An informative Bayesian structural equation model to assess source-specific health effects of air pollution

A primary objective of current air pollution research is the assessment of health effects related to specific sources of air particles or particulate matter (PM). Quantifying source-specific risk is a challenge because most PM health studies do not directly observe the contributions of the pollution sources themselves. Instead, given knowledge of the chemical characteristics of known sources, investigators infer pollution source contributions via a source apportionment or multivariate receptor analysis applied to a large number of observed elemental concentrations. Although source apportionment methods are well established for exposure assessment, little work has been done to evaluate the appropriateness of characterizing unobservable sources thus in health effects analyses. In this article, we propose a structural equation framework to assess source-specific health effects using speciated elemental data. This approach corresponds to fitting a receptor model and the health outcome model jointly, such that inferences on the health effects account for the fact that uncertainty is associated with the source contributions. Since the structural equation model (SEM) typically involves a large number of parameters, for small-sample settings, we propose a fully Bayesian estimation approach that leverages historical exposure data from previous related exposure studies. We compare via simulation the performance of our approach in estimating source-specific health effects to that of 2 existing approaches, a tracer approach and a 2-stage approach. Simulation results suggest that the proposed informative Bayesian SEM is effective in eliminating the bias incurred by the 2 existing approaches, even when the number of exposures is limited. We employ the proposed methods in the analysis of a concentrator study investigating the association between ST-segment, a cardiovascular outcome, and major sources of Boston PM and discuss the implications of our findings with respect to the design of future PM concentrator studies.     

山西汾河源头地区种子植物区系地理成分分析

汾河源头地处山西吕梁山北段的管涔山系腹地,暖温带北部.据调查,汾河源头共有种子植物94科398属875种(含种下等级,下同),其中裸子植物3科7属12种,被子植物91科391属863种.种子植物科、属、种各类分布型占总数百分比没有明显的相关性,科、属、种的区系成分特有现象不平衡.科的分布区类型中,世界分布40科,温带分布30科,没有中国特有科;属的分布区类型中,温带分布264属,北温带成分处于显著地位,中国特有属4属,反映出该区植物区系的温带性质;种的分布区类型中,中国特有分布最多,共501种,其次是温带亚洲和东亚分布,成为构成汾河源头地区森林植被和灌从植被的建群种和优势种的主要成分.     

A two-year report of pollen influx into Tauber traps in Mar Chiquita coastal lagoon,Buenos Aires,Argentina

Modern pollen deposition and its relationship to the surrounding vegetation were studied at a coastal lagoon from the southeast of Buenos Aires Province (Argentina). Tauber traps were monitored monthly over a 2-year period in a coastal dune barrier, salt marsh and continental freshwater lake. Pollen deposition exhibited seasonal patterns with maximum values during summer and a spatial variability of increasing deposition from the coast to inland sites. The pollen spectra suggest that airborne pollen originates mainly from local vegetation with scarce representation of extraregional sources. Herbaceous pollen predominates, comprising up to 90% of the total amount with Poaceae, Chenopodiineae and Asteroideae as the main types. Hydrophytic, psammophytic and extraregional types had little influence on the pollen spectra, generally comprising <5% of the total pollen. Pollen influx–vegetation abundance discrepancies were explained considering pollination syndrome, spatial distribution and structure of vegetation.     

Determinants for the Activation and Autoinhibition of the Diguanylate Cyclase Response Regulator WspR

The bacterial second messenger bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) controls secretion, cell adhesion, and motility, leading to biofilm formation and increased cytotoxicity. Diguanylate cyclases containing GGDEF and phosphodiesterases containing EAL or HD-GYP domains have been identified as the enzymes controlling cellular c-di-GMP levels, yet less is known regarding the molecular mechanisms governing regulation and signaling specificity. We recently determined a product-inhibition pathway for the diguanylate cyclase response regulator WspR from Pseudomonas, a potent molecular switch that controls biofilm formation. In WspR, catalytic activity is modulated by a helical stalk motif that connects its phospho-receiver and GGDEF domains. The stalks facilitate the formation of distinct oligomeric states that contribute to both activation and autoinhibition. Here, we provide novel insights into the regulation of diguanylate cyclase activity in WspR based on the crystal structures of full-length WspR, the isolated GGDEF domain, and an artificially dimerized catalytic domain. The structures highlight that inhibition is achieved by restricting the mobility of rigid GGDEF domains, mediated by c-di-GMP binding to an inhibitory site at the GGDEF domain. Kinetic measurements and biochemical characterization corroborate a model in which the activation of WspR requires the formation of a tetrameric species. Tetramerization occurs spontaneously at high protein concentration or upon addition of the phosphomimetic compound beryllium fluoride. Our analyses elucidate common and WspR-specific mechanisms for the fine-tuning of diguanylate cyclase activity.     

pH-Dependent Conformational Changes in Bacterial Hsp90 Reveal a Grp94-Like Conformation at pH 6 That Is Highly Active in Suppression of Citrate Synthase Aggregation

The molecular chaperone Hsp90 depends upon large conformational rearrangements for its function. One driving force for these rearrangements is the intrinsic ATPase activity of Hsp90, as seen with other chaperones. However, unlike other chaperones, structural and kinetic studies have shown that the ATPase cycle of Hsp90 is not conformationally deterministic. That is, rather than dictating the conformational state, ATP binding and hydrolysis shift the equilibrium between a preexisting set of conformational states in an organism-dependent manner. While many conformations of Hsp90 have been described, little is known about how they relate to chaperone function. In this study, we show that the conformational equilibrium of the bacterial Hsp90, HtpG, can be shifted with pH. Using small-angle X-ray scattering, we identify a two-state pH-dependent conformational equilibrium for apo HtpG. Our structural modeling reveals that this equilibrium is observed between the previously observed extended state and a second state that is strikingly similar to the recently solved Grp94 crystal structure. In the presence of nonhydrolyzable 5′-adenylyl-β,γ-imidodiphosphate, a third state, which is identical with the solved AMPPNP-bound structure from yeast Hsp90, is populated. Electron microscopy confirmed the observed conformational equilibria. We also identify key histidine residues that control this pH-dependent equilibrium; using mutagenesis, we successfully modulate the conformational equilibrium at neutral pH. Using these mutations, we show that the Grp94-like state provides stronger aggregation protection compared to the extended apo conformation in the context of a citrate synthase aggregation assay. These studies provide a more detailed view of HtpG's conformational dynamics and provide the first linkage between a specific conformation and chaperone function.     

Structural and Functional Studies of the Yeast Class II Hda1 Histone Deacetylase Complex

Yeast class II Hda1 histone deacetylase (HDAC) complex is an H2B- and H3-specific HDAC in Saccharomyces cerevisiae consisting of three previously identified subunits, the catalytic subunit scHda1p and two non-catalytic structural subunits scHda2p and scHda3p. We co-expressed and co-purified recombinant yeast class II HDAC complex from bacteria as a functionally active and trichostatin-A-sensitive hetero-tetrameric complex. According to an extensive analysis of domain organization and interaction of all subunits (or domains), the N-terminal domain of scHda1p associates through the C-terminal coiled-coil domains (CCDs) of the scHda2p-scHda3p sub-complex, yielding a truncated scHda1pHDAC-scHda2pCCD2-scHda3pCCD3 complex with indistinguishable deacetylase activity compared to the full-length complex in vitro. We characterized the interaction of the HDAC complex with either single-stranded or double-stranded DNA and identified the N-terminal halves of scHda2p and scHda3p as binding modules. A high-resolution structure of the scHda3p DNA-binding domain by X-ray crystallography is presented. The crystal structure shows an unanticipated structural homology with the C-terminal helicase lobes of SWI2/SNF2 chromatin-remodeling domains of the Rad54 family enzymes. DNA binding is unspecific for nucleotide sequence and structure, similar to the Rad54 enzymes in vitro. Our structural and functional analyses of the budding yeast class II Hda1 HDAC complex provide insight into DNA recognition and deacetylation of histones in nucleosomes.     

Sugars regulate sucrose transporter gene expression in citrus

We report the isolation and characterization of two sucrose transporter cDNAs (CitSUT1 and CitSUT2) from citrus. CitSUT1 and CitSUT2 encode putative proteins (CitSUT1 and CitSUT2) of 528 and 607 amino acids, respectively. CitSUT1 and CitSUT2 share high similarities with sucrose transporters isolated from other plants. The expression of CitSUT1 in mature leaf discs is repressed by exogenous sucrose, glucose, mannose, and the glucose analog 2-deoxyglucose but not by another glucose analog 3-O-methylglucose, indicating a hexokinase (HXK)-mediated signaling pathway. CitSUT2 expression is not affected by exogenous sugars. Whereas CitSUT1 expresses strongly in source, sugar exporting organs, CitSUT2 expresses more strongly in sink, sugar importing organs, suggesting different physiological roles for these sucrose transporters.     

Photoperiod gene control over partitioning between reproductive and vegetative growth

Summary The hypothesis tested was that lack of photoperiod gene activity allows inherent partitioning of photosynthate to continued growth of the earliest potential buds, flowers, pods, and seeds (the organs that give rise to the yield). Alternatively, and competitively, photoperiod gene activity causes the photosynthate to be partitioned predominantly toward continued growth of new vegetative organs plus later initiation of more reproductive (yield) organs. This hypothesis was tested by comparing an insensitive and a photoperiod-sensitive bean (Phaseolus vulgaris L.) cultivar and their F₁ with F₂ segregates of undetermined genotype. Randomly derived homozygous F₈ segregates were also compared. The F₈ generation included one photoperiod-insensitive and one photoperiod-sensitive genotype in a 1:1 ratio, which verified control by one photoperiod gene. Under long daylength (LD), in addition to early versus late flowering and maturity, the two genotypes expressed opposite levels of 23 other traits that would be changed by competitive partitioning of the photosynthate. In contrast, under short daylength (SD), both genotypes flowered and matured early, and both expressed the levels for all 25 traits that the photoperiod-insensitive genotype expressed in both SD and LD. The photoperiod gene interacted with daylength to control the levels of all three major physiological components of yield: the aerial biomass, harvest index, and days to maturity. Included among the other traits with levels altered by daylength-modulated photoperiod gene activity were: the number of branches, nodes, leaves and leaf area, the rate of yield accumulation, and sink activity.Department of Plant Breeding and Biometry paper no. 758