Biofunctional Nanodot Arrays in Living Cells Uncover Synergistic Co-Condensation of Wnt Signalodroplets

Qualitative and quantitative analysis of transient signaling platforms in the plasma membrane has remained a key experimental challenge. Here, biofunctional nanodot arrays (bNDAs) are developed to spatially control dimerization and clustering of cell surface receptors at the nanoscale. High-contrast bNDAs with spot diameters of ≈300 nm are obtained by capillary nanostamping of bovine serum albumin bioconjugates, which are subsequently biofunctionalized by reaction with tandem anti-green fluorescence protein (GFP) clamp fusions. Spatially controlled assembly of active Wnt signalosomes is achieved at the nanoscale in the plasma membrane of live cells by capturing the co-receptor Lrp6 into bNDAs via an extracellular GFP tag. Strikingly, co-recruitment is observed of co-receptor Frizzled-8 as well as the cytosolic scaffold proteins Axin-1 and Disheveled-2 into Lrp6 nanodots in the absence of ligand. Density variation and the high dynamics of effector proteins uncover highly cooperative liquid-liquid phase separation (LLPS)-driven assembly of Wnt "signalodroplets" at the plasma membrane, pinpointing the synergistic effects of LLPS for Wnt signaling amplification. These insights highlight the potential of bNDAs for systematically interrogating nanoscale signaling platforms and condensation at the plasma membrane of live cells

Meta-All: a system for managing metabolic pathway information

BACKGROUND: Many attempts are being made to understand biological subjects at a systems level. A major resource for these approaches are biological databases, storing manifold information about DNA, RNA and protein sequences including their functional and structural motifs, molecular markers, mRNA expression levels, metabolite concentrations, protein-protein interactions, phenotypic traits or taxonomic relationships. The use of these databases is often hampered by the fact that they are designed for special application areas and thus lack universality. Databases on metabolic pathways, which provide an increasingly important foundation for many analyses of biochemical processes at a systems level, are no exception from the rule. Data stored in central databases such as KEGG, BRENDA or SABIO-RK is often limited to read-only access. If experimentalists want to store their own data, possibly still under investigation, there are two possibilities. They can either develop their own information system for managing that own data, which is very time-consuming and costly, or they can try to store their data in existing systems, which is often restricted. Hence, an out-of-the-box information system for managing metabolic pathway data is needed. RESULTS: We have designed META-ALL, an information system that allows the management of metabolic pathways, including reaction kinetics, detailed locations, environmental factors and taxonomic information. Data can be stored together with quality tags and in different parallel versions. META-ALL uses Oracle DBMS and Oracle Application Express. We provide the META-ALL information system for download and use. In this paper, we describe the database structure and give information about the tools for submitting and accessing the data. As a first application of META-ALL, we show how the information contained in a detailed kinetic model can be stored and accessed. CONCLUSION: META-ALL is a system for managing information about metabolic pathways. It facilitates the handling of pathway-related data and is designed to help biochemists and molecular biologists in their daily research. It is available on the Web at and can be downloaded free of charge and installed locally

Expression of Prostate-Specific Membrane Antigen (PSMA) on Biopsies Is an Independent Risk Stratifier of Prostate Cancer Patients at Time of Initial Diagnosis

Background: Stratifying prostate cancer (PCa) patients into risk groups at time of initial diagnosis enabling a risk-adapted disease management is still a major clinical challenge. Existing studies evaluating the prognostic potential of PSMA (prostate-specific membrane antigen) for PCa were performed on radical prostatectomy specimens (RPE), i.e., decision making for disease management was already completed at time of sample analysis. Aim of our study was to assess the prognostic value of PSMA expression for PCa patients on biopsies at time of initial diagnosis.Methods: PSMA expression was assessed by immunohistochemistry on 294 prostate biopsies with corresponding RPE, 621 primary tumor foci from 242 RPE, 43 locally advanced or recurrent tumors, 34 lymph node metastases, 78 distant metastases and 52 benign prostatic samples. PSMA expression was correlated with clinico-pathologic features. Primary endpoint was recurrence free survival. Other clinicopathologic features included WHO/ISUP grade groups, PSA serum level, TNM-stage, and R-status. Chi-square test, ANOVA-analyses, Cox-regression, and log-rank tests were performed for statistical analyses.Results: High PSMA expression on both biopsy and RPE significantly associates with a higher risk of disease recurrence following curative surgery. The 5-year-recurrence free survival rates were 88.2, 74.2, 67.7 and 26.8% for patients exhibiting no, low, medium, or high PSMA expression on biopsy, respectively. High PSMA expression on biopsy was significant in multivariate analysis predicting a 4-fold increased risk of disease recurrence independently from established prognostic markers. PSMA significantly increases during PCa progression.Conclusion: PSMA is an independent prognostic marker on biopsies at time of initial diagnosis and can predict disease recurrence following curative therapy for PCa. Our study proposes the application of the routinely used IHC marker PSMA for outcome prediction and decision making in risk-adapted PCa management on biopsies at time of initial diagnosis

