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1.
Ecol Evol ; 14(7): e11698, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38994214

RESUMEN

Open science (OS) awareness and skills are increasingly becoming an essential part of everyday scientific work as e.g., many journals require authors to share data. However, following an OS workflow can seem challenging at first. Thus, instructions by journals and other guidelines are important. But how comprehensive are they in the field of ecology and evolutionary biology (Ecol Evol)? To find this out, we reviewed 20 published OS guideline articles aimed for ecologists or evolutionary biologists, together with the data policies of 17 Ecol Evol journals to chart the current landscape of OS guidelines in the field, find potential gaps, identify field-specific barriers for OS and discuss solutions to overcome these challenges. We found that many of the guideline articles covered similar topics, despite being written for a narrow field or specific target audience. Likewise, many of the guideline articles mentioned similar obstacles that could hinder or postpone a transition to open data sharing. Thus, there could be a need for a more widely known, general OS guideline for Ecol Evol. Following the same guideline could also enhance the uniformity of the OS practices carried on in the field. However, some topics, like long-term experiments and physical samples, were mentioned surprisingly seldom, although they are typical issues in Ecol Evol. Of the journals, 15 out of 17 expected or at least encouraged data sharing either for all articles or under specific conditions, e.g. for registered reports and 10 of those required data sharing at the submission phase. The coverage of journal data policies varied greatly between journals, from practically non-existing to very extensive. As journals can contribute greatly by leading the way and making open data useful, we recommend that the publishers and journals would invest in clear and comprehensive data policies and instructions for authors.

2.
Vet Dermatol ; 35(3): 325-336, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38169122

RESUMEN

BACKGROUND: Norway spruce (Picea abies) resin-based products are used in human medicine. A resin-based otic rinse also could be useful in supportive care of canine otitis externa (COE), yet information on its antimicrobial effect against canine pathogens or ototoxicity is lacking. OBJECTIVES: To investigate the antimicrobial properties and ototoxicity of a commercial resin-based otic product. MATERIALS AND METHODS: Antimicrobial effect was evaluated using a standardised challenge test on Staphylococcus pseudintermedius, Corynebacterium auriscanis, Pseudomonas aeruginosa, Escherichia coli, Malassezia pachydermatis, and Streptococcus halichoeri strains to measure reduction in growth after 24 h exposure to the product. Effect on cell morphology was investigated by exposing S. pseudintermedius, C. auriscanis, P. aeruginosa and M. pachydermatis to the product in 20% and 100% (v/v) concentrations for 6, 24 and 48 h, and evaluating cells by transmission (TEM) and scanning (SEM) electron microscopy. An in vitro microbial kill-rate assay also was performed. Auditory brain stem response test, clinical evaluation and postmortem histological evaluation of ear canals were undertaken on experimental guinea pigs treated with the test product or saline controls. RESULTS: The product showed >log 5 growth reduction for all strains in the challenge test. TEM and SEM images showed clear changes in the cells' inner structures and deterioration of cells, and 100% (v/v) test product exposure induced microbial killing in 1-2 h. Ototoxicity was not detected in guinea pigs. CONCLUSIONS AND CLINICAL RELEVANCE: The product may be an option in supportive care of COE because of antimicrobial effects and lack of ototoxic properties in a guinea pig model.


Asunto(s)
Enfermedades de los Perros , Picea , Animales , Perros , Proyectos Piloto , Enfermedades de los Perros/tratamiento farmacológico , Otitis Externa/veterinaria , Otitis Externa/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Corynebacterium/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Malassezia/efectos de los fármacos , Staphylococcus/efectos de los fármacos , Ototoxicidad , Cobayas , Antiinfecciosos/farmacología , Antiinfecciosos/toxicidad , Masculino , Pruebas de Sensibilidad Microbiana , Femenino
3.
Zoonoses Public Health ; 71(2): 127-135, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37926867

