Mechanistic analysis of an asymmetric palladium-catalyzed conjugate addition of arylboronic acids to β-substituted cyclic enones.

An asymmetric palladium-catalyzed conjugate addition reaction of arylboronic acids to enone substrates was investigated mechanistically. Desorption electrospray ionization coupled to mass spectrometry was used to identify intermediates of the catalytic cycle and delineate differences in substrate reactivity. Our findings provide evidence for the catalytic cycle proceeding through formation of an arylpalladium(II) cation, subsequent formation of an arylpalladium-enone complex, and, ultimately, formation of the new C-C bond. Reaction monitoring in both positive and negative ion modes revealed that 4-iodophenylboronic acid formed a relatively stable trimeric species under the reaction conditions

Movement patterns and athletic performance of leopards in the Okavango Delta

Although leopards are the most widespread of all the big cats and are known for their adaptability, they are elusive and little is known in detail about their movement and hunting energetics. We used high-resolution GPS/IMU (inertial measurement unit) collars to record position, activity and the first high-speed movement data on four male leopards in the Okavango Delta, an area with high habitat diversity and habitat fragmentation. Leopards in this study were generally active and conducted more runs during the night, with peaks in activity and number of runs in the morning and evening twilight. Runs were generally short (less than 100 m) and relatively slow (maximum speed 5.3 m s−1, mean of individual medians) compared to other large predators. Average daily travel distance was 11 km and maximum daily travel distance was 29 km. No direct correlation was found between average daily temperature and travel distance or between season and travel distance. Total daily energy requirements based on locomotor cost and basal metabolic rate varied little between individuals and over time. This study provides novel insights into movement patterns and athletic performance of leopards through quantitative high-resolution measurement of the locomotor, energetic, spatial and temporal movement characteristics. The results are unbiased by methodological and observational limitations characteristic of previous studies and demonstrate the utility of applying new technologies to field studies of elusive nocturnal species

Pre-Meal Whey Protein Alters Postprandial Insulinemia by Enhancing β-Cell Function and Reducing Insulin Clearance in T2D

CONTEXT: Treatments that reduce postprandial glycemia (PPG) independent of stimulating insulin secretion are appealing for the management of type 2 diabetes (T2D). Consuming pre-meal whey protein (WP) reduces PPG by delaying gastric emptying and increasing plasma insulin concentrations. However, its effects on β-cell function and insulin kinetics remains unclear. OBJECTIVE: To examine the PPG-regulatory effects of pre-meal WP by modeling insulin secretion rates (ISR), insulin clearance, and β-cell function. METHODS: This was a single-blind, randomized, placebo-controlled, crossover design study in 18 adults with T2D (HbA1c, 56.7 ± 8.8 mmol/mol) who underwent 2 240-minute mixed-meal tolerance tests. Participants consumed WP (15 g protein) or placebo (0 g protein) 10 minutes before a mixed-macronutrient breakfast meal. PPG, pancreatic islet, and incretin hormones were measured throughout. ISR was calculated by C-peptide deconvolution. Estimates of insulin clearance and β-cell function were modeled from glucose, insulin, and ISR. Changes in PPG incremental area under the curve (iAUC; prespecified) and insulin clearance (post hoc) were measured. RESULTS: β-cell function was 40% greater after WP (P = .001) and was accompanied with a -22% reduction in postprandial insulin clearance vs placebo (P < .0001). Both the peak change and PPG iAUC were reduced by WP (-1.5 mmol/L and -16%, respectively; both P < .05). Pre-meal WP augmented a 5.9-fold increase in glucagon and glucagon-like peptide 1 iAUC (both P < .0001), and a 1.5-fold increase in insulin iAUC (P < .001). Although the plasma insulin response was greater following WP, ISR was unaffected (P = .133). CONCLUSION: In adults with T2D, pre-meal WP reduced PPG by coordinating an enhancement in β-cell function with a reduction in insulin clearance. This enabled an efficient postprandial insulinemic profile to be achieved without requiring further β-cell stimulation.Trial registry ISRCTN ID: ISRCTN17563146 Website link: www.isrctn.com/ISRCTN17563146

Additive opportunistic capture explains group hunting benefits in African wild dogs

African wild dogs (Lycaon pictus) are described as highly collaborative endurance pursuit hunters based on observations derived primarily from the grass plains of East Africa. However, the remaining population of this endangered species mainly occupies mixed woodland savannah where hunting strategies appear to differ from those previously described. We used high-resolution GPS and inertial technology to record fine-scale movement of all members of a single pack of six adult African wild dogs in northern Botswana. The dogs used multiple short-distance hunting attempts with a low individual kill rate (15.5%), but high group feeding rate due to the sharing of prey. Use of high-level cooperative chase strategies (coordination and collaboration) was not recorded. In the mixed woodland habitats typical of their current range, simultaneous, opportunistic, short-distance chasing by dogs pursuing multiple prey (rather than long collaborative pursuits of single prey by multiple individuals) could be the key to their relative success in these habitats

A simple mathematical model of gradual Darwinian evolution: Emergence of a Gaussian trait distribution in adaptation along a fitness gradient

We consider a simple mathematical model of gradual Darwinian evolution in continuous time and continuous trait space, due to intraspecific competition for common resource in an asexually reproducing population in constant environment, while far from evolutionary stable equilibrium. The model admits exact analytical solution. In particular, Gaussian distribution of the trait emerges from generic initial conditions.Comment: 21 pages, 2 figures, as accepted to J Math Biol 2013/03/1

GPs' willingness to prescribe aspirin for cancer preventive therapy in Lynch syndrome: a factorial randomised trial investigating factors influencing decisions.

BACKGROUND: The National Institute for Health and Care Excellence (NICE) 2020 guidelines recommends aspirin for colorectal cancer prevention for people with Lynch syndrome. Strategies to change practice should be informed by understanding the factors influencing prescribing. AIM: To investigate the optimal type and level of information to communicate with GPs to increase willingness to prescribe aspirin. DESIGN AND SETTING: GPs in England and Wales (n = 672) were recruited to participate in an online survey with a 23 factorial design. GPs were randomised to one of eight vignettes describing a hypothetical patient with Lynch syndrome recommended to take aspirin by a clinical geneticist. METHOD: Across the vignettes, the presence or absence of three types of information was manipulated: 1) existence of NICE guidance; 2) results from the CAPP2 trial; 3) information comparing risks/benefits of aspirin. The main effects and all interactions on the primary (willingness to prescribe) and secondary outcomes (comfort discussing aspirin) were estimated. RESULTS: There were no statistically significant main effects or interactions of the three information components on willingness to prescribe aspirin or comfort discussing harms and benefits. In total, 80.4% (540/672) of GPs were willing to prescribe, with 19.7% (132/672) unwilling. GPs with prior awareness of aspirin for preventive therapy were more comfortable discussing the medication than those unaware (P = 0.031). CONCLUSION: It is unlikely that providing information on clinical guidance, trial results, and information comparing benefits and harms will increase aspirin prescribing for Lynch syndrome in primary care. Alternative multilevel strategies to support informed prescribing may be warranted

Immune-mediated competition in rodent malaria is most likely caused by induced changes in innate immune clearance of merozoites

Malarial infections are often genetically diverse, leading to competitive interactions between parasites. A quantitative understanding of the competition between strains is essential to understand a wide range of issues, including the evolution of virulence and drug resistance. In this study, we use dynamical-model based Bayesian inference to investigate the cause of competitive suppression of an avirulent clone of Plasmodium chabaudi (AS) by a virulent clone (AJ) in immuno-deficient and competent mice. We test whether competitive suppression is caused by clone-specific differences in one or more of the following processes: adaptive immune clearance of merozoites and parasitised red blood cells (RBCs), background loss of merozoites and parasitised RBCs, RBC age preference, RBC infection rate, burst size, and within-RBC interference. These processes were parameterised in dynamical mathematical models and fitted to experimental data. We found that just one parameter μ, the ratio of background loss rate of merozoites to invasion rate of mature RBCs, needed to be clone-specific to predict the data. Interestingly, μ was found to be the same for both clones in single-clone infections, but different between the clones in mixed infections. The size of this difference was largest in immuno-competent mice and smallest in immuno-deficient mice. This explains why competitive suppression was alleviated in immuno-deficient mice. We found that competitive suppression acts early in infection, even before the day of peak parasitaemia. These results lead us to argue that the innate immune response clearing merozoites is the most likely, but not necessarily the only, mediator of competitive interactions between virulent and avirulent clones. Moreover, in mixed infections we predict there to be an interaction between the clones and the innate immune response which induces changes in the strength of its clearance of merozoites. What this interaction is unknown, but future refinement of the model, challenged with other datasets, may lead to its discovery

Acceptability of aspirin for cancer preventive therapy: a survey and qualitative study exploring the views of the UK general population.

OBJECTIVES: Aspirin could be offered for colorectal cancer prevention for the UK general population. To ensure the views of the general population are considered in future guidance, we explored public perceptions of aspirin for preventive therapy. DESIGN: We conducted an online survey to investigate aspirin use, and awareness of aspirin for cancer prevention among the UK general population. We conducted semistructured interviews with a subsample of survey respondents to explore participants' acceptability towards aspirin for cancer preventive therapy. We analysed the interview data using reflexive thematic analysis and mapped the themes onto the Theoretical Domains Framework, and the Necessity and Concerns Framework. SETTING: Online survey and remote interviews. PARTICIPANTS: We recruited 400 UK respondents aged 50-70 years through a market research company to the survey. We purposefully sampled, recruited and interviewed 20 survey respondents. RESULTS: In the survey, 19.0% (76/400) of respondents were aware that aspirin can be used to prevent cancer. Among those who had previously taken aspirin, 1.9% (4/216) had taken it for cancer prevention. The interviews generated three themes: (1) perceived necessity of aspirin; (2) concerns about side effects; and (3) preferred information sources. Participants with a personal or family history of cancer were more likely to perceive aspirin as necessary for cancer prevention. Concerns about taking aspirin at higher doses and its side effects, such as gastrointestinal bleeding, were common. Many described wanting guidance and advice on aspirin to be communicated from sources perceived as trustworthy, such as healthcare professionals. CONCLUSIONS: Among the general population, those with a personal or family history of cancer may be more receptive towards taking aspirin for preventive therapy. Future policies and campaigns recommending aspirin may be of particular interest to these groups. Multiple considerations about the benefits and risks of aspirin highlight the need to support informed decisions on the medication