Trimethylation at histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) controls gene activity during development and differentiation. Whether H3K4me3 and H3K27me3 changes dynamically in response to ...altered microenvironmental conditions, including low-oxygen conditions commonly present in solid tumors, is relatively unknown. Demethylation of H3K4me3 and H3K27me3 is mediated by oxygen and 2-oxoglutarate dioxygenases enzymes, suggesting that oxygen deprivation (hypoxia) may influence histone trimethylation. Using the MCF7 breast epithelial adenocarcinoma cell model, we have determined the relationship between epigenomic and transcriptomic reprogramming as a function of fluctuating oxygen tension.
We find that in MCF7, H3K4me3 and H3K27me3 marks rapidly increase at specific locations throughout the genome and are largely reversed upon reoxygenation. Whereas dynamic changes are relatively highest for H3K27me3 marking under hypoxic conditions, H3K4me3 occupation is identified as the defining epigenetic marker of transcriptional control. In agreement with the global increase of H3K27 trimethylation, we provide direct evidence that the histone H3K27me3 demethylase KDM6B/JMJD3 is inactivated by limited oxygen. In situ immunohistochemical analysis confirms a marked rise of histone trimethylation in hypoxic tumor areas. Acquisition of H3K27me3 at H3K4me3-marked loci results in a striking increase in "bivalent" epigenetic marking. Hypoxia-induced bivalency substantially overlaps with embryonal stem cell-associated genic bivalency and is retained at numerous loci upon reoxygenation. Transcriptional activity is selectively and progressively dampened at bivalently marked loci upon repeated exposure to hypoxia, indicating that this subset of genes uniquely maintains the potential for epigenetic regulation by KDM activity.
These data suggest that dynamic regulation of the epigenetic state within the tumor environment may have important consequences for tumor plasticity and biology.
•Ability of AWBs for heavy metal detoxification was evaluated.•Influential factors on heavy metal biosorption were presented.•Insights of binding mechanism were revealed and essential tools were ...introduced.•Merits and demerits of pretreatment methods for better biosorbents were highlighted.•Recommendation to use AWBs as green and cost-effective biosorbents was made.
This critical review discusses the potential use of agricultural waste based biosorbents (AWBs) for sequestering heavy metals in terms of their adsorption capacities, binding mechanisms, operating factors and pretreatment methods. The literature survey indicates that AWBs have shown equal or even greater adsorption capacities compared to conventional adsorbents. Thanks to modern molecular biotechnologies, the roles of functional groups in biosorption process are better understood. Of process factors, pH appears to be the most influential. In most cases, chemical pretreatments bring about an obvious improvement in metal uptake capacity. However, there are still several gaps, which require further investigation, such as (i) searching for novel, multi-function AWBs, (ii) developing cost-effective modification methods and (iii) assessing AWBs under multi-metal and real wastewater systems. Once these challenges are settled, the replacement of traditional adsorbents by AWBs in decontaminating heavy metals from wastewater can be expected in the future.
We present a compilation of properties of the 105,783 quasars in the Sloan Digital Sky Survey Data Release 7 (DR7) quasar catalog. In this product, we compile continuum and emission line measurements ...around the H Delta *a, H Delta *b, Mg II, and C IV regions, as well as other quantities such as radio properties, and flags indicating broad absorption line quasars, disk emitters, etc. We also compile virial black hole mass estimates based on various calibrations. For the fiducial virial mass estimates we use the Vestergaard & Peterson (VP06) calibrations for H Delta *b and C IV, and our own calibration for Mg II which matches the VP06 H Delta *b masses on average. We describe the construction of this catalog and discuss its limitations. The catalog and its future updates will be made publicly available online.
Abstract Mutations in the LRRK2 gene represent the most common genetic cause of late onset Parkinson's disease. The physiological and pathological roles of LRRK2 are yet to be fully determined but ...evidence points towards LRRK2 mutations causing a gain in kinase function, impacting on neuronal maintenance, vesicular dynamics and neurotransmitter release. To explore the role of physiological levels of mutant LRRK2, we created knock-in (KI) mice harboring the most common LRRK2 mutation G2019S in their own genome. We have performed comprehensive dopaminergic, behavioral and neuropathological analyses in this model up to 24 months of age. We find elevated kinase activity in the brain of both heterozygous and homozygous mice. Although normal at 6 months, by 12 months of age, basal and pharmacologically induced extracellular release of dopamine is impaired in both heterozygous and homozygous mice, corroborating previous findings in transgenic models over-expressing mutant LRRK2. Via in vivo microdialysis measurement of basal and drug-evoked extracellular release of dopamine and its metabolites, our findings indicate that exocytotic release from the vesicular pool is impaired. Furthermore, profound mitochondrial abnormalities are evident in the striatum of older homozygous G2019S KI mice, which are consistent with mitochondrial fission arrest. We anticipate that this G2019S mouse line will be a useful pre-clinical model for further evaluation of early mechanistic events in LRRK2 pathogenesis and for second-hit approaches to model disease progression.
