The exceptionally high rate of spontaneous mutations in the polymerase delta proofreading exonuclease-deficient Saccharomyces cerevisiae strain starved for adenine

BACKGROUND: Mutagenesis induced in the yeast Saccharomyces cerevisiae by starvation for nutrilites is a well-documented phenomenon of an unknown mechanism. We have previously shown that the polymerase delta proofreading activity controls spontaneous mutagenesis in cells starved for histidine. To obtain further information, we compared the effect of adenine starvation on mutagenesis in wild-type cells and, in cells lacking the proofreading activity of polymerase delta (phenotype Exo(-), mutation pol3-01). RESULTS: Ade(+ )revertants accumulated at a very high rate on adenine-free plates so that their frequency on day 16 after plating was 1.5 × 10(-4 )for wild-type and 1.0 × 10(-2 )for the Exo(- )strain. In the Exo(- )strain, all revertants arising under adenine starvation are suppressors of the original mutation, most possessed additional nutritional requirements, and 50% of them were temperature sensitive. CONCLUSIONS: Adenine starvation is highly mutagenic in yeast. The deficiency in the polymerase delta proofreading activity in strains with the pol3-01 mutation leads to a further 66-fold increase of the rate of mutations. Our data suggest that adenine starvation induces genome-wide hyper-mutagenesis in the Exo(- )strain

Parasitic Energy Loss in the LEP Superconducting Cavities

The energy loss of bunches in the LEP superconducting (SC) cavities has been determined by measuring the closed orbit as a function of current with the beam position monitors located at finite dispersion. This method has already been used in earlier experiments to determine the distribution of the longitudinal impedance of different parts of LEP. In the present experiment the energy loss in two straight sections, containing only SC cavities, was compared with that in sections having both copper cavities and SC cavities. The results confirm the impedance calculations for the two types of cavities. The accuracy of the measurements was considerably improved by determining simultaneously the orbits of bunches with different currents. At the same time with these beam-based impedance measurements, the power dissipation was observed directly by local temperature monitors in different elements: the inter-cavity bellows inside the cryostat, the warm intermodule bellows, and Ferrite absorbers which were installed in two places to reduce the energy leaking out of cavities. These observations were correlated with the change of cryogenics power consumption, and showed an unexpected dependence of energy loss on beam energy

Prevalence of hepatic steatosis in patients with type 2 diabetes and response to glucose-lowering treatments. A multicenter retrospective study in Italian specialist care

Type 2 diabetes (T2D) is a risk factor for metabolic dysfunction-associated fatty liver disease (MAFLD), which is becoming the commonest cause of chronic liver disease worldwide. We estimated MAFLD prevalence among patients with T2D using the hepatic steatosis index (HSI) and validated it against liver ultrasound. We also examined whether glucose-lowering medications (GLM) beneficially affected HSI

Similar effectiveness of dapagliflozin and GLP-1 receptor agonists concerning combined endpoints in routine clinical practice: A multicentre retrospective study

Aims According to cardiovascular outcome trials, some sodium-glucose contransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) are recommended for secondary cardiovascular prevention in type 2 diabetes (T2D). In this real-world study, we compared the simultaneous reductions in HbA1c, body weight and systolic blood pressure after initiation of dapagliflozin or GLP-1RA as second or a more advanced line of therapy. Materials and methods DARWIN-T2D was a retrospective multi-centre study conducted at diabetes specialist clinics in Italy that compared T2D patients who initiated dapagliflozin or GLP-1RA (exenatide once weekly or liraglutide). Data were collected at baseline and at the first follow-up visit after 3 to 12 months. The primary endpoint was the proportion of patients achieving a simultaneous reduction in HbA1c, body weight and systolic blood pressure. To reduce confounding, we used multivariable adjustment (MVA) or propensity score matching (PSM). Results Totals of 473 patients initiating dapagliflozin and 336 patients initiating GLP-1RA were included. The two groups differed in age, diabetes duration, HbA1c, weight and concomitant medications. The median follow-up was 6 months in both groups. Using MVA or PSM, the primary endpoint was observed in 30% to 32% of patients, with no difference between groups. Simultaneous reduction of HbA1c, BP and SBP by specific threshold, as well as achievement of final goals, did not differ between groups. GLP-1RA reduced HbA1c by 0.3% more than the reduction achieved with dapagliflozin. Conclusion In routine specialist care, initiation of dapagliflozin can be as effective as initiation of a GLP-1RA for attainment of combined risk factor goals

Evidence for the presence of a second conditioning factor in plant cell cultures.

Plating efficiency (P.E.) of Daucus carota cells in culture is strongly dependent on cell density, either in the absence or presence of a conditioning factor (CF) previously described. The decrease of plating efficiency with cell dilution is not abolished by an increase of CF concentration or by CFs produced from different species. The dependence of the multiplication on cellular density is unchanged also after addition of Brassinosteroid, a hormone which increases the plating efficiency synergistically with CF. Direct contact of seeded cells with callus cultures, separated by a dialysis membrane, completely abolishes the phenomenon providing evidence for the presence of a second conditioning factor

Memoriale della Resistenza, Arcevia

Ricordare oggi, a distanza di oltre mezzo secolo, le vicende della Resistenza, presuppone la spiegazione e il racconto attraverso la messa a disposizione delle testimonianze: il valore della Memoria \ue8 stato alla base dell\u2019ipotesi progettuale. Ripercorrere attraverso il progetto uno degli scenari in cui si \ue8 rappresentato il dramma della lotta partigiana \u2013il rudere di una casa contadina data alle fiamme insieme ai suoi occupanti dai nazifascisti\u2013 corrisponde ad una sorta di eterno ritorno al luogo, in quanto suo ritrovamento: esso deve ogni volta fissarsi nella memoria. Il progetto scarta il ricorso a tipologie monumentali e celebrative, affidando il ricordo degli scomparsi nella lotta per la libert\ue0 ad un luogo dei vivi, spazio abitabile, attraversabile in ogni sua parte: luogo accomunante disponibile all\u2019incontro. L\u2019edificio \u2013contenente un piccolo museo che raccoglie le testimonianze della Resistenza nelle Marche e in particolare nel territorio montano di Arcevia, una sala per riunioni-convegni coi relativi servizi e un piccolo ufficio\u2013 \ue8 costituito da un corpo allungato seminterrato che, emergendo dal Monte Sant\u2019Angelo, si affaccia sulla valle

Stimulation of growth in Daucus carota L. cell cultures by Brassinosteroid.

In Daucus corota L. cell culture, the steroid hormone 24-epibrassinolide (BR) induces cell enlargement at 10−6 M, without having any effect on cell multiplication when tested on suspension cultured cells, and increases the plating efficiency when diluted cell suspensions are plated onto agarized culture medium. This improvement of the plating efficiency may be a direct consequence of cell enlargement