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1.
Anim Cogn ; 27(1): 45, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38913161

RESUMO

Due to their outstanding ability of vocal imitation, parrots are often kept as pets. Research has shown that they do not just repeat human words. They can use words purposefully to label objects, persons, and animals, and they can even use conversational phrases in appropriate contexts. So far, the structure of pet parrots' vocabularies and the difference between them and human vocabulary acquisition has been studied only in one individual. This study quantitatively analyses parrot and child vocabularies in a larger sample using a vocabulary coding method suitable for assessing the vocabulary structure in both species. We have explored the composition of word-like sounds produced by 21 grey parrots (Psittacus erithacus) kept as pets in Czech- or Slovak-speaking homes, and compared it to the composition of early productive vocabularies of 21 children acquiring Czech (aged 8-18 months), who were matched to the parrots by vocabulary size. The results show that the 'vocabularies' of talking grey parrots and children differ: children use significantly more object labels, activity and situation labels, and emotional expressions, while parrots produce significantly more conversational expressions, greetings, and multiword utterances in general. These differences could reflect a strong link between learning spoken words and understanding the underlying concepts, an ability seemingly unique to human children (and absent in parrots), but also different communicative goals of the two species.


Assuntos
Papagaios , Vocabulário , Animais , Feminino , Masculino , Humanos , Lactente , República Tcheca , Desenvolvimento da Linguagem , Animais de Estimação , Eslováquia
2.
J Neurosci ; 42(45): 8450-8459, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36351831

RESUMO

Since the discovery of conspicuously spatially tuned neurons in the hippocampal formation over 50 years ago, characterizing which, where, and how neurons encode navigationally relevant variables has been a major thrust of navigational neuroscience. While much of this effort has centered on the hippocampal formation and functionally-adjacent structures, recent work suggests that spatial codes, in some form or another, can be found throughout the brain, even in areas traditionally associated with sensation, movement, and executive function. In this review, we highlight these unexpected results, draw insights from comparison of these codes across contexts, regions, and species, and finally suggest an avenue for future work to make sense of these diverse and dynamic navigational codes.


Assuntos
Navegação Espacial , Navegação Espacial/fisiologia , Encéfalo/fisiologia , Mapeamento Encefálico , Hipocampo/fisiologia , Neurônios/fisiologia
3.
Int J Mol Sci ; 24(14)2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37511083

RESUMO

The environment is seldom optimal for plant growth and changes in abiotic and biotic signals, including temperature, water availability, radiation and pests, induce plant responses to optimise survival. The New Zealand native plant species and close relative to Arabidopsis thaliana, Pachycladon cheesemanii, grows under environmental conditions that are unsustainable for many plant species. Here, we compare the responses of both species to different stressors (low temperature, salt and UV-B radiation) to help understand how P. cheesemanii can grow in such harsh environments. The stress transcriptomes were determined and comparative transcriptome and network analyses discovered similar and unique responses within species, and between the two plant species. A number of widely studied plant stress processes were highly conserved in A. thaliana and P. cheesemanii. However, in response to cold stress, Gene Ontology terms related to glycosinolate metabolism were only enriched in P. cheesemanii. Salt stress was associated with alteration of the cuticle and proline biosynthesis in A. thaliana and P. cheesemanii, respectively. Anthocyanin production may be a more important strategy to contribute to the UV-B radiation tolerance in P. cheesemanii. These results allowed us to define broad stress response pathways in A. thaliana and P. cheesemanii and suggested that regulation of glycosinolate, proline and anthocyanin metabolism are strategies that help mitigate environmental stress.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Brassicaceae , Arabidopsis/metabolismo , Transcriptoma , Antocianinas/metabolismo , Brassicaceae/genética , Proteínas de Arabidopsis/genética , Estresse Fisiológico/genética , Resposta ao Choque Frio , Regulação da Expressão Gênica de Plantas
4.
Xenotransplantation ; 29(4): e12764, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35695327

