The potential role of T-cells and their interaction with antigen-presenting cells in mediating immunosuppression following trauma-hemorrhage

Objective: Trauma-hemorrhage results in depressed immune responses of antigen-presenting cells (APCs) and T-cells. Recent studies suggest a key role of depressed T-cell derived interferon (IFN)-g in this complex immune cell interaction. The aim of this study was to elucidate further the underlying mechanisms responsible for dysfunctional T-cells and their interaction with APCs following trauma-hemorrhage. Design: Adult C3H/HeN male mice were subjected to trauma-hemorrhage (3-cm midline laparotomy) followed by hemorrhage (blood pressure of 35�5mmHg for 90 min and resuscitation) or sham operation. At 24 h thereafter, spleens were harvested and T-cells (by Microbeads) and APCs (via adherence) were Isolated. Co-cultures of T-cells and APCs were established for 48 h and stimulated with concanavalin A and lipopolysaccharide. T-Cell specific cytokines known to affect APC function (i.e. interleukin(IL)-2, IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF)) were measured in culture supernatants by Multiplex assay. The expression of MHC class II as well as co-stimulatory surface molecules on T-cells and APCs was determined by flow cytometry. Results: The release of IL-4 and GM-CSF by T-cells was suppressed following trauma-hemorrhage, irrespective of whether sham or trauma-hemorrhage APCs were present. Antigen-presenting cells from animals subjected to trauma-hemorrhage did not affect T-cell derived cytokine release by sham T-cells. In contrast, T-cells from traumahemorrhage animals depressed MHC class II expression of CD11c(þ) cells, irrespective of whether APCs underwent sham or trauma-hemorrhage procedure. Surprisingly, co-stimulatory molecules on APCs (CD80, CD86) were not affected by trauma-hemorrhage. Conclusions: These results suggest that beside IFN-g other T-cell derived cytokines contribute to immunosuppression following trauma-hemorrhage causing diminished MHC II expression on APCs. Thus, T-cells appear to play an important role in this interaction at the time-point examined. Therapeutic approaches should aim at maintenance of T-cell function and their interaction with APCs to prevent extended immunosuppression following trauma-hemorrhage

The unusual ISM in blue and dusty gas-rich galaxies (BADGRS)

The Herschel-ATLAS unbiased survey of cold dust in the local Universe is dominated by a surprising population of very blue (FUV-K 0.5 fHI=MHI/(M∗+M+HI)>0.5 ). Dubbed ‘Blue and Dusty Gas-Rich Sources’ (BADGRS) they have cold diffuse dust temperatures, and the highest dust-to-stellar mass ratios of any galaxies in the local Universe. Here, we explore the molecular interstellar medium in a representative sample of BADGRS, using very deep CO(J up =1,2,3) CO(Jup=1,2,3) observations across the central and outer disc regions. We find very low CO brightnesses (Tp = 5–30 mK), despite the bright far-infrared emission and metallicities in the range 0.5 < Z/Z⊙ < 1.0. The CO line ratios indicate a range of conditions with R 21 =T 21 b /T 10 b =0.6−2.1 R21=Tb21/Tb10=0.6−2.1 and R 31 =T 32 b /T 10 b =0.2−1.2 R31=Tb32/Tb10=0.2−1.2 . Using a metallicity-dependent conversion from CO luminosity to molecular gas mass, we find M H 2 /M d ∼7−27 MH2/Md∼7−27 and Σ H 2 =0.5−6M ⊙ pc −2 ΣH2=0.5−6M⊙pc−2 , around an order of magnitude lower than expected. The BADGRS have lower molecular gas depletion time-scales (τd ∼ 0.5 Gyr) than other local spirals, lying offset from the Kennicutt–Schmidt relation by a similar factor to Blue Compact Dwarf galaxies. The cold diffuse dust temperature in BADGRS (13–16 K) requires an interstellar radiation field 10–20 times lower than that inferred from their observed surface brightness. We speculate that the dust in these sources has either a very clumpy geometry or a very different opacity in order to explain the cold temperatures and lack of CO emission. BADGRS also have low UV attenuation for their UV colour suggestive of an SMC-type dust attenuation curve, different star formation histories or different dust/star geometry. They lie in a similar part of the IRX-β space as z z ∼ 5 galaxies and may be useful as local analogues for high gas fraction galaxies in the early Universe

Грунти як об’єкт науки

Висвітлюються деякі аспекти розвитку наших уявлень про ґрунтознавство як науковий напрямок природознавства та про ґрунти як об’єкт науки.Освещаются некоторые аспекты развития наших представлений о почвоведении как научном направлении природоведения и о почвах как объекте науки.The author highlights several aspects of human knowledge about soil research as a field of natural science, and about soils as a research object

The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

Peer reviewedPublisher PD

Small Stem Total Hip Arthroplasty in Hypoplasia of the Femur

Total hip arthroplasty in hypoplastic femurs is technically difficult and the incidence of complications and aseptic loosening is relatively high. Cemented, uncemented, off-the-shelf, and custom-made stems all have been advocated in these cases. From 1978 to 1997, we performed 86 total hip arthroplasties in 77 patients with a hypoplastic femur using a cemented, off-the-shelf, small, curved, cobalt-chromium stem. We hypothesized results equaled those of the identical but larger-sized stems in normal-sized femora which were used as comparisons. Clinical and radiographic evaluations were performed. Minimum followup was 4.2 years (mean, 12 years; range, 4.2–20.3 years); mean Harris hip score was 88, and mean hip flexion was 104°. Six stems were revised: four because of aseptic loosening, one after a femoral fracture, and one because of malpositioning. Complications included one perforation and one fracture of the femur, one fracture, one nonunion of the greater trochanter, and one deep infection. Implant survivorship for all hips at 15 years with aseptic revision of the stem as the end point was 90% (confidence interval, 82–99) which equaled results of the larger stems. The small off-the-shelf cemented Weber stem has a high long-term survival and a low complication rate. Survival compares favorably with other small-sized total hip systems

JINGLE – IV. Dust, H I gas and metal scaling laws in the local Universe

Scaling laws of dust, Hi gas and metal mass with stellar mass, specific star formation rate and metallicity are crucial to our understanding of the buildup of galaxies through their enrichment with metals and dust. In this work, we analyse how the dust and metal content varies with specific gas mass (MHI/M?) across a diverse sample of 423 nearby galaxies. The observed trends are interpreted with a set of Dust and Element evolUtion modelS (DEUS) – including stellar dust production, grain growth, and dust destruction – within a Bayesian framework to enable a rigorous search of the multi-dimensional parameter space. We find that these scaling laws for galaxies with −1.0 . logMHI/M? . 0 can be reproduced using closed-box models with high fractions (37-89%) of supernova dust surviving a reverse shock, relatively low grain growth efficiencies (=30-40), and long dust lifetimes (1-2Gyr). The models have present-day dust masses with similar contributions from stellar sources (50-80%) and grain growth (20-50%). Over the entire lifetime of these galaxies, the contribution from stardust (>90%) outweighs the fraction of dust grown in the interstellar medium (<10%). Our results provide an alternative for the chemical evolution models that require extremely low supernova dust production efficiencies and short grain growth timescales to reproduce local scaling laws, and could help solving the conundrum on whether or not grains can grow efficiently in the interstellar medium

Risk factors for atherosclerotic and medial arterial calcification of the intracranial internal carotid artery

_Background and aims:_ Calcifications of the intracranial internal carotid artery (iICA) are an important risk factor for stroke. The calcifications can occur both in the intimal and medial layer of the vascular wall. The aim of this study is to assess whether medial calcification in the iICA is differently related to risk factors for cardiovascular disease, compared to intimal calcification. _Methods:_ Unenhanced thin slice computed tomography (CT) scans from 1132 patients from the Dutch acute stroke study cohort were assessed for dominant localization of calcification (medial or intimal) by one of three observers based on established methodology. Associations between known cardiovascular risk factors (age, gender, body mass index, pulse pressure, eGFR, smoking, hypertension, diabetes mellitus, hyperlipidemia, previous vascular disease, and family history) and the dominant localization of calcifications were assessed via logistic regression analysis. _Results:_ In the 1132 patients (57% males, mean age 67.4 years [SD 13.8]), dominant intimal calcification was present in 30.9% and dominant medial calcification in 46.9%. In 10.5%, no calcification was seen. Age, pulse pressure and family history were risk factors for both types of calcification. Multivariably adjusted risk factors for dominant intimal calcification only were smoking (OR 2.09 [CI 1.27–3.44]) and hypertension (OR 2.09 [CI 1.29–3.40]) and for dominant medial calcification diabetes mellitus (OR 2.39 [CI 1.11–5.14]) and previous vascular disease (OR 2.20 [CI 1.30–3.75]). _Conclusions:_ Risk factors are differently related to the dominant localizations of calcifications, a finding that supports the hypothesis that the intimal and medial calcification represents a distinct etiology