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Genetic background of phenotypic variation

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Progress in Natural Science:materials International 2007年第10期17卷 1119-1126页

作者： zsolt Boldogki Department of Biology Faculty of medicine University of Szeged Somogyi Bela st. 4 H-6720 Szeged Hungary

A noteworthy feature of the living world is its bewildering variability. A key issue in several biological disciplines is the achievement of an understanding of the hereditary basis of this variability. Two opposing, but not necessarily irreconcilable conceptions attempt to explain the underlying mechanism. The gene function paradigm postulates that phenotypic variance is generated by the polymorphism in the coding sequences of genes. However, comparisons of a great number of homologous gene and protein sequences have revealed that they predominantly remained functionally conserved even across distantly related phylogenic taxa. Alternatively, the gene regulation paradigm assumes that differences in the cis-regulatory region of genes do account for phenotype variation within species. An extension of this latter concept is that phenotypic variability is generated by the polymorphism in the overall gene expression profiles of gene networks. In other words, the activity of a particular gene is a system property determined both by the cis-regulatory sequences of the given genes and by the other genes of a gene network, whose expressions vary among individuals, too. Novel proponents of gene function paradigm claim that functional genetic variance within the coding sequences of regulatory genes is critical for the generation of morphological polymorphism. Note, however, that these developmental genes play direct regulatory roles in the control of gene expression.

关键词： evolution gene network gene regulation genetic variance phenotype variation.

Formability Investigations of High-Strength Dual-Phase Steels

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Acta metallurgica Sinica(English Letters) 2015年第12期28卷 1471-1481页

作者： miklós Tisza zsolt Lukács Department of materials Processing Technology Institute of Materials Science and Technology University of Miskolc

Car manufacturing is always regarded as the key industry behind sheet metal forming, and thus, the requirements of and developments in car manufacturing play a decisive role in the development of sheet metal forming. The automotive industry is faced with contradictory demands and requirements： better performance with lower consumption and less harmful emissions, more safety and comfort; these are extremely difficult to supply simultaneously with conventional materials and conventional manufacturing processes. The fulfillment of these often contradictory requirements is one of the main driving forces in the automotive industry and thus in the material and process developments in sheet metal forming, as well. In recent years, significant developments can be observed in the application of high-strength steels. In this respect, the application of various dual-phase steels is one of the best examples. However, the application of these highstrength steels often leads to formability and manufacturing problems. One formability problem is the springback occurring after sheet metal forming. In the current research, we have dealt mainly with advanced high-strength steels, primarily with dual-phase steels. When applying them, the springback phenomenon is one of the most critical issues. To reduce the tremendous amount of experimental work needed, we also applied numerical simulation using isotropic–kinematic hardening rules. The isotropic–kinematic hardening behavior of a given material in the applied Auto Form numerical package may be characterized with three independent material parameters c, v and K（a detailed explanation of their meaning will be given in the main part of this paper）. However, we found that the material data included in simulation packages for these new high-strength steels are not fully adequate. For the determination of more reliable material parameters and to achieve better simulation results, a new testing device was developed. Numerical simulations were

关键词： Springback Large-strain cyclic deformation High-strength dual-phase steels

Changes of the cytokine profile in inflammatory bowel diseases

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World Journal of Gastroenterology 2012年第41期18卷 5848-5861页

作者： Gyrgyi mzes Béla molnár zsolt Tulassay Ferenc Sipos 2nd Department of Internal medicine Semmelweis University1088 BudapestHungary molecular medicine Research Unit Hungarian Academy of Sciences1051 BudapestHungary

