Copper to Zinc Ratio as Disease Biomarker in Neonates with Early-Onset Congenital Infections

Copper (Cu) and zinc (Zn) are essential trace elements for regular development. Acute infections alter their metabolism, while deficiencies increase infection risks. A prospective observational case-control study was conducted with infected (n = 21) and control (n = 23) term and preterm newborns. We analyzed trace element concentrations by X-ray fluorescence, and ceruloplasmin (CP) by Western blot. Median concentration of Cu at birth (day 1) was 522.8 [387.1–679.7] μg/L, and Zn was 1642.4 ± 438.1 μg/L. Cu and Zn correlated positively with gestational age in control newborns. Cu increased in infected newborns from day 1 to day 3. CP correlated positively to Cu levels at birth in both groups and on day 3 in the group of infected neonates. The Cu/Zn ratio was relatively high in infected newborns. Interleukin (IL)-6 concentrations on day 1 were unrelated to Cu, Zn, or the Cu/Zn ratio, whereas C-reactive protein (CRP) levels on day 3 correlated positively to the Cu/Zn -ratio at both day 1 and day 3. We conclude that infections affect the trace element homeostasis in newborns: serum Zn is reduced, while Cu and CP are increased. The Cu/Zn ratio combines both alterations, independent of gestational age. It may, thus, constitute a meaningful diagnostic biomarker for early-onset infections. View Full-Tex

METANNOGEN: compiling features of biochemical reactions needed for the reconstruction of metabolic networks

BACKGROUND: One central goal of computational systems biology is the mathematical modelling of complex metabolic reaction networks. The first and most time-consuming step in the development of such models consists in the stoichiometric reconstruction of the network, i. e. compilation of all metabolites, reactions and transport processes relevant to the considered network and their assignment to the various cellular compartments. Therefore an information system is required to collect and manage data from different databases and scientific literature in order to generate a metabolic network of biochemical reactions that can be subjected to further computational analyses. RESULTS: The computer program METANNOGEN facilitates the reconstruction of metabolic networks. It uses the well-known database of biochemical reactions KEGG of biochemical reactions as primary information source from which biochemical reactions relevant to the considered network can be selected, edited and stored in a separate, user-defined database. Reactions not contained in KEGG can be entered manually into the system. To aid the decision whether or not a reaction selected from KEGG belongs to the considered network METANNOGEN contains information of SWISSPROT and ENSEMBL and provides Web links to a number of important information sources like METACYC, BRENDA, NIST, and REACTOME. If a reaction is reported to occur in more than one cellular compartment, a corresponding number of reactions is generated each referring to one specific compartment. Transport processes of metabolites are entered like chemical reactions where reactants and products have different compartment attributes. The list of compartmentalized biochemical reactions and membrane transport processes compiled by means of METANNOGEN can be exported as an SBML file for further computational analysis. METANNOGEN is highly customizable with respect to the content of the SBML output file, additional data-fields, the graphical input form, highlighting of project specific search terms and dynamically generated Web-links. CONCLUSION: METANNOGEN is a flexible tool to manage information for the design of metabolic networks. The program requires Java Runtime Environment 1.4 or higher and about 100 MB of free RAM and about 200 MB of free HD space. It does not require installation and can be directly Java-webstarted from

Structure-based classification and ontology in chemistry

<p>Abstract</p> <p>Background</p> <p>Recent years have seen an explosion in the availability of data in the chemistry domain. With this information explosion, however, retrieving <it>relevant </it>results from the available information, and <it>organising </it>those results, become even harder problems. Computational processing is essential to filter and organise the available resources so as to better facilitate the work of scientists. Ontologies encode expert domain knowledge in a hierarchically organised machine-processable format. One such ontology for the chemical domain is ChEBI. ChEBI provides a classification of chemicals based on their structural features and a role or activity-based classification. An example of a structure-based class is 'pentacyclic compound' (compounds containing five-ring structures), while an example of a role-based class is 'analgesic', since many different chemicals can act as analgesics without sharing structural features. Structure-based classification in chemistry exploits elegant regularities and symmetries in the underlying chemical domain. As yet, there has been neither a systematic analysis of the types of structural classification in use in chemistry nor a comparison to the capabilities of available technologies.</p> <p>Results</p> <p>We analyze the different categories of structural classes in chemistry, presenting a list of patterns for features found in class definitions. We compare these patterns of class definition to tools which allow for automation of hierarchy construction within cheminformatics and within logic-based ontology technology, going into detail in the latter case with respect to the expressive capabilities of the Web Ontology Language and recent extensions for modelling structured objects. Finally we discuss the relationships and interactions between cheminformatics approaches and logic-based approaches.</p> <p>Conclusion</p> <p>Systems that perform intelligent reasoning tasks on chemistry data require a diverse set of underlying computational utilities including algorithmic, statistical and logic-based tools. For the task of automatic structure-based classification of chemical entities, essential to managing the vast swathes of chemical data being brought online, systems which are capable of hybrid reasoning combining several different approaches are crucial. We provide a thorough review of the available tools and methodologies, and identify areas of open research.</p

