Interleukin 31 mediates MAP kinase and STAT1/3 activation in intestinal epithelial cells and its expression is upregulated in inflammatory bowel disease

Background/aim: Interleukin 31 (IL31), primarily expressed in activated lymphocytes, signals through a heterodimeric receptor complex consisting of the IL31 receptor alpha (IL31R\textgreeka) and the oncostatin M receptor (OSMR). The aim of this study was to analyse IL31 receptor expression, signal transduction, and specific biological functions of this cytokine system in intestinal inflammation.Methods: Expression studies were performed by RT-PCR, quantitative PCR, western blotting, and immunohistochemistry. Signal transduction was analysed by western blotting. Cell proliferation was measured by MTS assays, cell migration by restitution assays.Results: Colorectal cancer derived intestinal epithelial cell (IEC) lines express both IL31 receptor subunits, while their expression in unstimulated primary murine IEC was low. LPS and the proinflammatory cytokines TNF-\textgreeka, IL1\textgreekb, IFN-\textgreekg, and sodium butyrate stimulation increased IL31, IL31R\textgreeka, and OSMR mRNA expression, while IL31 itself enhanced IL8 expression in IEC. IL31 mediates ERK-1/2, Akt, STAT1, and STAT3 activation in IEC resulting in enhanced IEC migration. However, at low cell density, IL31 had significant antiproliferative capacities (p<0.005). IL31 mRNA expression was not increased in the TNF\textgreekDARE mouse model of ileitis but in inflamed colonic lesions compared to non-inflamed tissue in patients with Crohn's disease (CD; average 2.4-fold increase) and in patients with ulcerative colitis (UC; average 2.6-fold increase) and correlated with the IL-8 expression in these lesions (r = 0.564 for CD; r = 0.650 for UC; total number of biopsies analysed: n = 88).Conclusion: IEC express the functional IL31 receptor complex. IL31 modulates cell proliferation and migration suggesting a role in the regulation of intestinal barrier function particularly in intestinal inflammation

Algorithmic decision-making and the law

CITATION: Brand, D. J. 2020. Algorithmic decision-making and the law. Journal of Democracy and Open Government, 12(1):114-131, doi:10.29379/jedem.v12i1.576.The original publication is available at https://jedem.orgThe Fourth Industrial Revolution is reshaping the world we know dramatically and is characterised by a close interaction between the biological, digital and physical spheres. Digital technologies are impacting all facets of our lives and create a series of new opportunities but also various challenges. The Fourth Industrial Revolution does not follow a linear development trajectory, but due to the diverse nature and rapid pace of technological developments, could rather be compared to a series of networks with multiple connecting points. This has caused the development of the law which deals with these concerns to generally be slow and unable to match the pace and scope of technological developments. In the context of public law there are many questions and challenges relating to individual rights, for example the right to privacy, and the role and responsibilities of government relating to policy development and regulation dealing with the Fourth Industrial Revolution. The concept of a Rechtsstaat could arguably provide an appropriate legal framework for shaping the ethical framework, normative standards and a value-based governance model for the Fourth Industrial Revolution, including for algorithmic decision-making. The public law concept of accountability should be contextualised in order to apply it to algorithmic decision-making. In the data-driven economy of the 21st century the pace and scope of technological developments that impact humanity requires the development of appropriate legal frameworks to reflect and accommodate the needs of society, in particular relating to the recognition of fundamental human rights. It is concluded that a broad set of ethical and legal principles, which can guide the development of international and national legal frameworks to regulate algorithmic decision-making, is needed.https://jedem.org/index.php/jedem/article/view/576Publisher's versio

What constitutes adequate legal protection for the collection, use and sharing of mobility and location data in health care in South Africa?

Mobile phone technology has been a catalyst that has added an innovative dimension in health care and created new opportunities for digital health services. These digital devices can be viewed as an extension of the person using them due to the deluge of personal information that can be collected and stored on them. Data collected on mobile phones are used extensively in health services and research. Personal, mobility and location data are constantly collected. The unique mobile phone architecture provides for an easy flow of data between various role players such as application developers and phone manufacturers. The collection, storage and sharing of personal information on mobile phones elicit various legal questions relating to the protection of privacy, consent, liability and the accountability of stakeholders such as health insurance providers, hospital groups and national departments of health

The regulation of health data sharing in Africa:a comparative study

The sharing of health data is an essential component in the provision of healthcare, in medical research, and disease surveillance. Health data sharing is subject to regulatory frameworks that vary across jurisdictions. In Africa, numerous factors complicate the regulation of health data sharing, including technological, motivational, economic, and political barriers, as well as ethical and legal challenges. This comparative study examines the regulation of health data sharing in Africa by comparing and contrasting the legal and policy frameworks of five African countries. The study identifies gaps and inconsistencies in the current regulatory regimes and provides recommendations for improving the regulation of health data sharing in Africa