Alß Der Weyland Hoch-Ehrwürdige, in Gott Andächtige, und Hochgelahrte Herr, Herr Heinrich Gottlieb Schneider, Der H. Schrifft hochberühmter Doctor, Hoch-Fürstl. Sachsen-Merseburgischer Hochverordneter Consistorial-Assessor, Stiffts-Superintendens, und des Gymnasii Inspector, ... am 26. Julii a. c. ... sanfft und selig entschlaffen, und Demselben, am 22. Augusti darauf, in hiesiger ... Schloß- und Dom-Kirche zum wohlverdienten Ruhm, und Dessen ... hinterlassenen Frau Wittbe und Kindern zum Trost, eine Gedächtniß-Predigt gehalten wurde, Wolten ... hertzl. Mitleiden ... bezeugen Sämtliche Prediger und Diener des göttl. Worts bey denen Kirchen in der Hochfürstl. Sächß. Stiffts- und Residenz-Stadt Merseburg

Enth. 7 Trauergedichte der BeiträgerErscheinungsjahr bestimmt nach Sterbejah

M. Ernst Christian Philippi, Past. zu St. Ulrich, und des Gymn. Scholarchæ, Gründliche Widerlegung Eines sehr grossen Und doch auch, in praxi, leider! gantz gemeinen, Jrrthums vieler Lutheraner, Von ihrem, Vor wahr gehaltenen Hertzens- An sich selbst aber, Falschen, todten und verdammlichen Wahn- Heuchel- Schein- und Mund-Glauben: Geschehen in einer Predigt, Am XXI. Sonnt. nach Trinit. 1709. Uber Joh. IV. 47. 54. : Welche darauf, Nach zumahl ergangenem Ersuchen, Mit hinzu gethanen Zeugnissen Aus unseren Symbolischen Glaubens-Büchern, Luthero, und anderen Evangelischen Lehrern, Unter der Zuschrifft An seine ietzige, und vormahligen beyden Gemeinden Zu Dreßden und Liegnitz, Sonderlich zu Deroselben Erbauung, Zum Druck ist befördert worden ...

Autopsie nach Ex. der ULB Sachsen-AnhaltVorlageform des Erscheinungsvermerks: Halle, gedruckt und verlegt von Johann Montag, Univ. Buchdr. 1710

Christo Benedicente & Indultu atque Authoritate Magnifici ICtorum Ordinis, Disputationem Iuridicam De Querela Non-Numeratae Pecuniae contra Apocham movenda, Sub Praesidio Friderici Philippi ... Ad d. X. Aprilis Anno M.DC.LXXXIV. In Inclyta ac Florentissima hac Philurea ... P.P. Christianus Bütnerus, Hirschb. Sil. Autor

Nicht identisch mit VD17 12:149812B (dort ohne Widmung auf der Rückseite des Titelblatts

Dispvtatio Jvridica De Aldvlterio Desponsatorvm

Qvam ... Praeside Dn. Friderico Philippo, ... P. P. Christianvs Meltzer, Ciza-Misnicus. D. XXIX. Jan. Anno MDCXCIIAutopsie nach Ex. der ULB DüsseldorfVorlageform der Veröffentlichungsangabe: Lipsiae Litteris Schedianis. Recusa Anno 1730.Universität Leipzig, Dissertation, 29. Jan. 169