Role of core lipopolysaccharide biosynthetic genes in the infection and adsorption of broad-host-range bacteriophages of Rhizobium etli.

In this study, we examined the role of the lipopolysaccharide (LPS) core of Rhizobium etli in facilitating the adsorption and infection of phages with broad host range. When the plasmid-encoded LPS biosynthesis genes, wreU and wreV, were disrupted, distinct and contrasting effects on phage infection were observed. The wreU mutant strains exhibited wild-type adsorption and infection properties, whereas the wreV mutant demonstrated resistance to phage infection, but retained the capacity to adsorb phages. Complementation of the wreV mutant strains with a recombinant plasmid containing the wreU and wreV, restored the susceptibility to the phages. However, the presence of this recombinant plasmid in a strain devoid of the native lps-encoding plasmid was insufficient to restore phage susceptibility. These results suggest that the absence of wreV impedes the proper assembly of the complete LPS core, potentially affecting the formation of UDP-KdgNAg or KDO precursors for the O-antigen. In addition, a protein not yet identified, but residing in the native lps-encoding plasmid, may be necessary for complete phage infection.

Sequencing and description of the genome of a strain of Stenotrophomonas geniculata isolated from a patient infected with COVID-19 at Hospital Regional No.1 de Charo, Michoacán, México.

Stenotrophomonas is a bacterial genus that can be found in various environments, such as water, soil, and clinical samples. Due to their high genetic and phenotypic diversity, it is difficult to properly identify and classify all isolates. The COVID-19 pandemic caused an increase in nosocomial infections, which played a major role in the high mortality rate among patients in intensive care. This is the first report of the identification of S. geniculata as a nosocomial opportunistic pathogen isolated from a patient with COVID-19. Their genome was isolated, sequenced, and assembled, and it consists of 4,488,090 bp in 24 contigs, 4,103 coding sequences, and a G+C content of 66.58%.

Genomic Analysis Reveals the Genetic Determinants Associated With Antibiotic Resistance in the Zoonotic Pathogen Campylobacter spp. Distributed Globally.

The genus Campylobacter groups 32 Gram-negative bacteria species, several being zoonotic pathogens and a major cause of human gastroenteritis worldwide. Antibiotic resistant Campylobacter is considered by the World Health Organization as a high priority pathogen for research and development of new antibiotics. Genetic elements related to antibiotic resistance in the classical C. coli and C. jejuni species, which infect humans and livestock, have been analyzed in numerous studies, mainly focused on local geographical areas. However, the presence of these resistance determinants in other Campylobacter species, as well as in C. jejuni and C. coli strains distributed globally, remains poorly studied. In this work, we analyzed the occurrence and distribution of antibiotic resistance factors in 237 Campylobacter closed genomes available in NCBI, obtained from isolates collected worldwide, in different dates, from distinct hosts and comprising 22 Campylobacter species. Our data revealed 18 distinct genetic determinants, genes or point mutations in housekeeping genes, associated with resistance to antibiotics from aminoglycosides, ß-lactams, fluoroquinolones, lincosamides, macrolides, phenicols or tetracyclines classes, which are differentially distributed among the Campylobacter species tested, on chromosomes or plasmids. Three resistance determinants, the bla OXA-493 and bla OXA-576 genes, putatively related to ß-lactams resistance, as well as the lnu(AN2) gene, putatively related to lincosamides resistance, had not been reported in Campylobacter; thus, they represent novel determinants for antibiotic resistance in Campylobacter spp., which expands the insight on the Campylobacter resistome. Interestingly, we found that some of the genetic determinants associated with antibiotic resistance are Campylobacter species-specific; e.g., the bla OXA-493 gene and the T86V mutation in gyrA were found only in the C. lari group, whereas genes associated with aminoglycosides resistance were found only in C. jejuni and C. coli. Additional analyses revealed how are distributed the resistance and multidrug resistance Campylobacter genotypes assessed, with respect to hosts, geographical locations, and collection dates. Thus, our findings further expand the knowledge on the factors that can determine or favor the antibiotic resistance in Campylobacter species distributed globally, which can be useful to choose a suitable antibiotic treatment to control the zoonotic infections by these bacteria.

