Variation in Mating Dynamics across Five Species of Leiobunine Harvestmen (Arachnida: Opliones)

The study of mating choices often focuses on correlates of traits to the overall outcome of a mating interaction. However, mating interactions can proceed through a series of stages, with opportunities for assessment at each stage. We compared whether male or female size predicted mating interaction outcome across several stages of mating in five species of North American leiobunine harvestmen (commonly known as daddy longlegs). Leiobunine harvestmen have been previously shown to exhibit incredible morphological diversity consistent with a spectrum of male–female antagonism. Across all of the species, we found a general progression of female size predicting the outcome (success and timing) of early stages of interactions, and male size or male size relative to female size predicting the outcome and timing of later stages of interactions. We also found that size was not a strong predictor of outcome in the two species on the lower end of the antagonism spectrum. The variation in how female and male size predicted outcomes across species and stages of mating suggests that multiple mechanisms may operate to shape mating dynamics within and across species. Given the close relatedness of the species studied, the patterns we uncovered suggest a rapid evolution of the traits and processes predicting the outcome of mating interactions

Pasos Hacia La Salud: a randomized controlled trial of an internet-delivered physical activity intervention for Latinas.

BackgroundInternet access has grown markedly in Latinos during the past decade. However, there have been no Internet-based physical activity interventions designed for Latinos, despite large disparities in lifestyle-related conditions, such as obesity and diabetes, particularly in Latina women. The current study tested the efficacy of a 6-month culturally adapted, individually tailored, Spanish-language Internet-based physical activity intervention.MethodsInactive Latinas (N = 205) were randomly assigned to the Tailored Physical Activity Internet Intervention or the Wellness Contact Control Internet Group. Participants in both groups received emails on a tapered schedule over 6 months to alert them to new content on the website. The primary outcome was minutes/week of moderate to vigorous physical activity (MVPA) at 6 months as measured by the 7-Day Physical Activity Recall; activity was also measured by accelerometers. Data were collected between 2011 and 2014 and analyzed in 2015 at the University of California, San Diego.ResultsIncreases in minutes/week of MVPA were significantly greater in the Intervention Group compared to the Control Group (mean difference = 50.00, SE = 9.5, p < 0.01). Increases in objectively measured MVPA were also significantly larger in the Intervention Group (mean differences = 31.0, SE = 10.7, p < .01). The Intervention Group was also significantly more likely to meet national physical activity guidelines at 6 months (OR = 3.12, 95% CI 1.46-6.66, p < .05).ConclusionFindings from the current study suggest that this Internet-delivered individually tailored intervention successfully increased MVPA in Latinas compared to a Wellness Contact Control Internet Group.Trial registrationNCT01834287

Simultaneous PET/MRI with 13C magnetic resonance spectroscopic imaging (hyperPET): phantom-based evaluation of PET quantification

BACKGROUND: Integrated PET/MRI with hyperpolarized (13)C magnetic resonance spectroscopic imaging ((13)C-MRSI) offers simultaneous, dual-modality metabolic imaging. A prerequisite for the use of simultaneous imaging is the absence of interference between the two modalities. This has been documented for a clinical whole-body system using simultaneous (1)H-MRI and PET but never for (13)C-MRSI and PET. Here, the feasibility of simultaneous PET and (13)C-MRSI as well as hyperpolarized (13)C-MRSI in an integrated whole-body PET/MRI hybrid scanner is evaluated using phantom experiments. METHODS: Combined PET and (13)C-MRSI phantoms including a NEMA [(18)F]-FDG phantom, (13)C-acetate and (13)C-urea sources, and hyperpolarized (13)C-pyruvate were imaged repeatedly with PET and/or (13)C-MRSI. Measurements evaluated for interference effects included PET activity values in the largest sphere and a background region; total number of PET trues; and (13)C-MRSI signal-to-noise ratio (SNR) for urea and acetate phantoms. Differences between measurement conditions were evaluated using t tests. RESULTS: PET and (13)C-MRSI data acquisition could be performed simultaneously without any discernible artifacts. The average difference in PET activity between acquisitions with and without simultaneous (13)C-MRSI was 0.83 (largest sphere) and −0.76 % (background). The average difference in net trues was −0.01 %. The average difference in (13)C-MRSI SNR between acquisitions with and without simultaneous PET ranged from −2.28 to 1.21 % for all phantoms and measurement conditions. No differences were significant. The system was capable of (13)C-MRSI of hyperpolarized (13)C-pyruvate. CONCLUSIONS: Simultaneous PET and (13)C-MRSI in an integrated whole-body PET/MRI hybrid scanner is feasible. Phantom experiments showed that possible interference effects introduced by acquiring data from the two modalities simultaneously are small and non-significant. Further experiments can now investigate the benefits of simultaneous PET and hyperpolarized (13)C-MRI in vivo studies

