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

Eight grand challenges in socio-environmental systems modeling

Modeling is essential to characterize and explore complex societal and environmental issues in systematic and collaborative ways. Socio-environmental systems (SES) modeling integrates knowledge and perspectives into conceptual and computational tools that explicitly recognize how human decisions affect the environment. Depending on the modeling purpose, many SES modelers also realize that involvement of stakeholders and experts is fundamental to support social learning and decision-making processes for achieving improved environmental and social outcomes. The contribution of this paper lies in identifying and formulating grand challenges that need to be overcome to accelerate the development and adaptation of SES modeling. Eight challenges are delineated: bridging epistemologies across disciplines; multi-dimensional uncertainty assessment and management; scales and scaling issues; combining qualitative and quantitative methods and data; furthering the adoption and impacts of SES modeling on policy; capturing structural changes; representing human dimensions in SES; and leveraging new data types and sources. These challenges limit our ability to effectively use SES modeling to provide the knowledge and information essential for supporting decision making. Whereas some of these challenges are not unique to SES modeling and may be pervasive in other scientific fields, they still act as barriers as well as research opportunities for the SES modeling community. For each challenge, we outline basic steps that can be taken to surmount the underpinning barriers. Thus, the paper identifies priority research areas in SES modeling, chiefly related to progressing modeling products, processes and practices.</jats:p

Diversity of Haloquadratum and other haloarchaea in three, geographically distant, Australian saltern crystallizer ponds

Haloquadratum walsbyi is frequently a dominant member of the microbial communities in hypersaline waters. 16S rRNA gene sequences indicate that divergence within this species is very low but relatively few sites have been examined, particularly in the southern hemisphere. The diversity of Haloquadratum was examined in three coastal, but geographically distant saltern crystallizer ponds in Australia, using both culture-independent and culture-dependent methods. Two 97%-OTU, comprising Haloquadratum- and Halorubrum-related sequences, were shared by all three sites, with the former OTU representing about 40% of the sequences recovered at each site. Sequences 99.5% identical to that of Hqr. walsbyi C23T were present at all three sites and, overall, 98% of the Haloquadratum-related sequences displayed ≤2% divergence from that of the type strain. While haloarchaeal diversity at each site was relatively low (9–16 OTUs), seven phylogroups (clones and/or isolates) and 4 different clones showed ≤90% sequence identity to classified taxa, and appear to represent novel genera. Six of these branched together in phylogenetic tree reconstructions, forming a clade (MSP8-clade) whose members were only distantly related to classified taxa. Such sequences have only rarely been previously detected but were found at all three Australian crystallizers

“Clinical features of women with gout arthritis.” A systematic review

Clinically, gout is generally considered as a preferential male disease. However, it definitely does not occur exclusively in males. Our aim was to assess differences in the clinical features of gout arthritis between female and male patients. Five electronic databases were searched to identify relevant original studies published between 1977 and 2007. The included studies had to focus on adult patients with primary gout arthritis and on sex differences in clinical features. Two reviewers independently assessed eligibility and quality of the studies. Out of 355 articles, 14 were selected. Nine fulfilled the quality and score criteria. We identified the following sex differences in the clinical features of gout in women compared to men: the onset of gout occurs at a higher age, more comorbidity with hypertension or renal insufficiency, more often use of diuretics, less likely to drink alcohol, less often podagra but more often involvement of other joints, less frequent recurrent attacks. We found interesting sex differences regarding the clinical features of patients with gout arthritis. To diagnose gout in women, knowledge of these differences is essential, and more research is needed to understand and explain the differences , especially in the general population

Verified and potential pathogens of predatory mites (Acari: Phytoseiidae)

