Engineering In Situ Soil and Plant Microbiomes To Improve Agricultural Productivity

The world’s population is predicted to reach 9 billion people by 2050 thus increasing crop production on current agricultural land to meet the rising demand for food is paramount. Farmers routinely manage both plant and soil nutrition to increase crop yields. However, active management of in situ soil and plant microbiomes to improve productivity is uncommon. Here, we present a patented technology aiming to reliably engineer soil and plant microbiomes to increase crop production. Bioprime is a ferment of molasses that can be applied as seed coating, or as foliar and soil spray

A Fast and Inexpensive Molecular Biological Assay to Assess Soil Health

Soil health and biology is capturing public imagination due to its significance in organic and regenerative agriculture and its role in mitigating climate change (a location for potential carbon sequestration). Programs centred on soil health are supported by farmers and funding bodies such as the Soil Biology Initiative (Grains Research and Development Corporation), the National Landcare Program, and the Cooperative Research Centre for High Performance Soils. Additionally, global businesses are diverting resources into understanding soil and crop microbiomes to develop novel technologies that increase soil health and crop productivity to commercialise a variety of products including soil amendments (e.g. sea weeds, humic acids, other prebiotics) or microbial inocula (often termed “biologicals”, “probiotics”, “biopesticides”, or “biofungicides”)

The Evolution of Telecom Technologies: Current Trends and Near-Future Implications

A project commissioned by The Centre for Cross Border Studies with funding from eirco

ADvAnced PhysioTherapy in MuSculosKeletal Triage: Investigating prognostic factors, healthcare utilisation and clinical outcomes (ADAPT MSK) - a cohort study protocol. [version 1; peer review: 1 approved, 2 approved with reservations]

Background: Clinical specialist physiotherapist-led musculoskeletal triage clinics were introduced nationally in Ireland in 2011 to improve patient care and reduce waiting times for secondary care orthopaedics and rheumatology. Evidence has shown them to be effective in reducing waiting lists, however there are currently no data on longitudinal patient outcomes following clinic attendance. The primary aim of this cohort study is to identify predictors of pain and function outcomes up to one year following musculoskeletal triage review. Secondary aims include measuring self-reported use of healthcare resources over the 12-month follow-up period and to explore musculoskeletal phenotypes based on established prognostic factors for musculoskeletal pain. This is a prospective cohort study. Methods: ADvAnced PhysioTherapy in MuSculosKeletal Triage (ADAPT MSK) will recruit a cohort of 252 adults through musculoskeletal triage clinics across five secondary care sites in Ireland. The STrengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines will be adhered to for future reporting. Adults (≥ 18 years old) attending physiotherapist-led musculoskeletal triage clinics with musculoskeletal pain, who do not require surgical or consultant-led medical care will be considered for participation. Participant demographics, health literacy, healthcare utilisation, and self-report questionnaires on pain, function, musculoskeletal health, musculoskeletal risk stratification, fear of movement, and psychological distress will be obtained at baseline, with follow-ups at three, six, and 12 months. Primary outcomes are pain intensity and function. Secondary outcomes include musculoskeletal risk stratification status, musculoskeletal health, healthcare utilisation, and work-related factors. Descriptive statistics will be used to profile the participants and predictors of outcome will be assessed using multivariable linear regression. Musculoskeletal phenotypes will be explored using latent class analysis. Results: Results will be disseminated via peer-reviewed journal publication and presentation at national and international conferences. Engagement with a public patient involvement (PPI) panel will explore dissemination strategies for public and service user engagement

The impact of donor and recipient common clinical and genetic variation on estimated glomerular filtration rate in a European renal transplant population

