Rural continental aerosol properties and processes observed during the Hohenpeissenberg Aerosol Characterization Experiment (HAZE2002)

International audienceDetailed investigations of the chemical and microphysical properties of rural continental aerosols were performed during the HAZE2002 experiment, which was conducted in May 2002 at the Meteorological Observatory Hohenpeissenberg (DWD) in Southern Germany. Online measurements included: Size-resolved chemical composition of submicron particles; total particle number concentrations and size distributions over the diameter range of 3 nm to 9 ?m; gas-phase concentration of monoterpenes, CO, O3, OH, and H2SO4. Filter sampling and offline analytical techniques were used to determine: Fine particle mass (PM2.5), organic, elemental and total carbon in PM2.5 (OC2.5, EC2.5, TC2.5), and selected organic compounds (dicarboxylic acids, polycyclic aromatic hydrocarbons, proteins). Overall, the non-refractory components of submicron particles detected by aerosol mass spectrometry (PM1, 6.6±5.4 ?g m?3, arithmetic mean and standard deviation) accounted for ~62% of PM2.5 determined by filter gravimetry (10.6±4.7 ?g m?3). The relative proportions of non-refractory submicron particle components were: (23±39)% ammonium nitrate, (27±23)% ammonium sulfate, and (50±40)% organics (OM1). OM1 was closely correlated with PM1 (r2=0.9) indicating a near-constant ratio of non-refractory organics and inorganics. The average ratio of OM1 to OC2.5 was 2.1±1.4, indicating a high proportion of heteroelements in the organic fraction of the sampled rural aerosol. This is consistent with the high ratio of oxygenated organic aerosol (OOA) over hydrocarbon-like organic aerosol (HOA) inferred from the AMS results (4:1), and also with the high abundance of proteins (~3%) indicating a high proportion of primary biological material (~30%) in PM2.5. This finding was confirmed by low abundance of PAHs (?3) and EC (?3) in PM2.5 and detection of several secondary organic aerosol compounds (dicarboxylic acids) and their precursors (monoterpenes). New particle formation was observed almost every day with particle number concentrations exceeding 104 cm?3 (nighttime background level 1000?2000 cm?3). Closer inspection of two major events indicated that the observed nucleation agrees with ternary H2SO4/H2O/NH3 nucleation and that condensation of both organic and inorganic species contributed to particle growth

Mechanosensing is critical for axon growth in the developing brain.

During nervous system development, neurons extend axons along well-defined pathways. The current understanding of axon pathfinding is based mainly on chemical signaling. However, growing neurons interact not only chemically but also mechanically with their environment. Here we identify mechanical signals as important regulators of axon pathfinding. In vitro, substrate stiffness determined growth patterns of Xenopus retinal ganglion cell axons. In vivo atomic force microscopy revealed a noticeable pattern of stiffness gradients in the embryonic brain. Retinal ganglion cell axons grew toward softer tissue, which was reproduced in vitro in the absence of chemical gradients. To test the importance of mechanical signals for axon growth in vivo, we altered brain stiffness, blocked mechanotransduction pharmacologically and knocked down the mechanosensitive ion channel piezo1. All treatments resulted in aberrant axonal growth and pathfinding errors, suggesting that local tissue stiffness, read out by mechanosensitive ion channels, is critically involved in instructing neuronal growth in vivo.This work was supported by the German National Academic Foundation (scholarship to D.E.K.), Wellcome Trust and Cambridge Trusts (scholarships to A.J.T.), Winston Churchill Foundation of the United States (scholarship to S.K.F.), Herchel Smith Foundation (Research Studentship to S.K.F.), CNPq 307333/2013-2 (L.d.F.C.), NAP-PRP-USP and FAPESP 11/50761-2 (L.d.F.C.), UK EPSRC BT grant (J.G.), Wellcome Trust WT085314 and the European Research Council 322817 grants (C.E.H.); an Alexander von Humboldt Foundation Feodor Lynen Fellowship (K.F.), UK BBSRC grant BB/M021394/1 (K.F.), the Human Frontier Science Program Young Investigator Grant RGY0074/2013 (K.F.), the UK Medical Research Council Career Development Award G1100312/1 (K.F.) and the Eunice Kennedy Shriver National Institute Of Child Health & Human Development of the National Institutes of Health under Award Number R21HD080585 (K.F.).This is the author accepted manuscript. The final version is available from Nature Publishing Group via https://doi.org/10.1038/nn.439

Speed and sensitivity of phototransduction in Drosophila depend on degree of saturation of membrane phospholipids.

Drosophila phototransduction is mediated via a G-protein-coupled PLC cascade. Recent evidence, including the demonstration that light evokes rapid contractions of the photoreceptors, suggested that the light-sensitive channels (TRP and TRPL) may be mechanically gated, together with protons released by PLC-mediated PIP2 hydrolysis. If mechanical gating is involved we predicted that the response to light should be influenced by altering the physical properties of the membrane. To achieve this, we used diet to manipulate the degree of saturation of membrane phospholipids. In flies reared on a yeast diet, lacking polyunsaturated fatty acids (PUFAs), mass spectrometry showed that the proportion of polyunsaturated phospholipids was sevenfold reduced (from 38 to ∼5%) but rescued by adding a single species of PUFA (linolenic or linoleic acid) to the diet. Photoreceptors from yeast-reared flies showed a 2- to 3-fold increase in latency and time to peak of the light response, without affecting quantum bump waveform. In the absence of Ca(2+) influx or in trp mutants expressing only TRPL channels, sensitivity to light was reduced up to ∼10-fold by the yeast diet, and essentially abolished in hypomorphic G-protein mutants (Gαq). PLC activity appeared little affected by the yeast diet; however, light-induced contractions measured by atomic force microscopy or the activation of ectopic mechanosensitive gramicidin channels were also slowed ∼2-fold. The results are consistent with mechanosensitive gating and provide a striking example of how dietary fatty acids can profoundly influence sensory performance in a classical G-protein-coupled signaling cascade.This research was supported by the Biotechnology and Biological Sciences Research Council (BBSRC; to M.J.O.W. and Q.Z., BBSRC Grant BB/G006865/1 to R.C.H., BB/H013849/1 to M.J., and BBSRC doctoral awards to A.S.R. and S.A.D.), the State Key Laboratory of Cognitive Neuroscience and Learning Open Research Fund (to M.J.), Jane and Aatos Erkko Foundation Fellowship (to M.J.), the Leverhulme Trust Grant (RPG-2012-567 to M.J.), and the UK Medical Research Council (Career Development Award to K.F.).This is the final published version of the article, originally published in the Journal of Neuroscience, February 11, 2015, 35(6): 2731–2746, DOI: 10.1523/JNEUROSCI.1150-14.201

