Modeling Sediment Particle Movement in Regular and Extreme Flow Events Using a Stochastic Diffusion Jump Particle Tracking Model

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv

Modeling Turbidity Currents Using the Multiple-state Discrete-time Markov Chain Approach

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchive

Application of Batch Poisson Process to Random-sized Batch Arrival of Sediment Particles

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchive

Pulmonary IL- 33 orchestrates innate immune cells to mediate respiratory syncytial virus- evoked airway hyperreactivity and eosinophilia

BackgroundRespiratory syncytial virus (RSV) infection is epidemiologically linked to asthma. During RSV infection, IL- 33 is elevated and promotes immune cell activation, leading to the development of asthma. However, which immune cells are responsible for triggering airway hyperreactivity (AHR), inflammation and eosinophilia remained to be clarified. We aimed to elucidate the individual roles of IL- 33- activated innate immune cells, including ILC2s and ST2+ myeloid cells, in RSV infection- triggered pathophysiology.MethodsThe role of IL- 33/ILC2 axis in RSV- induced AHR inflammation and eosinophilia were evaluated in the IL- 33- deficient and YetCre- 13 Rosa- DTA mice. Myeloid- specific, IL- 33- deficient or ST2- deficient mice were employed to examine the role of IL- 33 and ST2 signaling in myeloid cells.ResultsWe found that IL- 33- activated ILC2s were crucial for the development of AHR and airway inflammation, during RSV infection. ILC2- derived IL- 13 was sufficient for RSV- driven AHR, since reconstitution of wild- type ILC2 rescued RSV- driven AHR in IL- 13- deficient mice. Meanwhile, myeloid cell- derived IL- 33 was required for airway inflammation, ST2+ myeloid cells contributed to exacerbation of airway inflammation, suggesting the importance of IL- 33 signaling in these cells. Local and peripheral eosinophilia is linked to both ILC2 and myeloid IL- 33 signaling.ConclusionsThis study highlights the importance of IL- 33- activated ILC2s in mediating RSV- triggered AHR and eosinophilia. In addition, IL- 33 signaling in myeloid cells is crucial for airway inflammation.Respiratory syncytial virus induces ILC2 to produce IL- 5 and IL- 13 through IL- 33, which is crucial for the development of airway hyperreactivity and airway inflammation. Myeloid cell- derived IL- 33 and suppression of tumorigenicity 2- positive myeloid cells contribute to cytokine production and cellular inflammation in airway. Both ILC2 and myeloid cell IL- 33 signaling contribute to local and peripheral eosinophilia.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154896/1/all14091.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154896/2/all14091-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154896/3/all14091_am.pd

Depression During Pregnancy and the Postpartum Among HIV-Infected Women on Antiretroviral Therapy in Uganda

Background: Among HIV-infected women, perinatal depression compromises clinical, maternal, and child health outcomes. Antiretroviral therapy (ART) is associated with lower depression symptom severity but the uniformity of effect through pregnancy and postpartum periods is unknown. Methods: We analyzed prospective data from 447 HIV-infected women (18–49 years) initiating ART in rural Uganda (2005–2012). Participants completed blood work and comprehensive questionnaires quarterly. Pregnancy status was assessed by self-report. Analysis time periods were defined as currently pregnant, postpartum (0–12 months post-pregnancy outcome), or non–pregnancy-related. Depression symptom severity was measured using a modified Hopkins Symptom Checklist 15, with scores ranging from 1 to 4. Probable depression was defined as >1.75. Linear regression with generalized estimating equations was used to compare mean depression scores over the 3 periods. Results: At enrollment, median age was 32 years (interquartile range: 27–37), median CD4 count was 160 cells per cubic millimeter (interquartile range: 95–245), and mean depression score was 1.75 (s = 0.58) (39% with probable depression). Over 4.1 median years of follow-up, 104 women experienced 151 pregnancies. Mean depression scores did not differ across the time periods (P = 0.75). Multivariable models yielded similar findings. Increasing time on ART, viral suppression, better physical health, and “never married” were independently associated with lower mean depression scores. Findings were consistent when assessing probable depression. Conclusions: Although the lack of association between depression and perinatal periods is reassuring, high depression prevalence at treatment initiation and continued incidence across pregnancy and non–pregnancy-related periods of follow-up highlight the critical need for mental health services for HIV-infected women to optimize both maternal and perinatal health

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE)

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Omega-3 fatty acids and genome-wide interaction analyses reveal DPP10-pulmonary function association

