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Inositol hexakisphosphate kinases (IP6Ks) have been studied for their role in glucose homeostasis, metabolic disease, fatty liver disease, chronic kidney disease, neurological development, and psychiatric disease. IP6Ks phosphorylate inositol hexakisphosphate (IP6) to the pyrophosphate, 5-diphosphoinositol-1,2,3,4,6-pentakisphosphate (5-IP7). Most of the currently known potent IP6K inhibitors contain a critical carboxylic acid which limits blood-brain barrier (BBB) penetration. In this work, the synthesis and testing of a variety of carboxylic acid isosteres resulted in several new compounds with improved BBB penetration. The most promising compound has an IP6K1 IC50 of 16 nM with an improved brain/plasma ratio and a favorable pharmacokinetic profile. This series of brain penetrant compounds may be used to investigate the role of IP6Ks in CNS disorders.
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Sustained attention, the ability to focus on a stimulus or task over extended periods, is crucial for higher level cognition, and is impaired in individuals diagnosed with neuropsychiatric and neurodevelopmental disorders, including attention-deficit/hyperactivity disorder, schizophrenia, and depression. Translational tasks like the rodent continuous performance test (rCPT) can be used to study the cellular mechanisms underlying sustained attention. Accumulating evidence points to a role for the prelimbic cortex (PrL) in sustained attention, as electrophysiological single unit and local field (LFPs) recordings reflect changes in neural activity in the PrL in mice performing sustained attention tasks. While the evidence correlating PrL electrical activity with sustained attention is compelling, limitations inherent to electrophysiological recording techniques, including low sampling in single unit recordings and source ambivalence for LFPs, impede the ability to fully resolve the cellular mechanisms in the PrL that contribute to sustained attention. In vivo endoscopic calcium imaging using genetically encoded calcium sensors in behaving animals can address these questions by simultaneously recording up to hundreds of neurons at single cell resolution. Here, we used in vivo endoscopic calcium imaging to record patterns of neuronal activity in PrL neurons using the genetically encoded calcium sensor GCaMP6f in mice performing the rCPT at three timepoints requiring differing levels of cognitive demand and task proficiency. A higher proportion of PrL neurons were recruited during correct responses in sessions requiring high cognitive demand and task proficiency, and mice intercalated non-responsive-disengaged periods with responsive-engaged periods that resemble attention lapses. During disengaged periods, the correlation of calcium activity between PrL neurons was higher compared to engaged periods, suggesting a neuronal network state change during attention lapses in the PrL. Overall, these findings illustrate that cognitive demand, task proficiency, and task engagement differentially recruit activity in a subset of PrL neurons during sustained attention.
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Nanocarriers (NCs) that can precisely deliver active agents, nutrients and genetic materials into plants will make crop agriculture more resilient to climate change and sustainable. As a research field, nano-agriculture is still developing, with significant scientific and societal barriers to overcome. In this Review, we argue that lessons can be learned from mammalian nanomedicine. In particular, it may be possible to enhance efficiency and efficacy by improving our understanding of how NC properties affect their interactions with plant surfaces and biomolecules, and their ability to carry and deliver cargo to specific locations. New tools are required to rapidly assess NC-plant interactions and to explore and verify the range of viable targeting approaches in plants. Elucidating these interactions can lead to the creation of computer-generated in silico models (digital twins) to predict the impact of different NC and plant properties, biological responses, and environmental conditions on the efficiency and efficacy of nanotechnology approaches. Finally, we highlight the need for nano-agriculture researchers and social scientists to converge in order to develop sustainable, safe and socially acceptable NCs.
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The presence in seawater of low-molecular-weight polyethylene (PE) and polydimethylsiloxane (PDMS), synthetic polymers with high chemical resistance, has been demonstrated in this study for the first time by developing a novel methodology for their recovery and quantification from surface seawater. These synthetic polymer debris (SPD) with very low molecular weights and sizes in the nano- and micro-metre range have escaped conventional analytical methods. SPD have been easily recovered from water samples (2 L) through filtration with a nitrocellulose membrane filter with a pore size of 0.45 µm. Dissolving the filter in acetone allowed the isolation of the particulates by centrifugation followed by drying. The isolated SPD were analysed by 1H nuclear magnetic resonance spectroscopy (1H NMR), identifying PE and PDMS. These polymers are thus persisting on seawater because of their low density and the ponderal concentrations were quantified in mg/m3. This method was used in an actual case study in which 120 surface seawater samples were collected during two sampling campaigns in the Mediterranean Sea (from the Gulf of Salerno to the Gulf of Policastro in South Italy). The developed analytical protocol allowed achieving unprecedented simplicity, rapidity and sensitivity. The 1H and 13C NMR structural analysis of the PE debris indicates the presence of oxidised polymer chains with very low molecular weights. Additionally, the origin of those low molecular weight polymers was investigated by analysing influents and effluents from a wastewater treatment plant (WWTP) in Salerno as a hot spot for the release of SPD: the analysis indicates the presence of low molecular weight polymers compatible with wax-PE, widely used for coating applications, food industry, cosmetics and detergents. Moreover, the origin of PDMS debris found in surface seawater can be ascribed to silicone-based antifoamers and emulsifiers.