Hair cortisol concentration, weight loss maintenance and body weight variability: A prospective study based on data from the european nohow trial

Several cross-sectional studies have shown hair cortisol concentration to be associated with adiposity, but the relationship between hair cortisol concentration and longitudinal changes in measures of adiposity are largely unknown. We included 786 adults from the NoHoW trial, who had achieved a successful weight loss of ≥5% and had a body mass index of ≥25 kg/m2 prior to losing weight. Hair cortisol concentration (pg/mg hair) was measured at baseline and after 12 months. Body weight and body fat percentage were measured at baseline, 6-month, 12-month and 18-month visits. Participants weighed themselves at home ≥2 weekly using a Wi-Fi scale for the 18-month study duration, from which body weight variability was estimated using linear and non-linear approaches. Regression models were conducted to examine log hair cortisol concentration and change in log hair cortisol concentration as predictors of changes in body weight, change in body fat percentage and body weight variability. After adjustment for lifestyle and demographic factors, no associations between baseline log hair cortisol concentration and outcome measures were observed. Similar results were seen when analysing the association between 12-month concurrent development in log hair cortisol concentration and outcomes. However, an initial 12-month increase in log hair cortisol concentration was associated with a higher subsequent body weight variability between month 12 and 18, based on deviations from a nonlinear trend (β: 0.02% per unit increase in log hair cortisol concentration [95% CI: 0.00, 0.04]; P =0.016). Our data suggest that an association between hair cortisol concentration and subsequent change in body weight or body fat percentage is absent or marginal, but that an increase in hair cortisol concentration during a 12-month weight loss maintenance effort may predict a slightly higher subsequent 6-months body weight variability. Clinical Trial Registration: ISRCTN registry, identifier ISRCTN88405328. [ABSTRACT FROM AUTHOR]info:eu-repo/semantics/publishedVersio

Identification of iridoid glucoside transporters in Catharanthus roseus

Monoterpenoid indole alkaloids (MIAs) are plant defense compounds and high-value pharmaceuticals. Biosynthesis of the universal MIA precursor, secologanin, is organized between internal phloem-associated parenchyma (IPAP) and epidermis cells. Transporters for intercellular transport of proposed mobile pathway intermediates have remained elusive. Screening of an Arabidopsis thaliana transporter library expressed in Xenopus oocytes identified AtNPF2.9 as a putative iridoid glucoside importer. Eight orthologs were identified in Catharanthus roseus, of which three, CrNPF2.4, CrNPF2.5 and CrNPF2.6, were capable of transporting the iridoid glucosides 7-deoxyloganic acid, loganic acid, loganin and secologanin into oocytes. Based on enzyme expression data and transporter specificity, we propose that several enzymes of the biosynthetic pathway are present in both IPAP and epidermis cells, and that the three transporters are responsible for transporting not only loganic acid, as previously proposed, but multiple intermediates. Identification of the iridoid glucoside-transporting CrNPFs is an important step toward understanding the complex orchestration of the seco-iridioid pathway

Consistent sleep onset and maintenance of body weight after weight loss:An analysis of data from the NoHoW trial

