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Constitutive heterochromatin, consisting of repetitive sequences, diverges very rapidly; therefore, its nucleotide sequences and chromosomal distributions are often largely different, even between closely related species. The chromosome C-banding patterns of two Gerbillinae species, Meriones unguiculatus and Gerbillus perpallidus, vary greatly, even though they belong to the same subfamily. To understand the evolution of C-positive heterochromatin in these species, we isolated highly repetitive sequences, determined their nucleotide sequences, and characterized them using chromosomal and filter hybridization. We obtained a centromeric repeat (MUN-HaeIII) and a chromosome 13-specific repeat (MUN-EcoRI) from M. unguiculatus. We also isolated a centromeric/pericentromeric repeat (GPE-MBD) and an interspersed-type repeat that was predominantly amplified in the X and Y chromosomes (GPE-EcoRI) from G. perpallidus. GPE-MBD was found to contain a 17-bp motif that is essential for binding to the centromere-associated protein CENP-B. This indicates that it may play a role in the formation of a specified structure and/or function of centromeres. The nucleotide sequences of the three sequence families, except GPE-EcoRI, were conserved only in Gerbillinae. GPE-EcoRI was derived from the long interspersed nuclear elements 1 retrotransposon and showed sequence homology throughout Muridae and Cricetidae species, indicating that the repeat sequence occurred at least in the common ancestor of Muridae and Cricetidae. Due to a lack of assembly data of highly repetitive sequences constituting heterochromatin in whole-genome sequences of vertebrate species published to date, the knowledge obtained in this study provides useful information for a deep understanding of the evolution of repetitive sequences in not only rodents but also in mammals.
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Heterocromatina , Secuencias Repetitivas de Ácidos Nucleicos , Humanos , Animales , Gerbillinae/genética , Secuencia de Bases , Heterocromatina/genética , Hibridación Fluorescente in Situ , Secuencias Repetitivas de Ácidos Nucleicos/genética , Centrómero/genética , Muridae/genética , Arvicolinae/genéticaRESUMEN
Social separation is thought to induce a strong stress response in social juvenile mammals, but little is known about how this response might vary throughout the development. The present study examines the long-term effects of early-life stress (ELS) induced by social separation on individual behaviors later in life using the social and precocious species Octodon degus. Four experimental groups were established a positive control group of mothers and siblings from six litters comprised the socially housed (SH) group, while pups from seven litters were randomly assigned to three treatments: pups experiencing no separation (NS) treatment while their siblings did; repeated bouts of consecutive separation (CS); intermittent separation (IS). We analyzed the effects of separation treatment on the frequency and duration of freezing, rearing and grooming behaviors. ELS was correlated with higher hyperactivity, and hyperactivity increased with more frequent separation. However, the behavioral trend of the NS group changed to hyperactive in long-term observation. The findings suggest that the NS group was indirectly affected by ELS. In addition, suggesting ELS acts to converge an individual's behavioral tendencies in a certain direction.
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Experiencias Adversas de la Infancia , Octodon , Animales , Femenino , Humanos , Mamíferos , Madres , HermanosRESUMEN
The Mongolian gerbil has historically been useful for brain ischemia experiments, owing to the gerbil's uniquely underdeveloped circle of Willis (CoW). This led to a gerbil model of cochlear ischemia being generated in our unit. However, we have found that the usual severe hearing loss seen in this model was not being induced consistently in recent experiments using the MON/Jms/GbsSlc gerbil (the sole commercially available gerbil in Japan). We set out to evaluate the posterior communicating artery (PcomA) in MON/Jms/GbsSlc, to re-establish whether this strain is appropriate for ischemia models. Having found that this unique feature is often lost, we then attempted to breed for the characteristic absent PcomA. India-ink perfusion revealed that the percentage of intact bilateral PcomA ("communicating type") in the MON/Jms/GbsSlc gerbil was 57%; unilateral only ("unilateral communicating type") was 39%; and completely absent PcomA ("non-communicating type") was 4%. We were able to obtain few examples of the indigenous old aged Japanese UNG/Mz gerbil strain (at University of Miyazaki). Unfortunately, the pure UNG/Mz female was too elderly for mating. Therefore, selective breeding crosses between MON/Jms/GbsSlc and male UNG/Mz were carried out. After five generations of selective breeding, the percentage of non-communicating type gerbils was significantly higher in the newly generated strain, MON/Jms/SlcMz (F6 generation; 63%) than in the MON/Jms/GbsSlc gerbil. Bilateral common carotid artery occlusion surgery demonstrated that the cerebral blood flow was significantly reduced in MON/Jms/SlcMz compared with MON/Jms/GbsSlc (p < 0.0001) and induced more hippocampal injuries in MON/Jms/SlcMz than in MON/Jms/GbsSlc (p < 0.01). In conclusion, the commercially available MON/Jms/GbsSlc gerbil can easily regain PcomA, and we established a new gerbil strain (MON/Jms/SlcMz) displaying non-PcomA.
