UAS Literary & Arts Journal

Proof copy provided by Tidal Echoes.Featuring the work of students, faculty, and staff of the University of Alaska Southeast and members of the community.A Note from Loren, Sometimes Known as Senior Editor -- A Letter from Josh, Affectionately Known as “Sugah” (say it with a southern accent) -- A Note from Emily Wall -- On the Move -- Dangly Jangly Things -- Taco Surf -- Midwestern Trash -- On the Distaff Side -- Christmas Joy -- The Three Little McCormicks -- Trollin’ Ray’s Brain: An Interview with Ray Troll -- His Long Coat Turning -- First Autumn -- Pinta Cove Birthday Gifts -- September Wings -- When in Rome -- Early Morning Conspiracy Theory -- Flesh Wound -- Two Ravens, Five Ways -- Shades of Brown: The Question -- Hayfield-Clarke Psychiatric Center -- Hardscrabble -- Smoked Meat Sandwiches -- Slime Squishing Through Gold: An Interview with Nora Marks Dauenhauer -- Berries -- Buds -- Grandpa Jakwteen in Eclipse -- Cross Talk -- Voices -- Trouble -- Flying Home -- Snorkeling at Hanauma Bay -- Genocide -- Raven, Saving It for Later -- Mama Abel’s -- Settling In -- Blue -- Dad at 27 -- Dad photographs mother -- Backyard theatre & Oz -- Love-in, Easter Day, 1968 -- Topanga Corral -- Swallowing Senora -- Keeping Time on the Kee Nax Trail -- Ode to Ching -- Beneath the Surface (chapter title) -- A Visit from the Wild -- Teacher’s Pets -- Centennial -- See Spot Rot -- With Salsa -- Moonbaby -- The Fine Art of Raising a Tarpaulin -- Prologue -- Epiphany 2008 -- View of Auke Lake -- Shark Fins -- Translating Pasternak -- Raven Boys -- Institutional Back Door -- Uneasy Disguise -- Christmas Wind -- The Life and Times of the Orlando Bloom Fan Club -- Writer & Artist Biographie

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Large-scale sequencing identifies multiple genes and rare variants associated with Crohn’s disease susceptibility

peer reviewe

Step In, Step Out from the First Lockdown: An Exploration of COVID-19 Perceptions in France and Quebec

International audienceObjective. The objective of this research was to describe and analyze the role of psychological and behavioral factors on perceptions of COVID-19 in France and Quebec at three different times during the pandemic. Design. We conducted three qualitative and quantitative studies (Study 1 N = 255, Study 2 N = 230, Study 3 N = 143). Participants were asked to evaluate psychological and behavioral measures: at the beginning of lockdown (Study 1), during lockdown (Study 2), and during lockdown exit (Study 3). Results. Results of Study 1 show that perceptions of COVID-19 are organized around fear and a sense of threat. During the lockdown, participants mentioned for the first time the health practices to prevent the spread of COVID-19 (Study 2). Psychological and social impacts constitute a central theme in participants’ discourse (Study 2 and 3). Conclusions. The results show that perceptions of risk during a pandemic are socially constructed. Perceptions seem to be influenced by the political and health management of a territory and by the evolution of behavioral and psychological responses

Associations of autozygosity with a broad range of human phenotypes

Abstract: In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding

Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility

Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn’s disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation