New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

REACTION-DIFFUSION MODELLING WITHIN COMPLEX BIOLOGICAL DOMAINS

Ph.DDOCTOR OF PHILOSOPHY (FOS-MBI

A Rare but Important Clinical Presentation of Induced Methemoglobinemia

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Activation of butterfly eyespots by Distal-less is consistent with a reaction-diffusion process

10.1242/dev.169367DEVELOPMENT146

Bicyclus_anynana_Wildtype_dorsal

Eyespots image of Bicyclus anynana Wildtype dorsal sid

exon 3 mutants

Images for Exon 3 mutant

exon 2 mutants

Images for Exon 2 mutant

Bicyclus_anynana_Wildtype_Ventral

Eyespots image of Bicyclus anynana Wildtype dorsal sid

A Rare but Important Clinical Presentation of Induced Methemoglobinemia

Phenazopyridine is considered one of the classic causes of drug-induced methemoglobinemia. It is often taught as such and seen in board review courses. Nevertheless, the epidemiology is unknown, presentation quite rare, and less than five cases have been reported in PubMed in over 35 years.1-4 We present a case with a different set of patient characteristics than seen in the few recent case reports, and an approach to treatment that validates further uniqueness, justifying reporting the case in the literature. In particular, the patient was a young otherwise-healthy adult, with the initial diagnosis and decision to treat based on clinical grounds versus laboratory values.

Data from: Distal-less activates butterfly eyespots consistent with a reaction diffusion process

Eyespots on the wings of nymphalid butterflies represent colorful examples of pattern formation, yet the developmental origins and mechanisms underlying eyespot center differentiation are still poorly understood. Using CRISPR-Cas9 we re-examine the function of Distal-less (Dll) as an activator or repressor of eyespots, a topic that remains controversial. We show that the phenotypic outcome of CRISPR mutations depends upon which specific exon is targeted. In Bicyclus anynana, exon 2 mutations are associated with both missing and ectopic eyespots and also exon-skipping. Exon 3 mutations, which do not lead to exon-skipping, produce only null phenotypes including missing eyespots, lighter wing coloration and loss of scales. Reaction-diffusion modeling of Dll function, using Wnt and Dpp as candidate morphogens, accurately replicates these complex crispant phenotypes. These results provide new insight into the function of Dll as a potential activator of eyespot development, scale growth, and melanization, and suggest that the tuning of Dll expression levels can generate a diversity of eyespot phenotypes, including their appearance on the wing