Macrophage TNF-α mediates parathion-induced airway hyperreactivity in guinea pigs.

Organophosphorus pesticides (OPs) are implicated in human asthma. We previously demonstrated that, at concentrations that do not inhibit acetylcholinesterase activity, the OP parathion causes airway hyperreactivity in guinea pigs as a result of functional loss of inhibitory M2 muscarinic receptors on parasympathetic nerves. Because macrophages are associated with asthma, we investigated whether macrophages mediate parathion-induced M2 receptor dysfunction and airway hyperreactivity. Airway physiology was measured in guinea pigs 24 h after a subcutaneous injection of parathion. Pretreatment with liposome-encapsulated clodronate induced alveolar macrophage apoptosis and prevented parathion-induced airway hyperreactivity in response to electrical stimulation of the vagus nerves. As determined by qPCR, TNF-α and IL-1β mRNA levels were increased in alveolar macrophages isolated from parathion-treated guinea pigs. Parathion treatment of alveolar macrophages ex vivo did not significantly increase IL-1β and TNF-α mRNA but did significantly increase TNF-α protein release. Consistent with these data, pretreatment with the TNF-α inhibitor etanercept but not the IL-1β receptor inhibitor anakinra prevented parathion-induced airway hyperreactivity and protected M2 receptor function. These data suggest a novel mechanism of OP-induced airway hyperreactivity in which low-level parathion activates macrophages to release TNF-α-causing M2 receptor dysfunction and airway hyperreactivity. These observations have important implications regarding therapeutic approaches for treating respiratory disease associated with OP exposures

Influence of mild feed restriction and mild reduction in dietary amino acid content on feeding behaviour of group-housed growing pigs

This study investigates changes in the feeding behaviour of pigs as a result of a restriction in their feed allowance and a reduction in dietary indispensable amino acid (AA) content. Ninety-six Topig Talent × PIC barrows were housed in 8 pens and individually fed either ad libitum (AL) or a restricted diet (RF) from 47 to 145 kg body weight (BW). The amount of feed given to RF pigs was close to their expected voluntary intake, but it was limited to proportions of 0.33, 0.66 and 1.00 of the estimated daily amount of feed in 3 time intervals, 00:01 to 8:00, 8:01 to 16:00 and 16:01 to 24:00 h, respectively. From 86 kg BW, the pigs in 4 of the pens were fed diets with conventional standardized ileal digestible AA content (CAA), while the pigs in the other pens received diets (LAA) in which the proportions of dietary indispensable AA were lowered with respect to CAA by 0.91 from 86 to 118 kg BW and by 0.82 from 118 to 145 kg BW. Automated feeders monitored individual feeding behaviour. Data were analysed by pig and feeding phase with a 2 × 2 factorial design. Over the whole experimental period, feed restriction resulted in a decrease in daily feed intake (7%, P < 0.001), the number of visits (27%, P < 0.001) and the time spent feeding (14%, P < 0.001), but an increase in feed consumption per visit (20%, P = 0.001) and feeding rate (10%, P = 0.032). The reduction in AA increased daily feed intake (7%, P = 0.031), tended to increase feeding rate (14%, P = 0.07) and interacted with feeding regime with respect to the number and duration of feeding visits. During growing and finishing, we observed high, negative, non-linear relationships between feed consumption per visit and visit frequency (R2 = 0.989 to 0.876), between visit duration and visit frequency (R2 = 0.648 to 0.695), and between feeding rate and time spent feeding in a day (R2 = 0.802 to 0.707), and positive linear relationships between visit duration and feed consumption per visit (R2 = 0.614 to 0.570). The individual feeding rate during growing was positively correlated with that during finishing (R2 = 0.458). We conclude that pigs try to adapt their feeding pattern to compensate for a reduction in feed allowance or nutrient restriction by, for example, increasing their feeding rate, which may reflect increased feeding motivation

Data Fusion of Objects Using Techniques Such as Laser Scanning, Structured Light and Photogrammetry for Cultural Heritage Applications

In this paper we present a semi-automatic 2D-3D local registration pipeline capable of coloring 3D models obtained from 3D scanners by using uncalibrated images. The proposed pipeline exploits the Structure from Motion (SfM) technique in order to reconstruct a sparse representation of the 3D object and obtain the camera parameters from image feature matches. We then coarsely register the reconstructed 3D model to the scanned one through the Scale Iterative Closest Point (SICP) algorithm. SICP provides the global scale, rotation and translation parameters, using minimal manual user intervention. In the final processing stage, a local registration refinement algorithm optimizes the color projection of the aligned photos on the 3D object removing the blurring/ghosting artefacts introduced due to small inaccuracies during the registration. The proposed pipeline is capable of handling real world cases with a range of characteristics from objects with low level geometric features to complex ones

The first accurate parallax distance to a black hole

Using astrometric VLBI observations, we have determined the parallax of the black hole X-ray binary V404 Cyg to be 0.418 +/- 0.024 milliarcseconds, corresponding to a distance of 2.39 +/- 0.14 kpc, significantly lower than the previously accepted value. This model-independent estimate is the most accurate distance to a Galactic stellar-mass black hole measured to date. With this new distance, we confirm that the source was not super-Eddington during its 1989 outburst. The fitted distance and proper motion imply that the black hole in this system likely formed in a supernova, with the peculiar velocity being consistent with a recoil (Blaauw) kick. The size of the quiescent jets inferred to exist in this system is less than 1.4 AU at 22 GHz. Astrometric observations of a larger sample of such systems would provide useful insights into the formation and properties of accreting stellar-mass black holes.Comment: Accepted for publication in ApJ Letters. 6 pages, 2 figure

Formation of ultra-compact X-ray binaries through circum-binary disk-driven mass transfer

The formation of ultra-compact X-ray binaries (UCXBs) has not been well understood. Previous works show that ultra-short orbital periods ($<1$ hr) may be reached through mass transfer driven by magnetic braking in normal low/intermediate-mass X-ray binaries (L/IMXBs) only for an extremely small range of initial binary parameters, which makes it difficult to account for the rather large population of UCXBs. In this paper we report the calculated results on mass transfer processes in L/IMXBs with a circum-binary disk. We show that when the orbital angular momentum loss due to a circum-binary disk is included, ultra-short orbital periods could be reached for a relatively wide range of initial binary parameters. The results of our binary models suggest an alternative formation channel for UCXBs.Comment: 25 pages, 8 figures, accepted for publication in Ap

α-Helical Peptides on Plasma-Treated Polymers Promote Ciliation of Airway Epithelial Cells

Airway respiratory epithelium forms a physical barrier through intercellular tight junctions, which prevents debris from passing through to the internal environment while ciliated epithelial cells expel particulate-trapping mucus up the airway. Polymeric solutions to loss of airway structure and integrity have been unable to fully restore functional epithelium. We hypothesized that plasma treatment of polymers would permit adsorption of α-helical peptides and that this would promote functional differentiation of airway epithelial cells. Five candidate plasma compositions are compared; Air, N2, H2, H2:N2 and Air:N2. X-ray photoelectron spectroscopy shows changes in at% N and C 1s peaks after plasma treatment while electron microscopy indicates successful adsorption of hydrogelating self-assembling fibres (hSAF) on all samples. Subsequently, adsorbed hSAFs support human nasal epithelial cell attachment and proliferation and induce differentiation at an air-liquid interface. Transepithelial measurements show that the cells form tight junctions and produce cilia beating at the normal expected frequency of 10-11 Hz after 28 days in culture. The synthetic peptide system described in this study offers potential superiority as an epithelial regeneration substrate over present “gold-standard” materials, such as collagen, as they are controllable and can be chemically functionalised to support a variety of in vivo environments. Using the hSAF peptides described here in combination with plasma-treated polymeric surfaces could offer a way of improving the functionality and integration of implantable polymers for aerodigestive tract reconstruction and regeneration

Effects of bacterial inoculants on the microbial community, mycotoxin contamination, and aerobic stability of corn silage infected in the field by toxigenic fungi

AbstractThis study aimed to evaluate the effects of inoculants on the microbial community and mycotoxins contamination of corn silage during aerobic exposure. Whole-crop corn infected with or without mycotoxigenic fungi were ensiled with Lentilactobacillus buchneri (LB, 1.0 × 106 cfu/g fresh weight (FW)), Lactiplantibacillus plantarum (LP, 1.0 × 106 cfu/g FW), or LBLP at 1.0 × 106 cfu/g FW each. The concentration of acetic acid (AcA) (P < 0.05) in LB and LBLP silages was higher than in control (C) and LP of non-fungal infection (NFI) silages. The fungal infection resulted in a larger increase of zearalenone (ZEN, P = 0.01), fumonisin B1 (FUB1, P = 0.02), and fumonisin B2 (FUB2, P = 0.02). The relative abundance (RA) of Issatchenkia in NFI was higher (P < 0.001) than FI silages, whereas the RA of Kazachstania (P < 0.001), Zygosaccharomyces (P = 0.047), and Candida (P = 0.025) in NFI were lower than these of FI silages. The aerobic stability was improved by the application of LB and LBLP as compared with the C of NFI silages. The LB and LBLP had the potential to improve aerobic stability and alleviate mycotoxins contamination of non-fungal infected corn silages. Graphical Abstrac

A Clash of Old and New Scientific Concepts in Toxicity, with Important Implications for Public Health

Background A core assumption of current toxicologic procedures used to establish health standards for chemical exposures is that testing the safety of chemicals at high doses can be used to predict the effects of low-dose exposures, such as those common in the general population. This assumption is based on the precept that “the dose makes the poison”: higher doses will cause greater effects. Objectives We challenge the validity of assuming that high-dose testing can be used to predict low-dose effects for contaminants that behave like hormones. We review data from endocrinology and toxicology that falsify this assumption and summarize current mechanistic understanding of how low doses can lead to effects unpredictable from high-dose experiments. Discussion Falsification of this assumption raises profound issues for regulatory toxicology. Many exposure standards are based on this assumption. Rejecting the assumption will require that these standards be reevaluated and that procedures employed to set health standards be changed. The consequences of these changes may be significant for public health because of the range of health conditions now plausibly linked to exposure to endocrine-disrupting contaminants. Conclusions We recommend that procedures to establish acceptable exposure levels for endocrine-disrupting compounds incorporate the inability for high-dose tests to predict low-dose results. Setting acceptable levels of exposure must include testing for health consequences at prevalent levels of human exposure, not extrapolations from the effects observed in high-dose experiments. Scientists trained in endocrinology must be engaged systematically in standard setting for endocrine-disrupting compounds

RNA editing signature during myeloid leukemia cell differentiation

Adenosine deaminases acting on RNA (ADARs) are key proteins for hematopoietic stem cell self-renewal and for survival of differentiating progenitor cells. However, their specific role in myeloid cell maturation has been poorly investigated. Here we show that ADAR1 is present at basal level in the primary myeloid leukemia cells obtained from patients at diagnosis as well as in myeloid U-937 and THP1 cell lines and its expression correlates with the editing levels. Upon phorbol-myristate acetate or Vitamin D3/granulocyte macrophage colony-stimulating factor (GM-CSF)-driven differentiation, both ADAR1 and ADAR2 enzymes are upregulated, with a concomitant global increase of A-to-I RNA editing. ADAR1 silencing caused an editing decrease at specific ADAR1 target genes, without, however, interfering with cell differentiation or with ADAR2 activity. Remarkably, ADAR2 is absent in the undifferentiated cell stage, due to its elimination through the ubiquitin–proteasome pathway, being strongly upregulated at the end of the differentiation process. Of note, peripheral blood monocytes display editing events at the selected targets similar to those found in differentiated cell lines. Taken together, the data indicate that ADAR enzymes play important and distinct roles in myeloid cells