Power provides protection : genetic robustness in yeast depends on the capacity to generate energy

The functional basis of genetic robustness, the ability of organisms to suppress the effects of mutations, remains incompletely understood. We exposed a set of 15 strains of Saccharomyces cerevisiae form diverse environments to increasing doses of the chemical mutagen EMS. The number of the resulting random mutations was similar for all tested strains. However, there were differences in immediate mortality after the mutagenic treatment and in defective growth of survivors. An analysis of gene expression revealed that immediate mortality was lowest in strains with lowest expression of transmembrane proteins, which are rich in thiol groups and thus vulnerable to EMS. A signal of genuine genetic robustness was detected for the other trait, the ability to grow well despite bearing non-lethal mutations. Increased tolerance of such mutations correlated with high expression of genes responsible for the oxidative energy metabolism, suggesting that the negative effect of mutations can be buffered if enough energy is available. We confirmed this finding in three additional tests of the ability to grow on (i) fermentable or non-fermentable sources of carbon, (ii) under chemical inhibition of the electron transport chain and (iii) during overexpression of its key component, cytochrome c. Our results add the capacity to generate energy as a general mechanism of genetic robustness

Games on graphs with a public signal monitoring

We study pure Nash equilibria in games on graphs with an imperfect monitoring based on a public signal. In such games, deviations and players responsible for those deviations can be hard to detect and track. We propose a generic epistemic game abstraction, which conveniently allows to represent the knowledge of the players about these deviations, and give a characterization of Nash equilibria in terms of winning strategies in the abstraction. We then use the abstraction to develop algorithms for some payoff functions.Comment: 28 page

The effects of prostaglandin E-2 treatment on the secretory function of mare corpus luteum depends on the site of application : an in vivo study

Research Areas: Veterinary SciencesWe examined the effect of prostaglandin (PG) E2 on the secretory function of equine corpus luteum (CL), according to the application site: intra-CL injection vs. an intrauterine (intra-U) administration. Moreover, the effect of intra-CL injection vs. intra-U administration of both luteotropic factors: PGE2 and human chorionic gonadotropin (hCG) as a positive control, on CL function was additionally compared. Mares were assigned to the groups (n = 6 per group): (1) an intra-CL saline injection (control); (2) an intra-CL injection of PGE2 (5 mg/ml); (3) an intra-CL injection of hCG (1,500 IU/ml); (4) an intra-U saline administration (control); (5) an intra-U administration of PGE2 (5 mg/5 ml); (6) an intra-U administration of hCG (1,500 IU/5 ml). Progesterone (P4) and PGE2 concentrations were measured in blood plasma samples collected at −2, −1, and 0 (pre-treatment), and at 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after treatments. Moreover, effects of different doses of PGE2 application on the concentration of total PGF2α (PGF2α and its main metabolite 13,14-dihydro-15-keto-prostaglandin F2α– PGFM) was determined. The time point of PGE2, hCG, or saline administration was defined as hour “0” of the experiment. An intra-CL injection of PGE2 increased P4 and PGE2 concentrations between 3 and 4 h or at 3 and 12 h, respectively (p < 0.05). While intra-U administration of PGE2 elevated P4 concentrations between 8 and 24 h, PGE2 was upregulated at 1 h and between 3 and 4 h (p < 0.05). An intra-CL injection of hCG increased P4 concentrations at 1, 6, and 12 h (p < 0.05), while its intra-U administration enhanced P4 and PGE2 concentrations between 1 and 12 h or at 3 h and between 6 and 10 h, respectively (p < 0.05). An application of PGE2, dependently on the dose, supports equine CL function, regardless of the application site, consequently leading to differences in both P4 and PGE2 concentrations in blood plasmainfo:eu-repo/semantics/publishedVersio

Implementation and evaluation of a transit dosimetry system for treatment verification

PURPOSE: To evaluate a formalism for transit dosimetry using a phantom study and prospectively evaluate the protocol on a patient population undergoing 3D conformal radiotherapy. METHODS: Amorphous silicon EPIDs were calibrated for dose and used to acquire images of delivered fields. The measured EPID dose map was back-projected using the planning CT images to calculate dose at pre-specified points within the patient using commercially available software, EPIgray (DOSIsoft, France). This software compared computed back-projected dose with treatment planning system dose. A series of tests were performed on solid water phantoms (linearity, field size effects, off-axis effects). 37 patients were enrolled in the prospective study. RESULTS: The EPID dose response was stable and linear with dose. For all tested field sizes the agreement was good between EPID-derived and treatment planning system dose in the central axis, with performance stability up to a measured depth of 18cm (agreement within -0.5% at 10cm depth on the central axis and within -1.4% at 2cm off-axis). 126 transit images were analysed of 37 3D-conformal patients. Patient results demonstrated the potential of EPIgray with 91% of all delivered fields achieved the initial set tolerance level of ΔD of 0±5-cGy or %ΔD of 0±5%. CONCLUSIONS: The in vivo dose verification method was simple to implement, with very few commissioning measurements needed. The system required no extra dose to the patient, and importantly was able to detect patient position errors that impacted on dose delivery in two of cases

Platelet‐Derived Growth Factor (PDGF) Gene Delivery for Application in Periodontal Tissue Engineering

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141045/1/jper0815.pd

Magnetic Phase Diagram of GdNi2B2C: Two-ion Magnetoelasticity and Anisotropic Exchange Couplings

Extensive magnetization and magnetostriction measurements were carried out on a single crystal of GdNi2B2C along the main tetragonal axes. Within the paramagnetic phase, the magnetic and strain susceptibilities revealed a weak anisotropy in the exchange couplings and two-ion tetragonal-preserving alpha-strain modes. Within the ordered phase, magnetization and magnetostriction revealed a relatively strong orthorhombic distortion mode and rich field-temperature phase diagrams. For H//(100) phase diagram, three field-induced transformations were observed, namely, at: Hd(T), related to the domain alignment; Hr(T), associated with reorientation of the moment towards the c-axis; and Hs(T), defining the saturation process wherein the exchange field is completely counterbalanced. On the other hand, For H//(001) phase diagram, only two field-induced transformations were observed, namely at: Hr(T) and Hs(T). For both phase diagrams, Hs(T) follows the relation Hs[1-(T/Tn)^2]^(1/2)kOe with Hs(T-->0)=128.5(5) kOe and Tn(H=0)=19.5 K. In contrast, the thermal evolution of Hr(T) along the c-axis (much simpler than along the a-axis) follows the relation Hr[1-T/Tr]^(1/3) kOe where Hr(T-->0)=33.5(5) kOe and Tr(H=0)=13.5 K. It is emphasized that the magnetoelastic interaction and the anisotropic exchange coupling are important perturbations and therefore should be explicitly considered if a complete analysis of the magnetic properties of the borocarbides is desired

Oceanography of Harmful Algal Blooms on the Ecuadorian Coast (1997–2017): Integrating Remote Sensing and Biological Data

Ocean climate drivers and phytoplankton life strategies interact in a complex dynamic to produce harmful algal blooms (HABs). This study aims to integrate historical biological data collected during “red tide” events along the Ecuadorian coast between 1997 and 2017 in relation to five ocean variables derived from satellite remote sensing data to explain the seasonal drivers of coastal processes associated with HABs dynamics. Seasonality of the occurrence of HABs was assessed in relation to oceanographic variables by applying multiple correspondence analysis (MCA) to the Ecuadorian central coast (Zone 1) and at the outer and inner Gulf of Guayaquil (Zone 2). Sixty-seven HABs events were registered between 1997 and 2017. From a total of 40 species of phytoplankton identified, 28 were identified as non-toxic and the remaining 12 are well known to produce toxins. Dinoflagellates were the taxonomic group most highly associated with potential HABs events along the entire Ecuadorian coast. HABs appear to be constrained by the Humboldt coastal upwelling, high precipitation, and associated coastal runoff, with higher biomass abundance in the Gulf of Guayaquil than in the central coast. Results from the MCA reveal that in the central Ecuadorian coast (oligotrophic system), toxic HABs occurred with low abundance of dinoflagellates, while in the Gulf of Guayaquil (eutrophic system), toxic HABs corresponded to a high abundance of dinoflagellates. In both cases, high values were found for sea surface temperature, precipitation, and irradiance—characteristic of wet seasons or El Niño years. Non-toxic HABs occurred with a high abundance of dinoflagellates, ciliates, and centric diatoms, corresponding to colder waters and low levels of precipitation and irradiance. These findings confirm that dinoflagellates display several strategies that enhance their productive capacity when ocean conditions are warmer, allowing them to produce toxins at high or at low concentrations. Considering that the Gulf of Guayaquil is essential to tourism, the shrimp industry, fisheries, and international shipping, these findings strongly suggest the need to establish an ecosystem health research program to monitor HABs and the development of a preventive policy for tourism and public health in Ecuador

The effect of extrinsic mortality on genome size evolution in prokaryotes

Mortality has a significant role in prokaryotic ecology and evolution, yet the impact of variations in extrinsic mortality on prokaryotic genome evolution has received little attention. We used both mathematical and agent-based models to reveal how variations in extrinsic mortality affect prokaryotic genome evolution. Our results suggest that the genome size of bacteria increases with increased mortality. A high extrinsic mortality increases the pool of free resources and shortens life expectancy, which selects for faster reproduction, a phenotype we called ‘scramblers’. This phenotype is realised by the expansion of gene families involved in nutrient acquisition and metabolism. In contrast, a low mortality rate increases an individual’s life expectancy, which results in natural selection favouring tolerance to starvation when conditions are unfavourable. This leads to the evolution of small, streamlined genomes (‘stayers’). Our models predict that large genomes, gene family expansion and horizontal gene transfer should be observed in prokaryotes occupying ecosystems exposed to high abiotic stress, as well as those under strong predator- and/or pathogen-mediated selection. A comparison of genome size of cyanobacteria in relatively stable marine versus more turbulent freshwater environments corroborates our predictions, although other factors between these environments could also be responsible

Membrane-Bound IL-21 Promotes Sustained Ex Vivo Proliferation of Human Natural Killer Cells

NK cells have therapeutic potential for a wide variety of human malignancies. However, because NK cells expand poorly in vitro, have limited life spans in vivo, and represent a small fraction of peripheral white blood cells, obtaining sufficient cell numbers is the major obstacle for NK-cell immunotherapy. Genetically-engineered artificial antigen-presenting cells (aAPCs) expressing membrane-bound IL-15 (mbIL15) have been used to propagate clinical-grade NK cells for human trials of adoptive immunotherapy, but ex vivo proliferation has been limited by telomere shortening. We developed K562-based aAPCs with membrane-bound IL-21 (mbIL21) and assessed their ability to support human NK-cell proliferation. In contrast to mbIL15, mbIL21-expressing aAPCs promoted log-phase NK cell expansion without evidence of senescence for up to 6 weeks of culture. By day 21, parallel expansion of NK cells from 22 donors demonstrated a mean 47,967-fold expansion (median 31,747) when co-cultured with aAPCs expressing mbIL21 compared to 825-fold expansion (median 325) with mbIL15. Despite the significant increase in proliferation, mbIL21-expanded NK cells also showed a significant increase in telomere length compared to freshly obtained NK cells, suggesting a possible mechanism for their sustained proliferation. NK cells expanded with mbIL21 were similar in phenotype and cytotoxicity to those expanded with mbIL15, with retained donor KIR repertoires and high expression of NCRs, CD16, and NKG2D, but had superior cytokine secretion. The mbIL21-expanded NK cells showed increased transcription of the activating receptor CD160, but otherwise had remarkably similar mRNA expression profiles of the 96 genes assessed. mbIL21-expanded NK cells had significant cytotoxicity against all tumor cell lines tested, retained responsiveness to inhibitory KIR ligands, and demonstrated enhanced killing via antibody-dependent cell cytotoxicity. Thus, aAPCs expressing mbIL21 promote improved proliferation of human NK cells with longer telomeres and less senescence, supporting their clinical use in propagating NK cells for adoptive immunotherapy