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.     

CDC2/SPDY transiently associates with endoplasmic reticulum exit sites during oocyte maturation

Background  

Fibronectin 1 (FN1), a glycoprotein component of the extracellular matrix, exerts different functions during reproductive processes such as fertilisation, gastrulation and implantation. FN1 expression has been described to increase significantly from the morula towards the early blastocyst stage, suggesting that FN1 may also be involved in early blastocyst formation. By alternative splicing at 3 defined regions, different FN1 isoforms are generated, each with a unique biological function. The analysis of the alternative FN1 splicing on the one hand and the search for candidate FN1 receptors on the other hand during early bovine embryo development may reveal more about its function during bovine preimplantation embryo development.     

HUWE1 interacts with PCNA to alleviate replication stress

Defects in DNA replication, DNA damage response, and DNA repair compromise genomic stability and promote cancer development. In particular, unrepaired DNA lesions can arrest the progression of the DNA replication machinery during S‐phase, causing replication stress, mutations, and DNA breaks. HUWE1 is a HECT‐type ubiquitin ligase that targets proteins involved in cell fate, survival, and differentiation. Here, we report that HUWE1 is essential for genomic stability, by promoting replication of damaged DNA. We show that HUWE1‐knockout cells are unable to mitigate replication stress, resulting in replication defects and DNA breakage. Importantly, we find that this novel role of HUWE1 requires its interaction with the replication factor PCNA, a master regulator of replication fork restart, at stalled replication forks. Finally, we provide evidence that HUWE1 mono‐ubiquitinates H2AX to promote signaling at stalled forks. Altogether, our work identifies HUWE1 as a novel regulator of the replication stress response.     

Inferring the biogeographic origins of inter‐continental disjunct endemics using a Bayes‐DIVA approach

The arcto‐Tertiary relictual flora is comprised of many genera that occur non‐contiguously in the temperate zones of eastern Asia, Europe, eastern North America, and western North America. Within each distributional area, species are typically endemic and may thus be widely separated from closely related species within the other areas. It is widely accepted that this common pattern of distribution resulted from of the fragmentation of a once more‐continuous arcto‐Tertiary forest. The historical biogeographic events leading to the present‐day disjunction have often been investigated using a phylogenetic approach. Limitations to these previous studies have included phylogenetic uncertainty and uncertainty in ancestral range reconstructions. However, the recently described Bayes‐DIVA method handles both types of uncertainty. Thus, we used Bayes‐DIVA analysis to reconstruct the stem lineage distributions for 185 endemic lineages from 23 disjunct genera representing 17 vascular plant families. In particular, we asked whether endemic lineages within each of the four distributional areas more often evolved from (1) widespread ancestors, (2) ancestors dispersed from other areas, or (3) endemic ancestors. We also considered which of these three biogeographic mechanisms may best explain the origins of arcto‐Tertiary disjunct endemics in the neotropics. Our results show that eastern Asian endemics more often evolved from endemic ancestors compared to endemics in Europe and eastern and western North America. Present‐day endemic lineages in the latter areas more often arose from widespread ancestors. Our results also provide anecdotal evidence for the importance of dispersal in the biogeographic origins of arcto‐Tertiary species endemic in the neotropics.     

Mouse models to unravel the role of inhaled pollutants on allergic sensitization and airway inflammation

Background

Nicotinic acetylcholine receptors (nAChR) have been identified on a variety of cells of the immune system and are generally considered to trigger anti-inflammatory events. In the present study, we determine the nAChR inventory of rat alveolar macrophages (AM), and investigate the cellular events evoked by stimulation with nicotine.

Methods

Rat AM were isolated freshly by bronchoalveolar lavage. The expression of nAChR subunits was analyzed by RT-PCR, immunohistochemistry, and Western blotting. To evaluate function of nAChR subunits, electrophysiological recordings and measurements of intracellular calcium concentration ([Ca²⁺]_i) were conducted.

Results

Positive RT-PCR results were obtained for nAChR subunits α3, α5, α9, α10, β1, and β2, with most stable expression being noted for subunits α9, α10, β1, and β2. Notably, mRNA coding for subunit α7 which is proposed to convey the nicotinic anti-inflammatory response of macrophages from other sources than the lung was not detected. RT-PCR data were supported by immunohistochemistry on AM isolated by lavage, as well as in lung tissue sections and by Western blotting. Neither whole-cell patch clamp recordings nor measurements of [Ca²⁺]_i revealed changes in membrane current in response to ACh and in [Ca²⁺]_i in response to nicotine, respectively. However, nicotine (100 μM), given 2 min prior to ATP, significantly reduced the ATP-induced rise in [Ca²⁺]_i by 30%. This effect was blocked by α-bungarotoxin and did not depend on the presence of extracellular calcium.

