RESUMEN
In the first billion years after the Big Bang, sources of ultraviolet (UV) photons are believed to have ionized intergalactic hydrogen, rendering the Universe transparent to UV radiation. Galaxies brighter than the characteristic luminosity L* (refs. 1,2) do not provide enough ionizing photons to drive this cosmic reionization. Fainter galaxies are thought to dominate the photon budget; however, they are surrounded by neutral gas that prevents the escape of the Lyman-α photons, which has been the dominant way to identify them so far. JD1 was previously identified as a triply-imaged galaxy with a magnification factor of 13 provided by the foreground cluster Abell 2744 (ref. 3), and a photometric redshift of z ≈ 10. Here we report the spectroscopic confirmation of this very low luminosity (≈0.05 L*) galaxy at z = 9.79, observed 480 Myr after the Big Bang, by means of the identification of the Lyman break and redward continuum, as well as multiple â³4σ emission lines, with the Near-InfraRed Spectrograph (NIRSpec) and Near-InfraRed Camera (NIRCam) instruments. The combination of the James Webb Space Telescope (JWST) and gravitational lensing shows that this ultra-faint galaxy (MUV = -17.35)-with a luminosity typical of the sources responsible for cosmic reionization-has a compact (≈150 pc) and complex morphology, low stellar mass (107.19 Mâ) and subsolar (≈0.6 Zâ) gas-phase metallicity.
RESUMEN
The placenta establishes a maternal-fetal exchange interface to transport nutrients and gases between the mother and the fetus. Establishment of this exchange interface relies on the development of multinucleated syncytiotrophoblasts (SynT) from trophoblast progenitors, and defect in SynT development often leads to pregnancy failure and impaired embryonic development. Here, we show that mouse embryos with conditional deletion of transcription factors GATA2 and GATA3 in labyrinth trophoblast progenitors (LaTPs) have underdeveloped placenta and die by ~embryonic day 9.5. Single-cell RNA sequencing analysis revealed excessive accumulation of multipotent LaTPs upon conditional deletion of GATA factors. The GATA factor-deleted multipotent progenitors were unable to differentiate into matured SynTs. We also show that the GATA factor-mediated priming of trophoblast progenitors for SynT differentiation is a conserved event during human placentation. Loss of either GATA2 or GATA3 in cytotrophoblast-derived human trophoblast stem cells (human TSCs) drastically inhibits SynT differentiation potential. Identification of GATA2 and GATA3 target genes along with comparative bioinformatics analyses revealed that GATA factors directly regulate hundreds of common genes in human TSCs, including genes that are essential for SynT development and implicated in preeclampsia and fetal growth retardation. Thus, our study uncovers a conserved molecular mechanism, in which coordinated function of GATA2 and GATA3 promotes trophoblast progenitor-to-SynT commitment, ensuring establishment of the maternal-fetal exchange interface.
Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Intercambio Materno-Fetal , Embarazo , Femenino , Humanos , Animales , Ratones , Placenta , Trofoblastos , Diferenciación Celular/fisiología , Desarrollo Fetal , Factores de Transcripción GATARESUMEN
Healthy progression of human pregnancy relies on cytotrophoblast (CTB) progenitor self-renewal and its differentiation toward multinucleated syncytiotrophoblasts (STBs) and invasive extravillous trophoblasts (EVTs). However, the underlying molecular mechanisms that fine-tune CTB self-renewal or direct its differentiation toward STBs or EVTs during human placentation are poorly defined. Here, we show that Hippo signaling cofactor WW domain containing transcription regulator 1 (WWTR1) is a master regulator of trophoblast fate choice during human placentation. Using human trophoblast stem cells (human TSCs), primary CTBs, and human placental explants, we demonstrate that WWTR1 promotes self-renewal in human CTBs and is essential for their differentiation to EVTs. In contrast, WWTR1 prevents induction of the STB fate in undifferentiated CTBs. Our single-cell RNA sequencing analyses in first-trimester human placenta, along with mechanistic analyses in human TSCs revealed that WWTR1 fine-tunes trophoblast fate by directly regulating WNT signaling components. Importantly, our analyses of placentae from pathological pregnancies show that extreme preterm births (gestational time ≤28 wk) are often associated with loss of WWTR1 expression in CTBs. In summary, our findings establish the critical importance of WWTR1 at the crossroads of human trophoblast progenitor self-renewal versus differentiation. It plays positive instructive roles in promoting CTB self-renewal and EVT differentiation and safeguards undifferentiated CTBs from attaining the STB fate.
