13C and 15N NMR evidence for peripheral intercalation of uniformly labeled fusogenic peptides incorporated in a biomimetic membrane

Membrane fusion requires drastic and transient changes of bilayer curvature and here we have studied the interaction of three de novo designed synthetic hydrophobic peptides with a biomimetic three-lipid mixture by solid state NMR. An experimental approach is presented for screening of peptide-lipid interactions and their aggregation, and their embedding in a biomimetic membrane system using established proton-decoupled 13C,15N and proton spin diffusion heteronuclear 1H-13C correlation NMR methods at high magnetic field. Experiments are presented for a set of de-novo designed fusion peptides in interaction with their lipid environment. The data provide additional support for the transmembrane model for the least fusogenic peptide, L16, while the peripheral intercalation model is preferred for the fusogenic peptides LV16 and LV16G8P9. This contributes to converging evidence that peripheral intercalation is both necessary and sufficient to trigger the fusion process for a lipid mixture close to a critical point for phase separation across the bilayer.     

The significance of morphometric and fecundity differences between the ‘biotypes' of the Brown Planthopper,Nilaparvata lugens

A morphometric analysis of biotypes 1, 2 and 3 from the International Rice Research Institute, Philippines, reared respectively on rice cultivars TN1, Mudgo and ASD7, showed significant differences, but some overlap between them. When the three biotypes were each reared for a single generation on TN1, morphometric differences were very greatly reduced and the distributions widely overlapped.Biotypes 2 and 3 were significantly less fecund than biotype 1 when reared on their normal host varieties. When all were reared on TN1, biotype 3 showed a somewhat lower fecundity than did 1 and 2, but the difference was less than previously reported.It is concluded that the evidence for the association of morphometric differences with virulence characteristics inN. lugens is not proved. Equally there is no evidence that morphometric data may be used to identify field populations with distinct patterns of virulence.

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La signification des différences morphométriques et de fécondité entre des biotypes deNilaparvata lugens

Résumé Ce que l'on a appelé des biotypes deN. lugens sont des populations caractérisées par différents types de virulence à l'égard de différents cultivars résistants de riz, mis en évidence par des essais variétaux systématiques. Différents chercheurs ont tenté de trouver des caractères morphologiques pour identifier ces biotypes.Nous avons fait une analyse morphométrique des biotypes 1, 2 et 3 de l'International Rice Research Institute (IRRI) Philippines. Quand ils sont élevés sur leur propre varieté — biotype 1 sur TN1, 2 sur Mudgo, 3 sur ASD7 — des différences significatives sont observées, bien qu'il y ait un chevauchement considérable. Quand les 3 populations biotypes sont élevées sur la variété sensible TN1, les différences morphométriques sont réduites et le chevauchement fortement augmenté. Nous pourrions alors conclure qu'une part importante de la différenciation morphométrique est due à des facteurs écologiques et non à des différences génétiques entre les populations. Des chercheurs avaient indiqué des différences de fécondité entre les biotypes de l'IRRI, le biotype 3 étant significativement moins fécond; les résultats publiés son contradictoires. Nos observations suggèrent une certaine diminution de la fécondité pour le biotype 3 élevé sur TN1, mais plus limitée que les autres auteurs ne l'avaient envisagée.Nous en concluons qu'il n'y a pas de véritable preuve pour étayer l'hypothèse que les biotypes deN. lugens sont caractérisés par des paramètres morphométriques génétiquement déterminés. Il est alors fallacieux de suggérer que de tels caractères pourraient être utilisés pour identifier des populations avec différents types de virulence. Nous repoussons aussi l'hypothèse que les biotypes représentent une étape dans le processus de spéciation.

     

Loss of cytoplasmic CDK1 predicts poor survival in human lung cancer and confers chemotherapeutic resistance

The dismal lethality of lung cancer is due to late stage at diagnosis and inherent therapeutic resistance. The incorporation of targeted therapies has modestly improved clinical outcomes, but the identification of new targets could further improve clinical outcomes by guiding stratification of poor-risk early stage patients and individualizing therapeutic choices. We hypothesized that a sequential, combined microarray approach would be valuable to identify and validate new targets in lung cancer. We profiled gene expression signatures during lung epithelial cell immortalization and transformation, and showed that genes involved in mitosis were progressively enhanced in carcinogenesis. 28 genes were validated by immunoblotting and 4 genes were further evaluated in non-small cell lung cancer tissue microarrays. Although CDK1 was highly expressed in tumor tissues, its loss from the cytoplasm unexpectedly predicted poor survival and conferred resistance to chemotherapy in multiple cell lines, especially microtubule-directed agents. An analysis of expression of CDK1 and CDK1-associated genes in the NCI60 cell line database confirmed the broad association of these genes with chemotherapeutic responsiveness. These results have implications for personalizing lung cancer therapy and highlight the potential of combined approaches for biomarker discovery.     