Rationale: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties that could benefit adults with comprised pulmonary health. Objective: To investigate n-3 PUFA associations with spirometric measures of pulmonary function tests (PFTs) and determine underlying genetic susceptibility. Methods: Associations of n-3 PUFA biomarkers (a-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid [DPA], and docosahexaenoic acid [DHA]) were evaluated with PFTs (FEV1, FVC, and FEV1/FVC) in meta-analyses across seven cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (N=16,134 of European or African ancestry). PFT-associated n-3 PUFAs were carried forward to genome-wide interaction analyses in the four largest cohorts (N=11,962) and replicated in one cohort (N=1,687). Cohort-specific results were combined using joint 2 degree-of-freedom (2df) meta-analyses of SNPassociations and their interactions with n-3PUFAs. Results: DPA and DHA were positively associated with FEV1 and FVC (P < 0.025), with evidence for effect modification by smoking and by sex. Genome-wide analyses identified a novel association of rs11693320-an intronic DPP10 SNP-with FVC when incorporating an interaction with DHA, and the finding was replicated (P-2df = 9.4 x 10(-9) across discovery and replication cohorts). The rs11693320-A allele (frequency, similar to 80%) was associated with lower FVC (P-SNP = 2.1 x 10(-9); beta(SNP) = 2161.0 ml), and the association was attenuated by higher DHA levels (P-SNPxDHA interaction = 2.1x10(-7); beta(SNPxDHA interaction) = 36.2 ml). Conclusions: We corroborated beneficial effects of n-3 PUFAs on pulmonary function. By modeling genome-wide n-3 PUFA interactions, we identified a novel DPP10 SNP association with FVC that was not detectable in much larger studies ignoring this interaction

Adiponectin circulating levels and 10-year (2002–2012) cardiovascular disease incidence:the ATTICA Study

Purpose: Adiponectin is an adipokine with anti-inflammatory and cardiovascular-protective properties. Existing epidemiological evidence is conflicting on the exact relationship between adiponectin and long-term cardiovascular disease (CVD) risk. Our aim was to prospectively assess whether circulating adiponectin is associated with long-term incident CVD. Methods: A population-based, prospective study in adults (>18 years) without previous CVD history (ATTICA study). Circulating total adiponectin levels were measured at baseline (2001–2002) in a sub-sample (n = 531; women/men: 222/309; age: 40 ± 11 years) of the ATTICA cohort and complete 10-year follow-up data were available in 366 of these participants (women/men: 154/212; age: 40 ± 12 years). Results: After adjusting for multiple factors, including age, sex, body mass index, waist circumference, smoking, physical activity, Mediterranean diet adherence, hypertension, diabetes, and hypercholesterolemia, our logistic regression analysis indicates that an increase in circulating total adiponectin levels by 1 unit was associated with 36% lower CVD risk (relative risk [RR]: 0.64, 95% confidence interval [CI] 0.42–0.96; p = 0.03). Further adjusting for interleukin-6 plasma levels had no significant impact (RR: 0.60, 95% CI 0.38–0.94; p = 0.03), while additional adjustment for circulating C-reactive protein (CRP) modestly attenuated this association (RR: 0.63, 95% CI 0.40–0.99; p = 0.046). Conclusions: In our study, elevated circulating total adiponectin levels were associated with lower 10-year CVD risk in adults without previous CVD, independently of other established CVD risk factors. This association appeared to be modestly attenuated by CRP, yet was not mediated by interleukin-6 which is the main endocrine/circulating pro-inflammatory cytokine

A Non-Canonical Function of Zebrafish Telomerase Reverse Transcriptase Is Required for Developmental Hematopoiesis

Although it is clear that telomerase expression is crucial for the maintenance of telomere homeostasis, there is increasing evidence that the TERT protein can have physiological roles that are independent of this central function. To further examine the role of telomerase during vertebrate development, the zebrafish telomerase reverse transcriptase (zTERT) was functionally characterized. Upon zTERT knockdown, zebrafish embryos show reduced telomerase activity and are viable, but develop pancytopenia resulting from aberrant hematopoiesis. The blood cell counts in TERT-depleted zebrafish embryos are markedly decreased and hematopoietic cell differentiation is impaired, whereas other somatic lineages remain morphologically unaffected. Although both primitive and definitive hematopoiesis is disrupted by zTERT knockdown, the telomere lengths are not significantly altered throughout early development. Induced p53 deficiency, as well as overexpression of the anti-apoptotic proteins Bcl-2 and E1B-19K, significantly relieves the decreased blood cells numbers caused by zTERT knockdown, but not the impaired blood cell differentiation. Surprisingly, only the reverse transcriptase motifs of zTERT are crucial, but the telomerase RNA-binding domain of zTERT is not required, for rescuing complete hematopoiesis. This is therefore the first demonstration of a non-canonical catalytic activity of TERT, which is different from “authentic” telomerase activity, is required for during vertebrate hematopoiesis. On the other hand, zTERT deficiency induced a defect in hematopoiesis through a potent and specific effect on the gene expression of key regulators in the absence of telomere dysfunction. These results suggest that TERT non-canonically functions in hematopoietic cell differentiation and survival in vertebrates, independently of its role in telomere homeostasis. The data also provide insights into a non-canonical pathway by which TERT functions to modulate specification of hematopoietic stem/progenitor cells during vertebrate development. (276 words