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Isquemia Encefálica , Círculo Arterial Cerebral , Animales , Masculino , Femenino , Gerbillinae/fisiología , Hipocampo , IsquemiaRESUMEN
Most mammalian ovarian follicles contain only a single oocyte having a single nucleus. However, two or more oocytes and nuclei are observed within one follicle and one oocyte, respectively, in several species, including cotton rat (CR, Sigmodon hispidus). The present study compared ovarian histology, focusing on folliculogenesis, between two inbred CR strains, HIS/Hiph and HIS/Mz. At 4 weeks of age, ovarian sections from both the strains were analyzed histologically. Multi-oocyte follicles (MOFs) and double-nucleated oocytes (DNOs) were observed in all stages of developing follicles in HIS/Hiph, whereas HIS/Mz had MOFs up to secondary stages and lacked DNOs. The estimated total follicles in HIS/Mz were almost half that of HIS/Hiph, but interstitial cells were well developed in HIS/Mz. Furthermore, immunostaining revealed no clear strain differences in the appearance of oocytes positive for Ki67, PCNA, and p63 in MOF or DNOs; no cell death was observed in these oocytes. Ultrastructural analysis revealed more abundant mitochondrial clouds in oocytes of HIS/Hiph than HIS/Mz. Thus, we clarified the strain differences in the CR ovary. These findings indicate that early events during folliculogenesis affect the unique ovarian phenotypes found in CRs, including MOFs or DNOs, and their strain differences.
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The speciose mammalian order Eulipotyphla (moles, shrews, hedgehogs, solenodons) combines an unusual diversity of semi-aquatic, semi-fossorial, and fossorial forms that arose from terrestrial forbearers. However, our understanding of the ecomorphological pathways leading to these lifestyles has been confounded by a fragmentary fossil record, unresolved phylogenetic relationships, and potential morphological convergence, calling for novel approaches. The net surface charge of the oxygen-storing muscle protein myoglobin (ZMb), which can be readily determined from its primary structure, provides an objective target to address this question due to mechanistic linkages with myoglobin concentration. Here, we generate a comprehensive 71 species molecular phylogeny that resolves previously intractable intra-family relationships and then ancestrally reconstruct ZMb evolution to identify ancient lifestyle transitions based on protein sequence alone. Our phylogenetically informed analyses confidently resolve fossorial habits having evolved twice in talpid moles and reveal five independent secondary aquatic transitions in the order housing the world's smallest endothermic divers.
The shrews, moles and hedgehogs that surround us all belong to the same large group of insect-eating mammals. While most members in this 'Eulipotyphla order' trot on land, some, like moles, have evolved to hunt their prey underground. A few species, such as the water shrews, have even ventured to adopt a semi-aquatic lifestyle, diving into ponds and streams to retrieve insects. These underwater foragers share unique challenges, burning a lot of energy and losing heat at a high rate while not being able to store much oxygen. It is still unclear how these semi-aquatic habits have come to be: the fossil record is fragmented and several species tend to display the same adaptations even though they have evolved separately. This makes it difficult to identify when and how many times the Eulipotyphla species started to inhabit water. The protein myoglobin, which gives muscles their red color, could help in this effort. This molecule helps muscles to capture oxygen from blood, a necessary step for cells to obtain energy. Penguins, seals and whales, which dive to get their food, often have much higher concentration of myoglobin so they can spend extended amount of time without having to surface for air. In addition, previous work has shown that eight groups of mammalian divers carry genetic changes that help newly synthetized myoglobin proteins to not stick to each other. This means that these animals can store more of the molecule in their muscles, increasing their oxygen intake and delivery. He et al. therefore speculated that all semi-aquatic Eulipotyphla species would carry genetic changes that made their myoglobin less likely to clump together; underground species, which also benefit from absorbing more oxygen, would display intermediate alterations. In addition, reconstructing the myoglobin sequences from the ancestors of living species would help to spot when the transition to aquatic life took place. A variety of approaches were harnessed to obtain myoglobin and other sequences from 55 eulipotyphlan mammals, which then were used to construct a strongly supported family tree for this group. The myoglobin results revealed that from terrestrial to subterranean to semi-aquatic species, genetic changes took place that would diminish the ability for the proteins to stick to each other. This pattern also showed that semi-aquatic lifestyles have independently evolved five separate times twice in moles, three times in shrews. By retracing the evolutionary history of specific myoglobin properties, He et al. shed light on how one of the largest orders of mammals has come to be fantastically diverse.
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Organismos Acuáticos/fisiología , Mamíferos/fisiología , Mioglobina/química , Mioglobina/genética , Filogenia , Secuencia de Aminoácidos , Animales , Organismos Acuáticos/química , Organismos Acuáticos/genética , ADN/genética , Evolución Molecular , Fósiles , Mamíferos/genética , Topos , Mioglobina/clasificación , Mioglobina/metabolismo , OxígenoRESUMEN
Octodon degus is said to be one of the most human-like rodents because of its improved cognitive function. Focusing on its high sociality, we cloned and characterized some sociality-related genes of degus, in order to establish degus as a highly socialized animal model in molecular biology. We cloned degus Neurexin and Neuroligin as sociality-related genes, which are genetically related to autism spectrum disorder in human. According to our results, amino acid sequences of Neurexin and Neuroligin expressed in degus brain, are highly conserved to that of human sequences. Most notably, degus Neuroligin4 is highly similar to human Neuroligin4X, which is one of the most important autism-related genes, whereas mouse Neuroligin4 is known to be poorly similar to human Neuroligin4X. Furthermore, our work also indicated that testosterone directly binds to degus Neurexin and intercepts intercellular Neurexin-Neuroligin binding. Moreover, it is of high interest that testosterone is another key molecule of the higher incidence of autism in male. These results indicated that degus has the potential for animal model of sociality, and furthermore may promote understanding toward the pathogenic mechanism of autism.
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Moléculas de Adhesión Celular Neuronal/metabolismo , Octodon/metabolismo , Receptores de Superficie Celular/metabolismo , Testosterona/metabolismo , Animales , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/metabolismo , Proteínas de Unión al Calcio/química , Moléculas de Adhesión Celular Neuronal/química , Moléculas de Adhesión Celular Neuronal/genética , Hipocampo/metabolismo , Humanos , Masculino , Moléculas de Adhesión de Célula Nerviosa/química , Unión Proteica/efectos de los fármacos , Dominios Proteicos , Receptores de Superficie Celular/química , Globulina de Unión a Hormona Sexual/química , Testosterona/farmacologíaRESUMEN
Quaternary environmental changes fundamentally influenced the genetic diversity of temperate-zone terrestrial animals, including those in the Japanese Archipelago. The genetic diversity of present-day populations is taxon- and region-specific, but its determinants are poorly understood. Here, we analyzed cytochrome b gene (Cytb) sequences (1140 bp) of mitochondrial DNA (mtDNA) to elucidate the factors determining the genetic variation in three species of large moles: Mogera imaizumii and Mogera wogura, which occur in central and southern mainland Japan (Honshu, Shikoku, and Kyushu), and Mogera robusta, which occurs on the nearby Asian continent. Network construction with the Cytb sequences revealed 10 star-shaped clusters with apparent geographic affinity. Mismatch distribution analysis showed that modes of pairwise nucleotide differences (τ values) were grouped into five classes in terms of the level, implying the occurrence of five stages for rapid expansion. It is conceivable that severe cold periods and subsequent warm periods during the late Quaternary were responsible for the population expansion events. The first and third oldest events included island-derived haplotypes, indicative of the involvement of land bridge formation between remote islands, hence suggesting an association of the ends of the penultimate (PGM, ca. 130,000 years ago) and last (LGM, ca. 15,000 years ago) glacial maxima, respectively. Since the third event was followed by the fourth, it is plausible that the termination of the Younger Dryas and subsequent abrupt warming ca. 11,500 years ago facilitated the fourth expansion event. The second event most likely corresponded to early marine isotope stage (MIS) 3 (ca. 53,000 years ago) when the glaciation and subsequent warming period were predicted to have influenced biodiversity. Utilization of the critical times of 130,000, 53,000, 15,000, and 11,500 years ago as calibration points yielded evolutionary rates of 0.03, 0.045, 0.10 and 0.10 substitutions/site/million years, respectively, showing a time-dependent manner whose pattern was similar to that seen in small rodents reported in our previous studies. The age of the fifth expansion event was calculated to be 5800 years ago with a rate of 0.10 substitutions/site/million years ago during the mid-Holocene, suggestive of the influence of humans or other unspecified reasons, such as the Jomon marine transgression.
