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Epithelial toll-like receptor 9 signaling in colorectal inflammation and cancer: Clinico-pathogenic aspects

World Journal of Gastroenterology 2013年第26期19卷 4119-4126页

作者： István Fri Ferenc Sipos Tiana M Germann alexandra kalmár Zsolt Tulassay Béla Molnár Gyrgyi Mzes 2nd Department of Internal Medicine Semmelweis University Faculty of Medicine Semmelweis University Molecular Medicine research Unit Hungarian Academy of Sciences

Toll-like receptors (TLrs) recognize specific motifs which are frequently present in bacteria, fungi, prokaryotes and viruses. Amongst TLrs, TLr9 can be activated by such bacterial or viral DNA fragments, immunoglobulin-DNA complexes or synthetic oligonucleotides, which all contain unmethylated cytosineguanine nucleotide sequences (CpGs). Emerging data indicate that TLr9 signaling has a role in, and may influence, colorectal carcinogenesis and colonic inflammation. CpGs are classified into three groups according to their influence on both the antigen-specific humoraland cellular immunity, and the production of type 1 interferons and proinflammatory cytokines. TLr9 activation via CpGs may serve as a new therapeutic target for several cancerous and various inflammatory conditions. Due to its probable anti-cancer effects, the application possibilities of TLr9-signaling modulation may be extremely diverse even in colorectal tumors. In this review we aimed to summarize the current knowledge about TLr-signaling in the pathogenesis and therapy of inflammatory bowel diseases and colorectal cancer. Due to the species-specific differences in TLr9 expression, however, one must be careful in translating the animal model data into the human system, because of the differences between CpG-oligodeoxynucleotide-responsive cells. TLr9 agonist DNA-based immunomodulatory sequences could also represent a promising therapeutic alternative in systemic inflammatory conditions and chronic colonic inflammations as their side effects are not significant.

关键词： Toll-like receptor 9 Synthetic oligodeoxy-nucleotide sequences DNA-based immunomodulatory sequences Colorectal cancer Inflammatory bowel diseases

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Diagnostic and prognostic potential of tissue and circulating long non-coding rNAs in colorectal tumors

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World Journal of Gastroenterology 2019年第34期25卷 5026-5048页

作者： Orsolya Galamb Barbara K Barták alexandra kalmár Zsófia B Nagy Krisztina A Szigeti Zsolt Tulassay Peter Igaz Béla Molnár Molecular Medicine research Group Hungarian Academy of SciencesBudapest H-1088Hungary 2nd Department of Internal Medicine Semmelweis UniversityBudapest H-1088Hungary

Long non-coding rNAs(lncrNAs)are members of the non-protein coding rNA family longer than 200 *** participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and immune responses,thereby playing a critical role in the development and progression of various cancers,including colorectal cancer(CrC).As CrC is one of the most frequently diagnosed malignancies worldwide with high mortality,its screening and early detection are crucial,so the identification of disease-specific biomarkers is *** are promising candidates as they are involved in carcinogenesis,and certain lncrNAs(e.g.,CCAT1,CrNDE,CrCAL1-4)show altered expression in adenomas,making them potential early diagnostic *** addition to being useful as tissue-specific markers,analysis of circulating lncrNAs(e.g.,CCAT1,CCAT2,BLACAT1,CrNDE,NEAT1,UCA1)in peripheral blood offers the possibility to establish minimally invasive,liquid biopsy-based diagnostic *** review article aims to describe the origin,structure,and functions of lncrNAs and to discuss their contribution to CrC ***,our purpose is to summarise lncrNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CrC.

关键词： Long non-coding rNA Colorectal cancer Colorectal adenoma Circulating long non-coding rNAs Exosome Biomarker Diagnostic marker Prognostic marker

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World Journal of Gastroenterology 2016年第47期22卷 10325-10340页

作者： Orsolya Galamb alexandra kalmár Barbara Kinga Barták árpád V Patai Katalin Leiszter Bálint Péterfia Barnabás Wichmann Gábor Valcz Gábor Veres Zsolt Tulassay Béla Molnár Molecular Medicine research Group Hungarian Academy of Sciences 2~(nd) Department of Internal Medicine Semmelweis University 1~(st) Department of Paediatrics Semmelweis University

AIM To analyze colorectal carcinogenesis and age-related DNA methylation alterations of gene sequences associated with epigenetic clock CpG sites. METHODS In silico DNA methylation analysis of 353 epigenetic clock Cp G sites published by Steve Horvath was performed using methylation array data for a set of 123 colonic tissue samples [64 colorectal cancer(CrC), 42 adenoma, 17 normal; GEO accession number: GSE48684]. Among the differentially methylated agerelated genes, secreted frizzled related protein 1(SFrP1) promoter methylation was further investigated in colonic tissue from 8 healthy adults, 19 normal children, 20 adenoma and 8 CrC patients using bisulfite-specific PCr followed by methylation-specific high resolution melting(MS-HrM) analysis. m rNA expression of age-related "epigenetic clock" genes was studied using Affymetrix HGU133 Plus2.0 whole transcriptome data of 153 colonic biopsy samples(49 healthy adult, 49 adenoma, 49 CrC, 6 healthy children)(GEO accession numbers: GSE37364, GSE10714, GSE4183, GSE37267). Whole promoter methylation analysis of genes showing inverse DNA methylationgene expression data was performed on 30 colonic samples using methyl capture *** Fifty-seven age-related Cp G sites including hypermethylated PPP1r16 B, SFrP1, SYNE1 and hypomethylated MGP, PIPOX were differentially methylated between CrC and normal tissues(P rmal comparison, 70 CpG sites differed significantly, including hypermethylated DKK3, SDC2, SFrP1, SYNE1 and hypomethylated CEMIP, SPATA18(P rM analysis, the SFrP1 promoter region was significantly hypermethylated in CrC(55.0% ± 8.4 %) and adenoma tissue samples(49.9% ± 18.1%) compared to normal adult(5.2% ± 2.7%) and young(2.2% ± 0.7%) colonic tissue(P rP1 promoter was slightly, but significantly increased in healthy adults compared to normal young samples(P rrelated with significantly increased S

关键词： DNA methylation Aging Colorectal cancer Adenoma Epigenetic drift Epigenetic clock Secreted frizzled related protein 1

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Small extrachromosomal circular DNA in amyotrophic lateral sclerosis matter

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Neural regeneration research 2025年第5期20卷 1411-1413页

作者： Marcos J.Arauzo-Bravo Daniela Gerovska Matthias Schwab alexandra Kretz Computational Biology and Systems Biomedicine Biodonostia Health Research InstituteSan SebastianSpain Basque Foundation for Science IKERBASQUEBilbaoSpainMax Planck Institute for Molecular BiomedicineComputational Biology and Bioinformatics GroupMünsterNorth Rhine-WestphaliaGermany Department of Cell Biology and Histology Faculty of Medicine and NursingUniversity of Basque Country(UPV/EHU)LeioaSpain Department of Neurology Jena University HospitalJenaThuringiaGermany

Comprehensive studies identify motor neuron spectrum disorders including amyotrophic lateral sclerosis(ALS)as globally rising fatal disorders with the highest prevalence in aging populations,influenced by ethnicity and ancestry(GBD 2016 Motor Neuron Disease Colla borators,2018).While~10% of diagnoses involve a family history(fALS),most cases are considered sporadic(sALS).However,population-based studies suggest that even cases without a common index mutation impart heritability(ryan et al.,2019),indicating a crucial role of rare and as yet unknown genetic denominators.

