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This is an article in the field of ceramics and composites. In order to study the adsorption effect of modified bentonite on heavy metal ions in sewage, the effects of pH value, initial concentration, time, solid-liquid ratio, temperature and particle size on the adsorption effect of bentonite were analyzed. And microscopic means were used to study the changes of the internal mineral composition of the bentonite before and after the adsorption of heavy metal ions and the change law of the infrared spectra. The results showed that when the modified bentonite content was 0.2 g, the adsorption time was 1.5 h, the temperature was set to 40 ℃, the pH value was set to 6, the initial concentration was set to 200 mg/L and the solid-to-liquid ratio was set to 0.8 g/L, the adsorption effect was the best. After the modified bentonite had undergone an adsorption test, an obvious CuSO4 diffraction peak could be detected. However, other mineral components inside the modified bentonite remained unchanged, which also showed that the modified bentonite could effectively adsorb copper ions in sewage.

The ongoing obesity epidemic has raised awareness of the complex physiology of adipose tissue. Abnormal adipocyte differentiation results in the development of systemic metabolic disorders such as insulin resistance and diabetes. The conjugation of NEDD8 (neural precursor cell expressed, developmentally downregulated 8) to target protein, termed neddylation, has been shown to mediate adipogenesis. However, much remains unknown about its role in adipogenesis. Here, we demonstrated that neddylation and its targets, the cullin (CUL) family members, are differentially regulated during mouse and human adipogenesis. Inhibition of neddylation by MLN4924 significantly reduced adipogenesis of 3T3-L1 and human stromal vascular cells. Deletion of NAE1, a subunit of the only NEDD8 E1 enzyme, suppressed neddylation and impaired adipogenesis. Neddylation deficiency did not affect mitotic cell expansion. Instead, it disrupted CREB/CEBPβ/PPARγ signaling, essential for adipogenesis. Interestingly, among the neddylation-targeted CUL family members, deletion of CUL3, but not CUL1, CUL2, or CUL4A, largely replicated the adipogenic defects observed with neddylation deficiency. A PPARγ agonist minimally rescued the adipogenic defects caused by the deletion of NAE1 and CUL3. In conclusion, our study demonstrates that neddylation and its targeted CUL3 are crucial for adipogenesis. These findings provide potential targets for therapeutic intervention in obesity and metabolic disorders.

Abstract Background The association between triglyceride–glucose (TyG) index and poor prognosis remains controversial. Whether renal function status affects the ability of the TyG index to predict poor prognosis has not yet been elucidated and merits further studies. Methods This retrospective cohort study included 22,031 participants from communities in the U.S. By juxtaposing the TyG categories with the estimated glomerular filtration rate (eGFR, either

Histone deacetylase (HDAC) 9 is a negative regulator of adipogenic differentiation, which is required for maintenance of healthy adipose tissues. We reported that HDAC9 expression is upregulated in adipose tissues during obesity, in conjunction with impaired adipogenic differentiation, adipocyte hypertrophy, insulin resistance, and hepatic steatosis, all of which were alleviated by global genetic deletion of Hdac9. Here, we developed a novel transgenic (TG) mouse model to test whether overexpression of Hdac9 is sufficient to induce adipocyte hypertrophy, insulin resistance, and hepatic steatosis in the absence of obesity. HDAC9 TG mice gained less body weight than wild-type (WT) mice when fed a standard laboratory diet for up to 40 weeks, which was attributed to reduced fat mass (primarily inguinal adipose tissue). There was no difference in insulin sensitivity or glucose tolerance in 18-week-old WT and HDAC9 TG mice; however, at 40 weeks of age, HDAC9 TG mice exhibited impaired insulin sensitivity and glucose intolerance. Tissue histology demonstrated adipocyte hypertrophy, along with reduced numbers of mature adipocytes and stromovascular cells, in the HDAC9 TG mouse adipose tissue. Moreover, increased lipids were detected in the livers of aging HDAC9 TG mice, as evaluated by oil red O staining. In conclusion, the experimental aging HDAC9 TG mice developed adipocyte hypertrophy, insulin resistance, and hepatic steatosis, independent of obesity. This novel mouse model may be useful in the investigation of the impact of Hdac9 overexpression associated with metabolic and aging-related diseases.

Dysregulation of the post-translational modification neddylation has been implicated in liver diseases such as fibrosis and hepatocellular carcinoma. Here the authors report that hepatic neddylation deficiency via genetic deletion of NEDD8 Activating Enzyme E1 Subunit 1 (NAE1) causes acute liver failure due to mitochondrial dysfunction and aberrant activation of NF-κB-inducing kinase in mice.

This study used multilocus sequence typing (MLST) to investigate the prevalence of Helicobacter pylori (H. pylori) mixed infections and H. pylori mixed infections involving unrelated strains; and determined the phylogeographic groups of H. pylori recovered from patients in Ningbo, China. A total of 156 H. pylori isolates were obtained from a convenience sample of 33 patients with culture-positive H. pylori infection. MLST was used to classify 150 H. pylori clinical isolates and 12 methodological control strains (6 clinical isolates and 6 strains of American Type Culture Collection H. pylori) into 43 and 12 sequence types (STs), respectively. In this study, 246 new alleles and 53 new STs were identified by MLST. The prevalence of mixed infections was 41% (11/27). The prevalence of H. pylori mixed infections involving unrelated strains was 46% (5/11) and the prevalence of H. pylori mixed infections involving completely unrelated strains (strains with all 7 housekeeping genes different) was 36% (4/11). A phylogenetic tree was created to determine the evolutionary relationships between different strains. The STs in this study were clustered within the hspEAsia subgroup (98%) and hpEurope group (2%). H. pylori mixed infections were common in Ningbo, China. The H. pylori isolates belonging to the hpEurope group were recovered from three different biopsy samples in a native Chinese patient. Most of H. pylori strains colonizing the antrum, corpus, and duodenum bulb were homologous.

Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with a poor prognosis. Although several serum metabolomic investigations have been reported, ESCC tumor-associated metabolic alterations and predictive biomarkers in sera have not been defined. Here, we enrolled 34 treatment-naive patients with ESCC and collected their pre- and post-esophagectomy sera together with the sera from 34 healthy volunteers for a metabolomic survey. Our comprehensive analysis identified ESCC tumor-associated metabolic alterations as represented by a panel of 12 serum metabolites. Notably, postoperative abrosia and parenteral nutrition substantially perturbed the serum metabolome. Furthermore, we performed an examination using sera from carcinogen-induced mice at the dysplasia and ESCC stages and identified three ESCC tumor-associated metabolites conserved between mice and humans. Notably, among these metabolites, the level of pipecolic acid was observed to be progressively increased in mouse sera from dysplasia to cancerization, and it could be used to accurately discriminate between mice at the dysplasia stage and healthy control mice. Furthermore, this metabolite is essential for ESCC cells to restrain oxidative stress-induced DNA damage and cell proliferation arrest. Together, this study revealed a panel of 12 ESCC tumor-associated serum metabolites with potential for monitoring therapeutic efficacy and disease relapse, presented evidence for refining parenteral nutrition composition, and highlighted serum pipecolic acid as an attractive biomarker for predicting ESCC tumorigenesis.

Summary: Cardiac maturation is crucial for postnatal cardiac development and is increasingly known to be regulated by a series of transcription factors. However, post-translational mechanisms regulating this process remain unclear. Here we report the indispensable role of neddylation in cardiac maturation. Mosaic deletion of NAE1, an essential enzyme for neddylation, in neonatal hearts results in the rapid development of cardiomyopathy and heart failure. NAE1 deficiency disrupts transverse tubule formation, inhibits physiological hypertrophy, and represses fetal-to-adult isoform switching, thus culminating in cardiomyocyte immaturation. Mechanistically, we find that neddylation is needed for the perinatal metabolic transition from glycolytic to oxidative metabolism in cardiomyocytes. Further, we show that HIF1α is a putative neddylation target and that inhibition of neddylation accumulates HIF1α and impairs fatty acid utilization and bioenergetics in cardiomyocytes. Together, our data show neddylation is required for cardiomyocyte maturation through promoting oxidative metabolism in the developing heart.

Cholesteryl ester (CE)-rich lipid droplets (LDs) accumulate in steroidogenic tissues under physiological conditions and constitute an important source of cholesterol as the precursor for the synthesis of all steroid hormones. The mechanisms specifically involved in CE-rich LD formation have not been directly studied and are assumed by most to occur in a fashion analogous to triacylglycerol-rich LDs. Seipin is an endoplasmic reticulum protein that forms oligomeric complexes at endoplasmic reticulum-LD contact sites, and seipin deficiency results in severe alterations in LD maturation and morphology as seen in Berardinelli-Seip congenital lipodystrophy type 2. While seipin is critical for triacylglycerol-rich LD formation, no studies have directly addressed whether seipin is important for CE-rich LD biogenesis. To address this issue, mice with deficient expression of seipin specifically in adrenal, testis, and ovary, steroidogenic tissues that accumulate CE-rich LDs under normal physiological conditions, were generated. We found that the steroidogenic-specific seipin-deficient mice displayed a marked reduction in LD and CE accumulation in the adrenals, demonstrating the pivotal role of seipin in CE-rich LD accumulation/formation. Moreover, the reduction in CE-rich LDs was associated with significant defects in adrenal and gonadal steroid hormone production that could not be completely reversed by addition of exogenous lipoprotein cholesterol. We conclude that seipin has a heretofore unappreciated role in intracellular cholesterol trafficking.

BackgroundNADH: ubiquinone oxidoreductase subunit C1(NDUFC1) encodes a subunit of the Complex I, which may support the structural stability of Complex I and assist in its biogenesis. The expression and functional roles of NDUFC1 in hepatocellular carcinoma (HCC) remain unknown.ResultWe knocked down the expression of NDUFC1 in HCC cell lines to explore the effects of NDUFC1 downregulation on HCC in vitro. MTT assay determined that downregulation of NDUFC1 significantly inhibited cell proliferation. Flow cytometry with (propidium iodide) PI staining indicated silencing of NDUFC1 arrested cell cycle of BEL-7404 cells at G2 phase and SK-HEP-1 cells at S/G2 phase. Annexin V-PI double staining and flow cytometric analysis showed that the downregulation of NDUFC1 significantly increased the population of apoptotic cells. Wound-healing assay and transwell assay indicated that the downregulation of NDUFC1 suppressed the migration and invasion of HCC cells. According to the detection of complex1 activity, we found that the activity of NDUFC1 silenced group decreased, whereas the content of ROS increased. Furthermore, combined with bioinformatics analysis of senescence-related genes, we found that the silence of NDUFC1 in HCC could induce senescence and inhibit autophagy. In addition, NDUFC1 could correlate positively with cancer-related pathways, among which the p53 pathways and the PI3K/Akt/mTOR pathways. Finally, NDUFC1 is high expression in HCC specimens. High NDUFC1 expression was associated with poor prognosis and was an independent risk factor for reduced overall survival (OS).ConclusionsOur study indicated, for the first time, that NDUFC1 is an independent risk factor for the poor prognosis of HCC patients. NDUFC1 may promote tumor progression by inhibiting mitochondrial Complex I and up-regulating ROS through multiple cancer-related and senescence-related pathways of HCC, including p53 pathways and PI3K/Akt/mTOR pathways. We suppose that NDUFC1 might be a potential target for the mitochondrial metabolism therapy of HCC.

Abstract Learning analytics (LA) is a field that examines data about learners and their context, for understanding and optimizing learning and the environments in which it occurs. Integration of multiple data sources, an important dimension of scalability, has the potential to provide rich insights within LA. Using a common standard such as the Experience API (xAPI) to describe learning activity data across multiple sources can alleviate obstacles for data integration. Despite their potential, however, research indicates that standards are seldom used for integration of multiple sources in LA. Our research aims to understand and address the challenges of using current learning activity data standards for describing learning context with regard to interoperability and data integration. In this paper, we present the results of an exploratory case study involving in-depth interviews with stakeholders having used xAPI in a real-world project. Based on the subsequent thematic analysis of interviews, and examination of xAPI, we identified challenges and limitations in describing learning context data, and developed recommendations (provided in this paper in summarized form) for enriching context descriptions and enhancing the expressibility of xAPI. By situating the research in a real-world setting, our research also contributes to bridge the gap between the academic community and practitioners in learning activity data standards and scalability, focusing on description of learning context.