Genomic diversity of prevalent Staphylococcus epidermidis multidrug-resistant strains isolated from a Children's Hospital in México City in an eight-years survey.

Staphylococcus epidermidis is a human commensal and pathogen worldwide distributed. In this work, we surveyed for multi-resistant S. epidermidis strains in eight years at a children's health-care unit in México City. Multidrug-resistant S. epidermidis were present in all years of the study, including resistance to methicillin, beta-lactams, fluoroquinolones, and macrolides. To understand the genetic basis of antibiotic resistance and its association with virulence and gene exchange, we sequenced the genomes of 17 S. epidermidis isolates. Whole-genome nucleotide identities between all the pairs of S. epidermidis strains were about 97% to 99%. We inferred a clonal structure and eight Multilocus Sequence Types (MLSTs) in the S. epidermidis sequenced collection. The profile of virulence includes genes involved in biofilm formation and phenol-soluble modulins (PSMs). Half of the S. epidermidis analyzed lacked the ica operon for biofilm formation. Likely, they are commensal S. epidermidis strains but multi-antibiotic resistant. Uneven distribution of insertion sequences, phages, and CRISPR-Cas immunity phage systems suggest frequent horizontal gene transfer. Rates of recombination between S. epidermidis strains were more prevalent than the mutation rate and affected the whole genome. Therefore, the multidrug resistance, independently of the pathogenic traits, might explain the persistence of specific highly adapted S. epidermidis clonal lineages in nosocomial settings.

Phylogenomic Rhizobium Species Are Structured by a Continuum of Diversity and Genomic Clusters.

The bacterial genus Rhizobium comprises diverse symbiotic nitrogen-fixing species associated with the roots of plants in the Leguminosae family. Multiple genomic clusters defined by whole genome comparisons occur within Rhizobium, but their equivalence to species is controversial. In this study we investigated such genomic clusters to ascertain their significance in a species phylogeny context. Phylogenomic inferences based on complete sets of ribosomal proteins and stringent core genome markers revealed the main lineages of Rhizobium. The clades corresponding to R. etli and R. leguminosarum species show several genomic clusters with average genomic nucleotide identities (ANI > 95%), and a continuum of divergent strains, respectively. They were found to be inversely correlated with the genetic distance estimated from concatenated ribosomal proteins. We uncovered evidence of a Rhizobium pangenome that was greatly expanded, both in its chromosomes and plasmids. Despite the variability of extra-chromosomal elements, our genomic comparisons revealed only a few chromid and plasmid families. The presence/absence profile of genes in the complete Rhizobium genomes agreed with the phylogenomic pattern of species divergence. Symbiotic genes were distributed according to the principal phylogenomic Rhizobium clades but did not resolve genome clusters within the clades. We distinguished some types of symbiotic plasmids within Rhizobium that displayed different rates of synonymous nucleotide substitutions in comparison to chromosomal genes. Symbiotic plasmids may have been repeatedly transferred horizontally between strains and species, in the process displacing and substituting pre-existing symbiotic plasmids. In summary, the results indicate that Rhizobium genomic clusters, as defined by whole genomic identities, might be part of a continuous process of evolutionary divergence that includes the core and the extrachromosomal elements leading to species formation.

Erythropoietin promotes expression of survivin via STAT3 activation and reduces sensitivity to cisplatin in cervical cancer cells.

