A Mutation in Amino Acid Permease AAP6 Reduces the Amino Acid Content of the Arabidopsis Sieve Elements but Leaves Aphid Herbivores Unaffected.

The aim of this study was to investigate the role of the amino acid permease gene AAP6 in regulating phloem amino acid composition and then to determine the effects of this altered diet on aphid performance. A genotype of Arabidopsis thaliana (L.) was produced in which the function of the amino acid permease gene AAP6 (At5g49630) was abolished. Plants homozygous for the insertionally inactivated AAP6 gene had a significantly larger mean rosette width than the wild type and a greater number of cauline leaves. Seeds from the aap6 mutant were also significantly larger than those from the wild-type plants. Sieve element (SE) sap was collected by aphid stylectomy and the amino acids derivatized, separated, and quantified using Capillary Electrophoresis with Laser Induced Fluorescence (CE-LIF). In spite of the large variation across samples, the total amino acid concentration of SE sap of the aap6 mutant plants was significantly lower than that of the wild-type plants. The concentrations of lysine, phenylalanine, leucine, and aspartic acid were all significantly lower in concentration in the aap6 mutant plants compared with wild-type plants. This is the first direct demonstration of a physiological role for an amino acid transporter in regulating SE composition in vivo. The amino acid availability in sieve element sap is thought to be the major limiting factor for aphid growth and reproduction. Despite the changes in their diet, the aphid Myzus persicae(Sulzer) displayed only small changes in feeding behaviour on mutant plants when measured using the Electronic Penetration Graph (EPG) technique. Salivation by the aphid into the SE (E1 phase) was increased on mutant plants but there was no significant effect on other feeding EPG behaviours, or in the rate of honeydew production. Consistent with the small effect on aphid feeding behaviour, there was only a small effect of reduced sieve element amino acid concentration on aphid reproduction. The data are discussed in relation to the regulation of phloem composition and the role of phloem amino acids in regulating aphid performance

Comparative pharmacokinetic and cytotoxic analysis of three different formulations of mitoxantrone in mice.

Two liposomal formulations of mitoxantrone (MTO) were compared with the aqueous solution (free MTO) in terms of their pharmacokinetic behaviour in ICR mice and cytotoxic activity in a nude mouse xenograft model. The three different formulations of MTO [free MTO, phosphatidic acid (PA)-MTO liposomes, pH-MTO liposomes] were administered intravenously (three mice per formulation and time point) at a dose of 4.7 micromol kg(-1) for free MTO, 6.1 micromol kg(-1) for PA-MTO and 4.5 micromol kg(-1) for pH-MTO. The concentrations of MTO were determined using high-performance liquid chromatography (HPLC) in blood, liver, heart, spleen and kidneys of the mice. Additionally, the toxicity and anti-tumour activity of MTO was evaluated in a xenograft model using a human LXFL 529/6 large-cell lung carcinoma. The dose administered was 90% of the maximum tolerated dose (MTD) of the corresponding formulation (8.1 micromol kg(-1) for free MTO, 12.1 micromol kg(-1) for PA-MTO and pH-MTO). The pharmacokinetic behaviour of PA-MTO in blood was faster than that of free MTO, but the cytotoxic effect was improved. In contrast, pH-MTO showed a tenfold increased area under the curve (AUC) in blood compared with free MTO, without improvement of the cytotoxic effect. This discrepancy between the pharmacokinetic and cytotoxic results could be explained by the fact that MTO in pH-MTO liposomes remains mainly in the vascular space, whereas MTO in PA-MTO liposomes is rapidly distributed into deep compartments, even more so than free MTO

Bile Acid Metabolites in Serum: Intraindividual Variation and Associations with Coronary Heart Disease, Metabolic Syndrome and Diabetes Mellitus

Bile acids (BAs) regulate glucose and lipid metabolism. In longitudinal and case-control-studies, we investigated the diurnal variation of serum concentrations of the 15 major BAs as well as the biosynthetic precursor 7α-hydroxy-4-cholesten-3-one (C4) and their associations, respectively, with coronary artery disease (CAD), diabetes mellitus type 2 (T2DM), and non-diabetic metabolic syndrome (MetS). In hourly taken blood samples of four healthy probands, the intraindividual 24 h variation of C4, conjugated and unconjugated BAs ranged from 42% to 72%, from 23% to 91%, and from 49% to 90%, respectively. Conjugated BA concentrations mainly increased following food intake. Serum levels of C4 and unconjugated BAs changed with daytime with maxima varying interindividually between 20h00 and 1h00 and between 3h00 and 8h00, respectively. Comparisons of data from 75 CAD patients with 75 CAD-free controls revealed no statistically significant association of CAD with BAs or C4. Comparisons of data from 50 controls free of T2DM or MetS, 50 MetS patients, and 50 T2DM patients revealed significantly increased fasting serum levels of C4 in patients with MetS and T2DM. Multiple regression analysis revealed body mass index (BMI) and plasma levels of triglycerides (TG) as independent determinants of C4 levels. Upon multivariate and principle component analyses the association of C4 with T2DM and/or MetS was not independent of or superior to the canonical MetS components. In conclusion, despite large intra- and interindividual variation, serum levels of C4,are significantly increased in patients with MetS and T2DM but confounded with BMI and TG

Cross-Level Replication and Extension of Steel and Rentsch's (1995) Longitudinal Absence Findings

Absenteeism findings published by Steel and Rentsch (1995) were replicated and extended by correlating attitudinal, personal-demographic, and job stress variables with 34 months of work group absenteeism scores obtained on employees of a U.S. federal mint. Attitudinal and job stress results were consistent with previous findings, but results involving personal-demographic variables were not.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44826/1/10869_2004_Article_344104.pd

