Detection of stellar light from quasar host galaxies at redshifts above 6.

The detection of starlight from the host galaxies of quasars during the reionization epoch (z > 6) has been elusive, even with deep Hubble Space Telescope observations1,2. The current highest redshift quasar host detected3, at z = 4.5, required the magnifying effect of a foreground lensing galaxy. Low-luminosity quasars4-6 from the Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP)7 mitigate the challenge of detecting their underlying, previously undetected host galaxies. Here we report rest-frame optical images and spectroscopy of two HSC-SSP quasars at z > 6 with the JWST. Using near-infrared camera imaging at 3.6 and 1.5 µm and subtracting the light from the unresolved quasars, we find that the host galaxies are massive (stellar masses of 13 × and 3.4 × 1010 M☉, respectively), compact and disc-like. Near-infrared spectroscopy at medium resolution shows stellar absorption lines in the more massive quasar, confirming the detection of the host. Velocity-broadened gas in the vicinity of these quasars enables measurements of their black hole masses (1.4 × 109 and 2.0 × 108 M☉, respectively). Their location in the black hole mass-stellar mass plane is consistent with the distribution at low redshift, suggesting that the relation between black holes and their host galaxies was already in place less than a billion years after the Big Bang.

An 800-million-solar-mass black hole in a significantly neutral Universe at a redshift of 7.5.

Quasars are the most luminous non-transient objects known and as a result they enable studies of the Universe at the earliest cosmic epochs. Despite extensive efforts, however, the quasar ULAS J1120 + 0641 at redshift z = 7.09 has remained the only one known at z > 7 for more than half a decade. Here we report observations of the quasar ULAS J134208.10 + 092838.61 (hereafter J1342 + 0928) at redshift z = 7.54. This quasar has a bolometric luminosity of 4 × 1013 times the luminosity of the Sun and a black-hole mass of 8 × 108 solar masses. The existence of this supermassive black hole when the Universe was only 690 million years old-just five per cent of its current age-reinforces models of early black-hole growth that allow black holes with initial masses of more than about 104 solar masses or episodic hyper-Eddington accretion. We see strong evidence of absorption of the spectrum of the quasar redwards of the Lyman α emission line (the Gunn-Peterson damping wing), as would be expected if a significant amount (more than 10 per cent) of the hydrogen in the intergalactic medium surrounding J1342 + 0928 is neutral. We derive such a significant fraction of neutral hydrogen, although the exact fraction depends on the modelling. However, even in our most conservative analysis we find a fraction of more than 0.33 (0.11) at 68 per cent (95 per cent) probability, indicating that we are probing well within the reionization epoch of the Universe.

SUMOylation facilitates the assembly of a Nuclear Factor-Y complex to enhance thermotolerance in Arabidopsis.

Heat stress (HS) has serious negative effects on plant development and has become a major threat to agriculture. A rapid transcriptional regulatory cascade has evolved in plants in response to HS. Nuclear Factor-Y (NF-Y) complexes are critical for this mechanism, but how NF-Y complexes are regulated remains unclear. In this study, we identified NF-YC10 (NF-Y subunit C10), a central regulator of the HS response in Arabidopsis thaliana, as a substrate of SUMOylation, an important post-translational modification. Biochemical analysis showed that the SUMO ligase SIZ1 (SAP AND MIZ1 DOMAIN-CONTAINING LIGASE1) interacts with NF-YC10 and enhances its SUMOylation during HS. The SUMOylation of NF-YC10 facilitates its interaction with and the nuclear translocation of NF-YB3, in which the SUMO interaction motif (SIM) is essential for its efficient association with NF-YC10. Further functional analysis indicated that the SUMOylation of NF-YC10 and the SIM of NF-YB3 are critical for HS-responsive gene expression and plant thermotolerance. These findings uncover a role for the SIZ1-mediated SUMOylation of NF-YC10 in NF-Y complex assembly under HS, providing new insights into the role of a post-translational modification in regulating transcription during abiotic stress responses in plants.

SUMOylation Stabilizes the Transcription Factor DREB2A to Improve Plant Thermotolerance.

Heat stress (HS) has serious effects on plant development, resulting in heavy agricultural losses. A critical transcription factor network is involved in plant adaptation to high temperature. DEHYDRATION RESPONSIVE ELEMENT-BINDING PROTEIN2A (DREB2A) is a key transcription factor that functions in plant thermotolerance. The DREB2A protein is unstable under normal temperature and is degraded by the 26S proteasome; however, the mechanism by which DREB2A protein stability dramatically increases in response to HS remains poorly understood. In this study, we found that the DREB2A protein of Arabidopsis (Arabidopsis thaliana) is stabilized under high temperature by the posttranslational modification SUMOylation. Biochemical data indicated that DREB2A is SUMOylated at K163, a conserved residue adjacent to the negative regulatory domain during HS. SUMOylation of DREB2A suppresses its interaction with BPM2, a ubiquitin ligase component, consequently increasing DREB2A protein stability under high temperature. In addition, analysis of plant heat tolerance and marker gene expression indicated that DREB2A SUMOylation is essential for its function in the HS response. Collectively, our data reveal a role for SUMOylation in the maintenance of DREB2A stability under high temperature, thus improving our understanding of the regulatory mechanisms underlying HS response in plant cells.

An ultraluminous quasar with a twelve-billion-solar-mass black hole at redshift 6.30.

So far, roughly 40 quasars with redshifts greater than z = 6 have been discovered. Each quasar contains a black hole with a mass of about one billion solar masses (10(9) M Sun symbol). The existence of such black holes when the Universe was less than one billion years old presents substantial challenges to theories of the formation and growth of black holes and the coevolution of black holes and galaxies. Here we report the discovery of an ultraluminous quasar, SDSS J010013.02+280225.8, at redshift z = 6.30. It has an optical and near-infrared luminosity a few times greater than those of previously known z > 6 quasars. On the basis of the deep absorption trough on the blue side of the Lyman-α emission line in the spectrum, we estimate the proper size of the ionized proximity zone associated with the quasar to be about 26 million light years, larger than found with other z > 6.1 quasars with lower luminosities. We estimate (on the basis of a near-infrared spectrum) that the black hole has a mass of ∼1.2 × 10(10) M Sun symbol, which is consistent with the 1.3 × 10(10) M Sun symbol derived by assuming an Eddington-limited accretion rate.

Inhibition of UDP-glucuronosyltransferases by different furoquinoline alkaloids.

Herbs are often administered in combination with therapeutic drugs, raising the possibility for herb-drug interactions (HDIs). Furoquinoline alkaloids are found in Rutaceae plants, which are structurally similar and have many medicinal properties. This study aims to investigate the inhibition of four furoquinoline alkaloids on the activity of UDP-glucuronosyltransferases (UGTs).The recombinant UGTs-catalyzed glucuronidation metabolism of 4-methylumbelliferone (4-MU) was utilized to investigate the inhibition potential. Inhibition type and parameters were determined, and in silico docking was employed to elucidate the inhibition difference of furoquinoline alkaloids towards UGTs.Dictamine, haplopine, γ-fagarine and skimmianine strongly inhibited UGT1A3, UGT1A7, UGT1A9 and UGT2B4, respectively. Among them, dictamnine inhibited more than 70% of the four UGTs. Inhibition kinetics determination showed that they all exerted competitive inhibition, and the inhibition kinetic constant (Ki) was determined to be 8.3, 7.2, 3.7 and 33.9 µM, respectively. In vitro-in vivo extrapolation (IVIVE) was employed to demonstrate the inhibition possibility for four alkaloids. Skimmianine was proved to be more suitable for clinical application. In silico docking study indicated that the hydrophobic interactions played a key role in the inhibition of furoquinoline alkaloids towards three of the four UGTs. In conclusion, monitoring the interactions between furoquinoline alkaloids and drugs mainly undergoing UGTs-catalyzed metabolism is necessary.

The Arabidopsis SUMO E3 Ligase AtMMS21 Dissociates the E2Fa/DPa Complex in Cell Cycle Regulation.

Development requires the proper execution and regulation of the cell cycle via precise, conserved mechanisms. Critically, the E2F/DP complex controls the expression of essential genes during cell cycle transitions. Here, we discovered the molecular function of the Arabidopsis thaliana SUMO E3 ligase METHYL METHANESULFONATE SENSITIVITY GENE21 (AtMMS21) in regulating the cell cycle via the E2Fa/DPa pathway. DPa was identified as an AtMMS21-interacting protein and AtMMS21 competes with E2Fa for interaction with DPa. Moreover, DPa is a substrate for SUMOylation mediated by AtMMS21, and this SUMOylation enhances the dissociation of the E2Fa/DPa complex. AtMMS21 also affects the subcellular localization of E2Fa/DPa. The E2Fa/DPa target genes are upregulated in the root of mms21-1 and mms21-1 mutants showed increased endoreplication. Overexpression of DPa affected the root development of mms21-1, and overexpression of AtMMS21 completely recovered the abnormal phenotypes of 35S:E2Fa-DPa plants. Our results suggest that AtMMS21 dissociates the E2Fa/DPa complex via competition and SUMOylation in the regulation of plant cell cycle.

A SUMO Ligase AtMMS21 Regulates the Stability of the Chromatin Remodeler BRAHMA in Root Development.

Chromatin remodeling is essential for gene expression regulation in plant development and response to stresses. Brahma (BRM) is a conserved ATPase in the SWI/SNF chromatin remodeling complex and is involved in various biological processes in plant cells, but the regulation mechanism on BRM protein remains unclear. Here, we report that BRM interacts with AtMMS21, a SUMO ligase in Arabidopsis (Arabidopsis thaliana). The interaction was confirmed in different approaches in vivo and in vitro. The mutants of BRM and AtMMS21 displayed a similar defect in root development. In the mms21-1 mutant, the protein level of BRM-GFP was significantly lower than that in wild type, but the RNA level of BRM did not change. Biochemical evidence indicated that BRM was modified by SUMO3, and the reaction was enhanced by AtMMS21. Furthermore, overexpression of wild-type AtMMS21 but not the mutated AtMMS21 without SUMO ligase activity was able to recover the stability of BRM in mms21-1 Overexpression of BRM in mms21-1 partially rescued the developmental defect of roots. Taken together, these results supported that AtMMS21 regulates the protein stability of BRM in root development.

Inhibition of Human Sulfotransferases by Phthalate Monoesters.

Objective: This study aimed to investigate the inhibition of human important phase II metabolic enzyme sulfotransferases (SULTs) by phthalate monoesters, which are important metabolites of phthalate esters (PAEs). Method: Recombinant SULT-catalyzed metabolism of p-nitrophenol (PNP) was employed as the probe reactions of SULTs to investigate the inhibition of 8 kinds of phthalate monoesters towards SULT isoforms. An in vitro incubation system was utilized for preliminary screening, and 100 µM of phthalate monoesters was used. Inhibition kinetics were carried out to determine the inhibition of SULTs by phthalate monoesters. Result: Multiple phthalate monoesters have been demonstrated to exert strong inhibition potential towards SULT1A1, SULT1B1, and SULT1E1, and no significant inhibition of phthalate monoesters towards SULT1A3 was found. The activity of SULT1A1 was strongly inhibited by mono-hexyl phthalate (MHP), mono-octyl phthalate (MOP), mono-benzyl phthalate (MBZP), and mono-ethylhexyl phthalate (MEHP). Monobutyl phthalate (MBP), MHP, MOP, mono-cyclohexyl phthalate (MCHP), and MEHP significantly inhibited the activity of SULT1B1. MHP, MOP, and MEHP significantly inhibited the activity of SULT1E1. MOP was chosen as the representative phthalate monoester to determine the inhibition kinetic parameters (Ki) towards SULT1B1 and SULT1E1. The inhibition kinetic parameters (Ki) were calculated to be 2.23 µM for MOP-SULT1B1 and 5.54 µM for MOP-SULT1E1. In silico docking method was utilized to understand the inhibition mechanism of SULT1B1 by phthalate monoesters. Conclusions: All these information will be beneficial for understanding the risk of phthalate monoester exposure from a new perspective.

Hydroxylated polychlorinated biphenyls (OH-PCBs) exert strong inhibitory effects towards human carboxylesterases (CESs).

Polychlorinated biphenyls (PCBs) have been reported to pose a severe risk towards human health, and hydroxylated polychlorinated biphenyls (OH-PCBs) were potential substances basis for PCBs' toxicity. This study aims to determine the inhibition of OH-PCBs towards human carboxylesterases (CESs), including CES1 and CES2. For phenotypic analysis of CES1 and CES2 activity, we used the hydrolysis metabolism of 2-(2-benzoyl3-methoxyphenyl) benzothiazole (BMBT) and fluorescein diacetate (FD) catalyzed by human liver microsomes (HLMs) as the probe reactions. Preliminary inhibition screening showed that the inhibition potential of OH-PCBs towards CES1 and CES2 increased with the increased numbers of chlorine atoms in OH-PCBs. Both 2'-OH-PCB61 and 2'-OH-PCB65 showed concentration-dependent inhibition towards both CES1 and CES2. Lineweaver-Burk plots showed that 2'-OH-PCB61 and 2'-OH-PCB65 exerted non-competitive inhibition towards CES1 and competitive inhibition towards CES2. The inhibition kinetics parameters (Ki) were 6.8 µM and 7.0 µM for 2'-OH-PCB61 and 2'-OH-PCB65 towards CES1, respectively. The inhibition kinetics parameters (Ki) were 1.4 µM and 1.0 µM for 2'-OH-PCB61 and 2'-OH-PCB65 towards CES2, respectively. In silico docking methods elucidate the contribution of hydrogen bonds and hydrophobic contacts towards the binding of 2'-OH-PCB61 and 2'-OH-PCB65 with CES1 and CES2. All these results will provide a new perspective for elucidation of toxicity mechanism of PCBs and OH-PCBs.

