cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.17198792
title: Isotopic and chemical facies for assessing the shallow water table aquifer quality in Goly Region, White Nile State, Sudan: focusing on nitrate source apportionment and human health risk

description: Groundwater from the shallow water table aquifer is the main supply of drinking water for residents in Goly Region, White Nile State, Sudan. The residents have complained about groundwater quality. This study aims to evaluate groundwater quality in in Goly Region and to assess the possible health risk of toxicants with focusing on nitrates. The study examined groundwater from wells distributed in 23 sites for hydrogeological, physiochemical, and isotopic facies. The ranges of facies levels (mg/L) were as follows: nitrate (6.2–655.6), fluoride (0.00–2.16), sodium (36.4–293.2), total dissolved solids (349–908), carbonate (0.00–24.0), nitrite (0.026–0.828), sulfate (1.00–77.00), ammonia (0.00–0.40), and chloride (12.78–42.60), besides pH (6.93–8.48). According to the National Sudanese Guidelines and the World Health Organization guidelines, 12 wells recorded unhealthy levels for nitrate, 1 well recorded unhealthy level for fluoride, and 2 wells recorded unhealthy levels for sodium, while all wells recorded healthy levels for the rest of facies. Additionally, groundwater consumption from 14 sites put both children and adults at potential health risk from nitrates based on hazard risk index. The Piper diagram shows that the trend of cation exchange in the aquifer was from (calcium + magnesium) to (sodium + potassium). Significant positive correlations were observed between several parameters, e.g. the combinations of static water level-depth (0.51), electrical conductivity (EC)-nitrate (0.60), EC-sulfate (0.73), EC-fluoride (0.55), EC-chloride (0.76), EC-sodium (0.84), pH-fluoride (0.73), and pH-sodium (0.59). The principal component analysis of the examined facies shows that the first two principal components, which have similar loadings (≈ 22% of each), represented natural and anthropogenic sources of major ions. The isotopes levels and relationship of δ<sup>15</sup>N and δ<sup>18</sup>O revealed that nitrate contamination was from animal waste and/or sewage. The relation between δ<sup>18</sup>O and δ<sup>2</sup>H isotopes of water demonstrates that groundwater samples were deviated from Meteoric Line of the Sudan and Global Meteoric Water Line.
DOI: 10.5281/zenodo.5112232
title: GPRChinaTemp1km: 1 km monthly minimum air temperature for China from January 1951 to December 2020

description: GPRChinaTemp1km is a new high-resolution (1-km) monthly gridded air temperature dataset for China from January 1951 to December 2020. The dataset includes monthly minimum air temperature covering the main land area of China during 1951-2020, which was interpolated by the Gaussian process regression (GPR) method based on the meteorological station data. The monthly gridded temperature dataset was evaluated by the observed values of the meteorological stations from the China Meteorological Data Service Centre. The dataset is in GeoTIFF format in the WGS84 (EPSG:4326) coordinate system. The unit of the data is degree Celsius (°C).
DOI: 10.5281/zenodo.5112231
title: GPRChinaTemp1km: 1 km monthly minimum air temperature for China from January 1951 to December 2020

description: GPRChinaTemp1km is a new high-resolution (1-km) monthly gridded air temperature dataset for China from January 1951 to December 2020. The dataset includes monthly minimum air temperature covering the main land area of China during 1951-2020, which was interpolated by the Gaussian process regression (GPR) method based on the meteorological station data. The monthly gridded temperature dataset was evaluated by the observed values of the meteorological stations from the China Meteorological Data Service Centre. The dataset is in GeoTIFF format in the WGS84 (EPSG:4326) coordinate system. The unit of the data is degree Celsius (°C).
DOI: 10.6084/m9.figshare.17257300
title: Evaluating the feasibility of Cas9 overexpression in 3T3-L1 cells for generation of genetic knock-out adipocyte cell lines

