Porous dipeptide crystals as volatile-drug vessels

Anesthetic vapors find temporary hospitality in porous dipeptide crystals, which behave as biologically friendly hosts and carriers

A guide to chemokines and their receptors

The chemokines (or chemotactic cytokines) are a large family of small, secreted proteins that signal through cell surface G‐protein coupled heptahelical chemokine receptors. They are best known for their ability to stimulate the migration of cells, most notably white blood cells (leukocytes). Consequently, chemokines play a central role in the development and homeostasis of the immune system, and are involved in all protective or destructive immune and inflammatory responses. Classically viewed as inducers of directed chemotactic migration, it is now clear that chemokines can stimulate a variety of other types of directed and undirected migratory behaviour, such as haptotaxis, chemokinesis, and haptokinesis, in addition to inducing cell arrest or adhesion. However, chemokine receptors on leukocytes can do more than just direct migration, and these molecules can also be expressed on, and regulate the biology of, many non‐leukocytic cell types. Chemokines are profoundly affected by post‐translational modification, by interaction with the extracellular matrix (ECM), and by binding to heptahelical ‘atypical’ chemokine receptors that regulate chemokine localisation and abundance. This guide gives a broad overview of the chemokine and chemokine receptor families; summarises the complex physical interactions that occur in the chemokine network; and, using specific examples, discusses general principles of chemokine function, focussing particularly on their ability to direct leukocyte migration

Hypomorphic mutation in the RAG2 gene affects dendritic cell distribution and migration.

In Omenn syndrome, altered dendritic cell distribution and impaired migration represent an additional level of immune dysregulation, contributing to the pathogenesis of autoimmunity. OS is a severe combined immunodeficiency characterized by erythrodermia and protracted diarrhea as a result of infiltration of oligoclonal-activated T cells, caused by hypomorphic mutations in RAGs. The RAG2(R229Q) mouse model fully recapitulates the clinical OS phenotype. We evaluated whether T and B cell defects, together with the abnormal lymphoid structure, could affect DC homeostasis and function. High density of LCs was observed in skin biopsies of Omenn patients and in the derma of RAG2(R229Q) mice, correlating with the presence of erythrodermia. In vivo models of cutaneous skin painting and CHS demonstrated a decreased migration of RAG2(R229Q) DCsin particular, LCsinto draining LNs. Interestingly, at steady state, RAG2(R229Q) mice showed a reduction in DC number in all hematopoietic organs except LNs. Analysis of the MHCII marker revealed a diminished expression also upon the LPS-driven inflammatory condition. Despite the decreased number of peripheral DCs, BM pre-cDCs were present in normal number compared with RAG2(+/+) controls, whereas pDCs and monocytes were reduced significantly. Overall, these results point to a secondary defect in the DC compartment, which contributes to clinical manifestations and autoimmunity in OS

Mechanism of interaction of hydrocalumites (Ca/Al-LDH) with methyl orange and acidic scarlet GR

The development of new materials for water purification is of universal importance. Among these types of materials are layered double hydroxides (LDHs). Non-ionic materials pose a significant problem as pollutants. The interaction of methyl orange (MO) and acidic scarlet GR (GR) adsorption on hydrocalumite (Ca/Al-LDH-Cl) were studied by X-ray diffraction (XRD), infrared spectroscopy (MIR), scanning electron microscope (SEM) and near-infrared spectroscopy (NIR). The XRD results revealed that the basal spacing of Ca/Al-LDH-MO was expanded to 2.45 nm, and the MO molecules were intercalated with a inter-penetrating bilayer model in the gallery of LDH, with 49o tilting angle. Yet Ca/Al-LDH-GR was kept the same d-value as Ca/Al-LDH-Cl. The NIR spectrum for Ca/Al-LDH-MO showed a prominent band around 5994 cm-1, assigned to the combination result of the N-H stretching vibrations, which was considered as a mark to assess MO- ion intercalation into Ca/Al-LDH-Cl interlayers. From SEM images, the particle morphology of Ca/Al-LDH-MO mainly changed to irregular platelets, with a “honey-comb” like structure. Yet the Ca/Al-LDH-GR maintained regular hexagons platelets, which was similar to that of Ca/Al-LDH-Cl. All results indicated that MO- ion was intercalated into Ca/Al-LDH-Cl interlayers, and acidic scarlet GR was only adsorped upon Ca/Al-LDH-Cl surfaces

The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis

Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P = 1.34×10<sup>−8</sup>, OR = 1.22, CI 95% = 1.14–1.30; rs2004640: P = 4.60×10<sup>−7</sup>, OR = 0.84, CI 95% = 0.78–0.90; rs10488631: P = 7.53×10<sup>−20</sup>, OR = 1.63, CI 95% = 1.47–1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P = 9.04×10<sup>−22</sup>, OR = 1.75, CI 95% = 1.56–1.97) better explained the observed association (likelihood P-value = 1.48×10<sup>−4</sup>), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific

Differential responsiveness to constitutive vs. inducible chemokines of immature and mature mouse dendritic cells

