Plants species diverge with regard to the time and place where they make flowers. Flowers can develop from apical meristems, lateral meristems, or both, resulting in three major inflorescence types known as racemes, cymes, and panicles, respectively. The mechanisms that determine a racemose architecture have been uncovered in Arabidopsis and Antirrhinum. To understand how cymes are specified, we studied mutations that alter the petunia inflorescence. Here we show that EVERGREEN (EVG) encodes a WOX homeodomain protein, which is exclusively expressed in incipient lateral inflorescence meristems (IMs), promoting their separation from the apical floral meristem (FM). This is essential for activation of DOUBLE TOP and specification of floral identity. Mutations that change the cymose petunia inflorescence into a solitary flower fully suppress the evg phenotype. Our data suggest a key role for EVG in the diversification of inflorescence architectures and reveal an unanticipated link between the proliferation and identity of meristems.

Flowering plants have developed many ways to arrange their flowers. A flower-bearing branch or system of branches is called an inflorescence. The number of flowers that an inflorescence contains ranges from a single flower to endless flower-clusters. Over the past centuries, botanists have classified inflorescences based on their morphology, which has led to an unfortunate maze of complex botanical terminology. With the rise of molecular developmental biology, research has become increasingly focused on how inflorescences develop, rather than on their morphology. It is the decisions taken by groups of stem cells at the growing tips of shoots, called meristems, on when and where to produce a flower or a shoot that specify the course of inflorescence development. Modelling is a helpful aid to follow the consequences of these decisions for inflorescence development. The so-called transient model can produce the broad inflorescence types: cyme, raceme, and panicle, into which most inflorescences found in nature can be classified. The analysis of several inflorescence branching mutants has led to a solid understanding of cymose inflorescence development in petunia (Petunia hybrida). The cyme of petunia is a distinct body plan compared with the well-studied racemes of Arabidopsis and Antirrhinum, which provides an excellent opportunity to study evolutionary developmental biology (evo-devo) related questions. However, thus far, limited use has been made of this opportunity, which may, at least in part, be due to researchers getting lost in the terminology. Some general issues are discussed here, while focusing on inflorescence development in petunia.

In order to identify genes whose expression is associated with resistance to the chemotherapeutic agent oxaliplatin, transcripts differentially expressed between an oxaliplatin sensitive and a stably resistant subline were compared in six independent replicates using Stanford cDNA microarrays for five cell lines. "Significance analysis of microarrays" (SAM) was used to identify genes whose expression was statistically significantly different in the sensitive versus resistant members of each cell line pair. The biochemical pathways of the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were searched to identify those pathways in which the number of SAM-identified genes exceeded the number expected. This identified four pathways in which upregulated genes were significantly associated with resistance in two of the cell line pairs, and two pathways in which the association was found in three cell line pairs. The search also identified 12 pathways in which downregulated genes were associated with resistance in two cell line pairs and one pathway in which the association reached statistical significance in three cell line pairs. Pathways identified included the ribosome pathway, the Huntington's disease pathway that includes caspase 8, and the ATP synthesis pathways. Determination of the chromosomal location of each SAM-identified gene revealed several locales within which genes lay in close proximity, including three genes (APACD, IF-2, and REV1L) located on chromosome 2 that lie immediately adjacent to each other and were significantly upregulated in three of five cell line pairs. Biochemical pathway and chromosomal mapping of genes identified by SAM as differentially expressed in related cell line pairs points to mechanisms and chromosomal sites not previously suspected of association with the oxaliplatin-resistant phenotype.

The transferrin/log(ferritin) ratio is a practical new tool that improves diagnosis of iron deficiency when ferritin levels are inconclusive.

BackgroundMacrocytic anaemia (MCV ≥ 100 fL) is a relatively common finding in general practice. However, literature on the prevalence of the different causes in this population is limited. The prevalence of macrocytic anaemia and its underlying aetiology were analysed in a general practice population. The potential effect of the different aetiology on survival was also evaluated.MethodsBetween the 1st of February 2007 and the 1st of February 2015, patients aged 50 years or older and presenting to their general practitioner with a newly diagnosed anaemia, were included in the study. Anaemia was defined as haemoglobin level below 13.7 g/dL in men and below 12.1 g/dL in women. A broad range of laboratory tests was performed for each patient. The causes of anaemia were consequently determined by two independent observers based on the laboratory results.ResultsOf the 3324 included patients, 249 (7.5 %) displayed a macrocytic anaemia and were subsequently analysed. An underlying explanation could be established in 204 patients (81.9 %) with 27 patients (13.2 %) displaying multiple causes. Classic aetiology (i.e. alcohol abuse, vitamin B12/folic acid deficiency, haemolysis and possible bone marrow disease) was found in 115 patients. Alternative causes (i.e. anaemia of chronic disease, iron deficiency, renal anaemia and other causes) were encountered in 101 patients. In addition, a notable finding was the median gamma GT of 277 U/L in patients diagnosed with alcohol abuse (N = 24, IQR 118.0-925.5) and 23 U/L in the remaining cohort (N = 138, IQR 14.0-61.0). The distribution of gamma GT values was statistically different (P < 0.001).Five year survival rates were determined for six categories of causes, ranging from 39.9 % (95 % CI 12.9-66.9) for renal anaemia to 76.2 % (95 % CI 49.4-103.0) for the category multiple causes.ConclusionIn addition to classic explanations for macrocytosis, alternative causes are frequently encountered in patients with macrocytic anaemia in general practice.

