Codling moth granulovirus: Variations in the susceptibility of local codling moth populations

This study is part of a BMELV (German Federal Ministry for, Food, Agriculture and Consumer Protection) project for prevention of codling moth damage by long-term population control in large areas. Specimens from local codling moth populations were collected in fall 2003 from three different orchards in the South of Germany; two of them having been treated with granulovirus of codling moth (CpGV Madex 2 and/or Gran-upom) over many years (Lake Constance II and South Baden) and one since two years (Lake Constance I). In autumn 2004, specimens from populations in four other orchards with serious CM problems were col-lected to investigate whether more populations were involved in that region. Furthermore, the population Lake Constance I and South Baden were tested again. During the season, the location South Baden was almost weekly treated with 100 ml/ha of Madex 2 to test whether the level of susceptibility would change after such heavy treatments. The susceptibility of the offsprings of the overwintering generation to CpGV was investigated in the spring of the following year in bioassays on artificial diet and compared to a laboratory strain of the codling moth. The results indicated significant differences in sensitivity to the virus between the local codling moth populations. The LC50-values showed that in 2004, South Baden and Lake Constance II were more than thousand fold less susceptible than the populations Lake Constance I and the laboratory strain. The results from the bio-assays in 2005 confirmed the low susceptibility of South Baden and of the new locations in Saarland and from an orchard 100 km away from South Baden. The population Lake Constance I, on the other hand, maintained its high sensitivity to the virus. The slope of the dose-mortality-regression lines of the unsuscep-tible populations was significantly lower than those of the susceptible ones, including that of the laboratory strain. This indicates a high inhomogeneity in the individual response of the unsusceptible larvae against the virus. Actually, the problem of reduced sensitivity to the virus seems to be limited to a few orchards in Germany, the majority of orchards being not affected

Persistence of the biological effect of codling moth granulovirus in the orchard - preliminary field trials

In 2000 and 2001, in a field trial, the persistence of the biological effect of codling moth granulovirus (CpGV) was investigated. With a single treatment at full concentration of CpGV (MADEX 3, 100 ml/ha) a considerable reduction of CM population was achieved over the whole vegetation period. This may indicate that over a considerable period of time after a treatment a biological effect of CpGV sufficient for an increased mortality of the larvae was present in the orchard. However, the onset of mortality was not fast enough to protect the fruit from damage. Further research has to be done to gain more experience in handling this effect. It could be very important for the reduction of the number of treatments in organic apple growing

Genotoxicity of nitroso compounds and sodium dichromate in a model combining organ cultures of human nasal epithelia and the comet assay

Genotoxic effects of xenobiotics are a possible step in tumor initiation in the mucosa of the upper aerodigestive tract. Using the comet assay, detecting genotoxicity in human tissue has been restricted to single incubations in vitro, but in vivo most xenobiotics harm their target in a repetitive or chronic manner. Therefore, we propose a model, which provides repetitive incubations in human upper aerodigestive tract mucosa cultures. Samples of human inferior nasal turbinate mucosa (n = 25) were cultured according to a modified version of a technique originally described by Steinsvag. On day 1 fresh samples and on days 7, 9 and 11 organ cultures were incubated with N-nitrosodiethylamine (NDEA), sodium dichromate (Na2Cr2O7) and N'-methyl-N-nitro-N-nitrosoguanidine(MNNG). Mucosa samples and organ cultures, respectively, underwent a modified comet assay on days 1, 7 and 11. Genotoxicity could be shown for NDEA, Na2Cr2O7 and MNNG on days 1, 7 and 11. Duration of tissue culture and repetitive incubations did not significantly influence the results for NDEA. Nevertheless, Na2Cr2O7 and MNNG caused higher genotoxic effects on cultures subjected to the comet assay on day 11. This model may help to assess genotoxic hazards posed by environ mental pollutants that have a cumulative character in repetitive or chronic exposure in vivo. Copyright (C) 2001 S. Karger AG, Basel

Apfelwickler-Granulovirus: Unterschiede in der Empfindlichkeit lokaler Apfelwickler-Populationen

This study is part of a BMELV (German Federal Ministry for, Food, Agriculture and Consumer Protection) project on prevention of codling moth damage by long-term population control on large areas. Local codling moth (CM) populations were collected in autumn 2003 from three different orchards in the South of Germany; two of them having been treated with granulovirus of codling moth for many years and one since two years. In autumn 2004, in addition to the three locations from the previous year, specimens from populations in four other orchards with serious CM problems were collected. The susceptibility of the offsprings of the overwintering larvae to CpGV was investi-gated in the spring of the following year in bioassays on artificial diet and compared to a laboratory strain of the codling moth. The results indicated significant differences in sensitivity to the virus between the local codling moth populations. The LC50-values showed that two of the populations sampled in 2003 were more than thousand fold less susceptible than the third population and the laboratory strain. The results from the bioassays from the descendents of the diapausing larvae sampled in 2004 and 2005 confirmed the low susceptibility of two already in 2003 sampled populations and showed an up to thousand fold resistance also for the larvae from the new locations. For the time being, the problem of reduced sensitivity to the virus seems to be limited to a few orchards in Germany, the majority of orchards being not affected