Upon exposure to immune or inflammatory stimuli, dendritic cells (DC) migrate from peripheral tissues to lymphoid organs, where they present antigen. The molecular basis for the peculiar trafficking properties of DC is largely unknown. In this study, mouse DC were generated from CD34+ bone marrow precursors and cultured with granulocyte-macrophage-CSF and Flt3 ligand for 9 days. Chemokines active on immature DC include MIP1alpha, RANTES, MIP1beta, MCP-1, MCP-3, and the constitutively expressed SDF1, MDC, and ELC. TNF-alpha-induced DC maturation caused reduction of migration to inducible chemokines (MIP1alpha, RANTES, MIP1beta, MCP-1, and MCP-3) and increased migration to SDF1, MDC, and ELC. Similar results were obtained by CD40 ligation or culture in the presence of bacterial lipopolysaccharide. TNF-alpha down-regulated CC chemokine receptor (CCR)1, CCR2, and CCR5 and up-regulated CCR7 mRNA levels, in agreement with functional data. This study shows that selective responsiveness of mature and immature DC to inducible vs. constitutively produced chemokines can contribute to the regulated trafficking of DC

What is quantitative plant biology?

Quantitative plant biology is an interdisciplinary field that builds on a long history of biomathematics and biophysics. Today, thanks to high spatiotemporal resolution tools and computational modelling, it sets a new standard in plant science. Acquired data, whether molecular, geometric or mechanical, are quantified, statistically assessed and integrated at multiple scales and across fields. They feed testable predictions that, in turn, guide further experimental tests. Quantitative features such as variability, noise, robustness, delays or feedback loops are included to account for the inner dynamics of plants and their interactions with the environment. Here, we present the main features of this ongoing revolution, through new questions around signalling networks, tissue topology, shape plasticity, biomechanics, bioenergetics, ecology and engineering. In the end, quantitative plant biology allows us to question and better understand our interactions with plants. In turn, this field opens the door to transdisciplinary projects with the society, notably through citizen science.Peer reviewe

Biological Activity of CXCL8 Forms Generated by Alternative Cleavage of the Signal Peptide or by Aminopeptidase-Mediated Truncation

Posttranslational modification of chemokines is one of the mechanisms that regulate leukocyte migration during inflammation. Multiple natural NH(2)-terminally truncated forms of the major human neutrophil attractant interleukin-8 or CXCL8 have been identified. Although differential activity was reported for some CXCL8 forms, no biological data are available for others.status: publishe

The Immune Inhibitory Receptor LAIR-1 Is Highly Expressed by Plasmacytoid Dendritic Cells and Acts Complementary with NKp44 to Control IFNα Production

Plasmacytoid dendritic cells (pDCs) are a subset of dendritic cells endowed with the capacity of producing large amounts of IFNα. Here we show that the Leukocyte-Associated Ig-like Receptor-1 (LAIR-1) is abundantly expressed on pDCs (the highest expression among all leukocytes) and its cross-linking inhibits IFNα production in response to Toll-like receptor ligands. Remarkably, LAIR-1 expression in pDCs is down-regulated in the presence of interleukin (IL)-3, thus indicating coordinated functions with NKp44, another pDC inhibitory receptor, which is conversely induced by IL-3. Nevertheless, the expression of NKp44 in pDCs isolated from secondary lymphoid organs, which is thought to be influenced by IL-3, is not coupled to a decreased expression of LAIR-1. Interestingly, pDCs isolated from peripheral blood of systemic lupus erithematosus (SLE) patients express lower levels of LAIR-1 while displaying slight but consistent expression of NKp44, usually undetectable on pDCs derived from healthy donors. Using sera derived from SLE patients, we show that LAIR-1 and NKp44 display synergistic inhibitory effects on IFNα production by interleukin IL-3 cultured pDCs stimulated with DNA immunocomplexes. In conclusion, our results indicate that the inhibitory function of LAIR-1 may play a relevant role in the mechanisms controlling IFNα production by pDCs both in normal and pathological innate immune responses

A robust binary supramolecular organic framework (SOF) with high CO2 adsorption and selectivity

A robust binary hydrogen-bonded supramolecular organic framework (SOF-7) has been synthesized by solvothermal reaction of 1,4-bis-(4-(3,5-dicyano-2,6 dipyridyl)dihydropyridyl)benzene (1) and 5,5’-bis-(azanediyl)-oxalyl-diisophthalic acid (2). Single crystal X-ray diffraction analysis shows that SOF-7 comprises 2 and 1,4-bis-(4-(3,5-dicyano-2,6-dipyridyl)pyridyl)benzene (3), the latter formed in situ from the oxidative dehydrogenation of 1. SOF-7 shows a three-dimensional four-fold interpenetrat-ed structure with complementary O−H···N hydrogen bonds to form channels that are decorated with cyano- and amide-groups. SOF-7 exhibits excellent thermal stability and sol-vent and moisture durability, as well as permanent porosity. The activated desolvated material SOF-7a shows high CO2 sorption capacity and selectivity compared with other po-rous organic materials assembled solely through hydrogen bonding