The mechanism of glycosphingolipid degradation revealed by a GALC-SapA complex structure.

Sphingolipids are essential components of cellular membranes and defects in their synthesis or degradation cause severe human diseases. The efficient degradation of sphingolipids in the lysosome requires lipid-binding saposin proteins and hydrolytic enzymes. The glycosphingolipid galactocerebroside is the primary lipid component of the myelin sheath and is degraded by the hydrolase β-galactocerebrosidase (GALC). This enzyme requires the saposin SapA for lipid processing and defects in either of these proteins causes a severe neurodegenerative disorder, Krabbe disease. Here we present the structure of a glycosphingolipid-processing complex, revealing how SapA and GALC form a heterotetramer with an open channel connecting the enzyme active site to the SapA hydrophobic cavity. This structure defines how a soluble hydrolase can cleave the polar glycosyl headgroups of these essential lipids from their hydrophobic ceramide tails. Furthermore, the molecular details of this interaction provide an illustration for how specificity of saposin binding to hydrolases is encoded

A microRNA cluster in the Fragile-X region expressed during spermatogenesis targets FMR1.

Testis-expressed X-linked genes typically evolve rapidly. Here, we report on a testis-expressed X-linked microRNA (miRNA) cluster that despite rapid alterations in sequence has retained its position in the Fragile-X region of the X chromosome in placental mammals. Surprisingly, the miRNAs encoded by this cluster (Fx-mir) have a predilection for targeting the immediately adjacent gene, Fmr1, an unexpected finding given that miRNAs usually act in trans, not in cis Robust repression of Fmr1 is conferred by combinations of Fx-mir miRNAs induced in Sertoli cells (SCs) during postnatal development when they terminate proliferation. Physiological significance is suggested by the finding that FMRP, the protein product of Fmr1, is downregulated when Fx-mir miRNAs are induced, and that FMRP loss causes SC hyperproliferation and spermatogenic defects. Fx-mir miRNAs not only regulate the expression of FMRP, but also regulate the expression of eIF4E and CYFIP1, which together with FMRP form a translational regulatory complex. Our results support a model in which Fx-mir family members act cooperatively to regulate the translation of batteries of mRNAs in a developmentally regulated manner in SCs

Invertebrate community structure predicts natural pest control resilience to insecticide exposure

1. Biological pest control has become one of the central principles of ecological intensification in agriculture. However, invertebrate natural enemies within agricultural ecosystems are exposed to a myriad of different pesticides at both lethal and sub‐lethal doses, that may limit their capacity to carry out pest control. An important question is how underlying diversity in invertebrate predator species, linked to their unique susceptibility to insecticides, can act to increase the resilience of natural pest control. 2. We explore this issue by assessing the effects of sub‐lethal insecticide exposure on the predation rates of 12 generalist predators feeding on the aphid Sitobion avenae (Aphididae). Predation rates within a 24‐hr period were assessed (predation assessment) for each species after receiving one of the following treatments: (a) no prior deltamethrin exposure before the predation assessment (control); (b) deltamethrin exposure immediately before the predation assessment (resistance) and (c) deltamethrin exposure 5 days before the predation assessment (recovery). Extrapolating from these species‐specific measures of resistance and recovery, we predicted the resilience of community level predation to insecticide exposure for predator communities associated with 256 arable fields in the UK. 3. There was large variation in sub‐lethal effects of the insecticide between even closely related species. This ranged from species showing no change in predation rates following sub‐lethal insecticide exposure (high resistance), species showing only immediate depressed feeding rates after 24 hr (high recovery) or those with depressed feeding rates after 5 days (low resistance and recovery). 4. The community level analysis showed that resistance and recovery of natural pest control was predicted by both community phylogenetic diversity (positively) and weighted mean body mass (negatively). However, the removal of numerically dominant species from the analysis modified these effects. 5. Synthesis and applications: Our results highlight the role of community diversity in maintaining the resilience of natural pest control following insecticide use. Importantly, less diverse assemblages dominated by predator species that show low resilience to insecticide exposure, may show a greater depression in pest control than diverse assemblages under insecticide based farmland management

Long-term trends in migrating Brassicogethes aeneus in the UK

Background The pollen beetle (Brassicogethes aeneus) causes significant yield loss in oilseed rape (Brassica napus). Predicting population changes remains a scientific challenge, especially since its phenology and abundance varies dramatically over space and time. We used generalized additive models to investigate the long-term trends in pollen beetle annual, seasonal and monthly counts from Rothamsted 12.2 m suction-traps. We hypothesised that the beetle's abundance is positively related to the area of oilseed rape at a national and regional level. We used random forest models to investigate the inter-generational relationship within years. Results Although B. aeneus annual counts and area of oilseed rape grown in the UK both increased by 162% and 113%, respectively, over the time period, they were not significantly related. The size of the immigrating pollen beetle population (up to June 1st) can be explained both by the size of the population in the previous summer and prevailing winter temperatures, indicating a positive feedback mechanism. Conclusion Currently, pollen beetle numbers continue to increase in the UK, meaning that control issues may persist, however the relationship between counts in spring, during the susceptible phase of the crop, and counts in the previous summer indicates that it may be possible to forecast the counts of the spring migration of B. aeneus a few months in advance using suction-trap samples, which could aid decisions on control options

Development of a Multidisciplinary Program to Expedite Care of Esophageal Emergencies

