scholarly journals CBMS-1 Targeting amino acid metabolic vulnerabilities in IDH-mutant and IDH-wildtype gliomas

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi2-vi2
Author(s):  
Shigeo Ohba ◽  
Akiyoshi Hirayama ◽  
Keisuke Hitachi ◽  
Hisateru Yamaguchi ◽  
Takao Teranishi ◽  
...  
Keyword(s):  
Antitumor Effect ◽  
Culture Medium ◽  
Cancer Metabolism ◽  
Lower Amount ◽  
Rna Seq ◽  
Artificial Cell ◽  
The Status ◽  
Normal Human ◽  
The Difference ◽  
Mutant Idh1

Abstract IDH-wildtype glioma and IDH-mutant glioma have different genetical and metabolic background although their histological appearances are similar. To reveal the difference in metabolites between IDH-wildtype and IDH-mutant glioma, and to find the effective treatment targeting cancer metabolism according to the status of IDH in gliomas, two artificial cell lines made from normal human astrocyte, NHAE6E7hTERTRas (IDH-wildtype) and NHAE6E7hTERTIDHmut (IDH-mutant), were investigated. RNA-seq analysis revealed that about 10% of changed genes were involved with metabolism. Capillary electrophoresis- and ion chromatography-coupled mass spectrometry revealed that the amount of asparagine was lower in NHAE6E7hTERTRas cells compared with NHAE6E7hTERTIDHmut cells. L-asparaginase, which converts asparagine into aspartate, was more effective in former cells. L-asparaginase induced autophagy and inhibition of autophagy by 3-MA suppressed L-asparaginase-induced antitumor effect. Adding asparagine into the culture medium rescued the antitumor effect of L-asparaginase. L-asparaginase increased the expression of asparagine synthetase (ASNS) and inhibition of ASNS enhanced the antitumor effect of L-asparaginase. Metabolic assay also showed the lower amount of glutamine, glutamate and 2-oxoglutarate in NHAE6E7hTERTIDHmut cells than NHAE6E7hTERTRas cells. Inhibition of GLUD1 which converts glutamate to 2-oxoglutarate, suppressed proliferation of the cells by inducing ROS and apoptosis in NHAE6E7hTERTIDHmut cells. Exogeneous dimethyl 2-oxoglutarate rescued the cytotoxicity by GLUD1 inhibitor, suggesting decreased 2-oxoglutarate was associated with GLUD1 inhibitor-induced cytotoxicity. ROS inhibitor, NAC suppressed GLUD1 inhibitor-induced ROS, apoptosis, and cytotoxicity in NHAE6E7hTERTIDHmut cells, revealing that cytotoxicity by GLUD1 inhibitor was at least partially due to the inhibitor-induced ROS. Other IDH-wildtype glioma cells, U251 and U87 showed similar sensitivity to L-asparaginase and GLUD1 inhibitor to NHAE6E7hTERTRas, whereas U251 expressing mutant IDH1 showed similar sensitivity to GLUD1 inhibitor to NHAE6E7hTERTIDHmut, which suggested that the difference of sensitivity to each reagent was due to the status of mutant IDH. L-asparaginase and GLUD1 inhibitor will be new therapeutic options for IDH-wildtype glioma and IDH-mutant glioma, respectively.

TAMI-56. TARGETING AMINO ACID METABOLIC VULNERABILITIES IN IDH-MUTANT AND IDH-WILDTYPE GLIOMAS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi209-vi210
Author(s):  
Shigeo Ohba ◽  
Akiyoshi Hirayama ◽  
Keisuke Hitachi ◽  
Hisateru Yamaguchi ◽  
Joydeep Mukherjee ◽  
...  
Keyword(s):  
Antitumor Effect ◽  
Culture Medium ◽  
Cancer Metabolism ◽  
Therapeutic Option ◽  
Lower Amount ◽  
Flight Mass Spectrometry ◽  
Artificial Cell ◽  
The Status ◽  
Normal Human ◽  
The Difference

Abstract IDH-wildtype glioma and IDH-mutant glioma have different genetical and metabolic background although their histological appearances are similar. The aim of the study is to reveal the difference in metabolites between IDH-wildtype glioma and IDH-mutant glioma, and to find the effective treatment targeting cancer metabolism according to the status of IDH in gliomas. Two artificial cell lines made from normal human astrocyte were used: NHAE6E7hTERTRas (IDH-wildtype) and NHAE6E7hTERTIDHmut (IDH-mutant). Capillary electrophoresis time-of-flight-mass spectrometry (CE-TOFMS) revealed that the amount of asparagine was lower in NHAE6E7hTERTRas cells compared with NHAE6E7hTERTIDHmut cells. L-asparaginase, which converts asparagine into aspartate, was more effective in the former cells than the latter cells. L-asparaginase induced autophagy and inhibition of autophagy by 3-MA suppressed L-asparaginase-induced antitumor effect. Adding asparagine into the culture medium rescued the antitumor effect of L-asparaginase. L-asparaginase increased the expression of asparagine synthetase (ASNS) and genetical or pharmacological inhibition of ASNS enhanced the antitumor effect of L-asparaginase. CE-TOFMS showed the lower amount of glutamine, glutamate and 2-oxoglutarate in NHAE6E7hTERTIDHmut cells than NHAE6E7hTERTRas cells. GLUD1 inhibitor inhibited proliferation by inducing higher ROS level and apoptosis in NHAE6E7hTERTIDHmut cells than NHAE6E7hTERTRas cells. ROS inhibitor, NAC suppressed GLUD1 inhibitor-induced ROS, apoptosis, and cytotoxicity in NHAE6E7hTERTIDHmut cells. Exogeneous dimethyl 2-oxoglutarate rescued the cytotoxicity induced by GLUD1 inhibitor. L-asparaginase and GLUD1 inhibitor will be new therapeutic option for IDH-wildtype glioma and IDH-mutant glioma, respectively.

Motivasi dan kepuasan kerja pegawai puskesmas BLUD dan non-BLUD Kabupaten Semarang

2018 ◽  
Vol 2 (3) ◽  
pp. 111
Author(s):  
Aswindar Adhi Gumilang ◽  
Tri Pitara Mahanggoro ◽  
Qurrotul Aini
Keyword(s):  
Public Health ◽  
Job Satisfaction ◽  
Financial Management ◽  
Work Motivation ◽  
P Value ◽  
The Public ◽  
The Status ◽  
The Difference ◽  
Demand For Health ◽  
Public Demand

The public demand for health service professionalism and transparent financial management made some Puskesmas in Semarang regency changed the status of public health center to BLUD. The implementation of Puskesmas BLUD and non-BLUD requires resources that it can work well in order to meet the expectations of the community. The aim of this study is to know the difference of work motivation and job satisfaction of employees in Puskesmas BLUD and non-BLUD. Method of this research is a comparative descriptive with a quantitative approach. The object of this research are work motivation and job satisfaction of employees in Puskesmas BLUD and non-BLUD Semarang regency. This Research showed that Sig value. (P-value) work motivation variable was 0.019 smaller than α value (0.05). It showed that there was a difference of work motivation of employees in Puskemas BLUD and non-BLUD. Sig value (P-value) variable of job satisfaction was 0.020 smaller than α value (0.05). It showed that there was a difference of job satisfaction of BLUD and non-BLUD. The average of non-BLUD employees motivation were 76.59 smaller than the average of BLUD employees were 78.25. The average of job satisfaction of BLUD employees were 129.20 bigger than the average of non-BLUD employee were 124.26. Job satisfaction of employees in Puskesmas BLUD was higher than non-BLUD employees.

Vier Arten von Römern unter den Franken im 6. bis 8. Jh.