RESUMO

The shortage of allogeneic donor organs leaves its supply far short of clinical need. There are great expectations on xenotransplantation, especially with pigs' organs. With the genetic modification of donor pigs, the rejection and cross-species transmission issues have now been widely addressed. However, research on the compatibility of genes between humans and pigs was limited. We performed a systematic screening analysis of predicted incompatible genes between humans and pigs, judged by low protein sequence similarities or different predicted protein domain compositions. By combining with gene set enrichment analysis, we screened out several key genes of hematopoiesis and the immune system with possible incompatibilities, which might be important for establishing chimera and xenotransplantation between humans and pigs. There were seven chemokine genes, including CCL1, CCL5, CCL24, CCL25, CCL28, CXCL12, and CXCL16, that exhibited limited similarity between humans and pigs (similarity < 0.8). Among hematopoiesis process-related genes, 15 genes of adhesion molecules, Notch ligands, and cytokine receptors exhibited differences between humans and pigs. In complement and coagulation cascades, 19 genes showed low similarity and 77 genes had different domain compositions between humans and pigs. Our study provides a good reference for further genetic modification of pigs, which might be beneficial for xenotransplantation.


Assuntos
Biologia Computacional , Rejeição de Enxerto , Animais , Hematopoese/genética , Humanos , Sistema Imunitário , Suínos , Transplante Heterólogo
5.
Xenobiotica ; 52(2): 165-176, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35345974

RESUMO

Oroxylin A, the main component of Scutellaria baicalensis Georigi has been widely studied due to its well-known pharmacological effects. According to previous studies, Oroxylin A with low bioavailability was converted into glucuronidation and sulphonated metabolites, which had high exposure in plasma and generated certain activities. It is necessary to study the metabolites and metabolic pathways of Oroxylin A.This study aimed to explore the metabolites of Oroxylin A in liver microsomes, primary hepatocyte incubation samples of five different species (human, monkey, dog, mouse, rat), and in bile, urine and faeces of rats.It would provide a systematic description of metabolic pathway of Oroxylin A. Also, a method of high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry detector (HPLC-Q-TOF-MS/MS) for identification of each metabolite in various biological matrices was developed.This experiment illustrated that phase II metabolites were the main form of Oroxylin A in vitro and in excretion of rats, accompanied with a small amount of phase I metabolites.Furthermore, there were obvious species differences among the metabolism in vitro, especially in phase II. Monkeys and rats may be more suitable for preclinical research than dogs and mice as non-rodent or rodent species.


Assuntos
Neoplasias , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão/métodos , Cães , Flavonoides , Camundongos , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodos
6.
Neuroimage ; 235: 118006, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33819611

RESUMO

A wide homology between human and macaque striatum is often assumed as in both the striatum is involved in cognition, emotion and executive functions. However, differences in functional and structural organization between human and macaque striatum may reveal evolutionary divergence and shed light on human vulnerability to neuropsychiatric diseases. For instance, dopaminergic dysfunction of the human striatum is considered to be a pathophysiological underpinning of different disorders, such as Parkinson's disease (PD) and schizophrenia (SCZ). Previous investigations have found a wide similarity in structural connectivity of the striatum between human and macaque, leaving the cross-species comparison of its functional organization unknown. In this study, resting-state functional connectivity (RSFC) derived striatal parcels were compared based on their homologous cortico-striatal connectivity. The goal here was to identify striatal parcels whose connectivity is human-specific compared to macaque parcels. Functional parcellation revealed that the human striatum was split into dorsal, dorsomedial, and rostral caudate and ventral, central, and caudal putamen, while the macaque striatum was divided into dorsal, and rostral caudate and rostral, and caudal putamen. Cross-species comparison indicated dissimilar cortico-striatal RSFC of the topographically similar dorsal caudate. We probed clinical relevance of the striatal clusters by examining differences in their cortico-striatal RSFC and gray matter (GM) volume between patients (with PD and SCZ) and healthy controls. We found abnormal RSFC not only between dorsal caudate, but also between rostral caudate, ventral, central and caudal putamen and widespread cortical regions for both PD and SCZ patients. Also, we observed significant structural atrophy in rostral caudate, ventral and central putamen for both PD and SCZ while atrophy in the dorsal caudate was specific to PD. Taken together, our cross-species comparative results revealed shared and human-specific RSFC of different striatal clusters reinforcing the complex organization and function of the striatum. In addition, we provided a testable hypothesis that abnormalities in a region with human-specific connectivity, i.e., dorsal caudate, might be associated with neuropsychiatric disorders.


