Spatial and temporal expression of surfactant proteins in hyperoxia-induced neonatal rat lung injury

Background

Although personal cigarette smoking is the most important cause and modulator of chronic obstructive pulmonary disease (COPD), secondhand smoke (SHS) exposure could influence the course of the disease. Despite the importance of this question, the impact of SHS exposure on COPD health outcomes remains unknown.

Methods

We used data from two waves of a population-based multiwave U.S. cohort study of adults with COPD. 77 non-smoking respondents with a diagnosis of COPD completed direct SHS monitoring based on urine cotinine and a personal badge that measures nicotine. We evaluated the longitudinal impact of SHS exposure on validated measures of COPD severity, physical health status, quality of life (QOL), and dyspnea measured at one year follow-up.

Results

The highest level of SHS exposure, as measured by urine cotinine, was cross-sectionally associated with poorer COPD severity (mean score increment 4.7 pts; 95% CI 0.6 to 8.9) and dyspnea (1.0 pts; 95% CI 0.4 to 1.7) after controlling for covariates. In longitudinal analysis, the highest level of baseline cotinine was associated with worse COPD severity (4.7 points; 95% CI -0.1 to 9.4; p = 0.054), disease-specific QOL (2.9 pts; -0.16 to 5.9; p = 0.063), and dyspnea (0.9 pts; 95% CI 0.2 to 1.6 pts; p < 0.05), although the confidence intervals did not always exclude the no effect level.

Conclusion

Directly measured SHS exposure appears to adversely influence health outcomes in COPD, independent of personal smoking. Because SHS is a modifiable risk factor, clinicians should assess SHS exposure in their patients and counsel its avoidance. In public health terms, the effects of SHS exposure on this vulnerable subpopulation provide a further rationale for laws prohibiting public smoking.     

Automatic layout and visualization of biclusters

Background  

Biclustering has emerged as a powerful algorithmic tool for analyzing measurements of gene expression. A number of different methods have emerged for computing biclusters in gene expression data. Many of these algorithms may output a very large number of biclusters with varying degrees of overlap. There are no systematic methods that create a two-dimensional layout of the computed biclusters and display overlaps between them.     

A novel population of neuronal cells expressing the olfactory marker protein (OMP) in the anterior/dorsal region of the nasal cavity

The olfactory marker protein (OMP) is expressed in mature chemosensory neurons in the nasal neuroepithelium. Here, we report the identification of a novel population of OMP-expressing neurons located bilaterally in the anterior/dorsal region of each nasal cavity at the septum. These cells are clearly separated from the regio olfactoria, harboring the olfactory sensory neurons. During mouse development, the arrangement of the anterior OMP-cells undergoes considerable change. They appear at about stage E13 and are localized in the nasal epithelium during early stages; by epithelial budding, ganglion-shaped clusters are formed in the mesenchyme during the perinatal phase, and a filiform layer directly underneath the nasal epithelium is established in adults. The anterior OMP-cells extend long axonal processes which form bundles and project towards the brain. The data suggest that the newly discovered group of OMP-cells in the anterior region of the nasal cavity may serve a distinct sensory function.     

Fine-scale population genetic structure of a wildlife disease vector: the southern house mosquito on the island of Hawaii

The southern house mosquito, Culex quinquefasciatus, is a widespread tropical and subtropical disease vector. In the Hawaiian Islands, where it was introduced accidentally almost two centuries ago, it is considered the primary vector of avian malaria and pox. Avian malaria in particular has contributed to the extinction and endangerment of Hawaii's native avifauna, and has altered the altitudinal distribution of native bird populations. We examined the population genetic structure of Cx. quinquefasciatus on the island of Hawaii at a smaller spatial scale than has previously been attempted, with particular emphasis on the effects of elevation on population genetic structure. We found significant genetic differentiation among populations and patterns of isolation by distance within the island. Elevation per se did not have a limiting effect on gene flow; however, there was significantly lower genetic diversity among populations at mid elevations compared to those at low elevations. A recent sample taken from just above the predicted upper altitudinal distribution of Cx. quinquefasciatus on the island of Hawaii was confirmed as being a temporary summer population and appeared to consist of individuals from more than one source population. Our results indicate effects of elevation gradients on genetic structure that are consistent with known effects of elevation on population dynamics of this disease vector.     

Prevalence and evolutionary relationships of haematozoan parasites in native versus introduced populations of common myna Acridotheres tristis

The success of introduced species is frequently explained by their escape from natural enemies in the introduced region. We tested the enemy release hypothesis with respect to two well studied blood parasite genera (Plasmodium and Haemoproteus) in native and six introduced populations of the common myna Acridotheres tristis. Not all comparisons of introduced populations to the native population were consistent with expectations of the enemy release hypothesis. Native populations show greater overall parasite prevalence than introduced populations, but the lower prevalence in introduced populations is driven by low prevalence in two populations on oceanic islands (Fiji and Hawaii). When these are excluded, prevalence does not differ significantly. We found a similar number of parasite lineages in native populations compared to all introduced populations. Although there is some evidence that common mynas may have carried parasite lineages from native to introduced locations, and also that introduced populations may have become infected with novel parasite lineages, it may be difficult to differentiate between parasites that are native and introduced, because malarial parasite lineages often do not show regional or host specificity.     

