We present an analysis of the growth of black holes through accretion and bulges through star formation in 33 galaxies at the centers of cooling flows. Most of these systems show evidence of cavities ...in the intracluster medium (ICM) inflated by radio jets emanating from their active galactic nuclei (AGNs). We present a new and extensive analysis of X-ray cavities in these systems. We find that AGNs are energetically able to balance radiative losses (cooling) from the ICM in more than half of our sample. We examine the relationship between cooling and star formation and find that the star formation rates are approaching or are comparable to X-ray and far-UV limits on the rates of gas condensation onto the central galaxy. The vast gulf between radiative losses and the sink of cooling material, which has been the primary objection to cooling flows, has narrowed significantly. Using the cavity (jet) powers, we place strong lower limits on the rate of growth of the central black holes, and we find that they are growing at an average rate of 60.1 M sub( )yr super(-1), with some systems growing as quickly as 61 M sub( )yr super(-1). We find a trend between bulge growth (star formation) and black hole growth that is approximately in accordance with the slope of the local (Magorrian) relation between black hole and bulge mass, but the scatter suggests that bulges and black holes do not necessarily grow in lockstep. Bondi accretion can power the low-luminosity sources, provided the nuclear gas density rises as 6r super(-1) to the Bondi radius, but is probably too feeble to fuel the most powerful outbursts.
Using broadband optical imaging and Chandra X-ray data for a sample of 46 cluster central dominant galaxies (CDGs), we investigate the connection between star formation, the intracluster medium ...(ICM), and the central active galactic nucleus (AGN). We report the discovery of a remarkably sharp threshold for the onset of star formation that occurs when the central cooling time of the hot atmosphere falls below image yr, or equivalently when the central entropy falls below image30 keV cm super(2). In addition to this criterion, star formation in cooling flows also appears to require that the X-ray and galaxy centroids lie within image20 kpc of each other and that the jet (cavity) power is smaller than the X-ray cooling luminosity. These three criteria, together with the high ratio of cooling time to AGN outburst (cavity) age across our sample, directly link the presence of star formation and AGN activity in CDGs to cooling instabilities in the intracluster plasma. Our results provide compelling evidence that AGN feedback into the hot ICM is largely responsible for regulating cooling and star formation in the cores of clusters, leading to the significant growth of supermassive black holes in CDGs at late times.
We present an analysis of 16 galaxy clusters, one group, and one galaxy drawn from the Chandra Data Archive. These systems possess prominent X-ray surface brightness depressions associated with ...cavities or bubbles that were created by interactions between powerful radio sources and the surrounding hot gas. The central galaxies in these systems harbor radio sources with luminosities ranging between approx2 x 10 super(38) and 7 x 10 super(44) ergs s super(-1). The cavities have an average radius of approx10 kpc, and they lie at an average projected distance of approx20 kpc from the central galaxy. The minimum energy associated with the cavities ranges from pV approx 10 super(55) ergs in galaxies, groups, and poor clusters to pV approx 10 super(60) ergs in rich clusters. We evaluate the hypothesis that cooling in the hot gas can be quenched by energy injected into the surrounding gas by the rising bubbles. We find that the instantaneous mechanical luminosities required to offset cooling range between 1pV and 20pV per cavity. Nearly half of the systems in this study may have instantaneous mechanical luminosities large enough to balance cooling, at least for a short period of time, if the cavities are filled with a relativistic gas. We find a trend or upper envelope in the distribution of central X-ray luminosity versus instantaneous mechanical luminosity, with the sense that the most powerful cavities are found in the most X-ray-luminous systems. Such a trend would be expected if many of these systems produce bubbles at a rate that scales in proportion to the cooling rate of the surrounding gas. Finally, we use the X-ray cavities to measure the mechanical power of radio sources over six decades of radio luminosity, independently of the radio properties themselves. We find that the ratio of the instantaneous mechanical (kinetic) luminosity to the 1.4 GHz synchrotron luminosity ranges typically between a few and roughly a few thousand for luminous radio sources but can be several thousand for weaker sources. This wide range implies that the 1.4 GHz synchrotron luminosity is an unreliable gauge of the mechanical power of radio sources.