RESUMEN

AIMS: Corynebacterium diphtheriae and Corynebacterium ulcerans, when producing toxin, are the cause of diphtheria, a potentially life-threatening illness in humans. Horses (Equus ferus caballus) are known to be susceptible to infection that may manifest clinically on rare occasions. In late 2021 and early 2022, specimens from five horses suffering from pastern dermatitis were cultured at the Laboratory of Clinical Microbiology at the Faculty of Veterinary Medicine, University of Helsinki, Finland. C. diphtheriae and/or C. ulcerans were recovered from all of these. This study aimed to (1) analyse the bacterial isolates and (2) describe the outbreak and identify possible sources of the infection and infection routes in the stable. METHODS AND RESULTS: Susceptibility testing, PCR for the tox gene, and Elek test for toxin production in PCR-positive isolates were performed. Whole genome sequencing was also conducted to achieve high-resolution strain typing. An epidemiological survey was done by means of a semi-structured interview of horses' caretaker, and contact tracing was done among people at the stable. Two tox gene-positive, toxin-producing C. diphtheriae belonged to sequence type (ST) 822. Other C. diphtheriae (n = 2, ST828) and C. ulcerans (n = 2, ST325 and ST838) isolates did not carry the tox gene. The epidemiological investigation explored numerous possible routes of transmission, but the definite source of infection was not identified. All established human contacts tested negative for diphtheriae. All horses recovered after antimicrobial treatment. CONCLUSIONS: Our study shows that C. diphtheriae and C. ulcerans may readily spread among horses at the same stable and complicate pastern dermatitis infections. These potentially zoonotic bacteria can cause outbreaks even in a country with a very low prevalence. Caretakers should be encouraged to wear gloves and practice good hand hygiene when treating infected skin lesions in horses.


Asunto(s)
Corynebacterium diphtheriae , Corynebacterium , Dermatitis , Difteria , Enfermedades de los Caballos , Humanos , Caballos , Animales , Corynebacterium diphtheriae/genética , Finlandia/epidemiología , Difteria/epidemiología , Difteria/microbiología , Difteria/veterinaria , Brotes de Enfermedades , Dermatitis/epidemiología , Dermatitis/veterinaria , Enfermedades de los Caballos/epidemiología
4.
Ecol Evol ; 12(11): e9525, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36415871

RESUMEN

Large areas of forests are annually damaged or destroyed by outbreaking insect pests. Understanding the factors that trigger and terminate such population eruptions has become crucially important, as plants, plant-feeding insects, and their natural enemies may respond differentially to the ongoing changes in the global climate. In northernmost Europe, climate-driven range expansions of the geometrid moths Epirrita autumnata and Operophtera brumata have resulted in overlapping and increasingly severe outbreaks. Delayed density-dependent responses of parasitoids are a plausible explanation for the 10-year population cycles of these moth species, but the impact of parasitoids on geometrid outbreak dynamics is unclear due to a lack of knowledge on the host ranges and prevalences of parasitoids attacking the moths in nature. To overcome these problems, we reviewed the literature on parasitism in the focal geometrid species in their outbreak range and then constructed a DNA barcode reference library for all relevant parasitoid species based on reared specimens and sequences obtained from public databases. The combined recorded parasitoid community of E. autumnata and O. brumata consists of 32 hymenopteran species, all of which can be reliably identified based on their barcode sequences. The curated barcode library presented here opens up new opportunities for estimating the abundance and community composition of parasitoids across populations and ecosystems based on mass barcoding and metabarcoding approaches. Such information can be used for elucidating the role of parasitoids in moth population control, possibly also for devising methods for reducing the extent, intensity, and duration of outbreaks.

5.
Sci Total Environ ; 642: 701-707, 2018 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-29913365

RESUMEN

The most common rodent control method worldwide is anticoagulant rodenticides (ARs), which cause death by internal bleeding. ARs can transfer to non-target predators via secondary exposure, i.e. by consuming contaminated rodents. Here we quantify the prevalence of seven AR substances in the liver tissues of altogether 17 mammalian or avian predator or scavenger species in Finland. In addition, we identify the environmental and biological factors potentially linked to secondary AR poisoning. No previous AR screenings have been conducted in the country, despite the widespread use of ARs and their potential impacts on the high levels of the ecosystem food chain. ARs were detected (≥0.3 µg/kg) in 82% of the 131 samples. The most prevalent and the AR with highest concentrations was bromadiolone (65% of samples). In 77% of the positive samples more than one (2-5) different ARs were detected. Of the environmental variables, we only found a weakly positive relationship between the coumatetralyl concentration and the livestock farm density. Conversely, overall AR concentration and number, as well as the concentration of three separate ARs (coumatetralyl, difenacoum and bromadiolone) differed among the three species groups tested, with the group "other mammals" (largely represented by red fox and raccoon dog) having higher values than the groups presented by mustelids or by birds. ARs are authorized only as biocides in Finland and a national strategy on risk management (e.g. for minimising secondary poisoning of non-target species) of ARs was adopted in 2011. Based on these results it appears that the risk mitigation measures (RMMs) either have not been followed or have not been effective in preventing wide scale secondary exposure. Continued monitoring of AR residues in non-target species is needed in order to evaluate the effectiveness of current RMMs and a need for new ones to reduce the risk of secondary poisoning.