Phylogenetic analysis of forkhead transcription factors in the Panarthropoda

Fox genes encode transcription factors that contain a DNA binding domain, the forkhead domain, and are known from diverse animal species. The exact homology of the Fox genes of different species is debated and this makes inferences about the evolution of the Fox genes, and their duplications and losses difficult. We have performed phylogenetic analyses of the Fox gene complements of 32 panarthropod species. Our results confirm an ancestral complement of FoxA, FoxB, FoxC, FoxD, FoxF, FoxG, FoxJ1, FoxJ2/3, FoxK, FoxL1, FoxL2, FoxN1/4, FoxN2/3, FoxO, FoxP, and FoxQ2 in the Arthropoda, and additionally FoxH and FoxQ1 in the Panarthropoda (including tardigrades and onychophorans). We identify a novel Fox gene sub-family, that we designate as FoxT that includes two genes in Drosophila melanogaster, Circadianly Regulated Gene (Crg-1) and forkhead domain 3F (fd3F). In a very recent paper, the same new Fox gene sub-family was identified in insects (Lin et al. 2021). Our analysis confirms the presence of FoxT and shows that its members are present throughout Panarthropoda. We show that the hitherto unclassified gene CG32006 from the fly Drosophila melanogaster belongs to FoxJ1. We also detect gene losses: FoxE and FoxM were lost already in the panarthropod ancestor, whereas the loss of FoxH occurred in the arthropod ancestor. Finally, we find an ortholog of FoxQ1 in the bark scorpion Centruroides sculpturatus, confirmed not only by phylogenetic analysis, but also by forming an evolutionarily conserved gene cluster with FoxF, FoxC, and FoxL1. This suggests that FoxQ1 belongs to the ancestral Fox gene complement in panarthropods and also in chelicerates, but has been lost at the base of the mandibulate arthropods

A comprehensive study of arthropod and onychophoran Fox gene expression patterns

Fox genes represent an evolutionary old class of transcription factor encoding genes that evolved in the last common ancestor of fungi and animals. They represent key-components of multiple gene regulatory networks (GRNs) that are essential for embryonic development. Most of our knowledge about the function of Fox genes comes from vertebrate research, and for arthropods the only comprehensive gene expression analysis is that of the fly Drosophila melanogaster. For other arthropods, only selected Fox genes have been investigated. In this study, we provide the first comprehensive gene expression analysis of arthropod Fox genes including representative species of all main groups of arthropods, Pancrustacea, Myriapoda and Chelicerata. We also provide the first comprehensive analysis of Fox gene expression in an onychophoran species. Our data show that many of the Fox genes likely retained their function during panarthropod evolution highlighting their importance in development. Comparison with published data from other groups of animals shows that this high degree of evolutionary conservation often dates back beyond the last common ancestor of Panarthropoda

BRENDA in 2015: exciting developments in its 25th year of existence.

The BRENDA enzyme information system (http://www.brenda-enzymes.org/) has developed into an elaborate system of enzyme and enzyme-ligand information obtained from different sources, combined with flexible query systems and evaluation tools. The information is obtained by manual extraction from primary literature, text and data mining, data integration, and prediction algorithms. Approximately 300 million data include enzyme function and molecular data from more than 30 000 organisms. The manually derived core contains 3 million data from 77 000 enzymes annotated from 135 000 literature references. Each entry is connected to the literature reference and the source organism. They are complemented by information on occurrence, enzyme/disease relationships from text mining, sequences and 3D structures from other databases, and predicted enzyme location and genome annotation. Functional and structural data of more than 190 000 enzyme ligands are stored in BRENDA. New features improving the functionality and analysis tools were implemented. The human anatomy atlas CAVEman is linked to the BRENDA Tissue Ontology terms providing a connection between anatomical and functional enzyme data. Word Maps for enzymes obtained from PubMed abstracts highlight application and scientific relevance of enzymes. The EnzymeDetector genome annotation tool and the reaction database BKM-react including reactions from BRENDA, KEGG and MetaCyc were improved. The website was redesigned providing new query options. Nucleic Acids Res 2015 Jan 28; 43(Database issue):D439-46

Neofunctionalization of a Duplicate dachshund Gene Underlies the Evolution of a Novel Leg Segment in Arachnids

The acquisition of a novel function, or neofunctionalization, protects duplicated genes from redundancy and subsequent loss, and is a major force that drives adaptive evolution. Neofunctionalization has been inferred for many duplicated genes based on differences in regulation between the parental gene and its duplicate. However, only few studies actually link the new function of a duplicated gene to a novel morphological or physiological character of the organism. Here we show that the duplication of dachshund (dac) in arachnids (spiders and allies) is linked with the evolution of a novel leg segment, the patella. We have studied dac genes in two distantly related spider species, the entelegyne spider Parasteatoda tepidariorum and the haplogyne spider Pholcus phalangioides. Both species possess two paralogous dac genes that duplicated before the split between entelegyne and haplogyne spiders. In contrast to the evolutionarily highly conserved dac1, its duplicate dac2 is strongly expressed in the patella leg segment during embryogenesis in both species. Using parental RNA interference in P. tepidariorum we show that dac2 is required for the development of the patella segment. If dac2 function is impaired, then the patella is fused with the tibia into a single leg segment. Thus, removing the function of dac2 experimentally reverts P. tepidariorum leg morphology into a stage before the duplication of dac and the evolution of the patella segment. Our results indicate that the origin of the patella is the result of the duplication and subsequent neofunctionalization of dac in the arachnid lineage