Observations on Abundance of Bluntnose Sixgill Sharks,Hexanchus griseus,in an Urban Waterway in Puget Sound, 2003-2005

The bluntnose sixgill shark, Hexanchus griseus, is a widely distributed but poorly understood large, apex predator. Anecdotal reports of diver-shark encounters in the late 1990’s and early 2000’s in the Pacific Northwest stimulated interest in the normally deep-dwelling shark and its presence in the shallow waters of Puget Sound. Analysis of underwater video documenting sharks at the Seattle Aquarium’s sixgill research site in Elliott Bay and mark-resight techniques were used to answer research questions about abundance and seasonality. Seasonal changes in relative abundance in Puget Sound from 2003–2005 are reported here. At the Seattle Aquarium study site, 45 sixgills were tagged with modified Floy visual marker tags, along with an estimated 197 observations of untagged sharks plus 31 returning tagged sharks, for a total of 273 sixgill observations recorded. A mark-resight statistical model based on analysis of underwater video estimated a range of abundance from a high of 98 sharks seen in July of 2004 to a low of 32 sharks seen in March of 2004. Both analyses found sixgills significantly more abundant in the summer months at the Seattle Aquarium’s research station.     

Stable Isotopes in Fish Eye Lenses as Potential Recorders of Trophic and Geographic History

We evaluated eye lenses as potential recorders of stable isotope histories in fish because they consist of metabolically inert optical proteins that are deposited in successive, concentric circles (laminae) much like otolith circuli and tree rings. We conducted four different tests on lenses from red snapper, red grouper, gag, and white grunt. The first test was a low-resolution screening of multiple individuals (4–5 radial groups of laminae per lens, all species except white grunt). Along the radial axis, all individuals exhibited substantial isotopic variability. Red snapper individuals separated into two groups based on δ ¹⁵N and gag separated into two groups based on δ ¹³C. Two gag with the greatest variation were chosen for high-resolution temporal analysis using individual laminae from their second eye lenses. The first-order patterns from the high-resolution analysis generally mimicked patterns from the low-resolution screening of grouped laminae, yet the high-resolution plots revealed early-life details that were not apparent in the low-resolution screenings. For the third test, left- versus right-eye variation was compared using high-resolution methods. White grunt left- and right-eye radial isotopic patterns were almost identical for both δ ¹³C and δ ¹⁵N, suggesting the variations observed among individual fish were not artifacts. The final test evaluated intra-laminar variation; multiple samples were analyzed from different parts of the same lamina. Seven laminae from three individuals of two species were analyzed in this manner; variations among laminae were found to be much higher than variations within laminae. However, nominal intra-laminar variations were comparable to nominal differences between left and right lenses, suggesting intra-laminar variation established measurement precision. Eye lens isotopes appear to be useful for reconstructing the isotopic histories of individual fish; these histories can be compared with spatially-derived isoscapes to reconstruct individual histories for site fidelity, movement and trophic position.     

An Antidote to the Imager's Fallacy,or How to Identify Brain Areas That Are in Limbo

Traditionally, fMRI data are analyzed using statistical parametric mapping approaches. Regardless of the precise thresholding procedure, these approaches ultimately divide the brain in regions that do or do not differ significantly across experimental conditions. This binary classification scheme fosters the so-called imager''s fallacy, where researchers prematurely conclude that region A is selectively involved in a certain cognitive task because activity in that region reaches statistical significance and activity in region B does not. For such a conclusion to be statistically valid, however, a test on the differences in activation across these two regions is required. Here we propose a simple GLM-based method that defines an “in-between” category of brain regions that are neither significantly active nor inactive, but rather “in limbo”. For regions that are in limbo, the activation pattern is inconclusive: it does not differ significantly from baseline, but neither does it differ significantly from regions that do show significant changes from baseline. This pattern indicates that measurement was insufficiently precise. By directly testing differences in activation, our procedure helps reduce the impact of the imager''s fallacy. The method is illustrated using concrete examples.