Blood-Stained Letter Received by HIV/AIDS Reference Laboratory in 1993 – A Historical Case Report

We describe an interesting historical case of a blood-stained letter received in 1993 by Slovenian HIV/AIDS Reference Laboratory. According to the statement of the sender, the letter was spotted with HIV-infected blood. The polymerase chain reaction (PCR) amplification with two gag and env primer sets excluded the presence of HIV proviral DNA in the spot punches obtained from the dried blood spots. Although the presence of HIV DNA was confirmed in 5 positive control blood spots using the same sets of primers, we still doubted in the accuracy of the HIV negative result. Fortunately, we obtained a serum sample of the author of the letter four months later from a psychiatric institution where he was hospitalized for paranoid schizophrenia. Since no anti HIV-1/2 antibodies were detected in his serum sample, our initial HIV negative findings based on PCR testing of blood spots were confirmed

Towards Minimal Barcodes

In the setting of persistent homology computation, a useful tool is the persistence barcode representation in which pairs of birth and death times of homology classes are encoded in the form of intervals. Starting from a polyhedral complex K (an object subdivided into cells which are polytopes) and an initial order of the set of vertices, we are concerned with the general problem of searching for filters (an order of the rest of the cells) that provide a minimal barcode representation in the sense of having minimal number of “k-significant” intervals, which correspond to homology classes with life-times longer than a fixed number k. As a first step, in this paper we provide an algorithm for computing such a filter for k = 1 on the Hasse diagram of the poset of faces of K

Just a wind-up? Ethnicity, religion and prejudice in Scottish football-related comedy

This article probes how media representations of football in Scotland sustain the hegemonic ideologies associated with ethnicity and religion. The paper probes the football-related comedy output of one radio programme; radio output and football comedy are both neglected cultural material in studies of sport in Scotland. It argues that ambiguity and allusive language in comedy construct multiple interpretative possibilities that can demean the social and cultural identity of particular groups in society. The discussion analyses specific sketches from the Scottish radio comedy show Watson's Wind Up. It is concluded that although humorous, these sketches reveal how ideas, myths and stereotypes that coalesce round Celtic FC and the Irish-descended and Catholic communities in Scotland reinforce and sustain anti-Irish and anti-Catholic bigotry

Inherited variants in CHD3 show variable expressivity in Snijders Blok-Campeau syndrome

Purpose Common diagnostic next-generation sequencing strategies are not optimized to identify inherited variants in genes associated with dominant neurodevelopmental disorders as causal when the transmitting parent is clinically unaffected, leaving a significant number of cases with neurodevelopmental disorders undiagnosed. Methods We characterized 21 families with inherited heterozygous missense or protein-truncating variants in CHD3, a gene in which de novo variants cause Snijders Blok-Campeau syndrome. Results Computational facial and Human Phenotype Ontology–based comparisons showed that the phenotype of probands with inherited CHD3 variants overlaps with the phenotype previously associated with de novo CHD3 variants, whereas heterozygote parents are mildly or not affected, suggesting variable expressivity. In addition, similarly reduced expression levels of CHD3 protein in cells of an affected proband and of healthy family members with a CHD3 protein-truncating variant suggested that compensation of expression from the wild-type allele is unlikely to be an underlying mechanism. Notably, most inherited CHD3 variants were maternally transmitted. Conclusion Our results point to a significant role of inherited variation in Snijders Blok-Campeau syndrome, a finding that is critical for correct variant interpretation and genetic counseling and warrants further investigation toward understanding the broader contributions of such variation to the landscape of human disease

The Role of Osteopontin (OPN/SPP1) Haplotypes in the Susceptibility to Crohn's Disease

Osteopontin represents a multifunctional molecule playing a pivotal role in chronic inflammatory and autoimmune diseases. Its expression is increased in inflammatory bowel disease (IBD). The aim of our study was to analyze the association of osteopontin (OPN/SPP1) gene variants in a large cohort of IBD patients. Genomic DNA from 2819 Caucasian individuals (n = 841 patients with Crohn's disease (CD), n = 473 patients with ulcerative colitis (UC), and n = 1505 healthy unrelated controls) was analyzed for nine OPN SNPs (rs2728127, rs2853744, rs11730582, rs11739060, rs28357094, rs4754 = p.Asp80Asp, rs1126616 = p.Ala236Ala, rs1126772 and rs9138). Considering the important role of osteopontin in Th17-mediated diseases, we performed analysis for epistasis with IBD-associated IL23R variants and analyzed serum levels of the Th17 cytokine IL-22. For four OPN SNPs (rs4754, rs1126616, rs1126772 and rs9138), we observed significantly different distributions between male and female CD patients. rs4754 was protective in male CD patients (p = 0.0004, OR = 0.69). None of the other investigated OPN SNPs was associated with CD or UC susceptibility. However, several OPN haplotypes showed significant associations with CD susceptibility. The strongest association was found for a haplotype consisting of the 8 OPN SNPs rs2728127-rs2853744-rs11730582-rs11439060-rs28357094-rs112661-rs1126772-rs9138 (omnibus p-value = 2.07×10⁻⁸). Overall, the mean IL-22 secretion in the combined group of OPN minor allele carriers with CD was significantly lower than that of CD patients with OPN wildtype alleles (p = 3.66×10⁻⁵). There was evidence for weak epistasis between the OPN SNP rs28357094 with the IL23R SNP rs10489629 (p = 4.18×10⁻²) and between OPN SNP rs1126616 and IL23R SNP rs2201841 (p = 4.18×10⁻²) but none of these associations remained significant after Bonferroni correction. Our study identified OPN haplotypes as modifiers of CD susceptibility, while the combined effects of certain OPN variants may modulate IL-22 secretion

Integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement, migration and neuroinflammatory signalling

BackgroundAnaphylaxis is an acute life-threatening allergic reaction and a concern at a global level; therefore, further progress in understanding the underlying mechanisms and more effective strategies for diagnosis, prevention and management are needed.ObjectiveWe sought to identify the global architecture of blood transcriptomic features of anaphylaxis by integrating expression data from human patients and mouse model of anaphylaxis.MethodsBulk RNA-sequencings of peripheral whole blood were performed in: i) 14 emergency department (ED) patients with acute anaphylaxis, predominantly to Hymenoptera venom, ii) 11 patients with peanut allergy undergoing double-blind, placebo-controlled food challenge (DBPCFC) to peanut, iii) murine model of IgE-mediated anaphylaxis. Integrative characterisation of differential gene expression, immune cell-type-specific gene expression profiles, and functional and pathway analysis was undertaken.Results1023 genes were commonly and significantly dysregulated during anaphylaxis in ED and DBPCFC patients; of those genes, 29 were also dysregulated in the mouse model. Cell-type-specific gene expression profiles showed a rapid downregulation of blood basophil and upregulation of neutrophil signature in ED and DBPCFC patients and the mouse model, but no consistent and/or significant differences were found for other blood cells. Functional and pathway analysis demonstrated that human and mouse blood transcriptomic signatures of anaphylaxis follow trajectories of upregulation of cell movement, migration and neuroinflammatory signalling, and downregulation of lipid activating nuclear receptors signalling.ConclusionOur study highlights the matched and extensive blood transcriptomic changes and suggests the involvement of discrete cellular components and upregulation of migration and neuroinflammatory pathways during anaphylaxis

Inherited variants in CHD3 show variable expressivity in Snijders Blok-Campeau syndrome

Purpose: Common diagnostic next-generation sequencing strategies are not optimized to identify inherited variants in genes associated with dominant neurodevelopmental disorders as causal when the transmitting parent is clinically unaffected, leaving a significant number of cases with neurodevelopmental disorders undiagnosed. Methods: We characterized 21 families with inherited heterozygous missense or protein-truncating variants in CHD3, a gene in which de novo variants cause Snijders Blok-Campeau syndrome. Results: Computational facial and Human Phenotype Ontology–based comparisons showed that the phenotype of probands with inherited CHD3 variants overlaps with the phenotype previously associated with de novo CHD3 variants, whereas heterozygote parents are mildly or not affected, suggesting variable expressivity. In addition, similarly reduced expression levels of CHD3 protein in cells of an affected proband and of healthy family members with a CHD3 protein-truncating variant suggested that compensation of expression from the wild-type allele is unlikely to be an underlying mechanism. Notably, most inherited CHD3 variants were maternally transmitted. Conclusion: Our results point to a significant role of inherited variation in Snijders Blok-Campeau syndrome, a finding that is critical for correct variant interpretation and genetic counseling and warrants further investigation toward understanding the broader contributions of such variation to the landscape of human disease

Acorn: Developing full-chain industrial carbon capture and storage in a resource- and infrastructure-rich hydrocarbon province

Research to date has identified cost and lack of support from stakeholders as two key barriers to the development of a carbon dioxide capture and storage (CCS) industry that is capable of effectively mitigating climate change. This paper responds to these challenges through systematic evaluation of the research and development process for the Acorn CCS project, a project designed to develop a scalable, full-chain CCS project on the north-east coast of the UK. Through assessment of Acorn's publicly-available outputs, we identify strategies which may help to enhance the viability of early-stage CCS projects. Initial capital costs can be minimised by infrastructure re-use, particularly pipelines, and by re-use of data describing the subsurface acquired during oil and gas exploration activity. Also, development of the project in separate stages of activity (e.g. different phases of infrastructure re-use and investment into new infrastructure) enables cost reduction for future build-out phases. Additionally, engagement of regional-level policy makers may help to build stakeholder support by situating CCS within regional decarbonisation narratives. We argue that these insights may be translated to general objectives for any CCS project sharing similar characteristics such as legacy infrastructure, industrial clusters and an involved stakeholder-base that is engaged with the fossil fuel industry