Starvation for amino acids induces Gcn4p, a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. In an effort to identify all genes regulated by Gcn4p during amino acid starvation, we performed cDNA microarray analysis. Data from 21 pairs of hybridization experiments using two different strains derived from S288c revealed that more than 1,000 genes were induced, and a similar number were repressed, by a factor of 2 or more in response to histidine starvation imposed by 3-aminotriazole (3AT). Profiling of a gcn4Δ strain and a constitutively induced mutant showed that Gcn4p is required for the full induction by 3AT of at least 539 genes, termed Gcn4p targets. Genes in every amino acid biosynthetic pathway except cysteine and genes encoding amino acid precursors, vitamin biosynthetic enzymes, peroxisomal components, mitochondrial carrier proteins, and autophagy proteins were all identified as Gcn4p targets. Unexpectedly, genes involved in amino acid biosynthesis represent only a quarter of the Gcn4p target genes. Gcn4p also activates genes involved in glycogen homeostasis, and mutant analysis showed that Gcn4p suppresses glycogen levels in amino acid-starved cells. Numerous genes encoding protein kinases and transcription factors were identified as targets, suggesting that Gcn4p is a master regulator of gene expression. Interestingly, expression profiles for 3AT and the alkylating agent methyl methanesulfonate (MMS) overlapped extensively, and MMS induced GCN4 translation. Thus, the broad transcriptional response evoked by Gcn4p is produced by diverse stress conditions. Finally, profiling of a gcn4Δ mutant uncovered an alternative induction pathway operating at many Gcn4p target genes in histidine-starved cells.

Transcriptional Profiling Shows that Gcn4p Is a Master Regulator of Gene Expression during Amino Acid Starvation in Yeast

The treatment of hepatitis C has dramatically improved over the past decade. Unlike any other chronic viral infection, a significant proportion of patients with chronic hepatitis C can be cured. However, the current standard therapy—pegylated interferon alpha and ribavirin—has its limitations. Limited efficacy in patients with hepatitis C virus (HCV) genotype 1 and the side effect profile will necessitate the development of new therapeutic approaches. This review describes the efficacy and optimisation of the current standard therapy of hepatitis C and its problems in special patient populations. New treatment directions beyond interferon alpha based therapies are on the horizon.

Early identification of patients with acute HCV infection is important for their optimal management. The rate of chronic evolution is 50–90%, and the natural course of chronic hepatitis C can be associated with severe complications. Patients with chronic hepatitis C have the potential risk of developing liver cirrhosis and hepatocellular carcinoma.1 The social burden of HCV infection is high, including for health care workers. Extrahepatic manifestations of HCV are often troublesome and may not be reversible with viral eradication.2 These are good reasons for the design of a prophylactic vaccine but as this has yet to be accomplished, early treatment of acute HCV infection with interferon alpha (IFN) is the only option to prevent chronicity.

Immediate treatment of patients with symptomatic acute hepatitis C with recombinant IFN or pegylated IFN (PEG-IFN) monotherapy for 24 weeks can prevent the development of chronic hepatitis C in approximately 90% of cases.3–5 Combination with ribavirin is not necessary.6 However, symptomatic patients also have a good chance to clear HCV spontaneously.7,8 This usually occurs in the first 12 weeks after the onset of symptoms. A wait and see strategy (that is, treatment of only those patients who remain HCV-RNA …

/pdf/treating-viral-hepatitis-c-efficacy-side-effects-and-d1lczqz62m.pdf

Treating viral hepatitis C: efficacy, side effects, and complications

Ever since the beginning of biochemical analysis, yeast has been a pioneering model for studying the regulation of eukaryotic metabolism. During the last three decades, the combination of powerful yeast genetics and genome-wide approaches has led to a more integrated view of metabolic regulation. Multiple layers of regulation, from suprapathway control to individual gene responses, have been discovered. Constitutive and dedicated systems that are critical in sensing of the intra- and extracellular environment have been identified, and there is a growing awareness of their involvement in the highly regulated intracellular compartmentalization of proteins and metabolites. This review focuses on recent developments in the field of amino acid, nucleotide, and phosphate metabolism and provides illustrative examples of how yeast cells combine a variety of mechanisms to achieve coordinated regulation of multiple metabolic pathways. Importantly, common schemes have emerged, which reveal mechanisms conserved among various pathways, such as those involved in metabolite sensing and transcriptional regulation by noncoding RNAs or by metabolic intermediates. Thanks to the remarkable sophistication offered by the yeast experimental system, a picture of the intimate connections between the metabolomic and the transcriptome is becoming clear.

https://www.genetics.org/content/genetics/190/3/885.full.pdf

Regulation of amino acid, nucleotide and phosphate metabolism in Saccharomyces cerevisiae

Motivation: Global gene expression profiling, both at the transcript level and at the protein level, can be a valuable tool in the understanding of genes, biological networks, and cellular states. As larger and larger gene expression data sets become available, data mining techniques can be applied to identify patterns of interest in the data. Association rules, used widely in the area of market basket analysis, can be applied to the analysis of expression data as well. Association rules can reveal biologically relevant associations between different genes or between environmental effects and gene expression. An association rule has the form LHS⇒RHS, where LHS and RHS are disjoint sets of items, the RHS set being likely to occur whenever the LHS set occurs. Items in gene expression data can include genes that are highly expressed or repressed, as well as relevant facts describing the cellular environment of the genes (e.g. the diagnosis of a tumor sample from which a profile was obtained). Results: We demonstrate an algorithm for efficiently mining association rules from gene expression data, using the data set from Hughes et al. (Cell, 102, 109‐ 126, 2000) of 300 expression profiles for yeast. Using the algorithm, we find numerous rules in the data. A cursory analysis of some of these rules reveals numerous associations between certain genes, many of which make sense biologically, others suggesting new hypotheses that may warrant further investigation. In a data set derived from the yeast data set, but with the expression values for each transcript randomly shifted with respect to the experiments, no rules were found, indicating that most all of the rules mined from the actual data set are not likely to have occurred by chance. Availability: An implementation of the algorithm using Microsoft SQL Server with Access 2000 is available at http://dot.ped.med.umich.edu:2000/pub/assoc rules/ assoc rules.zip. Our results from mining the yeast data set are available at http://dot.ped.med.umich.edu: 2000/pub/assoc rules/yeast results.zip. ∗ To whom correspondence should be addressed.

http://web.cs.mun.ca/~harold/Courses/Old/CS6754.W04/Diary/79.pdf

Mining gene expression databases for association rules

All cells undergo rapid transcriptional reprogramming in response to environmental changes by mobilizing transcriptional activators and repressors. Transcriptional activator proteins function by binding to specific DNA sequences and recruiting the transcriptional machinery to the promoters of genes

https://ec.asm.org/content/eukcell/1/1/22.full.pdf

Gcn4p, a Master Regulator of Gene Expression, Is Controlled at Multiple Levels by Diverse Signals of Starvation and Stress

The ARG11 Gene of Saccharomyces cerevisiae Encodes a Mitochondrial Integral Membrane Protein Required for Arginine Biosynthesis

Linkage disequilibrium analysis in Australian haemochromatosis patients indicates bipartite association with clinical expression

Background: There are many local black rice cultivars in Indonesia, yet only a few of these are formally described in the literature. It has been reported that black rice has many phytochemical variants which may contribute to its use as a functional food, including nutraceuticals and secondary metabolites such as anthocyanin, oryzanol, and more. The purpose of this article was to review literature describing black rice cultivars from Indonesia, with a particular focus on its potential use as a functional food. Our literature search revealed several articles that describe black rice in relation to its nutraceutical properties and its role in reducing non-communicable diseases. Other studies describe the diversity of local pigmented rice and its potential for lowering the risk of hyperlipidemia, hyperglycemia, and for cancer prevention. Black rice has been described as a functional food in several countries; however, there is great diversity among cultivars and further research on Indonesian varieties will determine whether local variants are candidates as well for the development of functional foods. Keywords : black rice cultivar, functional food, non-communicable diseases, nutraceutical, phytochemical

/pdf/black-rice-as-a-functional-food-in-indonesia-2rk6v31m5t.pdf

Black rice as a functional food in Indonesia

Indonesia has a wide range of rice cultivars and pigments. This rice can be used as a source of phytochemical compounds for cancer prevention. This research aims to analyze the cytotoxic activities of the ethanolic extract of black rice bran of 4 local cultivars i.e. ‘Cempo Ireng’, ‘Woja Laka’, ‘Toraja’ and ‘IR­64’ (white rice) on  cancer cells and to determine the compounds groups of those extracts. First step, rice bran was extracted with ethanol. This extract was applied to Raji (a human Burkitt Lymphoma cancer), HepG2 (a human liver cancer), and Vero (a nonhuman cell line) cells in order to measure the cytotoxic activities by using MTT assay. To determine descriptively the compounds groups of phenolics, flavonoids, terpenoids, steroids, and alkaloids the thin layer chromatography method was performed. The IC50 value was analyzed quantitatively by using probit analysis. Results showed that the IC50 values of ethanolic extract of rice bran ‘Woja Laka’, ‘Toraja’, ‘Cempo Ireng’ and ‘IR 64’ on HepG2 cells were 857.23±99.19; 1,896.55±83,8; 1,494.47±87.81 and 727.89±145,97 µg/ml respectively. The IC50 on Raji cells were 816.61±85.31; 1,079.93±28.31; 1,627.82; ±119.82, and 769.33±61.43 µg/ml respectively. The IC50 on Vero cells were 1,295.2±37; 1,232.07±165.51; 1,874.14±169.56, and 724.4±122.79 µg/ml respectively. The ethanolic extracts of rice bran from four cultivars contain phenolics, flavonoids, terpenoids, and steroids. However, alkaloids could not be detected. The variety of rice cultivars indicates the variation of cytotoxic activities on cancer cells. The ethanolic extracts of rice bran from those four rice cultivars contain similar kinds of organic compounds groups but vary in the Rf values.

https://jurnal.ugm.ac.id/ijbiotech/article/download/26814/16538

The effect of ethanolic extract of black and white rice bran (Oryza sativa L.) on cancer cells

Avocado Persea Americana Mill. is a commercially important crop and studies have shown that the pulp may have benefits to cardiovascular health, dermatological health and possibly anti-cancer activity. Avocado seeds have several medicinal properties such as anti-hyperglycemic, antimicrobial, antioxidant and anti-inflammation. This study aim to evaluate the effect of avocado seed extract on viability and apoptosis of breast cancer cell line MCF-7. The anticancer effect was evaluated by cytotoxic test using MTT assay and the effect on apoptosis and cell cycle was examined by flow cytometry method. The cytotoxic test showed that chloroform extract had strong cytotoxic activity against MCF-7 cell lines with IC50 value of 94.87 µg/mL. Furthermore, the chloroform extract was partitioned with methanol and yield of soluble methanol fraction (FLM) and non soluble methanol fraction (FTLM). The cytotoxic activity of the methanol soluble fraction (FLM) and non soluble methanol fraction (FTLM) against MCF-7 cell lines was increased with IC50 of 34.52 and 66.03 µg/mL, respectively. Flow cytometry analysis using annexin-V and propidium iodide staining revealed that methanol soluble fraction could induce apoptosis and modulating the cell cycle arrest in MCF-7 cell. This research indicated that avocado seed has a potency to induce apoptosis and as anti-proliferative to MCF-7 cells lines.

https://www.jurnal.ugm.ac.id/ijbiotech/article/download/32141/23711

Rarastoeti Pratiwi

Papers

The ARG11 Gene of Saccharomyces cerevisiae Encodes a Mitochondrial Integral Membrane Protein Required for Arginine Biosynthesis

Linkage disequilibrium analysis in Australian haemochromatosis patients indicates bipartite association with clinical expression

Black rice as a functional food in Indonesia

The effect of ethanolic extract of black and white rice bran (Oryza sativa L.) on cancer cells

Cytotoxic activity and apoptosis induction of avocado Persea americana Mill. seed extract on MCF-7 cancer cell line