/fisiología , Heridas y Lesiones/fisiopatología , Animales , Animales Modificados Genéticamente , Movimiento Celular , Dinoprostona/farmacología , Modelos Animales de Enfermedad , Inflamación/metabolismo , Lipoxinas/metabolismo , Lipoxinas/farmacología , Lipooxigenasas/metabolismo , Macrófagos/metabolismo , Macrófagos/patología , Neutrófilos/efectos de los fármacos , Fenotipo , Subtipo EP4 de Receptores de Prostaglandina E/metabolismo , Pez Cebra/genética , Pez Cebra/fisiologíaRESUMEN
Hematopoietic stem cell transplantation (HSCT) is an important therapy for patients with a variety of hematological malignancies. HSCT would be greatly improved if patient-specific hematopoietic stem cells (HSCs) could be generated from induced pluripotent stem cells in vitro. There is an incomplete understanding of the genes and signals involved in HSC induction, migration, maintenance, and niche engraftment. Recent studies in zebrafish have revealed novel genes that are required for HSC induction and niche regulation of HSC homeostasis. Manipulation of these signaling pathways and cell types may improve HSC bioengineering, which could significantly advance critical, lifesaving HSCT therapies.
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Hematopoyesis/fisiología , Trasplante de Células Madre Hematopoyéticas , Pez Cebra/fisiología , Animales , Células Madre/fisiologíaRESUMEN
Food web studies provide a useful tool to assess the organization and complexity of natural communities. Nevertheless, the seasonal dynamics of food web properties, their environmental correlates, and potential association with community diversity and stability remain poorly studied. Here, we condensed an incomplete 6-year community dataset of a subtropical coastal lake to examine how monthly variation in diversity impacts food web structure over an idealized time series for an averaged year. Phytoplankton, zooplankton, macroinvertebrates, and fish were mostly resolved to species level (n = 120 trophospecies). Our results showed that the seasonal organization of the food web could be aggregated into two clusters of months grouped here as 'summer' and 'winter'. During 'winter', the food web decreases in size and complexity, with the number of trophospecies dropping from 106 to 82 (a 22.6% decrease in the number of nodes) and the trophic interactions from 1,049 to 637 between month extremes (a 39.3% drop in the number of links). The observed simplification in food web structure during 'winter' suggests that community stability is more vulnerable to the impact of any change during this period.