Erythropoietin (Epo) is used for the treatment of cancer­associated anaemia. However, certain studies have identified that the administration of Epo mediates the acquisition of resistance to cisplatin, which is widely used to treat cervical cancer. Our group previously reported that cervical cancer cells express Epo receptor and that exogenous Epo induces cell proliferation and migration. However, the effect of Epo on cervical cancer cell death mediated by chemotherapeutic agents has not yet been evaluated. Thus, the aim of the present study was to assess the potential effect of Epo on the cytotoxic activity of cisplatin in cervical cancer cells. The effect of Epo was assessed in 3 cervical cancer­derived cell lines. It was observed that pre­incubation with Epo induced a significant reduction of cisplatin­induced apoptosis in vitro and in vivo. Incubation with Epo induced the expression and activation of the transcriptional factor signal transducer and activator of transcription 3 (STAT3), which in turn stimulated the expression and activation of the anti­apoptotic protein survivin. The cytotoxicity of cisplatin was partially restored by treating the cells with MY155, an inhibitor of survivin. Conversely, inhibition of STAT3 activation using sub­lethal doses of WP1066, completely abolished the cytoprotective effect of Epo. These observations indicated that Epo was able to hinder the cytotoxic effect of cisplatin in cervical cancer cells by activating anti­apoptotic responses regulated by STAT3.

Síntesis de biomateriales, pruebas de biocompatibilidad in vitro, primeros pasos en ingeniería tisular en Bolivia / Synthesis of biomaterials, in vitro biocompatibility tests, first steps in tissular engineering in Bolivia

El desarrollo de biomateriales bioactivos como andamios para la osteointegración o regeneración de tejidos ha dado grandes pasos, el presente trabajo, muestra los procesos de síntesis de biomateriales como la hidroxiapatita, biomateriales del sistema SiO2-CaO-P2O5-Al2O3 y biovidrios del sistema SiO2.Li2O, se ha logrado caracterizar los biomateriales obtenidos, con resultados similares a los de otros investigadores por técnicas con la Difracción de Rayos X y la Microscopía Electrónica de Barrido, se ha evaluado su comportamientoen pruebas de biocompatibilidad y bioactividad en soluciones de Plasma Rico en Factores de Crecimiento y Fluido corporal simulado, seguidamente y con el fin de evaluar la incorporación de sustancias antibacteriales se ha dopado uno de ellos con plata, logrando determinar que el material tiene esta capacidad, estos resultados son los primeros pasos para encarar posteriores trabajos en el campo de la Ingeniería Tisular en Bolivia, y de esta forma encarar procesos de ostointegración y regeneración de tejidos en general.

The development of bioactive biomaterials as scaffolds for osseointegration or tissue regeneration has taken great steps, the present work shows the synthesis processes of biomaterials such as hydroxyapatite, biomaterials of the SiO2-CaO-P2O5-Al2O3 system and bio-libraries of the SiO2 system. Li2O, it has been possible to characterize the biomaterials obtained, with results similar to those of other researchers by techniques with X-ray Diffraction and Scanning Electron Microscopy, their behavior in biocompatibility and bioactivity tests in Plasma Rico solutions has been evaluated in Growth factors and simulated body fluid, then and in order to evaluate the incorporation of antibacterial substances, one of them has been doped with silver, managing to determine that the material has this capacity, these results are the first steps to face further work in the field of Tissue Engineering in Bolivia, and thus face Osteintegration processes and tissue regeneration in general.

Using RegulonDB, the Escherichia coli K-12 Gene Regulatory Transcriptional Network Database.

In RegulonDB, for over 25 years, we have been gathering knowledge by manual curation from original scientific literature on the regulation of transcription initiation and genome organization in transcription units of the Escherichia coli K-12 genome. This unit describes six basic protocols that can serve as a guiding introduction to the main content of the current version (v9.4) of this electronic resource. These protocols include general navigation as well as searching for specific objects such as genes, gene products, transcription units, promoters, transcription factors, coexpression, and genetic sensory response units or GENSOR Units. In these protocols, the user will find an initial introduction to the concepts pertinent to the protocol, the content obtained when performing the given navigation, and the necessary resources for carrying out the protocol. This easy-to-follow presentation should help anyone interested in quickly seeing all that is currently offered in RegulonDB, including position weight matrices of transcription factors, coexpression values based on published microarrays, and the GENSOR Units unique to RegulonDB that offer regulatory mechanisms in the context of their signals and metabolic consequences. © 2018 by John Wiley & Sons, Inc.

