Novel deletions causing pseudoxanthoma elasticum underscore the genomic instability of the ABCC6 region

Mutations in ABCC6 cause pseudoxanthoma elasticum (PXE), a heritable disease that affects elastic fibers. Thus far, >200 mutations have been characterized by various PCR-based techniques (primarily direct sequencing), identifying up to 90% of PXE-causing alleles. This study wanted to assess the importance of deletions and insertions in the ABCC6 genomic region, which is known to have a high recombinational potential. To detect ABCC6 deletions/insertions, which can be missed by direct sequencing, multiplex ligation-dependent probe amplification (MLPA) was applied in PXE patients with an incomplete genotype. MLPA was performed in 35 PXE patients with at least one unidentified mutant allele after exonic sequencing and exclusion of the recurrent exon 23-29 deletion. Six multi-exon deletions and four single-exon deletions were detected. Using MLPA in addition to sequencing, we expanded the ABCC6 mutation spectrum with 9 novel deletions and characterized 25% of unidentified disease alleles. Our results further illustrate the instability of the ABCC6 genomic region and stress the importance of screening for deletions in the molecular diagnosis of PXE. Journal of Human Genetics (2010) 55, 112-117; doi: 10.1038/jhg.2009.132; published online 15 January 201

The underscore

Amidst the parched and hazy drought and wildfire season in Alberta’s Rocky Mountains and prairies, an AI start-up approaches a famous Instagram influencer to embed her likeness into its avatars. Set beyond the AI’s murky digital landscape, “The Underscore” explores the journey of four characters with interwoven narratives during two critical junctures: the proliferation of AI friendship and the dangers of a looming forest fire in Jasper. Sophie_Grace is a lauded millennial known for her social media empire who chooses to ignore the warning signs of her AI. Sophie’s best friend Iris risks her personal and professional connections despite her reservations and defends Sophie’s decisions until one event threatens to crater their relationship permanently. Rowan, Iris’s partner, is a Woodlands firefighter and quietly observes the changing social and climate environments before him, until a spark ignites a blaze that threatens to ravage Jasper. Annie is a young high-schooler enamoured with the Sophie_Grace. When Sophie_Grace uploads her personality into AI, Annie jumps at the chance to have realistic conversations with the famous influencer. A speculative work of realist fiction, “The Underscore” examines the pernicious elements of artificial intelligence through the very human and messy nature of genuine connection, heartache, and humour

State Trends in Premiums and Deductibles, 2003-2011: Eroding Protection and Rising Costs Underscore Need for Action

Rapidly rising health insurance premiums and higher cost-sharing continue to strain the budgets of U.S. working families and employers. Analysis of state trends in private employer-based health insurance from 2003 to 2011 reveals that premiums for family coverage increased 62 percent across states -- rising far faster than income for middle- and low-income families. At the same time, deductibles more than doubled in large and small firms. Workers are thus paying more but getting less-protective benefits. If trends continue at their historical rate, the average premium for family coverage will reach nearly $25,000 by 2020. The Affordable Care Act's reforms should begin to moderate costs while improving coverage. But with private insurance costs projected to increase faster than incomes over the next decade, further efforts are needed. If annual premium growth slowed by one percentage point, by 2020 employers and families would save$2,029 annually for family coverage.View the related infographic

Perpetuating Inequality by Taxing Wealth

This Article attempts to correct this shortcoming in the progressive argument by returning narrative to its central place in the estate tax debate. Drawing on psychological insights, I hope to underscore the difficulty of the effort to preserve progressive taxation and combat wealth inequality

The Epistemology of Anger in Argumentation

While anger can derail argumentation, it can also help arguers and audiences to reason together in argumentation. Anger can provide information about premises, biases, goals, discussants, and depth of disagreement that people might otherwise fail to recognize or prematurely dismiss. Anger can also enhance the salience of certain premises and underscore the importance of related inferences. For these reasons, we claim that anger can serve as an epistemic resource in argumentation