Assuntos
Núcleo Caudado/fisiologia , Córtex Cerebral/fisiologia , Conectoma , Rede Nervosa/fisiologia , Doença de Parkinson , Putamen/fisiologia , Esquizofrenia , Adulto , Idoso , Animais , Núcleo Caudado/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Conectoma/métodos , Conjuntos de Dados como Assunto , Feminino , Humanos , Macaca , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Putamen/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia , Esquizofrenia/fisiopatologia , Especificidade da Espécie , Adulto Jovem
7.
FEMS Yeast Res ; 21(6)2021 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-34427650

RESUMO

Responding to the recent interest of the yeast research community in non-Saccharomyces cerevisiae species of biotechnological relevance, the N.C.Yeastract (http://yeastract-plus.org/ncyeastract/) was associated to YEASTRACT + (http://yeastract-plus.org/). The YEASTRACT + portal is a curated repository of known regulatory associations between transcription factors (TFs) and target genes in yeasts. N.C.Yeastract gathers all published regulatory associations and TF-binding sites for Komagataellaphaffii (formerly Pichia pastoris), the oleaginous yeast Yarrowia lipolytica, the lactose fermenting species Kluyveromyces lactis and Kluyveromyces marxianus, and the remarkably weak acid-tolerant food spoilage yeast Zygosaccharomyces bailii. The objective of this review paper is to advertise the update of the existing information since the release of N.C.Yeastract in 2019, and to raise awareness in the community about its potential to help the day-to-day work on these species, exploring all the information available in the global YEASTRACT + portal. Using simple and widely used examples, a guided exploitation is offered for several tools: (i) inference of orthologous genes; (ii) search for putative TF binding sites and (iii) inter-species comparison of transcription regulatory networks and prediction of TF-regulated networks based on documented regulatory associations available in YEASTRACT + for well-studied species. The usage potentialities of the new CommunityYeastract platform by the yeast community are also discussed.


Assuntos
Regulação Fúngica da Expressão Gênica , Yarrowia , Bases de Dados Genéticas , Genômica , Saccharomyces cerevisiae , Leveduras/genética
8.
Int J Mol Sci ; 22(17)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34502375

RESUMO

Bioinformatics approaches have proven useful in understanding biological responses to spaceflight. Spaceflight experiments remain resource intensive and rare. One outstanding issue is how to maximize scientific output from a limited number of omics datasets from traditional animal models including nematodes, fruitfly, and rodents. The utility of omics data from invertebrate models in anticipating mammalian responses to spaceflight has not been fully explored. Hence, we performed comparative analyses of transcriptomes of soleus and extensor digitorum longus (EDL) in mice that underwent 37 days of spaceflight. Results indicate shared stress responses and altered circadian rhythm. EDL showed more robust growth signals and Pde2a downregulation, possibly underlying its resistance to atrophy versus soleus. Spaceflight and hindlimb unloading mice shared differential regulation of proliferation, circadian, and neuronal signaling. Shared gene regulation in muscles of humans on bedrest and space flown rodents suggest targets for mitigating muscle atrophy in space and on Earth. Spaceflight responses of C. elegans were more similar to EDL. Discrete life stages of D. melanogaster have distinct utility in anticipating EDL and soleus responses. In summary, spaceflight leads to shared and discrete molecular responses between muscle types and invertebrate models may augment mechanistic knowledge gained from rodent spaceflight and ground-based studies.


Assuntos
Músculo Esquelético/patologia , Atrofia Muscular/patologia , Ausência de Peso/efeitos adversos , Animais , Caenorhabditis elegans , Ritmo Circadiano/fisiologia , Bases de Dados Genéticas , Drosophila melanogaster , Meio Ambiente Extraterreno , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Elevação dos Membros Posteriores , Camundongos , Modelos Animais , Voo Espacial , Estresse Fisiológico/fisiologia , Transcriptoma/genética
9.
Int J Mol Sci ; 22(23)2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34884738

RESUMO

Despite the debilitating consequences following traumatic spinal cord injury (SCI), there is a lack of safe and effective therapeutics in the clinic. The species-specific responses to SCI present major challenges and opportunities for the clinical translation of biomolecular and pharmacological interventions. Recent transcriptional analyses in preclinical SCI studies have provided a snapshot of the local SCI-induced molecular responses in different animal models. However, the variation in the pathogenesis of traumatic SCI across species is yet to be explored. This study aims to identify and characterize the common and inconsistent SCI-induced differentially expressed genes across species to identify potential therapeutic targets of translational relevance. A comprehensive search of open-source transcriptome datasets identified four cross-compatible microarray experiments in rats, mice, and salamanders. We observed consistent expressional changes in extracellular matrix components across the species. Conversely, salamanders showed downregulation of intracellular MAPK signaling compared to rodents. Additionally, sequence conservation and interactome analyses highlighted the well-preserved sequences of Fn1 and Jun with extensive protein-protein interaction networks. Lastly, in vivo immunohistochemical staining for fibronectin was used to validate the observed expressional pattern. These transcriptional changes in extracellular and MAPK pathways present potential therapeutic targets for traumatic SCI with promising translational relevance.


Assuntos
Sistema de Sinalização das MAP Quinases , Terapia de Alvo Molecular , Traumatismos da Medula Espinal/metabolismo , Ambystoma mexicanum , Animais , Modelos Animais de Doenças , Camundongos , Ratos , Traumatismos da Medula Espinal/terapia
10.
Int J Mol Sci ; 22(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34445647

RESUMO

Unveiling the molecular features in the heart is essential for the study of heart diseases. Non-cardiomyocytes (nonCMs) play critical roles in providing structural and mechanical support to the working myocardium. There is an increasing amount of single-cell RNA-sequencing (scRNA-seq) data characterizing the transcriptomic profiles of nonCM cells. However, no tool allows researchers to easily access the information. Thus, in this study, we develop an open-access web portal, ExpressHeart, to visualize scRNA-seq data of nonCMs from five laboratories encompassing three species. ExpressHeart enables comprehensive visualization of major cell types and subtypes in each study; visualizes gene expression in each cell type/subtype in various ways; and facilitates identifying cell-type-specific and species-specific marker genes. ExpressHeart also provides an interface to directly combine information across datasets, for example, generating lists of high confidence DEGs by taking the intersection across different datasets. Moreover, ExpressHeart performs comparisons across datasets. We show that some homolog genes (e.g., Mmp14 in mice and mmp14b in zebrafish) are expressed in different cell types between mice and zebrafish, suggesting different functions across species. We expect ExpressHeart to serve as a valuable portal for investigators, shedding light on the roles of genes on heart development in nonCM cells.


