Over the past decade, N-heterocycliccarbene (NHc), bipyridine (bpy), and pyridine oxazoline (PyOx) ligands have been increasingly applied in nickel catalysis, where the combination of a low-oxidation-state 3d metal a...
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Over the past decade, N-heterocycliccarbene (NHc), bipyridine (bpy), and pyridine oxazoline (PyOx) ligands have been increasingly applied in nickel catalysis, where the combination of a low-oxidation-state 3d metal and an electron-rich ligand can enable otherwise challenging bond activations. Herein we report the synthesis and characterization of two Ni(0) complexes supported by an alternative, bidentate, c,N ligand, (h)IMesPy ("half-IMes-pyridine" or 1-(2,4,6-trimethylphenyl)-3-(2-pyridinyl)-imidazol-2-ylidene). The unsymmetric ligand combines the strong sigma-donating properties of an NHc with the pi-accepting properties of pyridine to afford homoleptic [Ni((h)IMesPy)(2)] and heteroleptic [Ni(cod)((h)IMesPy)] complexes. characterization through the combination of single-crystal X-ray diffraction analysis and NMR spectroscopy, as well as reactivity studies demonstrating reversible interconversion between the two species, provide a strong basis for future applications to overcome reactivity challenges.
Background Nucleosome-mediated chromatin compaction has a direct effect on the accessibility of trans-acting activators and repressors to DNA targets and serves as a primary regulatory agent of genetic expression. Und...
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Background Nucleosome-mediated chromatin compaction has a direct effect on the accessibility of trans-acting activators and repressors to DNA targets and serves as a primary regulatory agent of genetic expression. Understanding the nature and dynamics of chromatin is fundamental to elucidating the mechanisms and factors that epigenetically regulate gene expression. Previous work has shown that there are three types of canonical sequences that strongly regulate nucleosome positioning and thus chromatin accessibility: putative nucleosome-positioning elements, putative nucleosome-repelling sequences, and homopolymeric runs of A/T. It is postulated that these elements can be used to remodel chromatin in c. elegans. Here we show the utility of such elements in vivo, and the extreme efficacy of a newly discovered repelling sequence, PRS-322. Results In this work, we show that it is possible to manipulate nucleosome positioning in c. elegans solely using canonical and putative positioning sequences. We have not only tested previously described sequences such as the Widom 601, but also have tested additional nucleosome-positioning sequences: the Trifonov sequence, putative repelling sequence-322 (PRS-322), and various homopolymeric runs of A and T nucleotides. conclusions Using each of these types of putative nucleosome-positioning sequences, we demonstrate their ability to alter the nucleosome profile in c. elegans as evidenced by altered nucleosome occupancy and positioning in vivo. Additionally, we show the effect that PRS-322 has on nucleosome-repelling and chromatin remodeling.
During mitosis, phosphorylation and dephosphorylation of lamins triggers the nuclear envelope disassembly/assembly. However, it hasn't been known whether lamin proteins undergo any modification other than phosphor...
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During mitosis, phosphorylation and dephosphorylation of lamins triggers the nuclear envelope disassembly/assembly. However, it hasn't been known whether lamin proteins undergo any modification other than phosphorylation during the cell cycle. Glycosylation of lamin proteins is one of the less studied post-translational modification. Glycosylation and phosphorylation compete for the same positions and interplay between two modifications generate a post-translational code in the cell. Based on this, we hypothesized that glycosylation of lamin A/c protein may be important in the regulation of the structural organization of the nuclear lamina during interphase and mitosis. We analysed the glycan units of lamin A/c protein in lung carcinoma cells synchronized at G2/M and S phases via capLc-ESI-MS/MS. Besides, the outermost glycan units were determined using lectin blotting and gold-conjugated antibody and lectin staining. TEM studies also allowed us to observe the localization of glycosylated lamin A/c protein. With this study, we determined that lamin A/c protein shows O-glycosylation at G2/M and S phases of the cell cycle. In addition to O-GlcNAcylation and O-GalNAcylation, lamin A/c is found to be contain Gal, Fuc, Man, and Sia sugars at G2/M and S phases for the first time. Having found the glycan units of the lamin A/c protein suggests that glycosylation might have a role in the nuclear organization during the cell cycle.
In this cluster cross-over randomized trial in 5 in-patient cancer/transplant units neither clostridioides difficilenor vancomycin-resistant enterococci (VRE) transmission rates were reduced by UV-c light disinfection...
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In this cluster cross-over randomized trial in 5 in-patient cancer/transplant units neither clostridioides difficilenor vancomycin-resistant enterococci (VRE) transmission rates were reduced by UV-c light disinfection when used in patients' rooms daily and at time of discharge. Background Our objective was to determine if the addition of ultraviolet-c (UV-c) light to daily and discharge patient room cleaning reduces healthcare-associated infection rates of vancomycin-resistant enterococci (VRE) and clostridioides difficile in immunocompromised adults. Methods We performed a cluster randomized crossover control trial in 4 cancer and 1 solid organ transplant in-patient units at the Johns Hopkins Hospital, Baltimore, Maryland. For study year 1, each unit was randomized to intervention of UV-c light plus standard environmental cleaning or control of standard environmental cleaning, followed by a 5-week washout period. In study year 2, units switched assignments. The outcomes were healthcare-associated rates of VRE or c. difficile. Statistical inference used a two-stage approach recommended for cluster-randomized trials with Results In total, 302 new VRE infections were observed during 45787 at risk patient-days. The incidence in control and intervention groups was 6.68 and 6.52 per 1000 patient-days respectively;the unadjusted incidence rate ratio (IRR) was 0.98 (95% confidence interval [cI], .78 - 1.22;P = .54). There were 84 new c. difficile infections observed during 26118 at risk patient-days. The incidence in control and intervention periods was 2.64 and 3.78 per 1000 patient-days respectively;the unadjusted IRR was 1.43 (95% cI, .93 - 2.21;P = .98). conclusions When used daily and at post discharge in addition to standard environmental cleaning, UV-c disinfection did not reduce VRE or c. difficile infection rates in cancer and solid organ transplant units.
Introduction Posttransplant diabetes mellitus (PTDM) can increase morbidity and mortality in liver transplant recipients. Although hepatitis c seropositivity is a known risk factor for PTDM, the impact of viremia vers...
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Introduction Posttransplant diabetes mellitus (PTDM) can increase morbidity and mortality in liver transplant recipients. Although hepatitis c seropositivity is a known risk factor for PTDM, the impact of viremia versus no viremia at time of transplant is unknown. Project Aims This program evaluation sought to compare PTDM in hepatitis c seropositive patients with and without viremia at the time of liver transplant. Design This single-center retrospective review included adult hepatitis c seropositive liver transplant recipients transplanted between January 1, 2010 to September 5, 2017 without pretransplant diabetes. Primary outcome was PTDM within 1 year. Secondary outcomes included evaluating 1-year posttransplant death-censored graft loss, mortality, and metabolic outcomes. Results Fifty-seven liver transplant recipients with hepatitis c were included, of which 53% (n = 30) were viremic at transplant. Baseline characteristics were similar between groups. Significantly more patients with pretransplant viremia developed PTDM by 1-year posttransplant compared to the patients without viremia (43% vs 11%, P = 0.01). There were no differences between groups outside of more patients with viremia requiring antihypertensives by 1-year posttransplant compared to patients without viremia (57% vs 22%, P = 0.01). conclusion Liver transplant patients with hepatitis c viremia at transplant were more likely to develop PTDM at 1 year compared to those without pretransplant viremia. This is an added consideration when deciding the timing of direct-acting antiviral (DAA) utilization in the context of liver transplant for hepatitis c seropositive patients.
Three new steroidal glycosides, metapregnoside A-c (II-IV), together with one known compound, byzantionoside B (I), were isolated from the fresh whole herb of Metaplexis japonica by using high-speed countercurrent chr...
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Three new steroidal glycosides, metapregnoside A-c (II-IV), together with one known compound, byzantionoside B (I), were isolated from the fresh whole herb of Metaplexis japonica by using high-speed countercurrent chromatography and semi-preparative liquid chromatography. Their structures and relative configurations were elucidated by spectroscopic methods including 1D NMR, 2D NMR and HR-ESI-MS. The potential targets of compound I-IV were identified by virtual screening. And the potential inhibitory effects of these compounds on tyrosine protein kinases were compared by molecular docking. Byzantionoside B (I) was the first isolated compound from Metaplexis genus. The docking score of metapregnoside c (IV) was the highest. And the sugar chain residues at position c-20 in the pregn-4-en-3-one derivatives is the main factor affecting their docking scores on tyrosine protein kinases Fes/Fps.
Pacificcod (Gadus macrocephalus), as one of the most important economic fish, was seriously infected by the nervous necrosis virus (NNV), especially in the larvae stage. PolyI:c is an effective stimulus of the antivi...
