Monash University

About: Monash University is a education organization based out in Melbourne, Victoria, Australia. It is known for research contribution in the topics: Population & Poison control. The organization has 35920 authors who have published 100681 publications receiving 3027002 citations.

The Selaginella genome identifies genetic changes associated with the evolution of vascular plants.

Abstract: Vascular plants appeared ~410 million years ago, then diverged into several lineages of which only two survive: the euphyllophytes (ferns and seed plants) and the lycophytes. We report here the genome sequence of the lycophyte Selaginella moellendorffii (Selaginella), the first nonseed vascular plant genome reported. By comparing gene content in evolutionarily diverse taxa, we found that the transition from a gametophyte- to a sporophyte-dominated life cycle required far fewer new genes than the transition from a nonseed vascular to a flowering plant, whereas secondary metabolic genes expanded extensively and in parallel in the lycophyte and angiosperm lineages. Selaginella differs in posttranscriptional gene regulation, including small RNA regulation of repetitive elements, an absence of the trans-acting small interfering RNA pathway, and extensive RNA editing of organellar genes.

Aliskiren, ALTITUDE, and the implications for ATMOSPHERE

Abstract: Blockade of the renin–angiotensin system (RAS) is a core therapeutic strategy in systolic heart failure.1 The value of angiotensin-converting enzyme (ACE) inhibitors was proven in two pivotal trials conducted >20 years ago. More recently, angiotensin receptor blockers (ARBs) have also been shown to be beneficial in systolic heart failure both as an alternative to and when added to an ACE inhibitor. Separately, mineralocorticoid receptor antagonists (MRAs) reduce mortality and morbidity when added to an ACE inhibitor or ARB (MRAs are not considered further here). The latest approach to RAS blockade to be tested in clinical practice is renin inhibition. Currently the efficacy and safety of the renin inhibitor aliskiren is being tested in two clinical trials in heart failure, the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failure (ATMOSPHERE) and the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT), described previously in this journal.2,3 However, on 20 December 2011, treatment in another study, the Aliskiren Trial In Type 2 Diabetes Using Cardio-Renal Disease Endpoints (ALTITUDE), was stopped on the recommendation of its Data Monitoring Committee (DMC).2,3 ALTITUDE was comparing placebo or aliskiren 300 mg once daily, added to background ACE inhibitor or ARB therapy in patients with diabetes and either (i) increased urinary albumin excretion or (ii) both a reduced estimated glomerular filtration rate (eGFR 30–60 mL/min/1.73 m2) and established cardiovascular disease. The primary outcome in ALTITUDE is a composite of cardiovascular death, resuscitated sudden death, non-fatal myocardial infarction, non-fatal stroke, unplanned hospitalization for heart failure, end-stage renal disease, renal death, or doubling of baseline serum creatinine concentration, sustained for at least a month. As a result of the DMC recommendation, ALTITUDE is currently being closed out in an orderly fashion. The basis of the DMC recommendation was futility (i.e. no prospect of demonstrating the treatment benefit anticipated in the protocol) as well as safety concerns. These concerns included renal dysfunction, hyperkalaemia, and hypotension (which are unsurprising) as well as an excess of strokes. In the publically released information, the number of patients experiencing a non-fatal stroke in the placebo group was 85 (2.0%) and 112 (2.6%) in the aliskiren group (nominal, unadjusted, P-value 0.04).6 Although this unexpected finding has provoked concern and discussion, the reported numbers do not represent the final number of events in ALTITUDE (at the time of the DMC's recommendation it was estimated that approximately a third of events remained to be collected and adjudicated). Consequently, while the apparent imbalance in strokes may persist or increase, it may also attenuate. Furthermore, given all prior data relating use of antihypertensive therapy to a reduced incidence of stroke in patients with diabetes, it is also possible that the imbalance in strokes represents a chance finding.7–9 In response to these findings it has been recommended that dual aliskiren and ACE inhibitor/ARB therapy not be used in patients with both hypertension (the current indication for aliskiren) and diabetes or moderate to severe renal dysfunction (eGFR <60 mL/min/1.73 m2).10 This recommendation has led to questions about the use of dual aliskiren therapy in patients with diabetes in the ongoing ATMOSPHERE trial (and, to a lesser extent, also the ASTRONAUT trial which has almost finished recruitment and will complete follow-up this year). In ATMOSPHERE, patients with systolic heart failure and an elevated B-type natriuretic peptide (BNP) or N-terminal pro BNP ( NT-proBNP) concentration are randomized in equal proportions to receive either enalapril 10 mg twice daily, aliskiren 300 mg once daily, or the combination of both drugs.3 ATMOSPHERE is an event-driven trial with a primary composite outcome of cardiovascular death or heart failure hospitalization. We believe that the preliminary results of ALTITUDE should not lead to any alteration in the conduct of ATMOSPHERE. The reasons for taking this view are discussed in detail below.

Thermonuclear (Type I) X-Ray Bursts Observed by the Rossi X-Ray Timing Explorer

Abstract: We have assembled a sample of 1187 thermonuclear (type I) X-ray bursts from observations of 48 accreting neutron stars by the Rossi X-ray Timing Explorer, spanning more than 10 years. The sample contains examples of two of the three theoretical ignition regimes (confirmed via comparisons with numerical models) and likely examples of the third. We present a detailed analysis of the variation of the burst profiles, energetics, recurrence times, presence of photospheric radius expansion, and presence of burst oscillations, as a function of accretion rate. We estimated the distance for 35 sources exhibiting radius-expansion bursts, and found that the peak flux of such bursts varies typically by 13%. We classified sources into two main groups based on the burst properties: (1) both long and short bursts (indicating mixed H/He accretion), and (2) consistently short bursts (primarily He accretion), and we calculated the mean burst rate as a function of accretion rate for the two groups. The decrease in burst rate observed at > 0.06dot MEdd (~2 × 10^37 ergs s^−1) is associated with a transition in the persistent spectral state and (as has been suggested previously) may be related to the increasing role of steady He burning. We found many examples of bursts with recurrence times <30 minutes, including burst triplets and even quadruplets. We describe the oscillation amplitudes for 13 of the 16 burst oscillation sources, as well as the stages and properties of the bursts in which the oscillations are detected. The burst properties are correlated with the burst oscillation frequency; sources spinning at <400 Hz generally have consistently short bursts, while the more rapidly spinning systems have both long and short bursts. This correlation suggests either that shear-mediated mixing dominates the burst properties, or alternatively that the nature of the mass donor (and hence the evolutionary history) has an influence on the long-term spin evolution.