Assuntos
Células Endoteliais/metabolismo , Fibroblastos/metabolismo , Ventrículos do Coração/metabolismo , Internet , Macrófagos/metabolismo , Pericitos/metabolismo , Transcriptoma , Algoritmos , Animais , Perfilação da Expressão Gênica , Humanos , Camundongos , Análise de Sequência de RNA , Análise de Célula Única , Software , Peixe-Zebra
11.
BMC Genomics ; 21(1): 381, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32487021

RESUMO

BACKGROUND: The systematic interrogation of reproduction-related genes was key to gain a comprehensive understanding of the molecular mechanisms underlying male reproductive traits in mammals. Here, based on the data collected from the NCBI SRA database, this study first revealed the genes involved in porcine male reproduction as well their uncharacterized transcriptional characteristics. RESULTS: Results showed that the transcription of porcine genome was more widespread in testis than in other organs (the same for other mammals) and that testis had more tissue-specific genes (1210) than other organs. GO and GSEA analyses suggested that the identified test is-specific genes (TSGs) were associated with male reproduction. Subsequently, the transcriptional characteristics of porcine TSGs, which were conserved across different mammals, were uncovered. Data showed that 195 porcine TSGs shared similar expression patterns with other mammals (cattle, sheep, human and mouse), and had relatively higher transcription abundances and tissue specificity than low-conserved TSGs. Additionally, further analysis of the results suggested that alternative splicing, transcription factors binding, and the presence of other functionally similar genes were all involved in the regulation of porcine TSGs transcription. CONCLUSIONS: Overall, this analysis revealed an extensive gene set involved in the regulation of porcine male reproduction and their dynamic transcription patterns. Data reported here provide valuable insights for a further improvement of the economic benefits of pigs as well as future treatments for male infertility.


Assuntos
Perfilação da Expressão Gênica , Reprodução/genética , Processamento Alternativo , Animais , Evolução Molecular , Redes Reguladoras de Genes , Masculino , Especificidade de Órgãos , Suínos , Testículo/metabolismo , Transcrição Gênica
12.
J Exp Biol ; 222(Pt 20)2019 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-31558590

RESUMO

Macrotermes michaelseni and M. natalensis are two morphologically similar termite species occupying the same habitat across southern Africa. Both build large mounds and tend mutualistic fungal symbionts for nutrients, but despite these behavioural and physiological similarities, the mound superstructures they create differ markedly. The behavioural differences behind this discrepancy remain elusive, and are the subject of ongoing investigations. Here, we show that the two species demonstrate distinctive building activity in a laboratory-controlled environment consisting of still air with low ambient humidity. In these conditions, M. michaelseni transports less soil from a central reservoir, deposits this soil over a smaller area, and creates structures with a smaller volumetric envelope than M. natalensis In high humidity, no such systematic difference is observed. This result suggests a differential behavioural threshold or sensitivity to airborne moisture that may relate to the distinct macro-scale structures observed in the African bushland.


Assuntos
Comportamento Animal , Umidade , Isópteros/fisiologia , Animais , Especificidade da Espécie , Imagem com Lapso de Tempo
13.
Brain Topogr ; 32(5): 808-824, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31273565

RESUMO

Resting state electroencephalography (EEG) during eyes-closed and eyes-open conditions is widely used to evaluate brain states of healthy populations and brain dysfunctions in clinical conditions. Although several results have been obtained by measuring these brain activities in humans, it remains unclear whether the same results can be replicated in animals, i.e., whether the physiological properties revealed by these findings are phylogenetically conserved across species. In the present study, we describe a paradigm for recording resting state EEG activities during eyes-closed and eyes-open conditions from rats, and investigated the differences between eyes-closed and eyes-open conditions for humans and rats. We found that compared to the eyes-open condition, human EEG spectral amplitude in the eyes-closed condition was significantly higher at 8-12 Hz and 18-22 Hz in the occipital region, but significantly lower at 18-22 Hz and 30-100 Hz in the frontal region. In contrast, rat EEG spectral amplitude was significantly higher in the eyes-closed condition than in the eyes-open condition at 1-4 Hz, 8-12 Hz, and 13-17 Hz in the frontal-central region. In both species, the 1/f-like power spectrum scaling of resting state EEG activities was significantly higher in the eyes-closed condition than in the eyes-open condition at parietal-occipital and frontal regions. These results provided a neurophysiological basis for future translational studies from experimental animal findings to human psychophysiology, since the validity of such translation critically relies on a well-established experimental paradigm and a carefully-examined signal characteristic to bridge the gaps across different species.


Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Lobo Frontal/fisiologia , Lobo Occipital/fisiologia , Descanso/fisiologia , Adulto , Animais , Eletroencefalografia , Feminino , Humanos , Masculino , Ratos
14.
Oecologia ; 189(4): 905-917, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30877577

RESUMO

Seasonality is a key environmental factor that regularly promotes life history adaptation. Insects invading cold-temperate climates need to overwinter in a dormant state. We compared the role of temperature and photoperiod in dormancy induction in the laboratory, as well as winter survival and reproduction in the field and the laboratory, of 5 widespread European dung fly species (Diptera: Sepsidae) to investigate their extent of ecological differentiation and thermal adaptation. Unexpectedly, cold temperature is the primary environmental factor inducing winter dormancy, with short photoperiod playing an additional role mainly in species common at high altitudes and latitudes (Sepsis cynipsea, neocynipsea, fulgens), but not in those species also thriving in southern Europe (thoracica, punctum). All species hibernate as adults rather than juveniles. S. thoracica had very low adult winter survivorship under both (benign) laboratory and (harsh) field conditions, suggesting flexible quiescence rather than genetically fixed winter diapause, restricting their distribution towards the pole. All other species appear well suited for surviving cold, Nordic winters. Females born early in the season reproduce before winter while late-born females reproduce after winter, fulgens transitioning earliest before winter and thoracica and punctum latest; a bet-hedging strategy of reproduction during both seasons occurs rarely but is possible physiologically. Fertility patterns indicate that females can store sperm over winter. Winter dormancy induction mechanisms of European sepsids are congruent with their geographic distribution, co-defining their thermal niches. Flexible adult winter quiescence appears the easiest route for insects spreading towards the poles to evolve the necessary overwinter survival.


Assuntos
Dípteros , Simuliidae , Animais , Temperatura Baixa , Europa (Continente) , Feminino , Reprodução , Estações do Ano
15.
Xenobiotica ; 49(1): 43-53, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29206565

RESUMO

1. The absorption, distribution, metabolism, and excretion of CC-223 were studied following a single oral dose of [14C]CC-223 to rats (3 mg/kg; 90 µCi/kg), dogs (1.5 mg/kg; 10 µCi/kg), and healthy volunteers (20 mg; 200 nCi). 2. CC-223-derived radioactivity was widely distributed in rats. Excretion of radioactivity was rapid and nearly complete from rats (87%), dogs (78%), and humans (97%). Feces was the major excretion pathway for rats (67%) and dogs (70%), whereas urine (57.6%) was the major elimination route for humans. Urine and bile each contained approximately 20% administered radioactivity in rats, whereas bile (20%) played a more important role than urine (<10%) in the excretion of absorbed radioactivity in dogs. Based on excretion data, CC-223 had good absorption, with greater than 56%, 29%, and 57% of the oral dose absorbed in rats, dogs, and humans, respectively. 3. CC-223 was the prominent radioactive component in circulation of rats (>71% of the exposure to total radioactivity) and dogs (≥45.5%), whereas M1 (76.5%) was the predominant circulating metabolite in humans. M1 and M1-derived metabolites accounted for >66% of human dose. CC-223 was extensively metabolized in rats, dogs, and humans through glucuronidation, O-demethylation, oxidation, and combinations of these pathways.


