The spinal cord injury-induced immune deficiency syndrome: results of the SCIentinel study

Infections are prevalent after spinal cord injury (SCI), constitute the main cause of death and are a rehabilitation confounder associated with impaired recovery. We hypothesize that SCI causes an acquired lesion-dependent (neurogenic) immune suppression as an underlying mechanism to facilitate infections. The international prospective multicentre cohort study (SCIentinel; protocol registration DRKS00000122; n = 111 patients) was designed to distinguish neurogenic from general trauma-related effects on the immune system. Therefore, SCI patient groups differing by neurological level, i.e. high SCI [thoracic (Th)4 or higher]; low SCI (Th5 or lower) and severity (complete SCI; incomplete SCI), were compared with a reference group of vertebral fracture (VF) patients without SCI. The primary outcome was quantitative monocytic Human Leukocyte Antigen-DR expression (mHLA-DR, synonym MHC II), a validated marker for immune suppression in critically ill patients associated with infection susceptibility. mHLA-DR was assessed from Day 1 to 10 weeks after injury by applying standardized flow cytometry procedures. Secondary outcomes were leucocyte subpopulation counts, serum immunoglobulin levels and clinically defined infections. Linear mixed models with multiple imputation were applied to evaluate group differences of logarithmic-transformed parameters. Mean quantitative mHLA-DR [ln (antibodies/cell)] levels at the primary end point 84 h after injury indicated an immune suppressive state below the normative values of 9.62 in all groups, which further differed in its dimension by neurological level: high SCI [8.95 (98.3% confidence interval, CI: 8.63; 9.26), n = 41], low SCI [9.05 (98.3% CI: 8.73; 9.36), n = 29], and VF without SCI [9.25 (98.3% CI: 8.97; 9.53), n = 41, P = 0.003]. Post hoc analysis accounting for SCI severity revealed the strongest mHLA-DR decrease [8.79 (95% CI: 8.50; 9.08)] in the complete, high SCI group, further demonstrating delayed mHLA-DR recovery [9.08 (95% CI: 8.82; 9.38)] and showing a difference from the VF controls of -0.43 (95% CI: -0.66; -0.20) at 14 days. Complete, high SCI patients also revealed constantly lower serum immunoglobulin G [-0.27 (95% CI: -0.45; -0.10)] and immunoglobulin A [-0.25 (95% CI: -0.49; -0.01)] levels [ln (g/l × 1000)] up to 10 weeks after injury. Low mHLA-DR levels in the range of borderline immunoparalysis (below 9.21) were positively associated with the occurrence and earlier onset of infections, which is consistent with results from studies on stroke or major surgery. Spinal cord injured patients can acquire a secondary, neurogenic immune deficiency syndrome characterized by reduced mHLA-DR expression and relative hypogammaglobulinaemia (combined cellular and humoral immune deficiency). mHLA-DR expression provides a basis to stratify infection-risk in patients with SCI

X-ray stacking of Lyman break galaxies in the 4 Ms CDF-S: X-ray luminosities and star formation rates across cosmic time

Context. Lyman break galaxies (LBGs) are widely thought to be prototypical young galaxies in the early universe, particularly representative of those undergoing massive events of star formation. Therefore, LBGs should produce significant amounts of X-ray emission. Aims. We aim to trace the X-ray luminosity of LBGs across cosmic time and from that derive constraints on their star formation history. Methods. We utilize the newly released 4 Ms mosaic obtained with the Chandra X-ray Observatory, the deepest X-ray image to date, alongside with the superb spectroscopic data sets available in the CDF-S survey region to construct large but nearly uncontaminated samples of LBGs across a wide range of redshift (0.5 < z < 4.5) which can be used as input samples for stacking experiments. This approach allows us to trace the X-ray emission of LBGs to even lower, previously unreachable, flux density limits (~10 -18 mW m -2) and therefore to larger redshifts. Results. We reliably detect soft-band X-ray emission from all our input redshift bins except for the highest redshift (z ~ 4) one. From that we derive rest-frame 2-10 keV luminosities and infer star formation rates and stellar masses. We find that star formation in LBGs peaks at a redshift of z peak 3.5 and then decreases quickly. We also see a characteristic peak in the specific star formation rate (sSFR = SFR/M -) at this redshift. Furthermore, we calculate the contribution of LBGs to the total cosmic star formation rate density (SFRD) and find that the contribution of LBGs is negligible. Therefore, we conclude that most of the star formation in the early universe takes place in lower luminosity galaxies as suggested by hierarchical structure formation models

Eine explizite Version der Jacquet-Langlands-Korrespondenz für den dreidimensionalen hyperbolischen Raum