关键词： amyotrophic sclerosis

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Pressure-induced structural changes cause large enhancement of photoluminescence in halide perovskites: a quantitative relationship

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National Science review 2021年第9期8卷 13-14页

作者： alexandra Navrotsky Center for Materials of the Universe Arizona State University

Halide perovskites containing both organic and inorganic cations are receiving extensive attention for their promising optoelectronic properties, including photoluminescence (PL)[1,2]. Tuning these properties for specific applications and designing and synthesizing perovskites with optimized properties are major goals of materials science. These goals will be achieved faster and more economically by harnessing a fundamental understanding of structure–property relations, rather than by random searches for better materials. Chemical composition,temperature and pressure are the major‘knobs’ one can turn to adjust properties such as conductivity and bandgap[1,3]. Each of these variables has the potential to change interatomic distances,

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Small-scale genotypic richness stabilizes plot biomass and increases phenotypic variance in the invasive grass Phalaris arundinacea

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Journal of Plant Ecology 2018年第1期11卷 47-55页

作者： alexandra r.Collins Brian Beckage Jane Molofsky Division of Information Technology and Science Champlain College163 South WillardBurlingtonVermont05401USA Department of Plant Biology University of Vermont111 Jeffords Hall63 Carrigan DriveUniversity of VermontBurlingtonVermont 05405USA

Aims We aim to understand how small-scale genotypic richness and gen-otypic interactions influence the biomass and potential invasiveness of the invasive grass,Phalaris arundinacea under two different dis-turbance treatments:intact plots and disturbed plots,where all the native vegetation has been ***,we address the following questions(i)Does genotypic richness increase biomass production?(ii)Do genotypic interactions promote or reduce bio-mass production?(iii)Does the effect of genotypic richness and gen-otypic interactions differ in different disturbance treatments?Finally(iv)Is phenotypic variation greater as genotypic richness increases?Methods We conducted a 2-year common garden experiment in which we manipulated genotype richness using eight genotypes planted under both intact and disturbed conditions in a wetland in Burlington,Vermont(44°27′23″N,73°11′29″W).The experiment consisted of a randomized complete block design of three blocks,each containing 20 plots(0.5 m2)per disturbed *** calculated total plot biomass and partitioned the net biodiversity effect into three com-ponents:dominance effect,trait-dependent complementarity and trait-independent *** calculated the phenotypic variance for each different genotype richness treatment under the two disturbance *** Findings Our results indicate that local genotypic richness does not increase total biomass production of the invasive grass *** in either intact or disturbed ***,genotypic interactions underlying the responses showed very different patterns in response to increasing genotypic *** the intact treatment,genotypic interactions resulted in the observed biomass being greater than the predicted biomass from monoculture plots(e.g.,overyielding)and this was driven by ***,facilitation was reduced as genotypic richness *** the disturbed treatment,genotypic interactions resulted in underyielding w

关键词： invasive grass genotypic diversity Phalaris arundinacea tripartite method phenotypic variance

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“Pachyostosis” in aquatic amniotes: a review

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Integrative Zoology 2009年第4期4卷 325-340页

作者： alexandra HOUSSAYE Department of Earth History Museum of Natural HistoryParisFrance

During the course of amniote evolution,numerous taxa secondarily adapted to an aquatic *** appears that many of these taxa primitively display“pachyostosis,”an osseous specialization characterized by an increase in bone compactness and/or *** term“pachyostosis”is used in morphological and histological descriptions to describe what in fact corresponds to different *** aim of this paper is to present the current state of knowledge relative to this adaptation among aquatic *** the taxa that have returned to an aquatic environ-ment are ***,their degree of adaptation to the marine environment,their life environment,and the nature of their“pachyostotic”pattern,when present,are *** inventory enables the evaluation of the current quality of the data relative to this specialization and provides an indication of the work that remains to be *** functional consequences of“pachyostosis,”and notably its importance for buoyancy control in the context of hydrostatic regulation of the body trim,are discussed and opposed to the requirement of improved swimming abilities in the case of a hydrodynamic mode of trim *** are posed about the significa-tion of the polymorphism displayed by this specialization between different taxa,different specimens of the same taxon and different bones of the same specimen,and the problem of quantification of pachyostosis is discussed.

关键词： buoyancy control life environment locomotion “pachyostosis”sensu lato polymorphism.

