The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

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Initial sequencing and analysis of the human genome.

Salt and drought stress signal transduction consists of ionic and osmotic homeostasis signaling pathways, detoxification (i.e., damage control and repair) response pathways, and pathways for growth regulation. The ionic aspect of salt stress is signaled via the SOS pathway where a calcium-responsive SOS3-SOS2 protein kinase complex controls the expression and activity of ion transporters such as SOS1. Osmotic stress activates several protein kinases including mitogen-activated kinases, which may mediate osmotic homeostasis and/or detoxification responses. A number of phospholipid systems are activated by osmotic stress, generating a diverse array of messenger molecules, some of which may function upstream of the osmotic stress-activated protein kinases. Abscisic acid biosynthesis is regulated by osmotic stress at multiple steps. Both ABA-dependent and -independent osmotic stress signaling first modify constitutively expressed transcription factors, leading to the expression of early response transcriptional activators, which then activate downstream stress tolerance effector genes.

/pdf/salt-and-drought-stress-signal-transduction-in-plants-4bj87ki2ww.pdf

Salt and drought stress signal transduction in plants

We explored genomic expression patterns in the yeast Saccharomyces cerevisiae responding to diverse environmental transitions. DNA microarrays were used to measure changes in transcript levels over time for almost every yeast gene, as cells responded to temperature shocks, hydrogen peroxide, the superoxide-generating drug menadione, the sulfhydryl-oxidizing agent diamide, the disulfide-reducing agent dithiothreitol, hyper- and hypo-osmotic shock, amino acid starvation, nitrogen source depletion, and progression into stationary phase. A large set of genes (approximately 900) showed a similar drastic response to almost all of these environmental changes. Additional features of the genomic responses were specialized for specific conditions. Promoter analysis and subsequent characterization of the responses of mutant strains implicated the transcription factors Yap1p, as well as Msn2p and Msn4p, in mediating specific features of the transcriptional response, while the identification of novel sequence elements provided clues to novel regulators. Physiological themes in the genomic responses to specific environmental stresses provided insights into the effects of those stresses on the cell.

/pdf/genomic-expression-programs-in-the-response-of-yeast-cells-4xrnicxf7t.pdf

Genomic expression programs in the response of yeast cells to environmental changes.

BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

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▪ Abstract Plant responses to salinity stress are reviewed with emphasis on molecular mechanisms of signal transduction and on the physiological consequences of altered gene expression that affect biochemical reactions downstream of stress sensing. We make extensive use of comparisons with model organisms, halophytic plants, and yeast, which provide a paradigm for many responses to salinity exhibited by stress-sensitive plants. Among biochemical responses, we emphasize osmolyte biosynthesis and function, water flux control, and membrane transport of ions for maintenance and re-establishment of homeostasis. The advances in understanding the effectiveness of stress responses, and distinctions between pathology and adaptive advantage, are increasingly based on transgenic plant and mutant analyses, in particular the analysis of Arabidopsis mutants defective in elements of stress signal transduction pathways. We summarize evidence for plant stress signaling systems, some of which have components analogous to t...

Plant cellular and molecular responses to high salinity.

Yeast cells undergo diploid-specific developments such as spore formation via meiosis and pseudohyphal development under certain nutrient-limited conditions. Studies on these aspects require homozygous diploid mutants, which are generally constructed by crossing strains of opposite mating-type with the same genetic mutation. So far, there has been no direct way to generate and select diploids from haploid cells. Here, we developed a method for efficient construction of homozygous diploids using a PGAL1-HO gene (galactose-inducible mating-type switch) and a PSTE18-URA3 gene (counter selection marker for diploids). Diploids are generated by transient induction of the HO endonuclease, which is followed by mating of part of the haploid population. Since the STE18 promoter is repressed in diploids, diploids carrying PSTE18-URA3 can be selected on 5-fluoroorotic acid (5-FOA) plates where the uracil prototrophic haploids cannot grow. To demonstrate that this method is useful for genetic studies, we screened suppressor mutations of the complex colony morphology, strong agar invasion and/or hyper-filamentous growth caused by lack of the Hog1 MAPK in the diploid Σ1278b strain background. Following this approach, we identified 49 suppressor mutations. Those include well-known positive regulator genes for filamentous growth signaling pathways, genes involved in mitochondrial function, DNA damage checkpoint, chromatin remodeling, and cell cycle, and also previously uncharacterized genes. Our results indicate that combinatorial use of the PGAL1-HO and PSTE18-URA3 genes is suitable to efficiently construct and select diploids and that this approach is useful for genetic studies especially when combined with large-scale screening.

/pdf/efficient-construction-of-homozygous-diploid-strains-2a7y2clfx0.pdf

Efficient Construction of Homozygous Diploid Strains Identifies Genes Required for the Hyper-Filamentous Phenotype in Saccharomyces cerevisiae

https://pure.mpg.de/pubman/item/item_588349_3/component/file_2281823/588349.pdf

Structural mechanism of yeast aquaporin gating.

The nucleotide sequences of closely related members of a gene family can be used to investigate spontaneous mutations. Here we analyse the sequences of different yeast invertase genes which are more than 93% identical in the coding region and share some very similar, but not identical sequences in the noncoding flanking regions. Since all except one of the invertase genes are active, most of the base substitutions are silent. Within the coding region the base substitutions are unevenly distributed, indicating that parts of the genes were homogenized, probably via gene conversion. Transitions occurred more frequently than transversions in both, coding and noncoding regions. In the coding region pyrimidine transitions were the most abundant event due to silent changes mainly in the third codon position. In the noncoding region pyrimidine and purine transitions were found at equal frequencies. Transversions inverting base pairs (A-T and G-C) outnumber transversions changing base pairs (A-C and G-T). While the spectrum of mutations in the coding region is influenced by selective pressure to maintain the amino acid sequence, the spectrum in the noncoding region may be much less affected by selective pressure.

Comparison of the nucleotide sequences of a yeast gene family. I. Distribution and spectrum of spontaneous base substitutions.

We present a model of osmoadaptation in S. cerevisiae based on existing experimental and theoretical work. In order to investigate the impact of osmoadaptation on glycolysis, this model focuses on the interactions between glycolysis and osmoadaptation, namely the production of glycerol and its influence on flux towards pyruvate. Evaluation of this model shows that, depending on initial relations between glycerol and pyruvate production, the increased glycerol production can have a substantial negative effect on the pyruvate production rate. Existing experimental data and a detailed analysis of the model lead to the suggestion of an interaction between activated Hog1 and activators of glycolysis such as Pfk26.

http://www.med.uni-magdeburg.de/fme/sysbio/wp-content/uploads/papers/Kuehn2008GenInf20.pdf

Exploring the impact of osmoadaptation on glycolysis using time-varying response-coefficients

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/j.febslet.2011.10.029

Stefan Hohmann

Papers

Efficient Construction of Homozygous Diploid Strains Identifies Genes Required for the Hyper-Filamentous Phenotype in Saccharomyces cerevisiae

Structural mechanism of yeast aquaporin gating.

Comparison of the nucleotide sequences of a yeast gene family. I. Distribution and spectrum of spontaneous base substitutions.

Exploring the impact of osmoadaptation on glycolysis using time-varying response-coefficients

The Ashbya gossypii EF-1α promoter of the ubiquitously used MX cassettes is toxic to Saccharomyces cerevisiae.