Data sharing governance in sub-Saharan Africa during public health emergencies:gaps and guidance

While the COVID-19 pandemic has captured the attention of the global community since the end of 2019, deadly health pandemics are not new to Africa. Tuberculosis (TB), malaria and human immunodeficiency virus (HIV) count amongst other serious diseases that have had a catastrophic impact on the African continent. Effective responses to such pandemics require high-quality, comprehensive data sets that can inform policymaking and enhance healthcare decision-making. While data is driving the information economy in the 21st century, the scarcity in Africa of carefully curated, large epidemiologic data sources and analytical capacity to rapidly identify and understand emerging infectious diseases poses a major challenge to mounting a time-sensitive response to unfolding pandemics. Data access, sharing and transfer between countries are crucial to effectively managing current and future health pandemics. Data access and sharing, however, raises questions about personal privacy, the adequacy of governance mechanisms to regulate cross-border data flows, and ethical issues relating to the collection and use of personal data in the interests of public health. Sub-Saharan Africa’s most research-intensive countries are characterised by diverse data management and privacy governance frameworks. Such regional variance can impede time-sensitive data sharing and highlights the need for urgent governance reforms to facilitate effective decision-making in response to rapidly evolving public health threats.</p

Data sharing governance in sub-Saharan Africa during public health emergencies: Gaps and guidance

While the COVID-19 pandemic has captured the attention of the global community since the end of 2019, deadly health pandemics are not new to Africa. Tuberculosis (TB), malaria and human immunodeficiency virus (HIV) count amongst other serious diseases that have had a catastrophic impact on the African continent. Effective responses to such pandemics require high-quality, comprehensive data sets that can inform policymaking and enhance healthcare decision-making. While data is driving the information economy in the 21st century, the scarcity in Africa of carefully curated, large epidemiologic data sources and analytical capacity to rapidly identify and understand emerging infectious diseases poses a major challenge to mounting a time-sensitive response to unfolding pandemics. Data access, sharing and transfer between countries are crucial to effectively managing current and future health pandemics. Data access and sharing, however, raises questions about personal privacy, the adequacy of governance mechanisms to regulate cross-border data flows, and ethical issues relating to the collection and use of personal data in the interests of public health. Sub-Saharan Africa’s most research-intensive countries are characterised by diverse data management and privacy governance frameworks. Such regional variance can impede time-sensitive data sharing and highlights the need for urgent governance reforms to facilitate effective decision-making in response to rapidly evolving public health threats. Significance: We explore governance considerations that ought to apply to the collection, transfer, and use of data in public health emergencies. Specifically, we provide an overview of the prevailing data sharing governance landscape in selected African countries. In doing so, we identify limitations and gaps that impede effective data collation, sharing and analysis. This work could find utility amongst a range of stakeholders, including bioinformaticians, epidemiologists, artificial intelligence coders, and government decision-makers. While this work focuses primarily on an African context, the issues explored are of universal concern and therefore of relevance to a broader international audience

What constitutes adequate legal protection for the collection, use and sharing of mobility and location data in health care in South Africa?

Mobile phone technology has been a catalyst that has added an innovative dimension in health care and created new opportunities for digital health services. These digital devices can be viewed as an extension of the person using them due to the deluge of personal information that can be collected and stored on them. Data collected on mobile phones are used extensively in health services and research. Personal, mobility and location data are constantly collected. The unique mobile phone architecture provides for an easy flow of data between various role players such as application developers and phone manufacturers. The collection, storage and sharing of personal information on mobile phones elicit various legal questions relating to the protection of privacy, consent, liability and the accountability of stakeholders such as health insurance providers, hospital groups and national departments of health. SIGNIFICANCE : We analyse the major legal concerns of mobility and location data collection and processing through mobile phones in the context of health care and provide recommendations to develop data protection guidelines that are built on the principles of lawfulness, fairness and transparency. The issues explored are of relevance in an African context and to a broader international audiencehttp://www.sajs.co.zaam2024Public LawNon

Comparative expression profiling of E. coli and S. aureus inoculated primary mammary gland cells sampled from cows with different genetic predispositions for somatic cell score

