Die Auswirkung von Zigarettenrauch auf das Atemwegsepithelium von Drosophila melanogaster zur Modellierung von COPD-ähnlichen Phänotypen

Cigarette smoking is the major risk factor for Chronic obstructive pulmonary disease (COPD) and lung cancer. Although COPD is one of the most important chronic lung diseases, our knowledge about the underlying molecular framework is only fragmentary. Hence, this study introduces D. melanogaster as a novel model for basic COPD research. Various cigarette smoke exposure (CSE) models using different exposure regimes were implemented in the course of this study and the in vivo impact of CSE was analyzed using 3rd instar larvae. The airways showed a strong structural modification and an activation of JAK-STAT signaling in the epithelial cells of CS treated animals. Both, upd2 and upd3 and the receptor dome of the JAK-STAT pathway, were strongly expressed at the posterior end of the dorsal branches, indicative for an autocrine signaling. The exact function and role of these ligands, especially in the tracheal system of D. melanogaster is still poorly understood. In silico analysis of the structures of upd3 with IL-6 of mouse, implied an ancestral relationship between both cytokines. Moreover, an ectopic expression of the JAK-STAT pathway components in the trachea resulted into epithelial barrier disruption in form of meta- and hyperplasia. To unravel potential upstream regulators of these upd ligands, flies deficient in expression of either dFoxO or relish were used and exposed to CS. Especially, in dFoxO deficient flies, induction of upd2 and upd3 transcripts were significantly reduced. Electrophoretic mobility shift assays underlining the potential role of dFoxO in directly regulating upd2 and upd3 expression. Furthermore, CS results in structural remodeling including thickening of the epithelial layer, in parallel with JAK/STAT signaling activation that may be triggered by dFoxO. Beside this CSE based model for COPD research, destruction of the terminal airway structure via strong activation of cAMP signaling was induced.Tabakrauchen ist der größte Risikofaktor für COPD und Lungenkrebs. Unser Wissen über die zugrunde liegenden molekularen Signalwege und Gene ist derzeit nur bruchstückhaft. Die vorliegende Arbeit hatte daher zum Ziel, D. melanogaster als ein neues Modell für die Grundlagenforschung der COPD einzuführen. Die Relevanz von Zigarettenrauch im Atemwegsepithelium wurde untersucht und eine epitheliale Immunreaktion gezeigt. Die Applikation von Zigarettenrauch hatte eine Beeinträchtigung der epithelialen Barriere und eine Aktivierung des JAK-STAT-Signalwegs zur Folge. Es erfolgte eine induzierte Expression von Upd2 und Upd3 sowie des Rezeptors Domeless an den dorsalen Verzweigungen der primären Tracheen, was für ein autokrines Signalisierungssystem spricht. Die Funktion dieser Liganden sind vor allem in den Tracheen noch weitgehend unverstanden. Daher wurden sowohl strukturelle Vergleiche von upd3 mit der bekannten Kristallstruktur von IL-6 als auch eine funktionelle Überexpression dieser Liganden in den Tracheen vorgenommen, um diese näher charakterisieren zu können. Eine ektopische Expression im Atemwegsepithel führte zu einer Störung der Epithelbarriere in Form einer Meta- und Hyperplasie. Um mögliche Regulatorgene für die Expression der Upd-Liganden zu entschlüsseln, wurden Mutanten, defizient in den Transkriptionsfaktoren dFoxO und Relish verwendet und beraucht. Insbesondere in dFoxO defizienten Fliegen war die Induktion der Upd2 und Upd3- Transkripte deutlich reduziert. Bandshiftassays unterstreichen die potentielle Rolle von dFoxo in seiner direkten Regulation von Upd2 und Upd3. Weiterhin führt Zigarettenrauch zur Atemwegsmodelierung in Form einer verdickten Epithelschicht, das mit einer parallelen Aktivierung des JAK-STAT-Signalweges einhergeht, welcher vermutlich dFoxO abhängig ist. Neben dem Zigarettenrauch-Modell für die COPD-Forschung, wurde ein alternatives Modell entwickelt, das sich der Bedeutung des cAMP-Signalings im Atemwegsepithel widmet

