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Large exports of land-based contaminants to the ocean exacerbate the effects of climate change, pollute ocean waters, disrupt biogeochemical cycles, harm marine organisms, and consequently jeopardise food security and the livelihoods of ocean-dependent communities. The Canary Current Large Marine Ecosystem (CCLME) is characterised by a mix of the Atlantic Ocean basin waters, reverse flow from the Mediterranean Sea, and inland waters from adjacent countries. This biodiversity-rich ecosystem is a source of ecosystem goods and services that provide sustenance for populations in the coastal states of West Africa and beyond. However, with the ocean surface warming, ocean productivity and fisheries’ outputs have declined across multiple trophic levels. Therefore, in this diagnostic study based on a systematic literature review (publications from 2009 to 2020), we (a) provide an integrative assessment of the CCLME with the exception of Morocco, in the context of the modular large marine ecosystem framework using the categories ‘environmental’ (productivity, fish and fisheries, pollution, and ecosystem health) and ‘non-environmental’ (socioeconomic and governance), and (b) identify knowledge gaps and data scarce regions. The key drivers of change in the CCLME were identified as fishing pressure, land-based pollution, coastal habitat loss, and climate change. Productivity, land-based pollution, and ecosystem health were priority areas for data collection in the CCLME, with data deficiencies particularly apparent in The Gambia and Guinea. Therefore, to mitigate further degradation and accelerate progress toward sustainable management of the CCLME, research should be conducted in these priority areas of data deficiency. Furthermore, as most drivers of change in this ecosystem are related to weak management and a lack of regulatory enforcement, we recommend effective implementation, monitoring, and enforcement of existing national and transboundary regulations, as well as ecosystem-based human-centred management approaches, as proactive strategies for decoupling anthropogenic disturbances from climate change and optimising the productivity of the CCLME.

OZDRAVLJENIK Šta! "Van opasnosti?" Može li uobražena dama Ili nagnuti farisej prestati klevetati? Neće li me izdaja više milovati po ruci, Niti mržnja vrebati me oko vrata? – Nezahvalnost, uz otkazane beneficije, Nije zatvorila puni dlan da napravi pesnicu? Hoće li se zavist ne uzvraćati Za vrline na koje se bilo uzaludno ugledati?

BackgroundViral suppression among people living with HIV (PLHIV) is essential for protecting health and preventing HIV transmission, yet globally, rates of viral suppression are sub-optimal. Interventions to improve HIV prevention and care cascade outcomes remain vital. Financial incentives hold promise for improving these outcomes, yet to date, clinical trial results have been mixed.MethodsThis qualitative sub-study, embedded in a trial (NCT02890459) in Uganda to test whether incentives are effective for achieving viral suppression in PLHIV, sought to enhance our understanding of the factors that influence this outcome. Forty-nine (n = 49) PLHIV, purposely sampled to balance across gender, study arm, and viral suppression status, were interviewed to explore barriers and motivations for care engagement, adherence, and viral suppression, and attributions for decision-making, including perceived influence of incentives on behaviors.ResultsWhile many participants with undetectable viral load (VL) who received incentives said the incentives motivated their ART adherence, others expressed intrinsic motivation for adherence. All felt that incentives reduced burdens of transport costs, lost income due to time spent away from work, and food insecurity. Incentives may have activated attention and memory for some, as excitement about anticipating incentives helped them adhere to medication schedules. In comparison, participants who were randomized to receive incentives but had detectable VL faced a wider range, complexity and severity of challenges to care engagement. Notably, their narratives included more accounts of poor treatment in clinics, food insecurity, and severe forms of stigma. With or without incentives, adherence was reinforced through experiencing restored health due to ART, social support (especially from partners), and good quality counseling and clinical care.ConclusionsIn considering why incentives sometimes fail to achieve behavior change, it may be helpful to attend to the full set of factors- psychological, interpersonal, social and structural- that militate against the behavior change required to achieve behavioral outcomes. To be effective, incentives may need to be combined with other interventions to address the spectrum of barriers to care engagement.