Several species of phytoseiid mites (Acari: Phytoseiidae), including species of the genera Amblyseius, Galendromus, Metaseiulus, Neoseiulus, Phytoseiulus and Typhlodromus, are currently reared for biological control of various crop pests and/or as model organisms for the study of predator¿prey interactions. Pathogen-free phytoseiid mites are important to obtain high efficacy in biological pest control and to get reliable data in mite research, as pathogens may affect the performance of their host or alter their reproduction and behaviour. Potential and verified pathogens have been reported for phytoseiid mites during the past 25 years. The present review provides an overview, including potential pathogens with unknown host effects (17 reports), endosymbiotic Wolbachia (seven reports), other bacteria (including Cardinium and Spiroplasma) (four reports), cases of unidentified diseases (three reports) and cases of verified pathogens (six reports). From the latter group four reports refer to Microsporidia, one to a fungus and one to a bacterium. Only five entities have been studied in detail, including Wolbachia infecting seven predatory mite species, other endosymbiotic bacteria infecting Metaseiulus (Galendromus, Typhlodromus) occidentalis (Nesbitt), the bacterium Acaricomes phytoseiuli infecting Phytoseiulus persimilis Athias-Henriot, the microsporidium Microsporidium phytoseiuli infecting P. persimilis and the microsporidium Oligosproridium occidentalis infecting M. occidentalis. In four cases (Wolbachia, A. phytoseiuli, M. phytoseiuli and O. occidentalis) an infection may be connected with fitness costs of the host. Moreover, infection is not always readily visible as no obvious gross symptoms are present. Monitoring of these entities on a routine and continuous basis should therefore get more attention, especially in commercial mass-production. Special attention should be paid to field-collected mites before introduction into the laboratory or mass rearing, and to mites that are exchanged among rearing facilities. However, at present general pathogen monitoring is not yet practical as effects of many entities are unknown. More research effort is needed concerning verified and potential pathogens of commercially reared arthropods and those used as model organisms in research

Independent Validation of an Existing Model Enables Prediction of Hearing Loss after Childhood Bacterial Meningitis

Objective: This study aimed external validation of a formerly developed prediction model identifying children at risk for hearing loss after bacterial meningitis (BM). Independent risk factors included in the model are: duration of symptoms prior to admission, petechiae, cerebral spinal fluid (CSF) glucose level, Streptococcus pneumoniae and ataxia. Validation helps to evaluate whether the model has potential in clinical practice. Study design: 116 Dutch school-age BM survivors were included in the validation cohort and screened for sensorineural hearing loss (>25 dB). Risk factors were obtained from medical records. The model was applied to the validation cohort and its performance was compared with the development cohort. Validation was performed by application of the model on the validation cohort and by assessment of discrimination and goodness of fit. Calibration was evaluated by testing deviations in intercept and slope. Multiple imputation techniques were used to deal with missing values. Results: Risk factors were distributed equally between both cohorts. Discriminative ability (Area Under the Curve, AUC) of the model was 0.84 in the development and 0.78 in the validation cohort. Hosmer-Lemeshow test for goodness of fit was not significant in the validation cohort, implying good fit concerning the similarity of expected and observed cases. There were no significant differences in calibration slope and intercept. Sensitivity and negative predicted value were high, while specificity and positive predicted value were low which is comparable with findings in the development cohort. Conclusions: Performance of the model remained good in the validation cohort. This prediction model might be used as a screening tool and can help to identify those children that need special attention and a long follow-up period or more frequent auditory testing

On the Implications of a Sex Difference in the Reaction Times of Sprinters at the Beijing Olympics

Elite sprinters offer insights into the fastest whole body auditory reaction times. When, however, is a reaction so fast that it represents a false start? Currently, a false start is awarded if an athlete increases the force on their starting block above a given threshold before 100 ms has elapsed after the starting gun. To test the hypothesis that the fastest valid reaction times of sprinters really is 100 ms and that no sex difference exists in that time, we analyzed the fastest reaction times achieved by each of the 425 male and female sprinters who competed at the 2008 Beijing Olympics. After power transformation of the skewed data, a fixed effects ANOVA was used to analyze the effects of sex, race, round and lane position. The lower bounds of the 95, 99 and 99.9% confidence intervals were then calculated and back transformed. The mean fastest reaction time recorded by men was significantly faster than women (p<0.001). At the 99.9% confidence level, neither men nor women can react in 100 ms, but they can react in as little as 109 ms and 121 ms, respectively. However, that sex difference in reaction time is likely an artifact caused by using the same force threshold in women as men, and it permits a woman to false start by up to 21 ms without penalty. We estimate that female sprinters would have similar reaction times to male sprinters if the force threshold used at Beijing was lowered by 22% in order to account for their lesser muscle strength