Asunto(s)
Anticoagulantes/metabolismo , Exposición a Riesgos Ambientales/estadística & datos numéricos , Rodenticidas/metabolismo , Animales , Finlandia , Cadena Alimentaria , Prevalencia
6.
Oecologia ; 182(2): 487-98, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27342659

RESUMEN

Previous studies on intraguild predation have mainly focused on within-class assemblages, even though avian top predators may also influence mammalian mesopredator prey. By using nation-wide long-term data from Finland, northern Europe, we examined the impacts of golden eagles (Aquila chrysaetos) together with red foxes (Vulpes vulpes) and pine martens (Martes martes) on forest-dwelling herbivores, black grouse (Tetrao tetrix) and hazel grouse (Tetrastes bonasia). We hypothesized that eagles may alleviate the overall predation pressure on grouse by imposing intraguild predation risk on mesopredators. The predation impact of eagle was modelled using eagle density estimates and distance to eagle nest. Wildlife triangle counts were used as predation impact proxies of mammalian mesopredators and as measures of response in grouse. Our results show that eagle density correlated negatively with black grouse abundance indices while being positively associated with the proportion of juveniles in both grouse species, irrespective of the abundance of mesopredators. Yet, foxes and martens alone had a negative effect on the abundance indices and the proportion of young in the two grouse species. This suggests that the possible cascading effects of eagles are not mediated by decreased mesopredator numbers, but instead by fear effects. Alternatively, they may be mediated by other species than fox or marten studied here. In conclusion, we found support for the hypothesis that eagles provide protection for juvenile black and hazel grouse, whereas they are a threat for adult grouse. This important information helps us to better understand the role of avian top predators in terrestrial ecosystems.


Asunto(s)
Dinámica Poblacional , Conducta Predatoria , Animales , Águilas , Bosques , Galliformes
7.
BMC Cardiovasc Disord ; 15: 122, 2015 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-26464165

RESUMEN

BACKGROUND: The transforming growth factor (TGF)-ß is one of the key mediators in cardiac remodelling occurring after myocardial infarction (MI) and in hypertensive heart disease. The TGF-ß-stimulated clone 22 (TSC-22) is a leucine zipper protein expressed in many tissues and possessing various transcription-modulating activities. However, its function in the heart remains unknown. METHODS: The aim of the present study was to characterize cardiac TSC-22 expression in vivo in cardiac remodelling and in myocytes in vitro. In addition, we used TSC-22 gene transfer in order to examine the effects of TSC-22 on cardiac gene expression and function. RESULTS: We found that TSC-22 is rapidly up-regulated by multiple hypertrophic stimuli, and in post-MI remodelling both TSC-22 mRNA and protein levels were up-regulated (4.1-fold, P <0.001 and 3.0-fold, P <0.05, respectively) already on day 1. We observed that both losartan and metoprolol treatments reduced left ventricular TSC-22 gene expression. Finally, TSC-22 overexpression by local intramyocardial adenovirus-mediated gene delivery showed that TSC-22 appears to have a role in regulating collagen type IIIα1 gene expression in the heart. CONCLUSIONS: These results demonstrate that TSC-22 expression is induced in response to cardiac overload. Moreover, our data suggests that, by regulating collagen expression in the heart in vivo, TSC-22 could be a potential target for fibrosis-preventing therapies.