Most of the baryons in galaxy clusters reside between the galaxies in a hot, tenuous gas. The densest gas in their centres should cool and accrete onto giant central galaxies at rates of 10-1,000 ...solar masses per year. No viable repository for this gas, such as clouds or new stars, has been found. New X-ray observations, however, have revealed far less cooling below X-ray temperatures than expected, altering the previously accepted picture of cooling flows. As a result, most of the gas must be heated to and maintained at temperatures above ∼2 keV (ref. 3). The most promising heating mechanism is powerful radio jets emanating from supermassive black holes in the central galaxies of clusters. Here we report the discovery of giant cavities and shock fronts in a distant (z = 0.22) cluster caused by an interaction between a radio source and the hot gas surrounding it. The energy involved is ∼6 × 1061 erg, the most powerful radio outburst known. This is enough energy to quench a cooling flow for several Gyr, and to provide ∼1/3 keV per particle of heat to the surrounding cluster.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Myelin is required for the function of neuronal axons in the central nervous system, but the mechanisms that support myelin health are unclear. Although macrophages in the central nervous system have ...been implicated in myelin health
, it is unknown which macrophage populations are involved and which aspects they influence. Here we show that resident microglia are crucial for the maintenance of myelin health in adulthood in both mice and humans. We demonstrate that microglia are dispensable for developmental myelin ensheathment. However, they are required for subsequent regulation of myelin growth and associated cognitive function, and for preservation of myelin integrity by preventing its degeneration. We show that loss of myelin health due to the absence of microglia is associated with the appearance of a myelinating oligodendrocyte state with altered lipid metabolism. Moreover, this mechanism is regulated through disruption of the TGFβ1-TGFβR1 axis. Our findings highlight microglia as promising therapeutic targets for conditions in which myelin growth and integrity are dysregulated, such as in ageing and neurodegenerative disease
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The application of calcium- and magnesium-rich materials to soil, known as liming, has long been a foundation of many agro-ecosystems worldwide because of its role in counteracting soil acidity. ...Although liming contributes to increased rates of respiration from soil thereby potentially reducing soils ability to act as a CO₂ sink, the long-term effects of liming on soil organic carbon (Corg) sequestration are largely unknown. Here, using data spanning 129 years of the Park Grass Experiment at Rothamsted (UK), we show net Corg sequestration measured in the 0-23 cm layer at different time intervals since 1876 was 2-20 times greater in limed than in unlimed soils. The main cause of this large Corg accrual was greater biological activity in limed soils, which despite increasing soil respiration rates, led to plant C inputs being processed and incorporated into resistant soil organo-mineral pools. Limed organo-mineral soils showed: (1) greater Corg content for similar plant productivity levels (i.e. hay yields); (2) higher ¹⁴C incorporation after 1950s atomic bomb testing and (3) lower C : N ratios than unlimed organo-mineral soils, which also indicate higher microbial processing of plant C. Our results show that greater Corg sequestration in limed soils strongly reduced the global warming potential of long-term liming to permanent grassland suggesting the net contribution of agricultural liming to global warming could be lower than previously estimated. Our study demonstrates that liming might prove to be an effective mitigation strategy, especially because liming applications can be associated with a reduced use of nitrogen fertilizer which is a key cause for increased greenhouse gas emissions from agro-ecosystems.
Background
Mucinous differentiation occurs in 5–15 per cent of colorectal adenocarcinomas. This subtype of colorectal cancer responds poorly to chemoradiotherapy and has a worse prognosis. The ...genetic aetiology underpinning this cancer subtype lacks consensus. The aim of this study was to use meta‐analytical techniques to clarify the molecular associations of mucinous colorectal cancer.
Methods
This study adhered to MOOSE guidelines. Databases were searched for studies comparing KRAS, BRAF, microsatellite instability (MSI), CpG island methylator phenotype (CIMP), p53 and p27 status between patients with mucinous and non‐mucinous colorectal adenocarcinoma. A random‐effects model was used for analysis.