ABSTRACT Candida albicans biofilms are resistant to several clinical antifungal agents. Thus, it is necessary to develop new antibiofilm intervention measures. Pseudolaric acid A (PAA), a diterpenoid mainly derived from the pine bark of Pseudolarix kaempferi, has been reported to have an inhibitory effect on C. albicans. The primary aim of the current study was to investigate the antibiofilm effect of PAA when combined with fluconazole (FLC) and explore the underlying mechanisms. Biofilm activity was assessed by tetrazolium {XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt]} reduction assays. PAA (4 μg/mL) combined with FLC (0.5 μg/mL) significantly inhibited early, developmental, and mature biofilm formation compared with the effect of PAA or FLC alone (P

Abstract Background Heart failure (HF) is one of the leading causes of death worldwide and is associated with cardiac metabolic perturbations. Human Type 2 Berardinelli‐Seip Congenital Lipodystrophy (BSCL2) disease is caused by mutations in the BSCL2 gene. Global lipodystrophic Bscl2−/− mice exhibit hypertrophic cardiomyopathy with reduced cardiac steatosis. Whether BSCL2 plays a direct role in regulating cardiac substrate metabolism and/or contractile function remains unknown. Methods We generated mice with cardiomyocyte‐specific deletion of Bscl2 (Bscl2cKO) and studied their cardiac substrate utilisation, bioenergetics, lipidomics and contractile function under baseline or after either a treatment regimen using fatty acid oxidation (FAO) inhibitor trimetazidine (TMZ) or a prevention regimen with high‐fat diet (HFD) feeding. Mice with partial ATGL deletion and cardiac‐specific deletion of Bscl2 were also generated followed by cardiac phenotyping. Results Different from hypertrophic cardiomyopathy in Bscl2−/− mice, mice with cardiac‐specific deletion of Bscl2 developed systolic dysfunction with dilation. Myocardial BSCL2 deletion led to elevated ATGL expression and FAO along with reduced cardiac lipid contents. Cardiac dysfunction in Bscl2cKO mice was independent of mitochondrial dysfunction and oxidative stress, but associated with decreased metabolic reserve and ATP levels. Importantly, cardiac dysfunction in Bscl2cKO mice could be partially reversed by FAO inhibitor TMZ, or prevented by genetic abolishment of one ATGL allele or HFD feeding. Lipidomic analysis further identified markedly reduced glycerolipids, glycerophospholipids, NEFA and acylcarnitines in Bscl2cKO hearts, which were partially normalised by TMZ or HFD. Conclusions We identified a new form of cardiac dysfunction with excessive lipid utilisation which ultimately causes cardiac substrate depletion and bioenergetics failure. Our findings also uncover a crucial role of BSCL2 in controlling cardiac lipid catabolism and contractile function and provide novel insights into metabolically treating energy‐starved HF using FAO inhibitor or HFD.

Abstract There is a gap between people’s online sharing of personal data and their concerns about privacy. Till now, this gap is addressed by attempting to match individual privacy preferences with service providers’ options for data handling. This approach has ignored the role different contexts play in data sharing. This paper aims at giving privacy engineering a new direction putting context centre stage and exploiting the affordances of machine learning in handling contexts and negotiating data sharing policies. This research is explorative and conceptual, representing the first development cycle of a design science research project in privacy engineering. The paper offers a concise understanding of data privacy as a foundation for design extending the seminal contextual integrity theory of Helen Nissenbaum. This theory started out as a normative theory describing the moral appropriateness of data transfers. In our work, the contextual integrity model is extended to a socio-technical theory that could have practical impact in the era of artificial intelligence. New conceptual constructs such as ‘context trigger’, ‘data sharing policy’ and ‘data sharing smart contract’ are defined, and their application is discussed from an organisational and technical level. The constructs and design are validated through expert interviews; contributions to design science research are discussed, and the paper concludes with presenting a framework for further privacy engineering development cycles.

