A new fireworm (Amphinomidae) from the Cretaceous of Lebanon identified from three-dimensionally preserved myoanatomy

© 2015 Parry et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. The attached file is the published version of the article

A soft-bodied mollusc with radula from the Middle Cambrian Burgess Shale

Author Posting. © Nature Publishing Group, 2006. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 442 (2006): 159-163, doi:10.1038/nature04894.Odontogriphus omalus was originally described as a problematic non-biomineralized lophophorate organism. Here we reinterpret Odontogriphus based on 189 new specimens including numerous exceptionally well-preserved individuals from the Burgess Shale collections of the Royal Ontario Museum. This additional material provides compelling evidence that the feeding apparatus in Odontogriphus is a radula of molluscan architecture comprising two primary bipartite tooth rows attached to a radular membrane and showing replacement by posterior addition. Further characters supporting molluscan affinity include a broad foot bordered by numerous ctenidia located in a mantle groove and a stiffened cuticular dorsum. Odontogriphus has a radula similar to Wiwaxia corrugata but lacks a scleritome. We interpret these animals to be members of an early stem-group mollusc lineage that likely originated in the Neoproterozoic Ediacaran Period, providing support for the retention of a biomat-based grazing community from the late Precambrian until at least the Middle Cambrian.Our research was in part supported by a Post-Doctoral Natural Sciences and Engineering Research Council of Canada grant (to JBC-2005) and by a Swedish Research Council grant (to CS)

Insulin- and exercise-induced phosphoproteomics of human skeletal muscle identify REPS1 as a regulator of muscle glucose uptake

Skeletal muscle glucose uptake, essential for metabolic health, is regulated by both insulin and exercise. Using phosphoproteomics, we analyze skeletal muscle from healthy individuals following acute exercise or insulin stimulation, generating a valuable dataset. We identify 71 phosphosites on 55 proteins regulated by both stimuli in the same direction, suggesting a convergence of exercise and insulin signaling pathways. Among these, the vesicle-associated protein, REPS1, is highly phosphorylated at Ser709 in response to both stimuli. We identify p90 ribosomal S6 kinase (RSK) to be a key upstream kinase of REPS1 S709 phosphorylation and that the RSK-REPS1 signaling axis is involved in insulin-stimulated glucose uptake. Insulin-induced REPS1 Ser709 phosphorylation is closely linked to muscle and whole-body insulin sensitivity and is impaired in insulin-resistant mice and humans. These findings highlight REPS1 as a convergence point for insulin and exercise signaling, presenting a potential therapeutic target for treating individuals with insulin resistance.</p

Beta₂-adrenergic agonist salbutamol exhibits enantioselective disposition in skeletal muscle of lean young men following oral administration

Salbutamol is a common short-acting beta2-adrenergic agonist used in treatment of asthma and exercise-induced bronchoconstriction but also possesses anabolic and metabolic actions in skeletal muscle. As a chiral compound, salbutamol is a racemic 1:1 mixture of two enantiomers, (R)-salbutamol and (S)-salbutamol, which exhibit divergent pharmacokinetic and pharmacodynamic actions. Despite salbutamol being available for decades, information on the enantioselective disposition of salbutamol enantiomers in human skeletal muscle is absent. In this study, we determined concentrations of (R)-salbutamol and (S)-salbutamol by UHPLC–MS/MS in arterial plasma and vastus lateralis muscle samples from 12 lean young men 2½ and 7 h following ingestion of 24 mg oral salbutamol. Mean (range) arterial plasma concentrations were 10-fold higher (p &lt; 0.001) for (S)-salbutamol than (R)-salbutamol, being 33(9–62) and 49(30–84) ng·mL−1 for (S)-salbutamol and 4 (1-6) and 4 (2-5) ng·mL−1 for (R)-salbutamol 2½ and 7 h following administration, respectively, reflecting faster elimination of the (R)-enantiomer. Mean (range) muscle concentrations were higher (p &lt; 0.001) for (S)-salbutamol than (R)-salbutamol 2½ h (0.17 [0.1–0.26] vs. 0.04 [0.02–0.06]) and 7 h (0.31 [0.21–0.46] vs. 0.06 [0.04–0.12] ng·mgd.w.−1) after administration. However, muscle:plasma partition coefficient was two-fold higher (p &lt; 0.001) for (R)-salbutamol than (S)-salbutamol 7 h following administration. These observations demonstrate that oral salbutamol exhibits enantioselective disposition in systemic circulation and muscle favoring the (S)-enantiomer but with higher relative partitioning of the (R)-enantiomer in skeletal muscle. Furthermore, the concentration-time profiles of salbutamol enantiomers are different in skeletal muscle and systemic circulation following oral ingestion. These findings have implications for the application of chiral switch (R)-salbutamol in doping control.</p

Effect of one-week oral or inhaled salbutamol treatment with washout on repeated sprint performance in trained subjects

Background: Acute and chronic supratherapeutic treatment with the commonly usedbeta2-agonist salbutamol has the potential to enhance sprint performance and musclestrength. However, little is known about the performance effects of short-term dailypermitted inhaled treatment vs oral prohibited treatment in accordance with the 2020Prohibited List issued by the World Anti-Doping Agency (WADA).Methods: Herein, we investigated the effect of twice-daily treatment with 400 μginhaled or 4 mg oral salbutamol for 1 week on repeated sprint performance in 19healthy well-trained men and women utilizing a randomized open-label crossoverdesign. Before and after each treatment period, and a 12-16 hours washout to avoidan acute effect of salbutamol, subjects performed a repeated sprint test (3 × 30-second Wingate).Results: Neither oral nor inhaled salbutamol enhanced peak power (oral; 3.0 W; 95%CI −6.8 to 12.8 W; and inhaled; −3.8 W; 95% CI −14.3 to 6.8 W) or mean power(oral; −2.1 W; 95% CI −4.7 to 8.9 W and inhaled; −1.6 W; 95% CI −5.6 to 8.9 W)during the repeated sprint test irrespective of gender.Conclusions: These findings indicate that 1 week is insufficient for salbutamol toinduce any relevant effect on repeated sprint performance in trained individuals

Beta2 -adrenergic agonist clenbuterol increases energy expenditure and fat oxidation, and induces mTOR phosphorylation in skeletal muscle of young healthy men

Clenbuterol is a beta2-adrenoceptor agonist marketed as an asthma reliever but is not approved for human use in most countries due to concerns of adverse cardiac effects. Given its demonstrated hypertrophic and lipolytic actions in rodents, clenbuterol is one of the most widely abused doping substances amongt athletes and recreational body-builders seeking leanness. Herein, we examined the effect of clenbuterol ingestion on metabolic rate as well as skeletal muscle mammalian target of rapamycin (mTOR) phosphorylation and protein kinase A (PKA)-signaling in six young men. Before and 140 min after ingestion of 80 μg clenbuterol, resting metabolic rate and contractile function of the quadriceps muscle were measured, and blood samples as well as vastus lateralis muscle biopsies were collected. Clenbuterol increased resting energy expenditure by 21% (P P = 0.006), whereas carbohydrate oxidation was unchanged. Phosphorylation of mTORSer2448 and PKA substrates increased by 121% (P = 0.004) and 35% (P = 0.006), respectively, with clenbuterol. Maximal voluntary contraction torque decreased by 4% (P = 0.026) and the half-relaxation time shortened by 9% (P = 0.046), while voluntary activation, time to peak twitch, and peak twitch torque did not change significantly with clenbuterol. Glycogen content of the vastus lateralis muscle did not change with clenbuterol. Clenbuterol increased circulating levels of glucose (+30%; P P = 0.004), insulin (+130%; P = 0.009), and fatty acids (+180%; P = 0.001). Collectively, these findings indicate that clenbuterol is an efficient thermogenic substance that possibly also exerts muscle hypertrophic actions in humans. For these reasons, the restrictions imposed against clenbuterol in competitive sports seem warranted

Effect of one-week oral or inhaled salbutamol treatment with washout on repeated sprint performance in trained subjects

Background: Acute and chronic supratherapeutic treatment with the commonly used beta2-agonist salbutamol has the potential to enhance sprint performance and muscle strength. However, little is known about the performance effects of short-term daily permitted inhaled treatment vs oral prohibited treatment in accordance with the 2020 Prohibited List issued by the World Anti-Doping Agency (WADA). Methods: Herein, we investigated the effect of twice-daily treatment with 400 μg inhaled or 4 mg oral salbutamol for 1 week on repeated sprint performance in 19 healthy well-trained men and women utilizing a randomized open-label crossover design. Before and after each treatment period, and a 12-16 hours washout to avoid an acute effect of salbutamol, subjects performed a repeated sprint test (3 × 30-second Wingate). Results: Neither oral nor inhaled salbutamol enhanced peak power (oral; 3.0 W; 95% CI −6.8 to 12.8 W; and inhaled; −3.8 W; 95% CI −14.3 to 6.8 W) or mean power (oral; −2.1 W; 95% CI −4.7 to 8.9 W and inhaled; −1.6 W; 95% CI −5.6 to 8.9 W) during the repeated sprint test irrespective of gender. Conclusions: These findings indicate that 1 week is insufficient for salbutamol to induce any relevant effect on repeated sprint performance in trained individuals