Macrophage transactivation for chemokine production identified as a negative regulator of granulomatous inflammation using agent-based modeling

Cellular activation in trans by interferons, cytokines and chemokines is a commonly recognized mechanism to amplify immune effector function and limit pathogen spread. However, an optimal host response also requires that collateral damage associated with inflammation is limited. This may be particularly so in the case of granulomatous inflammation, where an excessive number and / or excessively florid granulomas can have significant pathological consequences. Here, we have combined transcriptomics, agent-based modeling and in vivo experimental approaches to study constraints on hepatic granuloma formation in a murine model of experimental leishmaniasis. We demonstrate that chemokine production by non-infected Kupffer cells in the Leishmania donovani-infected liver promotes competition with infected KCs for available iNKT cells, ultimately inhibiting the extent of granulomatous inflammation. We propose trans-activation for chemokine production as a novel broadly applicable mechanism that may operate early in infection to limit excessive focal inflammation

Age estimation of Calliphora (Diptera: Calliphoridae) larvae using cuticular hydrocarbon analysis and Artificial Neural Networks

Cuticular hydrocarbons were extracted daily from the larvae of two closely related blowflies Calliphora vicina and Calliphora vomitoria (Diptera: Calliphoridae). The hydrocarbons were then analysed using Gas Chromatography–Mass Spectrometry (GC–MS), with the aim of observing changes within their chemical profiles in order to determine the larval age. The hydrocarbons were examined daily for each species from 1 day old larvae until pupariation. The results show significant chemical changes occurring from the younger larvae to the post-feeding larvae. With the aid of a multivariate statistical method (Principal Component Analysis and Artificial Neural Networks), samples were clustered and classified, allowing for the larval age to be established. Results from this study allowed larvae to be aged to the day with at worst, 87% accuracy, which suggests there is great potential for the use of cuticular hydrocarbons present on larvae to give an indication of their age and hence potentially a valuable tool for minimum PMI estimations

The University of Iowa Biomass Energy Sustainability Index: A decision-making tool for the University of Iowa Biomass Partnership Project

Work continued on a plan to increase the renewable, sustainable fuel sources available to power operations at the University of Iowa in Iowa City. A team of researchers from multiple institutions collaborated to create a tool that would allow the UI to evaluate its alternative energy options more effectively

Electrophysiological and Imaging Calcium Biomarkers of Aging in Male and Female 5×FAD Mice

BACKGROUND: In animal models and tissue preparations, calcium dyshomeostasis is a biomarker of aging and Alzheimer\u27s disease that is associated with synaptic dysfunction, neuritic pruning, and dysregulated cellular processes. It is unclear, however, whether the onset of calcium dysregulation precedes, is concurrent with, or is the product of pathological cellular events (e.g., oxidation, amyloid-β production, and neuroinflammation). Further, neuronal calcium dysregulation is not always present in animal models of amyloidogenesis, questioning its reliability as a disease biomarker. OBJECTIVE: Here, we directly tested for the presence of calcium dysregulation in dorsal hippocampal neurons in male and female 5×FAD mice on a C57BL/6 genetic background using sharp electrodes coupled with Oregon-green Bapta-1 imaging. We focused on three ages that coincide with the course of amyloid deposition: 1.5, 4, and 10 months old. METHODS: Outcome variables included measures of the afterhyperpolarization, short-term synaptic plasticity, and calcium kinetics during synaptic activation. Quantitative analyses of spatial learning and memory were also conducted using the Morris water maze. Main effects of sex, age, and genotype were identified on measures of electrophysiology and calcium imaging. RESULTS: Measures of resting Oregon-green Bapta-1 fluorescence showed significant reductions in the 5×FAD group compared to controls. Deficits in spatial memory, along with increases in Aβ load, were detectable at older ages, allowing us to test for temporal associations with the onset of calcium dysregulation. CONCLUSION: Our results provide evidence that reduced, rather than elevated, neuronal calcium is identified in this 5×FAD model and suggests that this surprising result may be a novel biomarker of AD

Adult fly age estimations using cuticular hydrocarbons and Artificial Neural Networks in forensically important Calliphoridae species

Blowflies (Diptera: Calliphoridae) are forensically important as they are known to be one of the first to colonise human remains. The larval stage is typically used to assist a forensic entomologists with adult flies rarely used as they are difficult to age because they remain morphologically similar once they have gone through the initial transformation upon hatching. However, being able to age them is of interest and importance within the field. This study examined the cuticular hydrocarbons (CHC) of Diptera: Calliphoridae species Lucilia sericata, Calliphora vicina and Calliphora vomitoria. The CHCs were extracted from the cuticles of adult flies and analysed using Gas Chromatography–Mass Spectrometry (GC–MS). The chemical profiles were examined for the two Calliphora species at intervals of day 1, 5, 10, 20 and 30 and up to day 10 for L. sericata. The results show significant chemical changes occurring between the immature and mature adult flies over the extraction period examined in this study. With the aid of a Principal Component Analysis (PCA) and Artificial Neural Networks (ANN), samples were seen to cluster, allowing for the age to be established within the aforementioned time frames. The use of ANNs allowed for the automatic classification of novel samples with very good performance. This was a proof of concept study, which developed a method allowing to age post-emergence adults by using their chemical profiles

Age estimation of Calliphora (Diptera: Calliphoridae) larvae using cuticular hydrocarbon analysis and Artificial Neural Networks.