Assuntos
Pirazinas/metabolismo , Administração Oral , Animais , Líquidos Corporais/metabolismo , Cães , Humanos , Ratos , Serina-Treonina Quinases TOR/metabolismo
16.
Xenobiotica ; 49(2): 200-210, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29320949

RESUMO

1. The absorption, distribution, metabolism and excretion of enasidenib were studied following a single oral dose of [14C]enasidenib to rats (10 mg/kg; 100 µCi/kg) and healthy volunteers (100 mg; 318 nCi). 2. Enasidenib was readily absorbed, extensively metabolized and primarily eliminated via the hepatobiliary pathway. Enasidenib-derived radioactivity was widely distributed in rats. Excretion of radioactivity was approximately 95-99% of the dose from rats in 168 h post-dose and 82.4% from human volunteers in 504 h post-dose. In rat bile, approximately 35-42% of the administered dose was recovered, with less than 5% of the dose excreted as the parent drug. Renal elimination was a minor pathway, with <12% of the dose excreted in rat urine and <10% of the dose excreted in human urine. 3. Enasidenib was the prominent radioactive component in rat and human systemic circulation. Enasidenib was extensively metabolized in rats and human volunteers through N-dealkylation, oxidation, direct glucuronidation and combinations of these pathways. Glucuronidation was the major metabolic pathway in rats while N-dealkylation was the prominent metabolic pathway in human volunteers. All human metabolites were detected in rats.


Assuntos
Aminopiridinas/farmacocinética , Antineoplásicos/farmacocinética , Triazinas/farmacocinética , Aminopiridinas/sangue , Aminopiridinas/urina , Animais , Antineoplásicos/sangue , Antineoplásicos/urina , Bile/metabolismo , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Humanos , Isocitrato Desidrogenase/antagonistas & inibidores , Rim/metabolismo , Fígado/metabolismo , Redes e Vias Metabólicas , Ratos , Espectrometria de Massas em Tandem , Triazinas/sangue , Triazinas/urina
17.
J Neurophysiol ; 119(5): 1753-1766, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29364073

RESUMO

Both mice and primates are used to model the human auditory system. The primate order possesses unique cortical specializations that govern auditory processing. Given the power of molecular and genetic tools available in the mouse model, it is essential to understand the similarities and differences in auditory cortical processing between mice and primates. To address this issue, we directly compared temporal encoding properties of neurons in the auditory cortex of awake mice and awake squirrel monkeys (SQMs). Stimuli were drawn from a sinusoidal amplitude modulation (SAM) paradigm, which has been used previously both to characterize temporal precision and to model the envelopes of natural sounds. Neural responses were analyzed with linear template-based decoders. In both species, spike timing information supported better modulation frequency discrimination than rate information, and multiunit responses generally supported more accurate discrimination than single-unit responses from the same site. However, cortical responses in SQMs supported better discrimination overall, reflecting superior temporal precision and greater rate modulation relative to the spontaneous baseline and suggesting that spiking activity in mouse cortex was less strictly regimented by incoming acoustic information. The quantitative differences we observed between SQM and mouse cortex support the idea that SQMs offer advantages for modeling precise responses to fast envelope dynamics relevant to human auditory processing. Nevertheless, our results indicate that cortical temporal processing is qualitatively similar in mice and SQMs and thus recommend the mouse model for mechanistic questions, such as development and circuit function, where its substantial methodological advantages can be exploited. NEW & NOTEWORTHY To understand the advantages of different model organisms, it is necessary to directly compare sensory responses across species. Contrasting temporal processing in auditory cortex of awake squirrel monkeys and mice, with parametrically matched amplitude-modulated tone stimuli, reveals a similar role of timing information in stimulus encoding. However, disparities in response precision and strength suggest that anatomical and biophysical differences between squirrel monkeys and mice produce quantitative but not qualitative differences in processing strategy.


Assuntos
Córtex Auditivo/fisiologia , Percepção Auditiva/fisiologia , Eletroencefalografia/métodos , Camundongos/fisiologia , Neurônios/fisiologia , Saimiri/fisiologia , Percepção do Tempo/fisiologia , Animais , Feminino , Masculino , Modelos Animais , Especificidade da Espécie
18.
Gen Comp Endocrinol ; 259: 122-130, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29155262

RESUMO

Pregnancy is one of the defining characteristics of placental mammals. Key in the growth and development of the fetus during pregnancy are the dynamics of glucocorticoids (GCs) and their binding protein,corticosteroid-binding globulin (CBG), which determines how much of the GCs are free and biologically active. Out of more than 5000 species of placental mammals in 19 different orders, our understanding of the dynamics of maternal GCs and CBG during pregnancy is largely limited to the detailed study of 3 groups - sheep, laboratory rodents, and humans. The assumption is often made that what we see in these few species applies to the rest. To examine this generality, we compared patterns of maternal GCs over pregnancy from all placental mammals where data is available: in the blood of 13 species from 5 different orders and in metabolites in excreta in an additional 20 species from 9 orders. We found that maternal free GCs increase by late pregnancy in most taxa. This increase is achieved by either an increase in total GC secretion or a decrease in CBG. A major exception is found in the even-toed ungulates (sheep, cows, etc.) where maternal GCs and CBG remain stable, but where the fetal adrenals mature in late pregnancy and produce the majority of their own GCs. We conclude that patterns of change in maternal GCs and CBG during pregnancy are species-specific but are alternative means to the same end: increased fetal exposure to GCs in late pregnancy, which is essential for development.


Assuntos
Glucocorticoides/uso terapêutico , Mamíferos/crescimento & desenvolvimento , Transcortina/uso terapêutico , Animais , Feminino , Glucocorticoides/metabolismo , Glucocorticoides/farmacologia , Humanos , Gravidez , Ovinos , Transcortina/farmacologia
19.
New Phytol ; 216(4): 1072-1078, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28944478

RESUMO

What confers invasive alien plants a competitive advantage over native plants remains open to debate. Many of the world's worst invasive alien plants are clonal and able to share resources within clones (clonal integration), particularly in heterogeneous environments. Here, we tested the hypothesis that clonal integration benefits invasive clonal plants more than natives and thus confers invasives a competitive advantage. We selected five congeneric and naturally co-occurring pairs of invasive alien and native clonal plants in China, and grew pairs of connected and disconnected ramets under heterogeneous light, soil nutrient and water conditions that are commonly encountered by alien plants during their invasion into new areas. Clonal integration increased biomass of all plants in all three heterogeneous resource environments. However, invasive plants benefited more from clonal integration than natives. Consequently, invasive plants produced more biomass than natives. Our results indicate that clonal integration may confer invasive alien clonal plants a competitive advantage over natives. Therefore, differences in the ability of clonal integration could potentially explain, at least partly, the invasion success of alien clonal plants in areas where resources are heterogeneously distributed.


Assuntos
Espécies Introduzidas , Magnoliopsida/fisiologia , Reprodução Assexuada
20.
Proc Natl Acad Sci U S A ; 111(48): 17224-9, 2014 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-25413365

RESUMO

Although the similarities between humans and mice are typically highlighted, morphologically and genetically, there are many differences. To better understand these two species on a molecular level, we performed a comparison of the expression profiles of 15 tissues by deep RNA sequencing and examined the similarities and differences in the transcriptome for both protein-coding and -noncoding transcripts. Although commonalities are evident in the expression of tissue-specific genes between the two species, the expression for many sets of genes was found to be more similar in different tissues within the same species than between species. These findings were further corroborated by associated epigenetic histone mark analyses. We also find that many noncoding transcripts are expressed at a low level and are not detectable at appreciable levels across individuals. Moreover, the majority lack obvious sequence homologs between species, even when we restrict our attention to those which are most highly reproducible across biological replicates. Overall, our results indicate that there is considerable RNA expression diversity between humans and mice, well beyond what was described previously, likely reflecting the fundamental physiological differences between these two organisms.


Assuntos
DNA Intergênico/genética , Perfilação da Expressão Gênica/métodos , Especificidade de Órgãos/genética , Proteínas/genética , Animais , Epigenômica/métodos , Evolução Molecular , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Camundongos Endogâmicos C57BL , Análise de Sequência de RNA , Especificidade da Espécie , Transcriptoma/genética
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