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Pacificcod (Gadus macrocephalus), as one of the most important economic fish, was seriously infected by the nervous necrosis virus (NNV), especially in the larvae stage. PolyI:c is an effective stimulus of the antivirus system, but whether it can work in the larvae stage is still unknown. In this study, the transcriptomic profiles of 10 day-post hatching (dph) cod larvae challenged with polyI:c was analysed using next-generation sequencing technology. After assembly and annotation, a total of 77,562 unigenes were acquired and 780 differentially expressed genes (DEGs) were identified, including 508 upregulated and 272 downregulated genes. The DEGs were involved in diverse pathways including protein processing in endoplasmic reticulum, peroxisome, carbon metabolism, fatty acid metabolism, and PPAR signaling pathway. Gene expression patterns of five immune relevant genes belonging to IFN signal pathway, such as TLR3, IRF3, MDA5, IPS1 and ATG5, were detected using qPcR. The transcript levels of TLR3, IRF3, MAD5 and IPS1 in cod larvae seems very low, but these genes were upregulated significantly 48h post-challenged with polyI:c, while ATG5 was downregulated 12h after polyI:cchallenged. The results indicated that IFN system of cod larvae can be induced by polyI:c, thus considering polyI:c as a potential antivirus agent for cod larvae.
Fruit trees are perennial plant to have a characteristic requiring a long juvenile period until fruit set in general. Developing to release a new fruit cultivar is a laborious and cost- and time-consuming work. Especi...
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Fruit trees are perennial plant to have a characteristic requiring a long juvenile period until fruit set in general. Developing to release a new fruit cultivar is a laborious and cost- and time-consuming work. Especially, citrus breeding is not always feasible due to its cross-incompatible, sterile, and polyembryoniccharacteristics. Therefore, mutagenesis has been widely applied to citrus breeding to increase mutation frequency and genetic variability enabling development of new genotypes as an alternative method. Recently, various tangor (citrus unshiu x c. sinensis) cultivars were released through interspecific hybridization. Many attempts have been made to induce mutations in developing tangor cultivars, while their physiological effects have not been verified yet. To investigate the effect of gamma-irradiation exerted on tangor cultivar 'Kanpei', its scions were irradiated with 20, 40, 60, 80, and 100 Gy of gamma-rays. Then, we examined the SPAD values between the gamma-irradiated M-0 plants comparing with control 'Kanpei' (0 Gy). Interestingly, we found that there are variations in SPAD values among different treatments. This implies that mutation breeding should consider different factors other than the target traits.
The death of c. Richard conti, MD, MAcc in February 2022 marked the passing of a global leader in cardiology who played a pivotal role in the history of the American college of cardiology and the college's outreac...
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The death of c. Richard conti, MD, MAcc in February 2022 marked the passing of a global leader in cardiology who played a pivotal role in the history of the American college of cardiology and the college's outreach to the People's Republic of china.
Background The cell division cycle is a process that is exquisitely controlled by a complex interplay between E3 ubiquitin ligases and deubiquitinating enzymes (DUBs). We have previously reported that the DUB USP13 re...
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Background The cell division cycle is a process that is exquisitely controlled by a complex interplay between E3 ubiquitin ligases and deubiquitinating enzymes (DUBs). We have previously reported that the DUB USP13 regulates Aurora B levels along the cell cycle. That observation prompted us to explore any possible connection between USP13 and the APc/c-cDH1, the major E3 controlling Aurora B levels in cells. Methods We performed immunoprecipitation assays followed by western-blotting to assess the interaction between USP13 and cDH1. The cellular effects of USP13 gain or loss of function were analyzed by transfection of FLAG-tagged USP13 plasmid or small interfering RNAs and short hairpin RNAs directed against USP13. The levels of cDH1 and other proteins were quantified in cell extracts by western-blotting. Results We found that USP13 binds to the APc/c adaptor cDH1. In addition, we report for the first time that USP13 controls cDH1 protein levels in cells: overexpression of USP13 increased cDH1 levels, whereas depletion of USP13 decreased cDH1 levels. conclusions We unveil the existing interplay between USP13 and cDH1: USP13 is capable of stabilizing cDH1 levels. We previously reported that USP13 stabilizes Aurora B in cells, a known substrate of the APc/c-cDH1 E3 ubiquitin ligase, before their entry into mitosis. Altogether, our data identify and establish the USP13-cDH1-Aurora B axis as a new regulatory module required for flawless cell cycle progression in mammalian cells, whose misfunction may be involved in the rewiring of cell cycle pathways linked to cancer development.
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