In their post-traumatic course, trauma patients suffering from multiple injuries have a high risk for immune dysregulation, which may contribute to post-injury complications and late mortality. ...Monocytes as specific effector cells of the innate immunity play a crucial role in inflammation. Using their Pattern Recognition Receptors (PRRs), notably Toll-Like Receptors (TLR), the monocytes recognize pathogens and/or pathogen-associated molecular patterns (PAMPs) and organize their clearance. TLR2 is the major receptor for particles of gram-positive bacteria, and initiates their phagocytosis. Here, we investigated the phagocytizing capability of monocytes in a long-term porcine severe trauma model (polytrauma, PT) with regard to their TLR2 expression. Polytrauma consisted of femur fracture, unilateral lung contusion, liver laceration, hemorrhagic shock with subsequent resuscitation and surgical fracture fixation. After induction of PT, peripheral blood was withdrawn before (-1 h) and directly after trauma (0 h), as well as 3.5 h, 5.5 h, 24 h and 72 h later. CD14+ monocytes were identified and the expression levels of H(S)LA-DR and TLR2 were investigated by flow cytometry. Additionally, the phagocytizing activity of monocytes by applying S. aureus particles labelled with pHrodo fluorescent reagent was also assessed by flow cytometry. Furthermore, blood samples from 10 healthy pigs were exposed to a TLR2-neutralizing antibody and subsequently to S. aureus particles. Using flow cytometry, phagocytizing activity was determined. P below 0.05 was considered significant. The number of CD14+ monocytes of all circulating leukocytes remained constant during the observational time period, while the percentage of CD14+H(S)LA-DR+ monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of TLR2+ expressing cells out of all monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of phagocytizing monocytes decreased immediately and remained lower during the first 3.5 h after trauma, but increased after 24 h. Antagonizing TLR2 significantly decreased the phagocytizing activity of monocytes. Both, decreased percentage of activated as well as TLR2 expressing monocytes persisted as long as the reduced phagocytosis was observed. Moreover, neutralizing TLR2 led to a reduced capability of phagocytosis as well. Therefore, we assume that reduced TLR2 expression may be responsible for the decreased phagocytizing capacity of circulating monocytes in the early post-traumatic phase.
We present the Evolution of molecular Gas in Normal Galaxies (EGNoG) survey, an observational study of molecular gas in 31 star-forming galaxies from z = 0.05 to z = 0.5, with stellar masses of ...(4-30) x 10 super(10) M sub(middot in circle) and star formation rates of 4-100 M sub(middot in circle) yr super(-1). This survey probes a relatively un-observed redshift range in which the molecular gas content of galaxies is expected to have evolved significantly. To trace the molecular gas in the EGNoG galaxies, we observe the CO(J = 1 arrow right 0 ) and CO(J = 3 arrow right 2) rotational lines using the Combined Array for Research in Millimeter-wave Astronomy (CARMA). We detect 24 of 31 galaxies and present resolved maps of 10 galaxies in the lower redshift portion of the survey. We use a bimodal prescription for the CO to molecular gas conversion factor, based on specific star formation rate, and compare the EGNoG galaxies to a large sample of galaxies assembled from the literature. We find an average molecular gas depletion time of 0.76 + or - 0.54 Gyr for normal galaxies and 0.06 + or - 0.04 Gyr for starburst galaxies. We calculate an average molecular gas fraction of 7%-20% at the intermediate redshifts probed by the EGNoG survey. By expressing the molecular gas fraction in terms of the specific star formation rate and molecular gas depletion time (using typical values), we also calculate the expected evolution of the molecular gas fraction with redshift. The predicted behavior agrees well with the significant evolution observed from z ~ 2.5 to today.
Up to 20% of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) patients develop severe inflammatory complications with diffuse pulmonary inflammation, reflecting acute respiratory distress ...syndrome (ARDS). A similar clinical profile occurs in severe trauma cases. This review compares pathophysiological and therapeutic principles of severely injured trauma patients and severe coronavirus disease 2019 (COVID-19). The development of sequential organ failure in trauma parallels deterioration seen in severe COVID-19. Based on established pathophysiological models in the field of trauma, two complementary pathways of disease progression into severe COVID-19 have been identified. Furthermore, the transition from local contained disease into systemic and remote inflammation has been addressed. More specifically, the traumatology concept of sequential insults ('hits') resulting in immune dysregulation, is applied to COVID-19 disease progression modelling. Finally, similarities in post-insult humoral and cellular immune responses to severe trauma and severe COVID-19 are described. To minimize additional 'hits' to COVID-19 patients, we suggest postponing all elective surgery in endemic areas. Based on traumatology experience, we propose that immunoprotective protocols including lung protective ventilation, optimal thrombosis prophylaxis, secondary infection prevention and calculated antibiotic therapy are likely also beneficial in the treatment of SARS-CoV-2 infections. Finally, rising SARS-CoV-2 infection and mortality rates mandate exploration of out-of-the box treatment concepts, including experimental therapies designed for trauma care.
Extensive trauma surgery evokes an immediate cellular immune response including altered circulatory neutrophil numbers. The concurrent bone marrow (BM) response however is currently unclear. We ...hypothesize that these BM changes include (1) a relative reduction of the bone marrow neutrophil fraction and (2) increasing heterogeneity of the bone marrow neutrophil pool due to (3) the appearance of aged/returning neutrophils from circulation into the BM-compartment.
Eight pigs were included in a standardized extensive trauma surgery model. Blood and bone marrow samples were collected at baseline and after 3 hours of ongoing trauma surgery. Leukocyte and subtype counts and cell surface receptor expression levels were studied by flow cytometry.
All animals survived the interventions. A significant drop in circulating neutrophil counts from 9.3 to 3.2x10
cells/ml (P=0.001) occurred after intervention, whereas circulatory neutrophil cell surface expression of CD11b increased. The concurrent bone marrow response included an increase of the BM neutrophil fraction from 63 ± 3 to 71 ± 3 percent (P<0.05). Simultaneously, the BM neutrophil pool became increasingly mature with a relative increase of a CXCR4
-neutrophil subtype that was virtually absent at baseline.
The current study shows a shift in composition of the BM neutrophil pool during extensive trauma surgery that was associated with a relatively circulatory neutropenia. More specifically, under these conditions BM neutrophils were more mature than under homeostatic conditions and a CXCR4
-neutrophil subset became overrepresented possibly reflecting remigration of aged neutrophils to the BM. These findings may contribute to the development of novel interventions aimed to modify the trauma-induced immune response in the BM.
Context. We report on new simultaneous observations and modeling of the millimeter, near-infrared, and X-ray flare emission of the source Sagittarius A* (SgrA*) associated with the super-massive ...(4 × 106 M⊙) black hole at the Galactic center. Aims. We study the applicability of the adiabatic synchrotron source expansion model and study physical processes giving rise to the variable emission of SgrA* from the radio to the X-ray domain. Methods. Our observations were carried out on 18 May 2009 using the NACO adaptive optics (AO) instrument at the European Southern Observatory’s Very Large Telescope, the ACIS-I instrument aboard the Chandra X-ray Observatory, the LABOCA bolometer at the Atacama Pathfinder EXperiment (APEX), and the CARMA mm telescope array at Cedar Flat, California. Results. The X-ray flare had an excess 2 − 8 keV luminosity between 6 and 12 × 1033 erg s-1. The observations reveal flaring activity in all wavelength bands that can be modeled as the signal from an adiabatically expanding synchrotron self-Compton (SSC) component. Modeling of the light curves shows that the sub-mm follows the NIR emission with a delay of about three-quarters of an hour with an expansion velocity of about vexp ~ 0.009c. We find source component sizes of around one Schwarzschild radius, flux densities of a few Janskys, and spectral indices α of about +1 (S(ν) ∝ ν−α). At the start of the flare, the spectra of the two main components peak just short of 1 THz. To statistically explain the observed variability of the (sub-)mm spectrum of SgrA*, we use a sample of simultaneous NIR/X-ray flare peaks and model the flares using a synchrotron and SSC mechanism. Conclusions. These parameters suggest that either the adiabatically expanding source components have a bulk motion larger than vexp or the expanding material contributes to a corona or disk, confined to the immediate surroundings of SgrA*. For the bulk of the synchrotron and SSC models, we find synchrotron turnover frequencies in the range of 300−400 GHz. For the pure synchrotron models, this results in densities of relativistic particles of the order of 106.5 cm-3 and for the SSC models, the median densities are about one order of magnitude higher. However, to obtain a realistic description of the frequency-dependent variability amplitude of SgrA*, models with higher turnover frequencies and even higher densities are required.
Severely injured patients experience substantial immunological stress in the aftermath of traumatic insult, which often results in systemic immune dysregulation. Regulatory T cells (Treg) play a key ...role in the suppression of the immune response and in the maintenance of immunological homeostasis. Little is known about their presence and dynamics in blood after trauma, and nothing is known about Treg in the porcine polytrauma model. Here, we assessed different subsets of Treg in trauma patients (TP) and compared those to either healthy volunteers (HV) or data from porcine polytrauma.
Peripheral blood was withdrawn from 20 TP with injury severity score (ISS) ≥16 at the admittance to the emergency department (ED), and subsequently on day 1 and at day 3. Ten HV were included as controls (ctrl). The porcine polytrauma model consisted of a femur fracture, liver laceration, lung contusion, and hemorrhagic shock resulting in an ISS of 27. After polytrauma, the animals underwent resuscitation and surgical fracture fixation. Blood samples were withdrawn before and immediately after trauma, 24 and 72 h later. Different subsets of Treg, CD4
CD25
, CD4
CD25
FoxP3
, CD4
CD25
CD127
, and CD4
CD25
CD127
FoxP3
were characterized by flow cytometry.
Absolute cell counts of leukocytes were significantly increasing after trauma, and again decreasing in the follow-up in human and porcine samples. The proportion of human Treg in the peripheral blood of TP admitted to the ED was lower when compared to HV. Their numbers did not recover until 72 h after trauma. Comparable data were found for all subsets. The situation in the porcine trauma model was comparable with the clinical data. In porcine peripheral blood before trauma, we could identify Treg with the typical immunophenotype (CD4
CD25
CD127
), which were virtually absent immediately after trauma. Similar to the human situation, most of these cells expressed FoxP3, as assessed by intracellular FACS stain.
Despite minor percental differences in the recovery of Treg populations after trauma, our findings show a comparable decrease of Treg early after polytrauma, and strengthen the immunological significance of the porcine polytrauma model. Furthermore, the Treg subpopulation CD4
CD25
CD127
was characterized in porcine samples.
As observations of molecular gas in galaxies are pushed to lower star formation rate (SFR) galaxies at higher redshifts, it is becoming increasingly important to understand the conditions of the gas ...in these systems to properly infer their molecular gas content. In this paper, we present the results from the gas excitation sample of the Evolution of molecular Gas in Normal Galaxies (EGNoG) survey at the Combined Array for Research in Millimeter-wave Astronomy (CARMA). We conclude that the excitation of the gas in these massive, highly star-forming galaxies is consistent with normal star-forming galaxies such as local spirals, not star-bursting systems like local ultra-luminous infrared galaxies. Since the EGNoG gas excitation sample galaxies are selected from the main sequence (MS) of star-forming galaxies, we suggest that this result is applicable to studies of MS galaxies at intermediate and high redshifts, supporting the assumptions made in studies that find molecular gas fractions in star-forming galaxies at z ~ 1-2 to be an order of magnitude larger than what is observed locally.
