Pharmacokinetics of inorganic cobalt and a vitamin B12 supplement in the thoroughbred horse: differentiating cobalt abuse from supplementation

Background While cobalt is an essential micronutrient for vitamin B12 synthesis in the horse, at supraphysiological concentrations, it has been shown to enhance performance in human subjects and rats, and there is evidence that its administration in high doses to horses poses a welfare threat. Animal sport regulators currently control cobalt abuse via international race day thresholds, but this work was initiated to explore means of potentially adding to application of those thresholds since cobalt may be present in physiological concentrations. Objectives To devise a scientific basis for differentiation between presence of cobalt from bona fide supplementation and cobalt doping through the use of ratios. Study design Six Thoroughbred horses were given 10 mL vitamin B12/cobalt supplement (Hemo‐15®; Vetoquinol, Buckingham, Buckinghamshire, UK., 1.5 mg B12, 7 mg cobalt gluconate = 983 μg total Co) as an i.v. bolus then an i.v. infusion (15 min) of 100 mg cobalt chloride (45.39 mg Co) 6 weeks later. Pre‐and post‐administration plasma and urine samples were analysed for cobalt and vitamin B12. Methods Urine and plasma samples were analysed for vitamin B12 using an immunoassay and cobalt concentrations were measured via ICP‐MS. Baseline concentrations of cobalt in urine and plasma for each horse were subtracted from their cobalt concentrations post‐administration for the PK analysis. Compartmental analysis was used for the determination of plasma PK parameters for cobalt using commercially available software. Results On administration of a vitamin B12/cobalt supplement, the ratio of cobalt to vitamin B12 in plasma rapidly increased to approximately 3 and then rapidly declined below a ratio of 1 and then back to near baseline over the next week. On administration of 100 mg cobalt chloride, the ratio initially exceeded 10 in plasma and then declined with the lower 95% confidence interval remaining above a ratio of 1 for 7 days. For two horses with extended sampling, the plasma ratio remained above one for approximately 28 days after cobalt chloride administration. The effect of the administration of the vitamin B12/cobalt supplement on the urine ratio was transient and reached a peak value of 10 which then rapidly declined. However, a urine ratio of 10 was exceeded, with the lower 95% confidence interval remaining above a ratio of 10 for 7 days after cobalt chloride administration. For the two horses with extended sampling, the urine ratio remained above 10 for about 18 days (442 h) after cobalt chloride administration even though the absolute cobalt urine concentration had dropped below the international threshold of 100 ng/mL after 96 h. Main limitations Only one vitamin B12/cobalt product was evaluated, a limited number of horses were included, the horses were not in full race training and the results may be specific to this population of horses. Conclusions The results provide the basis for a potential strategy for allowing supplementation with vitamin B12 products, while controlling the misuse of high doses of cobalt, through a combination of international thresholds and ratios of cobalt to vitamin B12, in plasma and urine

The feasibility of producing oil palm with altered lignin content to control Ganoderma disease

Oil palm is a major crop which is grown for the production of vegetable oil used in foods, cosmetics and biodiesel. The palm is of major economic importance in southeast Asia where it is grown extensively in Malaysia and Indonesia. There is concern about Ganoderma rots of oil palm which need to be controlled to prevent major infection. However, the basic mechanism of white-rot infection has been ignored. White rot implies that fungi attack the lignin component of woody tissue leaving the white cellulose exposed. The fungus grows within palms by utilizing cellulose in the tree. By altering the lignin fraction of oil palm losses may be reduced. Methods for altering lignin in plants are reviewed here to indicate how similar transformations could be attempted for oil palm. In addition, progress in transforming oil palm is described. Lignin is extremely complex and this may explain why it has not been studied in oil palm. Some crops transformed with Bacillus thuringiensis toxin genes have increased lignin and modified oil palm have been produced using B. thuringiensis genes. These require to be tested for lignin concentration and structure. The nomenclature of the disease organism is discussed. The prospects for altered lignin oil palm are considered herein.Fundação para a Ciência e a Tecnologia (FCT) - SFRH ⁄ BPD ⁄ 34879 ⁄ 200

Changes of Functional MRI Findings in a Patient Whose Pathological Gambling Improved with Fluvoxamine

Legalized gambling is a growing industry, and is probably a factor in the presently increasing prevalence of pathological gambling. We present a case of a 36-year-old pathological gambler who was treated with fluvoxamine, a selective serotonin reuptake inhibitor, and who was assessed by functional MRI before and after drug administration. During activation periods, the pathological gambler was shown cards as stimuli, and fMRI results in several brain regions showed differential effects before and after medication and a maintenance period. This case demonstrates that the treatment response to fluvoxamine in a pathological gambler was observed not only by subjective self-report, but also by objective fMRI results. Therefore, fMRI may be a useful tool in the diagnosis and prediction of treatment response in patients afflicted with pathological gambling

A versatile gene trap to visualize and interrogate the function of the vertebrate proteome

We report a multifunctional gene-trapping approach, which generates full-length Citrine fusions with endogenous proteins and conditional mutants from a single integration event of the FlipTrap vector. We identified 170 FlipTrap zebrafish lines with diverse tissue-specific expression patterns and distinct subcellular localizations of fusion proteins generated by the integration of an internal citrine exon. Cre-mediated conditional mutagenesis is enabled by heterotypic lox sites that delete Citrine and “flip” in its place mCherry with a polyadenylation signal, resulting in a truncated fusion protein. Inducing recombination with Cerulean-Cre results in fusion proteins that often mislocalize, exhibit mutant phenotypes, and dramatically knock down wild-type transcript levels. FRT sites in the vector enable targeted genetic manipulation of the trapped loci in the presence of Flp recombinase. Thus, the FlipTrap captures the functional proteome, enabling the visualization of full-length fluorescent fusion proteins and interrogation of function by conditional mutagenesis and targeted genetic manipulation

Temporal Changes in Functional Magnetic Resonance Imaging Activation of Heterosexual Couples for Visual Stimuli of Loved Partners

ObjectiveaaPrevious neuroimaging studies on romantic love have focused on determining how the visual stimuli that serve as a representation of loved ones induce the neural activation patterns of romantic love. The purpose of this study was to investigate the temporal changes in romantic love over a period of 6 months and their correlated neurophysiological changes. MethodsaaFive heterosexual couples (n=10, mean age 21.1±1.97) who started dating not less than 100 days previously were recruited to measure their blood oxygen level dependent (BOLD) signals using functional magnetic resonance imaging (fMRI) while showing them pictures of their loved ones and their previously identified, opposite-sex friends. Subsequently, the subjects were scanned under the same experimental conditions to assess possible changes in their brain activities after 180 days. ResultsaaWe found that their Passionate Love Score (PLS) values (M: 118.6±9.1, F: 120.2 ±7.0) were significantly reduced after 6 months (M: 110.8±4.0, F: 106.2±3.0). Furthermore, significantly increased activations were found in the cingulate gyri, inferior frontal gyri, supramarginal gyri, etc., after 6 months, whereas the head and tail of the right caudate nucleus were deactivated, which is indicative of the inhibition of expression and sensory neglect. ConclusionaaThese findings suggest that dynamic neural processes in the cortical-subcortical regions are involved in temporal changes in romantic love

Temporal Changes in Functional Magnetic Resonance Imaging Activation of Heterosexual Couples for Visual Stimuli of Loved Partners

ObjectiveaaPrevious neuroimaging studies on romantic love have focused on determining how the visual stimuli that serve as a representation of loved ones induce the neural activation patterns of romantic love. The purpose of this study was to investigate the temporal changes in romantic love over a period of 6 months and their correlated neurophysiological changes. MethodsaaFive heterosexual couples (n=10, mean age 21.1±1.97) who started dating not less than 100 days previously were recruited to measure their blood oxygen level dependent (BOLD) signals using functional magnetic resonance imaging (fMRI) while showing them pictures of their loved ones and their previously identified, opposite-sex friends. Subsequently, the subjects were scanned under the same experimental conditions to assess possible changes in their brain activities after 180 days. ResultsaaWe found that their Passionate Love Score (PLS) values (M: 118.6±9.1, F: 120.2 ±7.0) were significantly reduced after 6 months (M: 110.8±4.0, F: 106.2±3.0). Furthermore, significantly increased activations were found in the cingulate gyri, inferior frontal gyri, supramarginal gyri, etc., after 6 months, whereas the head and tail of the right caudate nucleus were deactivated, which is indicative of the inhibition of expression and sensory neglect. ConclusionaaThese findings suggest that dynamic neural processes in the cortical-subcortical regions are involved in temporal changes in romantic love

Non-invasive brain stimulation for speech in Parkinson’s disease: A randomized controlled trial.

Background: Hypokinetic dysarthria is a common but difficult-to-treat symptom of Parkinson's disease (PD). Objectives: We evaluated the long-term effects of multiple-session repetitive transcranial magnetic stimulation on hypokinetic dysarthria in PD. Neural mechanisms of stimulation were assessed by functional MRI. Methods: A randomized parallel-group sham stimulation-controlled design was used. Patients were randomly assigned to ten sessions (2 weeks) of real (1 Hz) or sham stimulation over the right superior temporal gyrus. Stimulation effects were evaluated at weeks 2, 6, and 10 after the baseline assessment. Articulation, prosody, and speech intelligibility were quantified by speech therapist using a validated tool (Phonetics score of the Dysarthric Profile). Activations of the speech network regions and intrinsic connectivity were assessed using 3T MRI. Linear mixed models and post-hoc tests were utilized for data analyses. Results: Altogether 33 PD patients completed the study (20 in the real stimulation group and 13 in the sham stimulation group). Linear mixed models revealed significant effects of time (F(3, 88.1) = 22.7, p < 0.001) and time-by-group interactions: F(3, 88.0) = 2.8, p = 0.040) for the Phonetics score. Real as compared to sham stimulation led to activation increases in the orofacial sensorimotor cortex and caudate nucleus and to increased intrinsic connectivity of these regions with the stimulated area. Conclusions: This is the first study to show the long-term treatment effects of non-invasive brain stimulation for hypokinetic dysarthria in PD. Neural mechanisms of the changes are discussed. (c) 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Accurate determination of key surface properties that determine the efficient separation of bovine milk BSA and LF proteins

The aim of this work is to accurately measure fundamental surface properties, i.e., zeta potential, isoelectric point and protein size that determine the optimal separation conditions of Bovine serum albumin and lactoferrin, two high added value food proteins whose similarity in weight makes their separation a scientific and technical challenge. The systematic study of these proteins’ surface properties was performed under different conditions: (i) 3.0 < pH < 10.0, (ii) electrolyte type: KCl, NaCl and CaCl2 and concentration (0.01–0.1 M KCl) and (iii) protein concentration in the range of 0.04–4.0 g L-1 for BSA and 0.01–1.0 g L-1 for LF with the objective of establishing the optimal separation conditions. Finally, the comparison of the experimental and theoretically calculated values revealed significant deviations under specific conditions, highlighting the simplicity of the theoretical assumptions and leading to the conclusion that the use of experimental surface properties is still needed for the correct design of food protein separation processes.Financial support from the Projects CTQ2011-25262, CTM2011- 23912 and CTQ2012- 31639 (Ministerio de Economía y Competitividad-MINECO/SPAIN and Fondo Europeo de Desarrollo Regional-FEDER) is gratefully acknowledged