description: Cell lines recapitulating physiological processes can represent alternatives to animal or human studies. The 3T3-L1 cell line is used to mimic adipocyte function and differentiation. Since transfection of 3T3-L1 cells is difficult, we used a modified 3T3-L1 cell line overexpressing Cas9 for a straightforward generation of gene knock-outs. As an example, we intended to generate 3T3-L1 cell lines deficient for adhesion G protein-coupled receptors <i>Gpr64/Adgr2</i> and <i>Gpr126/Adgr6</i> using the CRISPR/Cas approach. Surprisingly, all the generated knock-out as well as scramble control cell lines were unresponsive to isoprenaline in respect to adiponectin secretion and lipolysis in contrast to the wild type 3T3-L1 cells. We, therefore, analysed the properties of these stable Cas9-overexpressing 3T3-L1 cells. We demonstrate that this commercially available cell line exhibits dysfunction in cAMP signalling pathways as well as reduced insulin sensitivity independent of gRNA transfection. We tried transient transfection of plasmids harbouring Cas9 as well as direct introduction of the Cas9 protein as alternate approaches to the stable expression of this enzyme. We find that transfection of the Cas9 protein is not only feasible but also does not impair adipogenesis and, therefore, represents a preferable alternative to achieve genetic knock-out.
DOI: 10.6084/m9.figshare.16945072
title: Application of a deep learning-based image analysis and live-cell imaging system for quantifying adipogenic differentiation kinetics of adipose-derived stem/stromal cells

description: Quantitative methods for assessing differentiative potency of adipose-derived stem/stromal cells may lead to improved clinical application of this multipotent stem cell, by advancing our understanding of specific processes such as adipogenic differentiation. Conventional cell staining methods are used to determine the formation of adipose areas during adipogenesis as a qualitative representation of adipogenic potency. Staining methods such as oil-red-O are quantifiable using absorbance measurements, but these assays are time and material consuming. Detection methods for cell characteristics using advanced image analysis by machine learning are emerging. Here, live-cell imaging was combined with a deep learning-based detection tool to quantify the presence of adipose areas and lipid droplet formation during adipogenic differentiation of adipose-derived stem/stromal cells. Different detection masks quantified adipose area and lipid droplet formation at different time points indicating kinetics of adipogenesis and showed differences between individual donors. Whereas <i>CEBPA</i> and <i>PPARG</i> expression seems to precede the increase in adipose area and lipid droplets, it might be able to predict expression of <i>ADIPOQ</i>. The applied method is a proof of concept, demonstrating that deep learning methods can be used to investigate adipogenic differentiation and kinetics <i>in vitro</i> using specific detection masks based on algorithm produced from annotation of image data.
DOI: 10.6084/m9.figshare.16950891
title: Association of cell death mechanisms and fibrosis in visceral white adipose tissue with pathological alterations in the liver of morbidly obese patients with NAFLD

description: The role of visceral white adipose tissue (vWAT) in the progression of non-alcoholic liver disease (NAFLD) with its sub entities non-alcoholic fatty liver and steatohepatitis (NAFL; NASH) is underinvestigated. We thus explored mechanisms of fibrosis and regulated cell death in vWAT and liver tissue. In NAFLD, women displayed significantly more fibrosis in vWAT than men, and collagen 1α mRNA expression was significantly upregulated. The degrees of fibrosis in vWAT and liver tissue correlated significantly. The size of vWAT-resident adipocytes in NAFLD correlated negatively with the local degree of fibrosis. The extent of apoptosis, as measured by circulating M30, positively correlated with the degree of fibrosis in vWAT; necrosis-associated HMGB1 mRNA expression was significantly downregulated in vWAT and liver tissue; (iii) necroptosis-related RIPK-3 mRNA expression was significantly upregulated in vWAT; and autophagy-related LC3 mRNA expression was significantly downregulated in vWAT, while upregulated in the liver. Thus, the different cell death mechanisms in the vWAT in NAFLD are regulated independently while not ruling out their interaction. Fibrosis in vWAT may be associated with reduced adipocyte size and thus partially protective against NAFLD progression. <b>Abbreviations:</b> ATG5: autophagy related 5; BAS: bariatric surgery; BMI: body mass index; ELISA: enzyme-linked immunosorbent assay; EtOH: ethanol; FFAs: free fatty acids; HCC: hepatocellular carcinoma; HMGB1: high-mobility group box 1 protein; IHC: immunohistochemistry; IL: interleukin; LC3: microtubule-associated proteins 1A/1B light chain 3B; M30: neoepitope K18Asp396-NE displayed on the caspase-cleaved keratin 18 fragment; M65: epitope present on both caspase-cleaved and intact keratin 18; NAFL: non-alcoholic fatty liver; NAFLD: non-alcoholic fatty liver disease; NAS: NAFLD activity score; NASH: non-alcoholic steatohepatitis; NLRP3: nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3; qRT-PCR: quantitative real-time polymerase-chain reaction; r: Pearson’s correlation coefficient (r); r<sub>s</sub>: Spearman’s rank correlation coefficient; RIPK3: receptor-interacting serine/threonine-protein kinase 3; T2DM: type 2 diabetes mellitus (T2DM); TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling; vWAT: visceral WAT; WAT: white adipose tissue
DOI: 10.6084/m9.figshare.16950891.v1
title: Association of cell death mechanisms and fibrosis in visceral white adipose tissue with pathological alterations in the liver of morbidly obese patients with NAFLD

description: The role of visceral white adipose tissue (vWAT) in the progression of non-alcoholic liver disease (NAFLD) with its sub entities non-alcoholic fatty liver and steatohepatitis (NAFL; NASH) is underinvestigated. We thus explored mechanisms of fibrosis and regulated cell death in vWAT and liver tissue. In NAFLD, women displayed significantly more fibrosis in vWAT than men, and collagen 1α mRNA expression was significantly upregulated. The degrees of fibrosis in vWAT and liver tissue correlated significantly. The size of vWAT-resident adipocytes in NAFLD correlated negatively with the local degree of fibrosis. The extent of apoptosis, as measured by circulating M30, positively correlated with the degree of fibrosis in vWAT; necrosis-associated HMGB1 mRNA expression was significantly downregulated in vWAT and liver tissue; (iii) necroptosis-related RIPK-3 mRNA expression was significantly upregulated in vWAT; and autophagy-related LC3 mRNA expression was significantly downregulated in vWAT, while upregulated in the liver. Thus, the different cell death mechanisms in the vWAT in NAFLD are regulated independently while not ruling out their interaction. Fibrosis in vWAT may be associated with reduced adipocyte size and thus partially protective against NAFLD progression. <b>Abbreviations:</b> ATG5: autophagy related 5; BAS: bariatric surgery; BMI: body mass index; ELISA: enzyme-linked immunosorbent assay; EtOH: ethanol; FFAs: free fatty acids; HCC: hepatocellular carcinoma; HMGB1: high-mobility group box 1 protein; IHC: immunohistochemistry; IL: interleukin; LC3: microtubule-associated proteins 1A/1B light chain 3B; M30: neoepitope K18Asp396-NE displayed on the caspase-cleaved keratin 18 fragment; M65: epitope present on both caspase-cleaved and intact keratin 18; NAFL: non-alcoholic fatty liver; NAFLD: non-alcoholic fatty liver disease; NAS: NAFLD activity score; NASH: non-alcoholic steatohepatitis; NLRP3: nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3; qRT-PCR: quantitative real-time polymerase-chain reaction; r: Pearson’s correlation coefficient (r); r<sub>s</sub>: Spearman’s rank correlation coefficient; RIPK3: receptor-interacting serine/threonine-protein kinase 3; T2DM: type 2 diabetes mellitus (T2DM); TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling; vWAT: visceral WAT; WAT: white adipose tissue
DOI: 10.6084/m9.figshare.17257300.v1
title: Evaluating the feasibility of Cas9 overexpression in 3T3-L1 cells for generation of genetic knock-out adipocyte cell lines

description: Cell lines recapitulating physiological processes can represent alternatives to animal or human studies. The 3T3-L1 cell line is used to mimic adipocyte function and differentiation. Since transfection of 3T3-L1 cells is difficult, we used a modified 3T3-L1 cell line overexpressing Cas9 for a straightforward generation of gene knock-outs. As an example, we intended to generate 3T3-L1 cell lines deficient for adhesion G protein-coupled receptors <i>Gpr64/Adgr2</i> and <i>Gpr126/Adgr6</i> using the CRISPR/Cas approach. Surprisingly, all the generated knock-out as well as scramble control cell lines were unresponsive to isoprenaline in respect to adiponectin secretion and lipolysis in contrast to the wild type 3T3-L1 cells. We, therefore, analysed the properties of these stable Cas9-overexpressing 3T3-L1 cells. We demonstrate that this commercially available cell line exhibits dysfunction in cAMP signalling pathways as well as reduced insulin sensitivity independent of gRNA transfection. We tried transient transfection of plasmids harbouring Cas9 as well as direct introduction of the Cas9 protein as alternate approaches to the stable expression of this enzyme. We find that transfection of the Cas9 protein is not only feasible but also does not impair adipogenesis and, therefore, represents a preferable alternative to achieve genetic knock-out.
DOI: 10.6084/m9.figshare.16945072.v1
title: Application of a deep learning-based image analysis and live-cell imaging system for quantifying adipogenic differentiation kinetics of adipose-derived stem/stromal cells

description: Quantitative methods for assessing differentiative potency of adipose-derived stem/stromal cells may lead to improved clinical application of this multipotent stem cell, by advancing our understanding of specific processes such as adipogenic differentiation. Conventional cell staining methods are used to determine the formation of adipose areas during adipogenesis as a qualitative representation of adipogenic potency. Staining methods such as oil-red-O are quantifiable using absorbance measurements, but these assays are time and material consuming. Detection methods for cell characteristics using advanced image analysis by machine learning are emerging. Here, live-cell imaging was combined with a deep learning-based detection tool to quantify the presence of adipose areas and lipid droplet formation during adipogenic differentiation of adipose-derived stem/stromal cells. Different detection masks quantified adipose area and lipid droplet formation at different time points indicating kinetics of adipogenesis and showed differences between individual donors. Whereas <i>CEBPA</i> and <i>PPARG</i> expression seems to precede the increase in adipose area and lipid droplets, it might be able to predict expression of <i>ADIPOQ</i>. The applied method is a proof of concept, demonstrating that deep learning methods can be used to investigate adipogenic differentiation and kinetics <i>in vitro</i> using specific detection masks based on algorithm produced from annotation of image data.
DOI: 10.6084/m9.figshare.17368208
title: Adipocytokines in Graves’ orbitopathy and the effect of high-dose corticosteroids

description: Graves’ orbitopathy (GO) is a serious, progressive eye condition seen in patients with autoimmune thyroid disease. GO is characterized by inflammation and swelling of soft orbital tissues. Adipose tissue produces cytokine mediators called adipokines. The present study focuses on the relationship between serum levels of selected adipokines in patients with GO, comparing them with the control group, and uniquely describes the effect of high-dose systemic corticosteroids (HDSC) on their levels. For the purposes of this study, we collected blood samples before and after the treatment with HDSC from 60 GO patients and 34 control subjects and measured serum levels of adiponectin, AIF-1, A-FABP and FGF-21. Levels of adiponectin significantly differed among the three study groups (ANOVA p = 0.03). AIF-1 levels were also significantly different among the study groups (ANOVA p &lt; 0.0001). AIF-1 was significantly associated with the presence of GO after adjusting for clinical factors (age, sex, smoking and BMI) and level of TSH (odds ratio 1.003, p &lt; 0.01). This finding could enforce targeting macrophages in treatment strategies for GO since AIF-1 is considered as a marker of their activation.
DOI: 10.6084/m9.figshare.17368208.v1
title: Adipocytokines in Graves’ orbitopathy and the effect of high-dose corticosteroids

description: Graves’ orbitopathy (GO) is a serious, progressive eye condition seen in patients with autoimmune thyroid disease. GO is characterized by inflammation and swelling of soft orbital tissues. Adipose tissue produces cytokine mediators called adipokines. The present study focuses on the relationship between serum levels of selected adipokines in patients with GO, comparing them with the control group, and uniquely describes the effect of high-dose systemic corticosteroids (HDSC) on their levels. For the purposes of this study, we collected blood samples before and after the treatment with HDSC from 60 GO patients and 34 control subjects and measured serum levels of adiponectin, AIF-1, A-FABP and FGF-21. Levels of adiponectin significantly differed among the three study groups (ANOVA p = 0.03). AIF-1 levels were also significantly different among the study groups (ANOVA p &lt; 0.0001). AIF-1 was significantly associated with the presence of GO after adjusting for clinical factors (age, sex, smoking and BMI) and level of TSH (odds ratio 1.003, p &lt; 0.01). This finding could enforce targeting macrophages in treatment strategies for GO since AIF-1 is considered as a marker of their activation.
DOI: 10.6084/m9.figshare.14480826
title: Serum amyloid A3 deficiency impairs in vitro and in vivo adipocyte differentiation

description: Obesity, caused by an excess adipose tissue, is one of the biggest health-threats of the 21<sup>st</sup> century. Adipose tissue expansion occurs through two processes: (i) hypertrophy, and (ii) hyperplasia, the formation of new adipocytes, also termed adipogenesis. Recently, serum amyloid A3 (Saa3) has been implicated in adipogenesis. Therefore, the aim of this study was to investigate the effect of Saa3 on adipogenesis using both an in vitro and in vivo murine model. Saa3 gene silenced pre-adipocytes ha a lower expression of pro-adipogenic markers and less lipid accumulation, indicating impaired adipogenesis. Furthermore, male NUDE mice, injected with Saa3 gene silenced pre-adipocytes developed smaller fat pads with smaller adipocytes and lower expression of pro-adipogenic markers than their control counterparts. This confirms that Saa3 gene silencing indeed impairs adipogenesis, both in vitro and in vivo. These results indicate a clear role for Saa3 in adipogenesis and open new perspectives in the battle against obesity.
DOI: 10.6084/m9.figshare.14480826.v1
title: Serum amyloid A3 deficiency impairs in vitro and in vivo adipocyte differentiation

description: Obesity, caused by an excess adipose tissue, is one of the biggest health-threats of the 21<sup>st</sup> century. Adipose tissue expansion occurs through two processes: (i) hypertrophy, and (ii) hyperplasia, the formation of new adipocytes, also termed adipogenesis. Recently, serum amyloid A3 (Saa3) has been implicated in adipogenesis. Therefore, the aim of this study was to investigate the effect of Saa3 on adipogenesis using both an in vitro and in vivo murine model. Saa3 gene silenced pre-adipocytes ha a lower expression of pro-adipogenic markers and less lipid accumulation, indicating impaired adipogenesis. Furthermore, male NUDE mice, injected with Saa3 gene silenced pre-adipocytes developed smaller fat pads with smaller adipocytes and lower expression of pro-adipogenic markers than their control counterparts. This confirms that Saa3 gene silencing indeed impairs adipogenesis, both in vitro and in vivo. These results indicate a clear role for Saa3 in adipogenesis and open new perspectives in the battle against obesity.
DOI: 10.6084/m9.figshare.14446822.v1
title: Cleavage of the vaspin N-terminus releases cell-penetrating peptides that affect early stages of adipogenesis and inhibit lipolysis in mature adipocytes

description: Vaspin expression and function is related to metabolic disorders and comorbidities of obesity. In various cellular and animal models of obesity, diabetes and atherosclerosis vaspin has shown beneficial, protective and/or compensatory action. While testing proteases for inhibition by vaspin, we noticed specific cleavage within the vaspin N-terminus and sequence analysis predicted cell-penetrating activity for the released peptides. These findings raised the question whether these proteolytic peptides exhibit biological activity. We synthesized various N-terminal vaspin peptides to investigate cell-penetrating activity and analyse uptake mechanisms. Focusing on adipocytes, we performed microarray analysis and functional assays to elucidate biological activities of the vaspin–derived peptide, which is released by KLK7 cleavage (vaspin residues 21-30; VaspinN). Our study provides first evidence that proteolytic processing of the vaspin N-terminus releases cell-penetrating and bioactive peptides with effects on adipocyte biology. The VaspinN peptide increased preadipocyte proliferation, interfered with clonal expansion during the early stage of adipogenesis and blunted adrenergic cAMP-signalling, downstream lipolysis as well as insulin signalling in mature adipocytes. Protease-mediated release of functional N-terminal peptides presents an additional facet of vaspin action. Future studies will address the mechanisms underlying the biological activities and clarify, if vaspin-derived peptides may have potential as therapeutic agents for the treatment of metabolic diseases.