The TyrA family of aromatic-pathway dehydrogenases in phylogenetic context

BACKGROUND: The TyrA protein family includes members that catalyze two dehydrogenase reactions in distinct pathways leading to L-tyrosine and a third reaction that is not part of tyrosine biosynthesis. Family members share a catalytic core region of about 30 kDa, where inhibitors operate competitively by acting as substrate mimics. This protein family typifies many that are challenging for bioinformatic analysis because of relatively modest sequence conservation and small size. RESULTS: Phylogenetic relationships of TyrA domains were evaluated in the context of combinatorial patterns of specificity for the two substrates, as well as the presence or absence of a variety of fusions. An interactive tool is provided for prediction of substrate specificity. Interactive alignments for a suite of catalytic-core TyrA domains of differing specificity are also provided to facilitate phylogenetic analysis. tyrA membership in apparent operons (or supraoperons) was examined, and patterns of conserved synteny in relationship to organismal positions on the 16S rRNA tree were ascertained for members of the domain Bacteria. A number of aromatic-pathway genes (hisH(b), aroF, aroQ) have fused with tyrA, and it must be more than coincidental that the free-standing counterparts of all of the latter fused genes exhibit a distinct trace of syntenic association. CONCLUSION: We propose that the ancestral TyrA dehydrogenase had broad specificity for both the cyclohexadienyl and pyridine nucleotide substrates. Indeed, TyrA proteins of this type persist today, but it is also common to find instances of narrowed substrate specificities, as well as of acquisition via gene fusion of additional catalytic domains or regulatory domains. In some clades a qualitative change associated with either narrowed substrate specificity or gene fusion has produced an evolutionary "jump" in the vertical genealogy of TyrA homologs. The evolutionary history of gene organizations that include tyrA can be deduced in genome assemblages of sufficiently close relatives, the most fruitful opportunities currently being in the Proteobacteria. The evolution of TyrA proteins within the broader context of how their regulation evolved and to what extent TyrA co-evolved with other genes as common members of aromatic-pathway regulons is now feasible as an emerging topic of ongoing inquiry

Downscaling Changing Coastlines in a Changing Climate: The Hybrid Approach

Shifts in the frequency of typical meteorological patterns in an ocean basin, over interannual to decadal time scales, cause shifts in the patterns of wave generation. Therefore, ocean basin-scale climate shifts produce shifts in the wave climates affecting the coastlines of the basin. We present a hybrid methodology for downscaling observed (or predicted) climate shifts into local nearshore wave climates and then into the associated coastline responses. A series of statistical analyses translate observed (or predicted) distributions of meteorological states into the deep water wave climate affecting a coastal region and dynamical modeling combined with statistical analyses transform the deep water wave climate into the nearshore wave climate affecting a particular coastline. Finally, dynamical modeling of coastline evolution hindcasts (or predicts) how coastline shapes respond to climate shifts. As a case study, we downscale from meteorological hindcast in the North Atlantic basin since 1870 to the responses of the shape of the coast of the Carolinas, USA. We test the hindcasts using shoreline change rates calculated from historical shorelines, because shifts in coastline shape equate to changes in the alongshore pattern of shoreline change rates from one historical period to another. Although limited by the availability of historical shorelines (and complicated by historical inlet openings), the observations are consistent with the predicted signal of ocean basin-scale climate change. The hybrid downscaling methodology, applied to the output of global climate models, can be used to help forecast future patterns of shoreline change related to future climate change scenarios.This work was partially funded by the “U.S. National Science Foundation, Coupled Natural Human Systems Program.” J. A. A. Antolínez is indebted to the MEC (Ministerio de Educación, Cultura y Deporte, Spain) for the funding provided in the FPU (Formación del Profesorado Universitario) studentship (BOE-A-2013-12235). J. A. A. Antolínez and F. J. Méndez acknowledge the support of the Spanish “Ministerio de Economia y Competitividad” under grant BIA2014-59643-R