BackgroundSeveral studies have suggested that reduced sleep duration and quality are associated with an increased risk of obesity and related metabolic disorders, but the role of sleep in long-term weight loss maintenance (WLM) has not been thoroughly explored using prospective data.Methods and findingsThe present study is an ancillary study based on data collected on participants from the Navigating to a Healthy Weight (NoHoW) trial, for which the aim was to test the efficacy of an evidence-based digital toolkit, targeting self-regulation, motivation, and emotion regulation, on WLM among 1,627 British, Danish, and Portuguese adults. Before enrolment, participants had achieved a weight loss of ≥5% and had a BMI of ≥25 kg/m2 prior to losing weight. Participants were enrolled between March 2017 and March 2018 and followed during the subsequent 12-month period for change in weight (primary trial outcome), body composition, metabolic markers, diet, physical activity, sleep, and psychological mediators/moderators of WLM (secondary trial outcomes). For the present study, a total of 967 NoHoW participants were included, of which 69.6% were women, the mean age was 45.8 years (SD 11.5), the mean baseline BMI was 29.5 kg/m2 (SD 5.1), and the mean weight loss prior to baseline assessments was 11.4 kg (SD 6.4). Objectively measured sleep was collected using the Fitbit Charge 2 (FC2), from which sleep duration, sleep duration variability, sleep onset, and sleep onset variability were assessed across 14 days close to baseline examinations. The primary outcomes were 12-month changes in body weight (BW) and body fat percentage (BF%). The secondary outcomes were 12-month changes in obesity-related metabolic markers (blood pressure, low- and high-density lipoproteins [LDL and HDL], triglycerides [TGs], and glycated haemoglobin [HbA1c]). Analysis of covariance and multivariate linear regressions were conducted with sleep-related variables as explanatory and subsequent changes in BW, BF%, and metabolic markers as response variables. We found no evidence that sleep duration, sleep duration variability, or sleep onset were associated with 12-month weight regain or change in BF%. A higher between-day variability in sleep onset, assessed using the standard deviation across all nights recorded, was associated with weight regain (0.55 kg per hour [95% CI 0.10 to 0.99]; P = 0.016) and an increase in BF% (0.41% per hour [95% CI 0.04 to 0.78]; P = 0.031). Analyses of the secondary outcomes showed that a higher between-day variability in sleep duration was associated with an increase in HbA1c (0.02% per hour [95% CI 0.00 to 0.05]; P = 0.045). Participants with a sleep onset between 19:00 and 22:00 had the greatest reduction in diastolic blood pressure (DBP) (P = 0.02) but also the most pronounced increase in TGs (P = 0.03). The main limitation of this study is the observational design. Hence, the observed associations do not necessarily reflect causal effects.ConclusionOur results suggest that maintaining a consistent sleep onset is associated with improved WLM and body composition. Sleep onset and variability in sleep duration may be associated with subsequent change in different obesity-related metabolic markers, but due to multiple-testing, the secondary exploratory outcomes should be interpreted cautiously.Trial registrationThe trial was registered with the ISRCTN registry (ISRCTN88405328)

Simultaneous hyperpolarized 13C-pyruvate MRI and 18F-FDG-PET in cancer (hyperPET):feasibility of a new imaging concept using a clinical PET/MRI scanner

In this paper we demonstrate, for the first time, the feasibility of a new imaging concept - combined hyperpolarized (13)C-pyruvate magnetic resonance spectroscopic imaging (MRSI) and (18)F-FDG-PET imaging. This procedure was performed in a clinical PET/MRI scanner with a canine cancer patient. We have named this concept hyper PET. Intravenous injection of the hyperpolarized (13)C-pyruvate results in an increase of (13)C-lactate, (13)C-alanine and (13)C-CO(2) ((13)C-HCO(3)) resonance peaks relative to the tissue, disease and the metabolic state probed. Accordingly, with dynamic nuclear polarization (DNP) and use of (13)C-pyruvate it is now possible to directly study the Warburg Effect through the rate of conversion of (13)C-pyruvate to (13)C-lactate. In this study, we combined it with (18)F-FDG-PET that studies uptake of glucose in the cells. A canine cancer patient with a histology verified local recurrence of a liposarcoma on the right forepaw was imaged using a combined PET/MR clinical scanner. PET was performed as a single-bed, 10 min acquisition, 107 min post injection of 310 MBq (18)F-FDG. (13)C-chemical shift imaging (CSI) was performed just after FDG-PET and 30 s post injection of 23 mL hyperpolarized (13)C-pyruvate. Peak heights of (13)C-pyruvate and (13)C-lactate were quantified using a general linear model. Anatomic (1)H-MRI included axial and coronal T1 vibe, coronal T2-tse and axial T1-tse with fat saturation following gadolinium injection. In the tumor we found clearly increased (13)C-lactate production, which also corresponded to high (18)F-FDG uptake on PET. This is in agreement with the fact that glycolysis and production of lactate are increased in tumor cells compared to normal cells. Yet, most interestingly, also in the muscle of the forepaw of the dog high (18)F-FDG uptake was observed. This was due to activity in these muscles prior to anesthesia, which was not accompanied by a similarly high (13)C-lactate production. Accordingly, this clearly demonstrates how the Warburg Effect directly can be demonstrated by hyperpolarized (13)C-pyruvate MRSI. This was not possible with (18)F-FDG-PET imaging due to inability to discriminate between causes of increased glucose uptake. We propose that this new concept of simultaneous hyperpolarized (13)C-pyruvate MRSI and PET may be highly valuable for image-based non-invasive phenotyping of tumors. This methods may be useful for treatment planning and therapy monitoring