THE PERMEATION OF BIOMACROMOLECULES THROUGH HUMAN SKIN: AN INSIGHT INTO THE FAMILY OF GLYCOSAMINOGLYCANS

This Ph.D was aimed to elucidate the physicochemical parameters that rule the penetration of different classes of glycosaminoglycans (GAGs) through human skin, with particular focus on hyaluronan (HA) and heparins. The research activity involved: 1) the investigation of the influence of the main structural features (sequence, molecular weight (Mw), polarity, and conformational behavior) on the percutaneous absorption of HA, heparin (UFH) and low molecular weight heparins (LMWHs); 2) the fine-tuning of a suitable enhancement strategy to improve the permeation of UFH through human epidermis. The overall results confirmed that Mw represents a fundamental factor in determining the permeability properties also of such polysaccharides. Indeed, in in vitro studies performed by using HA having different chain lengths, the diffusion through the skin decreased increasing the polymer\u2019s molecular mass. Similarly, LMWHs sodium salts permeated to a larger extent with respect to UFH and their permeated amounts varied with Mw according to an exponential relationship. However, the key parameter driving the permeation of such macromolecules through the skin resulted to be the polymer flexibility. In fact, the introduction of sulfate groups on HA chains, causing the disruption of the helical motif, led to less ordered structures, which were able to cross the skin to higher extent compared to unsubstituted HA, despite their increased polarity. Accordingly, the presence of divalent cations in LMWHs solution, limiting the chain flexibility through the formation of intramolecular chelates, negatively affected the skin permeability properties of calcium nadroparin. Furthermore, both classes of polysaccharides in study demonstrated to interact with stratum corneum components, in particular keratins, as confirmed by confocal miscroscopy images (HA) and ATR-FTIR spectra (UFH). Since the physicochemical features of these polysaccharides (hydrophilicity, negative charge and high Mw) precluded a significant diffusion through the human epidermis, the phage display technique was exploited to screen a skin penetrating peptide which could enhance the skin permeation of such molecules, allowing their transdermal delivery. The in vitro screening allowed to identify a neutral peptide, DRTTLTN, which resulted to be able to increase the UFH flux of 34-fold after chemical conjugation. These results demonstrated the suitability of skin penetrating peptides to improve the skin delivery of polysaccharide macromolecules

Interleukin-34 promotes tumorigenic signals for colon cancer cells

Colorectal carcinoma (CRC) is one of the most common forms of malignancy in the Western world. Accumulating evidence indicates that colon carcinogenesis is tightly controlled by tumour-associated immune cells and stromal cells, which can either stimulate or suppress CRC cell growth and survival, mainly via the production of cytokines. Interleukin-34 (IL-34), a cytokine known to regulate mainly monocyte/macrophage survival and function, is highly produced within the CRC microenvironment by several cell types, including cancer cells, tumour-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), and regulates the pro-tumoural functions of such cells. In this article, we summarize the available data supporting the multiple effects of IL-34 in human CRC

Rationalizing the design of hyaluronic acid-decorated liposomes for targeting epidermal layers: a combination of molecular dynamics and experimental evidence

This work provides information on the features of low molecular weight hyaluronic acid (HA)-decorated liposomes to target resveratrol (RSV) in the skin. Deformable liposomes were made of soy-phosphatidylcholine with Tween 80 as the fluidizing agent. For HA conjugation, three different phosphoethanolamines were tested: 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE), and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). The different phosphoethanolamine-HA conjugates were inserted into the liposome bilayer by hydration (HA on both faces of the bilayer) or by the postinsertion method (HA only on the external face of the bilayer). The effect of these variables on deformability was experimentally assessed by an in-house method (K value, the lower the value, the higher the deformability) and molecular dynamics (MD) simulations. The results showed that the K values of HA-liposomes obtained by hydration were higher than the K values of HA-liposomes prepared by postinsertion, and both were at least 10-fold higher than the K values of the corresponding plain liposomes. The nature of the lipid anchor played a key role in deformability (DMPE > DOPE > DPPE) with high variability in the case of DOPE formulations. These data were justified by the trends found in silico for the bilayer bending modulus and the HA end-to-end distance. In addition to liposome flexibility, the HA extent seems to be the key factor governing the skin penetration of RSV. When the extent is higher, the amount of the drug retained in the skin is larger. Regarding skin permeation, a parabolic trend was recorded, and the optimal amount to favor skin permeation was an approximately 30 HA/phospholipid (μg/mmol) ratio. This study reports the first piece of evidence that it is possible to control drug delivery in the skin by tuning the amount of HA on the vesicle surface