Reciprocity and the tragedies of maintaining and providing the commons

Social cooperation often requires collectively beneficial but individually costly restraint to maintain a public good, or it needs costly generosity to create one. Status quo effects predict that maintaining a public good is easier than providing a new one. Here, we show experimentally and with simulations that even under identical incentives, low levels of cooperation (the ‘tragedy of the commons’) are systematically more likely in maintenance than provision. Across three series of experiments, we find that strong and weak positive reciprocity, known to be fundamental tendencies underpinning human cooperation, are substantially diminished under maintenance compared with provision. As we show in a fourth experiment, the opposite holds for negative reciprocity (‘punishment’). Our findings suggest that incentives to avoid the ‘tragedy of the commons’ need to contend with dilemma specific reciprocity

Physicians perceived usefulness of high-cost diagnostic imaging studies: results of a referral study in a German medical quality network

BACKGROUND: Medical and technological progress has led to increased numbers of diagnostic tests, some of them inducing high financial costs. In Germany, high-cost diagnostic imaging is performed by a medical specialist after referral by a general practitioner (GP) or specialist in primary care. The aim of this study was to evaluate the physicians' perceived usefulness of high-cost diagnostic imaging in patients with different clinical conditions. METHODS: Thirty-four GPs, one neurologist and one orthopaedic specialist in ambulatory care from a Medical Quality Network documented 234 referrals concerning 97 MRIs, 96 CTs-scan and 41 intracardiac catheters in a three month period. After having received the test results, they indicated if these were useful for diagnosis and treatment of the patient. RESULTS: The physicians' perceived usefulness of tests was lowest in suspected cerebral disease (40% of test results were seen as useful), cervical spine problems (64%) and unexplained abdominal complaints (67%). The perceived usefulness was highest in musculoskeletal symptoms (94%) and second best in cardiological diseases (82%). CONCLUSION: The perceived usefulness of high-cost diagnostic imaging was lower in unexplained complaints than in specific diseases. Interventions to improve the effectiveness and efficiency of test ordering should focus on clinical decision making in conditions where GPs perceived low usefulness

Impact of exercise training on oxidative stress in individuals with a spinal cord injury

Individuals with a spinal cord injury (SCI) have an increased cardiovascular risk. We hypothesize that (anti)oxidative imbalance is associated with the increased cardiovascular risk in SCI, while exercise can reverse this status. The aim of the study is to compare baseline levels of oxidative stress and antioxidative capacity between individuals with SCI and able-bodied (AB) subjects, and to assess acute and long-term effects of functional electrical stimulation (FES) exercise on oxidative stress and antioxidative capacity in SCI. Venous blood was taken from subjects with an SCI (n = 9) and age- and gender-matched AB subjects (n = 9) to examine oxidative stress through malondialdehyde (MDA) levels, while superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme levels represented anti-oxidative capacity. Subsequently, subjects with an SCI performed an 8-week FES exercise training period. Blood was taken before and after the first exercise bout and after the last FES session to examine the acute and chronic effect of FES exercise, respectively. Baseline levels of MDA, SOD and GPx were not different between individuals with SCI and AB subjects. SCI demonstrated a correlation between initial fitness level and MDA (R = −0.83, P = 0.05). MDA, SOD and GPx levels were neither altered by a single FES exercise bout nor by 8 weeks FES training. In conclusion, although individuals with an SCI demonstrate a preserved (anti)oxidative status, the correlation between fitness level and (anti)oxidative balance suggests that higher fitness levels are related to improved (anti)oxidative status in SCI. Nonetheless, the FES exercise stimulus was insufficient to acutely or chronically change (anti)oxidative status in individuals with an SCI