Chronological aging leads to apoptosis in yeast

During the past years, yeast has been successfully established as a model to study mechanisms of apoptotic regulation. However, the beneficial effects of such a cell suicide program for a unicellular organism remained obscure. Here, we demonstrate that chronologically aged yeast cultures die exhibiting typical markers of apoptosis, accumulate oxygen radicals, and show caspase activation. Age-induced cell death is strongly delayed by overexpressing YAP1, a key transcriptional regulator in oxygen stress response. Disruption of apoptosis through deletion of yeast caspase YCA1 initially results in better survival of aged cultures. However, surviving cells lose the ability of regrowth, indicating that predamaged cells accumulate in the absence of apoptotic cell removal. Moreover, wild-type cells outlast yca1 disruptants in direct competition assays during long-term aging. We suggest that apoptosis in yeast confers a selective advantage for this unicellular organism, and demonstrate that old yeast cells release substances into the medium that stimulate survival of the clone.

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Why yeast cells can undergo apoptosis: death in times of peace, love, and war

The Journal of Cell Biology ◽

10.1083/jcb.200608098 ◽

2006 ◽

Vol 175 (4) ◽

pp. 521-525 ◽

Cited By ~ 117

Author(s):

Sabrina Büttner ◽

Tobias Eisenberg ◽

Eva Herker ◽

Didac Carmona-Gutierrez ◽

Guido Kroemer ◽

...

Keyword(s):

Cell Death ◽

Single Cells ◽

Yeast Cells ◽

Unicellular Organism ◽

Killer Toxins ◽

Cell Biol ◽

Cell Death Program ◽

A Cell ◽

Multicellular Organisms ◽

Cell Suicide

The purpose of apoptosis in multicellular organisms is obvious: single cells die for the benefit of the whole organism (for example, during tissue development or embryogenesis). Although apoptosis has also been shown in various microorganisms, the reason for this cell death program has remained unexplained. Recently published studies have now described yeast apoptosis during aging, mating, or exposure to killer toxins (Fabrizio, P., L. Battistella, R. Vardavas, C. Gattazzo, L.L. Liou, A. Diaspro, J.W. Dossen, E.B. Gralla, and V.D. Longo. 2004. J. Cell Biol. 166:1055–1067; Herker, E., H. Jungwirth, K.A. Lehmann, C. Maldener, K.U. Frohlich, S. Wissing, S. Buttner, M. Fehr, S. Sigrist, and F. Madeo. 2004. J. Cell Biol. 164:501–507, underscoring the evolutionary benefit of a cell suicide program in yeast and, thus, giving a unicellular organism causes to die for.

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Killing by Degradation: Regulation of Apoptosis by the Ubiquitin-Proteasome-System

Cells ◽

10.3390/cells10123465 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3465

Author(s):

Ruqaia Abbas ◽

Sarit Larisch

Keyword(s):

Apoptotic Cell ◽

Ubiquitin Proteasome System ◽

Cancer Therapies ◽

E3 Ligases ◽

Ubiquitin Proteasome ◽

A Cell ◽

Positive And Negative Feedback ◽

Apoptotic Proteins ◽

The Stability ◽

Cell Suicide

Apoptosis is a cell suicide process that is essential for development, tissue homeostasis and human health. Impaired apoptosis is associated with a variety of human diseases, including neurodegenerative disorders, autoimmunity and cancer. As the levels of pro- and anti-apoptotic proteins can determine the life or death of cells, tight regulation of these proteins is critical. The ubiquitin proteasome system (UPS) is essential for maintaining protein turnover, which can either trigger or inhibit apoptosis. In this review, we will describe the E3 ligases that regulate the levels of pro- and anti-apoptotic proteins and assisting proteins that regulate the levels of these E3 ligases. We will provide examples of apoptotic cell death modulations using the UPS, determined by positive and negative feedback loop reactions. Specifically, we will review how the stability of p53, Bcl-2 family members and IAPs (Inhibitor of Apoptosis proteins) are regulated upon initiation of apoptosis. As increased levels of oncogenes and decreased levels of tumor suppressor proteins can promote tumorigenesis, targeting these pathways offers opportunities to develop novel anti-cancer therapies, which act by recruiting the UPS for the effective and selective killing of cancer cells.

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An AIF orthologue regulates apoptosis in yeast

The Journal of Cell Biology ◽

10.1083/jcb.200404138 ◽

2004 ◽

Vol 166 (7) ◽

pp. 969-974 ◽

Cited By ~ 277

Author(s):

Silke Wissing ◽

Paula Ludovico ◽

Eva Herker ◽

Sabrina Büttner ◽

Silvia M. Engelhardt ◽

...

Keyword(s):

Cell Death ◽

Apoptotic Cell ◽

Cyclophilin A ◽

Yeast Cells ◽

Mammalian Development ◽

Oxygen Stress ◽

A Cell ◽

Death Effector ◽

Induced Apoptosis ◽

Apoptosis Inducing Factor

Apoptosis-inducing factor (AIF), a key regulator of cell death, is essential for normal mammalian development and participates in pathological apoptosis. The proapoptotic nature of AIF and its mode of action are controversial. Here, we show that the yeast AIF homologue Ynr074cp controls yeast apoptosis. Similar to mammalian AIF, Ynr074cp is located in mitochondria and translocates to the nucleus of yeast cells in response to apoptotic stimuli. Purified Ynr074cp degrades yeast nuclei and plasmid DNA. YNR074C disruption rescues yeast cells from oxygen stress and delays age-induced apoptosis. Conversely, overexpression of Ynr074cp strongly stimulates apoptotic cell death induced by hydrogen peroxide and this effect is attenuated by disruption of cyclophilin A or the yeast caspase YCA1. We conclude that Ynr074cp is a cell death effector in yeast and rename it AIF-1 (Aif1p, gene AIF1).

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Characterization of Episomal Replication of Bovine Papillomavirus Type 1 DNA in Long-Term Virion-Infected Saccharomyces Cerevisiae Culture

Virologica Sinica ◽

10.1007/s12250-021-00439-y ◽

2021 ◽

Author(s):

Quanmei Tu ◽

Weixu Feng ◽

Zhuo Chen ◽

Qijia Li ◽

Yu Zhao ◽

...

Keyword(s):

Time Course ◽

Blot Hybridization ◽

Yeast Cells ◽

Bovine Papillomavirus ◽

Two Dimensional Gel Electrophoresis ◽

Yeast Cultures ◽

Active Replication ◽

Replication Intermediates

AbstractWe have previously reported that bovine papillomavirus type 1 (BPV-1) DNA can replicate its genome and produce infectious virus-like particles in short term virion-infected S. cerevisiae (budding yeast) cultures (Zhao and Frazer 2002, Journal of Virology, 76:3359–64 and 76:12265–73). Here, we report the episomal replications of BPV-1 DNA in long term virion-infected S. cerevisiae culture up to 108 days. Episomal replications of the BPV-1 DNA could be divided into three patterns at three stages, early active replication (day 3–16), middle weak replication (day 23–34/45) and late stable replication (day 45–82). Two-dimensional gel electrophoresis analysis and Southern blot hybridization have revealed further that multiple replication intermediates of BPV-1 DNA including linear form, stranded DNA, monomers and higher oligomers were detected in the virion-infected yeast cells over the time course. Higher oligomers shown as covalently closed circular DNAs (cccDNAs) are the most important replication intermediates that serve as the main nuclear transcription template for producing all viral RNAs in the viral life cycle. In this study, the cccDNAs were generated at the early active replication stage with the highest frequencies and then at late stable replication, but they appeared to be suppressed at the middle weak replication. Our data provided a novel insight that BPV-1 genomic DNA could replicate episomally for the long period and produce the key replication intermediates cccDNAs in S. cerevisiae system.

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Shedding New Light on Mountainous Forest Growth: A Cross-Scale Evaluation of the Effects of Topographic Illumination Correction on 25 Years of Forest Cover Change across Nepal

Remote Sensing ◽

10.3390/rs13112131 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2131

Author(s):

Jamon Van Den Hoek ◽

Alexander C. Smith ◽

Kaspar Hurni ◽

Sumeet Saksena ◽

Jefferson Fox

Keyword(s):

Remote Sensing ◽

Geographic Distribution ◽

Classification Accuracy ◽

Forest Cover ◽

Forest Growth ◽

Forest Cover Change ◽

Scale Evaluation ◽

Beneficial Effects ◽

Affect Detection

Accurate remote sensing of mountainous forest cover change is important for myriad social and ecological reasons, but is challenged by topographic and illumination conditions that can affect detection of forests. Several topographic illumination correction (TIC) approaches have been developed to mitigate these effects, but existing research has focused mostly on whether TIC improves forest cover classification accuracy and has usually found only marginal gains. However, the beneficial effects of TIC may go well beyond accuracy since TIC promises to improve detection of low illuminated forest cover and thereby normalize measurements of the amount, geographic distribution, and rate of forest cover change regardless of illumination. To assess the effects of TIC on the extent and geographic distribution of forest cover change, in addition to classification accuracy, we mapped forest cover across mountainous Nepal using a 25-year (1992–2016) gap-filled Landsat time series in two ways—with and without TIC (i.e., nonTIC)—and classified annual forest cover using a Random Forest classifier. We found that TIC modestly increased classifier accuracy and produced more conservative estimates of net forest cover change across Nepal (−5.2% from 1992–2016) TIC. TIC also resulted in a more even distribution of forest cover gain across Nepal with 3–5% more net gain and 4–6% more regenerated forest in the least illuminated regions. These results show that TIC helped to normalize forest cover change across varying illumination conditions with particular benefits for detecting mountainous forest cover gain. We encourage the use of TIC for satellite remote sensing detection of long-term mountainous forest cover change.

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Prediction of Genetic Contributions and Generation Intervals in Populations With Overlapping Generations Under Selection

Genetics ◽

10.1093/genetics/151.3.1197 ◽

1999 ◽

Vol 151 (3) ◽

pp. 1197-1210 ◽

Cited By ~ 3

Author(s):

Piter Bijma ◽

John A Woolliams

Keyword(s):

Gene Flow ◽

Overlapping Generations ◽

Selective Advantage ◽

Turnover Time ◽

Breeding Value ◽

Age Classes ◽

Generation Interval ◽

Young Parents ◽

Genetic Contributions

Abstract A method to predict long-term genetic contributions of ancestors to future generations is studied in detail for a population with overlapping generations under mass or sib index selection. An existing method provides insight into the mechanisms determining the flow of genes through selected populations, and takes account of selection by modeling the long-term genetic contribution as a linear regression on breeding value. Total genetic contributions of age classes are modeled using a modified gene flow approach and long-term predictions are obtained assuming equilibrium genetic parameters. Generation interval was defined as the time in which genetic contributions sum to unity, which is equal to the turnover time of genes. Accurate predictions of long-term genetic contributions of individual animals, as well as total contributions of age classes were obtained. Due to selection, offspring of young parents had an above-average breeding value. Long-term genetic contributions of youngest age classes were therefore higher than expected from the age class distribution of parents, and generation interval was shorter than the average age of parents at birth of their offspring. Due to an increased selective advantage of offspring of young parents, generation interval decreased with increasing heritability and selection intensity. The method was compared to conventional gene flow and showed more accurate predictions of long-term genetic contributions.

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Long-Term Caloric Restriction Attenuates β-Amyloid Neuropathology and Is Accompanied by Autophagy in APPswe/PS1delta9 Mice

Nutrients ◽

10.3390/nu13030985 ◽

2021 ◽

Vol 13 (3) ◽

pp. 985

Author(s):

Luisa Müller ◽

Nicole Power Guerra ◽

Jan Stenzel ◽

Claire Rühlmann ◽

Tobias Lindner ◽

...

