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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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recent Advances in Catalytic Carbonylation reactions in Alternative reaction Media

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Chinese Journal of Chemistry 2024年第4期42卷 406-429页

作者： csaba Árvai László T.Mika department of Chemical and Environmental Process Engineering Faculty of Chemical Technology and BiotechnologyBudapest University of Technology and EconomicsMűegyetem rkp.3H-1111 BudapestHungary

Since the discovery of the hydroformylation(oxo-synthesis or roelen reaction)and the reppe-reaction,the transition metal-catalyzed carbonylation reactions,providing versatile,facile,and even atom-economic methods for the selective incorporation of C=O functionality to various skeletons,have gained tremendous importance in synthetic organic chemistry from laboratories to industrial *** carbonylation of carbon-carbon multiple bonds,aromatic halides,triflates,etc.,in the presence of various nucleophiles has led the way to produce aldehydes,carboxylic acids,esters,amides,etc.,in the fine chemical ***,these protocols usually proceed in conventional,fossil-based,and usually toxic reaction ***,several attempts have been directed to developing efficient carbonylation methods in alternative,less harmful,non-fossil-based and even in renewable reaction *** this review,we overview the recent applications of alternative solvents such as water,biomass-based alcohols,γ-valerolactone(GVL),2-methyltetrahydrofuran(2-MeTHF),ionic liquids(ILs),deep eutectic solvents(dES),alkyl levulinates,limonene,α-pinene,and dimethyl carbonate as well as fluorous media to improve efficiency,safety and environmentally benign nature of carbonylation protocols.

关键词： Carbonylation Catalysis Solvents Green chemistry Carbon monoxide Transition metals Homogeneous catalysis Palladium

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Niche differentiation among facultative filter feeders: Insights from invasive Ponto-Caspian mysids

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Current Zoology 2024年第4期70卷 513-521页

作者： Péter borza Varsha rani csaba F.Vada Institute of Aquatic Ecology Centre for Ecological ResearchKarolina ut 29.1113 BudapestHungary doctoral School of biology Institute of BiologyEotvos Lorand UniversityPazmany Péter sétany 1/C1117 BudapestHungary

The degree of dietary specialization has a fundamental impact on the ecological function and interactions of suspension *** niche differentiation by food particle size is common among obligate suspension feeders,its role is not evident in facultative *** this study,we aimed at providing new insights on the matter by focusing on sympatric mysid *** mysids use different mechanisms for raptorial and filter-feeding,they represent a more adequate model system than for example,the more extensively studied *** made morpholog-ical measurements on the 4 coexisting invasive Ponto-Caspian mysid species to determine the areas and mesh sizes of their *** also quantified their clearance rates on the microalga Cryptomonas *** a laboratory experiment to reveal how morphological differences manifest in their overall filtering *** found relatively small but consistent differences in the primary filter area among the species,indicating that morphological constraints due to the enclosed position of the setae might limit the possibility for *** primary filter mesh sizes were small in all 4 species(0.69-2.73μm)with moderate but consistent intraspecific differences,suggesting that the benefit of being able to capture small particles might outweigh the pressure for *** observed clearance rates were in accordance with the morphological characteristics of the species,highlighting that auxiliary filters(present in one of the species,Limnomysis benedeni)are needed to increase filtering capacity *** study confirmed that food particle size can contribute to the niche differentiation of facultative filter feeders,but also indicated that they can tolerate a higher overlap than obligate *** observed differences were related to the habitat preferences and predatory potentials of the species,suggesting that complementarity among the different niche axes might further facilitate theircoexistence.

关键词： clearance rate coexistence filter area filtermesh size.

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Methionine sources and genotype affect embryonic intestinal development,antioxidants,tight junctions,and growth-related gene expression in chickens

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Animal Nutrition 2024年第1期16卷 218-230页

作者： James K.Lugata Sawadi F.Ndunguru Gebrehaweria K.reda Xénia E.Ozsváth Eszter Angyal Levente Czeglédi Gabriella Gulyás renáta Knop János Oláh Zoltán Mészár rita Varga brigitta Csernus csaba Szabó department of Animal Nutrition and Physiology Faculty of Agriculture and Food Sciences and Environmental ManagementUniversity of DebrecenDebrecenHungary department of Animal Husbandry Faculty of Agriculture and Food Sciences and Environmental ManagementUniversity of DebrecenDebrecenHungary Faculty of Agriculture and Food Sciences and Environmental Management Doctoral School of Animal ScienceUniversity of DebrecenDebrecenHungary Institutes for Agricultural research and Educational Farm University of DebrecenDebrecenHungary department of Anatomy Histology and EmbryologyFaculty of MedicineUniversity of DebrecenDebrecenHungary department of Evolutionary Zoology and Human biology Faculty of Science and TechnologyUniversity of DebrecenDebrecenHungary

Methionine(Met)is an essential and first limiting amino acid in the poultry diet that plays a significant role in chicken embryonic development and *** present study examined the effect of in ovo injection of dL-Met and L-Met sources and genotypes on chicken embryonic-intestinal development and *** eggs of the two genotypes,TETrA-SL layer hybrid(TSL)—commercial layer hybrid and Hungarian Partridge colored hen breed(HPC)—a native genotype,were randomly distributed into four treatments for each *** treatment groups include the following:1)control non-injected eggs(NoIn);2)saline-injected(SaIn);3)dL-Met injected(dLM);and 4)L-Met injected(LM).The in ovo injection was carried out on 17.5 d of embryonic development;after hatching,eight chicks per group were sacrificed,and the jejunum was extracted for *** results showed that both dLM and LM groups had enhanced intestinal development as evidenced by increased villus width,villus height,and villus area(Pred to the *** dLM group had significantly reduced crypt depth,glutathione(GSH)content,glutathione S-transferase 3 alpha(GST3),occludin(OCLN)gene expression and increased villus height to crypt depth ratio in the TSL genotype than the LM group(Prexpressed insulin-like growth factor 1(IGF1)gene,tricellulin(Md2),occludin(OCLN),superoxide dismutase 1(SOd1),and GST3 genes than the TSL genotype(Pdings showed that in ovo injection of Met enhanced intestinal development,and function,with genotypes responding differently under normal *** also influenced the expression of intestinal antioxidants,tight junction,and growth-related genes.

关键词： dL-Methionine L-Methionine In ovo injection Intestinal development Poultry

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Single-cell transcriptome profiling of human HSCs during development:new insights into HSC ontogeny

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Signal Transduction and Targeted Therapy 2023年第3期8卷 877-878页

作者： Edgar Grinstein csaba Mahotka department of Hematology Oncology and Clinical ImmunologyMedical FacultyHeinrich Heine UniversityDüsseldorfGermany Institute of Pathology Medical FacultyHeinrich Heine UniversityDüsseldorfGermany

A study recently published in Nature reported a single-cell transcriptome map of human hematopoietic stem cells(HSCs)and a gene expression signature that distinguishes nascent HSCs from non-HSCs during prenatal development.1 This transcriptome map provides an important tool for further elucidation of human HSC ontogeny and could also serve as a guide for generation of transplantable HSCs ex vivo,1 to widen the therapeutic application of HSCs.

关键词： HSCs transcriptome hematopoietic

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The Importance of Flapping Kinematic Parameters in the Facilitation of the different Flight Modes of dragonflies

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Journal of bionic Engineering 2021年第2期18卷 419-427页

作者： Xiaohui Liu csaba Hefler Wei Shyy Huihe Qiu department of Mechanical and Aerospace Engineering The Hong Kong University of Science and TechnologyHong Kong SARChina

To better understand dragonflies’remarkable flapping wing aerodynamic performance,we measured the kinematic parameters of the wings in two different flight modes(Normal Flight Mode(NFM)and Escape Flight Mode(EFM)).When the specimens switched from normal to escape mode the flapping frequency was invariant,but the stroke plane of the wings was more horizontally *** flapping of both wings was adjusted to be more ventral with a change of the pitching angle that resulted in a larger angle of attack during downstroke and smaller during upstroke to affect the flow directions and the added mass ***,the phasing between the fore and hind pair of wings varies between two flight modes,which affects the wing-wing interaction as well as body *** is found that the momentum stream in the wake of EFM is qualitatively different from that in *** change of the stroke plane angle and the varied pitching angle of the wings diverts the momentum downwards,while the smaller flapping amplitude and less phase difference between the wings compresses the momentum *** seems that in order to achieve greater flight maneuverability a flight vehicle needs to actively control positional angle as well as the pitching angle of the flapping wings.

关键词： wing kinematics flight mode dragonfly flight aerodynamics

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Insight into the antifungal mechanism of Neosartorya fischeri antifungal protein

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Protein & Cell 2015年第7期6卷 518-528页

作者： Mate Viragh Annamaria Marton csaba Vizier Liliana Toth csaba Vagvolgyi Florentine Marx Laszlo Galgoczy department of Microbiology Faculty of Science and Informatics University of Szeged Szeged Hungary Institute of biochemistry Biological Research Centre Hungarian Academy of Sciences Szeged Hungary division of Molecular biology Biocenter Innsbruck Medical University Innsbruck Austria

Small, cysteine-rich, highly stable antifungal proteins secreted by filamentous Ascomycetes have great po- tential for the development of novel antifungal strate- gies. However, their practical application is still limited due to their not fully clarified mode of action. The aim of this work was to provide a deep insight into the anti-fungal mechanism of Neosartorya fischeri antifungal protein （NFAP）, a novel representative of this protein group. Within a short exposure time to NFAP, reduced cellular metabolism, apoptosis induction, changes in the actin distribution and chitin deposition at the hyphal tip were observed in NFAP-sensitive Aspergillus nidulans. NFAP did show neither a direct membrane disrupting- effect nor uptake by endocytosis. Investigation of A. nidulans signalling mutants revealed that NFAP acti- vates the cAMP/protein kinase A pathway via G-protein signalling which leads to apoptosis and inhibition of polar growth. In contrast, NFAP does not have any in- fluence on the cell wall integrity pathway, but an un- known cell wall integrity pathway-independent mitogen activated protein kinase A-activated target is assumed to be involved in the cell death induction. Taken to- gether, it was concluded that NFAP shows similarities, but also differences in its mode of antifungal action compared to two most investigated NFAP-related pro-teins from Aspergillus giganteus and Penicillium chrysogenum.

关键词： Neosartorya fischeri antifungal protein,Aspergillus nidulans cAMP/Pka signalling Pkc/Mpksignalling antifungal mechanism

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Increased duodenal expression of mi r-146a and-155 in pediatric Crohn's disease

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World Journal of Gastroenterology 2016年第26期22卷 6027-6035页

作者： dániel Szucs Nóra Judit béres réka rokonay Kriszta boros Katalin borka Zoltán Kiss András Arató Attila J Szabó ádám Vannay Erna Sziksz csaba bereczki Gábor Veres department of Pediatrics and Pediatric Health Care Center University of Szeged H-6725 Szeged Hungary 1st department of Pediatrics Semmelweis University H-1083 Budapest Hungary 2nd department of Pathology Semmelweis University H-1091 Budapest Hungary 1st department of Pediatrics Semmelweis University and MTA-SE Pediatrics and Nephrology Research Group H-1083 Budapest Hungary

AIM: To evaluate the role of microrNA (mir)-146a, -155 and -122 in the duodenal mucosa of pediatric patients with Crohn’s disease (Cd) and the effect of transforming growth factor-β (TGF-β) on these mirs in duodenal epithelial and fibroblast ***: Formalin-fixed, paraffin-embedded biopsies derived from the macroscopically inflamed (Cd inflamed: n = 10) and intact (Cd intact: n = 10) duodenal mucosa of pediatric Cd patients and control children (C: n = 10) were examined. Expression of mir-146a, -155 and -122 was determined by real-time polymerase-chain reaction (PCr). The expression of the above mirs was investigated in recombinant human TGF-β (1 nmol/L, 24 h) or vehicle treated small intestinal epithelial cells (CCL-241) and primary duodenal fibroblast cells derived from healthy children as ***: Expression of mir-146a was significantly higher in the inflamed duodenal mucosa compared to the intact duodenal mucosa of children with Cd (Cd inflamed: 3.21 ± 0.50 vs Cd intact: 0.62 ± 0.26, P ≤ 0.01) and to the control group (Cd inflamed: 3.21 ± 0.50 vs C: 1.00 ± 0.33, P ≤ 0.05). The expression of mir-155 was significantly increased in the inflamed region of the duodenum compared to the control group (Cd inflamed: 4.87 ± 1.02 vs Control: 1.00 ± 0.40, P ≤ 0.001). The expression of mir-122 was unchanged in the inflamed or intact mucosa of Cd patients compared to controls. TGF-β treatment significantly decreased the expression of mir-155 in small intestinal epithelial cells (TGF-β: 0.7 ± 0.083 vs Control: 1 ± 0.09, P ≤ 0.05) and also the expression of mir-146a (TGF-β: 0.67 ± 0.04 vs Control: 1 ± 0.15, P ≤ 0.01) and mir-155 (TGF-β: 0.72 ± 0.09 vs Control: 1 ± 0.06, P ≤ 0.05) in primary duodenal fibroblasts compared to corresponding vehicle treated control

关键词： Inflammatory bowel disease Crohn’ s disease Pediatric MicrorNAs Transforming growth factor-b2

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Effects of aspect ratio on flapping wing aerodynamics in animal flight

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Acta Mechanica Sinica 2014年第6期30卷 776-786页

作者： Jun-Jiang Fu csaba Hefler Hui-He Qiu Wei Shyy department of Mechanical and Aerospace Engineering The Hong Kong University of Science & Technology

Morphology as well as kinematics is a critical determinant of performance in flapping *** understand the effects of the structural traits on aerodynamics of bioflyers,three rectangular wings with aspect ratios（Ar）of1,2,and 4 performing hovering-like sinusoidal kinematics at wingtip based reynolds number of 5 300 are experimentally *** structures on sectional cuts along the wing span are *** K-H instability is found on the leading edge vortex of wings with higher aspect *** bursting only appears on the outer spanwise locations of high-aspect-ratio *** vortex bursting on high-aspect-ratio wings is perhaps one of the reasons why bio-flyers normally have low-aspect-ratio *** analysis exhibits larger dimensionless circulation of the leading edge vortex（LEV）over higher aspect ratio wings except when vortex bursting *** average dimensionless circulation of Ar1 and Ar2 along the span almost equals the dimensionless circulation at the 50%*** flow structure and the circulation analysis show that the sinusoidal kinematics suppresses breakdown of the LEV compared with simplified flapping kinematics used in similar *** reynolds number effect results on Ar4 show that in the current re range,the overall flow structure is not sensitive to reynolds number.

关键词： Aspect ratio Aerodynamics Leading edge vortex Flapping wing

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Improved Culture Media for Embryogenic Callus Generation in Sorghum [Sorghum bicolor (L.) Moench]

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Phyton-International Journal of Experimental botany 2020年第1期89卷 111-119页

作者： Paul Chege Andrea Palagyi csaba Lantos Erzsebet Kiss Janos Pauk Szent Istvan University Doctoral School of Plant ScienceGodolloPater K.u.1.H-2103Hungary Cereal research Non-profit Ltd. Department of BiotechnologySzegedAlsokikotosor 9.H-6701Hungary

Many attempts on optimization of sorghum[Sorghum bicolor(L.)Moench]tissue culture induction media have been made,but the culture system remains with some bottlenecks compared to that of other *** study aimed at assessing the suitability of various induction media to produce embryogenic callus(yellow and friable)with high induction rates and reduced phenolic *** six culture medium modifications:3 based on Murashige and Skoog(MS)medium and one each based on Chu N6,Gamborg b5 and 190-2 media respectively were applied in the culture of mature embryos from 10 sorghum *** there was a genotype influence on the attainment of a yellow callus,friability of the callus was determined to be dependent on the culture medium and not the *** strength MS medium with 0.2 mg/l 2,4-d with 2.8 g/l Gelrite®as the gelling agent modified with 1.0 g/l KH_(2)PO_(4),1.0 g/l L-proline,1.0 g/l L-asparagine and 0.16 mg/l CuSO_(4)·5H_(2)O(type E)was found to be the most effective resulting in about 60%yellow coloured callus induction with 25%*** of CuSO_(4)·5H_(2)O,KH_(2)PO_(4),L-proline and L-asparagine significantly reduced the phenolic *** strength MS medium was observed to contribute to quality callus production when compared to full strength MS media modified with the *** half strength MS medium was also observed to suppress phenolic *** 190-2 produced the highest regeneration frequency(40%)among the 3-regeneration media *** results provide information on a suitable sorghum callus induction medium necessary for embryogenesis.

关键词： Sorghum medium embryogenic callus half-strength MS

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