Profiles in Science: John Bennett Fenn

“Don’t ever try to be a scientist or engineer!” Had John Bennett Fenn listened to this advice given by his ninth grade teacher, he might not have gone on to pursue a career in analytical chemistry which would culminate in the attainment of the Nobel Prize in 2002. Gathered from interviews, publication analyses, glowing tributes, and his reminiscences, this paper outlines the academic and professional life of John Fenn from childhood through the end of his career in 2010

Use of Complementary and Alternative Medicine Among Patients With Arthritis

Introduction: Previous studies suggest that people with arthritis have high rates of using complementary and alternative medicine (CAM) approaches for managing their arthritis, in addition to conventional treatments such as prescription medications. However, little is known about the use of CAM by diagnosis, or which forms of CAM are most frequently used by people with arthritis. This study was designed to provide detailed information about use of CAM for symptoms associated with arthritis in patients followed in primary care and specialty clinics in North Carolina. Methods: Using a cross-sectional design, we drew our sample from primary care (n = 1,077) and specialist (n = 1,063) physician offices. Summary statistics were used to calculate differences within and between diagnostic groups, practice settings, and other characteristics. Logistic regression models clustered at the site level were used to determine the effect of patient characteristics on ever and current use of 9 CAM categories and an overall category of "any use." Results: Most of the participants followed by specialists (90.5%) and a slightly smaller percentage of those in the primary care sample (82.8%) had tried at least 1 complementary therapy for arthritis symptoms. Participants with fibromyalgia used complementary therapies more often than those with rheumatoid arthritis, osteoarthritis, or chronic joint symptoms. More than 50% of patients in both samples used over-the-counter topical pain relievers, more than 25% used meditation or drew on religious or spiritual beliefs, and more than 19% used a chiropractor. Women and participants with higher levels of education were more likely to report current use of alternative therapies. Conclusion: Most arthritis patients in both primary care and specialty settings have used CAM for their arthritis symptoms. Health care providers (especially musculoskeletal specialists) should discuss these therapies with all arthritis patients

Bridging topological and functional information in protein interaction networks by short loops profiling

Protein-protein interaction networks (PPINs) have been employed to identify potential novel interconnections between proteins as well as crucial cellular functions. In this study we identify fundamental principles of PPIN topologies by analysing network motifs of short loops, which are small cyclic interactions of between 3 and 6 proteins. We compared 30 PPINs with corresponding randomised null models and examined the occurrence of common biological functions in loops extracted from a cross-validated high-confidence dataset of 622 human protein complexes. We demonstrate that loops are an intrinsic feature of PPINs and that specific cell functions are predominantly performed by loops of different lengths. Topologically, we find that loops are strongly related to the accuracy of PPINs and define a core of interactions with high resilience. The identification of this core and the analysis of loop composition are promising tools to assess PPIN quality and to uncover possible biases from experimental detection methods. More than 96% of loops share at least one biological function, with enrichment of cellular functions related to mRNA metabolic processing and the cell cycle. Our analyses suggest that these motifs can be used in the design of targeted experiments for functional phenotype detection.This research was supported by the Biotechnology and Biological Sciences Research Council (BB/H018409/1 to AP, ACCC and FF, and BB/J016284/1 to NSBT) and by the Leukaemia & Lymphoma Research (to NSBT and FF). SSC is funded by a Leukaemia & Lymphoma Research Gordon Piller PhD Studentship

A randomized, comparative pilot trial of family-based interpersonal psychotherapy for reducing psychosocial symptoms, disordered-eating, and excess weight gain in at-risk preadolescents with loss-of-control-eating: SHOMAKER et al.

Preadolescent loss-of-control-eating (LOC-eating) is a risk factor for excess weight gain and binge-eating-disorder. We evaluated feasibility and acceptability of a preventive family-based interpersonal psychotherapy (FB-IPT) program. FB-IPT was compared to family-based health education (FB-HE) to evaluate changes in children’s psychosocial functioning, LOC-eating, and body mass

Projecting ocean acidification impacts for the Gulf of Maine to 2050: new tools and expectations

