Cell cycle-dependent localization of hexose transporter mRNA in Saccharomyces cerevisiae

Unicellular organisms like yeast face constantly changing environmental conditions. Especially fluctuating concentrations of glucose affect growth of S. cerevisiae. Thus yeast evolved several hexose transporters with different affinities and expression patterns. We observed that the high-affinity transporter Hxt2 is differentially localized during the cell cycle. Analyzing the localization of its mRNA, by Fluorescent In Situ Hybridization (FISH), unveiled a comparable distribution pattern. Under glucose-rich conditions, the mRNA is retained in the mother cell early in the cell cycle and only later, after Metaphase to Anaphase Transition (MAT), HXT2 mRNA is equally distributed. This is true for all four hexose transporters, we investigated. Furthermore, we could show that the release from the mother cell to the bud after MAT, is dependent on active translation and that the binding of HXT2 mRNA to polysomes confers its stability. Upon deleting the RNA-binding protein Scp160, which is associated with translational control and binds to ribosomes, we found that HXT2 mRNA is enriched in the bud after MAT. Moreover, the deletion of ASC1, that mediates binding of Scp160/Bfr1 to ribosomes, also leads to the enrichment of HXT2 mRNA. Interestingly, Asc1 was also described as being involved in the glucose responsiveness pathway of S. cerevisiae. Here, Asc1 is thought to inhibit the adenylyl cyclase. In fact, we could show that activation of the adenylyl cyclase and subsequently activating the cAMP-dependent protein kinase A, phenocopies the deletion of ASC1. Intriguingly, when we activated the glucose responsiveness pathway by re-feeding starved cells with glucose, we found that especially HXT2 mRNA is enriched in the bud after MAT. Moreover, this enrichment is transient and happens only during the first 1-2 cell divisions after coming from starvation. Next, we deleted the glucose receptor Gpr1 and its associated G-protein Gpa2 in order to investigate the involvement of upstream factors of the glucose responsiveness pathway. Whereas deletion of Gpr1/Gpa2 did not show an effect, a mutated version of Ras2, which does not elicits an increase of cAMP under glucose-shift conditions, inhibits the enrichment of HXT2 mRNA in the bud. Apart from establishing the involvement of the Ras2/cAMP/PKA pathway, we demonstrated that transcription as well as nuclear segregation are necessary, but not sufficient for the enrichment of HXT2 mRNA in the bud. Furthermore, we identified Kar9, which is involved in the asymmetric spindle pole body segregation, as well as Mlp1, Mlp2 and Nup2, which are components of the nuclear basket, as important trans-acting factors for the asymmetric distribution of HXT2 mRNA under glucose shift conditions. Finally, we were wondering, whether there is an advantage for the daughter cell to be provided with high levels of HXT2 mRNA. We carried out growth tests and observed that cells that express HXT2 as their sole hexose transporter grow faster than cells expressing other HXTs. Taken together, the results presented in this thesis suggest that S. cerevisiae enriches specifically HXT2 mRNA in the daughter cell, when coming from quiescence or starvation. Expression of HXT2 presumably enables the daughter cell to rapidly accumulate glucose, switch from respiration to fermentation and to start re-growth ahead of cells, that do not enrich HXT2 mRNA

Psychosocial Problems, Indoor Air-Related Symptoms, and Perceived Indoor Air Quality among Students in Schools without Indoor Air Problems : A Longitudinal Study

The effect of students' psychosocial problems on their reporting of indoor air quality (subjective IAQ) and indoor air-related (IA-related) symptoms has not been studied in schools in a longitudinal setting. Therefore, we analyzed whether changes in students' psychosocial problems (socioemotional difficulties and perceived teacher student relations) between the beginning of seventh grade (age 12-13 years) and the end of ninth grade (15-16 years) predicted subjective IAQ and IA-related symptoms at the end of ninth grade. In order to explore the independent effect of psychosocial factors, we focused only on students in schools without observed indoor air problems. The analysis was of longitudinal data (N = 986 students) using latent change modelling. Increased socioemotional difficulties were related to more IA-related symptoms (standardized beta = 0.20) and deteriorated subjective IAQ (standardized beta = 0.20). Increased problems in teacher student relations were related to deteriorated subjective IAQ (standardized beta = 0.21). Although students' psychosocial problems explained only 9-13% of the total variances, our findings support the notion that psychosocial factors also need to be taken into account in the evaluation of IAQ and the prevalence of IA-related symptoms in schools.Peer reviewe

Asymmetric distribution of glucose transporter mRNA provides a growth advantage in yeast

Asymmetric localization of mRNA is important for cell fate decisions in eukaryotes and provides the means for localized protein synthesis in a variety of cell types. Here, we show that hexose transporter mRNAs are retained in the mother cell of; S. cerevisiae; until metaphase-anaphase transition (MAT) and then are released into the bud. The retained mRNA was translationally less active but bound to ribosomes before MAT Importantly, when cells were shifted from starvation to glucose-rich conditions, HXT2 mRNA, but none of the other HXT mRNAs, was enriched in the bud after MAT This enrichment was dependent on the Ras/cAMP/PKA pathway, the APC ortholog Kar9, and nuclear segregation into the bud. Competition experiments between strains that only expressed one hexose transporter at a time revealed that; HXT2; only cells grow faster than their counterparts when released from starvation. Therefore, asymmetric distribution of HXT2 mRNA provides a growth advantage for daughters, who are better prepared for nutritional changes in the environment. Our data provide evidence that asymmetric mRNA localization is an important factor in determining cellular fitness

Fish Consumption and Omega-3 Polyunsaturated Fatty Acids in Relation to Depressive Episodes: A Cross-Sectional Analysis

High fish consumption and omega-3 polyunsaturated fatty acid (PUFA) intake are suggested to benefit mental well-being but the current evidence is conflicting. Our aim was to evaluate whether a higher level of fish consumption, a higher intake of omega-3 PUFAs, and a higher serum concentration of omega-3 PUFAs link to a lower 12-month prevalence of depressive episodes

Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease

<div><p>Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn’s disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits.</p></div

Neutrino Physics with JUNO

The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purposeunderground liquid scintillator detector, was proposed with the determinationof the neutrino mass hierarchy as a primary physics goal. It is also capable ofobserving neutrinos from terrestrial and extra-terrestrial sources, includingsupernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos,atmospheric neutrinos, solar neutrinos, as well as exotic searches such asnucleon decays, dark matter, sterile neutrinos, etc. We present the physicsmotivations and the anticipated performance of the JUNO detector for variousproposed measurements. By detecting reactor antineutrinos from two power plantsat 53-km distance, JUNO will determine the neutrino mass hierarchy at a 3-4sigma significance with six years of running. The measurement of antineutrinospectrum will also lead to the precise determination of three out of the sixoscillation parameters to an accuracy of better than 1\%. Neutrino burst from atypical core-collapse supernova at 10 kpc would lead to ~5000inverse-beta-decay events and ~2000 all-flavor neutrino-proton elasticscattering events in JUNO. Detection of DSNB would provide valuable informationon the cosmic star-formation rate and the average core-collapsed neutrinoenergy spectrum. Geo-neutrinos can be detected in JUNO with a rate of ~400events per year, significantly improving the statistics of existing geoneutrinosamples. The JUNO detector is sensitive to several exotic searches, e.g. protondecay via the $p\to K^++\bar\nu$ decay channel. The JUNO detector will providea unique facility to address many outstanding crucial questions in particle andastrophysics. It holds the great potential for further advancing our quest tounderstanding the fundamental properties of neutrinos, one of the buildingblocks of our Universe

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve