The Wettability of Titanium Diboride by Molten Aluminum Drops

Titanium diboride is widely accepted to be completely wet by liquid aluminum, yet few published wetting studies demonstrate this behavior, and reported contact angles vary widely. Sessile drop substrates from four different sources were selected and their microstructures and chemistries characterized. the results of sessile drop experiments using four techniques to modify oxide film behavior were compared. the Al-TiB2 interfaces were examined in metallographic sections or after chemical removal of the Al drop. Al wets a material containing 5.5 wt% Ni in vacuum experiments before the hold temperature of 1025°C is reached. the other TiB2 substrates are completely wet by Al at 1025°C, but only after prolonged holds under vacuum. Elimination of boron oxide from the TiB2 surface leads to a spreading condition. the role of the substrate microstructure (porosity, grain size, roughness, and carbon content) in altering the wetting kinetics is discussed. © 2005 Springer Science + Business Media, Inc

Ganzheitliche Untersuchungsmethoden zur Erfassung und Prüfung der Qualität ökologischer Lebensmittel: Stand der Entwicklung und Validierung

In dem wachsenden Markt ökologischer Lebensmittel werden Methoden zur produktorientierten Qualitätserfassung gefordert. Dabei geht es u.a. um die Unterscheidung von Produkten aus unterschiedlichen Anbauverfahren. Die Ziele des Projektes waren daher: 1. ausgewählte ganzheitliche Methoden gemäß ISO 17025 zu validieren, d.h. Laborprozesse festzulegen, sowie Einflussgrößen und Verfahrensmerkmale zu bestimmen, 2. zu testen, ob diese Verfahren eine Differenzierung von definierten Proben statistisch abgesichert zeigen können. . Diese Ziele konnten erreicht werden. Es wurde bestätigt, dass einige der Methoden auf Grundlage dokumentierter Prozeduren Lebensmittel aus definierten Anbauversuchen (u.a. aus dem DOK-Versuch am FIBL/CH) reproduzierbar unterscheiden können. Die Koordination und die Validierung der Kupferchlorid-Kristallisation sowie die Messung der Polyphenole lag bei der Universität Kassel, FG Ökologische Lebensmittelqualität und Ernährungskultur. Die KWALIS GmbH, Dipperz, validierte die Fluoreszenz-Anregungsspektroskopie und die Bestimmung des Physiologischen Aminosäurestatus, die EQC GmbH, Weidenbach die elektrochemischen Messungen. Dr. Kromidas, Saarbrücken übernahm die Beratung der Validierungsprozeduren. . An Blindproben wurde untersucht, ob die Verfahren für Weizen- und Möhrenproben aus definierten Anbau- und Sortenversuchen geeignet sind (Fragestellung der Validierung). Die Proben wurden von unabhängiger Stelle (OEL-FAL, Trenthorst) codiert. Die Proben wurden gleichzeitig an alle Partner versandt; dadurch konnten die Methoden auch untereinander verglichen werden. Die Methoden Kupferchlorid-Kristallisation, Fluoreszenz-Anregungsspektroskopie und Physiologischer Aminosäurestatus sind für die Fragestellung geeignet. Mit allen drei Methoden konnten die Proben differenziert und gruppiert werden. Darüber hinaus konnten mit der Fluoreszenz-Anregungsspektroskopie und über den physiologischen Aminosäurestatus die Proben auch den Anbauweisen richtig zugeordnet werden. Allerdings ist damit noch keine Aussage über die Fähigkeit dieser Verfahren möglich, generell Proben aus ökologischer und konventioneller Herkunft zu unterscheiden. Dafür sind weitere Untersuchungen sowohl an Proben definierter Herkunft als auch an Marktproben notwendig

A systematic, large-scale comparison of transcription factor binding site models

Background The modelling of gene regulation is a major challenge in biomedical research. This process is dominated by transcription factors (TFs) and mutations in their binding sites (TFBSs) may cause the misregulation of genes, eventually leading to disease. The consequences of DNA variants on TF binding are modelled in silico using binding matrices, but it remains unclear whether these are capable of accurately representing in vivo binding. In this study, we present a systematic comparison of binding models for 82 human TFs from three freely available sources: JASPAR matrices, HT-SELEX-generated models and matrices derived from protein binding microarrays (PBMs). We determined their ability to detect experimentally verified “real” in vivo TFBSs derived from ENCODE ChIP-seq data. As negative controls we chose random downstream exonic sequences, which are unlikely to harbour TFBS. All models were assessed by receiver operating characteristics (ROC) analysis. Results While the area- under-curve was low for most of the tested models with only 47 % reaching a score of 0.7 or higher, we noticed strong differences between the various position-specific scoring matrices with JASPAR and HT-SELEX models showing higher success rates than PBM-derived models. In addition, we found that while TFBS sequences showed a higher degree of conservation than randomly chosen sequences, there was a high variability between individual TFBSs. Conclusions Our results show that only few of the matrix-based models used to predict potential TFBS are able to reliably detect experimentally confirmed TFBS. We compiled our findings in a freely accessible web application called ePOSSUM (http:/mutationtaster.charite.de/ePOSSUM/) which uses a Bayes classifier to assess the impact of genetic alterations on TF binding in user-defined sequences. Additionally, ePOSSUM provides information on the reliability of the prediction using our test set of experimentally confirmed binding sites

Occupancy maps of 208 chromatin-associated proteins in one human cell type

Transcription factors are DNA-binding proteins that have key roles in gene regulation. Genome-wide occupancy maps of transcriptional regulators are important for understanding gene regulation and its effects on diverse biological processes. However, only a minority of the more than 1,600 transcription factors encoded in the human genome has been assayed. Here we present, as part of the ENCODE (Encyclopedia of DNA Elements) project, data and analyses from chromatin immunoprecipitation followed by high-throughput sequencing (ChIP–seq) experiments using the human HepG2 cell line for 208 chromatin-associated proteins (CAPs). These comprise 171 transcription factors and 37 transcriptional cofactors and chromatin regulator proteins, and represent nearly one-quarter of CAPs expressed in HepG2 cells. The binding profiles of these CAPs form major groups associated predominantly with promoters or enhancers, or with both. We confirm and expand the current catalogue of DNA sequence motifs for transcription factors, and describe motifs that correspond to other transcription factors that are co-enriched with the primary ChIP target. For example, FOX family motifs are enriched in ChIP–seq peaks of 37 other CAPs. We show that motif content and occupancy patterns can distinguish between promoters and enhancers. This catalogue reveals high-occupancy target regions at which many CAPs associate, although each contains motifs for only a minority of the numerous associated transcription factors. These analyses provide a more complete overview of the gene regulatory networks that define this cell type, and demonstrate the usefulness of the large-scale production efforts of the ENCODE Consortium

Similarity Regression predicts evolution of transcription factor sequence specificity

Transcription factor (TF) binding specificities (motifs) are essential to the analysis of noncoding DNA and gene regulation. Accurate prediction of the sequence specificities of TFs is critical, because the hundreds of sequenced eukaryotic genomes encompass hundreds of thousands of TFs, and assaying each is currently infeasible. There is ongoing controversy regarding the efficacy of motif prediction methods, as well as the degree of motif diversification among related species. Here, we describe Similarity Regression (SR), a significantly improved method for predicting motifs. We have updated and expanded the Cis-BP database using SR, and validate its predictive capacity with new data from diverse eukaryotic TFs. SR inherently quantifies TF motif evolution, and we show that previous claims of near-complete conservation of motifs between human and Drosophila are grossly inflated, with nearly half the motifs in each species absent from the other. We conclude that diversification in DNA binding motifs is pervasive, and present a new tool and updated resource to study TF diversity and gene regulation across eukaryotes

Sox17 and ß-catenin co-occupy Wnt-responsive enhancers to govern the endoderm gene regulatory network

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Mukherjee, S., Chaturvedi, P., Rankin, S. A., Fish, M. B., Wlizla, M., Paraiso, K. D., MacDonald, M., Chen, X., Weirauch, M. T., Blitz, I. L., Cho, K. W. Y., & Zorn, A. M. Sox17 and ß-catenin co-occupy Wnt-responsive enhancers to govern the endoderm gene regulatory network. Elife, 9, (2020): e58029, doi:10.7554/eLife.58029.Lineage specification is governed by gene regulatory networks (GRNs) that integrate the activity of signaling effectors and transcription factors (TFs) on enhancers. Sox17 is a key transcriptional regulator of definitive endoderm development, and yet, its genomic targets remain largely uncharacterized. Here, using genomic approaches and epistasis experiments, we define the Sox17-governed endoderm GRN in Xenopus gastrulae. We show that Sox17 functionally interacts with the canonical Wnt pathway to specify and pattern the endoderm while repressing alternative mesectoderm fates. Sox17 and β-catenin co-occupy hundreds of key enhancers. In some cases, Sox17 and β-catenin synergistically activate transcription apparently independent of Tcfs, whereas on other enhancers, Sox17 represses β-catenin/Tcf-mediated transcription to spatially restrict gene expression domains. Our findings establish Sox17 as a tissue-specific modifier of Wnt responses and point to a novel paradigm where genomic specificity of Wnt/β-catenin transcription is determined through functional interactions between lineage-specific Sox TFs and β-catenin/Tcf transcriptional complexes. Given the ubiquitous nature of Sox TFs and Wnt signaling, this mechanism has important implications across a diverse range of developmental and disease contexts.Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD073179) Ken WY Cho Aaron M Zorn National Institute of Diabetes and Digestive and Kidney Diseases (P30DK078392) Aaron M Zorn Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD093363) Aaron M Zor

Microcrystals coating the wing membranes of a living insect (Psocoptera: Psyllipsocidae) from a Brazilian cave

Two specimens of Psyllipsocus yucatan with black wings were found with normal individuals of this species on guano piles produced by the common vampire bat Desmodus rotundus. These specimens have both pairs of wings dorsally and ventrally covered by a black crystalline layer. They did not exhibit any signs of reduced vitality in the field and their morphology is completely normal. This ultrathin (1.5 µm) crystalline layer, naturally deposited on a biological membrane, is documented by photographs, SEM micrographs, energy dispersive spectroscopy (EDS) and X-ray diffractometry (XRD). The crystalline deposit contains iron, carbon and oxygen, but the mineral species could not be identified. Guano probably played a role in its formation; the presence of iron may be a consequence of the excretion of iron by the common vampire bat. This enigmatic phenomenon lacks obvious biological significance but may inspire bionic applications. Nothing similar has ever been observed in terrestrial arthropods

Gli3 utilizes Hand2 to synergistically regulate tissue-specific transcriptional networks.

Despite a common understanding that Gli TFs are utilized to convey a Hh morphogen gradient, genetic analyses suggest craniofacial development does not completely fit this paradigm. Using the mouse model (Mus musculus), we demonstrated that rather than being driven by a Hh threshold, robust Gli3 transcriptional activity during skeletal and glossal development required interaction with the basic helix-loop-helix TF Hand2. Not only did genetic and expression data support a co-factorial relationship, but genomic analysis revealed that Gli3 and Hand2 were enriched at regulatory elements for genes essential for mandibular patterning and development. Interestingly, motif analysis at sites co-occupied by Gli3 and Hand2 uncovered mandibular-specific, low-affinity, \u27divergent\u27 Gli-binding motifs (dGBMs). Functional validation revealed these dGBMs conveyed synergistic activation of Gli targets essential for mandibular patterning and development. In summary, this work elucidates a novel, sequence-dependent mechanism for Gli transcriptional activity within the craniofacial complex that is independent of a graded Hh signal

Identification of a regulatory pathway governing TRAF1 via an arthritis-associated non-coding variant

TRAF1/C5 was among the first loci shown to confer risk for inflammatory arthritis in the absence of an associated coding variant, but its genetic mechanism remains undefined. Using Immunochip data from 3,939 patients with juvenile idiopathic arthritis (JIA) and 14,412 control individuals, we identified 132 plausible common non-coding variants, reduced serially by single-nucleotide polymorphism sequencing (SNP-seq), electrophoretic mobility shift, and luciferase studies to the single variant rs7034653 in the third intron of TRAF1. Genetically manipulated experimental cells and primary monocytes from genotyped donors establish that the risk G allele reduces binding of Fos-related antigen 2 (FRA2), encoded by FOSL2, resulting in reduced TRAF1 expression and enhanced tumor necrosis factor (TNF) production. Conditioning on this JIA variant eliminated attributable risk for rheumatoid arthritis, implicating a mechanism shared across the arthritis spectrum. These findings reveal that rs7034653, FRA2, and TRAF1 mediate a pathway through which a non-coding functional variant drives risk of inflammatory arthritis in children and adults