Small Changes in the Primary Structure of Transportan 10 Alter the Thermodynamics and Kinetics of its Interaction with Phospholipid Vesicles

ABSTRACT: The kinetics and thermodynamics of binding of transportan 10 (tp10) and four of its variants to phospholipid vesicles, and the kinetics of peptide-induced dye efflux, were compared. Tp10 is a 21-residue, amphipathic, cationic, cell-penetrating peptide similar to helical antimicrobial peptides. The tp10 variants examined include amidated and free peptides, and replacements of tyrosine by tryptophan. Carboxy-terminal amidation or substitution of tryptophan for tyrosine enhance binding and activity. The Gibbs energies of peptide binding to membranes determined experimentally and calculated from the interfacial hydrophobicity scale are in good agreement. The Gibbs energy for insertion into the bilayer core was calculated using hydrophobicity scales of residue transfer from water to octanol and to the membrane/ water interface. Peptide-induced efflux becomes faster as the Gibbs energies for binding and insertion of the tp10 variants decrease. If anionic lipids are included, binding and efflux rate increase, as expected because all tp10 variants are cationic and an electrostatic component is added. Whether the most important effect of peptide amidation is the change in charge or an enhancement of helical structure, however, still needs to be established. Nevertheless, it is clear that the changes in efflux rate reflect the differences in the thermodynamics of binding and insertion of the free and amidated peptide groups. We have recently reported a detailed investigation (1) o

Association between high-dose erythropoiesis-stimulating agents, inflammatory biomarkers, and soluble erythropoietin receptors

<p>Abstract</p> <p>Background</p> <p>High-dose erythropoiesis-stimulating agents (ESA) for anemia of chronic kidney disease (CKD) have been associated with adverse clinical outcomes and do not always improve erythropoiesis. We hypothesized that high-dose ESA requirement would be associated with elevated inflammatory biomarkers, decreased adipokines, and increased circulating, endogenous soluble erythropoietin receptors (sEpoR).</p> <p>Methods</p> <p>A cross-sectional cohort of anemic 32 CKD participants receiving ESA were enrolled at a single center and cytokine profiles, adipokines, and sEpoR were compared between participants stratified by ESA dose requirement (usual-dose darbepoetin-α (< 1 μg/kg/week) and high-dose (≥1 μg/kg/week)).</p> <p>Results</p> <p>Baseline characteristics were similar between groups; however, hemoglobin was lower among participants on high-dose (1.4 μg/kg/week) vs usual-dose (0.5 μg/kg/week) ESA.</p> <p>In adjusted analyses, high-dose ESA was associated with an increased odds for elevations in c-reactive protein and interleukin-6 (p < 0.05 for both). There was no correlation between high-dose ESA and adipokines. Higher ESA dose correlated with higher levels of sEpoR (r_s= 0.39, p = 0.03). In adjusted analyses, higher ESA dose (per μcg/kg/week) was associated with a 53% greater odds of sEpoR being above the median (p < 0.05).</p> <p>Conclusion</p> <p>High-dose ESA requirement among anemic CKD participants was associated with elevated inflammatory biomarkers and higher levels of circulating sEpoR, an inhibitor of erythropoiesis. Further research confirming these findings is warranted.</p> <p>Trial registration</p> <p>Clinicaltrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00526747">NCT00526747</a></p

Population structure of the predatory mite Neoseiulus womersleyi in a tea field based on an analysis of microsatellite DNA markers

The predatory mite Neoseiulus womersleyi (Schicha) (Acari: Phytoseiidae) is an important natural enemy of the Kanzawa spider mite, Tetranychus kanzawaki Kishida (Acari: Tetranychidae), in tea fields. Attraction and preservation of natural enemies by habitat management to reduce the need for acaricide sprays is thought to enhance the activity of N. womersleyi. To better conserve N. womersleyi in the field, however, it is essential to elucidate the population genetic structure of this species. To this end, we developed ten microsatellite DNA markers for N. womersleyi. We then evaluated population structure of N. womersleyi collected from a tea field, where Mexican sunflower, Tithonia rotundifolia (Mill.), was planted to preserve N. womersleyi. Seventy-seven adult females were collected from four sites within 200 m. The fixation indexes FST among subpopulations were not significantly different. The kinship coefficients between individuals did not differ significantly within a site as a function of the sampling dates, but the coefficients gradually decreased with increasing distance. Bayesian clustering analysis revealed that the population consisted of three genetic clusters, and that subpopulations within 100 m, including those collected on T. rotundifolia, were genetically similar to each other. Given the previously observed population dynamics of N. womersleyi, it appears that the area inhabited by a given cluster of the mite did not exceed 100 m. The estimation of population structure using microsatellite markers will provide valuable information in conservation biological control

Het nemen van beslissingen door volwassenen met ADHD:Een systematisch literatuuronderzoek

Personen met aandachtstekortstoornis met hyperactiviteit (ADHD) hebben een grotere kans om minder goede (levens)beslissingen te nemen en om risicovolle activiteiten te ondernemen dan personen zonder ADHD. Mogelijk komt dit doordat de kenmerken van ADHD van invloed zijn op het besluitvormingsproces. Hoewel beslissingsproblematiek reeds uitgebreid is onderzocht bij kinderen en adolescenten met ADHD, is er nog relatief weinig bekend over de besluitvorming van volwassenen met ADHD. Om die reden was het doel van dit literatuuronderzoek de aard en omvang van eventuele tekorten in het besluitvormingsproces van volwassenen met ADHD vast te stellen. Hiertoe is de bestaande literatuur, waarin de prestatie van volwassenen met ADHD op beslissingstaken werd vergeleken met de prestatie van een gezonde controlegroep, systematisch doorzocht, waartoe de databases PsycINFO, MEDLINE en PubMed zijn geraadpleegd. In totaal werden er 31 studies geïncludeerd. In de meerderheid van de studies (i.e. 55 %) weken de prestaties van volwassenen met ADHD af op een of meer van de gebruikte beslissingstaken in vergelijking met de controlegroep(en). Dit literatuuronderzoek levert daarmee voorzichtig bewijs voor het bestaan van verschillen in het besluitvormingsproces tussen gezonde individuen en volwassenen met ADHD. De grote inconsistentie in de bevindingen wordt deels verklaard door de verscheidenheid aan domeinen van besluitvorming die werden onderzocht, de comorbide stoornissen van de participanten en het medicatiegebruik in de ADHD-groepen. Het literatuuronderzoek besluit met een bespreking van de implicaties die de bevindingen hebben voor theorieën over de onderliggende mechanismen van ADHD

Effective treatment of pelvic lymphocele by lymphaticovenular anastomosis.

OBJECTIVE: Pelvic lymphocele can be a severe complication associated with surgical procedures such as pelvic lymphadenectomy. Lymphaticovenular anastomosis (LVA) is increasing in popularity as a surgical treatment for lymphedema. The aim of this study was to evaluate whether LVA is an effective treatment for lymphocele, which is caused by an obstruction of the lymphatic flow in a manner similar to the development of lymphedema. METHODS: Eleven female patients, who presented with lymphocele, were treated with LVA. Before the operation, 3 of them were treated with a percutaneous catheter. Lymphocele size and the volume of daily drainage were measured before and after LVA. RESULTS: The lymphocele was completely resolved in 6 patients and partially resolved in the remaining 5 patients. The mean size of the pelvic lymphocele changed from 400 ml (range 50-1050 ml) to 43 ml (range 0-120 ml) (P&lt;0.01). In the 3 patients who had percutaneous drainage catheters, the volume of fluid drained decreased from 340 ml/day to 20 ml/day after LVA. CONCLUSIONS: Our technique is minimally invasive and is performed under local anesthesia. LVA is effective regardless of the size of the lymphocele. Therefore, LVA should be considered as a therapy for lymphocele because of its low invasiveness and its effectiveness in re-establishing circulation of lymphatic flow. Further studies should be performed to compare LVA with other minimally invasive techniques, such as percutaneous catheter and sclerotherapy

Curated genome annotation of Oryza sativa ssp. japonica and comparative genome analysis with Arabidopsis thaliana

We present here the annotation of the complete genome of rice Oryza sativa L. ssp. japonica cultivar Nipponbare. All functional annotations for proteins and non-protein-coding RNA (npRNA) candidates were manually curated. Functions were identified or inferred in 19,969 (70%) of the proteins, and 131 possible npRNAs (including 58 antisense transcripts) were found. Almost 5000 annotated protein-coding genes were found to be disrupted in insertional mutant lines, which will accelerate future experimental validation of the annotations. The rice loci were determined by using cDNA sequences obtained from rice and other representative cereals. Our conservative estimate based on these loci and an extrapolation suggested that the gene number of rice is ∼32,000, which is smaller than previous estimates. We conducted comparative analyses between rice and Arabidopsis thaliana and found that both genomes possessed several lineage-specific genes, which might account for the observed differences between these species, while they had similar sets of predicted functional domains among the protein sequences. A system to control translational efficiency seems to be conserved across large evolutionary distances. Moreover, the evolutionary process of protein-coding genes was examined. Our results suggest that natural selection may have played a role for duplicated genes in both species, so that duplication was suppressed or favored in a manner that depended on the function of a gene