At the crossroads: strigolactones mediate changes in cytokinin synthesis and signalling in response to nitrogen limitation.

Strigolactones (SLs) are key regulators of shoot growth and responses to environmental stimuli. Numerous studies have indicated that nitrogen (N) limitation induces SL biosynthesis, suggesting that SLs may play a pivotal role in coordinating systemic responses to N availability, but this idea has not been clearly demonstrated. Here, we generated triple knockout mutants in the SL synthesis gene TaDWARF17 (TaD17) in bread wheat and investigated their phenotypic and transcriptional responses under N limitation, aiming to elucidate the role of SLs in the adaptation to N limitation.

The Functional Diversity of the High-Affinity Nitrate Transporter Gene Family in Hexaploid Wheat: Insights from Distinct Expression Profiles.

High-affinity nitrate transporters (NRT) are key components for nitrogen (N) acquisition and distribution within plants. However, insights on these transporters in wheat are scarce. This study presents a comprehensive analysis of the NRT2 and NRT3 gene families, where the aim is to shed light on their functionality and to evaluate their responses to N availability.

The relative abundance of wheat Rubisco activase isoforms is post-transcriptionally regulated.

Diurnal rhythms and light availability affect transcription-translation feedback loops that regulate the synthesis of photosynthetic proteins. The CO-fixing enzyme Rubisco is the most abundant protein in the leaves of major crop species and its activity depends on interaction with the molecular chaperone Rubisco activase (Rca). In Triticum aestivum L.

Wheat amino acid transporters highly expressed in grain cells regulate amino acid accumulation in grain.

Amino acids are delivered into developing wheat grains to support the accumulation of storage proteins in the starchy endosperm, and transporters play important roles in regulating this process. RNA-seq, RT-qPCR, and promoter-GUS assays showed that three amino acid transporters are differentially expressed in the endosperm transfer cells (TaAAP2), starchy endosperm cells (TaAAP13), and aleurone cells and embryo of the developing grain (TaAAP21), respectively. Yeast complementation revealed that all three transporters can transport a broad spectrum of amino acids.

Phylogeny and gene expression of the complete NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER FAMILY in Triticum aestivum.

NPF genes encode membrane transporters involved in the transport of a large variety of substrates including nitrate and peptides. The NPF gene family has been described for many plants, but the whole NPF gene family for wheat has not been completely identified. The release of the wheat reference genome has enabled the identification of the entire wheat NPF gene family.

Phase Ib trial combining capecitabine, erlotinib and bevacizumab in pancreatic adenocarcinoma - REBECA trial.

Background Purpose of this phase Ib trial was to establish the maximum tolerable dose (MTD) of capecitabine and to escalate the dosages of erlotinib and bevacizumab to determine the recommended phase II dose (RP2D) in patients with advanced/metastatic pancreatic adenocarcinoma not pretreated for metastatic disease. Methods Starting doses were capecitabine 500 mg/m bid orally continuously, erlotinib 100 mg orally daily, and bevacizumab 5 mg/kg intravenously q 2 weeks. Dose escalation was performed according to a 3 + 3 design for capecitabine until MTD, for erlotinib and bevacizumab until the maximum doses registered by applying a substance-related, toxicity-based scheme accompanied by pharmacokinetic analysis.

Temperature and nitrogen supply interact to determine protein distribution gradients in the wheat grain endosperm.

Gradients exist in the distribution of storage proteins in the wheat (Triticum aestivum) endosperm and determine the milling properties and protein recovery rate of the grain. A novel image analysis technique was developed to quantify both the gradients in protein concentration, and the size distribution of protein bodies within the endosperm of wheat plants grown under two different (20 or 28 °C) post-anthesis temperatures, and supplied with a nutrient solution with either high or low nitrogen content. Under all treatment combinations, protein concentration was greater in the endosperm cells closest to the aleurone layer and decreased towards the centre of the two lobes of the grain, i.