We present an analysis of the molecular gas distributions in the 29 barred and 15 unbarred spirals in the BIMA CO (J= 1-0) Survey of Nearby Galaxies (SONG). For galaxies that are bright in CO, we ...confirm the conclusion by Sakamoto et al. that barred spirals have higher molecular gas concentrations in the central kiloparsec. The SONG sample also includes 27 galaxies below the CO brightness limit used by Sakamoto et al. Even in these less CO-bright galaxies we show that high central gas concentrations are more common in barred galaxies, consistent with radial inflow driven by the bar. However, there is a significant population of early-type (Sa-Sbc) barred spirals (6 of 19) that have no molecular gas detected in the nuclear region and have very little out to the bar corotation radius. This suggests that in barred galaxies with gas-deficient nuclear regions, the bar has already driven most of the gas within the bar corotation radius to the nuclear region, where it has been consumed by star formation. The median mass of nuclear molecular gas is over 4 times higher in early-type bars than in late-type (Sc-Sdm) bars. Since previous work has shown that the gas consumption rate is an order of magnitude higher in early-type bars, this implies that the early types have significantly higher bar-driven inflows. The lower accretion rates in late-type bars can probably be attributed to the known differences in bar structure between early and late types. Despite the evidence for bar-driven inflows in both early and late Hubble-type spirals, the data indicate that it is highly unlikely for a late-type galaxy to evolve into an early type via bar-induced gas inflow. Nonetheless, secular evolutionary processes are undoubtedly present, and pseudobulges are inevitable; evidence for pseudobulges is likely to be clearest in early-type galaxies because of their high gas inflow rates and higher star formation activity.
Myocardial infarction (MI) induces an inflammatory response in which neutrophils fulfill a prominent role. Mean neutrophil volume (MNV) represents the average size of the circulating neutrophil ...population. Our goal was to determine the effect of MI on MNV and investigate the mechanisms behind MNV elevation. MNV of 84 MI patients was compared with the MNV of 209 stable angina patients and correlated to simultaneously measured CK levels. Fourteen pigs were subjected to temporary coronary balloon occlusion and blood was sampled at multiple time points to measure MNV. Echocardiography was performed followed by ex vivo infarct size assessment after 72 h. MNV was higher in MI patients compared to stable angina patients (602 SD26 AU vs. 580 SD20 AU,
p
< 0.0001) and correlated with simultaneously measured CK levels (
R
= 0.357,
p
< 0.0001). In pigs, MNV was elevated post-MI (451 SD11 AU vs. 469 SD12 AU),
p
< 0.0001). MNV correlated with infarct size (
R
= 0.705,
p
= 0.007) and inversely correlated with left ventricular ejection fraction (
R
= −0.718,
p
= 0.009). Cell sorting revealed an increased presence of banded neutrophils after MI, which have a higher MNV compared to mature neutrophils post-MI (495 SD14 AU vs. 478 SD11 AU,
p
= 0.012). MNV from coronary sinus blood was higher than MNV of neutrophils from simultaneously sampled arterial blood (463 SD7.6 AU vs. 461 SD8.6 AU,
p
= 0.013) post-MI. The current study shows MNV is elevated and reflects cardiac damage post-MI. MNV increases due to altered neutrophil composition and systemic neutrophil activation. MNV may be an interesting parameter for prognostic assessment in MI and provide new insights into pathological innate immune responses evoked by ischemia–reperfusion.
The 229 GHz (lambda 1.3 mm) radio emission from Orion-KL was mapped with up to 0".4 angular resolution with CARMA, allowing measurements of the flux densities of Source I ("SrcI") and the ...Becklin-Neugebauer Object (BN), the two most massive stars in this region. We find integrated flux densities of 310 + or - 45 mJy for SrcI and 240 + or - 35 mJy for BN. SrcI is optically thick even at 229 GHz. No trace of the H30 alpha recombination line is seen in its spectrum, although the nu sub(2) = 1, 5(5,0)-6(4,3) transition of H sub(2)O, 3450 K above the ground state, is prominent. SrcI is elongated at position angle 140degrees, as in 43 GHz images. These results are most easily reconciled with models in which the radio emission from SrcI arises via the H- free-free opacity in a T < 4500 K disk, as considered by Reid et al. By contrast, the radio spectrum of BN is consistent with p super(+)/e super(-) free-free emission from a dense (ne ~ 5 x 10 super(7) cm super(-3)), but otherwise conventional, hypercompact H II region. The source is becoming optically thin at 229 GHz, and the H30 alpha recombination line, at V sub(LSR) = 23.2 + or - 0.5 km s super(-1), is prominent in its spectrum. A Lyman continuum flux of 5 x 10 super(45) photons s super(-1), consistent with that expected from a B star, is required to maintain the ionization. Supplementary 90 GHz observations were made to measure the H41 alpha and H42 alpha recombination lines toward BN. Published 43 and 86 GHz data suggest that SrcI brightened with respect to BN over the 15 year period from 1994 to 2009.
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