TFF3-dependent resistance of human colorectal adenocarcinoma cells HT-29/B6 to apoptosis is mediated by miR-491-5p regulation of lncRNA PRINS

Tumour necrosis factor-α (TNF-α) is a double-edged cytokine associated with pathogenesis of inflammatory-related cancers being also able to induce cancer cell death. In the process of tumour development or metastasis, cancer cells can become resistant to TNF-α. In trefoil factor 3 (TFF3) overexpressing colorectal adenocarcinoma cells (HT-29/B6), we observed enhanced resistance against TNF-α/interferon gamma-induced apoptosis. TFF3 is a secreted small peptide that supports intestinal tissue repair but is also involved in intestinal tumour progression and scattering. We hypothesised that TFF3 rescues intestinal epithelial cancer cells from TNF-α-induced apoptosis by involving regulatory RNA networks. In silico-based expression analysis revealed TFF3-mediated regulation of selected microRNAs as well as long non- coding RNAs (lncRNAs), whereas miR-491-5p was identified to target the lncRNA ‘psoriasis susceptibility-related RNA gene induced by stress’ (PRINS). RNA interference-based gain- and loss-of-function experiments examined miR-491-PRINS axis to exert the TFF3-mediated phenotype. Chemical inhibition of selected pathways showed that phosphatidylinositol 3-kinase/AKT accounts for TFF3-mediated downregulation of miR-491-5p and accumulation of PRINS. Moreover, we showed that PRINS colocalises with PMAIP1 (NOXA) in nuclei of HT-29/B6 possessing inhibitory effects. Immunoprecipitation experiments proved molecular interaction of PMAIP1 with PRINS. Our study provides an insight into RNA regulatory networks that determine resistance of colorectal cancer cells to apoptosis

Neutrophile-to-Lymphocyte Ratio (NLR) Identifies Patients with Coronavirus Infectious Disease 2019 (COVID-19) at High Risk for Deterioration and Mortality-A Retrospective, Monocentric Cohort Study

Among people infected with SARS-CoV-2, the determination of clinical features associated with poor outcome is essential to identify those at high risk of deterioration. Here, we aimed to investigate clinical phenotypes of patients hospitalized due to COVID-19 and to examine the predictive value of the neutrophil-to-lymphocyte ratio (NLR) in a representative patient collective of the Swiss population. We conducted a retrospective monocentriccohort study with patients hospitalized due to COVID-19 between 27 February and 31 December 2020. Data were analyzed descriptively, using the binary logistic regression model, proportional odds logistic regression model, competing risk analysis, and summary measure analysis. A total of 454 patients were included in our study. Dyspnea, elevated respiratory rate, low oxygen saturation at baseline, age, and presence of multiple comorbidities were associated with a more severe course of the disease. A high NLR at baseline was significantly associated with disease severity, unfavorable outcome, and mortality. In non-survivors, NLR further increased during hospital stay, whereas in survivors, NLR decreased. In conclusion, our data emphasize the importance of accurate history taking and clinical examination upon admission and confirm the role of baseline NLR as a surrogate marker for increased disease severity, unfavorable outcome, and mortality in patients hospitalized due to infection with SARS-CoV-2

MiR-124 is differentially expressed in derivatives of the sympathoadrenal cell lineage and promotes neurite elongation in chromaffin cells

The neural-crest-derived sympathoadrenal cell lineage gives rise to sympathetic neurons and to endocrine chromaffin cells of the adrenal medulla. Both cell types express a largely overlapping set of genes, including those coding for the molecular machinery related to the synthesis and exocytotic release of catecholamines. During their early development, sympathetic neurons and chromaffin cells rely on a shared transcription factor network that controls the establishment of these common features. Despite many similarities, mature sympathetic neurons and chromaffin cells significantly differ regarding their morphology and function. Most prominently, sympathetic neurons possess axons that are absent in mammalian adrenal chromaffin cells. The molecular mechanism underlying the divergent development of sympathoadrenal cells into neuronal and endocrine cells remains elusive. Mutational inactivation of the ribonuclease dicer hints at the importance of microRNAs in this diversification. We show here that miR-124 is detectable in developing sympathetic neurons but absent in chromaffin cell precursors. We further demonstrate that miR- 124 promotes neurite elongation when transfected into cultured chromaffin cells indicating its capability to support the establishment of a neuronal morphology in non- neuronal sympathoadrenal cells. Our results also show that treatment of PC12 cells with the neurotrophin nerve growth factor leads to an upregulation of miR-124 expression and that inhibition of miR-124 reduces nerve-growth-factor-induced neurite outgrowth in PC12 cells. Thus, our data indicate that miR-124 contributes to the establishment of specific neuronal features in developing sympathoadrenal cells