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Size and purity of metal phosphate and metal sulfide colloids can control the solubility, persistence, and bioavailability of metals in environmental systems. Despite their importance, methods for detecting and characterizing the diversity in the elemental composition of these colloids in complex matrices are missing. Here, we develop a single-particle inductively coupled plasma time-of-flight mass spectrometry (sp-icpTOF-MS) approach to characterize the elemental compositions of individual metal phosphate and sulfide colloids extracted from complex matrices. The stoichiometry was accurately determined for particles of known composition with an equivalent spherical diameter of ≥â¼200 nm. Assisted by machine learning (ML), the new method could distinguish particles of the copper sulfides covellite (CuS), chalcocite (Cu2S), and chalcopyrite particles (CuFeS2) with 75% (for Cu2S) to 99% (for CuFeS2) accuracy. Application of the sp-icpTOF-MS method to particles recovered from natural samples revealed that iron sulfide (FeS) particles in lake sediment contained â¼4% copper and zinc impurities, whereas pure pyrite (FeS2) was identified in hydraulic fracturing wastewater and confirmed by selected area electron diffraction. Colloidal mercury in an offshore marine sediment was present as pure mercury sulfide (HgS), whereas geogenic HgS recovered from an industrial process contained â¼0.08 wt % silver per Hg, enabling source apportionment of these colloids using ML. X-ray absorption spectroscopy confirmed that Hg was predominantly present as metacinnabar (ß-HgS) in the industrial process sample. The determination of impurities in individual colloids, such as zinc and copper in FeS, and silver in HgS may enable improved assessment of their origin, reactivity, and bioavailability potential.
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Coloides , Espectrometría de Masas , Fosfatos , Suelo , Sulfuros , Coloides/química , Sulfuros/química , Suelo/química , Fosfatos/química , Sedimentos Geológicos/química , Metales/químicaRESUMEN
Subsurface injection of colloidal activated carbon (CAC) is an in situ remediation strategy for perfluoroalkyl acids (PFAA), but the influence of groundwater solutes on longevity is uncertain, particularly for short-chain PFAA. We quantify the impact of inorganic anions, dissolved organic matter (DOM), and stabilizing polymer on PFAA adsorption to a commercial CAC. Surface characterization supported PFAA chain-length dependent adsorption results and mechanisms are provided. Inorganic anions decreased adsorption for short-chain PFAA (<7 perfluorinated carbons) due to competitive effects, while long-chain PFAA (≥ 7 perfluorinated carbons) were less impacted. DOM decreased adsorption of all PFAA in a chain-length dependent manner. High DOM concentrations (10 mg/L, â¼5 mg OC/L) decreased PFOA adsorption by a factor of 2, PFPeA by one order of magnitude, and completely hindered PFBA adsorption. High MW DOM has less impact on short-chain PFAA than low MW DOM, possibly due to differences in the ability to access CAC micropores. Low DOM concentrations (1 mg/L, â¼0.5 mg OC/L) did not impact adsorption. CMC (90 kDa average MW) had negligible impact on PFAA adsorption likely due to minimal CAC surface coverage. Longevity modeling demonstrated that groundwater solutes limit the capacity for PFAA in a CAC barrier, particularly for short-chain PFAA.
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Tobacco mild green mosaic virus (TMGMV)-like nanocarriers were designed for gene delivery to plant cells. High aspect ratio TMGMVs were coated with a polycationic biopolymer, poly(allylamine) hydrochloride (PAH), to generate highly charged nanomaterials (TMGMV-PAH; 56.20 ± 4.7 mV) that efficiently load (1:6 TMGMV:DNA mass ratio) and deliver single-stranded and plasmid DNA to plant cells. The TMGMV-PAH were taken up through energy-independent mechanisms in Arabidopsis protoplasts. TMGMV-PAH delivered a plasmid DNA encoding a green fluorescent protein (GFP) to the protoplast nucleus (70% viability), as evidenced by GFP expression using confocal microscopy and Western blot analysis. TMGMV-PAH were inactivated (iTMGMV-PAH) using UV cross-linking to prevent systemic infection in intact plants. Inactivated iTMGMV-PAH-mediated pDNA delivery and gene expression of GFP in vivo was determined using confocal microscopy and RT-qPCR. Virus-like nanocarrier-mediated gene delivery can act as a facile and biocompatible tool for advancing genetic engineering in plants.
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Arabidopsis , Proteínas Fluorescentes Verdes , Arabidopsis/virología , Arabidopsis/genética , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Técnicas de Transferencia de Gen , Plásmidos/genética , Poliaminas/química , Protoplastos/metabolismo , Nanoestructuras/química , ADN/química , ADN/administración & dosificaciónRESUMEN
Good site characterization is essential for the selection of remediation alternatives for impacted soils. The value of site characterization is critically dependent on the quality and quantity of the data collected. Current methods for characterizing impacted soils rely on expensive manual sample collection and off-site analysis. However, recent advances in terrestrial robotics and artificial intelligence offer a potentially revolutionary set of tools and methods that will help to autonomously explore natural environments, select sample locations with the highest value of information, extract samples, and analyze the data in real-time without exposing humans to potentially hazardous conditions. A fundamental challenge to realizing this potential is determining how to design an autonomous system for a given investigation with many, and often conflicting design criteria. This work presents a novel design methodology to navigate these criteria. Specifically, this methodology breaks the system into four components - sensing, sampling, mobility, and autonomy - and connects design variables to the investigation objectives and constraints. These connections are established for each component through a survey of existing technology, discussion of key technical challenges, and highlighting conditions where generality can promote multi-application deployment. An illustrative example of this design process is presented for the development and deployment of a robotic platform characterizing salt-impacted oil & gas reserve pits. After calibration, the relationship between the in situ robot chloride measurements and laboratory-based chloride measurements had a good linear relationship (R2-value = 0.861) and statistical significance (p-value = 0.003).
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Robótica , Suelo , Suelo/química , Monitoreo del Ambiente/métodos , Inteligencia ArtificialRESUMEN
Colloidal activated carbon (CAC) is an emerging technology for the in situ remediation of groundwater impacted by per- and polyfluoroalkyl substances (PFAS). In assessing the long-term effectiveness of a CAC barrier, it is crucial to evaluate the potential of emplaced CAC particles to be remobilized and migrate away from the sorptive barrier. We examine the effect of two polymer stabilizers, carboxymethyl cellulose (CMC) and polydiallyldimethylammonium chloride (PolyDM), on CAC deposition and remobilization in saturated sand columns. CMC-modified CAC showed high mobility in a wide ionic strength (IS) range from 0.1 to 100 mM, which is favorable for CAC delivery at a sufficient scale. Interestingly, the mobility of PolyDM-modified CAC was high at low IS (0.1 mM) but greatly reduced at high IS (100 mM). Notably, significant remobilization (release) of deposited CMC-CAC particles occurred upon the introduction of solution with low IS following deposition at high IS. In contrast, PolyDM-CAC did not undergo any remobilization following deposition due to its favorable interactions with the quartz sand. We further elucidated the CAC deposition and remobilization behaviors by analyzing colloid-collector interactions through the application of Derjaguin-Landau-Verwey-Overbeek theory, and the inclusion of a discrete representation of charge heterogeneity on the quartz sand surface. The classical colloid filtration theory was also employed to estimate the travel distance of CAC in saturated columns. Our results underscore the roles of polymer coatings and solution chemistry in CAC transport, providing valuable guidelines for the design of in situ CAC remediation with maximized delivery efficiency and barrier longevity.
