146 research outputs found
Public perception and knowledge on nanotechnology: A study based on a citizen science approach
Even with the widespread use of nanomaterials (NMs) in everyday life, consumer knowledge about the functionality, benefits, and possible dangers of nanotechnology (NT) is still modest. As with any developing technology, its public perception has direct implications on future policies and has to be taken into account by academia and industry alike. As part of the “Nan-O-Style” interdisciplinary research project, an online survey was conducted using a Citizen Science-guided approach. The main goal was to evaluate the current levels of knowledge and the attitude towards NT among the general Austrian public and to determine how differing sociodemographic factors may affect these. Over the course of 17 months, a total of 1067 responses were collected and quantitatively analysed. We found that while Austrians display a generally optimistic view and a positive attitude towards NT, there are still remaining concerns about its safety and possible risks. Participants expressed great desire for more information about NT and its applications, as well as for clear labelling and transparency of products containing NMs. Notably, we found that age did not affect the general attitude towards NT nor the levels of NT awareness. While participants with a university degree were generally more knowledgeable on this specific topic, surprisingly, there were no significant differences in the attitude towards NT among people from different educational backgrounds. Similar to previous studies, we observed that male participants demonstrated a more positive attitude towards NT and scored slightly higher in our NT quiz compared to female participants. However, female participants voiced greater desire for more information and transparency regarding NMs. Interestingly, while participants with a negative attitude towards NT scored lowest on the NT quiz, they also expressed the least interest in receiving more NT-related information. This illustrates a difficulty in mitigating public aversion solely by providing more information
Conducting a drought-specific THIRA (Threat and Hazard Identification and Risk Assessment): A powerful tool for integrating all-hazard mitigation and drought planning efforts to increase drought mitigation quality
In the United States, drought is the second costliest natural disaster, which leads to the need for increased drought mitigation efforts over time. However, drought planning has lagged behind other hazard mitigation efforts, which is likely due to the lack of a national drought planning policy. Although the Federal Emergency Management Agency (FEMA) requires all jurisdictions have a hazard mitigation plan (HMP) to receive pre-disaster mitigation funds, drought has only recently been a requirement in HMPs. In 2012, Nebraska witnessed its worse drought in recent history, which exposed the gaps in drought planning effectiveness at all jurisdictional levels. To address potential drought planning gaps, we developed, conducted, and evaluated a Threat and Hazard Identification and Risk Assessment (THIRA), a FEMA risk assessment process, which solely focused on drought. This drought-specific THIRA consisted of a one-day workshop in which stakeholders and agency experts from the Platte River Basin in Nebraska worked collaboratively to determine the necessary resources for successfully managing a worst-case drought scenario in the region. We analyzed the findings of this workshop and compared them against the current drought planning activities in the Platte River Basin and found that the current drought planning activities would not be effective against a worst-case drought, in terms of reducing drought vulnerability and increasing preparedness and response efforts. Our use of a drought-specific THIRA and drought plan evaluation provides both a quality process to increase drought mitigation efforts and a process to strengthen the integration between stand-alone drought plans and hazard mitigation plans
CD4 T lymphocyte autophagy is upregulated in the salivary glands of primary Sjögren’s syndrome patients and correlates with focus score and disease activity
Background: Primary Sjögren’s syndrome (pSS) is a common chronic autoimmune disease characterized by
lymphocytic infiltration of exocrine glands and peripheral lymphocyte perturbation. In the current study, we
aimed to investigate the possible pathogenic implication of autophagy in T lymphocytes in patients with pSS.
Methods: Thirty consecutive pSS patients were recruited together with 20 patients affected by sicca syndrome a
nd/or chronic sialoadenitis and 30 healthy controls. Disease activity and damage were evaluated according to SS
disease activity index, EULAR SS disease activity index, and SS disease damage index. T lymphocytes were analyzed
for the expression of autophagy-specific markers by biochemical, molecular, and histological assays in peripheral
blood and labial gland biopsies. Serum interleukin (IL)-23 and IL-21 levels were quantified by enzyme-linked
immunosorbent assay.
Results: Our study provides evidence for the first time that autophagy is upregulated in CD4+ T lymphocyte salivary
glands from pSS patients. Furthermore, a statistically significant correlation was detected between lymphocyte
autophagy levels, disease activity, and damage indexes. We also found a positive correlation between autophagy
enhancement and the increased salivary gland expression of IL-21 and IL-23, providing a further link between innate
and adaptive immune responses in pSS.
Conclusions: These findings suggest that CD4+ T lymphocyte autophagy could play a key role in pSS pathogenesis.
Additionally, our data highlight the potential exploitation of T cell autophagy as a biomarker of disease activity and
provide new ground to verify the therapeutic implications of autophagy as an innovative drug target in pSS
Fast analysis of antibody-derived therapeutics by automated multidimensional liquid chromatography - mass spectrometry
Characterization of post-translational modifications (PTMs) of therapeutic antibodies is commonly performed by bottom-up approaches, involving sample preparation and peptide analysis by liquid chromatography-mass spectrometry (LC-MS). Conventional sample preparation requires extensive hands-on time and can increase the risk of inducing artificial modifications as many off-line steps - denaturation, disulfide-reduction, alkylation and tryptic digestion - are performed. In this study, we developed an on-line multidimensional (mD)-LC-MS bottom-up approach for fast sample preparation and analysis of (formulated) monoclonal antibodies and antibody-derived therapeutics. This approach allows on-column reduction, tryptic digestion and subsequent peptide analysis by RP-MS. Optimization of the 1D -and 2D flow and temperature improved the trapping of small polar peptides during on-line peptide mapping analysis. These adaptations increased the sequence coverage (95-98% versus 86-94% for off-line approaches) and allowed identification of various PTMs (i.e. deamidation of asparagine, methionine oxidation and lysine glycation) within a single analysis. This workflow enables a fast (<2 h) characterization of antibody heterogeneities within a single run and a low amount of protein (10 mu g). Importantly, the new mD-LC-MS bottom-up method was able to detect the polar, fast-eluting peptides: Fc oxidation at Hc-Met-252 and the Fc N-glycosylation at Hc-Asn-297, which can be challenging using mD-LC-MS. Moreover, the method showed good comparability across the different measurements (RSD of retention time in the range of 0.2-1.8% for polar peptides). The LC system was controlled by only a standard commercial software package which makes implementation for fast characterization of quality attributes relatively easy. (C) 2021 The Author(s). Published by Elsevier B.V.Proteomic
Cellular gene expression during Hepatitis C virus replication as revealed by Ribosome Profiling
Background: Hepatitis C virus (HCV) infects human liver hepatocytes, often leading to liver cirrhosis and hepatocellular carcinoma (HCC). It is believed that chronic infection alters host gene expression and favors HCC development. In particular, HCV replication in Endoplasmic Reticulum (ER) derived membranes induces chronic ER stress. How HCV replication affects host mRNA translation and transcription at a genome wide level is not yet known. Methods: We used Riboseq (Ribosome Profiling) to analyze transcriptome and translatome changes in the Huh-7.5 hepatocarcinoma cell line replicating HCV for 6 days. Results: Established viral replication does not cause global changes in host gene expression—only around 30 genes are significantly differentially expressed. Upregulated genes are related to ER stress and HCV replication, and several regulated genes are known to be involved in HCC development. Some mRNAs (PPP1R15A/GADD34, DDIT3/CHOP, and TRIB3) may be subject to upstream open reading frame (uORF) mediated translation control. Transcriptional downregulation mainly affects mitochondrial respiratory chain complex core subunit genes. Conclusion: After establishing HCV replication, the lack of global changes in cellular gene expression indicates an adaptation to chronic infection, while the downregulation of mitochondrial respiratory chain genes indicates how a virus may further contribute to cancer cell-like metabolic reprogramming (“Warburg effect”) even in the hepatocellular carcinoma cells used here
A novel application of quantile regression for identification of biomarkers exemplified by equine cartilage microarray data
<p>Abstract</p> <p>Background</p> <p>Identification of biomarkers among thousands of genes arrayed for disease classification has been the subject of considerable research in recent years. These studies have focused on disease classification, comparing experimental groups of effected to normal patients. Related experiments can be done to identify tissue-restricted biomarkers, genes with a high level of expression in one tissue compared to other tissue types in the body.</p> <p>Results</p> <p>In this study, cartilage was compared with ten other body tissues using a two color array experimental design. Thirty-seven probe sets were identified as cartilage biomarkers. Of these, 13 (35%) have existing annotation associated with cartilage including several well-established cartilage biomarkers. These genes comprise a useful database from which novel targets for cartilage biology research can be selected. We determined cartilage specific Z-scores based on the observed M to classify genes with Z-scores ≥ 1.96 in all ten cartilage/tissue comparisons as cartilage-specific genes.</p> <p>Conclusion</p> <p>Quantile regression is a promising method for the analysis of two color array experiments that compare multiple samples in the absence of biological replicates, thereby limiting quantifiable error. We used a nonparametric approach to reveal the relationship between percentiles of M and A, where M is log<sub>2</sub>(R/G) and A is 0.5 log<sub>2</sub>(RG) with R representing the gene expression level in cartilage and G representing the gene expression level in one of the other 10 tissues. Then we performed linear quantile regression to identify genes with a cartilage-restricted pattern of expression.</p
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