Exercise, typically beneficial for skeletal health, has not yet been studied in lipodystrophy, a condition characterized by paucity of white adipose tissue, with eventual diabetes, and steatosis. We applied a mouse model of global deficiency of Bscl2 (SEIPIN), required for lipid droplet formation. Male twelve-week-old B6 knockouts (KO) and wild type (WT) littermates were assigned six-weeks of voluntary, running exercise (E) versus non-exercise (N=5-8). KO weighed 14% less than WT (p=0.01) and exhibited an absence of epididymal adipose tissue; KO liver Plin1 via qPCR was 9-fold that of WT (p=0.04), consistent with steatosis. Bone marrow adipose tissue (BMAT), unlike white adipose, was measurable, although 40.5% lower in KO vs WT (p=0.0003) via 9.4T MRI/advanced image analysis. SEIPIN ablation’s most notable effect marrow adiposity was in the proximal femoral diaphysis (-56% KO vs WT, p=0.005), with relative preservation in KO-distal-femur. Bone via μCT was preserved in SEIPIN KO, though some quality parameters were attenuated. Running distance, speed, and time were comparable in KO and WT. Exercise reduced weight (-24% WT-E vs WT p

BackgroundTelehealth seems feasible for use in home-based palliative care. However, acceptance among health care professionals (HCPs) is essential for the successful delivery of telehealth in practice. No scoping review has mapped the experiences and perspectives of HCPs on the use of telehealth for home-based palliative care. ObjectiveThe aim of this review is to systematically map published studies on HCPs’ experiences and perspectives on the use of telehealth in home-based palliative care. MethodsThe proposed scoping review will employ the methodology of Arksey and O’Malley. This protocol is guided by the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P). A systematic search will be performed in MEDLINE, PsycINFO, EMBASE, CINAHL, Allied and Complementary Medicine (AMED), and Web of Science for studies published between January 2000 and July 5, 2021. We will also hand search the reference lists of included papers to identify additional studies of relevance. The search will be updated in 2022. Pairs of authors will independently assess the eligibility of studies and extract data. The first 2 stages of thematic synthesis will be used to thematically organize the data. Because the scoping review methodology consists of reviewing and collecting data from publicly available materials, this study does not require ethics approval. ResultsThe database searches; testing of eligibility criteria; and screening of titles, abstracts, and full-text papers will be performed by fall 2021. The results from this scoping review will be presented as a descriptive summary of the results from all included papers, and will be inductively organized into descriptive themes. A frequency table illustrating which papers were included in which descriptive themes will be made. Results are anticipated by the fall of 2022. ConclusionsA mapping of studies could identify research gaps regarding HCPs’ experiences and perspectives on the use of telehealth in home-based palliative care and may determine the value and feasibility of conducting a full systematic review. International Registered Report Identifier (IRRID)PRR1-10.2196/33305

Abstract Learning analytics (LA) promises understanding and optimization of learning and learning environments. To enable richer insights regarding questions related to learning and education, LA solutions should be able to integrate data coming from many different data sources, which may be stored in different formats and have varying levels of structure. Data integration also plays a role for the scalability of LA, an important challenge in itself. The objective of this review is to assess the current state of LA in terms of data integration in the context of higher education. The initial search of six academic databases and common venues for publishing LA research resulted in 115 publications, out of which 20 were included in the final analysis. The results show that a few data sources (e.g., LMS) appear repeatedly in the research studies; the number of data sources used in LA studies in higher education tends to be limited; when data are integrated, similar data formats are often combined (a low-hanging fruit in terms of technical challenges); the research literature tends to lack details about data integration in the implemented systems; and, despite being a good starting point for data integration, educational data specifications (e.g., xAPI) seem to seldom be used. In addition, the results indicate a lack of stakeholder (e.g., teachers/instructors, technology vendors) involvement in the research studies. The review concludes by offering recommendations to address limitations and gaps in the research reported in the literature.

Obesity is a major risk factor for both metabolic and cardiovascular disease. We reported that, in obese male mice, histone deacetylase 9 (HDAC9) is upregulated in adipose tissues, and global deletion of HDAC9 protected against high fat diet (HFD)-induced obesity and metabolic disease. Here, we investigated the impact of adipocyte-specific HDAC9 gene deletion on diet-induced obesity in male and female mice. The HDAC9 gene expression was increased in adipose tissues of obese male and female mice and HDAC9 expression correlated positively with body mass index in humans. Interestingly, female, but not male, adipocyte-specific HDAC9 KO mice on HFD exhibited reduced body weight and visceral adipose tissue mass, adipocyte hypertrophy, and improved insulin sensitivity, glucose tolerance and adipogenic differentiation gene expression. Furthermore, adipocyte-specific HDAC9 gene deletion in female mice improved metabolic health as assessed by whole body energy expenditure, oxygen consumption, and adaptive thermogenesis. Mechanistically, compared to female mice, HFD-fed male mice exhibited preferential HDAC9 expression in the stromovascular fraction, which may have offset the impact of adipocyte-specific HDAC9 gene deletion in male mice. These results suggest that HDAC9 expressed in adipocytes is detrimental to obesity in female mice and provides novel evidence of sex-related differences in HDAC9 cellular expression and contribution to obesity-related metabolic disease.

