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Homodimeric PHD-domain containing Rco1 constitutes a critical interaction hub within the Rpd3S histone deacetylase complex. - The Journal of biological chemistry
Recognition of histone post-translational modifications (PTMs) is pivotal for directing chromatin-modifying enzymes to specific genomic regions and regulating their activities. Emerging evidence suggests that other structural features of nucleosomes also contribute to precise targeting of downstream chromatin complexes, such as linker DNA, the histone globular domain and nucleosome spacing. However, how chromatin complexes coordinate individual interactions to achieve high affinity and specificity remains unclear. The Rpd3S histone deacetylase utilizes the chromodomain-containing Eaf3 subunit and the PHD-domain-containing Rco1 subunit to recognize nucleosomes that are methylated at lysine 36 of histone H3 (H3K36me). We have shown previously that the binding of Eaf3 to H3K36me can be allosterically activated by Rco1. To investigate how this chromatin recognition module is regulated in the context of the Rpd3S complex, we first determined the subunit-interaction network of Rpd3S. Interestingly, we found that Rpd3S contains two copies of the essential subunit Rco1, and both copies of Rco1 are required for full functionality of Rpd3S. Our functional dissection of Rco1 revealed that besides its known chromatin-recognition interfaces, other regions of Rco1 are also critical for Rpd3S to recognize its nucleosomal substrates and function in vivo. This unexpected result uncovered an important and understudied aspect of chromatin recognition. It suggests that precisely reading modified chromatin may not only need the combined actions of reader domains but also require an internal signaling circuit that coordinates the individual actions in a productive way.Copyright Â© 2016, The American Society for Biochemistry and Molecular Biology.
Effects of phoxim on nutrient metabolism and insulin signaling pathway in silkworm midgut. - Chemosphere
Silkworm (Bombyx mori) is an important economic insect. Each year, poisoning caused by phoxim pesticide leads to huge economic losses in sericulture in China. Silkworm midgut is the major organ for food digestion and nutrient absorption. In this study, we found that the activity and expression of nutrition metabolism-related enzymes were dysregulated in midgut by phoxim exposure. DGE analysis revealed that 40 nutrition metabolism-related genes were differentially expressed. qRT-PCR results indicated that the expression levels of insulin/insulin growth factor signaling (IIS) pathway genes Akt, PI3K, PI3K60, PI3K110, IRS and PDK were reduced, whereas PTEN's expression was significantly increased in the midgut at 24Â h after phoxim treatment. However, the transcription levels of Akt, PI3K60, PI3K110, IRS, InR and PDK were elevated and reached the peaks at 48Â h, which were 1.48-, 1.35-, 1.21-, 2.24-, 2.89-, and 1.44-fold of those of the control, respectively. At 72Â h, the transcription of these genes was reduced. Akt phosphorylation level was increasing along with the growth of silkworms in the control group. However, phoxim treatment led to increased Akt phosphorylation that surged at 24Â h but gradually decreased at 48Â h and 72Â h. The results indicated that phoxim dysregulated the expression of IIS pathway genes and induced abnormal nutrient metabolism in silkworm midgut, which may be the reason of the slow growth of silkworms.Copyright Â© 2015 Elsevier Ltd. All rights reserved.
The magnetic and crystal structures of Sr1-Î´FeO2-xFx, a new oxyfluoride. - Chemical communications (Cambridge, England)
A new quasi-two-dimensional oxyfluoride, Sr1-Î´FeO2-xFx, has been successfully synthesized by combining topotactic fluoridation and CaH2 reduction. The introduction of F through this synthesis provides a new route to introducing charge carriers into the square layered lattice through the formation of Fe(1+) ions. While the average crystal symmetry and magnetic structure remain the same as in the parent compound, the addition of F results in an enhanced buckling of the Fe(O/F)2 square plaquettes that is most likely topologically driven.
Biotransformation and adsorption of pharmaceutical and personal care products by activated sludge after correcting matrix effects. - The Science of the total environment
This study reported significant suppressive matrix effects in analyses of six pharmaceutical and personal care products (PPCPs) in activated sludge, sterilized activated sludge and untreated sewage by ultra-performance liquid chromatography-tandem mass spectrometry. Quantitative matrix evaluation on selected PPCPs supplemented the limited quantification data of matrix effects on mass spectrometric determination of PPCPs in complex environment samples. The observed matrix effects were chemical-specific and matrix-dependent, with the most pronounced average effect (-55%) was found on sulfadiazine in sterilized activated sludge. After correcting the matrix effects by post-spiking known amount of PPCPs, the removal mechanisms and biotransformation kinetics of selected PPCPs in activated sludge system were revealed by batch experiment. Experimental data elucidated that the removal of target PPCPs in the activated sludge process was mainly by biotransformation while contributions of adsorption, hydrolysis and volatilization could be neglected. High biotransformation efficiency (52%) was observed on diclofenac while other three compounds (sulfadiazine, sulfamethoxazole and roxithromycin) were partially biotransformed by ~40%. The other two compounds, trimethoprim and carbamazepine, showed recalcitrant to biotransformation of the activated sludge.Copyright Â© 2015 Elsevier B.V. All rights reserved.
[Alarming effect of intraoperative neuroelectrophysiological monitoring in microvascular decompression for primary trigeminal neuralgia]. - Zhonghua yi xue za zhi
To explore the alarming effect of intraoperative neuroelectrophysiological monitoring in microvascular decompression (MVD) for primary trigeminal neuralgia.In 2014, a total of 44 patients with an initial diagnosis of primary trigeminal neuralgia were consecutively recruited for surgery. And 41 of them with an intraoperative confirmation of primary trigeminal neuralgia underwent MVD. Intraoperative neuroelectrophysiological monitoring was employed for brainstem auditory evoked potentials (BAEPs), spontaneous electromyogram for obicularis oculi, obicularisoris and masseter muscles. The real-time alarming report was offered to the operator who adjusted operations accordingly.There were abnormal changes in 23 cases (56.10%) with a total of 77 instances (BAEPs 27, trigeminal nerve 32, facial nerve 18). The outcomes were no facial pain (n=26), pain relief (n=15) and facial numbness (n=6, two with concurrent hearing disturbance). And the rates of facial pain disappearance and sequela occurrence were much better than those in controls without monitoring.Intraoperative neuroelectrophysiological monitoring helps enhance the MVD effect and decrease operative squela through alarming reporting.
Comparative efficacy and cost effectiveness of splenectomy and thrombopoietin prior to peginterferon and ribavirin therapy with compensatory cirrhosis associated with hepatitis C and thrombocytopenia. - Experimental and therapeutic medicine
The aim of the present study was to evaluate and compare the treatment efficacy and cost of two therapies, splenectomy and thrombopoietin, in order to optimize the treatment plans for patients with HCV-associated cirrhosis. A prospective randomized controlled trial was conducted on 69 patients with a platelet count <60,000/mm(3) that were enrolled between 2009 and 2013, including 38 cases as the research group and 31 cases as the observed group. The study included two stages: A 4-week initial treatment and a 48-week antiviral treatment, during which a number of parameters were evaluated, including platelet count, liver stiffness measure, albumin, total bilirubin, alanine aminotranferase and treatment cost-effectiveness. Of the 38 patients, 21 underwent a splenectomy and their platelet counts increased to 60,000/mm(3) after the 4-week initial treatment. The patients then started a 48-week P-R antiviral treatment, and 18 cases completed the treatment. In addition, 17/38 patients received thrombopoietin as a drug therapy. The platelet counts in 15 cases increased to >60,000/mm(3) and the patients received antiviral treatment, among which 9 cases completed the second treatment stage. The expense of the splenectomy group treatment was higher compared with that received by the thrombopoietin group. The results of the present study indicated that splenectomy was more effective at increasing platelet count. More splenectomy patients completed the full course of antiviral treatment and presented a sustained virologic response, compared with the thrombopoietin group. Therefore, splenectomy may be more expensive compared with thrombopoietin; however, the improved efficacy suggests that on balance it is the preferable treatment option.
FgMon1, a guanine nucleotide exchange factor of FgRab7, is important for vacuole fusion, autophagy and plant infection in Fusarium graminearum. - Scientific reports
The Ccz1-Mon1 protein complex, the guanine nucleotide exchange factor (GEF) of the late endosomal Rab7 homolog Ypt7, is required for the late step of multiple vacuole delivery pathways, such as cytoplasm-to-vacuole targeting (Cvt) pathway and autophagy processes. Here, we identified and characterized the yeast Mon1 homolog in Fusarium graminearum, named FgMon1. FgMON1 encodes a trafficking protein and is well conserved in filamentous fungi. Targeted gene deletion showed that the âˆ†Fgmon1 mutant was defective in vegetative growth, asexual/sexual development, conidial germination and morphology, plant infection and deoxynivalenol production. Cytological examination revealed that the âˆ†Fgmon1 mutant was also defective in vacuole fusion and autophagy, and delayed in endocytosis. Yeast two hybrid and in vitro GST-pull down assays approved that FgMon1 physically interacts with a Rab GTPase FgRab7 which is also important for the development, infection, membrane fusion and autophagy in F. graminearum. FgMon1 likely acts as a GEF of FgRab7 and constitutively activated FgRab7 was able to rescue the defects of the âˆ†Fgmon1 mutant. In summary, our study provides evidences that FgMon1 and FgRab7 are critical components that modulate vesicle trafficking, endocytosis and autophagy, and thereby affect the development, plant infection and DON production of F. graminearum.
LncRNA-UCA1 exerts oncogenic functions in non-small cell lung cancer by targeting miR-193a-3p. - Cancer letters
Recently, the long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been identified as an oncogenic gene in multiple human tumor entitles, and dysregulation of UCA1 was tightly linked to carcinogenesis and cancer progression. However, whether the aberrant expression of UCA1 in non-small cell lung cancer (NSCLC) is associated with malignancy, metastasis or prognosis has not been characterized. In this study, we found that UCA1 was upregulated in NSCLC tissues. Higher expression of UCA1 led to a significantly poorer survival time, and multivariate analysis revealed that UCA1 was an independent risk factor of prognosis. UCA1 overexpression enhanced, whereas UCA1 silencing impaired the proliferation and colony formation of NSCLC cells. Moreover, mechanistic investigations showed that UCA1 upregulated the expression of miR-193a-3p target gene ERBB4 through competitively 'spongeing' miR-193a-3p. Overall, we concluded that UCA1 functions as an oncogene in NSCLC, acting mechanistically by upregulating ERBB4 in part through 'spongeing' miR-193a-3p.Copyright Â© 2015 Elsevier Ireland Ltd. All rights reserved.
Evaluating the effects of Danhong injection in treatment of acute ischemic stroke: study protocol for a multicenter randomized controlled trial. - Trials
Danhong injection (DHI) has been widely prescribed to patients with acute ischemic stroke (AIS). However, due to methodological deficiencies, previous research has not yet provided rigorous evidence to support the use of DHI in the treatment of AIS. Therefore, we designed this multicenter, randomized, controlled, and double-blind trial to evaluate the efficacy and safety of DHI for AIS.It is a randomized, multicenter, double-blind, placebo-controlled, adaptive clinical trial. A total of 864 eligible patients will be randomized into either the DHI or placebo group in a 2:1 ratio. All patients will be given the standard medical care as recommended by guidelines. Participants will undergo a 2-week treatment regimen and 76-day follow-up period. The primary outcome is the proportion of patients with a favorable outcome, defined as a score of 0-1 on the modified Rankin scale at day 90. Secondary outcomes include a change in the total score of the Chinese medicine symptom scales of "Xueyu Zheng" (blood stasis syndrome), the proportion of patients with a Barthel Index score of â‰¥90, the proportion of patients with an improvement in NIHSS score of â‰¥4 or NIHSS score of 0-1, quality of life measured by the EQ-5D scale, etc. Safety outcomes such as global disability (mRS â‰¥3) at day 90 will also be assessed. The changes in mRNA and microRNA profiles in 96 patients selected from certain centers will also be assessed. As this is an adaptive design, two interim analyses are prospectively planned, which will be carried out after one-third and two-thirds of patients have completed the trial, respectively. Based on the results of the interim analyses, the Data Monitoring Committee (DMC) will decide how to modify the study.This trial will provide high-quality evidence for DHI in treatment of AIS.Clinical Trials.gov NCT01677208 (Date of registration 22 December 2012).
Metagenomic Assembly Reveals Hosts of Antibiotic Resistance Genes and the Shared Resistome in Pig, Chicken, and Human Feces. - Environmental science & technology
The risk associated with antibiotic resistance disseminating from animal and human feces is an urgent public issue. In the present study, we sought to establish a pipeline for annotating antibiotic resistance genes (ARGs) based on metagenomic assembly to investigate ARGs and their co-occurrence with associated genetic elements. Genetic elements found on the assembled genomic fragments include mobile genetic elements (MGEs) and metal resistance genes (MRGs). We then explored the hosts of these resistance genes and the shared resistome of pig, chicken and human fecal samples. High levels of tetracycline, multidrug, erythromycin, and aminoglycoside resistance genes were discovered in these fecal samples. In particular, significantly high level of ARGs (7762 Ã—/Gb) was detected in adult chicken feces, indicating higher ARG contamination level than other fecal samples. Many ARGs arrangements (e.g., macA-macB and tetA-tetR) were discovered shared by chicken, pig and human feces. In addition, MGEs such as the aadA5-dfrA17-carrying class 1 integron were identified on an assembled scaffold of chicken feces, and are carried by human pathogens. Differential coverage binning analysis revealed significant ARG enrichment in adult chicken feces. A draft genome, annotated as multidrug resistant Escherichia coli, was retrieved from chicken feces metagenomes and was determined to carry diverse ARGs (multidrug, acriflavine, and macrolide). The present study demonstrates the determination of ARG hosts and the shared resistome from metagenomic data sets and successfully establishes the relationship between ARGs, hosts, and environments. This ARG annotation pipeline based on metagenomic assembly will help to bridge the knowledge gaps regarding ARG-associated genes and ARG hosts with metagenomic data sets. Moreover, this pipeline will facilitate the evaluation of environmental risks in the genetic context of ARGs.
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