Using functional annotations to study pairwise interactions in urinary tract infection communities

The behaviour of microbial communities depends on environmental factors and on the interactions of the community members. This is also the case for urinary tract infection (UTI) microbial communities. Here, we devise a computational approach that uses indices of complementarity and competition based on metabolic gene annotation to rapidly predict putative interactions between pair of organisms with the aim to explain pairwise growth effects. We apply our method to 66 genomes selected from online databases, which belong to 6 genera representing members of UTI communities. This resulted in a selection of metabolic pathways with high correlation for each pairwise combination between a complementarity index and the experimentally derived growth data. Our results indicated that Enteroccus spp. were most complemented in its metabolism by the other members of the UTI community. This suggests that the growth of Enteroccus spp. can potentially be enhanced by complementary metabolites produced by other community members. We tested a few putative predicted interactions by experimental supplementation of the relevant predicted metabolites. As predicted by our method, folic acid supplementation led to the increase in the population density of UTI Enterococcus isolates. Overall, we believe our method is a rapid initial in silico screening for the prediction of metabolic interactions in microbial communities

Granulomatous skin lesions complicating Varicella infection in a patient with Rothmund-Thomson syndrome and immune deficiency: case report

Rothmund-Thomson syndrome (RTS)(OMIM 268400) is a rare autosomal recessive genodermatosis characterized by poikiloderma, small stature, skeletal and dental abnormalities, cataract and an increased risk of cancer. It is caused by mutations in RECQL4 at 8q24. Immune deficiency is not described as a classical feature of the disease. Here we report the appearance of granulomatous skin lesions complicating primary Varicella Zoster Virus infection in a toddler with Rothmund Thomson syndrome and immune deficiency. Although granulomatous disorders are sometimes seen after Herpes zoster, they are even more rare after Varicella primary infection. Granulomas have hitherto not been described in Rothmund-Thomson syndrome. With this report we aim to stress the importance of screening for immune deficiency in patients with Rothmund-Thomson syndrome

Introducing yesterday's phage therapy in today's medicine

The worldwide emergence of 'superbugs' and a dry antibiotic pipeline threaten modern society with a return to the preantibiotic era. Phages - the viruses of bacteria - could help fight antibiotic-resistant bacteria. Phage therapy was first attempted in 1919 by Felix d'Herelle and was commercially developed in the 1930s before being replaced by antibiotics in most of the western world. The current antibiotic crisis fueled a worldwide renaissance of phage therapy. The inherent potential of phages as natural biological bacterium controllers can only be put to use if the potential of the coevolutionary aspect of the couplet phage-bacterium is fully acknowledged and understood, including potential negative consequences. We must learn from past mistakes and set up credible studies to gather the urgently required data with regard to the efficacy of phage therapy and the evolutionary consequences of its (unlimited) use, Unfortunately, our current pharmaceutical economic model, implying costly and time-consuming medicinal product development and marketing, and requiring strong intellectual property protection, is not compatible with traditional sustainable phage therapy. A specific framework with realistic production and documentation requirements, which allows a timely (rapid) supply of safe, tailor-made, natural bacteriophages to patients, should be developed. Ultimately, economic models should be radically reshaped to cater for more sustainable approaches such as phage therapy. This is one of the biggest challenges faced by modern medicine and society as a whole

Variation in susceptibility of African Plasmodium falciparum malaria parasites to TEP1 mediated killing in Anopheles gambiae mosquitoes

Anopheles gambiae s.s. mosquitoes are efficient vectors for Plasmodium falciparum, although variation exists in their susceptibility to infection. This variation depends partly on the thioester-containing protein 1 (TEP1) and TEP depletion results in significantly elevated numbers of oocysts in susceptible and resistant mosquitoes. Polymorphism in the Plasmodium gene coding for the surface protein Pfs47 modulates resistance of some parasite laboratory strains to TEP1-mediated killing. Here, we examined resistance of P. falciparum isolates of African origin (NF54, NF165 and NF166) to TEP1-mediated killing in a susceptible Ngousso and a refractory L3-5 strain of A. gambiae. All parasite clones successfully developed in susceptible mosquitoes with limited evidence for an impact of TEP1 on transmission efficiency. In contrast, NF166 and NF165 oocyst densities were strongly reduced in refractory mosquitoes and TEP1 silencing significantly increased oocyst densities. Our results reveal differences between African P. falciparum strains in their capacity to evade TEP1-mediated killing in resistant mosquitoes. There was no significant correlation between Pfs47 genotype and resistance of a given P. falciparum isolate for TEP1 killing. These data suggest that polymorphisms in this locus are not the sole mediators of immune evasion of African malaria parasites

Quantifying synergies and trade-offs in the global water-land-food-climate nexus using a multi-model scenario approach

The human-earth system is confronted with the challenge of providing a range of resources for a growing and more prosperous world population while simultaneously reducing environmental degradation. The sustainable development goals and the planetary boundaries define targets to manage this challenge. Many of these are linked to the land system, such as biodiversity, water, food, nutrients and climate, and are strongly interconnected. A key question is how measures can be designed in the context of multi-dimensional sustainability targets to exploit synergies. To address this, a nexus approach is adopted that acknowledges the interconnectedness between the important sub-systems water, land, food, and climate. This study quantifies synergies and trade-offs from ambitious interventions in different components of this water-land-fod-climate nexus at the global scale. For this purpose, a set of six harmonized scenarios is simulated with the model of agricultural production and its impact on the environment and Integrated model to assess the global environment models. The multi-model approach improves robustness of the results while shedding light on variations coming from different modelling approaches. Our results show that measures in the food component towards healthy diets with low meat consumption have synergies with all other nexus dimensions: Increased natural land improving terrestrial biodiversity (+4% to +8%), lower greenhouse gas emissions from land (−45% to −58%), reduced irrigation water withdrawals to protect or restore hydrological environmental flows (−3% to −24%), and reductions in nitrogen surpluses (−23% to −35%). Climate mitigation measures in line with the Paris Agreement have trade-offs with the water and food components of the nexus, as they adversely affect irrigation water withdrawals (+5% to +30% in 2050 compared to reference scenario) and food prices (+1% to +20%). The analysis of a scenario combining all measures reveals how certain measures are in conflict while others reinforce each other. This study provides an example of a nexus approach to scenario analysis providing input to the next generation of pathways aiming to achieve multiple dimensions of sustainable development.SHAPEHorizon 2020 Framework Programmehttp://dx.doi.org/10.13039/100010661Deutsche Bundesstiftung Umwelthttp://dx.doi.org/10.13039/100007636Peer Reviewe

Reduction of blood culture contamination rate by an educational intervention

Background: Although mechanical dyssynchrony parameters derived by speckle tracking echocardiography (STE) may predict response to cardiac resynchronization therapy (CRT), comparability of parameters derived with different STE vendors is unknown. Methods: In the MARC study, echocardiographic images of heart failure patients obtained before CRT implantation were prospectively analysed with vendor specific STE software (GE EchoPac and Philips QLAB) and vendor-independent software (TomTec 2DCPA). Response was defined as change in left ventricular (LV) end-systolic volume between examination before and six-months after CRT implantation. Basic longitudinal strain and mechanical dyssynchrony parameters (septal to lateral wall delay (SL-delay), septal systolic rebound stretch (SRSsept), and systolic stretch index (SSI)) were obtained from either separate septal and lateral walls, or total LV apical four chamber. Septal strain patterns were categorized in three types. The coefficient of variation and intra-class correlation coefficient (ICC) were analysed. Dyssynchrony parameters were associated with CRT response using univariate regression analysis and C-statistics. Results: Two-hundred eleven patients were analysed. GE-cohort (n = 123): age 68 years (interquartile range (IQR): 61-73), 67% male, QRS-duration 177ms (IQR: 160-192), LV ejection fraction: 26 +/- 7%. Philips-cohort (n = 88): age 67 years (IQR: 59-74), 60% male, QRS-duration: 179 ms (IQR: 166-193), LV ejection fraction: 27 +/- 8. LV derived peak strain was comparable in the GE-(GE: -7.3 +/- 3.1%, TomTec: -6.4 +/- 2.8%, ICC: 0.723) and Philips-cohort (Philips: -7.7 +/- 2.7%, TomTec: -7.7 +/- 3.3%, ICC: 0.749). SL-delay showed low ICC values (GE vs. TomTec: 0.078 and Philips vs. TomTec: 0.025). ICC's of SRSsept and SSI were higher but only weak (GE vs. TomTec: SRSsept: 0.470, SSI: 0.467) (Philips vs. QLAB: SRSsept: 0.419, SSI: 0.421). Comparability of septal strain patterns was low (Cohen's kappa, GE vs. TomTec: 0.221 and Philips vs. TomTec: 0.279). Septal strain patterns, SRSsept and SSI were associated with changes in LV end-systolic volume for all vendors. SRSsept and SSI had relative varying C-statistic values (range: 0.530-0.705) and different cut-off values between vendors. Conclusions: Although global longitudinal strain analysis showed fair comparability, assessment of dyssynchrony parameters was vendor specific and not applicable outside the context of the implemented platform. While the standardization taskforce took an important step for global peak strain, further standardization of STE is still warranted

Taking Bacteriophage Therapy Seriously:A Moral Argument

The excessive and improper use of antibiotics has led to an increasing incidence of bacterial resistance. In Europe the yearly number of infections caused by multidrug resistant bacteria is more than 400.000, each year resulting in 25.000 attributable deaths. Few new antibiotics are in the pipeline of the pharmaceutical industry. Early in the 20th century, bacteriophages were described as entities that can control bacterial populations. Although bacteriophage therapy was developed and practiced in Europe and the former Soviet republics, the use of bacteriophages in clinical setting was neglected in Western Europe since the introduction of traditional antibiotics. Given the worldwide antibiotic crisis there is now a growing interest in making bacteriophage therapy available for use in modern western medicine. Despite the growing interest, access to bacteriophage therapy remains highly problematic. In this paper, we argue that the current state of affairs is morally unacceptable and that all stakeholders (pharmaceutical industry, competent authorities, lawmakers, regulators, and politicians) have the moral duty and the shared responsibility towards making bacteriophage therapy urgently available for all patients in need

A nanobody-based tracer targeting DPP6 for non-invasive imaging of human pancreatic endocrine cells

There are presently no reliable ways to quantify endocrine cell mass (ECM) in vivo, which prevents an accurate understanding of the progressive beta cell loss in diabetes or following islet transplantation. To address this unmet need, we coupled RNA sequencing of human pancreatic islets to a systems biology approach to identify new biomarkers of the endocrine pancreas. Dipeptidyl-Peptidase 6 (DPP6) was identified as a target whose mRNA expression is at least 25-fold higher in human pancreatic islets as compared to surrounding tissues and is not changed by proinflammatory cytokines. At the protein level, DPP6 localizes only in beta and alpha cells within the pancreas. We next generated a high-affinity camelid single-domain antibody (nanobody) targeting human DPP6. The nanobody was radiolabelled and in vivo SPECT/CT imaging and biodistribution studies were performed in immunodeficient mice that were either transplanted with DPP6-expressing Kelly neuroblastoma cells or insulin-producing human EndoC-βH1 cells. The human DPP6-expressing cells were clearly visualized in both models. In conclusion, we have identified a novel beta and alpha cell biomarker and developed a tracer for in vivo imaging of human insulin secreting cells. This provides a useful tool to non-invasively follow up intramuscularly implanted insulin secreting cells

SEAmester – South Africa’s first class afloat

publisher versionFrom Introduction: Marine science is a highly competitive environment. The need to improve the cohort of South African postgraduates, who would be recognised both nationally and internationally for their scientific excellence, is crucial. It is possible to attract students early on in their careers to this discipline via cutting-edge science, technology and unique field experiences. Through the engagement of students with real-life experiences such as SEAmester, universities supporting marine science postgraduate degree programmes can attract a sustainable throughput of numerically proficient students. By achieving a more quantitative and experienced input into our postgraduate degree programmes, we will, as a scientific community, greatly improve our long-term capabilities to accurately measure, model and predict the impacts of current climate change scenarios. The short-term goal is to attract and establish a cohort of proficient marine and atmospheric science graduates who will contribute to filling the capacity needs of South African marine science as a whole. The SEAmester programme, by involving researchers from across all the relevant disciplines and tertiary institutions, provides an opportunity to build a network of collaborative teaching within the marine field. In doing so, these researchers will foster and strengthen new and current collaborations between historically white and black universities (Figure 1). The long-term objective of SEAmester is to build critical mass within the marine sciences to ensure sustained growth of human capacity in marine science in South Africa – aligning closely with the current DST Research and Development strategies and the Operation Phakisa Oceans Economy initiative

Global South leadership towards inclusive tropical ecology and conservation

Strengthening participation of Global South researchers in tropical ecology and conservation is a target of our scientific community, but strategies for fostering increased engagement are mostly directed at Global North institutions and researchers. Whereas such approaches are crucial, there are unique challenges to addressing diversity, equity and inclusion (DEI) within the Global South given its socio-economic, cultural and scientific contexts. Sustainable solutions protecting biodiversity in the tropics depend on the leadership of Global South communities, and therefore DEI improvements in the Global South are paramount in our field. Here, we propose ten key actions towards equitable international collaborations in tropical ecology, which, led by Global South researchers, may improve DEI at institutional, national and international levels. At an institutional level, we recommend (1) becoming role models for DEI, (2) co-developing research with local stakeholders, and (3) promoting transparent funding management favouring local scientists. At a national level, we encourage (4) engagement in political actions protecting scientists and their research in tropical countries, (5) participation in improving biodiversity research policies, and (6) devising research that reaches society. At an international level, we encourage Global South researchers in international collaborations to (7) lead and direct funding applications, (8) ensure equitable workloads, and (9) procure equal benefits among national and foreign collaborators. Finally, (10) we propose that Global South leadership in DEI efforts has the most potential for worldwide improvements, supporting positive long-lasting changes in our entire scientific community. Supplementary materials provide this abstract in 18 other languages spoken in the Global South