Atrial fibrosis heterogeneity is a risk for atrial fibrillation in pigs with ischaemic heart failure.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia and is associated with considerable morbidity and mortality. Ischaemic heart failure (IHF) remains one of the most common causes of AF in clinical practice. However, ischaemia-mediated mechanisms leading to AF are still incompletely understood, and thus, current treatment approaches are limited. To improve our understanding of the pathophysiology, we studied a porcine IHF model. METHODS: In pigs, IHF was induced by balloon occlusion of the left anterior descending artery for 90 min. After 30 days of reperfusion, invasive haemodynamic measurements and electrophysiological studies were performed. Masson trichrome and immunofluorescence staining were conducted to assess interstitial fibrosis and myofibroblast activation in different heart regions. RESULTS: After 30 days of reperfusion, heart failure with significantly reduced ejection fraction (left anterior obique 30°, 34.78 ± 3.29% [IHF] vs. 62.03 ± 2.36% [control], p < .001; anterior-posterior 0°, 29.16 ± 3.61% vs. 59.54 ± 1.09%, p < .01) was observed. These pigs showed a significantly higher susceptibility to AF (33.90% [IHF] vs. 12.98% [control], p < .05). Histological assessment revealed aggravated fibrosis in atrial appendages but not in atrial free walls in IHF pigs (11.13 ± 1.44% vs. 5.99 ± .86%, p < .01 [LAA], 8.28 ± .56% vs. 6.01 ± .35%, p < .01 [RAA]), which was paralleled by enhanced myofibroblast activation (12.09 ± .65% vs. 9.00 ± .94%, p < .05 [LAA], 14.37 ± .60% vs. 10.30 ± 1.41%, p < .05 [RAA]). Correlation analysis indicated that not fibrosis per se but its cross-regional heterogeneous distribution across the left atrium was associated with AF susceptibility (r = .6344, p < .01). CONCLUSION: Our results suggest that left atrial cross-regional fibrosis difference rather than overall fibrosis level is associated with IHF-related AF susceptibility, presumably by establishing local conduction disturbances and heterogeneity.

Appleseed - restoration and resonance.

The successful restoration of the river that used to be the dirtiest in Europe shows that any water course can be brought back to life. Around the world, different approaches and different goals are being pursued in a multitude of river restoration projects, with barrier removals showing a growing trend.

The avisphere.

Florian Maderspacher introduces the 'birds' special issue.

Flightless birds.

"There is no greater anomaly in nature than a bird that cannot fly" - thus spoke Richard Owen, towering figure of Victorian biology, second only to Charles Darwin, who related this quote in his Origin of Species. Owen, who later became a strident critic of Darwin's theory, knew what he was talking about. In 1839, he received a bone fragment from New Zealand. Through his superior anatomy skills, Owen inferred that this was the femur of a bird, but a bird that must have been incredibly big and hence unable to fly. As more bones arrived, Owen concluded that they belonged to a group of bird that we now know as 'moa', some of which stood almost twice as tall as him and were among the largest birds that ever lived (Figure 1).

Genomics: an inordinate fondness for beetles.

Beetles are reckoned to make up about one quarter of animal species. Now, the first genome of a beetle--the red flour beetle Tribolium castaneum, a pest and developmental model system alike--has been sequenced.

Six easy species - vignettes of biodiversity.

Florian Maderspacher introduces the special issue on biodiversity.

Evolution and development: From the pet shop to the pelagic zone.

Flying fish and some of their relatives have evolved the ability to elegantly escape predators by gliding through air. A new study - involving a pet shop zebrafish mutant - offers glimpses into how fins might have been modified to enable this stunt.

Paleontology: Snow falling on dinosaurs.

A treasure trove of dinosaur bones and teeth from Northern Alaska - many from juveniles and yearlings - reveals that dinosaurs lived year-round in the cold and dark environment of the high Arctic.

Cecidology: Anatomy of a biohack.

Galls are abnormal plant growths induced by animals, especially insects, to foster their own developing offspring. Which molecular malware gall-inducers use to hack into the plant's genetic programs is unclear. In an aphid, a gene affecting gall color has been discovered, part of a large family of putative effectors.

Sexual Selection: A Cross-Sword Puzzle.

Swordtail fish with their eponymous male ornament have long been a paradigm for how sexual selection works. Two studies now aim to dissect the genetic and developmental basis of the sword. They home in on similar regions of the swordtail genome but arrive at different candidate genes.

All the queen's men.

Humans have an ancient and intimate relationship with honey bees--from the development of beekeeping in prehistoric times up to the recent sequencing of the honey bee genome. Yet, the intimacies of bee sexuality remained obscure and contentious until relatively recently. Their stepwise unravelling is a tale of advances and misconception that, in part, may have stemmed from an all too humanised view of bees.

Consider the microbe.

Florian Maderspacher introduces the microbiology special issue and asks how the study of microbes has shaped our understanding of evolution.

The long dark teatime of the cell.

Florian Maderspacher introduces the special issue 'the cell in evolution'.

Characterization of a porcine model of atrial arrhythmogenicity in the context of ischaemic heart failure.

Atrial fibrillation (AF) is a major healthcare challenge contributing to high morbidity and mortality. Treatment options are still limited, mainly due to insufficient understanding of the underlying pathophysiology. Further research and the development of reliable animal models resembling the human disease phenotype is therefore necessary to develop novel, innovative and ideally causal therapies. Since ischaemic heart failure (IHF) is a major cause for AF in patients we investigated AF in the context of IHF in a close-to-human porcine ischaemia-reperfusion model. Myocardial infarction (AMI) was induced in propofol/fentanyl/midazolam-anaesthetized pigs by occluding the left anterior descending artery for 90 minutes to model ischaemia with reperfusion. After 30 days ejection fraction (EF) was significantly reduced and haemodynamic parameters (pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), left ventricular enddiastolic pressure (LVEDP)) were significantly elevated compared to age/weight matched control pigs without AMI, demonstrating an IHF phenotype. Electrophysiological properties (sinus node recovery time (SNRT), atrial/AV nodal refractory periods (AERP, AVERP)) did not differ between groups. Atrial burst pacing at 1200 bpm, however, revealed a significantly higher inducibility of atrial arrhythmia episodes including AF in IHF pigs (3/15 vs. 10/16, p = 0.029). Histological analysis showed pronounced left atrial and left ventricular fibrosis demonstrating a structural substrate underlying the increased arrhythmogenicity. Consequently, selective ventricular infarction via LAD occlusion causes haemodynamic alterations inducing structural atrial remodeling which results in increased atrial fibrosis as the arrhythmogenic atrial substrate in pigs with IHF.

The captivating coral--the origins of early evolutionary imagery.

In the 'Origin of Species', Darwin sums up his ideas about the evolutionary process in a single diagram. Tracing the 'evolution' of this diagram reveals a host of sources that may have inspired Darwin's imagination.

Spectres of the Anthropocene.

Florian Maderspacher introduces the Anthropocene special issue.

Planet of the apes.

What makes us humans so special? Our language, our genes, our culture, our cognitive skills? At the Max-Planck-Institute for Evolutionary Anthropology in Leipzig, psychologists, linguists and biologists tackle this old question in a truly multidisciplinary way. Their results have implications not just for our understanding of human evolution--they also touch directly on many social and environmental issues. Florian Maderspacher reports.

Insect Olfaction: Once Swatted, Twice Shy.

While some mosquitoes are known to have an innate penchant for human hosts, new research details that they can learn, what they can learn and how they can learn.

Large-scale mapping of mutations affecting zebrafish development.

BACKGROUND: Large-scale mutagenesis screens in the zebrafish employing the mutagen ENU have isolated several hundred mutant loci that represent putative developmental control genes. In order to realize the potential of such screens, systematic genetic mapping of the mutations is necessary. Here we report on a large-scale effort to map the mutations generated in mutagenesis screening at the Max Planck Institute for Developmental Biology by genome scanning with microsatellite markers. RESULTS: We have selected a set of microsatellite markers and developed methods and scoring criteria suitable for efficient, high-throughput genome scanning. We have used these methods to successfully obtain a rough map position for 319 mutant loci from the Tübingen I mutagenesis screen and subsequent screening of the mutant collection. For 277 of these the corresponding gene is not yet identified. Mapping was successful for 80 % of the tested loci. By comparing 21 mutation and gene positions of cloned mutations we have validated the correctness of our linkage group assignments and estimated the standard error of our map positions to be approximately 6 cM. CONCLUSION: By obtaining rough map positions for over 300 zebrafish loci with developmental phenotypes, we have generated a dataset that will be useful not only for cloning of the affected genes, but also to suggest allelism of mutations with similar phenotypes that will be identified in future screens. Furthermore this work validates the usefulness of our methodology for rapid, systematic and inexpensive microsatellite mapping of zebrafish mutations.

Evolution: Flight of the Ratites.

The flightless ratite birds are scattered all across the Southern hemisphere, on landmasses that have long been separated from each other. But how did they get there? They flew in from the North.