My Early Years of Yeast Mitochondrial Genetics.

There have been massive technological advances in molecular biology and genetics over the past five decades. I have personally experienced these advances and here I reflect on those origins, from my perspective, studying yeast mitochondrial genetics leading up to deciphering the functions of the mitochondrial genome. The yeast contributions commenced in the middle of the last century with pure genetics, correlating mutants with phenotypes, in order to discover genes, just like the early explorations to discover new lands.

Simvastatin, Its Antimicrobial Activity and Its Prevention of Alzheimer's Disease.

Simvastatin, a blockbuster drug for treating hypercholesterolemia, has multifactorial benefits as an antimicrobial agent and plays a preventative role in reducing the incidence of Alzheimer's Disease (AD). Although most of the beneficial effects of simvastatin have been attributed to its ability to reduce cholesterol levels, recent scientific studies have suggested that its benefits are largely due to its pleiotropic effects in targeting other pathways, e.g.

Molecular Mechanisms of Alzheimer's Disease III.

This Special Issue of is the third in the series: [...

The Use of Yeast in Biosensing.

Yeast has been used as a model for several diseases as it is the simplest unicellular eukaryote, safe and easy to culture and harbors most of the fundamental processes that are present in almost all higher eukaryotes, including humans. From understanding the pathogenesis of disease to drug discovery studies, yeast has served as an important biosensor. It is not only due to the conservation of genetics, amenable modification of its genome and easily accessible analytical methods, but also some characteristic features such as its ability to survive with defective mitochondria, making it a highly flexible microbe for designing whole-cell biosensing systems.

Molecular mechanisms underlying the emergence of polygenetic antifungal drug resistance in mismatch repair mutants of .

Background: Fungal infections are common life-threatening diseases amongst immunodeficient individuals. Invasive fungal disease is commonly treated with an azole antifungal agent, resulting in selection pressure and the emergence of drug resistance. Antifungal resistance is associated with higher mortality rates and treatment failure, making the current clinical management of fungal disease very challenging.

Severity, Pathogenicity and Transmissibility of Delta and Lambda Variants of SARS-CoV-2, Toxicity of Spike Protein and Possibilities for Future Prevention of COVID-19.

The World Health Organization reports that SARS-CoV-2 has infected over 220 million people and claimed over 4.7 million lives globally. While there are new effective vaccines, the differences in behavior of variants are causing challenges in vaccine development or treatment.

-Chalcone Plus Baicalein Synergistically Reduce Intracellular Amyloid Beta (Aβ) and Protect from Aβ Induced Oxidative Damage in Yeast Models of Alzheimer's Disease.

Finding an effective therapeutic to prevent or cure AD has been difficult due to the complexity of the brain and limited experimental models. This study utilized unmodified and genetically modified as model organisms to find potential natural bioactive compounds capable of reducing intracellular amyloid beta 42 (Aβ) and associated oxidative damage. Eleven natural bioactive compounds including mangiferin, quercetin, rutin, resveratrol, epigallocatechin gallate (EGCG), urolithin A, oleuropein, rosmarinic acid, salvianolic acid B, baicalein and -chalcone were screened for their ability to reduce intracellular green fluorescent protein tagged Aβ (GFP-Aβ) levels.

A Toxic Synergy between Aluminium and Amyloid Beta in Yeast.

Alzheimer's disease (AD), the most prevalent, age-related, neurodegenerative disease, is associated with the accumulation of amyloid beta (Aβ) and oxidative stress. However, the sporadic nature of late-onset AD has suggested that other factors, such as aluminium may be involved. Aluminium (Al) is the most ubiquitous neurotoxic metal on earth, extensively bioavailable to humans.

Protein Homeostasis Networks and the Use of Yeast to Guide Interventions in Alzheimer's Disease.

Alzheimer's Disease (AD) is a progressive multifactorial age-related neurodegenerative disorder that causes the majority of deaths due to dementia in the elderly. Although various risk factors have been found to be associated with AD progression, the cause of the disease is still unresolved. The loss of proteostasis is one of the major causes of AD: it is evident by aggregation of misfolded proteins, lipid homeostasis disruption, accumulation of autophagic vesicles, and oxidative damage during the disease progression.

Utilization of an Industry Byproduct, Leaves, by to Produce Lovastatin.

Due to its ability to lower cholesterol levels, simvastatin is a leading drug for the prevention of strokes and heart disease: it also lowers the incidence of neurodegenerative diseases. Simvastatin is made from lovastatin, a precursor produced by the industrial fungus, . In this study, leaves were tested as a novel substrate for the growth of a new isolate of and a lovastatin-resistant strain of to produce lovastatin.

Tyramine and Amyloid Beta 42: A Toxic Synergy.

Implicated in various diseases including Parkinson's disease, Huntington's disease, migraines, schizophrenia and increased blood pressure, tyramine plays a crucial role as a neurotransmitter in the synaptic cleft by reducing serotonergic and dopaminergic signaling through a trace amine-associated receptor (TAAR1). There appear to be no studies investigating a connection of tyramine to Alzheimer's disease. This study aimed to examine whether tyramine could be involved in AD pathology by using expressing Aβ42.

from Kangaroo Scats: Possible Implication in Cellulose Digestion.

Microbiota in the kangaroo gut degrade cellulose, contributing to the kangaroo's energy and survival. In this preliminary study, to discover more about the gut microbes that contribute to the survival of kangaroos, cellulose-degrading bacteria were isolated from kangaroo scats by selection on solidified media containing carboxymethyl cellulose as the main carbon source. One frequently occurring aerobic bacterium was , a microbe previously isolated in fruit powder and from a patient with angular cheilitis.

Polyphasic Characterisation of sp. nov., a New Enteric Bacterium Isolated from the Koala Hindgut.

The genus is comprised of six rarely isolated species within the family. Representatives are Gram-negative motile bacilli, and are typically oxidase-negative, lipase-positive and resistant to colistin and cephalothin. In this study, a putative novel species (designated strain ZA_0188), isolated from the koala hindgut, was characterised using a polyphasic taxonomic approach.

Dietary Polyphenols: A Multifactorial Strategy to Target Alzheimer's Disease.

Ageing is an inevitable fundamental process for people and is their greatest risk factor for neurodegenerative disease. The ageing processes bring changes in cells that can drive the organisms to experience loss of nutrient sensing, disrupted cellular functions, increased oxidative stress, loss of cellular homeostasis, genomic instability, accumulation of misfolded protein, impaired cellular defenses and telomere shortening. Perturbation of these vital cellular processes in neuronal cells can lead to life threatening neurological disorders like Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Lewy body dementia, etc.

Simvastatin Efficiently Reduces Levels of Alzheimer's Amyloid Beta in Yeast.

A large-scale epidemiology study on statins previously showed that simvastatin was unique among statins in reducing the incidence of dementia. Since amyloid beta (Aβ42) is the protein that is most associated with Alzheimer's disease, this study has focused on how simvastatin influences the turnover of native Aβ42 and Aβ42 fused with green fluorescent protein (GFP), in the simplest eukaryotic model organism, . Previous studies have established that yeast constitutively producing Aβ42 fused to GFP offer a convenient means of analyzing yeast cellular responses to Aβ42.

Statin resistance in Candida glabrata.

Objectives: Reduced efficacy of statins has been observed in people but the mechanism of this resistance is unclear and no statin-resistance mutations in the catalytic domain of HMGCR have been reported. The present study focused on looking for statin-resistance mutations and examining the mechanism of statin resistance using Candida glabrata as a model organism.

Results: C.

Development of Convenient System for Detecting Yeast Cell Stress, Including That of Amyloid Beta.

(1) Background: As a model eukaryote, the study of stress responses in yeast can be employed for studying human health and disease, and the effects of various drugs that may impact health. "Reporting" of stress in yeast has frequently utilised enzymes like β-galactosidase that require laborious assays for quantitative results. The use of a stress reporter that can be measured quantitatively and with high sensitivity in living cells in a multi-well plate reader is a more desirable approach; (2) Methods: A multi-copy yeast- shuttle plasmid containing the promoter upstream of the mCherry reporter, along with the selectable marker was constructed and tested; (3) Results: Under certain stress conditions inducing the heat shock response, transformants containing the plasmid produced red fluorescence that could be readily quantitated in a microtitre plate reader.

Fungicidal effect of thymoquinone involves generation of oxidative stress in Candida glabrata.

The antifungal effect of thymoquinone, a component of black seed essential oil, has been studied on different types of fungi. Its mechanism of action as an antifungal has not been described yet. This study demonstrates the fungicidal effect of thymoquinone on different Candida species with particular emphasis on C.

Exploitation of Aspergillus terreus for the Production of Natural Statins.

The fungus has dominated the biological production of the "blockbuster" drugs known as statins. The statins are a class of drugs that inhibit HMG-CoA reductase and lead to lower cholesterol production. The statins were initially discovered in fungi and for many years fungi were the sole source for the statins.

Yeast Model of Amyloid-β and Tau Aggregation in Alzheimer's Disease.

The amyloid-β peptide (Aβ) and the phosphorylated protein tau have been widely implicated in Alzheimer's disease and are the focus of most research. Both agents have been extensively studied in mammalian cell culture and in animal studies, but new research is focusing on yeast models. Yeast are eukaryotes, just like us, and are amenable to effects and expression of Aβ and tau and appear able to 'report' with considerable relevance on the effects of these biomolecules.

, Friend and Foe.

is mostly good, but, at times, it is an opportunistic pathogen. Previously known as , it enjoyed a good reputation and was even present in starter cultures. Its haploid genome and lack of mating made it an attractive challenge for yeast genetics studies.

Yeast as a Model for Studies on Aβ Aggregation Toxicity in Alzheimer's Disease, Autophagic Responses, and Drug Screening.

The Aβ peptide is widely considered a major cause of Alzheimer's disease since it causes neuronal death in an oligomerisation-dependent manner. In order to identify new inhibitors of Aβ that may be chemo preventative for Alzheimer's disease, a yeast assay that qualitatively determines the amounts and state of the human Aβ42 peptide has been developed. Yeast assays such as this can be applied to studies on aggregation toxicity, autophagic responses and drug screening in Alzheimer's disease.