cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.25403/upresearchdata.27888939.v2
title: Ford Resource and Engagement Centre (FREC) programme's contribution to poverty eradication : participant perspectives

description: The aim of the Ford Resource and Engagement Centre (FREC) programme of the non-profit organisation Future Families is to create sustainable livelihoods through micro-enterprises in the communities of Mamelodi and Nellmapius, South Africa. The goal of the study was to explore participant perspectives on the FREC programme’s contribution in poverty reduction in Mamelodi and Nellmapius.The study used a qualitative research approach. It was an applied study, and the research design was an exploratory study. Purposive sampling was used to select ten enrolled participants of the FREC programme who were from the center. Data was collected by means of semi-structured, one-on-one interviews and thematically analysed. Ethical considerations for the study included confidentiality, informed consent, voluntary participation, and avoidance of harm. There following themes emerged: 1. Reasons for joining the FREC programme2. Expectations for livelihood outcomes3. The effect of the FREC programme on participants' socio-economic well-being4. The benefits from the FREC programme 5. Suggested changes to improve the FREC programme<br>
DOI: 10.25403/upresearchdata.27888939.v1
title: Ford Resource and Engagement Centre (FREC) programme's contribution to poverty eradication : participant perspectives

description: The aim of the Ford Resource and Engagement Centre (FREC) programme of the non-profit organisation Future Families is to create sustainable livelihoods through micro-enterprises in the communities of Mamelodi and Nellmapius, South Africa. The goal of the study was to explore participant perspectives on the FREC programme’s contribution in poverty reduction in Mamelodi and Nellmapius.The study used a qualitative research approach. It was an applied study, and the research design was an exploratory study. Purposive sampling was used to select ten enrolled participants of the FREC programme who were from the center. Data was collected by means of semi-structured, one-on-one interviews and thematically analysed. Ethical considerations for the study included confidentiality, informed consent, voluntary participation, and avoidance of harm. There following themes emerged: 1. Reasons for joining the FREC programme2. Expectations for livelihood outcomes3. The effect of the FREC programme on participants' socio-economic well-being4. The benefits from the FREC programme 5. Suggested changes to improve the FREC programme<br>
DOI: 10.6084/m9.figshare.28163331
title: PLK2 disrupts autophagic flux to promote SNCA/α-synuclein pathology

description: The aggregation and transmission of SNCA/α-synuclein (synuclein, alpha) is a hallmark pathology of Parkinson disease (PD). PLK2 (polo like kinase 2) is an evolutionarily conserved serine/threonine kinase that is more abundant in the brains of all family members, is highly expressed in PD, and is linked to SNCA deposition. However, in addition to its role in phosphorylating SNCA, the role of PLK2 in PD and the mechanisms involved in triggering neurodegeneration remain unclear. Here, we found that PLK2 regulated SNCA pathology independently of S129. Overexpression of PLK2 promoted SNCA preformed fibril (PFF)-induced aggregation of wild-type SNCA and mutant SNCA<sup>S129A</sup>. Genetic or pharmacological inhibition of PLK2 attenuated SNCA deposition and neurotoxicity. Mechanistically, PLK2 exacerbated the propagation of SNCA pathology by impeding the clearance of SNCA aggregates by blocking macroautophagic/autophagic flux. We further showed that PLK2 phosphorylated S1098 of DCTN1 (dynactin 1), a protein that controls the movement of organelles, leading to impaired autophagosome-lysosome fusion. Furthermore, genetic suppression of PLK2 alleviated SNCA aggregation and motor dysfunction <i>in vivo</i>. Our findings suggest that PLK2 negatively regulates autophagy, promoting SNCA pathology, suggesting a role for PLK2 in PD. <b>Abbreviation</b>: AD: Alzheimer disease; AMPK: AMP-activated protein kinase; CASP3: caspase 3; DCTN1: dynactin 1; LBs: lewy bodies; LDH: lactate dehydrogenase; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAP2: microtubule associated protein 2; MTOR: mechanistic target of rapamycin kinase; NH4Cl: ammonium chloride; p-SNCA: phosphorylation of SNCA at S129; PD: Parkinson disease; PFF: preformed fibril; PI: propidium iodide; PLK2: polo like kinase 2; PRKAA/AMPK: protein kinase AMP-activated catalytic subunit alpha; shRNA: short hairpin RNA; SNCA: synuclein, alpha; SQSTM1/p62: sequestosome 1; TH: tyrosine hydroxylase; TX: Triton X-100; ULK1: unc-51 like autophagy activating kinase 1.
DOI: 10.6084/m9.figshare.28163331.v1
title: PLK2 disrupts autophagic flux to promote SNCA/α-synuclein pathology

description: The aggregation and transmission of SNCA/α-synuclein (synuclein, alpha) is a hallmark pathology of Parkinson disease (PD). PLK2 (polo like kinase 2) is an evolutionarily conserved serine/threonine kinase that is more abundant in the brains of all family members, is highly expressed in PD, and is linked to SNCA deposition. However, in addition to its role in phosphorylating SNCA, the role of PLK2 in PD and the mechanisms involved in triggering neurodegeneration remain unclear. Here, we found that PLK2 regulated SNCA pathology independently of S129. Overexpression of PLK2 promoted SNCA preformed fibril (PFF)-induced aggregation of wild-type SNCA and mutant SNCA<sup>S129A</sup>. Genetic or pharmacological inhibition of PLK2 attenuated SNCA deposition and neurotoxicity. Mechanistically, PLK2 exacerbated the propagation of SNCA pathology by impeding the clearance of SNCA aggregates by blocking macroautophagic/autophagic flux. We further showed that PLK2 phosphorylated S1098 of DCTN1 (dynactin 1), a protein that controls the movement of organelles, leading to impaired autophagosome-lysosome fusion. Furthermore, genetic suppression of PLK2 alleviated SNCA aggregation and motor dysfunction <i>in vivo</i>. Our findings suggest that PLK2 negatively regulates autophagy, promoting SNCA pathology, suggesting a role for PLK2 in PD. <b>Abbreviation</b>: AD: Alzheimer disease; AMPK: AMP-activated protein kinase; CASP3: caspase 3; DCTN1: dynactin 1; LBs: lewy bodies; LDH: lactate dehydrogenase; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAP2: microtubule associated protein 2; MTOR: mechanistic target of rapamycin kinase; NH4Cl: ammonium chloride; p-SNCA: phosphorylation of SNCA at S129; PD: Parkinson disease; PFF: preformed fibril; PI: propidium iodide; PLK2: polo like kinase 2; PRKAA/AMPK: protein kinase AMP-activated catalytic subunit alpha; shRNA: short hairpin RNA; SNCA: synuclein, alpha; SQSTM1/p62: sequestosome 1; TH: tyrosine hydroxylase; TX: Triton X-100; ULK1: unc-51 like autophagy activating kinase 1.
DOI: 10.5281/zenodo.16359767
title: Country summaries for B-Shapes WP3 interview and focus group analysis

description: The interviews with candidates and campaigners in the 2024 European elections were carried out between April and August 2024. Focus groups with citizens (especially young citizens aged 18-35) were carried out between August and December 2024. All interviews and focus groups followed a common guide (in the local language) with the following four broad themes:



The (border) region 

Borders in the EU in general

The EU and European integration


In the politician interviews, we additionally asked for the role of the border in the 2024 European election campaign. In the focus groups, we included a Citizen Science element to supplement our media analyses and analyses of politician interviews.

The files are as follows:



DK_SE Int and FG – analysis of interviews and focus groups carried out in the Danish-Swedish border region (authors: Sara Svensson and Oriana Miraka)

FR_DE Int and FG – analysis of interviews and focus groups carried out in the Franco-German border region (authors: Pierrick Bruyas and Birte Wassenberg)

PL_DE_CZ CZ Int and FG – analysis of interviews and focus group carried out in the Czech part of the Polish-German-Czech border region (authors: Hynek Böhm and Artur Boháč)

PL_DE_CZ DE Int and FG – analysis of interviews and focus group carried out in the German part of the Polish-German-Czech border region (author: Katja Sarmiento-Mirwaldt)

PL_DE_CZ PL FG – analysis of focus group carried out in the Polish part of the Polish-German-Czech border region (author: Łukasz Moll)

PL_DE_CZ PL Int – analysis of interviews carried out in the Polish part of the Polish-German-Czech border region (author: Łukasz Moll)

SK_HU HU FG – analysis of focus group carried out in the Hungarian part of the Slovak-Hungarian border region (author: Péter Balogh)

SK_HU HU Int – analysis of interviews carried out in the Hungarian part of the Slovak-Hungarian border region (author: Péter Balogh)

SK_HU SK Int and FG – analysis of interviews and focus group carried out in the Slovak part of the Slovak-Hungarian border region (authors: Hynek Böhm and Artur Boháč)
DOI: 10.5281/zenodo.16359768
title: Country summaries for B-Shapes WP3 interview and focus group analysis

description: The interviews with candidates and campaigners in the 2024 European elections were carried out between April and August 2024. Focus groups with citizens (especially young citizens aged 18-35) were carried out between August and December 2024. All interviews and focus groups followed a common guide (in the local language) with the following four broad themes:



The (border) region 

Borders in the EU in general

The EU and European integration


In the politician interviews, we additionally asked for the role of the border in the 2024 European election campaign. In the focus groups, we included a Citizen Science element to supplement our media analyses and analyses of politician interviews.