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Coloides , Restauración y Remediación Ambiental , Agua Subterránea , Agua Subterránea/química , Coloides/química , Restauración y Remediación Ambiental/métodos , Polímeros/química , Carbón Orgánico/química , Arena/química , Contaminantes Químicos del Agua/química , Carbono/químicaRESUMEN
The next generation of the self-forming dynamic membrane, referred to in this study as the "Living Membrane (LM)", is a new patented technology based on an encapsulated biological layer that self-forms on a designed coarse-pore size support material during wastewater treatment and acts as a natural membrane filter. Integrating electrochemical processes with wastewater treatment using the LM approach has also been recently studied (the reactor is referred to as the Electro-Living Membrane Bioreactor or e-LMBR). This study investigated the effects of varying current densities, i.e., 0.3, 0.5, and 0.9 mA/cm2, on the performance of an e-LMBR. The results were also compared with those of the Living Membrane Bioreactor or LMBR (without applied current density). Higher pollutant removals were observed in the presence of the electric field. However, the effect of varying applied current densities on the COD (98-99 %), NH3-N (97-99 %), and PO43-P (100 %) removals was not statistically significant. The more prominent differences (p < 0.05) were observed in the decrease of NO3--N concentrations from mixed liquor to effluent, with increasing current density resulting in lower mean NO3--N effluent concentrations (0.3 mA/cm2: 6.13 mg/L; 0.5 mA/cm2: 4.38 mg/L; 0.9 mA/cm2: 3.70 mg/L). The reduction of NO3--N concentrations as wastewater permeated through the LM layer also confirmed its role in removing nitrogen-containing compounds. Higher current densities resulted in lower concentrations of fouling substances, particularly those of microbial extracellular polymeric substances (EPS) and transparent exopolymer particles (TEPs). The average values of the temporal variation of transmembrane pressure (d(TMP)/d(t)) in the e-LMBR were extremely low, in the range of 0.013-0.041 kPa/day, throughout the operation period. The highest (d(TMP)/d(t)) was observed for the highest current density. However, the TMP values remained below 2 kPa in all the e-LMBR runs even after the initial LM formation stage.
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Reactores Biológicos , Membranas Artificiales , Eliminación de Residuos Líquidos , Aguas Residuales , Eliminación de Residuos Líquidos/métodos , Aguas Residuales/química , Incrustaciones Biológicas/prevención & control , Contaminantes Químicos del Agua/análisisRESUMEN
Greenhouse gases (GHGs) emissions due to increasing energy demand have raised the need to identify effective solutions to produce clean and renewable energy. Biotechnologies are an effective platform to attain green transition objectives, especially when synergically integrated to promote health and environmental protection. In this context, microalgae-based biotechnologies are considered among the most effective tools for treating gaseous effluents and simultaneously capturing carbon sources for further biomass valorisation. The production of biodiesel is regarded as a promising avenue for harnessing value from residual algal biomass. Nonetheless, the existing techniques for extracting lipids still face certain limitations, primarily centred around the cost-effectiveness of the process.This study is dedicated to developing and optimising an innovative and cost-efficient technique for extracting lipids from algal biomass produced during gaseous emissions treatment based on algal-bacterial biotechnology. This integrated treatment technology combines a bio-scrubber for degrading gaseous contaminants and a photobioreactor for capturing the produced CO2 within valuable algal biomass. The cultivated biomass is then processed with the process newly designed to extract lipids simultaneously transesterificated in fatty acid methyl esters (FAME) via In Situ Transesterification (IST) with a Kumagawa-type extractor. The results of this study demonstrated the potential application of the optimised method to overcome the gap to green transition. Energy production was obtained from residuals produced during the necessary treatment of gaseous emissions. Using hexane-methanol (v/v = 19:1) mixture in the presence KOH in Kumagawa extractor lipids were extracted with extraction yield higher than 12% and converted in fatty acid methyl esters. The process showed the enhanced extraction of lipids converted in bio-sourced fuels with circular economy approach, broadening the applicability of biotechnologies as sustainable tools for energy source diversification.
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Lípidos , Microalgas , Biocombustibles , Promoción de la Salud , Ácidos Grasos , Gases , Biomasa , ÉsteresRESUMEN
Predicting and elucidating the impacts of materials on human health and the environment is an unending task that has taken on special significance in the context of nanomaterials research over the last two decades. The properties of materials in environmental and physiological media are dynamic, reflecting the complex interactions between materials and these media. This dynamic behavior requires special consideration in the design of databases and data curation that allow for subsequent comparability and interrogation of the data from potentially diverse sources. We present two data processing methods that can be integrated into the experimental process to encourage pre-mediated interoperability of disparate material data: Knowledge Mapping and Instance Mapping. Originally developed as a framework for the NanoInformatics Knowledge Commons (NIKC) database, this architecture and associated methods can be used independently of the NIKC and applied across multiple subfields of nanotechnology and material science.
