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Antimalarial drug discovery: efficacy models for compound screening
Different in vitro and in vivo screens for antimalarial drug discovery are suggested and a streamlined process for evaluating new compounds on the path from drug discovery to development is recommended. Expand
Innovative lead discovery strategies for tropical diseases
The different approaches to lead discovery for tropical diseases are discussed and a coordination strategy that involves highly integrated partnerships and networks between scientists in academic institutions and industry in both wealthy industrialized countries and disease-endemic countries is emphasized. Expand
Expression and Function of the Trehalase Genes NTH1 and YBR0106 in Saccharomyces cerevisiae(*)
It is shown here that only the most upstream start codon which initiates translation of the longest possible ORF is used for expression of NTH1 in vivo, and a requirement of the intact YBR0106 gene for thermotolerance is demonstrated in experiments with the respective mutants. Expand
Induction of neutral trehalase Nth1 by heat and osmotic stress is controlled by STRE elements and Msn2/Msn4 transcription factors: variations of PKA effect during stress and growth
There is direct evidence that Msn2/Msn4 and the STREs control the heat‐, osmotic stress‐ and diauxic shift‐dependent induction of Nth1, and expression of enzymes oftrehalose synthesis and hydrolysis help to maintain trehalose concentration during stress. Expand
Phenotypic features of trehalase mutants in Saccharomyces cerevisiae
Genetic evidence for the ‘poor‐heat‐shock‐recovery’ phenotype associated with NTH1 and YBR0106 mutants is presented and a growth defect of neutral and acid trehalase‐deficient mutants during transition from glucose to glycerol is shown, which is probably related to the ’poor‐ heat‐shock-reco recovery’ phenomenon. Expand
Genomic-scale prioritization of drug targets: the TDR Targets database
The development of the TDR Targets database is discussed, which encompasses extensive genetic, biochemical and pharmacological data related to tropical disease pathogens, as well as computationally predicted druggability for potential targets and compound desirability information, and aims to facilitate the identification and prioritization of candidate drug targets for pathogens. Expand
Deletion of the ATH1 gene in Saccharomyces cerevisiae prevents growth on trehalose
The results show that the vacuolar acid trehalase Ath1p is necessary for the phenotype of growth on trehalose, i.e. tre Halose utilization, in contrast to cytosolic neutral tre Halase Nth1p which is required for intracellular degradation of trehalOSE. Expand
Opposite roles of trehalase activity in heat-shock recovery and heat-shock survival in Saccharomyces cerevisiae.
It is suggested that trehalose breakdown is required for efficient recovery from heat shock, and that the presence of trehalase protein alone is not sufficient for efficient heat-stress recovery. Expand
Neutral trehalase Nth1p of Saccharomyces cerevisiae encoded by the NTH1 gene is a multiple stress responsive protein
It is shown that expression of the NTH1 gene and its product, neutral trehalase (Nth1p), are also induced by other stressors such as H2O2, CuSO4, NaAsO1, and cycloheximide (CHX), which is shown to be accompanied by accumulation of trehalose. Expand
Molecular biology of trehalose and the trehalases in the yeast Saccharomyces cerevisiae.
  • S. Nwaka, H. Holzer
  • Biology, Medicine
  • Progress in nucleic acid research and molecular…
  • 1998
The NTH1 and NTH2 genes have stress-related function and the gene products may be called stress proteins, and possible mechanisms of stress protective function of the trehalases are discussed. Expand