2016 ◽  
Vol 133 (1) ◽  
pp. 459-468
Author(s):  
Detlef Liebs
Keyword(s):  
Criminal Law ◽  
Civil Law ◽  
Roman Law ◽  
Procedural Law ◽  
The Status ◽  
The Difference ◽  
Law Texts ◽  
Fourth Kind

Abstract Four kinds of Romans in the Frankish kingdoms in the 6th to 8th centuries. Roman law texts from Merowingian Gaul make a difference between cives Romani, Latini and dediticii, all considered as Romans. This difference mattered only to slaves who had been freed. The status of Latin and dediticius was hereditary, whereas the descendants of one who had been freed as civis Romanus were free born Romans, who should be classified as a proper, a fourth kind of beeing Roman; it was the standard kind. The difference was important in civil law, procedural law and criminal law, especially in wergeld, the sum to be payed for expiation when somebody had been killed: Who had killed a Roman, had to pay different sums according to the status of the killed.

Optimization of the Expression of 1,3-1,4-β-glucanase Gene from Rhizomucor miehei in the Komagataella kurtzmanii yeast

2019 ◽  
Vol 35 (5) ◽  
pp. 3-11 ◽  
Author(s):  
I.I. Gubaidullin ◽  
A.S. Fedorov ◽  
D.G. Kozlov
Keyword(s):  
Target Gene ◽  
Rhizomucor Miehei ◽  
Leader Peptide ◽  
Promoter Regions ◽  
Functional Elements ◽  
Resource Center ◽  
The Status ◽  
Pichia Pastoris Yeast ◽  
The Difference ◽  
Genetic Constructs

Key functional elements of the vector (promoter, leader and terminator regions) that provide the expression of a target l,3-l,4-(3-glucanase gene from Rhizomucor miehei in the Komagataella kurtzmanii yeast have been optimized. It was shown that the promoter regions of the gene AOX1 from the Pichia pastoris yeast currently reclassified as Komagataella phaffti and from К. kurtzmanii yeast as parts of a vector provided equal levels of expression of the target gene in the cells of the recipient strain К. kurtzmanii Y727his4, i.e. they were completely interchangeable. This means that genetic constructs that were previously developed for the biosynthesis of recombinant proteins in К. phajfii are able to provide an effective expression in the К kurtzmanii yeast. The leader peptide MF4I (used as a variant of mif4I containing one amino acid substitution) and the leader peptide maxHH (containing the double proregion of the Hspl50 protein from Saccharomyces cerevisiae) confirmed the status of the most powerful elements among the five leader sequences analyzed. Their efficiency was 1.7 times higher than that of the standard leader from the yeast alpha-factor, and by 20% higher than the characteristics of the second group of artificial leaders. At the same time, it was found that, the choice of the terminator region had the strongest influence on the expression of the target gene among all of the vector functional elements. The best terminator elements were variants derived from the transcription termination region of the AOX1 gene, and the difference in the expression level of the target gene using different terminators was approximately 4.5 times. Based on the analysis of the obtained data, the optimal composition of the key functional elements of the expression vector was determined ; it included the promoter and terminator regions of the AOX1 yeast gene and one of the artificial leaders, mif4I or maxHH. β-glucanase, Komagataella kurtzmanii, yeast, secretion, strain producer The work was financially supported by the Ministry of Science and Higher education of the Russian Federation (Unique Project Identifier RFMEFI60717X0179) using the Unique Scientific Facility of the National Bio-Resource Center «All-Russian Collection of Industrial Microorganisms», NRC «Kurchatov Institute» - GOSNIIGENETIKA

Through the Lens of Gadamer’s Hermeneutics: In comparison between Amina Wadud’s and Mohammed Talbi’s Interpretations of Q. 4:34

SUHUF ◽  
2017 ◽  
Vol 9 (2) ◽  
pp. 193-214
Author(s):  
Afifur Rochman Sya'rani
Keyword(s):  
Gender Inequality ◽  
Married Couple ◽  
Contextual Approach ◽  
The Status ◽  
Similarities And Differences ◽  
The Difference ◽  
Muslim Scholars ◽  
The Way

