Functional Similarity between Archaeal and Bacterial CorA Magnesium Transporters

The constitutively expressed CorA Mg²⁺ transporter is the major Mg²⁺ influx system of Salmonella typhimurium and Escherichia coli. Genomic sequence data indicated the presence of a homolog in the archaeal organism Methanococcus jannaschii. The putative M. jannaschii CorA was expressed in an Mg²⁺-transport-deficient strain of S. typhimurium to determine its functional characteristics. The archaeal CorA homolog is a functional Mg²⁺ uptake system when expressed in S. typhimurium and has properties which are highly similar to those of the normal CorA transporter of S. typhimurium despite having a low level of sequence identity with the protein and being expressed in a lipid membrane of quite different composition than normal. This implies that the overall function of the proteins is the same and further suggests that their structures are very similar.     

Genetic dissection of hybrid incompatibilities between Drosophila simulans and D. mauritiana. I. Differential accumulation of hybrid male sterility effects on the X and autosomes

The genetic basis of hybrid incompatibility in crosses between Drosophila mauritiana and D. simulans was investigated to gain insight into the evolutionary mechanisms of speciation. In this study, segments of the D. mauritiana third chromosome were introgressed into a D. simulans genetic background and tested as homozygotes for viability, male fertility, and female fertility. The entire third chromosome was covered with partially overlapping segments. Many segments were male sterile, while none were female sterile or lethal, confirming previous reports of the rapid evolution of hybrid male sterility (HMS). A statistical model was developed to quantify the HMS accumulation. In comparison with previous work on the X chromosome, we estimate that the X has approximately 2.5 times the density of HMS factors as the autosomes. We also estimate that the whole genome contains approximately 15 HMS "equivalents"-i.e., 15 times the minimum number of incompatibility factors necessary to cause complete sterility. Although some caveats for the quantitative estimate of a 2.5-fold density difference are described, this study supports the notion that the X chromosome plays a special role in the evolution of reproductive isolation. Possible mechanisms of a "large X" effect include selective fixation of new mutations that are recessive or partially recessive and the evolution of sex-ratio distortion systems.     

Neural networks in intestinal immunoregulation

Key physiological functions of the intestine are governed by nerves and neurotransmitters. This complex control relies on two neuronal systems: an extrinsic innervation supplied by the two branches of the autonomic nervous system and an intrinsic innervation provided by the enteric nervous system. As a result of constant exposure to commensal and pathogenic microflora, the intestine developed a tightly regulated immune system. In this review, we cover the current knowledge on the interactions between the gut innervation and the intestinal immune system. The relations between extrinsic and intrinsic neuronal inputs are highlighted with regards to the intestinal immune response. Moreover, we discuss the latest findings on mechanisms underlying inflammatory neural reflexes and examine their relevance in the context of the intestinal inflammation. Finally, we discuss some of the recent data on the identification of the gut microbiota as an emerging player influencing the brain function.     

The Mouse GalR2 Galanin Receptor: Genomic Organization, cDNA Cloning, and Functional Characterization

Abstract: The diverse physiological actions of galanin are thought to be mediated through activation of galanin receptors (GalRs). We report the genomic and cDNA cloning of a mouse GalR that possesses a genomic structure distinct from that of GalR1 and encodes a functional galanin receptor. The mouse GalR gene consists of two exons separated by a single intron within the protein-coding region. The splicing site for the intron is located at the junction between the third transmembrane domain and the second intracellular loop. The cDNA encodes a 370-amino acid putative G protein-coupled receptor that is markedly different from human GalR1 and rat GalR3 (38 and 57%) but shares high homology with rat GalR2 (94%). In binding studies utilizing membranes from COS-7 cells transfected with mouse GalR2 cDNA, the receptor displayed high affinity ( K _D = 0.47 n M ) and saturable binding with ¹²⁵I-galanin ( B _max = 670 fmol/mg). The radioligand binding can be displaced by galanin and its analogues in a rank order: galanin ⋍ M40 ⋍ M15 ⋍ M35 ⋍ C7 ⋍ galanin (2–29) ⋍ galanin (1–16) ≫ galanin (10–29) ⋍ galanin (3–29), which resembles the pharmacological profile of the rat GalR2. Receptor activation by galanin in COS-7 cells stimulated phosphoinositide metabolism, which was not reversed by pertussis toxin. Thus, the galanin receptor encoded in the cloned mouse GalR gene is the type 2 galanin receptor and is active in both ligand binding and signaling assays.     

Demonstration of binding of dengue virus envelope protein to target cells.

The nature of the initial interaction of dengue virus with target cells and the extent to which this interaction defines tropism are unknown. Infection of some cells may involve antidengue antibody-mediated immune adherence to cells bearing immunoglobulin Fc receptors; however, this mechanism does not explain primary infection or the infection of cells without Fc receptors. We hypothesized that dengue virus envelope protein mediates initial binding to target cells. To test this hypothesis, a recombinant chimeric form of dengue type 2 virus envelope protein was used as a probe to investigate binding to the surfaces of potential target cells. Envelope protein was expressed amino terminal to the heavy-chain constant region of human immunoglobulin G containing the Fc receptor binding motif; the binding mediated by envelope determinants was distinguishable from the binding mediated by immunoglobulin Fc determinants. We found that the recombinant chimera bound to Vero, CHO, endothelial, and glial cells through envelope protein determinants and to monocytes and U937 cells by Fc-Fc receptor interactions. The highest level of binding was to Vero cells; binding was dose and time dependent and saturable. Examination of partial-length recombinant envelope proteins indicated that the binding motif was expressed between amino acids 281 and 423. Recombinant envelope protein inhibited infection of Vero cells by dengue virus, indicating the functional significance of the interaction of envelope protein and target cells in infectivity. These results suggest that envelope protein binding to a non-Fc receptor could explain the cell and tissue tropism of primary dengue virus infection.     

