SNP rs9939609 within the fat mass and obesity associated gene (FTO) is strongly associated with adult body mass index (BMI). However, influences of FTO on longitudinal BMI change from childhood to adulthood have not been examined. Knowledge is limited on FTO, modulating the association between birth weight and longitudinal change of BMI. This longitudinal study examined SNPs of FTO in 658 white subjects from childhood (3-17 years) to adulthood (18-45 years). No significant associations of FTO SNPs with either birth weight or longitudinal BMI over childhood were noted after multiple-test adjustment. However, three SNPs (rs9939609, rs17820875 and rs860713) with different inheritance patterns were identified to be associated with longitudinal BMI over adulthood after Bonferroni adjustment (P = 5.3 × 10(-5), 2.0 × 10(-4) and 0.001). In addition, interactions were discovered between birth weight and SNPs of rs17820875 (P = 0.001) and rs860713 (0.002). A negative association between birth weight and adult BMI were found in risk genotype AG of rs17820875 and GG of rs860713 in contrast to positive associations in other genotypes. These findings led to the conclusion that lower birth weight predisposes to higher adult BMI depending on FTO risk genotypes. Our studies underscore the importance of FTO influences on obesity and provide insights into the evolution of the long-term burden of obesity.
Sleep disorders, autonomic dysfunction, and abnormal cognition are important comorbidities in adult patients with heart failure and are associated with disease progression, morbidity, and mortality. The clinical incidence of these conditions is unknown in children with heart failure. We sought to determine the incidence of symptoms that may be attributable to autonomic dysfunction among children with dilated cardiomyopathy and heart failure. We performed a retrospective chart review of patients with dilated cardiomyopathy seen at our institution between 1999 and 2005. We reviewed charts for symptoms of dysautonomia, sleep problems, or abnormal cognition. From the records of 204 pediatric patients, we identified 69 patients aged 7-18 years with severe dilated cardiomyopathy. Of these, 55 (80%) had symptoms attributable to dysautonomia, 20 (29%) had evidence of sleep disturbance, and 3 (4%) had abnormal cognition. Dysautonomia and sleep disturbances are prevalent in children with heart failure, congruent with studies of adult patients. Based on our data, it is not possible to draw conclusions about any cognitive deficits in this population. Because relatively few subjects' charts explored symptoms of sleep disturbance, we speculate that sleep symptoms may be underappreciated.
IntroductionClinical radiology is a popular career. However, academic radiology in Australia and New Zealand (ANZ) has not traditionally been a strength of the specialty which has a focus on clinical medicine and has been influenced by corporatisation of the specialty. The aim of this study was to review the source(s) of radiologist‐led research in Australia and New Zealand, to identify areas of relative deficiency and propose plans to improve research output.MethodsA manual search was performed of all manuscripts in seven popular ANZ journals, where the corresponding or senior author was a radiologist. Publications between January 2017 and April 2022 were included.ResultsThere were 285 manuscripts from ANZ radiologists during the study period. This equates to 10.7 manuscripts per 100 radiologists based on RANZCR census data. Radiologists in Northern Territory, Victoria, Western Australia, South Australia and the Australian Capital Territory all produced manuscripts above the corrected mean incidence rate of 10.7 manuscripts per 100 radiologists. However, locations including Tasmania, New South Wales, New Zealand and Queensland were below the mean. The majority of manuscripts arose from public teaching hospitals with accredited trainees (86%), and there were a higher proportion of manuscripts published by female radiologists (11.5 compared to 10.4 per 100 radiologists).ConclusionRadiologists in ANZ are academically active; however, interventions aimed at increasing output could be targeted at certain locations and/or areas within a busy private sector. Time, culture, infrastructure and research support are vital, but personal motivation is also extremely important.
The amino acid methionine is highly susceptible to oxidation via reactive oxygen species, resulting in loss of function in proteins containing oxidized methionines. This loss of protein function has been implicated in numerous neurodegenerative and age‐related diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (Lou Gehrig's Disease), emphysema, and arthritis. The enzyme methionine sulfoxide reductase (MsrA) catalyzes the stereospecific reduction of oxidized methionine in free amino acids, peptides, and proteins, restoring function in the latter. The catalytic mechanism of MsrA has been studied extensively, but less is known about how MsrA is able to recognize its large variety of substrates, from single amino acids or small molecules to oxidized methionines in the context of a protein. Earlier work from our lab using intrinsic and extrinsic fluorescence spectroscopy suggests that the presence of sulfoxide group on a methionine in a target protein enhances existing weak hydrophobic interactions with MsrA. The current study builds on these findings using fluorescence spectroscopy to characterize how MsrA of E. coli recognizes its substrates and repairs specific oxidized methionine residues in an intrinsically‐disordered form of staphylococcal nuclease and a nonapeptide derived from it.Support or Funding InformationThis work was supported by a Research Corporation award (grant number CC5482) to VFS. The Office of Naval Research supported Trident Scholar research by JS. MJW was supported by a Garrigues Program scholarship award.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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