Chronological Lifespan in Yeast Is Dependent on the Accumulation of Storage Carbohydrates Mediated by Yak1, Mck1 and Rim15 Kinases

Upon starvation for glucose or any other macronutrient, yeast cells exit from the mitotic cell cycle and acquire a set of characteristics that are specific to quiescent cells to ensure longevity. Little is known about the molecular determinants that orchestrate quiescence entry and lifespan extension. Using starvation-specific gene reporters, we screened a subset of the yeast deletion library representing the genes encoding 'signaling' proteins. Apart from the previously characterised Rim15, Mck1 and Yak1 kinases, the SNF1/AMPK complex, the cell wall integrity pathway and a number of cell cycle regulators were shown to be necessary for proper quiescence establishment and for extension of chronological lifespan (CLS), suggesting that entry into quiescence requires the integration of starvation signals transmitted via multiple signaling pathways. The CLS of these signaling mutants, and those of the single, double and triple mutants of $\textit{RIM15}$, $\textit{YAK1}$ and $\textit{MCK1}$ correlates well with the amount of storage carbohydrates but poorly with transition-phase cell cycle status. Combined removal of the glycogen and trehalose biosynthetic genes, especially $\textit{GSY2}$ and $\textit{TPS1}$, nearly abolishes the accumulation of storage carbohydrates and severely reduces CLS. Concurrent overexpression of $\textit{GSY2}$ and $\textit{TSL1}$ or supplementation of trehalose to the growth medium ameliorates the severe CLS defects displayed by the signaling mutants ($\textit{rim15Δyak1Δ}$ or $\textit{rim15Δmck1Δ}$). Furthermore, we reveal that the levels of intracellular reactive oxygen species are cooperatively controlled by Yak1, Rim15 and Mck1, and the three kinases mediate the $\textit{TOR1}$-regulated accumulation of storage carbohydrates and CLS extension. Our data support the hypothesis that metabolic reprogramming to accumulate energy stores and the activation of anti-oxidant defence systems are coordinated by Yak1, Rim15 and Mck1 kinases to ensure quiescence entry and lifespan extension in yeast.This work was sponsored by a scholarship awarded by National University of Defense Technology of China (to LC) and a scholarship from Lucy Cavendish College, Cambridge (to ZQ). Reagents and tools were supported by the UNICELLSYS Collaborative Project (No. 201142) of the European Commission (awarded to SGO). NZ is grateful to the Wellcome Trust and the University of Cambridge for support and facilities

Monte Carlo Simulation of HERD Calorimeter

The High Energy cosmic-Radiation Detection (HERD) facility onboard China's Space Station is planned for operation starting around 2020 for about 10 years. It is designed as a next generation space facility focused on indirect dark matter search, precise cosmic ray spectrum and composition measurements up to the knee energy, and high energy gamma-ray monitoring and survey. The calorimeter plays an essential role in the main scientific objectives of HERD. A 3-D cubic calorimeter filled with high granularity crystals as active material is a very promising choice for the calorimeter. HERD is mainly composed of a 3-D calorimeter (CALO) surrounded by silicon trackers (TK) from all five sides except the bottom. CALO is made of 9261 cubes of LYSO crystals, corresponding to about 55 radiation lengths and 3 nuclear interaction lengths, respectively. Here the simulation results of the performance of CALO with GEANT4 and FLUKA are presented: 1) the total absorption CALO and its absorption depth for precise energy measurements (energy resolution: 1\% for electrons and gamma-rays beyond 100 GeV, 20\% for protons from 100 GeV to 1 PeV); 2) its granularity for particle identification (electron/proton separation power better than $10^{-5}$); 3) the homogenous geometry for detecting particles arriving from every unblocked direction for large effective geometrical factor ($>$3 ${\rm m}^{2}{\rm sr}$ for electron and diffuse gamma-rays, $>$2 ${\rm m}^{2}{\rm sr}$ for cosmic ray nuclei); 4) expected observational results such as gamma-ray line spectrum from dark matter annihilation and spectrum measurement of various cosmic ray chemical components

Internal R&D or external asset growth? A closer look at CEO narcissism and entrepreneurial orientation

PurposeIn today\u27s competitive business environment, understanding how leadership traits shape outcomes is critical. Chief executive officer (CEO) narcissism, an intriguing and debated trait, raises questions about its impact on organisational behaviour, particularly regarding entrepreneurial orientation (EO). This study aims to examine how CEO narcissism affects EO, both as aggregate and specific measures, encompassing internal and external growth. It also considers the organisational context by examining how factors such as capital intensity, firm ownership and CEO duality moderate this relationship.Design/methodology/approachTo test the hypotheses, the authors used a sample of firms drawn from China\u27s ChiNext database (2008–2017). After an initial screening, the final sample consists of 251 CEOs from 239 companies. Data on CEO narcissism are collected from the firm\u27s official website and major online sources, whilst additional data are extracted from the WIND daabase. The authors use multiple regression and ordinary least squares (OLS) for data analysis.FindingsThe results show that CEO narcissism leads to external asset growth investments but not internal research and development (R&D). There is a positive relationship between CEO narcissism and EO as an aggregate measure and also different managerial discretions play varying roles in the relationship. Specifically, capital intensity weakens this relationship, but state ownership strengthens it.Originality/valueThis study helps to clarify the relationship between CEO narcissism and EO and advances the literature by showing that firms\u27 EO actions may take various forms of innovation and venturing as new entry initiations of EO. The study findings have important implications for firms to capitalise on narcissistic CEOs\u27 entrepreneurial tendencies, balance internal R&D and external asset growth and leverage various managerial discretions

The Dynamics of Sustained Reentry in a Loop Model with Discrete Gap Junction Resistance

Dynamics of reentry are studied in a one dimensional loop of model cardiac cells with discrete intercellular gap junction resistance ($R$). Each cell is represented by a continuous cable with ionic current given by a modified Beeler-Reuter formulation. For $R$ below a limiting value, propagation is found to change from period-1 to quasi-periodic ($QP$) at a critical loop length ($L_{crit}$) that decreases with $R$. Quasi-periodic reentry exists from $L_{crit}$ to a minimum length ($L_{min}$) that is also shortening with $R$. The decrease of $L_{crit}(R)$ is not a simple scaling, but the bifurcation can still be predicted from the slope of the restitution curve giving the duration of the action potential as a function of the diastolic interval. However, the shape of the restitution curve changes with $R$.Comment: 6 pages, 7 figure

A Cellular Automata Model with Probability Infection and Spatial Dispersion

In this article, we have proposed an epidemic model by using probability cellular automata theory. The essential mathematical features are analyzed with the help of stability theory. We have given an alternative modelling approach for the spatiotemporal system which is more realistic and satisfactory from the practical point of view. A discrete and spatiotemporal approach are shown by using cellular automata theory. It is interesting to note that both size of the endemic equilibrium and density of the individual increase with the increasing of the neighborhood size and infection rate, but the infections decrease with the increasing of the recovery rate. The stability of the system around the positive interior equilibrium have been shown by using suitable Lyapunov function. Finally experimental data simulation for SARS disease in China and a brief discussion conclude the paper

A quality-assured dataset of nine radiation components observed at the Shangdianzi regional GAW station in China (2013–2022)

The New Baseline Surface Radiation (NBSR) system was established at the Shangdianzi (SDZ) regional Global Atmosphere Watch (GAW) station in 2013 to observe nine broadband radiation components, i.e. the global, direct, diffuse, and upwelling shortwave irradiance (GSWI, DSWI, DifSWI, and UpSWI); the photosynthetically active radiation (PAR); the ultraviolet irradiance (UVAI and UVBI); and the down- and upwelling longwave irradiance (DnLWI and UpLWI). To test the 1 min raw radiometric data, a Hybrid Algorithm for Radiation Data Quality Control (HARDQC) is presented in this study based on well-established methods, together with the solar irradiance dataset and the spectral features of the instrument bands. Subsequently, a NBSR dataset, which consists of radiation data at multiple timescales (i.e. 1 min, hourly, daily, monthly, monthly average hourly, and monthly average daily) over 2013–2022, is established and evaluated. Results show that more than 98.7 % of all radiation components passed the physical possibility test. The percentages of those that passed the extremely rare test are greater than 98.6 % for all radiation components except for the DnLWI (97.1 %). The percentages of those that passed the comparison test are greater than 83.3 % (GSWI), 78.3 % (DSWI), 81.7 % (DifSWI), 93.1 % (UpSWI), 88.9 % (PAR), 95.6 % (UVAI), 96.3 % (UVBI), 99.8 % (DnLWI), and 99.7 % (UpLWI), respectively. Due to data logger faults, removal of the instruments for calibration, and lightning strikes, some apparent data gaps in the upwelling radiation components (January 2015–August 2017) and all radiation components (December 2018; July to September 2021) were detected. Despite the existence of a few imperfections in the NBSR dataset, it is still reliable to apply it in many fields such as the validation of satellite products and numerical models, the investigation of relationships between radiation and atmospheric composition, and the detection of changes in the surface fluxes. The dataset described in this paper is available at https://doi.org/10.1594/PANGAEA.963330 (Quan et al., 2023b).</p