Asunto(s)
Placenta , Placentación , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ , Trofoblastos , Diferenciación Celular , Femenino , Vía de Señalización Hippo , Humanos , Recién Nacido , Placenta/metabolismo , Placentación/fisiología , Embarazo , Nacimiento Prematuro/fisiopatología , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ/genética , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ/metabolismo , Trofoblastos/citología , Trofoblastos/metabolismoRESUMEN
In the present study, ZnO-Fe3O4 nanoparticles were synthesized using the leaves of Camellia sinensis and immobilized in crosslinked alginate-chitosan polymer beads and tested for their photocatalytic applications. The prepared nanocomposite was used for the simultaneous adsorption and photocatalytic degradation of acid violet 7 (AV7) dye. The optimization of reaction conditions ensured higher dye removal efficacy up to 94.21 ± 1.02% using the nanocomposite under UV-C irradiation of 365 nm. The kinetics of the adsorption study fitted well with the pseudo-first-order reaction. The Langmuir model fitted better to the adsorption isotherms compared to the Freundlich and Temkin models. The mechanism of degradation was studied by analyzing the treated AV7 solution. The removal efficiency in tap water, groundwater, and lake water was 83.23 ± 0.4%, 69.13 ± 1.6%, and 67.89 ± 0.3%, respectively. The residual toxicity of the degraded AV7 solution was tested on model organisms like freshwater algae, Scenedesmus sp., and plant model, Allium cepa, demonstrating the lower toxicity of the degraded AV7 product. Finally, a cost-benefit analysis of the experiments was also carried out.
Asunto(s)
Camellia sinensis , Quitosano , Nanocompuestos , Contaminantes Químicos del Agua , Óxido de Zinc , Adsorción , Alginatos , Compuestos Azo , Concentración de Iones de Hidrógeno , Cinética , Naftalenosulfonatos , Extractos Vegetales , AguaRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, known as coronavirus disease 2019 (COVID-19) causes cytokine release syndrome (CRS), leading to acute respiratory distress syndrome (ARDS), acute kidney and cardiac injury, liver dysfunction, and multiorgan failure. Although several studies have discussed the role of 5-lipoxygenase (5-LOX) in viral infections, such as influenzae and SARS, it remains unexplored in the pathophysiology of COVID-19. 5-LOX acts on free arachidonic acid (AA) to form proinflammatory leukotrienes (LTs). Of note, numerous cells involved with COVID-19 (e.g., inflammatory and smooth muscle cells, platelets, and vascular endothelium) widely express leukotriene receptors. Moreover, 5-LOX metabolites induce the release of cytokines (e.g., tumour necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and interleukin-1ß [IL-1ß]) and express tissue factor on cell membranes and activate plasmin. Since macrophages, monocytes, neutrophils, and eosinophils can express lipoxygenases, activation of 5-LOX and the subsequent release of LTs may contribute to the severity of COVID-19. This review sheds light on the potential implications of 5-LOX in SARS-CoV-2-mediated infection and the anticipated therapeutic role of 5-LOX inhibitors.
Asunto(s)
Araquidonato 5-Lipooxigenasa/metabolismo , Tratamiento Farmacológico de COVID-19 , COVID-19/enzimología , COVID-19/fisiopatología , Interleucinas/metabolismo , Inhibidores de la Lipooxigenasa/farmacología , SARS-CoV-2 , Animales , Ácido Araquidónico/metabolismo , Síndrome de Liberación de Citoquinas , Citocinas/metabolismo , Inhibidores Enzimáticos/farmacología , Humanos , Inflamación , Leucotrienos/metabolismo , Resultado del Tratamiento , Virosis/tratamiento farmacológicoAsunto(s)
Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus , Pandemias , Neumonía Viral , COVID-19 , Infecciones por Coronavirus/epidemiología , Sistemas de Información Geográfica , Humanos , Incidencia , Italia/epidemiología , Neumonía Viral/epidemiología , SARS-CoV-2 , Programas InformáticosRESUMEN
GFNs have widespread applications but can harm marine systems due to excessive use and improper disposal. Algae-secreted EPS can mitigate nanomaterial harm, but their impact on GFN toxicity is understudied. Hence, in the present study, we investigated the toxicity of three GFNs, graphene oxide (GO), reduced graphene oxide (rGO), and graphene, in pristine and EPS-adsorbed forms in the marine alga Chlorella sp. At an environmentally relevant concentration of 1 mgL-1, all three GFNs induced considerable oxidative stress and impeded growth and photosynthetic activity of the algae. The order of the toxic potential followed GO > rGO > graphene. The various facets of adsorption of EPS (1:1 mixture of loosely bound, and tightly bound EPS) on GFNs were investigated through microscopy, surface chemical analyses, fluorescence quenching studies, and isotherm and kinetics studies. Amongst the pristine GFNs treated with algal cells, GO was found to exert the maximum negative effects on algal growth. Upon adsorption of EPS over the GFNs, a significant decline in growth inhibition was observed compared to the respective pristine forms which strongly correlated with reduced oxidative stress and enhanced photosynthetic parameters in the cells. The formation of a layer of eco-corona after interaction of GFNs with EPS possibly caused a barrier effect which in turn diminished their toxic potential. The findings from the present investigation offer valuable insights into the environmental toxicity of GFNs and show that the eco-corona formation may lessen the risk posed by these materials in the marine environment.
