Cryo-EM Elucidation of the Structure of Bacteriophage P22 Virions after Genome Release

Genome ejection proteins are required to facilitate transport of bacteriophage P22 double-stranded DNA safely through membranes of Salmonella. The structures and locations of all proteins in the context of the mature virion are known, with the exception of three ejection proteins. Furthermore, the changes that occur to the proteins residing in the mature virion upon DNA release are not fully understood. We used cryogenic electron microscopy to obtain what is, to our knowledge, the first asymmetric reconstruction of mature bacteriophage P22 after double-stranded DNA has been extruded from the capsid—a state representative of one step during viral infection. Results of icosahedral and asymmetric reconstructions at estimated resolutions of 7.8 and 12.5 Å resolutions, respectively, are presented. The reconstruction shows tube-like protein density extending from the center of the tail assembly. The portal protein does not revert to the more contracted, procapsid state, but instead maintains an extended and splayed barrel structure. These structural details contribute to our understanding of the molecular mechanism of P22 phage infection and also set the foundation for future exploitation serving engineering purposes.     

Loss of nucleoplasmic LAP2alpha-lamin A complexes causes erythroid and epidermal progenitor hyperproliferation

Lamina-associated polypeptide (LAP) 2alpha is a chromatin-associated protein that binds A-type lamins. Mutations in both LAP2alpha and A-type lamins are linked to human diseases called laminopathies, but the molecular mechanisms are poorly understood. The A-type lamin-LAP2alpha complex interacts with and regulates retinoblastoma protein (pRb), but the significance of this interaction in vivo is unknown. Here we address the function of the A-type lamin-LAP2alpha complex with the use of LAP2alpha-deficient mice. We show that LAP2alpha loss causes relocalization of nucleoplasmic A-type lamins to the nuclear envelope and impairs pRb function. This causes inefficient cell-cycle arrest in dense fibroblast cultures and hyperproliferation of epidermal and erythroid progenitor cells in vivo, leading to tissue hyperplasia. Our results support a disease-relevant model in which LAP2alpha defines A-type lamin localization in the nucleoplasm, which in turn affects pRb-mediated regulation of progenitor cell proliferation and differentiation in highly regenerative tissues.     

The histone H3K79 methyltransferase Dot1L is essential for mammalian development and heterochromatin structure

Dot1 is an evolutionarily conserved histone methyltransferase specific for lysine 79 of histone H3 (H3K79). In Saccharomyces cerevisiae, Dot1-mediated H3K79 methylation is associated with telomere silencing, meiotic checkpoint control, and DNA damage response. The biological function of H3K79 methylation in mammals, however, remains poorly understood. Using gene targeting, we generated mice deficient for Dot1L, the murine Dot1 homologue. Dot1L-deficient embryos show multiple developmental abnormalities, including growth impairment, angiogenesis defects in the yolk sac, and cardiac dilation, and die between 9.5 and 10.5 days post coitum. To gain insights into the cellular function of Dot1L, we derived embryonic stem (ES) cells from Dot1L mutant blastocysts. Dot1L-deficient ES cells show global loss of H3K79 methylation as well as reduced levels of heterochromatic marks (H3K9 di-methylation and H4K20 tri-methylation) at centromeres and telomeres. These changes are accompanied by aneuploidy, telomere elongation, and proliferation defects. Taken together, these results indicate that Dot1L and H3K79 methylation play important roles in heterochromatin formation and in embryonic development.     

Plant-mycorrhiza percent infection as evidence of coupled metabolism

A common feature of mycorrhizal observation is the growth of the infection on the plant root as a percent of the infected root or root tip length. Often, this is measured as a logistic curve with an eventual, though usually transient, plateau. It is shown in this paper that the periods of stable percent infection in the mycorrhizal growth cycle correspond to periods where both the plant and mycorrhiza growth rates and likely metabolism are tightly coupled.     

Debris-Rich Basal Ice as a Microbial Habitat,Taylor Glacier,Antarctica

Two ～4 m vertical sequences of basal ice were collected from tunnels dug into the northern lateral margin of Taylor Glacier, McMurdo Dry Valleys, Antarctica. In both cases the basal sequences exhibit two contrasting ice facies groups; clean (debris-free) and banded dispersed (debris-rich). Debris-rich ices exhibit elevated CO₂ and depleted O₂ concentrations compared to the clean facies. Bacterial cell numbers, respiration rates, and nutrient concentrations are highest in debris-rich layers. Together, our geochemical and biological data indicate that microbial heterotrophic respiration is likely occurring in situ within the basal ice matrix at ambient temperatures near ?15°C. This implies that the basal ice zone of polar glaciers and larger ice sheets is a viable subglacial microbial habitat and active biome of significant volume that has not previously been considered.     

Household Air Pollution from Solid Fuel Use and Risk of Adverse Pregnancy Outcomes: A Systematic Review and Meta-Analysis of the Empirical Evidence

Background

About 41% of households globally, mainly in developing countries rely on solid fuels for cooking with consequences for fetal growth and development. Previous reviews were limited in scope, assessing only two outcomes (birth weight, stillbirth). With important evidence accumulating, there is a need to improve the previous estimates and assess additional outcomes. We conducted a systematic review and meta-analysis to evaluate the quality and strength of available evidence on household air pollution (HAP) and the whole range of adverse pregnancy outcomes.

Methods

PubMed, Ovid Medline, Scopus and CINAHL were searched from their inception to the end of April 2013. All epidemiological study designs were eligible for inclusion in the review. The random-effects model was applied in computing the summary-effect estimates (EE) and their corresponding 95% confidence interval (CI).

Results

Of 1505 studies screened, 19 studies satisfied the inclusion criteria. Household combustion of solid fuels resulted in an 86.43 g (95% CI: 55.49, 117.37) reduction in birth weight, and a 35% (EE = 1.35, 95% CI: 1.23, 1.48) and 29% (EE = 1.29, 95% CI: 1.18, 1.41) increased risk of LBW and stillbirth respectively.

Conclusion

Combustion of solid fuels at home increases the risk of a wide range of adverse pregnancy outcomes. Access to clean household energy solutions is the surest way to combat HAP and mitigate their adverse effects.     

THE RECONSTRUCTION OF ANCESTRAL CHARACTER STATES

The problem of error in the phylogenetic reconstruction of ancestral character states is explored by developing the model of Frumhoff and Reeve (1994). Information about the evolutionary rate of change within a character is inferred from the distribution of its character states on a known phylogeny, and this information is used to impose confidence limits on the error associated with ancestral state inference. Ancestral state inference is found to be remarkably robust under the model assumptions for a wide range of parameter values; however, the probability of error increases when the number of species within a clade is small and/or state-transition probabilities are strongly skewed in favor of the non-ancestral state. The rationale for expecting such a skew, a hypothesis of parallelism, is shown to rely on assumptions of low rates of change in at least two phylogenetically inherited characters: the tendency to occupy a particular ecological niche and the tendency to respond in a particular way to selection. A means for judging the relative likelihoods of parallelism vs. straightforward homology as explanations for a given character-state distribution is suggested. General problems with the model are discussed, as are methods for making it more realistic.