Probing interactions of NMD factors in a distance-dependent manner by BioID

The understanding of molecular mechanisms requires the elucidation of protein-protein interaction in vivo. For large multi-factor complexes like those assembling on mRNA, co-immunoprecipitation assays often identify many peripheral interactors that complicate the interpretation of such results and that might conceal other insightful mechanistic connections. Here we address the protein-protein interaction network for key factors in the nonsense-mediated mRNA decay (NMD) pathway in a distant-dependent manner using BioID1,2. In this novel approach, the mutant E. coli biotin-protein ligase BirAR118G is fused to the bait protein and biotinylates proximal proteins promiscuously. Hence, interactors positioned close to the bait in vivo are enriched by streptavidin purification and identified by mass spectrometry or western blotting. We present a validation of the BioID assay and preliminary results for close interactors of UPF1 and other key players in NMD.

Probing interactions of NMD factors in a distance-dependent manner by BioID

The understanding of molecular mechanisms requires the elucidation of protein-protein interaction in vivo. For large multi-factor complexes like those assembling on mRNA, co-immunoprecipitation assays often identify many peripheral interactors that complicate the interpretation of such results and that might conceal other insightful mechanistic connections. Here we address the protein-protein interaction network for key factors in the nonsense-mediated mRNA decay (NMD) pathway in a distant-dependent manner using BioID1,2. In this novel approach, the mutant E. coli biotin-protein ligase BirAR118G is fused to the bait protein and biotinylates proximal proteins promiscuously. Hence, interactors positioned close to the bait in vivo are enriched by streptavidin purification and identified by mass spectrometry or western blotting. We present a validation of the BioID assay and preliminary results for close interactors of UPF1 and other key players in NMD.

Effect of irradiation distance on image contrast in epi-optoacoustic imaging of human volunteers

In combined clinical optoacoustic (OA) and ultrasound (US) imaging, epi-mode irradiation and detection integrated into one single probe offers flexible imaging of the human body. The imaging depth in epi-illumination is, however, strongly affected by clutter. As shown in previous phantom experiments, the location of irradiation plays an important role in clutter generation. We investigated the influence of the irradiation geometry on the local image contrast of clinical images, by varying the separation distance between the irradiated area and the acoustic imaging plane of a linear ultrasound transducer in an automated scanning setup. The results for different volunteers show that the image contrast can be enhanced on average by 25% and locally by more than a factor of two, when the irradiated area is slightly separated from the probe. Our findings have an important impact on the design of future optoacoustic probes for clinical application.

Long Distance Electron Transfer at the Metal/Alkanethiol/Ionic Liquid Interface

The rate constants of simple electron transfer (ET) reactions in room temperature ionic liquids (ILs) available now are rather high, typically at the edge of experimental accuracy. To consider ET phenomena in these media in view of theory developed earlier for molecular solvents, it is crucial to provide quantitative comparison of experimental kinetic data for certain reactions. We report this comparison for ferrocene/ferrocenium reaction. The ET distance is fixed by Au surface modification by alkanethiol self-assembled monolayers, which were characterized by in situ scanning tunneling microscopy. The dependence of ln kapp on barrier thickness in the range of ca. 6–20 Å is linear, with a slope typical for the same plots in aqueous media. This result confirms diabatic mode of Fc oxidation at long distance. The data for shorter ET distances point to the adiabatic regime of ET at a bare gold surface, although more detailed computational studies are required to justify this conclusion.

Long distance root–shoot signalling in plant–insect community interactions

Plants mediate interactions between insects, including leaf- and root-feeders; yet the underlying mechanisms and connection with ecological theory remain unresolved. In this review, based on novel insights into long-distance (i.e., leaf–leaf, root–shoot) defence signalling, we explore the role of phytohormones in driving broad-scale patterns of aboveground–belowground interactions that can be extrapolated to general plant–insect relationships. We propose that the outcome of intra-feeding guild interactions is generally negative due to induction of similar phytohormonal pathways, whereas between-guild interactions are often positive due to negative signal crosstalk. However, not all outcomes could be explained by feeding guild; we argue that future studies should target ecologically representative plant–insect systems, distinguish subguilds, and include plant growth hormones to improve our understanding of plant-mediated interactions.