RESUMEN
The Asian house shrew, Suncus murinus, is an insectivore (Eulipotyphla, Mammalia) and an important laboratory animal for life-science studies. The gastrointestinal tract of Suncus is simple: the length of the entire intestine is very short relative to body size, the large intestine is quite short, and there are no fermentative chambers such as the forestomach or cecum. These features imply that Suncus has a different nutritional physiology from those of humans and mice, but little is known about whether Suncus utilizes microbial fermentation in the large (LI) or small (SI) intestine. In addition, domestication may affect the gastrointestinal microbial diversity of Suncus. Therefore, we compared the gastrointestinal microbial diversity of Suncus between laboratory and wild Suncus and between the SI and LI (i.e., four groups: Lab-LI, Lab-SI, Wild-LI, and Wild-SI) using bacterial 16S rRNA gene library sequencing analyses with a sub-cloning method. We obtained 759 cloned sequences (176, 174, 195, and 214 from the Lab-LI, Lab-SI, Wild-LI, and Wild-SI samples, respectively), which revealed that the gastrointestinal microbiota of Suncus is rich in Firmicutes (mostly lactic acid bacteria), with few Bacteroidetes. We observed different bacterial communities according to intestinal region in laboratory Suncus, but not in wild Suncus. Furthermore, the gastrointestinal microbial diversity estimates were lower in laboratory Suncus than in wild Suncus. These results imply that Suncus uses lactic acid fermentation in the gut, and that the domestication process altered the gastrointestinal bacterial diversity.
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Microbioma Gastrointestinal , ARN Ribosómico 16S/análisis , Musarañas/microbiología , Animales , Animales de Laboratorio/microbiología , Animales Salvajes/microbiología , Femenino , MasculinoRESUMEN
Daily torpor is a physiological adaptation in small mammals and birds, characterised by drastic reductions in metabolism and body temperature. Energy-constraining conditions, such as cold and starvation, are known to cause the expression of daily torpor. However, the reason for high degrees of inter- and intra-individual variation in torpor expression (TE) in similar situations is not clear. As littermates of altricial animals are exposed to an uneven allocation of maternal resources from conception to weaning, we tested whether early nutritional experiences have long-term effects on TE in adults. We used full-sibling littermates of laboratory mice that as adults were starved overnight to induce torpor. We measured body mass from birth until adulthood as an indicator of nutritional status, and calculated the relative body mass (RBM) as an indicator of the difference in nutritional status within a litter. After maturation, we subjected mice to five repeated torpor induction trials involving 24â h of fasting and 5â days of recovery. Half of the female mice displayed great individual variation in TE whereas male mice rarely exhibited daily torpor. In females, RBM at birth influenced TE, irrespective of body mass in adulthood; thus, female mice born with low RBMs displayed high TE in adulthood. In conclusion, we provide evidence that TE in mice differs among littermates, and that this variation is linked closely to heterogeneous nutritional experiences during the fetal period.
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Peso al Nacer , Ratones/fisiología , Letargo/fisiología , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Femenino , Individualidad , Masculino , Ratones Endogámicos ICR , Factores SexualesRESUMEN
Pharyngeal pouches in mammals develop into specific derivatives. If the differentiation of the pharyngeal pouches is anomalous, their remnants can result in cysts, sinuses, and fistulae in the differentiated organs or around the neck. In the present study, we found several pharyngeal pouch remnants, such as cystic structures in thymus and parathyroid gland and fossulae extended from the piriform fossa, in the inbred cotton rats maintained at Hokkaido Institute of Public Health (HIS/Hiph) and University of Miyazaki (HIS/Mz). In HIS/Hiph, the fossulae extended from the apex of the piriform fossa into the thyroid glands and were lined with stratified squamous and cuboidal epithelium. Calcitonin-positive C-cells were present within their epithelium in HIS/Hiph. In contrast, the fossulae of HIS/Mz ran outside the thyroid glands toward the parathyroid glands; they were lined with columnar ciliated epithelium and a few goblet cells, but had no C-cells, which was consistent with the cystic structures in the thymus and the parathyroid gland. These results indicated that the fossulae were a remnant of the ultimobranchial body in HIS/Hiph and of the thymopharyngeal duct in HIS/Mz. Thus, the fossulae of the piriform fossa resembled the piriform sinus fistula in human. In conclusion, cotton rats frequently possessed pharyngeal pouch remnants, including the piriform sinus fistula, and therefore, might serve as a novel model to elucidate the mechanisms of pharyngeal pouch development.
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Faringe/anatomía & histología , Faringe/embriología , Sigmodontinae/anatomía & histología , Sigmodontinae/embriología , Animales , Animales Recién Nacidos , Desarrollo Embrionario , Femenino , Masculino , Glándulas Paratiroides/anatomía & histología , Glándulas Paratiroides/embriología , Timo/anatomía & histología , Timo/embriología , Glándula Tiroides/anatomía & histología , Glándula Tiroides/embriologíaRESUMEN
Daily torpor is a physiological adaptation in mammals and birds characterized by a controlled reduction of metabolic rate and body temperature during the resting phase of circadian rhythms. In laboratory mice, daily torpor is induced by dietary caloric restriction. However, it is not known which nutrients are related to daily torpor expression. To determine whether dietary protein is a key factor in inducing daily torpor in mice, we fed mice a protein-restricted (PR) diet that included only one-quarter of the amount of protein but the same caloric level as a control (C) diet. We assigned six non-pregnant female ICR mice to each group and recorded their body weights and core body temperatures for 4 weeks. Body weights in the C group increased, but those in the PR group remained steady or decreased. Mice in both groups did not show daily torpor, but most mice in a food-restricted group (n=6) supplied with 80% of the calories given to the C group exhibited decreased body weights and frequently displayed daily torpor. This suggests that protein restriction is not a trigger of daily torpor; torpid animals can conserve their internal energy, but torpor may not play a significant role in conserving internal protein. Thus, opportunistic daily torpor in mice may function in energy conservation rather than protein saving.
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Animales de Laboratorio/fisiología , Regulación de la Temperatura Corporal/fisiología , Dieta con Restricción de Proteínas , Proteínas en la Dieta/administración & dosificación , Ratones Endogámicos ICR/metabolismo , Ratones Endogámicos ICR/fisiología , Letargo/fisiología , Animales , Peso Corporal , Metabolismo Energético/fisiología , FemeninoRESUMEN
The penile and clitoral anatomy of four species of Talpid moles (broad-footed, star-nosed, hairy-tailed, and Japanese shrew moles) were investigated to define penile and clitoral anatomy and to examine the relationship of the clitoral anatomy with the presence or absence of ovotestes. The ovotestis contains ovarian tissue and glandular tissue resembling fetal testicular tissue and can produce androgens. The ovotestis is present in star-nosed and hairy-tailed moles, but not in broad-footed and Japanese shrew moles. Using histology, three-dimensional reconstruction, and morphometric analysis, sexual dimorphism was examined with regard to a nine feature masculine trait score that included perineal appendage length (prepuce), anogenital distance, and presence/absence of bone. The presence/absence of ovotestes was discordant in all four mole species for sex differentiation features. For many sex differentiation features, discordance with ovotestes was observed in at least one mole species. The degree of concordance with ovotestes was highest for hairy-tailed moles and lowest for broad-footed moles. In relationship to phylogenetic clade, sex differentiation features also did not correlate with the similarity/divergence of the features and presence/absence of ovotestes. Hairy-tailed and Japanese shrew moles reside in separated clades, but they exhibit a high degree of congruence. Broad-footed and hairy-tailed moles reside within the same clade but had one of the lowest correlations in features and presence/absence of ovotestes. Thus, phylogenetic affinity and the presence/absence of ovotestes are poor predictors for most sex differentiation features within mole external genitalia.
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Clítoris/anatomía & histología , Topos/anatomía & histología , Pene/anatomía & histología , Animales , Femenino , Masculino , Diferenciación Sexual/fisiologíaRESUMEN
The mammalian family Talpidae (moles, shrew moles, desmans) is characterized by diverse ecomorphologies associated with terrestrial, semi-aquatic, semi-fossorial, fossorial, and aquatic-fossorial lifestyles. Prominent specializations involved with these different lifestyles, and the transitions between them, pose outstanding questions regarding the evolutionary history within the family, not only for living but also for fossil taxa. Here, we investigate the phylogenetic relationships, divergence times, and biogeographic history of the family using 19 nuclear and 2 mitochondrial genes (â¼16 kb) from â¼60% of described species representing all 17 genera. Our phylogenetic analyses help settle classical questions in the evolution of moles, identify an ancient (mid-Miocene) split within the monotypic genus Scaptonyx, and indicate that talpid species richness may be nearly 30% higher than previously recognized. Our results also uniformly support the monophyly of long-tailed moles with the two shrew mole tribes and confirm that the Gansu mole is the sole living Asian member of an otherwise North American radiation. Finally, we provide evidence that aquatic specializations within the tribes Condylurini and Desmanini evolved along different morphological trajectories, though we were unable to statistically reject monophyly of the strictly fossorial tribes Talpini and Scalopini.
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Topos/genética , Musarañas/genética , Animales , Evolución Biológica , Clasificación/métodos , Bases de Datos de Ácidos Nucleicos , Variación Genética , Filogenia , Análisis de Secuencia de ADN/métodos , Especificidad de la EspecieRESUMEN
Here, we describe cDNA cloning and purification of the ghrelin gene sequences and ghrelin peptides from the Japanese true mole, Mogera imaizumii. The gene spans >2.9kbp, has four exons and three introns, and shares structural similarity with those of terrestrial animals. Mature mole ghrelin peptide was predicted to be 28 amino acids long (GSSFLSPEHQKVQQRKESKKPPSKPQPR) and processed from a prepropeptide of 116 amino acids. To further elucidate molecular characteristics, we purified ghrelin peptides from mole stomach. By mass spectrometry, we found that the mole ghrelin peptides had higher ratios of the odd-number fatty acids (C9 and C11 as much as C8) attached to the third serine residue than other vertebrate ghrelin. Truncated forms of ghrelins such as [1-27], [1-19], [1-16] and [1-15], and that lacked the 14th glutamine residue (des-Gln14 ghrelin) were produced in the stomach. Marked expression of ghrelin mRNA in lung was observed as in stomach and brain. Phylogenetic analysis indicated that the branch of M. imaizumii has slightly higher dN/dS ratios (the nucleotide substitution rates at non-synonymous and synonymous sites) than did other eulipotyphlans. Peptide length was positively correlated with human ghrelin receptor activation, whereas the length of fatty-acyl chains showed no obvious functional correlation. The basal higher luciferase activities of the 5'-proximal promoter region of mole ghrelin were detected in ghrelin-negative C2C12 cells and hypoxic culture conditions impaired transcriptional activity. These results indicated that moles have acquired diverse species of ghrelin probably through distinctive fatty acid metabolism because of their food preferences. The results provide a gateway to understanding ghrelin metabolism in fossorial animals.
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ADN Complementario/genética , Ghrelina/genética , Topos/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Expresión GénicaRESUMEN
The influence of human serum albumin (HSA) on the bile acid-mediated inhibition of liver microsomal type 1 11ß-hydroxysteroid dehydrogenase (11ß-HSD1) was studied in vitro. A rat liver microsomal fraction was prepared, and the 11ß-HSD1 enzyme activity in the presence of various concentrations of bile acids and HSA was determined using hydrocortisone as the substrate. The products of the reaction were extracted and analyzed using high-performance liquid chromatography. The magnitude of the inhibition decreased with the addition of HSA in a dose-dependent manner. Four percent human albumin decreased the inhibitory effects of 100 µM chenodeoxycholic acid and lithocholic acid from 89.9 ± 5.6 to 54.5 ± 6.1% and from 83.8 ± 4.8 to 20.8 ± 4.2%, respectively. In contrast, ursodeoxycholic acid and deoxycholic acid showed no inhibitory effect on the enzyme activity in the presence of 4% human serum albumin, and the addition of 1% γ-globulin to the assay mixture in the presence of bile acids did not affect the enzyme activity. Our in vitro study showed that the addition of HSA ameliorated the inhibition of 11ß-HSD1 and that the magnitude of the change is dependent on the species of bile acid, presumably based on the numbers of hydroxyl groups. These results suggest that HSA seems to protect the bile acid-mediated inhibition of 11ß-HSD1 in the healthy subject. On the other hand, in the patients with obstructive biliary diseases, not only elevated serum bile acid but also the accompanying hypoalbuminemia is important to evaluate the pathophysiology of the bile acid-mediated inhibition of 11ß-HSD1 of the disease.
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11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/antagonistas & inhibidores , Ácidos y Sales Biliares/metabolismo , Microsomas Hepáticos/metabolismo , Albúmina Sérica/metabolismo , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/metabolismo , Animales , Ácidos y Sales Biliares/química , Ácidos y Sales Biliares/farmacología , Ácido Quenodesoxicólico/farmacología , Ácido Cólico/farmacología , Humanos , Técnicas In Vitro , Cinética , Ácido Litocólico/farmacología , Masculino , Microsomas Hepáticos/efectos de los fármacos , Ratas , Ratas Wistar , Ácido Ursodesoxicólico/farmacologíaRESUMEN
Ecotropic murine leukemia viruses (Eco-MLVs) infect mouse and rat, but not other mammalian cells, and gain access for infection through binding the cationic amino acid transporter 1 (CAT1). Glycosylation of the rat and hamster CAT1s inhibits Eco-MLV infection, and treatment of rat and hamster cells with a glycosylation inhibitor, tunicamycin, enhances Eco-MLV infection. Although the mouse CAT1 is also glycosylated, it does not inhibit Eco-MLV infection. Comparison of amino acid sequences between the rat and mouse CAT1s shows amino acid insertions in the rat protein near the Eco-MLV-binding motif. In addition to the insertion present in the rat CAT1, the hamster CAT1 has additional amino acid insertions. In contrast, tunicamycin treatment of mink and human cells does not elevate the infection, because their CAT1s do not have the Eco-MLV-binding motif. To define the evolutionary pathway of the Eco-MLV receptor, we analyzed CAT1 sequences and susceptibility to Eco-MLV infection of other several murinae animals, including the southern vole (Microtus rossiaemeridionalis), large Japanese field mouse (Apodemus speciosus), and Eurasian harvest mouse (Micromys minutus). Eco-MLV infection was enhanced by tunicamycin in these cells, and their CAT1 sequences have the insertions like the hamster CAT1. Phylogenetic analysis of mammalian CAT1s suggested that the ancestral CAT1 does not have the Eco-MLV-binding motif, like the human CAT1, and the mouse CAT1 is thought to be generated by the amino acid deletions in the third extracellular loop of CAT1.
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Transportador de Aminoácidos Catiónicos 1/genética , Evolución Molecular , Virus de la Leucemia Murina/fisiología , Muridae/genética , Receptores Virales/genética , Infecciones por Retroviridae/virología , Enfermedades de los Roedores/virología , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Animales , Arvicolinae , Transportador de Aminoácidos Catiónicos 1/química , Transportador de Aminoácidos Catiónicos 1/metabolismo , Línea Celular , Cricetinae , Gerbillinae , Humanos , Ratones , Datos de Secuencia Molecular , Muridae/clasificación , Muridae/virología , Filogenia , Ratas , Receptores Virales/química , Receptores Virales/metabolismoRESUMEN
OBJECTIVES: The disease activities of rheumatoid arthritis (RA) tend to fluctuate between visits to doctors, and a self-assessment tool can help patients accommodate to their current status at home. The aim of the present study was to develop a novel modality to assess the disease activity of RA by a smartphone without the need to visit a doctor. SUBJECTS AND METHODS: This study included 65 patients with RA, 63.1 ± 11.9 years of age. The 28-joint disease activity score (DAS28) was measured for all participants at each clinic visit. The patients assessed their status with the modified Health Assessment Questionnaire (mHAQ), a self-assessed tender joint count (sTJC), and a self-assessed swollen joint count (sSJC) in a smartphone application. The patients' trunk acceleration while walking was also measured with a smartphone application. The peak frequency, autocorrelation (AC) peak, and coefficient of variance of the acceleration peak intervals were calculated as the gait parameters. RESULTS: Univariate analyses showed that the DAS28 was associated with mHAQ, sTJC, sSJC, and AC (p<0.05). In a stepwise linear regression analysis, mHAQ (ß = 0.264, p<0.05), sTJC (ß = 0.581, p<0.001), and AC (ß = -0.157, p<0.05) were significantly associated with DAS28 in the final model, and the predictive model explained 67% of the DAS28 variance. CONCLUSIONS: The results suggest that noninvasive self-assessment of a combination of joint symptoms, limitations of daily activities, and walking ability can adequately predict disease activity of RA with a smartphone application.
Asunto(s)
Artritis Reumatoide/fisiopatología , Teléfono Celular , Autoevaluación Diagnóstica , Aplicaciones Móviles , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Autocuidado/métodos , Encuestas y CuestionariosRESUMEN
The tribe Talpini is a group of strictly subterranean moles distributed across the Eurasian Continent whose phylogenetic relationships and taxonomy remain unresolved. Here we report a multi-locus nuclear-mitochondrial DNA dataset (9468 bp) from 11 talpine species encompassing all five recognized genera, together with analyses of their divergence times and evolutionary affinities inferred from maximum likelihood and Bayesian approaches. Our results finely resolved all relationships except the root of the four recognized Asian genera, which was placed sister to the genus Talpa. With respect to the Asian clade, we moreover provide the first molecular support for a sister-taxon relationship between Parascaptor and Scaptochirus and confirm that the genus Euroscaptor is paraphyletic. Further, and despite a relatively small sample size (22 specimens), our species delimitation analyses support the existence of at least two genetically distinct, and hence potentially cryptic species. Taken together, these findings argue that generic status should be given to E. mizura and illustrate that the taxonomic diversity of the tribe Talpini in mountainous regions of southwestern China and Southeast Asia is underestimated. Finally, results of our divergence time analyses support a rapid radiation of the endemic Asian genera in the late-Miocene, which temporally corresponds with enhanced aridity and cooling arising from a significant uplift of the Himalayan-Tibetan plateau.
Asunto(s)
Topos/genética , Filogenia , Animales , Teorema de Bayes , ADN Mitocondrial/genética , Topos/clasificación , Análisis de Secuencia de ADNRESUMEN
In this paper, we report the development of a lifelog sharing system for rheumatoid arthritis patients. Our system can objectively assess patients' condition from day to day via their smartphone use. We conducted a field experiment to investigate the feasibility of lifelog collection and sharing. The rate of patient assessment is very high. The system collects daily change in patients' activity as influenced by the disease.
Asunto(s)
Artritis Reumatoide/fisiopatología , Teléfono Celular , Monitoreo Ambulatorio/instrumentación , Actividades Cotidianas , Adulto , Anciano , Diseño de Equipo , Femenino , Humanos , Persona de Mediana EdadRESUMEN
We assessed dispersal and vicariant events in four species of Japanese moles in the genera Mogera and Euroscaptor to better understand the factors shaping intra- and interspecific differentiation in Japanese moles. We used the combined viewpoints of molecular phylogeny and historical geology using nucleotide sequences of mitochondrial (cytochrome b; Cytb) and nuclear (A2ab, Bmp4, Tcf25, vWf) genes. The divergence times estimated from the molecular data were verified with available geological data on the chronology of fluctuations in sea level in the Korea Strait, assuming sequential migration and speciation events. This produced possible migration times of 5.6, 3.5, 2.4, and 1.3 million years ago for four species of Japanese moles, Euroscaptor mizura, Mogera tokudae, M. imaizumii, and M. wogura, respectively. For the western Japanese mole M. wogura, Cytb sequences revealed four major phylogroups with strong geographic affinities in southwestern Central Honshu (I), western Honshu/Shikoku (II), Kyushu/westernmost Honshu (III), and Korea/Russian Primorye (IV). The nuclear gene sequences supported the distinctiveness of phylogroups I and IV, indicating long, independent evolutionary histories. In contrast, phylogroups II and III were merged into a single geographic group based on the nuclear gene data. Intraspecific divergences in M. imaizumii and M. tokudae were rather apparent in Cytb but not in nuclear gene sequences. The results suggest that repeated dispersal events have occurred between the Asian continent and the Japanese Islands, and intensive vicariant events associated with abiotic and biotic factors have created higher levels of species and genetic diversities in moles occurring on the Japanese Islands.