University of Milan

About: University of Milan is a education organization based out in Milan, Italy. It is known for research contribution in the topics: Population & Transplantation. The organization has 58413 authors who have published 139784 publications receiving 4636354 citations. The organization is also known as: Università degli Studi di Milano & Statale.

Fork Reversal and ssDNA Accumulation at Stalled Replication Forks Owing to Checkpoint Defects

Abstract: Checkpoint-mediated control of replicating chromosomes is essential for preventing cancer. In yeast, Rad53 kinase protects stalled replication forks from pathological rearrangements. To characterize the mechanisms controlling fork integrity, we analyzed replication intermediates formed in response to replication blocks using electron microscopy. At the forks, wild-type cells accumulate short single-stranded regions, which likely causes checkpoint activation, whereas rad53 mutants exhibit extensive single-stranded gaps and hemi-replicated intermediates, consistent with a lagging-strand synthesis defect. Further, rad53 cells accumulate Holliday junctions through fork reversal. We speculate that, in checkpoint mutants, abnormal replication intermediates begin to form because of uncoordinated replication and are further processed by unscheduled recombination pathways, causing genome instability.

How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

Abstract: Making a firm diagnosis of chronic heart failure with preserved ejection fraction (HFpEF) remains a challenge. We recommend a new stepwise diagnostic process, the 'HFA-PEFF diagnostic algorithm'. Step 1 (P=Pre-test assessment) is typically performed in the ambulatory setting and includes assessment for heart failure symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes mellitus, elderly, atrial fibrillation), and diagnostic laboratory tests, electrocardiogram, and echocardiography. In the absence of overt non-cardiac causes of breathlessness, HFpEF can be suspected if there is a normal left ventricular (LV) ejection fraction, no significant heart valve disease or cardiac ischaemia, and at least one typical risk factor. Elevated natriuretic peptides support, but normal levels do not exclude a diagnosis of HFpEF. The second step (E: Echocardiography and Natriuretic Peptide Score) requires comprehensive echocardiography and is typically performed by a cardiologist. Measures include mitral annular early diastolic velocity (e'), LV filling pressure estimated using E/e', left atrial volume index, LV mass index, LV relative wall thickness, tricuspid regurgitation velocity, LV global longitudinal systolic strain, and serum natriuretic peptide levels. Major (2 points) and Minor (1 point) criteria were defined from these measures. A score ≥5 points implies definite HFpEF; ≤1 point makes HFpEF unlikely. An intermediate score (2-4 points) implies diagnostic uncertainty, in which case Step 3 (F1 : Functional testing) is recommended with echocardiographic or invasive haemodynamic exercise stress tests. Step 4 (F2 : Final aetiology) is recommended to establish a possible specific cause of HFpEF or alternative explanations. Further research is needed for a better classification of HFpEF.

Radiative Transfer in a Clumpy Universe. III. The Nature of Cosmological Ionizing Sources

Abstract: The history of the transition from a neutral intergalactic medium (IGM) to one that is almost fully ionized can reveal the character of cosmological ionizing sources. We study the evolution of the volume filling factors of H II and He III regions in a clumpy IGM and discuss the implications for rival reionization scenarios of the rapid decline observed at z3 in the space density of optical and radio-loud quasars and of the large population of star-forming galaxies recently discovered at the same epoch. The hydrogen component in a highly inhomogeneous universe is completely reionized when the number of photons emitted above 1 ryd in one recombination time equals the mean number of hydrogen atoms. If stellar sources are responsible for keeping the IGM ionized at z=5, the rate of star formation at this epoch must be comparable or greater than the one inferred from optical observations of galaxies at z≈3 and the mean metallicity per baryon in the universe 0.002 solar. An early generation of stars in dark matter halos with circular velocities, vcirc≈50 km s-1, possibly one of the main sources of UV photons at high z, could be detectable with the Next Generation Space Telescope. Models in which the quasar emissivity declines rapidly at z3 predict a late He II reionization epoch, a feature that could explain the recent detection of patchy He II Lyα at z=2.9 by Reimers et al. and the abrupt change observed by Songaila at about the same epoch of the Si IV /C IV ratio, but appear unable to provide the required number of hydrogen-ionizing photons at z≈5.