Background Level 1 programs have improved outcomes by expediting the multidisciplinary care of critically ill patients. We established a novel level 1 program for the management of esophageal emergencies. Methods After institutional review board approval, we performed a retrospective analysis of patients referred to our level 1 esophageal emergency program from April 2013 through November 2015. A historical comparison group of patients treated for the same diagnosis in the previous 2 years was used. Results Eighty patients were referred and transported an average distance of 56 miles (range, 1–163 miles). Median time from referral to arrival was 2.4 hours (range, 0.4-12.9 hours). Referrals included 6 (7%) patients with esophageal obstruction and 71 (89%) patients with suspected esophageal perforation. Of the patients with suspected esophageal perforation, causes included iatrogenic (n = 26), Boerhaave’s syndrome (n = 32), and other (n = 13). Forty-six percent (n = 33) of patients were referred because of pneumomediastinum, but perforation could not be subsequently demonstrated. Initial management of patients with documented esophageal perforation included operative treatment (n = 25), endoscopic intervention (n = 8), and supportive care (n = 5). Retrospective analysis demonstrated a statistically significant difference in mean Pittsburgh severity index score (PSS) between esophageal perforation treatment groups (p < 0.01). In patients with confirmed perforations, there were 3 (8%) mortalities within 30 days. More patients in the esophageal level 1 program were transferred to our institution in less than 24 hours after diagnosis than in the historical comparison group (p < 0.01). Conclusions Development of an esophageal emergency referral program has facilitated multidisciplinary care at a high-volume institution, and early outcomes appear favorable

Integrated pest management strategies for cabbage stem flea beetle (Psylliodes chrysocephala) in oilseed rape

Oilseed rape (OSR) is the second largest source of vegetable oil globally and the most important biofuel feedstock in the European Union (EU) but production of this important crop is threatened by a small insect; Psylliodes chrysocepaha – the cabbage stem flea beetle (CSFB). The EU ban on use of neonicotinoid seed treatments and resistance of CSFB to pyrethroid insecticides have left farmers with limited control options resulting in drastic reductions in production. Integrated pest management (IPM) may offer a solution. We review the lifecycle of CSFB and the current options available, or in the research pipeline, for the eight IPM principles of the EU Sustainable Use of Pesticides Directive (Directive-2009/128/EC). A full IPM strategy for CSFB barely exists. Although there are a range of preventative measures these require scientific validation; critically, resistant/tolerant OSR cultivars are not yet available. Existing monitoring methods are time consuming and there are no commercial models to enable decision support based on predictions migration timing or population size. Available thresholds are not based on physiological tolerances of the plant making it hard to adapt them to changing market prices for the crop and costs of control. Non-synthetic alternatives tested and registered for use against CSFB are lacking, making resistance management impossible. CSFB control is therefore dependent upon conservation biocontrol. Natural enemies of CSFB are present, but quantification of their effects is needed and habitat management strategies to exploit their potential. Although some EU countries have local initiatives to reduce insecticide use and encourage use of ‘greener’ alternatives, there is no formal process for ranking these and little information available to help farmers make choices. We summarise the main knowledge gaps and future research needed to improve measures for CSFB control and to facilitate development of a full IPM strategy for this pest -and sustainable oilseeds production

Modelling the factors affecting the spatiotemporal distribution of cabbage stem flea beetle (Psylliodes chrysocephala) larvae in winter oilseed rape (Brassica napus) in the UK

BACKGROUND Cabbage stem flea beetle (CSFB; Psylliodes chrysocephala L.) management in oilseed rape (Brassica napus L.) has become an urgent issue in the absence of permitted and effective insecticides. Understanding the meteorological and management factors affecting their population dynamics has become critical to the development of pest management strategies. RESULTS The spatio-temporal changes in CSFB larval populations were assessed both in autumn and spring, in the UK from 2003 to 2017 (a period encompassing pre-and post-neonicotinoid insecticide restriction). After the neonicotinoid ban in 2013, the number of larvae both in autumn and spring increased 10-fold in the UK. When neonicotinoids were available, later sown crops contained fewer larvae than early sown crops, and bigger fields had fewer larvae than smaller fields, whereas after the ban, bigger fields tended to have more larvae than smaller fields. Wet and mild/hot Septembers were related with higher numbers of larvae when neonicotinoids were available and with lower larval numbers after the neonicotinoid ban. Low temperatures in December and January combined with high rainfall were related with high numbers of larvae in spring both before and after the neonicotinoid ban. CONCLUSION This study will help to produce decision support systems that allow future predictions of regional CSFB population changes and will help growers and consultants to adjust their management methods to reduce the risk of high infestations

Soil compaction effects on litter decomposition in an arable field: implications for management of crop residues and headlands

Soil compaction is a major threat to agricultural soils. Heavy machinery is responsible for damaging soil chemical, physical and biological properties. Among these, organic matter decomposition, which is predominantly mediated by the soil biota, is a necessary process since it underpins nutrient cycling and the provision of plant nutrients. Understanding factors which impact the functionality of the biota is therefore necessary to improve agricultural practices. To better understand the effects of compaction on the soil system, we determined the effects of soil bulk density and soil penetration resistance on the decomposition rates of litter in three distinct field zones: a grass margin, sown at the edge of the field adjacent to the crop, tramlines in the crop:margin interface, and crop. Three litters of different quality (ryegrass, straw residues and mixed litter) were buried for 1, 2, 4 and 6 months in litter bags comprising two different mesh sizes (0.02 and 2 mm). Bulk density and soil penetration resistance were greater in the compacted tramline than in the margin or the crop. The greatest amount of litter remaining in the bags after 6 months was found in the tramline, and the least in the grass margin. Differences between treatments increased with burial time. No significant differences in mass loss between the two mesh sizes was detected before the fourth month, implying that microbial activities were the main processes involved in the early stages of decomposition. Decomposition in the tramline was clearly affected by the degradation of soil structure due to heavy compaction. This study shows that soil conditions at the edges of arable fields affect major soil processes such as decomposition. It also reveals the potential to mitigate soil degradation by managing the headland, the crop residues and the machinery traffic in the field