Defending Our Public Biological Databases as a Global Critical Infrastructure

Progress in modern biology is being driven, in part, by the large amounts of freely available data in public resources such as the International Nucleotide Sequence Database Collaboration (INSDC), the world's primary database of biological sequence (and related) information. INSDC and similar databases have dramatically increased the pace of fundamental biological discovery and enabled a host of innovative therapeutic, diagnostic, and forensic applications. However, as high-value, openly shared resources with a high degree of assumed trust, these repositories share compelling similarities to the early days of the Internet. Consequently, as public biological databases continue to increase in size and importance, we expect that they will face the same threats as undefended cyberspace. There is a unique opportunity, before a significant breach and loss of trust occurs, to ensure they evolve with quality and security as a design philosophy rather than costly “retrofitted” mitigations. This Perspective surveys some potential quality assurance and security weaknesses in existing open genomic and proteomic repositories, describes methods to mitigate the likelihood of both intentional and unintentional errors, and offers recommendations for risk mitigation based on lessons learned from cybersecurity

Genomorama: genome visualization and analysis

<p>Abstract</p> <p>Background</p> <p>The ability to visualize genomic features and design experimental assays that can target specific regions of a genome is essential for modern biology. To assist in these tasks, we present Genomorama, a software program for interactively displaying multiple genomes and identifying potential DNA hybridization sites for assay design.</p> <p>Results</p> <p>Useful features of Genomorama include genome search by DNA hybridization (probe binding and PCR amplification), efficient multi-scale display and manipulation of multiple genomes, support for many genome file types and the ability to search for and retrieve data from the National Center for Biotechnology Information (NCBI) Entrez server.</p> <p>Conclusion</p> <p>Genomorama provides an efficient computational platform for visualizing and analyzing multiple genomes.</p

Biochemical Effects of Carbohydrate Supplementation in a Simulated Competition of Short Terrestrial Duathlon

The purpose of the present study was to investigate the biochemical effects of carbohydrate supplementation in a simulated competition of short terrestrial duathlon. Ten duathletes participated in a simulated competition of short terrestrial duathlon 30 minutes after the ingestion of a 6% (30 g/500 ml) maltodextrin solution (MALT) or a placebo (PLA). This solution was also ingested every 15 minutes during the competition (12 g/200 ml); and immediately after the competition (18 g/300 ml). Samples of blood were collected at 3 time points: 1) at rest 1 hour before the beginning of the competition; 2) during the competition (approximately 1 hour and 45 minutes after the 1st collection); 3) immediately after the competition. Blood was analyzed for blood glucose, lactate, insulin and cortisol. Significant differences were observed in relation to blood glucose levels between MALT and PLA in the post-competition phase. There was also a significant difference in the lactate levels observed between MALT and PLA during the competition phase. Similarly, a significant difference in the cortisol concentrations during and after the competition phases (MALT and PLA) were observed. We conclude that maltodextrin supplementation appears to be beneficial during short terrestrial duathlon competition as evidenced by biochemical markers

Innovative solutions to sticky situations: Antiadhesive strategies for treating bacterial infections

ABSTRACT Bacterial adherence to host tissue is an essential process in pathogenesis, necessary for invasion and colonization and often required for the efficient delivery of toxins and other bacterial effectors. As existing treatment options for common bacterial infections dwindle, we find ourselves rapidly approaching a tipping point in our confrontation with antibiotic-resistant strains and in desperate need of new treatment options. Bacterial strains defective in adherence are typically avirulent and unable to cause infection in animal models. The importance of this initial binding event in the pathogenic cascade highlights its potential as a novel therapeutic target. This article seeks to highlight a variety of strategies being employed to treat and prevent infection by targeting the mechanisms of bacterial adhesion. Advancements in this area include the development of novel antivirulence therapies using small molecules, vaccines, and peptides to target a variety of bacterial infections. These therapies target bacterial adhesion through a number of mechanisms, including inhibition of pathogen receptor biogenesis, competition-based strategies with receptor and adhesin analogs, and the inhibition of binding through neutralizing antibodies. While this article is not an exhaustive description of every advancement in the field, we hope it will highlight several promising examples of the therapeutic potential of antiadhesive strategies.</jats:p

Excess-noise-enhanced parametric down conversion

We calculate the influence of excess noise on parametric down conversion in an unstable optical parametric oscillator (OPO), using a quantum quasimode description. We find a strongly enhanced pair photon generation rate below threshold as compared to a conventional stable cavity setup of comparable gain and loss. In addition, the oscillation threshold is lowered due to the influence of the excess noise and the squeezing properties of the emitted light are significantly changed. In general, the maximal quantum-noise suppression in one quadrature component is reduced, which poses strong limitations for the practical usefulness of a geometrically unstable OPO source. The analytical results from our quasimode description are in good agreement with numerical simulations using a positive-P representation of the field in mode space and in position space