Asunto(s)
Colágeno Tipo III/genética , Hipertensión/metabolismo , Infarto del Miocardio/metabolismo , Miocardio/metabolismo , Proteínas Represoras/metabolismo , Regulación hacia Arriba , Animales , Antihipertensivos/uso terapéutico , Células Cultivadas , Femenino , Expresión Génica , Técnicas de Transferencia de Gen , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Losartán/uso terapéutico , Masculino , Metoprolol/uso terapéutico , Células Musculares/metabolismo , ARN Mensajero/metabolismo , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Ratas Sprague-Dawley , Transducción de Señal , Remodelación Ventricular
8.
PLoS One ; 10(6): e0130502, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26098115

RESUMEN

The phosphatase and actin regulator 1 (PHACTR1) locus is a very commonly identified hit in genome-wide association studies investigating coronary artery disease and myocardial infarction (MI). However, the function of PHACTR1 in the heart is still unknown. We characterized the mechanisms regulating Phactr1 expression in the heart, used adenoviral gene delivery to investigate the effects of Phactr1 on cardiac function, and analyzed the relationship between MI associated PHACTR1 allele and cardiac function in human subjects. Phactr1 mRNA and protein levels were markedly reduced (60%, P<0.01 and 90%, P<0.001, respectively) at 1 day after MI in rats. When the direct myocardial effects of Phactr1 were studied, the skeletal α-actin to cardiac α-actin isoform ratio was significantly higher (1.5-fold, P<0.05) at 3 days but 40% lower (P<0.05) at 2 weeks after adenovirus-mediated Phactr1 gene delivery into the anterior wall of the left ventricle. Similarly, the skeletal α-actin to cardiac α-actin ratio was lower at 2 weeks in infarcted hearts overexpressing Phactr1. In cultured neonatal cardiac myocytes, adenovirus-mediated Phactr1 overexpression for 48 hours markedly increased the skeletal α-actin to cardiac α-actin ratio, this being associated with an enhanced DNA binding activity of serum response factor. Phactr1 overexpression exerted no major effects on the expression of other cardiac genes or LV structure and function in normal and infarcted hearts during 2 weeks' follow-up period. In human subjects, MI associated PHACTR1 allele was not associated significantly with cardiac function (n = 1550). Phactr1 seems to regulate the skeletal to cardiac α-actin isoform ratio.


Asunto(s)
Actinas/metabolismo , Cardiomiopatías/metabolismo , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Infarto del Miocardio/metabolismo , Actinas/genética , Alelos , Animales , Cardiomiopatías/genética , Estudios de Casos y Controles , Células Cultivadas , Humanos , Masculino , Infarto del Miocardio/genética , Miocitos Cardíacos/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley
9.
Ecol Evol ; 5(2): 503-14, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25691975

RESUMEN

Top predators may induce extensive cascading effects on lower trophic levels, for example, through intraguild predation (IGP). The impacts of both mammalian and avian top predators on species of the same class have been extensively studied, but the effects of the latter upon mammalian mesopredators are not yet as well known. We examined the impact of the predation risk imposed by a large avian predator, the golden eagle (Aquila chrysaetos, L.), on its potential mammalian mesopredator prey, the red fox (Vulpes vulpes, L.), and the pine marten (Martes martes, L.). The study combined 23 years of countrywide data from nesting records of eagles and wildlife track counts of mesopredators in Finland, northern Europe. The predation risk of the golden eagle was modeled as a function of territory density, density of fledglings produced, and distance to nearest active eagle territory, with the expectation that a high predation risk would reduce the abundances of smaller sized pine martens in particular. Red foxes appeared not to suffer from eagle predation, being in fact most numerous close to eagle nests and in areas with more eagle territories. This is likely due to similar prey preferences of the two predators and the larger size of foxes enabling them to escape eagle predation risk. Somewhat contrary to our prediction, the abundance of pine martens increased from low to intermediate territory density and at close proximity to eagle nests, possibly because of similar habitat preferences of martens and eagles. We found a slightly decreasing trend of marten abundance at high territory density, which could indicate that the response in marten populations is dependent on eagle density. However, more research is needed to better establish whether mesopredators are intimidated or predated by golden eagles, and whether such effects could in turn cascade to lower trophic levels, benefitting herbivorous species.

10.
Front Zool ; 11(1): 80, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25386221

RESUMEN

INTRODUCTION: Food availability is an important environmental cue for animals for deciding how much to invest in reproduction, and it ultimately affects population size. The importance of food limitation has been extensively studied in terrestrial vertebrate populations, especially in birds, by experimentally manipulating food supply. However, the factors explaining variation in reproductive decisions in response to food supplementation remain unclear. By performing meta-analyses, we aim to quantify the extent to which supplementary feeding affects several reproductive parameters in birds, and identify the key factors (life-history traits, behavioural factors, environmental factors, and experimental design) that can induce variation in laying date, clutch size and breeding success (i.e., number of fledglings produced) in response to food supplementation. RESULTS: Food supplementation produced variable but mostly positive effects across reproductive parameters in a total of 201 experiments from 82 independent studies. The outcomes of the food effect were modulated by environmental factors, e.g., laying dates advanced more towards low latitudes, and food supplementation appeared not to produce any obvious effect on bird reproduction when the background level of food abundance in the environment was high. Moreover, the increase in clutch size following food addition was more pronounced in birds that cache food, as compared to birds that do not. Supplementation timing was identified as a major cause of variation in breeding success responses. We also document the absence of a detectable food effect on clutch size and breeding success when the target species had poor access to the feed due to competitive interactions with other animals. CONCLUSIONS: Our findings indicate that, from the pool of bird species and environments reviewed, extra food is allocated to immediate reproduction in most cases. Our results also support the view that bird species have evolved different life-history strategies to cope with environmental variability in food supply. However, we encourage more research at low latitudes to gain knowledge on how resource allocation in birds changes along a latitudinal gradient. Our results also emphasize the importance of developing experimental designs that minimise competition for the supplemented food and the risk of reproductive bottle-necks due to inappropriate supplementation timings.

11.
PLoS One ; 9(8): e105168, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25136830

RESUMEN

AIMS: Activating transcription factor 3 (ATF3) is a stress-activated immediate early gene suggested to have both detrimental and cardioprotective role in the heart. Here we studied the mechanisms of ATF3 activation by hypertrophic stimuli and ATF3 downstream targets in rat cardiomyocytes. METHODS AND RESULTS: When neonatal rat cardiomyocytes were exposed to endothelin-1 (ET-1, 100 nM) and mechanical stretching in vitro, maximal increase in ATF3 expression occurred at 1 hour. Inhibition of extracellular signal-regulated kinase (ERK) by PD98059 decreased ET-1- and stretch-induced increase of ATF3 protein but not ATF3 mRNA levels, whereas protein kinase A (PKA) inhibitor H89 attenuated both ATF3 mRNA transcription and protein expression in response to ET-1 and stretch. To characterize further the regulatory mechanisms upstream of ATF3, p38 mitogen-activated protein kinase (MAPK) signaling was investigated using a gain-of-function approach. Adenoviral overexpression of p38α, but not p38ß, increased ATF3 mRNA and protein levels as well as DNA binding activity. To investigate the role of ATF3 in hypertrophic process, we overexpressed ATF3 by adenovirus-mediated gene transfer. In vitro, ATF3 gene delivery attenuated the mRNA transcription of interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1), and enhanced nuclear factor-κB (NF-κB) and Nkx-2.5 DNA binding activities. Reduced PAI-1 expression was also detected in vivo in adult rat heart by direct intramyocardial adenovirus-mediated ATF3 gene delivery. CONCLUSIONS: These data demonstrate that ATF3 activation by ET-1 and mechanical stretch is partly mediated through ERK and cAMP-PKA pathways, whereas p38 MAPK pathway is involved in ATF3 activation exclusively through p38α isoform. ATF3 activation caused induction of modulators of the inflammatory response NF-κB and Nkx-2.5, as well as attenuation of pro-fibrotic and pro-inflammatory proteins IL-6 and PAI-1, suggesting cardioprotective role for ATF3 in the heart.


Asunto(s)
Factor de Transcripción Activador 3/fisiología , Cardiomiopatía Hipertrófica/metabolismo , Miocitos Cardíacos/metabolismo , Animales , Fenómenos Biomecánicos , Cardiomiopatía Hipertrófica/patología , Células Cultivadas , Endotelina-1/fisiología , Femenino , Proteína Homeótica Nkx-2.5 , Proteínas de Homeodominio/metabolismo , Mediadores de Inflamación/metabolismo , Isoenzimas/antagonistas & inhibidores , Isoenzimas/metabolismo , Masculino , Miocitos Cardíacos/efectos de los fármacos , FN-kappa B/metabolismo , Inhibidor 1 de Activador Plasminogénico/genética , Inhibidor 1 de Activador Plasminogénico/metabolismo , Unión Proteica , Inhibidores de Proteínas Quinasas/farmacología , Ratas Sprague-Dawley , Transducción de Señal , Factores de Transcripción/metabolismo , Activación Transcripcional , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
12.
Oecologia ; 174(1): 271-81, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24036931

