Associations of Pet Ownership with Wheezing and Lung Function in Childhood: Findings from a UK Birth Cohort

Background

Asthma is a heterogeneous condition and differential effects of pet ownership on non-atopic versus atopic asthma have been reported. The aim of this study was to investigate whether pet ownership during pregnancy and early childhood was associated with wheezing from birth to age 7 years and with lung function at age 8 years in a UK population-based birth cohort.

Methods

Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were used to investigate associations of pet ownership at six time-points from pregnancy to age 7 years with concurrent episodes of wheezing, wheezing trajectories (phenotypes) and lung function at age 8 years using logistic regression models adjusted for child’s sex, maternal history of asthma/atopy, maternal smoking during pregnancy, and family adversity.

Results

4,706 children had complete data on pet ownership and wheezing. From birth to age 7 years, cat ownership was associated with an overall 6% lower odds of wheezing (OR=0.94 (0.89-0.99)). Rabbit and rodent ownership was associated with 21% (OR=1.21 (1.12-1.31)) and 11% (OR=1.11 (1.02–1.21)) higher odds of wheezing, respectively, with strongest effects evident during infancy. Rabbit and rodent ownership was positively associated with a ‘persistent wheeze’ phenotype. Pet ownership was not associated with lung function at age 8 years, with the exception of positive associations of rodent and bird ownership with better lung function.

Conclusions

Cat ownership was associated with reduced risk, and rabbit and rodent ownership with increased risk, of wheezing during childhood. The mechanisms behind these differential effects warrant further investigation.     

Effects of BMI,Fat Mass,and Lean Mass on Asthma in Childhood: A Mendelian Randomization Study

Background

Observational studies have reported associations between body mass index (BMI) and asthma, but confounding and reverse causality remain plausible explanations. We aim to investigate evidence for a causal effect of BMI on asthma using a Mendelian randomization approach.

Methods and Findings

We used Mendelian randomization to investigate causal effects of BMI, fat mass, and lean mass on current asthma at age 7½ y in the Avon Longitudinal Study of Parents and Children (ALSPAC). A weighted allele score based on 32 independent BMI-related single nucleotide polymorphisms (SNPs) was derived from external data, and associations with BMI, fat mass, lean mass, and asthma were estimated. We derived instrumental variable (IV) estimates of causal risk ratios (RRs). 4,835 children had available data on BMI-associated SNPs, asthma, and BMI. The weighted allele score was strongly associated with BMI, fat mass, and lean mass (all p-values<0.001) and with childhood asthma (RR 2.56, 95% CI 1.38–4.76 per unit score, p = 0.003). The estimated causal RR for the effect of BMI on asthma was 1.55 (95% CI 1.16–2.07) per kg/m², p = 0.003. This effect appeared stronger for non-atopic (1.90, 95% CI 1.19–3.03) than for atopic asthma (1.37, 95% CI 0.89–2.11) though there was little evidence of heterogeneity (p = 0.31). The estimated causal RRs for the effects of fat mass and lean mass on asthma were 1.41 (95% CI 1.11–1.79) per 0.5 kg and 2.25 (95% CI 1.23–4.11) per kg, respectively. The possibility of genetic pleiotropy could not be discounted completely; however, additional IV analyses using FTO variant rs1558902 and the other BMI-related SNPs separately provided similar causal effects with wider confidence intervals. Loss of follow-up was unlikely to bias the estimated effects.

Conclusions

Higher BMI increases the risk of asthma in mid-childhood. Higher BMI may have contributed to the increase in asthma risk toward the end of the 20th century. Please see later in the article for the Editors'' Summary     

A Giant Protopaleodictyon from the Middle Cambrian of Western Canada

Abstract

A new ichnospecies of Protopaleodictyon Ksi??kiewicz, 1958 Ksi??kiewicz, M. 1958. Stratigraphy of the Magura Series in the ?redni Beskid (carpathians.). Biuletyn Instytutu Geologicznego 153:43–96. [In Polish, with English summary] [Google Scholar], Pr. aitkeni isp. n., is named from material recovered from the mid–Cambrian Stephen–Eldon formation transition in Banff National Park, Alberta, Canada. Specimens occur in convex hyporelief on the sole of a dolomitic lime mudstone bed, and exhibit straight to gently curving strands with a 'zigzag' shape up to 45?cm in length. Strands are fairly regular, with branching angles ranging from 110^° to 120^°. Branch segments forming the strand are approximately the same length and produce strands with open and occasionally closed hexagonal polygons arranged alternatively along the specimen's axis. Hexagons are 25–40?mm wide and string widths are 5–10?mm. The dimensions of Pr. aitkeni are large compared to other ichnospecies of the ichnogenus and graphoglyptids in general. The host interval is interpreted to have been deposited in a relatively shallow-water environment in the interior of a carbonate platform, contrasting with the deeper siliciclastic settings in which younger examples of the ichnogenus typically occur. This occurrence further supports the hypothesis that graphoglyptid ethology initially developed in shallow shelf environments before shifting into deeper facies over geologic time.     

Effects of body size,diet, and transience on the demography of the arboreal boid snake Corallus grenadensis on Carriacou (Grenada Grenadines,West Indies)

Remarkably little is known about the demography of snakes in the family Boidae. This lack of information may be attributed, in part, to low population densities on the Neotropical mainland, rendering capture-recapture methods impractical for many species. Conversely, islands support fewer species but snake densities can be much higher. Corallus grenadensis is an arboreal boid endemic to the Grenada Bank and, relative to mainland boids, can be amazingly abundant. As young, its diet is comprised largely of native Anolis lizards, a ubiquitous and abundant food source; it then undergoes an ontogenetic shift in diet to a less abundant resource, rodents. From 2015 to 2019, we marked 254 C. grenadensis and used capture–recapture models to estimate abundance, capture probabilities, survival, and the proportion of transients. We hypothesized that the transient effect would increase with body size (snout–vent length [SVL]), prompted by their ontogenetic shift in diet. Capture probabilities increased with sampling effort and decreased with increasing SVL. Abundance ranged from 96 to 141 individuals and annual resident survival was 0.71, 95% confidence interval (CI) = 0.54–0.83. The proportion of transients increased with increasing SVL, with the estimate being distinguishable from zero starting at ~810 mm SVL, coinciding with the size at which their dietary shift from ectothermic to endothermic prey begins. Ontogenetic dietary shifts are widespread in snakes and occur in at least 11 of 17 species of West Indian boids. Thus, the prominence of transients in our study may be indicative of its demographic and ecological importance among other snake species.     

Adenomatous polyposis coli protein regulates the cellular response to DNA replication stress

The adenomatous polyposis coli (APC) tumor suppressor traffics between nucleus and cytoplasm to perform distinct functions. Here we identify a specific role for APC in the DNA replication stress response. The silencing of APC caused an accumulation of asynchronous cells in early S phase and delayed S phase progression in cells released from hydroxyurea-mediated replication arrest. Immunoprecipitation assays revealed a selective binding of APC to replication protein A 32kDa subunit (RPA32), and the APC-RPA32 complex increased at chromatin after hydroxyurea treatment. Interestingly, APC knock-down prevented accumulation at chromatin of the stress-induced S33- and S29-phosphorylated forms of RPA32, and reduced the expression of ATR-phosphorylated forms of S317-phospho-Chk1 and γ-H2AX. Using RPA32-inducible cells we showed that reconstitution of RPA32 diminished the S-phase delay caused by loss of APC. In contrast to full-length APC, the truncated APC mutant protein expressed in SW480 colon cancer cells was impaired in its binding and regulation of RPA32, and failed to regulate cell cycle after replication stress. We propose that APC associates with RPA at stalled DNA replication forks and promotes the ATR-dependent phosphorylation of RPA32, Chk1 and γ-H2AX in response to DNA replication stress, thereby influencing the rate of re-entry into the cell cycle.     

Regulation of β-catenin nuclear dynamics by GSK-3β involves a LEF-1 positive feedback loop

Nuclear localization of β-catenin is integral to its role in Wnt signaling and cancer. Cellular stimulation by Wnt or lithium chloride (LiCl) inactivates glycogen synthase kinase-3β (GSK-3β), causing nuclear accumulation of β-catenin and transactivation of genes that transform cells. β-catenin is a shuttling protein; however, the mechanism by which GSK-3β regulates β-catenin nuclear dynamics is poorly understood. Here, fluorescence recovery after photobleaching assays were used to measure the β-catenin-green fluorescent protein dynamics in NIH 3T3 cells before and after GSK-3β inhibition. We show for the first time that LiCl and Wnt3a cause a specific increase in β-catenin nuclear retention in live cells and in fixed cells after detergent extraction. Moreover, LiCl reduced the rate of nuclear export but did not affect import, hence biasing β-catenin transport toward the nucleus. Interestingly, the S45A mutation, which blocks β-catenin phosphorylation by GSK-3β, did not alter nuclear retention or transport, implying that GSK-3β acts through an independent regulator. We compared five nuclear binding partners and identified LEF-1 as the key mediator of Wnt3a and LiCl-induced nuclear retention of β-catenin. Thus, Wnt stimulation triggered a LEF-1 positive feedback loop to enhance the nuclear chromatin-retained pool of β-catenin by 100-300%. These findings shed new light on regulation of β-catenin nuclear dynamics.     

Structure and function of BamE within the outer membrane and the β-barrel assembly machine

Insertion of folded proteins into the outer membrane of Gram-negative bacteria is mediated by the essential β-barrel assembly machine (Bam). Here, we report the native structure and mechanism of a core component of this complex, BamE, and show that it is exclusively monomeric in its native environment of the periplasm, but is able to adopt a distinct dimeric conformation in the cytoplasm. BamE is shown to bind specifically to phosphatidylglycerol, and comprehensive mutagenesis and interaction studies have mapped key determinants for complex binding, outer membrane integrity and cell viability, as well as revealing the role of BamE within the Bam complex.