Serological assessment of neutrophil elastase activity on elastin during lung ECM remodeling

BACKGROUND: During the pathological destruction of lung tissue, neutrophil elastase (NE) degrades elastin, one of the major constituents of lung parenchyma. However there are no non-invasive methods to quantify NE degradation of elastin. We selected specific elastin fragments generated by NE for antibody generation and developed an ELISA assay (EL-NE) for the quantification of NE-degraded elastin. METHODS: Monoclonal antibodies were developed against 10 NE-specific cleavage sites on elastin. One EL-NE assay was tested for analyte stability, linearity and intra- and inter-assay variation. The NE specificity was demonstrated using elastin cleaved in vitro with matrix metalloproteinases (MMPs), cathepsin G (CatG), NE and intact elastin. Clinical relevance was assessed by measuring levels of NE-generated elastin fragments in serum of patients diagnosed with idiopathic pulmonary fibrosis (IPF, n = 10) or lung cancer (n = 40). RESULTS: Analyte recovery of EL-NE for human serum was between 85% and 104%, the analyte was stable for four freeze/thaw cycles and after 24 h storage at 4°C. EL-NE was specific for NE-degraded elastin. Levels of NE-generated elastin fragments for elastin incubated in the presence of NE were 900% to 4700% higher than those seen with CatG or MMP incubation or in intact elastin. Serum levels of NE-generated elastin fragments were significantly increased in patients with IPF (137%, p = 0.002) and in patients with lung cancer (510%, p < 0.001) compared with age- and sex-matched controls. CONCLUSIONS: The EL-NE assay was specific for NE-degraded elastin. The EL-NE assay was able to specifically quantify NE-degraded elastin in serum. Serum levels of NE-degraded elastin might be used to detect excessive lung tissue degradation in lung cancer and IPF. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12890-015-0048-5) contains supplementary material, which is available to authorized users

Beneficial effect of mildly pasteurized whey protein on intestinal integrity and innate defense in preterm and near-term piglets

Background. The human digestive tract is structurally mature at birth, yet maturation of gut functions such as digestion and mucosal barrier continues for the next 1–2 years. Human milk and infant milk formulas (IMF) seem to impact maturation of these gut functions differently, which is at least partially related to high temperature processing of IMF causing loss of bioactive proteins and formation of advanced glycation end products (AGEs). Both loss of protein bioactivity and formation of AGEs depend on heating temperature and time. The aim of this study was to investigate the impact of mildly pasteurized whey protein concentrate (MP-WPC) compared to extensively heated WPC (EH-WPC) on gut maturation in a piglet model hypersensitive to enteral nutrition. Methods. WPC was obtained by cold filtration and mildly pasteurized (73 °C, 30 s) or extensively heat treated (73 °C, 30 s + 80 °C, 6 min). Preterm (~90% gestation) and near-term piglets (~96% gestation) received enteral nutrition based on MP-WPC or EH-WPC for five days. Macroscopic and histologic lesions in the gastro-intestinal tract were evaluated and intestinal responses were further assessed by RT-qPCR, immunohistochemistry and enzyme activity analysis. Results. A diet based on MP-WPC limited epithelial intestinal damage and improved colonic integrity compared to EH-WPC. MP-WPC dampened colonic IL1-β, IL-8 and TNF-α expression and lowered T-cell influx in both preterm and near-term piglets. Anti-microbial defense as measured by neutrophil influx in the colon was only observed in near-term piglets, correlated with histological damage and was reduced by MP-WPC. Moreover, MP-WPC stimulated iALP activity in the colonic epithelium and increased differentiation into enteroendocrine cells compared to EH-WPC. Conclusions. Compared to extensively heated WPC, a formula based on mildly pasteurized WPC limits gut inflammation and stimulates gut maturation in preterm and near-term piglets and might therefore also be beneficial for preterm and (near) term infants.</p

The PEP survey: clustering of infrared-selected galaxies and structure formation at z~2 in the GOODS South

ABRIDGED-This paper presents the first direct estimate of the 3D clustering properties of far-infrared sources up to z~3. This has been possible thanks to the Pacs Evolutionary Probe (PEP) survey of the GOODS South field performed with the PACS instrument onboard the Herschel Satellite. An analysis of the two-point correlation function over the whole redshift range spanned by the data reports for the correlation length, r_0~6.3 Mpc and r_0~6.7 Mpc, respectively at 100um and 160um, corresponding to dark matter halo masses M>~10^{12.4} M_sun. Objects at z~2 instead seem to be more strongly clustered, with r_0~19 Mpc and r_0~17 Mpc in the two considered PACS channels. This dramatic increase of the correlation length between z~1 and z~2 is connected with the presence of a wide, M>~10^{14} M_sun, filamentary structure which includes more than 50% of the sources detected at z~2. An investigation of the properties of such sources indicates the possibility for boosted star-forming activity in those which reside within the overdense environment with respect of more isolated galaxies found in the same redshift range. Lastly, we also present our results on the evolution of the relationship between luminous and dark matter in star-forming galaxies between z~1 and z~2. We find that the increase of (average) stellar mass in galaxies between z~1 and z~2 is about a factor 10 lower than that of the dark matter haloes hosting such objects ([z~1]/[z~2] ~ 0.4 vs M_{halo}[z~1]/M_{halo}[z~2] ~ 0.04). Our findings agree with the evolutionary picture of downsizing whereby massive galaxies at z~2 were more actively forming stars than their z~1 counterparts, while at the same time contained a lower fraction of their mass in the form of luminous matter.Comment: 14 pages, 8 figures, MNRAS accepte

