Two candidate Quantitative Trait Loci ( QTL ) (74.47- 75.33Mb; 80.20- 83.83Mb) and three potential candidate genes (ZBTB40, CNR2, and Lin28a ) of porcine BMD were detected in this study. © The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science.BACKGROUND Dopamine D1 receptor (D1R) signaling plays key roles in core domains of neural function, including cognition and reward processing; however, many questions remain about the functions of circuits modulated by D1R, largely because clinically viable, selective agonists have yet to be tested in humans. METHODS Using a novel, exploratory neurofunctional domains study design, we assessed the safety, tolerability, pharmacodynamics, and pharmacokinetics of PF-06412562, a selective D1/D5R partial agonist, in healthy male volunteers who met pre-specified criteria for low working memory capacity. Functional magnetic resonance imaging, electrophysiologic endpoints, and behavioral paradigms were used to assess working memory, executive function, and motivation/reward processing following multiple-dose administration of PF-06412562. A total of 77 subjects were assigned PF-06412562 (3 mg twice daily [BID] and 15 mg BID) or placebo, administered for 5 to 7 days. Due to the exploratory nature of the study, it was neither powered for any specific treatment effect nor corrected for multiple comparisons. RESULTS Nominally significant improvements from baseline in cognitive endpoints were observed in all 3 groups; however, improvements in PF-06412562-treated subjects were less than in placebo-treated subjects. Motivation/reward processing endpoints were variable. PF-06412562 was safe and well tolerated, with no serious adverse events (AEs), severe AEs, or AEs leading to dose reduction or temporary discontinuation, except for 1 permanent discontinuation due to increased orthostatic heart rate. CONCLUSIONS PF-06412562, in the dose range and patient population explored in this study, did not improve cognitive function or motivation/reward processing more than placebo over the 5- to 7-day treatment period.ClinicalTrials.gov Identifier NCT02306876. © The Author(s) 2020. Published by Oxford University Press on behalf of CINP.BACKGROUND Many patients with rheumatoid arthritis (RA) report symptom relief from certain foods. Earlier research indicates positive effects of food and food components on clinical outcomes in RA, but insufficient evidence exists to provide specific dietary advice. Food components may interact but studies evaluating combined effects are lacking. OBJECTIVES We aimed to investigate if an anti-inflammatory diet reduces disease activity in patients with RA. METHODS In this single-blinded crossover trial, 50 patients with RA were randomly assigned to an intervention diet containing a portfolio of suggested anti-inflammatory foods, or a control diet similar to the general dietary intake in Sweden, for 10 wk. After a 4-mo washout period the participants switched diet. Food equivalent to ∼50% of energy requirements was delivered weekly to their homes. For the remaining meals, they were encouraged to consume the same type of foods as the ones provided during each diet. Primary outcome was change in Disease Activity Setermine if this diet can cause clinically relevant improvements.This trial was registered at clinicaltrials.gov as NCT02941055. Copyright © The Author(s) 2020.Interactions among microorganisms and their mineralogical substrates govern the structure, function and emergent properties of microbial communities. These interactions are predicated on spatial relationships, which dictate metabolite exchange and access to key substrates. To quantitatively assess links between spatial relationships and metabolic activity, this study presents a novel approach to map all organisms, the metabolically active subset and associated mineral grains, all while maintaining spatial integrity of an environmental microbiome. We applied this method at an outgassing fumarole of Vanuatu’s Marum Crater, one of the largest point sources of several environmentally relevant gaseous compounds, including H2O, CO2 and SO2. With increasing distance from the sediment-air surface and from mineral grain outer boundaries, organism abundance decreased but the proportion of metabolically active organisms often increased. These protected niches may provide more stable conditions that promote consistent metabolic activity of a streamlined community. Conversely, exterior surfaces accumulate more organisms that may cover a wider range of preferred conditions, implying that only a subset of the community will be active under any particular environmental regime. More broadly, the approach presented here allows investigators to see microbial communities ‘as they really are’ and explore determinants of metabolic activity across a range of microbiomes. © FEMS 2020.Covering up to the end of 2019Iron- and α-ketoglutarate-dependent dioxygenases (Fe/αKGs) represent a versatile and intriguing enzyme family by virtue of their ability to directly functionalize unactivated C-H bonds at the cost of αKG and O2. Fe/αKGs play an important role in the biosynthesis of natural products, valuable biologically active secondary metabolites frequently pursued as drug leads. The field of natural product total synthesis seeks to contruct these molecules as effeciently as possible, although natural products continue to challenge chemists due to their intricate structural complexity. selleck kinase inhibitor Chemoenzymatic approaches seek to remedy the shortcomings of traditional synthetic methodology by combining Nature’s biosynthetic machinery with traditional chemical methods to efficiently construct natural products. Although other oxygenase families have been widely employed for this purpose, Fe/αKGs remain underutilized. The following review will cover recent chemoenzymatic total syntheses involving Fe/αKG enzymes. Additionally, related information involving natural product biosynthesis, methods development, and non-chemoenzymatic total syntheses will be discussed to inform retrosynthetic logic and synthetic design.