Liebig's law of the minimum, which states that only one element limits the growth of organisms at any given time, is widely used in ecology. This principle is routinely applied to organisms, populations and communities, but can it really be applied indistinguishably across these different scales? Here we show, by prediction of a resource ratio conceptual model and with an experimental test carried out in microcosms with bacteria that, unlike single species, communities are likely to adjust their stoichiometry to that of their resources. This adjustment results from competitive exclusion and coexistence mechanisms, and is sensitive to the overall diversity of species in the community. It guaranties co-limitation, i.e. simultaneous limitation by multiple resources, at the community scale and optimal use of resources and maximization of community biomass for wide ranges of resource ratios. These results question the applicability of the Liebig's law of the minimum at the community level, and the relevance of ecosystem models relying on this principle.

Pyruvate kinase deficiency (PKD) is the most common enzyme defect of glycolysis and an important cause of hereditary, nonspherocytic hemolytic anemia. The disease has a worldwide geographical distribution but there are no verified data regarding its frequency. Difficulties in the diagnostic workflow and interpretation of PK enzyme assay likely play a role. By the creation of a global PKD International Working Group in 2016, involving 24 experts from 20 Centers of Expertise we studied the current gaps in the diagnosis of PKD in order to establish diagnostic guidelines. By means of a detailed survey and subsequent discussions, multiple aspects of the diagnosis of PKD were evaluated and discussed by members of Expert Centers from Europe, USA, and Asia directly involved in diagnosis. Broad consensus was reached among the Centers on many clinical and technical aspects of the diagnosis of PKD. The results of this study are here presented as recommendations for the diagnosis of PKD and used to prepare a diagnostic algorithm. This information might be helpful for other Centers to deliver timely and appropriate diagnosis and to increase awareness in PKD.

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Emerging metabolomic tools can now be used to establish metabolic signatures of specialized circulating hematopoietic cells in physiologic or pathologic conditions and in human hematologic diseases. To determine metabolomes of normal and sickle cell erythrocytes, we used an extraction method of erythrocytes metabolites coupled with a liquid chromatography-mass spectrometrybased metabolite profiling method. Comparison of these 2 metabolomes identified major changes in metabolites produced by (1) endogenous glycolysis characterized by accumulation of many glycolytic intermediates; (2) endogenous glutathione and ascorbate metabolisms characterized by accumulation of ascorbate metabolism intermediates, such as diketogulonic acid and decreased levels of both glutathione and glutathione disulfide; (3) membrane turnover, such as carnitine, or membrane transport characteristics, such as amino acids; and (4) exogenous arginine and NO metabolisms, such as spermine, spermidine, or citrulline. Finally, metabolomic analysis of young and old normal red blood cells indicates metabolites whose levels are directly related to sickle cell disease. These results show the relevance of metabolic profiling for the follow-up of sickle cell patients or other red blood cell diseases and pinpoint the importance of metabolomics to further depict the pathophysiology of human hematologic diseases. (Blood. 2011; 117(6):e57-e66) IntroductionMetabolome is defined as the complete set of metabolites present in a given biologic system that can be unicellular organism, organ, tissue, cell, or biologically relevant liquid compartments. Complementary to genomics or proteomics, the aim of metabolome analysis is to describe qualitatively and quantitatively the final products of cellular regulatory pathways and can be seen as the ultimate response of a biologic system to genetic factors and/or environmental changes. 1 Presently, metabolomics is used to describe metabolites present in simple unicellular organisms, such as Escherichia coli, 2 or in important biologic fluids, such as plasma or urine, 3,4 but the cross-talks between cells in tissues or the complex metabolism in mammalian cells make the interpretation of metabolomics data challenging in human, although important metabolites involved in pathogenesis of cancer, 5,6 diabetes, 7 and cardiovascular 8,9 and mitochondrial diseases 10 are described.Mammalian mature red blood cell (RBC) is a cell without nucleus or cytoplasmic organelles, such as mitochondria or ribosomes, easy to collect and to purify in large quantity. In human, during their 120-day life span, RBCs are perfectly adapted to oxygen, carbon dioxide, and proton transport. RBCs have also an important role in interorgan transport of metabolites, such as amino acid transport to muscles resulting from numerous amino acids receptors on RBC membranes. RBCs are also used as reporters of exogenous metabolisms as exemplified by the level of hemoglobin A1c, which is a measure of erythrocyte hemoglobin glycation and reflects mean glycemia for the...

Hydroxyurea (HU) enhances fetal hemoglobin (Hb) production. An increase in total Hb level has been repeatedly reported during HU treatment in patients with sickle cell disease and in several patients with ␤-thalassemia intermedia. Effects in patients with ␤-thalassemia major are controversial. We now report a marked elevation of total Hb levels with HU that permitted regular transfusions to be stopped in 7 children with transfusiondependent ␤-thalassemia. The median follow-up was 19 ؎ 3 months (range, 13-21 months). We conclude that HU can eliminate transfusional needs in children with ␤-thalassemia major, which could be par-