Conclusions

Rat AM are equipped with modulatory nAChR with properties distinct from ionotropic nAChR mediating synaptic transmission in the nervous system. Their stimulation with nicotine dampens ATP-induced Ca²⁺-release from intracellular stores. Thus, the present study identifies the first acute receptor-mediated nicotinic effect on AM with anti-inflammatory potential.     

Gene-based microsatellites for cassava (Manihot esculenta Crantz): prevalence, polymorphisms, and cross-taxa utility

Background  

Cassava (Manihot esculenta Crantz), a starchy root crop grown in tropical and subtropical climates, is the sixth most important crop in the world after wheat, rice, maize, potato and barley. The repertoire of simple sequence repeat (SSR) markers for cassava is limited and warrants a need for a larger number of polymorphic SSRs for germplasm characterization and breeding applications.     

Analysis of the meiosis in the F_1 hybrids of Longiflorum × Asiatic(LA) of lilies(Lilium) using genomic in situ hybridization

Longiflorum and Asiatic lilies of the genus Lilium of the family Liliaceae are two important groups of modern lily cultivars.One of the main trends of lily breeding is to realize introgression between these groups.With cut style pollination and embryo rescue,distant hybrids between the two groups have been obtained.However,the F1 hybrids are highly sterile or some of them could produce a small number of 2n gametes,and their BC1 progenies are usually triploids.Dutch lily breeders have selected many cultivars...     

Irreversible Renal Damage after Transient Renin-Angiotensin System Stimulation: Involvement of an AT1-Receptor Mediated Immune Response

Transient activation of the renin-angiotensin system (RAS) induces irreversible renal damage causing sustained elevation in blood pressure (BP) in Cyp1a1-Ren2 transgenic rats. In our current study we hypothesized that activation of the AT₁-receptor (AT₁R) leads to a T-cell response causing irreversible impairment of renal function and hypertension. Cyp1a1-Ren2 rats harbor a construct for activation of the RAS by indole-3-carbinol (I3C). Rats were fed a I3C diet between 4–8 weeks of age to induce hypertension. Next, I3C was withdrawn and rats were followed-up for another 12 weeks. Additional groups received losartan (20 mg/kg/day) or hydralazine (100 mg/kg/day) treatment between 4–8 weeks. Rats were placed for 24h in metabolic cages before determining BP at week 8, 12 and 20. At these ages, subsets of animals were sacrificed and the presence of kidney T-cell subpopulations was investigated by immunohistochemistry and molecular marker analysis. The development of sustained hypertension was completely prevented by losartan, whereas hydralazine only caused a partial decrease in BP. Markers of renal damage: KIM-1 and osteopontin were highly expressed in urine and kidney samples of I3C-treated rats, even until 20 weeks of age. Additionally, renal expression of regulatory-T cells (Tregs) was highly increased in I3C-treated rats, whereas the expression of T-helper 1 (Th1) cells demonstrated a strong decrease. Losartan prevented these effects completely, whereas hydralazine was unable to affect these changes. In young Cyp1a1-Ren2 rats AT₁R activation leads to induction of an immune response, causing a shift from Th1-cells to Tregs, contributing to the development of irreversible renal damage and hypertension.     

Contributions toward understanding the biodiversity of Passiflora in North America: Updates and a new combination from the Baja California Peninsula,Mexico and vicinity

The Baja California Peninsula and surrounding landmasses harbor an abundant flora in an otherwise harsh and arid environment. Of the many plant groups native to this peninsular and insular region, passionflowers (Passiflora, Passifloraceae) are represented by several conspicuous taxa that all belong to a single lineage, section Dysosmia. Basic questions remain regarding this group, particularly the taxonomic status among the Passiflora arida complex. Therefore, we investigated the claims of endemism, habitat characteristics, and taxon boundaries with in section Dysosmia in the Baja California region using extensive sampling of herbarium specimens and iNaturalist observations. We confirmed that only one of the native Passiflora taxa (P. fruticosa) was endemic to the Baja California Peninsula, with an additional taxon (P. palmeri) considered near‐endemic. Environmental data revealed significant distinctions between the habitats of many of the native taxa as well as within the P. arida complex, especially with respect to precipitation and temperature tolerances. Geometric morphometric analyses of leaf shape were largely not successful at separating taxa, indicating leaf shape may not be a good indicator of taxon identity in this particular group. Based on ecological differences and discrete macro‐ and micromorphological features, a varietal name is here synonymized and a new combination is proposed: Passiflora pentaschista.