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Siedlecki, S. A., Salisbury, J., Gledhill, D. K., Bastidas, C., Meseck, S., McGarry, K., Hunt, C. W., Alexander, M., Lavoie, D., Wang, Z. A., Scott, J., Brady, D. C., Mlsna, I., Azetsu-Scott, K., Liberti, C. M., Melrose, D. C., White, M. M., Pershing, A., Vandemark, D., Townsend, D. W., Chen, C,. Mook, W., Morrison, R. Projecting ocean acidification impacts for the Gulf of Maine to 2050: new tools and expectations. Elementa: Science of the Anthropocene, 9(1), (2021): 00062, https://doi.org/10.1525/elementa.2020.00062.Ocean acidification (OA) is increasing predictably in the global ocean as rising levels of atmospheric carbon dioxide lead to higher oceanic concentrations of inorganic carbon. The Gulf of Maine (GOM) is a seasonally varying region of confluence for many processes that further affect the carbonate system including freshwater influences and high productivity, particularly near the coast where local processes impart a strong influence. Two main regions within the GOM currently experience carbonate conditions that are suboptimal for many organisms—the nearshore and subsurface deep shelf. OA trends over the past 15 years have been masked in the GOM by recent warming and changes to the regional circulation that locally supply more Gulf Stream waters. The region is home to many commercially important shellfish that are vulnerable to OA conditions, as well as to the human populations whose dependence on shellfish species in the fishery has continued to increase over the past decade. Through a review of the sensitivity of the regional marine ecosystem inhabitants, we identified a critical threshold of 1.5 for the aragonite saturation state (Ωa). A combination of regional high-resolution simulations that include coastal processes were used to project OA conditions for the GOM into 2050. By 2050, the Ωa declines everywhere in the GOM with most pronounced impacts near the coast, in subsurface waters, and associated with freshening. Under the RCP 8.5 projected climate scenario, the entire GOM will experience conditions below the critical Ωa threshold of 1.5 for most of the year by 2050. Despite these declines, the projected warming in the GOM imparts a partial compensatory effect to Ωa by elevating saturation states considerably above what would result from acidification alone and preserving some important fisheries locations, including much of Georges Bank, above the critical threshold.This research was financially supported by the Major Special Projects of the Ministry of Science and Technology of China (2016YFC020600), the Young Scholars Science Foundation of Lanzhou Jiaotong University (2018033), and the Talent Innovation and Entrepreneurship Projects of Lanzhou (2018-RC-84)

Phagocytosis in the retina promotes local insulin production in the eye

The retina is highly metabolically active, relying on glucose uptake and aerobic glycolysis. Situated in close contact to photoreceptors, a key function of cells in the retinal pigment epithelium (RPE) is phagocytosis of damaged photoreceptor outer segments (POS). Here we identify RPE as a local source of insulin in the eye that is stimulated by POS phagocytosis. We show that Ins2 messenger RNA and insulin protein are produced by RPE cells and that this production correlates with RPE phagocytosis of POS. Genetic deletion of phagocytic receptors (‘loss of function’) reduces Ins2, whereas increasing the levels of the phagocytic receptor MerTK (‘gain of function’) increases Ins2 production in male mice. Contrary to pancreas-derived systemic insulin, RPE-derived local insulin is stimulated during starvation, which also increases RPE phagocytosis. Global or RPE-specific Ins2 gene deletion decreases retinal glucose uptake in starved male mice, dysregulates retinal physiology, causes defects in phototransduction and exacerbates photoreceptor loss in a mouse model of retinitis pigmentosa. Collectively, these data identify RPE cells as a phagocytosis-induced local source of insulin in the retina, with the potential to influence retinal physiology and disease

Diagnosis of lethal or prenatal-onset autosomal recessive disorders by parental exome sequencing.

OBJECTIVE: Rare genetic disorders resulting in prenatal or neonatal death are genetically heterogeneous, but testing is often limited by the availability of fetal DNA, leaving couples without a potential prenatal test for future pregnancies. We describe our novel strategy of exome sequencing parental DNA samples to diagnose recessive monogenic disorders in an audit of the first 50 couples referred. METHOD: Exome sequencing was carried out in a consecutive series of 50 couples who had 1 or more pregnancies affected with a lethal or prenatal-onset disorder. In all cases, there was insufficient DNA for exome sequencing of the affected fetus. Heterozygous rare variants (MAF < 0.001) in the same gene in both parents were selected for analysis. Likely, disease-causing variants were tested in fetal DNA to confirm co-segregation. RESULTS: Parental exome analysis identified heterozygous pathogenic (or likely pathogenic) variants in 24 different genes in 26/50 couples (52%). Where 2 or more fetuses were affected, a genetic diagnosis was obtained in 18/29 cases (62%). In most cases, the clinical features were typical of the disorder, but in others, they result from a hypomorphic variant or represent the most severe form of a variable phenotypic spectrum. CONCLUSION: We conclude that exome sequencing of parental samples is a powerful strategy with high clinical utility for the genetic diagnosis of lethal or prenatal-onset recessive disorders. © 2017 The Authors Prenatal Diagnosis published by John Wiley & Sons Ltd

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN