RESUMO
This small-sample pilot study sought to uncover the role of palliative care education for general nurses providing care to patients with intractable cancer. While nurses serve as total care coordinators in patient recuperation, most general nurses in Japan dealing with such patients must independently update their knowledge. A questionnaire was developed comprising 28 items from the five supportive care need categories according to the Integrating Oncology and Palliative Care (IOP) model and 22 items from the Nurses' Difficulties in Cancer Care (NDCC) scale. General nurses who had worked in cancer care for over 5 years were recruited using snowball sampling. Based on the results, we planned a lecture and free study session on IOP using information and communication technology (ICT). Four lectures were delivered to 108 nurses from Hokkaido to Okinawa and remote islands. Overall, 90% of the participants were female nurses. They were categorized into two groups based on the number of times they attended the lectures (Group 1 [G1, attended once or twice]: 45; Group 2 [G2, attended three or four times]: 63). Comparing G1 and G2 showed that the practical ability of the participants in G2 increased for the items "Patient/Family Communication" and "Knowledge and Skills." Continued education using ICT may improve the practical skills of general nurses caring for patients with intractable cancer.
Assuntos
Neoplasias , Enfermeiras e Enfermeiros , Humanos , Feminino , Masculino , Cuidados Paliativos , Japão , Projetos Piloto , Inquéritos e Questionários , Aprendizagem , Neoplasias/terapiaRESUMO
BMP signaling plays pleiotropic roles in various tissues during embryogenesis and after birth. We have previously generated a constitutively activated Acvr1(ca-Acvr1) transgenic mouse line (line L35) through pronuclei injection to investigate impacts of enhanced BMP signaling in a tissue specific manner. However, line L35 shows a restricted expression pattern of the transgene. Here, we generated another ca-Acvr1 transgenic line, line A11, using embryonic stem (ES) transgenesis. The generated line A11 shows distinctive phenotypes from line L35, along with very limited expression levels of the transgene. When the transgene is activated in the neural crest cells in a Cre-dependent manner, line A11 exhibits cleft palate and shorter jaws, while line L35 develops ectopic cartilages and highly hypomorphic facial structures. When activated in limb buds, line A11 develops organized but smaller limb skeletal structures, while line L35 forms disorganized limbs with little mineralization. Additionally, no heterotopic ossification (HO) is identified in line A11 when bred with NFATc1-Cre mice even after induction of tissue injury, which is an established protocol for HO for line L35. Therefore, the newly generated conditional ca-Acvr1 mouse line A11 provides an additional resource to dissect highly context dependent functions of BMP signaling in development and disease.
Assuntos
Receptores de Ativinas Tipo I/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Marcação de Genes/métodos , Pleiotropia Genética , Transgenes , Receptores de Ativinas Tipo I/metabolismo , Animais , Cartilagem/metabolismo , Condrogênese , Botões de Extremidades/embriologia , Botões de Extremidades/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Ativação TranscricionalRESUMO
Podoplanin, PDPN, is a mucin-type transmembrane glycoprotein widely expressed in many tissues, including lung, kidney, lymph nodes, and mineralized tissues. Its function is critical for lymphatic formation, differentiation of type I alveolar epithelial lung cells, and for bone response to biomechanical loading. It has previously been shown that Pdpn null mice die at birth due to respiratory failure emphasizing the importance of Pdpn in alveolar lung development. During the course of generation of Pdpn mutant mice, we found that most Pdpn null mice in the 129S6 and C57BL6/J mixed genetic background die at the perinatal stage, similar to previously published studies with Pdpn null mice, while all Pdpn null mice bred with Swiss outbred mice survived. Surviving mutant mice in the 129S6 and C57BL6/J mixed genetic background showed alterations in the osteocyte lacunocanalicular network, especially reduced osteocyte canaliculi in the tibial cortex with increased tibial trabecular bone. However, adult Pdpn null mice in the Swiss outbred background showed no overt differences in their osteocyte lacunocnalicular network, bone density, and no overt differences when challenged with exercise. Together, these data suggest that genetic variations present in the Swiss outbred mice compensate for the loss of function of PDPN in lung, kidney, and bone.