Molerområdets geologi – sedimenter, fossiler, askelag og glaicaltektonik

Abstract in Danish I den vestlige del af Limfjorden findes en række kystklinter, hvor eocæne lag er blottet. Moler er en ca. 55-56 millioner år gammel diatomit, som indeholder lag af uforvitret vulkansk aske samt et stort antal velbevarede marine og terrestriske fossiler. Stolleklint Leret og Fur Formationen har et usædvanligt fossilselskab med mange repræsentanter for insekter, fisk, fugle og skildpadder men meget få kalkskallede, hvirvelløse dyr. De vulkanske askelag afspejler et stort antal gigantiske, eksplosive udbrud inden for en kort periode, hvor lavatilstrømningen var stor, samtidig med at udbruddene skete på lavt vand i den nydannede oceanbund. For ca. 25.000 år siden dannede fremrykkende iskapper folder og overskydninger i moler, askelag og glaciale sedimenter. Molerområdets geologi kan sammenfattes i følgende citat: ”…talrige tynde lag af sort vulkansk Aske...træde selv på lang Afstand tydelig frem i det hvide Moler …[Da de] ofte danner store Bugter og Folder, vil man forstaa, at de høje lyse Molerklinter i Solskin frembyde et malerisk og ejendommeligt Skue.” (N. V. Ussing i ’Danmarks Geologi’ 1904, s.143)

The Magnitude and Kinetics of the Mucosal HIV-Specific CD8+ T Lymphocyte Response and Virus RNA Load in Breast Milk

BACKGROUND: The risk of postnatal HIV transmission is associated with the magnitude of the milk virus load. While HIV-specific cellular immune responses control systemic virus load and are detectable in milk, the contribution of these responses to the control of virus load in milk is unknown. METHODS: We assessed the magnitude of the immunodominant GagRY11 and subdominant EnvKY9-specific CD8+ T lymphocyte response in blood and milk of 10 A*3002+, HIV-infected Malawian women throughout the period of lactation and correlated this response to milk virus RNA load and markers of breast inflammation. RESULTS: The magnitude and kinetics of the HIV-specific CD8+ T lymphocyte responses were discordant in blood and milk of the right and left breast, indicating independent regulation of these responses in each breast. However, there was no correlation between the magnitude of the HIV-specific CD8+ T lymphocyte response and the milk virus RNA load. Further, there was no correlation between the magnitude of this response and markers of breast inflammation. CONCLUSIONS: The magnitude of the HIV-specific CD8+ T lymphocyte response in milk does not appear to be solely determined by the milk virus RNA load and is likely only one of the factors contributing to maintenance of low virus load in milk

Approaches and techniques for modelling CO2 emissions from road transport

Transport accounts for around a quarter of CO2 emissions globally. Transport modelling provides a useful means to explore the dynamics, scale and magnitude of transport related emissions. This paper explores the modelling tools available for analysing the emissions of CO2 from transport. Covering a range of techniques from transport microsimulation to global techno-economic models, this review provides insight into the various advantages and shortcomings of these tools. The paper also examines the value of having a broad range of perspectives for analysing emissions from transport. The paper concludes by suggesting that the broad range of models creates a rich environment for exploring a spectrum of policy questions around the emissions from transport, and the potential for combining modelling approaches further enhances the understanding that can be attained

The Impact of Oral Health on Taste Ability in Acutely Hospitalized Elderly

Objective: To investigate to what extent various oral health variables are associated with taste ability in acutely hospitalized elderly. Background: Impaired taste may contribute to weight loss in elderly. Many frail elderly have poor oral health characterized by caries, poor oral hygiene, and dry mouth. However, the possible influence of such factors on taste ability in acutely hospitalized elderly has not been investigated. Materials and Methods: The study was cross-sectional. A total of 174 (55 men) acutely hospitalized elderly, coming from their own homes and with adequate cognitive function, were included. Dental status, decayed teeth, oral bacteria, oral hygiene, dry mouth and tongue changes were recorded. Growth of oral bacteria was assessed with CRTH Bacteria Kit. Taste ability was evaluated with 16 taste strips impregnated with sweet, sour, salty and bitter taste solutions in 4 concentrations each. Correct identification was given score 1, and maximum total taste score was 16. Results: Mean age was 84 yrs. (range 70–103 yrs.). Total taste score was significantly and markedly reduced in patients with decayed teeth, poor oral hygiene, high growth of oral bacteria and dry mouth. Sweet and salty taste were particularly impaired in patients with dry mouth. Sour taste was impaired in patients with high growth of oral bacteria. Conclusion: This study shows that taste ability was reduced in acutely hospitalized elderly with caries activity, high growt