Salience and Asymmetric Judgments of Physical Distance

Previous research has shown that distance estimates made from memory are often asymmetric. Specifically, when A is a prominent location (a land-mark) and B is not, people tend to recall a longer distance from A to B than from B to A. Results of two experiments showed that asymmetric judgments of distance are not restricted to judgments made from memory but occur also for judgments made when all relevant visual cues are still present. Furthermore, results indicated that situational salience is sufficient to produce asymmetric judgments and that distinctiveness (such as in the case of architectural landmarks) is not necessary.

Long distance dispersal shaped patterns of human genetic diversity in Eurasia

Most previous attempts at reconstructing the past history of human populations did not explicitly take geography into account, or considered very simple scenarios of migration and ignored environmental information. However, it is likely that the Last Glacial Maximum (LGM) affected the demography and the range of many species, including our own. Moreover, long-distance dispersal (LDD) may have been an important component of human migrations, allowing fast colonization of new territories and preserving high levels of genetic diversity. Here, we use a high-quality microsatellite dataset genotyped in 22 populations to estimate the posterior probabilities of several scenarios for the settlement of the Old World by modern humans. We considered models ranging from a simple spatial expansion to others including LDD and a LGM-induced range contraction, as well as Neolithic demographic expansions. We find that scenarios with LDD are much better supported by data than models without LDD. Nevertheless, we show evidence that LDD events to empty habitats were strongly prevented during the settlement of Eurasia. This unexpected absence of LDD ahead of the colonization wave front could have been caused by an Allee effect, either due to intrinsic causes such as an inbreeding depression built during the expansion, or to extrinsic causes such as direct competition with archaic humans. Overall, our results suggest only a relatively limited effect of the LGM-contraction on current patterns of human diversity. This is in clear contrast with the major role of LDD migrations, which have potentially contributed to the intermingled genetic structure of Eurasian populations.

The utility of preoperative six-minute-walk distance in lung transplantation

RATIONALE The use of 6-minute-walk distance (6MWD) as an indicator of exercise capacity to predict postoperative survival in lung transplantation has not previously been well studied. OBJECTIVES To evaluate the association between 6MWD and postoperative survival following lung transplantation. METHODS Adult, first time, lung-only transplantations per the United Network for Organ Sharing database from May 2005 to December 2011 were analyzed. Kaplan-Meier methods and Cox proportional hazards modeling were used to determine the association between preoperative 6MWD and post-transplant survival after adjusting for potential confounders. A receiver operating characteristic curve was used to determine the 6MWD value that provided maximal separation in 1-year mortality. A subanalysis was performed to assess the association between 6MWD and post-transplant survival by disease category. MEASUREMENTS AND MAIN RESULTS A total of 9,526 patients were included for analysis. The median 6MWD was 787 ft (25th-75th percentiles = 450-1,082 ft). Increasing 6MWD was associated with significantly lower overall hazard of death (P < 0.001). Continuous increase in walk distance through 1,200-1,400 ft conferred an incremental survival advantage. Although 6MWD strongly correlated with survival, the impact of a single dichotomous value to predict outcomes was limited. All disease categories demonstrated significantly longer survival with increasing 6MWD (P ≤ 0.009) except pulmonary vascular disease (P = 0.74); however, the low volume in this category (n = 312; 3.3%) may limit the ability to detect an association. CONCLUSIONS 6MWD is significantly associated with post-transplant survival and is best incorporated into transplant evaluations on a continuous basis given limited ability of a single, dichotomous value to predict outcomes.

