We present the stellar populations of 138 compact elliptical galaxies (cEs) in the redshift range of z < 0.05 using the Sloan Digital Sky Survey (SDSS) DR12. Our cEs are divided into those with cE(w) ...and without cE(w/o) a bright (Mr < −21 mag) host galaxy. We investigated the stellar population properties of cEs based on the Lick line indices extracted from SDSS spectra. cE(w)s show Z/H and /Fe distributions skewed toward higher values compared to those of the cE(w/o)s. No statistically significant difference in age distribution was found between the cE(w)s and cE(w/o)s. In the mass-metallicity distribution, cE(w)s deviate from the relation observed for early-type galaxies at a given stellar mass, whereas cE(w/o)s conform to the relation. Based on the different features in the stellar populations of cE(w)s and cE(w/o)s, we can propose two different cE formation channels tracing different original masses of the progenitors. cE(w)s would be the remnant cores of the massive progenitor galaxies whose outer parts are tidally stripped by a massive neighboring galaxy (i.e., a nurture origin). In contrast, cE(w/o)s are likely the faint end of early-type galaxies maintaining in situ evolution in an isolated environment with no massive galaxy nearby (i.e., a nature origin). Our results reinforce the propositions that cEs comprise a mixture of galaxies with two types of origins depending on their local environment.
Neutrophils in viral infection Naumenko, Victor; Turk, Madison; Jenne, Craig N. ...
Cell and tissue research,
03/2018, Letnik:
371, Številka:
3
Journal Article
Recenzirano
Neutrophils are the first wave of recruited immune cells to sites of injury or infection and are crucial players in controlling bacterial and fungal infections. Although the role of neutrophils ...during bacterial or fungal infections is well understood, their impact on antiviral immunity is much less studied. Furthermore, neutrophil function in tumor pathogenesis and cancer treatment has recently received much attention, particularly within the context of oncolytic virus infection where neutrophils produce antitumor cytokines and enhance oncolysis. In this review, multiple functions of neutrophils in viral infections and immunity are discussed. Understanding the role of neutrophils during viral infection may provide insight into the pathogenesis of virus infections and the outcome of virus-based therapies.
Inflammasome activation by danger signals in ischemia/reperfusion (I/R) injury is responsible for the sterile inflammatory response. Signals triggering formation and activation of the inflammasome ...involve the generation of oxidative stress. The aim of this study was to examine the molecular mechanisms of inflammasome activation and the involvement of reactive oxygen species in hepatic I/R. I/R induced the formation of nucleotide‐binding domain leucine‐rich repeat containing family pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes and the subsequent serum release of interleukin 1β. Pannexin‐1 inhibitor and anti‐cathepsin B antibody attenuated I/R‐induced inflammasome activation and hepatic injury. The expression of the thioredoxin‐interacting protein gene and the interaction between NLRP3 and the thioredoxin‐interacting protein increased after I/R. Treatment with the antioxidant N‐acetylcysteine significantly attenuated protein conversion of interleukin 1β after hepatic I/R. Moreover, pannexin‐1 protein expression and cathepsin B release were strongly attenuated by N‐acetylcysteine. The depletion of Kupffer cells with gadolinium chloride markedly decreased NLRP3 and AIM2 inflammasome expression and activation of their signaling pathways, and also reduced the level of caspase‐1 protein in F4/80‐positive cells. Our findings suggest that reactive‐oxygen‐species‐mediated activation of NLRP3 and AIM2 inflammasomes leads to I/R‐induced inflammatory responses in which Kupffer cells play a crucial role. STRUCTURED DIGITAL ABSTRACT: Panx1 physically interacts with Casp1 and asc by anti bait coip (View interaction) asc physically interacts with Aim2 by anti bait coip (View interaction)
Neutrophil extracellular traps (NETs; webs of DNA coated in antimicrobial proteins) are released into the vasculature during sepsis where they contribute to host defense, but also cause tissue damage ...and organ dysfunction. Various components of NETs have also been implicated as activators of coagulation. Using multicolor confocal intravital microscopy in mouse models of sepsis, we observed profound platelet aggregation, thrombin activation, and fibrin clot formation within (and downstream of) NETs in vivo. NETs were critical for the development of sepsis-induced intravascular coagulation regardless of the inciting bacterial stimulus (gram-negative, gram-positive, or bacterial products). Removal of NETs via DNase infusion, or in peptidylarginine deiminase-4–deficient mice (which have impaired NET production), resulted in significantly lower quantities of intravascular thrombin activity, reduced platelet aggregation, and improved microvascular perfusion. NET-induced intravascular coagulation was dependent on a collaborative interaction between histone H4 in NETs, platelets, and the release of inorganic polyphosphate. Real-time perfusion imaging revealed markedly improved microvascular perfusion in response to the blockade of NET-induced coagulation, which correlated with reduced markers of systemic intravascular coagulation and end-organ damage in septic mice. Together, these data demonstrate, for the first time in an in vivo model of infection, a dynamic NET–platelet–thrombin axis that promotes intravascular coagulation and microvascular dysfunction in sepsis.
•In vivo imaging reveals a NET–platelet–thrombin axis that promotes intravascular coagulation in sepsis.•Inhibition of NETs during sepsis reduces intravascular coagulation, improves microvascular perfusion, and reduces organ damage.
The orientation of galaxy spin vectors within the large-scale structure has been considered an important test of our understanding of structure formation. We investigate the angular changes of galaxy ...spin vectors in clusters-denser environments than are normally focused upon-using hydrodynamic zoomed simulations of 17 clusters YZiCS and a set of complementary controlled simulations. The magnitude by which galaxies change their spin vector is found to be a function of their rotational support, with larger cumulative angular changes of spin vectors when they have initially lower Vθ/ . We find that both mergers and tidal perturbations can significantly swing spin vectors, with larger changes in spin vector for smaller pericenter distances. Strong tidal perturbations are also correlated with the changes in stellar mass and specific angular momentum of satellite galaxies. However, changes in spin vector can often result in a canceling out of previous changes. As a result, the integrated angular change is always much larger than the angular change measured at any instant. Also, overall, the majority of satellite galaxies do not undergo mergers or sufficiently strong tidal perturbation after infall into clusters, and thus they end up suffering little change to their spin vectors. Taken as a whole, these results suggest that any signatures of spin alignment from the large-scale structure will be preserved in the cluster environment for many gigayears.
d-Galactosamine (GalN) and lipopolysaccharide (LPS) are commonly used to study mechanisms of hepatic malfunction that result in hepatic inflammation and subsequent fulminant hepatic failure. ...Inflammasomes are intracellular multiprotein complexes that in response to cellular danger signals trigger the biological maturation of proinflammatory cytokines. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that induces anti-inflammatory and antioxidant activity against oxidative cellular stress. This study examined activation of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome in GalN/LPS-induced hepatic injury and the role of HO-1 in the signaling pathways of inflammasome. Mice (C57BL/6) were pretreated twice with hemin (HO-1 inducer, 30mg/kg) and zinc protoporphyrin (ZnPP; HO-1 inhibitor, 10mg/kg) at 12 and 2h before GalN (800mg/kg)/LPS (40μg/kg) administration. HO-1 induction with hemin reversed the lethality induced by GalN/LPS administration, and ZnPP pretreatment blocked this change. Lipid peroxidation markedly increased after GalN/LPS treatment, whereas glutathione content decreased in the GalN/LPS group. These changes were attenuated by hemin, but ZnPP reversed the effects of hemin. Serum levels of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β increased after GalN/LPS treatment; these increases were attenuated by hemin. Hepatic mRNA levels of TNF-α, IL-1β, and NLRP3 increased after GalN/LPS treatment, and hemin attenuated increases in TNF-α and IL-1β. After GalN/LPS treatment, the hepatic expression of NLRP3, ASC, and caspase-1 (p10) was increased. In immunoprecipitation studies, hemin attenuated the interaction of NLRP3 with ASC and caspase-1. GalN/LPS induced expression of the thioredoxin-interacting protein (TXNIP) gene and the interaction between NLRP3 and TXNIP; again, hemin attenuated these effects. The effects of hemin were reversed by ZnPP. Our findings suggest that activation of the NLRP3 inflammasome leads to a GalN/LPS-induced inflammatory response through TXNIP–NLRP3 interaction. Furthermore, HO-1 overexpression may protect the liver against GalN/LPS-induced inflammation through suppression of the NLRP3 signaling pathway.
Two red clumps (RCs) observed in the color-magnitude diagram of the Milky Way bulge are widely accepted as evidence for an X-shaped structure that originated from the bar instability. A drastically ...different interpretation has been suggested, however, based on the He-enhanced multiple stellar population phenomenon as is observed in globular clusters (GCs). Because these two scenarios imply very different pictures of the formation of the bulge and elliptical galaxies, understanding the origin of the double RC is of crucial importance. Here we report our discovery that the stars in the two RCs show a significant (>5.3 ) difference in CN-band strength, in stark contrast to that expected in the X-shaped bulge scenario. The difference in CN abundance and the population ratio between the two RCs are comparable to those observed in GCs between the first- and later-generation stars. Because CN-strong stars trace a population with enhanced N, Na, and He abundances that originated in GCs, this is direct evidence that the double RC is due to the multiple population phenomenon, and that a significant population of stars in the Milky Way bulge were assembled from disrupted proto-GCs. Our result also calls for the major revision of the 3D structure of the Milky Way bulge, given that the current view is based on the previous interpretation of the double RC phenomenon.
Highlights • Platelets play a critical role in the host immune response as an immune cell. • Platelets contribute neutrophil extracellular trap production, maximize inflammation. • Uncontrolled NET ...production drives harmful effect on various inflammatory diseases. • NETs and their components also largely culminate in platelet activation.
Fear of Cancer Recurrence (FCR) in cancer survivors has been insufficiently addressed despite its imperativeness in cancer journey. Although several studies have investigated healthcare ...professionals' experience with FCR in cancer survivors, a medical social work perspective has rarely been reflected. This study aimed to explore Korean medical social workers' experience with intervening FCR in cancer survivors.
Snowball sampling recruited 12 experienced medical social workers intervening with cancer survivors at tertiary or university cancer hospitals in South Korea. Individual and focus-group interviews (FGI) were conducted with the medical social workers. The interviews were recorded, transcribed, and analyzed by using an inductive qualitative content analysis.
Content analysis of the interviews extracted the following major themes regarding FCR in cancer survivors. First, when and how FCR among cancer survivors emerged at the early stage of medical social work interventions was identified. Second, how medical social workers dealt with FCR in cancer survivors was illustrated. Third, the responses of cancer survivors to medical social work interventions for FCR were assessed. Finally, the internal and external issues underlying the medical social work interventions for FCR among cancer survivors were revealed and discussed.
Based on the results, this study suggested the implications on dealing with FCR in cancer survivors in the realm of medial social work profession. Furthermore, it expanded the discussion about FCR in cancer survivors from cancer hospitals to community.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although first-line crizotinib treatment leads to clinical benefit in
lung cancer, high prevalence of crizotinib-resistant ROS1-G2032R (ROS1
) mutation and progression in the central nervous system ...(CNS) represents a therapeutic challenge. Here, we investigated the antitumor activity of repotrectinib, a novel next-generation ROS1/TRK/ALK-tyrosine kinase inhibitor (TKI) in
patient-derived preclinical models.
Antitumor activity of repotrectinib was evaluated in
patient-derived preclinical models including treatment-naïve and ROS1
models and was further demonstrated in patients enrolled in an on-going phase I/II clinical trial (NCT03093116). Intracranial antitumor activity of repotrectinib was evaluated in a brain-metastasis mouse model.
Repotrectinib potently inhibited
and
tumor growth and ROS1 downstream signal in treatment-naïve YU1078 compared with clinically available crizotinib, ceritinib, and entrectinib. Despite comparable tumor regression between repotrectinib and lorlatinib in YU1078-derived xenograft model, repotrectinib markedly delayed the onset of tumor recurrence following drug withdrawal. Moreover, repotrectinib induced profound antitumor activity in the CNS with efficient blood-brain barrier penetrating properties. Notably, repotrectinib showed selective and potent
and
activity against ROS1
. These findings were supported by systemic and intracranial activity of repotrectinib observed in patients enrolled in the on-going clinical trial.
Repotrectinib is a novel next-generation ROS1-TKI with improved potency and selectivity against treatment-naïve and ROS1
with efficient CNS penetration. Our findings suggest that repotrectinib can be effective both as first-line and after progression to prior ROS1-TKI.
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