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Here, isotopically labeled 68ZnO NPs (ZnO NPs) and 68ZnO NPs with a thin 68Zn3(PO4)2 shell (ZnO_Ph NPs) were foliarly applied (40 µg Zn) to pepper plants (Capsicum annuum) to determine the effect of surface chemistry of ZnO NPs on the Zn uptake and systemic translocation to plant organs over 6 weeks. Despite similar dissolution of both Zn-based NPs after 3 weeks, the Zn3(PO4)2 shell on ZnO_Ph NPs (48 ± 12 nm; -18.1 ± 0.6 mV) enabled a leaf uptake of 2.31 ± 0.34 µg of Zn, which is 2.7 times higher than the 0.86 ± 0.18 µg of Zn observed for ZnO NPs (26 ± 8 nm; 14.6 ± 0.4 mV). Further, ZnO_Ph NPs led to higher Zn mobility and phloem loading, while Zn from ZnO NPs was stored in the epidermal tissues, possibly through cell wall immobilization as a storage strategy. These differences led to higher translocation of Zn from the ZnO_Ph NPs within all plant compartments. ZnO_Ph NPs were also more persistent as NPs in the exposed leaf and in the plant stem over time. As a result, the treatment of ZnO_Ph NPs induced significantly higher Zn transport to the fruit than ZnO NPs. As determined by spICP-TOFMS, Zn in the fruit was not in the NP form. These results suggest that the Zn3(PO4)2 shell on ZnO NPs can help promote the transport of Zn to pepper fruits when foliarly applied. This work provides insight into the role of Zn3(PO4)2 on the surface of ZnO NPs in foliar uptake and in planta biodistribution for improving Zn delivery to edible plant parts and ultimately improving the Zn content in food for human consumption.
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Differential absorption spectroscopy (DAS) quantifies changes in the UV-Visible absorbance of dissolved organic matter (DOM) caused by reactions of its chromophores. As a result of its precision and sensitvity, DAS serves as a powerful tool for characterizing the formation of disinfection by-products (DBPs) in generated in DOM chlorination reactions. However, the nonlinear relationship between the intensity of DAS and DBP concentrations as well as the need to develop site-specific fitting parameters limit its practical applications. This study investigated the physico-chemical nature of DAS of chlorinated DOM through experimental measurements and theoretical calculations. Results of this study provide molecular-level evidence that electrophilic substitution reactions involving DOM reactive sites result in the emergence of DAS feaures ascribed to the "fast" chromophores. The ring opening in the cyclic enones-like structures which can be present either in the original DOM or are generated as intermediates in its chlorination, leads to the emergence of DAS features associated with the "slow" chromophores and high yields of DBPs. The kinetic study of chlorination of real waters reveals a strong linear relationship (R2 > 0.91) between ln([DBP]) and the long-wavelength (λ > 325 nm) parameter of the DAS, notably (ln(-DA350)). This relationship varies among different water sources due to the differences in the heterogeneity of Band A3 whose maximum is near 350 nm. Band A3 is one of the Gaussian bands that comprise the overall UV-Visible spectrum of DOM. A new function (f(-DA350)) is proposed in this study to quantify DBP formation. This function, which is determined by the Band A3's area, allows establishing a universal linear relationship between f(-DA350) and ln([THMs]), as well as f(-DA350) and ln([HAAs]), across various water sources. The findings of this study will stimulate further development of spectroscopy-based DBP monitoring technology for monitoring and optimization of water disinfection processes.
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Purificación del Agua , Purificación del Agua/métodos , Desinfección , Aminas , Agua/químicaRESUMEN
Solar photoexcitation of chromophoric groups in dissolved organic matter (DOM), when coupled to photoreduction of ubiquitous Fe(III)-oxide nanoparticles, can significantly accelerate DOM degradation in near-surface terrestrial systems, but the mechanisms of these reactions remain elusive. We examined the photolysis of chromophoric soil DOM coated onto hematite nanoplatelets featuring (001) exposed facets using a combination of molecular spectroscopies and density functional theory (DFT) computations. Reactive oxygen species (ROS) probed by electron paramagnetic resonance (EPR) spectroscopy revealed that both singlet oxygen and superoxide are the predominant ROS responsible for DOM degradation. DFT calculations confirmed that Fe(II) on the hematite (001) surface, created by interfacial electron transfer from photoexcited chromophores in DOM, can reduce dioxygen molecules to superoxide radicals (â¢O2-) through a one-electron transfer process. 1H nuclear magnetic resonance (NMR) and electrospray ionization Fourier-transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) spectroscopies show that the association of DOM with hematite enhances the cleavage of aromatic groups during photodegradation. The findings point to a pivotal role for organic matter at the interface that guides specific ROS generation and the subsequent photodegradation process, as well as the prospect of using ROS signatures as a forensic tool to help interpret more complicated field-relevant systems.