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Catastrophic gastrointestinal complication of systemic immunosuppression

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World Journal of Gastroenterology 2015年第8期21卷 2542-2545页

作者： Lyn alexandra Smith Mitali Gangopadhyay Daniel r Gaya Gastroenterology Unit Glasgow Royal Infirmary Department of Pathology Southern General Hospital Glasgow

We present a case of acute upper gastrointestinal haemorrhage in a patient with systemic vasculitis immunosuppressed on cyclophosphamide and *** patient presented with a diffuse haemorrhagic oesophagitis and a non-specific *** taken from the oesophagus and duodenum demonstrated infection with herpes simplex virus(HSV)and cytomegalovirus(CMV)*** infection of the upper gastrointestinal tract is a recognised complication of immunosuppression and HSV is one of the most common *** on the other hand most commonly causes a colitis or less commonly *** enteritis is rare as is the synchronous infection with two viral agents in an immunocompromised patient having being described in a few case series *** infection of the gastrointestinal tract in immunocompromised patients should be treated with systemic anti-viral medication and consideration to withdrawal of the immunosuppressive therapy if possible and *** authors highlight the need for a high suspicion of viral infection in immunosuppressed patients presenting with upper gastrointestinal bleeding.

关键词： Immunosuppression Cytomegalovirus Gastrointestinal

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Efficiency of DNA barcodes for species delimitation:A case in Pterygiella Oliv.(Orobanchaceae)

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Journal of Systematics and Evolution 2011年第3期49卷 189-202页

作者： alexandra H.WOrTLEY royal Botanic Garden Edinburgh

DNA barcoding is becoming an increasingly popular means to identify *** obscure discrimination in the genus Pterygiella calls into question the re-assessment of the criterion for species *** collected 20 individuals,representing all five described species of this genus in its distributional *** aim was to use three proposed barcode DNA regions(rbcL,matK,and ITS) to diagnose Pterygiella species,and examine which barcode is more suitable for discerning the congeneric and related *** results showed that the core barcodes matK and rbcL were comparatively less ***,the ITS region,especially ITS-1 and ITS-2,successfully identified all species in the ***,the secondary structure of ITS-2 rNA,especially compensatory base changes,appears complementary to classical primary sequence analysis for DNA barcoding.

关键词： compensatory base changes(CBCs) DNA barcode ITS-2 non-monophyletic species Pterygiella Oliv. secondary structure.

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Bird species(Charadriiformes)does not impact endosymbiotic bacteria(Gammaproteobacteria)of their ectoparasites(Insecta:Phthiraptera:Ischnocera)

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Avian research 2024年第4期15卷 496-502页

作者： alexandra A.Grossi Min Zhang Fasheng Zou Daniel r.Gustafsson Guangdong Key Laboratory of Animal Conservation and resource Utilization Guangdong Public Library of Wild Animal Conservation and UtilizationInstitute of ZoologyGuangdong Academy of SciencesGuangzhou510260China Key Laboratory for Biodiversity Science and Ecological Engineering College of Life SciencesBeijing Normal UniversityBeijing100875China

Endosymbiotic bacteria of insects can facilitate host expansion into novel niches by providing their host with a fitness benefit such as vitamins or amino acids that are otherwise lacking in their hosts’*** close association can lead to cospeciation between insects and their symbionts;however,the symbionts’small genome size leaves it susceptible to genome derogation which can result in symbiont ***,we screen chewing lice infesting shorebirds and terns to see what endosymbiotic bacteria are present,and build a summary phylogeny that includes louse endosymbiont sequences from this study as well as those from other louse genera,insects and bacteria strains from *** found a Sodalis-allied endosymbiont in Carduiceps,Lunaceps,Quadraceps,and Saemundssonia,as well as symbionts belonging to the family Enterobacteriaceae in Lunaceps,and *** louse species were host to both endosymbionts;however,the birds Kentish Plover(Charadrius alexandrinus)and Greater Crested Tern(Thalasseus bergii)were host to two genera of lice,each of which was infested with a different group of *** the summary phylogeny the endosymbionts from shorebirds,and tern lice did not form a monophyletic group,and therefore likely acquired their bacterial endosymbionts multiple times.

关键词： Carduiceps Charadriiformes Endosymbiotic bacteria Phthiraptera Phylogeny Quadraceps-complex Sodalis

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