Abstract Background Few studies have explored how economic incentives influence behavioral outcomes. This study aimed to identify pathways of action of an incentives-based intervention to increase men’s participation in HIV testing. Methods The qualitative study was embedded in a randomized-controlled trial that compared effectiveness of gain-framed, loss-framed and lottery-based incentives to increase HIV testing among men. Following testing at a community health campaign, 60 in-depth interviews were conducted with men systematically sampled on the basis of age, incentive group, and campaign attendance. Data were coded deductively and inductively for thematic content analysis. Results Incentives addressed men’s structural, interpersonal and individual-level barriers to testing: offered at convenient locations, incentives offset costs of testing, in lost wages, which are exacerbated when livelihoods required mobility. Interpersonal barriers included anticipated stigma/fear of disclosure, social obligations, and negative peer influences. Providing incentives in public settings provided “social proof” that prizes could be won, and facilitated social support and positive norms by promoting testing with trusted others. Incentives had little influence when men appraised prize values to be low, disbelieved they would win a prize, or were already intrinsically motivated to test. Yet, incentives provided a behavioral ‘cue to action’ for many men who perceived themselves to be susceptible to HIV and perceived HIV disease to be severe, acting as secondary motivator for testing that “sweetened the deal”. Conclusion Incentives can be an important ‘lever’ to promote men’s healthy behaviors in resource-poor settings. HIV testing in convenient, public settings, when paired with incentives, provides multiple pathways to stimulate men’s testing uptake. Trial registration Registered with ClinicalTrials.gov on 08/10/2016, ID: NCT02890459. The first participant was enrolled on 11th April 2016.

Abstract Background It is widely accepted that crop yields will be affected by climate change. However, the role played by climate in affecting crop yields vis-a-vis non-climatic stresses, is often unclear, limiting decision choices around efforts to promote increased production in light of multiple stresses. Results This study quantifies the role of climatic and non-climatic factors affecting multiple crop yields in Uganda, utilizing a systematic approach which involves the use of a two-stage multiple linear regression to identify and characterize the most important drivers of crop yield, examine the location of the key drivers, identify the socio-economic implications of the drivers and identify policy options to enhance agricultural production. We find that non-climatic drivers of crop yields such as forest area dynamics (p = 0.012), wood fuel (p = 0.032) and usage of tractors (0.041) are more important determinants of crop yields than climatic drivers such as precipitation, temperature and CO2 emissions from forest clearance. Climatic drivers are found to multiply existing risks facing production, the significance of which is determined by variability and inadequate distribution of precipitation over the crop growing seasons. Conclusion The significance and validity of these results is observed in an f-statistic of 50 for the final optimized model when compared to the initial model with an f-statistic of 19.3. Research and agricultural policies have to be streamlined to include not only the climatic elements but also the non-climatic drivers of global, regional and national agricultural systems.

INTRODUCTION: Testicular self-examination (TSE) is a screening technique that involves inspection of the appearance and palpation of the testes to detect any changes from the normal. Globally, the incidence of cancer has increased among which is testicular cancer (TC). Data on this topic among male secondary school adolescents in Uganda is limited therefore this study sought to assess the knowledge and practice of testicular self-examination among secondary students at Ntare School, Mbarara District in south western Uganda. The objective of the study is to assess the knowledge and practice of testicular self-examination among secondary students at Ntare School in Mbarara district, south western Uganda. METHODS: we conducted a descriptive cross-sectional quantitative study among 165 students. Recruitment was made using simple random sampling technique. Respondents were selected among advanced level (A level) male students studying at Ntare School in Mbarara district, south western Uganda. Structured self-administered questionnaires was used for data collection.

Efforts to support the building of resilient pastoralism have been stepped up in Uganda through a number of activities. One of the activity is the provision of seasonal and medium-range climate forecasts to enable decisions concerning livestock herding. Seasonal weather forecasts are critical but there are challenges of timeliness and usability of the forecasts. The challenges are associated with the multiplicity of information sources, methods for data integration and dissemination channels. Institutions including public and Civil Society Organizations usually invest in collecting weather and other data which should be accessible. Often times this data remains hoarded necessitating other organizations to collect similar data. The inter-institutional relations notwithstanding, the lack of data sharing leads to minimal data available for open access. This paper illustrates that this challenge can be addressed by using combined multiple methods to elicit data on weather and other biophysical conditions for pastoralism in Karamoja. In this paper we additionally analyse the opportunities and challenges of using multiple sources of pastoral-relevant data to couple with weather information in support of herding decisions. Building resilient pastoralism that utilizes pasture and water availability will have to utilize available data. It is evident that more robust approaches for data sharing at global, regional and local levels are needed to understand how pastoralists can respond to climate shocks and changes. The paper illustrates the use of a multifaceted-methods approach including open data to develop climate forecast information for risk-reduction oriented information for decision-making. Integration of this data provides insights on how pastoralists have long adapted to a variable and changing climate, the methods and processes of adaptation to losses and damages from the climate shocks.