Tiempo, ansiedad y concentración:: influencia en la efectividad en tiros libres del baloncesto femenino / Time, anxiety and concentration: influence on the effectiveness in free throws of women's basketball

Introducción: La ansiedad y la concentración pueden ser variables que afecten el desempeño deportivo, la primera definida como una respuesta del organismo frente a estímulos externos e internos, y la segunda como un proceso psíquico donde se incluye el razonamiento en función de lograr un objetivo determinado. Otra variable como el tiempo de ejecución de la técnica del tiro libre podría en conjunto con las otras variables mencionadas influir en la efectividad técnico-táctica en el baloncesto femenino de la categoría senior. Objetivo: establecer la existencia de una relación entre las variables tiempo empleado para implementar la técnica del tiro libre en baloncesto femenino, y la influencia del nivel de ansiedad y concentración en la efectividad de los tiros libres. Métodos: Se realiza una investigación de tipo exploratoria, descriptiva e inferencial, investigando a la población de 18 jugadores del equipo femenino categoría senior de la Universidad Internacional Sek, Ecuador (18-34 años). Se estudiaron 12 juegos de baloncesto y 24 sesiones de entrenamiento, obteniendo la efectividad de los tiros libres (porcentajes de aciertos) y su correlación con el tiempo empleado para realizar la técnica del tiro libre, el nivel de concentración (Test de Tolouse Pieron), y el nivel de ansiedad (Test de Idare). Resultados: se determina la existencia de una correlación positiva débil entre el Tiempo empleado en los Tiros Libres Efectivos y el Porciento de la efectividad en tiros libres (r=0,169696301). Entre el Nivel de Ansiedad Reactiva o Ansiedad-Estado y la efectividad en los tiros libres se estableció una correlación negativa (r= -0,265917973); entre el nivel de Ansiedad-rasgo una correlación positiva moderada con la efectividad en tiros libres (r= 0,344253984), y una correlación lineal positiva moderada entre el Nivel de Concentración y la efectividad de los tiros libres (r= 0,301500746). Conclusiones: El tiempo empleado en la ejecución técnica de los tiros libres del baloncesto senior femenino, la atención y la concentración, poseen una influencia lineal normalmente positiva a nivel bajo y moderado en la efectividad porcentual de la técnica deportiva mencionada(AU)

Introduction: Anxiety and concentration can be variables that affect sports performance, the first defined as a response of organism to external and internal stimuli, and the second as a psychic process where reasoning is included in order to achieve a specific objective . Another variable such as the execution time of free-throw technique could, in conjunction with the other variables mentioned, influence the technical-tactical effectiveness in women's basketball in the senior category. Objective: to establish the existence of a relationship between the variables time used to implement the technique of free throw in women's basketball, and the influence of anxiety level and concentration on the free throws effectiveness. Methods: Exploratory, descriptive and inferential research was carried out, investigating the population of 18 players, senior category female team of Universidad Internacional SEK, Ecuador (18-34 years). 12 basketball games and 24 training sessions were studied, obtaining the effectiveness of free throws (success percentage) and its correlation with the time used to perform the free throw technique, the concentration level (Test of Tolouse Pieron), and the anxiety level (Idare Test). Results: the existence of a weak positive correlation between the Time used in free throws and the effectiveness percentage in free throws (r = 0.169696301), between the Reactive Anxiety Level or Anxiety-State, and Effectiveness index in free throws, a negative correlation was established (r = -0.265917973), between the Anxiety-trait level a moderate positive correlation in free throws effectiveness (r = 0.34425398484), and a moderate positive linear correlation between the Concentration Level and the free throws effectiveness (r = 0.301500746). Conclusions: The time spent in free throws technical execution of senior women's basketball, attention and concentration, have a linear influence that is normally positive at a low and moderate level in percentage effectiveness of the aforementioned sports technique(AU)

Complete Genome Sequences of Eight Rhizobium Symbionts Associated with Common Bean (Phaseolus vulgaris).

We present here the high-quality complete genome sequences of eight strains of Rhizobium-nodulating Phaseolus vulgaris Comparative analyses showed that some of them belonged to different genomic and evolutionary lineages with common symbiotic properties. Two novel symbiotic plasmids (pSyms) with P. vulgaris specificity are reported here.

The transcriptional regulator SsrB is involved in a molecular switch controlling virulence lifestyles of Salmonella.

The evolution of bacterial pathogenicity, heavily influenced by horizontal gene transfer, provides new virulence factors and regulatory connections that alter bacterial phenotypes. Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2) are chromosomal regions that were acquired at different evolutionary times and are essential for Salmonella virulence. In the intestine of mammalian hosts, Salmonella expresses the SPI-1 genes that mediate its invasion to the gut epithelium. Once inside the cells, Salmonella down-regulates the SPI-1 genes and induces the expression of the SPI-2 genes, which favor its intracellular replication. The mechanism by which the invasion machinery is deactivated following successful invasion of host cells is not known. Here, we show that the SPI-2 encoded transcriptional regulator SsrB, which positively controls SPI-2, acts as a dual regulator that represses expression of SPI-1 during intracellular stages of infection. The mechanism of this SPI-1 repression by SsrB was direct and acts upon the hilD and hilA regulatory genes. The phenotypic effect of this molecular switch activity was a significant reduction in invasion ability of S. enterica serovar Typhimurium while promoting the expression of genes required for intracellular survival. During mouse infections, Salmonella mutants lacking SsrB had high levels of hilA (SPI-1) transcriptional activity whereas introducing a constitutively active SsrB led to significant hilA repression. Thus, our results reveal a novel SsrB-mediated mechanism of transcriptional crosstalk between SPI-1 and SPI-2 that helps Salmonella transition to the intracellular lifestyle.

Complete Genome Sequences of Three Rhizobium gallicum Symbionts Associated with Common Bean (Phaseolus vulgaris).

The whole-genome sequences of three strains of Rhizobium gallicum reported here support the concept that the distinct nodulation host ranges displayed by the symbiovars gallicum and phaseoli can be largely explained by different symbiotic plasmids.

In silico clustering of Salmonella global gene expression data reveals novel genes co-regulated with the SPI-1 virulence genes through HilD.

A wide variety of Salmonella enterica serovars cause intestinal and systemic infections to humans and animals. Salmonella Patogenicity Island 1 (SPI-1) is a chromosomal region containing 39 genes that have crucial virulence roles. The AraC-like transcriptional regulator HilD, encoded in SPI-1, positively controls the expression of the SPI-1 genes, as well as of several other virulence genes located outside SPI-1. In this study, we applied a clustering method to the global gene expression data of S. enterica serovar Typhimurium from the COLOMBOS database; thus genes that show an expression pattern similar to that of SPI-1 genes were selected. This analysis revealed nine novel genes that are co-expressed with SPI-1, which are located in different chromosomal regions. Expression analyses and protein-DNA interaction assays showed regulation by HilD for six of these genes: gtgE, phoH, sinR, SL1263 (lpxR) and SL4247 were regulated directly, whereas SL1896 was regulated indirectly. Interestingly, phoH is an ancestral gene conserved in most of bacteria, whereas the other genes show characteristics of genes acquired by Salmonella. A role in virulence has been previously demonstrated for gtgE, lpxR and sinR. Our results further expand the regulon of HilD and thus identify novel possible Salmonella virulence genes.