ObjectivesThe aim of this study was to determine whether the Hem-Col method of obtaining and storing blood is an acceptable alternative to venepuncture for measuring Diabetes Care parameters. Design and methods: Hem-Col is a novel blood collection device that is designed to collect capillary blood drawn with a finger prick. Hem-Col is a microtube containing an anticoagulant and a preservation buffer to enhance analyte stability in whole blood. The Diabetes Care parameters cholesterol, creatinine, HbA1c, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides were measured both in blood/plasma collected via Hem-Col and blood/plasma collected with venepuncture. The results were compared to assess the agreement between the two methods. Results: HbA1c shows agreement after storage for up to 120 hours at temperatures ranging from 4 to 37 °C. Cholesterol, HDL cholesterol, LDL cholesterol, triglycerides and creatinine can be measured after 120 hours of storage in Hem-Col buffer, if high temperatures are avoided, and with the use of correction factors or adaptations to reported reference intervals. Conclusion: Hem-Col is suitable for the measurement of HbA1c after storage for up to 120 hours at temperatures ranging from 4 to 37 °C. Cholesterol, creatinine, HDL cholesterol, LDL cholesterol and triglycerides can be measured after 120 hours of storage in Hem-Col buffer, if high temperatures are avoided. Further studies are required to determine whether Hem-Col can replace the venepuncture for the Diabetes Care parameters.

There is a Blood Commentary on this article in this issue. 8. Brissot E, Labopin M, Beckers MM, et al. Tyrosine kinase inhibitors improve long-term outcome of allogeneic hematopoietic stem cell transplantation for adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia. Haematologica. 2015;100(3):392-399. 9. Zhang FH, Ling YW, Zhai X, et al. The effect of imatinib therapy on the outcome of allogeneic stem cell transplantation in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia. Hematology. 2013; 18(3):151-157. 10. Pfeifer H, Wassmann B, Bethge W, et al; GMALL Study Group. Randomized comparison of prophylactic and minimal residual disease-triggered imatinib after allogeneic stem cell transplantation for BCR-ABL1-positive acute lymphoblastic leukemia. Leukemia. 2013;27(6):1254-1262. 11. Kebriaei P, Saliba R, Rondon G, et al. Long-term follow-up of allogeneic hematopoietic stem cell transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: impact of tyrosine kinase inhibitors on treatment outcomes. Biol Blood Marrow Transplant. 2012;18(4):584-592. 12. Short NJ, Jabbour E, Sasaki K, et al. Impact of complete molecular response on survival in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2016;128(4):504-507. 13. Soverini S, Vitale A, Poerio A, et al. Philadelphia-positive acute lymphoblastic leukemia patients already harbor BCR-ABL kinase domain mutations at low levels at the time of diagnosis. Haematologica. 2011;96(4):552-557. 14. Soverini S, De Benedittis C, Papayannidis C, et al. Drug resistance and BCR-ABL kinase domain mutations in Philadelphia chromosomepositive acute lymphoblastic leukemia from the imatinib to the secondgeneration tyrosine kinase inhibitor era: the main changes are in the type of mutations, but not in the frequency of mutation involvement. Cancer. 2014;120(7):1002-1009.

Higher plant species diverged extensively with regard to the moment (flowering time) and position (inflorescence architecture) at which flowers are formed. This seems largely caused by variation in the expression patterns of conserved genes that specify floral meristem identity (FMI), rather than changes in the encoded proteins. Here, we report a functional comparison of the promoters of homologous FMI genes from Arabidopsis, petunia, tomato and Antirrhinum. Analysis of promoter-reporter constructs in petunia and Arabidopsis, as well as complementation experiments, showed that the divergent expression of LEAFY (LFY) and the petunia homolog ABERRANT LEAF AND FLOWER (ALF) results from alterations in the upstream regulatory network rather than cis-regulatory changes. The divergent expression of UNUSUAL FLORAL ORGANS (UFO) from Arabidopsis, and the petunia homolog DOUBLE TOP (DOT), however, is caused by the loss or gain of cis-regulatory promoter elements, which respond to trans-acting factors that are expressed in similar patterns in both species. Introduction of pUFO:UFO causes no obvious defects in Arabidopsis, but in petunia it causes the precocious and ectopic formation of flowers. This provides an example of how a change in a cis-regulatory region can account for a change in the plant body plan.