Distance from Sub-Saharan Africa Predicts Mutational Load in Diverse Human Genomes

The Out-of-Africa (OOA) dispersal ∼50,000 y ago is characterized by a series of founder events as modern humans expanded into multiple continents. Population genetics theory predicts an increase of mutational load in populations undergoing serial founder effects during range expansions. To test this hypothesis, we have sequenced full genomes and high-coverage exomes from seven geographically divergent human populations from Namibia, Congo, Algeria, Pakistan, Cambodia, Siberia, and Mexico. We find that individual genomes vary modestly in the overall number of predicted deleterious alleles. We show via spatially explicit simulations that the observed distribution of deleterious allele frequencies is consistent with the OOA dispersal, particularly under a model where deleterious mutations are recessive. We conclude that there is a strong signal of purifying selection at conserved genomic positions within Africa, but that many predicted deleterious mutations have evolved as if they were neutral during the expansion out of Africa. Under a model where selection is inversely related to dominance, we show that OOA populations are likely to have a higher mutation load due to increased allele frequencies of nearly neutral variants that are recessive or partially recessive.

Long-distance spore dispersal in wood-inhabiting Basidiomycetes

Eight species of wood-inhabiting basidiomycetes (Laurilia sulcata, Peniophora aurantiaca, Resinicium bicolor, Scytinostroma galactinum, Terana caerulea, Trichaptum abietinum, T. biforme and T. fuscoviolaceum) were used in a spore-trapping test to evaluate their individual ability for long-distance spore dispersal. Petri dishes with single spore mycelia were used as baits. In the experiment, carried out at the Botanical Institute in Göteborg, spores from the air were regularly captured. Surprisingly, spores were captured from species whose nearest known natural occurrence was located quite far from Göteborg. The closest population of Peniophora aurantiaca is about 1000 km south of Göteborg. The results from this experiment support the hypothesis that fungal spores are widely and efficiently dispersed. Such a broad and extensive dispersal ability is of vital importance, especially for wood-inhabiting species which are highly dependent on a substrate which is onlv temporarily available.

Long-distance transport of alkali metals in maturing wheat

The alkali metals cesium, rubidium, lithium and sodium were introduced together with strontium via flaps into leaf laminas or into the stem of maturing, intact winter wheat (Triticum aestivum L. cv. Arina) grown in a field. Long-distance transport of these elements and the influence of the application date and of different application positions were investigated. The phloem-immobile Sr served as a marker for the distribution of the xylem sap in the plants. Dry matter accumulation in the grains and the transpiration per shoot were not markedly affected by the treatments as compared to control plants. The phloem mobility was rather high for Cs and Rb. Li was almost immobile in the phloem (similarly to Sr). An application into the cut stem xylem below the second leaf node contributed more to the contents in the grains than an application into the flag leaf. An earlier feeding date led to a higher accumulation in the grains. The marked losses of the elements applied during maturation (most pronounced for Li) can be explained by leakage in the rain.

Long-distance transport of cobalt and nickel in maturing wheat

Cobalt, nickel and strontium were introduced via flaps into leaf laminas or into the stem of maturing, intact winter wheat (Triticum aestivum L., cv. `Arina') grown under natural conditions in a field. Long-distance transport of these elements and the influence of the application date and of different application positions were investigated. The dry-matter accumulation in the grains was not markedly affected by the treatments as compared to untreated control plants. The phloem-immobile strontium served as a marker for the distribution of the xylem sap in the plants. After foliar application, nickel accumulated more rapidly and in higher quantities in the grains than cobalt. Therefore, nickel has a slightly better phloem mobility than cobalt. Regardless of the application date, a higher percentage of the two elements was transported from the flag leaf lamina than from the second or third lamina from the top to the grains. These results indicate that the leaf position is highly relevant for the transfer of the heavy metals investigated to the ear. Introduction into the stem led to a higher accumulation of nickel and cobalt in the grains than introduction into one of the leaves. An earlier feeding date caused a higher accumulation of nickel and cobalt in the grains when introduced into the stem. In contrast, no major differences between earlier and later feeding dates were detected when the elements were introduced into the leaves. Losses of the applied elements were detected during maturation and can be explained by leakage in the rain.