BACKGROUND: During the past ten years many quantitative trait loci (QTL) affecting mastitis incidence and mastitis related traits like somatic cell score (SCS) were identified in cattle. However, little is known about the molecular architecture of QTL affecting mastitis susceptibility and the underlying physiological mechanisms and genes causing mastitis susceptibility. Here, a genome-wide expression analysis was conducted to analyze molecular mechanisms of mastitis susceptibility that are affected by a specific QTL for SCS on Bos taurus autosome 18 (BTA18). Thereby, some first insights were sought into the genetically determined mechanisms of mammary gland epithelial cells influencing the course of infection. METHODS: Primary bovine mammary gland epithelial cells (pbMEC) were sampled from the udder parenchyma of cows selected for high and low mastitis susceptibility by applying a marker-assisted selection strategy considering QTL and molecular marker information of a confirmed QTL for SCS in the telomeric region of BTA18. The cells were cultured and subsequently inoculated with heat-inactivated mastitis pathogens Escherichia coli and Staphylococcus aureus, respectively. After 1, 6 and 24 h, the cells were harvested and analyzed using the microarray expression chip technology to identify differences in mRNA expression profiles attributed to genetic predisposition, inoculation and cell culture. RESULTS: Comparative analysis of co-expression profiles clearly showed a faster and stronger response after pathogen challenge in pbMEC from less susceptible animals that inherited the favorable QTL allele 'Q' than in pbMEC from more susceptible animals that inherited the unfavorable QTL allele 'q'. Furthermore, the results highlighted RELB as a functional and positional candidate gene and related non-canonical Nf-kappaB signaling as a functional mechanism affected by the QTL. However, in both groups, inoculation resulted in up-regulation of genes associated with the Ingenuity pathways 'dendritic cell maturation' and 'acute phase response signaling', whereas cell culture affected biological processes involved in 'cellular development'. CONCLUSIONS: The results indicate that the complex expression profiling of pathogen challenged pbMEC sampled from cows inheriting alternative QTL alleles is suitable to study genetically determined molecular mechanisms of mastitis susceptibility in mammary epithelial cells in vitro and to highlight the most likely functional pathways and candidate genes underlying the QTL effect

Association of Human FOS Promoter Variants with the Occurrence of Knee-Osteoarthritis in a Case Control Association Study

Our aim was to analyse (i) the presence of single nucleotide polymorphisms (SNPs) in the JUN and FOS core promoters in patients with rheumatoid arthritis (RA), knee-osteoarthritis (OA), and normal controls (NC); (ii) their functional influence on JUN/FOS transcription levels; and (iii) their associations with the occurrence of RA or knee-OA. JUN and FOS promoter SNPs were identified in an initial screening population using the Non-Isotopic RNase Cleavage Assay (NIRCA); their functional influence was analysed using reporter gene assays. Genotyping was done in RA (n = 298), knee-OA (n = 277), and NC (n = 484) samples. For replication, significant associations were validated in a Finnish cohort (OA: n = 72, NC: n = 548). Initially, two SNPs were detected in the JUN promoter and two additional SNPs in the FOS promoter in perfect linkage disequilibrium (LD). JUN promoter SNP rs4647009 caused significant downregulation of reporter gene expression, whereas reporter gene expression was significantly upregulated in the presence of the FOS promoter SNPs. The homozygous genotype of FOS promoter SNPs showed an association with the susceptibility for knee-OA (odds ratio (OR) 2.12, 95% confidence interval (CI) 1.2-3.7, p = 0.0086). This association was successfully replicated in the Finnish Health 2000 study cohort (allelic OR 1.72, 95% CI 1.2-2.5, p = 0.006). FOS Promoter variants may represent relevant susceptibility markers for knee-OA.Peer reviewe

Association of Human FOS Promoter Variants with the Occurrence of Knee-Osteoarthritis in a Case Control Association Study

Our aim was to analyse (i) the presence of single nucleotide polymorphisms (SNPs) in the JUN and FOS core promoters in patients with rheumatoid arthritis (RA), knee-osteoarthritis (OA), and normal controls (NC); (ii) their functional influence on JUN/FOS transcription levels; and (iii) their associations with the occurrence of RA or knee-OA. JUN and FOS promoter SNPs were identified in an initial screening population using the Non-Isotopic RNase Cleavage Assay (NIRCA); their functional influence was analysed using reporter gene assays. Genotyping was done in RA (n = 298), knee-OA (n = 277), and NC (n = 484) samples. For replication, significant associations were validated in a Finnish cohort (OA: n = 72, NC: n = 548). Initially, two SNPs were detected in the JUN promoter and two additional SNPs in the FOS promoter in perfect linkage disequilibrium (LD). JUN promoter SNP rs4647009 caused significant downregulation of reporter gene expression, whereas reporter gene expression was significantly upregulated in the presence of the FOS promoter SNPs. The homozygous genotype of FOS promoter SNPs showed an association with the susceptibility for knee-OA (odds ratio (OR) 2.12, 95% confidence interval (CI) 1.2–3.7, p = 0.0086). This association was successfully replicated in the Finnish Health 2000 study cohort (allelic OR 1.72, 95% CI 1.2–2.5, p = 0.006). FOS Promoter variants may represent relevant susceptibility markers for knee-OA