Nucleosomes indicate the in vitro radiosensitivity of irradiated bronchoepithelial and lung cancer cells

Nucleosomes, which are typical cell death products, are elevated in the serum of cancer patients and are known to rapidly increase during radiotherapy. As both normal and malignant cells are damaged by irradiation, we investigated to which extent both cell types contribute to the release of nucleosomes. We cultured monolayers of normal bronchoepithelial lung cells (BEAS-2B, n = 18) and epithelial lung cancer cells (EPLC, n = 18), exposed them to various radiation doses (0, 10 and 30 Gy) and observed them for 5 days. Culture medium was changed every 24 h. Subsequently, nucleosomes were determined in the supernatant by the Cell Death Detection-ELISA(plus) ( Roche Diagnostics). Additionally, the cell number was estimated after harvesting the cells in a second preparation. After 5 days, the cell number of BEAS-2B cultures in the irradiated groups (10 Gy: median 0.03 x 10(6) cells/culture, range 0.02-0.08 x 10(6) cells/culture; 30 Gy: median 0.08 x 10(6) cells/culture, range 0.02-0.14 x 10(6) cells/culture) decreased significantly (10 Gy: p = 0.005; 30 Gy p = 0.005; Wilcoxon test) compared to the non-irradiated control group (median 4.81 x 10(6) cells/culture, range 1.50-9.54 x 10(6) cells/culture). Consistently, nucleosomes remained low in the supernatant of nonirradiated BEAS-2B. However, at 10 Gy, BEAS-2B showed a considerably increasing release of nucleosomes, with a maximum at 72 h ( before irradiation: 0.24 x 10(3) arbitrary units, AU, range 0.13-4.09 x 10(3) AU, and after 72 h: 1.94 x 10(3) AU, range 0.11-5.70 x 10(3) AU). At 30 Gy, the release was even stronger, reaching the maximum earlier (at 48 h, 11.09 x 10(3) AU, range 6.89-18.28 x 10(3) AU). In non-irradiated EPLC, nucleosomes constantly increased slightly. At 10 Gy, we observed a considerably higher release of nucleosomes in EPLC, with a maximum at 72 h (before irradiation: 2.79 x 10(3) AU, range 2.42-3.80 x 10(3) AU, and after 72 h: 7.16 x 10(3) AU, range 4.30-16.20 x 10(3) AU), which was more than 3.5 times higher than in BEAS-2B. At 30 Gy, the maximum (6.22 x 10(3) AU, range 5.13-9.71 x 10(3) AU) was observed already after 24 h. These results indicate that normal bronchoepithelial and malignant lung cancer cells contribute to the release of nucleosomes during irradiation in a dose-and time-dependent manner with cancer cells having a stronger impact at low doses. Copyright (C) 2004 S. Karger AG, Basel

The AIFELL Score as a Predictor of Coronavirus Disease 2019 (COVID-19) Severity and Progression in Hospitalized Patients

Since the beginning of the COVID-19 pandemic, SARS-CoV-2 has caused a global burden for health care systems due to high morbidity and mortality rates, leading to caseloads that episodically surpass hospital resources. Due to different disease manifestations, the triage of patients at high risk for a poor outcome continues to be a major challenge for clinicians. The AIFELL score was developed as a simple decision instrument for emergency rooms to distinguish COVID-19 patients in severe disease stages from less severe COVID-19 and non-COVID-19 cases. In the present study, we aimed to evaluate the AIFELL score as a prediction tool for clinical deterioration and disease severity in hospitalized COVID-19 patients. During the second wave of the COVID-19 pandemic in Switzerland, we analyzed consecutively hospitalized patients at the Triemli Hospital Zurich from the end of November 2020 until mid-February 2021. Statistical analyses were performed for group comparisons and to evaluate significance. AIFELL scores of patients developing severe COVID-19 stages IIb and III during hospitalization were significantly higher upon admission compared to those patients not surpassing stages I and IIa. Group comparisons indicated significantly different AIFELL scores between each stage. In conclusion, the AIFELL score at admission was useful to predict the disease severity and progression in hospitalized COVID-19 patients