Controlled Localized Metal–Organic Framework Synthesis on Anion Exchange Membranes

Metal–organic framework (MOF) films can be used in various applications. In this work, we propose a method that can be used to synthesize MOF films localized on a single side of an anion exchange membrane, preventing the transport of the metal precursor via Donnan exclusion. This is advantageous compared to the related contra-diffusion method that results in the growth of a MOF film on both sides of the support, differing in quality on both sides. Our proposed method has the advantage that the synthesis conditions can potentially be tuned to create the optimal conditions for crystal growth on a single side. The localized growth of the MOF is governed by Donnan exclusion of the anion exchange membrane, preventing metal ions from passing to the other compartment, and this leads to a local control of the precursor stoichiometry. In this work, we show that our method can localize the growth of both Cu-BTC and ZIF-8 in water and in methanol, respectively, highlighting that this method can used for preparing a variety of MOF films with varying characteristics using soluble precursors at room temperature

Electroforming of a metal-organic framework on porous copper hollow fibers

Porous copper hollow fibers have been used, for the first time, as both a support structure and a metal source for preparing thin metal-organic framework (Cu-BTC) films via a fast, facile and direct electrochemical route. The focus is on the effects of the presence of a supporting electrolyte and the magnitude of the applied electrical potential on the formation and the morphology of the films. In the absence of a supporting electrolyte, and at low potential, more uniform films with smaller particles are obtained. This is attributed to the more pronounced electric-field driven mass transport of the organic ligand from the liquid bulk towards the surface of the electrode combined with the slower dissolution of copper due to the lower overpotentials. In the presence of a supporting electrolyte the ligand transport is much slower and copper dissolution is higher due to higher overpotentials; this results in the formation of less homogeneous films and the growth of metal-organic framework crystals in the liquid bulk. The localized formation of thin metal-organic framework films on metal porous hollow fibers with high surface area to volume ratio is an important step towards various applications, including membranes, microfluidic devices, sensors and heterogeneous catalysts

Interferon-gamma impairs proliferation of hematopoietic stem cells in mice

Balancing the processes of hematopoietic stem cell (HSC) differentiation and self-renewal is critical for maintaining a lifelong supply of blood cells. The bone marrow (BM) produces a stable output of newly generated cells, but immunologic stress conditions inducing leukopenia increase the demand for peripheral blood cell supply. Here we demonstrate that the proinflammatory cytokine interferon-gamma (IFN-gamma) impairs maintenance of HSCs by directly reducing their proliferative capacity and that IFN-gamma impairs restoration of HSC numbers upon viral infection. We show that IFN-gamma reduces thrombopoietin (TPO)-mediated phosphorylation of signal transducer and activator of transcription (STAT) 5, an important positive regulator of HSC self-renewal. IFN-gamma also induced expression of suppressor of cytokine signaling (SOCS) 1 in HSCs, and we demonstrate that SOCS1 expression is sufficient to inhibit TPO-induced STAT5 phosphorylation. Furthermore, IFN-gamma deregulates expression of STAT5-mediated cell-cycle genes cyclin D1 and p57. These findings suggest that IFN-gamma is a negative modulator of HSC self-renewal by modifying cytokine responses and expression of genes involved in HSC proliferation. We postulate that the occurrence of BM failure in chronic inflammatory conditions, such as aplastic anemia, HIV, and graft-versus-host disease, is related to a sustained impairment of HSC self-renewal caused by chronic IFN-gamma signaling in these disorder

The Phosphatases STS1 and STS2 Regulate Hematopoietic Stem and Progenitor Cell Fitness

FLT3 and c-KIT are crucial regulators of hematopoietic stem and progenitor cells. We investigated the role of STS1 and STS2 on FLT3 and c-KIT phosphorylation, activity, and function in normal and stress-induced hematopoiesis. STS1/STS2-deficient mice show a profound expansion of multipotent progenitor and lymphoid primed multipotent progenitor cells with elevated colony-forming capacity. Although long-term hematopoietic stem cells are not increased in numbers, lack of STS1 and STS2 significantly promotes long-term repopulation activity, demonstrating a pivotal role of STS1/STS2 in regulating hematopoietic stem and progenitor cell fitness. Biochemical analysis identified STS1/STS2 as direct phosphatases of FLT3 and c-KIT. Loss of STS1/STS2 induces hyperphosphorylation of FLT3, enhances AKT signaling, and confers a strong proliferative advantage. Therefore, our study reveals that STS1 and STS2 may serve as novel pharmaceutical targets to improve hematopoietic recovery after bone marrow transplantation