Activation of T-bet, FOXP3, and EOMES in Target Organs From Piglets Infected With the Virulent PRRSV-1 Lena Strain

Transcription factors (TFs) modulate genes involved in cell-type-specific proliferative and migratory properties, metabolic features, and effector functions. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important pathogen agents in the porcine industry; however, TFs have been poorly studied during the course of this disease. Therefore, we aimed to evaluate the expressions of the TFs T-bet, GATA3, FOXP3, and Eomesodermin (EOMES) in target organs (the lung, tracheobronchial lymph node, and thymus) and those of different effector cytokines (IFNG, TNFA, and IL10) and the Fas ligand (FASL) during the early phase of infection with PRRSV-1 strains of different virulence. Target organs from mock-, virulent Lena-, and low virulent 3249-infected animals humanely euthanized at 1, 3, 6, 8, and 13 days post-infection (dpi) were collected to analyze the PRRSV viral load, histopathological lesions, and relative quantification through reverse transcription quantitative PCR (RT-qPCR) of the TFs and cytokines. Animals belonging to both infected groups, but mainly those infected with the virulent Lena strain, showed upregulation of the TFs T-bet, EOMES, and FOXP3, together with an increase of the cytokine IFN-g in target organs at the end of the study (approximately 2 weeks post-infection). These results are suggestive of a stronger polarization to Th1 cells and regulatory T cells (Tregs), but also CD4+ cytotoxic T lymphocytes (CTLs), effector CD8+ T cells, and gdT cells in virulent PRRSV-1-infected animals; however, their biological functionality should be the object of further studies

Ethanol-Induced Increase of Agouti-Related Protein (AgRP) Immunoreactivity in the Arcuate Nucleus of the Hypothalamus of C57BL/6J, but not 129/SvJ, Inbred Mice

The melanocortin (MC) system is composed of peptides that are cleaved from the polypeptide precursor, pro-opiomelanocortin (POMC). Previous research has shown that MC receptor (MCR) agonists reduce, and MCR antagonists increase, ethanol consumption in rats and mice. Consistently, genetic deletion of the endogenous MCR antagonist, agouti-related protein (AgRP), causes reductions of ethanol-reinforced lever pressing and binge-like ethanol drinking in C57BL/6J mice. Ethanol also has direct effects on the central MC system, as chronic exposure to an ethanol-containing diet causes significant reductions of α-melanocyte stimulating hormone (α-MSH) immunoreactivity in specific brain regions of Sprague-Dawley rats. Together, these observations suggest that the central MC system modulates neurobiological responses to ethanol. To further characterize the role of the MC system in responses to ethanol, here we compared AgRP and α-MSH immunoreactivity in response to an acute injection of saline or ethanol between high ethanol drinking C57BL/6J mice and moderate ethanol drinking 129/SvJ mice

Nucleus Accumbens MC4-R Stimulation Reduces Food and Ethanol Intake in Adult Rats Regardless of Binge-Like Ethanol Exposure during Adolescence

The melanocortin (MC) system regulates feeding and ethanol consumption. Recent evidence shows that melanocortin 4 receptor (MC4-R) stimulation within the nucleus accumbens (NAc) elicits anorectic responses and reduces ethanol consumption and ethanol palatability in adult rats. Ethanol exposure during adolescence causes long-lasting changes in neural pathways critically involved in neurobehavioral responses to ethanol. In this regard, binge-like ethanol exposure during adolescence reduces basal alpha-melanocyte-stimulating hormone (α-MSH) and alters the levels of agouti-related peptide (AgRP) in hypothalamic and limbic areas. Given the protective role of MC against excessive ethanol consumption, disturbances in the MC system induced by binge-like ethanol exposure during adolescence might contribute to excessive ethanol consumption during adulthood. In the present study, we evaluated whether binge-like ethanol exposure during adolescence leads to elevated ethanol intake and/or eating disturbance during adulthood. Toward that aim, Sprague-Dawley rats were treated with ethanol (3 g/kg i.p.; BEP group) or saline (SP group) for 14 days (PND 25 to PND 38). On PND73, all the groups were given access to 20% ethanol on an intermittent schedule. Our results showed that adult rats given intermittent access (IAE) to 20% ethanol achieved high spontaneous ethanol intake that was not significantly enhanced by binge-like ethanol pretreatment during adolescence. However, BEP group exhibited an increase in food intake without a parallel increase in body weight (BW) relative to SP group suggesting caloric efficiency disturbance. Additionally, we evaluated whether binge-like ethanol exposure during adolescence alters the expected reduction in feeding and ethanol consumption following NAc shell administration of a selective MC4-R agonist in adult rats showing high rates of ethanol consumption. For that, animals in each pretreatment condition (SP and BEP) were divided into three subgroups and given bilateral NAc infusions of the selective MC4-R agonist cyclo(NH-CH2-CH2-CO-His-D-Phe-Arg-Trp-Glu)-NH2 (0, 0.75 or 1.5 μg). Results revealed that MC4-R stimulation within the NAc reduced feeding and ethanol intake in high ethanol-drinking adult rats, regardless of previous binge-like ethanol exposure during adolescence, which adds new evidence regarding the dual ability of MC compounds to control excessive ethanol and food intake

Condición física relacionada con depresión y calidad de vida en personas mayores

El objetivo de esta investigación fue conocer la relación de la condición física con la depresión y la calidad de vida en personas mayores sedentarias y no sedentarias de los centros sociales del Ayuntamiento de Huelva. En este sentido se han medido las variables: condición física (Senior Fitness Test), la depresión (Escala de Depresión Geriátrica) y calidad de vida (SF36). Valoramos a 63 personas mayores sedentarias de entre 60 y 87 años (M=71.2; DS= 5.81) y 66 no sedentarios de entre 60 y 87 años (M= 69.71; DS=6.1). En función del género, en sedentarios el 22.2% fueron varones (n= 14) y un 77.8%, mujeres (n= 49) y en no sedentarios el 19.7% fueron hombres (n=13) y el 80.3% mujeres (n=53). La condición física de las personas mayores sedentarias está unos puntos por encima de los no sedentarios, salvo los valores de fuerza. En cuanto a la depresión, las mujeres tienen un estado depresivo mayor que los hombres y con valores más altos en las sedentarias respecto a las no sedentarias. Finalmente, en cuanto a la relación entre nivel de condición física y la depresión, existe una relación positiva, sobre todo un nivel óptimo de fuerza favorece una menor depresión. Las conclusiones del estudio mostraron que la condición física de las personas mayores sedentarias está por encima de los no sedentarios, excepto los valores de fuerza. En términos de depresión, las mujeres tienen un estado depresivo más alto que los hombres y con valores más altos en sedentarios versus no sedentarios.This research aimed to concretize the relationship between physical fitness with depression and quality of life in the sedentary and non-sedentary older people of the social centres of the City of Huelva. We have measured the variables: Physical Fitness (Senior Fitness Test), depression (Geriatric Depression Scale) and quality of life (SF36). We evaluated 63 sedentary older people between 60 and 87 years old (M = 71.2; SD = 5.81) and 66 non-sedentary older people between 60 and 87 years old (M= 69.71; DS=6.1). By gender, in sedentary older people 22.2% were men (n = 14) and 77.8% women (n = 49) and in non-sedentary 19.7 % were men (n=13) and 80.3% women (n=53). The physical fitness of the sedentary majors is some points above the non-sedentary ones, except the values of strength. In terms of depression, women have a higher depressive state than men and with higher values in sedentary versus non-sedentary. Finally, regarding the relationship between fitness level and depression, there is a positive relationship, especially an optimal level of strength favours a lower depression. The conclusions of the study emphasized that the physical fitness of the sedentary majors is above the non-sedentary ones, except the values of strength. In terms of depression, women have a higher depressive state than men and with higher values in sedentary versus non-sedentary.O objetivo desta pesquisa foi conhecer a relação da condição física com a depressão e a qualidade de vida em idosos sedentários e não sedentários dos centros sociais da cidade de Huelva. Nesse sentido, as variáveis foram medidas: aptidão física (Senior Fitness Test), depressão (Geriatric Depression Scale) e qualidade de vida (SF36). Avaliamos 63 idosos sedentários entre 60 e 87 anos (M = 71,2; DP = 5,81) e 66 pessoas não sedentárias entre 60 e 87 anos (M = 69,71; DS = 6,1). Dependendo do sexo, 22,2% eram sedentários nos homens (n = 14) e 77,8%, mulheres (n = 49) e 19,7% nos homens não sedentários (n = 13) e 80,3% mulheres (n = 53). A condição física dos idosos sedentários está alguns pontos acima dos não sedentários, exceto pelos valores de força. Em relação à depressão, as mulheres apresentam um estado depressivo maior que os homens e com valores mais altos nas mulheres sedentárias do que nas não sedentárias. Finalmente, em relação à relação entre nível de condicionamento físico e depressão, existe uma relação positiva, especialmente um nível ótimo de força que favorece uma depressão menor. As conclusões do estudo mostraram que a condição física dos idosos sedentários está acima dos não sedentários, exceto os valores de força. Em termos de depressão, as mulheres têm um estado depressivo mais alto que os homens e com valores mais altos em sedentários versus não sedentários

Condición física relacionada con depresión y calidad de vida en personas mayores

El objetivo de esta investigación fue conocer la relación de la condición física con la depresión y la calidad de vida en personas mayores sedentarias y no sedentarias de los centros sociales del Ayuntamiento de Huelva. En este sentido se han medido las variables: condición física (Senior Fitness Test), la depresión (Escala de Depresión Geriátrica) y calidad de vida (SF36). Valoramos a 63 personas mayores sedentarias de entre 60 y 87 años (M=71.2; DS= 5.81) y 66 no sedentarios de entre 60 y 87 años (M= 69.71; DS=6.1). En función del género, en sedentarios el 22.2% fueron varones (n= 14) y un 77.8%, mujeres (n= 49) y en no sedentarios el 19.7% fueron hombres (n=13) y el 80.3% mujeres (n=53). La condición física de las personas mayores sedentarias está unos puntos por encima de los no sedentarios, salvo los valores de fuerza. En cuanto a la depresión, las mujeres tienen un estado depresivo mayor que los hombres y con valores más altos en las sedentarias respecto a las no sedentarias. Finalmente, en cuanto a la relación entre nivel de condición física y la depresión, existe una relación positiva, sobre todo un nivel óptimo de fuerza favorece una menor depresión. Las conclusiones del estudio mostraron que la condición física de las personas mayores sedentarias está por encima de los no sedentarios, excepto los valores de fuerza. En términos de depresión, las mujeres tienen un estado depresivo más alto que los hombres y con valores más altos en sedentarios versus no sedentarios

Detection of Mycobacterium tuberculosis complex field infections in cattle using fecal volatile organic compound analysis through gas chromatography-ion mobility spectrometry combined with chemometrics

Bovine tuberculosis is considered a re-emerging disease caused by different species from the Mycobacterium tuberculosis complex (MTC), important not only for the livestock sector but also for public health due to its zoonotic character. Despite the numerous efforts that have been carried out to improve the performance of the current antemortem diagnostic procedures, nowadays, they still pose several drawbacks, such as moderate to low sensitivity, highlighting the necessity to develop alternative and innovative tools to complement control and surveillance frameworks. Volatilome analysis is considered an innovative approach which has been widely employed in animal science, including animal health field and diagnosis, due to the useful and interesting information provided by volatile metabolites. Therefore, this study assesses the potential of gas chromatography coupled to ion mobility spectrometry (GC-IMS) to discriminate cattle naturally infected (field infections) by MTC from non-infected animals. Volatile organic compounds (VOCs) produced from feces were analyzed, employing the subsequent information through chemometrics. After the evaluation of variable importance for the projection of compounds, the final discriminant models achieved a robust performance in cross-validation, as well as high percentages of correct classification (>90%) and optimal data of sensitivity (91.66%) and specificity (99.99%) in external validation. The tentative identification of some VOCs revealed some coincidences with previous studies, although potential new compounds associated with the discrimination of infected and non-infected subjects were also addressed. These results provide strong evidence that a volatilome analysis of feces through GC-IMS coupled to chemometrics could become a valuable methodology to discriminate the infection by MTC in cattle. IMPORTANCE Bovine tuberculosis is endemic in many countries worldwide and poses important concerns for public health because of their zoonotic condition. However, current diagnostic techniques present several hurdles, such as low sensitivity and complexity, among others. In this regard, the development of new approaches to improve the diagnosis and control of this disease is considered crucial. Volatile organic compounds are small molecular mass metabolites which compose volatilome, whose analysis has been widely employed with success in different areas of animal science including animal health. The present study seeks to evaluate the combination of fecal volatilome analysis with chemometrics to detect field infections by bovine tuberculosis (Mycobacterium tuberculosis complex) in cattle. The good robust performance of discriminant models as well as the optimal data of sensitivity and specificity achieved highlight volatilome analysis as an innovative approach with huge potential.European Commission GOP2I-CO-16-001

