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PurposeSome species of fish and seafood are high in trimethylamine N-oxide (TMAO), which accumulates in muscle where it protects against pressure and cold. Trimethylamine (TMA), the metabolic precursor to TMAO, is formed in fish during bacterial spoilage. Fish intake is promoted for its potential cardioprotective effects. However, numerous studies show TMAO has pro-atherothrombotic properties. Here, we determined the effects of fish or seafood consumption on circulating TMAO levels in participants with normal renal function.MethodsTMAO and omega-3 fatty acid content were quantified across multiple different fish or seafood species by mass spectrometry. Healthy volunteers (n = 50) were recruited for three studies. Participants in the first study consented to 5 consecutive weekly blood draws and provided dietary recall for the 24 h preceding each draw. In the second study, TMAO levels were determined following defined low and high TMAO diets. Finally, participants consumed test meals containing shrimp, tuna, fish sticks, salmon or cod. TMAO levels were quantified by mass spectrometry in blood collected before and after dietary challenge.ResultsTMAO + TMA content varied widely across fish and seafood species. Consumption of fish sticks, cod, and to a lesser extent salmon led to significant increases in circulating TMAO levels. Within 1 day, circulating TMAO concentrations in all participants returned to baseline levels.ConclusionsWe conclude that some fish and seafood contain high levels of TMAO, and may induce a transient elevation in TMAO levels in some individuals. Selection of low TMAO content fish is prudent for subjects with elevated TMAO, cardiovascular disease or impaired renal function.

The heightened cardiovascular disease (CVD) risk observed among omnivores is thought to be linked, in part, to gut microbiota-dependent generation of trimethylamine- N -oxide (TMAO) from l -carnitine, a nutrient abundant in red meat. Gut microbial transformation of l -carnitine into trimethylamine (TMA), the precursor of TMAO, occurs via the intermediate γ-butyrobetaine (γBB). However, the interrelationship of γBB, red meat ingestion and CVD risks, as well as the gut microbial genes responsible for the transformation of γBB to TMA, are unclear. In the present study, we show that plasma γBB levels in individuals from a clinical cohort ( n  = 2,918) are strongly associated with incident CVD event risks. Culture of human faecal samples and microbial transplantation studies in gnotobiotic mice with defined synthetic communities showed that the introduction of Emergencia timonensis , a human gut microbe that can metabolize γBB into TMA, is sufficient to complete the carnitine → γBB → TMA transformation, elevate TMAO levels and enhance thrombosis potential in recipients after arterial injury. RNA-sequencing analyses of E. timonensis identified a six-gene cluster, herein named the γBB utilization ( gbu ) gene cluster, which is upregulated in response to γBB. Combinatorial cloning and functional studies identified four genes ( gbuA , gbuB , gbuC and gbuE ) that are necessary and sufficient to recapitulate the conversion of γBB to TMA when coexpressed in Escherichia coli . Finally, reanalysis of samples ( n  = 113) from a clinical, randomized diet, intervention study showed that the abundance of faecal gbuA correlates with plasma TMAO and a red meat-rich diet. Our findings reveal a microbial gene cluster that is critical to dietary carnitine → γBB → TMA → TMAO transformation in hosts and contributes to CVD risk. The gbu gene cluster, present in the human gut microbiota member Emergencia timonensis , converts γ-butyrobetaine (γBB) to trimethylamine in the conversion of dietary l -carnitine, which is found in red meat, to the proatherosclerotic metabolite trimethylamine- N -oxide. Individuals with high plasma γBB levels had increased risk of cardiovascular events.

Two experiments assessed how racial ambiguity and racial salience moderates the cross-race effect (CRE). In experiment 1, White and Black participants studied and identified the race of Asian, Black, Latino, and White faces that varied in ethnic typicality (high or low ET). For White participants, the CRE was larger when comparing high-ET White faces to high-ET other-race faces than low-ET other-race faces. Black participants showed a similar CRE reduction by ethnic typicality, but also showed a less prevalent CRE than White participants. Experiment 2 replicated experiment 1 procedures, but without the race identification task and only with White participants. Experiment 2 findings were comparable to experiment 1. Furthermore, experiment 2 showed a noticeably smaller CRE on Black faces than experiment 1, eliciting questions about increased racial salience amplifying the CRE. Results’ general implications and the conceptual roots that indirectly link the CRE and racism will be discussed.

This project seeks to provide a glimpse into the impact of academic labels on student veterans via the student veterans' own voices. This project reflects on and builds from previous research projects that involve transition theories and pedagogical theories in the field of writing studies as well as veteran studies that involve student veterans. Through a locally situated multi-case study qualitative approach using questionnaires and interviews, I examine to what extent do academic labels have on student veterans from the student veterans’ own voices. Finally, I offer implications of this project for writing instructors, administrators, and future researchers involving student veterans.