Most of traditional Muslim exegetes interpret Q. 4:34 in terms of maintaining the superiority of men over women. Some progressive Muslim scholars then insist a contextual approach to the verse to criticize gender inequality. Among some progressive Muslim scholars, this article comparatively examines the interpretations of Amina Wadud and Mohammed Talbi of Q. 4:34. Although both of them propose a contextual reading of the verse, they have different intellectual background, approach and method in interpreting the Qur’ān. The questions are to what extent the similarities and differences of both Wadud’s and Talbi’s interpretation of Q. 4:34 and how far their interpretations reflect their respective intention and perspective? Applying Gadamer’s hermeneutical approach, the article concludes that [1] Both Wadud and Talbi argue that the verse does not establish the superiority of men over women, but acknowledges duties division among married couple; [2] the difference among their interpretations is on the status of relationship among married couple; [3] Wadud’s and Talbi’s interpretations represent their respective hermeneutical situations and the way they define ontologically the nature of  interpretation and Qur’anic hermeneutics affect on producing the meanings of the verse.

scholarly journals What Difference Does Posthumanism Make?

2021 ◽  
pp. 1-7
Author(s):  
Rachel J. Crellin ◽  
Oliver J.T. Harris
Keyword(s):  
Productive Force ◽  
The World ◽  
The Status ◽  
The Difference ◽  
The Relationship

In this paper we argue that to understand the difference Posthumanism makes to the relationship between archaeology, agency and ontology, several misconceptions need to be corrected. First, we emphasize that Posthumanism is multiple, with different elements, meaning any critique needs to be carefully targeted. The approach we advocate is a specifically Deleuzian and explicitly feminist approach to Posthumanism. Second, we examine the status of agency within Posthumanism and suggest that we may be better off thinking about affect. Third, we explore how the approach we advocate treats difference in new ways, not as a question of lack, or as difference ‘from’, but rather as a productive force in the world. Finally, we explore how Posthumanism allows us to re-position the role of the human in archaeology,

scholarly journals Extracellular Proteome Analysis Shows the Abundance of Histidine Kinase Sensor Protein, DNA Helicase, Putative Lipoprotein Containing Peptidase M75 Domain and Peptidase C39 Domain Protein in Leptospira interrogans Grown in EMJH Medium

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 852
Author(s):  
Abhijit Sarma ◽  
Dhandapani Gunasekaran ◽  
Devasahayam Arokia Balaya Rex ◽  
Thoduvayil Sikha ◽  
Homen Phukan ◽  
...  
Keyword(s):  
Culture Medium ◽  
Proteome Analysis ◽  
Dna Helicase ◽  
Extracellular Proteins ◽  
Surface Proteins ◽  
Secretory Proteins ◽  
Extracellular Proteome ◽  
Cell Pellet ◽  
The Difference ◽  
Leptospira Species

Leptospirosis is a re-emerging form of zoonosis that is caused by the spirochete pathogen Leptospira. Extracellular proteins play critical roles in the pathogenicity and survival of this pathogen in the host and environment. Extraction and analysis of extracellular proteins is a difficult task due to the abundance of enrichments like serum and bovine serum albumin in the culture medium, as is distinguishing them from the cellular proteins that may reach the analyte during extraction. In this study, extracellular proteins were separated as secretory proteins from the culture supernatant and surface proteins were separated during the washing of the cell pellet. The proteins identified were sorted based on the proportion of the cellular fractions and the extracellular fractions. The results showed the identification of 56 extracellular proteins, out of which 19 were exclusively extracellular. For those proteins, the difference in quantity with respect to their presence within the cell was found to be up to 1770-fold. Further, bioinformatics analysis elucidated characteristics and functions of the identified proteins. Orthologs of extracellular proteins in various Leptospira species were found to be closely related among different pathogenic forms. In addition to the identification of extracellular proteins, this study put forward a method for the extraction and identification of extracellular proteins.

scholarly journals Scanning Electron-Assisted Dielectric Microscopy Reveals Autophagosome Formation by LC3 and ATG12 in Cultured Mammalian Cells

2021 ◽  
Vol 22 (4) ◽  
pp. 1834
Author(s):  
Tomoko Okada ◽  
Toshihiko Ogura
Keyword(s):  
Mammalian Cells ◽  
Culture Medium ◽  
Related Gene ◽  
Autophagosome Formation ◽  
Intact Cells ◽  
Microtubule Associated Proteins ◽  
Associated Proteins ◽  
The Difference ◽  
Related Proteins ◽  
Scanning Electron

Autophagy is an intracellular self-devouring system that plays a central role in cellular recycling. The formation of functional autophagosomes depends on several autophagy-related proteins, including the microtubule-associated proteins 1A/1B light chain 3 (LC3) and the conserved autophagy-related gene 12 (Atg12). We have recently developed a novel scanning electron-assisted dielectric microscope (SE-ADM) for nanoscale observations of intact cells. Here, we used the SE-ADM system to observe LC3- and Atg12-containing autophagosomes in cells labelled in the culture medium with antibodies conjugated to colloidal gold particles. We observed that, during autophagosome formation, Atg12 localized along the actin meshwork structure, whereas LC3 formed arcuate or circular alignments. Our system also showed a difference in the distribution of LC3 and Atg12; Atg12 was broadly distributed while LC3 was more localized. The difference in the spatial distribution demonstrated by our system explains the difference in the size of fluorescent spots due to the fluorescently labelled antibodies observed using optical microscopy. The direct SE-ADM observation of cells should thus be effective in analyses of autophagosome formation.

scholarly journals Impacts of Gender Differences on Women’s Participation in Community Work in Abbay Chomman Woreda, Ethiopia

2019 ◽  
Vol 13 ◽  
pp. 86-118
Author(s):  
RATA B KENEA
Keyword(s):  
Economic Empowerment ◽  
Research Approach ◽  
Community Work ◽  
Quantitative And Qualitative Research ◽  
Women's Participation ◽  
Participation Of Women ◽  
The Status ◽  
The Difference ◽  
The Town ◽  
Status Of Women

Though the participation of women in economic development and community work usually realized low as a whole due to various reasons, the contribution of gender in creating the difference in terms of their status even among the participatory women is untouched area. For instance, the research conducted by Atinafu Diga (2013) on assessment of economic empowerment of women the related studies entitled Assessment of economic empowerment of Women in Kolobo kebele, Abay chomman Woreda dealt with only inadequate economic empowerment problems and low participation of Women in educational leadership areas respectively as their overall findings. As a result, this study is undertaken to assess the status of women disparity to participate in community work in case of kolobo kebele, Ambo town, Oromia Regional State; Ethiopia.This study is descriptive in nature. For this particular study, both quantitative and qualitative research approach were employed. In doing this research paper, of the total population,79 samples were selected from the town selected using simple random and purposive sampling techniques. Here, 79 were responded for the 20 close-ended questions of the questionnaire and another 10 were responded for open-ended questions of the interview. To analyses the quantitative data, techniques such as tabulation, percentages, and numerical figures were employed to. On the other hand, Narration and comparative discussion were covered to analyse the qualitatively collected data.

scholarly journals Territorial organization of the restaurant facilities of Kyiv agglomeration

2015 ◽  
pp. 79-82
Author(s):  
K. Dmytriieva
Keyword(s):  
Restaurant Industry ◽  
The Core ◽  
Industry Standards ◽  
The Status ◽  
Territorial Organization ◽  
The Difference ◽  
Surrounding Areas ◽  
Concentration Ratios

The article outlines the factors of development of the restaurant facilities in Kyiv and surrounding areas. The status of the territorial organization of the restaurant facilities of Kyiv and Kyiv region through the review of the main indicators of the industry by districts in 2013 has been analyzed. Comparison of the industry standards due to availability of these services to population needs has been performed. The result of the difference of efficiency of the restaurant industry through calculation of concentration ratios turnover has been received. Area that can be considered as the core of the restaurant industry of Kyiv agglomeration and area with the potential of growth has been identified. The article visualized by maps.

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