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Apoptotic retinal ganglion cell loss is accompanied by complement and cytokine response in theβB1-CTGF primary open-angle glaucoma mouse model

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Neural Regeneration Research 2023年第2期18卷 337-338页

作者： ana maria mueller-buehl Sabrina Reinehr Experimental Eye Research Institute University Eye HospitalRuhr-University BochumBochumGermany

Glaucoma is a multifactorial disease and occurs in many different *** humans,glaucoma is accounted one of the leading causes for blindness *** to glaucoma's complexity,it is still unclear what pathomechanisms may be involved in its development in humans as well as in other species,such as *** of glaucoma can be delayed because patients often do not notice a visual field loss until approximately30%of retinal ganglion cells(RGCs)are lost(Kerrigan-Baumrind et al.,2000).Although the exact undergoing pathomechanisms of glaucoma disease are not fully understood yet,an increased intraocular pressure(IOP)is related to RGCdeath and is considered the main risk factor.

关键词： glaucoma cytokine

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The HB40-JUB1 transcriptional regulatory network controls gibberellin homeostasis in Arabidopsis

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Molecular Plant 2022年第2期15卷 322-339页

作者： Shuchao Dong Danuse Tarkowska Mastoureh Sedaghatmehr Maryna Welsch Saurabh Gupta Bernd mueller-Roeber Salma Balazadeh Max-Planck Institute of Molecular Plant Physiology Am Mühlenberg 114476 Potsdam-GolmGermany Institute of Biology Leiden UniversitySylviusweg 722333 BE LeidenThe Netherlands Laboratory of Growth Regulators Czech Academy of SciencesInstitute of Experimental Botany&Palacky UniversityŠlechtitelû2778371 OlomoucCzech Republic University of Potsdam Institute of Biochemistry and BiologyKarl-Liebknecht-Stra?e 24-25Haus 2014476 Potsdam-GolmGermany

The gibberellins(GAs)are phytohormones that play fundamental roles in almost every aspect of plant growth and *** GA biosynthetic and signaling pathways are well understood,the mechanisms that control GA homeostasis remain largely unclear in ***,we demonstrate that the homeobox transcription factor(TF)HB40 of the HD-Zip family regulates GA content at two additive con-trol levels in Arabidopsis *** show that HB40 expression is induced by GA and in turn reduces the levels of endogenous bioactive GAs by simultaneously reducing GA biosynthesis and increasing GA ***,HB40 overexpression leads to typical GA-deficiency traits,such as small rosettes,reduced plant height,delayed flowering,and male *** contrast,a loss-of-function hb40 mutation enhances GA-controlled ***-wide RNA sequencing combined with molecular-genetic ana-lyses revealed that HB40 directly activates the transcription of JUNGBRUNNEN1(JJUB1),a key TF that re-presses growth by suppressing GA biosynthesis and ***40 also activates genes encoding GA 2-oxidases(GA2oxs),which are major GA-catabolic *** effect of HB40 on plant growth is ultimately mediated through the induction of nuclear growth-repressing DELLA ***,our results reveal the important role of the HB40-JUB1 regulatory network in controlling GA homeostasis during plant growth.

关键词： Arabidopsis growth gibberellin homeostasis transcription factor HB40 JUB1 GA 2-oxidase DELLA proteins

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Integrative phosphoproteomics defines two biologically distinct groups of KMT2A rearranged acute myeloid leukaemia with different drug response phenotypes

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Signal Transduction and Targeted Therapy 2023年第3期8卷 1318-1331页

作者： Pedro Casado ana Rio-Machin Juho JMiettinen Findlay Bewicke-Copley Kevin Rouault-Pierre Szilvia Krizsan Alun Parsons Vinothini Rajeeve Farideh Miraki-Moud David CTaussig Csaba Bödör John Gribben Caroline Heckman Jude Fitzgibbon Pedro R.Cutillas Cell Signalling and Proteomics Group Centre for Genomics and Computational BiologyBarts Cancer InstituteQueen Mary University of LondonLondon EC1M6BQUK Centre for Genomics and Computational Biology Barts Cancer InstituteQueen Mary University of LondonLondon EC1M6BQUK Institute for Molecular Medicine Finland-FIMM HiLIFE-Helsinki Institute of Life ScienceiCAN Digital Precision Cancer Medicine FlagshipUniversity of HelsinkiHelsinkiFinland Centre for Haemato-Oncology Barts Cancer InstituteQueen Mary University of LondonLondon EC1M6BQUK HCEMM-SU Molecular Oncohematology Research Group 1st Department of Pathology and Experimental Cancer ResearchSemmelweis University BudapestBudapestHungary Cancer Research UK Cancer Therapeutics Unit Division of Cancer TherapeuticsThe Institute of Cancer ResearchSuttonUK a The Alan Turing Institute The British Library2QR96 Euston RdLondon NW12DBUK

Acute myeloid leukaemia(AML)patients harbouring certain chromosome abnormalities have particularly adverse *** these patients,targeted therapies have not yet made a significant clinical *** understand the molecular landscape of poor prognosis AML we profiled 74 patients from two different centres(in UK and Finland)at the proteomic,phosphoproteomic and drug response phenotypic *** data were complemented with transcriptomics analysis for 39 *** integration highlighted a phosphoproteomics signature that define two biologically distinct groups of KMT2A rearranged leukaemia,which we term MLLGA and *** presented increased DOT1L phosphorylation,HOXA gene expression,CDK1 activity and phosphorylation of proteins involved in RNA metabolism,replication and DNA damage when compared to MLLGB and no KMT2A rearranged *** was particularly sensitive to 15 compounds including genotoxic drugs and inhibitors of mitotic kinases and inosine-5-monosphosphate dehydrogenase(IMPDH)relative to other ***-risk KMT2A-MLLT3 cases were mainly represented in a third group closer to MLLGA than to *** expression of IMPDH2 and multiple nucleolar proteins was higher in MLLGA and correlated with the response to IMPDH inhibition in KMT2A rearranged leukaemia,suggesting a role of the nucleolar activity in sensitivity to *** summary,our multilayer molecular profiling of AML with poor prognosis and KMT2A-MLLT3 karyotypes identified a phosphoproteomics signature that defines two biologically and phenotypically distinct groups of KMT2A rearranged *** data provide a rationale for the potential development of specific therapies for AML patients characterised by the MLLGA phosphoproteomics signature identified in this study.

关键词： metabolism signature biologically

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