Viologen-based covalent organic networks represent a burgeoning class of materials distinguished by their captivating properties. Here, supramolecular chemistry is harnessed to fabricate polyrotaxanated ionic covalent organic polymers (iCOP) through a Schiff-base condensation reaction under solvothermal conditions. The reaction between 1,1'-bis(4-aminophenyl)-[4,4'-bipyridine]-1,1'-diium dichloride (DPV-NH 2 ) and 1,3,5-triformylphloroglucinol (TPG) in various solvents yields an iCOP-1 and iCOP-2. Likewise, employing cucurbit[7]uril (CB[7]) in the reaction yielded polyrotaxanated iCOPs, denoted as iCOP-CB[7]-1 and iCOP-CB[7]-2. All four iCOPs exhibit exceptional stability under the acidic and basic conditions. iCOP-CB[7]-2 displays outstanding electrocatalytic Oxygen Evolution Reaction (OER) performance, demanding an overpotential of 296 and 332 mV at 10 and 20 mA cm -2 , respectively. Moreover, the CB[7] integrated iCOP-2 exhibits a long-term stable nature for 30 h in 1 m KOH environment. Further, intrinsic activity studies like TOF show a 4.2-fold increase in generation of oxygen (O 2 ) molecules than the bare iCOP-2. Also, it is found that iCOP-CB[7]-2 exhibits a high specific (19.48 mA cm -2 ) and mass activity (76.74 mA mg -1 ) at 1.59 V versus RHE. Operando-EIS study evident that iCOP-CB[7]-2 commences OER at a relatively low applied potential of 1.5 V versus RHE. These findings pave the way for a novel approach to synthesizing various mechanically interlocked molecules through straightforward solvothermal conditions., (© 2024 Wiley‐VCH GmbH.)

The complexation behaviour of Diphenyl viologens (DPVs) with Cucurbit[n]urils (CB[n]) was evaluated in detail and the results were reported. In this work, we present the synthesis of various DPVs functionalised with electron withdrawing and electron donating groups (EWGs & EDGs) and investigate their complexation behaviour with CB[7] and CB [8]. Carboxylic acid functionalized DPV's (DPV-COOH) complexation with CB[8] gives additional insights, i.e., indicates hydrogen bonding plays an effective role in the complexation. The formation of a 2:2 quaternary complex of DPV-COOH/CB[8] under neutral pH conditions was supported by various analytical techniques. The complexation of DPVs with CB[7] specifies that irrespective of the functional group attached, they all form a 1:2 ternary complex, but the findings elaborate that the pattern followed in the complexation depends on the EW or EDG attached to the DPVs. The competition experiments conducted between functionalized DPVs and CB[7], CB[8] shows that they have more affinity towards CB[8] than CB[7] because of the better macrocyclic confinement effect of CB[8], as confirmed using UV-Vis spectroscopy. The binding affinity among EWG and EDG functionalised DPVs with CB[8] concludes EDG functionalised DPVs show better affinity towards CB[8], because they can form a charge transfer complex inside the CB[8] cavity. Exploring these host-guest interactions in more complex biological or environmental settings and studying their impact on the functionality of DPVs could be an exciting avenue for future research., (© 2024. The Author(s).)

PIFE was first used as an acronym for protein-induced fluorescence enhancement, which refers to the increase in fluorescence observed upon the interaction of a fluorophore, such as a cyanine, with a protein. This fluorescence enhancement is due to changes in the rate of cis / trans photoisomerisation. It is clear now that this mechanism is generally applicable to interactions with any biomolecule. In this review, we propose that PIFE is thereby renamed according to its fundamental working principle as photoisomerisation-related fluorescence enhancement, keeping the PIFE acronym intact. We discuss the photochemistry of cyanine fluorophores, the mechanism of PIFE, its advantages and limitations, and recent approaches to turning PIFE into a quantitative assay. We provide an overview of its current applications to different biomolecules and discuss potential future uses, including the study of protein-protein interactions, protein-ligand interactions and conformational changes in biomolecules., (Creative Commons Attribution license.)