RegulonDB version 9.0: high-level integration of gene regulation, coexpression, motif clustering and beyond.

RegulonDB (http://regulondb.ccg.unam.mx) is one of the most useful and important resources on bacterial gene regulation,as it integrates the scattered scientific knowledge of the best-characterized organism, Escherichia coli K-12, in a database that organizes large amounts of data. Its electronic format enables researchers to compare their results with the legacy of previous knowledge and supports bioinformatics tools and model building. Here, we summarize our progress with RegulonDB since our last Nucleic Acids Research publication describing RegulonDB, in 2013. In addition to maintaining curation up-to-date, we report a collection of 232 interactions with small RNAs affecting 192 genes, and the complete repertoire of 189 Elementary Genetic Sensory-Response units (GENSOR units), integrating the signal, regulatory interactions, and metabolic pathways they govern. These additions represent major progress to a higher level of understanding of regulated processes. We have updated the computationally predicted transcription factors, which total 304 (184 with experimental evidence and 120 from computational predictions); we updated our position-weight matrices and have included tools for clustering them in evolutionary families. We describe our semiautomatic strategy to accelerate curation, including datasets from high-throughput experiments, a novel coexpression distance to search for 'neighborhood' genes to known operons and regulons, and computational developments.

In silico identification and experimental characterization of regulatory elements controlling the expression of the Salmonella csrB and csrC genes.

The small RNAs CsrB and CsrC of Salmonella indirectly control the expression of numerous genes encoding widespread cellular functions, including virulence. The expression of csrB and csrC genes, which are located in different chromosomal regions, is coordinated by positive transcriptional control mediated by the two-component regulatory system BarA/SirA. Here, we identified by computational analysis an 18-bp inverted repeat (IR) sequence located far upstream from the promoter of Salmonella enterica serovar Typhimurium csrB and csrC genes. Deletion analysis and site-directed mutagenesis of the csrB and csrC regulatory regions revealed that this IR sequence is required for transcriptional activation of both genes. Protein-DNA and protein-protein interaction assays showed that the response regulator SirA specifically binds to the IR sequence and provide evidence that SirA acts as a dimer. Interestingly, whereas the IR sequence was essential for the SirA-mediated expression of csrB, our results revealed that SirA controls the expression of csrC not only by binding to the IR sequence but also by an indirect mode involving the Csr system. Additional computational, biochemical, and genetic analyses demonstrated that the integration host factor (IHF) global regulator positively controls the expression of csrB, but not of csrC, by interacting with a sequence located between the promoter and the SirA-binding site. These findings contribute to the better understanding of the regulatory mechanism controlling the expression of CsrB and CsrC.

RegulonDB v8.0: omics data sets, evolutionary conservation, regulatory phrases, cross-validated gold standards and more.

This article summarizes our progress with RegulonDB (http://regulondb.ccg.unam.mx/) during the past 2 years. We have kept up-to-date the knowledge from the published literature regarding transcriptional regulation in Escherichia coli K-12. We have maintained and expanded our curation efforts to improve the breadth and quality of the encoded experimental knowledge, and we have implemented criteria for the quality of our computational predictions. Regulatory phrases now provide high-level descriptions of regulatory regions. We expanded the assignment of quality to various sources of evidence, particularly for knowledge generated through high-throughput (HT) technology. Based on our analysis of most relevant methods, we defined rules for determining the quality of evidence when multiple independent sources support an entry. With this latest release of RegulonDB, we present a new highly reliable larger collection of transcription start sites, a result of our experimental HT genome-wide efforts. These improvements, together with several novel enhancements (the tracks display, uploading format and curational guidelines), address the challenges of incorporating HT-generated knowledge into RegulonDB. Information on the evolutionary conservation of regulatory elements is also available now. Altogether, RegulonDB version 8.0 is a much better home for integrating knowledge on gene regulation from the sources of information currently available.

Anti-Sigma Factors in E. coli: Common Regulatory Mechanisms Controlling Sigma Factors Availability.

