Neuronal Platelet-Activating Factor Receptor Signal Transduction Involves a Pertussis Toxin-Sensitive G-Protein

In most nonneural systems, platelet-activating factor (PAF) receptor effects are mediated by G-proteins that are often pertussis toxin-sensitive. The activation of pertussis toxin-sensitive G-proteins linked to PAF receptors results in the mobilization of intracellular calcium, at least in part, through the second messenger inositol triphosphate. We have sought to determine if a pertussis toxin-sensitive G-protein is involved in the PAF receptor-mediated phenomena of growth cone collapse and of synaptic enhancement in primary neuronal culture. Using infrared differential interference contrast microscopy and patch-clamp recording techniques, pertussis toxin, but not the inactive B oligomer of the toxin, was found to block both the growth cone collapse and the enhanced synaptic release of excitatory transmitter induced by a nonhydrolyzable PAF receptor agonist, making it likely that G_o, G_q, or G_i is the G-protein transducer of PAF receptors in primary neurons. We believe that PAF acts directly on neuronal receptors, which are linked to pertussis toxin-sensitive G-proteins, on the tips of developing neurites, and on presynaptic nerve terminals, leading to growth cone collapse and enhanced synaptic release of transmitter.     

Maternal brooding in the children’s python <Emphasis Type="Italic">(Antaresia childreni)</Emphasis> promotes egg water balance

Parental care provides considerable benefits to offspring and is widespread among animals, yet it is relatively uncommon among squamate reptiles (e.g., lizards and snakes). However, all pythonine snakes show extended maternal egg brooding with some species being facultatively endothermic. While facultative endothermy provides thermal benefits, the presence of brooding in non-endothermic species suggests other potential benefits of brooding. In this study we experimentally tested the functional significance of maternal brooding relative to water balance in the children’s python, Antaresia childreni, a small species that does not exhibit facultative endothermy. Clutch evaporative water loss (EWL) was positively correlated with clutch mass and was much lower than expected values based on individual eggs. The conglomerate clutch behaved as a single unit with a decreasing surface area to volume ratio as clutch size increased. Maternal brooding had a dramatic impact on evaporation from eggs, reducing and possibly eliminating clutch EWL. In a separate experiment, we found that viability of unattended eggs is highly affected by humidity level, even in the narrow range from 75 to 100% relative humidity at 30.5°C (20–33 mg m⁻³ absolute humidity). However, the presence of the brooding female ameliorated this sensitivity, as viability of brooded clutches at 75% relative humidity was higher than that of non-brooded eggs at either the same absolute humidity or at near-saturated conditions. Overall, these results demonstrate that brooding behavior strongly promotes egg water balance (and thus egg viability) in children’s pythons.     

Identification of the IL-17 receptor related molecule IL-17RC as the receptor for IL-17F

The proinflammatory cytokines IL-17A and IL-17F have a high degree of sequence similarity and share many biological properties. Both have been implicated as factors contributing to the progression of inflammatory and autoimmune diseases. Moreover, reagents that neutralize IL-17A significantly ameliorate disease severity in several mouse models of human disease. IL-17A mediates its effects through interaction with its cognate receptor, the IL-17 receptor (IL-17RA). We report here that the IL-17RA-related molecule, IL-17RC is the receptor for IL-17F. Notably, both IL-17A and IL-17F bind to IL-17RC with high affinity, leading us to suggest that a soluble form of this molecule may serve as an effective therapeutic antagonist of IL-17A and IL-17F. We generated a soluble form of IL-17RC and demonstrate that it effectively blocks binding of both IL-17A and IL-17F, and that it inhibits signaling in response to these cytokines. Collectively, our work indicates that IL-17RC functions as a receptor for both IL-17A and IL-17F and that a soluble version of this protein should be an effective antagonist of IL-17A and IL-17F mediated inflammatory diseases.     

Endemic dengue associated with the co-circulation of multiple viral lineages and localized density-dependent transmission

Dengue is one of the most important infectious diseases of humans and has spread throughout much of the tropical and subtropical world. Despite this widespread dispersal, the determinants of dengue transmission in endemic populations are not well understood, although essential for virus control. To address this issue we performed a phylogeographic analysis of 751 complete genome sequences of dengue 1 virus (DENV-1) sampled from both rural (Dong Thap) and urban (Ho Chi Minh City) populations in southern Viet Nam during the period 2003-2008. We show that DENV-1 in Viet Nam exhibits strong spatial clustering, with likely importation from Cambodia on multiple occasions. Notably, multiple lineages of DENV-1 co-circulated in Ho Chi Minh City. That these lineages emerged at approximately the same time and dispersed over similar spatial regions suggests that they are of broadly equivalent fitness. We also observed an important relationship between the density of the human host population and the dispersion rate of dengue, such that DENV-1 tends to move from urban to rural populations, and that densely populated regions within Ho Chi Minh City act as major transmission foci. Despite these fluid dynamics, the dispersion rates of DENV-1 are relatively low, particularly in Ho Chi Minh City where the virus moves less than an average of 20 km/year. These low rates suggest a major role for mosquito-mediated dispersal, such that DENV-1 does not need to move great distances to infect a new host when there are abundant susceptibles, and imply that control measures should be directed toward the most densely populated urban environments.     

Clustering more than two million biomedical publications: comparing the accuracies of nine text-based similarity approaches

Background

We investigate the accuracy of different similarity approaches for clustering over two million biomedical documents. Clustering large sets of text documents is important for a variety of information needs and applications such as collection management and navigation, summary and analysis. The few comparisons of clustering results from different similarity approaches have focused on small literature sets and have given conflicting results. Our study was designed to seek a robust answer to the question of which similarity approach would generate the most coherent clusters of a biomedical literature set of over two million documents.

Methodology

We used a corpus of 2.15 million recent (2004-2008) records from MEDLINE, and generated nine different document-document similarity matrices from information extracted from their bibliographic records, including titles, abstracts and subject headings. The nine approaches were comprised of five different analytical techniques with two data sources. The five analytical techniques are cosine similarity using term frequency-inverse document frequency vectors (tf-idf cosine), latent semantic analysis (LSA), topic modeling, and two Poisson-based language models – BM25 and PMRA (PubMed Related Articles). The two data sources were a) MeSH subject headings, and b) words from titles and abstracts. Each similarity matrix was filtered to keep the top-n highest similarities per document and then clustered using a combination of graph layout and average-link clustering. Cluster results from the nine similarity approaches were compared using (1) within-cluster textual coherence based on the Jensen-Shannon divergence, and (2) two concentration measures based on grant-to-article linkages indexed in MEDLINE.

Conclusions

PubMed''s own related article approach (PMRA) generated the most coherent and most concentrated cluster solution of the nine text-based similarity approaches tested, followed closely by the BM25 approach using titles and abstracts. Approaches using only MeSH subject headings were not competitive with those based on titles and abstracts.     

Quantitative imaging of protein interactions in the cell nucleus

Over the past decade, genetically encoded fluorescent proteins have become widely used as noninvasive markers in living cells. The development of fluorescent proteins, coupled with advances in digital imaging, has led to the rapid evolution of live-cell imaging methods. These approaches are being applied to address biological questions of the recruitment, co-localization, and interactions of specific proteins within particular subcellular compartments. In the wake of this rapid progress, however, come important issues associated with the acquisition and analysis of ever larger and more complex digital imaging data sets. Using protein localization in the mammalian cell nucleus as an example, we will review some recent developments in the application of quantitative imaging to analyze subcellular distribution and co-localization of proteins in populations of living cells. In this report, we review the principles of acquiring fluorescence resonance energy transfer (FRET) microscopy measurements to define the spatial relationships between proteins. We then discuss how fluorescence lifetime imaging microscopy (FLIM) provides a method that is independent of intensity-based measurements to detect localized protein interactions with spatial resolution. Finally, we consider potential problems associated with the expression of proteins fused to fluorescent proteins for FRET-based measurements from living cells.     

Bullera hoabinhensis sp. nov., a new ballistoconidiogenous yeast isolated from a plant leaf collected in Vietnam

VY-68, a ballistoconidiogenous yeast strain, isolated from a plant leaf at Cuc Phuong National Park of Ninh Binh Province, Vietnam, was assigned to the genus Bullera based on morphological and chemotaxonomical characteristics. Based on the sequence analyses of 18S rDNA, D1/D2 region of 26S rDNA, and internal transcribed spacer regions (ITS), VY-68 was phylogenetically closely related to Bullera pseudoalba and Cryptococcus cellulolyticus. DNA-DNA reassociation experiments among VY-68, B. pseudoalba and C. cellulolyticus revealed that strain VY-68 is a distinct species, and the latter two are conspecific. Bullera hoabinhensis is proposed for VY-68.