Ausgehend von Eigenfunktionen des Laplace-Beltrami-Operators zu kokompakten Quaternionengruppen über einem imaginär-quadratischen Zahlkörper K, die auf dem 3-dimensionalen hyperbolischen Halbraum operieren, werden in dieser Arbeit explizit Eigenfunktionen des Laplace-Beltrami-Operators zu gewissen kofiniten Untergruppen von PSL(2;O_K) mit gleichem Eigenwert konstruiert. Dies wird dabei bewirkt durch einen Integraloperator, dessen Kern eine geeignete Siegelsche Thetafunktion bildet. Für die Transformationseigenschaften dieser Thetafunktion wird eine Verallgemeinerung eines Transformationssatzes von C.L. Siegel auf beliebige imaginär-quadratische Zahlkörper und beliebige ganze Hauptideale bewiesen. Für Klassenzahl 1 zeigt sich, dass die konstruierten Eigenfunktionen Spitzenfunktionen sind. Die Darstellung der Fourierentwicklung dieser Spitzenfunktionen kann schließlich für den Fall einer maximalen Ordnung mit Hilfe der Hecke-Theorie vereinfacht werden

Eine explizite Version der Jacquet-Langlands-Korrespondenz für den dreidimensionalen hyperbolischen Raum

Ausgehend von Eigenfunktionen des Laplace-Beltrami-Operators zu kokompakten Quaternionengruppen über einem imaginär-quadratischen Zahlkörper K, die auf dem 3-dimensionalen hyperbolischen Halbraum operieren, werden in dieser Arbeit explizit Eigenfunktionen des Laplace-Beltrami-Operators zu gewissen kofiniten Untergruppen von PSL(2;O_K) mit gleichem Eigenwert konstruiert. Dies wird dabei bewirkt durch einen Integraloperator, dessen Kern eine geeignete Siegelsche Thetafunktion bildet. Für die Transformationseigenschaften dieser Thetafunktion wird eine Verallgemeinerung eines Transformationssatzes von C.L. Siegel auf beliebige imaginär-quadratische Zahlkörper und beliebige ganze Hauptideale bewiesen. Für Klassenzahl 1 zeigt sich, dass die konstruierten Eigenfunktionen Spitzenfunktionen sind. Die Darstellung der Fourierentwicklung dieser Spitzenfunktionen kann schließlich für den Fall einer maximalen Ordnung mit Hilfe der Hecke-Theorie vereinfacht werden

J. Biol. Chem

The activity of vesicular monoamine transporters (VMATs) is down-regulated by the G-protein {alpha}-subunits of Go2 and Gq, but the signaling pathways are not known. We show here that no such regulation is observed when VMAT1 or VMAT2 are expressed in Chinese hamster ovary (CHO) cells. However, when the intracellular compartments of VMAT-expressing CHO cells are preloaded with different monoamines, transport becomes susceptible to G-protein-dependent regulation, with differences between the two transporter isoforms. Epinephrine induces G-protein-mediated inhibition of transmitter uptake in CHOVMAT1 cells but prevents inhibition induced by dopamine in CHOVMAT2 cells. Epinephrine also antagonizes G-protein-mediated inhibition of monoamine uptake by VMAT2 expressing platelets or synaptic vesicles. In CHOVMAT2 cells G-protein-mediated inhibition of monoamine uptake can be induced by 5-hydroxytryptamine (serotonin) 1B receptor agonists, whereas {alpha}1 receptor agonists modulate uptake into CHOVMAT1 cells. Accordingly, 5-hydroxytryptamine 1B receptor antagonists prevent G-proteinmediated inhibition of uptake in partially filled platelets and synaptic vesicles expressing VMAT2. CHO cells expressing VMAT mutants with a shortened first vesicular loop transport monoamines. However, no or a reduced G-protein regulation of uptake can be initiated. In conclusion, vesicular content is involved in the activation of vesicle associated G-proteins via a structure sensing the luminal monoamine content. The first luminal loop of VMATs may represent a G-protein-coupled receptor that adapts vesicular filling

Adverse effect of neurogenic, infective, and inflammatory fever on acutely injured human spinal cord.

This study aims to determine the effect of neurogenic, inflammatory, and infective fevers on acutely injured human spinal cord. In 86 patients with acute, severe traumatic spinal cord injuries (American spinal injury association Impairment Scale, grades A-C) we monitored (starting within 72 hours of injury, for up to a week) axillary temperature as well as injury site cord pressure, microdialysis, and oxygen. High fever (temperature >38 oC) was classified as neurogenic, infective, or inflammatory. The effect of these three fever types on injury site physiology, metabolism and inflammation was studied by analysing 2,864 hours of intraspinal pressure, 1,887 hours of microdialysis, and 840 hours of tissue oxygen data. High fever occurred in 76.7 % of the patients. The data show that temperature was higher in neurogenic than non-neurogenic fever. Neurogenic fever only occurred with injuries rostral to T4. Compared with normothermia, fever was associated with reduced tissue glucose (all fevers), increased tissue lactate to pyruvate ratio (all fevers), reduced tissue oxygen (neurogenic + infective fevers) and elevated levels of pro-inflammatory cytokines/chemokines (infective fever). Spinal cord metabolic derangement preceded the onset of infective but not neurogenic or inflammatory fever. By considering five clinical characteristics (level of injury, axillary temperature, leukocyte count, C-reactive protein, serum procalcitonin), it is possible to confidently distinguish neurogenic from non-neurogenic high fever in 59.3 % cases. We conclude that neurogenic, infective, and inflammatory fevers occur commonly after acute, severe, traumatic spinal cord injury and are detrimental to the injured spinal cord with infective fever the most injurious. Further studies are required to determine whether treating fever improves outcome. Accurately diagnosing neurogenic fever, as described, may reduce unnecessary septic screens and overuse of antibiotics in these patients