This work is intended to explore and analyze the process of transition from one discourse to another different discourse.

The Department of Justice is finding increasingly more to say these days about the District's correctional system. Closely following Deputy Attorney General Lowell Jensen's announcement that the District of Columbia needs two new prisons, his colleague, Assistant Attorney General Lois Haight Herrington, poses a pointed question: \"Do We Have Enough Prisons?\" [Free for All, Feb. 15].

Amblyomma americanum Linnaeus (Ixodida: Ixodidae) is ubiquitously present throughout the southeastern United States and is capable of vectoring several pathogens. White-tailed deer are the main host for adult A. americanum. However, this tick species is a generalist that will feed on most vertebrates, including humans, deer, livestock, and pets. Management of this species can be challenging due to a lack of cost-effective strategies. Acaricides are often utilized, however, this may lead to pesticide resistance. The Food and Agriculture Organization of the United Nations (FAO) larval packet test (LPT) was performed on susceptible A. americanum to determine the lethal concentration (LC) and discriminating concentration (DC) values for permethrin. The FAO LPT was used at these pre-established values to compare levels of resistance in ticks collected from a captive deer farm and wild areas representing high and low permethrin exposure settings, respectively. Resistance ratios (RR) calculated from the LC values for the ticks collected from farmed and wild deer ranged between 1 and 2. A. americanum collected from farmed and wild deer were not found to be resistant, however, some samples had slightly elevated RRs as compared to the susceptible laboratory strain, which may suggest tolerance development. Although the A. americanum sampled in this study were not resistant to permethrin, the DC calculated in this study will allow for rapid evaluation of resistance in a permethrin resistance monitoring program such that alternate management strategies can be adopted if resistance is detected.

Background: Medication-related problems (MRPs) occur across the continuum of emergency department (ED) care: they may contribute to ED presentation, occur in the ED/short-stay unit (SSU), at hospital admission, or shortly after discharge to the community. This project aimed to determine predictors for MRPs across the continuum of ED care and incorporate these into screening tools (one for use at ED presentation and one at ED/SSU discharge), to identify patients at greatest risk, who could be targeted by ED pharmacists. Methods: A prospective, observational, multicenter study was undertaken in nine EDs, between July 2016 and August 2017. Blocks of ten consecutive adult patients presenting at pre-specified times were identified. Within 1 week of ED discharge, a pharmacist interviewed patients and undertook a medical record review to determine a medication history, patient understanding of treatment, risk factors for MRPs and to manage the MRPs. Logistic regression was undertaken to determine predictor variables. Multivariable regression beta coefficients were used to develop a scoring system for the two screening tools. Results: Of 1,238 patients meeting all inclusion criteria, 904 were recruited. Characteristics predicting MRPs related to ED presentation were: patient self-administers regular medications (OR = 7.95, 95%CI = 3.79–16.65), carer assists with medication administration (OR = 15.46, 95%CI = 6.52–36.67), or health-professional administers (OR = 5.01, 95%CI = 1.77–14.19); medication-related ED presentation (OR = 9.95, 95%CI = 4.92–20.10); age ≥80 years (OR = 3.63, 95%CI = 1.96–6.71), or age 65–79 years (OR = 2.01, 95%CI = 1.17–3.46); potential medication adherence issue (OR = 2.27, 95%CI = 1.38–3.73); medical specialist seen in past 6-months (OR = 2.02, 95%CI = 1.42–2.85); pharmaceutical benefit/pension/concession cardholder (OR = 1.89, 95%CI = 1.28–2.78); inpatient in previous 4-weeks (OR = 1.60, 95%CI = 1.02–2.52); being male (OR = 1.48, 95%CI = 1.05–2.10); and difficulties reading labels (OR = 0.63, 95%CI = 0.40–0.99). Characteristics predicting MRPs related to ED discharge were: potential medication adherence issue (OR = 6.80, 95%CI = 3.97–11.64); stay in ED > 8 h (OR = 3.23, 95%CI = 1.47–7.78); difficulties reading labels (OR = 2.33, 95%CI = 1.30–4.16); and medication regimen changed in ED (OR = 3.91, 95%CI = 2.43–6.30). For ED presentation, the model had a C-statistic of 0.84 (95% CI 0.81–0.86) (sensitivity = 80%, specificity = 70%). For ED discharge, the model had a C-statistic of 0.78 (95% CI 0.73–0.83) (sensitivity = 82%, specificity = 57%). Conclusion: Predictors of MRPs are readily available at the bedside and may be used to screen for patients at greatest risk upon ED presentation and upon ED/SSU discharge to the community. These screening tools now require external validation and implementation studies to evaluate the impact of using such tools on patient care outcomes.