Results
Data from 46 studies describing 17 746 patients were included. Mucinous colorectal adenocarcinoma was associated positively with KRAS (odds ratio (OR) 1·46, 95 per cent c.i. 1·08 to 2·00, P = 0·014) and BRAF (OR 3·49, 2·50 to 4·87; P < 0·001) mutation, MSI (OR 3·98, 3·30 to 4·79; P < 0·001) and CIMP (OR 3·56, 2·85 to 4·43; P < 0·001), and negatively with altered p53 expression (OR 0·46, 0·31 to 0·67; P < 0·001).
Conclusion
The genetic origins of mucinous colorectal adenocarcinoma are predominantly associated with BRAF, MSI and CIMP pathways. This pattern of molecular alterations may in part explain the resistance to standard chemotherapy regimens seen in mucinous adenocarcinoma.
Mucinous colorectal cancer is more likely to be BRAF‐mutated, mismatch repair‐deficient and CpG island methylator phenotype – high. These genetic aberrations may account in some part for the resistance to chemoradiotherapy observed in this tumour subtype.
Mucinous cancer explored
ABSTRACT
The Chandra X‐ray Observatory has revealed X‐ray bubbles in the intracluster medium (ICM) of many nearby cooling‐flow clusters. The bubbles trace feedback that is thought to couple the ...central active galactic nucleus (AGN) to the ICM, helping to stabilize cooling flows and govern the evolution of massive galaxies. However, the prevalence and duty cycle of such AGN outbursts is not well understood. To this end, we study how cooling is balanced by bubble heating for complete samples of clusters (the Brightest 55 clusters of galaxies, hereafter B55, and the HIghest X‐ray FLUx Galaxy Cluster Sample, HIFLUGCS). We find that the radio luminosity of the central galaxy only exceeds 2.5 × 1030 erg s−1 Hz−1 in cooling‐flow clusters. This result implies a connection between the central radio source and the ICM, as expected if AGN feedback is operating. Additionally, we find a duty cycle for radio‐mode feedback, the fraction of time that a system possesses bubbles inflated by its central radio source, of ≳69 per cent for the B55 and ≳63 per cent for the HIFLUGCS. These duty cycles are lower limits since some bubbles are likely missed in existing images. We used simulations to constrain the bubble power that might be present and remain undetected in the cooling‐flow systems without detected bubbles. Among theses systems, almost all could have significant bubble power. Therefore, our results imply that the duty cycle of AGN outbursts with the potential to heat the gas significantly in cooling‐flow clusters is at least 60 per cent and could approach 100 per cent.
Response to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer is variable. Identification of biomarkers to predict response is desirable in order to provide prognostic information ...and targeted therapy. Several studies have investigated microsatellite instability (MSI) as a predictor of response to CRT with contradictory results. This study aims to clarify the effect of MSI status on response to CRT in locally advanced rectal cancer through systematic review and meta-analysis.
A systematic search of PubMed, Embase and Cochrane databases was performed for all studies relating to MSI and response to CRT in rectal cancer using the search algorithm (Microsatellite Instability) AND (Chemoradiotherapy) AND (Rectal Cancer). From each included study the number of patients with MSI tumors and Microsatellite Stable (MSS) tumors and the numbers achieving pathological complete response (pCR) were recorded. Pooled outcome measures were determined using a random effects model and the odds ratio estimated with variance and 95% confidence interval.
Nine published studies were identified reporting data on MSI and its effect on outcome after CRT for locally advanced rectal cancer. Five studies describing 5,877 patients included data on MSI and the number of patients achieving pCR. There was no significant association between MSI and pCR (MSI Vs MSS: 10.1% Vs 6.6%, OR 1.38, 95% CI: 0.7–2.72, p = 0.35).
This meta-analysis concludes that there appears to be no significant difference in pCR rate following CRT in patients with MSI versus MSS rectal tumors.
•Identification of biomarkers of response to neoadjuvant therapy is desirable.•Studies of MSI in neoadjuvant therapy are conflicting.•Meta-analysis finds no convincing association between MSI and response.
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