Natural product (L)-gossypol inhibits colon cancer cell growth by targeting RNA-binding protein Musashi-1

Musashi-1 (MSI1) is an RNA-binding protein that acts as a translation activator or repressor of target mRNAs. The best-characterized MSI1 target is Numb mRNA, whose encoded protein negatively regulates Notch signaling. Additional MSI1 targets include the mRNAs for the tumor suppressor protein APC that regulates Wnt signaling and the cyclin-dependent kinase inhibitor P21WAF−1. We hypothesized that increased expression of NUMB, P21 and APC, through inhibition of MSI1 RNA-binding activity might be an effective way to simultaneously downregulate Wnt and Notch signaling, thus blocking the growth of a broad range of cancer cells. We used a fluorescence polarization assay to screen for small molecules that disrupt the binding of MSI1 to its consensus RNA binding site. One of the top hits was (−)-gossypol (Ki = 476 ± 273 nM), a natural product from cottonseed, known to have potent anti-tumor activity and which has recently completed Phase IIb clinical trials for prostate cancer. Surface plasmon resonance and nuclear magnetic resonance studies demonstrate a direct interaction of (−)-gossypol with the RNA binding pocket of MSI1. We further showed that (−)-gossypol reduces Notch/Wnt signaling in several colon cancer cell lines having high levels of MSI1, with reduced SURVIVIN expression and increased apoptosis/autophagy. Finally, we showed that orally administered (−)-gossypol inhibits colon cancer growth in a mouse xenograft model. Our study identifies (−)-gossypol as a potential small molecule inhibitor of MSI1-RNA interaction, and suggests that inhibition of MSI1's RNA binding activity may be an effective anti-cancer strategy

Toward optimal implementation of cancer prevention and control programs in public health: A study protocol on mis-implementation

Abstract Background Much of the cancer burden in the USA is preventable, through application of existing knowledge. State-level funders and public health practitioners are in ideal positions to affect programs and policies related to cancer control. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. Greater attention to mis-implementation should lead to use of effective interventions and more efficient expenditure of resources, which in the long term, will lead to more positive cancer outcomes. Methods This is a three-phase study that takes a comprehensive approach, leading to the elucidation of tactics for addressing mis-implementation. Phase 1: We assess the extent to which mis-implementation is occurring among state cancer control programs in public health. This initial phase will involve a survey of 800 practitioners representing all states. The programs represented will span the full continuum of cancer control, from primary prevention to survivorship. Phase 2: Using data from phase 1 to identify organizations in which mis-implementation is particularly high or low, the team will conduct eight comparative case studies to get a richer understanding of mis-implementation and to understand contextual differences. These case studies will highlight lessons learned about mis-implementation and identify hypothesized drivers. Phase 3: Agent-based modeling will be used to identify dynamic interactions between individual capacity, organizational capacity, use of evidence, funding, and external factors driving mis-implementation. The team will then translate and disseminate findings from phases 1 to 3 to practitioners and practice-related stakeholders to support the reduction of mis-implementation. Discussion This study is innovative and significant because it will (1) be the first to refine and further develop reliable and valid measures of mis-implementation of public health programs; (2) bring together a strong, transdisciplinary team with significant expertise in practice-based research; (3) use agent-based modeling to address cancer control implementation; and (4) use a participatory, evidence-based, stakeholder-driven approach that will identify key leverage points for addressing mis-implementation among state public health programs. This research is expected to provide replicable computational simulation models that can identify leverage points and public health system dynamics to reduce mis-implementation in cancer control and may be of interest to other health areas