The files are as follows:



DK_SE Int and FG – analysis of interviews and focus groups carried out in the Danish-Swedish border region (authors: Sara Svensson and Oriana Miraka)

FR_DE Int and FG – analysis of interviews and focus groups carried out in the Franco-German border region (authors: Pierrick Bruyas and Birte Wassenberg)

PL_DE_CZ CZ Int and FG – analysis of interviews and focus group carried out in the Czech part of the Polish-German-Czech border region (authors: Hynek Böhm and Artur Boháč)

PL_DE_CZ DE Int and FG – analysis of interviews and focus group carried out in the German part of the Polish-German-Czech border region (author: Katja Sarmiento-Mirwaldt)

PL_DE_CZ PL FG – analysis of focus group carried out in the Polish part of the Polish-German-Czech border region (author: Łukasz Moll)

PL_DE_CZ PL Int – analysis of interviews carried out in the Polish part of the Polish-German-Czech border region (author: Łukasz Moll)

SK_HU HU FG – analysis of focus group carried out in the Hungarian part of the Slovak-Hungarian border region (author: Péter Balogh)

SK_HU HU Int – analysis of interviews carried out in the Hungarian part of the Slovak-Hungarian border region (author: Péter Balogh)

SK_HU SK Int and FG – analysis of interviews and focus group carried out in the Slovak part of the Slovak-Hungarian border region (authors: Hynek Böhm and Artur Boháč)
DOI: 10.6084/m9.figshare.28490535
title: TAX1BP1-dependent autophagic degradation of STING1 impairs anti-tumor immunity

description: The activation of STING1 can lead to the production and secretion of cytokines, initiating antitumor immunity. Here, we screened an ion channel ligand library and identified tetrandrine, a bis-benzylisoquinoline alkaloid, as an immunological adjuvant that enhances antitumor immunity by preventing the autophagic degradation of the STING1 protein. This tetrandrine effect is independent of its known function as a calcium or potassium channel blocker. Instead, tetrandrine inhibits lysosomal function, impairing cathepsin maturation, and autophagic degradation. Proteomic analysis of lysosomes identified TAX1BP1 as a novel autophagic receptor for the proteolysis of STING1. TAX1BP1 recognizes STING1 through the physical interaction of its coiled-coil domain with the cyclic dinucleotide binding domain of STING1. Systematic mutation of lysine (K) residues revealed that K63-ubiquitination of STING1 at the K224 site ignites TAX1BP1-dependent STING1 degradation. Combined treatment with tetrandrine and STING1 agonists promotes antitumor immunity by converting “cold” pancreatic cancers into “hot” tumors. This process is associated with enhanced cytokine release and increased infiltration of cytotoxic T-cells into the tumor microenvironment. The antitumor immunity mediated by tetrandrine and STING1 agonists is limited by neutralizing antibodies to the type I interferon receptor or CD8<sup>+</sup> T cells. Thus, these findings establish a potential immunotherapeutic strategy against pancreatic cancer by preventing the autophagic degradation of STING1.
DOI: 10.6084/m9.figshare.28490535.v2
title: TAX1BP1-dependent autophagic degradation of STING1 impairs anti-tumor immunity

description: The activation of STING1 can lead to the production and secretion of cytokines, initiating antitumor immunity. Here, we screened an ion channel ligand library and identified tetrandrine, a bis-benzylisoquinoline alkaloid, as an immunological adjuvant that enhances antitumor immunity by preventing the autophagic degradation of the STING1 protein. This tetrandrine effect is independent of its known function as a calcium or potassium channel blocker. Instead, tetrandrine inhibits lysosomal function, impairing cathepsin maturation, and autophagic degradation. Proteomic analysis of lysosomes identified TAX1BP1 as a novel autophagic receptor for the proteolysis of STING1. TAX1BP1 recognizes STING1 through the physical interaction of its coiled-coil domain with the cyclic dinucleotide binding domain of STING1. Systematic mutation of lysine (K) residues revealed that K63-ubiquitination of STING1 at the K224 site ignites TAX1BP1-dependent STING1 degradation. Combined treatment with tetrandrine and STING1 agonists promotes antitumor immunity by converting “cold” pancreatic cancers into “hot” tumors. This process is associated with enhanced cytokine release and increased infiltration of cytotoxic T-cells into the tumor microenvironment. The antitumor immunity mediated by tetrandrine and STING1 agonists is limited by neutralizing antibodies to the type I interferon receptor or CD8<sup>+</sup> T cells. Thus, these findings establish a potential immunotherapeutic strategy against pancreatic cancer by preventing the autophagic degradation of STING1.
DOI: 10.6084/m9.figshare.28490535.v1
title: TAX1BP1-dependent autophagic degradation of STING1 impairs anti-tumor immunity

description: The activation of STING1 can lead to the production and secretion of cytokines, initiating antitumor immunity. Here, we screened an ion channel ligand library and identified tetrandrine, a bis-benzylisoquinoline alkaloid, as an immunological adjuvant that enhances antitumor immunity by preventing the autophagic degradation of the STING1 protein. This tetrandrine effect is independent of its known function as a calcium or potassium channel blocker. Instead, tetrandrine inhibits lysosomal function, impairing cathepsin maturation, and autophagic degradation. Proteomic analysis of lysosomes identified TAX1BP1 as a novel autophagic receptor for the proteolysis of STING1. TAX1BP1 recognizes STING1 through the physical interaction of its coiled-coil domain with the cyclic dinucleotide binding domain of STING1. Systematic mutation of lysine (K) residues revealed that K63-ubiquitination of STING1 at the K224 site ignites TAX1BP1-dependent STING1 degradation. Combined treatment with tetrandrine and STING1 agonists promotes antitumor immunity by converting “cold” pancreatic cancers into “hot” tumors. This process is associated with enhanced cytokine release and increased infiltration of cytotoxic T-cells into the tumor microenvironment. The antitumor immunity mediated by tetrandrine and STING1 agonists is limited by neutralizing antibodies to the type I interferon receptor or CD8<sup>+</sup> T cells. Thus, these findings establish a potential immunotherapeutic strategy against pancreatic cancer by preventing the autophagic degradation of STING1.
DOI: 10.6084/m9.figshare.28637321
title: Microplastics exacerbate ferroptosis via mitochondrial reactive oxygen species-mediated autophagy in chronic obstructive pulmonary disease

description: Microplastics (MPs) induce mitochondrial dysfunction and iron accumulation, contributing to mitochondrial macroautophagy/autophagy and ferroptosis, which has increased susceptibility to the exacerbation of chronic obstructive pulmonary disease (COPD); however, the underlying mechanism remains unclear. We demonstrated that MPs intensified inflammation in COPD by enhancing autophagy-dependent ferroptosis (ADF) in vitro and in vivo. In the lung tissues of patients with COPD, the concentrations of MPs, especially polystyrene microplastics (PS-MPs), were significantly higher than that of the control group, as detected by pyrolysis gas chromatography mass spectrometry (Py-GCMS), with increased iron accumulation. The exposure to PS-MPs, 2 μm in size, resulted in their being deposited in the lungs of COPD model mice detected by optical in vivo imaging, and observed in bronchial epithelial cells traced by GFP-labeled PS-MPs. There were mitochondrial impairments accompanied by mitochondrial reactive oxygen species (mito-ROS) overproduction and significantly increased levels of lysosome biogenesis and acidification in pDHBE cells with PS-MP stimulation, triggering occurrence of ferritinophagy and enhancing ADF in COPD, which triggered acute exacerbation of COPD (AECOPD). Reestablishing autophagy-dependent ferroptosis via mitochondria-specific ROS scavenging or ferroptosis inhibition alleviated excessive inflammation and ameliorated AECOPD induced by PS-MPs. Collectively, our data initially revealed that MPs exacerbate ferroptosis via mito-ROS-mediated autophagy in COPD, which sheds light on further hazard assessments of MPs on human respiratory health and potential therapeutic agents for patients with COPD. <b>Abbreviations:</b> ADF: autophagy-dependent ferroptosis; AECOPD: acute exacerbation of chronic obstructive pulmonary disease; Cchord: static compliance; COPD: chronic obstructive pulmonary disease; CQ: chloroquine; CS: cigarette smoke; DEGs: differentially expressed genes; Fer-1: ferrostatin-1; FEV 0.1: forced expiratory volume in first 100 ms; FVC: forced vital capacity; GSH: glutathione; HE: hematoxylin and eosin; IL1B/IL-1β: interleukin 1 beta; IL6: interleukin 6; MDA: malondialdehyde; Mito-ROS: mitochondrial reactive oxygen species; MMA: methyl methacrylate; MMF: maximal mid-expiratory flow curve; MMP: mitochondrial membrane potential; MOI: multiplicity of infection; MPs: microplastics; MV: minute volume; PA: polyamide; PBS: phosphate-buffered saline; PC: polycarbonate; pDHBE: primary human bronchial epithelial cell from COPD patients; PET: polyethylene terephthalate; PIF: peak inspiratory flow; PLA: polylactic acid; pNHBE: primary normal human bronchial epithelial cell; PS-MPs: polystyrene microplastics; PVA: polyvinyl acetate; PVC: polyvinyl chloride; Py-GCMS: pyrolysis gas chromatography mass spectrometry; SEM: scanning electron microscopy; Te: expiratory times; Ti: inspiratory times; TNF/TNF-α: tumor necrosis factor.
DOI: 10.6084/m9.figshare.28637321.v2
title: Microplastics exacerbate ferroptosis via mitochondrial reactive oxygen species-mediated autophagy in chronic obstructive pulmonary disease

description: Microplastics (MPs) induce mitochondrial dysfunction and iron accumulation, contributing to mitochondrial macroautophagy/autophagy and ferroptosis, which has increased susceptibility to the exacerbation of chronic obstructive pulmonary disease (COPD); however, the underlying mechanism remains unclear. We demonstrated that MPs intensified inflammation in COPD by enhancing autophagy-dependent ferroptosis (ADF) in vitro and in vivo. In the lung tissues of patients with COPD, the concentrations of MPs, especially polystyrene microplastics (PS-MPs), were significantly higher than that of the control group, as detected by pyrolysis gas chromatography mass spectrometry (Py-GCMS), with increased iron accumulation. The exposure to PS-MPs, 2 μm in size, resulted in their being deposited in the lungs of COPD model mice detected by optical in vivo imaging, and observed in bronchial epithelial cells traced by GFP-labeled PS-MPs. There were mitochondrial impairments accompanied by mitochondrial reactive oxygen species (mito-ROS) overproduction and significantly increased levels of lysosome biogenesis and acidification in pDHBE cells with PS-MP stimulation, triggering occurrence of ferritinophagy and enhancing ADF in COPD, which triggered acute exacerbation of COPD (AECOPD). Reestablishing autophagy-dependent ferroptosis via mitochondria-specific ROS scavenging or ferroptosis inhibition alleviated excessive inflammation and ameliorated AECOPD induced by PS-MPs. Collectively, our data initially revealed that MPs exacerbate ferroptosis via mito-ROS-mediated autophagy in COPD, which sheds light on further hazard assessments of MPs on human respiratory health and potential therapeutic agents for patients with COPD. <b>Abbreviations:</b> ADF: autophagy-dependent ferroptosis; AECOPD: acute exacerbation of chronic obstructive pulmonary disease; Cchord: static compliance; COPD: chronic obstructive pulmonary disease; CQ: chloroquine; CS: cigarette smoke; DEGs: differentially expressed genes; Fer-1: ferrostatin-1; FEV 0.1: forced expiratory volume in first 100 ms; FVC: forced vital capacity; GSH: glutathione; HE: hematoxylin and eosin; IL1B/IL-1β: interleukin 1 beta; IL6: interleukin 6; MDA: malondialdehyde; Mito-ROS: mitochondrial reactive oxygen species; MMA: methyl methacrylate; MMF: maximal mid-expiratory flow curve; MMP: mitochondrial membrane potential; MOI: multiplicity of infection; MPs: microplastics; MV: minute volume; PA: polyamide; PBS: phosphate-buffered saline; PC: polycarbonate; pDHBE: primary human bronchial epithelial cell from COPD patients; PET: polyethylene terephthalate; PIF: peak inspiratory flow; PLA: polylactic acid; pNHBE: primary normal human bronchial epithelial cell; PS-MPs: polystyrene microplastics; PVA: polyvinyl acetate; PVC: polyvinyl chloride; Py-GCMS: pyrolysis gas chromatography mass spectrometry; SEM: scanning electron microscopy; Te: expiratory times; Ti: inspiratory times; TNF/TNF-α: tumor necrosis factor.