Assuntos
Células Epiteliais Alveolares/metabolismo , Diferenciação Celular/genética , Linfangiogênese/genética , Glicoproteínas de Membrana/genética , Animais , Calcificação Fisiológica/genética , Osso Esponjoso/crescimento & desenvolvimento , Osso Esponjoso/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Rim/crescimento & desenvolvimento , Pulmão/crescimento & desenvolvimento , Pulmão/metabolismo , Linfonodos/crescimento & desenvolvimento , Camundongos , Osteócitos/metabolismo , Tíbia/crescimento & desenvolvimento , Tíbia/metabolismoRESUMO
The characterization of gene expression in gametes has advanced our understanding of the molecular basis for ecological variation in reproductive success and the evolution of reproductive isolation. These advances are especially significant for ecologically important keystone predators such as the coral-eating crown-of-thorns sea stars (COTS, Acanthaster) which are the most influential predator species in Indo-Pacific coral reef ecosystems and the focus of intensive management efforts. We used RNA-seq and transcriptome assemblies to characterize the expression of genes in mature COTS gonads. We described the sequence and domain organization of eight genes with sex-specific expression and well known functions in fertilization in other echinoderms. We found unexpected expression of genes in one ovary transcriptome that are characteristic of males and sperm, including genes that encode the sperm-specific guanylate cyclase receptor for an egg pheromone, and the sperm acrosomal protein bindin. In a reassembly of previously published RNA-seq data from COTS testes, we found a complementary pattern: strong expression of four genes that are otherwise well known to encode egg-specific fertilization proteins, including the egg receptor for bindin (EBR1) and the acrosome reaction-inducing substance in the egg coat (ARIS1, ARIS2, ARIS3). We also found histological evidence of both eggs and sperm developing in the same gonad in several COTS individuals from a parallel study. These results suggest the occurrence of hermaphrodites, and the potential for reproductive assurance via self-fertilization. Our findings have implications for management of COTS populations, especially in consideration of the large size and massive fecundity of these sea stars.
Assuntos
Recifes de Corais , Estrelas-do-Mar/genética , Animais , Ecossistema , Receptores de Superfície Celular/genética , Transcriptoma/genéticaRESUMO
Glucagon-like peptide 1 (GLP-1), an incretin gastrointestinal hormone, is secreted when stimulated by nutrients including metabolizable sugars such as glucose and fructose. d-Allulose (allulose), also known as d-psicose, is a C-3 isomer of d-fructose and a rare sugar with anti-diabetic or anti-obese effects in animal models. In the present study, we examined whether an oral administration of allulose could stimulate GLP-1 secretion in rats, and investigated the underlying mechanisms. Oral, but not intraperitoneal, administration of allulose (0.5-2.0â¯g/kg body weight) elevated plasma GLP-1 levels for more than 2â¯h in a dose-dependent manner. The effects of allulose on GLP-1 secretion were higher than that of dextrin, fructose, or glucose. In addition, oral allulose increased total and active GLP-1, but not glucose-dependent insulinotropic polypeptide (GIP), levels in the portal vein. In anesthetized rats equipped with a portal catheter, luminal (duodenum and ileum) administration of allulose increased portal GLP-1 levels, indicating the luminal effect of allulose. Allulose-induced GLP-1 secretion was abolished in the presence of xanthohumol (a glucose/fructose transport inhibitor), but not in the presence of inhibitors of the sodium-dependent glucose cotransporter 1 or the sweet taste receptor. These results demonstrate a potent and lasting effect of orally administered allulose on GLP-1 secretion in rats, without affecting GIP secretion. The potent and selective GLP-1-releasing effect of allulose holds promise for the prevention and treatment of glucose intolerance through promoting endogenous GLP-1 secretion.
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For endemic benthos inhabiting hydrothermal vent fields, larval recruitment is critical for population maintenance and colonization via migration among separated sites. The vent-endemic limpet, Lepetodrilus nux, is abundant at deep-sea hydrothermal vents in the Okinawa Trough, a back-arc basin in the northwestern Pacific; nonetheless, it is endangered due to deep-sea mining. This species is associated with many other vent species and is an important successor in these vent ecosystems. However, limpet genetic diversity and connectivity among local populations have not yet been examined. We conducted a population genetics study of L. nux at five hydrothermal vent fields (maximum geographic distance, ~545 km; depths ~700 m to ~1650 m) using 14 polymorphic microsatellite loci previously developed. Genetic diversity has been maintained among these populations. Meanwhile, fine population genetic structure was detected between distant populations, even within this back-arc basin, reflecting geographic distances between vent fields. There was a significant, positive correlation between genetic differentiation and geographic distance, but no correlation with depth. Contrary to dispersal patterns predicted by an ocean circulation model, genetic migration is not necessarily unidirectional, based on relative migration rates. While ocean circulation contributes to dispersal of L. nux among vent fields in the Okinawa Trough, genetic connectivity may be maintained by complex, bidirectional dispersal processes over multiple generations.
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Human adenoviruses species D (HAdV-D) are known to cause severe epidemic keratoconjunctivitis. However, the isolation rate of HAdV-D is not high, because HAdV-D is usually slow to propagate. Although new types of HAdV-D have been reported, accurate surveillance has not been performed because of difficulties in culturing the viruses and lack of a practical identification method. In this study, HAdV-Ds were detected and identified from patients with epidemic keratoconjunctivitis in the Fukui Prefecture during 1995-2010 by PCR, loop-mediated isothermal amplification (LAMP) of DNA, and conventional virus isolation and neutralization tests. All samples were subjected to culture and PCR and LAMP. A total of 124 strains of HAdV-D were detected from 157 patients with epidemic keratoconjunctivitis. The strains consisted of the following types: D8 (n = 8), D19 (n = 4), D37 (n = 40), D53 (n = 5), D54 (n = 66), and D56 (n = 1). Among these, D53, D54, and D56 are new types that have been reported recently. The results of this study demonstrated that new types of HAdV-D caused epidemic keratoconjunctivitis during 1995-2010, and included an outbreak of keratoconjunctivitis caused by HAdV-D54. The LAMP method was able to detect and identify HAdV-D53 and HAdV-D54 in 1 hr, and may therefore be applicable for use at the bedside.
Assuntos
Infecções por Adenoviridae/epidemiologia , Infecções por Adenoviridae/virologia , Adenovírus Humanos/isolamento & purificação , Ceratoconjuntivite/epidemiologia , Ceratoconjuntivite/virologia , Adenovírus Humanos/classificação , Adenovírus Humanos/genética , Genótipo , Humanos , Japão/epidemiologia , Dados de Sequência Molecular , Testes de Neutralização , Técnicas de Amplificação de Ácido Nucleico , Análise de Sequência de DNA , Cultura de VírusRESUMO
Devastating bleaching of coral communities at Amitori Bay, Iriomote Island, Japan, occurred in 2016 during the third global mass bleaching event in 2014-2017. The present study documented changes in coral communities in Amitori Bay from just before until after the 2016 bleaching event (2016-2020), by measuring coral cover and recruitment at nine sites (with two additional sites in 2018) in the bay. Spawning rates of acroporid corals were also monitored from 2017 to 2019 by visual observation and using bundle collectors to observe how long the effect of bleaching persisted. Reductions of 64.7 and 89.5% from 2016 to 2017 were observed in cover and recruitment of all coral families, respectively. Coral cover of all coral families recovered to pre-bleaching levels by 2020 and recruitment in 2020 was about two times greater than the pre-bleaching level. These results mirrored those of acroporids. Spawning rates of Acropora corals increased significantly from 40.6% in 2017 to 90.0% in 2019. Recovery of coral cover 4 years after the severe bleaching event was likely related to regrowth of remnants and of surviving juveniles of < 5 cm. The sudden increase in recruitment was likely driven by a combination of larval supply from other populations, increased numbers of reproductive adults, increases in spawning rates, and increased larval retention in the bay due to wind conditions in 2020. This study suggests that coral communities as in Amitori Bay will be critical for local-scale community persistence, serving as both source and sink populations. Supplementary Information: The online version contains supplementary material available at 10.1007/s00227-022-04091-2.
RESUMO
Human adenovirus type 53 (HAdV-53) has commonly been detected in samples from epidemic keratoconjunctivitis (EKC) patients in Japan since 1996. HAdV-53 is an intermediate virus, containing hexon-chimeric, penton base and fiber structures similar to HAdV-22 and -37, HAdV-37 and HAdV-8, respectively. HAdV-53-like intermediate strains were first isolated from EKC samples in Japan in the 1980s. Here, the complete genome sequences of three such HAdV-53-like intermediate strains (870006C, 880249C and 890357C) and four HAdV-53 strains were determined, and their relationships were analysed. The seven HAdV strains were classified into three groups, 870006C/880249C, 890357C and the four HAdV-53 strains, on the basis of phylogenetic analyses of the partial and complete genome sequences. HAdV strains within the same group showed the highest nucleotide identities (99.87-100.00â%). Like HAdV-53, the hexon loop 1 and 2 regions of 870006C, 880249C and 890357C showed the highest identity with HAdV-22. However, these strains did not show a hexon-chimeric structure similar to HAdV-22 and -37, or a penton base similar to HAdV-37. The fiber genes of 870006C and 880249C were identical to that of HAdV-37, but not HAdV-8. Thus, the three intermediate HAdVs isolated in the 1980s were similar to each other but not to HAdV-53. The recombination breakpoints were inferred by the Recombination Detection Program (rdp) using whole-genome sequences of these seven HAdV and of 12 HAdV-D strains from GenBank. HAdV-53 may have evolved from intermediate HAdVs circulating in the 1980s, and from HAdV-8, -22 and -37, by recombination of sections cut at the putative breakpoints.
Assuntos
Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/genética , Genoma Viral , Ceratoconjuntivite/virologia , Recombinação Genética , Infecções por Adenovirus Humanos/epidemiologia , Adenovírus Humanos/classificação , Adenovírus Humanos/isolamento & purificação , Humanos , Japão/epidemiologia , Ceratoconjuntivite/epidemiologia , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNARESUMO
Cranial neural crest cells (CNCCs) are a population of multipotent stem cells that give rise to craniofacial bone and cartilage during development. Bone morphogenetic protein (BMP) signaling and autophagy have been individually implicated in stem cell homeostasis. Mutations that cause constitutive activation of the BMP type I receptor ACVR1 cause the congenital disorder fibrodysplasia ossificans progressiva (FOP), which is characterized by ectopic cartilage and bone in connective tissues in the trunk and sometimes includes ectopic craniofacial bones. Here, we showed that enhanced BMP signaling through the constitutively activated ACVR1 (ca-ACVR1) in CNCCs in mice induced ectopic cartilage formation in the craniofacial region through an autophagy-dependent mechanism. Enhanced BMP signaling suppressed autophagy by activating mTORC1, thus blocking the autophagic degradation of ß-catenin, which, in turn, caused CNCCs to adopt a chondrogenic identity. Transient blockade of mTORC1, reactivation of autophagy, or suppression of Wnt-ß-catenin signaling reduced ectopic cartilages in ca-Acvr1 mutants. Our results suggest that BMP signaling and autophagy coordinately regulate ß-catenin activity to direct the fate of CNCCs during craniofacial development. These findings may also explain why some patients with FOP develop ectopic bones through endochondral ossification in craniofacial regions.
Assuntos
Receptores de Ativinas Tipo I/metabolismo , Condrogênese , Crista Neural/metabolismo , Transdução de Sinais , Crânio/metabolismo , beta Catenina/metabolismo , Receptores de Ativinas Tipo I/genética , Animais , Proteínas Morfogenéticas Ósseas/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Miosite Ossificante , Crista Neural/fisiologia , Osteogênese , Proteólise , Crânio/fisiologiaRESUMO
Mammalian genomes contain numerous evolutionary harbored mobile elements, a part of which are still active and may cause genomic instability. Their movement and positional diversity occasionally result in phenotypic changes and variation by causing altered expression or disruption of neighboring host genes. Here, we describe a novel microarray-based method by which dispersed genomic locations of a type of retrotransposon in a mammalian genome can be identified. Using this method, we mapped the DNA elements for a mouse retrotransposon, intracisternal A-particle (IAP), within genomes of C3H/He and C57BL/6J inbred mouse strains; consequently we detected hundreds of probable IAP cDNA-integrated genomic regions, in which a considerable number of strain-specific putative insertions were included. In addition, by comparing genomic DNAs from radiation-induced myeloid leukemia cells and its reference normal tissue, we detected three genomic regions around which an IAP element was integrated. These results demonstrate the first successful genome-wide mapping of a retrotransposon type in a mammalian genome.
Assuntos
Mapeamento Cromossômico/métodos , Genes de Partícula A Intracisternal , Genômica/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Animais , Feminino , Leucemia Induzida por Radiação/genética , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Sequências Repetidas TerminaisRESUMO
Ocean acidification is now recognized as a threat to marine ecosystems; however, the effect of ocean acidification on fertilization in marine organisms is still largely unknown. In this study, we focused on sperm flagellar motility in broadcast spawning reef invertebrates (a coral and a sea cucumber). Below pH 7.7, the pH predicted to occur within the next 100 years, sperm flagellar motility was seriously impaired in these organisms. Considering that sperm flagellar motility is indispensable for transporting the paternal haploid genome for fertilization, fertilization taking place in seawater may decline in the not too distant future. Urgent surveys are necessary for a better understanding of the physiological consequences of ocean acidification on sperm flagellar motility in a wide range of marine invertebrates.
Assuntos
Antozoários/fisiologia , Flagelos/fisiologia , Pepinos-do-Mar/fisiologia , Água do Mar , Poluição Química da Água , Ácidos , Animais , Conservação dos Recursos Naturais , Oceanos e MaresRESUMO
The aim of the present study was to identify novel prognostic biomarkers and therapeutic targets for breast cancer; thus, genes that are frequently overexpressed in several types of breast cancer were screened. Kinesin family member 20A (KIF20A) was identified as a candidate molecule during this process. Immunohistochemical staining performed using tissue microarrays from 257 samples of different breast cancer subtypes revealed that KIF20A was expressed in 195 (75.9%) of these samples, whereas it was seldom expressed in normal breast tissue. KIF20A protein was expressed in all types of breast cancer observed. However, it was more frequently expressed in human epidermal growth factor receptor 2 (HER2)positive and triplenegative breast cancer than in the luminal type. Moreover, KIF20A expression was significantly associated with the poor prognosis of patients with breast cancer. A multivariate analysis indicated that KIF20A expression was an independent prognostic factor for patients with breast cancer. The suppression of endogenous KIF20A expression using small interfering ribonucleic acids or via treatment with paprotrain, a selective inhibitor of KIF20A, significantly inhibited breast cancer cell growth through cell cycle arrest at the G2/M phase and subsequent mitotic cell death. These results suggest that KIF20A is a candidate prognostic biomarker and therapeutic target for different types of breast cancer.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Cinesinas/metabolismo , Idoso , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Cinesinas/antagonistas & inibidores , Cinesinas/genética , Pessoa de Meia-Idade , PrognósticoRESUMO
During palatogenesis, the palatal shelves first grow vertically on either side of the tongue before changing their direction of growth to horizontal. The extracellular matrix (ECM) plays an important role in these dynamic changes in palatal shelf morphology. Tenascin-C (TNC) is an ECM glycoprotein that shows unique expression in the posterior part of the palatal shelf, but little is known about the regulation of TNC expression. Since transforming growth factor-beta-3 (TGF-ß3) and sonic hedgehog (SHH) signaling are known to play important roles in palatogenesis, we investigated whether TGF-ß3 and SHH are involved in the regulation of TNC expression in the developing palate. TGF-ß3 increased the expression of TNC mRNA and protein in primary mouse embryonic palatal mesenchymal cells (MEPM) obtained from palatal mesenchyme dissected at embryonic day 13.5-14.0. Interestingly, immunohistochemistry experiments revealed that TNC expression was diminished in K14-cre;Tgfbr2 fl/fl mice that lack the TGF-ß type II receptor in palatal epithelial cells and exhibit cleft soft palate, whereas TNC expression was maintained in Wnt1-cre;Tgfbr2 fl/fl mice that lack the TGF-ß type II receptor in palatal mesenchymal cells and exhibit a complete cleft palate. SHH also increased the expression of TNC mRNA and protein in MEPM cells. However, although TGF-ß3 up-regulated TNC mRNA and protein expression in O9-1 cells (a cranial neural crest cell line), SHH did not. Furthermore, TGF-ß inhibited the expression of osteoblastic differentiation markers (osterix and alkaline phosphatase) and induced the expression of fibroblastic markers (fibronectin and periostin) in O9-1 cells, whereas SHH did not affect the expression of osteoblastic and fibroblastic markers in O9-1 cells. However, immunohistochemistry experiments showed that TNC expression was diminished in the posterior palatal shelves of Shh-/+ ;MFCS4 +/- mice, which have deficient SHH signaling in the posterior palatal epithelium. Taken together, our findings support the proposal that TGF-ß and SHH signaling in palatal epithelium co-ordinate the expression of TNC in the posterior palatal mesenchyme through a paracrine mechanism. This signal cascade may work in the later stage of palatogenesis when cranial neural crest cells have differentiated into fibroblast-like cells. The spatiotemporal regulation of ECM-related proteins by TGF-ß and SHH signaling may contribute not only to tissue construction but also to cell differentiation or determination along the anterior-posterior axis of the palatal shelves.
RESUMO
OBJECTIVE: High-dose radiation exposure induces acute myeloid leukemia (AML) in C3H mice, most of which have a frequent hemizygous deletion around the D2Mit15 marker on chromosome 2. This region includes PU.1, a critical candidate gene for initiation of leukemogenesis. To identify novel cooperative genes with PU.1, relevant to radiation-induced leukemogenesis, we analyzed the copy number alterations of tumor-related gene loci by array CGH, and their expressions in primary and transplanted AMLs. MATERIALS AND METHODS: For the induction of AMLs, C3H/He Nrs mice were exposed to 3 Gy of x-rays or gamma-rays. The genomic alterations of 35 primary AMLs and 34 transplanted AMLs obtained from the recipient mice transplanted the primary AMLs were analyzed by array CGH. According to the genomic alterations and mutations of the 235th arginine of PU.1 allele, we classified the radiogenic AMLs into three types such as Chr2(del) PU.1(del/R235-) AML, Chr2(del) PU.1(del/R235+) AML and Chr2(intact) PU.1(R235+/R235+) AML, to compare the expression levels of 8 tumor-related genes quantitatively by real-time polymerase chain reaction and cell-surface antigen expression. Results. In addition to well-known loss of PU.1 with hemizygous deletion of chromosome 2, novel genomic alterations such as partial gain of chromosome 6 were recurrently detected in AMLs. In this study, we found similarity between cell-surface antigen expressions of bone marrows and those of spleens in AML mice and significantly higher expressions of c-myc and PU.1 expression, especially in the PU.1-deficient (Chr2(del) PU.1(del/R235-)) AML and Chr2(del) PU.1(del/R235+) compared to Chr2(intact) PU.1(R235+/R235+) AMLs. CONCLUSION: The new finding on upregulation of c-myc and PU.1 in both and hemizygous PU.1-deficient AMLs and different genomic alterations detected by array CGH suggests that the molecular mechanism for development of radiation-induced AML should be different among three types of AML.
Assuntos
Transformação Celular Neoplásica/efeitos da radiação , Aberrações Cromossômicas/efeitos da radiação , Cromossomos de Mamíferos/genética , Raios gama/efeitos adversos , Regulação Leucêmica da Expressão Gênica/efeitos da radiação , Leucemia Mieloide Aguda/genética , Neoplasias Induzidas por Radiação/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas/genética , Transativadores/genética , Raios X/efeitos adversos , Animais , Transformação Celular Neoplásica/genética , Deleção de Genes , Regulação Leucêmica da Expressão Gênica/genética , Genoma/efeitos da radiação , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Camundongos , Camundongos Endogâmicos C3H , Transplante de Neoplasias , Neoplasias Induzidas por Radiação/metabolismo , Neoplasias Induzidas por Radiação/patologia , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-myc/biossíntese , Locos de Características Quantitativas/efeitos da radiação , Transativadores/metabolismoRESUMO
The treatment of ulceration or stomatitis with laser therapy is known to accelerate healing and relieve pain, but the underlying biological mechanism is not fully understood. The present study used a mouse model of ulceration to investigate the molecular mechanisms by which CO2 laser therapy accelerated the wound healing process. An ulcer was experimentally created in the palatal mucosa of the mouse and irradiated with light from a CO2 laser. Compared with controls (no irradiation), laser irradiation induced the proliferation of epithelial cells and faster re-epithelialization of the wound area. Immunohistochemistry experiments showed that heat shock protein-70 (HSP70) was expressed mainly in the epithelium of normal palatal tissue, whereas there was little tenascin C (TnC) expression in the epithelium and mesenchyme under normal conditions. Laser irradiation induced HSP70 mRNA and protein expression in the lamina propria as well as TnC expression in the mesenchyme underlying the renewing epithelium. Epithelial cells and fibroblasts were exposed to heated culture medium or laser irradiation to establish whether hyperthermia mimicked the effect of laser irradiation. Culture of fibroblasts in heated medium increased the expressions of both TnC and TGF-ß1, whereas laser irradiation induced only TnC expression. The present study indicates that CO2 laser irradiation exerts a photobiogenic effect to up-regulate TnC expression without inducing TGF-ß1 expression. We suggest that CO2 laser therapy has an advantage over thermal stimulation.
Assuntos
Proteínas de Choque Térmico HSP70/biossíntese , Terapia a Laser , Lasers de Gás , Úlceras Orais/patologia , Tenascina/biossíntese , Cicatrização/efeitos da radiação , Animais , Proteínas de Choque Térmico HSP70/efeitos da radiação , Masculino , Camundongos , Camundongos Endogâmicos ICR , Tenascina/efeitos da radiaçãoRESUMO
Radiation-induced thymic lymphoma in mice is a useful model for studying both the mechanism of radiation carcinogenesis and genetic susceptibility to tumor development. Using array-comparative genomic hybridization, we analyzed genome-wide changes in DNA copy numbers in radiation-induced thymic lymphomas that had developed in susceptible C57BL/6 and resistant C3H mice and their hybrids, C3B6F1 and B6C3F1 mice. Besides aberrations at known relevant genetic loci including Ikaros and Bcl11b and trisomy of chromosome 15, we identified strain-associated genomic imbalances on chromosomes 5, 10 and 16 and strain-unassociated trisomy of chromosome 14 as frequent aberrations. In addition, biallelic rearrangements at Tcrb were detected more frequently in tumors from C57BL/6 mice than in those from C3H mice, suggesting aberrant V(D)J recombination and a possible link with tumor susceptibility. The frequency and spectrum of these copy-number changes in lymphomas from C3B6F1 and B6C3F1 mice were similar to those in C57BL/6 mice. Furthermore, the loss of heterozygosity analyses of tumors in F(1) mice indicated that allelic losses at Ikaros and Bcl11b were caused primarily by multilocus deletions, whereas those at the Cdkn2a/Cdkn2b and Pten loci were due mainly to uniparental disomy. These findings provide important clues to both the mechanisms for accumulation of aberrations during radiation-induced lymphomagenesis and the different susceptibilities of C57BL/6 and C3H mice.
