RESUMO
Melon (Cucumis melo) is an important economic crop cultivated worldwide. A unique SUN gene family plays a crucial role in regulating plant growth and fruit development, but many SUN family genes and their function have not been well-characterized in melon. In the present study, we performed genome-wide identification and bioinformatics analysis and identified 24 CmSUN family genes that contain integrated and conserved IQ67 domain in the melon genome. Transcriptome data analysis and qRT-PCR results showed that most CmSUNs are specifically enriched in melon reproductive organs, such as young flowers and ovaries. Through genetic transformation in melons, we found that overexpression of CmSUN23-24 and CmSUN25-26-27c led to an increased fruit shape index, suggesting that they act as essential regulators in melon fruit shape variation. Subcellular localization revealed that the CmSUN23-24 protein is located in the cytoplasmic membrane. A direct interaction between CmSUN23-24 and a Calmodulin protein CmCaM5 was found by yeast two-hybrid assay, which indicated their participation in the calcium signal transduction pathway in regulating plant growth. These findings revealed the molecular characteristics, expression profile, and functional pattern of the CmSUN genes, and may provide the theoretical basis for the genetic improvement of melon fruit breeding.
Assuntos
Cucumis melo , Cucurbitaceae , Cucumis melo/genética , Frutas/genética , Cucurbitaceae/genética , Melhoramento Vegetal , Perfilação da Expressão GênicaRESUMO
AGRP (agouti-related neuropeptide) expressing inhibitory neurons sense caloric needs of an animal to coordinate homeostatic feeding. Recent evidence suggests that AGRP neurons also suppress competing actions and motivations to mediate adaptive behavioral selection during starvation. Here, in adult mice of both sexes we show that AGRP neurons form inhibitory synapses onto â¼30% neurons in the medial preoptic area (mPOA), a region critical for maternal care. Remarkably, optogenetically stimulating AGRP neurons decreases maternal nest-building while minimally affecting pup retrieval, partly recapitulating suppression of maternal behaviors during food restriction. In parallel, optogenetically stimulating AGRP projections to the mPOA or to the paraventricular nucleus of hypothalamus but not to the LHA (lateral hypothalamus area) similarly decreases maternal nest-building. Chemogenetic inhibition of mPOA neurons that express Vgat (vesicular GABA transporter), the population targeted by AGRP terminals, also decreases maternal nest-building. In comparison, chemogenetic inhibition of neurons in the LHA that express vesicular glutamate transporter 2, another hypothalamic neuronal population critical for feeding and innate drives, is ineffective. Importantly, nest-building during low temperature thermal challenge is not affected by optogenetic stimulation of AGRPâmPOA projections. Finally, via optogenetic activation and inhibition we show that distinctive subsets of mPOA Vgat+ neurons likely underlie pup retrieval and maternal nest-building. Together, these results show that AGRP neurons can modulate maternal nest-building, in part through direct projections to the mPOA. This study corroborates other recent discoveries and underscores the broad functions that AGRP neurons play in antagonizing rivalry motivations to modulate behavioral outputs during hunger.SIGNIFICANCE STATEMENT In order for animals to initiate ethologically appropriate behaviors, they must typically decide between behavioral repertoires driven by multiple and often conflicting internal states. How neural pathways underlying individual behaviors interact to coherently modulate behavioral outputs, in particular to achieve a proper balance between behaviors that serve immediate individual needs versus those that benefit the propagation of the species, remains poorly understood. Here, by investigating projections from a neuronal population known to drive hunger behaviors to a brain region critical for maternal care, we show that activation of AGRPâmPOA projections in females dramatically inhibits maternal nest-building while leaving mostly intact pup retrieval behavior. Our findings shed new light on neural organization of behaviors and neural mechanisms that coordinate behavioral selection.
Assuntos
Proteína Relacionada com Agouti/fisiologia , Comportamento Materno/fisiologia , Rede Nervosa/fisiologia , Comportamento de Nidação/fisiologia , Neurônios/fisiologia , Área Pré-Óptica/fisiologia , Proteína Relacionada com Agouti/genética , Animais , Temperatura Baixa , Feminino , Privação de Alimentos , Região Hipotalâmica Lateral/fisiologia , Masculino , Camundongos , Camundongos Transgênicos , Optogenética , Núcleo Hipotalâmico Paraventricular/fisiologia , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/metabolismoRESUMO
Canine bufavirus (CBuV) is a novel protoparvovirus of dogs that was first reported in 2018 in Italy. The prevalence and genetic diversity of CBuV in China are not clear. In this study, a total of 115 canine fecal samples were collected from northern China in 2019, and two of the samples tested positive for CBuV DNA by PCR. These two field CBuV strains were designated Henan38 and Henan44. The complete genomic sequences of Henan38 and Henan44 were obtained by gap-filling PCR, sequenced, and assembled. Phylogenetic analysis demonstrated that the two strains clustered together in a novel group that was distant from previously reported CBuV strains. This study will strengthen our understanding of the epidemiology and genetic diversity of CBuV in China.
Assuntos
Evolução Molecular , Variação Genética , Infecções por Parvoviridae/veterinária , Parvovirus Canino/classificação , Filogenia , Animais , Sequência de Bases , China , Doenças do Cão/virologia , Cães , Fezes/virologia , Genoma Viral , Parvovirus Canino/isolamento & purificaçãoRESUMO
Equine Hepacivirus (EqHV) is a newly discovered equine virus that is classified under the Hepacivirus genus of the Flaviviridae family. There are three sub-types of EqHV worldwide namely; sub-types 1-3. The majority of EqHV sub-type 1 strains were found in China. While different sub-types have been found in Japan and USA, therefore, to investigate whether the other sub-types of EqHV strains were present in China, a total of 60 horse serum samples were collected and screened for EqHV RNA through RT-PCR. The results revealed that 19 serum samples were RNA-positive (19/60) and the EqHV detection rate was 31.67%. One EqHV strain named GD23 was obtained and its near-complete genome sequence was acquired. Analysis of nucleotide p-distance with reference to the entire polyprotein gene revealed that GD23 was classified into sub-type 3. In addition, the phylogenetic analysis demonstrated that GD23 was clustered together with EqHV strains of sub-type 3 in other countries. The present study is the first to identify an EqHV sub-type 3 strain in China.
Assuntos
Genoma Viral , Hepacivirus , Hepatite C , Cavalos/virologia , RNA Viral , Animais , China , Hepacivirus/classificação , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C/veterinária , Hepatite C/virologia , FilogeniaRESUMO
In the filamentous multicellular cyanobacterium Anabaena sp. strain PCC 7120, 5 to 10% of the cells differentiate into heterocysts, which are specialized in N2 fixation. Heterocysts and vegetative cells are mutually dependent for filament growth through nutrient exchange. Thus, the heterocyst frequency should be optimized to maintain the cellular carbon and nitrogen (C/N) balance for filament fitness in the environment. Here, we report the identification of patD, whose expression is directly activated in developing cells by the transcription factor NtcA. The inactivation of patD increases heterocyst frequency and promotes the upregulation of the positive regulator of heterocyst development hetR, whereas its overexpression decreases the heterocyst frequency. The change in heterocyst frequency resulting from the inactivation of patD leads to the reduction in competitiveness of the filaments under combined-nitrogen-depleted conditions. These results indicate that patD regulates heterocyst frequency in Anabaena sp. PCC 7120, ensuring its optimal filament growth.IMPORTANCE Microorganisms have evolved various strategies in order to adapt to the environment and compete with other organisms. Heterocyst differentiation is a prokaryotic model for studying complex cellular regulation. The NtcA-regulated gene patD controls the ratio of heterocysts relative to vegetative cells on the filaments of Anabaena sp. strain PCC 7120. Such a regulation provides a mechanism through which carbon fixation by vegetative cells and nitrogen fixation by heterocysts are properly balanced to ensure optimal growth and keep a competitive edge for long-term survival.
Assuntos
Anabaena/genética , Proteínas de Bactérias/genética , Anabaena/metabolismo , Carbono/metabolismo , Regulação Bacteriana da Expressão Gênica/genética , Nitrogênio/metabolismo , Fixação de Nitrogênio/genética , Fatores de Transcrição/genética , Regulação para Cima/genéticaRESUMO
Brain-derived neurotrophic factor (BDNF) regulates diverse processes such as neuronal survival, differentiation, and plasticity. Accumulating evidence suggests that molecular events that direct sexual differentiation of the brain interact with BDNF signaling pathways. This Mini-Review first examines potential hormonal and epigenetic mechanisms through which sex influences BDNF signaling. We then examine how sex-specific regulation of BDNF signaling supports the development and function of sexually dimorphic neural circuits that underlie male-specific genital reflexes in rats and song production in birds. Finally, we discuss the implications of sex differences in BDNF signaling for gender-biased presentation of neurological and psychiatric diseases such as Alzheimer's disease. Although this Mini-Review focuses on BDNF, we try to convey the general message that sex influences brain functions in complex ways and underscore the requirement for and challenge of expanding research on sex differences in neuroscience. © 2016 Wiley Periodicals, Inc.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Encéfalo/metabolismo , Caracteres Sexuais , Transdução de Sinais/fisiologia , Animais , Epigênese Genética , Humanos , Transtornos Mentais/metabolismo , Doenças do Sistema Nervoso/metabolismo , Plasticidade Neuronal/fisiologia , Receptor trkB/metabolismoRESUMO
When deprived of a combined-nitrogen source in the growth medium, the filamentous cyanobacterium Anabaena sp. PCC 7120 (Anabaena) can form heterocysts capable of nitrogen fixation. The process of heterocyst differentiation takes about 20 to 24 h, during which extensive metabolic and morphological changes take place. Guanosine tetraphosphate (ppGpp) is the signal of the stringent response that ensures cell survival by adjusting major cellular activities in response to nutrient starvation in bacteria, and ppGpp accumulates at the early stage of heterocyst differentiation (J. Akinyanju, R. J. Smith, FEBS Lett. 107:173-176, 1979; J Akinyanju, R. J. Smith, New Phytol. 105:117-122, 1987). Here we show that all1549 (here designated relana) in Anabaena, homologous to relA/spoT, is upregulated in response to nitrogen deprivation and predominantly localized in vegetative cells. The disruption of relana strongly affects the synthesis of ppGpp, and the resulting mutant, all1549Ωsp/sm, fails to form heterocysts and to grow in the absence of a combined-nitrogen source. This phenotype can be complemented by a wild-type copy of relana. Although the upregulation of hetR is affected in the mutant, ectopic overexpression of hetR cannot rescue the phenotype. However, we found that the mutant rapidly loses its viability, within a time window of 3 to 6 h, following the deprivation of combined nitrogen. We propose that ppGpp plays a major role in rebalancing the metabolic activities of the cells in the absence of the nitrogen source supply and that this regulation is necessary for filament survival and consequently for the success of heterocyst differentiation.
Assuntos
Anabaena/metabolismo , Regulação Bacteriana da Expressão Gênica/fisiologia , Guanosina Tetrafosfato/metabolismo , Anabaena/efeitos dos fármacos , Anabaena/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sobrevivência Celular , Mutação , Nitrogênio/metabolismo , Nitrogênio/farmacologia , PlasmídeosRESUMO
The success of vision transformers (ViTs) has given rise to their application in classification tasks of small environmental microorganism (EM) datasets. However, due to the lack of multi-scale feature maps and local feature extraction capabilities, the pure transformer architecture cannot achieve good results on small EM datasets. In this work, a novel hybrid model is proposed by combining the transformer with a convolution neural network (CNN). Compared to traditional ViTs and CNNs, the proposed model achieves state-of-the-art performance when trained on small EM datasets. This is accomplished in two ways. 1) Instead of the original fixed-size feature maps of the transformer-based designs, a hierarchical structure is adopted to obtain multi-scale feature maps. 2) Two new blocks are introduced to the transformer's two core sections, namely the convolutional parameter sharing multi-head attention block and the local feed-forward network block. The ways allow the model to extract more local features compared to traditional transformers. In particular, for classification on the sixth version of the EM dataset (EMDS-6), the proposed model outperforms the baseline Xception by 6.7 percentage points, while being 60 times smaller in parameter size. In addition, the proposed model also generalizes well on the WHOI dataset (accuracy of 99%) and constitutes a fresh approach to the use of transformers for visual classification tasks based on small EM datasets.
Assuntos
Algoritmos , Redes Neurais de ComputaçãoRESUMO
African swine fever virus (ASFV) causes an acute, hemorrhagic, and highly contagious disease in domestic swine, leading to significant economic losses to the global porcine industry. Restriction factors of innate immunity play a critical in host antiviral action. However, function of swine restriction factors of innate immunity on ASFV has been seldomly investigated. In this study, we determined five homologues of swine interferon-induced transmembrane proteins (SwIFITM [named SwIFITM1a, -1b, -2, -3, and -5]), and we found that they all exhibit potent antiviral activity against ASFV. Expression profile analysis indicated that these SwIFITMs are constitutively expressed in most porcine tissues. Whether infected with ASFV or treated with swine interferon, the expression levels of SwIFITMs were induced in vitro. The subcellular localization of SwIFITMs was similar to that of their human homologues. SwIFITM1a and -1b localized to the plasma membrane, SwIFITM2 and -3 focused on the cytoplasm and the perinuclear region, while SwIFITM5 accumulated in the cell surface and cytoplasm. The overexpression of SwIFITM1a, -1b, -2, -3, or -5 could significantly inhibit ASFV replication in Vero cells, whereas knockdown of these genes could enhance ASFV replication in PAMs. We blocked the constitutive expression of endogenous IFITMs in Vero cells using a CRISPR-Cas9 system and then infected them with ASFV. The results indicated that the knockout of endogenous IFITMs could enhance ASFV replication. Finally, we expressed five SwIFITMs in knockout Vero cell lines and then challenged them with ASFV. The results showed that all of the SwIFITMs had a strong antiviral effect on ASFV. This research will further expand the understanding of the anti-ASFV activity of porcine IFITMs.
Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Vírus da Febre Suína Africana/genética , Animais , Antivirais/metabolismo , Antivirais/farmacologia , Chlorocebus aethiops , Interferons/metabolismo , Proteínas de Membrana/metabolismo , Suínos , Células Vero , Replicação ViralRESUMO
Bovine hepacivirus (BovHepV) is a novel virus that was recently discovered in Ghana and Germany in 2015. Until now, this virus has been identified in cattle population worldwide and is classified into subtypes A-G. To fully understand the epidemic situation and genetic characteristic of BovHepV in China, a total of 612 cattle serum samples were collected from 20 farms in seven provinces and municipality in China between 2018 and 2020 and were tested for the presence of BovHepV RNA via semi-nested PCR. The results demonstrated that 49 (8.0%) samples were BovHepV RNA-positive. It is noted that BovHepV infection in yak was confirmed for the first time. BovHepV was detected in all the seven provinces, with the positive rate ranging from 3.1% to 13.3%, which indicates a wide geographical distribution pattern of BovHepV in China. Sequencing results revealed that 5' UTR of the 49 field BovHepV strains have a nucleotide similarity of 96.3%-100% between each other and 93.9%-100% with previously reported BovHepV strains. In addition, genetic analysis identified five critical nucleotide sites in 5' UTR to distinguish different subtypes, which was further verified by genomic sequencing and nucleotide similarity analysis. All the 49 Chinese field BovHepV strains were classified into subtype G and this subtype is only determined in cattle in China currently. This study will provide insights for us to better understand the epidemiology and genetic diversity of BovHepV.
