Airway epithelial specific deletion of Jun-N-terminal kinase 1 attenuates pulmonary fibrosis in two independent mouse models

© 2020 van der Velden et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The stress-induced kinase, c-Jun-N-terminal kinase 1 (JNK1) has previously been implicated in the pathogenesis of lung fibrosis. However, the exact cell type(s) wherein JNK1 exerts its pro-fibrotic role(s) remained enigmatic. Herein we demonstrate prominent activation of JNK in bronchial epithelia using the mouse models of bleomycin- or AdTGFβ1-induced fibrosis. Furthermore, in lung tissues of patients with idiopathic pulmonary fibrosis (IPF), active JNK was observed in various regions including type I and type II pneumocytes and fibroblasts. No JNK activity was observed in adjacent normal tissue or in normal control tissue. To address the role of epithelial JNK1, we ablated Jnk1 form bronchiolar and alveolar type II epithelial cells using CCSP-directed Cre recombinase-mediated ablation of LoxP-flanked Jnk1 alleles. Our results demonstrate that ablation of Jnk1 from airway epithelia resulted in a strong protection from bleomycin- or adenovirus expressing active transforming growth factor beta-1 (AdTGFβ1)-induced fibrosis. Ablation of the Jnk1 allele at a time when collagen increases were already present showed a reversal of existing increases in collagen content. Epithelial Jnk1 ablation resulted in attenuation of mesenchymal genes and proteins in lung tissue and preserved expression of epithelial genes. Collectively, these data suggest that epithelial JNK1 contributes to the pathogenesis of pulmonary fibrosis. Given the presence of active JNK in lungs from patients with IPF, targeting JNK1 in airway epithelia may represent a potential treatment strategy to combat this devastating disease

Long-term survival of a woman with well differentiated papillary mesothelioma of the peritoneum: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare subtype of epitheloid mesothelioma, which is usually seen in young women. WDPMP is generally considered of low malignant potential, however the long-term nature of the tumor remains poorly defined.</p> <p>Case presentation</p> <p>We describe the long-term follow-up of a 60-year-old woman of West African descent who has survived 24 years with WDPMP after receiving extensive local and systemic adjuvant chemotherapy. Her clinical course has included three exploratory laparotomies with intraperitoneal and intravenous chemotherapy over two decades. Her course was complicated by anthracycline-induced cardiomyopathy, for which she underwent an orthotopic heart transplant. Our patient is alive with stable radiological evidence of peritoneal disease, and continues to suffer from chronic abdominal pain.</p> <p>Conclusion</p> <p>No consensus exists regarding optimal treatment strategies for WDPMP. However, given the low malignant potential of the tumor, careful consideration should be made before proceeding with aggressive interventions. Further, long-term follow-up reports are required to fully characterize this tumor.</p

Cystic mucinous adenocarcinoma of the lung: a case report

Mucinous cystic tumors of the lung are uncommon, the preoperative pathologic diagnosis is difficult and their biological behavior is still controversial. We report the case of a patient with a clinically benign cystic lesion that post-operatively showed to be consistent with an invasive adenocarcinoma arising in a mucinous cystadenoma of the lung

Modeling the effects of forest management on in situ and ex situ longleaf pine forest carbon stocks

Assessment of forest carbon storage dynamics requires a variety of techniques including simulation models. We developed a hybrid model to assess the effects of silvicultural management systems on carbon (C) budgets in longleaf pine (Pinus palustris Mill.) plantations in the southeastern U.S. To simulate in situ C pools, the model integrates a growth and yield model with species-specific allometric and biometric equations and explicitly accounts for the impacts of both thinning and prescribed fire. To estimate the ex situ C pool, the model used the outputs of merchantable products from the growth and yield model with current values of forest product conversion efficiencies and forest product decay rates. The model also accounts for C emissions due to transportation and silvicultural activities. Site productivity (site quality) was the major factor controlling stand C density followed by rotation length. Thinning reduced C sequestration, as the slow growth rate of longleaf pine reduced the potential of C sequestration in forest products. Prescribed burning reduced average C stock by about 16–19%, with the majority of the reduction in the forest floor. In a comparison of longleaf pine C dynamics with slash pine (Pinus elliottii Engelm.), both species reached a similar average C stock at age 75 years, but when averaged across the whole rotation, slash pine sequestered more C. Nevertheless, for medium quality sites, C sequestration was similar between thinned 75-year rotation longleaf pine and unthinned 25-year rotation slash pine. This longleaf pine plantation C sequestration model, based on empirical and biological relationships, provides an important new tool for developing testable research hypotheses, estimating C stocks for regional assessments or C credit verification, and for guiding future longleaf pine management.Keywords: Prescribed burning, Carbon stock modeling, Pinus palustris plantations, Silviculture, Biomas

Re-evaluation of histological diagnoses of malignant mesothelioma by immunohistochemistry

<p>Abstract</p> <p>Background</p> <p>In order to provide reliable tissue material for malignant mesothelioma (MM) studies, we re-evaluated biopsies and autopsy material from 61 patients with a diagnosis of MM from the period of 1980-2002.</p> <p>Methods</p> <p>Basic positive (Calretinin, EMA, Podoplanin, Mesothelin) and negative (CEA, Ber-Ep4) immunohistochemical (IHC) marker reactions were determined. If needed, more markers were used. Histological diagnoses were made by three pathologists. Survival data were calculated.</p> <p>Results</p> <p>49 cases (80%) were considered being MM by a high degree of likelihood, five more cases possible MM. Of the remaining seven cases, three were diagnosed as adenocarcinoma, three as pleomorphic lung carcinoma, in one peritoneal case a clear entity diagnosis could not be given. One of the possible MM cases and two of the lung carcinoma cases had this already as primary diagnoses, but were registered as MM.</p> <p>With a sensitivity of 100%, Calretinin and CEA were the most reliable single markers. The amount of MM cells with positive immunoreactivity (IR) for Podoplanin and Mesothelin showed most reliable inverse relation to the degree of atypia.</p> <p>In the confirmed MM cases, there had been applied either no IHC or between one and 18 markers.</p> <p>The cases not confirmed by us had either lacked IHC (n = 1), non-specific markers were used (n = 4), IR was different (n = 1), or specific markers had not shown positive IR in the right part of the tumour cells (n = 3).</p> <p>46 of the 49 confirmed and three of the not confirmed cases had been diagnosed by us as most likely MM before IHC was carried out.</p> <p>Conclusions</p> <p>In order to use archival tissue material with an earlier MM diagnosis for studies, histopathological re-evaluation is important. In possible sarcomatous MM cases without any positive IR for positive MM markers, radiology and clinical picture are essential parts of diagnostics. IHC based on a panel of two positive and two negative MM markers has to be adapted to the differential diagnostic needs in each single case. New diagnostic tools and techniques are desirable for cases where IHC and other established methods cannot provide a clear entity diagnosis, and in order to improve MM treatment.</p

Folliculin mutations are not associated with severe COPD

<p>Abstract</p> <p>Background</p> <p>Rare loss-of-function folliculin (<it>FLCN</it>) mutations are the genetic cause of Birt-Hogg-Dubé syndrome, a monogenic disorder characterized by spontaneous pneumothorax, fibrofolliculomas, and kidney tumors. Loss-of-function folliculin mutations have also been described in pedigrees with familial spontaneous pneumothorax. Because the majority of patients with folliculin mutations have radiographic evidence of pulmonary cysts, folliculin has been hypothesized to contribute to the development of emphysema.</p> <p>To determine whether folliculin sequence variants are risk factors for severe COPD, we genotyped seven previously reported Birt-Hogg-Dubé or familial spontaneous pneumothorax associated folliculin mutations in 152 severe COPD probands participating in the Boston Early-Onset COPD Study. We performed bidirectional resequencing of all 14 folliculin exons in a subset of 41 probands and subsequently genotyped four identified variants in an independent sample of345 COPD subjects from the National Emphysema Treatment Trial (cases) and 420 male smokers with normal lung function from the Normative Aging Study (controls).</p> <p>Results</p> <p>None of the seven previously reported Birt-Hogg-Dubé or familial spontaneous pneumothorax mutations were observed in the 152 severe, early-onset COPD probands. Exon resequencing identified 31 variants, including two non-synonymous polymorphisms and two common non-coding polymorphisms. No significant association was observed for any of these four variants with presence of COPD or emphysema-related phenotypes.</p> <p>Conclusion</p> <p>Genetic variation in folliculin does not appear to be a major risk factor for severe COPD. These data suggest that familial spontaneous pneumothorax and COPD have distinct genetic causes, despite some overlap in radiographic characteristics.</p

Modelling the limits on the response of net carbon exchange to fertilization in a south-eastern pine forest

Using a combination of model simulations and detailed measurements at a hierarchy of scales conducted at a sandhills forest site, the effect of fertilization on net ecosystem exchange ( NEE ) and its components in 6-year-old Pinus taeda stands was quantified. The detailed measurements, collected over a 20-d period in September and October, included gas exchange and eddy covariance fluxes, sampled for a 10-d period each at the fertilized stand and at the control stand. Respiration from the forest floor and above-ground biomass was measured using chambers during the experiment. Fertilization doubled leaf area index (LAI) and increased leaf carboxylation capacity by 20%. However, this increase in total LAI translated into an increase of only 25% in modelled sunlit LAI and in canopy photosynthesis. It is shown that the same climatic and environmental conditions that enhance photosynthesis in the September and October periods also cause an increase in respiration The increases in respiration counterbalanced photosynthesis and resulted in negligible NEE differences between fertilized and control stands. The fact that total biomass of the fertilized stand exceeded 2·5 times that of the control, suggests that the counteracting effects cannot persist throughout the year. In fact, modelled annual carbon balance showed that gross primary productivity ( GPP ) increased by about 50% and that the largest enhancement in NEE occurred in the spring and autumn, during which cooler temperatures reduced respiration more than photosynthesis. The modelled difference in annual NEE between fertilized  and  control  stands  (approximately  200 1;g 2;C 3;m −2 y −1 )  suggest that the effect of fertilization was sufficiently large to transform the stand from a net terrestrial carbon source to a net sink.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73712/1/j.1365-3040.2002.00896.x.pd

Soil Respiration in Relation to Photosynthesis of Quercus mongolica Trees at Elevated CO2

Knowledge of soil respiration and photosynthesis under elevated CO2 is crucial for exactly understanding and predicting the carbon balance in forest ecosystems in a rapid CO2-enriched world. Quercus mongolica Fischer ex Ledebour seedlings were planted in open-top chambers exposed to elevated CO2 (EC = 500 µmol mol−1) and ambient CO2 (AC = 370 µmol mol−1) from 2005 to 2008. Daily, seasonal and inter-annual variations in soil respiration and photosynthetic assimilation were measured during 2007 and 2008 growing seasons. EC significantly stimulated the daytime soil respiration by 24.5% (322.4 at EC vs. 259.0 mg CO2 m−2 hr−1 at AC) in 2007 and 21.0% (281.2 at EC vs. 232.6 mg CO2 m−2 hr−1 at AC) in 2008, and increased the daytime CO2 assimilation by 28.8% (624.1 at EC vs. 484.6 mg CO2 m−2 hr−1 at AC) across the two growing seasons. The temporal variation in soil respiration was positively correlated with the aboveground photosynthesis, soil temperature, and soil water content at both EC and AC. EC did not affect the temperature sensitivity of soil respiration. The increased daytime soil respiration at EC resulted mainly from the increased aboveground photosynthesis. The present study indicates that increases in CO2 fixation of plants in a CO2-rich world will rapidly return to the atmosphere by increased soil respiration