Genetic variation across the HLA is known to influence renal‐transplant outcome. However, the impact of genetic variation beyond the HLA is less clear. We tested the association of common genetic variation and clinical characteristics, from both the donor and recipient, with post‐transplant eGFR at different time‐points, out to 5‐years post‐transplantation. We conducted GWAS meta‐analyses across 10,844 donors and recipients from five European ancestry cohorts. We also analysed the impact of polygenic risk scores (PRS), calculated using genetic variants associated with non‐transplant eGFR, on post‐transplant eGFR. PRS calculated using the recipient genotype alone, as well as combined donor and recipient genotypes were significantly associated with eGFR at 1‐year post‐transplant. 32% of the variability in eGFR at 1‐year post‐transplant was explained by our model containing clinical covariates (including weights for death/graft‐failure), principal components and combined donor‐recipient PRS, with 0.3% contributed by the PRS. No individual genetic variant was significantly associated with eGFR post‐transplant in the GWAS. This is the first study to examine PRS, composed of variants that impact kidney function in the general population, in a post‐transplant context. Despite PRS being a significant predictor of eGFR post‐transplant, the effect size of common genetic factors is limited compared to clinical variables

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical Covid-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalisation2-4 following SARS-CoV-2 infection. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from critically-ill cases with population controls in order to find underlying disease mechanisms. Here, we use whole genome sequencing in 7,491 critically-ill cases compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical Covid-19. We identify 16 new independent associations, including variants within genes involved in interferon signalling (IL10RB, PLSCR1), leucocyte differentiation (BCL11A), and blood type antigen secretor status (FUT2). Using transcriptome-wide association and colocalisation to infer the effect of gene expression on disease severity, we find evidence implicating multiple genes, including reduced expression of a membrane flippase (ATP11A), and increased mucin expression (MUC1), in critical disease. Mendelian randomisation provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5, CD209) and coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of Covid-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication, or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between critically-ill cases and population controls is highly efficient for detection of therapeutically-relevant mechanisms of disease

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A)

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care(1) or hospitalization(2-4) after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease. © 2022, The Author(s)

Quantifying neutralising antibody responses against SARS-CoV-2 in dried blood spots (DBS) and paired sera

The ongoing SARS-CoV-2 pandemic was initially managed by non-pharmaceutical interventions such as diagnostic testing, isolation of positive cases, physical distancing and lockdowns. The advent of vaccines has provided crucial protection against SARS-CoV-2. Neutralising antibody (nAb) responses are a key correlate of protection, and therefore measuring nAb responses is essential for monitoring vaccine efficacy. Fingerstick dried blood spots (DBS) are ideal for use in large-scale sero-surveillance because they are inexpensive, offer the option of self-collection and can be transported and stored at ambient temperatures. Such advantages also make DBS appealing to use in resource-limited settings and in potential future pandemics. In this study, nAb responses in sera, venous blood and fingerstick blood stored on filter paper were measured. Samples were collected from SARS-CoV-2 acutely infected individuals, SARS-CoV-2 convalescent individuals and SARS-CoV-2 vaccinated individuals. Good agreement was observed between the nAb responses measured in eluted DBS and paired sera. Stability of nAb responses was also observed in sera stored on filter paper at room temperature for 28 days. Overall, this study provides support for the use of filter paper as a viable sample collection method to study nAb responses.</p

Global Spatial Risk Assessment of Sharks Under the Footprint of Fisheries

Effective ocean management and conservation of highly migratory species depends on resolving overlap between animal movements and distributions and fishing effort. Yet, this information is lacking at a global scale. Here we show, using a big-data approach combining satellite-tracked movements of pelagic sharks and global fishing fleets, that 24% of the mean monthly space used by sharks falls under the footprint of pelagic longline fisheries. Space use hotspots of commercially valuable sharks and of internationally protected species had the highest overlap with longlines (up to 76% and 64%, respectively) and were also associated with significant increases in fishing effort. We conclude that pelagic sharks have limited spatial refuge from current levels of high-seas fishing effort. Results demonstrate an urgent need for conservation and management measures at high-seas shark hotspots and highlight the potential of simultaneous satellite surveillance of megafauna and fishers as a tool for near-real time, dynamic management