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The photoprotective role of anthocyanin remains controversial. In this study, we explored the effects of anthocyanin on photosynthesis and photoprotection using transgenic ‘Galaxy Gala’ apple plants overexpressing MdMYB10 under high light stress. The overexpression of MdMYB10 dramatically enhanced leaf anthocyanin accumulation, allowing more visible light to be absorbed, particularly in the green region. However, through post-transcriptional regulation, anthocyanin accumulation lowered leaf photosynthesis in both photochemical reaction and CO2 fixation capacities. Anthocyanin accumulation also led to a decreased de-epoxidation state of the xanthophyll cycle and antioxidant capacities, but this is most likely a response to the light-shielding effect of anthocyanin, as indicated by a higher chlorophyll concentration and lower chlorophyll a/b ratio. Under laboratory conditions when detached leaves lost carbon fixation capacity due to the limitation of CO2 supply, the photoinhibition of detached transgenic red leaves was less severe under strong white, green, or blue light, but it became more severe in response to strong red light compared with that of the wild type. In field conditions when photosynthesis was performed normally in both green and transgenic red leaves, the degree of photoinhibition was comparable between transgenic red leaves and wild type leaves, but it was less severe in transgenic young shoot bark compared with the wild type. Taken together, these data show that anthocyanin protects plants from high light stress by absorbing excessive visible light despite reducing photosynthesis.

Human muscle biopsies are often required to study or diagnose diseases. However, traditional approaches are challenging due to limited sample size, quality, or participant discomfort. Fine-gauge needle biopsies (≥ 14-gauge), present an alternative but may yield insufficient tissue for comprehensive analysis. Ultrasound guidance, coupled with vacuum-assisted, single needle-insertion multiple sampling addresses these challenges. In 19 healthy participants (mean age: 30.1 ± 10 years, 42% male), 2–3 samples were collected from a single needle insertion into the vastus lateralis (VL) and tibialis anterior (TA). Summed VL and TA sample masses averaged 148 ± 38 mg and 166 ± 64 mg, with dimensions of 15.83 ± 8 × 2.9 ± 0.6mm 2 (VL) and 15.07 ± 7 × 3.1 ± 0.9mm 2 (TA). VL had a mean fiber cross-sectional area of 4,347 ± 1,931µm 2 , with 221 ± 86 fibers quantified. Samples were of sufficient size and quality for thorough analyses from a single biopsy procedure, including mitochondrial respirometry, RT-PCR, collagen content, and biomechanical function. Fibers produced typical isometric stress values of 187 kPa with a passive modulus of 239 kPa (peak) and 79 kPa (stress-relaxed). The procedure was well tolerated, with an average immediate pain rating of 1.5 ± 1 (range:0–4, scale: 0–10) and 24-hour follow-up rating of 1.7 ± 1 (range:0–4). This report describes an approach that yields high-quality muscle samples suitable for histological and biochemical analyses while minimizing discomfort.

Mouse models are valuable in preclinical studies of inflammatory arthritis. However, current methods for measuring disease severity or responses to treatment are not optimal. In this study a smart cage system using multiple sensors to measure locomotor activity was evaluated in the K/BxN serum transfer model of inflammatory arthritis. Arthritis was induced in C57BL/6 mice with injections of K/BxN serum. Clinical index and ankle thickness were measured for 14 days. Locomotor activity was measured in smart cages for 23 h periods on Days 0, 7, and 13. The same measurements were taken in mice consuming diets supplemented or not with fish oil to evaluate a preventative treatment. Initiation, peak and resolution phases of disease could be measured with the smart cages. Locomotor activity including speed, travel distance, number of active movements and rear movements were all significantly lower on Days 7-8 of illness (peak) compared to Days 0 and 13-14 (resolution) (one-way repeated measures analyses, p<0.05). The clinical index and ankle thickness measurements did not capture differences between dietary groups. Significantly increased activity was measured in most of the locomotor parameters in the fish oil group compared to the control mice at both Days 8 and 14 (2-way repeated measures ANOVA, p<0.05). The measurement of locomotor activity provided a more detailed evaluation of the impact of inflammatory arthritis on animal well-being and mobility than that provided by measuring clinical index and ankle thickness, and could be a valuable tool in preclinical studies of inflammatory arthritis.

Ground motion is a severe problem for many particle accelerators, since it excites beam oscillations, which decrease the beam quality and create beam-beam offset (at colliders). Orbit feedback systems can only compensate ground motion effects at frequencies significantly smaller than the beam repetition rate. In linear colliders, where the repetition rate is low, additional counter measures have to be put in place. For this reason, a ground motion mitigation method based on feed-forward control is presented in this paper. It has several advantages compared to other techniques (stabilization systems and intratrain feedback systems) such as cost reduction and potential performance improvement. An analytical model is presented that allows the derivation of hardware specification and performance estimates for a specific accelerator and ground motion model. At the Accelerator Test Facility (ATF2), ground motion sensors have been installed to verify the feasibility of important parts of the mitigation strategy. In experimental studies, it has been shown that beam excitations due to ground motion can be predicted from ground motion measurements on a pulse-to-pulse basis. Correlations of up to 80% between the estimated and measured orbit jitter have been observed. Additionally, an orbit jitter source was identified and has been removed, which halved the orbit jitter power at ATF2 and shows that the feed-forward scheme is also very useful for the detection of installation issues. We believe that the presented mitigation method has the potential to reduce costs and improve the performance of linear colliders and potentially other linear accelerators.

Despite their evolutionary novelty, lizard venoms are much less studied in comparison to the intense research on snake venoms. While the venoms of helodermatid lizards have long been assumed to be for defensive purposes, there is increasing evidence of toxic activities more useful for predation than defence (such as paralytic neurotoxicity). This study aimed to ascertain the effects of Heloderma, Lanthanotus, and Varanus lizard venoms on the coagulation and cardiovascular systems. Anticoagulant toxicity was demonstrated for the Varanus species studied, with the venoms prolonging clotting times in human and bird plasma due to the destructive cleavage of fibrinogen. In contrast, thromboelastographic analyses on human and bird plasmas in this study demonstrated a procoagulant bioactivity for Heloderma venoms. A previous study on Heloderma venom using factor-depleted plasmas as a proxy model suggested a procoagulant factor was present that activated either Factor XI or Factor XII, but could not ascertain the precise target. Our activation studies using purified zymogens confirmed FXII activation. Comparisons of neonate and adult H. exasperatum, revealed the neonates to be more potent in the ability to activate FXII, being more similar to the venom of the smaller species H. suspectum than the adult H. exasperatum. This suggests potent FXII activation a basal trait in the genus, present in the small bodied last common ancestor. This also indicates an ontogenetic difference in prey preferences in the larger Heloderma species paralleing the change in venom biochemistry. In addition, as birds lack Factor XII, the ability to clot avian plasma suggested an additional procoagulant site of action, which was revealed to be the activation of Factor VII, with H. horridum being the most potent. This study also examined the effects upon the cardiovascular system, including the liberation of kinins from kininogen, which contributes to hypotension induction. This form of toxicity was previously described for Heloderma venoms, and was revealed in this study was to also be a pathophysiological effect of Lanthanotus and Varanus venoms. This suggests that this toxic activity was present in the venom of the last common ancestor of the anguimorph lizards, which is consistent with kallikrein enzymes being a shared toxin trait. This study therefore uncovered novel actions of anguimorph lizard venoms, not only contributing to the evolutionary biology body of knowledge but also revealing novel activities to mine for drug design lead compounds.

Soxhlet (SE), microwave-assisted (MAE) and ultrasound-assisted (UAE) extraction were compared using ten extraction solvents for their efficiency to extract phenolic and flavonoid antioxidants from Eastern Canada propolis. Extracts were compared for total phenolic (TPC) and total flavonoid (TFC) content, and radical scavenging activities. Anti-inflammatory activity through inhibition of 5-lipoxygenase (5-LO) products biosynthesis in HEK293 cells was also evaluated. The results showed that SE extracts using polar solvents had the highest TPC and TFC. Extracts obtained with ethanol, methanol and acetone were effective free radical scavengers, and showed 5-LO inhibition similar to zileuton. UAE was an effective extraction method since the extracts obtained were comparable to those using SE and the MAE while being done at room temperature. With UAE, extracts of less polar solvents showed similar free radical scavenging and 5-LO inhibition to extracts of much more polar solvents such as methanol or ethanol. Reversed-phase liquid chromatography tandem mass spectrometry confirmed the presence of 21 natural compounds in the propolis extracts based on the comparison of intact mass, chromatographic retention time and fragmentation patterns derived from commercial analytical standards. The current study is the first of its kind to concurrently investigate solvent polarity as well as extraction techniques of propolis.

Glioblastoma multiforme (GBM) is an aggressive brain tumor that correlates with short patient survival and for which therapeutic options are limited. Polyphenolic compounds, including caffeic acid phenethyl ester (CAPE, 1a), have been investigated for their anticancer properties in several types of cancer. To further explore these properties in brain cancer cells, a series of caffeic and ferulic acid esters bearing additional oxygens moieties (OH or OCH3) were designed and synthesized. (CAPE, 1a), but not ferulic acid phenethyl ester (FAPE, 1b), displayed substantial cytotoxicity against two glioma cell lines. Some but not all selected compounds derived from both (CAPE, 1a) and (FAPE, 1b) also displayed cytotoxicity. All CAPE-derived compounds were able to significantly inhibit 5-lipoxygenase (5-LO), however FAPE-derived compounds were largely ineffective 5-LO inhibitors. Molecular docking revealed new hydrogen bonds and π-π interactions between the enzyme and some of the investigated compounds. Overall, this work highlights the relevance of exploring polyphenolic compounds in cancer models and provides additional leads in the development of novel therapeutic strategies in gliomas.

Purpose The aim of this study was to investigate the effects of different ω-3 polyunsaturated fatty acid (PUFA) enriched diets, including a novel renewable plant source of ω-3 fatty acids ( Buglossoides arvensis ), on the development and progression of rheumatoid arthritis (RA). Methods RA was induced in mice consuming experimental diets using the K/BxN model. The experimental diets consisted of either a western control diet (control), diets containing B. arvensis oil or fish oil . The effects of the diets on platelets, platelet microvesicles (PMVs), and inflammatory markers such as clinical index, ankle thickness and cytokine/chemokine release were measured. Results While ω-3 PUFA-enriched diets did not prevent the development of arthritis in the K/BxN model, a significant decrease in ankle swelling was observed compared to the control group. Platelets isolated from mice consuming either low content of B. arvensis oil or fish oil diets exhibited significantly decreased PMVs production compared to mice consuming the control diet. Conclusion Our study provides insight into the contribution of ω-3 PUFA supplementation in modulating the pro-inflammatory phenotype of platelets in RA pathology. Furthermore, our study suggests that low concentrations of dietary B. arvensis oil may have similar anti-inflammatory potential seen with dietary fish oil supplementation.

Animal models are commonly used to test the efficacy of impact loading regimens on bone strength. We designed an inexpensive force platform to concurrently measure the separate peak vertical impact forces produced by the fore and hindfeet of immature F-344 rats when dropped onto the platform. The force platform consisted of three load cells placed in a triangular pattern under a flat plate. Rats were dropped from heights of 30, 45 and 60 cm onto the platform so that they landed on all four feet concurrently. The peak vertical impact forces produced by the feet of the rats were measured using a sampling frequency of 100 kHz. The location of each foot at landing relative to the load cells, and the force received by each load cell were combined in a series of static equations to solve for the vertical impact forces produced by the fore and hindfeet. The forces produced by feet when rats stood on the single platform were similarly determined. The forces exerted separately by the fore and hindfeet of young rats when landing on the plate as a ratio to standing forces were then calculated. Rats when standing bore more weight on their hindfeet but landed with more weight on their forefeet, which provides rationale for the greater response to landing forces of bones in the forelimbs than those in the hindlimbs. This system provided a useful method to simultaneously measure peak vertical impact forces in fore and hindfeet in rats.

Due to their robust antioxidant properties, phenolic acids and their analogs are extensively studied for their ability to activate cellular antioxidant pathways, including nuclear factor (erythroid-derived-2)-like 2 (Nrf2)-antioxidant response element (ARE) pathway. Caffeic, ferulic, and gallic acid are well-studied members of phenolic acids. Constant efforts are made to improve the pharmacological effects and bioavailability of phenolic acids by synthesizing their chemical derivatives. This study determines how modifications of the chemical structure of these phenolic acids affect their antioxidant and cytoprotective activities. We have selected six superior antioxidant compounds (12, 16, 26, 35, 42, and 44) of the 48 caffeic acid phenethyl ester (CAPE) analogs based on their ability to scavenge free radicals in vitro using standard antioxidant assays. These compounds exhibited minimal toxicity as indicated by cell cycle and cytochrome C release assays. Among these compounds, 44, the ketone analog of CAPE, exhibited the ability to increase p-Nrf2 (Ser40) levels in 293T cells (p < 0.05). Further, 44, exhibited its antioxidant effect in Drosophila Melanogaster as indicated by an increase in mRNA levels of Nrf2 and GPx (p < 0.05). Finally, the ability of 44 to activate the antioxidant pathway was abolished in the presence of extracellular signal-regulated kinase (ERK) inhibitor in 293T cells. Thus, we identify 44, the ketone analog of CAPE, as a unique antioxidant molecule with the function of ERK-mediated Nrf2 activation.