Dyeing of protein fabrics exploring locally available weed plants

In the present study weed plants i.e. Lantana camara, Solanum nigrum, Eupatorium adenophorum, Tridax procumbens, Parthenium histerophorus, Sida acuta, Ipomea cairica, Rumex nepalensis, Eclipta prostrate, Girardinia diversifolia, Erigeron bellidioides, Bidens pilosa and Athatoda vasica available in hilly as well as Tarai regions of Uttarakhand were collected, dried and powdered. The powdered dye materialswere extracted in distilled water. Subsequently dyeing of wool and silk fabrics was carried out. It was found that various plants like E. adenophorum, R. nepalensis and B. pilosa gave acceptable colour on silk and wool fabric. Therefore some weed plants can be used for textile dyeing which will provide a scope for management of weed plants as well as safety of other useful indigenous plant

Conservation of Tubulin-Binding Sequences in TRPV1 throughout Evolution

Transient Receptor Potential Vanilloid sub type 1 (TRPV1), commonly known as capsaicin receptor can detect multiple stimuli ranging from noxious compounds, low pH, temperature as well as electromagnetic wave at different ranges. In addition, this receptor is involved in multiple physiological and sensory processes. Therefore, functions of TRPV1 have direct influences on adaptation and further evolution also. Availability of various eukaryotic genomic sequences in public domain facilitates us in studying the molecular evolution of TRPV1 protein and the respective conservation of certain domains, motifs and interacting regions that are functionally important. analysis reveals that the TBS-1 and TBS-2 of TRPV1 can form helical structures and may play important role in TRPV1 function.Our analysis identifies the regions of TRPV1, which are important for structure – function relationship. This analysis indicates that tubulin binding sequence-1 (TBS-1) near the TRP-box forms a potential helix and the tubulin interactions with TRPV1 via TBS-1 have evolutionary significance. This interaction may be required for the proper channel function and regulation and may also have significance in the context of Taxol®-induced neuropathy

Bone marrow aspiration cytology in the diagnosis of hematologic and non-hematologic diseases in a multi-specialty hospital in Nepal

Background: Peripheral blood smear examination and other routine laboratory assays are not always sufficient to diagnose various diseases which affect the blood and bone marrow. A bone marrow aspirate examination is essential in most of the cases.Methods: This work was a hospital-based cross sectional analytical observational study carried out in the department of pathology at the Chitwan Medical College, Teaching Hospital, Nepal, over a period of 3 years from January, 2013 to December 2015. Bone marrow was aspirated from posterior superior iliac crest under local anesthesia; sternum was the alternative site in obese patients. Univariate analysis was performed for each variable using frequency distribution and means with the help of Statistical Package for Social Sciences 20.0 (SPSS 20.0) software.Results: One hundred and fifty-nine patients were included in the study. Eight cases of 'dry tap' were excluded, for whom bone marrow biopsy was advised. Anemia was the largest group followed by malignancy, infection and miscellaneous diseases. Among anemia, megaloblastic anemia was the most common, followed by aplastic anemia, dyserythropoietic anemia and myelopthisic anemia. The category 'malignancy' consisted of leukemia, multiple myeloma and myelodysplastic syndrome. Regarding individual diseases, megaloblastic anemia was the most common haematological disorder followed by immune thrombocytopenic purpura, leukemia and aplastic anemia.Conclusions: Bone marrow aspiration cytology is a mildly invasive technique which can diagnose many haematological and non-hematologic diseases that can be confirmed by more advanced investigations, if needed: serological, biochemical or molecular. However, bone marrow sample cannot be obtained (dry tap) in a proportion of cases. In such cases, a bone marrow biopsy needs to be performed

Role of Systemic Factors in Improving the Prognosis of Diabetic Retinal Disease and Predicting Response to Diabetic Retinopathy Treatment

Diabetic retinopathy; Prediction; Systemic factorsRetinopatía diabética; Predicción; Factores sistémicosRetinopatia diabètica; Predicció; Factors sistèmicsTopic To review clinical evidence on systemic factors that might be relevant to update diabetic retinal disease (DRD) staging systems, including prediction of DRD onset, progression, and response to treatment. Clinical relevance Systemic factors may improve new staging systems for DRD to better assess risk of disease worsening and predict response to therapy. Methods The Systemic Health Working Group of the Mary Tyler Moore Vision Initiative reviewed systemic factors individually and in multivariate models for prediction of DRD onset or progression (i.e., prognosis) or response to treatments (prediction). Results There was consistent evidence for associations of longer diabetes duration, higher glycosylated hemoglobin (HbA1c), and male sex with DRD onset and progression. There is strong trial evidence for the effect of reducing HbA1c and reducing DRD progression. There is strong evidence that higher blood pressure (BP) is a risk factor for DRD incidence and for progression. Pregnancy has been consistently reported to be associated with worsening of DRD but recent studies reflecting modern care standards are lacking. In studies examining multivariate prognostic models of DRD onset, HbA1c and diabetes duration were consistently retained as significant predictors of DRD onset. There was evidence of associations of BP and sex with DRD onset. In multivariate prognostic models examining DRD progression, retinal measures were consistently found to be a significant predictor of DRD with little evidence of any useful marginal increment in prognostic information with the inclusion of systemic risk factor data apart from retinal image data in multivariate models. For predicting the impact of treatment, although there are small studies that quantify prognostic information based on imaging data alone or systemic factors alone, there are currently no large studies that quantify marginal prognostic information within a multivariate model, including both imaging and systemic factors. Conclusion With standard imaging techniques and ways of processing images rapidly evolving, an international network of centers is needed to routinely capture systemic health factors simultaneously to retinal images so that gains in prediction increment may be precisely quantified to determine the usefulness of various health factors in the prognosis of DRD and prediction of response to treatment

Molecular Phylogeny of OVOL Genes Illustrates a Conserved C2H2 Zinc Finger Domain Coupled by Hypervariable Unstructured Regions

OVO-like proteins (OVOL) are members of the zinc finger protein family and serve as transcription factors to regulate gene expression in various differentiation processes. Recent studies have shown that OVOL genes are involved in epithelial development and differentiation in a wide variety of organisms; yet there is a lack of comprehensive studies that describe OVOL proteins from an evolutionary perspective. Using comparative genomic analysis, we traced three different OVOL genes (OVOL1-3) in vertebrates. One gene, OVOL3, was duplicated during a whole-genome-duplication event in fish, but only the copy (OVOL3b) was retained. From early-branching metazoa to humans, we found that a core domain, comprising a tetrad of C2H2 zinc fingers, is conserved. By domain comparison of the OVOL proteins, we found that they evolved in different metazoan lineages by attaching intrinsically-disordered (ID) segments of N/C-terminal extensions of 100 to 1000 amino acids to this conserved core. These ID regions originated independently across different animal lineages giving rise to different types of OVOL genes over the course of metazoan evolution. We illustrated the molecular evolution of metazoan OVOL genes over a period of 700 million years (MY). This study both extends our current understanding of the structure/function relationship of metazoan OVOL genes, and assembles a good platform for further characterization of OVOL genes from diverged organisms

Electrification using Decentralized Micro Hydropower Plants in North-eastern Afghanistan

Electricity supply database from the Afghan national authority for electricity supply shows that about only 20% of the population in Afghanistan had access to grid electricity by 2010. The national utility has a total capacity of about 842 MW, out of which about 696 MW was operational. Additionally, many decentralized units (Micro Hydropower (MHP) plants, diesel generators and solar home systems) supply electricity to about 7% of the population. The donors supported National Solidarity Programme (NSP) has promoted hundreds of rural electrification projects. MHP plants are the major renewable energy based projects among them. In order to identify the operational status of installed MHP plants in four North-eastern provinces (i.e. Badakhshan, Baghlan, Balkh and Takhar) and to assess their socio-economic impacts, an extensive field monitoring had been carried out. The major parameters studied were spatial distribution of MHP plants, investment costs, operational models, end user electricity tariffs, productive use of electricity, community satisfaction, etc. Altogether, 421 MHP installations (about 11 MW installed capacity) were visited. The outcomes obtained from those surveys are presented in detail in this paper

Role of Systemic Factors in Improving the Prognosis of Diabetic Retinal Disease and Predicting Response to Diabetic Retinopathy Treatment

TOPIC: To review clinical evidence on systemic factors that might be relevant to update diabetic retinal disease (DRD) staging systems, including prediction of DRD onset, progression, and response to treatment.CLINICAL RELEVANCE: Systemic factors may improve new staging systems for DRD to better assess risk of disease worsening and predict response to therapy.METHODS: The Systemic Health Working Group of the Mary Tyler Moore Vision Initiative reviewed systemic factors individually and in multivariate models for prediction of DRD onset or progression (i.e., prognosis) or response to treatments (prediction).RESULTS: There was consistent evidence for associations of longer diabetes duration, higher glycosylated hemoglobin (HbA1c), and male sex with DRD onset and progression. There is strong trial evidence for the effect of reducing HbA1c and reducing DRD progression. There is strong evidence that higher blood pressure (BP) is a risk factor for DRD incidence and for progression. Pregnancy has been consistently reported to be associated with worsening of DRD but recent studies reflecting modern care standards are lacking. In studies examining multivariate prognostic models of DRD onset, HbA1c and diabetes duration were consistently retained as significant predictors of DRD onset. There was evidence of associations of BP and sex with DRD onset. In multivariate prognostic models examining DRD progression, retinal measures were consistently found to be a significant predictor of DRD with little evidence of any useful marginal increment in prognostic information with the inclusion of systemic risk factor data apart from retinal image data in multivariate models. For predicting the impact of treatment, although there are small studies that quantify prognostic information based on imaging data alone or systemic factors alone, there are currently no large studies that quantify marginal prognostic information within a multivariate model, including both imaging and systemic factors.CONCLUSION: With standard imaging techniques and ways of processing images rapidly evolving, an international network of centers is needed to routinely capture systemic health factors simultaneously to retinal images so that gains in prediction increment may be precisely quantified to determine the usefulness of various health factors in the prognosis of DRD and prediction of response to treatment.FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p

Overestimation of Postpartum Depression Prevalence Based on a 5-item Version of the EPDS:Systematic Review and Individual Participant Data Meta-analysis

Objective:The Maternal Mental Health in Canada, 2018/2019, survey reported that 18% of 7,085 mothers who recently gave birth reported "feelings consistent with postpartum depression" based on scores >= 7 on a 5-item version of the Edinburgh Postpartum Depression Scale (EPDS-5). The EPDS-5 was designed as a screening questionnaire, not to classify disorders or estimate prevalence; the extent to which EPDS-5 results reflect depression prevalence is unknown. We investigated EPDS-5 >= 7 performance relative to major depression prevalence based on a validated diagnostic interview, the Structured Clinical Interview for DSM (SCID).Methods:We searched Medline, Medline In-Process & Other Non-Indexed Citations, PsycINFO, and the Web of Science Core Collection through June 2016 for studies with data sets with item response data to calculate EPDS-5 scores and that used the SCID to ascertain depression status. We conducted an individual participant data meta-analysis to estimate pooled percentage of EPDS-5 >= 7, pooled SCID major depression prevalence, and the pooled difference in prevalence.Results:A total of 3,958 participants from 19 primary studies were included. Pooled prevalence of SCID major depression was 9.2% (95% confidence interval [CI] 6.0% to 13.7%), pooled percentage of participants with EPDS-5 >= 7 was 16.2% (95% CI 10.7% to 23.8%), and pooled difference was 8.0% (95% CI 2.9% to 13.2%). In the 19 included studies, mean and median ratios of EPDS-5 to SCID prevalence were 2.1 and 1.4 times.Conclusions:Prevalence estimated based on EPDS-5 >= 7 appears to be substantially higher than the prevalence of major depression. Validated diagnostic interviews should be used to establish prevalence