Interdisciplinary evidence-based recommendations for the follow-up of testicular cancer patients: a joint effort

Detailed recommendations for the treatment of testicular cancer exist and due to the stringent application of the standard therapies, most patients can nowadays be cured. Moreover in the treatment of early stage disease, active surveillance is now a cornerstone of treatment. Hence there is a clear need for recommendations regarding the long term follow-up of these young patients. These have to be safe, feasible and the intensity of procedures have to reflect the known risk of recurrence. Different proposals have been published but they differ widely especially in terms of frequency and modality of imaging. In the last few years, new evidence has become available regarding the relapse pattern of different disease stages of testicular cancer, the use of imaging in follow-up and the risks of excessive radiation due to imaging, in particular with CT scans. In this article, an interdisciplinary, multinational working group has reviewed the evidence and based on this has formulated practical recommendations for the follow-up of patients with testicular cancer

Synapsin condensation controls synaptic vesicle sequestering and dynamics

Neuronal transmission relies on the regulated secretion of neurotransmitters, which are packed in synaptic vesicles (SVs). Hundreds of SVs accumulate at synaptic boutons. Despite being held together, SVs are highly mobile, so that they can be recruited to the plasma membrane for their rapid release during neuronal activity. However, how such confinement of SVs corroborates with their motility remains unclear. To bridge this gap, we employ ultrafast single-molecule tracking (SMT) in the reconstituted system of native SVs and in living neurons. SVs and synapsin 1, the most highly abundant synaptic protein, form condensates with liquid-like properties. In these condensates, synapsin 1 movement is slowed in both at short (i.e., 60-nm) and long (i.e., several hundred-nm) ranges, suggesting that the SV-synapsin 1 interaction raises the overall packing of the condensate. Furthermore, two-color SMT and super-resolution imaging in living axons demonstrate that synapsin 1 drives the accumulation of SVs in boutons. Even the short intrinsically-disordered fragment of synapsin 1 was sufficient to restore the native SV motility pattern in synapsin triple knock-out animals. Thus, synapsin 1 condensation is sufficient to guarantee reliable confinement and motility of SVs, allowing for the formation of mesoscale domains of SVs at synapses in vivo

Crohn's disease activity index and Vienna classification - Is it worthwhile to calculate before surgery?

Background: Crohn's disease (CD) patients with increased disease activity may reveal an increased risk for perioperative complications. The `Crohn's disease activity index' (CDAI) and the `Vienna classification' (VC) were developed for standardized disease activity estimations. The significance of these scores to predict extent, type and early outcome of surgery in CD patients was analyzed. Methods: In 179 surgically treated CD patients, the CDAI and VC were assessed from a prospective database. Relations of the scores with CD risk factors, type, number, location and complications of surgery were analyzed. Results: VC behavior and location subtypes were associated with distinct types of surgery (i.e. `strictureplasty' in `stricturing disease', `colon surgery' in `colon involvement'), but not with surgery type and extent or outcome. Surgery extent (i.e. with 5 vs. 3 `surgical sites' 425 +/- 25 vs. 223.3 +/- 25) and complications (357.1 +/- 36.9 (with) vs. 244.4 +/- 13 (without)) were associated with elevated CDAI levels; however, nicotine abuse remained the only significant risk factor for perioperative complications after multiple logistic regression. Conclusion: The significance of VC or CDAI for predicting the extent of surgery or complications is limited. None of the tested variables except preoperative nicotine abuse influenced the likelihood for perioperative complications. Copyright (c) 2006 S. Karger AG, Base

ABCC1: a gateway for pharmacological compounds to the ischaemic brain

By preventing access of drugs to the CNS, the blood-brain barrier hampers developments in brain pharmacotherapy. Strong efforts are currently being made to identify drugs that accumulate more efficaciously in ischaemic brain tissue. We identified an ATP-binding cassette (ABC) transporter, ABCC1, which is expressed on the abluminal surface of the brain capillary endothelium and mildly downregulated in response to focal cerebral ischaemia, induced by intraluminal middle cerebral artery occlusion. In biodistribution studies we show that ABCC1 promotes the accumulation of known neuroprotective and neurotoxic compounds in the ischaemic and non-ischaemic brain, ABCC1 deactivation reducing tissue concentrations by up to two orders of magnitude. As such, ABCC1's expression and functionality in the brain differs from the liver, spleen and testis, where ABCC1 is strongly expressed on parenchymal cells, resulting -- in case of liver and testis -- in directed transport from the tissue into the blood. After focal cerebral ischaemia, ABCC1 deactivation abolished the efficacy of both neuroprotective and neurotoxic compounds. Our data indicate that ABCC1 acts as gateway for pharmacological compounds to the stroke brain. We suggest that the tailoring of compounds binding to abluminal but not luminal ABC transporters may facilitate stroke pharmacotherap

Tips to Advance Business Writing Skills at EFL Classes (Through the Example of "Letter of Complaint")

Writing is a creative communicative skill to express thoughts. It is cognitively complex, requires much practice and is best learned through experience. Writing is one of the most challenging, time-consuming tasks in acquiring a foreign language. To improve students’ writing skills and accuracy, a teacher should encourage writing-thinking, provide instructions and examples of good writing in the target language, and give feedback focusing both on error correction (cohesion) and organization of writing (clarity, idea development, coherence). This paper explores difficulties of the development of business writing skills and gives recommendations on writing a letter of complaint at English as a foreign language classes