Parallelism and divergence in immune responses: a comparison of expression levels in two lakes

Question: How do immune phenotypes differ between infected and uninfected wild individuals, and is the effect the same in different populations? Organisms: Threespine stickleback (Gasterosteus aculeatus) from two lake populations on the island of North Uist, Scotland, sampled in May 2015. Methods: For each fish, we recorded length, sex, reproductive status, condition, and parasitic infection. We measured the expression levels of eight genes that act as key markers of immune system function using qPCR, and then examined the relationship between measured factors and immune gene expression profiles within each population. Conclusions: Populations differed significantly in their immune gene expression profiles. Within each population, multiple factors, including condition, reproductive status, and Schistocephalus solidus infection levels, were found to correlate with expression levels of different arms of the immune system

No evidence of local adaptation of immune responses to Gyrodactylus in three-spined stickleback (Gasterosteus aculeatus)

Parasitism represents one of the most widespread lifestyles in the animal kingdom, with the potential to drive coevolutionary dynamics with their host population. Where hosts and parasites evolve together, we may find local adaptation. As one of the main host defences against infection, there is the potential for the immune response to be adapted to local parasites. In this study, we used the three-spined stickleback and its Gyrodactylus parasites to examine the extent of local adaptation of parasite infection dynamics and the immune response to infection. We took two geographically isolated host populations infected with two distinct Gyrodactylus species and performed a reciprocal cross-infection experiment in controlled laboratory conditions. Parasite burdens were monitored over the course of the infection, and individuals were sampled at multiple time points for immune gene expression analysis. We found large differences in virulence between parasite species, irrespective of host, and maladaptation of parasites to their sympatric host. The immune system responded to infection, with a decrease in expression of innate and Th1-type adaptive response genes in fish infected with the less virulent parasite, representing a marker of a possible resistance mechanism. There was no evidence of local adaptation in immune gene expression levels. Our results add to the growing understanding of the extent of host-parasite local adaptation, and demonstrate a systemic immune response during infection with a common ectoparasite. Further immunological studies using the stickleback-Gyrodactylus system can continue to contribute to our understanding of the function of the immune response in natural populations

Measuring the immune system of the three-spined stickleback: investigating natural variation by quantifying immune expression in the laboratory and the wild

Current understanding of the immune system comes primarily from lab-based studies. There has been substantial interest in examining how it functions in the wild, but studies have been limited by a lack of appropriate assays and study species. The three-spined stickleback (Gasterosteus aculeatus L.) provides an ideal system in which to advance the study of wild immunology, but requires the development of suitable immune assays. We demonstrate that meaningful variation in the immune response of stickleback can be measured using real-time PCR to quantify the expression of eight genes, representing the innate response and Th1, Th2 and Treg type adaptive responses. Assays are validated by comparing the immune expression profiles of wild and laboratory raised stickleback, and by examining variation across populations on North Uist, Scotland. We also compare the immune response potential of laboratory raised individuals from two Icelandic populations by stimulating cells in culture. Immune profiles of wild fish differed from laboratory-raised fish from the same parental population, with immune expression patterns in the wild converging relative to those in the laboratory. Innate measures differed between wild populations, whilst the adaptive response was associated with variation in age, relative size of fish, reproductive status and S. solidus infection levels. Laboratory-raised individuals from different populations showed markedly different innate immune response potential. The ability to combine studies in the laboratory and in the wild underline the potential of this toolkit to advance our understanding of the ecological and evolutionary relevance of immune system variation in a natural setting

Measuring the immune system of the three-spined stickleback: investigating natural variation by quantifying immune expression in the laboratory and the wild

