Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases

Genomewide Association Studies of LRRK2 Modifiers of Parkinson's Disease.

OBJECTIVE: The aim of this study was to search for genes/variants that modify the effect of LRRK2 mutations in terms of penetrance and age-at-onset of Parkinson's disease. METHODS: We performed the first genomewide association study of penetrance and age-at-onset of Parkinson's disease in LRRK2 mutation carriers (776 cases and 1,103 non-cases at their last evaluation). Cox proportional hazard models and linear mixed models were used to identify modifiers of penetrance and age-at-onset of LRRK2 mutations, respectively. We also investigated whether a polygenic risk score derived from a published genomewide association study of Parkinson's disease was able to explain variability in penetrance and age-at-onset in LRRK2 mutation carriers. RESULTS: A variant located in the intronic region of CORO1C on chromosome 12 (rs77395454; p value = 2.5E-08, beta = 1.27, SE = 0.23, risk allele: C) met genomewide significance for the penetrance model. Co-immunoprecipitation analyses of LRRK2 and CORO1C supported an interaction between these 2 proteins. A region on chromosome 3, within a previously reported linkage peak for Parkinson's disease susceptibility, showed suggestive associations in both models (penetrance top variant: p value = 1.1E-07; age-at-onset top variant: p value = 9.3E-07). A polygenic risk score derived from publicly available Parkinson's disease summary statistics was a significant predictor of penetrance, but not of age-at-onset. INTERPRETATION: This study suggests that variants within or near CORO1C may modify the penetrance of LRRK2 mutations. In addition, common Parkinson's disease associated variants collectively increase the penetrance of LRRK2 mutations. ANN NEUROL 2021;90:82-94

Effectiveness of school food environment policies on children's dietary behaviors: A systematic review and meta-analysis.

BACKGROUND: School food environment policies may be a critical tool to promote healthy diets in children, yet their effectiveness remains unclear. OBJECTIVE: To systematically review and quantify the impact of school food environment policies on dietary habits, adiposity, and metabolic risk in children. METHODS: We systematically searched online databases for randomized or quasi-experimental interventions assessing effects of school food environment policies on children's dietary habits, adiposity, or metabolic risk factors. Data were extracted independently and in duplicate, and pooled using inverse-variance random-effects meta-analysis. Habitual (within+outside school) dietary intakes were the primary outcome. Heterogeneity was explored using meta-regression and subgroup analysis. Funnel plots, Begg's and Egger's test evaluated potential publication bias. RESULTS: From 6,636 abstracts, 91 interventions (55 in US/Canada, 36 in Europe/New Zealand) were included, on direct provision of healthful foods/beverages (N = 39 studies), competitive food/beverage standards (N = 29), and school meal standards (N = 39) (some interventions assessed multiple policies). Direct provision policies, which largely targeted fruits and vegetables, increased consumption of fruits by 0.27 servings/d (n = 15 estimates (95%CI: 0.17, 0.36)) and combined fruits and vegetables by 0.28 servings/d (n = 16 (0.17, 0.40)); with a slight impact on vegetables (n = 11; 0.04 (0.01, 0.08)), and no effects on total calories (n = 6; -56 kcal/d (-174, 62)). In interventions targeting water, habitual intake was unchanged (n = 3; 0.33 glasses/d (-0.27, 0.93)). Competitive food/beverage standards reduced sugar-sweetened beverage intake by 0.18 servings/d (n = 3 (-0.31, -0.05)); and unhealthy snacks by 0.17 servings/d (n = 2 (-0.22, -0.13)), without effects on total calories (n = 5; -79 kcal/d (-179, 21)). School meal standards (mainly lunch) increased fruit intake (n = 2; 0.76 servings/d (0.37, 1.16)) and reduced total fat (-1.49%energy; n = 6 (-2.42, -0.57)), saturated fat (n = 4; -0.93%energy (-1.15, -0.70)) and sodium (n = 4; -170 mg/d (-242, -98)); but not total calories (n = 8; -38 kcal/d (-137, 62)). In 17 studies evaluating adiposity, significant decreases were generally not identified; few studies assessed metabolic factors (blood lipids/glucose/pressure), with mixed findings. Significant sources of heterogeneity or publication bias were not identified. CONCLUSIONS: Specific school food environment policies can improve targeted dietary behaviors; effects on adiposity and metabolic risk require further investigation. These findings inform ongoing policy discussions and debates on best practices to improve childhood dietary habits and health

Dearth by a Thousand Cuts? Accounting for Gender Differences in Top-Ranked Publication Rates in Social Psychology

Publication in the Journal of Personality and Social Psychology, a flagship indicator of scientific prestige, shows dramatic gender disparities. A bibliometric analysis included yoked-control authors matched for Ph.D. prestige and cohort. Though women publish less, at slower annual rates, they are more cited in handbooks and textbooks per JPSP-article-published. No gender differences emerged on variables reflecting differential qualifications. Many factors explain gender discrepancy in productivity. Among top publishers, per-year rate and first authorship especially differ by gender; rate uniquely predicts top-male productivity, whereas career-length uniquely predicts top-female productivity. Among men, across top-publishers and controls, productivity correlates uniquely with editorial negotiating and being married. For women, no personal variables predict productivity. A separate inquiry shows tiny gender differences in acceptance rates per JPSP article submitted; discrimination would be a small-but-plausible contributor, absent independent indicators of manuscript quality. Recent productivity rates mirror earlier gender disparities, suggesting gender gaps will continue

'Impossible to Keep': Home Renovation and the Australian Suburban Gothic in Sonya Hartnett's Golden Boys

Australia is in the grip of an obsession with renovation. In contemporary popular culture renovation television programs, books and new media platforms have become “a social phenomenon, one that is both expressive and constructive of social relations”. This essay argues that Sonya Hartnett uses the suburban gothic to subvert conventional representations of renovation that appear in popular culture, which uncritically present renovation as a practice “oriented towards upward mobility through the complete and often radical transformation of bodies, homes and lifestyles”. The figure of the renovator in Sonya‘s Golden Boys (2014) is a pedophile, “that most feared and hated of suburban bogeymen”, whose renovations are designed to draw neighborhood children into his home. One dominant Gothic trope is the decaying castle, manor and, later, suburban house, that threatens to exceed its boundaries. In the novel, renovation is a gothic practice that, while attempting to renew and refresh the Jenson home, sets in motion its inevitable destruction through revealing Rex Jenson’s pedophilia. I contend that Hartnett’s suburban gothic subverts the aspirational appeal of contemporary fascinations with renovation, and situates the renovated house as a significant contemporary gothic site