Cytokines are indispensable signals of the mucosaassociated immune system for maintaining normal gut *** imbalance of their profile in favour of inflammation initiation may lead to disease states,such as that is observed in inflammatory bowel diseases(IBD).Although Crohn's disease(CD) is often described as a prototype of T-helper 1-type diseases,and ulcerative colitis(UC) is traditionally viewed as a T-helper 2-mediated condition,the classic paradigm,which categorises cytokines into pro-and anti-inflammatory groups,has recently been *** inflammation regulatory pathways may not be mutually exclusive as individual cytokines can have diverse and even opposing functions in various clinical and immunological *** the less there are many common immunological responses in IBD that are mediated by *** they regulate and influence the development,course and recurrence of the inflammatory process,the concrete pathogenic role of these small signaling molecules is sometimes not unambiguous in the subtypes of the *** aim is to review the current information about pro-and anti-inflammatory effects of traditionally studied and recently discovered cytokines in the pathogenesis of UC and *** better understanding of their production and functional activity may lead to the development of new therapeutic modalities.

关键词： Ulcerative colitis Crohn's disease Interleu-kin-33 Tumor necrosis factor-like factor Interleukin-8 Interleukin-35 Interleukin-25 Interleukin-4 Tumornecrosis factor ligand superfamily member 14

CYP24A1 inhibition facilitates the anti-tumor effect of vitamin D3 on colorectal cancer cells

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World Journal of Gastroenterology 2013年第17期19卷 2621-2628页

作者： János P Kósa Péter Horváth János Wlfling Dóra Kovács Bernadett Balla Péter mátyus Evelin Horváth Gábor Speer István Takács zsolt Nagy Henrik Horváth Péter Lakatos 1 st Department of Internal medicine Semmelweis University Department of Organic Chemistry University of Szeged Department of Organic Chemistry Semmelweis University

AIm:The effects of vitamin D3 have been investigated on various tumors, including colorectal cancer (CRC). 25-hydroxyvitamin-D3-24-hydroxylase (CYP24A1), the enzyme that inactivates the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 (1,25-D3), is considered to be the main enzyme determining the biological halflife of 1,25-D3. During colorectal carcinogenesis, the expression and concentration of CYP24A1 increases significantly, suggesting that this phenomenon could be responsible for the proposed efficacy of 1,25-D3 in the treatment of CRC. The aim of this study was to investigate the anti-tumor effects of vitamin D3 on the human CRC cell line Caco-2 after inhibition of the cytochrome P450 component of CYP24A1 activity. mETHODS:We examined the expression of CYP24A1 mRNA and the effects of 1,25-D3 on the cell line Caco-2 after inhibition of CYP24A1. Cell viability and proliferation were determined by means of sulforhodamine-B staining and bromodeoxyuridine incorporation, respectively, while cytotoxicity was estimated via the lactate dehydrogenase content of the cell culture supernatant. CYP24A1 expression was measured by realtime reverse transcription polymerase chain reaction. A number of tetralone compounds were synthesized to investigate their CP24A1 inhibitory activity. RESULTS:In response to 1,25-D3, CYP24A1 mRNA expression was enhanced significantly, in a time- and dose-dependent manner. Caco-2 cell viability and proliferation were not influenced by the administration of 1,25-D3 alone, but were markedly reduced by coadministration of 1,25-D3 and KD-35, a CYP24A1-inhibiting tetralone. Our data suggest that the mechanism of action of co-administered KD-35 and 1,25-D3 does not involve a direct cytotoxic effect, but rather the inhibition of cell proliferation. CONCLUSION:These findings demonstrate that the selective inhibition of CYP24A1 by compounds such as KD-35 may be a new approach for enhancement of the anti-tumor effect of 1,25-D3 on CRC.

关键词： Colorectal cancer CYP24A1 inhibition Vitamin D3 Tetralone derivatives Caco-2 cell culture

Interplay of autophagy and innate immunity in Crohn's disease: A key immunobiologic feature

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World Journal of Gastroenterology 2013年第28期19卷 4447-4454页

作者： Gyrgyi müzes zsolt Tulassay Ferenc Sipos 2nd Department of Internal medicine Semmelweis University 1088 Budapest Hungary

Crohn's disease representing a clinical phenotype of inflammatory bowel disease is a polygenic immune disorder with complex multifactor etiology. Recent genome-wide association studies of susceptibility loci have highlighted on the importance of the autophagy pathway, which previously had not been implicated in disease pathology. Autophagy represents an evolutionarily highly conserved multi-step process of cellular self-digestion due to sequestration of excessive, damaged, or aged proteins and intracellular organelles in double-membranous vesicles of autophagosomes, terminally self-digested in lysosomes. Autophagy is deeply involved in regulation of cell development and differentiation, survival and senescence, and it also fundamentally affects the inflammatory pathways, as well as the innate and adaptive arms of immune responses. Autophagy is mainly activated due to sensors of the innate immunity, i.e., by pattern recognition receptor signaling. The interplay of genes regulating immune functions is strongly influenced by the environment, especially gut resident microbiota. The basic challenge for intestinal immune recognition is the requirement of a simultaneous delicate balance between tolerance and responsiveness towards microbes. On the basis of autophagy-related risk genetic polymorphisms (ATG16L1, IRGm , NOD2 , XBP1 ) impaired sensing and handling of intracellular bacteria by innate immunity, closely interrelated with the autophagic and unfolded protein pathways seem to be the most relevant immunobiologic events. Autophagy is now widely considered as a key regulator mechanism with the capacity to integrate several aspects of Crohn's disease pathogenesis. In this review, recent advances in the exciting crosstalk of susceptibility coding variants-related autophagy and innate immunity are discussed.

关键词： Crohn’s disease Innate immunity Autophagy genes Autophagy Gut microbiota

Effect of ageing on colonic mucosal regeneration

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World Journal of Gastroenterology 2011年第25期17卷 2981-2986页

作者： Ferenc Sipos Katalin Leiszter zsolt Tulassay 2nd Department of Internal medicine Semmelweis University molecular medicine Research Unit Hungarian Academy of Sciences

The physiologic and pathologic cellular and molecular changes occurring with age in the human colon affect both the inflammatory process leading to mucosal injury and the regenerative capacity of the *** the one hand,age-related telomere shortening and inflamm-ageing may lead to the development of colonic inflammation,which results in epithelial *** the other hand,the altered migration and function of regenerative stem cells,the age-related methylation of mucosal healing-associated genes,together with the alterations of growth factor signaling with age,may be involved in delayed mucosal *** connections of these alterations to the process of ageing are not fully *** understanding and customtailored modification of these mechanisms are of great clinical importance with regard to disease prevention and modern therapeutic ***,we aim to summarize the age-related microscopic and molecular changes of the human colon,as well as their role in altered mucosal healing.

关键词： Colon mucosal repair Ageing Colorectalcancer Telomere shortening DNA methylation

Helicobacter pylori infection: New pathogenetic and clinical aspects

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World Journal of Gastroenterology 2014年第21期20卷 6386-6399页

作者： Krisztina Hagymási zsolt Tulassay 2~(nd) Department of Internal medicine Semmelweis UniversityH-1088 BudapestHungary

Helicobacter pylori (H. pylori) infects more than half of the world’s human population, but only 1% to 3% of infected people consequently develop gastric adenocarcinomas. The clinical outcome of the infection is determined by host genetic predisposition, bacterial virulence factors, and environmental factors. The association between H. pylori infection and chronic active gastritis, peptic ulcer disease, gastric cell carcinoma, and B cell mucosa-associated lymphoid tissue lymphoma has been well established. With the exception of unexplained iron deficiency anemia and idiopathic thrombocytopenic purpura, H. pylori infection has no proven role in extraintestinal diseases. On the other hand, there is data showing that H. pylori infection could be beneficial for some human diseases. The unpredictability of the long-term consequences of H. pylori infection and the economic challenge in eradicating it is why identification of high-risk individuals is crucial.

关键词： Helicobacter pylori Virulence factor Host factors Gastroduodenal diseases Extraintestinal disorders

Symmetric carbon tetramers forming spin qubits in hexagonal boron nitride

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npj Computational materials 2023年第1期9卷 407-416页

作者： zsolt Benedek Rohit Babar Ádám Ganyecz Tibor Szilvási Örs Legeza Gergely Barcza Viktor Ivády Strongly Correlated Systems Lendület Research Group Wigner Research Centre for PhysicsPO Box 49H-1525 BudapestHungary mTA-ELTE Lendület“momentum”NewQubit Research Group Pázmány PéterSétány 1/A1117 BudapestHungary Department of Chemical and Biological Engineering The University of AlabamaTuscaloosaAL 35487USA Institute for Advanced Study Technical University of MunichLichtenbergstrasse 2a85748 GarchingGermany Department of Physics of Complex Systems Eötvös Loránd UniversityEgyetem tér 1-3H-1053 BudapestHungary Department of Physics Chemistry and BiologyLinköping UniversitySE-58183 LinköpingSweden

Point defect quantum bits in semiconductors have the potential to revolutionize sensing at atomic ***,vacancy-related defects are at the forefront of high spatial resolution and low-dimensional *** the other hand,it is expected that impurity-related defect structures may give rise to new features that could further advance quantum sensing in low ***,we study the symmetric carbon tetramer clusters in hexagonal boron nitride and propose them as spin qubits for *** utilize periodic-DFT and quantum chemistry approaches to reliably and accurately predict the electronic,optical,and spin properties of the studied *** show that the nitrogen-centered symmetric carbon tetramer gives rise to spin state-dependent optical signals with strain-sensitive intersystem crossing ***,the weak hyperfine coupling of the defect to their spin environments results in a reduced electron spin resonance linewidth that can enhance sensitivity.

关键词： hexagonal boron quantum

Changing human-environment interactions in medium mountains:the Apuseni mts(Romania)as a case study

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Journal of mountain Science 2016年第9期13卷 1675-1687页

作者： TELBISZ Tamas ImECS Zoltan mARl Laszlo BOTTLIK zsolt Department of Physical Geography Eotvos University1117BudapestPazrnany Peter setany 1/CBudapestHungary Department of Geography in Hungarian Babes-Bolyai University400006Cluj-NapocaStr.Clinicilor 5-7Romania Department of Regional Science Eotoos University1117BudapestPazmany Peter setany 1/CBudapestHungary

The study of human-environment relationships in mountain areas is important for both theoretical and practical reasons, as many mountain areas suffer similar problems, such as depopulation, unemployment and natural hazards. medium mountains constitute a special case within mountains, because they are more populated but less attractive as tourist destinations than high mountains. In this context, the Apuseni mts （Romania） are considered as a ease study. In this paper, we apply GIS-based, quantitative methods to characterize the strength and dynamics of human-environment interactions, taking into consideration some environmental factors （elevation, relative height, slope, river distance, lithology, land cover, natural attractions） as well as historical population and recent tourism data. We found that population density has strong （r2〉0.8） relationships with all relief factors （elevation, relative height, slope, river distance）, and that best-fit functions are nonlinear. We outlined the varying demographic scenarios by elevation zones and interpreted the historically switching sign of population change versus elevation relationship. We demonstrated that lithology also has an impact on the spatial distribution of population, although it is not independent from the relief effect. The land cover of the mainly cultural landscape is very strongly correlated with relief parameters （especially slope）, which suggests good adaptation. We pointed out the dominance of karst objects in the natural tourism potential of the Apuseni mts and also explored further components of real tourism （spas, heritage, towns）. Finally, we concluded that the environmental settings investigated do in fact constrain the spatial framework of society, but soeio-economic changes in history can be explained from the side of society, which conforms to the theory of cultural possibilism.

关键词： Human-environment relations Apusenimountains Geographical information system (GIS) Possibilism Tourism Karst