Genomic diversity and CRISPR-Cas systems in the cyanobacterium Nostoc in the High Arctic.

Nostoc (Nostocales, Cyanobacteria) has a global distribution in the Polar Regions. However, the genomic diversity of Nostoc is little known and there are no genomes available for polar Nostoc. Here we carried out the first genomic analysis of the Nostoc commune morphotype with a recent sample from the High Arctic and a herbarium specimen collected during the British Arctic Expedition (1875-76). Comparisons of the polar genomes with 26 present-day non-polar members of the Nostocales family highlighted that there are pronounced genetic variations among Nostoc strains and species. Osmoprotection and other stress genes were found in all Nostoc strains, but the two Arctic strains had markedly higher numbers of biosynthetic gene clusters for uncharacterised non-ribosomal peptide synthetases, suggesting a high diversity of secondary metabolites. Since viral-host interactions contribute to microbial diversity, we analysed the CRISPR-Cas systems in the Arctic and two temperate Nostoc species. There were a large number of unique repeat-spacer arrays in each genome, indicating diverse histories of viral attack. All Nostoc strains had a subtype I-D system, but the polar specimens also showed evidence of a subtype I-B system that has not been previously reported in cyanobacteria, suggesting diverse cyanobacteria-virus interactions in the Arctic.

Germline RUNX1 variants in paediatric patients in a French specialised centre.

Familial platelet disorder with associated myeloid malignancy (FPD-MM; OMIM 601399) is related to germline RUNX1 mutation. The pathogenicity of RUNX1 variants was initially linked to FPD-MM phenotype, but the discovery of new variants through the expansion of genetic explorations in leukaemia is questioning this assertion. In this study, we add 10 families with germline RUNX1 variant explored at Armand Trousseau Hospital for leukaemia diagnosis or thrombocytopenia, to the 259 described so far. Detailed description of their personal and family history of haematological pathologies allows identifying three phenotypes related to germline RUNX1 variants: thrombocytopenia and/or malignant haematological disease with family history of haematological diseases, thrombocytopenia with no family history of haematological diseases and acute lymphoblastic leukaemia (ALL) with no family history of haematological diseases. In the latter phenotype, ALL characteristics involving RUNX1 suggest the implication of germline variants in the onset of the malignancy.

Performance evaluation of the fully automated random-access multiparameter Sysmex CN-6000 hemostasis analyzer at a core laboratory with a high sample throughput.

INTRODUCTION: We aimed to evaluate the performance of the fully automated multiparameter CN-6000 hemostasis analyzer. METHODS: Performance evaluation of the CN-6000 analyzer was conducted for 10 tests including prothrombin time (PT), activated partial prothrombin time (aPTT), fibrinogen level, anti-Xa activity, and antithrombin activity using a unique portfolio of liquid ready-to-use reagents. Precision, sample and reagent carryovers, throughput, and sample turnaround time (STAT) function were prospectively assessed. Results from 343 samples (normal subjects, critically ill patients, patients receiving anticoagulants, subjects with high or low fibrinogen levels, and patients with decreased levels of factor II, V, VII, and X) were compared to those obtained on the STA-R Max 2® analyzer using dedicated reagents. RESULTS: Total precision (coefficient of variation) was below 7% for all parameters in both normal and pathological ranges. For all analyzed parameters, results obtained on the CN-6000 were strongly correlated with those obtained on the STA-R Max 2®analyzer. Agreement between both instruments was excellent for all assays. The CN-6000 demonstrated a 30% higher throughput compared to the STA-R Max 2® (258 vs 185 tests per hour for a panel of tests including PT, aPTT, fibrinogen, factor V, anti-Xa, and D-Dimer). STAT turnaround time for critical care samples testing was <7 minutes. CONCLUSIONS: The CN-6000 analyzer performs equivalently or better than the STA-R Max 2® with a significantly improved throughput. This new hemostasis multiparameter analyzer appears to be particularly well suited for coagulation laboratories which require high sample throughput and manage high numbers of nonstandard and critical care samples.

Influence of diet on acute endocannabinoidome mediator levels post exercise in active women, a crossover randomized study.