Asunto(s)
Chlorella , Grafito , Nanoestructuras , Grafito/toxicidad , Nanoestructuras/toxicidad , Estrés OxidativoRESUMEN
During embryonic development the placental vasculature acts as a major hematopoietic niche, where endothelial to hematopoietic transition ensures emergence of hematopoietic stem cells (HSCs). However, the molecular mechanisms that regulate the placental hematoendothelial niche are poorly understood. Using a parietal trophoblast giant cell (TGC)-specific knockout mouse model and single-cell RNA-sequencing, we show that the paracrine factors secreted by the TGCs are critical in the development of this niche. Disruptions in the TGC-specific paracrine signaling leads to the loss of HSC population and the concomitant expansion of a KDR+/DLL4+/PROM1+ hematoendothelial cell-population in the placenta. Combining single-cell transcriptomics and receptor-ligand pair analyses, we also define the parietal TGC-dependent paracrine signaling network and identify Integrin signaling as a fundamental regulator of this process. Our study elucidates novel mechanisms by which non-autonomous signaling from the primary parietal TGCs maintain the delicate placental hematopoietic-angiogenic balance and ensures embryonic and extraembryonic development.
RESUMEN
Methyltransferase-like 3 (METTL3), the catalytic enzyme of methyltransferase complex for m6A methylation of RNA, is essential for mammalian development. However, the importance of METTL3 in human placentation remains largely unexplored. Here, we show that a fine balance of METTL3 function in trophoblast cells is essential for successful human placentation. Both loss-of and gain-in METTL3 functions are associated with adverse human pregnancies. A subset of recurrent pregnancy losses and preterm pregnancies are often associated with loss of METTL3 expression in trophoblast progenitors. In contrast, METTL3 is induced in pregnancies associated with fetal growth restriction (FGR). Our loss of function analyses showed that METTL3 is essential for the maintenance of human TSC self-renewal and their differentiation to extravillous trophoblast cells (EVTs). In contrast, loss of METTL3 in human TSCs promotes syncytiotrophoblast (STB) development. Global analyses of RNA m6A modification and METTL3-RNA interaction in human TSCs showed that METTL3 regulates m6A modifications on the mRNA molecules of critical trophoblast regulators, including GATA2, GATA3, TEAD1, TEAD4, WWTR1, YAP1, TFAP2C and ASCL2, and loss of METTL3 leads to depletion of mRNA molecules of these critical regulators. Importantly, conditional deletion of Mettl3 in trophoblast progenitors of an early post-implantation mouse embryo also leads to arrested self-renewal. Hence, our findings indicate that METLL3 is a conserved epitranscriptomic governor in trophoblast progenitors and ensures successful placentation by regulating their self-renewal and dictating their differentiation fate.
RESUMEN
Ferrocene functionalized rGO-ZnO nanocomposite was synthesized via the facile hydrothermal method. ZnO was reduced over the 3-dimensional rGO framework (3D-Fc@rGO) using Camellia sinensis extract. The Fc@rGO-ZnO nanocomposite was employed for pharmaceutical degradation (sulfamethoxazole (SMX) and ciprofloxacin (CIP)) in an aqueous solution under UV C light. The physicochemical properties of the as-prepared photocatalyst were characterized using FTIR, XRD, FESEM, EDS mapping, HR-TEM, XPS, and DR-UV Vis. The as-synthesized Fc@rGO-ZnO photocatalyst performed remarkably against pristine ZnO, with a fivefold increase in removal efficiency. This superior activity was attributed to its improved light harvesting, charge carrier interface, and enhanced charge separation. Additionally, the photocatalyst obeyed the Lagergen model for pseudo-first-order kinetics. Congruously, the integrated approach of Fc@rGO and ZnO as oxidizing agents was proficient in removing >95% of antibiotics (CIP and SMX) within 180 min. Furthermore, the heterostructure configuration developed between Fc@rGO and ZnO helps in charge migration and generation of abundant â¢OH and â¢O2- radicals for photodegradation activities. The toxicity assessment of the treated solutions showed improved cell viability in the algal strains of Scenedesmus and Chlorella sp. Moreover, this novel approach for the synthesis of a photoactive nanocomposite is found to be low-cost and reusable for three cycles. The nanocomposite is environmentally sustainable paving the way for practical applications in the treatment of different classes of antibiotics.
Asunto(s)
Chlorella , Óxido de Zinc , Antibacterianos/química , Ciprofloxacina/química , Sulfametoxazol , Óxido de Zinc/química , Adsorción , AguaRESUMEN
Pesticides are often used in different applications, including agriculture, forestry, aquaculture, food industry, etc., for the purpose of controlling insect pests and weeds. The indiscriminate usage of pesticides poses a massive threat to food, environmental, and human health safety. Hence, the fabrication of a sensitive and reliable sensor for the detection of pesticide residues in agro products and environmental samples is a critical subject to be considered. Recently, the graphene family including graphene oxide (GO) and reduced graphene oxide (rGO) have been frequently employed in the construction of sensors owing to their biocompatibility, high surface-area-to-volume ratio, and excellent physiochemical, optical, and electrical properties. The integration of biorecognition molecules with GO/rGO nanomaterials offers a promising detection strategy with outstanding repeatability, signal intensity, and low background noise. This review focuses on the latest developments (2018 to 2022) in the different types of GO/rGO-based biosensors, such as surface plasmon resonance (SPR), fluorescence resonance energy transfer (FRET), and electrochemical-based techniques, among other, for pesticide analysis. The critical discussions on the advantages, limitations, and sensing mechanisms of emerging GO/rGO-based biosensors are also highlighted. Additionally, we explore the existing hurdles in GO/rGO-based biosensors, such as handling difficult biological samples, reducing the total cost, and so on. This review also outlines the research gaps and viewpoints for future innovations in GO/rGO-based biosensors for pesticide determination mainly in areas with insufficient resources.
Asunto(s)
Técnicas Biosensibles , Grafito , Nanoestructuras , Plaguicidas , Humanos , Grafito/química , Nanoestructuras/química , Técnicas Biosensibles/métodosRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the cytokine release syndrome (CRS) and leads to multiorgan dysfunction. Mitochondrial dynamics are fundamental to protect against environmental insults, but they are highly susceptible to viral infections. Defective mitochondria are potential sources of reactive oxygen species (ROS). Infection with SARS-CoV-2 damages mitochondria, alters autophagy, reduces nitric oxide (NO), and increases both nicotinamide adenine dinucleotide phosphate oxidases (NOX) and ROS. Patients with coronavirus disease 2019 (COVID-19) exhibited activated toll-like receptors (TLRs) and the Nucleotide-binding and oligomerization domain (NOD-), leucine-rich repeat (LRR-), pyrin domain-containing protein 3 (NLRP3) inflammasome. The activation of TLRs and NLRP3 by SARS-CoV-2 induces interleukin 6 (IL-6), IL-1ß, IL-18, and lactate dehydrogenase (LDH). Herein, we outline the inflammatory circuit of COVID-19 and what occurs behind the scene, the interplay of NOX/ROS and their role in hypoxia and thrombosis, and the important role of ROS scavengers to reduce COVID-19-related inflammation.
Asunto(s)
COVID-19 , Inflamasomas , Humanos , Inflamasomas/metabolismo , Interleucina-18 , Interleucina-6 , Lactato Deshidrogenasas , Leucina , NADP , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Óxido Nítrico , Oxidorreductasas , Especies Reactivas de Oxígeno/metabolismo , SARS-CoV-2 , Receptores Toll-LikeRESUMEN
In the present study, we report an efficient method for tetracycline (TC) removal from contaminated wastewater using alginate beads, immobilized with bio nanocomposite (BNC) consisting of Fe3O4 (iron oxide) and TiO2 (titanium dioxide) nanoparticles along with dead biomass of TC-resistant bacteria Acinetobacter sp. Chemically synthesized Fe3O4 nanoparticles and commercially available TiO2 (P25) nanoparticles were combined to form nanocomposite followed by encapsulation within alginate beads along with heat-killed biomass of Acinetobactersp. for the efficient degradation and adsorption of the target pollutant. The primary characterization of chemically synthesized nanoparticles was carried out with Fourier transform infrared, scanning electron microscopy-energy-dispersive X-ray spectrometry, transmission electron microscopy, and X-ray diffraction techniques. The batch studies for TC removal were performed by varying the reaction parameters such as bead weight, initial TC concentration, and pH in a photoreactor with UV-C irradiation. TC concentration of 10 mg/L, bead weight 10 g, and pH 6 were fixed as the optimum condition where 98 ± 0.5% of TC was removed from the solution. The possible removal mechanism was investigated with the help of UV-visible, total organic carbon, oxidation-reduction potential, Brunauer-Emmett-Teller, and liquid chromatography-mass spectroscopy analyses. The applicability of the process was successfully tested with the natural water systems spiked with TC at 10 mg/L. To assess the ecotoxic effects of the treated effluents, the cell viability assay was performed with the algal strains, Chlorella, and Scenedesmussp. and the bacterial strains, Pseudomonas aeruginosaand Escherichia coli. Finally, the reusability of the BNC bead was successfully established up to the 4th cycle.