Eosinophil Secretion of Granule-Derived Cytokines

Eosinophils are tissue-dwelling leukocytes, present in the thymus, and gastrointestinal and genitourinary tracts of healthy individuals at baseline, and recruited, often in large numbers, to allergic inflammatory foci and sites of active tissue repair. The biological significance of eosinophils is vast and varied. In health, eosinophils support uterine and mammary gland development, and maintain bone marrow plasma cells and adipose tissue alternatively activated macrophages, while in response to tissue insult eosinophils function as inflammatory effector cells, and, in the wake of an inflammatory response, promote tissue regeneration, and wound healing. One common mechanism driving many of the diverse eosinophil functions is the regulated and differential secretion of a vast array of eosinophil-derived cytokines. Eosinophils are distinguished from most other leukocytes in that many, if not all, of the over three dozen eosinophil-derived cytokines are pre-synthesized and stored within intracellular granules, poised for very rapid, stimulus-induced secretion. Eosinophils engaged in cytokine secretion in situ utilize distinct pathways of cytokine release that include classical exocytosis, whereby granules themselves fuse with the plasma membrane and release their entire contents extracellularly; piecemeal degranulation, whereby granule-derived cytokines are selectively mobilized into vesicles that emerge from granules, traverse the cytoplasm and fuse with the plasma membrane to release discrete packets of cytokines; and eosinophil cytolysis, whereby intact granules are extruded from eosinophils, and deposited within tissues. In this latter scenario, extracellular granules can themselves function as stimulus-responsive secretory-competent organelles within the tissue. Here, we review the distinctive processes of differential secretion of eosinophil granule-derived cytokines

Vibrationally Resolved Decay Width of Interatomic Coulombic Decay in HeNe

We investigate the ionization of HeNe from below the He 1s3p excitation to the He ionization threshold. We observe HeNe$^+$ ions with an enhancement by more than a factor of 60 when the He side couples resonantly to the radiation field. These ions are an experimental proof of a two-center resonant photoionization mechanism predicted by Najjari et al. [Phys. Rev. Lett. 105, 153002 (2010)]. Furthermore, our data provide electronic and vibrational state resolved decay widths of interatomic Coulombic decay (ICD) in HeNe dimers. We find that the ICD lifetime strongly increases with increasing vibrational state.Comment: 7 pages, 5 figure

An observational prospective study of topical acidified nitrite for killing methicillin-resistant Staphylococcus aureus (MRSA) in contaminated wounds

Background Endogenous nitric oxide (NO) kills bacteria and other organisms as part of the innate immune response. When nitrite is exposed to low pH, NO is generated and has been used as an NO delivery system to treat skin infections. We demonstrated eradication of MRSA carriage from wounds using a topical formulation of citric acid (4.5%) and sodium nitrite (3%) creams co-applied for 5 days to 15 wounds in an observational prospective pilot study of 8 patients. Findings Following treatment with topical citric acid and sodium nitrite, 9 of 15 wounds (60%) and 3 of 8 patients (37%) were cleared of infection. MRSA isolates from these patients were all sensitive to acidified nitrite in vitro compared to methicillin-sensitive S. aureus and a reference strain of MRSA. Conclusions Nitric oxide and acidified nitrite offer a novel therapy for control of MRSA in wounds. Wounds that were not cleared of infection may have been re-contaminated or the bioavailability of acidified nitrite impaired by local factors in the tissue

The Internal Architecture of Leukocyte Lipid Body Organelles Captured by Three-Dimensional Electron Microscopy Tomography

Lipid bodies (LBs), also known as lipid droplets, are complex organelles of all eukaryotic cells linked to a variety of biological functions as well as to the development of human diseases. In cells from the immune system, such as eosinophils, neutrophils and macrophages, LBs are rapidly formed in the cytoplasm in response to inflammatory and infectious diseases and are sites of synthesis of eicosanoid lipid mediators. However, little is known about the structural organization of these organelles. It is unclear whether leukocyte LBs contain a hydrophobic core of neutral lipids as found in lipid droplets from adipocytes and how diverse proteins, including enzymes involved in eicosanoid formation, incorporate into LBs. Here, leukocyte LB ultrastructure was studied in detail by conventional transmission electron microscopy (TEM), immunogold EM and electron tomography. By careful analysis of the two-dimensional ultrastructure of LBs from human blood eosinophils under different conditions, we identified membranous structures within LBs in both resting and activated cells. Cyclooxygenase, a membrane inserted protein that catalyzes the first step in prostaglandin synthesis, was localized throughout the internum of LBs. We used fully automated dual-axis electron tomography to study the three-dimensional architecture of LBs in high resolution. By tracking 4 nm-thick serial digital sections we found that leukocyte LBs enclose an intricate system of membranes within their “cores”. After computational reconstruction, we showed that these membranes are organized as a network of tubules which resemble the endoplasmic reticulum (ER). Our findings explain how membrane-bound proteins interact and are spatially arranged within LB “cores” and support a model for LB formation by incorporating cytoplasmic membranes of the ER, instead of the conventional view that LBs emerge from the ER leaflets. This is important to understand the functional capabilities of leukocyte LBs in health and during diverse diseases in which these organelles are functionally involved

Interatomic-Coulombic-decay-induced recapture of photoelectrons in helium dimers

We investigate the onset of photoionization shakeup induced interatomic Coulombic decay (ICD) in He2 at the He+*(n = 2) threshold by detecting two He+ ions in coincidence. We find this threshold to be shifted towards higher energies compared to the same threshold in the monomer. The shifted onset of ion pairs created by ICD is attributed to a recapture of the threshold photoelectron after the emission of the faster ICD electron.Comment: 5 Pages, 2 Figure

A measurement of the evolution of Interatomic Coulombic Decay in the time domain

During the last 15 years a novel decay mechanism of excited atoms has been discovered and investigated. This so called ''Interatomic Coulombic Decay'' (ICD) involves the chemical environment of the electronically excited atom: the excitation energy is transferred (in many cases over long distances) to a neighbor of the initially excited particle usually ionizing that neighbor. It turned out that ICD is a very common decay route in nature as it occurs across van-der-Waals and hydrogen bonds. The time evolution of ICD is predicted to be highly complex, as its efficiency strongly depends on the distance of the atoms involved and this distance typically changes during the decay. Here we present the first direct measurement of the temporal evolution of ICD using a novel experimental approach.Comment: 6 pages, 4 figures, submitted to PR

Regulating Clothing Outwork: A Sceptic's View

By applying the strategies of international anti-sweatshop campaigns to the Australian context, recent regulations governing home-based clothing production hold retailers responsible for policing the wages and employment conditions of clothing outworkers who manufacture clothing on their behalf. This paper argues that the new approach oversimplifies the regulatory challenge by assuming (1) that Australian clothing production is organised in a hierarchical ‘buyer-led’ linear structure in which core retail firms have the capacity to control their suppliers’ behaviour; (2) that firms act as unitary moral agents; and (3) that interventions imported from other times and places are applicable to the contemporary Australian context. After considering some alternative regulatory approaches, the paper concludes that the new regulatory strategy effectively privatises responsibility for labour market conditions – a development that cries out for further debate

An investigation of the effects of stage of ensilage on Nassella neesiana seeds, for reducing seed viability and injury to livestock

The noxious weed Nassella neesiana is established on a wide range of productive land throughout southeastern Australia. N. neesiana seeds, when mature, are sharp, causing injury to livestock, thus posing a problem in fodder bales. To reduce infestations of agricultural weeds in situ, production of silage from weed-infested pastures is practised as part of integrated weed management (IWM). However, there is little data to demonstrate whether this process is useful to reduce infestations or the harmful properties of N. neesiana. Therefore, the minimum duration of ensilage required to reduce the viability of N. neesiana seeds was investigated, both with and without addition of ensilage inoculants in this process. Also, the decreasing propensity of the seeds to injure livestock, after various times and conditions of ensilage, was assessed. Ensilage inoculant reduced seed germination probability to zero after 35 days. When no inoculant was added, zero viability was achieved after 42 days. A qualitative assessment of the hardness of ensilaged seeds found seed husks were softer (and therefore safer) after 42 days, whether inoculant was used or not. Therefore, we suggest that both the viability of N. neesiana seeds and hardness of seed casings are significantly reduced after 42 days, thereby reducing the risks of seed dispersal and injury to livestock