Four different XNAs — polymers with backbone chemistries not found in nature, namely, arabino nucleic acids, 2′-fluoroarabino nucleic acids, hexitol nucleic acids and cyclohexene nucleic acids — are found to be able to support the evolution of synthetic enzymes (XNAzymes) that catalyse several chemical reactions. 'XNAzymes' have catalytic potential The development of nucleic acid catalysis may have been key to the emergence of life on Earth. RNA enzymes retain key functions in living systems, notably in translation and RNA processing, and a various RNA and DNA enzymes have been created by in vitro evolution approaches. Alexander Taylor et al . have now synthesized a series of catalytic polymers using four different backbone chemistries (XNAs) not found in nature. The most efficient XNAzyme, based on 2′-fluoroarabino nucleic acids, was used to generate an in trans RNA endonuclease, an RNA ligase and an XNA–XNA ligase. These results establish technologies for the discovery of catalysts in a wide range of polymer scaffolds not found in nature. The emergence of catalysis in early genetic polymers such as RNA is considered a key transition in the origin of life 1 , pre-dating the appearance of protein enzymes. DNA also demonstrates the capacity to fold into three-dimensional structures and form catalysts in vitro 2 . However, to what degree these natural biopolymers comprise functionally privileged chemical scaffolds 3 for folding or the evolution of catalysis is not known. The ability of synthetic genetic polymers (XNAs) with alternative backbone chemistries not found in nature to fold into defined structures and bind ligands 4 raises the possibility that these too might be capable of forming catalysts (XNAzymes). Here we report the discovery of such XNAzymes, elaborated in four different chemistries (arabino nucleic acids, ANA 5 ; 2′-fluoroarabino nucleic acids, FANA 6 ; hexitol nucleic acids, HNA; and cyclohexene nucleic acids, CeNA 7 ) directly from random XNA oligomer pools, exhibiting in trans RNA endonuclease and ligase activities. We also describe an XNA–XNA ligase metalloenzyme in the FANA framework, establishing catalysis in an entirely synthetic system and enabling the synthesis of FANA oligomers and an active RNA endonuclease FANAzyme from its constituent parts. These results extend catalysis beyond biopolymers and establish technologies for the discovery of catalysts in a wide range of polymer scaffolds not found in nature 8 . Evolution of catalysis independent of any natural polymer has implications for the definition of chemical boundary conditions for the emergence of life on Earth and elsewhere in the Universe 9 .

Cell proliferation and quiescence are intimately coordinated during metazoan development. Here, we adapt a cyclin-dependent kinase (CDK) sensor to uncouple these key events of the cell cycle in Caenorhabditis elegans and zebrafish through live-cell imaging. The CDK sensor consists of a fluorescently tagged CDK substrate that steadily translocates from the nucleus to the cytoplasm in response to increasing CDK activity and consequent sensor phosphorylation. We show that the CDK sensor can distinguish cycling cells in G1 from quiescent cells in G0, revealing a possible commitment point and a cryptic stochasticity in an otherwise invariant C. elegans cell lineage. Finally, we derive a predictive model of future proliferation behavior in C. elegans based on a snapshot of CDK activity in newly born cells. Thus, we introduce a live-cell imaging tool to facilitate in vivo studies of cell-cycle control in a wide-range of developmental contexts. All living things are made up of cells that form the different tissues, organs and structures of an organism. The human body, for example, is thought to consist of some 37 trillion cells and harbor over 200 cell types. To maintain a working organism, cells divide to create new cells and replace the ones that have died. Cell division is a tightly controlled process consisting of several steps, and cells continuously face a Shakespearean dilemma of deciding whether to continue dividing (also known as cell proliferation) or to halt the process (known as quiescence). This difficult balancing act is critical during all stages of life, from embryonic development to tissue growth in an adult. Problems in the underlying pathways can result in diseases such as cancer. Cell division is driven by proteins called CDKs, which help cells to complete their cell cycle in the correct sequence. To gain more insight into this complex process, scientists have developed tools for monitoring CDKs. One such tool is a fluorescent biosensor, a molecule that can be inserted into cells that glows and moves in response to CDK activity. The biosensor can be studied and measured in each cell using a microscope. Adikes, Kohrman, Martinez et al. adapted and optimized an existing CDK biosensor to help study cell division and the switch between proliferation and quiescence in two common research organisms, the nematode Caenorhabditis elegans and the zebrafish. Analysis of this biosensor showed that CDK activity at the end of cell division is higher if the cells will divide again but is low if the cells are going to become quiescent. This could suggest that the decision of a cell between proliferation and quiescence may happen earlier than expected. The optimized biosensor is sensitive enough to detect these differences and can even measure variations that influence proliferation in a region on C. elegans that was once thought to be unchanging. The development of this biosensor provides a useful research tool that could be used in other living organisms. Many research questions relate to cell division and so the applications of this tool are wide ranging.