Keyword(s):

Caloric Restriction ◽

Neuroprotective Effect ◽

Resonance Spectroscopy ◽

Neuroprotective Effects ◽

Beneficial Effects ◽

Positron Emission ◽

Pet Ct ◽

Amyloid Aβ ◽

Β Amyloid

Caloric restriction (CR) slows the aging process, extends lifespan, and exerts neuroprotective effects. It is widely accepted that CR attenuates β-amyloid (Aβ) neuropathology in models of Alzheimer’s disease (AD) by so-far unknown mechanisms. One promising process induced by CR is autophagy, which is known to degrade aggregated proteins such as amyloids. In addition, autophagy positively regulates glucose uptake and may improve cerebral hypometabolism—a hallmark of AD—and, consequently, neural activity. To evaluate this hypothesis, APPswe/PS1delta9 (tg) mice and their littermates (wild-type, wt) underwent CR for either 16 or 68 weeks. Whereas short-term CR for 16 weeks revealed no noteworthy changes of AD phenotype in tg mice, long-term CR for 68 weeks showed beneficial effects. Thus, cerebral glucose metabolism and neuronal integrity were markedly increased upon 68 weeks CR in tg mice, indicated by an elevated hippocampal fluorodeoxyglucose [18F] ([18F]FDG) uptake and increased N-acetylaspartate-to-creatine ratio using positron emission tomography/computer tomography (PET/CT) imaging and magnet resonance spectroscopy (MRS). Improved neuronal activity and integrity resulted in a better cognitive performance within the Morris Water Maze. Moreover, CR for 68 weeks caused a significant increase of LC3BII and p62 protein expression, showing enhanced autophagy. Additionally, a significant decrease of Aβ plaques in tg mice in the hippocampus was observed, accompanied by reduced microgliosis as indicated by significantly decreased numbers of iba1-positive cells. In summary, long-term CR revealed an overall neuroprotective effect in tg mice. Further, this study shows, for the first time, that CR-induced autophagy in tg mice accompanies the observed attenuation of Aβ pathology.

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N-acetyl-L-cysteine Improves the Developmental Competence of Bovine Oocytes and Embryos Cultured In Vitro by Attenuating Oxidative Damage and Apoptosis

Antioxidants ◽

10.3390/antiox10060860 ◽

2021 ◽

Vol 10 (6) ◽

pp. 860

Author(s):

Wu-Sheng Sun ◽

Hoon Jang ◽

Mi-Ryung Park ◽

Keon Bong Oh ◽

Haesun Lee ◽

...

Keyword(s):

Embryonic Development ◽

Early Stage ◽

Developmental Competence ◽

Beneficial Effects ◽

Developmental Rates ◽

A Cell ◽

Bovine Oocytes ◽

Dose Dependent

Oxidative stress has been suggested to negatively affect oocyte and embryo quality and developmental competence, resulting in failure to reach full term. In this study, we investigated the effect of N-acetyl-L-cysteine (NAC), a cell-permeating antioxidant, on developmental competence and the quality of oocytes and embryos upon supplementation (0.1–10 mM) in maturation and culture medium in vitro using slaughterhouse-derived oocytes and embryos. The results show that treating oocytes with 1.0 mM NAC for 8 h during in vitro maturation attenuated the intracellular reactive oxygen species (ROS) (p < 0.05) and upregulated intracellular glutathione levels (p < 0.01) in oocytes. Interestingly, we found that NAC affects early embryonic development, not only in a dose-dependent, but also in a stage-specific, manner. Significantly (p < 0.05) decreased cleavage rates (90.25% vs. 81.46%) were observed during the early stage (days 0–2), while significantly (p < 0.05) increased developmental rates (38.20% vs. 44.46%) were observed during the later stage (from day 3) of embryonic development. In particular, NAC supplementation decreased the proportion of apoptotic blastomeres significantly (p < 0.05), resulting in enhanced hatching capability and developmental rates during the in vitro culture of embryos. Taken together, our results suggest that NAC supplementation has beneficial effects on bovine oocytes and embryos through the prevention of apoptosis and the elimination of oxygen free radicals during maturation and culture in vitro.

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Immune-Modulatory Effects upon Oral Application of Cumin-Essential-Oil to Mice Suffering from Acute Campylobacteriosis

Pathogens ◽

10.3390/pathogens10070818 ◽

2021 ◽

Vol 10 (7) ◽

pp. 818

Author(s):

Soraya Mousavi ◽

Dennis Weschka ◽

Stefan Bereswill ◽

Markus Heimesaat

Keyword(s):

Essential Oil ◽

Infectious Diseases ◽

Post Infection ◽

Apoptotic Cell ◽

Natural Compounds ◽

Mesenteric Lymph Nodes ◽

Beneficial Effects ◽

Cell Responses ◽

Food Borne ◽

Human Campylobacteriosis

Human campylobacteriosis, commonly caused by Campylobacter jejuni, is a food-borne infection with rising prevalence causing significant health and socioeconomic burdens worldwide. Given the threat from emerging antimicrobial resistances, the treatment of infectious diseases with antibiotics-independent natural compounds is utmost appreciated. Since the health-beneficial effects of cumin-essential-oil (EO) have been known for centuries, its potential anti-pathogenic and immune-modulatory effects during acute experimental campylobacteriosis were addressed in the present study. Therefore, C. jejuni-challenged secondary abiotic IL-10-/- mice were treated perorally with either cumin-EO or placebo starting on day 2 post-infection. On day 6 post-infection, cumin-EO treated mice harbored lower ileal pathogen numbers and exhibited a better clinical outcome when compared to placebo controls. Furthermore, cumin-EO treatment alleviated enteropathogen-induced apoptotic cell responses in colonic epithelia. Whereas, on day 6 post-infection, a dampened secretion of pro-inflammatory mediators, including nitric oxide and IFN-γ to basal levels, could be assessed in mesenteric lymph nodes of cumin-EO treated mice, systemic MCP-1 concentrations were elevated in placebo counterparts only. In conclusion, our preclinical intervention study provides first evidence for promising immune-modulatory effects of cumin-EO in the combat of human campylobacteriosis. Future studies should address antimicrobial and immune-modulatory effects of natural compounds as adjunct antibiotics-independent treatment option for infectious diseases.

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Yields and nitrogen uptake of grain sorghum in various rotations, including lucerne, annual legume and long fallow

Australian Journal of Agricultural Research ◽

10.1071/ar9890255 ◽

1989 ◽

Vol 40 (2) ◽

pp. 255 ◽

Cited By ~ 1

Author(s):

ICR Holford

Keyword(s):

Nitrogen Uptake ◽

Grain Sorghum ◽

Grazing Management ◽

First Year ◽

Red Clay ◽

Beneficial Effects ◽

South Wales ◽

Establishment Method ◽

Soil Evidence

Long-term yields, nitrogen uptake and responsiveness of grain sorghum following three lucerne rotations, an annual legume rotation, long fallowing, and continuous wheat growing were measured on a black earth and red clay in northern New South Wales. The three lucerne rotations compared two methods of lucerne establishment (with or without a cover crop) and two methods of grazing management (short or extended grazing).There were large beneficial effects of lucerne leys on the first grain sorghum crop, whether they were measured as grain yield, nitrogen content of the foliage and grain, or nitrogen uptake. The effect was much smaller in the second year but it increased in the third and fourth years, in direct relation to the rainfall during the sorghum flowering period. The effect was larger on the black earth than on the red clay, reflecting the much higher lucerne yields on the former soil. Evidence indicated that the nitrogen contribution from lucerne after the first year was no greater than the nitrogen accumulated by long fallowing, and this was attributed to very low rainfall and lucerne yields during the four year ley period.The annual legume rotation suffered from drought and insect damage in most years, and following sorghum yields tended to be lower than those achieved by long fallowing.Differences in the effects of establishment method and grazing management on total lucerne yields were reflected in the differences in subsequent grain sorghum yields. Largest differences were on the black earth where extended grazing lowered the total yields of lucerne and subsequent grain sorghum. Sowing lucerne under wheat had little effect on total yields of lucerne or sorghum.

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