The extended endocannabinoid system, also termed endocannabinoidome, participates in multiple metabolic functions in health and disease. Physical activity can both have an acute and chronic impact on endocannabinoid mediators, as does diet. In this crossover randomized controlled study, we investigated the influence of diet on the peripheral response to acute maximal aerobic exercise in a sample of active adult women (n = 7) with no underlying metabolic conditions. We compared the impact of 7-day standardized Mediterranean diet (MedDiet) and control diet inspired by Canadian macronutrient intake (CanDiet) on endocannabinoidome and short-chain fatty acid metabolites post maximal aerobic exercise. Overall, plasmatic endocannabinoids, their congeners and some polyunsaturated fatty acids increased significantly post maximal aerobic exercise upon cessation of exercise and recovered their initial values within 1 h after exercise. Most N-acylethanolamines and polyunsaturated fatty acids increased directly after exercise when the participants had consumed the MedDiet, but not when they had consumed the CanDiet. This impact was different for monoacylglycerol endocannabinoid congeners, which in most cases reacted similarly to acute exercise while on the MedDiet or the CanDiet. Fecal microbiota was only minimally affected by the diet in this cohort. This study demonstrates that endocannabinoidome mediators respond to acute maximal aerobic exercise in a way that is dependent on the diet consumed in the week prior to exercise.

Hemostasis testing in patients with liver dysfunction: Advantages and caveats.

Due to concomitant changes in pro- and anti-coagulant mechanisms, patients with liver dysfunction have a "rebalanced hemostasis", which can easily be tipped toward either a hypo- or a hypercoagulable phenotype. Clinicians are often faced with the question whether patients with chronic liver disease undergoing invasive procedures or surgery and those having active bleeding require correction of the hemostasis abnormalities. Conventional coagulation screening tests, such as the prothrombin time/international normalized ratio and the activated partial thromboplastin time have been demonstrated to have numerous limitations in these patients and do not predict the risk of bleeding prior to high-risk procedures. The introduction of global coagulation assays, such as viscoelastic testing (VET), has been an important step forward in the assessment of the overall hemostasis profile. A growing body of evidence now suggests that the use of VET might be of significant clinical utility to prevent unnecessary infusion of blood products and to improve outcomes in numerous settings. The present review discusses the advantages and caveats of both conventional and global coagulation assays to assess the risk of bleeding in patients with chronic liver disease as well as the current role of transfusion and hemostatic agents to prevent or manage bleeding.

Competition experiments in a soil microcosm reveal the impact of genetic and biotic factors on natural yeast populations.

The ability to measure microbial fitness directly in natural conditions and in interaction with other microbes is a challenge that needs to be overcome if we want to gain a better understanding of microbial fitness determinants in nature. Here we investigate the influence of the natural microbial community on the relative fitness of the North American populations SpB, SpC and SpC* of the wild yeast Saccharomyces paradoxus using DNA barcodes and a soil microcosm derived from soil associated with oak trees. We find that variation in fitness among these genetically distinct groups is influenced by the microbial community. Altering the microbial community load and diversity with an irradiation treatment significantly diminishes the magnitude of fitness differences among populations. Our findings suggest that microbial interactions could affect the evolution of yeast lineages in nature by modulating variation in fitness.

Transient increase of CA 19-9 serum concentrations in a liver transplant recipient with cystic fibrosis and hepatic abscess: a case report and brief literature review.

CA 19-9 (carbohydrate antigen 19-9) is a tumor marker widely used for surveillance of patients with pancreatic cancer. However, even high levels of CA 19-9 may not necessarily be cancer-associated thereby complicating the diagnosis. This case report highlights a transient increase of CA 19-9 in a triple transplanted patient with cystic fibrosis and continuous immunosuppression for 20 years who was under antibiotics. This case emphasizes the need for a balanced interpretation of biological results, especially in cases where many confounding factors are present such as diabetes, chronic renal failure, cystic fibrosis and infections. This case also provides an opportunity to formulate a number of recommendations for the interpretation of tumor marker results in order to avoid long and costly further investigations.

A collection of barcoded natural isolates of Saccharomyces paradoxus to study microbial evolutionary ecology.

While the use of barcoded collections of laboratory microorganisms and the development of barcode-based cell tracking are rapidly developing in genetics and genomics research, tools to track natural populations are still lacking. The yeast Saccharomyces paradoxus is an emergent microbial model in ecology and evolution. More than five allopatric and sympatric lineages have been identified and hundreds of strains have been isolated for this species, allowing to assess the impact of natural diversity on complex traits. We constructed a collection of 550 barcoded and traceable strains of S. paradoxus, including all three North American lineages SpB, SpC, and SpC*. These strains are diploid, many have their genome fully sequenced and are barcoded with a unique 20 bp sequence that allows their identification and quantification. This yeast collection is functional for competitive experiments in pools as the barcodes allow to measure each lineage's and individual strains' fitness in common conditions. We used this tool to demonstrate that in the tested conditions, there are extensive genotype-by-environment interactions for fitness among S. paradoxus strains, which reveals complex evolutionary potential in variable environments. This barcoded collection provides a valuable resource for ecological genomics studies that will allow gaining a better understanding of S. paradoxus evolution and fitness-related traits.