Effect of Temperature and Cell Viability on Uranium Biomineralization by the Uranium Mine Isolate Penicillium simplicissimum

This work was supported by the Bundesministerium fur Bildung und Forschung (BMBF) grant no. 02NUK030 F (TransAqua). Funding of TEM TALOS at the HZDR Ion Beam Center TEM facilities by the German Federal Ministry of Education and Research (BMBF grant no. 03SF0451) in the framework of HEMCP is acknowledged. The open-access publication fees were kindly covered by the library of the Helmholtz-Zentrum Dresden-Rossendorf (Germany). SS was partially supported during his research stay in Granada (Spain) by the Talent Acquisition Program ("Programa de Captacion de Talento en Grados Universitarios"), funded by the University of Granada (Spain).The remediation of heavy-metal-contaminated sites represents a serious environmental problem worldwide. Currently, cost- and time-intensive chemical treatments are usually performed. Bioremediation by heavy-metal-tolerant microorganisms is considered a more eco-friendly and comparatively cheap alternative. The fungus Penicillium simplicissimum KS1, isolated from the flooding water of a former uranium (U) mine in Germany, shows promising U bioremediation potential mainly through biomineralization. The adaption of P. simplicissimum KS1 to heavy-metal-contaminated sites is indicated by an increased U removal capacity of up to 550 mg U per g dry biomass, compared to the non-heavy-metal-exposed P. simplicissimum reference strain DSM 62867 (200 mg U per g dry biomass). In addition, the effect of temperature and cell viability of P. simplicissimum KS1 on U biomineralization was investigated. While viable cells at 30°C removed U mainly extracellularly via metabolism-dependent biomineralization, a decrease in temperature to 4°C or use of dead-autoclaved cells at 30°C revealed increased occurrence of passive biosorption and bioaccumulation, as confirmed by scanning transmission electron microscopy. The precipitated U species were assigned to uranyl phosphates with a structure similar to that of autunite, via cryo-time-resolved laser fluorescence spectroscopy. The major involvement of phosphates in U precipitation by P. simplicissimum KS1 was additionally supported by the observation of increased phosphatase activity for viable cells at 30°C. Furthermore, viable cells actively secreted small molecules, most likely phosphorylated amino acids, which interacted with U in the supernatant and were not detected in experiments with dead-autoclaved cells. Our study provides new insights into the influence of temperature and cell viability on U phosphate biomineralization by fungi, and furthermore highlight the potential use of P. simplicissimum KS1 particularly for U bioremediation purposes.Federal Ministry of Education & Research (BMBF) 02NUK030 F 03SF0451Talent Acquisition Program ("Programa de Captacion de Talento en Grados Universitarios") - University of Granada (Spain

TcoF-DB: dragon database for human transcription co-factors and transcription factor interacting proteins

The initiation and regulation of transcription in eukaryotes is complex and involves a large number of transcription factors (TFs), which are known to bind to the regulatory regions of eukaryotic DNA. Apart from TF–DNA binding, protein–protein interaction involving TFs is an essential component of the machinery facilitating transcriptional regulation. Proteins that interact with TFs in the context of transcription regulation but do not bind to the DNA themselves, we consider transcription co-factors (TcoFs). The influence of TcoFs on transcriptional regulation and initiation, although indirect, has been shown to be significant with the functionality of TFs strongly influenced by the presence of TcoFs. While the role of TFs and their interaction with regulatory DNA regions has been well-studied, the association between TFs and TcoFs has so far been given less attention. Here, we present a resource that is comprised of a collection of human TFs and the TcoFs with which they interact. Other proteins that have a proven interaction with a TF, but are not considered TcoFs are also included. Our database contains 157 high-confidence TcoFs and additionally 379 hypothetical TcoFs. These have been identified and classified according to the type of available evidence for their involvement in transcriptional regulation and their presence in the cell nucleus. We have divided TcoFs into four groups, one of which contains high-confidence TcoFs and three others contain TcoFs which are hypothetical to different extents. We have developed the Dragon Database for Human Transcription Co-Factors and Transcription Factor Interacting Proteins (TcoF-DB). A web-based interface for this resource can be freely accessed at http://cbrc.kaust.edu.sa/tcof/ and http://apps.sanbi.ac.za/tcof/

Network analysis of microRNAs and their regulation in human ovarian cancer

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are small non-coding RNA molecules that repress the translation of messenger RNAs (mRNAs) or degrade mRNAs. These functions of miRNAs allow them to control key cellular processes such as development, differentiation and apoptosis, and they have also been implicated in several cancers such as leukaemia, lung, pancreatic and ovarian cancer (OC). Unfortunately, the specific machinery of miRNA regulation, involving transcription factors (TFs) and transcription co-factors (TcoFs), is not well understood. In the present study we focus on computationally deciphering the underlying network of miRNAs, their targets, and their control mechanisms that have an influence on OC development.</p> <p>Results</p> <p>We analysed experimentally verified data from multiple sources that describe miRNA influence on diseases, miRNA targeting of mRNAs, and on protein-protein interactions, and combined this data with <it>ab initio </it>transcription factor binding site predictions within miRNA promoter regions. From these analyses, we derived a network that describes the influence of miRNAs and their regulation in human OC. We developed a methodology to analyse the network in order to find the nodes that have the largest potential of influencing the network's behaviour (network hubs). We further show the potentially most influential miRNAs, TFs and TcoFs, showing subnetworks illustrating the involved mechanisms as well as regulatory miRNA network motifs in OC. We find an enrichment of miRNA targeted OC genes in the highly relevant pathways cell cycle regulation and apoptosis.</p> <p>Conclusions</p> <p>We combined several sources of interaction and association data to analyse and place miRNAs within regulatory pathways that influence human OC. These results represent the first comprehensive miRNA regulatory network analysis for human OC. This suggests that miRNAs and their regulation may play a major role in OC and that further directed research in this area is of utmost importance to enhance our understanding of the molecular mechanisms underlying human cancer development and OC in particular.</p

A spin-wave frequency doubler by domain wall oscillation

We present a new mechanism for spin-wave excitation using a pinned domain wall which is forced to oscillate at its eigenfrequency and radiates spin waves. The domain wall acts as a frequency doubler, as the excited spin waves have twice the frequency of the domain wall oscillation. The investigations have been carried out using micromagnetic simulations and enable the determination of the main characteristics of the excited spin-waves such as frequency, wavelength, and velocity. This behavior is understood by the oscillation in the perpendicular magnetization which shows two anti-nodes oscillating out of phase with respect to each other.Comment: 8 pages, 3 figure

Derivation of subset product lines in FeatureIDE

The development and configuration of software product lines can be challenging tasks. During development, engineers often need to focus on a particular subset of features that is relevant for them. In such cases, it would be beneficial to hide other features and their implementation. During product configuration, requirements of potentially multiple stakeholders need to be considered. Therefore, configuration often happens in stages, in which different people contribute configuration decisions for different features. Moreover, in some cases, stakeholders want to share a set of products rather than a specific one. In all these cases, the necessary operation is the same: some features from the product line are assigned a value (e.g., via a partial configuration) while other features remain configurable. In this work, we propose a subset operation that takes a product line and a partial configuration to derive a subset product line comprising only the desired subset of features and implementation artifacts. Furthermore, we present, evaluate, and publish our implementation of the proposed subset operation within the FeatureIDE framework

Crystal Structure of an Anti-Ang2 CrossFab Demonstrates Complete Structural and Functional Integrity of the Variable Domain.

Bispecific antibodies are considered as a promising class of future biotherapeutic molecules. They comprise binding specificities for two different antigens, which may provide additive or synergistic modes of action. There is a wide variety of design alternatives for such bispecific antibodies, including the "CrossMab" format. CrossMabs contain a domain crossover in one of the antigen-binding (Fab) parts, together with the "knobs-and-holes" approach, to enforce the correct assembly of four different polypeptide chains into an IgG-like bispecific antibody. We determined the crystal structure of a hAng-2-binding Fab in its crossed and uncrossed form and show that CH1-CL-domain crossover does not induce significant perturbations of the structure and has no detectable influence on target binding

Comparison of a ceiling-mounted 3D flat panel detector vs. conventional intraoperative 2D fluoroscopy in plate osteosynthesis of distal radius fractures with volar locking plate systems

Methods Using a common volar approach on 12 cadaver forearms, total intraarticular distal radius fractures were induced, manually reduced and internally fixated with a 2.4 distal radius locking compression plate. 2D (anterior-posterior and lateral) and 3D (rotational) fluoroscopic images were taken as well as computed tomographies. Fluoroscopic images, Cone Beam CT (CBCT), 360° rotating sequences (so called "Movies") and CT scans were co-evaluated by a specialist orthopedic surgeon and a specialist radiologist regarding quality of fracture reduction, position of plate, position of the three distal locking screws and position of the three diaphyseal screws. In reference to gold standard CT, sensitivity and specifity were analyzed. Results "Movie" showed highest sensitivity for detection of insufficient fracture reduction (88%). Sensitivity for detection of incorrect position of plate was 100% for CBCT and 90% for "Movie." For intraarticular position of screws, 2D fluoroscopy and CBCT showed highest sensitivity and specifity (100 and 91%, respectively). Regarding detection of only marginal intraarticular position of screws, sensitivity and specifity of 2D fluoroscopy reached 100% (CBCT: 100 and 83%). "Movie" showed highest sensitivity for detection of overlapping position of screws (100%). When it comes to specifity, CBCT achieved 100%. Regarding detection of only marginal overlapping position of screws, 2D fluoroscopy and "Movie" showed highest sensitivity (100%). CBCT achieved highest specifity (100%). Conclusion As for assessment of quality of fracture reduction and detection of incorrect position of plate as well as overlapping position of the three diaphyseal screws CBCT and "Movie" are comparable to CT - especially when combined. Particularly sensitivity is high compared to standard 2D fluoroscopy

DDEC: Dragon database of genes implicated in esophageal cancer

<p>Abstract</p> <p>Background</p> <p>Esophageal cancer ranks eighth in order of cancer occurrence. Its lethality primarily stems from inability to detect the disease during the early organ-confined stage and the lack of effective therapies for advanced-stage disease. Moreover, the understanding of molecular processes involved in esophageal cancer is not complete, hampering the development of efficient diagnostics and therapy. Efforts made by the scientific community to improve the survival rate of esophageal cancer have resulted in a wealth of scattered information that is difficult to find and not easily amendable to data-mining. To reduce this gap and to complement available cancer related bioinformatic resources, we have developed a comprehensive database (Dragon Database of Genes Implicated in Esophageal Cancer) with esophageal cancer related information, as an integrated knowledge database aimed at representing a gateway to esophageal cancer related data.</p> <p>Description</p> <p>Manually curated 529 genes differentially expressed in EC are contained in the database. We extracted and analyzed the promoter regions of these genes and complemented gene-related information with transcription factors that potentially control them. We further, precompiled text-mined and data-mined reports about each of these genes to allow for easy exploration of information about associations of EC-implicated genes with other human genes and proteins, metabolites and enzymes, toxins, chemicals with pharmacological effects, disease concepts and human anatomy. The resulting database, DDEC, has a useful feature to display potential associations that are rarely reported and thus difficult to identify. Moreover, DDEC enables inspection of potentially new 'association hypotheses' generated based on the precompiled reports.</p> <p>Conclusion</p> <p>We hope that this resource will serve as a useful complement to the existing public resources and as a good starting point for researchers and physicians interested in EC genetics. DDEC is freely accessible to academic and non-profit users at <url>http://apps.sanbi.ac.za/ddec/</url>. DDEC will be updated twice a year.</p

Spherical representations of Lie supergroups

The classical Cartan-Helgason theorem characterises finite-dimensional spherical representations of reductive Lie groups in terms of their highest weights. We generalise the theorem to the case of a reductive symmetric supergroup pair $(G,K)$ of even type. Along the way, we compute the Harish-Chandra $c$-function of the symmetric superspace $G/K$. By way of an application, we show that all spherical representations are self-dual in type AIII|AIII.Comment: 37 pages; title changed; substantially revised version; accepted for publication, J. Func. Anal. (2014

Deciphering the transcriptional circuitry of microRNA genes expressed during human monocytic differentiation

<p>Abstract</p> <p>Background</p> <p>Macrophages are immune cells involved in various biological processes including host defence, homeostasis, differentiation, and organogenesis. Disruption of macrophage biology has been linked to increased pathogen infection, inflammation and malignant diseases. Differential gene expression observed in monocytic differentiation is primarily regulated by interacting transcription factors (TFs). Current research suggests that microRNAs (miRNAs) degrade and repress translation of mRNA, but also may target genes involved in differentiation. We focus on getting insights into the transcriptional circuitry regulating miRNA genes expressed during monocytic differentiation.</p> <p>Results</p> <p>We computationally analysed the transcriptional circuitry of miRNA genes during monocytic differentiation using <it>in vitro </it>time-course expression data for TFs and miRNAs. A set of TF→miRNA associations was derived from predicted TF binding sites in promoter regions of miRNA genes. Time-lagged expression correlation analysis was utilised to evaluate the TF→miRNA associations. Our analysis identified 12 TFs that potentially play a central role in regulating miRNAs throughout the differentiation process. Six of these 12 TFs (ATF2, E2F3, HOXA4, NFE2L1, SP3, and YY1) have not previously been described to be important for monocytic differentiation. The remaining six TFs are CEBPB, CREB1, ELK1, NFE2L2, RUNX1, and USF2. For several miRNAs (miR-21, miR-155, miR-424, and miR-17-92), we show how their inferred transcriptional regulation impacts monocytic differentiation.</p> <p>Conclusions</p> <p>The study demonstrates that miRNAs and their transcriptional regulatory control are integral molecular mechanisms during differentiation. Furthermore, it is the first study to decipher on a large-scale, how miRNAs are controlled by TFs during human monocytic differentiation. Subsequently, we have identified 12 candidate key controllers of miRNAs during this differentiation process.</p