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Sample records for agouti dasyprocta leporina

  1. Perimortality in a Captive Reared Agouti (Dasyprocta leporina)

    OpenAIRE

    Gary Wayne Garcia

    2015-01-01

    erinatal mortality has been reported in cattle, swine, goats, sheep and rabbits; however, there have been no documented reports on this phenomenon in agouti (Dasyprocta leporina). The agouti is a Neotropical polytocous rodent, hunted for its meat. This study reports on an incident of perinatal mortalities in a captive reared agouti from the wildlife unit of the Faculty of Food and Agriculture. The pluriparous female agouti was reared in captivity from birth and had delivered three (3) previou...

  2. The role of seed mass on the caching decision by agoutis, Dasyprocta leporina (Rodentia: Agoutidae

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    Mauro Galetti

    2010-06-01

    Full Text Available It has been shown that the local extinction of large-bodied frugivores may cause cascading consequences for plant recruitment and overall plant diversity. However, to what extent the resilient mammals can compensate the role of seed dispersal in defaunated sites is poorly understood. Caviomorph rodents, especially Dasyprocta spp., are usually resilient frugivores in hunted forests and their seed caching behavior may be important for many plant species which lack primary dispersers. We compared the effect of the variation in seed mass of six vertebrate-dispersed plant species on the caching decision by the red-rumped agoutis Dasyprocta leporina Linnaeus, 1758 in a land-bridge island of the Atlantic forest, Brazil. We found a strong positive effect of seed mass on seed fate and dispersal distance, but there was a great variation between species. Agoutis never cached seeds smaller than 0.9 g and larger seeds were dispersed for longer distances. Therefore, agoutis can be important seed dispersers of large-seeded species in defaunated forests.

  3. Interactions Among Different Devices and Electrical Stimulus on the Electroejaculation of Captive Agoutis (Dasyprocta leporina).

    Science.gov (United States)

    Castelo, T S; Souza, A L P; Lima, G L; Peixoto, G C X; Campos, L B; Oliveira, M F; Silva, A R

    2015-06-01

    The interactions among different electroejaculation devices associated with serial or continuous stimuli were investigated to improve the efficiency of the electroejaculation for semen collection in agoutis. Ten sexually matured male Dasyprocta leporina were restrained by the intramuscular administration of xylazine-ketamine association. Each individual was randomly subjected to four electroejaculation protocols, by combining two devices (one presenting longitudinal electrodes emitting square waves and other presenting ring electrodes emitting sine waves) and two electrical stimuli protocols (serial or continuous). A total of 40 attempts for electroejaculation were conducted in agoutis, being 10 per treatment. The most efficient treatment in providing ejaculates containing sperm (p electroejaculator connected to a probe with ring electrodes and associated with serial stimuli (4/7; 57%). In spite of semen parameters obtained by sine waves were adequate for using the samples for assisted reproduction, higher values for sperm motility and functional membrane integrity were obtained in the use of the square wave, independently of the electric stimulation protocol used (p electroejaculation in adults D. leporina. PMID:25800458

  4. Liquid and Frozen Storage of Agouti (Dasyprocta leporina) Semen Extended with UHT Milk, Unpasteurized Coconut Water, and Pasteurized Coconut Water

    OpenAIRE

    Garcia, G. W.; Mollineau, W. M.; Adogwa, A. O.

    2010-01-01

    This study evaluated the effects of semen extension and storage on forward progressive motility % (FPM%) in agouti semen. Three extenders were used; sterilized whole cow's milk (UHT Milk), unpasteurized (CW) and pasteurized coconut water (PCW), and diluted to 50, 100, 150, and 200 × 106 spermatozoa/ml. Experiment 1: 200 ejaculates were extended for liquid storage at 5 ∘ C and evaluated every day for 5 days to determine FPM% and its rate of deterioration. Experiment 2: 150 ejaculates were exte...

  5. Habitat use and relative abundance of the Spotted Paca Cuniculus paca (Linnaeus, 1766 (Rodentia: Cuniculidae and the Red-rumped Agouti Dasyprocta leporina (Linnaeus, 1758 (Rodentia: Dasyproctidae in Guatopo National Park, Venezuela

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    Elinor Jax

    2015-01-01

    Full Text Available The Spotted Paca Cuniculus paca and the Red-rumped Agouti Dasyprocta leporina are affected by habitat loss and hunting.  In Venezuela, their conservation status is unknown, even within protected areas.  The objective of this study was to estimate the relative abundance, activity patterns, habitat use, and effect of human activities on these species in Venezuela.  To achieve this, 26 camera-trap stations (20.8km2 were established in Guatopo National Park between February and April 2011, characterization of the habitat was undertaken and occupancy models were created.  The relative abundance of the Spotted Paca was 1.62 captures/100trap-nights, with a fully nocturnal activity pattern.  The relative abundance of the Red-rumped Agouti was 2.32 captures/100trap-nights, with a pronounced diurnal activity pattern. The occupation probability of the Red-rumped Agouti (0.61 SE 0.02 was higher than that of the Spotted Paca (0.27 SE 0.02. Spotted Pacas were mainly found in areas with mature forest and high tree density, whereas the  Red-rumped Agoutis were most frequently found in valleys with little disturbed forest.  A positive correlation was found between illegal hunting activities and areas occupied by the Spotted Paca.  It is important to strengthen the park control measurements to reduce illegal hunting of Spotted Pacas.

  6. Parasitism of two zoonotic reservoirs Dasyprocta leporina and D. fuliginosa (Rodentia from Amazonas, with Trichostrongylina nematodes (Heligmonellidae: description of a new genus and a new species

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    Alessandra Queiroga Gonçalves

    2007-09-01

    Full Text Available A new genus and a new species of Heligmonellidae nematodes are described parasiting the stomach of three agoutis (two Dasyprocta fuliginosa and one D. leporina captured in the middle and high Negro river microregion, state of Amazonas, Brazil. The new genus, as well as its type-species, are closely related to the trichostrongylids included in Fuellebornema, particularly on what concerns the pattern of the caudal bursa, but differing from them by the characteristics of the synlophe, that presents a poorly developed carene, when compared to the referred number of body ridges in Freitastrongylus n. gen. and consequently in F. angelae n. sp.,in which the ridges are well developed and the carene at mid-body has a similar size when compared to the ridge situated in front of the right field (ridge no. 5. Caudal bursa is of the type 1-4, with rays 9 shorter than rays 10, with a very long genital cone.

  7. Monitoramento do ciclo estral de cutias (Dasyprocta leporina Lichtenstein, 1823 através de citologia esfoliativa vaginal e ultrassonografia

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    Lívia B. Campos

    2015-02-01

    Full Text Available O objetivo deste estudo foi monitorar o ciclo estral em cutias (Dasyprocta leporina criadas em cativeiro no semiárido brasileiro. Durante 70 dias, cinco cutias foram diariamente submetidas a citologia esfoliativa vaginal, e o monitoramento ultrassonográfico ovariano foi realizado a cada três dias. Um total de 8 ciclos estrais foi completamente monitorado, com duração de 28,2±0,7 dias, variando de 24 a 31 dias. Pela citologia esfoliativa vaginal, houve uma predominância de células superficiais nas fases de proestro e estro (P0,05. Os folículos foram identificados durante as fases estrogênicas (proestro e estro, com diâmetro médio de 1±0,5mm. Em apenas 12,5% das fases luteais, corpos lúteos medindo 1,4±0,9mm foram identificados. Conclui-se que a associação da citologia vaginal e da ultrassonografia ovariana constitui uma alternativa viável para o monitoramento de ciclos estrais e identificação das fases estrogênicas em cutias da espécie Dasyprocta leporina

  8. Fatal anemia and dermatitis in captive agoutis (Dasyprocta mexicana) infested with Echidnophaga fleas.

    Science.gov (United States)

    Cucchi-Stefanoni, Karina; Juan-Sallés, Carles; Parás, Alberto; Garner, Michael M

    2008-08-17

    Two captive agoutis (Dasyprocta mexicana) died of anemia with centrilobular hepatocellular necrosis (2/2), severe flea ectoparasitism (2/2), and cardiomegaly attributed to anemia (1/2). Other agoutis were similarly parasitized and one had anemia. Fleas were manually removed and all agoutis treated topically with propoxur and selamectin and moved to another enclosure. No additional cases of fatal anemia were seen. Cutaneous lesions suggestive of hypersensitivity were observed in three additional agoutis with dorsal alopecia (3/3), a penetrating wound associated with pruritus and self-mutilation in the flank (2/3), flea ectoparasitism at the time of morphologic diagnosis (1/3), and hyperplastic perivascular dermatitis (3/3). One of these died of bacterial infection of the wound. Similar but milder skin disease was seen in 3 out of over 30 maras (Dolichotis patagonum) housed in the same exhibit. Fleas collected from all the fatal agouti cases and maras were classified in the genus Echidnophaga based on the angular front margin of head, contracted thorax, absence of genal and pronotal combs, and the fact that fleas did not jump. These findings suggest that flea ectoparasitism may be an important cause of morbidity and mortality in captive rodents. PMID:18556127

  9. The subplacenta of the red-rumped agouti (Dasyprocta leporina L)

    DEFF Research Database (Denmark)

    Rodrigues, Rosangela Felipe; Carter, Anthony M.; Ambrosio, Carlos Eduardo;

    2006-01-01

    fetal circulation. Within it the vessels pursue a tortuous course with sinusoidal dilatations and constrictions. CONCLUSION: The functions that have been attributed to the subplacenta include hormone production. Our findings are consistent with this interpretation, but suggest that hormone secretion is...... directed towards the fetal circulation rather than the maternal tissues........ Clusters of multinuclear giant cells occur in the transition zone between the subplacenta and decidua. There are prominent intercellular spaces between the cytotrophoblast cells. The basal membrane of these cells is often close to fetal blood vessels. The syncytiotrophoblast surrounds an extensive system...

  10. Infección inducida en el roedor selvático Dasyprocta leporina (Rodentia: Dasyproctidae, con huevos larvados de Lagochilascaris minor (Nematoda: Ascarididae Induced infection in the wild rodent Dasyprocta leporina (Rodentia: Dasyproctidae with larval eggs of Lagochilascaris minor (Nematoda: Ascarididae

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    S. Gregorio

    1990-12-01

    Full Text Available Ejemplares de Dasyprocta leporina Linnaeus, 1758 fueron criados alejados de su ambiente natural. A los 3 ó 4 meses de edad, se los inoculó por vía oral con huevos de Lagochilascaris minor Leiper, 1909 obtenidos de una paciente nativa. Los huevos se los incubó por más de 80 dias, para que de ellos fuese posible obtener por compresión mecánica, larvas que se mantuviesen vivas en medio acuoso por 48 horas o más. Sacrificados los animales a los 14 ó 46 dias posteriores a la infección, se hallaron en los músculos esqueléticos larvas ovilladas dentro de nódulos inflamatorios, los cuales no presentaban reacción a cuerpo extraño, abscedación o calcificación. El desarollo de los nódulos no parecía afectar la normalidad de los hospedadores. Las larvas obtenidas eran similares a las descritas por SPRENT como de tercer estadio para estos helmintos. Ratones blancos infectados con material similar, no presentaron nódulos en sus músculos ni se pudo recuperar de sus tejidos larva alguna. Por los hallazgos obtenidos con la infección de estos animales, se postula que el helminto no posee ciclo pulmonar y que su desarrollo requiere de un hospedador intermediario.Specimens of Dasyprocta leporina (Linnaeus, 1758 were raised out their natural environment. At three to four months of age they were orally inoculated with Lagochilascaris minor (Leiper, 1909 eggs obtained from a native patient. The eggs were incubated for more than 80 days so that it was possible to obtain, by mechanical compression, larvae that could be maintained alive in liquid medium for 48 hours or more. The animals were sacrificed 14-46 days after infection and tangled larva in inflammatory nodules were found in skeletal muscle without foreign body reaction, abscess formation or calcification. The development of the nodules did not seem to affect the hosts. The larvae obtained were similar to those described by SPRENT as the third stage of these helminths. When white mice were

  11. Electrocardiogram assessment in non-anaesthetized clinically healthy agouti (Dasyprocta primnolopha, Wagler 1831

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    Anaemilia das N. Diniz

    2013-12-01

    Full Text Available The agouti is one of the most intensely hunted species throughout the Amazon and the semiarid regions of north-eastern Brazil. Considering the current tendency of wild animal management in captivity, the objective of this study was to determine heart reference values for agouti raised in captivity, based on electrocardiographic assessments (ECG. Adult agouti were selected without clinical signs of heart disease (n=30. The animals were restrained physically and then the ECG was performed. Standardized measurements were taken to establish the statistical analysis of the data. Analysis of the QRS complex showed values compatible with previous reports in peer animals and the limited data available for other wild and exotic species, except for the T wave that showed similar amplitude to the R wave in all the animals studied. The data obtained provided the first reference values for ECG tracings in agouti, contributing to a better understanding of heart electrophysiology in identifying myocardial pathology in these animals.

  12. Colheita de sêmen por eletroejaculação em cutia-parda (Dasyprocta azarae Semen collection by electroejaculation in Azara´s agouti (Dasyprocta azarae

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    Antonio C. Martinez

    2013-01-01

    Full Text Available As cutias são animais que vivem nas Américas Central e do Sul, com potencial zootécnico e que despertam crescente interesse científico. O objetivo deste estudo foi estabelecer um padrão para colheita de sêmen por eletroejaculação em cutia-parda (Dasyprocta azarae. Foram utilizados machos adultos (n=4 anestesiados e submetidos a quatro séries de 20 estímulos eletroejaculatórios, com 3 segundos de duração cada, com uma intensidade de 2, 4, 6 e 8 volts, com dois minutos de intervalo entre cada série. A colheita de sêmen foi obtida em todos os animais, com ereção parcial com 2 volts, ereção evidente com 4 volts, ejaculação com 6 volts e exacerbação da glande e exteriorização das espículas penianas com 8 volts, observando-se espermatozoides em 100% das amostras. A técnica descrita para colheita de sêmen em cutia-parda foi eficaz.Agoutis are animals that live in South and Central America, present rearing potential and call increasing scientific interest. The aim of this paper was to establish a model for semen collection by electroejaculation in Azara´s agouti (Dasyprocta azarae. Anesthetized adult males (n=4 were submitted to four series of 20 electroejaculatory stimuli, during 3 seconds each and with 2, 4, 6 and 8 volts, with a 2 minutes rest among series. Semen collection was accomplished in every animal, with partial penis erection at 2 volts, makeable erection at 4 volts, ejaculation at 6 volts, glans and penis spines exposition at 8 volts, and sperm collected in all samples. The described technique for Azara's agouti semen collection was efficient.

  13. Thoracic and heart biometrics of non-anesthetized agouti (Dasyprocta primnolopha Wagler, 1831 measured on radiographic images

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    Anaemilia das N. Diniz

    2013-03-01

    Full Text Available The agouti is a species intensively hunted throughout the Amazon and the semi-arid regions of northeastern Brazil. Considering the current trend in conservation management of wild species, the aim of this study was to determine the morphometric reference to the heart of agouti raised in captivity, based on thoracic and cardiac measurements in these animals. Thirty adult agoutis, 1 to 3 years of age, without clinical signs of cardiac disease were selected. The animals were physically restrained and radiographies in laterolateral (LL and ventrodorsal (VD recumbence were produced. The following measures were taken: the apicobasilar length of the heart (at the most cranial height of the Carina region to the heart apex (AB, maximum width of the heart perpendicular to AB (CD, heart inclination angle (AIC, trachea inclination angle (AIT, distance from the right heart wall (DPTd, distance from the left heart wall (DPTe and vertical depth of the thorax, and the ventral face of the vertebral column to the dorsal border of the sternum at the level of the trachea bifurcation (H. The ratios between AB/CD, AB/H and CD/H were also analyzed. To calculate the vertebral heart scale (VHS, the AB and CD measurements were laid over the thoracic vertebra starting at T4. Radiographic evaluation showed values consistent with those reported in small animals and some wild and exotic species. The main biometric values in the chest cavity and heart of agouti are arranged as follows: (1 The ratios between AB/H ratio and CD/H were not sensitive for identifying heart increases (p>0.05, while the ratio AB/CD was more sensitive in this identification (p<0.05; (2 AIC: 21.2±6.4º (mean between male and famale; (3 AIT for males and females: 9.93±3.23° and 8.4±3.94°; (4 DPTd and DPTe for males: 0.97±0.40cm and 0.7±0.30cm; (5 DPTd and DPTe for females: 1.12±0.42cm and 01.02±0.43cm; (6 VHS for males and females: 7.75±0.48v e 7.61±0.34v; (7 The caudal vena cava (CVC was

  14. Isolation, expansion and differentiation of cellular progenitors obtained from dental pulp of agouti (Dasyprocta prymnolopha Wagler, 1831

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    Yulla K.P. de Carvalho

    2015-06-01

    Full Text Available Abstract: The study aimed to isolate, expand, differentiate and characterize progenitor cells existent in the dental pulp of agouti. The material was washed with PBS solution and dissociated mechanically with the aid of a scalpel blade on plates containing culture medium D-MEM/F-12, and incubated at 5% CO2-37⁰C. The growth curve, CFU assay, osteogenic/adipogenic differentiation and characterization were obtained from the isolation. The cells began to be released from the explant tissue around the 7th day of culture. By day 22 of culture, cells reached 80% confluence. At the UFC test, 81 colonies were counted with 12 days of cultivation. The growth curves before and after freezing showed a regular growth with intense proliferation and clonogenic potential. The cell differentiation showed formation of osteoblasts and fat in culture, starting at 15 days of culture in a specific medium. Flow cytometry (FACs was as follows: CD34 (positive, CD14 (negative, CD45 (negative, CD73 (positive, CD79 (negative, CD90 (positive, CD105 (positive, demonstrating high specificity and commitment of isolated cells with mesenchymal stem cells strains. These results suggest the existence of a cell population of stem cells with mesenchymal features from the isolated tissue in the explants of agouti dental pulp, a potential model for study of stem cell strains obtained from the pulp tissue.

  15. Colheita de sêmen por eletroejaculação em cutia-parda (Dasyprocta azarae) Semen collection by electroejaculation in Azara´s agouti (Dasyprocta azarae)

    OpenAIRE

    Antonio C. Martinez; Fabrício S. Oliveira; Cassiana O. Abreu; Leandro L. Martins; Ana P. Pauloni; Nei Moreira

    2013-01-01

    As cutias são animais que vivem nas Américas Central e do Sul, com potencial zootécnico e que despertam crescente interesse científico. O objetivo deste estudo foi estabelecer um padrão para colheita de sêmen por eletroejaculação em cutia-parda (Dasyprocta azarae). Foram utilizados machos adultos (n=4) anestesiados e submetidos a quatro séries de 20 estímulos eletroejaculatórios, com 3 segundos de duração cada, com uma intensidade de 2, 4, 6 e 8 volts, com dois minutos de intervalo entre cada...

  16. Morphology of the male agouti accessory genital glands (Dasyprocta prymnolopha Wagler, 1831 Morfologia das glândulas genitais acessórias em cutias (Dasyprocta prymnolopha Wagler, 1831

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    Danilo J. Ayres de Menezes

    2010-09-01

    Full Text Available The morphology of the accessory genital glands of the male agouti was studied in twenty-three animals that were raised in captivity. Twenty animals had their genital glands dissected in situ for macroscopic description. The samples of each gland were recovered, embedded in paraffin, sliced and stained by Hematoxylin-Eosin technique. It was founded four pairs of glands: the vesicular glands, the coagulating glands, the prostate and the bulbourethral glands. Histological characteristics of the vesicular, coagulating and prostate glands showed similar morphology, within the pseudostratified columnar epithelium. The tubulo-alveolar type of the bulbourethral glands showed a lack of connective tissue among the tubules, a small amount of red stained presented it the cytoplasm, and the presence of vacuoles in the tissue. This study concluded that the agouti showed to have similar morphological aspect described in the others species of rodents.A morfologia das glândulas genitais acessórias de cutias foram estudados em 23 animais criados em cativeiros. Vinte animais tiveram suas glândulas genitais dissecadas in situ para as descrições macroscópicas. Para o estudo microscópico foram utilizados três animais. Os fragmentos de cada glândula foram embebidos em parafina, seccionados e corados em hematoxilina e eosina. Foram encontrados quatro pares de glândulas: vesiculares, coaguladoras, próstata e bulbouretrais. As características histológicas da glândula vesicular, coaguladora e próstata mostraram morfologia similar, com epitélio colunar pseudoestratificado. O tipo tuboalveolar da glândula bulbouretral mostrou uma deficiência de tecido conjuntivo, citoplasma pouco corado e presença de vacúolos. Este estudo concluiu que a cutia apresenta as mesmas características morfológicas das glândulas genitais acessórias encontradas em roedores.

  17. Thoracic and heart biometrics of non-anesthetized agouti (Dasyprocta primnolopha Wagler, 1831 measured on radiographic images Biometria torácica e cardíaca de cutias não anestesiadas (Dasyprocta primnolopha Wagler, 1831 mensuradas em imagens radiográficas

    Directory of Open Access Journals (Sweden)

    Anaemilia das N. Diniz

    2013-03-01

    Full Text Available The agouti is a species intensively hunted throughout the Amazon and the semi-arid regions of northeastern Brazil. Considering the current trend in conservation management of wild species, the aim of this study was to determine the morphometric reference to the heart of agouti raised in captivity, based on thoracic and cardiac measurements in these animals. Thirty adult agoutis, 1 to 3 years of age, without clinical signs of cardiac disease were selected. The animals were physically restrained and radiographies in laterolateral (LL and ventrodorsal (VD recumbence were produced. The following measures were taken: the apicobasilar length of the heart (at the most cranial height of the Carina region to the heart apex (AB, maximum width of the heart perpendicular to AB (CD, heart inclination angle (AIC, trachea inclination angle (AIT, distance from the right heart wall (DPTd, distance from the left heart wall (DPTe and vertical depth of the thorax, and the ventral face of the vertebral column to the dorsal border of the sternum at the level of the trachea bifurcation (H. The ratios between AB/CD, AB/H and CD/H were also analyzed. To calculate the vertebral heart scale (VHS, the AB and CD measurements were laid over the thoracic vertebra starting at T4. Radiographic evaluation showed values consistent with those reported in small animals and some wild and exotic species. The main biometric values in the chest cavity and heart of agouti are arranged as follows: (1 The ratios between AB/H ratio and CD/H were not sensitive for identifying heart increases (p>0.05, while the ratio AB/CD was more sensitive in this identification (pA cutia é uma espécie intensamente caçada em toda a Amazônia e nas regiões semi-áridas do Nordeste do Brasil. Considerando a tendência atual em gestão de conservação das espécies selvagens, o objetivo deste estudo foi determinar referências morfométricas para o coração de cutia criadas em cativeiro, com base em

  18. Seed predation and defleshing in the agouti-dispersed palm Astrocaryum standleyanum

    NARCIS (Netherlands)

    Jansen, P.A.; Elschot, K.; Verkerk, P.J.; Wright, S.J.

    2010-01-01

    The agouti (Dasyprocta punctata) meticulously defleshes Astrocaryum standleyanum palm seeds before scatter hoarding. On Barro Colorado Island, Panama, we experimentally tested three hypotheses on how this behaviour could reduce seed predation to the mutual benefit of the tree and the rodent. The fir

  19. Prey refuges as predator hotspots: ocelot (Leopardus pardalis) attraction to agouti (Dasyprocta punctata) dens

    NARCIS (Netherlands)

    Emsens, W.J.; Hirsch, B.T.; Kays, R.; Jansen, P.A.

    2014-01-01

    We tested the hypothesis that prey refuges attract predators, leading to elevated predator activity in the vicinity of refuges. We used camera traps to determine whether the spatial activity of a predator, the ocelot (Leopardus pardalis), was biased toward refuge locations of its principal prey, the

  20. Morfologia da laringe de cutia (Dasyprocta sp.)

    OpenAIRE

    Andrezza B.S. Silva; Thais M.V. Santos; Maria Acelina M. Carvalho; Paulo S.L. Guerra; Marcia S. Rizzo; Waldilleny R. Araújo; Cristiane B.B. Torres; Airton M. Conde Junior

    2014-01-01

    A cutia (Dasyprocta sp.) é um roedor silvestre com distribuição mundial. Atualmente, além de importante papel ecológico que exerce, está sendo utilizada como modelo em experimento animal. Estudos sobre a morfologia destes animais são importantes porque podem ser uma alternativa para o estudo de diversos processos patológicos, além de contribuirem para a preservação da espécie. A laringe é um órgão localizado entre a faringe e a traqueia, no qual está envolvido nas funções de respiração, deglu...

  1. Morfologia da laringe de cutia (Dasyprocta sp.

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    Andrezza B.S. Silva

    2014-06-01

    Full Text Available A cutia (Dasyprocta sp. é um roedor silvestre com distribuição mundial. Atualmente, além de importante papel ecológico que exerce, está sendo utilizada como modelo em experimento animal. Estudos sobre a morfologia destes animais são importantes porque podem ser uma alternativa para o estudo de diversos processos patológicos, além de contribuirem para a preservação da espécie. A laringe é um órgão localizado entre a faringe e a traqueia, no qual está envolvido nas funções de respiração, deglutição e fonação. O presente estudo propôs realizar uma descrição morfológica macroscópica e microscópica da laringe da cutia. Para tanto, foram utilizadas quinze cutias pertencentes ao Centro de Ciências Agrárias da Universidade Federal do Piauí e provenientes do Núcleo de Estudos e Preservação de Animais Silvestres com licença do IBAMA (Nº 02/08-618, CTF Nº 474064. Todos os animais foram identificados, promovida a sexagem e, posteriormente, a laringe acessada e dissecada sendo os fragmentos cartilagíneos encaminhados para rotina histológica e corados pelo método de hematoxilina-eosina. As lâminas obtidas foram visualizadas em microscopia óptica de luz e foto documentadas. A laringe da cutia apresenta cinco cartilagens, com ausência da cartilagem cuneiforme e presença da incisura caudal na cartilagem tireoide. O tecido epitelial da laringe varia de epitélio estratificado pavimentoso queratinizado à não queratinizado e ciliado com células caliciformes.

  2. Genetic Organization of the agouti Region of the Mouse

    OpenAIRE

    Linda D. Siracusa; Russell, Liane B.; Eicher, Eva M; Corrow, Dorcas J.; Neal G Copeland; Jenkins, Nancy A

    1987-01-01

    The agouti locus on mouse chromosome 2 acts via the hair follicle to control the melanic type and distribution of hair pigments. The diverse phenotypes associated with various agouti mutations have led to speculation about the organization of the agouti locus. Earlier studies indicated that two presumed agouti alleles, lethal yellow (Ay) and lethal light-bellied nonagouti (ax), are pseudoallelic. We present genetic data showing probable recombination between Ay and three agouti mutations (...

  3. New records for helminths of hystricognath rodents from the middle and high Rio Negro microregion, State of Amazonas, Brazil Novos registros para helmintos de roedores histricognatos da microrregião do médio e alto Rio Negro, Estado do Amazonas, Brasil

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    Alessandra Q. Gonçalves

    2006-09-01

    Full Text Available Four nematodes and one cestode species from three Brazilian agoutis - two Dasyprocta fuliginosa Wagler, 1832 and one Dasyprocta leporina (Linnaeus, 1758 - and six pacas - Agouti paca (Linnaeus, 1766 - captured in tributaries rivers in the middle and high Rio Negro microregion, State of Amazonas, Brazil, were studied. The nematodes Physaloptera torresi (Travassos, 1920 Ortlepp, 1922, Physocephalus mediospiralis (Molin, 1859 Hall, 1916 and the cestode Raillietina (R. trinitatae (Cameron & Reesal, 1951 Baer & Sandars, 1956 are reported from the State of Amazonas for the first time. The studied helminths (the nematodes P. torresi, P. mediospiralis, Trichuris gracilis (Rud., 1819 Hall, 1916, Helminthoxys urichi (Cameron & Reesal, 1951 Hugot, 1986 and the cestode R. (R. trinitatae represent new host record for Dasyprocta fuliginosa. New morphometric data and remarks about each species are provided.Foram estudadas quatro espécies de nematóides e uma de cestóide coletados de três cutias - duas Dasyprocta fuliginosa Wagler, 1832 e uma Dasyprocta leporina (Linnaeus, 1758 - e seis pacas - Agouti paca (Linnaeus, 1766 - capturadas em rios afluentes na microrregião do médio e alto Rio Negro, Estado do Amazonas, Brasil. Os nematóides Physaloptera torresi (Travassos, 1920 Ortlepp, 1922, Physocephalus mediospiralis (Molin, 1859 Hall, 1916 e o cestóide Raillietina (R. trinitatae (Cameron & Reesal, 1951 Baer & Sandars, 1956 são registrados pela primeira vez no Estado do Amazonas. Os helmintos estudados (os nematóides P. torresi, P. mediospiralis, Trichuris gracilis (Rud., 1819 Hall, 1916, Helminthoxys urichi (Cameron & Reesal, 1951 Hugot, 1986 e o cestóide R. (R. trinitatae representam novos registros para Dasyprocta fuliginosa. Novos dados morfométricos e observações sobre cada espécie são fornecidos.

  4. The coronary arteries of the agouti (Agouti paca, Linnaeus, 1766

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    Fabrício Singaretti de Oliveira

    2009-12-01

    Full Text Available The present study aimed to describe the coronary arteries in the agouti. Twelve hearts set, in a 10% formaldehyde aqueous solution, were used. The presence of left and right coronary arteries was observed in all hearts. The fi rst arose from the aorta, between the left auricle and the pulmonary trunk, and gave off into a circumfl ex branch, whichever was directed to the right surface of this viscerae, and an interventricular paraconal branch that went through the cardiac apex, on the left atrioventricular sulcus. In 91.6% of the cases, at its origin, the paraconal branch gave off a thick side branch to the left ventricle wall, and in 100% of the cases, went deep, characterizing a large myocardial bridge. In 8.4% of the cases, this thick side branch to the left ventricle wall originated directly from the left coronary artery and not from the paraconal branch, and alterations such those to the circumfl ex branch did not occur. Regarding the right coronary artery, the origin of this vessel was from the aorta, on the atrial surface, in the direction of the right ventricular border, going through the subsinuous interventricular sulcus as an interventricular subsinuous branch.

  5. Modulation of social behavior by the agouti pigmentation gene

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    Valeria eCarola

    2014-08-01

    Full Text Available Agouti is a secreted neuropeptide that acts as an endogenous antagonist of melanocortin receptors. Mice and rats lacking agouti (called non-agouti have dark fur due to a disinhibition of melanocortin signaling and pigment deposition in the hair follicle. Non-agouti animals have also been reported to exhibit altered behavior, despite no evidence for the expression of agouti outside the skin. Here we confirm that non-agouti mice show altered social behavior and uncover expression of agouti in the preputial gland, a sebaceous organ in the urinary tract that secretes molecules involved in social behavior. Non-agouti mice had enlarged preputial glands and altered levels of putative preputial pheromones and surgical removal of the gland reversed the behavioral phenotype. These findings demonstrate the existence of an autologous, out-of-skin pathway for the modulation of social behavior.

  6. Genetic organization of the agouti region of the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Siracusa, L.D.; Russell, L.B.; Eicher, E.M.; Corrow, D.J.; Copeland, N.G.; Jenkins, N.A.

    1987-09-01

    The agouti locus on mouse chromosome 2 acts via the hair follicle to control the melanic type and distribution of hair pigments. The diverse phenotypes associated with various agouti mutations have led to speculation about the organization of the agouti locus. Earlier studies indicated that two presumed agouti alleles, lethal yellow (A/sup y/) and lethal light-bellied nonagouti (a/sup x/), are pseudoallelic. The authors present genetic data showing probable recombination between A/sup y/ and three agouti mutations (a/sup t/, a, and a/sup x/), which suggest that A/sup y/ is a pseudoallele of the agouti locus. The close linkage of an endogenous ecotropic murine leukemia provirus, Emv-15, to A/sup y/ provides a molecular access to genes at or near the agouti locus. However, previous studies suggested that the Emv-15 locus can recombine with some agouti alleles and therefore they analyzed mice from recombinant inbred strains and backcrosses to measure the genetic distance between various agouti alleles and the Emv-15 locus. The data indicate that the Emv-15 locus is less the 0.3 cM from the agouti locus. These experiments provide a conceptual framework for initiating chromosome walking experiments designed to retrieve sequences from the agouti locus and give new insight into the genetic organization of the agouti region.

  7. Splenic melanosis in agouti and black mice.

    Science.gov (United States)

    Michalczyk-Wetula, Dominika; Wieczorek, Justyna; Płonka, Przemysław M

    2015-01-01

    An interesting example of extradermal deposition of melanin in vertebrates, notably in mammals, is splenic melanosis. In particular, if the phenomenon of splenic melanosis is correlated with hair or skin pigmentation, it must reflect the amount and perhaps the quality of pigment produced in hair follicle melanocytes. The present paper is our first study on splenic pigmentation in mice of phenotype agouti. We used untreated mixed background mice C57BL/6;129/SvJ (black - a/a, agouti - A/a, A/A), and as a control - black C57BL/6 and agouti fur from 129/SvJ mice, Mongolian gerbils (Meriones unguiculatus) and golden hamsters (Mesocricetus auratus). After euthanasia skin and spleen was evaluated macroscopically, photographed and collected for further analysis using Fontana-Masson and hematoxylin-eosin staining and electron paramagnetic resonance (EPR) at X-band. Spleens of the agouti mice revealed splenic melanosis but were slightly weaker pigmented than their black counterparts, while the presence of pheomelanin was difficult to determine. The fur of both phenotypes was of similar melanin content, with the same tendency as in the spleens. The contribution of pheomelanin in the agouti fur was on the border of detectability by EPR. Histological and EPR analysis confirmed the presence of melanin in the melanotic spleens. The shape of the EPR signal showed a dominance of eumelanin in fur and in melanized spleens in both phenotypes of mice. Therefore, splenic melanosis does reflect the hair follicle pigmentation not only in black, but also in agouti mice. PMID:26291042

  8. INDICADORES HEMATOLÓGICOS Y HEMOQUÍMICOS DE Dasyprocta fuliginosa (GUARA, GUATÍN O ÑEQUE EN CAUTIVERIO

    Directory of Open Access Journals (Sweden)

    Lizcano L.

    2006-11-01

    Full Text Available Los indicadores hematológicos y hemoquímicos de la Dasyprocta fuliginosa (guara, guatín o ñeque en cautiverio se realizaron en el municipio de Florencia, Caquetá (Colombia, pretendiendo iniciar una referencia de datos para estudios de conservación, manejo productivo y clínico de la especie. Fueron utilizados diez animales machos en dos estados de desarrollo (juveniles y adultos. Para hemograma se determinaron hematocrito (técnica de microhematocrito, hemoglobina (método espectrofotométrico de la cianometahemoglobina, recuento total de leucocitos (técnica del hemocitómetro y recuento diferencial de leucocitos (frotis sanguíneo coloreado, y en hemoquímica se determinó glicemia (método GOD-PAP, colesterol (método CHOD-PAP, triglicéridos (método GPO-PAP, proteínas totales (método Biuret y creatinina (método colorimétrico simétrico. Los valores promedios para los parámetros evaluados en hemograma fueron: hematocrito 49,9 ± 2,9%; hemoglobina 16,5 ± 1,1 g/dl; recuento leucocitario total 6650 ± 1276,9 leucocitos/mm3; neutrófilos 17,7 ± 12,9%; linfocitos 77,6 ± 12,4%, y eosinófilos 5,1 ± 3,2 %. Para hemoquímica los resultados fueron: glicemia 249,9 ± 47,1 mg/dl; colesterol 108,1 ± 20,1 mg/dl; triglicéridos 108,1 ± 20,1 mg/dl, proteínas totales 5,7 ± 0,6 g/dl, y creatinina 1,7 ± 0,2 mg/dl. En algunos individuos los valores se desviaron significativamente del promedio, debiéndose tal vez a circunstancias fisiológicas e individuales (estrés, respuesta a mecanismos externos o por lesiones que padecían días antes a la toma de la muestra. Los indicadores del hemograma estuvieron en promedios similares a los de otros roedores del piedemonte amazónico: Proechimys sp., Agouti paca e Hydrochaeris hydrochaeris, al igual que en los hemoquímicos, salvo en glicemia, en donde se encontraron mayores valores para Dasyprocta fuliginosa, debido posiblemente al régimen alimenticio que se basaba sobre todo en frutas y

  9. Rasgos alimenticios, reproductivos y potencial productivo del tepezcuintle (Agouti paca

    Directory of Open Access Journals (Sweden)

    Montes-Pérez, RC.

    1997-01-01

    Full Text Available The present article reviews the bibliographie date available on the feeding of tepezcuintle (Agouti paca. It also reports about the reproductive rates and the meat production in captivity and mentions some alternatives to improve this characteristics.

  10. DESCRIÇÃO HISTOLÓGICA DOS INCISIVOS DA CUTIA Dasyprocta prymnolopha (Wagler, 1831)

    OpenAIRE

    Weber Leal de Moura; Adriana Maria Viana Nunes Pinheiro; Débora Cavalcante Braz; Maria Acelina de Carvalho

    2006-01-01

    Esse trabalho objetivou descrever a histologia do dente e do periodonto de cutia. Utilizaram-se dez exemplares de Dasyprocta prymnolopha, desconsiderando idade e sexo. Realizado o processamento histológico clássico, o esmalte e o cemento desintegraram-se na descalcificação, evidenciando-se que o cemento apresenta uma quantidade de tecido mineralizado maior que a dentina. Na dentina, observaram-se túbulos dentinários, estriações paralelas, flexíveis, sinuosas e perpendiculares ao eixo maior do...

  11. Analysis of the function of the agouti gene in obesity and diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Mynatt, R.L.; Miltenberger, R.J.; Klebig, M.L. [and others

    1996-09-01

    This chapter discusses the agouti gene and dominant mutations in that gene that lead to agouti-induced obesity, and recent work with transgenic mice to elucidate the role of agouti in obesity. Agouti was cloned in 1992 by the lab of Rick Woychik at Oak Ridge National Laboratory, making it the first of many recently cloned mouse obesity genes. Sequence analysis predicted that mouse agouti is a secreted protein of 131 amino acids. The mature protein has a basic central region (lys57-arg85), a proline-rich domain (pro86-pro91) and a C-terminal region (cys 92-cys 13 1) containing 10 cysteine residues which form 5 disulfide bonds. The human homologue of agouti has also been cloned by the Woychik lab and maps to human chromosome 20q 11.2. Human agouti is 132 amino acids long and is 85% similar to the mouse agouti protein and is normally expressed in adipose tissue. The researchers have been able to recapitulate obesity, hyperinsulinemia, and hyperglycemia with the ubiquitous expression of agouti. Agouti expression in either liver and adipose tissue alone does not cause obesity, and there`s a dose-dependent effect of agouti on body weight, food efficiency, body temperature, and insulin and glucose levels.

  12. DESCRIÇÃO HISTOLÓGICA DOS INCISIVOS DA CUTIA Dasyprocta prymnolopha (Wagler, 1831

    Directory of Open Access Journals (Sweden)

    Weber Leal de Moura

    2006-10-01

    Full Text Available Esse trabalho objetivou descrever a histologia do dente e do periodonto de cutia. Utilizaram-se dez exemplares de Dasyprocta prymnolopha, desconsiderando idade e sexo. Realizado o processamento histológico clássico, o esmalte e o cemento desintegraram-se na descalcificação, evidenciando-se que o cemento apresenta uma quantidade de tecido mineralizado maior que a dentina. Na dentina, observaram-se túbulos dentinários, estriações paralelas, flexíveis, sinuosas e perpendiculares ao eixo maior do dente, presentes em maior quantidade na região próxima à pré-dentina. A dentina foi classificada em peritubular, intertubular e interglobular, além da pré-dentina, delgada porção não mineralizada. Os odontoblastos mostraram-se acidófilos, paralelos, dispostos ‘’em paliçada’’, ocupando o espaço entre a dentina e a polpa. A polpa apresentou tecido conjuntivo frouxo bastante vascularizado e inervado, cujas células predominantes foram fibroblastos de aspecto estrelado e fusiforme com longos prolongamentos citoplasmáticos. O periodonto mostrou cemento, ligamento periodontal e osso alveolar. O ligamento foi classificado em inferior (conjuntivo denso e superior (conjuntivo frouxo com o primeiro apresentando áreas globulares provenientes da comunicação do osso alveolar e o segundo um epitélio juncional pseudo-estratificado. As fibras de Sharpey partiam do ligamento, inserindo-se no osso alveolar,cujas lamelas formariam delgadas trabéculas e de osso compacto formado pelos sistemas de Havers. PALAVRAS-CHAVE: Dente, dentino-pulpar, Dasyprocta periodonto.

  13. Induction of brain region-specific forms of obesity by agouti.

    OpenAIRE

    Kas, M. J. H.; Tiesjema, B; Dijk, G. van; Garner, KM; Barsh, GS; ter Brake, O; Verhaagen, J.; Adan, RAH

    2004-01-01

    Disruption of melanocortin ( MC) signaling, such as by ectopic Agouti overexpression, leads to an obesity syndrome with hyperphagia, obesity, and accelerated body weight gain during high-fat diet. To investigate where in the brain disruption of MC signaling results in obesity, long-term Agouti expression was induced after local injections of recombinant adeno-associated viral particles in selected brain nuclei of adult rats. Agouti expression in the paraventricular nucleus, a hypothalamic reg...

  14. Familial osteopetrosis in Agouti paca: report of nine cases Osteopetrose familiar em Agouti paca: relato de nove casos

    OpenAIRE

    P.S. Coutinho; N.M. Ocarino; Ferreira, M B; Resende, R.; Silva, V. L.; R.M.C. Guedes; R. Serakides

    2008-01-01

    Nine cases of familial osteopetrosis were studied in Agouti paca rodents maintained in captivity. Animals were distributed in three groups depending on the severity of their skeletal lesions. Based upon clinical, radiological, and microscopic findings, it was concluded that one animal had level I lesions, three animals had level II lesions, and five animals had level III osteopetrosis and osteonecrosis. Throughout the entire axial and appendicular skeleton, there was an increased amount of bo...

  15. Induction of brain region-specific forms of obesity by Agouti

    NARCIS (Netherlands)

    Kas, M.J.H.; Tiesjema, B; van Dijk, G; Garner, KM; Barsh, GS; Ter Brake, O; Verhaagen, J; Adan, RAH

    2004-01-01

    Disruption of melanocortin ( MC) signaling, such as by ectopic Agouti overexpression, leads to an obesity syndrome with hyperphagia, obesity, and accelerated body weight gain during high-fat diet. To investigate where in the brain disruption of MC signaling results in obesity, long-term Agouti expre

  16. Induction of brain-region-specific forms of obesity by agouti

    NARCIS (Netherlands)

    Kas, Martien J H; Tiesjema, Birgitte; van Dijk, Gertjan; Garner, Keith M; Barsh, Gregory S; ter Brake, Olivier; Verhaagen, Joost; Adan, Roger A H

    2004-01-01

    Disruption of melanocortin (MC) signaling, such as by ectopic Agouti overexpression, leads to an obesity syndrome with hyperphagia, obesity, and accelerated body weight gain during high-fat diet. To investigate where in the brain disruption of MC signaling results in obesity, long-term Agouti expres

  17. Molecular analysis of the mouse agouti gene and the role of dominant agouti-locus mutations in obesity and insulin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Klebig, M.L.; Woychik, R.P. [Oak Ridge National Lab., TN (United States); Wilkinson, J.E. [Univ. of Tennessee, Knoxville, TN (United States)

    1994-09-01

    The lethal yellow (A{sup y/-}) and viable yellow (A{sup vy/-}) mouse agouti mutants have a predominantly yellow pelage and display a complex syndrome that includes obesity, hyperinsulinemia, and insulin resistance, hallmark features of obesity-associated noninsulin-dependent diabetes mellitus (NIDDM) in humans. A new dominant agouti allele, A{sup iapy}, has recently been identified; like the A{sup vy} allele, it is homozygous viable and confers obesity and yellow fur in heterozygotes. The agouti gene was cloned and characterized at the molecular level. The gene is expressed in the skin during hair growth and is predicted to encode a 131 amino acid protein, that is likely to be a secreted factor. In both Ay/- and A{sup iapy}/- mice, the obesity and other dominant pleiotropic effects are associated with an ectopic expression of agouti in many tissues where the gene product is normally not produced. In Ay, a 170-kb deletion has occurred that causes an upstream promoter to drive the ectopic expression of the wild-type agouti coding exons. In A{sup iapy}, the coding region of the gene is expressed from a cryptic promoter within the LTR of an intracisternal A-particle (IAP), which has integrated within the region just upstream of the first agouti coding exon. Transgenic mice ubiquitously expressing the cloned agouti gene under the influence of the beta-actin and phosphoglycerate kinase promoters display obesity, hyperinsulinemia, and yellow coat color. This demonstrates unequivocally that ectopic expression of agouti is responsible for the yellow obese syndrome.

  18. Cariotipo Citogenético de la Guagua (agouti paca

    Directory of Open Access Journals (Sweden)

    López Ortiz Juan Bautista

    1997-12-01

    Full Text Available El presente trabajo reporta la dotación cromosómica de Agouti paca, una especie considerada en vía de extinción. Además, se muestra la estandarización de la técnica para la obtención de cromosomas en sangre periférica y el tiempo óptimo del pulso terminal de 5-bromo-2 'deoxiuridina (BrdUrd para la obtención de bandas R-replicativas de alta resolución. También, se compara el cariotipo obtenido usando tinción convencional de Giemsa, con el realizado utilizando bandeo replicativo de alta resolución. El análisis de la morfología cromosómica del cariotipo de Agouti paca, muestra 29 pares de cromosomas subtelocéntricos, 2 cromosomas acrocéntricos y 5 pares cromosómicos metacéntricos. De todo el cariotipo, el cromosoma X es el más grande y lo clasificamos como: submetacéntrico. El cromosoma Y es el más pequeño y lo consideramos acrocéntrico. Además, al igual que en todas las hembras de mamíferos, la hembra de guagua exhibe un cromosoma X inactivo de replicación tardía. Con base en los resultados obtenidos, se determina el número cromosómico 2n = 74. De acuerdo con la ISCI (1995, propusimos una clasificación en 5 grupos: grupo A del 1 al 10, grupo B del 11 al 20, grupo C del 21 al 29, grupo D del 30 al 31 y grupo E del 32 al 36, además del parsexual (XX si es hembra, XY si es macho. Estos hallazgos posibilitarán en el futuro, establecer la correlación entre anormalidades cromosómicas y cambios fenotípicos o trastornos reproductivos de la especie; además, servirá como parámetro citogenético en la comparación de Agouti paca con otros Hystricomorfos relacionados. Este resultado se constituye en el primer cariotipo de Agouti paca (guagua, reportado; además, es el primer estudio citogenético donde se realizan bandas R-replicativas de alta resolución para cariotipar especies animales promisorias

  19. Experimental heteroxenous cycle of Lagochilascaris minor Leiper, 1909 (Nematoda: Ascarididae in white mice and in cats

    Directory of Open Access Journals (Sweden)

    Gregorio S. Volcan

    1992-12-01

    Full Text Available Reports of natural infections of sylvatic carnivores by adult worms of species similar to Lagochilascaris minor in the Neotropical region led to attempts to estabilish experimental cycles in laboratory mice and in cats. Also, larval development was seen in the skeletal muscle of an agouti (Dasyprocta leporina infected per os with incubated eggs of the parasite obtained from a human case. In cats, adult worms develop and fertile eggs are expelled in the feces: in mice, larval stages of the parasite develop, and are encapsulate in the skeletal muscle, and in the adipose and subcutaneous connective tissue. From our observations, we conclude that the larva infective for the mouse is the early 3rd stage, while for the final host the infective form is the later 3rd stage. A single moult was seen in the mouse, giving rise to a small population of 4th stage larvae, long after the initial infection.

  20. Identification of Distant Agouti-Like Sequences and Re-Evaluation of the Evolutionary History of the Agouti-Related Peptide (AgRP)

    Science.gov (United States)

    Västermark, Åke; Krishnan, Arunkumar; Houle, Michael E.; Fredriksson, Robert; Cerdá-Reverter, José Miguel; Schiöth, Helgi B.

    2012-01-01

    The Agouti-like peptides including AgRP, ASIP and the teleost-specific A2 (ASIP2 and AgRP2) peptides have potent and diverse functional roles in feeding, pigmentation and background adaptation mechanisms. There are contradictory theories about the evolution of the Agouti-like peptide family as well the nomenclature. Here we performed comprehensive mining and annotation of vertebrate Agouti-like sequences. We identified A2 sequences from salmon, trout, seabass, cod, cichlid, tilapia, gilt-headed sea bream, Antarctic toothfish, rainbow smelt, common carp, channel catfish and interestingly also in lobe-finned fish. Moreover, we surprisingly found eight novel homologues from the kingdom of arthropods and three from fungi, some sharing the characteristic C-x(6)-C-C motif which are present in the Agouti-like sequences, as well as approximate sequence length (130 amino acids), positioning of the motif sequence and sharing of exon-intron structures that are similar to the other Agouti-like peptides providing further support for the common origin of these sequences. Phylogenetic analysis shows that the AgRP sequences cluster basally in the tree, suggesting that these sequences split from a cluster containing both the ASIP and the A2 sequences. We also used a novel approach to determine the statistical evidence for synteny, a sinusoidal Hough transform pattern recognition technique. Our analysis shows that the teleost AgRP2 resides in a chromosomal region that has synteny with Hsa 8, but we found no convincing synteny between the regions that A2, AgRP and ASIP reside in, which would support that the Agouti-like peptides were formed by whole genome tetraplodization events. Here we suggest that the Agouti-like peptide genes were formed through classical subsequent gene duplications where the AgRP is the most distantly related to the three other members of that group, first splitting from a common ancestor to ASIP and A2, and then later the A2 split from ASIP followed by a

  1. Familial osteopetrosis in Agouti paca: report of nine cases Osteopetrose familiar em Agouti paca: relato de nove casos

    Directory of Open Access Journals (Sweden)

    P.S. Coutinho

    2008-12-01

    Full Text Available Nine cases of familial osteopetrosis were studied in Agouti paca rodents maintained in captivity. Animals were distributed in three groups depending on the severity of their skeletal lesions. Based upon clinical, radiological, and microscopic findings, it was concluded that one animal had level I lesions, three animals had level II lesions, and five animals had level III osteopetrosis and osteonecrosis. Throughout the entire axial and appendicular skeleton, there was an increased amount of both trabecular and cortical bone tissue. All analyzed bones showed thickened cortex and reduced medullary canals. Bone trabeculae were thick and confluent. Cortex showed a narrowing of Haversian canals. Numerous cementing lines resulted in typical mosaic patterns. Osteocytes were pycnotic. Osteonecrosis was characterized by the disappearance of osteocytes and bone matrix decomposition.Descreveram-se nove casos de osteopetrose familiar em Agouti paca mantidas em cativeiro. Os animais foram distribuídos em três grupos de acordo com a gravidade das lesões do esqueleto. Com base nos exames clínico, radiológico e microscópico, foi concluído que um animal apresentou lesões de nível I, três animais tiveram lesões de nível II e cinco animais tiveram osteopetrose de nível III. Por todo o esqueleto axial e apendicular, a quantidade de osso trabecular e osteônico estava aumentada. Todos os ossos analisados mostraram córtex espesso e canais medulares reduzidos. As trabéculas ósseas eram espessas e confluentes. No córtex, verificou-se um estreitamento de canais de Havers. Numerosas linhas de cimentação resultaram em um padrão de mosaico típico. Osteócitos estavam picnóticos e a osteonecrose foi caracterizada pela morte dos osteócitos, com desintegração da matriz óssea.

  2. The effects of calcium channel blockade on agouti-induced obesity

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Han; Moustaid, N.; Zemel, M.B. [Univ. of Tennessee, Knoxville, TN (United States)] [and others

    1996-12-01

    We have previously observed that obese viable yellow (A{sup vy}/a) mice exhibit increased intracellular Ca{sup 2+} ([Ca{sup 2+}]i) and fatty acid synthase (FAS) gene expression; further, recombinant agouti protein increases in cultured adipocytes and these effects are inhibited by Ca{sup 2+} channel blockade. Accordingly, we determined the effect of Ca{sup 2+} channel blockade (nifedipine for 4 wk) on FAS and obesity in transgenic mice expressing the agouti gene in a ubiquitous manner. The transgenic mice initially were significantly heavier (30.5 {+-} 0.6 vs. 27.3 {+-} 0.3 g; P<0.001) and exhibited a 0.81{degrees}C lower initial core temperature (P<0.0005), an approximately twofold increase in fat pad weights (P=0.002), a sevenfold increase in adipose FAS activity (P=0.009), and a twofold increase in plasma insulin level (P<0.05) compared to control mice. Nifedipine treatment resulted in an 18% decrease in fat pad weights (P<0.007) and a 74% decrease in adipose FAS activity (P=0.03), normalized circulating insulin levels and insulin sensitivity (P,0.05), and transiently elevated core temperature in the transgenic mice, but was without effect in the control mice. These data suggest that agouti regulates FAS, fat storage, and possibly thermogenesis, at least partially, via a [Ca{sup 2+}]{sub i}-dependent mechanism, and that Ca{sup 2+} channel blockade may partially attenuate agouti-induced obesity. 42 refs., 4 figs., 1 tab.

  3. Molecular basis of the pleiotropic phenotype of mice carrying the hypervariable yellow (A{sup hvy}) mutation at the agouti locus

    Energy Technology Data Exchange (ETDEWEB)

    Argeson, A.C.; Nelson, K.K.; Siracusa, L.D. [Jefferson Cancer Center, Philadelphia, PA (United States)

    1996-02-01

    The murine agouti locus regulates a switch in pigment synthesis between eumelanin (black/brown pigment) and phaeomelanin (yellow/red pigment) by hair bulb melanocytes. We recently described a spontaneous mutation, hypervariable yellow (A{sup hvy}) and demonstrated that A{sup hvy} is responsible for the largest range of phenotypes yet identified at the agouti locus, producing mice that are obese with yellow coats to mice that are of normal weight with black coats. Here, we show that agouti expression is altered both temporally and spatially in A{sup hvy} mutants. Agouti expression levels are positively correlated with the degree of yellow pigmentation in individual A{sup hvy} mice, consistent with results from other dominant yellow agouti mutations. Sequencing of 5{prime} RACE and genomic PCR products revealed that A{sup hvy} resulted from the integration of an intracisternal A particle (IAP) in an antisense orientation within the 5{prime} untranslated agouti exon 1C. This retrovirus-like element is responsible for deregulating agouti expression in A{sup hvy} mice; agouti expression is correlated with the methylation state of CpG residues in the IAP long terminal repeat as well as in host genomic DNA. In addition, the data suggest that the variable phenotype of A{sup hvy} offspring is influenced in part by the phenotype of their A{sup hvy} female parent. 42 refs., 7 figs., 1 tab.

  4. Características reprodutivas da paca fêmea (Agouti paca criada em cativeiro Reprodutive characteristics of the female paca (Agouti paca raised in captivity

    Directory of Open Access Journals (Sweden)

    Diva Anelie de Araújo Guimarães

    2008-01-01

    Full Text Available O objetivo do trabalho foi estudar a biologia reprodutiva da Agouti paca criada em cativeiro. Os resultados demonstraram que, a duração média do ciclo estral foi de 32,5 + 3,7 dias e o período gestacional de 148,6 + 4,8 dias. O intervalo entre partos foi de 224,5 + 52,2 dias e o primeiro cio pós-parto foi de 25,6 + 8,8 dias. A maioria (55,6 % das fêmeas apresentou dois partos por ano, com o nascimento de um filhote por parto, sendo 44,7 % fêmeas e 55,3 % machos. Ao nascer o peso médio das fêmeas foi de 605,9 + 87,5 g e dos machos 736,7 + 108,4 g (P The objective of this paper was to study the reproductive biology of the Agouti paca raised in captivity. It was observed that the estrous cycle average was 32.5 + 3.7 days, gestation length 148.6 + 4.8 days, parturition interval 224.5 + 52.2 days, and the first post-partum 25.6 + 8.8 days. It was also observed that 55.5% of the females presented two parturitions per year with one young per parturition, of which 44.7% were females and 55.3% were males. The birth weight was 605.9 + 87.8 g for females and 736.7 + 108.4 g for males (P<0.05. Puberty in females occurred between 8 to 12 months; for this, however, more detailed investigations are necessary.

  5. Teriflunomide attenuates immunopathological changes in the Dark Agouti rat model of experimental autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Garth E. Ringheim

    2013-10-01

    Full Text Available Teriflunomide is an oral disease-modifying therapy recently approved in several locations for relapsing forms of multiple sclerosis. To gain insight into the effects of teriflunomide, immunocyte population changes were measured during progression of experimental autoimmune encephalomyelitis in Dark Agouti rats. Treatment with teriflunomide attenuated levels of spinal cord-infiltrating T cells, natural killer cells, macrophages, and neutrophils. Teriflunomide also mitigated the disease-induced changes in immune cell populations in the blood and spleen suggesting an inhibitory effect on pathogenic immune responses.

  6. Recombinant Inbred Strain and Interspecific Backcross Analysis of Molecular Markers Flanking the Murine Agouti Coat Color Locus

    OpenAIRE

    Siracusa, L. D.; Buchberg, A M; Copeland, N. G.; Jenkins, N.A.

    1989-01-01

    Recombinant inbred strain and interspecific backcross mice were used to create a molecular genetic linkage map of the distal portion of mouse chromosome 2. The orientation and distance of the Ada, Emv-13, Emv-15, Hck-1, Il-1a, Pck-1, Psp, Src-1 and Svp-1 loci from the β(2)-microglobulin locus and the agouti locus were established. Our mapping results have provided the identification of molecular markers both proximal and distal to the agouti locus. The recombinants obtained provide valuable r...

  7. An obesity-dependent lactation defect in the viable yellow agouti mouse is associated with mammary inflammation

    Science.gov (United States)

    Maternal obesity is known to delay lactogenesis in breast-feeding women, as well as negatively impact lactation in other species. Obesity is also understood to be associated with inflammation. Work with the viable yellow agouti (Avy) mouse in our laboratory has documented a lactation defect in obese...

  8. Liver-specific expression of the agouti gene in transgenic mice promotes liver carcinogenesis in the absence of obesity and diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Kuklin, Alexander [ORNL; Mynatt, Randall [ORNL; Klebig, Mitch [ORNL; Kiefer, Laura [Glaxo Wellcome, Research Triangle Park, NC; Wilkison, William O [Glaxo Wellcome, Research Triangle Park, NC; Woychik, Richard P [Jackson Laboratory, The, Bar Harbor, ME; Michaud III, Edward J [ORNL

    2004-01-01

    Background: The agouti protein is a paracrine factor that is normally present in the skin of many species of mammals. Agouti regulates the switch between black and yellow hair pigmentation by signalling through the melanocortin 1 receptor (Mc1r) on melanocytes. Lethal yellow (Ay) and viable yellow (Avy) are dominant regulatory mutations in the mouse agouti gene that cause the wild- ype protein to be produced at abnormally high levels throughout the body. Mice harboring these mutations exhibit a pleiotropic syndrome characterized by yellow coat color, obesity, hyperglycemia, hyperinsulinemia, and increased susceptibility to hyperplasia and carcinogenesis in numerous tissues, including the liver. The goal of this research was to determine if ectopic expression of the agouti gene in the liver alone is sufficient to recapitulate any aspect of this syndrome. For this purpose, we generated lines of transgenic mice expressing high levels of agouti in the liver under the regulatory control of the albumin promoter. Expression levels of the agouti transgene in the liver were quantified by Northern blot analysis. Functional agouti protein in the liver of transgenic mice was assayed by its ability to inhibit binding of the -melanocyte stimulating hormone ( MSH) to the Mc1r. Body weight, plasma insulin and blood glucose levels were analyzed in control and transgenic mice. Control and transgenic male mice were given a single intraperitoneal injection (10 mg/kg) of the hepatocellular carcinogen, diethylnitrosamine (DEN), at 15 days of age. Mice were euthanized at 36 or 40 weeks after DEN injection and the number of tumors per liver and total liver weights were recorded. Results: The albumin-agouti transgene was expressed at high levels in the livers of mice and produced a functional agouti protein. Albumin-agouti transgenic mice had normal body weights and normal levels of blood glucose and plasma insulin, but responded to chemical initiation of the liver with an increased number

  9. Liver-specific expression of the agouti gene in transgenic mice promotes liver carcinogenesis in the absence of obesity and diabetes

    Directory of Open Access Journals (Sweden)

    Kiefer Laura L

    2004-06-01

    Full Text Available Abstract Background The agouti protein is a paracrine factor that is normally present in the skin of many species of mammals. Agouti regulates the switch between black and yellow hair pigmentation by signalling through the melanocortin 1 receptor (Mc1r on melanocytes. Lethal yellow (Ay and viable yellow (Avy are dominant regulatory mutations in the mouse agouti gene that cause the wild-type protein to be produced at abnormally high levels throughout the body. Mice harboring these mutations exhibit a pleiotropic syndrome characterized by yellow coat color, obesity, hyperglycemia, hyperinsulinemia, and increased susceptibility to hyperplasia and carcinogenesis in numerous tissues, including the liver. The goal of this research was to determine if ectopic expression of the agouti gene in the liver alone is sufficient to recapitulate any aspect of this syndrome. For this purpose, we generated lines of transgenic mice expressing high levels of agouti in the liver under the regulatory control of the albumin promoter. Expression levels of the agouti transgene in the liver were quantified by Northern blot analysis. Functional agouti protein in the liver of transgenic mice was assayed by its ability to inhibit binding of the α-melanocyte stimulating hormone (αMSH to the Mc1r. Body weight, plasma insulin and blood glucose levels were analyzed in control and transgenic mice. Control and transgenic male mice were given a single intraperitoneal injection (10 mg/kg of the hepatocellular carcinogen, diethylnitrosamine (DEN, at 15 days of age. Mice were euthanized at 36 or 40 weeks after DEN injection and the number of tumors per liver and total liver weights were recorded. Results The albumin-agouti transgene was expressed at high levels in the livers of mice and produced a functional agouti protein. Albumin-agouti transgenic mice had normal body weights and normal levels of blood glucose and plasma insulin, but responded to chemical initiation of the liver

  10. Agouti and Agouti-related Proteins%Agouti和Agouti相关蛋白的一些生物学内涵

    Institute of Scientific and Technical Information of China (English)

    杨云青; 高丹玫; 郭宗圣

    2008-01-01

    Agouti 有多方面的意义.首先,它是分属几种不同物种的哺乳动物的俗称.其次,它是一些啮齿类动物的属名.第三,它代表了一种啮齿类动物特有的毛色.第四,它是一个与黑素皮质素受体信号转导途径的调控有关,存在于从人(Homo sapiens)到啮齿类动物,乃至斑马鱼(Danio rerio)的一个特定基因的名称,又是该基因产生的一种特定信号蛋白的名称.Agouti和Agouti相关蛋白是肿瘤、肥胖与糖尿病等人类疾病的研究热点之一.Agouti黄色肥胖小鼠最近成了表观遗传学研究的一个重要模型动物.本文阐述并区分了与agouti有关的一些重要概念与科学术语,并综述了相关领域的研究进展.

  11. BIOMETRY OF PACA NEWBORNS BRED IN CAPTIVITY(AGOUTI PACA, LINNAEUS, 1766 NOTA CIENTÍFICA: BIOMETRIA DOS NEONATOS DE PACA CRIADOS EM CATIVEIRO (AGOUTI PACA, LINNAEUS, 1766

    Directory of Open Access Journals (Sweden)

    Júlio Carlos Canola

    2007-12-01

    Full Text Available

    Biometry provides important data on weight and length of wild animal newborns. After ultrasound pregnancy detection, 22 female pacas were separated in individual bails and kept until weaning of newborns. Newborns were measured with a metric tape (between the tips of the muzzle rostrally and the tail distally and weighted in a digital weight scale. Considering males and females, the average newborn length (average length ± standard deviation was 33.37 ± 0.57cm. Among males, the average weight was 33.30 ± 0.52 cm and among females 33.45 ± 0.62cm. Considering males and females, newborns weighted (average weight ± standard deviation 741.14 ± 51.23g. Among males, average weight was 717.75 ± 49.06g and among females 764.53 ± 53.40g. Female newborns are higher and heavier than males, but averages of weight and length of males and females did not differ themselves by the Tukey test (P<0.05.

    Key-words: Agouti paca, biometry, newborns.

    A biometria proporciona dados importantes no peso e comprimento de neonatos de animais selvagens. Após detecção ultra-sonográfica da prenhez, 22 pacas fêmeas foram separadas em baias individuais e mantidas até o desmame dos filhotes. Os neonatos eram medidos com uma fita métrica flexível (entre as extremidades do focinho e da caudal e então pesados em balança digital de precisão. Considerando-se machos e fêmeas, o comprimento dos neonatos (comprimento ± desvio padrão foi 33,37 ± 0,57 cm. Entre os machos, o comprimento médio foi 33,30 ± 0,52 cm e entre as fêmeas foi de 33,45 ± 0,62 cm. Em relação ao peso e considerando-se machos e fêmeas, os neonatos pesavam (peso ± desvio padrão 741,14 ± 51,23g. Entre os machos, o peso médio foi 717,75 ± 49,06g e entre as fêmeas 764,53 ± 53,40g. Os neonatos fêmeas são maiores e mais pesados que os neonatos machos de paca, mas as médias de peso e de comprimento de machos e fêmeas n

  12. Erupção dental em pacas (Agouti paca criadas em cativeiro Dental eruption in pacas (Agouti paca bred in captivity

    Directory of Open Access Journals (Sweden)

    F.S. Oliveira

    2007-04-01

    Full Text Available Fez-se o acompanhamento radiográfico mensal da erupção dental de cinco fêmeas e sete machos da espécie Agouti paca durante 30 meses. Os animais foram radiografados mês-a-mês. As pacas nasceram com três dentes em cada hemiarcada dental, um incisivo de crescimento contínuo por toda a vida, um pré-molar decíduo (o único que é decíduo e um molar. No quarto mês houve a erupção do segundo molar. O nivelamento da superfície de oclusão dos dentes inferiores ocorreu no sexto mês e o dos superiores ao redor do nono mês. No 14° mês, houve o início da erupção do terceiro molar e, no 16° mês, a evidenciação radiográfica do pré-molar permanente, ainda com preservação de correspondente decíduo. No 21° mês, ocorreu o nivelamento da superfície de oclusão dos quatro dentes superiores e inferiores. Entre o 22° e o 24° mês, iniciou-se a queda dos pré-molares decíduos inferiores e, entre o 23º e o 24° mês, a dos superiores. Entre o 24º e o 25º mês, a superfície de oclusão dos dentes inferiores estava nivelada, e a dos dentes superiores aconteceu no 27º mês.Five females and seven males of Agouti paca were used to study dental eruption. In a monthly radiographic survey of the dental eruption, during 30 consecutive months, animals were radiographed. Pacas were born with three teeth in each dental hemiarcade, one incisor of continuous growth, one premolar (the only one deciduous and one molar. The second molar erupted in the fourth month. The occlusal surfaces of lower teeth were at the same level in the sixth month and the upper teeth around ninth month. The beginning of the third molar eruption occurred in the 14th month. Perception of the first permanent premolar was around the 16th month, and its correspondent deciduous was still retained. The occlusal surfaces of upper and lower teeth were at the same level in the 21st month. The eruption of the first lower deciduous premolar occurred between the 22nd and 24th

  13. A polymorphism in the agouti signalling protein (ASIP) is associated with decreased levels of mRNA.

    Science.gov (United States)

    Voisey, J; Gomez-Cabrera, M Del C; Smit, D J; Leonard, J H; Sturm, R A; van Daal, A

    2006-06-01

    To date, a role for agouti signalling protein (ASIP) in human pigmentation has not been well characterized. It is known that agouti plays a pivotal role in the pigment switch from the dark eumelanin to the light pheomelanin in the mouse. However, because humans do not have an agouti banded hair pattern, its role in human pigmentation has been questioned. We previously identified a single polymorphism in the 3'-untranslated region (UTR) of ASIP that was found at a higher frequency in African-Americans compared with other population groups. To compare allele frequencies between European-Australians and indigenous Australians, the g.8818A --> G polymorphism was genotyped. Significant differences were seen in allele frequencies between these groups (P Australian Aborigines. In the Caucasian sample set a strong association was observed between the G allele and dark hair colour (P = 0.004) (odds ratio 4.6; 95% CI 1.4-15.27). The functional consequences of this polymorphism are not known but it was postulated that it might result in message instability and premature degradation of the transcript. To test this hypothesis, ASIP mRNA levels were quantified in melanocytes carrying the variant and non-variant alleles. Using quantitative real-time polymerase chain reaction the mean ASIP mRNA ratio of the AA genotype to the AG genotype was 12 (P < 0.05). This study suggests that the 3'-UTR polymorphism results in decreased levels of ASIP and therefore less pheomelanin production. PMID:16704456

  14. Agouti signalling protein (ASIP) gene: molecular cloning, sequence characterisation and tissue distribution in domestic goose.

    Science.gov (United States)

    Zhang, J; Wang, C; Liu, Y; Liu, J; Wang, H Y; Liu, A F; He, D Q

    2016-06-01

    Agouti signalling protein (ASIP) is an endogenous antagonist of melanocortin-1 receptor (MC1R) and is involved in the regulation of pigmentation in mammals. The objective of this study was to identify and characterise the ASIP gene in domestic goose. The goose ASIP cDNA consisted of a 44-nucleotide 5'-terminal untranslated region (UTR), a 390-nucleotide open-reading frame (ORF) and a 45-nucleotide 3'-UTR. The length of goose ASIP genomic DNA was 6176 bp, including three coding exons and two introns. Bioinformatic analysis indicated that the ORF encodes a protein of 130 amino-acid residues with a molecular weight of 14.88 kDa and an isoelectric point of 9.73. Multiple sequence alignments and phylogenetic analysis showed that the amino-acid sequence of ASIP was conserved in vertebrates, especially in the avian species. RT-qPCR showed that the goose ASIP mRNA was differentially expressed in the pigment deposition tissues, including eye, foot, feather follicle, skin of the back, as well as in skin of the abdomen. The expression level of the ASIP gene in skin of the abdomen was higher than that in skin of the back. Those findings will contribute to further understanding the functions of the ASIP gene in geese plumage colouring. PMID:26750999

  15. Transient Ectopic Overexpression of Agouti-Signalling Protein 1 (Asip1) Induces Pigment Anomalies in Flatfish

    Science.gov (United States)

    Cal, Rosa; Rotllant, Josep; Cerdá-Reverter, José Miguel

    2012-01-01

    While flatfish in the wild exhibit a pronounced countershading of the dorso-ventral pigment pattern, malpigmentation is commonly observed in reared animals. In fish, the dorso-ventral pigment polarity is achieved because a melanization inhibition factor (MIF) inhibits melanoblast differentiation and encourages iridophore proliferation in the ventrum. A previous work of our group suggested that asip1 is the uncharacterized MIF concerned. In order to further support this hypothesis, we have characterized asip1 mRNAs in both turbot and sole and used deduced peptide alignments to analyze the evolutionary history of the agouti-family of peptides. The putative asip precursors have the characteristics of a secreted protein, displaying a putative hydrophobic signal. Processing of the potential signal peptide produces mature proteins that include an N-terminal region, a basic central domain with a high proportion of lysine residues as well as a proline-rich region that immediately precedes the C-terminal poly-cysteine domain. The expression of asip1 mRNA in the ventral area was significantly higher than in the dorsal region. Similarly, the expression of asip1 within the unpigmented patches in the dorsal skin of pseudoalbino fish was higher than in the pigmented dorsal regions but similar to those levels observed in the ventral skin. In addition, the injection/electroporation of asip1 capped mRNA in both species induced long term dorsal skin paling, suggesting the inhibition of the melanogenic pathways. The data suggest that fish asip1 is involved in the dorsal-ventral pigment patterning in adult fish, where it induces the regulatory asymmetry involved in precursor differentiation into mature chromatophore. Adult dorsal pseudoalbinism seems to be the consequence of the expression of normal developmental pathways in an inaccurate position that results in unbalanced asip1 production levels. This, in turn, generates a ventral-like differentiation environment in dorsal regions

  16. VALOR AGREGADO DE LAS ESPECIES Brycon erythropterum (SÁBALO), Colossoma macropomum (GAMITANA), Arapaima gigas (PAICHE) y Agouti paca (MAJAS)

    OpenAIRE

    Doylith Vásquez Jurafo; Cinthya Córdova Ríos; Wendy Olórtegui Morey; Nirsa Cachique Oliveira; Luis Silva Ramos; Ricardo García Pinchi

    2012-01-01

    El presente trabajo tiene como objetivo  la obtención de  productos mínimamente procesados (PMP) de Brycon erythropterum (SÁBALO), Colossoma macropomum (GAMITANA), Arapaima gigas (PAICHE), y Agouti paca (MAJAS) congelado y empacado al vacio. Para las especies piscícolas, se ha aplicado un diseño factorial de 32 con dos factores de estudios: concentración de NaCl en la solución osmótica con tres niveles (15, 20 y 25 %) y temperatura de proceso  con tres niveles de estudio (5, 10 y 15 °C). Para...

  17. Atributos de qualidade da carne de paca (Agouti paca: perfil sensorial e força de cisalhamento Quality attributes of paca meat (Agouti paca: sensory profile and shear force

    Directory of Open Access Journals (Sweden)

    C. Gomes

    2013-04-01

    Full Text Available Avaliaram-se as características sensoriais e determinou-se a força de cisalhamento de cortes de carne de paca (Agouti paca. As análises foram realizadas nos cortes desossados de paleta, lombo e pernil de nove pacas, preparados por cocção até a temperatura interna de 70ºC. A avaliação de aspecto, cor, sabor, odor e maciez foi realizada pela aplicação de teste afetivo a 146 provadores, utilizando-se escala hedônica, e a força de cisalhamento foi determinada pela técnica Warner Bratzler. Na avaliação sensorial, os cortes de paleta, lombo e pernil de paca mostraram diferença significativa (p0,05 entre os cortes, que se mostraram igualmente macios. A carne de paca apresentou-se sensorialmente semelhante à carne suína e com boa aceitação pelos consumidores. O estudo evidenciou o potencial da paca como uma espécie silvestre para a produção comercial de carne para o mercado de carnes vermelhas ou exóticas.Sensory characteristics and shear force of paca meat (Agouti paca were assessed in this study. Analyses were performed in the bonelessshoulder,loin andhamobtained from nine paca carcassesprepared by cookinguntil reaching the internal temperatureof 70°C. The evaluation of flavor, aroma, color, appearance and tenderness was carried out by the application of an affective test using the hedonic scaleand a 146 consumer panel. Shear force was determined by the Warner-Bratzler technique. Shoulder, loin and ham had significant differences (p 0.05 among the cuts, which were similarly tender. Paca meat was found to resemble pork meat in sensory evaluation and had good acceptance by consumers. This study showed the potential of paca (Agouti paca asa wild species for meat production in the red or exotic meat market.

  18. VALOR AGREGADO DE LAS ESPECIES Brycon erythropterum (SÁBALO, Colossoma macropomum (GAMITANA, Arapaima gigas (PAICHE y Agouti paca (MAJAS

    Directory of Open Access Journals (Sweden)

    Doylith Vásquez Jurafo

    2012-12-01

    Full Text Available El presente trabajo tiene como objetivo  la obtención de  productos mínimamente procesados (PMP de Brycon erythropterum (SÁBALO, Colossoma macropomum (GAMITANA, Arapaima gigas (PAICHE, y Agouti paca (MAJAS congelado y empacado al vacio. Para las especies piscícolas, se ha aplicado un diseño factorial de 32 con dos factores de estudios: concentración de NaCl en la solución osmótica con tres niveles (15, 20 y 25 % y temperatura de proceso  con tres niveles de estudio (5, 10 y 15 °C. Para el Agouti paca (majas se aplico un diseño factorial completamente aleatorizado con tres factores de estudio: tiempo de proceso (30, 60 y 90 minutos, método de ahumado (ahumado líquido y ahumado en caliente y tipo de corte del músculo (partes y filetes. Para trabajar se ha diseñado y montado un deshidratador Osmótico teniendo en cuenta, diámetro de tubería, deshidratador propiamente dicho con doble chaqueta, capacidad del deshidratador en función del volumen de la Salmuera.  Todos los productos se obtuvieron  en procesos con 10 °C y tiempos entre 30 min y  90 min. El tiempo de vida en almacenamiento en las evaluaciones de aroma y color en majas tienen una vida útil de 4 meses de almacenados a -18 °C. Los análisis microbiológicos realizados a los PMP no pasan los límites de la NTS Nº 071 MINSA/DIGESA V01.

  19. Trichostrongylina (Nematoda, Heligmosomoidea coparasites in Dasyprocta fuliginosa Wagler (Rodentia, Dasyproctidae from Brazil, with the re-establishment of the genus Avellaria Freitas & Lent and the description of two new species Trichostrongylina (Nematoda, Heligmosomoidea co-parasitos em Dasyprocta fuliginosa Wagler (Rodentia, Dasyproctidae do Brasil, com o restabelecimento do gênero Avellaria Freitas & Lent e a descrição de duas novas espécies

    Directory of Open Access Journals (Sweden)

    Marie C. Durette-Desset

    2006-06-01

    Full Text Available Two new tichostrongylid nematodes of the family Viannaiidae Durette-Desset & Chabaud, 1981 coparasites in Dasyprocta fuliginosa Wagler, 1832 from the State of Amazonas, Brazil, are described: Viannella trichospicula sp. nov. is differentiated from the other species of the genus by the extreme slenderness of its spicules. Avellaria intermedia sp. nov. is distinguished from the single type species Avellaria avellari Freitas & Lent, 1934, by a smaller number of cuticular ridges (17 versus 27, a higher ratio of spicule length/ body length (8% versus 5.6% and spicules with a single tip. This genus, synonymized with the genus Viannella Travassos, 1918, by Durette-Desset (1968 is re-established, the female being didelphic. It is the first record of a nematode of the family Viannaiidae in a host of the family Dasyproctidae Bonaparte, 1838.Dois novos nematóides tricostrongilídeos da família Viannaiidae Durette-Desset & Chabaud, 1981 co-parasitos em um espécime de Dasyprocta fuliginosa Wagler, 1832 do Estado do Amazonas, Brasil, são descritos: Viannella trichospicula sp. nov. distingue-se das espécies do gênero, pelos espículos extremamente delgados. Avellaria intermedia sp. nov. diferencia-se da espécie tipo e única do gênero Avellaria avellari Freitas & Lent, 1934, pelo menor número de arestas cuticulares (17 comparado a 27, pela maior relação entre o tamanho do espículo e o comprimento do corpo (8% comparado a 5,6% e espículos com extremidade única. Este gênero, que havia sido considerado sinônimo de Viannella Travassos, 1918, por Durette-Desset (1968, é restabelecido; as fêmeas são didelfas. Este é o primeiro registro de um nematóide da família Viannaiidae em um hospedeiro da família Dasyproctidae Bonaparte, 1838.

  20. Dietary Calcium and Dairy Modulation of Oxidative Stress and Mortality in aP2-Agouti and Wild-type Mice

    Directory of Open Access Journals (Sweden)

    Antje Bruckbauer

    2009-08-01

    Full Text Available Oxidative and inflammatory stress have been implicated as major contributors to the aging process. Dietary Ca reduced both factors in short-term interventions, while milk exerted a greater effect than supplemental Ca. In this work, we examined the effects of life-long supplemental and dairy calcium on lifespan and life-span related biomarkers in aP2-agouti transgenic (model of diet-induced obesity and wild-type mice fed obesigenic diets until their death. These data demonstrate that dairy Ca exerts sustained effects resulting in attenuated adiposity, protection against age-related muscle loss and reduction of oxidative and inflammatory stress in both mouse strains. Although these effects did not alter maximum lifespan, they did suppress early mortality in wild-type mice, but not in aP2-agouti transgenic mice.

  1. Cyclic Lactam Hybrid α-MSH/Agouti-Related Protein (AGRP) Analogues with Nanomolar Range Binding Affinities at the Human Melanocortin Receptors

    OpenAIRE

    Mayorov, Alexander V.; Cai, Minying; Palmer, Erin S.; Tanaka, Dustin K.; Cain, James P.; Dedek, Matthew M.; Tan, Bahar; Trivedi, Dev; Victor J. Hruby

    2011-01-01

    A novel hybrid melanocortin pharmacophore was designed based on the topographical similarities between the pharmacophores of Agouti related protein (AGRP) an endogenous melanocortin antagonist, and α-melanocyte-stimulating hormone (α-MSH), an endogenous melanocortin agonist. When employed in two different 23-membered macrocyclic lactam peptide templates, the designed hybrid AGRP/MSH pharmacophore yielded non-competitive ligands with nanomolar range binding affinities. The topography-based pha...

  2. Who's behind that mask and cape? The Asian leopard cat's Agouti (ASIP) allele likely affects coat colour phenotype in the Bengal cat breed.

    Science.gov (United States)

    Gershony, L C; Penedo, M C T; Davis, B W; Murphy, W J; Helps, C R; Lyons, L A

    2014-12-01

    Coat colours and patterns are highly variable in cats and are determined mainly by several genes with Mendelian inheritance. A 2-bp deletion in agouti signalling protein (ASIP) is associated with melanism in domestic cats. Bengal cats are hybrids between domestic cats and Asian leopard cats (Prionailurus bengalensis), and the charcoal coat colouration/pattern in Bengals presents as a possible incomplete melanism. The complete coding region of ASIP was directly sequenced in Asian leopard, domestic and Bengal cats. Twenty-seven variants were identified between domestic and leopard cats and were investigated in Bengals and Savannahs, a hybrid with servals (Leptailurus serval). The leopard cat ASIP haplotype was distinguished from domestic cat by four synonymous and four non-synonymous exonic SNPs, as well as 19 intronic variants, including a 42-bp deletion in intron 4. Fifty-six of 64 reported charcoal cats were compound heterozygotes at ASIP, with leopard cat agouti (A(P) (be) ) and domestic cat non-agouti (a) haplotypes. Twenty-four Bengals had an additional unique haplotype (A2) for exon 2 that was not identified in leopard cats, servals or jungle cats (Felis chaus). The compound heterozygote state suggests the leopard cat allele, in combination with the recessive non-agouti allele, influences Bengal markings, producing a darker, yet not completely melanistic coat. This is the first validation of a leopard cat allele segregating in the Bengal breed and likely affecting their overall pelage phenotype. Genetic testing services need to be aware of the possible segregation of wild felid alleles in all assays performed on hybrid cats. PMID:25143047

  3. Histochemical characterization, distribution and morphometric analysis of NADPH diaphorase neurons in the spinal cord of the agouti

    Directory of Open Access Journals (Sweden)

    Marco Aurelio M Freire

    2008-05-01

    Full Text Available We evaluated the neuropil distribution of the enzymes NADPH diaphorase (NADPH-d and cytochrome oxidase (CO in the spinal cord of the agouti, a medium-sized diurnal rodent, together with the distribution pattern and morphometrical characteristics of NADPH-d reactive neurons across different spinal segments. Neuropil labeling pattern was remarkably similar for both enzymes in coronal sections: reactivity was higher in regions involved with pain processing. We found two distinct types of NADPH-d reactive neurons in the agouti’s spinal cord: type I neurons had large, heavily stained cell bodies while type II neurons displayed relatively small and poorly stained somata. We concentrated our analysis on type I neurons. These were found mainly in the dorsal horn and around the central canal of every spinal segment, with a few scattered neurons located in the ventral horn of both cervical and lumbar regions. Overall, type I neurons were more numerous in the cervical region. Type I neurons were also found in the white matter, particularly in the ventral funiculum. Morphometrical analysis revealed that type I neurons located in the cervical region have dendritic trees that are more complex than those located in both lumbar and thoracic regions. In addition, NADPH-d cells located in the ventral horn had a larger cell body, especially in lumbar segments. The resulting pattern of cell body and neuropil distribution is in accordance with proposed schemes of segregation of function in the mammalian spinal cord.

  4. INDUCCIÓN SINCRÓNICA DEL CICLO ESTRAL EN LA GUAGUA NEGRA (Agouti taczanowskii EN CAUTIVERIO SYNCHRONOUS INDUCTION OF THE ESTRAL CYCLE IN THE BLACK GUAGUA (Agouti taczanowskii IN CAPTIVITY

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    Luis Emilio Trujillo Aramburo

    2006-06-01

    Full Text Available Para la inducción y sincronización del ciclo estral en la guagua negra Agouti taczanowskii en cautiverio, se aplicó a cada una de seis hembras, con edades entre cuatro y siete años, un cuarto de dosis de norgestomet y 1,25 mg de valerato de estradiol. A partir del día de la aplicación del implante se les realizó medición del diámetro del orificio vulvar tres veces por semana hasta el día 52 y con igual frecuencia, a partir del día del retiro del implante, se realizó muestreo sanguíneo para determinar los niveles de progesterona por radioinmunoanálisis. El tratamiento hormonal indujo y sincronizó el ciclo estral en tres de las seis hembras tratadas, las cuales presentaron aumento en los niveles de progesterona ³ 10 ng/ml precedidos de apertura del orificio vulvar. El ciclo estral inducido tuvo una duración variable entre 11 y 29 días. El ciclo estral espontáneo que se presentó después del inducido con el tratamiento hormonal, presentó duración variable entre 10 y 30 días. Durante el tiempo de experimentación se presentó una correlación negativa entre los niveles de progesterona y el diámetro de la apertura vulvar. Se concluye que la aplicación de un implante de norgestomet acompañado de una inyección de valerato de estradiol puede inducir y sincronizar el ciclo estral en la guagua negra.To induce and synchronize the estral cycle in the black guagua Agouti taczanowskii in captivity, each of six females varying from four to seven years of age were implanted with a quarter dose of norgestomet and injected with 1,25 mg of estradiol valerate. Starting on the day of the application of the implant, the diameter of the vulvar orifice was measured three times per week until day 52, and with same frequency beginning on the day the implant was removed, blood sampling was conducted to determine progesterone levels for radioimunoassay. The hormonal treatment induced and synchronized the estral cycle in three of the six treated

  5. LOBAÇÃO, ÁRVORE BRÔNQUICA E VASCULARIZAÇÃO ARTERIAL DO PULMÃO DA PACA (Agouti paca, LINAEUS, 1766 LOBATION, BRONCHIAL TREE AND ARTERIAL SUPPLY OF PACA LUNG (Agouti paca, LINAEUS, 1766

    Directory of Open Access Journals (Sweden)

    Márcia Rita Fernandes Machado

    2008-07-01

    Full Text Available

    Os pulmões são os principais órgãos do sistema respiratório, e o conhecimento morfológico da lobação, árvore brônquica e vascularização arterial torna-se imprescindível na prática clínica e cirúrgica. Os troncos pulmonares de dez pulmões de pacas foram injetados com látex e as peças fixadas em solução aquosa de formaldeído a 10%. Mediante dissecação, observou-se que, em 100% dos casos, o pulmão direito era constituído pelos lobos cranial, caudal, médio e acessório; o lobo médio era bilobado em partes cranial e caudal. O esquerdo possuía o lobo cranial, bilobado em partes cranial e caudal, lobo caudal e um pequeno lobo acessório. A artéria pulmonar direita emitia dois ramos para o lobo cranial, além dos ramos para as partes cranial e caudal do lobo médio, o ramo do lobo acessório e o do lobo caudal; a artéria pulmonar esquerda emitia dois ramos para a porção cranial e um para a porção caudal do lobo cranial; o lobo caudal esquerdo era irrigado pela continuação da artéria pulmonar esquerda, que emitia de cinco a seis ramos dorsais e de sete a oito ramos ventrais. Não houve variação nos pulmões estudados em relação aos lobos, nem no padrão de distribuição brônquica.

     

    PALAVRAS-CHAVE: Agouti paca, artéria pulmonar, pulmões, roedor

    Lungs are the main organs of the respiratory system and the morphological knowledge of lobation, bronchial tree and arterial vascularization becomes indispensable on clinics and surgery practice. The pulmonary trunks of 10 lungs were filled with latex and the anatomical sets were put in a 10% formaldehyde aqueous solution. By dissection, it was observed that, in 100% of the cases, the right lung was constituted by cranial, medium, caudal and accessory lobes. The medium lobe was divided into cranial and caudal portions. The left lung presented a cranial lobe

  6. Long-Term Effects of (-)-Epigallocatechin Gallate (EGCG) on Pristane-Induced Arthritis (PIA) in Female Dark Agouti Rats.

    Science.gov (United States)

    Leichsenring, Anna; Bäcker, Ingo; Furtmüller, Paul G; Obinger, Christian; Lange, Franziska; Flemmig, Jörg

    2016-01-01

    Rheumatoid arthritis (RA)-a widespread chronic inflammatory disease in industrialized countries-is characterized by a persistent and progressive joint destruction. The chronic pro-inflammatory state results from a mutual activation of the innate and the adaptive immune system, while the exact pathogenesis mechanism is still under discussion. New data suggest a role of the innate immune system and especially polymorphonuclear granulocytes (PMNs, neutrophils) not only during onset and the destructive phase of RA but also at the chronification of the disease. Thereby the enzymatic activity of myeloperoxidase (MPO), a peroxidase strongly abundant in neutrophils, may be important: While its peroxidase activity is known to contribute to cartilage destruction at later stages of RA the almost MPO-specific oxidant hypochlorous acid (HOCl) is also discussed for certain anti-inflammatory effects. In this study we used pristane-induced arthritis (PIA) in Dark Agouti rats as a model for the chronic course of RA in man. We were able to shown that a specific detection of the HOCl-producing MPO activity provides a sensitive new marker to evaluate the actual systemic inflammatory status which is only partially detectable by the evaluation of clinical symptoms (joint swelling and redness measurements). Moreover, we evaluated the long-term pharmacological effect of the well-known anti-inflammatory flavonoid epigallocatechin gallate (EGCG). Thereby only upon early and continuous oral application of this polyphenol the arthritic symptoms were considerably diminished both in the acute and in the chronic phase of the disease. The obtained results were comparable to the treatment control (application of methotrexate, MTX). As revealed by stopped-flow kinetic measurements, EGCG may regenerate the HOCl-production of MPO which is known to be impaired at chronic inflammatory diseases like RA. It can be speculated that this MPO activity-promoting effect of EGCG may contribute to the

  7. Hypothalamic Agouti-Related Peptide mRNA is Elevated During Natural and Stress-Induced Anorexia.

    Science.gov (United States)

    Dunn, I C; Wilson, P W; D'Eath, R B; Boswell, T

    2015-09-01

    As part of their natural lives, animals can undergo periods of voluntarily reduced food intake and body weight (i.e. animal anorexias) that are beneficial for survival or breeding, such as during territorial behaviour, hibernation, migration and incubation of eggs. For incubation, a change in the defended level of body weight or 'sliding set point' appears to be involved, although the neural mechanisms reponsible for this are unknown. We investigated how neuropeptide gene expression in the arcuate nucleus of the domestic chicken responded to a 60-70% voluntary reduction in food intake measured both after incubation and after an environmental stressor involving transfer to unfamiliar housing. We hypothesised that gene expression would not change in these circumstances because the reduced food intake and body weight represented a defended level in birds with free access to food. Unexpectedly, we observed increased gene expression of the orexigenic peptide agouti-related peptide (AgRP) in both incubating and transferred animals compared to controls. Also pro-opiomelanocortin (POMC) mRNA was higher in incubating hens and significantly increased 6 days after exposure to the stressor. Conversely expression of neuropeptide Y and cocaine- and amphetamine-regulated transcript gene was unchanged in both experimental situations. We conclude that AgRP expression remains sensitive to the level of energy stores during natural anorexias, which is of adaptive advantage, although its normal orexigenic effects are over-ridden by inhibitory signals. In the case of stress-induced anorexia, increased POMC may contribute to this inhibitory role, whereas, for incubation, reduced feeding may also be associated with increased expression in the hypothalamus of the anorexigenic peptide vasoactive intestinal peptide. PMID:26017156

  8. UN ÍNDICE PARA LA EVALUACIÓN DEL HÁBITAT DE AGOUTI TACZANOWSK/1 (RODENTIA: AGOUTIDAE) EN ÁREAS DE BOSQUE ANDINO NUBLADO

    OpenAIRE

    Jairo Pérez-Torres

    2002-01-01

    Se presenta un índice que permitirá evaluar el hábitat de la "Lapa andiim" o "Tinajo" (Agouti taczanowskii) en zonas de bosque andino nublado. El objetivo fundamental de este índice, es obtener elementos que sirvan para la toma de decisiones en cuanto al diseño de áreas de reserva y planes de manejo sobre esta especie. Este índice se basa en la aplicación de criterios tanto cualitativos como cuantitativos, los cuales son tabulados y computados para sacar un valor de calidad de hábitat para ca...

  9. Dietary Calcium and Dairy Modulation of Oxidative Stress and Mortality in aP2-Agouti and Wild-type Mice

    OpenAIRE

    Antje Bruckbauer; Zemel, Michael B

    2009-01-01

    Oxidative and inflammatory stress have been implicated as major contributors to the aging process. Dietary Ca reduced both factors in short-term interventions, while milk exerted a greater effect than supplemental Ca. In this work, we examined the effects of life-long supplemental and dairy calcium on lifespan and life-span related biomarkers in aP2-agouti transgenic (model of diet-induced obesity) and wild-type mice fed obesigenic diets until their death. These data demonstrate that dairy Ca...

  10. Electroacupuncture Improves Insulin Resistance by Reducing Neuroprotein Y/Agouti-Related Protein Levels and Inhibiting Expression of Protein Tyrosine Phosphatase 1B in Diet-induced Obese Rats.

    Science.gov (United States)

    Liu, Xia; He, Jun-Feng; Qu, Ya-Ting; Liu, Zhi-Jun; Pu, Qing-Yang; Guo, Sheng-Tong; Du, Jia; Jiang, Peng-Fei

    2016-04-01

    Electroacupuncture (EA) has been shown to exert beneficial effects on obesity, but the mechanism is unclear. This study investigated the effects of EA on diet-induced obese (DIO) rats. Fifty male Sprague-Dawley rats were randomly divided into low-fat diet (LFD, 10 rats) and high-fat diet (HFD, 40 rats) groups. After the DIO models had been established, successful model rats were randomly divided into HFD, EA, and orlistat (OLST) groups. The EA group received EA at Zusanli (ST36) and Quchi (LI11) for 20 minutes once per day for 28 days. The OLST group was treated with orlistat by gavage. The body weight, homeostasis model assessment-insulin resistance index, adipocyte diameters, and neuroprotein Y/agouti-related protein and protein tyrosine phosphatase 1B levels were significantly lower in the EA group than in the HFD group. The rats of the OLST group showed watery stools and yellow hairs whereas those of the EA group had regular stools and sleek coats. The effect of EA on weight loss may be related to improved insulin resistance caused by changes in the adipocyte size and by reductions in the expressions of neuroprotein Y/agouti-related protein and protein tyrosine phosphatase 1B. This study indicates that EA may be a better method of alternative therapy for treating obesity and other metabolic diseases. PMID:27079226

  11. Agouti signalling protein is an inverse agonist to the wildtype and agonist to the melanic variant of the melanocortin-1 receptor in the grey squirrel (Sciurus carolinensis).

    Science.gov (United States)

    McRobie, Helen R; King, Linda M; Fanutti, Cristina; Symmons, Martyn F; Coussons, Peter J

    2014-06-27

    The melanocortin-1 receptor (MC1R) is a key regulator of mammalian pigmentation. Melanism in the grey squirrel is associated with an eight amino acid deletion in the mutant melanocortin-1 receptor with 24 base pair deletion (MC1RΔ24) variant. We demonstrate that the MC1RΔ24 exhibits a higher basal activity than the wildtype MC1R (MC1R-wt). We demonstrate that agouti signalling protein (ASIP) is an inverse agonist to the MC1R-wt but is an agonist to the MC1RΔ24. We conclude that the deletion in the MC1RΔ24 leads to a receptor with a high basal activity which is further activated by ASIP. This is the first report of ASIP acting as an agonist to MC1R. PMID:24879893

  12. Association between diencephalic thyroliberin and arterial blood pressure in agouti-yellow and ob/ob mice may be mediated by leptin.

    Science.gov (United States)

    Burgueño, Adriana L; Landa, Maria S; Schuman, Mariano L; Alvarez, Azucena L; Carabelli, Julieta; García, Silvia I; Pirola, Carlos J

    2007-10-01

    Leptin, a hormone secreted by the adipose tissue, stimulates anorexigenic peptides and also inhibits orexigenic peptides in hypothalamic arcuate nuclei-located neurons. It also counteracts the starvation-induced suppression of thyroid hormones by up-regulating the expression of preproTRH gene. On the other hand, in addition to its role as a modulator of the thyroid-hypothalamic-hypophysial axis, thyrotropin-releasing hormone (TRH) acts as a modulator of the cardiovascular system. In fact, we reported that overexpression of diencephalic TRH (dTRH) induces hypertension. We have recently shown that, in rats with obesity-induced hypertension, hyperleptinemia may produce an increase of dTRH together with an elevation of arterial blood pressure (ABP) through an increase of sympathetic activity and that these alterations were reversed by antisense oligonucleotide and small interfering RNA against preproTRH treatments. Here we explore the possible role of dTRH as a mediator involved in leptin-induced hypertension in 2 obesity mouse models: agouti-yellow mice, which are hyperleptinemic and hypertensive, and ob/ob mice, which lack functional circulating leptin. These 2 models share some characteristics, but ob/ob mice show lower ABP and plasma catecholamines levels. Then, for the first time, we report that there is a clear association between ABP and dTRH levels in both mouse models, as we have found that dTRH content was elevated in agouti-yellow mice and diminished in ob/ob mice compared with their controls. We also show that, after 3 days of subcutaneous leptin injections (10 microg/12 hours), ABP and dTRH increased significantly in ob/ob mice with no alterations of thyroid hormone levels. These results add evidence to the putative molecular mechanisms for the strong association between obesity and hypertension. PMID:17884458

  13. Solid-Phase Peptide Head-to-Side Chain Cyclodimerization: Discovery of C2-Symmetric Cyclic Lactam Hybrid α-Melanocyte-Stimulating Hormone (MSH)/Agouti-Signaling Protein (ASIP) Analogues with Potent Activities at the Human Melanocortin Receptors

    OpenAIRE

    Mayorov, Alexander V.; Cai, Minying; Palmer, Erin S.; Liu, Zhihua; Cain, James P.; Vagner, Josef; Trivedi, Dev; Victor J. Hruby

    2010-01-01

    A novel hybrid melanocortin pharmacophore was designed based on the pharmacophores of the Agouti signaling protein (ASIP), an endogenous melanocortin antagonist, and α-melanocyte-stimulating hormone (α-MSH), an endogenous melanocortin agonist. The designed hybrid ASIP/MSH pharmacophore was explored in monomeric cyclic, and cyclodimeric templates. The monomeric cyclic disulfide series yielded peptides with hMC3R-selective non-competitive binding affinities. The direct on-resin peptide lactam c...

  14. Effect of a Single Session of Aerobic and Circuit-Resistance Exercise on Plasma Ghrelin and Agouti-Related Peptide (AgRP) Levels in Well-Trained Females

    OpenAIRE

    Mahdiyeh Ebrahimnia; Amir Rashidlamir; Mehdi Seyed-Alhosseini

    2014-01-01

    Background: Ghrelin and agouti-related protein (AgRP) are orexigenic peptides secreted from stomach mucosa and the arcuate nucleus of the hypothalamus, respectively. Both peptides affect feeding behavior and play a role in energy balance, glucose homeostasis, and adiposity. The purpose of the present study was to investigate the effect of two types of exercises, aerobic and single circuit resistance exercise on plasma ghrelin and AgRP levels. Materials and Methods: The current study is sem...

  15. Leishmaniose cutânea na Amazônia: isolamento de Leishmania (Viannia lainsoni do roedor Agouti paca (Rodentia: Dasyproctidae, no estado do Pará, Brasil Cutaneous leishmaniasis in the Amazon Region: isolation of Leishmania (Viannia lainsoni from the rodent Agouti paca (Rodentia: Dasyproctidae in Pará State, Brazil

    Directory of Open Access Journals (Sweden)

    Fernando T. Silveira

    1991-02-01

    Full Text Available Fez-se o registro, pela primeira vez, do isolamento de Leishmania (V. lainsoni de um mamífero silvestre, o roedor Agouti paca (Rodentia: Dasyproctidae, no Estado do Pará, Brasil. As amostras do parasita foram isoladas da pele, aparentemente íntegra, de 3 espécimes desse roedor, capturados no município de Tucuruí (ilha de Tocantins, em área que seria inundada pela formação do lago da hidrelétrica construída naquele município. Nenhum isolamento foi obtido de vísceras de qualquer dos animais. A identificação das amostras de L. (V. lainsoni baseou-se na morfologia de amastigotas e promastigotas, no comportamento da infecção em "hamsters", na análise bioquímica de isoenzimas e, ainda, através de testes com anticorpos monoclonais. A natureza inaparente da infecção nos animais faz supor que o mamífero em questão possa representar um hospedeiro definitivo do parasita na região Amazônica.The isolation of Leishmania (V. lainsoni is recorded for the first time from a wild animal, the rodent Agouti paca (Rodentia: Dasyproctidae, from Pará State, north Brazil. Isolates of the parasite were made from apparently normal skin of 3 specimens of this rodent captured on the Island of Tocantins, in the municipality of Tucuruí, an area subsequently flooded in the formation of the lake associated with the Tucuruí hydroeletric dam. No isolations were made from the viscera. Identification of the parasite was in each case based on morphology of the amastigotes and promastigotes, behavior of the organism in hamsters, isoenzymes profiles and the use of monoclonal antibodies. The inapparent nature of the infection leads us to suggest that the "paca", Agouti paca, represents a primitive host of L. (V. lainsoni in the Amazon Region.

  16. Distinct Roles for JNK and IKK Activation in Agouti-Related Peptide Neurons in the Development of Obesity and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Eva Tsaousidou

    2014-11-01

    Full Text Available Activation of c-Jun N-terminal kinase 1 (JNK1- and inhibitor of nuclear factor kappa-B kinase 2 (IKK2-dependent signaling plays a crucial role in the development of obesity-associated insulin and leptin resistance not only in peripheral tissues but also in the CNS. Here, we demonstrate that constitutive JNK activation in agouti-related peptide (AgRP-expressing neurons of the hypothalamus is sufficient to induce weight gain and adiposity in mice as a consequence of hyperphagia. JNK activation increases spontaneous action potential firing of AgRP cells and causes both neuronal and systemic leptin resistance. Similarly, activation of IKK2 signaling in AgRP neurons also increases firing of these cells but fails to cause obesity and leptin resistance. In contrast to JNK activation, IKK2 activation blunts insulin signaling in AgRP neurons and impairs systemic glucose homeostasis. Collectively, these experiments reveal both overlapping and nonredundant effects of JNK- and IKK-dependent signaling in AgRP neurons, which cooperate in the manifestation of the metabolic syndrome.

  17. Long-Term Effects of (–)-Epigallocatechin Gallate (EGCG) on Pristane-Induced Arthritis (PIA) in Female Dark Agouti Rats

    Science.gov (United States)

    Leichsenring, Anna; Bäcker, Ingo; Furtmüller, Paul G.; Obinger, Christian; Lange, Franziska; Flemmig, Jörg

    2016-01-01

    Rheumatoid arthritis (RA)—a widespread chronic inflammatory disease in industrialized countries—is characterized by a persistent and progressive joint destruction. The chronic pro-inflammatory state results from a mutual activation of the innate and the adaptive immune system, while the exact pathogenesis mechanism is still under discussion. New data suggest a role of the innate immune system and especially polymorphonuclear granulocytes (PMNs, neutrophils) not only during onset and the destructive phase of RA but also at the chronification of the disease. Thereby the enzymatic activity of myeloperoxidase (MPO), a peroxidase strongly abundant in neutrophils, may be important: While its peroxidase activity is known to contribute to cartilage destruction at later stages of RA the almost MPO-specific oxidant hypochlorous acid (HOCl) is also discussed for certain anti-inflammatory effects. In this study we used pristane-induced arthritis (PIA) in Dark Agouti rats as a model for the chronic course of RA in man. We were able to shown that a specific detection of the HOCl-producing MPO activity provides a sensitive new marker to evaluate the actual systemic inflammatory status which is only partially detectable by the evaluation of clinical symptoms (joint swelling and redness measurements). Moreover, we evaluated the long-term pharmacological effect of the well-known anti-inflammatory flavonoid epigallocatechin gallate (EGCG). Thereby only upon early and continuous oral application of this polyphenol the arthritic symptoms were considerably diminished both in the acute and in the chronic phase of the disease. The obtained results were comparable to the treatment control (application of methotrexate, MTX). As revealed by stopped-flow kinetic measurements, EGCG may regenerate the HOCl-production of MPO which is known to be impaired at chronic inflammatory diseases like RA. It can be speculated that this MPO activity-promoting effect of EGCG may contribute to the

  18. Effect of a Single Session of Aerobic and Circuit-Resistance Exercise on Plasma Ghrelin and Agouti-Related Peptide (AgRP Levels in Well-Trained Females

    Directory of Open Access Journals (Sweden)

    Mahdiyeh Ebrahimnia

    2014-06-01

    Full Text Available Background: Ghrelin and agouti-related protein (AgRP are orexigenic peptides secreted from stomach mucosa and the arcuate nucleus of the hypothalamus, respectively. Both peptides affect feeding behavior and play a role in energy balance, glucose homeostasis, and adiposity. The purpose of the present study was to investigate the effect of two types of exercises, aerobic and single circuit resistance exercise on plasma ghrelin and AgRP levels. Materials and Methods: The current study is semi-experimental. Twenty two athletes young females randomly selected and assigned into two experimental groups and one control group. Blood samples were collected before and after the enforced protocol. Plasma AgRP and ghrelin levels were measured using the enzyme-linked immunosorbent assay (ELISA method. Results: Results showed a significant increase in plasma AgRP (p=0.001 and ghrelin concentration in control and aerobic (p=0.001 and circulate-resistance (p=0.001 groups. Conclusion: In healthy females a single session of aerobic and circuit-resistance exercise could be associated with the increase of these peptides in response to the negative balance of energy produced by exercising for increasing appetite to compensate energy resources body subjects.

  19. Establishment and assessment of rheumatoid arthritis model induced by pristane in Dark-Agouti rats%降植烷诱导的DA大鼠类风湿性关节炎模型的建立和评估

    Institute of Scientific and Technical Information of China (English)

    张利文; 文凯; 袁泉

    2013-01-01

    Objective: To establish animal model of rheumatoid arthritis( RA) and measure the indexes for RA,to provide evidence for reseach and clinical treatments of RA. Methods; The present study was performed on the Dark-Agouti (DA) rats. The RA model was induced by intracutaneous injection of pristane (300 fjul) into the root of the tail. The body weight, pathological score for joints, paw volume, motion of joint, mechanical withdrawal threshold (MWT) , heat withdrawal latency (HWL) were examined before and after the establishment of the RA model. Results; Arthritic manifestations occurred in all the DA rats 7-14 days after injection of pristane,including joint swelling in metacarpophalangeal joints, interphalangeal joint and ankle joint, increase in paw volume, trouble walking, decline in range of motion, decrease in mechanical withdrawal threshold, and so on. All these manifestations reached the peak at 21-28 days. Conclusion; The RA model induced by pristane in DA rats have some characteristics such as high incidence,simple operation,similar to the patients with RA. Thus,it could be conclude that pristane induced arthritis (PIA) model in DA rats is a better model for RA.%目的:建立大鼠类风湿性关节炎(rheumatoid arthritis,RA)模型及检测相关指标,为研究RA的发病机制及其临床治疗提供依据.方法:本研究以Dark-Agouti (DA)大鼠为模型动物,采用尾根部皮内一次性注射降植烷300μl的方法建立RA模型,并检测不同时间点大鼠体重、关节病理评分、爪容积、后爪关节活动度、机械缩爪阈值、热缩爪潜伏期等指标.结果:注射降植烷后7 ~ 14 d DA大鼠100%发病,表现为四肢掌指关节、指间关节以及踝关节红肿,爪容积增加,动物行走障碍,关节活动度下降,机械缩爪阈值明显下降,第21~28天达高峰.结论:降植烷尾根部注射引起的DA大鼠关节炎发病率高,操作简单易行,与临床RA患者表现有高度相似性,是一种较好的RA模型.

  20. A combination of probiotics and whey proteins enhances anti-obesity effects of calcium and dairy products during nutritional energy restriction in aP2-agouti transgenic mice.

    Science.gov (United States)

    Yoda, Kazutoyo; Sun, Xiaocum; Kawase, Manabu; Kubota, Akira; Miyazawa, Kenji; Harata, Gaku; Hosoda, Masataka; Hiramatsu, Masaru; He, Fang; Zemel, Michael B

    2015-06-14

    Lactobacillus rhamnosus GG, Lactobacillus paracasei TMC0409, Streptococcus thermophilus TMC1543 and whey proteins were used to prepare fermented milk. For the experiment aP2- agouti transgenic mice were pre-treated with a high-sucrose/high-fat diet for 6 weeks to induce obesity. The obese mice were fed a diet containing 1·2% Ca and either non-fat dried milk (NFDM) or probiotic-fermented milk (PFM) with nutritional energy restriction for 6 weeks. The animals were examined after the treatment for changes in body weight, fat pad weight, fatty acid synthase (FAS) activity, lypolysis, the expression levels of genes related to lipid metabolism, insulin sensitivity in adipocytes and skeletal muscle and the presence of biomarkers for oxidative and inflammatory stress in plasma. It was found that the PFM diet significantly reduced body weight, fat accumulation, and adipocyte FAS activity, and increased adipocyte lipolysis as compared with the effects of the NFDM diet (P<0·05). The adipose tissue gene expression of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) was significantly suppressed in mice that were fed PFM as compared with those that were fed NFDM (P<0·05). PFM caused a greater up-regulation of skeletal muscle PPARα, PPARδ, uncoupling protein 3 (UCP3) and GLUT4 expression and a significant decrease in the plasma concentration of insulin, malondialdehyde, TNF-α, monocyte chemotactic protein-1 and C-reactive protein as compared with the effects of NFDM (P<0·05). Fermentation of milk with selected probiotics and supplementation of milk with whey proteins may thus enhance anti-obesity effects of Ca and dairy products by the suppression of adipose tissue lipogenesis, activation of fat oxidation in skeletal muscle and reduction of oxidative and inflammatory stress. PMID:25871498

  1. An Autochthonous Case of Echinococcus vogeli Rausch & Bernstein, 1972 Polycystic Echinococcosis in the State of Rondônia, Brazil

    Directory of Open Access Journals (Sweden)

    Rosângela Rodrigues-Silva

    2002-01-01

    Full Text Available The present case report refers to a patient from the State of Rondônia, North region of Brazil, attended with clinical suspicion of hepatic echinococcosis. Examination by imaging (ultrasonography and computerized tomography revealed a conglomerate of cystic lesions, with mobile contents within the cyst. The serology (immunoblot for Echinococcus sp. was positive (21 and 31 kDa bands. This case is the first reported in Rondônia, suggesting the need to investigate the polycystic echinococcosis in individuals with hepatic cysts from areas of tropical forest and hunting habits where wild life was present as wild dogs, cats and rodents, particularly Agouti paca (paca and Dasyprocta aguti (agouti.

  2. Discovery of a β-Hairpin Octapeptide, c[Pro-Arg-Phe-Phe-Dap-Ala-Phe-DPro], Mimetic of Agouti-Related Protein(87-132) [AGRP(87-132)] with Equipotent Mouse Melanocortin-4 Receptor (mMC4R) Antagonist Pharmacology.

    Science.gov (United States)

    Ericson, Mark D; Wilczynski, Andrzej; Sorensen, Nicholas B; Xiang, Zhimin; Haskell-Luevano, Carrie

    2015-06-11

    Agouti-related protein (AGRP) is a potent orexigenic peptide that antagonizes the melanocortin-3 and -4 receptors (MC3R and MC4R). While the C-terminal domain of AGRP, AGRP(87-132), is equipotent to the full-length peptide, further truncation decreases potency at the MC3R and MC4R. Herein, we report AGRP-derived peptides designed to mimic the active β-hairpin secondary structure that contains the hypothesized Arg-Phe-Phe pharmacophore. The most potent scaffold, c[Pro-Arg-Phe-Phe-Asn-Ala-Phe-DPro], comprised the hexa-peptide β-hairpin loop from AGRP cyclized through a DPro-Pro motif. A 20 compound library was synthesized from this scaffold for further structure-activity relationship studies. The most potent peptide from this library was an asparagine to diaminopropionic acid substitution that possessed sub-nanomolar antagonist activity at the mMC4R and was greater than 160-fold selective for the mMC4R versus the mMC3R. The reported ligands may serve as probes to characterize the melanocortin receptors in vivo and leads in the development of novel therapeutics. PMID:25898270

  3. Serological survey for Leishmania sp. infection in wild animals from the municipality of Maringá, Paraná state, Brazil

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    EM Voltarelli

    2009-01-01

    Full Text Available Leishmania sp. infection was investigated in wild animals from the Ingá Park, in the municipality of Maringá, Paraná state, Brazil, where American cutaneous leishmaniasis (ACL is an endemic disease. Sixty-five mammals, comprising Didelphis albiventris, Cerdocyon thous, Lycalopex vetulus, Cebus apella, Dasyprocta azarae, Dasypus novemcinctus, Procyon cancrivorus and Nasua nasua, were captured. Blood samples were collected for parasite cultivation. Antibodies were investigated by direct agglutination test (DAT using Leishmania (Viannia braziliensis as antigen. Flagellates were observed in blood cultures of 14 (35.9% Didelphis albiventris. Anti-Leishmania antibodies were detected in 31 (51.6% specimens of Cerdocyon thous, Lycalopex vetulus, Cebus apella, Dasyprocta azarae, Procyon cancrivorus and Nasua nasua. These results suggest that Cerdocyon thous and Lycalopex vetulus (crab-eating fox, Cebus apella (capuchin monkey, Dasyprocta azarae (agouti, Procyon cancrivorus (crab-eating raccoon and Nasua nasua (coati play an important role in the ACL transmission cycle in the northwestern region of Paraná, Brazil.

  4. Ecological relationships of meso-scale distribution in 25 neotropical vertebrate species.

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    Lincoln José Michalski

    Full Text Available Vertebrates are a vital ecological component of Amazon forest biodiversity. Although vertebrates are a functionally important part of various ecosystem services they continue to be threatened by anthropogenic impacts throughout the Amazon. Here we use a standardized, regularly spaced arrangement of camera traps within 25km2 to provide a baseline assessment of vertebrate species diversity in a sustainable use protected area in the eastern Brazilian Amazon. We examined seasonal differences in the per species encounter rates (number of photos per camera trap and number of cameras with photos. Generalized linear models (GLMs were then used to examine the influence of five variables (altitude, canopy cover, basal area, distance to nearest river and distance to nearest large river on the number of photos per species and on functional groups. GLMs were also used to examine the relationships between large predators [Jaguar (Panthera onca and Puma (Puma concolor] and their prey. A total of 649 independent photos of 25 species were obtained from 1,800 camera trap days (900 each during wet and dry seasons. Only ungulates and rodents showed significant seasonal differences in the number of photos per camera. The number of photos differed between seasons for only three species (Mazama americana, Dasyprocta leporina and Myoprocta acouchy all of which were photographed more (3 to 10 fold increase during the wet season. Mazama americana was the only species where a significant difference was found in occupancy, with more photos in more cameras during the wet season. For most groups and species variation in the number of photos per camera was only explained weakly by the GLMs (deviance explained ranging from 10.3 to 54.4%. Terrestrial birds (Crax alector, Psophia crepitans and Tinamus major and rodents (Cuniculus paca, Dasyprocta leporina and M. acouchy were the notable exceptions, with our GLMs significantly explaining variation in the distribution of all

  5. Uniparidade em pacas criadas em cativeiro (Agouti paca, Linnaeus, 1766 Uniparity in pacas bred in captivity (Agouti paca, Linnaeus, 1766

    Directory of Open Access Journals (Sweden)

    F.S. Oliveira

    2007-04-01

    Full Text Available Durante quatro anos foram detectadas 25 prenhezes, em 13 diferentes pacas, por meio de ultra-sonografia. Após a detecção ultra-sonográfica, as fêmeas foram separadas em baias individuais para o nascimento dos filhotes e aí mantidas até o desmame. Houve nascimento de apenas um animal por parto, ressaltando a característica reprodutiva de uniparidade, o que sugere a tendência de nascimento de apenas um filhote por parto, nessa espécie.During four years 25 pregnancies were detected in 13 different pacas by means of ultrasonography at a wild animal section. After ultrasound detection, females were separated in individual sets for delivering and kept until weaning of newborns. Only one newborn by delivery occurred, remarking the reproductive characteristic of uniparity, what suggests the trend of only one newborn in each delivery.

  6. Zygomycetes from herbivore dung in the ecological reserve of Dois Irmãos, Northeast Brazil

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    André Luiz Cabral Monteiro de Azevedo Santiago

    2011-03-01

    Full Text Available Thirty-eight taxa of Zygomycetes distributed in 15 genera were recorded from tapir (Tapirus terrestris, camel (Camelus bactrianus, horse (Equus caballus, deer (Cervus elaphus, agouti (Dasyprocta aguti, donkey (Equus asinus, llama (Llama glama and waterbuck (Kobus ellipsiprymnus dung collected at the Reserva Ecológica de Dois Irmãos located in Recife, State of Pernambuco, Northeast Brazil. The samples were collected on a monthly basis from June 2005 to May 2006, taken to the laboratory and incubated in moist chambers. Higher number of taxa was observed in the excrements of tapir, followed by deer and donkey. The highest number of species was detected for Mucor, followed by Pilobolus. Statistical analyses showed significant differences in richness of Zygomycetes taxa between the herbivore dung types. Differences of species composition, however, were weak. Seasonality influenced the Zygomycetes species composition but not its richness. Variations in taxa composition between ruminants and non-ruminants dung were non significant.

  7. Wild Rodents as Experimental Intermediate Hosts of Lagochilascaris minor Leiper, 1909

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    Julieta Machado Paçô

    1999-07-01

    Full Text Available A total of 25 specimens of Cavia porcellus (guinea pig, 5 Dasyprocta agouti (agouti, and 22 Calomys callosus (vesper mice were inoculated with infective eggs of Lagochilascaris minor. The inoculum was prepared with embryonated eggs and orally administered to each individual animal through an esophagus probe. In parallel, 100 specimens of Felis catus domesticus were individually fed with 55-70 nodules containing 3rd-stage larvae encysted in tissues of infected rodents. Animals were examined and necropsied at different time intervals. The migration and encystment of L3 larva was observed in viscera, skeletal muscle, adipose and subcutaneous tissues from all rodents. Adult worms localized at abscesses in the cervical region, rhino, and oropharynx were recovered from domestic cats inoculated with infected rodent tissues. Through this study we can conclude that: (1 wild rodents act as intermediate hosts, characterizing this ascarid heteroxenic cycle; (2 in natural conditions rodents could possibly act as either intermediate hosts or paratenic hosts of Lagochilascaris minor; (3 despite the occurrence of an auto-infecting cycle, in prime-infection of felines (definite hosts the cycle is only completed when intermediate hosts are provided; and (4 in the wild, rodents could serve as a source of infection for humans as they are frequently used as food in regions with the highest incidence of human lagochilascariasis.

  8. New Late Miocene .i.Alilepus./i. (Lagomorpha, Mammalia) from Eastern Europe - a new light on the evolution of the earliest old world Leporinae

    Czech Academy of Sciences Publication Activity Database

    Čermák, Stanislav; Angelone, Ch.; Sinitsa, M. V.

    2015-01-01

    Roč. 90, č. 2 (2015), s. 431-451. ISSN 1214-1119 Institutional support: RVO:67985831 Keywords : Alilepus * Eastern Europe * Late Miocene * phylogeny * Pliocene * taxonomy Subject RIV: EG - Zoology Impact factor: 1.515, year: 2014

  9. Agouti-related peptide plays a critical role in leptin's effects on female puberty and reproduction

    OpenAIRE

    Sheffer-Babila, Sharone; Sun, Yan; Israel, Davelene D.; Liu, Shun-Mei; Neal-Perry, Genevieve; Streamson C Chua

    2013-01-01

    Deficient leptin signaling causes infertility via reduced activity of GnRH neurons, causing a hypogonadal state in both rodents and humans. Because GnRH neurons do not express leptin receptors, leptin's effect on GnRH neurons must be indirect. Neurons within the hypothalamic arcuate nucleus that coexpress AGRP and NPY are considered to be important intermediate neurons involved in leptin regulation of GnRH neurons. Previously, we reported that the absence of AGRP and haploinsufficiency of MC4...

  10. Utilização dos recursos naturais por comunidades humanas do Parque Ecoturístico do Guamá, Belém, Pará Utilization of natural resources by the human communities of the Guamá Ecotouristic Park, Belém, Pará

    Directory of Open Access Journals (Sweden)

    Ana Sílvia Sardinha Ribeiro

    2007-06-01

    Full Text Available O trabalho apresenta dados sobre o uso dos recursos naturais por populações humanas em pequenas comunidades (vilas localizadas no entorno (n = 6 e no interior (n = 1 do Parque Ecoturístico do Guamá (PEG, visando avaliar os impactos sobre a fauna e flora local, ante a implantação de um projeto de infra-estrutura rodoviária local. A metodologia consistiu da aplicação de dois modelos de questionários. Um direcionado a pessoas-chave, como: moradores mais antigos, presidentes de associações, agentes de saúde, etc, e o outro aplicado aleatoriamente aos adultos locais. Buscou-se atingir pelo menos 50% das famílias das pequenas localidades (11 famílias. Em todos os casos é realizado o extrativismo da fauna e flora, principalmente com o objetivo de subsistência. As espécies mais caçadas foram Agouti paca,Dasyprocta agouti,Nasua nasua, Euphractus sexcintus e Hydrochaeris hydrochaeris. A complementação da renda familiar através do comércio de caça sob encomenda é realizada em todas as comunidades estudadas. Frutíferas como Euterpe oleracea Mart., Musa spp e Theobroma cacao foram encontradas em 100% das comunidades (n=7. Plantas medicinais são rotineiramente cultivadas e empregadas. As espécies madeireiras exploradas são utilizadas com o objetivo de produção de carvão, construção de casas e de meios de transporte, predominando o Inga edulis, Virola surinamensis (Rol. Warb e Simaruba amara (Aubl.. O trabalho discute os resultados sob o aspecto da implantação do projeto viário, oferecendo recomendações para a minimização dos impactos do mesmo sobre a fauna, a flora e o modo tradicional de vida das comunidades.This work shows data about the use of natural resources by the human population located in (n=1 and around (n=6 the Guamá Ecotouristic Park (GEP, in order to evaluate the impact on the local fauna and flora in view of the project for constructing a road through the park. The methodology utilized in this community

  11. Scatter hoarding of seeds confers survival advantages and disadvantages to large-seeded tropical plants at different life stages.

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    Erin K Kuprewicz

    Full Text Available Scatter hoarding of seeds by animals contributes significantly to forest-level processes, including plant recruitment and forest community composition. However, the potential positive and negative effects of caching on seed survival, germination success, and seedling survival have rarely been assessed through experimental studies. Here, I tested the hypothesis that seed burial mimicking caches made by scatter hoarding Central American agoutis (Dasyprocta punctate enhances seed survival, germination, and growth by protecting seeds from seed predators and providing favorable microhabitats for germination. In a series of experiments, I used simulated agouti seed caches to assess how hoarding affects seed predation by ground-dwelling invertebrates and vertebrates for four plant species. I tracked germination and seedling growth of intact and beetle-infested seeds and, using exclosures, monitored the effects of mammals on seedling survival through time. All experiments were conducted over three years in a lowland wet forest in Costa Rica. The majority of hoarded palm seeds escaped predation by both invertebrates and vertebrates while exposed seeds suffered high levels of infestation and removal. Hoarding had no effect on infestation rates of D. panamensis, but burial negatively affected germination success by preventing endocarp dehiscence. Non-infested palm seeds had higher germination success and produced larger seedlings than infested seeds. Seedlings of A. alatum and I. deltoidea suffered high mortality by seed-eating mammals. Hoarding protected most seeds from predators and enhanced germination success (except for D. panamensis and seedling growth, although mammals killed many seedlings of two plant species; all seedling deaths were due to seed removal from the plant base. Using experimental caches, this study shows that scatter hoarding is beneficial to most seeds and may positively affect plant propagation in tropical forests, although

  12. Molecular identification of trypanosomatids in wild animals.

    Science.gov (United States)

    Tenório, M S; Oliveira e Sousa, L; Alves-Martin, M F; Paixão, M S; Rodrigues, M V; Starke-Buzetti, W A; Araújo Junior, J P; Lucheis, S B

    2014-06-16

    Diverse wild animal species can be reservoirs of zoonotic flagellate parasites, which can cause pathologic Chagas disease. The present study aimed to detect the natural occurrence of flagellate parasites through direct microscopic examination of the parasites in blood samples and through PCR of whole blood and blood culture (haemoculture) samples from 38 captive and 65 free-living wild animals in the Centre for Conservation of Wild Fauna (CCWF), an area endemic for leishmaniasis. For this study, PCR was accomplished using primers for the ribosomal region (ITS-1) of the flagellate parasites. The amplified fragments were cloned and sequenced to identify DNA of the Trypanosomatid parasite species, observed in blood cultures from 3.9% (04/103) of the animals. Through these techniques, Trypanosoma cruzi was identified in haemoculture samples of the following three free-living species: common agouti (Dasyprocta aguti), white-eared opossum (Didelphis albiventris), and nine-banded armadillo (Dasypus novemcinctus). Furthermore, Trypanosoma minasense was identified in whole blood samples from 01 (0.9%) captive animal (black howler monkey-Alouatta caraya). These results demonstrated the first report of T. cruzi isolation in wild species from the CCWF using blood culture, which can be applied in addition to molecular tools for epidemiological studies and to identify trypanosomatids in wild animals. PMID:24636787

  13. Le mini-élevage, son développement villageoiset l'action de BEDIM

    Directory of Open Access Journals (Sweden)

    Jacques Hardouin

    1997-01-01

    Full Text Available Minilivestock, village development and the role of BEDIM.Minilivestock encompasses all animals of small site, and little-known in terras of production but usable as food, feed or revenues if not eaten. Sustainable breeding becomes possible, and should progressively replace uncontrolled gathering in the wild. Amongst vertebrates, an important meat supply is based on edible rodents like Thryonomys, Cricetomys, Xerus, Atherurus, Tenrec; Hydrochoerus, Dasyprocta, Myocastor, Capromys, Dolichotis, Agouti, etc. The saine applies to the guinea-pig Cavia porcellus and to frogs. Invertebrates farming is also practised through breeding of maggots, termites, butterflies (pupae and adults for consumption or sale; giant snails are also highly appreciated in many African countries. Minilivestock development is usually a back-yard activity, hence its interest as it relies on local species, substrates and raw materials for infrastructure. The demand for minilivestock product is high but there is still reluctance often from the official authorities, unfortunately. However minilivestock is not an utopia, and a country like Papua-New-Guinea, which bas officially adopted minilivestock production as a tool to help to develop remote villages, is an excellent example of success

  14. PESO PÓS-PARTO, FREQÜÊNCIA E PREVALÊNCIA DO TIPO DE PARTO DE CUTIAS (Dasyprocta sp) CRIADAS EM CATIVEIRO

    OpenAIRE

    Maria Acelina Martins Carvalho; Airton Mendes Conde Júnior; Luís Madeira Martins Júnior; Sandovaldo Gonçalves de Moura; Mônica Marcos de Almeida; Rildênio Renato Cavalcante; João Batista Lopes

    2006-01-01

    A pesquisa objetivou avaliar parâmetros de desenvolvimento de cutias, buscando fornecer dados para contribuir com a seleção, o melhoramento genético e formas adequadas de manejo para estes animais. Foram observados o peso pós-parto, freqüência e a prevalência do tipo de parto em função da época do ano em 33 fêmeas. Constatou-se que não houve interação entre época do ano e tipo de parto (P>0,05). O peso médio pós-parto foi de 2,24 Kg e 2,39 Kg, para o período de janeiro a dezembro, respecti...

  15. Efeito das atividades de ecoturismo sobre a riqueza e a abundância de espécies de mamíferos de médio e grande porte na região do Cristalino, Mato Grosso, Brasil Effect of ecotourism activities on richness and abundance of species of medium and large mammals in the Cristalino region, Mato Grosso, Brazil

    Directory of Open Access Journals (Sweden)

    Ednaldo Cândido Rocha

    2012-12-01

    Full Text Available Este estudo foi desenvolvido nas Reservas Particulares do Patrimônio Natural Cristalino (670 ha e Lote Cristalino (6.539 ha e no Parque Estadual Cristalino (184.900 ha. Essas unidades de conservação são contíguas e estão localizadas no extremo centro-norte do estado do Mato Grosso, em locais considerados prioritários para a conservação, em função da alta biodiversidade e endemismos, além da elevada pressão antrópica. Desta forma, este trabalho objetivou conhecer, avaliar e comparar a estrutura das populações de mamíferos de médio e grande porte, em termos de riqueza e abundância das espécies em ambientes sem turismo e com atividades de ecoturismo na região do Cristalino. Para tanto, no período compreendido entre maio de 2008 a fevereiro de 2010 foram amostrados ambientes com floresta primária, os quais apresentavam dois níveis de perturbação antrópica: sem turismo e com atividades de ecoturismo. Os dados foram coletados utilizando a amostragem de distâncias em transecções lineares, que totalizou 468,3 Km percorridos nos períodos diurno e noturno, e registro de pegadas em parcelas previamente preparadas (n = 660 parcelas vistoriadas, além de percursos fluviais no rio Cristalino e buscas aleatórias nos locais onde não ocorriam caminhos. Registros de 37 espécies de mamíferos foram obtidos, sendo 33 de médio e grande porte e quatro de pequeno porte. Não houve diferença estatisticamente significativa na riqueza de espécies dos ambientes sem turismo e com ecoturismo, sendo que a similaridade de espécies entre eles foi alta (88%. No entanto, três táxons apresentaram abundância inferior nos ambientes com turismo: Dasyprocta leporina (Linnaeus, 1766, Mazama spp. e Dasypus kappleri Krauss, 1862. Percebe-se, portanto, que o impacto negativo das atividades de ecoturismo desenvolvidas na área de estudo foi de pequena magnitude, em termos de riqueza e abundância de mamíferos de médio e grande porte. Assim

  16. Hemi-ovariossalpingohisterectomia em pacas prenhes e posterior ocorrência de prenhez (Agouti paca, Linnaeus, 1766 Hemiovarysalpingohysterectomy in pregnant pacas and further occurrency of pregnancy (Agouti paca, Linnaeus, 1766

    Directory of Open Access Journals (Sweden)

    Fabrício Singaretti de Oliveira

    2003-06-01

    Full Text Available Foi descrita a hemi-ovariossalpingohisterectomia em cinco pacas prenhes mantidas em cativeiro no Setor de Animais Silvestres da Faculdade de Ciências Agrárias e Veterinárias (FCAV-UNESP de Jaboticabal, São Paulo, Brasil, a fim de observar futura prenhez no corno restante. A tranqüilização foi obtida após aplicação de azaperone (4mg/kg seguida da aplicação de sulfato de atropina (0,06mg/kg e da associação de cloridrato de quetamina (20mg/kg e cloridrato de xilazina (1,5mg/kg, ambos na mesma seringa, para indução da anestesia. A anestesia geral foi obtida mediante inalação de halotano por máscara. Por meio de laparotomia mediana, foram retirados o corno uterino prenhe, o ovário e a tuba uterina, todos do mesmo antímero. Antibióticos (30.000UI/kg de três penicilinas e 12,5mg/kg de duas estreptomicinas e analgésico (0,02mg/kg de buprenorfina foram aplicados imediatamente após a cirurgia, sendo repetidos após dois dias. Todas as aplicações foram feitas por via intramuscular. Apesar da permanência de apenas um ovário após a cirurgia, nova prenhez ocorreu no corno restante nas cinco fêmeas submetidas à cirurgia, com o nascimento de filhotes (apenas um por parto após 215, 248, 276, 302 e 310 dias da hemi-ovariossalpingohisterectomia.The hemiovarysalpingohysterectomy in five captive pregnant pacas kept on the Wild Animal Section at the College of Agricultural and Veterinarian Sciences (FCAV-UNESP in Jaboticabal, São Paulo, Brazil, was conducted aiming at verifying the further occurrence of pregnancy on the remaining uterine horn. The tranquilization was achieved by using azaperone (4mg/kg and consequent application of atropine sulphate (0.06mg/kg and the association of ketamine (20mg/kg and xylazine (1.5mg/kg cloridrates, on the same syringe, for induction of anesthesia. The general anesthesia was performed via a face mask with halothane. By means of median laparotomy, the uterine horn with the fetus, the ovary and the uterine tube, all from the same antimere, were taken out. Antibiotics (30,000IU/kg of three penicillins and 12.5mg/kg of two streptomycins and analgesic (buprenorfine 0.02 mg/kg were injected immediately after surgery and repeated after two days. All injections were made intramuscularly. In spite of the permanence of only one ovary after surgery, new pregnancy occurred in the remaining uterine horn in the five females which went through surgery, and the birth (solely one by delivery happened 210, 248, 276, 302 and 310 days after the hemiovarysalpingohysterectomy.

  17. Hemi-ovariossalpingohisterectomia em pacas prenhes e posterior ocorrência de prenhez (Agouti paca, Linnaeus, 1766) Hemiovarysalpingohysterectomy in pregnant pacas and further occurrency of pregnancy (Agouti paca, Linnaeus, 1766)

    OpenAIRE

    Fabrício Singaretti de Oliveira; Gilson Hélio Toniollo; Márcia Rita Fernandes Machado; Daniela Paura

    2003-01-01

    Foi descrita a hemi-ovariossalpingohisterectomia em cinco pacas prenhes mantidas em cativeiro no Setor de Animais Silvestres da Faculdade de Ciências Agrárias e Veterinárias (FCAV-UNESP) de Jaboticabal, São Paulo, Brasil, a fim de observar futura prenhez no corno restante. A tranqüilização foi obtida após aplicação de azaperone (4mg/kg) seguida da aplicação de sulfato de atropina (0,06mg/kg) e da associação de cloridrato de quetamina (20mg/kg) e cloridrato de xilazina (1,5mg/kg), ambos na mes...

  18. ANÁLISE DA ORIGEM E DISTRIBUIÇÃO DOS NERVOS PERIFÉRICOS DO PLEXO BRAQUIAL DA PACA (Agouti paca, LINNAEUS, 1766) ORIGIN AND DITRIBUTION ANALYSIS OF THE BRACHIAL PLEXUS PERIPHERAL NERVES OF PACA (Agouti paca, LINNAEUS, 1766)

    OpenAIRE

    Sílvia Helena Brendolan Gerbasi; Fabrício Singaretti de Oliveira; Gregório Corrêa Guimarães; Márcia Rita Fernandes Machado; Alessandra Regina Freixo Scavone

    2008-01-01

    O plexo braquial é um conjunto de nervos que surge na região medular cervicotorácica e que se distribui pelos membros torácicos e porção interna do tórax. O plexo braquial de oito pacas foi dissecado para evidenciação da origem e distribuição de seus nervos. O nervo supraescapular distribuía-se para os músculos supra e infra-espinhal, e o subescapular para o músculo subescapular. O nervo axilar ramificava-se para os músculos redondo maior, subescapular, redondo menor e deltóide. Os nervos uln...

  19. Rhizobium grahamii sp. nov., from nodules of Dalea leporina, Leucaena leucocephala and Clitoria ternatea, and Rhizobium mesoamericanum sp. nov., from nodules of Phaseolus vulgaris, siratro, cowpea and Mimosa pudica.

    Science.gov (United States)

    López-López, Aline; Rogel-Hernández, Marco A; Barois, Isabelle; Ortiz Ceballos, Angel I; Martínez, Julio; Ormeño-Orrillo, Ernesto; Martínez-Romero, Esperanza

    2012-09-01

    Two novel related Rhizobium species, Rhizobium grahamii sp. nov. and Rhizobium mesoamericanum sp. nov., were identified by a polyphasic approach using DNA-DNA hybridization, whole-genome sequencing and phylogenetic and phenotypic characterization including nodulation of Leucaena leucocephala and Phaseolus vulgaris (bean). As similar bacteria were found in the Los Tuxtlas rainforest in Mexico and in Central America, we suggest the existence of a Mesoamerican microbiological corridor. The type strain of Rhizobium grahamii sp. nov. is CCGE 502(T) (= ATCC BAA-2124(T) = CFN 242(T) = Dal4(T) = HAMBI 3152(T)) and that of Rhizobium mesoamericanum sp. nov. is CCGE 501(T) (= ATCC BAA-2123(T) = HAMBI 3151(T) = CIP 110148(T) = 1847(T)). PMID:22081714

  20. [Seasonal evaluation of mammal species richness and abundance in the "Mário Viana" municipal reserve, Mato Grosso, Brasil].

    Science.gov (United States)

    Rocha, Ednaldo Cândido; Silva, Elias; Martins, Sebastião Venâncio; Barreto, Francisco Cândido Cardoso

    2006-09-01

    We evaluated seasonal species presence and richness, and abundance of medium and large sized mammalian terrestrial fauna in the "Mário Viana" Municipal Biological Reserve, Nova Xavantina, Mato Grosso, Brazil. During 2001, two monthly visits were made to an established transect, 2,820 m in length. Records of 22 mammal species were obtained and individual footprint sequences quantified for seasonal calculation of species richness and relative abundance index (x footprints/km traveled). All 22 species occurred during the rainy season, but only 18 during the dry season. Pseudalopex vetulus (Lund, 1842) (hoary fox), Eira barbara (Linnaeus, 1758) (tayra), Puma concolor (Linnaeus, 1771) (cougar) and Hydrochaeris hydrochaeris (Linnaeus, 1766) (capybara) were only registered during the rainy season. The species diversity estimated using the Jackknife procedure in the dry season (19.83, CI = 2.73) was smaller than in the rainy season (25.67, CI = 3.43). Among the 18 species common in the two seasons, only four presented significantly different abundance indexes: Dasypus novemcinctus Linnaeus, 1758 (nine-banded armadillo), Euphractus sexcinctus (Linnaeus, 1758) (six-banded armadillo), Dasyprocta azarae Lichtenstein, 1823 (Azara's Agouti) and Tapirus terrestris (Linnaeus, 1758) (tapir). On the other hand, Priodontes maximus (Kerr, 1792) (giant armadillo) and Leopardus pardalis (Linnaeus, 1758) (ocelot) had identical abundance index over the two seasons. Distribution of species abundance in the sampled area followed the expected pattern for communities in equilibrium, especially in the rainy season, suggesting that the environment still maintains good characteristics for mammal conservation. The present study shows that the reserve, although only 470 ha in size, plays an important role for conservation of mastofauna of the area as a refuge in an environment full of anthropic influence (mainly cattle breeding in exotic pasture). PMID:18491629

  1. Seguimiento y monitoreo participativo de la actividad de cacería en la región de Puerto Nariño, Amazonas, Colombia

    Directory of Open Access Journals (Sweden)

    Rodríguez Carlos

    2004-12-01

    Full Text Available Se describen los patrones generales de la actividad de cacería en el casco urbano de Puerto Nariño a partir del registro continuo de las jornadas de caza durante el período de aguas ascendentes (enero-julio, 2003, a través de un análisis comparativo entre el aprovechamiento de fauna en las zonas de várzea y tierra firme, con una perspectiva integrada que incluye principios históricos, culturales y biológicos. Se determinan los parámetros de captura, esfuerzo y captura por unidad de esfuerzo (CPUE y se describe la composición y distribución de la captura. La captura total fue de 238 individuos correspondientes a 44 especies. Las especies
    con mayores valores de captura fueron Alouatta seniculus, Ara manilata y Phalacrocorax olivaceus, en la zona de várzea y en tierra firme fueron Agouti paca, Dasypus novemcinctus y Dasyprocta fuliginosa. Tomando la jornada como unidad de esfuerzo, se definen los tipos de jornada identificados, se analiza el esfuerzo perdido con base en las jornadas no exitosas y se describe la tipología de los cazadores. Entre algunos de los aspectos socioculturales que enmarcan la actividad de cacería, se describe la visión actual de la cacería por parte de los indígenas Ticuna de Puerto Nariño y los aspectos tradicionales que aún forman parte de esta actividad. El proyecto se abordó a través de una metodología participativa en la cual los pobladores locales se involucraron activamente en el monitoreo, proceso que permitió a los cazadores organizarse y continuar autónomamente con la toma de registros durante el período de aguas bajas.

  2. Dispersal of seeds of Hymenaea courbaril (Fabaceae in a logged rain forest in the Peruvian Amazonian Dispersão de sementes de Hymenaea courbaril (Fabaceae em uma floresta tropical úmida com exploração madeireira na Amazônia peruana

    Directory of Open Access Journals (Sweden)

    David L. Gorchov

    2004-01-01

    Full Text Available Seed dispersal of Hymenaea courbaril was studied by following the fate of 585 seeds embedded with small magnets and set in displays in and near a logged strip in rain forest in the Peruvian Amazonian. Mammals took fruits from all displays, which were located in the forest, edge, and cleared strip. Overall removal rates were low - a median of 8.1 fruits / month from displays maintained with 8-10 fruits - but were higher in August than in earlier months. Most fruits were dropped near the display or had their seeds eaten, but > 13% were successfully dispersed. Most of the dispersed seeds were buried, which increases probability of germination. Maximum dispersal distance of live seeds was 12.1 m (median 3.1 m, but other magnets were transported up to 34 m, indicating seeds were dispersed further, but then eaten. Acouchies (most likely Myoprocta pratti and agoutis (Dasyprocta fuliginosa were apparently the main dispersal agents. Dispersal of seeds from the forest into the logged strip was rare, suggesting that although rodents disperse H. courbaril, they cannot be relied on for the reseeding this and similar species in recent clearings.Foi estudada a dispersão de sementes de Hymenaea courbaril, seguindo o destino de 585 sementes marcadas com imãs e expostas a potenciais dispersores, colocadas em agregados no interior e próximo de uma faixa de floresta cortada, na Amazónia peruana. Mamíferos retiraram frutos de todos os agregados, localizados no interior da floresta, na sua borda, e na clareira. As taxas de remoção foram baixas - mediana de 8.1 frutos/mês em agregados mantidos com 8-10 frutos - mas foram mais altas em agosto que nos primeiros meses do ano. A maior parte dos frutos foi abandonada próxima do agregado de origem ou as suas sementes foram consumidas, mas > 13% foram dispersos com sucesso. A maior parte das sementes dispersas foi enterrada, o que favorece a germinação. A distância máxima de dispersão de sementes vivas foi de

  3. Effects of Portabella mushrooms on collagen-induced arthritis, inflammatory cytokines, and body composition in dilute brown non-agouti (DBA1 mice

    Directory of Open Access Journals (Sweden)

    Stanley A. Lightfoot

    2011-09-01

    Full Text Available Background:Exotic mushrooms have long been used in Asia for treatment and/or prevention of chronic diseases due to their immunomodulatory properties. However, the health benefits of portabella mushrooms (PM (brown Agaricus bisporous, on collagen-induced arthritis (CIA and associated complications, (i.e. loss of lean mass, increased fat mass and inflammatory cytokines, have not been previously investigated.Methods:We investigated CIA pathogenesis, body composition and plasma levels of IL- 6, TNF-α and sICAM1 in DBA1 female mice fed either the AIN76 diet or the same diet fortified with 5% lyophilized PM (n=19-20/group. Ten mice/group were immunized with 100 μg bovine collagen type II on day 42 of the protocol, followed by 50 μg lipopolysaccharides on day 62, and euthanized on day 73-74. Cytokines were measured by ELISA.Results:Compared to baseline diet, PM had: no protective effect from CIA since all collagen-immunized mice developed severe edema, bone erosion, and mononuclear cell infiltration in paws. In mice with and those without CIA, feeding a PM-fortified diet resulted in higher percent of body fat than feeding the baseline diet (p<0.05. After CIA induction, PM provided the followingFunctional Foods in Health and Disease 2011; 9:279-296beneficial effects: (a a smaller reduction in lean mass and absolute thymus weight; (b a higher fat mass loss; and (c lower plasma TNF-α levels (p <0.05. PM-fortification did not alter plasma IL-6 and sICAM1 regardless of CIA status; but it increased in vitro IL-6 secretion by mitogen-treated spleen cells.Conclusion:Our data suggest that PM may reduce plasma TNF-α, attenuate lean mass loss and thymus atrophy associated with arthritis, and protect spleen cell function assessed by IL-6 secretion. However, PM-fortification did not attenuate overall CIA pathogenesis which may be due to lack of effect on plasma IL-6. Decreased TNF-α without alterations in IL-6 may reduce the risk of other conditions associated with chronic inflammation such as cardiovascular disease.

  4. Polypores on Spruce in Northeast China

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Poroid species of wood-inhabiting fungi growing on spruce (Picea koraiensis Nakai or Picea yezoensis (Sieb. & Zucc.) Carriere) in Northeast China were investigated during 1993-2002, and 71 species were recorded from these trees or their wood. Skeletocutis lilacina A. David & Jean Keller and Skeletocutis papyracea A. David are new to China. Fomitopsis pinicola (Sw.:Fr.) P. Karst., Onnia leporina (Fr.) H. Jahn, Perenniporia subacida (Peck) Donk, Phaeolus sckweinitzii (Fr.:Fr.) Pat., Phellinidium sulphuras...

  5. Epigenetic’s role in fish pigmentation

    Directory of Open Access Journals (Sweden)

    Laura Cal Delgado

    2014-04-01

    Full Text Available The agouti coat colour gene encodes a paracrine signalling molecule whose differential expression produces the characteristic dorsal-ventral pigment pattern observed in most mammals. We have recently demonstrated that this well-characterised mechanism from mammals also applies to fish with their much more complex pigment patterns. However, the developmental mechanism through which agouti acts to establish these colour differences remains unclear. The present study was undertaken to explore the molecular mechanisms that regulate agouti gene expression by in-vivo functional characterization of the agouti promoter and identification of possible putative regulatory elements that govern basal promoter activity. Specifically, the investigation was focused on the occurrence and role of CpG dinucleotides methylation in the agouti putative promoter sequence and on a possible epigenetic level of regulation of agouti expression. We report here expression analyses of eGFP expression from transgenic zebrafish containing an 8kb-agouti-Tol2-eGFP construct. eGFP expression was specifically found in the brain area and neural tube of Tol2 transposon vector transgenic embryos. Computer-based analysis revealed a putative CpG island immediately proximal to the translation start site. Global inhibition of methylation with 5-aza-2'-deoxycytidine promoted agouti production in association with decreasing CpG methylation. Taken together, these data identify a contributory role for DNA methylation in regulating agouti expression in zebrafish embryogenesis.

  6. Presence of Antibodies to Infectious Bursal Disease Virus in Semi-intensively Reared Pearl Guinea Fowls in Nigeria

    Directory of Open Access Journals (Sweden)

    Nwagu, BI.

    1997-01-01

    Full Text Available The present article reviews the bibliographie date available on the feeding of tepezcuintle (Agouti paca. It also reports about the reproductive rates and the meat production in captivity and mentions some alternatives to improve this characteristics.

  7. Dorsoventral patterning of the mouse coat by Tbx15.

    OpenAIRE

    Candille, Sophie I.; Van Raamsdonk, Catherine D.; Changyou Chen; Sanne Kuijper; Yanru Chen-Tsai; Andreas Russ; Frits Meijlink; Barsh, Gregory S.

    2004-01-01

    Many members of the animal kingdom display coat or skin color differences along their dorsoventral axis. To determine the mechanisms that control regional differences in pigmentation, we have studied how a classical mouse mutation, droopy ear (de(H)), affects dorsoventral skin characteristics, especially those under control of the Agouti gene. Mice carrying the Agouti allele black-and-tan (a(t)) normally have a sharp boundary between dorsal black hair and yellow ventral hair; the de(H) mutati...

  8. The mouse pink-eyed dilution allele of the P-gene greatly inhibits eumelanin but not pheomelanin synthesis.

    Science.gov (United States)

    Hirobe, Tomohisa; Ito, Shosuke; Wakamatsu, Kazumasa

    2011-02-01

    The mouse pink-eyed dilution (p) locus is known to control eumelanin synthesis, melanosome morphology, and tyrosinase activity in melanocytes. However, it has not been fully determined whether the mutant allele, p affects pheomelanin synthesis. Effects of the p allele on eumelanin and phemelanin synthesis were investigated by chemical analysis of dorsal hairs of 5-week-old mice obtained from the F(2) generations (black, pink-eyed black, recessive yellow, pink-eyed recessive yellow, agouti, and pink-eyed agouti) between C57BL/10JHir (B10)-congenic pink-eyed black mice (B10-p/p) and recessive yellow (B10-Mc1r(e)/Mc1r(e)) or agouti (B10-A/A) mice. The eumelanin content was dramatically (>20-fold) decreased in pink-eyed black and pink-eyed agouti mice, whereas the pheomelanin content did not decrease in pink-eyed black, pink-eyed recessive yellow, or pink-eyed agouti mice compared to the corresponding P/- mice. These results suggest that the pink-eyed dilution allele greatly inhibits eumelanin synthesis, but not pheomelanin synthesis. PMID:21232027

  9. Genetic polymorphism of adult reindeer coat colour in a herding cooperative in Finnish Lapland

    OpenAIRE

    Jean J. Lauvergne; Mauri Nieminen

    2011-01-01

    In a random sample of 188 adult reindeer belonging to a reindeer herding cooperative in Finnish Lapland, the following coat colour mutants were identified: Abf at the locus Agouti (A), kalppinokka (WNk) at the locus White Nose (WN) and white at the locus W (White). Coefficients of coat colour phenotypic polymorphism K were estimated, in order to quantify this genetic polymorphism. Estimations of K were 12.8% for the locus A (Agouti), 5.1% for the locus WN (White Nose), and 7.5% for the locus ...

  10. New mammalian records in the Parque Nacional Cerros de Amotape, northwestern Peru

    Directory of Open Access Journals (Sweden)

    Cindy M. Hurtado

    2015-04-01

    Full Text Available The Pacific Tropical Rainforest and Equatorial Dry Forest are found only in southern Ecuador and northern Peru, and are among the most poorly known ecosystems of South America. Even though these forests are protected in Parque Nacional Cerros de Amotape (PNCA, they are threatened by fragmentation because of farming and agriculture. The aim of this study was to determine the medium and large mammalian species richness, using transect census, camera trapping, and specimen bone collection. Nine transects were established and 21 camera trap stations were placed along 16 km2 in three localities of PNCA, from August 2012 to April 2013. Total sampling effort was 215 km of transects and 4077 camera-days. We documented 22 species; including 17 with camera trapping, 11 with transect census, and 10 with specimen collection.  Camera traps were the most effective method, and four species (Dasyprocta punctata, Cuniculus paca, Leopardus wiedii and Puma concolor were documented only with this method. This comprised the first Peruvian record for Dasyprocta punctata, and the first record for the western slope of the Peruvian Andes for Cuniculus paca. Also, both specimen collections and sightings confirm the presence of Potos flavus, first record in the western slope of the Peruvian Andes. Panthera onca, Tremarctos ornatus and Saimiri sciureus are considered locally extinct, while several species are in need of further research. We highlight the importance of the high diversity of this rainforests and encourage local authorities to give the area the highest priority in conservation.

  11. Presença de anticorpos da classe IgM de Leptospira interrogans em animais silvestres do Estado do Tocantins, 2002 Presence of IgM antibodies for Leptospira interrogans in wild animals from Tocantins State, 2002

    Directory of Open Access Journals (Sweden)

    Milton Formiga de Souza Júnior

    2006-06-01

    Full Text Available Quatrocentos e vinte e sete amostras de soro provenientes de animais silvestres foram testadas frente a 18 sorovariedades de Leptospira interrogans. De 286 amostras de Cebus apella, 46 (16,1% foram positivas para as sorovariedades pomona, brasiliensis, mini, swajizak, grippothyphosa, sarmin, fluminense, autumnalis, hebdomadis, guaratuba, javanica e icterohaemorhagiae. Das 82 de Alouatta caraya, 2 (2,4% foram positivas para as sorovariedades mangus e fluminense. Das 31 de Nasua nasua, 4 (12,9% foram positivas para as sorovariedades fluminense e javanica. Das 10 amostras de Cerdocyon thous, 2 (20% foram positivas para as sorovariedades fluminense e brasiliensis. Sete de Dasyprocta sp, 6 de Tamandua tetradactila e 5 de Euphractus sexcintus não apresentaram reatividade.Four hundred and twenty-seven serum samples of wild animals were tested against 18 serovars of Leptospira interrogans. Of 286 samples of Cebus apella, 46 (16.1% were positive for the serovars pomona, brasiliensis, mini, swajizak, grippotyphosa, sarmin, fluminense, autumnalis, hebdomadis, guaratuba, javanica and icterohaemorrhagiae. Of 82 samples of Alouatta caraya, 2 (2.4% were positive for the serovars mangus and fluminense. Of 31 samples of Nasua nasua, 4 (12.9% were positive for the serovars fluminense and javanica, and of 10 samples of Cerdocyon thous, 2 (20 % were positive for the serovars fluminense and brasiliensis. Seven samples of Dasyprocta sp, 6 of Tamandua tetradactyla and 5 of Euphractus sexcintus did not present reactivity.

  12. Molecular mechanism of agonism and inverse agonism in the melanocortin receptors: Zn(2+) as a structural and functional probe

    DEFF Research Database (Denmark)

    Holst, Birgitte; Schwartz, Thue W

    2003-01-01

    Among the rhodopsin-like 7TM receptors, the MC receptors are functionally unique because their high constitutive signaling activity is regulated not only by endogenous peptide agonists-MSH peptides-but also by endogenous inverse agonists, namely, the proteins agouti and AGRP. Moreover, the metal...

  13. Adaptive variation in beach mice produced by two interacting pigmentation genes.

    Directory of Open Access Journals (Sweden)

    Cynthia C Steiner

    2007-09-01

    Full Text Available Little is known about the genetic basis of ecologically important morphological variation such as the diverse color patterns of mammals. Here we identify genetic changes contributing to an adaptive difference in color pattern between two subspecies of oldfield mice (Peromyscus polionotus. One mainland subspecies has a cryptic dark brown dorsal coat, while a younger beach-dwelling subspecies has a lighter coat produced by natural selection for camouflage on pale coastal sand dunes. Using genome-wide linkage mapping, we identified three chromosomal regions (two of major and one of minor effect associated with differences in pigmentation traits. Two candidate genes, the melanocortin-1 receptor (Mc1r and its antagonist, the Agouti signaling protein (Agouti, map to independent regions that together are responsible for most of the difference in pigmentation between subspecies. A derived mutation in the coding region of Mc1r, rather than change in its expression level, contributes to light pigmentation. Conversely, beach mice have a derived increase in Agouti mRNA expression but no changes in protein sequence. These two genes also interact epistatically: the phenotypic effects of Mc1r are visible only in genetic backgrounds containing the derived Agouti allele. These results demonstrate that cryptic coloration can be based largely on a few interacting genes of major effect.

  14. Cannabinoid treatment renders neurons less vulnerable than oligodendrocytes in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Hasseldam, Henrik; Johansen, Flemming Fryd

    2011-01-01

    effects. EAE was induced using MOG(1-125) in Dark Agouti rats and treatment was initiated at symptom debut and continued until first relapse culminated. The central nervous system (CNS) cell death including caspase and calpain activation, axonal degeneration and demyelination as well as a wide range of...

  15. Infecções experimentaes na Leishmaniose visceral americana Experimental infections in american visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Aristides Marques da Cunha

    1938-01-01

    Leishmaniae being located mainly in the mucous membrane, in infiltration cells located amongst Lieberkuehn's glands and some parasited macrophages could also be observed in the sub-mucosa. Mice as well as the rodents Dasyprocta agouti and Proechymis oris when inoculated, did not become infeced. From the exposed we may conclude that the experimental infections obtained, present a complete analogy with those described in the Mediterrean Kala-azar. On the other hand, the sero-agglutination test, as shown by us in a previous paper, allows no distinction of the species of Leishmania, as all the strains when recently isolated, have the same antigenic constitution which later on undergoes modifications when the Leishmaniae are preserved in culture for a long time. Thus, we feel authorized to conclude that the agent of the visceral american leishmaniasis is identical with L. infantum.

  16. Arborescent palm seed morphology and seedling distribution.

    Science.gov (United States)

    Salm, Rodolfo

    2005-11-01

    This study examines how the seed morphology of two large arborescent palms, Attalea maripa (Aubl.) Mart. and Astrocaryum aculeatum G. Mey, may affect their seed shadow in a seasonally dry Amazonian forest. In addition to being smaller and produced in larger numbers than those of A. aculeatum, A. maripa seeds also presented a substantially lower amount of nutritional reserves available for the embryo. However, A. maripa seedlings were found in much higher numbers than those of A. aculeatum. The results suggest that, within the spatial scale considered, the seed rain of A. maripa is more restricted to the area surrounding around reproductive conspecifics than that of A. aculeatum. Furthermore, in comparison with those of A. aculeatum, the smaller seeds of A. maripa might be less attractive to scatterhoarding rodents (e.g. Dasyprocta aguti). The pattern observed emphasizes the importance of scatterhoarding rodents as dispersers of large-seeded plant species in Neotropical forests. PMID:16532195

  17. Notas sôbre a evolução do virus vacínico em animais silvestres da fauna brasileira

    Directory of Open Access Journals (Sweden)

    Cicero Alves Moreira

    1956-06-01

    Full Text Available A note on the evolution of cow-pox virus in wild animals of Brazilian fauna. We have tried the sensibility of wild animals of Brazilian fauna to the cow-pox virus. The following specimens were submitted to experiences: Procyon cancrivorus, Hydrochoerus capybara, Cavea aperea, Coendu villosus, Didelphis aurita, Bradypus tridactylus, Euphractus sexcintus, Tamandua tetradactylus, Nasua narica, Dasyprocta aguti and Testudo tabulata. In all these animals, - excepting Bradypus tridactylus - we have obtained an infection with incubation (five days, aspect and duration similar to cow-pox of the laboratorial animals (calf and rabbit. In the Bradypus tridactylus howewer, the incubation was very long. Only after 30 days of inoculation we verified the infection with the formation of vesiculae and postulae.

  18. Composição e abundância relativa dos mamíferos de médio e grande porte no Parque Estadual do Turvo, Rio Grande do Sul, Brasil Composition and relative abundance of the medium-large ized mammals of Turvo State Park, Rio Grande do Sul, Brazil

    OpenAIRE

    Carlos B. Kasper; Fábio D. Mazim; José B. G. Soares; Tadeu G. de Oliveira; Marta E. Fabián

    2007-01-01

    Entre janeiro de 2005 e dezembro de 2006 foram realizados estudos sobre a composição e abundância relativa dos mamíferos de médio e grande porte do Parque Estadual do Turvo. Para tanto, foram utilizados registros de armadilhas fotográficas além de visualizações e dados sobre presença e ausência de pegadas ao longo de transectos pré-determinados. No total foram registradas 29 espécies de mamíferos de médio e grande porte, das quais Dasyprocta azarae Lichtenstein, 1823 e Sylvilagus brasiliensis...

  19. Genetic polymorphism of adult reindeer coat colour in a herding cooperative in Finnish Lapland

    Directory of Open Access Journals (Sweden)

    Jean J. Lauvergne

    2011-04-01

    Full Text Available In a random sample of 188 adult reindeer belonging to a reindeer herding cooperative in Finnish Lapland, the following coat colour mutants were identified: Abf at the locus Agouti (A, kalppinokka (WNk at the locus White Nose (WN and white at the locus W (White. Coefficients of coat colour phenotypic polymorphism K were estimated, in order to quantify this genetic polymorphism. Estimations of K were 12.8% for the locus A (Agouti, 5.1% for the locus WN (White Nose, and 7.5% for the locus W (White. This polymorphism results probably from a change in fitness coefficient of genotypes carrying colour mutants following domestication in a random mating context which has not yet been proved.

  20. The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin

    OpenAIRE

    Kim, M. S.; Small, C J; Stanley, S. A.; Morgan, D. G. A.; Seal, L.J.; Kong, W.M.; Edwards, C M B; Abusnana, S.; Sunter, D.; Ghatei, M. A.; Bloom, S R

    2000-01-01

    Prolonged fasting is associated with a downregulation of the hypothalamo-pituitary thyroid (H-P-T) axis, which is reversed by administration of leptin. The hypothalamic melanocortin system regulates energy balance and mediates a number of central effects of leptin. In this study, we show that hypothalamic melanocortins can stimulate the thyroid axis and that their antagonist, agouti-related peptide (Agrp), can inhibit it. Intracerebroventricular (ICV) administration of Agrp (83-132) decreased...

  1. Adaptive radiation-induced epigenetic alterations mitigated by antioxidants

    OpenAIRE

    Bernal, Autumn J.; Dolinoy, Dana C; Huang, Dale; Skaar, David A.; Weinhouse, Caren; Jirtle, Randy L

    2013-01-01

    Humans are exposed to low-dose ionizing radiation (LDIR) from a number of environmental and medical sources. In addition to inducing genetic mutations, there is concern that LDIR may also alter the epigenome. Such heritable effects early in life can either be positively adaptive or result in the enhanced formation of diseases, including cancer, diabetes, and obesity. Herein, we show that LDIR significantly increased DNA methylation at the viable yellow agouti (Avy) locus in a sex-specific man...

  2. Obesity is associated with macrophage accumulation in adipose tissue

    OpenAIRE

    Weisberg, Stuart P.; McCann, Daniel; Desai, Manisha; Rosenbaum, Michael; Leibel, Rudolph L.; Ferrante, Anthony W

    2003-01-01

    Obesity alters adipose tissue metabolic and endocrine function and leads to an increased release of fatty acids, hormones, and proinflammatory molecules that contribute to obesity associated complications. To further characterize the changes that occur in adipose tissue with increasing adiposity, we profiled transcript expression in perigonadal adipose tissue from groups of mice in which adiposity varied due to sex, diet, and the obesity-related mutations agouti (Ay) and obese (Lepob). We fou...

  3. NEUROENDOCRINE ACTIONS AND REGULATION OF HYPOTHALAMIC NEUROPEPTIDE Y DURING LACTATION

    OpenAIRE

    Crowley, W,R.; Ramoz, G.; Torto, R.; Keefe, K.A.; Wang, J.J.; Kalra, S.P.

    2007-01-01

    The expression of neuropeptide Y (NPY) and its co-messenger, agouti-related peptide (AgRP), in arcuate neurons of the hypothalamus is increased during lactation in rats. Our research has been addressing the questions of the physiological actions of these peptides during lactation and the physiological signals associated with lactation that result in increased expression of their genes. Our studies indicate that NPY and AgRP exert pleiotropic actions during lactation that help integrate neuroe...

  4. Inheritance of a Parotid Secretory Protein in Mice and Its Use in Determining Salivary Amylase Quantitative Variants

    OpenAIRE

    Owerbach, David; Hjorth, J. Peter

    1980-01-01

    Among inbred strains of mice, a major protein, PSP, produced and secreted by the parotid glands, shows variation in electrophoretic mobility and in the peptides produced by cyanogen bromide treatment. This variation is inherited as a single Mendelian factor with two alleles showing co-dominant expression. In genetic crosses, it segregates independently from the amylase complex and is closely linked to the agouti locus on chromosome 2. The protein ratios between amylase and PSP in saliva, obta...

  5. Melanocortin-1 receptor-mediated signalling pathways activated by NDP-MSH and HBD3 ligands

    OpenAIRE

    Beaumont, Kimberley A.; Smit, Darren J.; Liu, Yan Yan; Chai, Eric; Patel, Mira P.; Millhauser, Glenn L.; Smith, Jennifer J.; Alewood, Paul F.; Sturm, Richard A.

    2012-01-01

    Binding of melanocortin peptide agonists to the melanocortin-1 receptor of melanocytes results in eumelanin production, whereas binding of the agouti signalling protein inverse agonist results in pheomelanin synthesis. Recently, a novel melanocortin-1 receptor ligand was reported. A β-defensin gene mutation was found to beresponsible for black coat colour in domestic dogs. Notably, the human equivalent, β-defensin 3, was found to bind with high affinity to the melanocortin-1 receptor; however...

  6. Starvation after AgRP neuron ablation is independent of melanocortin signaling

    OpenAIRE

    Wu, Qi; Howell, Maureen P.; Cowley, Michael A.; Palmiter, Richard D.

    2008-01-01

    Ablation of inhibitory agouti-related protein (AgRP)-expressing neurons in the arcuate nucleus that also synthesize γ-amino-butyric acid (GABA) and neuropeptide Y in adult mice leads to starvation within 1 week. The removal of inhibition from the AgRP neurons onto neighboring proopiomelanocortin neurons and their common postsynaptic neurons is predicted to stimulate melanocortin signaling, which is known to inhibit appetite. To examine the importance of uncontrolled melanocortin signaling in ...

  7. Effects of Leptin and Melanocortin Signaling Interactions on Pubertal Development and Reproduction

    OpenAIRE

    Israel, Davelene D.; Sheffer-Babila, Sharone; de Luca, Carl; Jo, Young-Hwan; Liu, Shun Mei; Xia, Qiu; Spergel, Daniel J.; Dun, Siok L.; Dun, Nae J.; Chua, Streamson C.

    2012-01-01

    Leptin and melanocortin signaling control ingestive behavior, energy balance, and substrate utilization, but only leptin signaling defects cause hypothalamic hypogonadism and infertility. Although GnRH neurons do not express leptin receptors, leptin influences GnRH neuron activity via regulation of immediate downstream mediators including the neuropeptides neuropeptide Y and the melanocortin agonist and antagonist, α-MSH, agouti-related peptide, respectively. Here we show that modulation of m...

  8. Methotrexate ameliorates pristane-induced arthritis by decreasing IFN-γ and IL-17A expressions*

    OpenAIRE

    Hou, Wei-kun; Meng, Lie-su; Zheng, Fang; Wen, Yu-rong; Zhu, Wen-Hua; Jiang, Cong-shan; He, Xiao-Jing; Zhou, Yan; Lu, She-Min

    2011-01-01

    Objective: This study was carried out to test the effects of methotrexate (MTX) and black seed oil (BSO) on pristane-induced arthritis (PIA) in rats. Methods: Inbred dark agouti (DA) rats were induced by a single subcutaneous injection of pristane, and then treated with MTX or BSO. Arthritis severity was evaluated macroscopically and microscopically. Plasma nitric oxide (NO) concentration was determined by the Griess method and cytokine mRNA expression in the spleen was detected by the real-t...

  9. The Melanocortinergic Pathway Is Rapidly Recruited by Emotional Stress and Contributes to Stress-Induced Anorexia and Anxiety-Like Behavior

    OpenAIRE

    Liu, Jing; Garza, Jacob C.; Truong, Ha V.; Henschel, John; Zhang, Wei; Lu, Xin-Yun

    2007-01-01

    Neurons producing melanocortin receptor agonist, α-MSH derived from proopiomelanocortin, and antagonist, agouti-related protein, are known to be sensitive to metabolic stress such as food deprivation and glucoprivation. However, how these neurons respond to emotional/psychological stress remained to be elucidated. We report here that acute emotional stressors, i.e. restraint and forced swim, evoked mRNA expression of c-fos, a neuronal activation marker, in a high percentage of proopiomelanoco...

  10. Dorsoventral patterning of the mouse coat by Tbx15.

    Directory of Open Access Journals (Sweden)

    Sophie I Candille

    2004-01-01

    Full Text Available Many members of the animal kingdom display coat or skin color differences along their dorsoventral axis. To determine the mechanisms that control regional differences in pigmentation, we have studied how a classical mouse mutation, droopy ear (de(H, affects dorsoventral skin characteristics, especially those under control of the Agouti gene. Mice carrying the Agouti allele black-and-tan (a(t normally have a sharp boundary between dorsal black hair and yellow ventral hair; the de(H mutation raises the pigmentation boundary, producing an apparent dorsal-to-ventral transformation. We identify a 216 kb deletion in de(H that removes all but the first exon of the Tbx15 gene, whose embryonic expression in developing mesenchyme correlates with pigmentary and skeletal malformations observed in de(H/de(H animals. Construction of a targeted allele of Tbx15 confirmed that the de(H phenotype was caused by Tbx15 loss of function. Early embryonic expression of Tbx15 in dorsal mesenchyme is complementary to Agouti expression in ventral mesenchyme; in the absence of Tbx15, expression of Agouti in both embryos and postnatal animals is displaced dorsally. Transplantation experiments demonstrate that positional identity of the skin with regard to dorsoventral pigmentation differences is acquired by E12.5, which is shortly after early embryonic expression of Tbx15. Fate-mapping studies show that the dorsoventral pigmentation boundary is not in register with a previously identified dermal cell lineage boundary, but rather with the limb dorsoventral boundary. Embryonic expression of Tbx15 in dorsolateral mesenchyme provides an instructional cue required to establish the future positional identity of dorsal dermis. These findings represent a novel role for T-box gene action in embryonic development, identify a previously unappreciated aspect of dorsoventral patterning that is widely represented in furred mammals, and provide insight into the mechanisms that underlie

  11. Pleiotropy in the melanocortin system, coloration and behavioural syndromes.

    OpenAIRE

    Ducrest A.L.; Keller L; Roulin A.

    2008-01-01

    In vertebrates, melanin-based coloration is often associated with variation in physiological and behavioural traits. We propose that this association stems from pleiotropic effects of the genes regulating the synthesis of brown to black eumelanin. The most important regulators are the melanocortin 1 receptor and its ligands, the melanocortin agonists and the agouti-signalling protein antagonist. On the basis of the physiological and behavioural functions of the melanocortins, we predict five ...

  12. Dorsoventral Patterning of the Mouse Coat by Tbx15

    Directory of Open Access Journals (Sweden)

    Candille Sophie I

    2004-01-01

    Full Text Available Many members of the animal kingdom display coat or skin color differences along their dorsoventral axis. To determine the mechanisms that control regional differences in pigmentation, we have studied how a classical mouse mutation, droopy ear (deH, affects dorsoventral skin characteristics, especially those under control of the Agouti gene. Mice carrying the Agouti allele black-and-tan (at normally have a sharp boundary between dorsal black hair and yellow ventral hair; the deH mutation raises the pigmentation boundary, producing an apparent dorsal-to-ventral transformation. We identify a 216 kb deletion in deH that removes all but the first exon of the Tbx15 gene, whose embryonic expression in developing mesenchyme correlates with pigmentary and skeletal malformations observed in deH/deH animals. Construction of a targeted allele of Tbx15 confirmed that the deH phenotype was caused by Tbx15 loss of function. Early embryonic expression of Tbx15 in dorsal mesenchyme is complementary to Agouti expression in ventral mesenchyme; in the absence of Tbx15, expression of Agouti in both embryos and postnatal animals is displaced dorsally. Transplantation experiments demonstrate that positional identity of the skin with regard to dorsoventral pigmentation differences is acquired by E12.5, which is shortly after early embryonic expression of Tbx15. Fate-mapping studies show that the dorsoventral pigmentation boundary is not in register with a previously identified dermal cell lineage boundary, but rather with the limb dorsoventral boundary. Embryonic expression of Tbx15 in dorsolateral mesenchyme provides an instructional cue required to establish the future positional identity of dorsal dermis. These findings represent a novel role for T-box gene action in embryonic development, identify a previously unappreciated aspect of dorsoventral patterning that is widely represented in furred mammals, and provide insight into the mechanisms that underlie region

  13. Linkage and Segregation Analysis of Black and Brindle Coat Color in Domestic Dogs

    OpenAIRE

    Kerns, Julie A.; Cargill, Edward J; Clark, Leigh Anne; Candille, Sophie I.; Berryere, Tom G.; Olivier, Michael; Lust, George; Todhunter, Rory J.; Schmutz, Sheila M.; Murphy, Keith E; Barsh, Gregory S

    2007-01-01

    Mutations of pigment type switching have provided basic insight into melanocortin physiology and evolutionary adaptation. In all vertebrates that have been studied to date, two key genes, Agouti and Melanocortin 1 receptor (Mc1r), encode a ligand-receptor system that controls the switch between synthesis of red–yellow pheomelanin vs. black–brown eumelanin. However, in domestic dogs, historical studies based on pedigree and segregation analysis have suggested that the pigment type-switching sy...

  14. Genetic and epigenetic control of 4NQO-induced tongue carcinogenesis in the rats

    OpenAIRE

    TANUMA, JUN-ICHI; タヌマ, ジュンイチ

    2006-01-01

    Oral administration of 4-nitroquinoline l-oxide (4NQO) can induce a high incidence of tongue cancers (TCs) in rats; inbred Dark-Agouti (DA) strain rats are highly susceptible, whereas Wistar/Furth (WF) rats are resistant. Our earlier studies confirmed that susceptibility depended on the respective genetic background, and 5 quantitative trait loci (QTLs), Tongue squamous cell carcinoma 1-5 (Tsccl-5), were identified as influencing susceptibility/resistance to 4NQO-induced TCs; however, the gen...

  15. Fatty acids composition of fruits of selected Central European sedges (Carex L. Cyperaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Bogucka-Kocka, A.; Janyszek, M.

    2010-07-01

    Fatty acids in the fruits of 13 sedge species (Ca rex L., Cyperaceae) were analyzed. The oil contents in the fruits of the studied sedges ranged from 3.73 and 46.52%. In the studied fruit oils 14 different fatty acids were identified. The main unsaturated fatty acids were: linoleic, a-linolenic, oleic, oleo palmitic n-7; oleo palmitic n-9, octadecenic, and eicosenoic acids. The following acids were found in the greatest quantities: linoleic, oleic, a-linolenic and palmitic acids. Based on the fatty acid composition, studied taxa can be divided in two groups. The first group (C. flava, C. pseudocyperus, C. riparia, C. leporina) is a very good source of linoleic acid. The second group, including the remaining species, is a good source of a-linolenic acid. The highest oleic acid contents were observed in C. vulpina. The studied material has shown a low concentration of saturated fatty acids, among which palmitic acid was the main one.Results of the analyses allow for the inclusion of the studied species among plants whose fruits are characterized by a high content of unsaturated fatty acids. (Author)

  16. Agent-based modeling for the landuse change of hunter-gather societies and the impacts on biodiversity in Guyana

    Science.gov (United States)

    Iwamura, T.; Fragoso, J.; Lambin, E.

    2012-12-01

    The interactions with animals are vital to the Amerindian, indigenous people, of Rupunini savannah-forest in Guyana. Their connections extend from basic energy and protein resource to spiritual bonding through "paring" to a certain animal in the forest. We collected extensive dataset of 23 indigenous communities for 3.5 years, consisting 9900 individuals from 1307 households, as well as animal observation data in 8 transects per communities (47,000 data entries). In this presentation, our research interest is to model the driver of land use change of the indigenous communities and its impacts on the ecosystem in the Rupunini area under global change. Overarching question we would like to answer with this program is to find how and why "tipping-point" from hunting gathering society to the agricultural society occurs in the future. Secondary question is what is the implication of the change to agricultural society in terms of biodiversity and carbon stock in the area, and eventually the well-being of Rupunini people. To answer the questions regarding the society shift in agriculture activities, we built as simulation with Agent-Based Modeling (Multi Agents Simulation). We developed this simulation by using Netlogo, the programming environment specialized for spatially explicit agent-based modeling (ABM). This simulation consists of four different process in the Rupunini landscape; forest succession, animal population growth, hunting of animals, and land clearing for agriculture. All of these processes are carried out by a set of computational unit, called "agents". In this program, there are four types of agents - patches, villages, households, and animals. Here, we describe the impacts of hunting on the biodiversity based on actual demographic data from one village named Crush Water. Animal population within the hunting territory of the village stabilized but Agouti/Paca dominates the landscape with little population of armadillos and peccaries. White-tailed deers

  17. Diversidad de mamíferos terrestres de talla grande y media de una selva subcaducifolia del noreste de Oaxaca, México Diversity of large and medium sized land mammals of a subcaducifolious tropical forest of north eastern of Oaxaca, Mexico

    Directory of Open Access Journals (Sweden)

    Gabriela Pérez-Irineo

    2012-03-01

    Full Text Available El estado de Oaxaca en el sureste de México alberga una biodiversidad extraordinaria. Sin embargo, las actividades humanas han propiciado alteraciones considerables, incluida la disminución de diferentes ambientes naturales, especialmente de los bosques tropicales; por ello es importante documentar la diversidad de estos ambientes, así como su respuesta a las transformaciones antropocéntricas. Este trabajo tiene como objetivo estimar la diversidad de mamíferos terrestres en una selva mediana en el noreste del estado de Oaxaca, México. Se recorrieron 3 senderos para la búsqueda de rastros, captura de organismos, avistamientos y fototrampeo de septiembre de 2007 a agosto de 2008. Se registraron 15 especies de 6 órdenes, 11 familias y 14 géneros, entre ellas 7 nuevas para la región. Las especies más abundantes fueron Nasua narica, Pecari tajacu, Dasyprocta mexicana, Cuniculus paca y Leopardus pardalis. A pesar de presentar un índice de diversidad bajo con respecto a otros estudios comparables, la presencia de especies consideradas en riesgo por la legislación mexicana, como L. pardalis, L. wiedii, Eira barbara y Tamandua mexicana hacen a la zona valiosa para la conservación de la diversidad en la región.The state of Oaxaca, in southeast Mexico is home to an extraordinary biodiversity. But human activities have led to significant changes, including reduction of different natural habitats, especially tropical forests, so it is important to document the diversity of these environments, and their response to the anthropocentric changes. Therefore, this study aimed to estimate the diversity of terrestrial mammals in a tropical forest in northeastern of the state of Oaxaca, Mexico. Three transects were walked to search for tracks, catches of organisms, sightings, and phototrapping from September 2007 to August 2008. There were recorded 15 species of 6 orders, 11 families, and 14 genera, 7 of this not previously known in the region. The

  18. Comprehensive Assessment of Oxidatively Induced Modifications of DNA in a Rat Model of Human Wilson's Disease.

    Science.gov (United States)

    Yu, Yang; Guerrero, Candace R; Liu, Shuo; Amato, Nicholas J; Sharma, Yogeshwar; Gupta, Sanjeev; Wang, Yinsheng

    2016-03-01

    Defective copper excretion from hepatocytes in Wilson's disease causes accumulation of copper ions with increased generation of reactive oxygen species via the Fenton-type reaction. Here we developed a nanoflow liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry coupled with the isotope-dilution method for the simultaneous quantification of oxidatively induced DNA modifications. This method enabled measurement, in microgram quantities of DNA, of four oxidative stress-induced lesions, including direct ROS-induced purine cyclonucleosides (cPus) and two exocyclic adducts induced by byproducts of lipid peroxidation, i.e. 1,N(6)-etheno-2'-deoxyadenosine (εdA) and 1,N(2)-etheno-2'-deoxyguanosine (εdG). Analysis of liver tissues of Long-Evans Cinnamon rats, which constitute an animal model of human Wilson's disease, and their healthy counterparts [i.e. Long-Evans Agouti rats] showed significantly higher levels of all four DNA lesions in Long-Evans Cinnamon than Long-Evans Agouti rats. Moreover, cPus were present at much higher levels than εdA and εdG lesions. In contrast, the level of 5-hydroxymethyl-2'-deoxycytidine (5-HmdC), an oxidation product of 5-methyl-2'-deoxycytidine (5-mdC), was markedly lower in the liver tissues of Long-Evans Cinnamon than Long-Evans Agouti rats, though no differences were observed for the levels of 5-mdC. In vitro biochemical assay showed that Cu(2+) ions could directly inhibit the activity of Tet enzymes. Together, these results suggest that aberrant copper accumulation may perturb genomic stability by elevating oxidatively induced DNA lesions, and by altering epigenetic pathways of gene regulation. PMID:26362317

  19. Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

    OpenAIRE

    Mayado Andrea; Torres Elisa; Gutierrez-Lopez Maria D; Colado Maria I; O'Shea Esther

    2011-01-01

    Abstract Background Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA. Methods Male Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p.) 96 h before receiving neurotoxic MDMA (12.5 mg/kg, ...

  20. Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

    OpenAIRE

    Tadashi Okamura; Xiang Yuan Pei; Ichiro Miyoshi; Yukiko Shimizu; Rieko Takanashi-Yanobu; Yasumasa Mototani; Takao Kanai; Jo Satoh; Noriko Kimura; Noriyuki Kasai

    2013-01-01

    Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA) rat derived from Long-Evans (LE) strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose into...

  1. The orphan receptor Gpr83 regulates systemic energy metabolism via ghrelin-dependent and ghrelin-independent mechanisms

    OpenAIRE

    Müller, Timo D.; Müller, Anne; Yi, Chun-Xia; M Habegger, Kirk; Meyer, Carola W.; Gaylinn, Bruce D.; Finan, Brian; Heppner, Kristy; Trivedi, Chitrang; Bielohuby, Maximilian; Abplanalp, William; Meyer, Franziska; Piechowski, Carolin L.; Pratzka, Juliane; Stemmer, Kerstin

    2013-01-01

    The G protein-coupled receptor 83 (Gpr83) is widely expressed in brain regions regulating energy metabolism. Here we report that hypothalamic expression of Gpr83 is regulated in response to nutrient availability and is decreased in obese mice compared with lean mice. In the arcuate nucleus, Gpr83 colocalizes with the ghrelin receptor (Ghsr1a) and the agouti-related protein. In vitro analyses show heterodimerization of Gpr83 with Ghsr1a diminishes activation of Ghsr1a by acyl-ghrelin. The orex...

  2. The Cytokine Ciliary Neurotrophic Factor (CNTF) Activates Hypothalamic Urocortin-Expressing Neurons Both In Vitro and In Vivo

    OpenAIRE

    Purser, Matthew J.; Dalvi, Prasad S.; Wang, Zi C.; Belsham, Denise D.

    2013-01-01

    Ciliary neurotrophic factor (CNTF) induces neurogenesis, reduces feeding, and induces weight loss. However, the central mechanisms by which CNTF acts are vague. We employed the mHypoE-20/2 line that endogenously expresses the CNTF receptor to examine the direct effects of CNTF on mRNA levels of urocortin-1, urocortin-2, agouti-related peptide, brain-derived neurotrophic factor, and neurotensin. We found that treatment of 10 ng/ml CNTF significantly increased only urocortin-1 mRNA by 1.84-fold...

  3. Genetic analysis of the cat population of north and south of cali, colombia

    OpenAIRE

    PEÑA-CRUZ, Andrés F.; SANDOVAL ARANGO, Stephania; Angie PATIÑO MONTOYA; BEDOYA, Mailyn; RODRÍGUEZ ORTIZ, Alejandra; ORJUELA VASQUEZ, Juan; Ortega, Alejandra; F. LÓPEZ, Juan; Edward MOLINA HENAO; Angélica GUZMÁN; GIL, Julian; Heiber CÁRDENAS HENAO

    2014-01-01

    The coat genetic markers and skeleton abnormalities have allowed characterize the profile from more than 400 domestic cat populations around the world. 15 years ago, that profile was established in the city of Cali (Colombia). In this study it was determined if north and south of the city are subpopulations and it was compared the total profile against past study. A decrease in allele frequency of a (non-agouti) and d (dilution) was found, but an increase of five alleles was found, especially...

  4. STEAROYL-CoA DESATURASE-1 DEFICIENCY ATTENUATES OBESITY AND INSULIN RESISTANCE IN LEPTIN-RESISTANT OBESE MICE

    OpenAIRE

    Miyazaki, Makoto; Sampath, Harini; Liu, Xueqing; Flowers, Matthew T.; Chu, Kiki; Dobrzyn, Agnieszka; Ntambi, James M.

    2009-01-01

    Obesity and adiposity greatly increase the risk for secondary conditions such as insulin resistance. Mice deficient in the enzyme stearoyl-CoA desaturase-1 (SCD1) are lean and protected from diet-induced obesity and insulin resistance. In order to determine the effect of SCD1 deficiency on various mouse models of obesity, we introduced a global deletion of the Scd1 gene into leptin-deficient ob/ob mice, leptin-resistant Agouti (Ay/a) mice, and high-fat diet-fed obese (DIO) mice. SCD1 deficien...

  5. Role of hypothalamic melanocortin system in adaptation of food intake to food protein increase in mice.

    OpenAIRE

    Pillot, Bruno; Duraffourd, Céline; Bégeot, Martine; Joly, Aurélie; Luquet, Serge; Houberdon, Isabelle; Naville, Danielle; Vigier, Michèle; Gautier-Stein, Amandine; Magnan, Christophe; Mithieux, Gilles

    2011-01-01

    The hypothalamic melanocortin system--the melanocortin receptor of type 4 (MC4R) and its ligands: α-melanin-stimulating hormone (α-MSH, agonist, inducing hypophagia), and agouti-related protein (AgRP, antagonist, inducing hyperphagia)--is considered to play a central role in the control of food intake. We tested its implication in the mediation of the hunger-curbing effects of protein-enriched diets (PED) in mice. Whereas there was a 20% decrease in food intake in mice fed on the PED, compare...

  6. Regulation of eumelanin / pheomelanin synthesis and visible pigmentation in melanocytes by ligands of the melanocortin 1 receptor

    OpenAIRE

    Le Pape, Elodie; Wakamatsu, Kazumasa; Ito, Shosuke; Wolber, Rainer; Hearing, Vincent J.

    2008-01-01

    The production of melanin in the hair and skin is tightly regulated by the melanocortin 1 receptor (MC1R) whose activation is controlled by 2 secreted ligands, α-melanocyte stimulating hormone (αMSH) and agouti signal protein (ASP). Since melanin is extremely stable, lasting years in biological tissues, the mechanism underlying the relatively rapid decrease in visible pigmentation elicited by ASP is of obvious interest. In this study, the effects of ASP and αMSH on the regulation of melanin s...

  7. Natural regeneration and dispersion of seeds of the imbuzeiro (spondias tuberosa Arruda in the Pernambuco hinterland, Brazil

    Directory of Open Access Journals (Sweden)

    Luiza Teixeira de Lima Brito

    2009-08-01

    Full Text Available This work had as objective to evaluate the dispersion of the seeds of imbuzeiro (Spondias tuberosa Arruda for the animals and the survival of plants in caatinga. The work was carried out in the period from October of 2002 to December of 2005 in degraded and native area of caatinga. They had been selected to perhaps, 16 plants of imbuzeiro, being eight plants in each area. In each plant twelve transectos of 1 m of width for 25 m had been demarcated, where the seeds found in the young ground and plants. The used experimental delineation was block-type to perhaps in factorial project 5 x 2, with four repetitions. 1003.5 seeds.m-2 had been, on average, in the first units you show of caatinga native and in caatinga degraded, it was observed, on average, 31.25 seeds m-2. In the native area of caatinga they had been registered 2.5 plants m-2, on average, in the first units you show during the rainy station. The dispersive ones of the seeds observed in the native area of catinga had been the deer-catingueiro (Mazama gouazoubira, the cotia (Dasyprocta cf. prymnolopha, caititu (Tayassu tajacu, the fox (Dusicyon thous, the teiú (Tupinambis merianae, the tatu-peba (Euphractus sexcinctus of the guará (Procyon cancrivous the area of caatinga e na área de caatinga degraded the sheep (Capra hircus.Key-words: rain, tree, seedlings, emergency, germination.

  8. Polyspecific associations between squirrel monkeys (Saimiri sciureus) and other primates in eastern Amazonia.

    Science.gov (United States)

    Pinheiro, Tatyana; Ferrari, Stephen F; Lopes, Maria Aparecida

    2011-11-01

    One of the most common types of polyspecific association observed in Neotropical primate communities is that between squirrel monkeys (Saimiri) and capuchins (Cebus). The present study focused on association patterns in two Saimiri sciureus groups in eastern Brazilian Amazonia, between March and October, 2009. The associations were analyzed in terms of the species involved, the degree of association, and niche breadth and overlap. The study involved two S. sciureus groups (B4 and GI) on the right and left bank of the Tocantins River, respectively, within the area of the Tucuruí reservoir in southeastern Pará. Relations between species were classified as associations (individuals within 50 m and moving in the same direction), and encounters (individuals within 50 m and no coordinated movement). Group B4 was in association with Cebus apella during 100% of monitoring, and with Chiropotes satanas in 20.2%. By contrast, Group GI associated with Cebus 54.8% of the time, and with Chiropotes utahickae 2.5%. Encounters with Alouatta belzebul and Saguinus niger were recorded at both sites, with Aotus azarae and Dasyprocta prymnolopha at B4, and with Callicebus moloch, Dasyproct aleporina, Mazama gouazoubira, and Nasua nasua at GI. Overall, Saimiri had a broader niche than Cebus in terms of vertical spacing and diet, but not for substrate use. This pattern did not appear to be affected by association. While group GI spent significantly (P foraging patterns at the two sites, and the varying potential benefits of association for Saimiri. PMID:21809365

  9. Diversity and habitat preference of medium and large-sized mammals in an urban forest fragment of southwestern Amazon

    Directory of Open Access Journals (Sweden)

    Luiz H. M. Borges

    2014-06-01

    Full Text Available We assessed the species composition and abundance of medium and large-sized mammals in an urban forest fragment in the Brazilian Amazon, and recorded the preference of some species for particular phytophysiognomies. We placed nine transects with 20 sand plots each in three phytophysiognomies: open rainforest with a dominance of bamboos (OFB, open rainforest with palm trees (OFP, and dense rainforest (DF. We calculated species abundance as the number of records/plot.day, in a total of 2,700 plots.day. We recorded twelve mammal species; Sylvilagus brasiliensis (Linnaeus, 1758 and Dasyprocta fuliginosa (Wagler, 1831 were the most abundant. The results differed among phytophysiognomies: DF presented the highest mammal diversity, whereas the species composition of OFP was less similar than that of other phytophysiognomies. Rodents showed higher preference for OFP and Sylvilagus brasiliensis was more abundant in OFB. The study area showed high species richness, with the occurrence of mesopredators, but there was a predominance of common species adaptable to disturbed environments, which reflects the severe isolation degree of the forest fragment and the hunting pressure that is still present.

  10. Hunting and use of terrestrial fauna used by Caiçaras from the Atlantic Forest coast (Brazil

    Directory of Open Access Journals (Sweden)

    Alves Rômulo RN

    2009-11-01

    Full Text Available Abstract Background The Brazilian Atlantic Forest is considered one of the hotspots for conservation, comprising remnants of rain forest along the eastern Brazilian coast. Its native inhabitants in the Southeastern coast include the Caiçaras (descendants from Amerindians and European colonizers, with a deep knowledge on the natural resources used for their livelihood. Methods We studied the use of the terrestrial fauna in three Caiçara communities, through open-ended interviews with 116 native residents. Data were checked through systematic observations and collection of zoological material. Results The dependence on the terrestrial fauna by Caiçaras is especially for food and medicine. The main species used are Didelphis spp., Dasyprocta azarae, Dasypus novemcinctus, and small birds (several species of Turdidae. Contrasting with a high dependency on terrestrial fauna resources by native Amazonians, the Caiçaras do not show a constant dependency on these resources. Nevertheless, the occasional hunting of native animals represents a complimentary source of animal protein. Conclusion Indigenous or local knowledge on native resources is important in order to promote local development in a sustainable way, and can help to conserve biodiversity, particularly if the resource is sporadically used and not commercially exploited.

  11. Evaluación sobre el uso de la fauna silvestre en la Tierra Comunitaria de Origen Tacana, Bolivia

    Directory of Open Access Journals (Sweden)

    Renata Tejada

    2006-10-01

    Full Text Available En el marco del proyecto del Consejo Indígena del Pueblo Tacana CIPTA,“Elaboración de una Estrategia de Desarrollo Sostenible de la TCO Tacana con base en el Manejo de los Recursos Naturales”, se realizó un diagnóstico sobre el uso de la vida silvestre en 20 comunidades tacanas en el área de su demanda territorial. Sobre la base de talleres participativos se registró un total de 181 vertebrados que son utilizados con diferentes fines. De un total de 43 especies de mamíferos que están utilizadas por los Tacana, 40 son utilizados como alimento. En el caso de las aves, 56 de 72 especies registradas para uso son utilizadas como alimento. Nueve de las 16 especies de reptiles utilizadas tienen fines alimenticios. En el caso de los peces de 50 especies registradas para algún uso, 40 son utilizadas como alimento. El resto de las especies de vertebrados registradas con algún uso son utilizadas exclusivamente con fines artesanales, medicinales y lúdicos. Las entrevistas realizadas sugieren que las especies más frecuentemente cazadas son Tapirus terrestris, Mazama americana, Dasyprocta variegata, Cuniculus paca, Pecari tajacu,Ateles chamek, Alouatta sara,Penelope jacquacu y Mitu tuberosa. Los peces más frecuentemente consumidos son Pseudoplatystoma triginun, P. fasciatum, Prochilodus nigricans y Colossoma macropomum.

  12. Monitoring the status and trends of tropical forest terrestrial vertebrate communities from camera trap data: a tool for conservation.

    Science.gov (United States)

    Ahumada, Jorge A; Hurtado, Johanna; Lizcano, Diego

    2013-01-01

    Reducing the loss of biodiversity is key to ensure the future well being of the planet. Indicators to measure the state of biodiversity should come from primary data that are collected using consistent field methods across several sites, longitudinal, and derived using sound statistical methods that correct for observation/detection bias. In this paper we analyze camera trap data collected between 2008 and 2012 at a site in Costa Rica (Volcan Barva transect) as part of an ongoing tropical forest global monitoring network (Tropical Ecology Assessment and Monitoring Network). We estimated occupancy dynamics for 13 species of mammals, using a hierarchical modeling approach. We calculated detection-corrected species richness and the Wildlife Picture Index, a promising new indicator derived from camera trap data that measures changes in biodiversity from the occupancy estimates of individual species. Our results show that 3 out of 13 species showed significant declines in occupancy over 5 years (lowland paca, Central American agouti, nine-banded armadillo). We hypothesize that hunting, competition and/or increased predation for paca and agouti might explain these patterns. Species richness and the Wildlife Picture Index are relatively stable at the site, but small herbivores that are hunted showed a decline in diversity of about 25%. We demonstrate the usefulness of longitudinal camera trap deployments coupled with modern statistical methods and advocate for the use of this approach in monitoring and developing global and national indicators for biodiversity change. PMID:24023898

  13. Monitoring the status and trends of tropical forest terrestrial vertebrate communities from camera trap data: a tool for conservation.

    Directory of Open Access Journals (Sweden)

    Jorge A Ahumada

    Full Text Available Reducing the loss of biodiversity is key to ensure the future well being of the planet. Indicators to measure the state of biodiversity should come from primary data that are collected using consistent field methods across several sites, longitudinal, and derived using sound statistical methods that correct for observation/detection bias. In this paper we analyze camera trap data collected between 2008 and 2012 at a site in Costa Rica (Volcan Barva transect as part of an ongoing tropical forest global monitoring network (Tropical Ecology Assessment and Monitoring Network. We estimated occupancy dynamics for 13 species of mammals, using a hierarchical modeling approach. We calculated detection-corrected species richness and the Wildlife Picture Index, a promising new indicator derived from camera trap data that measures changes in biodiversity from the occupancy estimates of individual species. Our results show that 3 out of 13 species showed significant declines in occupancy over 5 years (lowland paca, Central American agouti, nine-banded armadillo. We hypothesize that hunting, competition and/or increased predation for paca and agouti might explain these patterns. Species richness and the Wildlife Picture Index are relatively stable at the site, but small herbivores that are hunted showed a decline in diversity of about 25%. We demonstrate the usefulness of longitudinal camera trap deployments coupled with modern statistical methods and advocate for the use of this approach in monitoring and developing global and national indicators for biodiversity change.

  14. Behind melanocortin antagonist overexpression in the zebrafish brain: A behavioral and transcriptomic approach.

    Science.gov (United States)

    Guillot, Raúl; Cortés, Raúl; Navarro, Sandra; Mischitelli, Morena; García-Herranz, Víctor; Sánchez, Elisa; Cal, Laura; Navarro, Juan Carlos; Míguez, Jesús M; Afanasyev, Sergey; Krasnov, Aleksei; Cone, Roger D; Rotllant, Josep; Cerdá-Reverter, Jose Miguel

    2016-06-01

    Melanocortin signaling is regulated by the binding of naturally occurring antagonists, agouti-signaling protein (ASIP) and agouti-related protein (AGRP) that compete with melanocortin peptides by binding to melanocortin receptors to regulate energy balance and growth. Using a transgenic model overexpressing ASIP, we studied the involvement of melanocortin system in the feeding behaviour, growth and stress response of zebrafish. Our data demonstrate that ASIP overexpression results in enhanced growth but not obesity. The differential growth is explained by increased food intake and feeding efficiency mediated by a differential sensitivity of the satiety system that seems to involve the cocaine- and amphetamine- related transcript (CART). Stress response was similar in both genotypes. Brain transcriptome of transgenic (ASIP) vs wild type (WT) fish was compared using microarrays. WT females and males exhibited 255 genes differentially expressed (DEG) but this difference was reduced to 31 after ASIP overexpression. Statistical analysis revealed 1122 DEG when considering only fish genotype but 1066 and 981 DEG when comparing ASIP males or females with their WT counterparts, respectively. Interaction between genotype and sex significantly affected the expression of 97 genes. Several neuronal systems involved in the control of food intake were identified which displayed a differential expression according to the genotype of the fish that unravelling the flow of melanocortinergic information through the central pathways that controls the energy balance. The information provided herein will help to elucidate new central systems involved in control of obesity and should be of invaluable use for sustaining fish production systems. PMID:27156808

  15. Preliminary study on MC1R polymorphism in some cattle breeds raised in Italy

    Directory of Open Access Journals (Sweden)

    C. Renieri

    2011-03-01

    Full Text Available Most of the Western European cattle breeds consist of standardised breeds with a definite coat colour (Renieri et al., 1984. Thus coat colour could be useful to detect genetic markers for cattle breed identification. In cattle the pigmentation is determined by the distribution of two pigments: eu- and pheomelanin, producing brown or black and red to yellow pigmentation respectively. Tyrosinase, the rate-limiting enzyme involved in the synthesis of both melanins, is regulated by the melanocyte stimulating hormone (αMSH. This hormone and several other melanotropic peptides stimulate melanin formation in melanocytes by binding to the melanocortin-1-receptor (MC1R, a G-protein-coupled receptor encoded by the Extension gene (Robbins et al., 1993. In addition, the amounts of eu- and pheomelanin in the melanocyte are controlled by the agouti gene encoding the Agouti Signal Protein (ASP, that acts as an antagonist of MSH signalling through the MC1R, even if its mechanism of action is controversial (Furumura et al., 1998..........

  16. Environmentally associated ticks (Acari: Ixodidae in Campo Grande, Mato Grosso do Sul, Brazil Carrapatos (Acari: Ixodidae associados com o ambiente em Campo Grande, Mato Grosso do Sul, Brasil

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    Marcos Valério Garcia

    2013-03-01

    Full Text Available Herein, we report tick species found on wild and domestic animals and in the environment during a one-year sampling period at the Brazilian Farming Research Company beef cattle unit (Embrapa Beef Cattle, which is located within the urban area of Campo Grande, Mato Grosso do Sul, Brazil. From 55 wild hosts including six different species (Nasua nasua, Cebus spp., Cerdocyon thous, Myrmecophaga tridactyla, Tamandua tetradactyla and Dasyprocta aguti, 323 ticks were collected. Amblyomma ovale ticks were found solely on coatis, and Amblyomma nodosum was identified solely on anteaters. No ticks were found on capuchin monkeys. However, Amblyomma cajennense was found on all parasitized host species with the exception of capuchin monkeys. Giant anteaters displayed the highest infestation abundance, with a mean of 53 ticks∕animal. Environmental sampling yielded 166 adult A. cajennense ticks. The tick species found on domestic animals (Rhipicephalus (Boophilus microplus, R. sanguineus, Dermacentor nitens and A. cajennense were those typically found on these hosts in Brazil. The most prevalent tick species, A. cajennense, was found on both wild and domestic animals and was also prevalent in the environment. Thus, this tick species is the primary vector that allows pathogens to bridge wild and domestic animals in the Cerrado.Neste trabalho são descritas as espécies de carrapatos de animais selvagens e domésticos e do ambiente coletados por um ano na EMBRAPA Gado de Corte localizado na área urbana de Campo Grande, Mato Grosso do Sul, Brasil. Dos 55 hospedeiros selvagens de seis espécies diferentes (Nasua nasua, Cebus spp., Cerdocyon thous, Myrmecophaga tridactyla, Tamandua tetradactyla e Dasyprocta aguti foram coletados 323 carrapatos. Amblyomma ovale foi encontrado apenas em quatis e Amblyomma nodosum apenas sobre tamanduás. Nenhum carrapato foi encontrado sobre macacos-prego. Por outro lado, Amblyomma cajennense foi encontrado em todos os hospedeiros

  17. Observações sobre calazar em Jacobina, Bahia. VI - Investigações sobre reservatórios silvestres e comensais

    Directory of Open Access Journals (Sweden)

    I. A. Sherlock

    1988-03-01

    Full Text Available Durante os anos de 1982 a 1986, a investigação sobre mamíferos comensais e silvestres, da periferia da cidade de Jacobina, Bahia, mostrou, ao lado do escasso número de exemplares, uma reduzida variedade específica dessa fauna. Capturou-se apenas 11 espécies, entre as quais, predominou o Didelphis albiventris, que abrangeu 44% dos 213 espécimens capturados. Entre os 193 com exames já concluídos, 84 eram exemplares de D. albiventris e 2 estavam infectados pela Leishmania donovani senso lato, 1 por L. mexicana amazonensis, 1 por L. braziliensis, subespécie e 3 por Trypanosoma cruzi Também foram observadas formas suspeitas de serem amastigotas de leishmanics, nos esfregaços de órgãos de 3 exemplares de Dasyprocta aguti, 1 Cercomys cunicularius - e 1 Oryzomys eliurus. 0 restante dos exemplares, inclusive 14 de Lycalopex vetulus, estava negativo para flagelados. Apesar de reforçado por outros indicadores epidemiológicos, como a predominância específica, a freqüência domiciliar, a atratividade para a vetora Lutzomyia longipalpis, e a concomitância com casos humanos nos mesmos locais, o índice de 2,3% de infecção natural do Didelphis albiventris, não autoriza a conclusão definitiva de ser o marsupial o mais importante reservatório natural da leishmaniose visceral em Jacobina.From 1982 to 1986, investigations on the natural infection with leishmanias of the sylvatic and commensal mammals were carried out around the city of Jacobina, Bahia, one of the oldest endemic foci of visceral leishmaniasis in Brazil. The species of Marsupialia Didelphis albiventris predominated, with the rate of 44%, over the total of 213 specimens belonging to only 11 different species of mammals collected there. Among the 84 specimens of D. albiventris examined, 2(2.3% were infected with Leishmania donovani sensu lato; 1 with L. mexicana amazonensis, 1 with L. braziliensis sub species, and 3 with Trypanosoma cruzi. Also, amastigote suspected bodies were

  18. Composição e abundância relativa dos mamíferos de médio e grande porte no Parque Estadual do Turvo, Rio Grande do Sul, Brasil Composition and relative abundance of the medium-large ized mammals of Turvo State Park, Rio Grande do Sul, Brazil

    Directory of Open Access Journals (Sweden)

    Carlos B. Kasper

    2007-12-01

    Full Text Available Entre janeiro de 2005 e dezembro de 2006 foram realizados estudos sobre a composição e abundância relativa dos mamíferos de médio e grande porte do Parque Estadual do Turvo. Para tanto, foram utilizados registros de armadilhas fotográficas além de visualizações e dados sobre presença e ausência de pegadas ao longo de transectos pré-determinados. No total foram registradas 29 espécies de mamíferos de médio e grande porte, das quais Dasyprocta azarae Lichtenstein, 1823 e Sylvilagus brasiliensis (Linnaeus, 1758 foram as espécies com maior número de registros. No que se refere a Carnivora, Nasua nasua (Linnaeus, 1766 e Leopardus pardalis (Linnaeus, 1758 tiveram os maiores índices de registro, enquanto Leopardus tigrinus (Schreber, 1775, Leopardus wiedii (Schinz, 1782 e Galictis cuja (Molina 1782 os menores. Entre os ungulados apenas Pecari tajacu (Linnaeus, 1758 mostrou-se freqüente, sendo a quarta espécie em número de registros. Algumas espécies comuns em outros ambientes apresentaram baixos índices de registro no Parque Estadual do Turvo, tais como Dasypus novemcinctus Linnaeus, 1758 e Didelphis albiventris Lund, 1840. Finalmente, constata-se a provável extinção local de Tayassu pecari (Link, 1795, uma vez que não foram obtidos registros de sua presença ao longo do estudo. A conservação dos mamíferos de médio e grande porte do Parque está fortemente associada à preservação do "Corredor Verde de Misiones", que provavelmente representa uma área fonte para diversas espécies.Between January of 2005 and December of 2006, studies on the composition and relative abundance of medium and large sized mammals were carried out in Turvo State Park. Records came from camera-trapping, in addition to visualization and presence and absence data from track surveys along pre determined transects. At total, 29 species of medium-large sized mammals were listed. Of these, Dasyprocta azarae Lichtenstein, 1823 and Sylvilagus

  19. Composição e caracterização da fauna de mamíferos de médio e grande porte em uma pequena reserva de cerrado em Mato Grosso, Brasil Composition and characterization of the medium and large size mammal fauna in a small cerrado reserve in Mato Grosso, Brazil

    Directory of Open Access Journals (Sweden)

    Ednaldo Cândido Rocha

    2006-08-01

    Full Text Available Este estudo foi realizado na Reserva Biológica Municipal "Mário Viana", Nova Xavantina, MT, objetivando inventariar e avaliar a abundância e diversidade de mamíferos terrestres de médio e grande porte. Para tanto, foram realizadas duas visitas mensais a um transecto com 2.820 m de extensão, durante todo o ano de 2001, para o levantamento de pegadas (rastreamentos e outras evidências de mamíferos. Um total de 29 espécies foram registradas na área de estudo, sendo que 22 ocorreram no transecto e tiveram suas seqüências individuais de pegadas quantificadas para realização do cálculo dos índices de abundância e de diversidade de Shannon-Wiener (H'. De acordo com seus índices de abundância, as espécies foram classificadas em raras, comuns e abundantes. Dentre outras, onça-parda (Puma concolor - Linnaeus, 1771 e tatu-canastra (Priodontes maximus - Keer, 1792 mostraram-se raras; jaguatirica (Leopardus pardalis - Linnaeus, 1758, e tamanduá-bandeira (Myrmecophaga tridactyla - Linnaeus, 1758, comuns; e cutia (Dasyprocta azarae - Lichtenstein, 1823 e tapeti (Sylvilagus brasiliensis - Linnaeus, 1758, abundantes. O H' encontrado foi 2,40, sendo considerado significativo. O presente trabalho apontou que, apesar de pequena (470 ha, a área de estudo desempenha importante papel para a conservação da mastofauna da região de Nova Xavantina, MT.This study was carried out at the 'Mario Viana' Municipal Biological Reserve in Nova Xavantina, MT, aiming to make an inventory and evaluate the abundance and diversity of terrestrial mammals of medium and large size. Thus, two monthly visits were made to a 2.820 m long transect throughout 2001 to assess tracking and other evidences of mammals. Twenty-nine species were recorded in the study area, with 22 in the transect and two individual tracking sequences being quantified for calculation of the Shannon-Wiener (H' abundance and diversity indices. According to the abundance indices, the species were

  20. Observações sobre calazar em Jacobina, Bahia. VI - Investigações sobre reservatórios silvestres e comensais

    Directory of Open Access Journals (Sweden)

    I. A. Sherlock

    1988-03-01

    Full Text Available Durante os anos de 1982 a 1986, a investigação sobre mamíferos comensais e silvestres, da periferia da cidade de Jacobina, Bahia, mostrou, ao lado do escasso número de exemplares, uma reduzida variedade específica dessa fauna. Capturou-se apenas 11 espécies, entre as quais, predominou o Didelphis albiventris, que abrangeu 44% dos 213 espécimens capturados. Entre os 193 com exames já concluídos, 84 eram exemplares de D. albiventris e 2 estavam infectados pela Leishmania donovani senso lato, 1 por L. mexicana amazonensis, 1 por L. braziliensis, subespécie e 3 por Trypanosoma cruzi Também foram observadas formas suspeitas de serem amastigotas de leishmanics, nos esfregaços de órgãos de 3 exemplares de Dasyprocta aguti, 1 Cercomys cunicularius - e 1 Oryzomys eliurus. 0 restante dos exemplares, inclusive 14 de Lycalopex vetulus, estava negativo para flagelados. Apesar de reforçado por outros indicadores epidemiológicos, como a predominância específica, a freqüência domiciliar, a atratividade para a vetora Lutzomyia longipalpis, e a concomitância com casos humanos nos mesmos locais, o índice de 2,3% de infecção natural do Didelphis albiventris, não autoriza a conclusão definitiva de ser o marsupial o mais importante reservatório natural da leishmaniose visceral em Jacobina.

  1. Tyrosinase Depletion Prevents the Maturation of Melanosomes in the Mouse Hair Follicle

    Science.gov (United States)

    Paterson, Elyse K.; Fielder, Thomas J.; MacGregor, Grant R.; Ito, Shosuke; Wakamatsu, Kazumasa; Gillen, Daniel L.; Eby, Victoria; Boissy, Raymond E.; Ganesan, Anand K.

    2015-01-01

    The mechanisms that lead to variation in human skin and hair color are not fully understood. To better understand the molecular control of skin and hair color variation, we modulated the expression of Tyrosinase (Tyr), which controls the rate-limiting step of melanogenesis, by expressing a single-copy, tetracycline-inducible shRNA against Tyr in mice. Moderate depletion of TYR was sufficient to alter the appearance of the mouse coat in black, agouti, and yellow coat color backgrounds, even though TYR depletion did not significantly inhibit accumulation of melanin within the mouse hair. Ultra-structural studies revealed that the reduction of Tyr inhibited the accumulation of terminal melanosomes, and inhibited the expression of genes that regulate melanogenesis. These results indicate that color in skin and hair is determined not only by the total amount of melanin within the hair, but also by the relative accumulation of mature melanosomes. PMID:26619124

  2. Peromyscus as a Mammalian Epigenetic Model

    Directory of Open Access Journals (Sweden)

    Kimberly R. Shorter

    2012-01-01

    Full Text Available Deer mice (Peromyscus offer an opportunity for studying the effects of natural genetic/epigenetic variation with several advantages over other mammalian models. These advantages include the ability to study natural genetic variation and behaviors not present in other models. Moreover, their life histories in diverse habitats are well studied. Peromyscus resources include genome sequencing in progress, a nascent genetic map, and >90,000 ESTs. Here we review epigenetic studies and relevant areas of research involving Peromyscus models. These include differences in epigenetic control between species and substance effects on behavior. We also present new data on the epigenetic effects of diet on coat-color using a Peromyscus model of agouti overexpression. We suggest that in terms of tying natural genetic variants with environmental effects in producing specific epigenetic effects, Peromyscus models have a great potential.

  3. Tyrosinase Depletion Prevents the Maturation of Melanosomes in the Mouse Hair Follicle.

    Directory of Open Access Journals (Sweden)

    Elyse K Paterson

    Full Text Available The mechanisms that lead to variation in human skin and hair color are not fully understood. To better understand the molecular control of skin and hair color variation, we modulated the expression of Tyrosinase (Tyr, which controls the rate-limiting step of melanogenesis, by expressing a single-copy, tetracycline-inducible shRNA against Tyr in mice. Moderate depletion of TYR was sufficient to alter the appearance of the mouse coat in black, agouti, and yellow coat color backgrounds, even though TYR depletion did not significantly inhibit accumulation of melanin within the mouse hair. Ultra-structural studies revealed that the reduction of Tyr inhibited the accumulation of terminal melanosomes, and inhibited the expression of genes that regulate melanogenesis. These results indicate that color in skin and hair is determined not only by the total amount of melanin within the hair, but also by the relative accumulation of mature melanosomes.

  4. Tyrosinase Depletion Prevents the Maturation of Melanosomes in the Mouse Hair Follicle.

    Science.gov (United States)

    Paterson, Elyse K; Fielder, Thomas J; MacGregor, Grant R; Ito, Shosuke; Wakamatsu, Kazumasa; Gillen, Daniel L; Eby, Victoria; Boissy, Raymond E; Ganesan, Anand K

    2015-01-01

    The mechanisms that lead to variation in human skin and hair color are not fully understood. To better understand the molecular control of skin and hair color variation, we modulated the expression of Tyrosinase (Tyr), which controls the rate-limiting step of melanogenesis, by expressing a single-copy, tetracycline-inducible shRNA against Tyr in mice. Moderate depletion of TYR was sufficient to alter the appearance of the mouse coat in black, agouti, and yellow coat color backgrounds, even though TYR depletion did not significantly inhibit accumulation of melanin within the mouse hair. Ultra-structural studies revealed that the reduction of Tyr inhibited the accumulation of terminal melanosomes, and inhibited the expression of genes that regulate melanogenesis. These results indicate that color in skin and hair is determined not only by the total amount of melanin within the hair, but also by the relative accumulation of mature melanosomes. PMID:26619124

  5. Locked Nucleic Acid-Based In Situ Hybridization Reveals miR-7a as a Hypothalamus-Enriched MicroRNA with a Distinct Expression Pattern

    DEFF Research Database (Denmark)

    Herzer, S; Silahtaroglu, A; Meister, B

    2012-01-01

    part of the brain that controls vital bodily functions, we employed locked nucleic acid (LNA) - fluorescent in situ hybridization (FISH). The expression pattern of the mature miRNAs miR-7a, miR-7b, miR-137 and miR-153 in mouse brain tissue sections was investigated. Whereas all studied miRNAs were...... shown that miR-7a was preferentially present in small orexigenic neuropeptide Y (NPY)/agouti-related protein (AgRP)-containing-neurons located in the ventromedial aspect of the arcuate nucleus, but not in large pro-opiomelanocortin (POMC)/cocaine- and amphetamine-regulated transcript (CART...... the arcuate nucleus, a subregion with a weak blood-brain barrier, raises the possibility that miR-7a is influenced by circulating hormones and is a regulator of the genes involved in body weight control. © 2012 The Authors. Journal of Neuroendocrinology © 2012 Blackwell Publishing Ltd....

  6. Effects of "Bioactive" amino acids leucine, glutamate, arginine and tryptophan on feed intake and mRNA expression of relative neuropeptides in broiler chicks

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    Wang Songbo

    2012-08-01

    Full Text Available Abstract Feed intake control is vital to ensuring optimal nutrition and achieving full potential for growth and development in poultry. The aim of the present study was to investigate the effects of L-leucine, L-glutamate, L-tryptophan and L-arginine on feed intake and the mRNA expression levels of hypothalamic Neuropeptide involved in feed intake regulation in broiler chicks. Leucine, glutamate, tryptophan or arginine was intra-cerebroventricularly (ICV administrated to 4d-old broiler chicks respectively and the feed intake were recorded at various time points. Quantitative PCR was performed to determine the hypothalamic mRNA expression levels of Neuropeptide Y (NPY, agouti related protein (AgRP, pro-opiomelanocortin (POMC, melanocortin receptor 4 (MC4R and corticotrophin releasing factor (CRF. Our results showed that ICV administration of L-leucine (0.15 or 1.5  μmol significantly (P P 

  7. Determinants of body weight regulation in humans.

    Science.gov (United States)

    Moehlecke, Milene; Canani, Luis Henrique; Silva, Lucas Oliveira Junqueira E; Trindade, Manoel Roberto Maciel; Friedman, Rogerio; Leitão, Cristiane Bauermann

    2016-04-01

    Body weight is regulated by the ability of hypothalamic neurons to orchestrate behavioral, endocrine and autonomic responses via afferent and efferent pathways to the brainstem and the periphery. Weight maintenance requires a balance between energy intake and energy expenditure. Although several components that participate in energy homeostasis have been identified, there is a need to know in more detail their actions as well as their interactions with environmental and psychosocial factors in the development of human obesity. In this review, we examine the role of systemic mediators such as leptin, ghrelin and insulin, which act in the central nervous system by activating or inhibiting neuropeptide Y, Agouti-related peptide protein, melanocortin, transcript related to cocaine and amphetamine, and others. As a result, modifications in energy homeostasis occur through regulation of appetite and energy expenditure. We also examine compensatory changes in the circulating levels of several peripheral hormones after diet-induced weight loss. PMID:26910628

  8. Temporal profile of calcineurin phosphatase activity during acute allograft rejection in the heterotopic rat heart transplantation model

    DEFF Research Database (Denmark)

    Karamperis, N; Koefoed-Nielsen, P B; Marcussen, N;

    2008-01-01

    it can be utilized as a pharmacodynamic marker to identify and monitor the rejection process. METHODS: The heterotopic cervical rat heart transplantation model was used (dark Agouti to Lewis). We performed 25 control isogeneic and 46 allogeneic transplantations. Rats were sacrificed at various...... as a pharmacodynamic biomarker of acute allograft rejection in the heterotopic rat heart transplantation model. Further research is required in order to reveal the precise role of CaN during acute allograft rejection....... postoperative time points. CaN activity was measured in isolated peripheral blood and spleen mononuclear cells and in graft heart homogenates. CaN activity was measured as the release of radiolabeled phosphate from a previously phosphorylated 19 amino acid peptide. RESULTS: We have shown that CaN's activity...

  9. Epigenomic Adaptation to Low Dose Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Gould, Michael N. [Univ. of Wisconsin, Madison, WI (United States)

    2015-06-30

    The overall hypothesis of this grant application is that the adaptive responses elicited by low dose ionizing radiation (LDIR) result in part from heritable DNA methylation changes in the epigenome. In the final budget period at the University of Wisconsin-Madison, we will specifically address this hypothesis by determining if the epigenetically labile, differentially methylated regions (DMRs) that regulate parental-specific expression of imprinted genes are deregulated in agouti mice by low dose radiation exposure during gestation. This information is particularly important to ascertain given the 1) increased human exposure to medical sources of radiation; 2) increased number of people predicted to live and work in space; and 3) enhanced citizen concern about radiation exposure from nuclear power plant accidents and terrorist ‘dirty bombs.’

  10. Mammalian comparative sequence analysis of the Agrp locus.

    Directory of Open Access Journals (Sweden)

    Christopher B Kaelin

    Full Text Available Agouti-related protein encodes a neuropeptide that stimulates food intake. Agrp expression in the brain is restricted to neurons in the arcuate nucleus of the hypothalamus and is elevated by states of negative energy balance. The molecular mechanisms underlying Agrp regulation, however, remain poorly defined. Using a combination of transgenic and comparative sequence analysis, we have previously identified a 760 bp conserved region upstream of Agrp which contains STAT binding elements that participate in Agrp transcriptional regulation. In this study, we attempt to improve the specificity for detecting conserved elements in this region by comparing genomic sequences from 10 mammalian species. Our analysis reveals a symmetrical organization of conserved sequences upstream of Agrp, which cluster into two inverted repeat elements. Conserved sequences within these elements suggest a role for homeodomain proteins in the regulation of Agrp and provide additional targets for functional evaluation.

  11. Impact of animal strain on gene expression in a rat model of acute cardiac rejection

    Directory of Open Access Journals (Sweden)

    Norsworthy Kelly J

    2009-06-01

    Full Text Available Abstract Background The expression levels of many genes show wide natural variation among strains or populations. This study investigated the potential for animal strain-related genotypic differences to confound gene expression profiles in acute cellular rejection (ACR. Using a rat heart transplant model and 2 different rat strains (Dark Agouti, and Brown Norway, microarrays were performed on native hearts, transplanted hearts, and peripheral blood mononuclear cells (PBMC. Results In heart tissue, strain alone affected the expression of only 33 probesets while rejection affected the expression of 1368 probesets (FDR 10% and FC ≥ 3. Only 13 genes were affected by both strain and rejection, which was Conclusion In ACR, genetic background has a large impact on the transcriptome of immune cells, but not heart tissue. Gene expression studies of ACR should avoid study designs that require cross strain comparisons between leukocytes.

  12. Genetic identification of a neural circuit that suppresses appetite.

    Science.gov (United States)

    Carter, Matthew E; Soden, Marta E; Zweifel, Larry S; Palmiter, Richard D

    2013-11-01

    Appetite suppression occurs after a meal and in conditions when it is unfavourable to eat, such as during illness or exposure to toxins. A brain region proposed to play a role in appetite suppression is the parabrachial nucleus, a heterogeneous population of neurons surrounding the superior cerebellar peduncle in the brainstem. The parabrachial nucleus is thought to mediate the suppression of appetite induced by the anorectic hormones amylin and cholecystokinin, as well as by lithium chloride and lipopolysaccharide, compounds that mimic the effects of toxic foods and bacterial infections, respectively. Hyperactivity of the parabrachial nucleus is also thought to cause starvation after ablation of orexigenic agouti-related peptide neurons in adult mice. However, the identities of neurons in the parabrachial nucleus that regulate feeding are unknown, as are the functionally relevant downstream projections. Here we identify calcitonin gene-related peptide-expressing neurons in the outer external lateral subdivision of the parabrachial nucleus that project to the laterocapsular division of the central nucleus of the amygdala as forming a functionally important circuit for suppressing appetite. Using genetically encoded anatomical, optogenetic and pharmacogenetic tools, we demonstrate that activation of these neurons projecting to the central nucleus of the amygdala suppresses appetite. In contrast, inhibition of these neurons increases food intake in circumstances when mice do not normally eat and prevents starvation in adult mice whose agouti-related peptide neurons are ablated. Taken together, our data demonstrate that this neural circuit from the parabrachial nucleus to the central nucleus of the amygdala mediates appetite suppression in conditions when it is unfavourable to eat. This neural circuit may provide targets for therapeutic intervention to overcome or promote appetite. PMID:24121436

  13. Candidate Gene Analysis Suggests Untapped Genetic Complexity in Melanin-Based Pigmentation in Birds.

    Science.gov (United States)

    Bourgeois, Yann X C; Bertrand, Joris A M; Delahaie, Boris; Cornuault, Josselin; Duval, Thomas; Milá, Borja; Thébaud, Christophe

    2016-07-01

    Studies on melanin-based color variation in a context of natural selection have provided a wealth of information on the link between phenotypic and genetic variation. Here, we evaluated associations between melanic plumage patterns and genetic polymorphism in the Réunion grey white-eye (Zosterops borbonicus), a species in which mutations on MC1R do not seem to play any role in explaining melanic variation. This species exhibits 5 plumage color variants that can be grouped into 3 color forms which occupy discrete geographic regions in the lowlands of Réunion, and a fourth high-elevation form which comprises 2 color morphs (grey and brown) and represents a true color polymorphism. We conducted a comprehensive survey of sequence variation in 96 individuals at a series of 7 candidate genes other than MC1R that have been previously shown to influence melanin-based color patterns in vertebrates, including genes that have rarely been studied in a wild bird species before: POMC, Agouti, TYR, TYRP1, DCT, Corin, and SLC24A5 Of these 7 genes, 2 (Corin and TYRP1) displayed an interesting shift in allele frequencies between lowland and highland forms and a departure from mutation-drift equilibrium consistent with balancing selection in the polymorphic highland form only. Sequence variation at Agouti, a gene frequently involved in melanin-based pigmentation patterning, was not associated with color forms or morphs. Thus, we suggest that functionally important changes in loci other than those classically studied are involved in the color polymorphism exhibited by the Réunion grey white-eye and possibly many other nonmodel species. PMID:26995742

  14. Identification of a small-molecule ligand that activates the neuropeptide receptor GPR171 and increases food intake.

    Science.gov (United States)

    Wardman, Jonathan H; Gomes, Ivone; Bobeck, Erin N; Stockert, Jennifer A; Kapoor, Abhijeet; Bisignano, Paola; Gupta, Achla; Mezei, Mihaly; Kumar, Sanjai; Filizola, Marta; Devi, Lakshmi A

    2016-01-01

    Several neuropeptide systems in the hypothalamus, including neuropeptide Y and agouti-related protein (AgRP), control food intake. Peptides derived from proSAAS, a precursor implicated in the regulation of body weight, also control food intake. GPR171 is a heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) for BigLEN (b-LEN), a peptide derived from proSAAS. To facilitate studies exploring the physiological role of GPR171, we sought to identify small-molecule ligands for this receptor by performing a virtual screen of a compound library for interaction with a homology model of GPR171. We identified MS0015203 as an agonist of GPR171 and demonstrated the selectivity of MS0015203 for GPR171 by testing the binding of this compound to 80 other membrane proteins, including family A GPCRs. Reducing the expression of GPR171 by shRNA (short hairpin RNA)-mediated knockdown blunted the cellular and tissue response to MS0015203. Peripheral injection of MS0015203 into mice increased food intake and body weight, and these responses were significantly attenuated in mice with decreased expression of GPR171 in the hypothalamus. Together, these results suggest that MS0015203 is a useful tool to probe the pharmacological and functional properties of GPR171 and that ligands targeting GPR171 may eventually lead to therapeutics for food-related disorders. PMID:27245612

  15. Heparanase affects food intake and regulates energy balance in mice.

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    Linda Karlsson-Lindahl

    Full Text Available Mutation of the melanocortin-receptor 4 (MC4R is the most frequent cause of severe obesity in humans. Binding of agouti-related peptide (AgRP to MC4R involves the co-receptor syndecan-3, a heparan sulfate proteoglycan. The proteoglycan can be structurally modified by the enzyme heparanase. Here we tested the hypothesis that heparanase plays a role in food intake behaviour and energy balance regulation by analysing body weight, body composition and food intake in genetically modified mice that either lack or overexpress heparanase. We also assessed food intake and body weight following acute central intracerebroventricular administration of heparanase; such treatment reduced food intake in wildtype mice, an effect that was abolished in mice lacking MC4R. By contrast, heparanase knockout mice on a high-fat diet showed increased food intake and maturity-onset obesity, with up to a 40% increase in body fat. Mice overexpressing heparanase displayed essentially the opposite phenotypes, with a reduced fat mass. These results implicate heparanase in energy balance control via the central melanocortin system. Our data indicate that heparanase acts as a negative modulator of AgRP signaling at MC4R, through cleavage of heparan sulfate chains presumably linked to syndecan-3.

  16. Increased hypothalamic 5-HT2A receptor gene expression and effects of pharmacologic 5-HT2A receptor inactivation in obese Ay mice

    International Nuclear Information System (INIS)

    Serotonin (5-hydroxytryptamine; 5-HT) 2A receptors contribute to the effects of 5-HT on platelet aggregation and vascular smooth muscle cell proliferation, and are reportedly involved in decreases in plasma levels of adiponectin, an adipokine, in diabetic subjects. Here, we report that systemic administration of sarpogrelate, a 5-HT2A receptor antagonist, suppressed appetite and increased hypothalamic pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript, corticotropin releasing hormone, 5-HT2C, and 5-HT1B receptor gene expression. Ay mice, which have ectopic expression of the agouti protein, significantly increased hypothalamic 5-HT2A receptor gene expression in association with obesity compared with wild-type mice matched for age. Systemic administration of sarpogrelate suppressed overfeeding, body weight gain, and hyperglycemia in obese Ay mice, whereas it did not increase plasma adiponectin levels. These results suggest that obesity increases hypothalamic 5-HT2A receptor gene expression, and pharmacologic inactivation of 5-HT2A receptors inhibits overfeeding and obesity in Ay mice, but did not increase plasma adiponectin levels

  17. Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

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    Tadashi Okamura

    2013-01-01

    Full Text Available Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA rat derived from Long-Evans (LE strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction of β-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus.

  18. Use of FK506 and bone marrow mesenchymal stem cells for rat hind limb allografts

    Institute of Scientific and Technical Information of China (English)

    Youxin Song; Zhujun Wang; Zhixue Wang; Hong Zhang; Xiaohui Li; Bin Chen

    2012-01-01

    Dark Agouti rat donor hind limbs were orthotopically transplanted into Lewis rat recipients to verify the effects of bone marrow mesenchymal stem cells on neural regeneration and functional recovery of allotransplanted limbs in the microenvironment of immunotolerance. bone marrow mesenchymal stem cells were intramuscularly (gluteus maximus) injected with FK506 (tacrolimus) daily, and were transplanted to the injured nerves. Results indicated that the allograft group not receiving therapy showed severe rejection, with transplanted limbs detaching at 10 days after transplantation with complete necrosis. The number of myelinated axons and Schwann cells in the FK506 and FK506 + bone marrow mesenchymal stem cells groups were significantly increased. We observed a lesser degree of gastrocnemius muscle degeneration, and increased polymorphic fibers along with other pathological changes in the FK506 + bone marrow mesenchymal stem cells group. The FK506 + bone marrow mesenchymal stem cells group showed significantly better recovery than the autograft and FK506 groups. The results demonstrated that FK506 improved the immune microenvironment. FK506 combined with bone marrow mesenchymal stem cells significantly promoted sciatic nerve regeneration, and improved sensory recovery and motor function in hind limb allotransplant.

  19. Mouse estrous cycle identification tool and images.

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    Shannon L Byers

    Full Text Available The efficiency of producing timed pregnant or pseudopregnant mice can be increased by identifying those in proestrus or estrus. Visual observation of the vagina is the quickest method, requires no special equipment, and is best used when only proestrus or estrus stages need to be identified. Strain to strain differences, especially in coat color can make it difficult to determine the stage of the estrous cycle accurately by visual observation. Presented here are a series of images of the vaginal opening at each stage of the estrous cycle for 3 mouse strains of different coat colors: black (C57BL/6J, agouti (CByB6F1/J and albino (BALB/cByJ. When all 4 stages (proestrus, estrus, metestrus, and diestrus need to be identified, vaginal cytology is regarded as the most accurate method. An identification tool is presented to aid the user in determining the stage of estrous when using vaginal cytology. These images and descriptions are an excellent resource for learning how to determine the stage of the estrous cycle by visual observation or vaginal cytology.

  20. Orally available selective melanocortin-4 receptor antagonists stimulate food intake and reduce cancer-induced cachexia in mice.

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    Philipp Weyermann

    Full Text Available BACKGROUND: Cachexia is among the most debilitating and life-threatening aspects of cancer. It represents a metabolic syndrome affecting essential functional circuits involved in the regulation of homeostasis, and includes anorexia, fat and muscle tissue wasting. The anorexigenic peptide alpha-MSH is believed to be crucially involved in the normal and pathologic regulation of food intake. It was speculated that blockade of its central physiological target, the melanocortin (MC-4 receptor, might provide a promising anti-cachexia treatment strategy. This idea is supported by the fact that in animal studies, agouti-related protein (AgRP, the endogenous inverse agonist at the MC-4 receptor, was found to affect two hallmark features of cachexia, i.e. to increase food intake and to reduce energy expenditure. METHODOLOGY/PRINCIPAL FINDINGS: SNT207707 and SNT209858 are two recently discovered, non peptidic, chemically unrelated, orally active MC-4 receptor antagonists penetrating the blood brain barrier. Both compounds were found to distinctly increase food intake in healthy mice. Moreover, in mice subcutaneously implanted with C26 adenocarcinoma cells, repeated oral administration (starting the day after tumor implantation of each of the two compounds almost completely prevented tumor induced weight loss, and diminished loss of lean body mass and fat mass. CONCLUSIONS/SIGNIFICANCE: In contrast to the previously reported peptidic and small molecule MC-4 antagonists, the compounds described here work by the oral administration route. Orally active compounds might offer a considerable advantage for the treatment of cachexia patients.

  1. Goldfish Leptin-AI and Leptin-AII: Function and Central Mechanism in Feeding Control

    Science.gov (United States)

    Yan, Ai-Fen; Chen, Ting; Chen, Shuang; Ren, Chun-Hua; Hu, Chao-Qun; Cai, Yi-Ming; Liu, Fang; Tang, Dong-Sheng

    2016-01-01

    In mammals, leptin is a peripheral satiety factor that inhibits feeding by regulating a variety of appetite-related hormones in the brain. However, most of the previous studies examining leptin in fish feeding were performed with mammalian leptins, which share very low sequence homologies with fish leptins. To elucidate the function and mechanism of endogenous fish leptins in feeding regulation, recombinant goldfish leptin-AI and leptin-AII were expressed in methylotrophic yeast and purified by immobilized metal ion affinity chromatography (IMAC). By intraperitoneal (IP) injection, both leptin-AI and leptin-AII were shown to inhibit the feeding behavior and to reduce the food consumption of goldfish in 2 h. In addition, co-treatment of leptin-AI or leptin-AII could block the feeding behavior and reduce the food consumption induced by neuropeptide Y (NPY) injection. High levels of leptin receptor (lepR) mRNA were detected in the hypothalamus, telencephalon, optic tectum and cerebellum of the goldfish brain. The appetite inhibitory effects of leptins were mediated by downregulating the mRNA levels of orexigenic NPY, agouti-related peptide (AgRP) and orexin and upregulating the mRNA levels of anorexigenic cocaine-amphetamine-regulated transcript (CART), cholecystokinin (CCK), melanin-concentrating hormone (MCH) and proopiomelanocortin (POMC) in different areas of the goldfish brain. Our study, as a whole, provides new insights into the functions and mechanisms of leptins in appetite control in a fish model. PMID:27249000

  2. Neuropeptide co-expression in hypothalamic kisspeptin neurons of laboratory animals and the human

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    Katalin eSkrapits

    2015-02-01

    Full Text Available Hypothalamic peptidergic neurons using kisspeptin (KP and its co-transmitters for communication are critically involved in the regulation of mammalian reproduction and puberty. This article provides an overview of neuropeptides present in KP neurons, with a focus on the human species. Immunohistochemical studies reveal that large subsets of human KP neurons synthesize neurokinin B, as also shown in laboratory species. In contrast, dynorphin described in KP neurons of rodents and sheep is found rarely in KP cells of human males and postmenopausal females. Similarly, galanin is detectable in mouse, but not human, KP cells, whereas substance P, cocaine- and amphetamine-regulated transcript and proenkephalin-derived opioids are expressed in varying subsets of KP neurons in humans, but not reported in ARC of other species. Human KP neurons do not contain neurotensin, cholecystokinin, proopiomelanocortin-derivatives, agouti-related protein, neuropeptide Y, somatostatin or tyrosine hydroxylase (dopamine. These data identify the possible co-transmitters of human KP cells. Neurochemical properties distinct from those of laboratory species indicate that humans use considerably different neurotransmitter mechanisms to regulate fertility.

  3. The acute effect in rats of 3,4-methylenedioxyethamphetamine (MDEA, "eve") on body temperature and long term degeneration of 5-HT neurones in brain: a comparison with MDMA ("ecstasy").

    Science.gov (United States)

    Colado, M I; Granados, R; O'Shea, E; Esteban, B; Green, A R

    1999-06-01

    Administration of a single dose of the recreationally used drug 3,4-methylenedioxyethamphetamine (MDEA or "eve") to Dark Agouti rats resulted in an acute dose-dependent hyperthermic response. The peak effect and duration of hyperthermia of a dose of MDEA of 35 mg/kg intraperitoneally was similar to a dose of 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") of 15 mg/kg intraperitoneally. Seven days later this dose of MDMA produced a marked (approximately 50%) loss of 5-HT and its metabolite 5-HIAA in cortex, hippocampus and striatum and a similar loss of [3H]-paroxetine binding in cortex: these losses reflecting the MDMA-induced neurotoxic degeneration of 5-HT nerve endings. In contrast, administration of MDEA (15, 25 or 35 mg/kg), even at the highest dose, produced only a 20% loss in cortex and hippocampus and no decrease in striatum. The neurotoxic effect of MDEA was only weakly dose-dependent. Neither MDEA (35 mg/kg) nor MDMA (15 mg/kg) altered striatal dopamine content 7 days later. MDEA appeared to have about half the potency of MDMA in inducing acute hyperthermia and 25% of the potency in inducing degeneration of cerebral 5-HT neurones. However since higher doses of MDEA (compared to MDMA) are probably necessary to induce mood changing effects, these data do not support any contention that this compound is a "safer" recreational drug than MDMA in terms of either acute toxicity or long term neurodegeneration. PMID:10401727

  4. Pro-inflammatory cytokines play a key role in the development of radiotherapy-induced gastrointestinal mucositis

    International Nuclear Information System (INIS)

    Mucositis is a toxic side effect of anti-cancer treatments and is a major focus in cancer research. Pro-inflammatory cytokines have previously been implicated in the pathophysiology of chemotherapy-induced gastrointestinal mucositis. However, whether they play a key role in the development of radiotherapy-induced gastrointestinal mucositis is still unknown. Therefore, the aim of the present study was to characterise the expression of pro-inflammatory cytokines in the gastrointestinal tract using a rat model of fractionated radiotherapy-induced toxicity. Thirty six female Dark Agouti rats were randomly assigned into groups and received 2.5 Gys abdominal radiotherapy three times a week over six weeks. Real time PCR was conducted to determine the relative change in mRNA expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF in the jejunum and colon. Protein expression of IL-1β, IL-6 and TNF in the intestinal epithelium was investigated using qualitative immunohistochemistry. Radiotherapy-induced sub-acute damage was associated with significantly upregulated IL-1β, IL-6 and TNF mRNA levels in the jejunum and colon. The majority of pro-inflammatory cytokine protein expression in the jejunum and colon exhibited minimal change following fractionated radiotherapy. Pro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting

  5. How the leopard hides its spots: ASIP mutations and melanism in wild cats.

    Science.gov (United States)

    Schneider, Alexsandra; David, Victor A; Johnson, Warren E; O'Brien, Stephen J; Barsh, Gregory S; Menotti-Raymond, Marilyn; Eizirik, Eduardo

    2012-01-01

    The occurrence of melanism (darkening of the background coloration) is documented in 13 felid species, in some cases reaching high frequencies at the population level. Recent analyses have indicated that it arose multiple times in the Felidae, with three different species exhibiting unique mutations associated with this trait. The causative mutations in the remaining species have so far not been identified, precluding a broader assessment of the evolutionary dynamics of melanism in the Felidae. Among these, the leopard (Panthera pardus) is a particularly important target for research, given the iconic status of the 'black panther' and the extremely high frequency of melanism observed in some Asian populations. Another felid species from the same region, the Asian golden cat (Pardofelis temminckii), also exhibits frequent records of melanism in some areas. We have sequenced the coding region of the Agouti Signaling Protein (ASIP) gene in multiple leopard and Asian golden cat individuals, and identified distinct mutations strongly associated with melanism in each of them. The single nucleotide polymorphism (SNP) detected among the P. pardus individuals was caused by a nonsense mutation predicted to completely ablate ASIP function. A different SNP was identified in P. temminckii, causing a predicted amino acid change that should also induce loss of function. Our results reveal two additional cases of species-specific mutations implicated in melanism in the Felidae, and indicate that ASIP mutations may play an important role in naturally-occurring coloration polymorphism. PMID:23251368

  6. Ribosomal S6K1 in POMC and AgRP Neurons Regulates Glucose Homeostasis but Not Feeding Behavior in Mice

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    Mark A. Smith

    2015-04-01

    Full Text Available Hypothalamic ribosomal S6K1 has been suggested as a point of convergence for hormonal and nutrient signals in the regulation of feeding behavior, bodyweight, and glucose metabolism. However, the long-term effects of manipulating hypothalamic S6K1 signaling on energy homeostasis and the cellular mechanisms underlying these roles are unclear. We therefore inactivated S6K1 in pro-opiomelanocortin (POMC and agouti-related protein (AgRP neurons, key regulators of energy homeostasis, but in contrast to the current view, we found no evidence that S6K1 regulates food intake and bodyweight. In contrast, S6K1 signaling in POMC neurons regulated hepatic glucose production and peripheral lipid metabolism and modulated neuronal excitability. S6K1 signaling in AgRP neurons regulated skeletal muscle insulin sensitivity and was required for glucose sensing by these neurons. Our findings suggest that S6K1 signaling is not a general integrator of energy homeostasis in the mediobasal hypothalamus but has distinct roles in the regulation of glucose homeostasis by POMC and AgRP neurons.

  7. Energy Balance Regulating Neuropeptides Are Expressed through Pregnancy and Regulated by Interleukin-6 Deficiency in Mouse Placenta

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    Patricia Pazos

    2014-01-01

    Full Text Available The placenta produces a number of signaling molecules including metabolic and reproductive hormones as well as several inflammatory mediators. Among them, Interleukin-6 (IL-6, a well-known immune and metabolic regulator, acts peripherally modulating metabolic function and centrally increasing energy expenditure and reducing body fat. IL-6 interacts with key hypothalamic neuropeptidergic systems controlling energy homeostasis such as those producing the orexigenic/anabolic: neuropeptide Y (NPY and agouti-related peptide (AgRP and anorectic/catabolic neuropeptides: proopiomelanocortin (POMC and cocaine and amphetamine regulated transcript (CART. Human and rat placenta have been identified as source of these neuropeptides, but their expression and regulation in murine placental tissues remain unknown. Therefore, placental mRNA levels of IL-6, NPY, AgRP, POMC, and CART at different pregnancy stages (gestational days 13, 15, and 18 were analyzed by real time PCR, as were the effect of IL-6 deficiency (IL-6 knockout mice on their placental expression. Our results showed that placenta-derived neuropeptides were regulated by gestational age and IL-6 throughout the second half of mouse pregnancy. These data suggest that IL-6 may participate in the fine tune control of energy balance during pregnancy by extending its action as a metabolic signal to the main organ at the fetomaternal interface: the placenta.

  8. New inducible genetic method reveals critical roles of GABA in the control of feeding and metabolism.

    Science.gov (United States)

    Meng, Fantao; Han, Yong; Srisai, Dollada; Belakhov, Valery; Farias, Monica; Xu, Yong; Palmiter, Richard D; Baasov, Timor; Wu, Qi

    2016-03-29

    Currently available inducibleCre/loxPsystems, despite their considerable utility in gene manipulation, have pitfalls in certain scenarios, such as unsatisfactory recombination rates and deleterious effects on physiology and behavior. To overcome these limitations, we designed a new, inducible gene-targeting system by introducing an in-frame nonsense mutation into the coding sequence of Cre recombinase (nsCre). Mutant mRNAs transcribed fromnsCretransgene can be efficiently translated into full-length, functional Cre recombinase in the presence of nonsense suppressors such as aminoglycosides. In a proof-of-concept model, GABA signaling from hypothalamic neurons expressing agouti-related peptide (AgRP) was genetically inactivated within 4 d after treatment with a synthetic aminoglycoside. Disruption of GABA synthesis in AgRP neurons in young adult mice led to a dramatic loss of body weight due to reduced food intake and elevated energy expenditure; they also manifested glucose intolerance. In contrast, older mice with genetic inactivation of GABA signaling by AgRP neurons had only transient reduction of feeding and body weight; their energy expenditure and glucose tolerance were unaffected. These results indicate that GABAergic signaling from AgRP neurons plays a key role in the control of feeding and metabolism through an age-dependent mechanism. This new genetic technique will augment current tools used to elucidate mechanisms underlying many physiological and neurological processes. PMID:26976589

  9. Neuroregulation of nonexercise activity thermogenesis and obesity resistance.

    Science.gov (United States)

    Kotz, Catherine M; Teske, Jennifer A; Billington, Charles J

    2008-03-01

    High levels of spontaneous physical activity in lean people and the nonexercise activity thermogenesis (NEAT) derived from that activity appear to protect lean people from obesity during caloric challenge, while obesity in humans is characterized by dramatically reduced spontaneous physical activity. We have similarly demonstrated that obesity-resistant rats have significantly greater spontaneous physical activity than obesity-prone rats, and that spontaneous physical activity predicts body weight gain. Although the energetic cost of activity varies between types of activity and may be regulated, individual level of spontaneous physical activity is important in determining propensity for obesity. We review the current status of knowledge about the brain mechanisms involved in controlling the level of spontaneous physical activity and the NEAT so generated. Focus is on potential neural mediators of spontaneous physical activity and NEAT, including orexin A (also known as hypocretin 1), agouti-related protein, ghrelin, and neuromedin U, in addition to brief mention of neuropeptide Y, corticotrophin releasing hormone, cholecystokinin, estrogen, leptin, and dopamine effects on spontaneous physical activity. We further review evidence that strain differences in orexin stimulation pathways for spontaneous physical activity and NEAT appear to track with the body weight phenotype, thus providing a potential mechanistic explanation for reduced activity and weight gain. PMID:18160530

  10. The cytokine ciliary neurotrophic factor (CNTF activates hypothalamic urocortin-expressing neurons both in vitro and in vivo.

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    Matthew J Purser

    Full Text Available Ciliary neurotrophic factor (CNTF induces neurogenesis, reduces feeding, and induces weight loss. However, the central mechanisms by which CNTF acts are vague. We employed the mHypoE-20/2 line that endogenously expresses the CNTF receptor to examine the direct effects of CNTF on mRNA levels of urocortin-1, urocortin-2, agouti-related peptide, brain-derived neurotrophic factor, and neurotensin. We found that treatment of 10 ng/ml CNTF significantly increased only urocortin-1 mRNA by 1.84-fold at 48 h. We then performed intracerebroventricular injections of 0.5 mg/mL CNTF into mice, and examined its effects on urocortin-1 neurons post-exposure. Through double-label immunohistochemistry using specific antibodies against c-Fos and urocortin-1, we showed that central CNTF administration significantly activated urocortin-1 neurons in specific areas of the hypothalamus. Taken together, our studies point to a potential role for CNTF in regulating hypothalamic urocortin-1-expressing neurons to mediate its recognized effects on energy homeostasis, neuronal proliferaton/survival, and/or neurogenesis.

  11. Pulmonary Immune Responses to Aspergillus Fumigatus in Rats

    Institute of Scientific and Technical Information of China (English)

    MIRKOV Ivana; EL-MUZGHI Amal Atia Mhfuod; DJOKIC Jelena; NINKOV Marina; POPOV ALEKSANDROV Aleksandra; GLAMOCLIJA Jasmina; KATARANOVSKI Milena

    2014-01-01

    Objective To evaluate immunologic mechanisms underlying Aspergillus fumigatus pulmonary infections in immunocompetent Dark Agouti (DA) and Albino Oxford (AO) rats recognized as being susceptible to some inflammatory diseases in different manners. Methods Lung fungal burden (quantitative colony forming units, CFU, assay), leukocyte infiltration (histology, cell composition) and their function (phagocytosis, oxidative activity, CD11b adhesion molecule expression) and cytokine interferon-γ(IFN-γ) and interleukin-17 and-4 (IL-17 and IL-4) lung content were evaluated following infection (intratracheally, 1x107 conidia). Results Slower reduction of fungal burden was observed in AO rats in comparison with that in DA rats, which was coincided with less intense histologically evident lung cell infiltration and leukocyte recovery as well as lower level of most of the their activities including intracellular myeloperoxidase activity, the capacity of nitroblue tetrazolium salt reduction and CD11b adhesion molecule expression (except for phagocytosis of conidia) in these rats. Differential patterns of changes in proinflammatory cytokine levels (unchanged levels of IFN-γand transient increase of IL-17 in AO rats vs continuous increase of both cytokines in DA rats) and unchanged levels of IL-4 were observed. Conclusion Genetically-based differences in the pattern of antifungal lung leukocyte activities and cytokine milieu, associated with differential efficiency of fungal elimination might be useful in the future use of rat models in studies of pulmonary aspergillosis.

  12. A new species of Callicebus Thomas, 1903 (Primates, Pitheciidae from the states of Mato Grosso and Pará, Brazil

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    Juliana Gualda-Barros

    2012-01-01

    Full Text Available A new species of titi monkey, genus Callicebus Thomas, 1903, is described based on four individuals, one from a small tributary of the left bank of Rio Teles Pires, northern state of Mato Grosso, and three others from Largo do Souza, Rio Iriri, Pará, Brazil. The new species belongs to the Callicebus moloch species group, and the main diagnostic characteristics of the new species are the whitish forehead, sideburns and beard coloration, which are contiguous, forming a frame around the blackish face; overall body pelage coloration is pale grayish-brown agouti; hands, feet and tip of the tail whitish; belly and inner sides of fore and hind limbs uniformly orange. The pattern of pelage coloration and qualitative and quantitative skull morphology are described and compared to the other species of the Callicebus moloch group. Species of the Callicebus moloch group show great similarity in skull morphology and morphometrics, making the external morphological characters, specially the chromatic fields, the most reliable diagnostic trait to identify the species.

  13. A novel role for pigment genes in the stress response in rainbow trout (Oncorhynchus mykiss)

    KAUST Repository

    Khan, Uniza Wahid

    2016-07-04

    In many vertebrate species visible melanin-based pigmentation patterns correlate with high stress- and disease-resistance, but proximate mechanisms for this trait association remain enigmatic. Here we show that a missense mutation in a classical pigmentation gene, melanocyte stimulating hormone receptor (MC1R), is strongly associated with distinct differences in steroidogenic melanocortin 2 receptor (MC2R) mRNA expression between high- (HR) and low-responsive (LR) rainbow trout (Oncorhynchus mykiss). We also show experimentally that cortisol implants increase the expression of agouti signaling protein (ASIP) mRNA in skin, likely explaining the association between HR-traits and reduced skin melanin patterning. Molecular dynamics simulations predict that melanocortin 2 receptor accessory protein (MRAP), needed for MC2R function, binds differently to the two MC1R variants. Considering that mRNA for MC2R and the MC1R variants are present in head kidney cells, we hypothesized that MC2R activity is modulated in part by different binding affinities of the MC1R variants for MRAP. Experiments in mammalian cells confirmed that trout MRAP interacts with the two trout MC1R variants and MC2R, but failed to detect regulation of MC2R signaling, possibly due to high constitutive MC1R activity.

  14. Peptides: Basic determinants of reproductive functions.

    Science.gov (United States)

    Celik, Onder; Aydin, Suleyman; Celik, Nilufer; Yilmaz, Musa

    2015-10-01

    Mammalian reproduction is a costly process in terms of energy consumption. The critical information regarding metabolic status is signaled to the hypothalamus mainly through peripheral peptides from the adipose tissue and gastrointestinal tract. Changes in energy stores produce fluctuations in leptin, insulin, ghrelin and glucose signals that feedback mainly to the hypothalamus to regulate metabolism and fertility. In near future, possible effects of the nutritional status on GnRH regulation can be evaluated by measuring serum or tissue levels of leptin and ghrelin in patiens suffering from infertility. The fact that leptin and ghrelin are antagonistic in their effects on GnRH neurons, their respective agonistic and antagonistic roles make them ideal candidates to use instead of GnRH agonist and antagonist. Similarly, kisspeptin expressing neurons are likely to mediate the well-established link between energy balance and reproductive functions. Exogenous kisspeptin can be used for physiological ovarian hyperstimulation for in-vitro fertilization. Moreover, kisspeptin antagonist therapy can be used for the treatment of postmenapousal women, precocious puberty, PCOS, endometriosis and uterine fibroids. In this review, we will analyze the central mechanisms involved in the integration of metabolic information and their contribution to the control of the reproductive function. Particular attention will be paid to summarize the participation of leptin, kisspeptin, ghrelin, NPY, orexin, urocortin, VIP, insulin, galanin, galanin like peptide, oxytocin, agouti gene-related peptide, and POMC neurons in this process and their possible interactions to contribute to the metabolic control of reproduction. PMID:26074346

  15. Understanding how discrete populations of hypothalamic neurons orchestrate complicated behavioral states

    Directory of Open Access Journals (Sweden)

    Allison eGraebner

    2015-08-01

    Full Text Available A major question in systems neuroscience is how a single population of neurons can interact with the rest of the brain to orchestrate complex behavioral states. The hypothalamus contains many such discrete neuronal populations that individually regulate arousal, feeding, and drinking. For example, hypothalamic neurons that express hypocretin (Hcrt neuropeptides can sense homeostatic and metabolic factors affecting wakefulness and orchestrate organismal arousal. Neurons that express agouti-related protein (AgRP can sense the metabolic needs of the body and orchestrate a state of hunger. The organum vasculosum of the lamina terminalis (OVLT can detect the hypertonicity of blood and orchestrate a state of thirst. Each hypothalamic population is sufficient to generate complicated behavioral states through the combined efforts of distinct efferent projections. The principal challenge to understanding these brain systems is therefore to determine the individual roles of each downstream projection for each behavioral state. In recent years, the development and application of temporally precise, genetically encoded tools have greatly improved our understanding of the structure and function of these neural systems. This review will survey recent advances in our understanding of how these individual hypothalamic populations can orchestrate complicated behavioral states due to the combined efforts of individual downstream projections.

  16. Effects of risperidone treatment on the expression of hypothalamic neuropeptide in appetite regulation in Wistar rats.

    Science.gov (United States)

    Kursungoz, Canan; Ak, Mehmet; Yanik, Tulin

    2015-01-30

    Although the use of atypical antipsychotic drugs has been successful in the treatment of schizophrenia, they can cause some complications in the long-term use, including weight gain. Patients using these drugs tend to disrupt treatment primarily due to side effects. The atypical antipsychotic mechanism of action regulates a number of highly disrupted neurotransmitter pathways in the brains of psychotic patients but may also cause impairment of neurohormonal pathways in different brain areas. In this study, we investigated the circulating levels of hypothalamic neurohormones, which are related to appetite regulation; neuropeptide Y (NPY); alpha melanocyte stimulating hormone (α-MSH); cocaine and amphetamine regulated transcript (CART); agouti-related peptide (AgRP); and leptin in male Wistar rats, which were treated with risperidone, a serotonin antagonist, for four weeks. Alterations in the mRNA expression levels of these candidate genes in the hypothalamus were also analyzed. We hypothesized that risperidone treatment might alter both hypothalamic and circulating levels of neuropeptides through serotonergic antagonism, resulting in weight gain. Gene expression studies revealed that the mRNA expression levels of proopiomelanocortin (POMC), AgRP, and NPY decreased as well as their plasma levels, except for NPY. Unexpectedly, CART mRNA levels increased when their plasma levels decreased. Because POMC neurons express the serotonin receptor (5HT2C), the serotonergic antagonism of risperidone on POMC neurons may cause an increase in appetite and thus increase food consumption even in a short-term trial in rats. PMID:25449893

  17. Transgenic n-3 PUFAs enrichment leads to weight loss via modulating neuropeptides in hypothalamus.

    Science.gov (United States)

    Ma, Shuangshuang; Ge, Yinlin; Gai, Xiaoying; Xue, Meilan; Li, Ning; Kang, Jingxuan; Wan, Jianbo; Zhang, Jinyu

    2016-01-12

    Body weight is related to fat mass, which is associated with obesity. Our study explored the effect of fat-1 gene on body weight in fat-1 transgenic mice. In present study, we observed that the weight/length ratio of fat-1 transgenic mice was lower than that of wild-type mice. The serum levels of triglycerides (TG), cholesterol (CT), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and blood glucose (BG) in fat-1 transgenic mice were all decreased. The weights of peri-bowels fat, perirenal fat and peri-testicular fat in fat-1 transgenic mice were reduced. We hypothesized that increase of n-3 PUFAs might alter the expression of hypothalamic neuropeptide genes and lead to loss of body weight in fat-1 transgenic mice. Therefore, we measured mRNA levels of appetite neuropeptides, Neuropeptide Y (NPY), Agouti-related peptides (AgRP), Proopiomelanocortin (POMC), Cocaine and amphetamine regulated transcript (CART), ghrelin and nesfatin-1 in hypothalamus by real-time PCR. Compared with wild-type mice, the mRNA levels of CART, POMC and ghrelin were higher, while the mRNA levels of NPY, AgRP and nesfatin-1 were lower in fat-1 transgenic mice. The results indicate that fat-1 gene or n-3 PUFAs participates in regulation of body weight, and the mechanism of this phenomenon involves the expression of appetite neuropeptides and lipoproteins in fat-1 transgenic mice. PMID:26610903

  18. Glucocorticoids inhibited hypothalamic target of rapamycin in high fat diet-fed chicks.

    Science.gov (United States)

    Liu, L; Wang, X; Jiao, H; Zhao, J; Lin, H

    2015-09-01

    The present study was conducted with broiler chicks exposed to dexamethasone (DEX) to explore its effects on hypothalamic target of rapamycin (TOR) signaling and regulating appetite in diets containing different energy levels. At 5 d age, 48 chicks were divided into one of 4 groups: high-fat diet (HFD) or low-fat diet (LFD) and intracerebroventricular (ICV) injected with either dexamethasone (DEX; 4 μg/2 μL) or saline at 10 d age. The results showed that DEX significantly inhibited gene expression of cocaine- and amphetamine-regulated transcripts (CART), melanocortin receptor 4 (MC4R), and corticotropin-releasing hormone (CRH), and inhibited the protein level of the phospho-TOR compared with the control in HFD-fed chicks (P0.05). After DEX treatment, hypothalamic agouti-related peptide levels were decreased significantly in HFD-fed chicks (P0.05). Compared to the control, DEX-treated chicks did not present any significant changes in neuropeptide Y gene expression with either HFD or LFD (P>0.05), but pro-opiomelanocortin levels were depressed by ICV DEX treatment with both diets (Pgene expression of CART, CRH, and MC4R in HFD-fed chicks, suggesting that the regulatory network formed by these genes is associated with the appetite control during stress. The TOR pathway may be involved in the regulation of GC on appetite-related genes. PMID:26188033

  19. Goldfish Leptin-AI and Leptin-AII: Function and Central Mechanism in Feeding Control.

    Science.gov (United States)

    Yan, Ai-Fen; Chen, Ting; Chen, Shuang; Ren, Chun-Hua; Hu, Chao-Qun; Cai, Yi-Ming; Liu, Fang; Tang, Dong-Sheng

    2016-01-01

    In mammals, leptin is a peripheral satiety factor that inhibits feeding by regulating a variety of appetite-related hormones in the brain. However, most of the previous studies examining leptin in fish feeding were performed with mammalian leptins, which share very low sequence homologies with fish leptins. To elucidate the function and mechanism of endogenous fish leptins in feeding regulation, recombinant goldfish leptin-AI and leptin-AII were expressed in methylotrophic yeast and purified by immobilized metal ion affinity chromatography (IMAC). By intraperitoneal (IP) injection, both leptin-AI and leptin-AII were shown to inhibit the feeding behavior and to reduce the food consumption of goldfish in 2 h. In addition, co-treatment of leptin-AI or leptin-AII could block the feeding behavior and reduce the food consumption induced by neuropeptide Y (NPY) injection. High levels of leptin receptor (lepR) mRNA were detected in the hypothalamus, telencephalon, optic tectum and cerebellum of the goldfish brain. The appetite inhibitory effects of leptins were mediated by downregulating the mRNA levels of orexigenic NPY, agouti-related peptide (AgRP) and orexin and upregulating the mRNA levels of anorexigenic cocaine-amphetamine-regulated transcript (CART), cholecystokinin (CCK), melanin-concentrating hormone (MCH) and proopiomelanocortin (POMC) in different areas of the goldfish brain. Our study, as a whole, provides new insights into the functions and mechanisms of leptins in appetite control in a fish model. PMID:27249000

  20. Perinatal stress: characteristics and effects on adult eating behavior

    Directory of Open Access Journals (Sweden)

    Matilde Cesiana da Silva

    2013-08-01

    Full Text Available Many studies have pointed out the importance of mother-child interaction in the early months of life. A few decades ago, a method called kangaroo care was developed and its main goal was to keep underweight or premature newborns in direct contact with the mother. This method has reduced the morbidity and mortality of these newborns, increasing their growth rate, breastfeeding time and mother-child contact. In rodents, the dam's presence is crucial for avoiding aggression factors that may trigger phenotypic adaptations in the pups with irreversible morphological, functional and behavioral consequences. Eating behavior is an adaptive response stemming from the external environment demand and modulated by opportunities and limitations imposed by the external environment. This behavior is regulated by a complex interaction of peripheral and central mechanisms that control hunger and satiety. The hypothalamus is a brain structure that integrates central and peripheral signals to regulate energy homeostasis and body weight. The hypothalamic nucleus have orexigenic peptides, such as neuropeptide Y and the Agouti-related peptide, and anorexigenic peptides, such as cocaine and amphetamine regulated transcript and proopiomelanocortin. An innovative study of eating behavior in experimental models of neonatal stress separates the mother from the offspring during lactation. This review describes the effects of stress during the neonatal period on general physiological factors, particularly on the control of eating behavior.

  1. Glutamate and GABA as rapid effectors of hypothalamic peptidergic neurons

    Directory of Open Access Journals (Sweden)

    Cornelia eSchöne

    2012-11-01

    Full Text Available Vital hypothalamic neurons regulating hunger, wakefulness, reward-seeking, and body weight are often defined by unique expression of hypothalamus-specific neuropeptides. Gene-ablation studies show that some of these peptides, notably orexin/hypocretin (hcrt/orx, are themselves critical for stable states of consciousness and metabolic health. However, neuron-ablation studies often reveal more severe phenotypes, suggesting key roles for co-expressed transmitters. Indeed, most hypothalamic neurons, including hcrt/orx cells, contain fast transmitters glutamate and GABA, as well as several neuropeptides. What are the roles and relations between different transmitters expressed by the same neuron? Here, we consider signaling codes for releasing different transmitters in relation to transmitter and receptor diversity in behaviorally-defined, widely-projecting peptidergic neurons, such as hcrt/orx cells. We then discuss latest optogenetic studies of endogenous transmitter release from defined sets of axons in situ, which suggest that recently-characterized vital peptidergic neurons (e.g. hcrt/orx, proopiomelanocortin , and agouti-related peptide cells, as well as classical modulatory neurons (e.g. dopamine and acetylcholine cells, all use fast transmitters to control their postsynaptic targets. These optogenetic insights are complemented by recent observations of behavioral deficiencies caused by genetic ablation of fast transmission from specific neuropeptidergic and aminergic neurons. Powerful and fast (millisecond-scale GABAergic and glutamatergic signaling from neurons previously considered to be primarily modulatory raises new questions about the roles of slower co-transmitters they co-express.

  2. Antigen dose and strain variation as factors in the genetic control of the immune response to sperm whale myoglobin

    International Nuclear Information System (INIS)

    The primary and secondary immune response to the antigen sperm whale myoglobin was investigated in DBA/2, 129 and B10.BR mice over a dose range of immunization from 10 to 2000 μg. Using an antigen excess technique, the quantity of antibody produced after secondary immunization followed a sigmoidal dose-response curve and the maximal plateau level was found to be different for each strain of mice. Furthermore, the genetic control of the immune response was investigated in twelve different inbred strains of mice following secondary immunization with 500 μg of of myoglobin. A continuous distribution for the mean antibody responses was obtained for the twelve different strains of mice. High responsiveness was associated with H-2 haplotypes d, f and k located on chromosome 17, the non-agouti gene 'a' located on chromosome 2 and the chinchilla gene 'csup(ch)' located on chromosome 7. It is concluded that either a large number of IR-genes to myoglobin are present in many loci located on different chromosomes or the antibody differences could be explained by a cross-tolerance mechanism requiring no IR-genes at all. (author)

  3. Failure to upregulate Agrp and Orexin in response to activity based anorexia in weight loss vulnerable rats characterized by passive stress coping and prenatal stress experience.

    Science.gov (United States)

    Boersma, Gretha J; Liang, Nu-Chu; Lee, Richard S; Albertz, Jennifer D; Kastelein, Anneke; Moody, Laura A; Aryal, Shivani; Moran, Timothy H; Tamashiro, Kellie L

    2016-05-01

    We hypothesize that anorexia nervosa (AN) poses a physiological stress. Therefore, the way an individual copes with stress may affect AN vulnerability. Since prenatal stress (PNS) exposure alters stress responsivity in offspring this may increase their risk of developing AN. We tested this hypothesis using the activity based anorexia (ABA) rat model in control and PNS rats that were characterized by either proactive or passive stress-coping behavior. We found that PNS passively coping rats ate less and lost more weight during the ABA paradigm. Exposure to ABA resulted in higher baseline corticosterone and lower insulin levels in all groups. However, leptin levels were only decreased in rats with a proactive stress-coping style. Similarly, ghrelin levels were increased only in proactively coping ABA rats. Neuropeptide Y (Npy) expression was increased and proopiomelanocortin (Pomc) expression was decreased in all rats exposed to ABA. In contrast, agouti-related peptide (Agrp) and orexin (Hctr) expression were increased in all but the PNS passively coping ABA rats. Furthermore, DNA methylation of the orexin gene was increased after ABA in proactive coping rats and not in passive coping rats. Overall our study suggests that passive PNS rats have innate impairments in leptin and ghrelin in responses to starvation combined with prenatal stress associated impairments in Agrp and orexin expression in response to starvation. These impairments may underlie decreased food intake and associated heightened body weight loss during ABA in the passively coping PNS rats. PMID:26907996

  4. Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Stanisavljević, S; Lukić, J; Momčilović, M; Miljković, M; Jevtić, B; Kojić, M; Golić, N; Mostarica Stojković, M; Miljković, D

    2016-06-01

    Gut microbiota and gut-associated lymphoid tissue have been increasingly appreciated as important players in pathogenesis of various autoimmune diseases, including multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis that can be induced with an injection of spinal cord homogenate emulsified in complete Freund's adjuvant in Dark Agouti (DA) rats, but not in Albino Oxford (AO) rats. In this study, mesenteric lymph nodes (MLN), Peyer's patches (PP) and gut microbiota were analysed in these two rat strains. There was higher proportion of CD4(+) T cells and regulatory T cells in non-immunised DA rats in comparison to AO rats. Also, DA rat MLN and PP cells were higher producers of pro-inflammatory cytokines interferon-γ and interleukin-17. Finally, microbial analyses showed that uncultivated species of Turicibacter and Atopostipes genus were exclusively present in AO rats, in faeces and intestinal tissue, respectively. Thus, it is clear that in comparison of an EAE-susceptible with an EAE-resistant strain of rats, various discrepancies at the level of gut associated lymphoid tissue, as well as at the level of gut microbiota can be observed. Future studies should determine if the differences have functional significance for EAE pathogenesis. PMID:26839070

  5. Donor Heart Treatment With COMP-Ang1 Limits Ischemia-Reperfusion Injury and Rejection of Cardiac Allografts.

    Science.gov (United States)

    Syrjälä, S O; Nykänen, A I; Tuuminen, R; Raissadati, A; Keränen, M A I; Arnaudova, R; Krebs, R; Koh, G Y; Alitalo, K; Lemström, K B

    2015-08-01

    The major cause of death during the first year after heart transplantation is primary graft dysfunction due to preservation and ischemia-reperfusion injury (IRI). Angiopoietin-1 is a Tie2 receptor-binding paracrine growth factor with anti-inflammatory properties and indispensable roles in vascular development and stability. We used a stable variant of angiopoietin-1 (COMP-Ang1) to test whether ex vivo intracoronary treatment with a single dose of COMP-Ang1 in donor Dark Agouti rat heart subjected to 4-h cold ischemia would prevent microvascular dysfunction and inflammatory responses in the fully allogeneic recipient Wistar Furth rat. COMP-Ang1 reduced endothelial cell-cell junction disruption of the donor heart in transmission electron microscopy during 4-h cold ischemia, improved myocardial reflow, and reduced microvascular leakage and cardiomyocyte injury of transplanted allografts during IRI. Concurrently, the treatment reduced expression of danger signals, dendritic cell maturation markers, endothelial cell adhesion molecule VCAM-1 and RhoA/Rho-associated protein kinase activation and the influx of macrophages and neutrophils. Furthermore, COMP-Ang1 treatment provided sustained anti-inflammatory effects during acute rejection and prevented the development of cardiac fibrosis and allograft vasculopathy. These results suggest donor heart treatment with COMP-Ang1 having important clinical implications in the prevention of primary and subsequent long-term injury and dysfunction in cardiac allografts. PMID:25932532

  6. Targeted disruption of the mouse adenine phosphoribosyltransferase (aprt) gene and the production of APRT-deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Engle, S.J.; Chen, J.; Tischfield, J.A. [Indiana Univ., School of Medicine, Indianapolis, IN (United States)] [and others

    1994-09-01

    Adenine phosphoribosyltransferase (APRT: EC 2.4.2.7), a ubiquitously expressed purine salvage enzyme, catalyzes the synthesis of AMP and inorganic pyrophosphate from existing adenine and 5-phosphoribosyl-1-pyrophosphate. Deficiency of this enzyme in humans results in the accumulation of 2,8-dihydroxyadenine leading to crystalluria and nephrolithiasis. In order to facilitate our study of this rare, autosomal recessive disorder, we applied the advances in gene targeting technology and mouse embryonic stem (ES) cell culture to the production of APRT-deficient mice. A positive-negative targeting strategy was used. The tageting vector contain 5.6 kb of the mouse APRT gene, a neomycin resistance gene in exon 3 as a positive selection marker, and a HSV thymidine kinase gene at the 3{prime} end of the homology as a negative selection marker. The vector was introduced into D3 ES cells by electroporation and the cells were selected for G418 and ganciclovir (GANC) resistance. G418-GANC resistant clones were screened by Southern blot. One of several correctly targeted clones was expanded and used for blastocyst microinjection to produce chimeric mice. Chimeric animals were bred and agouti progeny heterozygous for the targeted allele were obtained. Heterozygous animals have been bred to produce APRT-deficient animals. Matings are currently underway to determine the phenotype of APRT/HPRT-deficient animals.

  7. A 6-bp deletion in exon 8 and two mutations in introns of TYRP1 are associated with blond coat color in Liangshan pigs.

    Science.gov (United States)

    Wu, Xiaoqian; Zhang, Yi; Shen, Linyuan; Du, Jingjing; Luo, Jia; Liu, Chendong; Pu, Qiang; Yang, Runlin; Li, Xuewei; Bai, Lin; Tang, Guoqing; Zhang, Shunhua; Zhu, Li

    2016-03-01

    Melanocortin receptor 1 (MC1R), Agouti signaling protein (ASIP), and Tyrosinase-related protein 1 (TYRP1) are reported critical genes that regulate pheomelanin and eumelanin synthesis in mammals. Liangshan pig is a special Chinese indigenous pig breed with two completely different coat colors, solid black and blond. In this study, we detected polymorphisms of the above three genes and assessed the relationships between the variations and coat color phenotypes in Liangshan pigs. The findings revealed that the blond phenotype of Liangshan pig was related to dominant mutations in TYRP1, but not related to mutations in MC1R or ASIP. We found three closely linked mutations in TYRP1, g.8406G>A in intron 4, g.11100A>G in intron 5, and g.17599_17604del in exon 8, that were completely associated with blond coat color in Liangshan pigs. Further analysis revealed that a 6-bp deletion mutation resulted in deletion of Met and Gly residues at positions 495 and 496 in TYRP1 protein, and altered the structure of transmembrane domain of TYRP1. Together, our findings indicated that these three mutations in TYRP1 cause the blond phenotype in Liangshan pigs. PMID:26680103

  8. Melanocortin 1 Receptor: Structure, Function, and Regulation

    Science.gov (United States)

    Wolf Horrell, Erin M.; Boulanger, Mary C.; D’Orazio, John A.

    2016-01-01

    The melanocortin 1 receptor (MC1R) is a melanocytic Gs protein coupled receptor that regulates skin pigmentation, UV responses, and melanoma risk. It is a highly polymorphic gene, and loss of function correlates with a fair, UV-sensitive, and melanoma-prone phenotype due to defective epidermal melanization and sub-optimal DNA repair. MC1R signaling, achieved through adenylyl cyclase activation and generation of the second messenger cAMP, is hormonally controlled by the positive agonist melanocortin, the negative agonist agouti signaling protein, and the neutral antagonist β-defensin 3. Activation of cAMP signaling up-regulates melanin production and deposition in the epidermis which functions to limit UV penetration into the skin and enhances nucleotide excision repair (NER), the genomic stability pathway responsible for clearing UV photolesions from DNA to avoid mutagenesis. Herein we review MC1R structure and function and summarize our laboratory’s findings on the molecular mechanisms by which MC1R signaling impacts NER. PMID:27303435

  9. A high-throughput fluorescence-based assay system for appetite-regulating gene and drug screening.

    Directory of Open Access Journals (Sweden)

    Yasuhito Shimada

    Full Text Available The increasing number of people suffering from metabolic syndrome and obesity is becoming a serious problem not only in developed countries, but also in developing countries. However, there are few agents currently approved for the treatment of obesity. Those that are available are mainly appetite suppressants and gastrointestinal fat blockers. We have developed a simple and rapid method for the measurement of the feeding volume of Danio rerio (zebrafish. This assay can be used to screen appetite suppressants and enhancers. In this study, zebrafish were fed viable paramecia that were fluorescently-labeled, and feeding volume was measured using a 96-well microplate reader. Gene expression analysis of brain-derived neurotrophic factor (bdnf, knockdown of appetite-regulating genes (neuropeptide Y, preproinsulin, melanocortin 4 receptor, agouti related protein, and cannabinoid receptor 1, and the administration of clinical appetite suppressants (fluoxetine, sibutramine, mazindol, phentermine, and rimonabant revealed the similarity among mechanisms regulating appetite in zebrafish and mammals. In combination with behavioral analysis, we were able to evaluate adverse effects on locomotor activities from gene knockdown and chemical treatments. In conclusion, we have developed an assay that uses zebrafish, which can be applied to high-throughput screening and target gene discovery for appetite suppressants and enhancers.

  10. Plasticity of the melanocortin system: determinants and possible consequences on food intake

    Directory of Open Access Journals (Sweden)

    Danaé eNuzzaci

    2015-09-01

    Full Text Available The melanocortin system is one of the most important neuronal pathways involved in the regulation of food intake and is probably the best characterized. Agouti-related peptide (AgRP and proopiomelanocortin (POMC expressing neurons located in the arcuate nucleus of the hypothalamus are key elements of this system. These two neuronal populations are sensitive to circulating molecules and receive many excitatory and inhibitory inputs from various brain areas. According to sensory and metabolic information they integrate, these neurons control different aspects of feeding behavior and orchestrate autonomic responses aimed at maintaining energy homeostasis. Interestingly, composition and abundance of pre-synaptic inputs onto arcuate AgRP and POMC neurons vary in the adult hypothalamus in response to changes in the metabolic state, a phenomenon that can be recapitulated by treatment with hormones such as leptin or ghrelin. As described in other neuroendrocrine systems, glia might be determinant to shift the synaptic configuration of AgRP and POMC neurons. Here, we discuss the physiological outcome of the synaptic plasticity of the melanocortin system, and more particularly its contribution to the control of energy balance. The discovery of this attribute has changed how we view obesity and related disorders, and opens new perspectives for their management.

  11. Melanocortin 1 Receptor: Structure, Function and Regulation

    Directory of Open Access Journals (Sweden)

    Erin Marissa Wolf Horrell

    2016-05-01

    Full Text Available The melanocortin 1 receptor (MC1R is a melanocytic Gs protein coupled receptor that regulates skin pigmentation, UV responses, and melanoma risk. It is a highly polymorphic gene, and loss of function correlates with a fair, UV-sensitive, and melanoma-prone phenotype due to defective epidermal melanization and sub-optimal DNA repair. MC1R signaling, achieved through adenylyl cyclase activation and generation of the second messenger cAMP, is hormonally controlled by the positive agonist melanocortin, the negative agonist agouti signaling protein, and the neutral antagonist β-defensin 3. Activation of cAMP signaling up-regulates melanin production and deposition in the epidermis which functions to limit UV penetration into the skin and enhances nucleotide excision repair, the genomic stability pathway responsible for clearing UV photolesions from DNA to avoid mutagenesis. Herein we review MC1R structure and function and summarize our laboratory’s findings on the molecular mechanisms by which MC1R signaling impacts nucleotide excision repair.

  12. Recurrent evolution of melanism in South American felids.

    Directory of Open Access Journals (Sweden)

    Alexsandra Schneider

    2015-02-01

    Full Text Available Morphological variation in natural populations is a genomic test bed for studying the interface between molecular evolution and population genetics, but some of the most interesting questions involve non-model organisms that lack well annotated reference genomes. Many felid species exhibit polymorphism for melanism but the relative roles played by genetic drift, natural selection, and interspecies hybridization remain uncertain. We identify mutations of Agouti signaling protein (ASIP or the Melanocortin 1 receptor (MC1R as independent causes of melanism in three closely related South American species: the pampas cat (Leopardus colocolo, the kodkod (Leopardus guigna, and Geoffroy's cat (Leopardus geoffroyi. To assess population level variation in the regions surrounding the causative mutations we apply genomic resources from the domestic cat to carry out clone-based capture and targeted resequencing of 299 kb and 251 kb segments that contain ASIP and MC1R, respectively, from 54 individuals (13-21 per species, achieving enrichment of ~500-2500-fold and ~150x coverage. Our analysis points to unique evolutionary histories for each of the three species, with a strong selective sweep in the pampas cat, a distinctive but short melanism-specific haplotype in the Geoffroy's cat, and reduced nucleotide diversity for both ancestral and melanism-bearing chromosomes in the kodkod. These results reveal an important role for natural selection in a trait of longstanding interest to ecologists, geneticists, and the lay community, and provide a platform for comparative studies of morphological variation in other natural populations.

  13. Effects of hypothalamic neurodegeneration on energy balance.

    Directory of Open Access Journals (Sweden)

    Allison Wanting Xu

    2005-12-01

    Full Text Available Normal aging in humans and rodents is accompanied by a progressive increase in adiposity. To investigate the role of hypothalamic neuronal circuits in this process, we used a Cre-lox strategy to create mice with specific and progressive degeneration of hypothalamic neurons that express agouti-related protein (Agrp or proopiomelanocortin (Pomc, neuropeptides that promote positive or negative energy balance, respectively, through their opposing effects on melanocortin receptor signaling. In previous studies, Pomc mutant mice became obese, but Agrp mutant mice were surprisingly normal, suggesting potential compensation by neuronal circuits or genetic redundancy. Here we find that Pomc-ablation mice develop obesity similar to that described for Pomc knockout mice, but also exhibit defects in compensatory hyperphagia similar to what occurs during normal aging. Agrp-ablation female mice exhibit reduced adiposity with normal compensatory hyperphagia, while animals ablated for both Pomc and Agrp neurons exhibit an additive interaction phenotype. These findings provide new insight into the roles of hypothalamic neurons in energy balance regulation, and provide a model for understanding defects in human energy balance associated with neurodegeneration and aging.

  14. Hypothalamic POMC Deficiency Improves Glucose Tolerance Despite Insulin Resistance by Increasing Glycosuria.

    Science.gov (United States)

    Chhabra, Kavaljit H; Adams, Jessica M; Fagel, Brian; Lam, Daniel D; Qi, Nathan; Rubinstein, Marcelo; Low, Malcolm J

    2016-03-01

    Hypothalamic proopiomelanocortin (POMC) is essential for the physiological regulation of energy balance; however, its role in glucose homeostasis remains less clear. We show that hypothalamic arcuate nucleus (Arc)POMC-deficient mice, which develop severe obesity and insulin resistance, unexpectedly exhibit improved glucose tolerance and remain protected from hyperglycemia. To explain these paradoxical phenotypes, we hypothesized that an insulin-independent pathway is responsible for the enhanced glucose tolerance. Indeed, the mutant mice demonstrated increased glucose effectiveness and exaggerated glycosuria relative to wild-type littermate controls at comparable blood glucose concentrations. Central administration of the melanocortin receptor agonist melanotan II in mutant mice reversed alterations in glucose tolerance and glycosuria, whereas, conversely, administration of the antagonist Agouti-related peptide (Agrp) to wild-type mice enhanced glucose tolerance. The glycosuria of ArcPOMC-deficient mice was due to decreased levels of renal GLUT 2 (rGLUT2) but not sodium-glucose cotransporter 2 and was associated with reduced renal catecholamine content. Epinephrine treatment abolished the genotype differences in glucose tolerance and rGLUT2 levels, suggesting that reduced renal sympathetic nervous system (SNS) activity is the underlying mechanism for the observed glycosuria and improved glucose tolerance in ArcPOMC-deficient mice. Therefore, the ArcPOMC-SNS-rGLUT2 axis is potentially an insulin-independent therapeutic target to control diabetes. PMID:26467632

  15. Neuroendorine and Epigentic Mechanisms Subserving Autonomic Imbalance and HPA Dysfunction in the Metabolic Syndrome

    Science.gov (United States)

    Lemche, Erwin; Chaban, Oleg S.; Lemche, Alexandra V.

    2016-01-01

    Impact of environmental stress upon pathophysiology of the metabolic syndrome (MetS) has been substantiated by epidemiological, psychophysiological, and endocrinological studies. This review discusses recent advances in the understanding of causative roles of nutritional factors, sympathomedullo-adrenal (SMA) and hypothalamic-pituitary adrenocortical (HPA) axes, and adipose tissue chronic low-grade inflammation processes in MetS. Disturbances in the neuroendocrine systems for leptin, melanocortin, and neuropeptide Y (NPY)/agouti-related protein systems have been found resulting directly in MetS-like conditions. The review identifies candidate risk genes from factors shown critical for the functioning of each of these neuroendocrine signaling cascades. In its meta-analytic part, recent studies in epigenetic modification (histone methylation, acetylation, phosphorylation, ubiquitination) and posttranscriptional gene regulation by microRNAs are evaluated. Several studies suggest modification mechanisms of early life stress (ELS) and diet-induced obesity (DIO) programming in the hypothalamic regions with populations of POMC-expressing neurons. Epigenetic modifications were found in cortisol (here HSD11B1 expression), melanocortin, leptin, NPY, and adiponectin genes. With respect to adiposity genes, epigenetic modifications were documented for fat mass gene cluster APOA1/C3/A4/A5, and the lipolysis gene LIPE. With regard to inflammatory, immune and subcellular metabolism, PPARG, NKBF1, TNFA, TCF7C2, and those genes expressing cytochrome P450 family enzymes involved in steroidogenesis and in hepatic lipoproteins were documented for epigenetic modifications. PMID:27147943

  16. A novel role for pigment genes in the stress response in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Khan, Uniza Wahid; Øverli, Øyvind; Hinkle, Patricia M; Pasha, Farhan Ahmad; Johansen, Ida Beitnes; Berget, Ingunn; Silva, Patricia I M; Kittilsen, Silje; Höglund, Erik; Omholt, Stig W; Våge, Dag Inge

    2016-01-01

    In many vertebrate species visible melanin-based pigmentation patterns correlate with high stress- and disease-resistance, but proximate mechanisms for this trait association remain enigmatic. Here we show that a missense mutation in a classical pigmentation gene, melanocyte stimulating hormone receptor (MC1R), is strongly associated with distinct differences in steroidogenic melanocortin 2 receptor (MC2R) mRNA expression between high- (HR) and low-responsive (LR) rainbow trout (Oncorhynchus mykiss). We also show experimentally that cortisol implants increase the expression of agouti signaling protein (ASIP) mRNA in skin, likely explaining the association between HR-traits and reduced skin melanin patterning. Molecular dynamics simulations predict that melanocortin 2 receptor accessory protein (MRAP), needed for MC2R function, binds differently to the two MC1R variants. Considering that mRNA for MC2R and the MC1R variants are present in head kidney cells, we hypothesized that MC2R activity is modulated in part by different binding affinities of the MC1R variants for MRAP. Experiments in mammalian cells confirmed that trout MRAP interacts with the two trout MC1R variants and MC2R, but failed to detect regulation of MC2R signaling, possibly due to high constitutive MC1R activity. PMID:27373344

  17. Role of hypothalamic melanocortin system in adaptation of food intake to food protein increase in mice.

    Directory of Open Access Journals (Sweden)

    Bruno Pillot

    Full Text Available The hypothalamic melanocortin system--the melanocortin receptor of type 4 (MC4R and its ligands: α-melanin-stimulating hormone (α-MSH, agonist, inducing hypophagia, and agouti-related protein (AgRP, antagonist, inducing hyperphagia--is considered to play a central role in the control of food intake. We tested its implication in the mediation of the hunger-curbing effects of protein-enriched diets (PED in mice. Whereas there was a 20% decrease in food intake in mice fed on the PED, compared to mice fed on an isocaloric starch-enriched diet, there was a paradoxical decrease in expression of the hypothalamic proopiomelanocortin gene, precursor of α-MSH, and increase in expression of the gene encoding AgRP. The hypophagia effect of PED took place in mice with invalidation of either MC4R or POMC, and was even strengthened in mice with ablation of the AgRP-expressing neurons. These data strongly suggest that the hypothalamic melanocortin system does not mediate the hunger-curbing effects induced by changes in the macronutrient composition of food. Rather, the role of this system might be to defend the body against the variations in food intake generated by the nutritional environment.

  18. Fto colocalizes with a satiety mediator oxytocin in the brain and upregulates oxytocin gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Olszewski, Pawel K., E-mail: olsze005@umn.edu [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Minnesota Obesity Center, Saint Paul, MN 55108 (United States); Fredriksson, Robert; Eriksson, Jenny D. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Mitra, Anaya [Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Radomska, Katarzyna J. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Gosnell, Blake A. [Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Solvang, Maria N. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Levine, Allen S. [Minnesota Obesity Center, Saint Paul, MN 55108 (United States); Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Schioeth, Helgi B. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden)

    2011-05-13

    Highlights: {yields} The majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto. {yields} The level of colocalization is similar in the male and female brain. {yields} Fto overexpression in hypothalamic neurons increases oxytocin mRNA levels by 50%. {yields} Oxytocin does not affect Fto expression through negative feedback mechanisms. -- Abstract: Single nucleotide polymorphisms in the fat mass and obesity-associated (FTO) gene have been associated with obesity in humans. Alterations in Fto expression in transgenic animals affect body weight, energy expenditure and food intake. Fto, a nuclear protein and proposed transcription co-factor, has been speculated to affect energy balance through a functional relationship with specific genes encoding feeding-related peptides. Herein, we employed double immunohistochemistry and showed that the majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto in the brain of male and female mice. We then overexpressed Fto in a murine hypothalamic cell line and, using qPCR, detected a 50% increase in the level of oxytocin mRNA. Expression levels of several other feeding-related genes, including neuropeptide Y (NPY) and Agouti-related protein (AgRP), were unaffected by the FTO transfection. Addition of 10 and 100 nmol oxytocin to the cell culture medium did not affect Fto expression in hypothalamic cells. We conclude that Fto, a proposed transcription co-factor, influences expression of the gene encoding a satiety mediator, oxytocin.

  19. Modulation of leptin resistance by food compounds.

    Science.gov (United States)

    Aragonès, Gerard; Ardid-Ruiz, Andrea; Ibars, Maria; Suárez, Manuel; Bladé, Cinta

    2016-08-01

    Leptin is mainly secreted by white adipose tissue and regulates energy homeostasis by inhibiting food intake and stimulating energy expenditure through its action in neuronal circuits in the brain, particularly in the hypothalamus. However, hyperleptinemia coexists with the loss of responsiveness to leptin in common obese conditions. This phenomenon has been defined as leptin resistance and the restoration of leptin sensitivity is considered to be a useful strategy to treat obesity. This review summarizes the existing literature on potentially valuable nutrients and food components to reverse leptin resistance. Notably, several food compounds, such as teasaponins, resveratrol, celastrol, caffeine, and taurine among others, are able to restore the leptin signaling in neurons by overexpressing anorexigenic peptides (proopiomelanocortin) and/or repressing orexigenic peptides (neuropeptide Y/agouti-related peptide), thus decreasing food intake. Additionally, some nutrients, such as vitamins A and D, can improve leptin transport through the blood-brain barrier. Therefore, food components can improve leptin resistance by acting at different levels of the leptin pathway; moreover, some compounds are able to target more than one feature of leptin resistance. However, systematic studies are necessary to define the actual effectiveness of each compound. PMID:26842874

  20. Arcuate AgRP neurons and the regulation of energy balance

    Directory of Open Access Journals (Sweden)

    Céline eCansell

    2012-12-01

    Full Text Available The arcuate nucleus of the hypothalamus contains at least two crucial populations of neurons that continuously monitor signals reflecting energy status and promote the appropriate behavioral and metabolic responses to changes in energy demand. Neurons making pro-opiomelanocortin (POMC decrease food intake and increase energy expenditure through activation of G protein-coupled receptors melanocortin receptors (MCR via the release of a-melanocyte stimulating hormone. A prevailing idea until recently was that the neighboring neurons expressing the orexigenic neuropeptides, agouti-related protein (AgRP and neuropeptide Y (NPY (AgRP neurons increased feeding by opposing the anorexigenic actions of the POMC neurons. AgRP neurons activation but not POMC neurons inhibition was recently demonstrated to be necessary and sufficient to promote feeding. AgRP expressing axons were identified in mesolimbic, midbrain and pontine structure where they regulate feeding but also feeding-independent functions such as reward or peripheral nutrient partitioning. Post-synaptic Gamma aminobutyric acid (GABA, lasting in a timeline similar to neuromodulation, was identified as the core mechanism by which hunger-activated neurons regulate feeding and non-food related processes in a melanocortin independent manner.

  1. Defining the Contribution of MC1R Physiological Ligands to ATR Phosphorylation at Ser435, a Predictor of DNA Repair in Melanocytes.

    Science.gov (United States)

    Jarrett, Stuart G; Wolf Horrell, Erin M; Boulanger, Mary C; D'Orazio, John A

    2015-12-01

    The melanocortin 1 receptor (MC1R), a GS-coupled receptor that signals through cAMP and protein kinase A (PKA), regulates pigmentation, adaptive tanning, and melanoma resistance. MC1R-cAMP signaling promotes PKA-mediated phosphorylation of ataxia telangiectasia and rad3-related (ATR) at Ser435 (ATR-pS435), a modification that enhances nucleotide excision repair (NER) by facilitating recruitment of the XPA protein to sites of UV-induced DNA damage. High-throughput methods were developed to quantify ATR-pS435, measure XPA-photodamage interactions, and assess NER function. We report that melanocyte-stimulating hormone (α-MSH) or ACTH induce ATR-pS435, enhance XPA's association with UV-damaged DNA and optimize melanocytic NER. In contrast, MC1R antagonists agouti signaling protein (ASIP) or human β-defensin 3 (HBD3) interfere with ATR-pS435 generation, impair the XPA-DNA interaction, and reduce DNA repair. Although ASIP and HBD3 each blocked α-MSH-mediated induction of the signaling pathway, only ASIP depleted basal ATR-pS435. Our findings confirm that ASIP diminishes agonist-independent MC1R basal signaling whereas HBD3 is a neutral MC1R antagonist that blocks activation by melanocortins. Furthermore, our data suggest that ATR-pS435 may be a useful biomarker for the DNA repair-deficient MC1R phenotype. PMID:26168232

  2. Altered regulation of energy homeostasis in older rats in response to thyroid hormone administration.

    Science.gov (United States)

    Walrand, Stephane; Short, Kevin R; Heemstra, Lydia A; Novak, Colleen M; Levine, James A; Coenen-Schimke, Jill M; Nair, K Sreekumaran

    2014-03-01

    Hyperthyroidism causes increased energy intake and expenditure, although anorexia and higher weight loss have been reported in elderly individuals with hyperthyroidism. To determine the effect of age on energy homeostasis in response to experimental hyperthyroidism, we administered 200 μg tri-iodothyronine (T3) in 7- and 27-mo-old rats for 14 d. T3 increased energy expenditure (EE) in both the young and the old rats, although the old rats lost more weight (147 g) than the young rats (58 g) because of the discordant effect of T3 on food intake, with a 40% increase in the young rats, but a 40% decrease in the old ones. The increased food intake in the young rats corresponded with a T3-mediated increase in the appetite-regulating proteins agouti-related peptide, neuropeptide Y, and uncoupling protein 2 in the hypothalamus, but no increase occurred in the old rats. Evidence of mitochondrial biogenesis in response to T3 was similar in the soleus muscle and heart of the young and old animals, but less consistent in old plantaris muscle and liver. Despite the comparable increase in EE, T3's effect on mitochondrial function was modulated by age in a tissue-specific manner. We conclude that older rats lack compensatory mechanisms to increase caloric intake in response to a T3-induced increase in EE, demonstrating a detrimental effect of age on energy homeostasis. PMID:24344330

  3. Strain differences of cadmium-induced toxicity in rats: Insight from spleen and lung immune responses.

    Science.gov (United States)

    Demenesku, Jelena; Popov Aleksandrov, Aleksandra; Mirkov, Ivana; Ninkov, Marina; Zolotarevski, Lidija; Kataranovski, Dragan; Brceski, Ilija; Kataranovski, Milena

    2016-08-10

    The impact of genetic background on effects of acute i.p. cadmium administration (0.5mg/kg and 1mg/kg) on basic immune activity of spleen and lungs was examined in two rat strains, Albino Oxford (AO) and Dark Agouti (DA), known to react differently to chemicals. More pronounced inhibition of Concanavalin A (ConA)-induced and Interleukin (IL)-2 stimulated spleen cell proliferation as well as higher levels of nitric oxide (known to decrease cell's proliferative ability) in DA rats at 1mg/kg, along with greater inhibition of ConA-induced Interferon (IFN-γ)-production by total and mononuclear (MNC) spleen cells and IL-17 production by spleen MNC in DA vs. AO rats at this dose show greater susceptibility of this strain to Cd effects on spleen cells response. More pronounced infiltration of neutrophils/CD11b(+) cells to lungs of DA rats treated with 1mg/kg of Cd and decreased IL-17 lung cell responses noted solely in DA rats speaks in favor of their higher susceptibility to this metal. However, lack of strain disparity in lung cells IFN-γ responses show that there are regional differences as well. Novel data from this study depict complexity of the influence of genetic background on the effects of cadmium on host immune reactivity. PMID:27234498

  4. Hyper abundant mesopredators and bird extinction in an Atlantic forest island

    Directory of Open Access Journals (Sweden)

    Mauro Galetti

    2009-06-01

    Full Text Available Islands can serve as model systems for understanding how biological invasions affect native species. Here we examine the negative effects of mesopredator mammals on bird richness at Anchieta Island, an 826 ha offshore island in the coast of Brazil. Anchieta Island has the highest density of mammals of the entire Atlantic forest, especially nest predators such as marmosets and coatis, introduced more than 20 years ago. This indiscriminate introduction of mammals may have affected directly the bird community, nowadays represented by 100 species comprised mainly by water-crossing birds, being 73 forest-dwelling species. A small component of these remnant bird species nests in tree holes and on the forest floor, null model analysis suggest that birds within these two nest types are under-represented on Anchieta Island. All guilds were affected negatively, but "opportunist insectivorous/omnivorous". Experiments using artificial nests showed a predation of 73% of nests on the floor while only 26% on the mainland. Camera traps recorded predation by coatis, agoutis, and opossums. The restoration of the bird community on this island is highly constrained by the high density of hyper abundant nest predators.

  5. Fto colocalizes with a satiety mediator oxytocin in the brain and upregulates oxytocin gene expression

    International Nuclear Information System (INIS)

    Highlights: → The majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto. → The level of colocalization is similar in the male and female brain. → Fto overexpression in hypothalamic neurons increases oxytocin mRNA levels by 50%. → Oxytocin does not affect Fto expression through negative feedback mechanisms. -- Abstract: Single nucleotide polymorphisms in the fat mass and obesity-associated (FTO) gene have been associated with obesity in humans. Alterations in Fto expression in transgenic animals affect body weight, energy expenditure and food intake. Fto, a nuclear protein and proposed transcription co-factor, has been speculated to affect energy balance through a functional relationship with specific genes encoding feeding-related peptides. Herein, we employed double immunohistochemistry and showed that the majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto in the brain of male and female mice. We then overexpressed Fto in a murine hypothalamic cell line and, using qPCR, detected a 50% increase in the level of oxytocin mRNA. Expression levels of several other feeding-related genes, including neuropeptide Y (NPY) and Agouti-related protein (AgRP), were unaffected by the FTO transfection. Addition of 10 and 100 nmol oxytocin to the cell culture medium did not affect Fto expression in hypothalamic cells. We conclude that Fto, a proposed transcription co-factor, influences expression of the gene encoding a satiety mediator, oxytocin.

  6. How the leopard hides its spots: ASIP mutations and melanism in wild cats.

    Directory of Open Access Journals (Sweden)

    Alexsandra Schneider

    Full Text Available The occurrence of melanism (darkening of the background coloration is documented in 13 felid species, in some cases reaching high frequencies at the population level. Recent analyses have indicated that it arose multiple times in the Felidae, with three different species exhibiting unique mutations associated with this trait. The causative mutations in the remaining species have so far not been identified, precluding a broader assessment of the evolutionary dynamics of melanism in the Felidae. Among these, the leopard (Panthera pardus is a particularly important target for research, given the iconic status of the 'black panther' and the extremely high frequency of melanism observed in some Asian populations. Another felid species from the same region, the Asian golden cat (Pardofelis temminckii, also exhibits frequent records of melanism in some areas. We have sequenced the coding region of the Agouti Signaling Protein (ASIP gene in multiple leopard and Asian golden cat individuals, and identified distinct mutations strongly associated with melanism in each of them. The single nucleotide polymorphism (SNP detected among the P. pardus individuals was caused by a nonsense mutation predicted to completely ablate ASIP function. A different SNP was identified in P. temminckii, causing a predicted amino acid change that should also induce loss of function. Our results reveal two additional cases of species-specific mutations implicated in melanism in the Felidae, and indicate that ASIP mutations may play an important role in naturally-occurring coloration polymorphism.

  7. A novel role for pigment genes in the stress response in rainbow trout (Oncorhynchus mykiss)

    Science.gov (United States)

    Khan, Uniza Wahid; Øverli, Øyvind; Hinkle, Patricia M.; Pasha, Farhan Ahmad; Johansen, Ida Beitnes; Berget, Ingunn; Silva, Patricia I. M.; Kittilsen, Silje; Höglund, Erik; Omholt, Stig W.; Våge, Dag Inge

    2016-01-01

    In many vertebrate species visible melanin-based pigmentation patterns correlate with high stress- and disease-resistance, but proximate mechanisms for this trait association remain enigmatic. Here we show that a missense mutation in a classical pigmentation gene, melanocyte stimulating hormone receptor (MC1R), is strongly associated with distinct differences in steroidogenic melanocortin 2 receptor (MC2R) mRNA expression between high- (HR) and low-responsive (LR) rainbow trout (Oncorhynchus mykiss). We also show experimentally that cortisol implants increase the expression of agouti signaling protein (ASIP) mRNA in skin, likely explaining the association between HR-traits and reduced skin melanin patterning. Molecular dynamics simulations predict that melanocortin 2 receptor accessory protein (MRAP), needed for MC2R function, binds differently to the two MC1R variants. Considering that mRNA for MC2R and the MC1R variants are present in head kidney cells, we hypothesized that MC2R activity is modulated in part by different binding affinities of the MC1R variants for MRAP. Experiments in mammalian cells confirmed that trout MRAP interacts with the two trout MC1R variants and MC2R, but failed to detect regulation of MC2R signaling, possibly due to high constitutive MC1R activity. PMID:27373344

  8. A first genotyping assay of French cattle breeds based on a new allele of the extension gene encoding the melanocortin-1 receptor (Mc1r

    Directory of Open Access Journals (Sweden)

    Julien Raymond

    2000-09-01

    Full Text Available Abstract The seven transmembrane domain melanocortin-1 receptor (Mc1r encoded by the coat color extension gene (E plays a key role in the signaling pathway of melanin synthesis. Upon the binding of agonist (melanocortin hormone, α-MSH or antagonist (Agouti protein ligands, the melanosomal synthesis of eumelanin and/or phaeomelanin pigments is stimulated or inhibited, respectively. Different alleles of the extension gene were cloned from unrelated animals belonging to French cattle breeds and sequenced. The wild type E allele was mainly present in Normande cattle, the dominant ED allele in animals with black color (i.e. Holstein, whereas the recessive e allele was identified in homozygous animals exhibiting a more or less strong red coat color (Blonde d'Aquitaine, Charolaise, Limousine and Salers. A new allele, named E1, was found in either homozygous (E1/E1 or heterozygous (E1/E individuals in Aubrac and Gasconne breeds. This allele displayed a 4 amino acid duplication (12 nucleotides located within the third cytoplasmic loop of the receptor, a region known to interact with G proteins. A first genotyping assay of the main French cattle breeds is described based on these four extension alleles.

  9. Changes in Ghrelin-Related Factors in Gastroesophageal Reflux Disease in Rats

    Directory of Open Access Journals (Sweden)

    Miwa Nahata

    2013-01-01

    Full Text Available To examine gastrointestinal hormone profiles and functional changes in gastroesophageal reflux disease (GERD, blood levels of the orexigenic hormone ghrelin were measured in rats with experimentally induced GERD. During the experiment, plasma acyl ghrelin levels in GERD rats were higher than those in sham-operated rats, although food intake was reduced in GERD rats. Although plasma levels of the appetite-suppressing hormone leptin were significantly decreased in GERD rats, no changes were observed in cholecystokinin levels. Repeated administration of rat ghrelin to GERD rats had no effect on the reduction in body weight or food intake. Therefore, these results suggest that aberrantly increased secretion of peripheral ghrelin and decreased ghrelin responsiveness may occur in GERD rats. Neuropeptide Y and agouti-related peptide mRNA expression in the hypothalamus of GERD rats was significantly increased, whereas proopiomelanocortin mRNA expression was significantly decreased compared to that in sham-operated rats. However, melanin-concentrating hormone (MCH and prepro-orexin mRNA expression in the hypothalamus of GERD rats was similar to that in sham-operated rats. These results suggest that although GERD rats have higher plasma ghrelin levels, ghrelin signaling in GERD rats may be suppressed due to reduced MCH and/or orexin synthesis in the hypothalamus.

  10. The functional requirements of mammalian hair: a compromise between crypsis and thermoregulation?

    Science.gov (United States)

    Wacker, Chris B.; McAllan, Bronwyn M.; Körtner, Gerhard; Geiser, Fritz

    2016-08-01

    Mammalian fur often shows agouti banding with a proximal dark band near the skin and a lighter distal band. We examined the function of both bands in relation to camouflage, thermal properties of pelts, and thermal energetics of dunnarts ( Sminthopsis crassicaudata), which are known to use torpor and basking. Although the distal band of dunnart fur darkened with increasing latitude, which is important for camouflage, it did not affect the thermal properties and the length of the dark band and total hair length were not correlated. In contrast, the length of the proximal dark band of preserved pelts exposed to sunlight was positively correlated ( r 2 = 0.59) with the temperature underneath the pelt ( T pelt). All dunnarts offered radiant heat basked by exposing the dark band of the hair during both rest and torpor. Basking dunnarts with longer dark bands had lower resting metabolism ( r 2 = 0.69), warmed faster from torpor ( r 2 = 0.77), required less energy to do so ( r 2 = 0.32), and reached a higher subcutaneous temperature ( T sub) at the end of rewarming ( r 2 = 0.75). We provide the first experimental evidence on the possible dual function of the color banding of mammalian fur. The distal colored band appears to be important for camouflage, whereas the length of the dark proximal hair band facilitates heat gain for energy conservation and allows animals to rewarm quickly and economically from torpor.

  11. Entire litters developed from transferred eggs in whole body x-irradiated female mice

    International Nuclear Information System (INIS)

    The sensitivity of mouse eggs to sublethal x-irradiation was determined in vitro and in vivo with regard to the development of donor litters in foster mothers. One thousand seven hundred fifty-eight unfertilized eggs of agouti dark-eyed donor mice were transferred into 293 unirradiated or x-irradiated, mated female pink-eyed mice. Two hundred thirty-nine recipients became pregnant; of these 35 produced litters containing solely dark-eyed fetuses. Sublethal doses of x-radiation administered to donor eggs in vitro before transferring into unirradiated recipients did not influence significantly the number of litters of exclusively dark-eyed fetuses produced. However, recipients irradiated by 250 roentgens (r) produced more solely dark-eyed litters than did those irradiated with 100 r. In 21 pregnant females irradiated by 100 r, only 3 (14%) developed solely dark-eyed fetuses as compared to 22 pregnant females irradiated by 250 r, of which 13 (59%) developed solely dark-eyed fetuses, all from unirradiated, transferred eggs. Of another group of 22 pregnant females which received 250 r body irradiation and subsequently received eggs also irradiated by 250 r, only 7 (32%) produced litters of dark-eyed fetuses. No one female of these three groups carried native fetuses. Such radiation-induced infertility resulting from damage of native eggs rather than loss of mother's ability to carry a pregnancy, is frequently remedied by egg transfer

  12. Mechanisms regulating c-met overexpression in liver-metastatic B16-LS9 melanoma cells.

    Science.gov (United States)

    Elia, G; Ren, Y; Lorenzoni, P; Zarnegar, R; Burger, M M; Rusciano, D

    2001-01-01

    Liver selected B16-LS9 melanoma cells show a dramatic overexpression of the proto-oncogene c-met, the cellular receptor for hepatocyte growth factor/scatter factor. As a consequence, c-met becomes constitutively active, and the cells become more responsive to hepatocyte growth factor stimulation. We have investigated the molecular mechanisms regulating c-met expression in both the parental line B16-F1, which has low expression levels, and the liver-specific B16-LS9, overexpressing c-met. Overexpression is observed at the protein and mRNA levels, however without further evidence of gene amplification or rearrangement. c-met promoter activity was higher in B16-LS9 than B16-F1 cells, and also a nuclear run-off showed higher transcription levels in B16-LS9 cells. Moreover, we found that c-met mRNA had a longer half-life in B16-LS9 cells, thus indicating also the involvement of post-transcriptional regulation mechanisms. Finally, we found evidence that autonomous activation of the melanocortin receptor-1 (MCR-1) is at least partially responsible for c-met upregulation in B16-LS9 cells, since treatment of the cells with a potent MSH antagonist (the agouti peptide) has strong down-regulatory effects. PMID:11255230

  13. Effect of corticosterone on gene expression of feed intake regulatory peptides in laying hens.

    Science.gov (United States)

    Liu, Lei; Song, Zhigang; Sheikhahmadi, Ardashir; Jiao, Hongchao; Lin, Hai

    2012-08-01

    The present study was conducted to explore the effects of corticosterone (CORT) on the regulation of appetite-associated genes in laying hens. Forty eight laying hens were randomly divided into two groups: one received subcutaneous injection of CORT (2mg/kg body weight, CORT-exposed) and the other received sham-treatment (Control). Treatment of hens with CORT stimulated an increase (P0.05) on the mRNA levels of neuropeptide Y (NPY), corticotropin-releasing hormone (CRH), melanocortin receptor 4 and 5 (MCR-4 and MCR-5) and cholecystokinin (CCK) in the hypothalamus when compared with control hens. However, the expression of pro-opiomelanocortin (POMC), agouti-related protein (AgRP) and melanocortin recepter 1 (MCR-1) were significantly (P0.05) effect on the mRNA levels of CCK in the glandular stomach and the duodenum, and those of ghrelin in the glandular stomach, the duodenum and the jejunum. However, the mRNA levels of CCK in the jejunum and the ileum, and those of ghrelin in the ileum were significantly (P<0.05) suppressed by CORT treatment. In conclusion, these results suggest that CORT plays a unique role in some special neuropeptides (e.g., ghrelin, CART, POMC, CCK and MCRs) and a dynamic balance between these appetite-associated peptides in the hypothalamus and the gastrointestinal tract defines the feeding status of CORT-exposed laying hens. PMID:22554475

  14. Signature of balancing selection at the MC1R gene in Kunming dog populations.

    Directory of Open Access Journals (Sweden)

    Guo-dong Wang

    Full Text Available Coat color in dog breeds is an excellent character for revealing the power of artificial selection, as it is extremely diverse and likely the result of recent domestication. Coat color is generated by melanocytes, which synthesize pheomelanin (a red or yellow pigment or eumelanin (a black or brown pigment through the pigment type-switching pathway, and is regulated by three genes in dogs: MC1R (melanocortin receptor 1, CBD103 (β-defensin 103, and ASIP (agouti-signaling protein precursor. The genotypes of these three gene loci in dog breeds are associated with coat color pattern. Here, we resequenced these three gene loci in two Kunming dog populations and analyzed these sequences using population genetic approaches to identify evolutionary patterns that have occurred at these loci during the recent domestication and breeding of the Kunming dog. The analysis showed that MC1R undergoes balancing selection in both Kunming dog populations, and that the Fst value for MC1R indicates significant genetic differentiation across the two populations. In contrast, similar results were not observed for CBD103 or ASIP. These results suggest that high heterozygosity and allelic differences at the MC1R locus may explain both the mixed color coat, of yellow and black, and the difference in coat colors in both Kunming dog populations.

  15. Juvenile-onset loss of lipid-raft domains in attractin-deficient mice

    International Nuclear Information System (INIS)

    Mutations at the attractin (Atrn) locus in mice result in altered pigmentation on an agouti background, higher basal metabolic rate and juvenile-onset hypomyelination leading to neurodegeneration, while studies on human immune cells indicate a chemotaxis regulatory function. The underlying biochemical defect remains elusive. In this report we identify a role for attractin in plasma membrane maintenance. In attractin's absence there is a decline in plasma membrane glycolipid-enriched rafts from normal levels at 8 weeks to a complete absence by 24 weeks. The structural integrity of lipid rafts depends upon cholesterol and sphingomyelin, and can be identified by partitioning within of ganglioside GM1. Despite a significant fall in cellular cholesterol with maturity, and a lesser fall in both membrane and total cellular GM1, these parameters lag behind raft loss, and are normal when hypomyelination/neurodegeneration has already begun thus supporting consequence rather than cause. These findings can be recapitulated in Atrn-deficient cell lines propagated in vitro. Further, signal transduction through complex membrane receptor assemblies is not grossly disturbed despite the complete absence of lipid rafts. We find these results compatible with a role for attractin in plasma membrane maintenance and consistent with the proposal that the juvenile-onset hypomyelination and neurodegeneration represent a defect in attractin-mediated raft-dependent myelin biogenesis

  16. Feeding behavior and gene expression of appetite-related neuropeptides in mice lacking for neuropeptide Y Y5 receptor subclass

    Institute of Scientific and Technical Information of China (English)

    Hiroshi Higuchi; Takeshi Nild; Tomohiro Shiiya

    2008-01-01

    Neuropeptide Y (NPY) is a potent neurotransmitter for feeding. Besides NPY, orexigenic neuropeptides such as agouti-related protein (AgRP), and anorexi-genic neuropeptides such as a-melatonin stimulating hormone (MSH) and cocaine-amphetamine-regulated transcript (CART) are also involved in central feeding regulation. During fasting, NPY and AgRP gene expres-sions are up-regulated and POMC and CART gene ex-pressions are down-regulated in hypothalamus. Based on the network of peptidergic neurons, the former are involved in positive feeding regulation, and the latter are involved in negative feeding, which exert these feeding-regulated peptides especially in paraventricular nucleus (PVN). To clarify the compensatory mecha-nism of knock-out of NPY system on feeding, change in gene expressions of appetite-related neuropeptides and the feeding behavior was studied in NPY Y5-KO mice. Food intake was increased in Y5-KO mice. Fast-ing increased the amounts of food and water intake in the KO mice more profoundly. These data indicated the compensatory phenomenon of feeding behavior in YS-KO mice. RT-PCR and [SH suggested that the compensation of feeding is due to change in gene ex-pressions of AgRP, CART and POMC in hypothalamus. Thus, these findings indicated that the compensatory mechanism involves change in POMC/CART gene ex-pression in arcuate nucleus (ARC). The POMC/CART gene expression is important for central compensatory regulation in feeding behavior.

  17. Inflammation severely alters thyroid hormone signaling in the central nervous system during experimental allergic encephalomyelitis in rat: Direct impact on OPCs differentiation failure.

    Science.gov (United States)

    Fernández, Mercedes; Baldassarro, Vito A; Sivilia, Sandra; Giardino, Luciana; Calzà, Laura

    2016-09-01

    Differentiation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes is severely impaired by inflammatory cytokines and this could lead to remyelination failure in inflammatory/demyelinating diseases. Due to the role of thyroid hormone in the maturation of OPCs and developmental myelination, in this study we investigated (i) the possible occurrence of dysregulation of thyroid hormone signaling in the CNS tissue during experimental neuroinflammation; (ii) the possible impact of inflammatory cytokines on thyroid hormone signaling and OPCs differentiation in vitro. The disease model is the experimental allergic encephalomyelitis in female Dark-Agouti rats, whereas in vitro experiments were carried out in OPCs derived from neural stem cells. The main results are the following: (i) a strong upregulation of cytokine mRNA expression level was found in the spinal cord during experimental allergic encephalomyelitis; (ii) thyroid hormone signaling in the spinal cord (thyroid hormone receptors; deiodinase; thyroid hormone membrane transporter) is substantially downregulated, due to the upregulation of the thyroid hormone inactivating enzyme deiodinase 3 and the downregulation of thyroid hormone receptors, as investigated at mRNA expression level; (iii) when exposed to inflammatory cytokines, deiodinase 3 is upregulated in OPCs as well, and OPCs differentiation is blocked; (iv) deiodinase 3 inhibition by iopanoic acid recovers OPCs differentiation in the presence on inflammatory cytokines. These data suggest that cellular hypothyroidism occurs during experimental allergic encephalomyelitis, possibly impacting on thyroid hormone-dependent cellular processes, including maturation of OPCs into myelinating oligodendrocytes. GLIA 2016;64:1573-1589. PMID:27404574

  18. Interactions between SNP Alleles at Multiple Loci Contribute to Skin Color Differences between Caucasoid and Mongoloid Subjects

    Directory of Open Access Journals (Sweden)

    Sumiko Anno, Takashi Abe, Takushi Yamamoto

    2008-01-01

    Full Text Available This study aimed to identify single nucleotide polymorphism (SNP alleles at multiple loci associated with racial differences in skin color using SNP genotyping. A total of 122 Caucasians in Toledo, Ohio and 100 Mongoloids in Japan were genotyped for 20 SNPs in 7 candidate genes, encoding the Agouti signaling protein (ASIP, tyrosinase-related protein 1 (TYRP1, tyrosinase (TYR, melanocortin 1 receptor (MC1R, oculocutaneous albinism II (OCA2, microphthalmia-associated transcription factor (MITF, and myosin VA (MYO5A. Data were used to analyze associations between the 20 SNP alleles using linkage disequilibrium (LD. Combinations of SNP alleles were jointly tested under LD for associations with racial groups by performing a χ2 test for independence. Results showed that SNP alleles at multiple loci can be considered the haplotype that contributes to significant differences between the two population groups and suggest a high probability of LD. Confirmation of these findings requires further study with other ethnic groups to analyze the associations between SNP alleles at multiple loci and skin color variation among races.

  19. Genetic Analysis of the Cat Population of North and South of Cali, Colombia

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    Andrés F. PEÑA-CRUZ

    2014-05-01

    Full Text Available The coat genetic markers and skeleton abnormalities have allowed characterize the profile from more than 400 domestic cat populations around the world. 15 years ago, that profile was established in the city of Cali (Colombia. In this study it was determined if north and south of the city are subpopulations and it was compared the total profile against past study. A decrease in allele frequency of a (non-agouti and d (dilution was found, but an increase of five alleles was found, especially in l (long hair and cs (siamese. These differences could be attributed to human selection of more attractive characteristics and gene flow resulting from demographic growth city, which would also explain the first report of inhibitor and ticked abyssinian alleles. Hardy-Weinberg equilibrium was evaluated for the north, south and both areas together, using white spotting and orange loci, determining disequilibrium in orange for the three evaluated areas due to a heterozygotes deficit. North and south were divided into two, each sub-sample showed Hardy-Weinberg equilibrium, although allele frequencies and heterozygosities highlighted microgeographic structure and a relationship between founding time of the neighborhood and heterozygosity. North and south are a single population and aren´t subpopulations (FST= 0,0004, D= 0,0017, as well as nine Colombian populations with which this city was compared. It is suggested to make a microgeographical gene flow analysis and the definition of possible cat colonies in Cali.ANÁLISIS GENÉTICO DE LA POBLACIÓN DE GATOS DEL NORTE Y SUR DE CALI, COLOMBIALos marcadores genéticos del pelaje y malformaciones óseas han permitido caracterizar el perfil genético de más de 400 poblaciones del gato doméstico alrededor del mundo. Unos 15 años atrás se estableció dicho perfil en la ciudad de Cali (Colombia. En este estudio se determinó si el norte y sur de Cali se comportan como subpoblaciones y se comparó el perfil total

  20. Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

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    Mayado Andrea

    2011-11-01

    Full Text Available Abstract Background Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA. Methods Male Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p. 96 h before receiving neurotoxic MDMA (12.5 mg/kg, i.p.. IL-1β and IL1ra levels and 5-HT transporter density in frontal cortex were quantified at 1 h, 3 h or 7 days. IL-1β, IL-1ra and IL-1RI were determined between 3 h and 96 h after low dose MDMA. sIL-1RI combined with low dose MDMA or IL-1β were given 96 h before neurotoxic MDMA and toxicity assessed 7 days later. Results Pretreatment with low dose MDMA attenuated both the 5-HT transporter loss and elevated IL-1β levels induced by neurotoxic MDMA while producing an increase in IL-1ra levels. Low dose MDMA produced an increase in IL-1β at 3 h and in IL-1ra at 96 h. sIL-1RI expression was also increased after low dose MDMA. Coadministration of sIL-1RI (3 μg, i.c.v. prevented the protection against neurotoxic MDMA provided by low dose MDMA. Furthermore, IL-1β (2.5 pg, intracortical given 96 h before neurotoxic MDMA protected against the 5-HT neurotoxicity produced by the drug, thus mimicking preconditioning. Conclusions These results suggest that IL-1β plays an important role in the development of delayed preconditioning by low dose MDMA.

  1. Essential role of UCP1 modulating the central effects of thyroid hormones on energy balance

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    Alvarez-Crespo, Mayte; Csikasz, Robert I.; Martínez-Sánchez, Noelia; Diéguez, Carlos; Cannon, Barbara; Nedergaard, Jan; López, Miguel

    2016-01-01

    Objective Classically, metabolic effects of thyroid hormones (THs) have been considered to be peripherally mediated, i.e. different tissues in the body respond directly to thyroid hormones with an increased metabolism. An alternative view is that the metabolic effects are centrally regulated. We have examined here the degree to which prolonged, centrally infused triiodothyronine (T3) could in itself induce total body metabolic effects and the degree to which brown adipose tissue (BAT) thermogenesis was essential for such effects, by examining uncoupling protein 1 (UCP1) KO mice. Methods Wildtype and UPC1 KO mice were centrally-treated with T3 by using minipumps. Metabolic measurements were analyzed by indirect calorimetry and expression analysis by RT-PCR or western blot. BAT morphology and histology were studied by immunohistochemistry. Results We found that central T3-treatment led to reduced levels of hypothalamic AMP-activated protein kinase (AMPK) and elevated body temperature (0.7 °C). UCP1 was essential for the T3-induced increased rate of energy expenditure, which was only observable at thermoneutrality and notably only during the active phase, for the increased body weight loss, for the increased hypothalamic levels of neuropeptide Y (NPY) and agouti-related peptide (AgRP) and for the increased food intake induced by central T3-treatment. Prolonged central T3-treatment also led to recruitment of BAT and britening/beiging (“browning”) of inguinal white adipose tissue (iWAT). Conclusions We conclude that UCP1 is essential for mediation of the central effects of thyroid hormones on energy balance, and we suggest that similar UCP1-dependent effects may underlie central energy balance effects of other agents. PMID:27069867

  2. Experimental autoimmune encephalomyelitis (EAE): lesion visualization on a 3 tesla Clinical whole-body system after intraperitoneal contrast injection

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    Heckl, S.; Naegele, T.; Klose, U. [Dept. of Neuroradiology, Medical School, Univ. of Tuebingen (Germany); Herrmann, M.; Gaertner, S.; Weissert, R. [Dept. of Neurology, Medical School, Univ. of Tuebingen (Germany); Schick, F. [Dept. of Radiology, Medical School, Univ. of Tuebingen (Germany); Kueker, W. [Dept. of Neuroradiology, Medical School, Univ. of Tuebingen (Germany); Dept. of Neuroradiology, Radcliffe Infirmary, Oxford, England (United Kingdom)

    2004-11-01

    Purpose: To investigate the intravital visibility of CNS lesions in rats with experimental autoimmune encephalomyelitis (EAE), the animal correlate of multiple sclerosis, using a 3-Tesla (T) wholebody MR system. Materials and Methods: Three healthy Dark Agouti (DA) rats and 16 DA rats with clinical signs of EAE were examined on a 3T whole body-system using a normal wrist coil. In total, 25 examinations were preformed using T2- and T1-weighted images in transverse and sagittal orientation with a slice thickness of 2 mm or 1 mm (voxel size up to 0.2 x 0.2 x 1 mm). Sedation was achieved by intraperitoneal injection of ketamine and xylazine. In addition, T1-weighted images were obtained after the instillation of 1.0 ml of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) (0.5 mmol/ml) into the peritoneal cavity. Results: T2- and T1-weighted images of the brain and spinal cord with high spatial and contrast resolution could be obtained in all animals. The anatomical details of the olfactory bulb glomeruli, cerebellum foliae, ventricles and corpus callosum were clearly visible. The EAE lesions presented as hyperintense area in T2-weighted images and could be demonstrated in all clinically affected animals by MRI and histologically verified. In total, the 16 affected rats had 28 cerebral and 2 spinal cord lesions (range 1 to 4, median 2). Contrast enhancement was noted in 12 animals and ranked as severe in ten and moderate in two cases. No adverse effects were noted due to sedation or intraperitoneal contrast injection. Conclusions: The intravital demonstration of cerebral and spinal cord EAE lesions in rats is possible on a 3T whole-body MR scanner using a normal wrist coil. Intraperitoneal injection of ketamine/xylazine and contrast agent is an easy, safe and effective procedure in rats. (orig.)

  3. Lateral hypothalamic melanocortin receptor signaling modulates binge-like ethanol drinking in C57BL/6J mice.

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    Sprow, Gretchen M; Rinker, Jennifer A; Lowery-Gointa, Emily G; Sparrow, Angela M; Navarro, Montserrat; Thiele, Todd E

    2016-07-01

    Binge ethanol drinking is a highly pervasive and destructive behavior yet the underlying neurobiological mechanisms remain poorly understood. Recent work suggests that overlapping neurobiological mechanisms modulate feeding disorders and excessive ethanol intake, and converging evidence indicates that the melanocortin (MC) system may be a promising candidate. The aims of the present work were to examine how repeated binge-like ethanol drinking, using the 'drinking in the dark' (DID) protocol, impacts key peptides within the MC system and if site-specific manipulation of MC receptor (MCR) signaling modulates binge-like ethanol drinking. Male C57BL/6J mice were exposed to one, three or six cycles of binge-like ethanol, sucrose or water drinking, after which brain tissue was processed via immunohistochemistry (IHC) for analysis of key MC peptides, including alpha-melanocyte stimulating hormone (α-MSH) and agouti-related protein (AgRP). Results indicated that α-MSH expression was selectively decreased, while AgRP expression was selectively increased, within specific hypothalamic subregions following repeated binge-like ethanol drinking. To further explore this relationship, we used site-directed drug delivery techniques to agonize or antagonize MCRs within the lateral hypothalamus (LH). We found that the nonselective MCR agonist melanotan-II (MTII) blunted, while the nonselective MCR antagonist AgRP augmented, binge-like ethanol consumption when delivered into the LH. As these effects were region-specific, the present results suggest that a more thorough understanding of the MC neurocircuitry within the hypothalamus will help provide novel insight into the mechanisms that modulate excessive binge-like ethanol intake and may help uncover new therapeutic targets aimed at treating alcohol abuse disorders. PMID:25975524

  4. Targeting central melanocortin receptors: a promising novel approach for treating alcohol abuse disorders

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    Jeffrey eOlney

    2014-06-01

    Full Text Available The melanocortin (MC peptides are produced centrally by propiomelanocortin (POMC neurons within the arcuate nucleus of the hypothalamus and act through five seven-transmembrane G-protein coupled melanocortin receptor (MCR subtypes. The MC3R and MC4R subtypes, the most abundant central MCRs, are widely expressed in brain regions known to modulate neurobiological responses to ethanol, including regions of the hypothalamus and extended amygdala. Agouti-related protein (AgRP, also produced in the arcuate nucleus, is secreted in terminals expressing MCRs and functions as an endogenous MCR antagonist. This review highlights recent genetic and pharmacological findings that have implicated roles for the MC and AgRP systems in modulating ethanol consumption. Ethanol consumption is associated with significant alterations in the expression levels of various MC peptides/protein, which suggests that ethanol-induced perturbations of MC/AgRP signaling may modulate excessive ethanol intake. Consistently, MCR agonists decrease, and AgRP increases, ethanol consumption in mice. MCR agonists fail to blunt ethanol intake in mutant mice lacking the MC4R, suggesting that the protective effects of MCR agonists are modulated by the MC4R. Interestingly, recent evidence reveals that MCR agonists are more effective at blunting binge-like ethanol intake in mutant mice lacking the MC3R, suggesting that the MC3R has opposing effects on the MC4R. Finally, mutant mice lacking AgRP exhibit blunted voluntary and binge-like ethanol drinking, consistent with pharmacological studies. Collectively, these preclinical observations provide compelling evidence that compounds that target the MC system may provide therapeutic value for treating alcohol abuse disorders and that the utilization of currently available MC-targeting compounds- such as those being used to treat eating disorders- may be used as effective treatments to this end.

  5. Involvement of the melanocortin-1 receptor in acute pain and pain of inflammatory but not neuropathic origin.

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    Ada Delaney

    Full Text Available BACKGROUND: Response to painful stimuli is susceptible to genetic variation. Numerous loci have been identified which contribute to this variation, one of which, MC1R, is better known as a gene involved in mammalian hair colour. MC1R is a G protein-coupled receptor expressed in melanocytes and elsewhere and mice lacking MC1R have yellow hair, whilst humans with variant MC1R protein have red hair. Previous work has found differences in acute pain perception, and response to analgesia in mice and humans with mutations or variants in MC1R. METHODOLOGY AND PRINCIPAL FINDINGS: We have tested responses to noxious and non-noxious stimuli in mutant mice which lack MC1R, or which overexpress an endogenous antagonist of the receptor, as well as controls. We have also examined the response of these mice to inflammatory pain, assessing the hyperalgesia and allodynia associated with persistent inflammation, and their response to neuropathic pain. Finally we tested by a paired preference paradigm their aversion to oral administration of capsaicin, which activates the noxious heat receptor TRPV1. Female mice lacking MC1R showed increased tolerance to noxious heat and no alteration in their response to non-noxious mechanical stimuli. MC1R mutant females, and females overexpressing the endogenous MC1R antagonist, agouti signalling protein, had a reduced formalin-induced inflammatory pain response, and a delayed development of inflammation-induced hyperalgesia and allodynia. In addition they had a decreased aversion to capsaicin at moderate concentrations. Male mutant mice showed no difference from their respective controls. Mice of either sex did not show any effect of mutant genotype on neuropathic pain. CONCLUSIONS: We demonstrate a sex-specific role for MC1R in acute noxious thermal responses and pain of inflammatory origin.

  6. Surfactant protein d deficiency in mice is associated with hyperphagia, altered fat deposition, insulin resistance, and increased basal endotoxemia.

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    Jacob V Stidsen

    Full Text Available Pulmonary surfactant protein D (SP-D is a host defence lectin of the innate immune system that enhances clearance of pathogens and modulates inflammatory responses. Recently it has been found that systemic SP-D is associated with metabolic disturbances and that SP-D deficient mice are mildly obese. However, the mechanism behind SP-D's role in energy metabolism is not known.Here we report that SP-D deficient mice had significantly higher ad libitum energy intake compared to wild-type mice and unchanged energy expenditure. This resulted in accumulation but also redistribution of fat tissue. Blood pressure was unchanged. The change in energy intake was unrelated to the basal levels of hypothalamic Pro-opiomelanocortin (POMC and Agouti-related peptide (AgRP gene expression. Neither short time systemic, nor intracereberoventricular SP-D treatment altered the hypothalamic signalling or body weight accumulation.In ad libitum fed animals, serum leptin, insulin, and glucose were significantly increased in mice deficient in SP-D, and indicative of insulin resistance. However, restricted diets eliminated all metabolic differences except the distribution of body fat. SP-D deficiency was further associated with elevated levels of systemic bacterial lipopolysaccharide.In conclusion, our findings suggest that lack of SP-D mediates modulation of food intake not directly involving hypothalamic regulatory pathways. The resulting accumulation of adipose tissue was associated with insulin resistance. The data suggest SP-D as a regulator of energy intake and body composition and an inhibitor of metabolic endotoxemia. SP-D may play a causal role at the crossroads of inflammation, obesity, and insulin resistance.

  7. Development of a novel pink-eyed dilution mouse model showing progressive darkening of the eyes and coat hair with aging.

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    Ishikawa, Akira; Sugiyama, Makoto; Hondo, Eiichi; Kinoshita, Keiji; Yamagishi, Yuki

    2015-01-01

    Oca2(p-cas) (oculocutaneous albinism II; pink-eyed dilution castaneus) is a coat color mutant gene on mouse chromosome 7 that arose spontaneously in wild Mus musculus castaneus mice. Mice homozygous for Oca2(p-cas) usually exhibit pink eyes and gray coat hair on the non-agouti genetic background, and this ordinary phenotype remains unchanged throughout life. During breeding of a mixed strain carrying this gene on the C57BL/6J background, we discovered a novel spontaneous mutation that causes darkening of the eyes and coat hair with aging. In this study, we developed a novel mouse model showing this unique phenotype. Gross observations revealed that the pink eyes and gray coat hair of the novel mutant young mice became progressively darker in color by approximately 3 months after birth. Light and transmission-electron microscopic observations revealed a marked increase in melanin pigmentation of coat hair shafts and choroid of the eye in the novel mice compared to that in the ordinary mice. Sequence analysis of Oca2(p-cas) revealed a 4.1-kb deletion involving exons 15 and 16 of its wild-type gene. However, there was no sequence difference between the two types of mutant mice. Mating experiments suggested that the novel mutant phenotype was not inherited in a simple fashion, due to incomplete penetrance. The novel spontaneous mutant mouse is the first example of progressive hair darkening animals and is an essential animal model for understanding of the regulation mechanisms of melanin biosynthesis with aging. PMID:25739360

  8. Review of Research Progress on the Related Genes with the Coat Color of Alpaca%羊驼毛色相关基因研究进展的综述

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    邸文达; 杨川

    2012-01-01

    羊驼毛纤维颜色丰富,具有22种天然色,与其他哺乳动物一样,主要由遗传基因决定。掌握控制羊驼毛色基因的改变,可以有效地控制羊驼毛色的转变。哺乳动物的毛色表型与动物体内黑色素的种类、数量、合成及分布有关。在羊驼皮肤组织中,Agouti基因、MC1R基因、酪氨酸酶基因家族、KIT基因、AIF基因、β-catenin基因、Wnt3α基因、Mitf-M基因、EDNRA基因、EDNRB基因、CDK5基因、PRS5基因、P基因及花斑突变都参与羊驼毛色的形成与调控。综述了羊驼毛色相关基因的研究进展。%The hair fiber color of alpaca,with 22 natural colors, is mainly determined by heredity gene like other mammals . To master and control the changes the hair color genes of alpaca could effectively regulate the changes of hair colors of alpaca. The hair phenotypes of mammals are related to the types, amount,composition and distribution of melanin in animals. In the skin tissue of alpaca, Agouti gene ,MC1R gene, tyrosine gene family, KIT gene ,A1F gene ,~-catenin gene, Wnt3et gene ,Mitf-M gene ,EDNRA gene ,EDNRB gene, CDK5 gene, PRS5 gene, P gene and piebaldness mutation all participated in the formation and regulation of alpaca hair color.

  9. AgRP Neuron-Specific Deletion of Glucocorticoid Receptor Leads to Increased Energy Expenditure and Decreased Body Weight in Female Mice on a High-Fat Diet.

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    Shibata, Miyuki; Banno, Ryoichi; Sugiyama, Mariko; Tominaga, Takashi; Onoue, Takeshi; Tsunekawa, Taku; Azuma, Yoshinori; Hagiwara, Daisuke; Lu, Wenjun; Ito, Yoshihiro; Goto, Motomitsu; Suga, Hidetaka; Sugimura, Yoshihisa; Oiso, Yutaka; Arima, Hiroshi

    2016-04-01

    Agouti-related protein (AgRP) expressed in the arcuate nucleus is a potent orexigenic neuropeptide, which increases food intake and reduces energy expenditure resulting in increases in body weight (BW). Glucocorticoids, key hormones that regulate energy balance, have been shown in rodents to regulate the expression of AgRP. In this study, we generated AgRP-specific glucocorticoid receptor (GR)-deficient (knockout [KO]) mice. Female and male KO mice on a high-fat diet (HFD) showed decreases in BW at the age of 6 weeks compared with wild-type mice, and the differences remained significant until 16 weeks old. The degree of resistance to diet-induced obesity was more robust in female than in male mice. On a chow diet, the female KO mice showed slightly but significantly attenuated weight gain compared with wild-type mice after 11 weeks, whereas there were no significant differences in BW in males between genotypes. Visceral fat pad mass was significantly decreased in female KO mice on HFD, whereas there were no significant differences in lean body mass between genotypes. Although food intake was similar between genotypes, oxygen consumption was significantly increased in female KO mice on HFD. In addition, the uncoupling protein-1 expression in the brown adipose tissues was increased in KO mice. These data demonstrate that the absence of GR signaling in AgRP neurons resulted in increases in energy expenditure accompanied by decreases in adiposity in mice fed HFD, indicating that GR signaling in AgRP neurons suppresses energy expenditure under HFD conditions. PMID:26889940

  10. Inhibition of myeloid differentiation factor 88 signaling mediated by histidine-grafted poly(β-amino ester ester nanovector induces donor-specific liver allograft tolerance

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    Hu F

    2015-07-01

    Full Text Available Fanguo Hu,1,* Hanjie Wang,2,* Shuangnan Zhang,2 Yao Peng,2 Lin Su,2 Jin Chang,2 Gang Liu11Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2School of Life Sciences, Tianjin University, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin, People’s Republic of China*These authors contributed equally to this workAbstract: Toll-like receptors (TLRs activate biochemical pathways that evoke activation of innate immunity, which leads to dendritic cell maturation and initiation of adaptive immune responses that provoke allograft rejection. We aimed to prolong allograft survival by selectively inhibiting expression of myeloid differentiation factor 88 (MyD88, which is an essential adaptor in TLR signaling. We designed and synthesized a novel histidine-grafted poly(β-amino ester(HGPAE nanovector, which was shown to be safe and efficient both in vitro and in vivo for the delivery of a plasmid containing shRNA targeting MyD88 (pMyD88. We also demonstrated that the pMyD88/HGPAE complex mediated remarkable inhibition of MyD88 expression in rat liver in vivo. We transplanted Dark Agouti rat livers lacking MyD88 as result of transfection with the pMyD88/HGPAE complex into Lewis rats. The recipients survived longer and graft rejection of the donor liver as well as serum levels of IL-2 and IFN-γ in the recipient were significantly reduced.Keywords: immune recognition, allograft rejection, MyD88, short hairpin RNA (shRNA, gene delivery, PAE

  11. Risperidone-induced weight gain and reduced locomotor activity in juvenile female rats: The role of histaminergic and NPY pathways.

    Science.gov (United States)

    Lian, Jiamei; De Santis, Michael; He, Meng; Deng, Chao

    2015-01-01

    Second generation antipsychotic drugs (SGAs) such as risperidone are increasingly prescribed (mostly for off-label use) to children and adolescents for treating various mental disorders. SGAs cause serious weight gain/obesity and other metabolic side-effects. This study aimed to establish an animal model of risperidone-induced weight gain in female juvenile rats, and to investigate the effects of risperidone on the expression of hypothalamic histaminergic H1 receptors (H1R) and neuropeptides, and their association with weight gain. Female Sprague Dawley rats were treated orally with risperidone (0.3mg/kg, 3 times/day) or vehicle (control) starting from postnatal day (PD) 23 (±1 day) for 3 weeks (a period corresponding to the childhood-adolescent period in humans). In the female juvenile rats, risperidone treatment increased food intake and body weight gain, which started to appear after 12 days' treatment. Risperidone also significantly decreased the locomotor activity of the female rats. Consistently, risperidone significantly elevated mRNA expression of hypothalamic H1R, neuropeptide Y (NPY), and agouti-related peptide (AgRP) compared to controls, and H1R and NPY levels were correlated with risperidone enhanced weight gain and food intake in the female juvenile rats. However, risperidone did not affect hypothalamic proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) mRNA expression. Therefore, these results suggested that risperidone elevated appetite and body weight gain in juveniles via regulation of the hypothalamic H1R, NPY and AgRP pathways, as well as by reducing activity. PMID:25782398

  12. Nuclear genes involved in mitochondria-to-nucleus communication in breast cancer cells

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    Gabrielson Edward

    2002-11-01

    Full Text Available Abstract Background The interaction of nuclear and mitochondrial genes is an essential feature in maintenance of normal cellular function. Of 82 structural subunits that make up the oxidative phosphorylation system in the mitochondria, mitochondrial DNA (mtDNA encodes 13 subunits and rest of the subunits are encoded by nuclear DNA. Mutations in mitochondrial genes encoding the 13 subunits have been reported in a variety of cancers. However, little is known about the nuclear response to impairment of mitochondrial function in human cells. Results We isolated a Rho0 (devoid of mtDNA derivative of a breast cancer cell line. Our study suggests that depletion of mtDNA results in oxidative stress, causing increased lipid peroxidation in breast cancer cells. Using a cDNA microarray we compared differences in the nuclear gene expression profile between a breast cancer cell line (parental Rho+ and its Rho0 derivative impaired in mitochondrial function. Expression of several nuclear genes involved in cell signaling, cell architecture, energy metabolism, cell growth, apoptosis including general transcription factor TFIIH, v-maf, AML1, was induced in Rho0 cells. Expression of several genes was also down regulated. These include phospholipase C, agouti related protein, PKC gamma, protein tyrosine phosphatase C, phosphodiestarase 1A (cell signaling, PIBF1, cytochrome p450, (metabolism and cyclin dependent kinase inhibitor p19, and GAP43 (cell growth and differentiation. Conclusions Mitochondrial impairment in breast cancer cells results in altered expression of nuclear genes involved in signaling, cellular architecture, metabolism, cell growth and differentiation, and apoptosis. These genes may mediate the cross talk between mitochondria and the nucleus.

  13. A study on the mechanisms by which minocycline protects against MDMA ('ecstasy')-induced neurotoxicity of 5-HT cortical neurons.

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    Orio, Laura; Llopis, Noemi; Torres, Elisa; Izco, Maria; O'Shea, Esther; Colado, M Isabel

    2010-08-01

    3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is a selective 5-HT neurotoxin in rat brain which has been shown to produce acute neuroinflammation characterized by activation of microglia and release of interleukin-1beta (IL-1beta). We aimed to determine whether or not minocycline, a semi-synthetic tetracycline antibiotic capable of inhibiting microglial activation, could prevent the inflammatory response and reduce the toxicity induced by MDMA. Adult male Dark Agouti rats were given minocycline twice a day for 2 days (45 mg/kg on the first day and 90 mg/kg on the second day; 12-h apart, i.p.). MDMA (12.5 mg/kg; i.p.) was given after the third minocycline injection and animals were killed either 1 h later for the determination of NFkappaB binding activity, 3 h later for the determination of IL-1beta, 24 h later for the determination of microglial activation or 7 days later for the determination of [(3)H]-paroxetine binding as a measure of 5-HT neurotoxicity. MDMA increased NFkappaB activation, IL-1beta release and microglial activation both in the frontal cortex and in the hypothalamus and 7 days later produced a reduction in the density of 5-HT uptake sites in both these brain areas. Minocycline prevented the MDMA-induced increase in NFkappaB activation, IL-1beta release and microglial activation in the frontal cortex and prevented the 5-HT neurotoxicity 7 days later. However, in the hypothalamus, in spite of preventing MDMA-induced microglial activation, minocycline failed to prevent MDMA-induced NFkappaB activation, IL-1beta release and neurotoxicity. This suggests that the protective mechanism of minocycline against MDMA-induced neurotoxicity in frontal cortex involves inhibition of MDMA-induced NFkappaB activation possibly through a reduction in IL-1beta signalling. PMID:19777321

  14. [CHANGES IN LIFESTYLE FACTORS AFFECT THE LEVELS OF NEUROPEPTIDES, INVOLVED IN THE CONTROL OF EATING BEHAVIOR, INSULIN RESISTANCE AND LEVEL OF CHRONIC SYSTEMIC INFLAMMATION IN YOUNG OVERWEIGHT PERSONS].

    Science.gov (United States)

    Shevchenko, Yu; Mamontova, T; Baranova, A; Vesnina, L; Kaidashev, I

    2015-11-01

    The continuous rise of overweight and obesity is a major concern for present and future healthcare management. The aim of our study was to evaluate the influence of lifestyle changes on central regulatory mechanisms of maintaining energy homeostasis, insulin resistance and chronic systemic inflammation in 18-25 year old overweight patients. The anthropometric measurements were done for each patient, including body weight, height, waist circumference (WC), hip circumference (HC), waist to hip ratio, and body mass index (BMI). Patients were divided into two groups according to their BMI. 20 males and 21 females with BMI > 25 kg/m2 were included in the first, study, group. The second, control, group consisted of 16 males and 11 females with BMI - 18.5 - 24.9 kg/m 2. Lipid profile, fasting glucose and insulin levels, HOMA-IR, TNF-α, ceruloplasmin, neuropeptides Agouti-related protein - AgRP and kokain- and amphetamine-mediated transcript - CART were examined at the beginning of the study (Day 1) and after 10 week treatment period (Day 70). During the 10 week treatment period, people in the study group underwent physical exercise programs of 40-60 minute duration three times per week, and brisk walking during the remaining days. The mean calorie expenditure during the exercise was 500 kcal/day. Each patient in the study group was given balanced, healthy diet with 20% calorie restriction from baseline diet. Our study reveled that negative energy balance caused a statistically significant decrease in AgRP, reduction of visceral fat stores, increase of HDL, reduction of TNF-α and dissolution of insulin resistance signs. Significant but not statistically significant reduction of CART level was observed after increased physical activity program and calorie restriction diet, which might play an important role in the mechanism of decreasing weight. However, further investigations are required in order to determine its place in body weight regulation. PMID:26656551

  15. Colocalization of cocaine- and amphetamine-regulated transcript with kisspeptin and neurokinin B in the human infundibular region.

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    Katalin Skrapits

    Full Text Available Kisspeptin (KP- and neurokinin B (NKB- synthesizing neurons of the hypothalamic arcuate nucleus play a pivotal role in the regulation of pulsatile gonadotropin-releasing hormone (GnRH secretion. Unlike in rodents and sheep, the homologous KP and NKB neurons in the human infundibular region rarely express dynorphin- but often exhibit Substance P (SP immunoreactivity, indicating remarkable species differences in the neurochemical phenotype of these neurons. In search for additional neuropeptides in human KP and NKB neurons, we carried out immunofluorescent studies on hypothalamic sections obtained from five postmenopausal women. Colocalization experiments provided evidence for the presence of cocaine- and amphetamine-regulated transcript (CART in 47.9 ± 6.6% of KP-immunoreactive (IR and 30.0 ± 4.9% of NKB-IR perikarya and in 17.0 ± 2.3% of KP-IR and 6.2 ± 2.0% of NKB-IR axon varicosities. All three neuropeptides were present in 33.3 ± 4.9% of KP-IR and 28.2 ± 4.6% of NKB-IR somata, respectively, whereas triple-labeling showed lower incidences in KP-IR (14.3 ± 1.8% and NKB-IR (5.9 ± 2.0% axon varicosities. CART-IR KP and NKB neurons established contacts with other peptidergic cells, including GnRH-IR neurons and also sent projections to the infundibular stalk. KP and NKB fibers with CART often contained SP as well, while being distinct from CART fibers co-containing the orexigenic peptide agouti-related protein. Presence of CART in human, but not rodent, KP and NKB neurons represents a new example of species differences in the neuropeptide repertoire of mediobasal hypothalamic KP and NKB neurons. Target cells, receptor sites and physiological significance of CART in the efferent communication of KP and NKB neurons in primates require clarification.

  16. Alloimmune activation promotes anti-cancer cytotoxicity after rat liver transplantation.

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    Stéphanie Lacotte

    Full Text Available Liver transplantation for hepatocellular carcinoma (HCC results in a specific condition where the immune response is potentially directed against both allogeneic and cancer antigens. We have investigated the level of anti-cancer immunity during allogeneic immune response. Dark Agouti-to-Lewis and Lewis-to-Lewis rat liver transplantations were performed and the recipients anti-cancer immunity was analysed at the time of alloimmune activation. The occurrence of rejection in the allogeneic recipients was confirmed by a shorter survival (p<0.01, increased liver function tests (p<0.01, the presence of signs of rejection on histology, and a donor-specific ex vivo mixed lymphocyte reaction. At the time of alloimmune activation, blood mononuclear cells of the allogeneic group demonstrated increased anti-cancer cytotoxicity (p<0.005, which was related to an increased natural killer (NK cell frequency (p<0.05 and a higher monocyte/macrophage activation level (p<0.01. Similarly, liver NK cell anti-cancer cytotoxicity (p<0.005, and liver monocyte/macrophage activation levels (p<0.01 were also increased. The alloimmune-associated cytotoxicity was mediated through the NKG2D receptor, whose expression was increased in the rejected graft (p<0.05 and on NK cells and monocyte/macrophages. NKG2D ligands were expressed on rat HCC cells, and its inhibition prevented the alloimmune-associated cytotoxicity. Although waiting for in vivo validation, alloimmune-associated cytotoxicity after rat liver transplantation appears to be linked to increased frequencies and levels of activation of NK cells and monocyte/macrophages, and is at least in part mediated through the NKG2D receptor.

  17. Leptin Induces Hypertension and Endothelial Dysfunction via Aldosterone-Dependent Mechanisms in Obese Female Mice.

    Science.gov (United States)

    Huby, Anne-Cécile; Otvos, Laszlo; Belin de Chantemèle, Eric J

    2016-05-01

    Obesity is a major risk factor for cardiovascular disease in males and females. Whether obesity triggers cardiovascular disease via similar mechanisms in both the sexes is, however, unknown. In males, the adipokine leptin highly contributes to obesity-related cardiovascular disease by increasing sympathetic activity. Females secrete 3× to 4× more leptin than males, but do not exhibit high sympathetic tone with obesity. Nevertheless, females show inappropriately high aldosterone levels that positively correlate with adiposity and blood pressure (BP). We hypothesized that leptin induces hypertension and endothelial dysfunction via aldosterone-dependent mechanisms in females. Leptin control of the cardiovascular function was analyzed in female mice sensitized to leptin via the deletion of protein tyrosine phosphatase 1b (knockout) and in agouti yellow obese hyperleptinemic mice (Ay). Hypersensitivity to leptin (wild-type, 115±2; protein tyrosine phosphatase 1b knockout, 124±2 mm Hg;Pantagonism restored BP and endothelial function in protein tyrosine phosphatase 1b knockout and Ay mice. Hypersensitivity to leptin and obesity reduced BP response to ganglionic blockade in both strains and plasma catecholamine levels in protein tyrosine phosphatase 1b knockout mice. Hypersensitivity to leptin and obesity significantly increased plasma aldosterone levels and adrenal CYP11B2 expression. Chronic leptin receptor antagonism reduced aldosterone levels. Furthermore, chronic leptin and mineralocorticoid receptor blockade reduced BP and improved endothelial function in both leptin-sensitized and obese hyperleptinemic female mice. Together, these data demonstrate that leptin induces hypertension and endothelial dysfunction via aldosterone-dependent mechanisms in female mice and suggest that obesity leads to cardiovascular disease via sex-specific mechanisms. PMID:26953321

  18. The local effect of octreotide on mechanical pain sensitivity is more sensitive in DA rats than DA.1U rats.

    Science.gov (United States)

    Yao, Fan-Rong; Wang, Hui-Sheng; Guo, Yuan; Zhao, Yan

    2016-02-01

    A recent study by the authors indicated that major histocompatibility complex (MHC) genes are associated with the differences in basal pain sensitivity and in formalin model between Dark-Agouti (DA) and novel congenic DA.1U rats, which have the same genetic background as DA rats except for the u alleles of MHC. The objective of the present study is to investigate whether there is a difference in the pristane-induced arthritis (PIA) model and local analgesic effect of octreotide (OCT) between DA and DA.1U rats. The hindpaw mechanical withdrawal threshold (MWT) and heat withdrawal latency (HWL) were observed. The C unit firings of the tibial nerve evoked by non-noxious and noxious toe movements were recorded by electrophysiological methods in normal and PIA models in DA and DA.1U rats before and after local OCT administration. The expression of somatostatin receptor 2A (SSTR2A) was observed by immunohistochemistry. The results demonstrate that DA rats have a higher mechanical sensitivity than DA.1U rats after PIA. Local OCT administration significantly elevated MWT in DA rats under normal and PIA sate, but not in DA.1U rats. The electrophysiological experiments showed OCT significantly attenuated the firings of C units evoked by non-noxious and noxious stimulation in DA rats more than those in DA.1U rats both in normal and PIA states. In addition, the expression of SSTR2A in the dorsal horn of the spinal cord was significantly higher in DA than in DA.1U rats. All of the findings suggest a higher local analgesic effect of OCT in DA rats than DA.1U rats, which might be associated with the MHC genes. PMID:26606866

  19. The connection of monocytes and reactive oxygen species in pain.

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    Dagmar Hackel

    Full Text Available The interplay of specific leukocyte subpopulations, resident cells and proalgesic mediators results in pain in inflammation. Proalgesic mediators like reactive oxygen species (ROS and downstream products elicit pain by stimulation of transient receptor potential (TRP channels. The contribution of leukocyte subpopulations however is less clear. Local injection of neutrophilic chemokines elicits neutrophil recruitment but no hyperalgesia in rats. In meta-analyses the monocytic chemoattractant, CCL2 (monocyte chemoattractant protein-1; MCP-1, was identified as an important factor in the pathophysiology of human and animal pain. In this study, intraplantar injection of CCL2 elicited thermal and mechanical pain in Wistar but not in Dark Agouti (DA rats, which lack p47(phox, a part of the NADPH oxidase complex. Inflammatory hyperalgesia after complete Freund's adjuvant (CFA as well as capsaicin-induced hyperalgesia and capsaicin-induced current flow in dorsal root ganglion neurons in DA were comparable to Wistar rats. Macrophages from DA expressed lower levels of CCR2 and thereby migrated less towards CCL2 and formed limited amounts of ROS in vitro and 4-hydroxynonenal (4-HNE in the tissue in response to CCL2 compared to Wistar rats. Local adoptive transfer of peritoneal macrophages from Wistar but not from DA rats reconstituted CCL2-triggered hyperalgesia in leukocyte-depleted DA and Wistar rats. A pharmacological stimulator of ROS production (phytol restored CCL2-induced hyperalgesia in vivo in DA rats. In Wistar rats, CCL2-induced hyperalgesia was completely blocked by superoxide dismutase (SOD, catalase or tempol. Likewise, inhibition of NADPH oxidase by apocynin reduced CCL2-elicited hyperalgesia but not CFA-induced inflammatory hyperalgesia. In summary, we provide a link between CCL2, CCR2 expression on macrophages, NADPH oxidase, ROS and the development CCL2-triggered hyperalgesia, which is different from CFA-induced hyperalgesia. The study

  20. Seasonal changes in body mass, serum leptin levels and hypothalamic neuropeptide gene expression in male Eothenomys olitor.

    Science.gov (United States)

    Wan-long, Zhu; Zheng-kun, Wang

    2015-06-01

    The present study examined seasonal changes in body mass and energy metabolism in the Chaotung vole (Eothenomys olitor) and the physiological mechanisms underpinning these changes. Seasonal changes in the following parameters were measured in male E. olitor, body mass, food intake, thermogenesis, enzyme activity, masses of tissues and organs, hormone concentrations and expression of hypothalamic arcuate nucleus energy balance genes including neuropeptide Y (NPY), agouti-related protein (AgRP), pro-opiomelanocortin (POMC), and cocaine- and amphetamine-regulated transcript (CART). Body mass was constant over the year, but the masses of tissues and organs differed significantly between seasons. There were significant changes in body fat mass and serum leptin levels over the four seasons. E. olitor showed significant seasonal changes in food intake and thermogenesis, uncoupling protein 1 (UCP1) content, enzyme activity, and serum tri-iodothyronine (T3) and thyroxine (T4) levels. Moreover, mRNA expression in the hypothalamus showed significant seasonal changes. All of our results suggested that E. olitor had constant body mass over the year, which was inconsistent with the prediction of the 'set-point' hypothesis. However, body fat mass and serum leptin levels were significantly different among the four seasons, providing support for the 'set-point' hypothesis. The changes in leptin, NPY, AgRP, POMC, and CART mRNA levels may play a role in the regulation of energy intake in E. olitor. Furthermore, the role of leptin and hypothalamic neuropeptide gene in the regulation of energy metabolism and body mass may be different in animals that are acclimated to different seasons. PMID:25700741

  1. Seasonal Differences in Relative Gene Expression of Putative Central Appetite Regulators in Arctic Charr (Salvelinus alpinus) Do Not Reflect Its Annual Feeding Cycle.

    Science.gov (United States)

    Striberny, Anja; Ravuri, Chandra Sekhar; Jobling, Malcolm; Jørgensen, Even Hjalmar

    2015-01-01

    The highly seasonal anadromous Arctic charr (Salvelinus alpinus) was used to investigate the possible involvement of altered gene expression of brain neuropeptides in seasonal appetite regulation. Pro-opiomelanocortin (POMCA1, POMCA2), Cocaine and amphetamine regulated transcript (CART), Agouti related Peptide (AgRP), Neuropeptide Y (NPY) and Melanocortin Receptor 4 (MC4-R) genes were examined. The function of centrally expressed Leptin (Lep) in fish remains unclear, so Lep (LepA1, LepA2) and Leptin Receptor (LepR) genes were included in the investigation. In a ten months study gene expression was analysed in hypothalamus, mesencephalon and telencephalon of immature charr held under natural photoperiod (69°38'N) and ambient temperature and given excess feed. From April to the beginning of June the charr did not feed and lost weight, during July and August they were feeding and had a marked increase in weight and condition factor, and from November until the end of the study the charr lost appetite and decreased in weight and condition factor. Brain compartments were sampled from non-feeding charr (May), feeding charr (July), and non-feeding charr (January). Reverse transcription real-time quantitative PCR revealed temporal patterns of gene expression that differed across brain compartments. The non-feeding charr (May, January) had a lower expression of the anorexigenic LepA1, MC4-R and LepR in hypothalamus and a higher expression of the orexigenic NPY and AgRP in mesencephalon, than the feeding charr (July). In the telencephalon, LepR was more highly expressed in January and May than in July. These results do not indicate that changes in central gene expression of the neuropeptides investigated here directly induce seasonal changes in feeding in Arctic charr. PMID:26421838

  2. Orexigenic Gene Expression in Late Gestation Ovine Foetal Hypothalamus is Sensitive to Maternal Undernutrition and Realimentation.

    Science.gov (United States)

    Adam, C L; Williams, P A; Milne, J S; Aitken, R P; Wallace, J M

    2015-10-01

    Adverse nutritional effects on developing foetal hypothalamic appetitive pathways may contribute to programmed hyperphagia and obesity in intra-uterine growth-restricted, low birth weight offspring. In the present study, for the first time, hypothalamic gene expression for primary orexigenic and anorexigenic genes was examined in late gestation ovine foetuses (130 days; term=145 days) whose mothers were undernourished (UN) or well-nourished (C) throughout pregnancy, or transferred from UN to C on day 90 (UN-C). Pregnancies resulted from singleton embryo transfer into adolescent growing ewes. Body weight, carcass fat content and perirenal adipose tissue (PAT) mass were all lower for UN (n=9) than C (n=7) and intermediate for UN-C foetuses (n=6), with no effect of sex. PAT leptin gene expression (by the reverse transcriptase-polymerase chain reaction) was lower in UN than C and UN-C groups, and lower in males than females. Gene expression (by in situ hybridisation with radiolabelled riboprobes) in the arcuate nucleus was greater in UN than C foetuses for neuropeptide Y (NPY), agouti-related peptide (AGRP) and leptin receptor (OBRb) but not different for pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript. Gene expression in UN-C foetuses was intermediate for NPY and AGRP and not different from C foetuses for OBRb. Gene expression for NPY, AGRP and OBRb correlated negatively with foetal carcass fat content and with PAT leptin gene expression across all groups. Males had greater mRNA expression for AGRP than females, with NPY and OBRb showing similar trends. Therefore, maternal undernutrition throughout pregnancy increased orexigenic gene expression in the late gestation foetal hypothalamus, and expression levels were largely normalised by improved maternal nutrition in the last third of pregnancy. These findings may have implications for avoiding or correcting prenatal programming of postnatal hyperphagia and obesity. PMID:26212239

  3. Seasonal Differences in Relative Gene Expression of Putative Central Appetite Regulators in Arctic Charr (Salvelinus alpinus Do Not Reflect Its Annual Feeding Cycle.

    Directory of Open Access Journals (Sweden)

    Anja Striberny

    Full Text Available The highly seasonal anadromous Arctic charr (Salvelinus alpinus was used to investigate the possible involvement of altered gene expression of brain neuropeptides in seasonal appetite regulation. Pro-opiomelanocortin (POMCA1, POMCA2, Cocaine and amphetamine regulated transcript (CART, Agouti related Peptide (AgRP, Neuropeptide Y (NPY and Melanocortin Receptor 4 (MC4-R genes were examined. The function of centrally expressed Leptin (Lep in fish remains unclear, so Lep (LepA1, LepA2 and Leptin Receptor (LepR genes were included in the investigation. In a ten months study gene expression was analysed in hypothalamus, mesencephalon and telencephalon of immature charr held under natural photoperiod (69°38'N and ambient temperature and given excess feed. From April to the beginning of June the charr did not feed and lost weight, during July and August they were feeding and had a marked increase in weight and condition factor, and from November until the end of the study the charr lost appetite and decreased in weight and condition factor. Brain compartments were sampled from non-feeding charr (May, feeding charr (July, and non-feeding charr (January. Reverse transcription real-time quantitative PCR revealed temporal patterns of gene expression that differed across brain compartments. The non-feeding charr (May, January had a lower expression of the anorexigenic LepA1, MC4-R and LepR in hypothalamus and a higher expression of the orexigenic NPY and AgRP in mesencephalon, than the feeding charr (July. In the telencephalon, LepR was more highly expressed in January and May than in July. These results do not indicate that changes in central gene expression of the neuropeptides investigated here directly induce seasonal changes in feeding in Arctic charr.

  4. A Novel Analytical Strategy to Identify Fusion Transcripts between Repetitive Elements and Protein Coding-Exons Using RNA-Seq.

    Directory of Open Access Journals (Sweden)

    Tianyuan Wang

    Full Text Available Repetitive elements (REs comprise 40-60% of the mammalian genome and have been shown to epigenetically influence the expression of genes through the formation of fusion transcript (FTs. We previously showed that an intracisternal A particle forms an FT with the agouti gene in mice, causing obesity/type 2 diabetes. To determine the frequency of FTs genome-wide, we developed a TopHat-Fusion-based analytical pipeline to identify FTs with high specificity. We applied it to an RNA-seq dataset from the nucleus accumbens (NAc of mice repeatedly exposed to cocaine. Cocaine was previously shown to increase the expression of certain REs in this brain region. Using this pipeline that can be applied to single- or paired-end reads, we identified 438 genes expressing 813 different FTs in the NAc. Although all types of studied repeats were present in FTs, simple sequence repeats were underrepresented. Most importantly, reverse-transcription and quantitative PCR validated the expression of selected FTs in an independent cohort of animals, which also revealed that some FTs are the prominent isoforms expressed in the NAc by some genes. In other RNA-seq datasets, developmental expression as well as tissue specificity of some FTs differed from their corresponding non-fusion counterparts. Finally, in silico analysis predicted changes in the structure of proteins encoded by some FTs, potentially resulting in gain or loss of function. Collectively, these results indicate the robustness of our pipeline in detecting these new isoforms of genes, which we believe provides a valuable tool to aid in better understanding the broad role of REs in mammalian cellular biology.

  5. Modulation of orexigenic and anorexigenic peptides gene expression in the rat DVC and hypothalamus by acute immobilization stress

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    Fatiha eChigr

    2014-07-01

    Full Text Available We studied the long term effects of a single exposure to immobilization stress (IS (1 hour on the expression of anorexigenic (Pro-opiomelanocortin: POMC and cocaine amphetamine related transcript: CART and orexigenic (neuropeptide Y:NPY, Agouti related peptide: AgRP factors in hypothalamus and dorso vagal complex (DVC. We showed, by using RT-PCR that in the hypothalamus, that the mRNAs of POMC and CART were up-regulated at the end of IS and up to 24 hours. This up regulation persists until 48-72h after IS for CART only. In the DVC, their expressions peak significantly at 24h post stress and decline afterwards; CART mRNA is down regulated after 48h post stress. NPY and AgRP mRNAs show a gradual increase just after the end of IS. The up regulation is significant only at 24 hours after stress for AgRP but remains significantly higher for NPY compared to controls. In DVC, the mRNAs of the two factors show generally a similar post stress pattern. A significant increase jut after the end of IS of rats which persists up to 24 hours after is firstly noticed. The levels tend then to reach the basal levels although, they were slightly but significantly higher up to 72 hours after stress for mRNA NPY. The comparison between the expression profiles of anorexigenic and the two orexigenic peptides investigated shows the presence of a parallelism between that of POMC and AgRP and that of CART and NPY when each brain region (hypothalamus and DVC is considered separately. It seems that any surge in the expression of each anorexigenic factor stimulates the expression of those of corresponding and appropriated orexigenic one. These last reactions from orexigenic peptides tend to attenuate the anorexigenic effects of CART and POMC and by consequent to abolish the anorexia state generated by stress.

  6. A Novel Analytical Strategy to Identify Fusion Transcripts between Repetitive Elements and Protein Coding-Exons Using RNA-Seq.

    Science.gov (United States)

    Wang, Tianyuan; Santos, Janine H; Feng, Jian; Fargo, David C; Shen, Li; Riadi, Gonzalo; Keeley, Elizabeth; Rosh, Zachary S; Nestler, Eric J; Woychik, Richard P

    2016-01-01

    Repetitive elements (REs) comprise 40-60% of the mammalian genome and have been shown to epigenetically influence the expression of genes through the formation of fusion transcript (FTs). We previously showed that an intracisternal A particle forms an FT with the agouti gene in mice, causing obesity/type 2 diabetes. To determine the frequency of FTs genome-wide, we developed a TopHat-Fusion-based analytical pipeline to identify FTs with high specificity. We applied it to an RNA-seq dataset from the nucleus accumbens (NAc) of mice repeatedly exposed to cocaine. Cocaine was previously shown to increase the expression of certain REs in this brain region. Using this pipeline that can be applied to single- or paired-end reads, we identified 438 genes expressing 813 different FTs in the NAc. Although all types of studied repeats were present in FTs, simple sequence repeats were underrepresented. Most importantly, reverse-transcription and quantitative PCR validated the expression of selected FTs in an independent cohort of animals, which also revealed that some FTs are the prominent isoforms expressed in the NAc by some genes. In other RNA-seq datasets, developmental expression as well as tissue specificity of some FTs differed from their corresponding non-fusion counterparts. Finally, in silico analysis predicted changes in the structure of proteins encoded by some FTs, potentially resulting in gain or loss of function. Collectively, these results indicate the robustness of our pipeline in detecting these new isoforms of genes, which we believe provides a valuable tool to aid in better understanding the broad role of REs in mammalian cellular biology. PMID:27415830

  7. Prey preferences of the jaguar Panthera onca reflect the post-Pleistocene demise of large prey.

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    Matt W Hayward

    2016-01-01

    Full Text Available Documenting the impacts of the Pleistocene megafaunal extinctions on predator-prey interactions is a challenge because of the incomplete fossil record and depauperate extant community structure. We used a comparative ecological approach to investigate whether the existing prey preference patterns of jaguars Panthera onca were potentially affected by the Pleistocene extinctions in the Americas compared with large felids in Africa and Asia. We reviewed the literature and found 25 studies reporting 3214 jaguar kills recorded throughout the species’ distribution. We found that jaguars significantly preferred capybara Hydrochaeris hydrochaeris and giant anteater Myrmecophaga tridactyla, and avoided agoutis, carnivorans, primates, black-eared opossum Didelphis marsupialis and tapirs. Generalised linear models showed that jaguars select prey primarily based on socio-ecological and behavioural traits (abundance and herd size, rather than morphological characteristics (body size. Nonetheless, their accessible prey weight range was 6-60 kg, preferred prey weight range was 45-85 kg, and mean mass of significantly preferred prey was 32 ± 13 kg leading to a predator to prey body mass ratio of 1:0.53, which is much less than that of other solitary felids. Compared with other large, solitary felids, jaguars have an unusual predator to prey body mass ratio, show limited effect of prey morphology as a driver of prey selection, lack evidence of optimal foraging beyond their preferred prey, and an absence of preferentially hunting on Cetartiodactyla herbivores. These features, coupled with the reduction in jaguar body mass since the Pleistocene, suggest that the loss of larger potential prey items within the preferred and accessible weight ranges at the end-Pleistocene still affects jaguar predatory behaviour. It may be that jaguars survived this mass extinction event by preferentially preying on relatively small species.

  8. Imprinted genes and transpositions: epigenomic targets for low dose radiation effects. Final report

    International Nuclear Information System (INIS)

    The overall hypothesis of this grant application is that low dose ionizing radiation (LDIR) elicits adaptive responses in part by causing heritable DNA methylation changes in the epigenome. This novel postulate was tested by determining if the level of DNA methylation at the Agouti viable yellow (Avy) metastable locus is altered, in a dose-dependent manner, by low dose radiation exposure (vy locus in a sex-specific manner (p=0.004). Average DNA methylation was significantly increased in male offspring exposed to doses between 0.7 cGy and 7.6 cGy with maximum effects at 1.4 cGy and 3.0 cGy (p<0.01). Offspring coat color was concomitantly shifted towards pseudoagouti (p<0.01). Maternal dietary antioxidant supplementation mitigated both the DNA methylation changes and coat color shift in the irradiated offspring (p<0.05). Thus, LDIR exposure during gestation elicits epigenetic alterations that lead to positive adaptive phenotypic changes that are negated with antioxidants, indicating they are mediated in part by oxidative stress. These findings provide evidence that in the isogenic Avy mouse model epigenetic alterations resulting from LDIR play a role in radiation hormesis, bringing into question the assumption that every dose of radiation is harmful. Our findings not only have significant implications concerning the mechanism of hormesis, but they also emphasize the potential importance of this phenomenon in determining human risk at low radiation doses. Since the epigenetic regulation of genes varies markedly between species, the effect of LDIR on other epigenetically labile genes (e.g. imprinted genes) in animals and humans needs to be defined

  9. Impact of hypothalamic reactive oxygen species in the control of energy metabolism and food intake

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    Anne eDrougard

    2015-02-01

    Full Text Available Hypothalamus is a key area involved in the control of metabolism and food intake via the integrations of numerous signals (hormones, neurotransmitters, metabolites from various origins. These factors modify hypothalamic neurons activity and generate adequate molecular and behavioral responses to control energy balance. In this complex integrative system, a new concept has been developed in recent years, that includes reactive oxygen species (ROS as a critical player in energy balance. ROS are known to act in many signaling pathways in different peripheral organs, but also in hypothalamus where they regulate food intake and metabolism by acting on different types of neurons, including proopiomelanocortin (POMC and agouti-related protein (AgRP/neuropeptide Y (NPY neurons. Hypothalamic ROS release is under the influence of different factors such as pancreatic and gut hormones, adipokines (leptin, apelin,..., neurotransmitters and nutrients (glucose, lipids,.... The sources of ROS production are multiple including NADPH oxidase, but also the mitochondria which is considered as the main ROS producer in the brain. ROS are considered as signaling molecules, but conversely impairment of this neuronal signaling ROS pathway contributes to alterations of autonomic nervous system and neuroendocrine function, leading to metabolic diseases such as obesity and type 2 diabetes.In this review we focus our attention on factors that are able to modulate hypothalamic ROS release in order to control food intake and energy metabolism, and whose deregulations could participate to the development of pathological conditions. This novel insight reveals an original mechanism in the hypothalamus that controls energy balance and identify hypothalamic ROS signaling as a potential therapeutic strategy to treat metabolic disorders.

  10. Type 1 cannabinoid receptor modulates water deprivation-induced homeostatic responses.

    Science.gov (United States)

    Ruginsk, Silvia G; Vechiato, Fernanda M V; Uchoa, Ernane T; Elias, Lucila L K; Antunes-Rodrigues, Jose

    2015-12-01

    The present study investigated the type 1 cannabinoid receptor (CB1R) as a potential candidate to mediate the homeostatic responses triggered by 24 h of water deprivation, which constitutes primarily a hydroelectrolytic challenge and also significantly impacts energy homeostasis. The present results demonstrated for the first time that CB1R mRNA expression is increased in the hypothalamus of water-deprived (WD) rats. Furthermore, the administration of ACEA, a CB1R selective agonist, potentiated WD-induced dipsogenic effect, whereas AM251, a CB1R antagonist, attenuated not only water but also salt intake in response to WD. In parallel with the modulation of thirst and salt appetite, we confirmed that CB1Rs are essential for the development of appropriated neuroendocrine responses. Although the administration of ACEA or AM251 did not produce any effects on WD-induced arginine vasopressin (AVP) secretion, oxytocin (OXT) plasma concentrations were significantly decreased in WD rats treated with ACEA. At the genomic level, ACEA significantly decreased AVP and OXT mRNA expression in the hypothalamus of WD rats, whereas AM251 potentiated both basal and WD-induced stimulatory effects on the transcription of AVP and OXT genes. In addition, we showed that water deprivation alone upregulated proopiomelanocortin, Agouti-related peptide, melanin-concentrating hormone, and orexin A mRNA levels in the hypothalamus, and that CB1Rs regulate main central peptidergic pathways controlling food intake, being that most of these effects were also significantly influenced by the hydration status. In conclusion, the present study demonstrated that CB1Rs participate in the homeostatic responses regulating fluid balance and energy homeostasis during water deprivation. PMID:26468265

  11. Enhanced susceptibility of ovaries from obese mice to 7,12-dimethylbenz[a]anthracene-induced DNA damage

    International Nuclear Information System (INIS)

    7,12-Dimethylbenz[a]anthracene (DMBA) depletes ovarian follicles and induces DNA damage in extra-ovarian tissues, thus, we investigated ovarian DMBA-induced DNA damage. Additionally, since obesity is associated with increased offspring birth defect incidence, we hypothesized that a DMBA-induced DNA damage response (DDR) is compromised in ovaries from obese females. Wild type (lean) non agouti (a/a) and KK.Cg-Ay/J heterozygote (obese) mice were dosed with sesame oil or DMBA (1 mg/kg; intraperitoneal injection) at 18 weeks of age, for 14 days. Total ovarian RNA and protein were isolated and abundance of Ataxia telangiectasia mutated (Atm), X-ray repair complementing defective repair in Chinese hamster cells 6 (Xrcc6), breast cancer type 1 (Brca1), Rad 51 homolog (Rad51), poly [ADP-ribose] polymerase 1 (Parp1) and protein kinase, DNA-activated, catalytic polypeptide (Prkdc) were quantified by RT-PCR or Western blot. Phosphorylated histone H2AX (γH2AX) level was determined by Western blotting. Obesity decreased (P < 0.05) basal protein abundance of PRKDC and BRCA1 proteins but increased (P < 0.05) γH2AX and PARP1 proteins. Ovarian ATM, XRCC6, PRKDC, RAD51 and PARP1 proteins were increased (P < 0.05) by DMBA exposure in lean mice. A blunted DMBA-induced increase (P < 0.05) in XRCC6, PRKDC, RAD51 and BRCA1 was observed in ovaries from obese mice, relative to lean counterparts. Taken together, DMBA exposure induced γH2AX as well as the ovarian DDR, supporting that DMBA causes ovarian DNA damage. Additionally, ovarian DDR was partially attenuated in obese females raising concern that obesity may be an additive factor during chemical-induced ovotoxicity. - Highlights: • DMBA induces markers of ovarian DNA damage. • Obesity induces low level ovarian DNA damage. • DMBA-induced DNA repair response is altered by obesity

  12. Nitric Oxide Exerts Basal and Insulin-Dependent Anorexigenic Actions in POMC Hypothalamic Neurons.

    Science.gov (United States)

    Wellhauser, Leigh; Chalmers, Jennifer A; Belsham, Denise D

    2016-04-01

    The arcuate nucleus of the hypothalamus represents a key center for the control of appetite and feeding through the regulation of 2 key neuronal populations, notably agouti-related peptide/neuropeptide Y and proopimelanocortin (POMC)/cocaine- and amphetamine-regulated transcript neurons. Altered regulation of these neuronal networks, in particular the dysfunction of POMC neurons upon high-fat consumption, is a major pathogenic mechanism involved in the development of obesity and type 2 diabetes mellitus. Efforts are underway to preserve the integrity or enhance the functionality of POMC neurons in order to prevent or treat these metabolic diseases. Here, we report for the first time that the nitric oxide (NO(-)) donor, sodium nitroprusside (SNP) mediates anorexigenic actions in both hypothalamic tissue and hypothalamic-derived cell models by mediating the up-regulation of POMC levels. SNP increased POMC mRNA in a dose-dependent manner and enhanced α-melanocortin-secreting hormone production and secretion in mHypoA-POMC/GFP-2 cells. SNP also enhanced insulin-driven POMC expression likely by inhibiting the deacetylase activity of sirtuin 1. Furthermore, SNP enhanced insulin-dependent POMC expression, likely by reducing the transcriptional repression of Foxo1 on the POMC gene. Prolonged SNP exposure prevented the development of insulin resistance. Taken together, the NO(-) donor SNP enhances the anorexigenic potential of POMC neurons by promoting its transcriptional expression independent and in cooperation with insulin. Thus, increasing cellular NO(-) levels represents a hormone-independent method of promoting anorexigenic output from the existing POMC neuronal populations and may be advantageous in the fight against these prevalent disorders. PMID:26930171

  13. The MC1R and ASIP Coat Color Loci May Impact Behavior in the Horse.

    Science.gov (United States)

    Jacobs, Lauren N; Staiger, Elizabeth A; Albright, Julia D; Brooks, Samantha A

    2016-05-01

    Shared signaling pathways utilized by melanocytes and neurons result in pleiotropic traits of coat color and behavior in many mammalian species. For example, in humans polymorphisms at MC1R cause red hair, increased heat sensitivity, and lower pain tolerance. In deer mice, rats, and foxes, ASIP polymorphisms causing black coat color lead to more docile demeanors and reduced activity. Horse (Equus caballus) base coat color is primarily determined by polymorphisms at the Melanocortin-1 Receptor (MC1R) and Agouti Signaling Protein (ASIP) loci, creating a black, bay, or chestnut coat. Our goal was to investigate correlations between genetic loci for coat color and temperament traits in the horse. We genotyped a total of 215 North American Tennessee Walking Horses for the 2 most common alleles at the MC1R (E/e) and ASIP (A/a) loci using previously published PCR and RFLP methods. The horses had a mean age of 10.5 years and comprised 83 geldings, 25 stallions, and 107 mares. To assess behavior, we adapted a previously published survey for handlers to score horses from 1 to 9 on 20 questions related to specific aspects of temperament. We utilized principle component analysis to combine the individual survey scores into 4 factors of variation in temperament phenotype. A factor component detailing self-reliance correlated with genotypes at the ASIP locus; black mares (aa) were more independent than bay mares (A_) (P = 0.0063). These findings illuminate a promising and novel animal model for future study of neuroendocrine mechanisms in complex behavioral phenotypes. PMID:26884605

  14. Lipopolysacharide Rapidly and Completely Suppresses AgRP Neuron-Mediated Food Intake in Male Mice.

    Science.gov (United States)

    Liu, Yang; Huang, Ying; Liu, Tiemin; Wu, Hua; Cui, Huxing; Gautron, Laurent

    2016-06-01

    Although Agouti-related peptide (AgRP) neurons play a key role in the regulation of food intake, their contribution to the anorexia caused by proinflammatory insults has yet to be identified. Using a combination of neuroanatomical and pharmacogenetics experiments, this study sought to investigate the importance of AgRP neurons and downstream targets in the anorexia caused by the peripheral administration of a moderate dose of lipopolysaccharide (LPS) (100 μg/kg, ip). First, in the C57/Bl6 mouse, we demonstrated that LPS induced c-fos in select AgRP-innervated brain sites involved in feeding but not in any arcuate proopiomelanocortin neurons. Double immunohistochemistry further showed that LPS selectively induced c-Fos in a large subset of melanocortin 4 receptor-expressing neurons in the lateral parabrachial nucleus. Secondly, we used pharmacogenetics to stimulate the activity of AgRP neurons during the course of LPS-induced anorexia. In AgRP-Cre mice expressing the designer receptor hM3Dq-Gq only in AgRP neurons, the administration of the designer drug clozapine-N-oxide (CNO) induced robust food intake. Strikingly, CNO-mediated food intake was rapidly and completely blunted by the coadministration of LPS. Neuroanatomical experiments further indicated that LPS did not interfere with the ability of CNO to stimulate c-Fos in AgRP neurons. In summary, our findings combined together support the view that the stimulation of select AgRP-innervated brain sites and target neurons, rather than the inhibition of AgRP neurons themselves, is likely to contribute to the rapid suppression of food intake observed during acute bacterial endotoxemia. PMID:27111742

  15. RMI1 deficiency in mice protects from diet and genetic-induced obesity.

    Science.gov (United States)

    Suwa, Akira; Yoshino, Masayasu; Yamazaki, Chihiro; Naitou, Masanori; Fujikawa, Rie; Matsumoto, Shun-Ichiro; Kurama, Takeshi; Shimokawa, Teruhiko; Aramori, Ichiro

    2010-02-01

    The aim of this study is to discover and characterize novel energy homeostasis-related molecules. We screened stock mouse embryonic stem cells established using the exchangeable gene trap method, and examined the effects of deficiency of the target gene on diet and genetic-induced obesity. The mutant strain 0283, which has an insertion at the recQ-mediated genome instability 1 (RMI1) locus, possesses a number of striking features that allow it to resist metabolic abnormalities. Reduced RMI1 expression, lower fasting-blood glucose and a reduced body weight (normal diet) were observed in the mutant mice. When fed a high-fat diet, the mutant mice were resistant to obesity, and also showed improved glucose intolerance and reduced abdominal fat tissue mass and food intake. In addition, the mutants were also resistant to obesity induced by the lethal yellow agouti (A(y)) gene. Endogenous RMI1 genes were found to be up-regulated in the liver and adipose tissue of KK-A(y) mice. RMI1 is a component of the Bloom's syndrome gene helicase complex that maintains genome integrity and activates cell-cycle checkpoint machinery. Interestingly, diet-induced expression of E2F8 mRNA, which is an important cell cycle-related molecule, was suppressed in the mutant mice. These results suggest that the regulation of energy balance by RMI1 is attributable to the regulation of food intake and E2F8 expression in adipose tissue. Taken together, these findings demonstrate that RMI1 is a novel molecule that regulates energy homeostasis. PMID:20050919

  16. Glucose Alters Per2 Rhythmicity Independent of AMPK, Whereas AMPK Inhibitor Compound C Causes Profound Repression of Clock Genes and AgRP in mHypoE-37 Hypothalamic Neurons.

    Directory of Open Access Journals (Sweden)

    Johanneke E Oosterman

    Full Text Available Specific neurons in the hypothalamus are regulated by peripheral hormones and nutrients to maintain proper metabolic control. It is unclear if nutrients can directly control clock gene expression. We have therefore utilized the immortalized, hypothalamic cell line mHypoE-37, which exhibits robust circadian rhythms of core clock genes. mHypoE-37 neurons were exposed to 0.5 or 5.5 mM glucose, comparable to physiological levels in the brain. Per2 and Bmal1 mRNAs were assessed every 3 hours over 36 hours. Incubation with 5.5 mM glucose significantly shortened the period and delayed the phase of Per2 mRNA levels, but had no effect on Bmal1. Glucose had no significant effect on phospho-GSK3β, whereas AMPK phosphorylation was altered. Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1, agouti-related peptide (AgRP, carnitine palmitoyltransferase 1C (Cpt1c, and O-linked N-acetylglucosamine transferase (Ogt were measured. Remarkably, Compound C dramatically reduced transcript levels of Per2, Bmal1, Cry1, and AgRP, but not Cpt1c or Ogt. Because AMPK was not inhibited at the same time or concentrations as the clock genes, we suggest that the effect of Compound C on gene expression occurs through an AMPK-independent mechanism. The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. Importantly, the effects of the most commonly used AMPK inhibitor Compound C should be interpreted with caution, considering its role in AMPK-independent repression of specific genes, and especially clock gene rhythm dysregulation.

  17. Methotrexate ameliorates pristane-induced arthritis by decreasing IFN-γ and IL-17A expressions

    Institute of Scientific and Technical Information of China (English)

    Wei-kun HOU; Lie-su MENG; Fang ZHENG; Yu-rong WEN; Wen-hua ZHU; Cong-shan JIANG; Xiao-jing HE; Yan ZHOU; She-min LU

    2011-01-01

    Objective:This study was carried out to test the effects of methotrexate(MTX)and black seed oil(BSO)on pristane-induced arthritis(PIA)in rats.Methods:Inbred dark agouti(DA)rats were induced by a single subcutaneous injection of pristane,and then treated with MTX or BSO.Arthritis severity was evaluated macroscopic,ally and microscopically.Plasma nitric oxide(NO)concentration was determined by the Griess method and cytokine mRNA expression in the spleen was detected by the real-time reverse transcription-polymerase chain reaction(RT-PCR).Results:The clinical arthritis severity was decreased after MTX treatment,while the BSO groups did not show significant changes compared with the disease group.The plasma NO level of the MTX group was significantly decreased compared with the disease group,but the BSO groups showed no difference from the disease group in plasma NO levels.The interferon-γ(IFN-γ)and interleukin-17A(IL-17A)mRNA expressions in the spleens were significantly decreased in the MTX group,but only showed a declining trend in the BSO groups compared with the disease group.Neither MTX nor BSO had an effect on the mRNA expressions of IL-4,transforming growth factor β(TGF-β),and tumor necrosis factor-α(TNF-α)in the spleen.Conclusions:MTX,but not BSO,can reduce the arthritis severity and decrease the mRNA expressions of IFN-γ and IL-17A in pristane-induced arthritis of rats.

  18. Enhanced susceptibility of ovaries from obese mice to 7,12-dimethylbenz[a]anthracene-induced DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Nteeba, Jackson, E-mail: nteeba@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

    2014-12-01

    7,12-Dimethylbenz[a]anthracene (DMBA) depletes ovarian follicles and induces DNA damage in extra-ovarian tissues, thus, we investigated ovarian DMBA-induced DNA damage. Additionally, since obesity is associated with increased offspring birth defect incidence, we hypothesized that a DMBA-induced DNA damage response (DDR) is compromised in ovaries from obese females. Wild type (lean) non agouti (a/a) and KK.Cg-Ay/J heterozygote (obese) mice were dosed with sesame oil or DMBA (1 mg/kg; intraperitoneal injection) at 18 weeks of age, for 14 days. Total ovarian RNA and protein were isolated and abundance of Ataxia telangiectasia mutated (Atm), X-ray repair complementing defective repair in Chinese hamster cells 6 (Xrcc6), breast cancer type 1 (Brca1), Rad 51 homolog (Rad51), poly [ADP-ribose] polymerase 1 (Parp1) and protein kinase, DNA-activated, catalytic polypeptide (Prkdc) were quantified by RT-PCR or Western blot. Phosphorylated histone H2AX (γH2AX) level was determined by Western blotting. Obesity decreased (P < 0.05) basal protein abundance of PRKDC and BRCA1 proteins but increased (P < 0.05) γH2AX and PARP1 proteins. Ovarian ATM, XRCC6, PRKDC, RAD51 and PARP1 proteins were increased (P < 0.05) by DMBA exposure in lean mice. A blunted DMBA-induced increase (P < 0.05) in XRCC6, PRKDC, RAD51 and BRCA1 was observed in ovaries from obese mice, relative to lean counterparts. Taken together, DMBA exposure induced γH2AX as well as the ovarian DDR, supporting that DMBA causes ovarian DNA damage. Additionally, ovarian DDR was partially attenuated in obese females raising concern that obesity may be an additive factor during chemical-induced ovotoxicity. - Highlights: • DMBA induces markers of ovarian DNA damage. • Obesity induces low level ovarian DNA damage. • DMBA-induced DNA repair response is altered by obesity.

  19. Inhibition of melanocortin 1 receptor slows melanoma growth, reduces tumor heterogeneity and increases survival.

    Science.gov (United States)

    Kansal, Rita G; McCravy, Matthew S; Basham, Jacob H; Earl, Joshua A; McMurray, Stacy L; Starner, Chelsey J; Whitt, Michael A; Albritton, Lorraine M

    2016-05-01

    Melanoma risk is increased in patients with mutations of melanocortin 1 receptor (MC1R) yet the basis for the increased risk remains unknown. Here we report in vivo evidence supporting a critical role for MC1R in regulating melanoma tumor growth and determining overall survival time. Inhibition of MC1R by its physiologically relevant competitive inhibitor, agouti signaling protein (ASIP), reduced melanin synthesis and morphological heterogeneity in murine B16-F10 melanoma cells. In the lungs of syngeneic C57BL/6 mice, mCherry-marked, ASIP-secreting lung tumors inhibited MC1R on neighboring tumors lacking ASIP in a dose dependent manner as evidenced by a proportional loss of pigment in tumors from mice injected with 1:1, 3:1 and 4:1 mixtures of parental B16-F10 to ASIP-expressing tumor cells. ASIP-expressing B16-F10 cells formed poorly pigmented tumors in vivo that correlated with a 20% longer median survival than those bearing parental B16-F10 tumors (p=0.0005). Mice injected with 1:1 mixtures also showed survival benefit (p=0.0054), whereas injection of a 4:1 mixture showed no significant difference in survival. The longer survival time of mice bearing ASIP-expressing tumors correlated with a significantly slower growth rate than parental B16-F10 tumors as judged by quantification of numbers of tumors and total tumor load (p=0.0325), as well as a more homogeneous size and morphology of ASIP-expressing lung tumors. We conclude that MC1R plays an important role in regulating melanoma growth and morphology. Persistent inhibition of MC1R provided a significant survival advantage resulting in part from slower tumor growth, establishing MC1R as a compelling new molecular target for metastatic melanoma. PMID:27028866

  20. Multiple rodent models and behavioral measures reveal unexpected responses to FTY720 and DMF in experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    de Bruin, N M W J; Schmitz, K; Schiffmann, S; Tafferner, N; Schmidt, M; Jordan, H; Häußler, A; Tegeder, I; Geisslinger, G; Parnham, M J

    2016-03-01

    Experimental autoimmune encephalomyelitis (EAE) is a widely-used rodent model for multiple sclerosis (MS), but a single model can hardly capture all features of MS. We investigated whether behavioral parameters in addition to clinical motor function scores could be used to assess treatment efficacy during score-free intervals in the relapsing-remitting EAE model in SJL/J mice. We studied the effects of the clinical reference compounds FTY720 (fingolimod, 0.5mg/kg/day) and dimethyl fumarate (DMF, 20-30 mg/kg/day) on clinical scores in several rodent EAE models in order to generate efficacy profiles. SJL/J mice with relapsing-remitting EAE were studied using behavioral tests, including rotarod, gait analysis, locomotor activity and grip strength. SJL/J mice were also examined according to Crawley's sociability and preference for social novelty test. Prophylactic treatment with FTY720 prevented clinical scores in three of the four EAE rodent models: Dark Agouti (DA) and Lewis rats and C57BL/6J mice. Neither prophylactic nor late-therapeutic treatment with FTY720 reduced clinical scores or reversed deficits in the rotarod test in SJL/J mice, but we observed effects on motor functions and sociability in the absence of clinical scores. Prophylactic treatment with FTY720 improved the gait of SJL/J mice whereas late-therapeutic treatment improved manifestations of reduced social (re)cognition or preference for social novelty. DMF was tested in three EAE models and did not improve clinical scores at the dose used. These data indicate that improvements in behavioral deficits can occur in absence of clinical scores, which indicate subtle drug effects and may have translational value for human MS. PMID:26692368

  1. Glutamate and GABA in appetite regulation

    Directory of Open Access Journals (Sweden)

    Teresa Cardoso Delgado

    2013-08-01

    Full Text Available Appetite is regulated by a coordinated interplay between gut, adipose tissue and brain. A primary site for the regulation of appetite is the hypothalamus where interaction between orexigenic neurons, expressing Neuropeptide Y/Agouti-related protein, and anorexigenic neurons, expressing Pro-opiomelanocortin cocaine/Amphetamine-related transcript, controls energy homeostasis. Within the hypothalamus, several peripheral signals have been shown to modulate the activity of these neurons, including the orexigenic peptide ghrelin and the anorexigenic hormones insulin and leptin. In addition to the accumulated knowledge on neuropeptide signaling, presence and function of amino acid neurotransmitters in key hypothalamic neurons brought a new light into appetite regulation. Therefore, the principal aim of this review will be to describe the current knowledge of the role of amino acid neurotransmitters in the mechanism of neuronal activation during appetite regulation and the associated neuronal-astrocytic metabolic coupling mechanisms.Glutamate and GABA dominate synaptic transmission in the hypothalamus and administration of their receptors agonists into hypothalamic nuclei stimulates feeding. By using 13C High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance spectroscopy based analysis, the Cerdán group has shown that increased neuronal firing in mice hypothalamus, as triggered by appetite during the feeding-fasting paradigm, may stimulate the use of lactate as neuronal fuel leading to increased astrocytic glucose consumption and glycolysis. Moreover, fasted mice showed increased hypothalamic [2-13C]GABA content, which may be explained by the existence of GABAergic neurons in key appetite regulation hypothalamic nuclei. Interestingly, increased [2-13C]GABA concentration in the hypothalamus of fasted animals appears to result mainly from reduction in GABA metabolizing pathways, rather than increased GABA synthesis by augmented activity of the

  2. Plasticity in gastrointestinal morphology and enzyme activity in lactating striped hamsters (Cricetulus barabensis).

    Science.gov (United States)

    Zhang, Ji-Ying; Zhao, Xiao-Ya; Wen, Jing; Tan, Song; Zhao, Zhi-Jun

    2016-05-01

    In small mammals, marked phenotypic plasticity of digestive physiology has been shown to make it easier for them to cope with energetically stressful periods, such as lactation. It has been proposed that the capacity of the gut to digest and absorb food is not the limiting factor to sustained energy intake (SusEI) during peak lactation. In this study, plasticity in energy intake and gastrointestinal morphology was examined in striped hamsters at different stages of reproduction and when raising litters of different sizes. Mechanisms associated with digestive enzymes and neuroendocrine hormones underpinning the plasticity were also examined. Females significantly increased energy intake, digestibility, digestive tract mass and the activity of stomach pepsin and small intestine maltase, sucrase and aminopeptidase in peak lactation compared with the non-productive and post-lactating periods. Further, females raising large litters significantly increased energy intake, digestibility, gastrointestinal mass and activity of digestive enzymes, and weaned heavier offspring compared with those nursing small and medium litters, indicating that the significant plasticity of digestive physiology increased reproductive performance. Agouti-related protein (AgRP) mRNA expression in the hypothalamus was up-regulated significantly in females raising large litters relative to those raising small litters. Serum leptin levels, and mRNA expression of hypothalamus neuropeptide Y (NPY) and the anorexigenic neuropeptides pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) did not differ among females raising small, medium and large litters. Leptin levels in lactation may only reflect a state of energy balance rather than being the prime driver of hyperphagia. Some hypothalamic neuropeptides, such as NPY, POMC and CART, may be involved in the limits to the SusEI during lactation. PMID:26944487

  3. Leptin regulates energy intake but fails to facilitate hibernation in fattening Daurian ground squirrels (Spermophilus dauricus).

    Science.gov (United States)

    Xing, Xin; Tang, Gang-Bin; Sun, Ming-Yue; Yu, Chao; Song, Shi-Yi; Liu, Xin-Yu; Yang, Ming; Wang, De-Hua

    2016-04-01

    Body fat storage before hibernation affects the timing of immergence in Daurian ground squirrels (Spermophilus dauricus). Leptin is an adipose signal and plays vital role in energy homeostasis mainly by action in brain. To test the hypothesis that leptin plays a role in facilitating the process of hibernation, squirrels were administrated with recombinant murine leptin (1μg/day) through intracerebroventricular (ICV) injection for 12 days during fattening. From day 7 to 12, animals were moved into a cold room (5±1°C) with constant darkness which functioned as hibernaculum. Energy intake, body mass and core body temperature (Tb) were continuously monitored throughout the course of experiment. Resting metabolic rate (RMR) was measured under both warm and cold conditions. At the end of leptin administration, we measured the serum concentration of hormones related to energy regulation, mRNA expression of hypothalamic neuropeptides and uncoupling protein 1 (UCP1) levels in brown adipose tissue (BAT). Our results showed that during leptin administration, the cumulative food intake and increase of body mass were suppressed while Tb and RMR were unaltered. The proportion of torpid squirrels was not different between two groups. At the end of leptin administration, the expressions of hypothalamic neuropeptide Y and agouti gene-related protein were suppressed. There were no differences in UCP1 mRNA expression or protein content in BAT between groups. Our data suggest that leptin can affect energy intake via hypothalamic neuropeptides, but is not involved in the initiation of hibernation in fattening Daurian ground squirrels. PMID:27033037

  4. Cloning, characterization and targeting of the mouse HEXA gene

    Energy Technology Data Exchange (ETDEWEB)

    Wakamatsu, N.; Trasler, J.M.; Gravel, R.A. [McGill Univ., Quebec (Canada)] [and others

    1994-09-01

    The HEXA gene, encoding the {alpha} subunit of {beta}-hexosaminidase A, is essential for the metabolism of ganglioside G{sub M2}, and defects in this gene cause Tay-Sachs disease in humans. To elucidate the role of the gene in the nervous system of the mouse and to establish a mouse model of Tay-Sachs disease, we have cloned and characterized the HEXA gene and targeted a disruption of the gene in mouse ES cells. The mouse HEXA gene spans {approximately}26 kb and consists of 14 exons, similar to the human gene. A heterogeneous transcription initiation site was identified 21-42 bp 5{prime} of the initiator ATG, with two of the sites fitting the consensus CTCA (A = start) as seen for some weak initiator systems. Promoter analysis showed that the first 150 bp 5{prime} of the ATG contained 85% of promoter activity observed in constructs containing up to 1050 bp of 5{prime} sequence. The active region contained a sequence matching that of the adenovirus major late promoter upstream element factor. A survey of mouse tissues showed that the highest mRNA levels were in (max to min): testis (5.5 x brain cortex), adrenal, epididymis, heart, brain, lung, kidney, and liver (0.3 x brain cortex). A 12 kb BstI/SalI fragment containing nine exons was disrupted with the insertion of the bacterial neo{sup r} gene in exon 11 and was targeted into 129/Sv ES cells by homologous recombination. Nine of 153 G418 resistant clones were correctly targeted as confirmed by Southern blotting. The heterozygous ES cells were microinjected into mouse blastocysts and implanted into pseudo-pregnant mice. Nine male chimeric mice, showing that 40-95% chimerism for the 129/Sv agouti coat color marker, are being bred in an effort to generate germline transmission of the disrupted HEXA gene.

  5. Myosin Va plays a role in nitrergic smooth muscle relaxation in gastric fundus and corpora cavernosa of penis.

    Directory of Open Access Journals (Sweden)

    Arun Chaudhury

    Full Text Available The intracellular motor protein myosin Va is involved in nitrergic neurotransmission possibly by trafficking of neuronal nitric oxide synthase (nNOS within the nerve terminals. In this study, we examined the role of myosin Va in the stomach and penis, proto-typical smooth muscle organs in which nitric oxide (NO mediated relaxation is critical for function. We used confocal microscopy and co-immunoprecipitation of tissue from the gastric fundus (GF and penile corpus cavernosum (CCP to localize myosin Va with nNOS and demonstrate their molecular interaction. We utilized in vitro mechanical studies to test whether smooth muscle relaxations during nitrergic neuromuscular neurotransmission is altered in DBA (dilute, brown, non-agouti mice which lack functional myosin Va. Myosin Va was localized in nNOS-positive nerve terminals and was co-immunoprecipitated with nNOS in both GF and CCP. In comparison to C57BL/6J wild type (WT mice, electrical field stimulation (EFS of precontracted smooth muscles of GF and CCP from DBA animals showed significant impairment of nitrergic relaxation. An NO donor, Sodium nitroprusside (SNP, caused comparable levels of relaxation in smooth muscles of WT and DBA mice. These normal postjunctional responses to SNP in DBA tissues suggest that impairment of smooth muscle relaxation resulted from inhibition of NO synthesis in prejunctional nerve terminals. Our results suggest that normal physiological processes of relaxation of gastric and cavernosal smooth muscles that facilitate food accommodation and penile erection, respectively, may be disrupted under conditions of myosin Va deficiency, resulting in complications like gastroparesis and erectile dysfunction.

  6. Betulinic acid regulates generation of neuroinflammatory mediators responsible for tissue destruction in multiple sclerosis in vitro

    Science.gov (United States)

    Blaževski, Jana; Petković, Filip; Momčilović, Miljana; Paschke, Reinhard; Kaluđerović, Goran N; Mostarica Stojković, Marija; Miljković, Djordje

    2013-01-01

    Aim: To investigate the influences of betulinic acid (BA), a triterpenoid isolated from birch bark, on neuroinflammatory mediators involved in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis in vitro. Methods: Encephalitogenic T cells were prepared from draining lymph nodes and spinal cords of Dark Agouti rats 8 to 10 d after immunization with myelin basic protein (MBP) and complete Freund's adjuvant. Macrophages were isolated from the peritoneal cavity of adult untreated rats. Astrocytes were isolated from neonatal rat brains. The cells were cultured and then treated with different agents. IFN-γ, IL-17, iNOS and CXCL12 mRNA levels in the cells were analyzed with RT-PCR. iNOS and CXCL12 protein levels were detected using immunoblot. NO and ROS generation was measured using Griess reaction and flow cytometry, respectively. Results: In encephalitogenic T cells stimulated with MBP (10 μg/mL), addition of BA inhibited IL-17 and IFN-γ production in a dose-dependent manner. The estimated IC50 values for IL-17 and IFN γ were 11.2 and 63.8 μmol/L, respectively. When the macrophages were stimulated with LPS (10 ng/mL), addition of BA (50 μmol/L) significantly increased ROS generation, and suppressed NO generation. The astrocytes were stimulated with ConASn containing numerous inflammatory mediators, which mimicked the inflammatory milieu within CNS; addition of BA (50 μmol/L) significantly increased ROS generation, and blocked ConASn-induced increases in iNOS and CXCL12 mRNA levels, but did not affect iNOS and CXCL12 protein levels. Importantly, in both the macrophages and astrocytes, addition of BA (50 μmol/L) inhibited lipid peroxidation. Conclusion: Besides inhibiting encephalitogenic T cell cytokines and reducing NO generation, BA induces tissue-damaging ROS generation within CNS. PMID:23377550

  7. Dietary emu oil supplementation suppresses 5-fluorouracil chemotherapy-induced inflammation, osteoclast formation, and bone loss.

    Science.gov (United States)

    Raghu Nadhanan, Rethi; Abimosleh, Suzanne M; Su, Yu-Wen; Scherer, Michaela A; Howarth, Gordon S; Xian, Cory J

    2012-06-01

    Cancer chemotherapy can cause osteopenia or osteoporosis, and yet the underlying mechanisms remain unclear, and currently, no preventative treatments are available. This study investigated damaging effects of 5-fluorouracil (5-FU) on histological, cellular, and molecular changes in the tibial metaphysis and potential protective benefits of emu oil (EO), which is known to possess a potent anti-inflammatory property. Female dark agouti rats were gavaged orally with EO or water (1 ml·day(-1)·rat(-1)) for 1 wk before a single ip injection of 5-FU (150 mg/kg) or saline (Sal) was given. The treatment groups were H(2)O + Sal, H(2)O + 5-FU, EO + 5-FU, and EO + Sal. Oral gavage was given throughout the whole period up to 1 day before euthanasia (days 3, 4, and 5 post-5-FU). Histological analysis showed that H(2)O + 5-FU significantly reduced heights of primary spongiosa on days 3 and 5 and trabecular bone volume of secondary spongiosa on days 3 and 4. It reduced density of osteoblasts slightly and caused an increase in the density of osteoclasts on trabecular bone surface on day 4. EO supplementation prevented reduction of osteoblasts and induction of osteoclasts and bone loss caused by 5-FU. Gene expression studies confirmed an inhibitory effect of EO on osteoclasts since it suppressed 5-FU-induced expression of proinflammatory and osteoclastogenic cytokine TNFα, osteoclast marker receptor activator of nuclear factor-κB, and osteoclast-associated receptor. Therefore, this study demonstrated that EO can counter 5-FU chemotherapy-induced inflammation in bone, preserve osteoblasts, suppress osteoclast formation, and potentially be useful in preventing 5-FU chemotherapy-induced bone loss. PMID:22436700

  8. A Novel Analytical Strategy to Identify Fusion Transcripts between Repetitive Elements and Protein Coding-Exons Using RNA-Seq

    Science.gov (United States)

    Feng, Jian; Fargo, David C.; Shen, Li; Riadi, Gonzalo; Keeley, Elizabeth; Rosh, Zachary S.; Nestler, Eric J.; Woychik, Richard P.

    2016-01-01

    Repetitive elements (REs) comprise 40–60% of the mammalian genome and have been shown to epigenetically influence the expression of genes through the formation of fusion transcript (FTs). We previously showed that an intracisternal A particle forms an FT with the agouti gene in mice, causing obesity/type 2 diabetes. To determine the frequency of FTs genome-wide, we developed a TopHat-Fusion-based analytical pipeline to identify FTs with high specificity. We applied it to an RNA-seq dataset from the nucleus accumbens (NAc) of mice repeatedly exposed to cocaine. Cocaine was previously shown to increase the expression of certain REs in this brain region. Using this pipeline that can be applied to single- or paired-end reads, we identified 438 genes expressing 813 different FTs in the NAc. Although all types of studied repeats were present in FTs, simple sequence repeats were underrepresented. Most importantly, reverse-transcription and quantitative PCR validated the expression of selected FTs in an independent cohort of animals, which also revealed that some FTs are the prominent isoforms expressed in the NAc by some genes. In other RNA-seq datasets, developmental expression as well as tissue specificity of some FTs differed from their corresponding non-fusion counterparts. Finally, in silico analysis predicted changes in the structure of proteins encoded by some FTs, potentially resulting in gain or loss of function. Collectively, these results indicate the robustness of our pipeline in detecting these new isoforms of genes, which we believe provides a valuable tool to aid in better understanding the broad role of REs in mammalian cellular biology. PMID:27415830

  9. Litter size variation in hypothalamic gene expression determines adult metabolic phenotype in Brandt's voles (Lasiopodomys brandtii.

    Directory of Open Access Journals (Sweden)

    Xue-Ying Zhang

    Full Text Available BACKGROUND: Early postnatal environments may have long-term and potentially irreversible consequences on hypothalamic neurons involved in energy homeostasis. Litter size is an important life history trait and negatively correlated with milk intake in small mammals, and thus has been regarded as a naturally varying feature of the early developmental environment. Here we investigated the long-term effects of litter size on metabolic phenotype and hypothalamic neuropeptide mRNA expression involved in the regulation of energy homeostasis, using the offspring reared from large (10-12 and small (3-4 litter sizes, of Brandt's voles (Lasiopodomys brandtii, a rodent species from Inner Mongolia grassland in China. METHODOLOGY/PRINCIPAL FINDINGS: Hypothalamic leptin signaling and neuropeptides were measured by Real-Time PCR. We showed that offspring reared from small litters were heavier at weaning and also in adulthood than offspring from large litters, accompanied by increased food intake during development. There were no significant differences in serum leptin levels or leptin receptor (OB-Rb mRNA in the hypothalamus at weaning or in adulthood, however, hypothalamic suppressor of cytokine signaling 3 (SOCS3 mRNA in adulthood increased in small litters compared to that in large litters. As a result, the agouti-related peptide (AgRP mRNA increased in the offspring from small litters. CONCLUSIONS/SIGNIFICANCE: These findings support our hypothesis that natural litter size has a permanent effect on offspring metabolic phenotype and hypothalamic neuropeptide expression, and suggest central leptin resistance and the resultant increase in AgRP expression may be a fundamental mechanism underlying hyperphagia and the increased risk of overweight in pups of small litters. Thus, we conclude that litter size may be an important and central determinant of metabolic fitness in adulthood.

  10. Changes in interleukin-1 signal modulators induced by 3,4-methylenedioxymethamphetamine (MDMA: regulation by CB2 receptors and implications for neurotoxicity

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    O'Shea Esther

    2011-05-01

    Full Text Available Abstract Background 3,4-Methylenedioxymethamphetamine (MDMA produces a neuroinflammatory reaction in rat brain characterized by an increase in interleukin-1 beta (IL-1β and microglial activation. The CB2 receptor agonist JWH-015 reduces both these changes and partially protects against MDMA-induced neurotoxicity. We have examined MDMA-induced changes in IL-1 receptor antagonist (IL-1ra levels and IL-1 receptor type I (IL-1RI expression and the effects of JWH-015. The cellular location of IL-1β and IL-1RI was also examined. MDMA-treated animals were given the soluble form of IL-1RI (sIL-1RI and neurotoxic effects examined. Methods Dark Agouti rats received MDMA (12.5 mg/kg, i.p. and levels of IL-1ra and expression of IL-1RI measured 1 h, 3 h or 6 h later. JWH-015 (2.4 mg/kg, i.p. was injected 48 h, 24 h and 0.5 h before MDMA and IL-1ra and IL-1RI measured. For localization studies, animals were sacrificed 1 h or 3 h following MDMA and stained for IL-1β or IL-1RI in combination with neuronal and microglial markers. sIL-1RI (3 μg/animal; i.c.v. was administered 5 min before MDMA and 3 h later. 5-HT transporter density was determined 7 days after MDMA injection. Results MDMA produced an increase in IL-ra levels and a decrease in IL-1RI expression in hypothalamus which was prevented by CB2 receptor activation. IL-1RI expression was localized on neuronal cell bodies while IL-1β expression was observed in microglial cells following MDMA. sIL-1RI potentiated MDMA-induced neurotoxicity. MDMA also increased IgG immunostaining indicating that blood brain-barrier permeability was compromised. Conclusions In summary, MDMA produces changes in IL-1 signal modulators which are modified by CB2 receptor activation. These results indicate that IL-1β may play a partial role in MDMA-induced neurotoxicity.

  11. Effects of Pax3 modifier genes on craniofacial morphology, pigmentation, and viability: A murine model of Waardenburg syndrome variation

    Energy Technology Data Exchange (ETDEWEB)

    Asher, J.H. Jr.; Harrison, R.W.; Morell, R.; Carey, M.L. [Michigan State Univ., East Lansing, MI (United States)] [and others

    1996-06-15

    Waardenburg syndrome type 1 is caused by mutations in PAX3. Over 50 human PAX3 mutations that lead to hearing, craniofacial, limb, and pigmentation anomalies have been identified. A PAX3 mutant allele, segregating in a family, can show reduced penetrance and variable expressivity that cannot be explained by the nature of the mutation alone. The Mus musculus Pax3 mutation Sp{sup d} (Splotch-delayed, Pax3{sup Sd}p), coisogenic on the C57BL/6J (B{sub 6}) genetic background, produces in heterozygotes a white belly spot with 100% penetrance and very few other anomalies. By contrast, many Sp{sup d}/+ BC{sub 1} progeny [F{sub 1} {female} Sp{sup d}/+ ({female} Sp{sup d}/+ B{sub 6} x {male} +/+ Mus spretus) x {male} +/+ B{sub 6}] exhibit highly variable craniofacial and pigmentary anomalies. Of the BC{sub 1} Sp{sup d}/+ progeny, 23.9% are estimated to be nonviable, and 32.1% are nonpenetrant for the white belly spot. The penetrance and expressivity of the Sp{sup d}/+ genotype are controlled in part by the genetic background and the sex of the individual. A minimum of two genes interact with Sp{sup d} to influence the craniofacial features of these mice. One of these genes may be either X-linked or sex-influenced, while the other is autosomal. The A-locus (Agouti) or a gene closely linked to A also plays a role in determining craniofacial features. At least one additional gene, possibly the A-locus or a gene linked to A, interacts with Sp{sup d} and determines the presence and size of the white belly spot. The viability of BC{sub 1} mice is influenced by at least three factors: Sp{sup d}, A-locus alleles or a gene closely linked to the A-locus, and the sex of the mouse. The BC{sub 1} mice provide an opportunity to identify genes that interact with and modify the expression of Pax3 and serve as a model to identify the genes that modify the expression of human PAX3 mutations. 65 refs., 3 figs., 6 tabs.

  12. Sestamibi is a substrate for MDR1 and MDR2 P-glycoprotein genes

    Energy Technology Data Exchange (ETDEWEB)

    Joseph, Brigid; Malhi, Harmeet; Gupta, Sanjeev [Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Ullmann 625, 1300 Morris Park Avenue, NY 10461, Bronx (United States); Bhargava, Kuldeep K.; Palestro, Christopher J. [Division of Nuclear Medicine, Long Island Jewish Medical Center, New York (United States); Schilsky, Michael L. [Division of Liver Diseases, Mount Sinai School of Medicine, New York (United States); Jain, Diwakar [Division of Nuclear Cardiology, MCP-Hahnemann University School of Medicine, Philadephia (United States)

    2003-07-01

    Technetium-99m sestamibi has attracted interest for assessment of the function of P-glycoproteins, which are well expressed in the liver and have roles in biliary transport and the removal of chemotherapeutic drugs. To further examine the cross-reactivity of {sup 99m}Tc-sestamibi for P-glycoprotein family members, we conducted studies in animals. Hepatobiliary secretion of {sup 99m}Tc-sestamibi was determined in normal FVB/N mice, mutant mice with specific P-glycoprotein deficiencies in the FVB/N background, normal Long-Evans Agouti (LEA) rats, and Long-Evans Cinnamon (LEC) rats with abnormal copper transport and liver disease but intact P-glycoprotein expression. After intrasplenic injection, {sup 99m}Tc-sestamibi was rapidly incorporated in the mouse and rat liver, with maximal accumulation after 102{+-}31 and 109{+-}16 s, respectively (P=NS). In normal mice and rats, 55%{+-}11% and 55%{+-}6%, respectively, of the maximal sestamibi activity was retained in the liver after 1 h (P=NS). In double knockout mice lacking both mdr1a and mdr1b homologs of the human MDR1 (ABCB1) gene, 88%{+-}11% of maximal sestamibi activity was retained in the liver after 1 h (P<0.001). In knockout mice deficient in either mdr1a gene or mdr2 (ABCB4) gene, biliary sestamibi excretion was also impaired, although this impairment was relatively less pronounced in ABCB4-deficient mice than in double knockout mice lacking both ABCB1 gene homologs (P<0.03). Hepatobiliary sestamibi excretion in LEC rats was not different from that in control normal rats, despite the presence of significant liver disease in the former. Hepatobiliary sestamibi excretion requires P-glycoproteins and is unperturbed in chronic liver disease. Sestamibi appears to be a substrate for both ABCB1 and ABCB4 genes, although the former utilizes it far more efficiently. Assessment of P-glycoprotein activity with sestamibi should consider how regulation of ABCB1 and related family members might modulate sestamibi incorporation

  13. Epigenetic Effects of Environmental Chemicals Bisphenol A and Phthalates

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    Steven Shoei-Lung Li

    2012-08-01

    Full Text Available The epigenetic effects on DNA methylation, histone modification, and expression of non-coding RNAs (including microRNAs of environmental chemicals such as bisphenol A (BPA and phthalates have expanded our understanding of the etiology of human complex diseases such as cancers and diabetes. Multiple lines of evidence from in vitro and in vivo models have established that epigenetic modifications caused by in utero exposure to environmental toxicants can induce alterations in gene expression that may persist throughout life. Epigenetics is an important mechanism in the ability of environmental chemicals to influence health and disease, and BPA and phthalates are epigenetically toxic. The epigenetic effect of BPA was clearly demonstrated in viable yellow mice by decreasing CpG methylation upstream of the Agouti gene, and the hypomethylating effect of BPA was prevented by maternal dietary supplementation with a methyl donor like folic acid or the phytoestrogen genistein. Histone H3 was found to be trimethylated at lysine 27 by BPA effect on EZH2 in a human breast cancer cell line and mice. BPA exposure of human placental cell lines has been shown to alter microRNA expression levels, and specifically, miR-146a was strongly induced by BPA treatment. In human breast cancer MCF7 cells, treatment with the phthalate BBP led to demethylation of estrogen receptor (ESR1 promoter-associated CpG islands, indicating that altered ESR1 mRNA expression by BBP is due to aberrant DNA methylation. Maternal exposure to phthalate DEHP was also shown to increase DNA methylation and expression levels of DNA methyltransferases in mouse testis. Further, some epigenetic effects of BPA and phthalates in female rats were found to be transgenerational. Finally, the available new technologies for global analysis of epigenetic alterations will provide insight into the extent and patterns of alterations between human normal and diseased tissues.

  14. Optogenetic Stimulation of Arcuate Nucleus Kiss1 Neurons Reveals a Steroid-Dependent Glutamatergic Input to POMC and AgRP Neurons in Male Mice.

    Science.gov (United States)

    Nestor, Casey C; Qiu, Jian; Padilla, Stephanie L; Zhang, Chunguang; Bosch, Martha A; Fan, Wei; Aicher, Sue A; Palmiter, Richard D; Rønnekleiv, Oline K; Kelly, Martin J

    2016-06-01

    Kisspeptin (Kiss1) neurons are essential for reproduction, but their role in the control of energy balance and other homeostatic functions remains unclear. Proopiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons, located in the arcuate nucleus (ARC) of the hypothalamus, integrate numerous excitatory and inhibitory inputs to ultimately regulate energy homeostasis. Given that POMC and AgRP neurons are contacted by Kiss1 neurons in the ARC (Kiss1(ARC)) and they express androgen receptors, Kiss1(ARC) neurons may mediate the orexigenic action of testosterone via POMC and/or AgRP neurons. Quantitative PCR analysis of pooled Kiss1(ARC) neurons revealed that mRNA levels for Kiss1 and vesicular glutamate transporter 2 were higher in castrated male mice compared with gonad-intact males. Single-cell RT-PCR analysis of yellow fluorescent protein (YFP) ARC neurons harvested from males injected with AAV1-EF1α-DIO-ChR2:YFP revealed that 100% and 88% expressed mRNAs for Kiss1 and vesicular glutamate transporter 2, respectively. Whole-cell, voltage-clamp recordings from nonfluorescent postsynaptic ARC neurons showed that low frequency photo-stimulation (0.5 Hz) of Kiss1-ChR2:YFP neurons elicited a fast glutamatergic inward current in POMC and AgRP neurons. Paired-pulse, photo-stimulation revealed paired-pulse depression, which is indicative of greater glutamate release, in the castrated male mice compared with gonad-intact male mice. Group I and group II metabotropic glutamate receptor agonists depolarized and hyperpolarized POMC and AgRP neurons, respectively, which was mimicked by high frequency photo-stimulation (20 Hz) of Kiss1(ARC) neurons. Therefore, POMC and AgRP neurons receive direct steroid- and frequency-dependent glutamatergic synaptic input from Kiss1(ARC) neurons in male mice, which may be a critical pathway for Kiss1 neurons to help coordinate energy homeostasis and reproduction. PMID:27093227

  15. MC1R and the response of melanocytes to ultraviolet radiation

    Energy Technology Data Exchange (ETDEWEB)

    Rouzaud, Francois [Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Building 37, Room 2132, Bethesda, MD 20892 (United States); Kadekaro, Ana Luisa [Department of Dermatology, University of Cincinnati, College of Medicine, Cincinnati, OH 45267 (United States); Abdel-Malek, Zalfa A. [Department of Dermatology, University of Cincinnati, College of Medicine, Cincinnati, OH 45267 (United States); Hearing, Vincent J. [Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Building 37, Room 2132, Bethesda, MD 20892 (United States)]. E-mail: hearingv@nih.gov

    2005-04-01

    The constitutive color of our skin plays a dramatic role in our photoprotection from solar ultraviolet radiation (UVR) that reaches the Earth and in minimizing DNA damage that gives rise to skin cancer. More than 120 genes have been identified and shown to regulate pigmentation, one of the key genes being melanocortin 1 receptor (MC1R) that encodes the melanocortin 1 receptor (MC1R), a seven-transmembrane G protein-coupled receptor expressed on the surface of melanocytes. Modulation of MC1R function regulates melanin synthesis by melanocytes qualitatively and quantitatively. The MC1R is regulated by the physiological agonists {alpha}-melanocyte-stimulating hormone ({alpha}MSH) and adrenocorticotropic hormone (ACTH), and antagonist agouti signaling protein (ASP). Activation of the MC1R by binding of an agonist stimulates the synthesis of eumelanin primarily via activation of adenylate cyclase. The significance of cutaneous pigmentation lies in the photoprotective effect of melanin, particularly eumelanin, against sun-induced carcinogenesis. Epidermal melanocytes and keratinocytes respond to UVR by increasing their expression of {alpha}MSH and ACTH, which up-regulate the expression of MC1R, and consequently enhance the response of melanocytes to melanocortins. Constitutive skin pigmentation dramatically affects the incidence of skin cancer. The pigmentary phenotype characterized by red hair, fair complexion, inability to tan and tendency to freckle is an independent risk factor for all skin cancers, including melanoma. The MC1R gene is highly polymorphic in human populations, and allelic variation at this locus accounts, to a large extent, for the variation in pigmentary phenotypes and skin phototypes (SPT) in humans. Several allelic variants of the MC1R gene are associated with the red hair and fair skin (RHC) phenotype, and carrying one of these variants is thought to diminish the ability of the epidermis to respond to DNA damage elicited by UVR. The MC1R gene is

  16. Imprinted genes and transpositions: epigenomic targets for low dose radiation effects. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Jirtle, Randy L.

    2012-10-11

    The overall hypothesis of this grant application is that low dose ionizing radiation (LDIR) elicits adaptive responses in part by causing heritable DNA methylation changes in the epigenome. This novel postulate was tested by determining if the level of DNA methylation at the Agouti viable yellow (A{sup vy}) metastable locus is altered, in a dose-dependent manner, by low dose radiation exposure (<10 cGy) during early gestation. This information is particularly important to ascertain given the increased use of CT scans in disease diagnosis, increased number of people predicted to live and work in space, and the present concern about radiological terrorism. We showed for the first time that LDIR significantly increased DNA methylation at the A{sup vy} locus in a sex-specific manner (p=0.004). Average DNA methylation was significantly increased in male offspring exposed to doses between 0.7 cGy and 7.6 cGy with maximum effects at 1.4 cGy and 3.0 cGy (p<0.01). Offspring coat color was concomitantly shifted towards pseudoagouti (p<0.01). Maternal dietary antioxidant supplementation mitigated both the DNA methylation changes and coat color shift in the irradiated offspring (p<0.05). Thus, LDIR exposure during gestation elicits epigenetic alterations that lead to positive adaptive phenotypic changes that are negated with antioxidants, indicating they are mediated in part by oxidative stress. These findings provide evidence that in the isogenic Avy mouse model epigenetic alterations resulting from LDIR play a role in radiation hormesis, bringing into question the assumption that every dose of radiation is harmful. Our findings not only have significant implications concerning the mechanism of hormesis, but they also emphasize the potential importance of this phenomenon in determining human risk at low radiation doses. Since the epigenetic regulation of genes varies markedly between species, the effect of LDIR on other epigenetically labile genes (e.g. imprinted genes) in

  17. Arthritis suppression by NADPH activation operates through an interferon-β pathway

    Directory of Open Access Journals (Sweden)

    Andersson Sofia

    2007-05-01

    Full Text Available Abstract Background A polymorphism in the activating component of the nicotinamide adenine dinucleotide phosphate (NADPH oxidase complex, neutrophil cytosolic factor 1 (NCF1, has previously been identified as a regulator of arthritis severity in mice and rats. This discovery resulted in a search for NADPH oxidase-activating substances as a potential new approach to treat autoimmune disorders such as rheumatoid arthritis (RA. We have recently shown that compounds inducing NCF1-dependent oxidative burst, e.g. phytol, have a strong ameliorating effect on arthritis in rats. However, the underlying molecular mechanism is still not clearly understood. The aim of this study was to use gene-expression profiling to understand the protective effect against arthritis of activation of NADPH oxidase in the immune system. Results Subcutaneous administration of phytol leads to an accumulation of the compound in the inguinal lymph nodes, with peak levels being reached approximately 10 days after administration. Hence, global gene-expression profiling on inguinal lymph nodes was performed 10 days after the induction of pristane-induced arthritis (PIA and phytol administration. The differentially expressed genes could be divided into two pathways, consisting of genes regulated by different interferons. IFN-γ regulated the pathway associated with arthritis development, whereas IFN-β regulated the pathway associated with disease protection through phytol. Importantly, these two molecular pathways were also confirmed to differentiate between the arthritis-susceptible dark agouti (DA rat, (with an Ncf-1DA allele that allows only low oxidative burst, and the arthritis-protected DA.Ncf-1E3 rat (with an Ncf1E3 allele that allows a stronger oxidative burst. Conclusion Naturally occurring genetic polymorphisms in the Ncf-1 gene modulate the activity of the NADPH oxidase complex, which strongly regulates the severity of arthritis. We now show that the Ncf-1 allele that

  18. Novel role for SLPI in MOG-induced EAE revealed by spinal cord expression analysis

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    Aigner Ludwig

    2008-05-01

    Full Text Available Abstract Background Experimental autoimmune encephalomyelitis (EAE induced by myelin oligodendrocyte protein (MOG in female Dark Agouti (DA rats is a chronic demyelinating animal model of multiple sclerosis (MS. To identify new candidate molecules involved in the evolution or repair of EAE-lesions we used Affymetrix oligonucleotide microarrays to compare the spinal cord transcriptome at the peak of EAE, during remission and at the first relapse with healthy DA rats. Methods Untreated DA rats and DA rats immunised with MOG protein were sacrificed at defined time points. Total RNA was isolated from spinal cord tissue and used for hybridization of Affymetrix rat genome arrays RG U34 A-C. Selected expression values were confirmed by RealTime PCR. Adult neural stem cells were incubated with recombinant secretory leukocyte protease inhibitor (SLPI. Proliferation was assessed by BrdU incorporation, cyclin D1 and HES1 expression by RealTime PCR, cell differentiation by immunofluorescence analysis and IkappaBalpha degradation by Western blot. Results Among approximately 26,000 transcripts studied more than 1,100 were differentially regulated. Focussing on functional themes, we noticed a sustained downregulation of most of the transcripts of the cholesterol biosynthesis pathway. Furthermore, we found new candidate genes possibly contributing to regenerative processes in the spinal cord. Twelve transcripts were solely upregulated in the recovery phase, including genes not previously associated with repair processes. Expression of SLPI was upregulated more than hundredfold during EAE attack. Using immunohistochemistry, SLPI was identified in macrophages, activated microglia, neuronal cells and astrocytes. Incubation of adult neural stem cells (NSC with recombinant SLPI resulted in an increase of cell proliferation and of differentiation towards oligodendrocytes. These processes were paralleled by an upregulation of the cell-cycle promotor cyclin D1 and a

  19. Somato-dendritic localization and signaling by leptin receptors in hypothalamic POMC and AgRP neurons.

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    Sangdeuk Ha

    Full Text Available Leptin acts via neuronal leptin receptors to control energy balance. Hypothalamic pro-opiomelanocortin (POMC and agouti-related peptide (AgRP/Neuropeptide Y (NPY/GABA neurons produce anorexigenic and orexigenic neuropeptides and neurotransmitters, and express the long signaling form of the leptin receptor (LepRb. Despite progress in the understanding of LepRb signaling and function, the sub-cellular localization of LepRb in target neurons has not been determined, primarily due to lack of sensitive anti-LepRb antibodies. Here we applied light microscopy (LM, confocal-laser scanning microscopy (CLSM, and electron microscopy (EM to investigate LepRb localization and signaling in mice expressing a HA-tagged LepRb selectively in POMC or AgRP/NPY/GABA neurons. We report that LepRb receptors exhibit a somato-dendritic expression pattern. We further show that LepRb activates STAT3 phosphorylation in neuronal fibers within several hypothalamic and hindbrain nuclei of wild-type mice and rats, and specifically in dendrites of arcuate POMC and AgRP/NPY/GABA neurons of Leprb (+/+ mice and in Leprb (db/db mice expressing HA-LepRb in a neuron specific manner. We did not find evidence of LepRb localization or STAT3-signaling in axon-fibers or nerve-terminals of POMC and AgRP/NPY/GABA neurons. Three-dimensional serial EM-reconstruction of dendritic segments from POMC and AgRP/NPY/GABA neurons indicates a high density of shaft synapses. In addition, we found that the leptin activates STAT3 signaling in proximity to synapses on POMC and AgRP/NPY/GABA dendritic shafts. Taken together, these data suggest that the signaling-form of the leptin receptor exhibits a somato-dendritic expression pattern in POMC and AgRP/NPY/GABA neurons. Dendritic LepRb signaling may therefore play an important role in leptin's central effects on energy balance, possibly through modulation of synaptic activity via post-synaptic mechanisms.

  20. Supplementation of branched-chain amino acids to a reduced-protein diet improves growth performance in piglets: involvement of increased feed intake and direct muscle growth-promoting effect.

    Science.gov (United States)

    Zheng, Liufeng; Wei, Hongkui; Cheng, Chuanshang; Xiang, Quanhang; Pang, Jiaman; Peng, Jian

    2016-06-01

    The aim of this study was to investigate whether supplementing branched-chain amino acids (AA) (BCAA) along with a reduced-protein diet increases piglet growth, and whether elevated feed intake and muscle growth-promoting effect contribute to this improvement. In Expt 1, twenty-eight weanling piglets were randomly fed one of the following four diets: a positive control (PC) diet, a reduced-protein negative control (NC) diet, an NC diet supplemented with BCAA to the same levels as in the PC diet (test 1 (T1)) and an NC diet supplemented with a 2-fold dose of BCAA in T1 diet (test 2 (T2)) for 28 d. In Expt 2, twenty-one weanling piglets were randomly assigned to NC, T1 and pair-fed T1 (P) groups. NC and T1 diets were the same as in Expt 1, whereas piglets in the P group were individually pair-fed with the NC group. In Expt 1, the NC group had reduced piglet growth and feed intake compared with the PC group, which were restored in T1 and T2 groups, but no differences were detected between T1 and T2 groups. In Expt 2, T1 and P groups showed increases in growth and mass of some muscles compared with the NC group. Increased feed intake after BCAA supplementation was associated with increased mRNA expressions of agouti-related peptide and co-express neuropeptide Y (NPY) and phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase 1 (S6K1), as well as decreased mRNA expressions of melanocortin-4 receptor and cocaine- and amphetamine-regulated transcript and phosphorylation of eukaryotic initiation factor 2α in the hypothalamus. No differences were observed among PC, T1 and T2 groups except for higher NPY mRNA expression in the T2 group than in the PC group (Expt 1). Phosphorylation of mTOR and S6K1 in muscle was enhanced after BCAA supplementation, which was independent of change in feed intake (Expt 2). In conclusion, supplementing BCAA to reduced-protein diets increases feed intake and muscle mass, and contributes to better growth

  1. Alterations in the hypothalamic melanocortin pathway in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Vercruysse, Pauline; Sinniger, Jérôme; El Oussini, Hajer; Scekic-Zahirovic, Jelena; Dieterlé, Stéphane; Dengler, Reinhard; Meyer, Thomas; Zierz, Stephan; Kassubek, Jan; Fischer, Wilhelm; Dreyhaupt, Jens; Grehl, Torsten; Hermann, Andreas; Grosskreutz, Julian; Witting, Anke; Van Den Bosch, Ludo; Spreux-Varoquaux, Odile; Ludolph, Albert C; Dupuis, Luc

    2016-04-01

    Amyotrophic lateral sclerosis, the most common adult-onset motor neuron disease, leads to death within 3 to 5 years after onset. Beyond progressive motor impairment, patients with amyotrophic lateral sclerosis suffer from major defects in energy metabolism, such as weight loss, which are well correlated with survival. Indeed, nutritional intervention targeting weight loss might improve survival of patients. However, the neural mechanisms underlying metabolic impairment in patients with amyotrophic lateral sclerosis remain elusive, in particular due to the lack of longitudinal studies. Here we took advantage of samples collected during the clinical trial of pioglitazone (GERP-ALS), and characterized longitudinally energy metabolism of patients with amyotrophic lateral sclerosis in response to pioglitazone, a drug with well-characterized metabolic effects. As expected, pioglitazone decreased glycaemia, decreased liver enzymes and increased circulating adiponectin in patients with amyotrophic lateral sclerosis, showing its efficacy in the periphery. However, pioglitazone did not increase body weight of patients with amyotrophic lateral sclerosis independently of bulbar involvement. As pioglitazone increases body weight through a direct inhibition of the hypothalamic melanocortin system, we studied hypothalamic neurons producing proopiomelanocortin (POMC) and the endogenous melanocortin inhibitor agouti-related peptide (AGRP), in mice expressing amyotrophic lateral sclerosis-linked mutant SOD1(G86R). We observed lowerPomcbut higherAgrpmRNA levels in the hypothalamus of presymptomatic SOD1(G86R) mice. Consistently, numbers of POMC-positive neurons were decreased, whereas AGRP fibre density was elevated in the hypothalamic arcuate nucleus of SOD1(G86R) mice. Consistent with a defect in the hypothalamic melanocortin system, food intake after short term fasting was increased in SOD1(G86R) mice. Importantly, these findings were replicated in two other amyotrophic lateral

  2. Anorexia is Associated with Stress-Dependent Orexigenic Responses to Exogenous Neuropeptide Y.

    Science.gov (United States)

    Yi, J; Delp, M S; Gilbert, E R; Siegel, P B; Cline, M A

    2016-05-01

    Chicken lines that have been divergently selected for either low (LWS) or high (HWS) body weight at 56 days of age for more than 57 generations have different feeding behaviours in response to a range of i.c.v. injected neurotransmitters. The LWS have different severities of anorexia, whereas the HWS become obese. Previously, we demonstrated that LWS chicks did not respond, whereas HWS chicks increased food intake, after central injection of neuropeptide Y (NPY). The present study aimed to determine the molecular mechanisms underlying the loss of orexigenic function of NPY in LWS. Chicks were divided into four groups: stressed LWS and HWS on day of hatch, and control LWS and HWS. The stressor was a combination of food deprivation and cold exposure. On day 5 post-hatch, each chick received an i.c.v. injection of vehicle or 0.2 nmol of NPY. Only the LWS stressed group did not increase food intake in response to i.c.v. NPY. Hypothalamic mRNA abundance of appetite-associated factors was measured at 1 h post-injection. Interactions of genetic line, stress and NPY treatment were observed for the mRNA abundance of agouti-related peptide (AgRP) and synaptotagmin 1 (SYT1). Intracerebroventricular injection of NPY decreased and increased AgRP and SYT1 mRNA, respectively, in the stressed LWS and increased AgRP mRNA in stressed HWS chicks. Stress was associated with increased NPY, orexin receptor 2, corticotrophin-releasing factor receptor 1, melanocortin receptor 3 (MC3R) and growth hormone secretagogue receptor expression. In conclusion, the loss of responsiveness to exogenous NPY in stressed LWS chicks may be a result of the decreased and increased hypothalamic expression of AgRP and MC3R, respectively. This may induce an intensification of anorexigenic melanocortin signalling pathways in LWS chicks that block the orexigenic effect of exogenous NPY. These results provide insights onto the anorexic condition across species, and especially for forms of inducible anorexia

  3. MC1R and the response of melanocytes to ultraviolet radiation

    International Nuclear Information System (INIS)

    The constitutive color of our skin plays a dramatic role in our photoprotection from solar ultraviolet radiation (UVR) that reaches the Earth and in minimizing DNA damage that gives rise to skin cancer. More than 120 genes have been identified and shown to regulate pigmentation, one of the key genes being melanocortin 1 receptor (MC1R) that encodes the melanocortin 1 receptor (MC1R), a seven-transmembrane G protein-coupled receptor expressed on the surface of melanocytes. Modulation of MC1R function regulates melanin synthesis by melanocytes qualitatively and quantitatively. The MC1R is regulated by the physiological agonists α-melanocyte-stimulating hormone (αMSH) and adrenocorticotropic hormone (ACTH), and antagonist agouti signaling protein (ASP). Activation of the MC1R by binding of an agonist stimulates the synthesis of eumelanin primarily via activation of adenylate cyclase. The significance of cutaneous pigmentation lies in the photoprotective effect of melanin, particularly eumelanin, against sun-induced carcinogenesis. Epidermal melanocytes and keratinocytes respond to UVR by increasing their expression of αMSH and ACTH, which up-regulate the expression of MC1R, and consequently enhance the response of melanocytes to melanocortins. Constitutive skin pigmentation dramatically affects the incidence of skin cancer. The pigmentary phenotype characterized by red hair, fair complexion, inability to tan and tendency to freckle is an independent risk factor for all skin cancers, including melanoma. The MC1R gene is highly polymorphic in human populations, and allelic variation at this locus accounts, to a large extent, for the variation in pigmentary phenotypes and skin phototypes (SPT) in humans. Several allelic variants of the MC1R gene are associated with the red hair and fair skin (RHC) phenotype, and carrying one of these variants is thought to diminish the ability of the epidermis to respond to DNA damage elicited by UVR. The MC1R gene is considered a

  4. Missense and nonsense mutations in melanocortin 1 receptor (MC1R gene of different goat breeds: association with red and black coat colour phenotypes but with unexpected evidences

    Directory of Open Access Journals (Sweden)

    Davoli Roberta

    2009-08-01

    Full Text Available Abstract Background Agouti and Extension loci control the relative amount of eumelanin and pheomelanin production in melanocytes that, in turn, affects pigmentation of skin and hair. The Extension locus encodes the melanocortin 1 receptor (MC1R whose permanent activation, caused by functional mutations, results in black coat colour, whereas other inactivating mutations cause red coat colour in different mammals. Results The whole coding region of the MC1R gene was sequenced in goats of six different breeds showing different coat colours (Girgentana, white cream with usually small red spots in the face; Maltese, white with black cheeks and ears; Derivata di Siria, solid red; Murciano-Granadina, solid black or solid brown; Camosciata delle Alpi, brown with black stripes; Saanen, white; F1 goats and the parental animals. Five single nucleotide polymorphisms (SNPs were identified: one nonsense mutation (p.Q225X, three missense mutations (p.A81V, p.F250V, and p.C267W, and one silent mutation. The stop codon at position 225 should cause the production of a shorter MC1R protein whose functionality may be altered. These SNPs were investigated in a larger sample of animals belonging to the six breeds. The Girgentana breed was almost fixed for the p.225X allele. However, there was not complete association between the presence of red spots in the face and the presence of this allele in homozygous condition. The same allele was identified in the Derivata di Siria breed. However, its frequency was only 33%, despite the fact that these animals are completely red. The p.267W allele was present in all Murciano-Granadina black goats, whereas it was never identified in the brown ones. Moreover, the same substitution was present in almost all Maltese goats providing evidence of association between this mutation and black coat colour. Conclusion According to the results obtained in the investigated goat breeds, MC1R mutations may determine eumelanic and pheomelanic

  5. Interleukin 6 deficiency modulates the hypothalamic expression of energy balance regulating peptides during pregnancy in mice.

    Directory of Open Access Journals (Sweden)

    Patricia Pazos

    Full Text Available Pregnancy is associated with hyperphagia, increased adiposity and multiple neuroendocrine adaptations. Maternal adipose tissue secretes rising amounts of interleukin 6 (IL6, which acts peripherally modulating metabolic function and centrally increasing energy expenditure and reducing body fat. To explore the role of IL6 in the central mechanisms governing dam's energy homeostasis, early, mid and late pregnant (gestational days 7, 13 and 18 wild-type (WT and Il6 knockout mice (Il6-KO were compared with virgin controls at diestrus. Food intake, body weight and composition as well as indirect calorimetry measurements were performed in vivo. Anabolic and orexigenic peptides: neuropeptide Y (Npy and agouti-related peptide (Agrp; and catabolic and anorectic neuropeptides: proopiomelanocortin (Pomc, corticotrophin and thyrotropin-releasing hormone (Crh and Trh mRNA levels were determined by in situ hybridization. Real time-PCR and western-blot were used for additional tissue gene expression and protein studies. Non-pregnant Il6-KO mice were leaner than WT mice due to a decrease in fat but not in lean body mass. Pregnant Il6-KO mice had higher fat accretion despite similar body weight gain than WT controls. A decreased fat utilization in absence of Il6 might explain this effect, as shown by increased respiratory exchange ratio (RER in virgin Il6-KO mice. Il6 mRNA levels were markedly enhanced in adipose tissue but reduced in hypothalamus of mid and late pregnant WT mice. Trh expression was also stimulated at gestational day 13 and lack of Il6 blunted this effect. Conversely, in late pregnant mice lessened hypothalamic Il6 receptor alpha (Il6ra, Pomc and Crh mRNA were observed. Il6 deficiency during this stage up-regulated Npy and Agrp expression, while restoring Pomc mRNA levels to virgin values. Together these results demonstrate that IL6/IL6Ra system modulates Npy/Agrp, Pomc and Trh expression during mouse pregnancy, supporting a role of IL6 in the

  6. Evolution of alanine:glyoxylate aminotransferase 1 peroxisomal and mitochondrial targeting. A survey of its subcellular distribution in the livers of various representatives of the classes Mammalia, Aves and Amphibia.

    Science.gov (United States)

    Danpure, C J; Fryer, P; Jennings, P R; Allsop, J; Griffiths, S; Cunningham, A

    1994-08-01

    As part of a wider study on the molecular evolution of alanine:glyoxylate aminotransferase 1 (AGT1) intracellular compartmentalization, we have determined the subcellular distribution of immunoreactive AGT1, using postembedding protein A-gold immunoelectron microscopy, in the livers of various members of the classes Mammalia, Aves, and Amphibia. As far as organellar distribution is concerned, three categories could be distinguished. In members of the first category (type I), all, or nearly all, of the immunoreactive AGT1 was concentrated within the peroxisomes. In the second category (type II), AGT1 was found more evenly distributed in both peroxisomes and mitochondria. In the third category (type III), AGT1 was localized mainly within the mitochondria with much lower, but widely variable, amounts in the peroxisomes. Type I animals include the human, two great apes (gorilla, orangutan), two Old World monkeys (anubis baboon, Japanese macaque), a New World monkey (white-faced Saki monkey), a lago, morph (European rabbit), a bat (Seba's short-tailed fruit bat), two caviomorph rodents (guinea pig, orange-rumped agouti), and two Australian marsupials (koala, Bennett's wallaby). Type II animals include two New World monkeys (common marmoset, cotton-top tamarin), three prosimians (brown lemur, fat-tailed dwarf lemur, pygmy slow loris), five rodents (a hybrid crested porcupine, Colombian ground squirrel, laboratory rat, laboratory mouse, golden hamster), an American marsupial (grey short-tailed opossum), and a bird (raven). Type III animals include the large tree shrew, three insectivores (common Eurasian mole, European hedgehog, house shrew), four carnivores (domestic cat, ocelot, domestic dog, polecat ferret), and an amphibian (common frog). In addition to these categories, some animals (e.g. guinea pig, common frog) possessed significant amounts of cytosolic AGT1. Whereas the subcellular distribution of AGT1 in some orders (e.g. Insectivora and Carnivora) did not appear

  7. Induction of Foxp3-expressing regulatory T-cells by donor blood transfusion is required for tolerance to rat liver allografts.

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    Yuta Abe

    Full Text Available BACKGROUND: Donor-specific blood transfusion (DST prior to solid organ transplantation has been shown to induce long-term allograft survival in the absence of immunosuppressive therapy. Although the mechanisms underlying DST-induced allograft tolerance are not well defined, there is evidence to suggest DST induces one or more populations of antigen-specific regulatory cells that suppress allograft rejection. However, neither the identity nor the regulatory properties of these tolerogenic lymphocytes have been reported. Therefore, the objective of this study was to define the kinetics, phenotype and suppressive function of the regulatory cells induced by DST alone or in combination with liver allograft transplantation (LTx. METHODOLOGY/PRINCIPAL FINDINGS: Tolerance to Dark Agouti (DA; RT1(a rat liver allografts was induced by injection (iv of 1 ml of heparinized DA blood to naïve Lewis (LEW; RT1(l rats once per week for 4 weeks prior to LTx. We found that preoperative DST alone generates CD4(+ T-cells that when transferred into naïve LEW recipients are capable of suppressing DA liver allograft rejection and promoting long-term survival of the graft and recipient. However, these DST-generated T-cells did not express the regulatory T-cell (Treg transcription factor Foxp3 nor did they suppress alloantigen (DA-induced activation of LEW T-cells in vitro suggesting that these lymphocytes are not fully functional regulatory Tregs. We did observe that DST+LTx (but not DST alone induced the time-dependent formation of CD4(+Foxp3(+ Tregs that potently suppressed alloantigen-induced activation of naïve LEW T-cells in vitro and liver allograft rejection in vivo. Finally, we present data demonstrating that virtually all of the Foxp3-expressing Tregs reside within the CD4(+CD45RC(- population whereas in which approximately 50% of these Tregs express CD25. CONCLUSIONS/SIGNIFICANCE: We conclude that preoperative DST, in the absence of liver allograft

  8. 大鼠腹腔内心脏移植模型的构建和体会%Experiences of establishing an abdominal heart transplantation model in rats

    Institute of Scientific and Technical Information of China (English)

    陈浩; 梅运清; Michael A Solomon

    2012-01-01

    Objective To review the experiences and key factors of establishing an abdominal cardiac transplantation model in rats at National Institutes of Health Clinical Center.Methods Dark Agouti rats served as donor while Brown Norway rats as recipient.Cardiac transplantations were performed with a modified version of heterotopic cardiac transplantation.Proficiency was defined as 20 consecutive operations with < 15% mortality and no significant major co-morbidities.Results We performed 10 donor harvestalone operations and 70 transplantations to reach the proficiency level The survival rate of the last 20 consecutive surgeries was 95%.The mean total operative duration was 55 ruin and mean ischemic time of donor hearts 35 min.Conclusion To ensure a consistently high operative success rate,a surgeon must not only be proficient in micro-surgical skills,but also closely follow the standardized training procedures and strictly observe the animal care and use guidelines.%目的 总结在美国国立卫生研究院临床中心建立大鼠腹腔内心脏移植模型的经验,探讨手术成功的主要影响因素.方法 以80只Dark Agouti大鼠为供体,70只Brown Norway大鼠为受体,制作大鼠心脏移植模型.以连续20例手术死亡率低于15%且无明显合并症为手术合格标准.结果 为达到合格标准,共施行了10例大鼠供体手术,70例大鼠移植手术.最后20例移植手术成功率为95%,平均手术时间为55 min,供心平均缺血时间为35 min.结论 精准的显微外科技术,加上标准化手术训练和严格的动物管理,是保证手术成功率的关键因素.

  9. Effect of residual feed intake on hypothalamic gene expression and meat quality in Angus-sired cattle grown during the hot season.

    Science.gov (United States)

    Perkins, S D; Key, C N; Marvin, M N; Garrett, C F; Foradori, C D; Bratcher, C L; Kriese-Anderson, L A; Brandebourg, T D

    2014-04-01

    The relationship between heat stress, meat quality, and residual feed intake (RFI) is unknown in growing steers. To address this issue, high RFI (HRFI) and low RFI (LRFI) individuals were compared by assessing RFI in 48 Angus-sired steers during a 70-d feeding trial conducted during July through September to identify steers with calculated RFI at least 2 SD apart. The association of RFI with indices of meat quality and expression of genes within hypothalamic and adipose tissue was then determined in LRFI and HRFI steers. While on test, feed intake was recorded daily with BW and hip heights recorded every 14 d. Ultrasound measurements of rib eye area (REA) and backfat (BF) were recorded initially and before harvest. Carcass and growth data were analyzed using a mixed model with RFI level (LRFI and HRFI) as the independent variable. The least square means for RFI were -1.2 and 0.99 kg DMI/d, respectively, for the LRFI and HRFI cohorts (P grade (P meat quality. Hypothalamic neuropeptide Y (NPY), agouti related protein (AGRP), relaxin-3 (RLN3), melanocortin 3 receptor, and relaxin/insulin-like family peptide receptor 1 (RXFP1) mRNA were expressed 280, 185, 202, 183, and 163% greater, respectively (P < 0.01), while proopiomelanocortin (POMC) mRNA was expressed 42% lower in LRFI than HRFI animals (P < 0.05). Hypothalamic GnRH mRNA expression was 67% lower while gonadotropin inhibiting hormone (GnIH) mRNA was 209% higher in LRFI than HRFI animals (P < 0.01). Pituitary expression of FSHβ and LHβ correlated to hypothalamic GnRH levels (P < 0.05) indicating changes in gene expression within the hypothalamus had functional consequences. Leptin mRNA expression levels were not different between adipose tissue of LRFI or HRFI steers (P < 0.84). These data indicate that animals with superior RFI evaluated during warm conditions have higher expression of orexigenic neuropeptide genes independent of the expression of adipose-derived leptin. Furthermore, the gonadotropin axis may

  10. Residual feed intake studies in Angus-sired cattle reveal a potential role for hypothalamic gene expression in regulating feed efficiency.

    Science.gov (United States)

    Perkins, S D; Key, C N; Garrett, C F; Foradori, C D; Bratcher, C L; Kriese-Anderson, L A; Brandebourg, T D

    2014-02-01

    Mechanisms underlying variation in residual feed intake (RFI), a heritable feed efficiency measure, are poorly understood while the relationship between RFI and meat quality is uncertain. To address these issues, 2 divergent cohorts consisting of High (HRFI) and Low (LRFI) RFI individuals were created by assessing RFI in 48 Angus-sired steers during a 70 d feeding trial to identify steers with divergent RFI. The association of RFI with indices of meat quality and expression of genes within hypothalamic and adipose tissue was then determined in LRFI and HRFI steers. While on test, feed intake was recorded daily with BW and hip heights recorded at 14 d intervals. Ultrasound measurements of rib eye area (REA) and backfat (BF) were recorded initially and before harvest. Carcass and growth data were analyzed using a mixed model with RFI level (LRFI, HRFI) as the independent variable. The least-square means (lsmeans) for RFI were -1.25 and 1.51 for the LRFI and HRFI cohorts (P grade (P meat quality. Neuropeptide-Y (NPY), relaxin-3 (RLN3), melanocortin 4 receptor (MC4R), and GnRH mRNA expression was 64%, 59%, 58%, 86% lower (P < 0.05), respectively, while gonadotropin inhibiting hormone (GnIH) and pro-opiomelanocortin (POMC) mRNA expression was 198% and 350% higher (P < 0.01) in the arcuate nucleus of LRFI steers. Expression of agouti-related protein (AGRP), relaxin/insulin-like family peptide receptor 1 (RXFP1), and melanocortin 3 receptor mRNA was similar between LRFI and HRFI animals. Pituitary expression of FSHβ (P < 0.03) and LHβ (P < 0.01) was correlated to hypothalamic GnRH levels suggesting that changes in gene expression within the arcuate nucleus had functional consequences. Leptin mRNA expression was 245% higher in the adipose tissue of LRFI steers consistent with lower levels of NPY and higher expression of POMC in their hypothalami. These data support the hypothesis that differences in hypothalamic neuropeptide gene expression underlie variation in feed

  11. Rats with a truncated ghrelin receptor (GHSR) do not respond to ghrelin, and show reduced intake of palatable, high-calorie food.

    Science.gov (United States)

    MacKay, Harry; Charbonneau, Valerie R; St-Onge, Veronique; Murray, Emma; Watts, Alexander; Wellman, Martin K; Abizaid, Alfonso

    2016-09-01

    Ghrelin, a peptide hormone produced by the stomach, is the endogenous ligand for the Growth Hormone Secretagogue Receptor (GHSR). Ghrelin acts on the GHSR to increase food intake, appetitive behaviors, and adiposity. Recently, a rat model with a null mutation to the GHSR gene (FHH-GHSR(m1/Mcwi)) was generated and used in behavioral studies, but the basic metabolic phenotype of this strain as well as that of the background strain (Fawn Hooded Hypertensive, FHH) has not been characterized in detail. Here we compared male FHH-GHSR(m1/Mcwi) rats with their wild-type littermates (FHH-WT) in a number of metabolic parameters. In the 24h of recovery following an acute overnight fast, FHH-GHSR(m1/Mcwi) rats consumed less food than FHH-WT animals, and relative to their body weights, adult FHH-GHSR(m1/Mcwi) rats consumed fewer calories when placed on a high-fat diet. Despite this, FHH-GHSR(m1/Mcwi) rats did not show a difference in diet-induced obesity or weight gain. Fasted FHH-GHSR(m1/Mcwi) rats exhibited increased Agouti-Related Peptide (AgRP) and Neuropeptide Y (NPY) expression in the Arcuate Nucleus (ARC), indicative of altered central regulation of feeding and energy balance. FHH-GHSR(m1/Mcwi) rats exhibited lower levels of home cage locomotor behavior over the entire light/dark cycle, and reduced levels of food anticipatory activity when placed on a restricted feeding schedule. Finally, FHH-GHSR(m1/Mcwi) rats consumed less of a palatable dessert (cookie dough) given after the completion of the scheduled meal. Altogether, our data show that rats lacking a functional GHSR tend to eat less than their wild-type counterparts in the face of acute fasts, chronic high-fat diet exposure, and exposure to a palatable dessert, despite not showing differences in body weight and glucose homeostasis that are characteristic of GHSR null mice. These data indicate that many, but not all responses to GHSR ablation are conserved between rats and mice. The FHH-GHSR(m1/Mcwi) rat thus

  12. - Un modelo descriptivo del sistema reproductor hembra del coipo (Myocastor coypus I: el ovario (A descriptive model of the female reproductive system of coypu (Myocastor coypus I: the ovary

    Directory of Open Access Journals (Sweden)

    Felipe, A. E.

    2005-12-01

    conformada por tejido conectivo en disposición plexiforme, en el cual las fibras se orientaron en todas direcciones. Se observaron también fibras elásticas y argentófilas. En los ejemplares estudiados fue posible identificar todos los tipos foliculares y determinar la presencia de distintos grados de atresia correspondientes a folículos en diferentes etapas de desarrollo. Los folículos en crecimiento (secundarios atrésicos se caracterizaron por el engrosamiento de la zona pelúcida, la vacuolización citoplasmática de células foliculares, picnosis, vacuolización de la teca interna y tejido conectivo de sustitución. Con respecto a las estructuras consideradas como cuerpos lúteos, pudieron establecerse y caracterizarse tres grados de desarrollo de los mismos (inicial, medio y maduro así como determinarse diferentes estadíos de regresión o atresia. Todos los ovarios del coipo contuvieron cuerpos lúteos accesorios. Los mismos se diferenciaron de los verdaderos por su menor tamaño y la persistencia de un remanente ovocitario con una zona pelúcida degenerada. El diámetro medio de estas estructuras fue de 273.44 ± 78.22 mm. Las observaciones presentadas en este trabajo indican que el ovario de coipos sexualmente maduros es semejante al de otros mamíferos como la chinchilla (Chinchilla laniger, el cobayo (Cavia sp., la casiragua (Proechimys guairae, el carpincho (Hydrochoerus hydrochaeris, la mara (Dolichotis patagonum, el aguti (Dasyprocta aguti, el puercoespín africano austral (Hystrix africaeaustralis y el puercoespín africano común (Atherurus africanus. In the present investigation mature females of coypu (Myocastor coypus were used to determine the anatomic and histomorphologic features of the ovaries. As in all mammals, the ovary was suspended from the dorsal wall of the peritoneal cavity by the mesovarium. In the studied animals, the mesovarium did not form a bursa. The ovary of the coypu is similar to the ovary of other adult hystricomorph rodents: it

  13. Combate ao Desmodus rotundus rotundus (E. Geoffroy,1810 na região cárstica de Cordisburgo e Curvelo, Minas Gerais

    Directory of Open Access Journals (Sweden)

    Almeida E.O.

    2002-01-01

    Full Text Available Com o objetivo de avaliar em uma região cárstica o tipo de refúgio, as espécies de morcegos, a população de animais domésticos, as associações interespecíficas nas coabitações com outros mamíferos silvestres suscetíveis à raiva e a eficácia da warfarina aplicada no dorso do Desmodus rotundus rotundus foi realizada uma pesquisa de maio de 1998 a março de 2000, nos municípios de Cordisburgo e Curvelo, Minas Gerais. Em 49 refúgios vistoriados, 29 naturais e 20 artificiais, localizados em 14 propriedades, encontrou-se o Desmodus rotundus rotundus em 18 abrigos naturais. Destes, 17 eram cavernas formadas pela dissolução ou abatimento de rocha calcária, típica do carste, e um era túnel escavado na terra pela ação das águas de um rio. As características geomorfológicas e de localização espacial foram registradas com base nas coordenadas geográficas, obtidas com auxílio de um sensor geográfico de posição. Nesses abrigos foram capturados e identificados 1457 morcegos de 14 espécies, sendo 640 Glossophaga soricina (Pallas, 1766, 566 Desmodus rotundus (E. Geoffroy, 1810, 73 Anoura geoffroyi (Gray 1838, 58 Trachops cirrhosus (Spix, 1823, 38 Diphylla ecaudata ecaudata (Spix, 1823, 23 Platyhrrinus lineatus (E. Geoffroy, 1810, 16 Lasiurus ega (Gervais, 1856, 14 Carollia perspicillata (Linnaeus, 1758, 13 Phyllostomus hastatus hastatus (Pallas, 1767, 9 Artibeus lituratus (Olfers, 1818, 3 Mimmon bennettii (Gray, 1838, 2 Myotis nigricans (Schinz, 1821, 1 Eptesicus brasiliensis (Desmarest, 1819 e 1 Pygoderma bilabiatum (Wagner, 1843. Não se conseguiu isolar ou detectar o vírus rábico no cérebro de 25 hematófagos selecionados e em 52 de outras espécies. A maioria desses abrigos também era usada por pacas (Agouti paca Linnaues, 1766, capivaras (Hydrochaeris hydrochaeris, Linnaues, 1766, guaxinins (Procyon cancrivorus, G. Cuvier, 1798 e raposas (Lycalopex vetulus, Lund, 1842 que são suscetíveis à raiva. Em 546 Desmodus

  14. 大鼠内细胞团和胎儿神经干细胞构建嵌合体的潜力%The Potential of Rat Inner Cell Mass and Fetal Neural Stem Cells to Generate Chimeras

    Institute of Scientific and Technical Information of China (English)

    郭继彤; 李雪峰; Shahnaz Fida; 苟克勉; Nakisa Malakooti; ZHANG Chun-fang; John R Morrison; Alan O Trounson; DU Zhong-tao

    2009-01-01

    嵌合体大鼠是研究人类疾病的重要动物模犁.用囊胚注射法研究了大鼠内细胞团(ICM)和胎儿神经干细胞(FNS)构建嵌合体的潜力.结果发现来自黑色(DA)大鼠第5天(D5)和第6天(D6)囊胚的ICM细胞注入D5 Sprague-Dawley(SD)大鼠囊胚后得到3只嵌合体大鼠:D5 SD大鼠ICM细胞注射入D5 DA囊胚后得到4只嵌合体大鼠:而体外培养的DA或SD人鼠ICM细胞注射后均未能获得嵌合体大鼠.本研究用大鼠胎儿神经干细胞(rFNS)和LacZ转染的rFNS构建嵌介体,未能获得嵌合体人鼠:但在LacZ转染的SD rFNS注射到DA大鼠囊胚后发育来的41只胎儿中,有2只胎儿其组织切片中发现少量LacZ阳性细胞.结果表明DA和SD大鼠ICM具有参与嵌合体发育的潜力,但ICM细胞经体外培养后构建嵌合体的潜力显著F降(P<0.05);大鼠胎儿神经干细胞构建嵌合体的潜力较低,可能仅具有参与早期胚胎发育的潜力.%The rat chimera is an important animal model for the study of complex human diseases. In the present study we evaluated the chimeric potential of rat inner cell masses (ICMs) and fetal neural stem (FNS) cells. In result, three rat chimeras were produced by day 5 (D5) Sprague-Dawley (SD) blastocysts injected with ICMs derived from day 6 (D6) and D5 Dark Agouti (DA) blastocysts; four rat chimeras had been generated by D5 DA blastocyst injected with D5 SD ICMs. For the requirement of gene modification, cultured rat inner cell mass cells were assessed to produce chimeras, but no chimeras were generated from injected embryos. The potential to generate chimeras from rFNS and transfected rFNS cells were tested, but no chimeric pups were produced. Only 2 of 41 fetuses derived from D5 DA blastocyst injection with SD LacZ transfected rFNS cells showed very low number of LacZ positive cells in the section. These results indicate that DA and SD rat ICMs are able to contribute to chimeras, but their potential decreases significantly after

  15. Long-term neuronal damage and recovery after a single dose of MDMA: expression and distribution of serotonin transporter in the rat brain.

    Science.gov (United States)

    Kirilly, Eszter

    2010-09-01

    "Ecstasy", 3,4-methylenedioxymethamphetamine (MDMA), an amphetamine analogue is one of the most widely used recreational drugs. In spite of the fact that neurotoxic effects of MDMA has been found in several species from rodents to non-human primates, and results increasingly point to damage also in human MDMA users, data about the sensitivity of different brain areas and the recovery after neuronal damage are scarce. Serotonin transporter (5-HTT) mRNA in the raphe nuclei also has not been examined. Humans with genetic predisposition for the slow metabolism of MDMA, the so-called "poor metabolizers" of debrisoquin are at higher risk. Five- 9% of the Caucasian population is considered to carry this phenotype. These studies were carried out in Dark Agouti rats, a special strain that show decreased microsomal CYP2D1 isoenzyme activity, and thus may serve as a model of vulnerable human users. These works were designed to characterize MDMA-induced damage and recovery of the serotonergic system including sleep and morphological changes within 180 days. In our experiments we investigated the 5-HTT mRNA expression in the brainstem and medullary raphe nuclei, 5-HTT immunoreactive (IR) fibre densities in several brain areas, and 16 functional measures of sleep in response to a single dose of +/- MDMA (15mg\\kg). Furthermore, behavioural experiments were performed 21 days after MDMA treatment. We found similar changes in 5-HTT mRNA expression in the examined raphe nuclei, namely transient increases 7 days after MDMA treatment followed by transient decreases at 21 days. Significant (20-40%), widespread reductions in 5-HTT-IR fibre density were detected in most brain areas at 7 and 21 days after MDMA administration. All cortical, but only some brainstem areas were damaged. Parallel to the neuronal damage we observed significant reductions in rapid eye movement (REM) sleep latency, increased fragmentation of sleep and increases in delta power spectra in non-REM sleep. At 180 days

  16. Age-associated changes in rat immune system: lessons learned from experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Djikić, Jasmina; Nacka-Aleksić, Mirjana; Pilipović, Ivan; Stojić-Vukanić, Zorica; Bufan, Biljana; Kosec, Duško; Dimitrijević, Mirjana; Leposavić, Gordana

    2014-10-01

    Aging is associated with the decline in immune response to infectious agents and tumors and increasing risk of autoimmunity, but the incidence of autoimmune diseases does not increase in the elderly. To elucidate the cellular and molecular mechanisms influencing clinical expression of autoimmunity in aged animals, the phenotypic and functional characteristics of mononuclear cells isolated from the spinal cords of 3-month-old (young) and 26-month-old (aged) Dark Agouti rats immunized to induce experimental autoimmune encephalomyelitis (EAE) - the model of multiple sclerosis, the most common autoimmune disease of the central nervous system, were examined. Aged rats were less susceptible to EAE induction, and the neurological and histological picture was milder in those rats which developed the clinically manifested disease. At the peak of the disease, several times fewer mononuclear cells and T lymphocytes were isolated from the spinal cords of aged rats compared with the young ones. The frequency of CD4+ cells among TCRαβ+ lymphocytes, as well as that of reactivated CD134(OX40)+ cells within its CD4+ T-lymphocyte subpopulation, was less in spinal cords of aged compared with young rats. Additionally, CD134 surface density on CD4+ lymphocytes was decreased in the spinal cord of aged rats. The changes in CD134 expression most likely reflected in part age-related intrinsic changes in CD4+ lymphocytes as the expression of this molecule was also impaired on in vitro stimulated naïve CD4+ splenocytes from aged rats compared with young animals. In addition, greater frequency of CD8+ lymphocytes with regulatory phenotypes could also contribute to impaired CD4+ cell reactivation in aged rats. The increased apoptosis of CD4+ cells from aged rats was consistent with their impaired reactivation and it was accompanied by the greater frequency of CD4+CD11b+CD45(int/high) cells, which are supposed to be actively engaged in apoptotic cell phagocytosis and to have immunoregulatory

  17. Book Reviews

    Directory of Open Access Journals (Sweden)

    Redactie KITLV

    2001-07-01

    Full Text Available -Stanley L. Engerman, Heather Cateau ,Capitalism and slavery fifty years later: Eric Eustace Williams - A reassessment of the man and his work. New York: Peter Lang, 2000. xvii + 247 pp., S.H.H. Carrington (eds -Philip D. Morgan, B.W. Higman, Writing West Indian histories. London: Macmillan Caribbean, 1999. xiv + 289 pp. -Daniel Vickers, Alison Games, Migration and the origins of the English Atlantic world. Cambridge MA: Harvard University Press, 1999. xiii + 322 pp. -Christopher L. Brown, Andrew Jackson O'Shaughnessy, An empire divided: The American revolution and the British Caribbean. Philadelphia: University of Pennsylvania Press, 2000. xviii + 357 pp. -Lennox Honychurch, Samuel M. Wilson, The indigenous people of the Caribbean. Gainesville: University Press of Florida, 1997. xiv + 253 pp. -Kenneth Bilby, Bev Carey, The Maroon story: The authentic and original history of the Maroons in the history of Jamaica 1490-1880. St. Andrew, Jamaica: Agouti Press, 1997. xvi + 656 pp. -Bernard Moitt, Doris Y. Kadish, Slavery in the Caribbean Francophone world: Distant voices, forgotten acts, forged identities. Athens: University of Georgia Press, 2000. xxiii + 247 pp. -Michael J. Guasco, Virginia Bernhard, Slaves and slaveholders in Bermuda, 1616-1782. Columbia: University of Missouri Press, 1999. xviii + 316 pp. -Michael J. Jarvis, Roger C. Smith, The maritime heritage of the Cayman Islands. Gainesville: University Press of Florida, 2000. xxii + 230 pp. -Paul E. Hoffman, Peter R. Galvin, Patterns of pillage: A geography of Caribbean-based piracy in Spanish America, 1536-1718. New York: Peter Lang, 1999. xiv + 271 pp. -David M. Stark, Raúl Mayo Santana ,Cadenas de esclavitud...y de solidaridad: Esclavos y libertos en San Juan,siglo XIX. Río Piedras: Centro de Investigaciones Sociales, Universidad de Puerto Rico, 1997. 204 pp., Mariano Negrón Portillo, Manuel Mayo López (eds -Ada Ferrer, Philip A. Howard, Changing history: Afro-Cuban Cabildos and

  18. Influence of reference genes on expression of TYR, MITF and ASIP genes in tissues of Silky Fowl%内参基因对 TYR、MITF和ASIP基因在白绒乌骨鸡各组织表达水平的影响

    Institute of Scientific and Technical Information of China (English)

    郑嫩珠; 李丽; 辛清武; 缪中纬; 朱志明; 刘凤辉; 吴俭飞; 卢立志

    2015-01-01

    that taking GA PD H as a reference gene , the expressionlevelof TYR,ASIPandMITFgeneswiththemelanincontentintissueshadthesametrend:skin >kidney > gizzard > liver > muscle , but the expression level of A SIP gene was opposite to melanin deposition content , which implied that each target gene expression was matched with their respective function on regulating melanin deposition . For instance , high expression of TYR and MITF genes promoted melanin deposition , while the ASIP gene inhibited melanin deposition . Taking 18S rRNA and ACTB as reference genes , the expression of TYR,MITFandASIPgeneswerenotrelatedtothemelanindeposition,andanidealcalibrationresultcouldnot be obtained . In conclusion , reference gene plays an important role in the expression of target gene . In this paper , GA PD H gene not only had highest expression stability in tissues , but also could truly reflect the regulation effect of the targetgenes(TYR,MITFandASIP) onmelanindeposition.Thus,GAPDHgeneisthemostsuitablereference gene for normalizing the mRNA expression of genes in tissues of Silky Fowl .%以健康白绒乌骨鸡肌肉、肾、肝、肌胃和皮肤为试验素材,应用实时荧光定量聚合酶链反应技术探讨β‐肌动蛋白(beta‐actin ,ACTB)、3‐磷酸甘油醛脱氢酶(glyceraldehyde‐3‐phosphate dehydrogenase ,GA PDH)和18S核糖体RNA(18S ribosomal RNA ,18S rRNA )3个内参基因的组织表达稳定性及其对酪氨酸酶( tyrosinase ,TYR)、小眼畸形相关转录因子(microphthalmia‐associated transcription factor ,MITF)和刺鼠信号蛋白(agouti signaling pro tein ,A S I P)等目的基因在白绒乌骨鸡各组织表达水平的影响,并采用紫外分光光度法分析各组织黑色素沉积规律,从中筛选出理想的内参基因.geNorm和NormFinder软件分析结果显示,内参基因GA PD H在白绒乌骨鸡各组织表达稳定性最高,ACTB表达稳定性最低.相对定量和黑色素沉积结果表明,GA PDH作为内参基因时,各组织 MITF

  19. Desnutrición y amenorrea hipotalámica funcional: Neuropéptidos periféricos (Leptina, Adiponectina, Ghrelina y su relación con la homeostasis metabólica

    Directory of Open Access Journals (Sweden)

    León Fiszlejder

    2009-09-01

    AHF, promueve la oxidación de los ácidos grasos libres en el músculo esquelético, produce una reducción de triglicéridos en esos tejidos, inhibe directamente la captación y oxidación de los ácidos grasos libres en el hígado, disminuyendo también los triglicéridos en esta víscera. Estas acciones inducen el aumento de la sensibilidad a la insulina, una de las características en la patología de estas pacientes. Además, esta citokina disminuye la liberación de glucosa desde el hígado y músculo esquelético y estimula directamente la captación de glucosa en estos tejidos, mediante la activación de la AMP proteinkinasa. En consecuencia, la elevación de la adiponectina jugaría un rol de colaboración en el mantenimiento de la homeostasis metabólica-energética en condiciones de mal nutrición, como la que impera en la anorexia nerviosa y en otras causas de AHF. La osteosporosis, la inmunodepresión, el aumento del riesgo cardiovascular y la AHF pueden ser interpretados como efectos que derivan de procesos de adaptación que llevan a cabo hormonas hipotalámicas y neuropétidos periféricos. La amenorrea podría ser considerada un efecto protector.Functional hypothalamic amenorrhea (FHA is usually associated with an inadequate qualitative and quantitative diet which influences the energetic balance, modifies the body composition and produces hormonal reactions in order to keep metabolic homeostasis. This adaptive process is regulated by a "central circuit" (hypothalamic hormones, a "peripheral circuit" originated by adipocyte tissue (leptin, adiponectin, among other cytokines and the superior gastrointestinal tract through a neuropetide: ghrelin. Leptin acts in the hypothalamus stimulating the synthesis of MSH and inhibits the NPY and the AgRP (Agouti-related-peptide both with orexigen action. NPY stimulates CRH and both inhibit GnRH in the hypothalamus. Low levels of leptin in FHA increases NPY-CRH system blocking Gn-RH pulsatility, a key process in