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The prognostic significance of HIST1H3B/c and H3F3A K27M mutations in diffuse midline gliomas is influenced by patient age

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JOURNAL OF NEURO-ONcOLOGY 2022年第3期158卷 405-412页

作者： Vuong, Huy Gia Tam N M Ngo Hieu Trong Le Dunn, Ian F. Oklahoma Univ Dept Neurosurg Hlth Sci Ctr Oklahoma City OK 73104 USA Pham Ngoc Thach Univ Med Fac Med Ho Chi Minh City 700000 Vietnam Univ Med & Pharm Ho Chi Minh City Dept Pathol Ho Chi Minh City 700000 Vietnam

Introduction Diffuse midline gliomas (DMGs) are infiltrative midline gliomas harboring H3K27M mutations and are generally associated with poor outcomes. H3K27M mutations include mutations in HIST1H3B/c (H3.1), HIST2H3B/D (H3.2), or H3F3A (H3.3) genes. It is still unclear whether these mutations each portend a universally poor prognosis, or if there are any factors which modulate outcome. The main objective of this study was to study overall survival (OS) of H3.1 versus H3.3 K27M-mutant DMGs in pediatric and adult patients. Methods PubMed and Web of Science were searched, and we included studies if they have individual patient data of DMGs with available H3K27M genotype. Kaplan-Meier analysis and cox regression models were used to analyze the survival of H3.1 and H3.3 mutations in each subgroup. Results We included 26 studies with 102 and 529 H3.1 and H3.3-mutant DMGs, respectively. The H3.1 mutation was more commonly seen in younger age. In pediatric population, H3.3 mutation conferred a shorter survival (median OS of 10.1 vs 14.2 months;p < 0.001) in comparison to H3.1-positive patients, which was further confirmed in the multivariate cox analysis. conversely, H3.3 was associated with a prolonged survival in adult patients as compared with H3.1 mutation (median OS of 14.4 vs 1.7 months;p = 0.019). conclusion We demonstrated that the prognosis of H3.1 and H3.3 K27M mutation in DMG patients is modulated by patient age. Routine H3K27M mutation genotyping in newly diagnosed DMGs may further stratify patients with these difficult tumors.

关键词： Histone H3 c Midline glioma

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NanoBRET in c. elegans illuminates functional receptor interactions in real time

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BMc MOLEcULAR AND cELL BIOLOGY 2022年第1期23卷 1页

作者： Gross, Victoria Elisabeth Gershkovich, Miron Mikhailowitsch Schoeneberg, Torsten Kaiser, Anette Proemel, Simone Univ Leipzig Med Fac Rudolf Schonheimer Inst Biochem D-04103 Leipzig Germany Heinrich Heine Univ Dusseldorf Dept Biol Inst Cell Biol D-40225 Dusseldorf Germany Univ Leipzig Fac Life Sci Inst Biochem D-04103 Leipzig Germany

Background Protein-protein interactions form the basis of every organism and thus, investigating their dynamics, intracellular protein localization, trafficking and interactions of distinct proteins such as receptors and their ligand-binding are of general interest. Bioluminescence resonance energy transfer (BRET) is a powerful tool to investigate these aspects in vitro. Since in vitro approaches mostly neglect the more complex in vivo situation, we established BRET as an in vivo tool for studying protein interactions in the nematode c. elegans. Results We generated worms expressing NanoBRET sensors and elucidated the interaction of two ligand-G protein-coupled receptor (GPcR) pairs, the neuropeptide receptor NPR-11 and the Adhesion GPcR LAT-1. Furthermore, we adapted the enhanced bystander BRET technology to measure subcellular protein localization. Using this approach, we traced ligand-induced internalization of NPR-11 in vivo. conclusions Our results indicate that in vivo NanoBRET is a tool to investigate specific protein interactions and localization in a physiological setting in real time in the living organism c. elegans.

关键词： NanoBRET c elegans Receptor-ligand interaction Enhanced bystander BRET

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MiR-144 regulates adipogenesis by mediating formation of c/EBPa-FOXO1 protein complex

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BIOcHEMIcAL AND BIOPHYSIcAL RESEARcH cOMMUNIcATIONS 2022年 612卷 126-133页

作者： Lin, Weimin Wen, Xianyu Li, Xuexin chen, Lei Wei, Wei Zhang, Lifan chen, Jie Nanjing Agr Univ Coll Anim Sci & Technol Nanjing 210095 Jiangsu Peoples R China

ceRNA effect was an important regulation mode of miRNA mediated bio-activities, however, most of the researches of ceRNA were on ncRNAs synergetic with mRNAs, the exploration of ceRNA effect regulated mRNA interaction was still lack of. Besides, c/EBPa was one of the most crucial adipogenic regulators, which has been demonstrated to form a protein complex with FOXO1 to mediate AdipoQ expression. So that, we try to explore whether the ceRNA effect mediated the interaction of c/EBPa and FOXO1, and identified the key miRNAs of their ceRNA effect. In this paper, we found the ceRNA effect of c/EBPa and FOXO1 mediated their protein complex formation, furthermore regulated its transcriptional role for AdipoQ, thereby influencing pre-adipocytes adipogenesis. More importantly, we demonstrated that the miR-144 was the decisive factor that mediated the ceRNA effect of c/EBPa and FOXO1 to influence AdipoQ, thus regulated pre-adipocytes adipogenesis. This research will provide a new supplementary idea of the miRNA role in mediating coding RNA interaction that regulates pre-adipocyte adipogenesis. (c) 2022 Elsevier Inc. All rights reserved.

关键词： c EBP a FOXO1 miR-144 AdipoQ Adipogenesis

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Manipulating chromatin architecture in c. elegans

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EPIGENETIcS & cHROMATIN 2022年第1期15卷 1-12页

作者： carter, John L. Kempton, colton E. Hales, Emily D. S. Johnson, Steven M. Brigham Young Univ Dept Microbiol & Mol Biol Coll Life Sci Provo UT 84602 USA

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.

关键词： chromatin c elegans Transgene Nucleosomes Nucleosome positioning Nucleosome occupancy Epigenetics PRS-322 Widom 601

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Synthesis and characterization of Ni(0) complexes supported by an unsymmetric c,N ligand

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JOURNAL OF cOORDINATION cHEMISTRY 2022年第11-14期75卷 1841-1852页

作者： craig, Sarah M. Malyk, Kaycie R. Silk, Elliot S. Nakamura, Daniel T. Brennessel, William W. Kennedy, c. Rose Univ Rochester Dept Chem Rochester NY 14627 USA

Over the past decade, N-heterocyclic carbene (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.

关键词： carbene ligands c N ligands Nickel pyridine ligands X-ray diffraction

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Glycan analysis of Lamin A/c protein at G2/M and S phases of the cell cycle

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cELL BIOcHEMISTRY AND BIOPHYSIcS 2022年第4期80卷 689-698页

作者： Uslupehlivan, Ecem Sener Deveci, Remziye Sahar, Umut Izzetoglu, Savas Ege Univ Fac Sci Dept Biol Mol Biol Sect Izmir Turkey

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.

关键词： Lamin A c Glycan Monosaccharide capLc-ESI MS-MS TEM

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Effect of Hepatitis c Viremia on Posttransplant Diabetes Mellitus in Liver Transplant Recipients

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PROGRESS IN TRANSPLANTATION 2022年第1期32卷 73-77页

作者： Klein, Kelsey Nelson, Joelle Long, christina Speeg, Kermit Alkhouri, Naim Hall, Reed Univ Hlth Syst San Antonio TX USA Univ Texas Hlth Sci Ctr San Antonio San Antonio TX 78229 USA Univ Texas Austin Coll Pharm Austin TX 78712 USA Univ Incarnate Word Feik Sch Pharm San Antonio TX USA Arizona Liver Hlth Chandler AZ USA

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.

关键词： clinical outcomes diabetes posttransplant type 2 clinical outcomes endocrinology general clinical outcomes hepatitis B c liver transplantation immunology infection

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Ultraviolet-c Light Evaluation as Adjunct Disinfection to Remove Multidrug-Resistant Organisms

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cLINIcAL INFEcTIOUS DISEASES 2022年第1期75卷 35-40页

作者： Rock, clare Hsu, Yea-Jen curless, Melanie S. carroll, Karen c. Ross Howard, Tracy carson, Kathryn A. cummings, Stephanie Anderson, Michael Milstone, Aaron M. Maragakis, Lisa L. Johns Hopkins Univ Dept Med Sch Med Baltimore MD USA Johns Hopkins Univ Hosp Dept Hosp Epidemiol & Infect Control Baltimore MD USA Johns Hopkins Bloomberg Sch Publ Hlth Dept Hlth Policy & Management Baltimore MD USA Johns Hopkins Univ Dept Pathol Sch Med Baltimore MD USA Johns Hopkins Bloomberg Sch Publ Hlth Dept Epidemiol Baltimore MD USA Johns Hopkins Univ Dept Pediat Sch Med Baltimore MD USA

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.

关键词： UV-c light environmental cleaning and disinfection c difficile transmission infection prevention VRE transmission

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The effect of gamma-irradiation on the changes of photosynthetic efficiency in Kanpei (citrus unshiu x c. sinensis)

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PLANT BIOTEcHNOLOGY REPORTS 2022年第2期16卷 251-255页

作者： Heo, Seong choi, Jung Min Anh Tuan Le Eun, chang-Ho Kim, In-Jung chung, Yong Suk Kongju Natl Univ Dept Hort Yesan 32439 South Korea Jeju Natl Univ Dept Plant Resources & Environm Jeju 63243 South Korea Jeju Natl Univ Subtrop Hort Res Inst Jeju 63243 South Korea Jeju Natl Univ Coll Appl Life Sci Fac Biotechnol SARI Jeju 63243 South Korea Jeju Natl Univ Res Inst Subtrop Agr & Biotechnol SARI Jeju 63243 South Korea

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 polyembryonic characteristics. 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.

关键词： Mutagenesis Gamma-ray SPAD value citrus breeding citrus unshiu c sinensis

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Immune response of pacific cod larvae stimulated with PolyI:c

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AQUAcULTURE RESEARcH 2022年第9期53卷 3392-3400页

作者： Jie-Lan Jiang Xu, Jia Yu-Meng Liu Yun-Xiang Mao Hai-Shan Wang Sun, Yao Ming-Guang Mao Hainan Trop Ocean Univ Minist Educ Key Lab Utilizat & Conservat Trop Marine Bioresou Sanya 572022 Peoples R China Hainan Trop Ocean Univ Hainan Key Lab Conservat & Utilizat Trop Marine F Sanya Peoples R China Dalian Ocean Univ Coll Fisheries & Life Sci Dalian Peoples R China

Pacific cod (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:c challenged. 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.

关键词： differential expressed genes Gadus macrocephalus larvae PolyI c transcriptome

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