Smoothened antagonists for hair inhibition

A series of aminomethylpyrazoles were prepared and evaluated using cell-based Smoothened β-lactamase reporter assay and Smoothened binding assay. Potent Smoothened antagonists 10k and 10l were found to inhibit hair growth in vivo in the C3H/HeN mouse hair growth model. The more selective compound 10l was tested negative in the 3T3 NRU assay, indicating a low risk for causing photo-irritation and was efficacious using the C3H/HeN mouse hair growth model although it was slightly less efficacious than that of the reference compound eflornithine (7).     

Low phosphorus supply constrains plant responses to elevated CO2: A meta‐analysis

Phosphorus (P) is an essential macro‐nutrient required for plant metabolism and growth. Low P availability could potentially limit plant responses to elevated carbon dioxide (eCO₂), but consensus has yet to be reached on the extent of this limitation. Here, based on data from experiments that manipulated both CO₂ and P for young individuals of woody and non‐woody species, we present a meta‐analysis of P limitation impacts on plant growth, physiological, and morphological response to eCO₂. We show that low P availability attenuated plant photosynthetic response to eCO₂ by approximately one‐quarter, leading to a reduced, but still positive photosynthetic response to eCO₂ compared to those under high P availability. Furthermore, low P limited plant aboveground, belowground, and total biomass responses to eCO₂, by 14.7%, 14.3%, and 12.4%, respectively, equivalent to an approximate halving of the eCO₂ responses observed under high P availability. In comparison, low P availability did not significantly alter the eCO₂‐induced changes in plant tissue nutrient concentration, suggesting tissue nutrient flexibility is an important mechanism allowing biomass response to eCO₂ under low P availability. Low P significantly reduced the eCO₂‐induced increase in leaf area by 14.3%, mirroring the aboveground biomass response, but low P did not affect the eCO₂‐induced increase in root length. Woody plants exhibited stronger attenuation effect of low P on aboveground biomass response to eCO₂ than non‐woody plants, while plants with different mycorrhizal associations showed similar responses to low P and eCO₂ interaction. This meta‐analysis highlights crucial data gaps in capturing plant responses to eCO₂ and low P availability. Field‐based experiments with longer‐term exposure of both CO₂ and P manipulations are critically needed to provide ecosystem‐scale understanding. Taken together, our results provide a quantitative baseline to constrain model‐based hypotheses of plant responses to eCO₂ under P limitation, thereby improving projections of future global change impacts.     

Targeted Identification of Protein Interactions in Eukaryotic mRNA Translation

To identify protein–protein interactions and phosphorylated amino acid sites in eukaryotic mRNA translation, replicate TAP‐MudPIT and control experiments are performed targeting Saccharomyces cerevisiae genes previously implicated in eukaryotic mRNA translation by their genetic and/or functional roles in translation initiation, elongation, termination, or interactions with ribosomal complexes. Replicate tandem affinity purifications of each targeted yeast TAP‐tagged mRNA translation protein coupled with multidimensional liquid chromatography and tandem mass spectrometry analysis are used to identify and quantify copurifying proteins. To improve sensitivity and minimize spurious, nonspecific interactions, a novel cross‐validation approach is employed to identify the most statistically significant protein–protein interactions. Using experimental and computational strategies discussed herein, the previously described protein composition of the canonical eukaryotic mRNA translation initiation, elongation, and termination complexes is calculated. In addition, statistically significant unpublished protein interactions and phosphorylation sites for S. cerevisiae’s mRNA translation proteins and complexes are identified.     

TMEM59 defines a novel ATG16L1‐binding motif that promotes local activation of LC3

Selective autophagy underlies many of the important physiological roles that autophagy plays in multicellular organisms, but the mechanisms involved in cargo selection are poorly understood. Here we describe a molecular mechanism that can target conventional endosomes for autophagic degradation. We show that the human transmembrane protein TMEM59 contains a minimal 19‐amino‐acid peptide in its intracellular domain that promotes LC3 labelling and lysosomal targeting of its own endosomal compartment. Interestingly, this peptide defines a novel protein motif that mediates interaction with the WD‐repeat domain of ATG16L1, thus providing a mechanistic basis for the activity. The motif is represented with the same ATG16L1‐binding ability in other molecules, suggesting a more general relevance. We propose that this motif may play an important role in targeting specific membranous compartments for autophagic degradation, and therefore it may facilitate the search for adaptor proteins that promote selective autophagy by engaging ATG16L1. Endogenous TMEM59 interacts with ATG16L1 and mediates autophagy in response to Staphylococcus aureus infection.