Increasing alkyl chain length in a series of layered metal–organic frameworks aids ultrasonic exfoliation to form nanosheets

Metal–organic framework nanosheets (MONs) are attracting increasing attention as a diverse class of two-dimensional materials derived from metal–organic frameworks (MOFs). The principles behind the design of layered MOFs that can readily be exfoliated to form nanosheets, however, remain poorly understood. Here we systematically investigate an isoreticular series of layered MOFs functionalized with alkoxy substituents in order to understand the effect of substituent alkyl chain length on the structure and properties of the resulting nanosheets. A series of 2,5-alkoxybenzene-1,4-dicarboxylate ligands (O2CC6H2(OR)2CO2, R = methyl–pentyl, 1–5, respectively) was used to synthesize copper paddle-wheel MOFs. Rietveld and Pawley fitting of powder diffraction patterns for compounds Cu(3–5)(DMF) showed they adopt an isoreticular series with two-dimensional connectivity in which the interlayer distance increases from 8.68 Å (R = propyl) to 10.03 Å (R = pentyl). Adsorption of CO2 by the MOFs was found to increase from 27.2 to 40.2 cm3 g–1 with increasing chain length, which we attribute to the increasing accessible volume associated with increasing unit-cell volume. Ultrasound was used to exfoliate the layered MOFs to form MONs, with shorter alkyl chains resulting in higher concentrations of exfoliated material in suspension. The average height of MONs was investigated by AFM and found to decrease from 35 ± 26 to 20 ± 12 nm with increasing chain length, with the thinnest MONs observed being only 5 nm, corresponding to five framework layers. These results indicate that careful choice of ligand functionalities can be used to tune nanosheet structure and properties, enabling optimization for a variety of applications

Implementation of standard testbeds for numerical relativity

We discuss results that have been obtained from the implementation of the initial round of testbeds for numerical relativity which was proposed in the first paper of the Apples with Apples Alliance. We present benchmark results for various codes which provide templates for analyzing the testbeds and to draw conclusions about various features of the codes. This allows us to sharpen the initial test specifications, design a new test and add theoretical insight.Comment: Corrected versio

Neurons are MHC Class I-Dependent Targets for CD8 T Cells upon Neurotropic Viral Infection

Following infection of the central nervous system (CNS), the immune system is faced with the challenge of eliminating the pathogen without causing significant damage to neurons, which have limited capacities of renewal. In particular, it was thought that neurons were protected from direct attack by cytotoxic T lymphocytes (CTL) because they do not express major histocompatibility class I (MHC I) molecules, at least at steady state. To date, most of our current knowledge on the specifics of neuron-CTL interaction is based on studies artificially inducing MHC I expression on neurons, loading them with exogenous peptide and applying CTL clones or lines often differentiated in culture. Thus, much remains to be uncovered regarding the modalities of the interaction between infected neurons and antiviral CD8 T cells in the course of a natural disease. Here, we used the model of neuroinflammation caused by neurotropic Borna disease virus (BDV), in which virus-specific CTL have been demonstrated as the main immune effectors triggering disease. We tested the pathogenic properties of brain-isolated CD8 T cells against pure neuronal cultures infected with BDV. We observed that BDV infection of cortical neurons triggered a significant up regulation of MHC I molecules, rendering them susceptible to recognition by antiviral CTL, freshly isolated from the brains of acutely infected rats. Using real-time imaging, we analyzed the spatio-temporal relationships between neurons and CTL. Brain-isolated CTL exhibited a reduced mobility and established stable contacts with BDV-infected neurons, in an antigen- and MHC-dependent manner. This interaction induced rapid morphological changes of the neurons, without immediate killing or impairment of electrical activity. Early signs of neuronal apoptosis were detected only hours after this initial contact. Thus, our results show that infected neurons can be recognized efficiently by brain-isolated antiviral CD8 T cells and uncover the unusual modalities of CTL-induced neuronal damage

Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities

In order to improve the efficacy of conventional radiotherapy, attention has been paid to immune cells, which not only modulate cancer cell response to therapy but are also highly recruited to tumours after irradiation. Particularly, the effect of ionizing radiation on macrophages, using therapeutically relevant doses, is not well understood. To evaluate how radiotherapy affects macrophage behaviour and macrophage-mediated cancer cell activity, human monocyte derived-macrophages were subjected, for a week, to cumulative ionizing radiation doses, as used during cancer treatment (2Gy/fraction/day). Irradiated macrophages remained viable and metabolically active, despite DNA damage. NF-kappaB transcription activation and increased Bcl-xL expression evidenced the promotion of pro-survival activity. A significant increase of pro-inflammatory macrophage markers CD80, CD86 and HLA-DR, but not CCR7, TNF and IL1B was observed after 10Gy cumulative doses, while anti-inflammatory markers CD163, MRC1, VCAN and IL-10 expression decreased, suggesting the modulation towards a more proinflammatory phenotype. Moreover, ionizing radiation induced macrophage morphological alterations and increased their phagocytic rate, without affecting matrix metalloproteases (MMP)2 and MMP9 activity. Importantly, irradiated macrophages promoted cancer cell-invasion and cancer cell-induced angiogenesis. Our work highlights macrophage ability to sustain cancer cell activities as a major concern that needs to be addressed to improve radiotherapy efficacy

Comparison of the Antimicrobial Activity of Deactivated Human Macrophages Challenged with Aspergillus fumigatus and Listeria monocytogenes

The anticonidial activity of human monocytes deactivated by cytokines interleukin (IL)-4 and IL-10 and the hormone dexamethasone was studied and compared with antilisterial activity. Dexamethasone had the largest effect on the anticonidial activity and suppressed germination-inhibiting activity and elimination of ingested spores by macrophages more than the cytokines did. Maximally active concentrations of IL-10 had a similar but significantly smaller deactivating effect. IL-4, in contrast to IL-10 and dexamethasone, did not reduce anticonidial activity. However, IL-4 and IL-10 were equally potent in deactivating human macrophages against Listeria monocytogenes, whereas dexamethasone was significantly less potent in the Listeria model. These observations indicate that all three mediators lessen antimicrobial activity but that this effect depends on the test organism studied and is apparently mediated through regulation of different antimicrobial systems operating against a particular microorganis