Cuticular hydrocarbons were extracted daily from the larvae of two closely related blowflies Calliphora vicina and Calliphora vomitoria (Diptera: Calliphoridae). The hydrocarbons were then analysed using Gas Chromatography-Mass Spectrometry (GC-MS), with the aim of observing changes within their chemical profiles in order to determine the larval age. The hydrocarbons were examined daily for each species from 1day old larvae until pupariation. The results show significant chemical changes occurring from the younger larvae to the post-feeding larvae. With the aid of a multivariate statistical method (Principal Component Analysis and Artificial Neural Networks), samples were clustered and classified, allowing for the larval age to be established. Results from this study allowed larvae to be aged to the day with at worst, 87% accuracy, which suggests there is great potential for the use of cuticular hydrocarbons present on larvae to give an indication of their age and hence potentially a valuable tool for minimum PMI estimations

Electronic-cigarette use among young people in Wales: evidence from two cross-sectional surveys

Objectives To examine the prevalence of electronic(e)-cigarette use, prevalence of e-cigarette and tobacco use by age, and associations of e-cigarette use with sociodemographic characteristics, tobacco and cannabis use among young people in Wales. Design Data from two nationally-representative cross-sectional surveys undertaken in 2013–2014. Logistic regression analyses, adjusting for school-level clustering, examined sociodemographic characteristics of e-cigarette use, and associations between e-cigarette use and smoking. Setting Primary and secondary schools in Wales. Participants Primary-school children aged 10–11 (n=1601) and secondary-school students aged 11–16 (n=9055). Results Primary-school children were more likely to have used e-cigarettes (5.8%) than tobacco (1.6%). Ever use of e-cigarettes remained more prevalent than ever use of tobacco until age 14–15. Overall, 12.3% of secondary-school students (aged 11–16) reported ever using e-cigarettes, with no differences according to gender, ethnicity or family affluence. The percentage of ‘never smokers’ reporting having used e-cigarettes was 5.3% at age 10–11 to 8.0% at age 15–16. The proportion of children who had ever used an e-cigarette and reported currently smoking increased from 6.9% among 10–11 year olds to 39.2% in 15–16 year olds. Only 1.5% (n=125) of 11–16 year-olds, including 0.3% of never smokers, reported regular e-cigarette use (use at least once a month). Current weekly smokers were 100 times more likely than non-smokers to report regular e-cigarette use (relative risk ratio (RRR=121.15; 95% CI 57.56 to 254.97). Regular e-cigarette use was also more likely among those who had smoked cannabis (RRR 53.03; 95% CI 38.87 to 80.65). Conclusions Many young people (including never-smokers) have tried e-cigarettes. However, regular use is less common, and is associated with tobacco cigarette use. Longitudinal research is needed to understand age-related trajectories of e-cigarette use and to understand the temporal nature of relationships between e-cigarette and tobacco use

On the Possibility of Superluminal Neutrino Propagation

We analyze the possibility of superluminal neutrino propagation delta v = (v - c)/c > 0 as indicated by OPERA data, in view of previous phenomenological constraints from supernova SN1987a and gravitational Cerenkov radiation. We argue that the SN1987a data rule out delta v ~ (E_\nu/M_N)^N for N \le 2 and exclude, in particular, a Lorentz-invariant interpretation in terms of a 'conventional' tachyonic neutrino. We present two toy Lorentz-violating theoretical models, one a Lifshitz-type fermion model with superluminality depending quadratically on energy, and the other a Lorentz-violating modification of a massless Abelian gauge theory with axial-vector couplings to fermions. In the presence of an appropriate background field, fermions may propagate superluminally or subluminally, depending inversely on energy, and on direction. Reconciling OPERA with SN1987a would require this background field to depend on location.Comment: 15 pages, replacement has an expanded and revised version of the second model; Notes added on how this model evades the Cohen-Glashow constraint

M Dwarfs in SDSS Stripe 82: Photometric Light Curves and Flare Rate Analysis

We present a flare rate analysis of 50,130 M dwarf light curves in SDSS Stripe 82. We identified 271 flares using a customized variability index to search ~2.5 million photometric observations for flux increases in the u- and g-bands. Every image of a flaring observation was examined by eye and with a PSF-matching and image subtraction tool to guard against false positives. Flaring is found to be strongly correlated with the appearance of H-alpha in emission in the quiet spectrum. Of the 99 flare stars that have spectra, we classify 8 as relatively inactive. The flaring fraction is found to increase strongly in stars with redder colors during quiescence, which can be attributed to the increasing flare visibility and increasing active fraction for redder stars. The flaring fraction is strongly correlated with |Z| distance such that most stars that flare are within 300 pc of the Galactic plane. We derive flare u-band luminosities and find that the most luminous flares occur on the earlier-type M dwarfs. Our best estimate of the lower limit on the flaring rate (averaged over Stripe 82) for flares with \Delta u \ge 0.7 magnitudes on stars with u < 22 is 1.3 flares hour^-1 square degree^-1 but can vary significantly with the line-of-sight.Comment: 44 pages, 13 figure