Assessment of Voluntary Ethanol Consumption and the Effects of a Melanocortin (MC) Receptor Agonist on Ethanol Intake in Mutant C57BL/6J Mice Lacking the MC-4 Receptor: ETHANOL AND MC-4 RECEPTOR

The melanocortin (MC) system is composed of peptides that are cleaved from the polypeptide precursor proopiomelanocortin (POMC). Recent evidence shows that chronic exposure to ethanol significantly blunts central MC peptide immunoreactivity and MC receptor (MCR) agonists protect against high ethanol intake characteristic of C57BL/6J mice. Here we assessed the role of the MC-4 receptor (MC4R) in voluntary ethanol intake and in modulating the effects of the non-selective MCR agonist melanotan-II (MTII) on ethanol consumption

Evidence that Melanocortin Receptor Agonist Melanotan-II Synergistically Augments the Ability of Naltrexone to Blunt Binge-Like Ethanol Intake in Male C57BL/6J Mice

The non-selective opioid receptor antagonist, naltrexone (NAL), reduces alcohol (ethanol) consumption in animals and humans and is an approved medication for treating alcohol abuse disorders. Proopiomelanocortin (POMC)-derived melanocortin (MC) and opioid peptides are produced in the same neurons in the brain, and recent pre-clinical evidence shows that MC receptor (MCR) agonists reduce excessive ethanol drinking in animal models. Interestingly, there is a growing body of literature revealing interactions between the MC and opioid systems in the modulation of pain, drug tolerance, and food intake

MC4-R signaling within the nucleus accumbens shell, but not the lateral hypothalamus, modulates ethanol palatability in rats

The Melanocortin (MC) system is one of the crucial neuropeptidergic systems that modulate energy balance. The roles of endogenous MC and MC-4 receptor (MC4-R) signaling within the hypothalamus in the control of homeostatic aspects of feeding are well established. Additional evidence points to a key role for the central MC system in ethanol consumption. Recently, we have shown that nucleus accumbens (NAc), but not lateral hypothalamic (LH), infusion of a selective MC4-R agonist decreases ethanol consumption. Given that MC signaling might contribute to non-homeostatic aspects of feeding within limbic circuits, we assessed here whether MC4-R signaling within the NAc and the lateral hypothalamus (LH) alters normal ingestive hedonic and/or aversive responses to ethanol in rats as measured by a taste reactivity test. Adult male Sprague-Dawley rats were given NAc- or LH- bilateral infusion of the selective MC4-R agonist cyclo (NH-CH2-CH2-CO-His-D-Phe-Arg-Trp-Glu)-NH2 (0, 0.75 or 1.5 µg/0.5µl/site) and following 30 min, the animals received 1 ml of ethanol solution (6% w/v) intraoral for 1 minute and aversive and hedonic behaviors were recorded. We found that NAc-, but not LH-administration, of a selective MC4-R agonist decreased total duration of hedonic reactions and significantly increased aversive reactions relative to saline-infused animals which support the hypothesis that MC signaling within the NAc may contribute to ethanol consumption by modulating non-homeostatic aspects (palatability) of intake