The most precise determination of the neutron lifetime using the beam method was completed in 2005 and reported a result of τ(n)=(886.3±1.2stat±3.2syst) s. The dominant uncertainties were attributed ...to the absolute determination of the fluence of the neutron beam (2.7 s). The fluence was measured with a neutron monitor that counted the neutron-induced charged particles from absorption in a thin, well-characterized 6Li deposit. The detection efficiency of the monitor was calculated from the areal density of the deposit, the detector solid angle, and the evaluated nuclear data file, ENDF/B-VI 6Li(n,t)4He thermal neutron cross section. In the current work, we measure the detection efficiency of the same monitor used in the neutron lifetime measurement with a second, totally absorbing neutron detector. This direct approach does not rely on the 6Li(n,t)4He cross section or any other nuclear data. The detection efficiency is consistent with the value used in 2005 but is measured with a precision of 0.057%, which represents a fivefold improvement in the uncertainty. We verify the temporal stability of the neutron monitor through ancillary measurements, allowing us to apply the measured neutron monitor efficiency to the lifetime result from the 2005 experiment. The updated lifetime is τ(n)=(887.7±1.2stat±1.9syst) s.
Using a homogenous sample of 38,208 quasars with a sky coverage of ~4000 deg2 drawn from the Sloan Digital Sky Survey Data Release Five quasar catalog, we study the dependence of quasar clustering on ...luminosity, virial black hole (BH) mass, quasar color, and radio loudness. At z < 2.5, quasar clustering depends weakly on luminosity and virial BH mass, with typical uncertainty levels ~10% for the measured correlation lengths. These weak dependences are consistent with models in which substantial scatter between quasar luminosity, virial BH mass, and the host dark matter halo mass has diluted any clustering difference, where halo mass is assumed to be the relevant quantity that best correlates with clustering strength. However, the most luminous and most massive quasars are more strongly clustered (at the ~2 sigma level) than the remainder of the sample, which we attribute to the rapid increase of the bias factor at the high-mass end of host halos. We do not observe a strong dependence of clustering strength on quasar colors within our sample. On the other hand, radio-loud quasars are more strongly clustered than are radio-quiet quasars matched in redshift and optical luminosity (or virial BH mass), consistent with local observations of radio galaxies and radio-loud type 2 active galactic nuclei. Thus, radio-loud quasars reside in more massive and denser environments in the biased halo clustering picture. Using the Sheth et al. (2001) formula for the linear halo bias, the estimated host halo mass for radio-loud quasars is ~1013 h -1 M , compared to ~2 X 1012 h -1 M for radio-quiet quasar hosts at z ~ 1.5.
Activation of p38 mitogen-activated protein kinase (MAPK) plays an important role in apoptotic cell death. The role of p38 MAPK in myocardial injury caused by ischemia/reperfusion, an extreme stress ...to the heart, is unknown.
Studies were performed with isolated, Langendorff-perfused rabbit hearts. Ischemia alone caused a moderate but transient increase in p38 MAPK activity (3.5-fold increase, P<0.05 versus basal). Ischemia followed by reperfusion further activated p38 MAPK, and the maximal level of activation (6.3-fold, P<0.01) was reached 10 minutes after reperfusion. Administration of SB 203580, a p38 MAPK inhibitor, decreased myocardial apoptosis (14.7+/-3.2% versus 30.6+/-3.5% in vehicle, P<0.01) and improved postischemic cardiac function. The cardioprotective effects of SB 203580 were closely related to its inhibition of p38 MAPK. Administering SB 203580 before ischemia and during reperfusion completely inhibited p38 MAPK activation and exerted the most cardioprotective effects. In contrast, administering SB 203580 10 minutes after reperfusion (a time point when maximal MAPK activation had already been achieved) failed to convey significant cardioprotection. Moreover, inhibition of p38 MAPK attenuated myocardial necrosis after a prolonged reperfusion.
These results demonstrate that p38 MAPK plays a pivotal role in the signal transduction pathway mediating postischemic myocardial apoptosis and that inhibiting p38 MAPK may attenuate reperfusion injury.
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