RESUMEN

The negative impacts of mammalian herbivores on plants have been studied quite extensively, but typically with only a single herbivore species at a time. We conducted a novel comparison of the browsing effects of voles, hares and cervids upon the growth and survival of boreal tree seedlings. This was done by excluding varying assemblages of these key mammalian herbivores from silver birch, Scots pine and Norway spruce seedlings for 3 years. We hypothesised that the pooled impacts of the herbivores would be greater than that of any individual group, while the cervids would be the group with the strongest impact. Growth of birch seedlings advanced when cervids were excluded whereas growth of seedlings accessible to cervids was hindered. Survival of all seedlings was lowest when they were accessible to voles and voles plus hares, whereas cervids seemed not to influence seedling survival. Our results show that the impact of herbivores upon woody plants can be potent in the boreal forests, but the mechanism and strength of this link depends on the tree and herbivore species in question. Risk of abated stand regeneration appears highest for the deciduous birch, though there is need for seedling protection also in coniferous stands. The clear cervid-mediated growth limitation of birch also indicates potential for a trophic cascade effect by mammalian top predators, currently returning to boreal ecosystems.


Asunto(s)
Ecosistema , Herbivoria , Plantones/crecimiento & desarrollo , Árboles/crecimiento & desarrollo , Animales , Arvicolinae , Betula/crecimiento & desarrollo , Ciervos , Finlandia , Liebres , Picea/crecimiento & desarrollo , Pinus sylvestris/crecimiento & desarrollo
13.
J Mol Cell Cardiol ; 67: 86-93, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24361238

RESUMEN

cAMP-dependent protein kinase (PKA) regulates the L-type calcium channel, the ryanodine receptor, and phospholamban (PLB) thereby increasing inotropy. Cardiac contractility is also regulated by p38 MAPK, which is a negative regulator of cardiac contractile function. The aim of this study was to identify the mechanism mediating the positive inotropic effect of p38 inhibition. Isolated adult and neonatal cardiomyocytes and perfused rat hearts were utilized to investigate the molecular mechanisms regulated by p38. PLB phosphorylation was enhanced in cardiomyocytes by chemical p38 inhibition, by overexpression of dominant negative p38α and by p38α RNAi, but not with dominant negative p38ß. Treatment of cardiomyocytes with dominant negative p38α significantly decreased Ca(2+)-transient decay time indicating enhanced sarco/endoplasmic reticulum Ca(2+)-ATPase function and increased cardiomyocyte contractility. Analysis of signaling mechanisms involved showed that inhibition of p38 decreased the activity of protein phosphatase 2A, which renders protein phosphatase inhibitor-1 phosphorylated and thereby inhibits PP1. In conclusion, inhibition of p38α enhances PLB phosphorylation and diastolic Ca(2+) uptake. Our findings provide evidence for novel mechanism regulating cardiac contractility upon p38 inhibition.


Asunto(s)
Contracción Muscular/fisiología , Miocitos Cardíacos/fisiología , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Calcio/metabolismo , Proteínas de Unión al Calcio/metabolismo , Activación Enzimática/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Fosforilación , Interferencia de ARN , Ratas , Proteínas Quinasas p38 Activadas por Mitógenos/farmacología
14.
Can J Physiol Pharmacol ; 89(8): 539-50, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21812548

RESUMEN

The muscle-CAT (M-CAT) promoter element is found on promoters of most muscle-specific cardiac genes, but its role in cardiac pathology is poorly understood. Here we studied whether the M-CAT element is involved in hypertrophic process activated by mechanical stretch, and identified the intracellular pathways mediating the response. When an in vitro stretch model of cultured neonatal rat cardiomyocytes and luciferase reporter construct driven by rat B-type natriuretic peptide (BNP) promoter were used, mutation of M-CAT element inhibited not only the basal reporter activity (88%), but also the stretch-activated BNP transcription (58%, p < 0.001). Stretch-induced BNP promoter activation was associated with an increase in transcriptional enhancer factor-1 (TEF-1) binding activity after 24 h mechanical stretch (p < 0.05). Inhibition of mitogen-activated protein kinases ERK, JNK, or p38 attenuated stretch-induced BNP activation. Interestingly, as opposed to p38 and JNK, inhibition of ERK had no additional effect on transcriptional activity of BNP promoter harboring the M-CAT mutation, suggesting a pivotal role for ERK in regulating stretch-induced BNP transcription via M-CAT binding site. Finally, immunoprecipitation studies showed that mechanical stretch induced myocyte enhancer factor-2 (MEF-2) binding to TEF-1. These data suggest a central role for M-CAT element in regulation of mechanical stretch-induced hypertrophic response via ERK activation.


Asunto(s)
Proteínas de Unión al ADN/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Péptido Natriurético Encefálico/genética , Elementos Reguladores de la Transcripción , Animales , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/biosíntesis , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Células Cultivadas , Proteínas de Unión al ADN/metabolismo , Hipertrofia/metabolismo , MAP Quinasa Quinasa 4/metabolismo , Sistema de Señalización de MAP Quinasas , Factores de Transcripción MEF2 , Mutación , Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Factores Reguladores Miogénicos/metabolismo , Péptido Natriurético Encefálico/biosíntesis , Regiones Promotoras Genéticas , Ratas , Ratas Sprague-Dawley , Activación Transcripcional , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
15.
Mol Cell Endocrinol ; 338(1-2): 18-27, 2011 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-21354263

RESUMEN

Persistent controversy underlies the functional roles of specific p38 MAPK isoforms in cardiac biology and regulation of hypertrophy-associated genes. Here we show that adenoviral gene transfer of p38ß but not p38α increased B-type natriuretic peptide (BNP) mRNA levels in vitro as well as atrial natriuretic peptide mRNA levels both in vitro and in vivo. Overexpression of p38α, in turn, augmented the expression fibrosis-related genes connective tissue growth factor, basic fibroblast growth factor and matrix metalloproteinase-9 both in vitro and in vivo. p38ß-induced BNP transcription was diminished by mutation of GATA-4 binding site, whereas overexpression of MKK6b, an upstream regulator of p38α and p38ß, activated BNP transcription through both GATA-4 and AP-1. Overexpression of MKK3, upstream regulator of p38α, induced BNP transcription independently from AP-1 and GATA-4. These data provide new evidence for diversity in downstream targets and functional roles of p38 pathway kinases in regulation of hypertrophy-associated cardiac genes.


Asunto(s)
Regulación de la Expresión Génica , Péptido Natriurético Encefálico/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Cardiomiopatía Hipertrófica/genética , Cardiomiopatía Hipertrófica/metabolismo , Muerte Celular , Células Cultivadas , Factor de Crecimiento del Tejido Conjuntivo/genética , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Factor 2 de Crecimiento de Fibroblastos/genética , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Factor de Transcripción GATA4/metabolismo , Imidazoles/farmacología , Isoenzimas/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Péptido Natriurético Encefálico/metabolismo , Regiones Promotoras Genéticas , Piridinas/farmacología , Ratas , Transducción de Señal/genética , Transcripción Genética , Activación Transcripcional , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores
16.
Compr Psychiatry ; 45(3): 213-8, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15124152

RESUMEN

Despite the operational criteria in diagnostic systems there is still marked diversity between clinical and research diagnoses in populations with psychotic disorders. The objective of the current study was to explore the association of patient-related factors with diagnostic agreement between clinical diagnoses and Schedules for Clinical Assessment in Neuropsychiatry (SCAN-2) diagnoses in first-episode psychosis. The sample included 80 consecutive patients. As explanatory variables we used demographic characteristics (gender, age, living circumstances, education, and social activities), measures of psychopathology (Positive and Negative Symptom scale [PANSS], Hamilton Depression Scale, Global Assessment of Functioning Scale [GAF], and Strauss-Carpenter Scale), duration of untreated psychosis, and diagnostic category according to SCAN-2 interview. The overall agreement value between the clinical and research diagnoses was 0.55 (kappa). In the whole sample low scores on the PANSS negative subscale, low level of education, and high score on the PANSS item for delusions predicted diagnostic discrepancy. Acute and transient psychotic disorder as a research diagnosis predicted diagnostic agreement. In the schizophrenia group, young age and lack of social activities predicted diagnostic agreement. Bivariate comparisons of treatment compliance, perceived medication side effects, or negative attitudes towards treatment showed no associations with diagnostic agreement. The results confirm some of the findings in the few previous studies. The diagnosis of schizophrenia is likely to be delayed and there is a need for further education with clinicians in recognizing the symptoms of schizophrenia.


Asunto(s)
Trastornos Psicóticos/diagnóstico , Adulto , Factores de Edad , Diagnóstico Diferencial , Escolaridad , Femenino , Humanos , Entrevista Psicológica , Masculino , Análisis Multivariante , Valor Predictivo de las Pruebas , Escalas de Valoración Psiquiátrica , Esquizofrenia/diagnóstico , Sensibilidad y Especificidad , Apoyo Social
17.
Oecologia ; 139(1): 157-62, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-14730443

RESUMEN

Many prey animals experience temporal variation in the risk of predation and therefore face the problem of allocating their time between antipredator efforts and other activities like feeding and breeding. We investigated time allocation of prey animals that balanced predation risk and feeding opportunities. The predation risk allocation hypothesis predicts that animals should forage more in low- than in high-risk situations and that this difference should increase with an increasing attack ratio (i.e. difference between low- and high-risk situations) and proportion of time spent at high risk. To test these predictions we conducted a field test using bank voles ( Clethrionomys glareolus) as a prey and the least weasel ( Mustela nivalis nivalis) as a predator. The temporal pattern and intensity of predation risk were manipulated in large outdoor enclosures and the foraging effort and patch use of voles were measured by recording giving-up densities. We did not observe any variation in feeding effort due to changes in the level of risk or the proportion of time spent under high-risk conditions. The only significant effect was found when the attack ratio was altered: the foraging effort of voles was higher in the treatment with a low attack ratio than in the treatment with a high attack ratio. Thus the results did not support the predation risk allocation hypothesis and we question the applicability of the hypothesis to our study system. We argue that the deviation between the observed pattern of feeding behaviour of bank voles and that predicted by the predation risk allocation hypothesis was mostly due to the inability of voles to accurately assess the changes in the level of risk. However, we also emphasise the difficulties of testing hypotheses under outdoor conditions and with mammals capable of flexible behavioural patterns.


Asunto(s)
Arvicolinae , Conducta Alimentaria , Cadena Alimentaria , Modelos Teóricos , Animales , Carnívoros , Femenino , Masculino , Densidad de Población , Conducta Predatoria , Factores de Riesgo
18.
Psychiatry Res ; 110(1): 39-48, 2002 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-12007592

RESUMEN

Compliance behaviour is a multi-factorial phenomenon. In psychotic patients, it includes patient-related, medication-related, and environmental components. Compliance is a crucial factor in relation to outcome. The aim of this study was to explore indicators of compliance in a sample of 59 patients with a first-onset psychosis during their initial phase of treatment. Dependent variables in the logistic regression analysis included predictions made by the patients about their compliance in the initial phase and the observed compliance during the first 3 months according to patient record data. Explanatory variables comprised age, sex, living situation, education and social activities, Positive and Negative Syndrome Scale (PANSS) score, Hamilton Depression Scale score, Global Assessment of Functioning Scale score, Strauss-Carpenter Outcome Scale score, self-rated side effects, and insight and treatment-related variables. Predictions made by the patients about their compliance were determined by their self-rated attitude and insight measures. Determinants of observed non-compliance included experienced harmful side effects, male sex, lack of social activities, low score on PANSS positive symptoms, high PANSS total score and young age. The duration of untreated psychosis was not associated with compliance. Indicators of compliance in first-episode psychosis resemble those in the overall psychotic population. During the acute phase of psychosis, insight and attitudes toward treatment are the sole determinants of the patients' prediction of compliance.


Asunto(s)
Antipsicóticos/uso terapéutico , Cooperación del Paciente/psicología , Trastornos Psicóticos/tratamiento farmacológico , Esquizofrenia/tratamiento farmacológico , Adulto , Sistemas de Registro de Reacción Adversa a Medicamentos , Antipsicóticos/efectos adversos , Concienciación , Femenino , Finlandia , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto , Escalas de Valoración Psiquiátrica , Trastornos Psicóticos/psicología , Factores de Riesgo , Psicología del Esquizofrénico , Negativa del Paciente al Tratamiento/psicología
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