Hybrid solid polymer electrolytes (HSPE) comprising poly(ethylene oxide) (PEO), LiTFSI, barium titanate (BaTiO 3 ), and viologen are prepared by a facile hot press. The physical properties of the HSPE membranes are studied by using small-angle and wide-angle X-ray scattering, thermogravimetric analysis, differential scanning calorimetry, and tensile strength. The prepared hybrid solid polymer electrolytes are also investigated by means of ionic conductivity and transport number measurements. The employed analyses collectively reveal that each additive in the PEO host contributes to a specific property: LiTFSI is essential in providing ionic species, while BaTiO 3 and viologen enhance the thermal stability, ionic conductivity, and transport number. The enhanced value in the Li + -transport number of HSPE are presumably attributed to the electrostatic attraction of TFSI anions and the positive charges of viologen. Synergistically, the added BaTiO 3 and viologen improve the electrochemical properties of HSPE for the applications in all-solid-state-lithium polymer batteries., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Single-molecule Förster-resonance energy transfer (smFRET) experiments allow the study of biomolecular structure and dynamics in vitro and in vivo. We performed an international blind study involving 19 laboratories to assess the uncertainty of FRET experiments for proteins with respect to the measured FRET efficiency histograms, determination of distances, and the detection and quantification of structural dynamics. Using two protein systems with distinct conformational changes and dynamics, we obtained an uncertainty of the FRET efficiency ≤0.06, corresponding to an interdye distance precision of ≤2 Å and accuracy of ≤5 Å. We further discuss the limits for detecting fluctuations in this distance range and how to identify dye perturbations. Our work demonstrates the ability of smFRET experiments to simultaneously measure distances and avoid the averaging of conformational dynamics for realistic protein systems, highlighting its importance in the expanding toolbox of integrative structural biology., (© 2023. The Author(s).)

Introduction: This study examines predictors of trajectories of cigarette and e-cigarette use among a cohort of US adolescents transitioning into young adulthood. Comparing trajectories of each tobacco product is important to determine if different intervention targets are needed to prevent progression to daily use., Methods: Latent trajectory class analyses identified cigarette and e-cigarette use (never, ever excluding past 12-month, past 12-month (excluding past 30-day (P30D)), P30D 1-5 days, P30D 6+ days) trajectory classes, separately, among US youth (12-17; N = 10,086) using the first 4 waves (2013-2017) of data from the nationally representative PATH Study. Weighted descriptive analyses described the class characteristics. Weighted multinomial logistic regression analyses examined demographic, psychosocial, and behavioral predictors of class membership., Results: Younger adolescents 12-15 years had lower tobacco use compared to 16-17 year olds and less stable classes. In the 16-17 year group, there were five unique trajectories of cigarette smoking, including a Persistent High Frequency class. Four e-cigarette use trajectories were identified; but not a persistent use class. Shared predictors of class membership for cigarettes and e-cigarettes included mental health problems, other tobacco use, marijuana use, and poorer academic achievement. Male sex and household tobacco use were unique e-cigarette trajectory class predictors., Conclusions: There was no evidence that initiation with e-cigarettes as the first product tried was associated with cigarette progression (nor cigarettes as first product and e-cigarette progression). Interventions should focus on well-established risk factors such as mental health and other substance use to prevent progression of use for both tobacco products., Implications: Using nationally representative data and definitions of use that take into account frequency and recency of use, longitudinal 4-year trajectories of e-cigarette and cigarette use among US adolescents transitioning into young adulthood were identified. Results among 16-17-year olds revealed a class of persistent high frequency cigarette smoking that was not identified for e-cigarette use. Cigarette use progression was not associated with e-cigarettes as the first product tried. Risk factors for progression of use of both products included mental health and other substance use, which are important prevention targets for both tobacco products., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

The smfBox is a recently developed cost-effective, open-source instrument for single-molecule Förster Resonance Energy Transfer (smFRET), which makes measurements on freely diffusing biomolecules more accessible. This overview includes a step-by-step protocol for using this instrument to make measurements of precise FRET efficiencies in duplex DNA samples, including details of the sample preparation, instrument setup and alignment, data acquisition, and complete analysis routines. The presented approach, which includes how to determine all the correction factors required for accurate FRET-derived distance measurements, builds on a large body of recent collaborative work across the FRET Community, which aims to establish standard protocols and analysis approaches. This protocol, which is easily adaptable to a range of biomolecular systems, adds to the growing efforts in democratising smFRET for the wider scientific community.

