Genetic determinants of micronucleus formation in vivo.

Genomic instability arising from defective responses to DNA damage1 or mitotic chromosomal imbalances2 can lead to the sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of ageing and diseases associated with genomic instability, the catalogue of genetic players that regulate the generation of MN remains to be determined. Here we analyse 997 mouse mutant lines, revealing 145 genes whose loss significantly increases (n = 71) or decreases (n = 74) MN formation, including many genes whose orthologues are linked to human disease. We found that mice null for Dscc1, which showed the most significant increase in MN, also displayed a range of phenotypes characteristic of patients with cohesinopathy disorders. After validating the DSCC1-associated MN instability phenotype in human cells, we used genome-wide CRISPR-Cas9 screening to define synthetic lethal and synthetic rescue interactors. We found that the loss of SIRT1 can rescue phenotypes associated with DSCC1 loss in a manner paralleling restoration of protein acetylation of SMC3. Our study reveals factors involved in maintaining genomic stability and shows how this information can be used to identify mechanisms that are relevant to human disease biology1.

Will climate change drive alien invasive plants into areas of high protection value? An improved model-based regional assessment to prioritise the management of invasions.

Species distribution models (SDMs) studies suggest that, without control measures, the distribution of many alien invasive plant species (AIS) will increase under climate and land-use changes. Due to limited resources and large areas colonised by invaders, management and monitoring resources must be prioritised. Choices depend on the conservation value of the invaded areas and can be guided by SDM predictions. Here, we use a hierarchical SDM framework, complemented by connectivity analysis of AIS distributions, to evaluate current and future conflicts between AIS and high conservation value areas. We illustrate the framework with three Australian wattle (Acacia) species and patterns of conservation value in Northern Portugal. Results show that protected areas will likely suffer higher pressure from all three Acacia species under future climatic conditions. Due to this higher predicted conflict in protected areas, management might be prioritised for Acacia dealbata and Acacia melanoxylon. Connectivity of AIS suitable areas inside protected areas is currently lower than across the full study area, but this would change under future environmental conditions. Coupled SDM and connectivity analysis can support resource prioritisation for anticipation and monitoring of AIS impacts. However, further tests of this framework over a wide range of regions and organisms are still required before wide application.

Acute intoxication by endosulfan.

The authors report six patients with acute endosulfan intoxication. The symptoms of nausea, vomiting, headache, and dizziness began 2.7 +/- 0.5 h after ingestion; in four cases the patients had been hospitalized but were asymptomatic. All had severe metabolic acidosis with high anion gap and hyperglycemia; five of six had decreased blood platelets. Three patients had pulmonary aspiration, and five required mechanical ventilation. The one fatality followed acute renal failure, disseminated intravascular coagulation, thrombi in the pulmonary arteries and aorta, and cardiogenic shock. In this patient the blood endosulfan was 2.85 mg/L versus a mean of 0.48 mg/L in the survivors.

Spontaneous rupture of an intra-aortic balloon pump.

Circulatory assistance with an intraaortic balloon pump is not free from risks and complications. Among the latter, rupture is extremely rare. We report a case of spontaneous rupture of an intraaortic balloon, which occurred after 29 h of counterpulsation in a patient with cardiogenic shock following an acute myocardial infarction. The probable cause of the rupture was the constant abrasion and eventual perforation of the balloon membrane by a sharp calcified aortic plaque.