Inhibition of UDP-glucuronosyltransferases (UGTs) by bromophenols (BPs).

Bromophenols (BPs) are important organic compounds which have become dominant pollutants during these years. Our present study investigated the potential inhibition behaviour of BPs on the activity of one of the most important phase II drug-metabolizing enzymes (DMEs), UDP-glucuronosyltransferases (UGTs). Recombinant UDP-glucuronosyltransferases (UGTs)-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was utilized as the probe reaction. 100 µM of BPs was utilized as the inhibition screening concentrations, and the complete inhibition profile of UGT isoforms by BPs was obtained. UGT1A7 was the most vulnerable UGT isoform towards BPs. Some structure-activity relationship for the inhibition of UGTs by BPs was found, and this relationship can be furtherly explained by the hydrophobic contacts of BPs with the activity cavity of UGTs using in silico docking method. The inhibition kinetics determination showed that the inhibition kinetic parameter Ki value was calculated to be 2.85, 3.99 and 31.00 µM for the inhibition of UGT1A3, UGT1A7, and UGT2B7 by representative BPs, 2,4,6-TBP. Combined with in vivo exposure concentration of 2,4,6-TBP, in vitro-in vivo extrapolation (IVIVE) was employed to demonstrate the moderate possibility for the inhibition of UGT1A3 and UGT1A7 by 2,4,6-TBP. In conclusion, our study gave the full description towards the inhibition of BPs towards UGT isoforms, which will provide a new perspective for elucidating the toxicity mechanism of bromophenols (BPs).

A SUMO ligase AtMMS21 regulates activity of the 26S proteasome in root development.

The 26S proteasome is a multi-subunit protease controlling most of the cytosolic and nuclear protein turnover, regulating many cellular events in eukaryotes. However, functional modification on this complex remains unclear. Here, we showed a novel mechanism that a SUMO ligase AtMMS21 regulates activity of the 26S proteasome in root development of Arabidopsis. Our in vitro and in vivo data supported that AtMMS21 interacts with RPT2a, a subunit of the 26S proteasome. The mutants of AtMMS21 and RPT2a display similar developmental defect of roots, suggesting their association in this process. In addition, RPT2a is modified by SUMO3, potentially related to AtMMS21. During development, the activity of the 26S proteasome is lower in both mutants of AtMMS21 and RPT2a, compared with that of wild type. Furthermore, the protein level but not the RNA level of RPT2a is decreased in the absence of AtMMS21, implying stability regulation of the proteasome complex through the AtMMS21-RPT2a interaction. Taken together, the current study would improve our understanding on the regulatory mechanism of the 26S proteasome via protein modification in root development.

Regeneration of Solanum nigrum by somatic embryogenesis, involving frog egg-like body, a novel structure.

A new protocol was established for the regeneration of Solanum nigrum by frog egg-like bodies (FELBs), which are novel somatic embryogenesis (SE) structures induced from the root, stem, and leaf explants. The root, stem, and leaf explants (93.33%, 85.10%, and 100.00%, respectively) were induced to form special embryonic calli on Murashige and Skoog (MS) medium containing 1.0 mg/L 2,4-dichlorophenoxyacetic acid, under dark condition. Further, special embryonic calli from the root, stem, and leaf explants (86.97%, 83.30%, and 99.47%, respectively) were developed into FELBs. Plantlets of FELBs from the three explants were induced in vitro on MS medium supplemented with 5.0 mg/L 6-benzylaminopurine and 0.1 mg/L gibberellic acid, and 100.00% plantlet induction rates were noted. However, plantlet induction in vivo on MS medium supplemented with 20 mg/L thidiazuron showed rates of 38.63%, 15.63%, and 61.30% for the root, stem, and leaf explants, respectively, which were lower than those of the in vitro culture. Morphological and histological analyses of FELBs at different development stages revealed that they are a novel type of SE structure that developed from the mesophyll (leaf) or cortex (stem and root) cells of S. nigrum.

Meta-analysis of randomized trials comparing the effectiveness of on-pump and off-pump coronary artery bypass.

BACKGROUND: The growing enthusiasm for coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) is emerging, but the role of off-pump coronary artery bypass (OPCAB) in clinical practice remains controversial. The purpose of this study was to assess differences in the incidences of stroke, atrial fibrillation (AF), and myocardial infarction (MI) between OPCAB and conventional coronary artery bypass grafting (CCABG) by meta-analyses of randomized clinical trials. METHODS: A literature search for the period before March 2010 supplemented with manual bibliographic review was performed for all Chinese or English publications in Medline, the Science Citation Index Expanded, the Cochrane Central Register of Controlled Trials (CENTRAL) and CBMdisc. A systematic overview (meta-analyses) of randomized clinical trials was conducted to evaluate the differences between OPCAB and CCABG in the incidences of stroke, AF, and MI. The meta-analysis was performed using RevMan 5 software. RESULTS: Forty-three randomized clinical trials were selected for meta-analysis after screening a total of 356 references, with 8104 patients in the OPCAB group and 8724 cases in the CCABG group. The meta-analyses of these trials showed no significant difference between OPCAB and CCABG in the incidences of stroke (odds ratio (OR) = 0.80, 95% confidence interval (CI) = 0.52 - 1.22, P = 0.30) and MI (OR = 0.73, 95%CI = 0.52 - 1.02, P = 0.06). However, we found a significantly reduced risk of AF (OR = 0.65, 95%CI = 0.52 - 0.82, P = 0.0002) in off-pump patients. CONCLUSIONS: Our meta-analyses suggest that OPCAB reduces the risk of postoperative AF compared with CCABG, but there is no significant difference in the incidences of stroke and MI between OPCAB and CCABG.

Comparison of compensatory sweating and quality of life following thoracic sympathetic block for palmar hyperhidrosis: electrocautery hook versus titanium clip.

BACKGROUND: Video-assisted thoracic sympathetic block is an effective, safe, and minimally invasive method for treatment of primary hyperhidrosis. The purpose of this study was to decide which one of using electrocautery hook and titanium clip is the appropriate procedure for primary palmar hyperhidrosis by assessing the compensatory sweating (CS) and quality of life (QOL) of patients after sympathetic block. METHODS: Between October 2007 to August 2010, 120 patients with primary palmar hyperhidrosis were randomly divided into two groups, electrocautery hook group (60 patients) and titanium clip group (60 patients). All patients were treated by sympathetic block at T4 level. The CS was graded based on severity and location; the QOL was classified to 5 different levels based upon the summed total scores (range from 20 to 100) before and after surgery. The variables were compared. RESULTS: The postoperative follow-up period was 2 months. All patients were cured. Three patients in electrocautery hook group and 1 patient in titanium clip group had a unilateral pneumothorax on chest X-ray, but none of them was necessary to have chest drainage. Neither perioperative mortality nor serious complications such as cardiac arrhythmia or arrest were observed during the operation. No bradycardia or Horner's syndrome occured. CS was not more common in patients in titanium clip group than in those in electrocautery hook group (P = 0.001). Moderate and severe CS was few in all patients, and there was no significant difference between two groups (P = 0.193). Most of the patients feel a notable improvement of the the QOL; nevertheless, there was no significant difference between the groups (P = 0.588). CONCLUSIONS: Both electrocautery hook and titanium clip used for sympathetic block at the T4 level are effective, safe, and minimally invasive for palmar hyperhidrosis. Because of the lower severity of CS and the similar improvements in the QOL after operation, we prefer to use of titanium clip for treating palmar hyperhidrosis.

XAF1 as a prognostic biomarker and therapeutic target in squamous cell lung cancer.

BACKGROUND: X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is a new tumor suppressor. Low expression of XAF1 is associated with poor prognosis of human cancers. However, the effect of XAF1 on lung cancer remains unknown. In this study, we investigated the expression of XAF1 and its role in squamous cell lung cancer. METHODS: Cancer tissues, cancer adjacent tissues and normal lung tissues were collected from 51 cases of squamous cell lung cancer. The expression of XAF1 mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR). The expression of XAF1 protein was determined by Western blotting and immunohistochemical staining. Ad5/F35-XAF1 virus was generated. Cell proliferation and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and flow cytometry (FACS), respectively. RESULTS: The levels of XAF1 protein and mRNA in cancer tissues were significantly lower than those in cancer adjacent and normal lung tissues (P < 0.05). The low expression of XAF1 was associated with tumor grade, disease stage, differentiation status and lymph node metastasis in squamous cell lung cancer patients. The restoration of XAF1 expression mediated by Ad5/F35-XAF1 virus significantly inhibited cell proliferation and induced apoptosis in a dose- and time-dependent manner. CONCLUSION: XAF1 is a valuable prognostic marker in squamous cell lung cancer and may be a potential candidate gene for lung cancer therapy.