Current understanding of the immune system comes primarily from lab-based studies. There has been substantial interest in examining how it functions in the wild, but studies have been limited by a lack of appropriate assays and study species. The three-spined stickleback (Gasterosteus aculeatus L.) provides an ideal system in which to advance the study of wild immunology, but requires the development of suitable immune assays. We demonstrate that meaningful variation in the immune response of stickleback can be measured using real-time PCR to quantify the expression of eight genes, representing the innate response and Th1, Th2 and Treg type adaptive responses. Assays are validated by comparing the immune expression profiles of wild and laboratory raised stickleback, and by examining variation across populations on North Uist, Scotland. We also compare the immune response potential of laboratory raised individuals from two Icelandic populations by stimulating cells in culture. Immune profiles of wild fish differed from laboratory-raised fish from the same parental population, with immune expression patterns in the wild converging relative to those in the laboratory. Innate measures differed between wild populations, whilst the adaptive response was associated with variation in age, relative size of fish, reproductive status and S. solidus infection levels. Laboratory-raised individuals from different populations showed markedly different innate immune response potential. The ability to combine studies in the laboratory and in the wild underline the potential of this toolkit to advance our understanding of the ecological and evolutionary relevance of immune system variation in a natural setting

The treatment of booking gestational diabetes mellitus (TOBOGM) pilot randomised controlled trial

Background: We piloted a randomised controlled trial (RCT) comparing pregnancy outcomes among women with booking gestational diabetes (GDM) receiving immediate or deferred treatment. Methods: Consecutive, consenting women < 20 weeks gestation, with GDM risk factors attending the hospital book-in clinic, completed an oral glucose tolerance test (OGTT). Clinicians were blinded to OGTT results. Women fulfilling World Health Organisation GDM criteria were randomised to either clinic referral /ongoing treatment (Treated Group n = 11), or no treatment (No Treatment Group n = 10). Women without ‘Booking GDM’ (‘Decoys’ n = 58) and those in the No Treatment Group had a repeat OGTT at 24–28 weeks (with GDM treated if diagnosed). Midwives and mothers were asked to complete surveys and attend focus groups before and after the study respectively regarding their experiences and expectations of the study protocol. Results: Sufficient women completed each step of the RCT. Gestation at OGTT was late at 18 ± 2 weeks with Treated and No Treatment groups largely similar. At 24–28 weeks gestation, GDM was present in 8/9 (89%) in the No Treatment group and 11/56 (20%) Decoys. NICU admission was highest in the Treated group (36% vs 0% p = 0.043), largely due to small for gestational age, and Large for Gestational Age babies greatest in the No Treatment group (0% vs 33% p = 0.030). Conclusion: An RCT deferring ‘Booking GDM’ treatment is feasible. Most women with untreated ‘Booking GDM’ in mid 2nd trimester had GDM at 24–28 weeks. Early treatment may have both benefits and harms. A full RCT is needed

Multiple Sclerosis: LIFNano-CD4 for Trojan Horse Delivery of the Neuro-Protective Biologic “LIF” Into the Brain: Preclinical Proof of Concept

Multiple sclerosis (MS) is a demyelinating autoimmune disease that attacks the brain, with year-on-year loss of brain volume, starting late teens and becoming manifest late twenties. There is no cure, and current therapies are immunosuppressive only. LIF is a vital stem cell growth factor active throughout life—and essential for health of the central nervous system (CNS), being tolerogenic, myelinogenic, and neuroprotective. Nano-formulation of LIF (LIFNano) using FDA-approved PLGA captures LIF's compound therapeutic properties, increasing potency 1,000-fold when targeted to CD4 (LIFNano-CD4). Moreover, circulating CD4+ lymphocytes are themselves regulated by LIF to express the Treg phenotype, known to release T cell-derived LIF upon engagement with cognate antigen, perpetuating antigen-specific self-tolerance. With the longer-term aim of treating inflammatory lesions of MS, we asked, does LIFNano-CD4 cross the blood–brain barrier (BBB)? We measure pK and pD using novel methodologies, demonstrate crossing of the BBB, show LIF-cargo-specific anti-inflammatory efficacy in the frontal cortex of the brain, and show safety of intravenous delivery of LIFNano-CD4 at doses known to provide efficacious concentrations of LIF cargo behind the BBB

Ecology and diversity of culturable fungal species associated with soybean seedling diseases in the Midwestern United States

Aims: To isolate and characterize fungi associated with diseased soybean seedlings in Midwestern soybean production fields and to determine the influence of environmental and edaphic factors on their incidence. Methods and Results: Seedlings were collected from fields with seedling disease history in 2012 and 2013 for fungal isolation. Environmental and edaphic data associated with each field was collected. 3036 fungal isolates were obtained and assigned to 76 species. The most abundant genera recovered were Fusarium (73%) and Trichoderma (11.2%). Other genera included Mortierella, Clonostachys, Rhizoctonia, Alternaria, Mucor, Phoma, Macrophomina and Phomopsis. Most recovered species are known soybean pathogens. However, non-pathogenic organisms were also isolated. Crop history, soil density, water source, precipitation and temperature were the main factors influencing the abundance of fungal species. Conclusion: Key fungal species associated with soybean seedling diseases occurring in several US production regions were characterized. This work also identified major environment and edaphic factors affecting the abundance and occurrence of these species. Significance and Impact of the Study: The identification and characterization of the main pathogens associated with seedling diseases across major soybean-producing areas could help manage those pathogens, and devise more effective and sustainable practices to reduce the damage they cause

Crop Updates 2011 - Farming Systems

This session covers twelve papers from different authors: 1. Fallowing 50% of the farm each year – does it pay? Janette Drew and Rob Grima Department of Agriculture and Food 2. How crop sequences affect the productivity and resilience of cropping systems in two Western Australian environments, Bob French, Raj Malik, Mark Seymour, Department of Agriculture and Food 3. When is continuous wheat or barley sustainable? Christine Zaicou-Kunesch and Rob Grima Department of Agriculture and Food 4. Identifying constraints to bridging the yield gap, Glenn McDonald, Department of Agriculture and Food 5. Land constraints limiting wheat yields in the Bridging the Yield Gap project area, Brendan Nicholas and Dennis van Gool, Department of Agriculture and Food 6. Can livestock have a long-term role in no-till cropping systems? James Fisher1, Peter Tozer2, and Doug Abrecht3, 1Désirée Futures, York, WA, 2PRT Consulting, West Wyalong, NSW and 3Department of Agriculture and Food 7. Pros and cons of dry seeding to counter variable seasonal breaks, Michael Robertson1, Cameron Weeks2, Michael O’Connor1, Doug Abrecht3, Rob Grima3, Peter Newman3, 1CSIRO, 2PlanFarm, 3Department of Agriculture and Food 8. Defining economic optimum plant densities of open pollinated and hybrid canola in WA, Mark Seymour, Department of Agriculture and Food 9. Alternative uses for unproductive soils examined in the North Eastern Agricultural Region (NEAR), Mike Clarke and Andrew Blake, Department of Agriculture and Food MARKETS 10. What the world wants from Australian wheat, Gordon MacAulay, Principal Economist, BRI Australia, Emeritus Professor of Agricultural Economics, University of Sydney 11. Effect of lupin flour incorporation on the physical and sensory quality of pasta, Vijay Jayasena1,2 and Syed M. Nasar-Abbas1,2, 1Food Science and Technology, School of Public Health, Curtin Health Innovation Research Institute, Curtin University, 2Centre for Food and Genomic Medicine 12. Wheat quality requirements for Saudi Arabia: baking quality and blending potential of some Australian exporting grades, Larisa Cato1, Robert Loughman1 and Ken Quail2, 1Department of Agriculture and Food, 2BRI Australi

Proprioceptive Movement Illusions Due to Prolonged Stimulation: Reversals and Aftereffects

Background. Adaptation to constant stimulation has often been used to investigate the mechanisms of perceptual coding, but the adaptive processes within the proprioceptive channels that encode body movement have not been well described. We investigated them using vibration as a stimulus because vibration of muscle tendons results in a powerful illusion of movement. Methodology/Principal Findings. We applied sustained 90 Hz vibratory stimulation to biceps brachii, an elbow flexor and induced the expected illusion of elbow extension (in 12 participants). There was clear evidence of adaptation to the movement signal both during the 6-min long vibration and on its cessation. During vibration, the strong initial illusion of extension waxed and waned, with diminishing duration of periods of illusory movement and occasional reversals in the direction of the illusion. After vibration there was an aftereffect in which the stationary elbow seemed to move into flexion. Muscle activity shows no consistent relationship with the variations in perceived movement. Conclusion. We interpret the observed effects as adaptive changes in the central mechanisms that code movement in direction-selective opponent channels

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden