Lectins of members of the Amaryllidaceae are encoded by multigene families which show extensive homology

Nitrate uptake and reduction are highly regulated processes. In many plant species, nitrate uptake is induced by nitrate, Little, however, is known about the genetic and molecular aspects of nitrate transport. Reduction of nitrate to ammonia is carried out by nitrate and nitrite reductases. Nitrate and light enhance expression of the nitrate and nitrite reductase genes in most species. Mutants have been selected and characterized to identify genes controlling nitrate reductase in several higher plant species. Six loci are known to control the synthesis or assembly of the molybdenum cofactor of nitrate reductase, xanthine dehydrogenase and aldehyde oxidase. The nitrate reductase apoenzyme is encoded by a single gene, except in allopolyploid species and in those species possessing both NADH-specific and NAD(P)H-bispecific nitrate reductases. Comparison of NADH-specific nitrate reductase amino acid sequences deduced from cloned genes reveals considerable sequence conservation in regions believed to encode the functional domains of nitrate reductase, but less conservation in the N-terminal and hinge regions of the enzyme. For both nitrate and nitrite reductases, sequence identity is greater among species of the same subclass than between Monocotyledoneae and Dicotyledoneae subclass species.     

Prospective Evaluation of First-Line Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Carrying an Activating EGFR Mutation: A Multicenter Academic Phase II Study in Caucasian Patients (FIELT)

Introduction

Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibition is the preferred first-line treatment of advanced adenocarcinoma of the lung that harbors EGFR activating tyrosine kinase domain mutations. Most data available pertain to Asian populations in which such mutations are more prevalent. We report on the long-term results of first-line treatment with erlotinib in Caucasian patients with advanced adenocarcinoma of the lung that have a somatic EGFR mutation in their tumor.

Methods

Multicenter academic prospective phase II study with erlotinib in patients with an activating EGFR tyrosine kinase (TK) domain somatic mutation (any exon encoding the kinase domain) in the tumor and no prior treatment for their advanced disease.

Results

Phenotypic preselecting of 229 patients led to a high EGFR mutation detection rate of 24% of which 46 patients were included in the phase II study. With a progression free survival (PFS) of 81% at three months the study met its primary endpoint for presumed superiority over chemotherapy. With an overall median PFS of 11 months and a median overall survival (OS) of 23 months, the results compare favorably with results obtained in randomized studies using TKI in first line in EGFR mutation positive adenocarcinoma of the lung.

Conclusion

The present study reinforces the use of EGFR tyrosine kinase inhibition (TKI) as a first line treatment of choice for advanced adenocarcinoma of the lung carrying an activating EGFR mutation. The mutation rate in preselected Caucasian patients is higher than previously reported. Issues relevant for clinical practice are discussed.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00339586","term_id":"NCT00339586"}}NCT00339586     

A comparative study of seed yield parameters in Arabidopsis thaliana mutants and transgenics

Because seed yield is the major factor determining the commercial success of grain crop cultivars, there is a large interest to obtain more understanding of the genetic factors underlying this trait. Despite many studies, mainly in the model plant Arabidopsis thaliana, have reported transgenes and mutants with effects on seed number and/or seed size, knowledge about seed yield parameters remains fragmented. This study investigated the effect of 46 genes, either in gain- and/or loss-of-function situations, with a total of 64 Arabidopsis lines being examined for seed phenotypes such as seed size, seed number per silique, number of inflorescences, number of branches on the main inflorescence and number of siliques. Sixteen of the 46 genes, examined in 14 Arabidopsis lines, were reported earlier to directly affect in seed size and/or seed number or to indirectly affect seed yield by their involvement in biomass production. Other genes involved in vegetative growth, flower or inflorescence development or cell division were hypothesized to potentially affect the final seed size and seed number. Analysis of this comprehensive data set shows that of the 14 lines previously described to be affected in seed size or seed number, only nine showed a comparable effect. Overall, this study provides the community with a useful resource for identifying genes with effects on seed yield and candidate genes underlying seed QTL. In addition, this study highlights the need for more thorough analysis of genes affecting seed yield.     

A Population Genomics Study of the Arabidopsis Core Cell Cycle Genes Shows the Signature of Natural Selection

Large-scale comparison of sequence polymorphism and divergence at numerous genomic loci within and between closely related species can reveal signatures of natural selection. Here, we present a population genomics study based on direct sequencing of 61 mitotic cell cycle genes from 30 Arabidopsis thaliana accessions and comparison of the resulting data to the close relative Arabidopsis lyrata. We found that the Arabidopsis core cell cycle (CCC) machinery is not highly constrained but is subject to different modes of selection. We found patterns of purifying selection for the cyclin-dependent kinase (CDK), CDK subunit, retinoblastoma, and WEE1 gene families. Other CCC gene families often showed a mix of one or two constrained genes and relaxed purifying selection on the other genes. We found several large effect mutations in CDKB1;2 that segregate in the species. We found a strong signature of adaptive protein evolution in the Kip-related protein KRP6 and departures from equilibrium at CDKD;1 and CYCA3;3 consistent with the operation of selection in these gene regions. Our data suggest that within Arabidopsis, the genetic robustness of cell cycle–related processes is more due to functional redundancy than high selective constraint.     

Linkage Mapping Identifies the Sex Determining Region as a Single Locus in the Pennate Diatom Seminavis robusta

The pennate diatom Seminavis robusta, characterized by an archetypical diatom life cycle including a heterothallic mating system, is emerging as a model system for studying the molecular regulation of the diatom cell and life cycle. One of its main advantages compared with other diatom model systems is that sexual crosses can be made routinely, offering unprecedented possibilities for forward genetics. To date, nothing is known about the genetic basis of sex determination in diatoms. Here, we report on the construction of mating type-specific linkage maps for S. robusta, and use them to identify a single locus sex determination system in this diatom. We identified 13 mating type plus and 15 mating type minus linkage groups obtained from the analysis of 463 AFLP markers segregating in a full-sib family, covering 963.7 and 972.2 cM, respectively. Five linkage group pairs could be identified as putative homologues. The mating type phenotype mapped as a monogenic trait, disclosing the mating type plus as the heterogametic sex. This study provides the first evidence for a genetic sex determining mechanism in a diatom.     

Steady-state measurement of NO and CO lung diffusing capacity on moderate exercise in men.

Using a rapidly responding nitric oxide (NO) analyzer, we measured the steady-state NO diffusing capacity (DL(NO)) from end-tidal NO. The diffusing capacity of the alveolar capillary membrane and pulmonary capillary blood volume were calculated from the steady-state diffusing capacity for CO (measured simultaneously) and the specific transfer conductance of blood per milliliter for NO and for CO. Nine men were studied bicycling at an average O(2) consumption of 1.3 +/- 0.2 l/min (mean +/- SD). DL(NO) was 202.7 +/- 71.2 ml. min(-1). Torr(-1) and steady-state diffusing capacity for CO, calculated from end-tidal (assumed alveolar) CO(2), mixed expired CO(2), and mixed expired CO, was 46.9 +/- 12.8 ml. min(-1). Torr(-1). NO dead space = (VT x FE(NO) - VT x FA(NO))/(FI(NO) - FA(NO)) = 209 +/- 88 ml, where VT is tidal volume and FE(NO), FI(NO), and FA(NO) are mixed exhaled, inhaled, and alveolar NO concentrations, respectively. We used the Bohr equation to estimate CO(2) dead space from mixed exhaled and end-tidal (assumed alveolar) CO(2) = 430 +/- 136 ml. Predicted anatomic dead space = 199 +/- 22 ml. Membrane diffusing capacity was 333 and 166 ml. min(-1). Torr(-1) for NO and CO, respectively, and pulmonary capillary blood volume was 140 ml. Inhalation of repeated breaths of NO over 80 s did not alter DL(NO) at the concentrations used.     

Cutting edge: resistance to HIV-1 infection among African female sex workers is associated with inhibitory KIR in the absence of their HLA ligands

NK cells are regulated in part by killer Ig-like receptors (KIR) that interact with HLA molecules on potential target cells. KIR and HLA loci are highly polymorphic and certain KIR/HLA combinations were found to protect against HIV disease progression. We show in this study that KIR/HLA interactions also influence resistance to HIV transmission. HIV-exposed but seronegative female sex workers in Abidjan, C?te d'Ivoire, frequently possessed inhibitory KIR genes in the absence of their cognate HLA genes: KIR2DL2/KIR2DL3 heterozygosity in the absence of HLA-C1 and KIR3DL1 homozygosity in the absence of HLA-Bw4. HIV-seropositive female sex workers were characterized by corresponding inhibitory KIR/HLA pairings: KIR2DL3 homozygosity together with HLA-C1 and a trend toward KIR3DL1/HLA-Bw4 homozygosity. Absence of ligands for inhibitory KIR could lower the threshold for NK cell activation. In addition, exposed seronegatives more frequently possessed AB KIR genotypes, which contain more activating KIR. The data support an important role for NK cells and KIR/HLA interactions in antiviral immunity.