Exploring the properties of low-frequency radio emission and magnetic fields in a sample of compact galaxy groups using the LOFAR Two-Metre Sky Survey (LoTSS)

International audienceWe use the LOFAR Two-metre Sky Survey (LoTSS) Data Release I to identify the groups of galaxies (and individual galaxies) from the Hickson compact groups (HCG) and magnitude-limited compact groups (MLCG) samples that emit at the frequency of 150 MHz, characterise their radio emission (extended or limited to the galaxies), and compare new results to earlier observations and theoretical predictions. The detection of 73 systems (and 7 more-probably) out of 120, of which as many as 17 show the presence of extended radio structures, confirms the previous hypothesis of the common character of the magnetic field inside galaxy groups and its detectability. In order to investigate the future potential of low-frequency radio studies of galaxy groups, we also present a more detailed insight into four radio-emitting systems, for which the strength of the magnetic field inside their intergalactic medium (IGM) is calculated. The estimated values are comparable to that found inside star-forming galaxies, suggesting a dynamical and evolutionary importance of the magnetic field in galaxy groups

The spinal cord injury-induced immune deficiency syndrome: results of the SCIentinel study

Infections are prevalent after spinal cord injury (SCI), constitute the main cause of death and are a rehabilitation confounder associated with impaired recovery. We hypothesize that SCI causes an acquired lesion-dependent (neurogenic) immune suppression as an underlying mechanism to facilitate infections. The international prospective multicentre cohort study (SCIentinel; protocol registration DRKS00000122; n = 111 patients) was designed to distinguish neurogenic from general trauma-related effects on the immune system. Therefore, SCI patient groups differing by neurological level, i.e. high SCI [thoracic (Th)4 or higher]; low SCI (Th5 or lower) and severity (complete SCI; incomplete SCI), were compared with a reference group of vertebral fracture (VF) patients without SCI. The primary outcome was quantitative monocytic Human Leukocyte Antigen-DR expression (mHLA-DR, synonym MHC II), a validated marker for immune suppression in critically ill patients associated with infection susceptibility. mHLA-DR was assessed from Day 1 to 10 weeks after injury by applying standardized flow cytometry procedures. Secondary outcomes were leucocyte subpopulation counts, serum immunoglobulin levels and clinically defined infections. Linear mixed models with multiple imputation were applied to evaluate group differences of logarithmic-transformed parameters. Mean quantitative mHLA-DR [ln (antibodies/cell)] levels at the primary end point 84 h after injury indicated an immune suppressive state below the normative values of 9.62 in all groups, which further differed in its dimension by neurological level: high SCI [8.95 (98.3% confidence interval, CI: 8.63; 9.26), n = 41], low SCI [9.05 (98.3% CI: 8.73; 9.36), n = 29], and VF without SCI [9.25 (98.3% CI: 8.97; 9.53), n = 41, P = 0.003]. Post hoc analysis accounting for SCI severity revealed the strongest mHLA-DR decrease [8.79 (95% CI: 8.50; 9.08)] in the complete, high SCI group, further demonstrating delayed mHLA-DR recovery [9.08 (95% CI: 8.82; 9.38)] and showing a difference from the VF controls of −0.43 (95% CI: −0.66; −0.20) at 14 days. Complete, high SCI patients also revealed constantly lower serum immunoglobulin G [−0.27 (95% CI: −0.45; −0.10)] and immunoglobulin A [−0.25 (95% CI: −0.49; −0.01)] levels [ln (g/l × 1000)] up to 10 weeks after injury. Low mHLA-DR levels in the range of borderline immunoparalysis (below 9.21) were positively associated with the occurrence and earlier onset of infections, which is consistent with results from studies on stroke or major surgery. Spinal cord injured patients can acquire a secondary, neurogenic immune deficiency syndrome characterized by reduced mHLA-DR expression and relative hypogammaglobulinaemia (combined cellular and humoral immune deficiency). mHLA-DR expression provides a basis to stratify infection-risk in patients with SCI