Monitoring of erlotinib in pancreatic cancer patients during long-time administration and comparison to a physiologically based pharmacokinetic model.

Purpose: In this study, a therapeutic drug monitoring (TDM) of erlotinib in pancreatic cancer patients was performed over 50 weeks to reveal possible alterations in erlotinib plasma concentrations. Additionally, a physiologically based pharmacokinetic (PBPK) model was created to assess such variations in silico.

Methods: Patients with advanced pancreatic cancer received a chemotherapeutic combination of 100 mg erlotinib q.

Characterization of the Wheat Leaf Metabolome during Grain Filling and under Varied N-Supply.

Progress in improving crop growth is an absolute goal despite the influence multifactorial components have on crop yield and quality. An Avalon × Cadenza doubled-haploid wheat mapping population was used to study the leaf metabolome of field grown wheat at weekly intervals during the time in which the canopy contributes to grain filling, i.e.

Identification and expression profiling of Pht1 phosphate transporters in wheat in controlled environments and in the field.

Phosphorus (P) is an important macronutrient with critical functions in plants. Phosphate (Pi) transporters, which mediate Pi acquisition and Pi translocation within the plant, are key factors in Pi deficiency responses. However, their relevance for adaptation to long-term Pi limitation under agronomic conditions, particularly in wheat, remains unknown.

The role of ZIP transporters and group F bZIP transcription factors in the Zn-deficiency response of wheat (Triticum aestivum).

Understanding the molecular basis of zinc (Zn) uptake and transport in staple cereal crops is critical for improving both Zn content and tolerance to low-Zn soils. This study demonstrates the importance of group F bZIP transcription factors and ZIP transporters in responses to Zn deficiency in wheat (Triticum aestivum). Seven group F TabZIP genes and 14 ZIPs with homeologs were identified in hexaploid wheat.

Three new species and one new subspecies of Depressariinae (Lepidoptera) from Europe.

The species Corley, , Corley, and Buchner & Junnilainen, and the subspecies Depressaria saharae Gastón & Vives ssp. tabelli Buchner, are described. was first found in Spain in 1969 and recognised as apparently new but the specimens in NHMUK have remained undescribed.

Assessment of Pharmacokinetic Interaction Between Capecitabine and Cetuximab in Metastatic Colorectal Cancer Patients.

Aim: This study focuses on the plasma disposition and metabolic activation of capecitabine (CCB) when administered alone or when combined with cetuximab (CTX).

Patients And Methods: Twenty-four chemo-naïve patients with KRAS wild-type colorectal cancer were randomized into two arms and received either CCB alone (1,000 mg/m(2) bid p.o.

Genetic diversity for root plasticity and nitrogen uptake in wheat seedlings.

Enhancing nitrogen use efficiency (NUE) of wheat is a major focus for wheat breeding programs. NUE may be improved by identifying genotypes that are competitive for nitrogen (N) uptake in early vegetative stages of growth and are able to invest that N in grain. Breeders tend to select high yielding genotypes under conditions of medium to high N supply, but it is not known whether this influences the selection of root plasticity traits or whether, over time, breeders have selected genotypes with higher N uptake efficiency.

Two new species of Agonopterix (Depressariidae, Lepidoptera) from Europe.

The species Agonopterix tripunctaria sp. nov. and Agonopterix medelichensis sp.

Expression patterns of C- and N-metabolism related genes in wheat are changed during senescence under elevated CO2 in dry-land agriculture.

Projected climatic impacts on crop yield and quality, and increased demands for production, require targeted research to optimise nutrition of crop plants. For wheat, post-anthesis carbon and nitrogen remobilisation from vegetative plant parts and translocation to grains directly affects grain carbon (C), nitrogen (N) and protein levels. We analysed the influence of increased atmospheric CO2 on the expression of genes involved in senescence, leaf carbohydrate and nitrogen metabolism and assimilate transport in wheat under field conditions (Australian Grains Free Air CO2 Enrichment; AGFACE) over a time course from anthesis to maturity, the key period for grain filling.

A simple method for comparing enzymatic capecitabine activation in various mono- and combination chemotherapies.

Before being able to develop a pharmacodynamic effect, a number of drugs have to be activated by enzymes, which are known to be potentially influenced by manifold factors, leading to a possible alteration of their activity behaviour. Based on capecitabine, we report a simple and rapid method for the estimation and comparison of the so-called 'apparent enzyme activity' (R), not only intra- (different dose levels) but also inter-schedule, to contribute to therapeutic success. Dividing the area under the curve (AUC) of the product by the AUC of the precursor generates a factor which indicates the apparent activity of the enzyme involved in the biotransformation of a compound.

Overexpression of a NAC transcription factor delays leaf senescence and increases grain nitrogen concentration in wheat.

Increasing the duration of leaf photosynthesis during grain filling using slow-senescing functional stay-green phenotypes is a possible route for increasing grain yields in wheat (Triticum aestivum L.). However, delayed senescence may negatively affect nutrient remobilisation and hence reduce grain protein concentrations and grain quality.

Environmental sampling for Clostridium difficile on alcohol-based hand rub dispensers in an academic medical center.

Background: Clostridum difficile is a gram-positive, spore-forming anaerobic bacillus that has substantial associated morbidity, mortality, and associated healthcare burdens. Clostridium difficile spores are not destroyed by alcohol. Alcohol gel dispensers are used commonly as the hand sanitization method of choice in hospitals.

Clinical pharmacokinetics of capecitabine and its metabolites in combination with the monoclonal antibody bevacizumab.

Aim: Capecitabine, designed as a pro-drug to the cytotoxic agent 5-fluorouracil, is widely used in the management of colorectal cancer. This study was designed to investigate whether co-administration of the monoclonal antibody bevacizumab (BVZ) shows potential to modulate the plasma disposition of capecitabine (CCB) and its metabolites.

Patients And Methods: Nine patients treated with CCB and BVZ for advanced colorectal cancer entered this pharmacokinetic study.

Complex phylogeny and gene expression patterns of members of the NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER family (NPF) in wheat.

NPF (formerly referred to as low-affinity NRT1) and 'high-affinity' NRT2 nitrate transporter genes are involved in nitrate uptake by the root, and transport and distribution of nitrate within the plant. The NPF gene family consists of 53 members in Arabidopsis thaliana, however only 11 of these have been functionally characterized. Although homologous genes have been identified in genomes of different plant species including some cereals, there is little information available for wheat (Triticum aestivum).

Disposition of Erlotinib and Its Metabolite OSI420 in a Patient with High Bilirubin Levels.

Erlotinib is an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor approved for the treatment of non-small cell lung cancer and when combined with gemcitabine for pancreatic cancer. Dose reduction of erlotinib in patients with severe hepatic impairment has been established. We present the case of a male patient suffering from an adenocarcinoma of the pancreas with metastases in the liver and lung, whose disease progression led to highly elevated bilirubin levels of >14 mg/dl accompanied by icterus and pruritus.

Validation of a simple assay for the quantification of the capecitabine metabolites 5'-DFCR and 5'-DFUR for drug monitoring in patients receiving outpatient chemotherapy.

A simple and precise analytical method for the determination of 5'deoxy-5-fluorocytidine (DFCR) and 5'deoxy-5-fluorouridine (DFUR), the enzymatically formed metabolites of capecitabine in plasma, was developed using a reversed-phase high performance liquid chromatography gradient method with external standard method. Blood samples were analyzed after separation of DFCR/DFUR by solid-phase extraction from matrix compounds using a C16 amide reversed-phase column operated at a flow rate of 0.8 ml/min in gradient elution mode with a mobile phase composed of water-methanol (10 mM ammonium acetate in water; m/v).