Ephrin-mediated restriction of ERK1/2 activity delimits the number of pigment cells in the Ciona CNS

Recent evidence suggests that ascidian pigment cells are related to neural crest-derived melanocytes of vertebrates. Using live-imaging, we determine a revised cell lineage of the pigment cells in Ciona intestinalis embryos. The neural precursors undergo successive rounds of anterior–posterior (A–P) oriented cell divisions, starting at the blastula 64-cell stage. A previously unrecognized fourth A–P oriented cell division in the pigment cell lineage leads to the generation of the post-mitotic pigment cell precursors. We provide evidence that MEK/ERK signals are required for pigment cell specification until approximately 30 min after the final cell division has taken place. Following each of the four A–P oriented cell divisions, ERK1/2 is differentially activated in the posterior sister cells, into which the pigment cell lineage segregates. Eph/ephrin signals are critical during the third A–P oriented cell division to spatially restrict ERK1/2 activation to the posterior daughter cell. Targeted inhibition of Eph/ephrin signals results in, at neurula stages, anterior expansion of both ERK1/2 activation and a pigment cell lineage marker and subsequently, at larval stages, supernumerary pigment cells. We discuss the implications of these findings with respect to the evolution of the vertebrate neural crest.     

A generalizable NLP framework for fast development of pattern-based biomedical relation extraction systems

Background

Text mining is increasingly used in the biomedical domain because of its ability to automatically gather information from large amount of scientific articles. One important task in biomedical text mining is relation extraction, which aims to identify designated relations among biological entities reported in literature. A relation extraction system achieving high performance is expensive to develop because of the substantial time and effort required for its design and implementation. Here, we report a novel framework to facilitate the development of a pattern-based biomedical relation extraction system. It has several unique design features: (1) leveraging syntactic variations possible in a language and automatically generating extraction patterns in a systematic manner, (2) applying sentence simplification to improve the coverage of extraction patterns, and (3) identifying referential relations between a syntactic argument of a predicate and the actual target expected in the relation extraction task.

Results

A relation extraction system derived using the proposed framework achieved overall F-scores of 72.66% for the Simple events and 55.57% for the Binding events on the BioNLP-ST 2011 GE test set, comparing favorably with the top performing systems that participated in the BioNLP-ST 2011 GE task. We obtained similar results on the BioNLP-ST 2013 GE test set (80.07% and 60.58%, respectively). We conducted additional experiments on the training and development sets to provide a more detailed analysis of the system and its individual modules. This analysis indicates that without increasing the number of patterns, simplification and referential relation linking play a key role in the effective extraction of biomedical relations.

Conclusions

In this paper, we present a novel framework for fast development of relation extraction systems. The framework requires only a list of triggers as input, and does not need information from an annotated corpus. Thus, we reduce the involvement of domain experts, who would otherwise have to provide manual annotations and help with the design of hand crafted patterns. We demonstrate how our framework is used to develop a system which achieves state-of-the-art performance on a public benchmark corpus.     

Ultrastructure of cilia and flagella - back to the future!

Eukaryotic cilia and flagella perform motility and sensory functions which are essential for cell survival in protozoans, and to organism development and homoeostasis in metazoans. Their ultrastructure has been studied from the early beginnings of electron microscopy, and these studies continue to contribute to much of our understanding about ciliary biology. In the light of the progress made in the visualization of cellular structures over the last decade, we revisit the ultrastructure of cilia and flagella. We briefly describe the typical features of a 9+2 axoneme before focusing extensively on the transition zone, the ciliary necklace, the singlet zone, the ciliary cap and the ciliary crown. We discuss how the singlet zone is linked to sensory and/or motile function, the contribution of the ciliary crown to ovocyte and mucosal propulsion, and the relationship between the ciliary cap and microtubule growth and shortening, and its relation to ciliary beat. We further examine the involvement of the transition zone/the ciliary necklace in axonemal stabilization, autotomy and as a diffusion barrier.     

Evaluation of 4-poster acaricide applicators to manage tick populations associated with disease risk in a Tennessee retirement community

In 1993, four residents of a retirement community in middle Tennessee were hospitalized with symptoms of ehrlichiosis causing community managers to implement mitigation methods to reduce tick numbers. For the past four years, managers have utilized 4-poster acaricide applicators that aim to reduce disease risk to residents by killing ticks that feed on deer. To determine the efficacy of this technique, we assessed Amblyomma americanum abundance in the vicinity of the devices by dragging 400 m vegetation transects once per month while ticks were active. In 2009, adult tick activity peaked in May, nymphal tick activity peaked in June, and larval activity peaked in September. Close to 4-poster devices, larval, nymphal, and adult tick abundances were reduced by 91%, 68%, and 49%, respectively (larval and nymphal p<0.001, adult p=0.005), relative to nearby untreated areas. No significant reduction in nymphal or adult A. americanum ticks was evident >300 m from 4-poster devices, however a ～90% reduction in larvae was observed to our sampling limit (400 m). At the low density at which these devices are currently being used (average distance between devices = 6.6 km), we conclude that they will have little large-scale effect on the health risk posed by ticks in this community.