In bacteria, transcriptional regulation is a key step in cellular gene expression. All bacteria contain a core RNA polymerase that is catalytically competent but requires an additional σ factor for specific promoter recognition and correct transcriptional initiation. The RNAP core is not able to selectively bind to a given σ factor. In contrast, different σ factors have different affinities for the RNAP core. As a consequence, the concentration of alternate σ factors requires strict regulation in order to properly control the delicate interplay among them, which favors the competence for the RNAP core. This control is archived by different σ/anti-σ controlling mechanisms that shape complex regulatory networks and cascades, and enable the response to sudden environmental cues, whose global understanding is a current challenge for systems biology. Although there have been a number of excellent studies on each of these σ/anti-σ post-transcriptional regulatory systems, no comprehensive comparison of these mechanisms in a single model organism has been conducted. Here, we survey all these systems in E. coli dissecting and analyzing their inner workings and highlightin their differences. Then, following an integral approach, we identify their commonalities and outline some of the principles exploited by the cell to effectively and globally reprogram the transcriptional machinery. These principles provide guidelines for developing biological synthetic circuits enabling an efficient and robust response to sudden stimuli.

Extracting regulatory networks of Escherichia coli from RegulonDB.

RegulonDB contains the largest and currently best-known data set on transcriptional regulation in a single free-living organism, that of Escherichia coli K-12 (Gama-Castro et al. Nucleic Acids Res 36:D120-D124, 2008). This organized knowledge has been the gold standard for the implementation of bioinformatic predictive methods on gene regulation in bacteria (Collado-Vides et al. J Bacteriol 191:23-31, 2009). Given the complexity of different types of interactions, the difficulty of visualizing in a single figure of the whole network, and the different uses of this knowledge, we are making available different views of the genetic network. This chapter describes case studies about how to access these views, via precomputed files, web services and SQL, including sigma-gene relationships corresponding to transcription of alternative RNA polymerase holoenzyme promoters; as well as, transcription factor (TF)-genes, TF-operons, TF-TF, and TF-regulon interactions. 17.

RegulonDB version 7.0: transcriptional regulation of Escherichia coli K-12 integrated within genetic sensory response units (Gensor Units).

RegulonDB (http://regulondb.ccg.unam.mx/) is the primary reference database of the best-known regulatory network of any free-living organism, that of Escherichia coli K-12. The major conceptual change since 3 years ago is an expanded biological context so that transcriptional regulation is now part of a unit that initiates with the signal and continues with the signal transduction to the core of regulation, modifying expression of the affected target genes responsible for the response. We call these genetic sensory response units, or Gensor Units. We have initiated their high-level curation, with graphic maps and superreactions with links to other databases. Additional connectivity uses expandable submaps. RegulonDB has summaries for every transcription factor (TF) and TF-binding sites with internal symmetry. Several DNA-binding motifs and their sizes have been redefined and relocated. In addition to data from the literature, we have incorporated our own information on transcription start sites (TSSs) and transcriptional units (TUs), obtained by using high-throughput whole-genome sequencing technologies. A new portable drawing tool for genomic features is also now available, as well as new ways to download the data, including web services, files for several relational database manager systems and text files including BioPAX format.

The BioPAX community standard for pathway data sharing.

Biological Pathway Exchange (BioPAX) is a standard language to represent biological pathways at the molecular and cellular level and to facilitate the exchange of pathway data. The rapid growth of the volume of pathway data has spurred the development of databases and computational tools to aid interpretation; however, use of these data is hampered by the current fragmentation of pathway information across many databases with incompatible formats. BioPAX, which was created through a community process, solves this problem by making pathway data substantially easier to collect, index, interpret and share. BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks. Using BioPAX, millions of interactions, organized into thousands of pathways, from many organisms are available from a growing number of databases. This large amount of pathway data in a computable form will support visualization, analysis and biological discovery.