A5084814331- Fungal and yeast genetics research
- Cellular transport and secretion
- Endoplasmic Reticulum Stress and Disease
- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Enzyme Production and Characterization
- Peptidase Inhibition and Analysis
- Protein Hydrolysis and Bioactive Peptides
- Neurogenetic and Muscular Disorders Research
- Voice and Speech Disorders
- Ubiquitin and proteasome pathways
- Genetic Neurodegenerative Diseases
- Biochemical and Molecular Research
- Assistive Technology in Communication and Mobility
- Biofuel production and bioconversion
- Muscle Physiology and Disorders
- Plant nutrient uptake and metabolism
- Cardiomyopathy and Myosin Studies
- Context-Aware Activity Recognition Systems
- Enzyme Catalysis and Immobilization
- Stuttering Research and Treatment
- Microbial Metabolites in Food Biotechnology
- Biotin and Related Studies
- Microbial Metabolic Engineering and Bioproduction
- Polyamine Metabolism and Applications
Roche (Switzerland)
2000-2023
Society for Chemical Engineering and Biotechnology
2018
John Wiley & Sons (Germany)
2018
University of Stuttgart
1991-2006
Czech Academy of Sciences, Institute of Physiology
1997
Czech Academy of Sciences
1997
Consejo Superior de Investigaciones Científicas
1995
Friedrich-Alexander-Universität Erlangen-Nürnberg
1993
Novartis (Switzerland)
1992
University of Freiburg
1972-1989
Protein degradation in the vacuole (lysosome) is an important event cellular regulation. In yeast, as mammalian cells, a major route of protein uptake for into has been found to be autophagocytosis. The discovery this process yeast enables elucidation its mechanisms via genetic and molecular biological investigations. Here we report isolation mutants defective autophagocytosis ( aut mutants), using rapid colony screening procedure.
Ubiquitous digital technologies such as smartphone sensors promise to fundamentally change biomedical research and treatment monitoring in neurological diseases PD, creating a new domain of biomarkers.The present study assessed the feasibility, reliability, validity smartphone-based biomarkers PD clinical trial setting.During 6-month, phase 1b with 44 Parkinson participants, an independent, 45-day 35 age-matched healthy controls, participants completed six daily motor active tests (sustained...
Abstract Digital health technologies enable remote and therefore frequent measurement of motor signs, potentially providing reliable valid estimates sign severity progression in Parkinson’s disease (PD). The Roche PD Mobile Application v2 was developed to measure bradykinesia, bradyphrenia speech, tremor, gait balance. It comprises 10 smartphone active tests (with ½ administered daily), as well daily passive monitoring via a smartwatch. studied 316 early-stage participants who performed at...
We have cloned the yeast PRE2 gene by complementation of pre2 mutants, which are defective in chymotrypsin-like activity 20 S proteasome (multicatalytic-multifunctional proteinase complex). The gene, a beta-type member proteasomal family, is essential for life and codes 287-amino acid subunit with predicted molecular mass 31.6 kDa. Missense mutations two mutant alleles were identified. They led to enhanced sensitivity cells against stress. At same time, mutants accumulated ubiquitinated...
Mutants deficient in the vacuolar (lysosomal) endopeptidases proteinase yscA and yscB of yeast Saccharomyces cerevisiae exhibit a drastically reduced protein degradation rate under nutritional stress conditions. The differentiation process sporulation is considerably disturbed by absence two endopeptidases. Also vegetative growth conditions false synthesis, some effect on degradation, which is, however, much less pronounced as found starvation Proteinase deficiency leads to rapid cell death...
Abstract We have demonstrated a prototypical hybrid classical and quantum computational workflow for the quantification of protein–ligand interactions. The combines density matrix embedding theory (DMET) procedure with variational eigensolver (VQE) approach finding molecular electronic ground states. A series ‐secretase (BACE1) inhibitors is rank‐ordered using binding energy differences calculated on latest superconducting transmon (IBM) trapped‐ion (Quantinuum) noisy intermediate scale...
Stuttgurt 80, Germuny Proteinase yscE, the yeast proteasome, is a member of nonlysosomal, high molecular mass ( ~7 0 kDa) multifunctional proteinase complexes that are highly conserved from to man.We have isolated mutants defective in one three proteolytic activities enzyme complex, i.e. cleavage peptide bonds after acidic amino acids.Using these p r e d -l ) , we cloned PRE4 gene and uncovered an open reading frame with 266 acids coding for predicted protein 29.4 kDa.The proved be subunit...
A mutant of yeast lacking proteinase C (carboxypeptidase Y) activity has been found by using a histochemical stain to screen mutagenized colonies. This defect segregates 2:2 in meiotic tetrads. Cell extracts lacked the esterolytic, amidase, and proteolytic activities associated with C. The absence does not affect mitotic growth no obvious effect on formation viable ascospores or segregation. grows peptides known be cleaved vitro. finding is consistent idea that other enzymes exist vivo...
When Saccharomyces cerevisiae cells growing on galactose are transferred onto glucose medium containing cycloheximide, an inhibitor of protein synthesis, a rapid reduction Gal2p-mediated uptake is observed. We show that glucose-induced inactivation Gal2p due to its degradation. Stabilization in pra1 mutant devoid vacuolar proteinase activity Subcellular fractionation and indirect immunofluorescence showed the Gal2 transporter accumulates vacuole cells, directly demonstrating degradation...
The search for proteolytic enzymes active in the neutral pH range has been extended.Studies were done on a mutant lacking four well-known proteinases involved protein degradation, two endoproteinases A and B carboxypeptidases Y S. Twenty-nine chromogenic peptides (amino terminally blocked peptidyl-4-nitroanilides) as well [3H]methylcasein used substrates this search.For detection of endoproteolytic activity using peptide versions assay used.In one system direct cleavage 4-nitroanilide bond...
Proteinase A and proteinase B, two vacuolar enzymes in Saccharomyces cerevisiae, are synthesized as larger precursors with apparent molecular weights of approximately 52,000 42,000, respectively. These precursor molecules processed to their mature forms 42,000 weight for 33,000 B. In the presence tunicamycin, an inhibitor synthesis protein-asparagine linked carbohydrate moieties, smaller each were synthesized, indicating that contains N-linked which is apparently not required processing....
Autophagocytosis is a starvation-induced process responsible for transport of cytoplasmic proteins to the vacuole. In Saccharomyces cerevisiae, autophagy characterized by phenotypic appearance autophagic vesicles inside vacuole strains deficient in proteinase yscB. The AUT1 gene, essential autophagy, was isolated complementation sporulation deficiency diploid aut1-1 mutant strain yeast genomic library and characterized. located on right arm chromosome XIV, 10 kb from centromere, encodes...
The maltose transporter of Saccharomyces cerevisiae is rapidly degraded during fermentation in the absence a nitrogen source. location and mechanism degradation have been investigated. Using mutants defective endocytosis, we shown that this requires internalization by endocytosis. In addition, studies proteasome or vacuolar proteolysis revealed occurs vacuole independent function. results also Sec18p raised question whether activity internalized recycled back to plasma membrane.
Yeast fatty acid synthase consists of two independent polypeptide strains, a and 8.The functional multienzyme complex, composed six a-and &subunits, is rather stable against proteolysis in vivo.Mutations one the subunits or deletion subunit lead to degradation nonmutated remaining protein.We show that unassembled a- this enzyme short-lived, depends on presence active cytoplasmic proteinase yscE, yeast proteasome.The Bsubunit degraded by nonvacuolar proteolytic system under vegetative growth...
We have cloned the BLH1 gene of yeast Saccharomyces cerevisiae coding for a peptidase with significant homology to rabbit bleomycin hydrolase. Bleomycin is glycopeptide antibiotic used treatment human cancers. The antitumor activity drug limited by its metabolic inactivation caused hydrolase, member cysteine protease family. open reading frame consists 1,449 base pairs encoding 55.4-kDa protein consistent molecular mass found in sodium dodecyl sulfate-polyacrylamide gel electrophoresis....
A new peptidase, which we call proteinase yscE, was purified from the yeast Saccharomyces cerevisiae. The enzyme cleaves synthetic substrates Cbz-Gly-Gly-Leu-4-nitroanilide, Cbz-Ala-Ala-Leu-4-nitroanilide, and Suc-Phe-Leu-Phe-4-nitroanilide (Cbz Suc are defined as benzyloxycarbonyl succinyl, respectively) at 4-nitroanilide bond exhibits a slight activity against [3H]methylcasein. Optimum pH for cleavage of chromogenic is found to be in range 8.2 8.6. has an apparent Stokes radius Rs = 75.2...
Smartphone-based assessments have been considered a potential solution to passively monitor gait and mobility in early-stage Parkinson's disease (PD) patients. In the Multiple Ascending Dose clinical trial of PRX002/RG7935, 44 PD patients 35 age-and gender-matched healthy individuals performed smartphone-based for up 24 weeks 6 respectively. For "passive monitoring", subjects carried smartphone with them as part their daily routine, while sensors recording movement data continuously. total,...
Affective disorders are associated with atypical voice patterns; however, automated analyses suffer from small sample sizes and untested generalizability on external data. We investigated a generalizable approach to aid clinical evaluation of depression remission using transfer learning: train machine learning models easily accessible non-clinical datasets test them novel data in different language.A Mixture Experts model was trained infer happy/sad emotional state three publicly available...
Background Remote monitoring of Huntington disease (HD) signs and symptoms using digital technologies may enhance early clinical diagnosis tracking progression, guide treatment decisions, monitor response to disease-modifying agents. Several recent studies in neurodegenerative diseases have demonstrated the feasibility symptom monitoring. Objective The aim this study was evaluate a novel smartwatch- smartphone-based platform remotely HD. Methods This analysis aimed determine reliability...
We have studied the structure, biosynthesis, intracellular routing, and vacuolar localization of carboxypeptidase ysCS in yeast Saccharomyces cerevisiae. Nondenaturing polyacrylamide gel electrophoresis revealed two forms yscS with different electrophoretic mobility. Antibodies specific for recognized glycoproteins 77- 74-kDa apparent molecular mass which differ by one N-linked carbohydrate residue. Both observations suggest that exists catalytically active forms. The enzyme was found to be...