Introduction: Concurrent use of tobacco cigarettes and e-cigarettes ("dual use") is common among tobacco users. Little is known about differences in demographics and toxicant exposure among subsets of dual users., Aims and Methods: We analyzed data from adult dual users (current every/some day users of tobacco cigarettes and e-cigarettes, n = 792) included in the PATH Study Wave 1 (2013-2014) and provided urine samples. Samples were analyzed for biomarkers of exposure to nicotine and selected toxicants (tobacco-specific nitrosamine NNK [NNAL], lead, cadmium, naphthalene [2-naphthol], pyrene [1-hydroxypyrene], acrylonitrile [CYMA], acrolein [CEMA], and acrylamide [AAMA]). Subsets of dual users were compared on demographic, behavioral, and biomarker measures to exclusive cigarette smokers (n = 2411) and exclusive e-cigarette users (n = 247)., Results: Most dual users were predominant cigarette smokers (70%), followed by daily dual users (13%), non-daily concurrent dual users (10%), and predominant vapers (7%). Dual users who smoked daily showed significantly higher biomarker concentrations compared with those who did not smoke daily. Patterns of e-cigarette use had little effect on toxicant exposure. Dual users with high toxicant exposure were generally older, female, and smoked more cigarettes per day. Dual users who had low levels of biomarkers of exposure were generally younger, male, and smoked non-daily., Conclusions: In 2013-2014, most dual users smoked cigarettes daily and used e-cigarettes occasionally. Cigarette smoking appears to be the primary driver of toxicant exposure among dual users, with little-to-no effect of e-cigarette use on biomarker levels. Results reinforce the need for dual users to stop smoking tobacco cigarettes to reduce toxicant exposure., Implications: With considerable dual use of tobacco cigarettes and e-cigarettes in the United States, it is important to understand differences in toxicant exposure among subsets of dual users, and how these differences align with user demographics. Findings suggest most dual users smoke daily and use e-cigarettes intermittently. Low exposure to toxicants was most common among younger users, males, and intermittent smokers; high exposure to toxicants was most common among older users, females, and heavier cigarette smokers. Results underscore the heterogeneity occurring within dual users, and the need to quit smoking cigarettes completely in order to reduce toxicant exposure., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Single-molecule FRET (smFRET) has become a mainstream technique for studying biomolecular structural dynamics. The rapid and wide adoption of smFRET experiments by an ever-increasing number of groups has generated significant progress in sample preparation, measurement procedures, data analysis, algorithms and documentation. Several labs that employ smFRET approaches have joined forces to inform the smFRET community about streamlining how to perform experiments and analyze results for obtaining quantitative information on biomolecular structure and dynamics. The recent efforts include blind tests to assess the accuracy and the precision of smFRET experiments among different labs using various procedures. These multi-lab studies have led to the development of smFRET procedures and documentation, which are important when submitting entries into the archiving system for integrative structure models, PDB-Dev. This position paper describes the current 'state of the art' from different perspectives, points to unresolved methodological issues for quantitative structural studies, provides a set of 'soft recommendations' about which an emerging consensus exists, and lists openly available resources for newcomers and seasoned practitioners. To make further progress, we strongly encourage 'open science' practices., Competing Interests: EL, AB, JH, BA, VB, SB, RB, HS, TC, TC, AD, JD, JF, RG, IG, TH, CH, GH, NH, SH, SH, TH, AI, CJ, AK, HK, TL, NL, TL, EL, EM, JM, XM, SM, DN, TP, EP, YR, NR, BS, HS, CT, RV, DL, CS, SW No competing interests declared

We present CHARMM-compatible force field parameters for a series of fluorescent dyes from the Alexa, Atto, and Cy families, commonly used in Förster resonance energy transfer (FRET) experiments. These dyes are routinely used in experiments to resolve the dynamics of proteins and nucleic acids at the nanoscale. However, little is known about the accuracy of the theoretical approximations used in determining the dynamics from the spectroscopic data. Molecular dynamics simulations can provide valuable insights into these dynamics at an atomistic level, but this requires accurate parameters for the dyes. The complex structure of the dyes and the importance of this in determining their spectroscopic properties mean that parameters generated by analogy to existing parameters do not give meaningful results. Through validation relative to quantum chemical calculation and experiments, the new parameters are shown to significantly outperform those that can be generated automatically, giving better agreement in both the charge distributions and structural properties. These improvements, in particular with regard to orientation of the dipole moments on the dyes, are vital for accurate simulation of FRET processes.

