Introduction

Non peer reviewe

Population dynamics of Phytophthora infestans in the Netherlands reveals expansion and spread of dominant clonal lineages and virulence in sexual offspring

For a comprehensive survey of the structure and dynamics of the Dutch Phytophthora infestans population, 652 P. infestans isolates were collected from commercial potato fields in the Netherlands during the 10-year period 2000–2009. Genotyping was performed using 12 highly informative microsatellite markers and mitochondrial haplotypes. In addition, for each isolate, the mating type was determined. STRUCTURE analysis grouped the 322 identified genotypes in three clusters. Cluster 1 consists of a single clonal lineage NL-001, known as “Blue_13”; all isolates in this cluster have the A2 mating type and the Ia mitochondrial haplotype. Clusters 2 and 3 display a more elaborate substructure containing many unique genotypes. In Cluster 3, several distinct clonal lineages were also identified. This survey witnesses that the Dutch population underwent dramatic changes in the 10 years under study. The most notable change was the emergence and spread of A2 mating type strain NL-001 (or “Blue_13”). The results emphasize the importance of the sexual cycle in generating genetic diversity and the importance of the asexual cycle as the propagation and dispersal mechanism for successful genotypes. Isolates were also screened for absence of the Avrblb1/ipiO class I gene, which is indicative for virulence on Rpi-blb1. This is also the first report of Rpi-blb1 breakers in the Netherlands. Superimposing the virulence screening on the SSR genetic backbone indicates that lack the Avrblb1/ipiO class I gene only occurred in sexual progeny. So far, the asexual spread of the virulent isolates identified has been limited

Gastrostomy in patients with amyotrophic lateral sclerosis (ProGas): a prospective cohort study

Background Gastrostomy feeding is commonly used to support patients with amyotrophic lateral sclerosis who develop severe dysphagia. Although recommended by both the American Academy of Neurology and the European Federation of Neurological Societies, currently little evidence indicates the optimum method and timing for gastrostomy insertion. We aimed to compare gastrostomy insertion approaches in terms of safety and clinical outcomes. Methods In this large, longitudinal, prospective cohort study (ProGas), we enrolled patients with a diagnosis of definite, probable, laboratory supported, or possible amyotrophic lateral sclerosis who had agreed with their treating clinicians to undergo gastrostomy at 24 motor neuron disease care centres or clinics in the UK. The primary outcome was 30-day mortality after gastrostomy. This study was registered on the UK Clinical Research Network database, identification number 9923. Findings Between Nov 2, 2010, and Jan 31, 2014, 345 patients were recruited of whom 330 had gastrostomy. 163 (49%) patients underwent percutaneous endoscopic gastrostomy, 121 (37%) underwent radiologically inserted gastrostomy, 43 (13%) underwent per-oral image-guided gastrostomy, and three (1%) underwent surgical gastrostomy. 12 patients (4%, 95% CI 2·1–6·2) died within the first 30 days after gastrostomy: five (3%) of 163 after percutaneous endoscopic gastrostomy, four (3%) of 121 after radiologically inserted gastrostomy, and three (7%) of 43 after per-oral image-guided gastrostomy (p=0·46). Including repeat attempts in 14 patients, 21 (6%) of 344 gastrostomy procedures could not be completed: 11 (6%) of 171 percutaneous endoscopic gastrostomies, seven (6%) of 121 radiologically inserted gastrostomies, and three (6%) of 45 per-oral image-guided gastrostomies (p=0·947). Interpretation The three methods of gastrostomy seemed to be as safe as each other in relation to survival and procedural complications. In the absence of data from randomised trials, our findings could inform clinicians and patients in reaching decisions about gastrostomy and will stimulate further research into the nutritional management in patients with amyotrophic lateral sclerosis

Guide-free Cas9 from pathogenic Campylobacter jejuni bacteria causes severe damage to DNA

CRISPR-Cas9 systems are enriched in human pathogenic bacteria and have been linked to cytotoxicity by an unknown mechanism. Here, we show that upon infection of human cells, Campylobacter jejuni secretes its Cas9 (CjeCas9) nuclease into their cytoplasm. Next, a native nuclear localization signal enables CjeCas9 nuclear entry, where it catalyzes metal-dependent nonspecific DNA cleavage leading to cell death. Compared to CjeCas9, native Cas9 of Streptococcus pyogenes (SpyCas9) is more suitable for guide-dependent editing. However, in human cells, native SpyCas9 may still cause some DNA damage, most likely because of its ssDNA cleavage activity. This side effect can be completely prevented by saturation of SpyCas9 with an appropriate guide RNA, which is only partially effective for CjeCas9. We conclude that CjeCas9 plays an active role in attacking human cells rather than in viral defense. Moreover, these unique catalytic features may therefore make CjeCas9 less suitable for genome editing applications

A visual display enhancing comfort by counteracting airsickness

simulator study has been conducted demonstrating a positive effect on airsickness by utilizing a 3D artificial Earth-fixed visual pattern. Participants were exposed to the same turbulent physical aircraft motion in a simulator three times in a row, each time using a different visual cue. In one condition only the interior of the simulator cabin was visible. In another condition an Earth-fixed star field moving opposite the simulator cabin was projected in front of the participant. In a third condition the same star field was used, however with additional anticipatory information by means of a rollercoaster like track showing the trajectory to go. Participants were asked for their misery and joyfulness ratings at fixed time instants using an 11-points misery scale (no problems-vomiting) and joyfulness scale (unpleasant-pleasant). The results showed that viewing an Earth-fixed visual frame moving instantaneously opposite the cabin motion did reduce motion sickness significantly by a factor of 1.6, thereby improving comfort. This condition could be applied in air transport, where often a monitor is available in the back of the seat ahead. The largest effect, i.e., a reduction by a factor of 4.2 was realized by adding anticipatory information. Although it is not possible to predict the effect of turbulence on the aircraft motion yet, an anticipatory display might already be applicable in other domains, such as at sea by using a wave radar and a ship motion model. © 2011 Elsevier B.V. All rights reserved

A visual display enhancing comfort by counteracting airsickness

A simulator study has been conducted demonstrating a positive effect on airsickness by utilizing a 3D artificial Earth-fixed visual pattern. Participants were exposed to the same turbulent physical aircraft motion in a simulator three times in a row, each time using a different visual cue. In one condition only the interior of the simulator cabin was visible. In another condition an Earth-fixed star field moving opposite the simulator cabin was projected in front of the participant. In a third condition the same star field was used, however with additional anticipatory information by means of a rollercoaster like track showing the trajectory to go. Participants were asked for their misery and joyfulness ratings at fixed time instants using an 11-points misery scale (no problems-vomiting) and joyfulness scale (unpleasant-pleasant). The results showed that viewing an Earth-fixed visual frame moving instantaneously opposite the cabin motion did reduce motion sickness significantly by a factor of 1.6, thereby improving comfort. This condition could be applied in air transport, where often a monitor is available in the back of the seat ahead. The largest effect, i.e., a reduction by a factor of 4.2 was realized by adding anticipatory information. Although it is not possible to predict the effect of turbulence on the aircraft motion yet, an anticipatory display might already be applicable in other domains, such as at sea by using a wave radar and a ship motion model. © 2011 Elsevier B.V. All rights reserved