BackgroundFalling is one of the most common and serious age-related issues, and falls can significantly impair the quality of life of older adults. Approximately one-third of people over 65 experience a fall annually. Previous research has shown that physical exercise could help reduce falls among older adults and improve their health. However, older adults often find it challenging to follow and adhere to physical exercise programs. Interventions using mixed reality (MR) technology could help address these issues. MR combines artificial augmented computer-generated elements with the real world. It has frequently been used for training and rehabilitation purposes. ObjectiveThe aim of this systematic literature review and meta-analysis was to investigate the use of the full spectrum of MR technologies for fall prevention intervention and summarize evidence of the effectiveness of this approach. MethodsIn our qualitative synthesis, we analyzed a number of features of the selected studies, including aim, type of exercise, technology used for intervention, study sample size, participant demographics and history of falls, study design, involvement of health professionals or caregivers, duration and frequency of the intervention, study outcome measures, and results of the study. To systematically assess the results of the selected studies and identify the common effect of MR interventions, a meta-analysis was performed. ResultsSeven databases were searched, and the initial search yielded 5838 results. With the considered inclusion and exclusion criteria, 21 studies were included in the qualitative synthesis and 12 were included in meta-analysis. The majority of studies demonstrated a positive effect of an MR intervention on fall risk factors among older participants. The meta-analysis demonstrated a statistically significant difference in Berg Balance Scale score between the intervention and control groups (ES: 0.564; 95% CI 0.246-0.882; P

Active contour models driven by local binary fitting energy can segment images with inhomogeneous intensity, while being prone to falling into a local minima. However, the segmentation result largely depends on the location of the initial contour. We propose an active contour model with global and local image information. The local information of the model is obtained by bilateral filters, which can also enhance the edge information while smoothing the image. The local fitting centers are calculated before the contour evolution, which can alleviate the iterative process and achieve fast image segmentation. The global information of the model is obtained by simplifying the C-V model, which can assist contour evolution, thereby increasing accuracy. Experimental results show that our algorithm is insensitive to the initial contour position, and has higher precision and speed.

Objective: Understanding the mechanisms that control brown adipose tissue (BAT) mass and functionality is crucial for our understanding of how the disruption of energy homeostasis leads to obesity. Bernerdinali Seip Congenital Lipodystrophy (BSCL) type 2 (BSCL2, a.k.a. SEIPIN), a lipodystrophy-associated protein, has been shown to not be required for brown adipogenesis, but it has been shown to be essential for perinatal BAT development. However, its role in mature BAT maintenance and thermogenic programing remains poorly understood. Methods: We subjected Bscl2f/f and Bscl2UCP1-BKO (BKO) mice with a brown adipose-specific loss of BSCL2 through UCP1 promoter-driven Cre to environmental, pharmacological and diet interventions to challenge BAT functionality and reprogramming. We carried out physiological, molecular and transcriptomic analyses of BAT. Results: The deletion of BSCL2 in mature brown adipocytes increased sympathetic nervous system-independent cAMP/protein kinase A (PKA) signaling in BAT. Such activation reduced BAT triglyceride content and mass and was sufficient to reduce plasma triglyceride, but not enough to combat thermoneutral and high fat diet-induced obesity. Surprisingly, BKO mice displayed an impaired response to acute and chronic cold challenges despite cAMP/PKA activation. When subjected to chronic cold exposure or the administration of a β3-adrenergic agonist, CL 316,243, BKO mice failed to induce BAT recruitment and underwent dramatic brown adipocyte loss. Transcriptomic analysis revealed pathological BAT remodeling with inflammation and fibrosis, which was further exacerbated by a chronic thermogenic challenge in BKO mice. Mechanistically, we found abnormal mitochondrial shapes and function in BAT of BKO mice housed at 21 °C; as well as mitochondrial DNA depletion and necroptotic-mediated brown adipocyte death after chronic thermogenic insult. Conclusion: BSCL2-mediated lipid catabolism within BAT is crucial for mature brown adipocyte function and survival both during times of activation and quiescence. BSCL2 is an important regulator of mature brown adipocyte mitochondrial metabolism, necroptosis and thus adaptive thermogenesis.

