Modeled larval fish prey fields and growth rates help predict recruitment success of cod and anchovy in the North Sea

Abstract. We introduce a new, coupled modeling approach for simulating ecosystem-wide patterns in larval fish foraging and growth. An application of the method reveals how interplay between temperature and plankton dynamics during 1970-2009 impacted a cold-water species (Atlantic cod Gadus morhua) and a warm-water species (European anchovy Engraulis encrasicolus) in the North Sea. Larval fish growth rates were estimated by coupling models depicting traitbased foraging and bioenergetics of individuals, spatiotemporal changes in their prey field, and the biogeochemistry and hydrodynamics of the region. The biomass composition of modeled prey fields varied from 89% nano-, 10% micro-, and 1% mesoplankton to 15% nano-, 20% micro-, and 65% mesoplankton. The mean slope of the normalized biomass size spectrum was near -1.2, consistent with theoretical and empirical estimates. Median larval fish growth rates peaked in June for cod (24% d(-1)) and in July for anchovy (17% d(-1)). Insufficient prey resources played a substantial role in limiting the growth rates of cod larvae. Anchovy were consistently limited by cold temperatures. Faster median larval growth during specific months was significantly (p < 0.05) positively associated with detrended (i.e. higher than expected) juvenile recruitment indices in cod (rank correlation Kendall's tau = 22%) and anchovy (tau = 42%). For cod, the most predictive month was February, which was also when food limitation was most prevalent. The continued development of modeling tools based on first principles can help further a mechanistic understanding of how changes in the environment affect the productivity of living marine resources

NHLRC2 and extracellular matrix proteins in idiopathic pulmonary fibrosis and lung cancer

Abstract Idiopathic pulmonary fibrosis (IPF) and lung cancer share poor prognosis, similar genetic and epigenetic alterations, and common risk factors such as smoking. Myofibroblasts, which are often referred to as cancer-associated fibroblasts in tumors, are believed to act as principal pathogenetic cell types in both IPF and lung cancer. Certain variants of NHL repeat-containing protein 2 (NHLRC2) gene are associated with fibrotic interstitial lung disease in early childhood. However, its cell type-specific expression in human lung tissues is unknown. The aim of this study was to examine the gene expression profiles of cultured fibroblasts derived from patients with IPF and lung adenocarcinoma (ADC) as well as from normal lung by microarray analysis. Additionally, NHLRC2 expression was evaluated in lung cell and tissue samples from patients with IPF, ADC, and squamous cell carcinoma (SCC). The microarray analysis revealed that 20 genes were similarly dysregulated in IPF and ADC compared to control. However, most of the altered genes, including several extracellular matrix genes, in IPF and ADC were differently expressed. Collagen α1(IV) chain as well as matrix metalloproteinases-1 and -3 were differentially expressed in IPF compared to control and ADC. Periostin expression was higher in both IPF and ADC in comparison to control. NHLRC2 was expressed mainly in alveolar and bronchiolar epithelium and macrophages in normal lung, hyperplastic alveolar epithelial cells in IPF, and in cancer cells and inflammatory cells in lung cancer tumors. Additionally, the immunohistochemical expression of NHLRC2 determined by digital image analysis method was higher in IPF, ADC and SCC than in control lung. Furthermore, NHLRC2 expression was higher in ADC than in SCC. NHLRC2 expression was associated with smoking in IPF patients and with survival and mitotic activity in ADC patients. Further studies are needed to confirm the connections between IPF and lung cancer and to clarify the pathogenetic role of NHLRC2 in IPF and lung cancer.Tiivistelmä Sekä idiopaattisella keuhkofibroosilla (IPF) että keuhkosyövällä on huono ennuste, samantyyppiset solu- ja molekyylibiologiset muutokset sekä samoja riskitekijöitä, kuten tupakointi. Molemmissa sairauksissa esiintyy aktiivisia sidekudossoluja, joita kutsutaan myofibroblasteiksi tai syövän tapauksessa syöpään liittyviksi fibroblasteiksi. NHLRC2 (NHL repeat containing protein 2) -geenin eräiden varianttien on havaittu olevan yhteydessä vakavaan monielinsairauteen, johon liittyy fibrotisoiva keuhkosairaus nuorilla lapsilla. NHLRC2:n soluspesifistä ilmentymistä keuhkokudoksessa ei kuitenkaan ole aiemmin julkaistu. Tämän tutkimuksen tavoitteena oli verrata mikroarray-menetelmän avulla geenien ilmentymistä fibroblasteissa, jotka on kerätty IPF:ää ja keuhkosyöpää sairastavilta potilailta sekä normaalirakenteisesta keuhkosta. Lisäksi tavoitteena oli selvittää, missä solutyypeissä NHLRC2 ilmenee keuhkokudoksessa, verrata sen ilmentymistä IPF:ssä tai keuhkosyövässä ja normaalirakenteisessa keuhkossa, sekä selvittää, onko sillä yhteyttä IPF ja keuhkosyöpäpotilaiden kliinisiin tietoihin, kuten elinaikaan ja tupakointitaustaan, tai histologisiin tietoihin. Mikroarray-menetelmällä saatujen tulosten mukaan kahdenkymmenen geenin ilmentyminen oli IPF:ssä ja keuhkosyövässä samalla tavalla korkeampi tai matalampi kontrolliin verrattuna. Useimpien geenien, joihin sisältyy soluvälitilan proteiineihin liittyviä tekijöitä, ilmentyminen kuitenkin erosi IPF:ssä ja keuhkosyövässä. Tyypin IV kollageenin α1-ketjun sekä matriksin metalloproteaasien 1 ja 3 ilmentyminen erosi IPF:n ja keuhkosyövän välillä. Periostiinin ilmentyminen oli puolestaan kohonnut sekä IPF:ssä että keuhkosyövässä kontrolliin verrattuna. NHLRC2 ilmentyi pääasiassa alveoliepiteelissä, pienten ilmateiden epiteelissä sekä makrofageissa normaalissa keuhkossa, hyperplastisessa alveoliepiteelissä IPF:ssä, ja syöpäsoluissa sekä tulehdussoluissa keuhkosyövässä. NHLRC2:n määrä oli sekä IPF:ssä että keuhkosyövissä korkeampi kuin kontrollissa. Lisäksi NHLRC2:n määrä oli korkeampi keuhkon adenokarsinoomassa kuin levyepiteelikarsinoomassa. NHLRC2:n ilmentyminen oli yhteydessä tupakointiin IPF-potilailla sekä elinaikaan ja syöpäsolujen mitoottiseen aktiivisuuteen adenokarsinoomapotilailla. Lisätutkimuksia tarvitaan IPF:n ja keuhkosyövän yhteyden selvittämiseksi sekä selventämään NHLRC2:n roolia IPF:n ja keuhkosyövän patogeneesissa

Extracellular matrix proteins produced by stromal cells in idiopathic pulmonary fibrosis and lung adenocarcinoma

Abstract Idiopathic pulmonary fibrosis (IPF) and lung cancer share common risk factors, epigenetic and genetic alterations, the activation of similar signaling pathways and poor survival. The aim of this study was to examine the gene expression profiles of stromal cells from patients with IPF and lung adenocarcinoma (ADC) as well as from normal lung. The gene expression levels of cultured stromal cells derived from non-smoking patients with ADC from the tumor (n = 4) and the corresponding normal lung (n = 4) as well as from patients with IPF (n = 4) were investigated with Affymetrix microarrays. The expression of collagen type IV alpha 1 chain, periostin as well as matrix metalloproteinase-1 and -3 in stromal cells and lung tissues were examined with quantitative real-time reverse transcriptase polymerase chain reaction and immunohistochemistry, respectively. Twenty genes were similarly up- or down-regulated in IPF and ADC compared to control, while most of the altered genes in IPF and ADC were differently expressed, including several extracellular matrix genes. Collagen type IV alpha 1 chain as well as matrix metalloproteinases-1 and -3 were differentially expressed in IPF compared to ADC. Periostin was up-regulated in both IPF and ADC in comparison to control. All studied factors were localized by immunohistochemistry in stromal cells within fibroblast foci in IPF and stroma of ADC. Despite the similarities found in gene expressions of IPF and ADC, several differences were also detected, suggesting that the molecular changes occurring in these two lung illnesses are somewhat different

Decline in mast cell density during diffuse alveolar damage in idiopathic pulmonary fibrosis

Abstract Mast cells (MCs) are known to be involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF), although their role in acute exacerbations of IPF has not been investigated. The aims of the study were to evaluate the numbers of MCs in fibrotic and non-fibrotic areas of lung tissue specimens of idiopathic pulmonary fibrosis (IPF) patients with or without an acute exacerbation of IPF, and to correlate the MC density with clinical parameters. MCs of IPF patients were quantified from surgical lung biopsy (SLB) specimens (n = 47) and lung tissue specimens taken at autopsy (n = 7). MC density was higher in the fibrotic areas of lung tissue compared with spared alveolar areas or in controls. Female gender, low diffusion capacity for carbon monoxide, diffuse alveolar damage, and smoking were associated with a low MC density. MC densities of fibrotic areas had declined significantly in five subjects in whom both SLB in the stable phase and autopsy after an acute exacerbation of IPF had been performed. There were no correlations of MC densities with survival time or future acute exacerbations. The MC density in fibrotic areas was associated with several clinical parameters. An acute exacerbation of IPF was associated with a significant decline in MC counts. Further investigations will be needed to clarify the role of these cells in IPF and in the pathogenesis of acute exacerbation as this may help to identify some potential targets for medical treatment for this serious disease

NHLRC2 expression is increased in idiopathic pulmonary fibrosis

Abstract Background: Variants of NHL repeat-containing protein 2 (NHLRC2) have been associated with severe fibrotic interstitial lung disease in early childhood and NHLRC2 has been listed as a differentially expressed gene between rapidly and slowly progressing idiopathic pulmonary fibrosis (IPF) patients. However, its cell type-specific localization in human lung tissue is unknown. The aim of this study was to evaluate NHLRC2 mRNA and protein expression in different cell types of lung tissue samples and to investigate the effect of transforming growth factor (TGF)-β1 exposure on NHLRC2 expression in vitro. Methods: The NHLRC2 expression in lung tissue samples was studied by immunohistochemistry (50 IPF, 10 controls) and mRNA in situ hybridization (8 IPF, 3 controls). The immunohistochemical NHLRC2 expression was quantified with image analysis software and associated with the clinical and smoking data of the patients. NHLRC2 expression levels in primary stromal and small airway epithelial cell lines after exposure to TGF-β1 was measured by quantitative reverse transcription polymerase chain reaction and Western blot analysis. Results: NHLRC2 expression was detected especially in bronchiolar epithelial cells, type II pneumocytes and macrophages in normal lung. In the lungs of IPF patients, NHLRC2 was mainly expressed in hyperplastic alveolar epithelial cells lining fibroblast foci and honeycombs. NHLRC2 expression assessed by image analysis was higher in IPF compared to controls (p &lt; 0.001). Ever-smokers had more prominent NHLRC2 staining than non-smokers (p = 0.037) among IPF patients. TGF-β1 exposure did not influence NHLRC2 levels in lung cell lines. Conclusions: NHLRC2 expression was higher in IPF compared to controls being widely expressed in type II pneumocytes, macrophages, bronchiolar epithelium, and hyperplastic alveolar epithelium. Additionally, its expression was not regulated by the exposure to TGF-β1 in vitro. Further studies are needed to clarify the role of NHLRC2 in IPF

High NHLRC2 expression is associated with shortened survival in lung adenocarcinoma

Abstract Background: Certain variants of NHL repeat (named after NCL-1, HT2A and LIN-41)-containing protein 2 (NHLRC2) gene have been linked to severe fibrotic interstitial lung disease in children. The aim of the current study was to evaluate the expression of NHLRC2 in lung cell and tissue samples from patients with lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Methods: The expression of NHLRC2 in lung tissue samples was studied by immunohistochemistry (102 ADC, 111 SCC), mRNA in situ hybridization (4 ADC, 3 SCC), and Western blot analysis (3 ADC, 2 SCC). The immunohistochemical NHLRC2 expression was measured by image analysis software and the percentage of NHLRC2-positive cancer cells was evaluated by semiquantitative analysis. The immunohistochemical results of NHLRC2 were compared with the clinical and histological characteristics of the patients. NHLRC2 protein levels in primary stromal and epithelial lung cancer cell lines were measured by Western blot analysis. Results: NHLRC2 was mainly expressed in cancer cells and inflammatory cells within the tumor. The NHLRC2 expression evaluated by image analysis method was significantly higher in ADC compared with that in SCC (P&lt;0.001). High NHLRC2 expression was associated with reduced disease specific survival (P=0.002), overall survival (P=0.001), and high mitotic activity (P=0.042) in ADC. Additionally, the proportion of NHLRC2-positive cancer cells analyzed by the semiquantitative method was significantly higher in ADC than in SCC (P&lt;0.001). Conclusions: NHLRC2 expression was higher in lung ADC than in SCC and its expression was associated with poor survival in ADC patients. Further studies are required to clarify the pathogenetic role of NHLRC2 in lung cancer