Assuntos
Hepacivirus , Nucleotídeos , Regiões 5' não Traduzidas , Animais , Bovinos , China/epidemiologia , Estudos Epidemiológicos , Variação Genética , Genótipo , Hepacivirus/genética , FilogeniaRESUMO
The dysfunctions of human umbilical vein endothelial cells (HUVECs) are important features of atherosclerosis (AS). Circular RNAs (circRNAs) are regulators of a wide range of human diseases, including AS. The present study aimed to investigate the role of circUSP36 in the ectopic phenotype of HUVECs and to provide evidence of the involvement of circUSP36 in the pathogenesis of AS. AS cell models in vitro were established using HUVECs exposed to oxidized lowdensity lipoprotein (oxLDL). Cell viability, cell cycle progression and apoptosis, and cell migration and invasion were assessed by cell counting kit8 (CCK8) assay, flow cytometric assay and Transwell assay, respectively. The expression levels or releases of proinflammatory factors were detected by western blot analysis or enzymelinked immunosorbent assay (ELISA). The mRNA expression of circUSP36, miR20a5p and Rhoassociated coiledcoil kinase 2 (ROCK2) was detected by reverse transcriptionquantitative polymerase chain reaction (RTqPCR), and the protein level of ROCK2 was detected by western blot analysis. The targeted association between miR20a5p and circUSP36 or ROCK2 was verified by dualluciferase reporter assay and RNA immunoprecipitation (RIP) assay. The results revealed that circUSP36 was highly expressed in oxLDLexposed HUVECs. CircUSP36 knockdown attenuated oxLDLinduced cell cycle arrest, cell apoptosis and inflammatory responses, and promoted cell migration and invasion which had been blocked by oxLDL. miR20a5p was found to be a target of circUSP36, and miR20a5p inhibition reversed the effects of circUSP36 knockdown. Moreover, miR20a5p directly bound to ROCK2, and miR20a5p inhibition aggravated oxLDLinduced injury by increasing the ROCK2 level. More importantly, circUSP36 targeted miR20a5p to regulate the expression of ROCK2. On the whole, the present study demonstrates that, circUSP36 regulates oxLDLinduced HUVEC injury and inflammation by modulating ROCK2 via competitively targeting miR20a5p.
Assuntos
Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Lipoproteínas LDL/farmacologia , Ubiquitina Tiolesterase/metabolismo , Quinases Associadas a rho/metabolismo , Apoptose/genética , Apoptose/fisiologia , Aterosclerose/metabolismo , Western Blotting , Ciclo Celular/genética , Ciclo Celular/fisiologia , Movimento Celular/genética , Movimento Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Biologia Computacional , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoprecipitação , Estresse Oxidativo/efeitos dos fármacos , Ubiquitina Tiolesterase/genética , Quinases Associadas a rho/genéticaRESUMO
Lumpy skin disease (LSD) is a viral disease of cattle caused by LSD virus (LSDV). This disease poses a significant threat to stockbreeding and is listed as one of bovine notifiable diseases by OIE. Before 2019, LSD has not been reported in China. The first LSD outbreak was determined in China on August 3, 2019. Since then, a total of 7 LSD outbreaks have been reported in other 6 provinces in China, infecting 91 and killing 7 cattle. As of now, LSDV was detected in western and eastern China and also in Taiwan Island outside Mainland China. LSD is undoubtedly an emerging threat to the cattle industry in China.
Assuntos
Surtos de Doenças/veterinária , Doença Nodular Cutânea/epidemiologia , Animais , Bovinos , China/epidemiologia , Doença Nodular Cutânea/virologia , Vírus da Doença Nodular Cutânea/fisiologia , Taiwan/epidemiologiaRESUMO
Parvovirus is a common element of the feline virus group and usually causes gastroenteritis and leukopenia in cats. In this study, we identified a novel protoparvovirus from the Chinese domestic cats, which is genetically similar to canine bufavirus (98.0%-99.8%), but sharing low amino acid identities in the viral structural proteins 2 (VP2) (36.1-37.2%) to the well-known canine parvovirus type 2 and feline panleukopenia virus. This virus was provisionally designated as feline bufavirus (FBuV). Screening of fecal samples revealed a prevalence of 7.4% (19/257) in domestic cats. Diarrhea was present in 52.6% (10/19) of cats positive for FBuV. However, statistical analysis showed no association between FBuV and clinical signs. VP2 gene of the 19 field FBuV was sequenced and phylogenetic analysis demonstrated that FBuV determined from China had a genetic diversity. This study will strengthen the understanding of the epidemiology and genetic diversity of bufavirus and provide a foundation for further studies.
Assuntos
Infecções por Parvoviridae , Parvovirus Canino , Parvovirus , Animais , Gatos , China/epidemiologia , Cães , Vírus da Panleucopenia Felina/genética , Infecções por Parvoviridae/epidemiologia , Infecções por Parvoviridae/veterinária , Parvovirus/genética , Parvovirus Canino/genética , FilogeniaRESUMO
It is widely accepted that the stria vascularis (SV) in cochlea plays a critical role in the generation of endocochlear potential (EP) and the secretion of the endolymph. 17ß-estradiol (E2) is the most potent and abundant endogenous estrogen during the premenopausal period, thus, considered as the reference estrogen. This study aimd to investigate the protective effect of E2 by promoting the expression of vascular endothelial growth factor (VEGF) and thus promoting the vascular regeneration of the SV in elderly mice. After being treated with E2 either in vivo or in vitro, the hearing threshold changes of C57BL/6J elder mice continuously reduced, endothelial cell morphology improved, the number of endothelial cells (ECs) tubular nodes increased significantly, the ability of tubular formation enhanced significantly and the expression of VEGF increased. In vitro, cell model in conjunction with in vivo ovariectomized model was established to demonstrate for the first time that E2 promotes angiogenesis by promoting the secretion of VEGF through the phosphatidylinositol 3-kinase (PI3K)/AKT pathway (PI3K/AKT). In conclusion, E2 demonstrated potent angiogenesis properties with significant protection against Age-Related Hearing Loss (ARHL), which provides a new idea for the improvement of ARHL.
Assuntos
Indutores da Angiogênese/farmacologia , Estradiol/farmacologia , Perda Auditiva/prevenção & controle , Neovascularização Fisiológica/efeitos dos fármacos , Estria Vascular/efeitos dos fármacos , Envelhecimento/fisiologia , Indutores da Angiogênese/uso terapêutico , Animais , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Estradiol/uso terapêutico , Feminino , Perda Auditiva/fisiopatologia , Humanos , Camundongos , Técnicas de Cultura de Órgãos , Regeneração/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Estria Vascular/fisiologia , Fator A de Crescimento do Endotélio Vascular/agonistas , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Adult male mice emit highly complex ultrasonic vocalizations (USVs) in response to female conspecifics. Such USVs, thought to facilitate courtship behaviors, are routinely measured as a behavioral index in mouse models of neurodevelopmental and psychiatric disorders such as autism. While the regulation of USVs by genetic factors has been extensively characterized, the neural mechanisms that control USV production remain largely unknown. Here, we report that optogenetic activation of the medial preoptic area (mPOA) elicited the production of USVs that were acoustically similar to courtship USVs in adult mice. Moreover, mPOA vesicular GABA transporter-positive (Vgat +) neurons were more effective at driving USV production than vesicular glutamate transporter 2-positive neurons. Furthermore, ablation of mPOA Vgat+ neurons resulted in altered spectral features and syllable usage of USVs in targeted males. Together, these results demonstrate that the mPOA plays a crucial role in modulating courtship USVs and this may serve as an entry point for future dissection of the neural circuitry underlying USV production.
Assuntos
Corte/psicologia , Área Pré-Óptica/fisiologia , Ultrassom , Vocalização Animal/fisiologia , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Optogenética , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/antagonistas & inibidores , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/metabolismoRESUMO
The medial preoptic area (mPOA) differs between males and females in nearly all species examined to date, including humans. Here, using fiber photometry recordings of Ca2+ transients in freely behaving mice, we show ramping activities in the mPOA that precede and correlate with sexually dimorphic display of male-typical mounting and female-typical pup retrieval. Strikingly, optogenetic stimulation of the mPOA elicits similar display of mounting and pup retrieval in both males and females. Furthermore, by means of recording, ablation, optogenetic activation, and inhibition, we show mPOA neurons expressing estrogen receptor alpha (Esr1) are essential for the sexually biased display of these behaviors. Together, these results underscore the shared layout of the brain that can mediate sex-specific behaviors in both male and female mice and provide an important functional frame to decode neural mechanisms governing sexually dimorphic behaviors in the future.
Assuntos
Encéfalo/fisiologia , Neurônios/fisiologia , Área Pré-Óptica/fisiologia , Comportamento Sexual Animal , Animais , Encéfalo/metabolismo , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/metabolismo , Optogenética/métodos , Área Pré-Óptica/metabolismo , Fatores SexuaisRESUMO
Despite recent progress on neural pathways underlying individual behaviors, how an animal balances and prioritizes behavioral outputs remains poorly understood. While studying the relationship between hunger-induced feeding and pup-induced maternal behaviors in virgin female mice, we made the unexpected discovery that presence of pups strongly delayed and decreased food consumption. Strikingly, presence of pups also suppressed feeding induced by optogenetic activation of Agrp neurons. Such a suppressive effect inversely correlated with the extents of maternal behaviors, but did not rely on the display of these behaviors, and was also present in virgin males. Furthermore, chemogenetic activation of Vglut2+ neurons in the medial preoptic area (mPOA), a region critical for maternal behaviors and motivation, was sufficient to suppress hunger-induced feeding. However, muscimol inhibition of the mPOA, while disrupting maternal behaviors, did not prevent pup suppression of feeding, indicating that neural pathways in other brain regions may also mediate such an effect. Together, these results provide novel insights into neural coordination of pup care and feeding in mice and organizations of animal behaviors in general.
Assuntos
Comportamento Alimentar/fisiologia , Fome/fisiologia , Comportamento Materno/fisiologia , Neurônios/fisiologia , Comportamento Paterno/fisiologia , Área Pré-Óptica/fisiologia , Proteína Relacionada com Agouti/genética , Proteína Relacionada com Agouti/metabolismo , Animais , Animais Recém-Nascidos , Feminino , Agonistas de Receptores de GABA-A/farmacologia , Masculino , Comportamento Materno/psicologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Muscimol/farmacologia , Neurônios/citologia , Optogenética , Comportamento Paterno/psicologia , Área Pré-Óptica/citologia , Área Pré-Óptica/efeitos dos fármacos , Reprodução , Caracteres Sexuais , Proteína Vesicular 2 de Transporte de Glutamato/metabolismoAssuntos
Alphavirus , Doenças dos Cavalos , Alphavirus/genética , Animais , China/epidemiologia , Cavalos , Humanos , Análise de Sequência de DNARESUMO
BACKGROUND/AIMS: JX-594 is an oncolytic virus derived from the Wyeth vaccinia strain that causes replication-dependent cytolysis and antitumor immunity. Starting with a cross-examination of clinical-trial samples from advanced hepatocellular carcinoma patients having high levels of aldosterone and virus amplification in JX-594 treatment, we investigated the association between virus amplification and aldosterone in human cancer cell lines. METHODS: Cell proliferation was determined by a cell-counting-kit-based colorimetric assay, and vaccinia virus quantitation was performed by quantitative polymerase chain reaction (qPCR) and a viral plaque assay. Also, the intracellular pH was measured using a pH-sensitive dye. RESULTS: Simultaneous treatment with JX-594 and aldosterone significantly increased viral replication in A2780, PC-3, and HepG2 cell lines, but not in U2OS cell lines. Furthermore, the aldosterone treatment time altered the JX-594 replication according to the cell line. The JX-594 replication peaked after 48 and 24 hours of treatment in PC-3 and HepG2 cells, respectively. qPCR showed that JX-594 entry across the plasma membrane was increased, however, the changes are not significant by the treatment. This was inhibited by treatment with spironolactone (an aldosterone-receptor inhibitor). JX-594 entry was significantly decreased by treatment with EIPA [5-(N-ethyl-N-isopropyl)amiloride; a Na(+)/H(+)-exchange inhibitor], but aldosterone significantly restored JX-594 entry even in the presence of EIPA. Intracellular alkalization was observed after aldosterone treatment but was acidified by EIPA treatment. CONCLUSIONS: Aldosterone stimulates JX-594 amplification via increased virus entry by affecting the H(+) gradient.