Single-molecule Förster Resonance Energy Transfer (smFRET) is a powerful technique capable of resolving both relative and absolute distances within and between structurally dynamic biomolecules. High instrument costs, and a lack of open-source hardware and acquisition software have limited smFRET's broad application by non-specialists. Here, we present the smfBox, a cost-effective confocal smFRET platform, providing detailed build instructions, open-source acquisition software, and full validation, thereby democratising smFRET for the wider scientific community.

Biogenic amines (BA) are biomolecules of low molecular weight with organic basic functionalities (amine group) that are formed by the microbial decarboxylation of amino acids of fermented food/beverages. Hence BAs are an important indicator in estimating the freshness and quality of meat, seafood, and industrial food products with high protein content. The reaction of BAs with nitrites available in certain meat products forms nitrosoamine, a carcinogenic compound. Hence BAs are in general considered to be a food hazard and monitoring the level of BAs in food samples becomes crucial as their high concentrations may lead to health problems. This review offers an overview of the available chemical and electrochemical methods that are typically used for the sensing of BAs in food samples. Certain compounds are known to selectively interact with BAs via chemical or non-covalent interactions and these interactions are often accompanied by fluorescence or visible color changes (sometimes visual detection) that could be monitored/assessed using a fluorescence spectrophotometer or UV-vis spectrophotometer (colorimetric methods). The colorimetric methods are limited by sensitivity and selectivity as they are based on straight-forward chemical reactions. In the case of electrochemical sensing of BAs, mediators are often used which undergo oxidation/reduction to produce intermediates that could interact with BAs accompanied by changes in their electrochemical potential. Overall, this review summarizes the available chemical and electrochemical strategies towards the sensing of BAs with a discussion on further prospects.

Flavored cigar use is common among cigar smokers, particularly those at younger ages. Several US localities have implemented policies restricting the sale of flavored tobacco products, including cigars. We estimated the population health benefits of removal of flavored cigars throughout the US in terms of reductions in cigar smoking-attributable mortality due to increased cessation and reductions in cigar smoking prevalence due to decreased initiation and continuing use. Monte Carlo simulation was used to estimate possible ranges for these values. We used published estimates of cigar use and attributable mortality in the US, as well as prior study conclusions on the effect of local and national flavor restriction policies. We estimated that removal of flavored cigars would result in approximately 800 (90% prediction interval = 400-1200) fewer cigar smoking-attributable deaths in the US each year and 112,000 fewer cigar smokers (90% prediction interval = 76,000-139,000) in each cohort of 18 year olds. The removal of characterizing flavors in cigars sold in the US is thus projected to have substantial public health benefits over time.

Prolonging function of the corpus luteum (CL) is a method of suppressing estrus that relies on continued secretion of endogenous progesterone to keep mares out of heat naturally. The use of oxytocin treatment to prolong CL function is gaining increasing use, and the most common treatment protocol involves administration of 60 units of oxytocin intramuscularly (IM) once daily on days 7-14 after ovulation (eight daily treatments). Although that protocol induces prolonged CL function in ≥70% of treated mares, the need for daily administration is a drawback to its use. Therefore, the objective of this study was to evaluate the efficacy of a proprietary slow-release oxytocin formulation (SR-OT) for prolonging CL function that requires only two treatments. Mares were examined via transrectal palpation and ultrasonography to determine the day of ovulation (day 0) and then randomly assigned to a nontreated control group and an SR-OT treatment group (n = 8 mares/group). Mares in the treated group received 1.0 mL of SR-OT containing 2,400 IU oxytocin IM once on day 7 and again on day 10 after ovulation. Jugular blood samples were collected on day 0 and then every Monday, Wednesday, and Friday for 50 days for determination of the serum progesterone concentration. Mares were classified as having prolonged CL function if their progesterone concentration remained >1.0 ng/mL continuously for at least 30 days. Corpus luteum function was prolonged in 0/8 (0%) control mares and 6/8 (75%) of the SR-OT-treated mares (P < .01). The demonstrated efficacy of this two-injection, SR-OT protocol represents a 75% reduction in the number of oxytocin treatments compared with daily administration of oxytocin from day 7-14, making it a more practical treatment protocol., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Importance: Use of electronic cigarettes (e-cigarettes) is increasing. Measures of exposure to known tobacco-related toxicants among e-cigarette users will inform potential health risks to individual product users., Objectives: To estimate concentrations of tobacco-related toxicants among e-cigarette users and compare these biomarker concentrations with those observed in combustible cigarette users, dual users, and never tobacco users., Design, Setting, and Participants: A population-based, longitudinal cohort study was conducted in the United States in 2013-2014. Cross-sectional analysis was performed between November 4, 2016, and October 5, 2017, of biomarkers of exposure to tobacco-related toxicants collected by the Population Assessment of Tobacco and Health Study. Participants included adults who provided a urine sample and data on tobacco use (N = 5105)., Exposures: The primary exposure was tobacco use, including current exclusive e-cigarette users (n = 247), current exclusive cigarette smokers (n = 2411), and users of both products (dual users) (n = 792) compared with never tobacco users (n = 1655)., Main Outcomes and Measures: Geometric mean concentrations of 50 individual biomarkers from 5 major classes of tobacco product constituents were measured: nicotine, tobacco-specific nitrosamines (TSNAs), metals, polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs)., Results: Of the 5105 participants, most were aged 35 to 54 years (weighted percentage, 38%; 95% CI, 35%-40%), women (60%; 95% CI, 59%-62%), and non-Hispanic white (61%; 95% CI, 58%-64%). Compared with exclusive e-cigarette users, never users had 19% to 81% significantly lower concentrations of biomarkers of exposure to nicotine, TSNAs, some metals (eg, cadmium and lead), and some VOCs (including acrylonitrile). Exclusive e-cigarette users showed 10% to 98% significantly lower concentrations of biomarkers of exposure, including TSNAs, PAHs, most VOCs, and nicotine, compared with exclusive cigarette smokers; concentrations were comparable for metals and 3 VOCs. Exclusive cigarette users showed 10% to 36% lower concentrations of several biomarkers than dual users. Frequency of cigarette use among dual users was positively correlated with nicotine and toxicant exposure., Conclusions and Relevance: Exclusive use of e-cigarettes appears to result in measurable exposure to known tobacco-related toxicants, generally at lower levels than cigarette smoking. Toxicant exposure is greatest among dual users, and frequency of combustible cigarette use is positively correlated with tobacco toxicant concentration. These findings provide evidence that using combusted tobacco cigarettes alone or in combination with e-cigarettes is associated with higher concentrations of potentially harmful tobacco constituents in comparison with using e-cigarettes alone.

Single-molecule Förster resonance energy transfer (smFRET) is increasingly being used to determine distances, structures, and dynamics of biomolecules in vitro and in vivo. However, generalized protocols and FRET standards to ensure the reproducibility and accuracy of measurements of FRET efficiencies are currently lacking. Here we report the results of a comparative blind study in which 20 labs determined the FRET efficiencies (E) of several dye-labeled DNA duplexes. Using a unified, straightforward method, we obtained FRET efficiencies with s.d. between ±0.02 and ±0.05. We suggest experimental and computational procedures for converting FRET efficiencies into accurate distances, and discuss potential uncertainties in the experiment and the modeling. Our quantitative assessment of the reproducibility of intensity-based smFRET measurements and a unified correction procedure represents an important step toward the validation of distance networks, with the ultimate aim of achieving reliable structural models of biomolecular systems by smFRET-based hybrid methods.

Human flap endonuclease-1 (hFEN1) catalyzes the divalent metal ion-dependent removal of single-stranded DNA protrusions known as flaps during DNA replication and repair. Substrate selectivity involves passage of the 5'-terminus/flap through the arch and recognition of a single nucleotide 3'-flap by the α2-α3 loop. Using NMR spectroscopy, we show that the solution conformation of free and DNA-bound hFEN1 are consistent with crystal structures; however, parts of the arch region and α2-α3 loop are disordered without substrate. Disorder within the arch explains how 5'-flaps can pass under it. NMR and single-molecule FRET data show a shift in the conformational ensemble in the arch and loop region upon addition of DNA. Furthermore, the addition of divalent metal ions to the active site of the hFEN1-DNA substrate complex demonstrates that active site changes are propagated via DNA-mediated allostery to regions key to substrate differentiation. The hFEN1-DNA complex also shows evidence of millisecond timescale motions in the arch region that may be required for DNA to enter the active site. Thus, hFEN1 regional conformational flexibility spanning a range of dynamic timescales is crucial to reach the catalytically relevant ensemble.