Increased Reliability of Nuclear Magnetic Resonance Protein Structures by Consensus Structure Bundles

SummaryNuclear magnetic resonance (NMR) structures are represented by bundles of conformers calculated from different randomized initial structures using identical experimental input data. The spread among these conformers indicates the precision of the atomic coordinates. However, there is as yet no reliable measure of structural accuracy, i.e., how close NMR conformers are to the “true” structure. Instead, the precision of structure bundles is widely (mis)interpreted as a measure of structural quality. Attempts to increase precision often overestimate accuracy by tight bundles of high precision but much lower accuracy. To overcome this problem, we introduce a protocol for NMR structure determination with the software package CYANA, which produces, like the traditional method, bundles of conformers in agreement with a common set of conformational restraints but with a realistic precision that is, throughout a variety of proteins and NMR data sets, a much better estimate of structural accuracy than the precision of conventional structure bundles

Depressariinae of Madeira and the Azores Islands (Lepidoptera: Depressariidae)

Wir überprüfen und illustrieren die von Madeira und den Azoren bekannten Depressariinae. Folgende sechs Arten werden behandelt: Agonopterix scopariella (Heinemann, 1870), A. conciliatella (Rebel, 1892), A. vendettella (Chretien, 1908) (neu für Madeira), A. perezi Walsingham, 1908, Depressaria marcella Rebel, 1901 (neu für Madeira und die Azoren), und D. halophilella Chretien, 1908. Letztere ersetzt Depressaria ultimella Stainton, 1849 in der Liste der von Madeira nachgewiesenen Lepidoptera. Depressaria iliensis Rebel, 1936 ist ein Synonym von Agonopterix vendettella (Chretien, 1908) (syn. nov.). Depressaria halophilella ist neu für die Kanarischen Inseln. Neben kurzen Notizen zu jeder Art verweisen wir auf die zur richtigen Bestimmung entscheidenden Merkmale und diskutieren frühere Fehlbestimmungen bei Depessariinae von Madeira.We review and illustrate the species of Depressariinae known from Madeira and the Azores Islands. The following six species are treated: Agonopterix scopariella (Heinemann, 1870), A. conciliatella (Rebel, 1892), A. vendettella (Chretien, 1908) (new to Madeira), A. perezi Walsingham, 1908, Depressaria marcella Rebel, 1901 (new to Madeira and the Azores), and D. halophilella Chretien, 1908. The latter replaces Depressaria ultimella Stainton, 1849 in the list of Lepidoptera found in Madeira. Depressaria iliensis Rebel, 1936 is a synonym of Agonopterix vendettella (Chretien, 1908) (syn. nov.). Depressaria halophilella is new to the Canary Islands. We provide brief notes on each of the species and give short diagnoses for correctly identifying them, and we discuss previous misidentifications of Madeiran Depressariinae

Risk-Adjusted Capitation Payments: How Well Do Principal Inpatient Diagnosis-Based Models Work in the German Situation? Results From a Large Data Set

The Risk Adjustment Reform Act of 2001 mandates that a health-status-based risk adjustment mechanism has to be implemented in Germany's Statutory Health Insurance system by January 1, 2007. German parliament decided this as with the existing demographic risk adjustment model, that means there is cream skimming and sickness funds hesitate to engage in managing care for the chronical ill. Four approaches were used to test the feasibility of incorporating use of diagnosis as a proxy measure for health status in a German risk adjustment formula. The first two models used standard demographic and socio-demographic variables. The other two models are separately incorporating a simple binary indicator for hospitilization and Hierarchical Coexisting Conditions (HCCs: DxCG® Risk Adjustment Software Release 6.1) using inpatient diagnosis. Age and gender grouping accounted for 3.2% of the variation in total expenditures for concurrent as well as prospective models. The current German risk adjusters age, sex, and invalidity status account for 5.1% and 4.5% of the variance in the concurrent and prospective models respectively. There are substantial increases in explanatory power, however, when HCCs are added. Age, gender, invalidity status and HCC covariates explain about 37% of the variations of the total expenditures in a concurrent model and roughly 12% of the variations of total expenditures in a prospective model. For high-risk (cost) groups, substantial underprediction remains; conversely, for the low-risk group, represented by enrolees who did not show any health care expense in the base year, all of the models over-predict expenditure. --Risk Adjustment,HCCs,Germany

Evolutionary Relationships and Functional Diversity of Plant Sulfate Transporters

Sulfate is an essential nutrient cycled in nature. Ion transporters that specifically facilitate the transport of sulfate across the membranes are found ubiquitously in living organisms. The phylogenetic analysis of known sulfate transporters and their homologous proteins from eukaryotic organisms indicate two evolutionarily distinct groups of sulfate transport systems. One major group named Tribe 1 represents yeast and fungal SUL, plant SULTR, and animal SLC26 families. The evolutionary origin of SULTR family members in land plants and green algae is suggested to be common with yeast and fungal SUL and animal anion exchangers (SLC26). The lineage of plant SULTR family is expanded into four subfamilies (SULTR1–SULTR4) in land plant species. By contrast, the putative SULTR homologs from Chlorophyte green algae are in two separate lineages; one with the subfamily of plant tonoplast-localized sulfate transporters (SULTR4), and the other diverged before the appearance of lineages for SUL, SULTR, and SLC26. There also was a group of yet undefined members of putative sulfate transporters in yeast and fungi divergent from these major lineages in Tribe 1. The other distinct group is Tribe 2, primarily composed of animal sodium-dependent sulfate/carboxylate transporters (SLC13) and plant tonoplast-localized dicarboxylate transporters (TDT). The putative sulfur-sensing protein (SAC1) and SAC1-like transporters (SLT) of Chlorophyte green algae, bryophyte, and lycophyte show low degrees of sequence similarities with SLC13 and TDT. However, the phylogenetic relationship between SAC1/SLT and the other two families, SLC13 and TDT in Tribe 2, is not clearly supported. In addition, the SAC1/SLT family is absent in the angiosperm species analyzed. The present study suggests distinct evolutionary trajectories of sulfate transport systems for land plants and green algae

Redescription of the alpine Incurvaria stangei Rebel, 1903 (Lepidoptera, Incurvariidae), reinstated from Prodoxidae

Incurvaria stangei Rebel, 1903 revised combination, placed without justification in Prodoxidae, is redescribed and transferred back to the Incurvariidae. Male and female genitalia of this south-eastern alpine endemic species are illustrated for the first time. DNA barcode sequences as well as morphological traits support the revised family assignment

Incurvaria pirinella sp. nov., a new species of the vetulella species-group (Lepidoptera, Incurvariidae) from Bulgaria, with release of DNA barcodes for European species of Incurvaria

Incurvaria pirinella Junnilainen, Kaitila & Mutanen, sp. nov. is described from Bulgaria based on specimens collected by netting and artificial light from several low-elevation localities in Bulgaria. The species is morphologically and genetically most similar to I. triglavensis Hauder, 1912. Differences between these two species are present in external appearance and genitalia of both sexes. Additionally, I. pirinella shows a distance of 4.74% to its nearest neighbour I. triglavensis in the standard DNA barcoding marker (COI-5P). We provide preliminary observations of phylogenetic affinities of European Incurvaria and briefly discuss habitat preferences of some species. All species have distinct barcodes with minimum K2P divergences between species averaging 7.05% (range 1.2–12.8%). A world checklist of Incurvaria Haworth, 1828 is provided and DNA barcodes for all European species are here released. Finally, we document morphological variation in male genitalia within I. triglavensis Hauder, 1912

Automated solid-state NMR resonance assignment of protein microcrystals and amyloids

Solid-state NMR is an emerging structure determination technique for crystalline and non-crystalline protein assemblies, e.g., amyloids. Resonance assignment constitutes the first and often very time-consuming step to a structure. We present ssFLYA, a generally applicable algorithm for automatic assignment of protein solid-state NMR spectra. Application to microcrystals of ubiquitin and the Ure2 prion C-terminal domain, as well as amyloids of HET-s(218-289) and α-synuclein yielded 88-97% correctness for the backbone and side-chain assignments that are classified as self-consistent by the algorithm, and 77-90% correctness if also assignments classified as tentative by the algorithm are include

PSMA-positive nodal recurrence in prostate cancer

Purpose This analysis compares salvage lymph node dissection (SLND) to salvage lymph node radiotherapy (SLNRT) of 68Ga-PSMA PET-positive nodal recurrences after radical prostatectomy (RPE). Methods A total of 67 SLNRT and 33 SLND consecutive patients with pelvic and/or para-aortic nodal recurrences after RPE were retrospectively analyzed. Biochemical recurrence-free survival rates (bRFS; PSA <0.2 ng/mL) were calculated according to Kaplan–Meier and survival curves were compared using the log rank test. For multivariable analysis, binary logistic regression analysis was performed (p < 0.05). Results Median follow-up was 17 months (range, 6–53 months) in SLND patients and 31 months (range, 3–56 months) in SLNRT patients (p = 0.027). SLNRT patients had significantly more tumours of pT3 and pT4 category (82% vs. 67%; p = 0.006), pathologically involved lymph nodes (45% vs. 27%; p = 0.001) and positive surgical margins (54% vs. 12%; p = 0.001) at time of RPE than SLND patients. PSA persistence after RPE was significantly more frequently observed in the SLNRT cohort (73% vs. 27%; p = 0.001). There was no significant difference in the distribution of PET-positive lymph nodes. Median PSA before SLND was higher than before SLNRT (3.07 ng/ml vs. 1.3 ng/ml; p = 0.393). The 2‑year bRFS was significantly higher in the SLNRT vs. the SLND cohort (92% vs. 30%; p = 0.001) with lower rates of distant metastases (21% vs. 52%; p = 0.002) and secondary treatments (5% vs. 39%; p = 0.011) irrespective of ongoing androgen deprivation therapy at last contact. In multivariable analysis, SLNRT was significantly associated with prolonged bRFS (regression coefficient 1.436, hazard ratio 4.204, 95% CI 1.789–9.878; p = 0.001). Conclusion Based on this retrospective study SLNRT might be the preferred treatment option for patients with nodal recurrence after previous RPE