Abstract Privacy and data protection are a major stumbling blocks for a data-driven educational future. Privacy policies are based on legal regulations, which in turn get their justification from political, cultural, economical and other kinds of discourses. Applied to learning analytics, do these policies also need a pedagogical grounding? This paper is based on an actual conundrum in developing a technical specification on privacy and data protection for learning analytics for an international standardisation organisation. Legal arguments vary a lot around the world, and seeking ontological arguments for privacy does not necessarily lead to a universal acclaim of safeguarding the learner meeting the new data-driven practices in education. Maybe it would be easier to build consensus around educational values, but is it possible to do so? This paper explores the legal and cultural contexts that make it a challenge to define universal principles for privacy and data protection. If not universal principles, consent could be the point of departure for assuring privacy? In education, this is not necessarily the case as consent will be balanced by organisations’ legitimate interests and contract. The different justifications for privacy, the legal obligation to separate analysis from intervention, and the way learning and teaching works makes it necessary to argue data privacy from a pedagogical perspective. The paper concludes with three principles that are proposed to inform an educational maxim for privacy and data protection in learning analytics.

Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) is caused by loss-of-function mutations in SEIPIN, a protein implicated in both adipogenesis and lipid droplet expansion but whose molecular function remains obscure. Here, we identify physical and functional interactions between SEIPIN and microsomal isoforms of glycerol-3-phosphate acyltransferase (GPAT) in multiple organisms. Compared to controls, GPAT activity was elevated in SEIPIN-deficient cells and tissues and GPAT kinetic values were altered. Increased GPAT activity appears to underpin the block in adipogenesis and abnormal lipid droplet morphology associated with SEIPIN loss. Overexpression of Gpat3 blocked adipogenesis, and Gpat3 knockdown in SEIPIN-deficient preadipocytes partially restored differentiation. GPAT overexpression in yeast, preadipocytes, and fly salivary glands also formed supersized lipid droplets. Finally, pharmacological inhibition of GPAT in Seipin−/− mouse preadipocytes partially restored adipogenesis. These data identify SEIPIN as an evolutionarily conserved regulator of microsomal GPAT and suggest that GPAT inhibitors might be useful for the treatment of human BSCL2 patients.

The use of information and communications technology (ICT) in higher education institutions has increased in the past 20 years. While ICT has brought many benefits to students and faculty, research shows that it also creates barriers and challenges for students with disabilities due to the inaccessibility of digital tools and learning materials. Faculty members play an important role in inclusive higher education. Previous studies have emphasised the need to train faculty about digital accessibility to achieve inclusion in higher education. This systematic literature review aims to study existing work on increasing the faculty members' competence in providing accessible and inclusive digital learning materials and environments to students in higher education. Sixteen peer-reviewed papers were included and analysed. Most trainings included topics on disability and awareness, legislation, and methods of producing accessible digital materials and providing inclusive digital learning environments. While surveys and interviews were mostly used to evaluate training outcomes, there was a lack of objective data and commonly accepted instrument for evaluation. Good practices and further research opportunities are identified. This study has implications for researchers and higher education institutions that are interested in research and practice on increasing general competence in digital accessibility and inclusive education.

University libraries offer services that generate data about how students and faculty use knowledge sources and engage with teaching and learning. In an era of Big Data there is mounting pressure to use these data, something that challenges the professional ethics of librarians. This paper explores how Norwegian librarians position themselves in relation to the new phenomenon of learning analytics, which would like to process library data to help improve learning and its contexts. A literature review shows that librarians in general are highly sceptical to let any information that is not anonymised out of their hands to be used by other professions. However, library data is increasingly being shared with third parties as part of development of library systems and practices. In a survey presented in this paper Norwegian librarians were asked about their willingness to take part in analytics and data sharing. The findings show that even if librarians in general do not want to share data that reveals personal information, their resistance will depend on the consent of the students, and to which degree librarians themselves are involved in processing and analysis of the data. This study identifies learning analytics as a field the library community should engage with, and the authors give their advice on what should be focussed to sustain librarians’ professional ethics related to use of library data.

The global population is ageing rapidly. The ageing population faces not only the risk of health-related problems but also the challenge of social isolation and loneliness. While mainstream technology is designed to improve daily life, elderly people’s unique needs are often neglected. These technology designs can be difficult for older adults to learn and use. Tangible user interface (TUI) gives physical form to digital information, with the aim of bridging the gap between the digital world and the physical world. Thus, it can be a more natural and intuitive interface for the older adults. The objective of this research is to review the existing research on TUI for enhancing the social interactions of elderly people. Results show that very little research has been published, given that the TUI concept was introduced 20 years ago. Our systematic literature review also resulted in several recommendations for future research, which includes getting elderly people involved in the process, from designing to evaluating the prototype and investigating the effect of TUI on older adults’ social interactions and health.

Mutations in BSCL2/SEIPIN cause Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), but the mechanisms whereby Bscl2 regulates adipose tissue function are unclear. Here, we generated adipose tissue (mature) Bscl2 knockout (Ad-mKO) mice, in which Bscl2 was specifically ablated in adipocytes of adult animals, to investigate the impact of acquired Bscl2 deletion on adipose tissue function and energy balance. Ad-mKO mice displayed reduced adiposity and were protected against high fat diet-induced obesity, but not insulin resistance or hepatic steatosis. Gene expression profiling and biochemical assays revealed increased lipolysis and fatty acid oxidation in white adipose tissue (WAT) and brown adipose tissue , as well as browning of WAT, owing to induction of cAMP/protein kinase A signaling upon Bscl2 deletion. Interestingly, Bscl2 deletion reduced food intake and downregulated adipose β3-adrenergic receptor (ADRB3) expression. Impaired ADRB3 signaling partially offsets upregulated browning-induced energy expenditure and thermogenesis in Ad-mKO mice housed at ambient temperature. However, this counter-regulatory response was abrogated under thermoneutral conditions, resulting in even greater body mass loss in Ad-mKO mice. These findings suggest that Bscl2 regulates adipocyte lipolysis and β-adrenergic signaling to produce complex effects on adipose tissues and whole-body energy balance.

Mutations in BSCL2 underlie human congenital generalized lipodystrophy type 2 disease. We previously reported that Bscl2 (-/-) mice develop lipodystrophy of white adipose tissue (WAT) due to unbridled lipolysis. The residual epididymal WAT (EWAT) displays a browning phenotype with much smaller lipid droplets (LD) and higher expression of brown adipose tissue marker proteins. Here we used targeted lipidomics and gene expression profiling to analyze lipid profiles as well as genes involved in lipid metabolism in WAT of wild-type and Bscl2(-/-) mice. Analysis of total saponified fatty acids revealed that the residual EWAT of Bscl2(-/-) mice contained a much higher proportion of oleic 18:1n9 acid concomitant with a lower proportion of palmitic 16:0 acid, as well as increased n3- polyunsaturated fatty acids (PUFA) remodeling. The acyl chains in major species of triacylglyceride (TG) and diacylglyceride (DG) in the residual EWAT of Bscl2(-/-) mice were also enriched with dietary fatty acids. These changes could be reflected by upregulation of several fatty acid elongases and desaturases. Meanwhile, Bscl2(-/-) adipocytes from EWAT had increased gene expression in lipid uptake and TG synthesis but not de novo lipogenesis. Both mitochondria and peroxisomal β-oxidation genes were also markedly increased in Bscl2(-/-) adipocytes, highlighting that these machineries were accelerated to shunt the lipolysis liberated fatty acids through uncoupling to dissipate energy. The residual subcutaneous white adipose tissue (ScWAT) was not browning but displays similar changes in lipid metabolism. Overall, our data emphasize that, other than being essential for adipocyte differentiation, Bscl2 is also important in fatty acid remodeling and energy homeostasis.