Zirconium-based MOFs and their biodegradable polymer composites for controlled and sustainable delivery of herbicides

YesAdsorption and controlled release of agrochemicals has been studied widely using different nanomaterials and a variety of formulations. However, the potential for application of high surface-area metal-organic frameworks (MOFs) for the controlled release of agrochemicals has not been thoroughly explored. Herein, we report controlled and sustainable release of a widely used herbicide (2-methyl-4-chlorophenoxyacetic acid, MCPA) via incorporation in a range of zirconium-based MOFs and their biodegradable polymer composites. Three Zr-based MOFs, viz., UiO-66, UiO-66-NH2, and UiO-67 were loaded with MCPA either postsynthetically or in situ during synthesis of the MOFs. The MCPA-loaded MOFs were then incorporated into a biodegradable polycaprolactone (PCL) composite membrane. All three MOFs and their PCL composites were thoroughly characterized using FT-IR, TGA, SEM, PXRD, BET, and mass spectrometry. Release of MCPA from each of these MOFs and their PCL composites was then studied in both distilled water and in ethanol for up to 72 h using HPLC. The best performance for MCPA release was observed for the postsynthetically loaded MOFs, with PS-MCPA@UiO-66-NH2 showing the highest MCPA concentrations in ethanol and water of 0.056 and 0.037 mg/mL, respectively. Enhanced release of MCPA was observed in distilled water when the MOFs were incorporated in PCL. The concentrations of herbicides in the release studies provide us with a range of inhibitory concentrations that can be utilized depending on the crop, making this class of composite materials a promising new route for future agricultural applications.L.A.M.M. and S.N. acknowledge funding for a studentship by the Erasmus+ KA107 Student Mobility programme. V.P.T and L.R.T. acknowledge funding from the EPSRC (EP/R01650X/1

The Pediatric Cell Atlas: defining the growth phase of human development at single-cell resolution

Single-cell gene expression analyses of mammalian tissues have uncovered profound stage-specific molecular regulatory phenomena that have changed the understanding of unique cell types and signaling pathways critical for lineage determination, morphogenesis, and growth. We discuss here the case for a Pediatric Cell Atlas as part of the Human Cell Atlas consortium to provide single-cell profiles and spatial characterization of gene expression across human tissues and organs. Such data will complement adult and developmentally focused HCA projects to provide a rich cytogenomic framework for understanding not only pediatric health and disease but also environmental and genetic impacts across the human lifespan

Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility

Glaucoma is a multi-factorial blinding disease in which genetic factors play an important role. Elevated intraocular pressure is a highly heritable risk factor for primary open angle glaucoma and currently the only target for glaucoma therapy. Our study helps to better understand underlying genetic and molecular mechanisms that regulate intraocular pressure, and identifies a new candidate gene, Cacna2d1, that modulates intraocular pressure and a promising therapeutic, pregabalin, which binds to CACNA2D1 protein and lowers intraocular pressure significantly. Because our study utilizes a genetically diverse population of mice with kno

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r =-0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r =-0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation

Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH

Aggregation, adsorption, and surface properties of multiply end-functionalized polystyrenes

The properties of polystyrene blends containing deuteriopolystyrene, multiply end-functionalized with C8F17 fluorocarbon groups, are strikingly analogous to those of surfactants in solution. These materials, denoted FxdPSy, where x is the number of fluorocarbon groups and y is the molecular weight of the dPS chain in kg/mol, were blended with unfunctionalized polystyrene, hPS. Nuclear reaction analysis experiments show that FxdPSy polymers adsorb spontaneously to solution and blend surfaces, resulting in a reduction in surface energy inferred from contact angle analysis. Aggregation of functionalized polymers in the bulk was found to be sensitive to FxdPSy structure and closely related to surface properties. At low concentrations, the functionalized polymers are freely dispersed in the hPS matrix, and in this range, the surface excess concentration grows sharply with increasing bulk concentration. At higher concentrations, surface excess concentrations and contact angles reach a plateau, small-angle neutron scattering data indicate small micellar aggregates of six to seven F2dPS10 polymer chains and much larger aggregates of F4dPS10. Whereas F2dPS10 aggregates are miscible with the hPS matrix, F4dPS10 forms a separate phase of multilamellar vesicles. Using neutron reflectometry (NR), we found that the extent of the adsorbed layer was approximately half the lamellar spacing of the multilamellar vesicles. NR data were fitted using an error function profile to describe the concentration profile of the adsorbed layer, and reasonable agreement was found with concentration profiles predicted by the SCFT model. The thermodynamic sticking energy of the fluorocarbon-functionalized polymer chains to the blend surface increases from 5.3kBT for x = 2 to 6.6kBT for x = 4 but appears to be somewhat dependent upon the blend concentration

Evolution of the global carbon cycle and climate regulation on Earth

The existence of stabilizing feedbacks within Earth's climate system is generally thought to be necessary for the persistence of liquid water and life. Over the course of Earth's history, Earth's atmospheric composition appears to have adjusted to the gradual increase in solar luminosity, resulting in persistently habitable surface temperatures. With limited exceptions, the Earth system has been observed to recover rapidly from pulsed climatic perturbations. Carbon dioxide (CO₂) regulation via negative feedbacks within the coupled global carbon‐silica cycles are classically viewed as the main processes giving rise to climate stability on Earth. Here we review the long‐term global carbon cycle budget, and how the processes modulating Earth's climate system have evolved over time. Specifically, we focus on the relative roles that shifts in carbon sources and sinks have played in driving long‐term changes in atmospheric pCO₂. We make the case that marine processes are an important component of the canonical silicate weathering feedback, and have played a much more important role in CO₂ regulation than traditionally imagined. Notably, geochemical evidence indicate that the weathering of marine sediments and off‐axis basalt alteration act as major carbon sinks. However, this sink was potentially dampened during Earth's early history when oceans had higher levels of dissolved silicon (Si), iron (Fe), and magnesium (Mg), and instead likely fostered more extensive carbon recycling within the ocean‐atmosphere system via reverse weathering—that in turn acted to elevate ocean‐atmosphere CO₂ levels