Assuntos
Dosagem de Genes , Linfoma/genética , Neoplasias Induzidas por Radiação/genética , Neoplasias do Timo/genética , Animais , Suscetibilidade a Doenças , Feminino , Imunofenotipagem , Perda de Heterozigosidade , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Hibridização de Ácido Nucleico , Especificidade da EspécieRESUMO
CONCLUSIONS: This study showed that vestibular evoked myogenic potentials (VEMPs) evoked by cochlear implant (CI), could be related to the comfortable level (C level), particularly in the channels that are closer to the apical turn of the cochlea. OBJECTIVE: The purpose of this study was to investigate the correlation between VEMPs and C level of each channel. SUBJECTS AND METHODS: We investigated 24 children who underwent cochlear implantation. VEMPs were recorded from the operated ears with the CI switched 'off' or 'on'. To investigate the correlation between VEMPs and C level, we selected 13 patients with Nucleus 24 (SPrint), and divided them into group A (normal VEMPs) and B (absence of VEMPs). In these children, all the 22 electrodes were active, and were mapped in the same frequency range for each channel. RESULTS: Twenty children (83%) showed no VEMPs with the CI 'off'. Among them, 10 elicited VEMPs with the CI 'on', but the other 10 did not. In all channels, the mean C levels of CI were higher in group A than in group B. The p values in channels 1-12 were >0.10, in channels 13-16 were 0.06-0.09, and in channels 17-22 were 0.05-0.06, which were lower but not statistically significant.
Assuntos
Limiar Auditivo/fisiologia , Implantes Cocleares , Surdez/reabilitação , Eletromiografia , Potencial Evocado Motor/fisiologia , Tono Muscular/fisiologia , Músculos do Pescoço/inervação , Processamento de Sinais Assistido por Computador , Testes de Função Vestibular/métodos , Nervo Vestibular/fisiopatologia , Estimulação Acústica , Adolescente , Criança , Pré-Escolar , Nervo Coclear/fisiopatologia , Surdez/fisiopatologia , Feminino , Movimentos da Cabeça/fisiologia , Humanos , Masculino , Desenho de Prótese , Valores de Referência , Sáculo e Utrículo/fisiopatologiaRESUMO
Studying population genetics of deep-sea animals helps us understand their history of habitat colonization and population divergence. Here, we report a population genetic study of the deep-sea mussel Bathymodiolus platifrons (Bivalvia: Mytilidae) widely distributed in chemosynthesis-based ecosystems in the Northwest Pacific. Three mitochondrial genes (i.e., atp6, cox1, and nad4) and 6,398 genomewide single nucleotide polymorphisms (SNPs) were obtained from 110 individuals from four hydrothermal vents and two methane seeps. When using the three mitochondrial genes, nearly no genetic differentiation was detected for B. platifrons in the Northwest Pacific. Nevertheless, when using SNP datasets, all individuals in the South China Sea (SCS) and three individuals in Sagami Bay (SB) together formed one genetic cluster that was distinct from the remaining individuals. Such genetic divergence indicated a genetic barrier to gene flow between the SCS and the open Northwest Pacific, resulting in the co-occurrence of two cryptic semi-isolated lineages. When using 125 outlier SNPs identified focusing on individuals in the Okinawa Trough (OT) and SB, a minor genetic subdivision was detected between individuals in the southern OT (S-OT) and those in the middle OT (M-OT) and SB. This result indicated that, although under the influence of the Kuroshio Current and the North Pacific Intermediate Water, subtle geographic barriers may exist between the S-OT and the M-OT. Introgression analyses based on these outlier SNPs revealed that Hatoma Knoll in the S-OT represents a possible contact zone for individuals in the OT-SB region. Furthermore, migration dynamic analyses uncovered stronger gene flow from Dai-yon Yonaguni Knoll in the S-OT to the other local populations, compared to the reverse directions. Taken together, the present study offered novel perspectives on the genetic connectivity of B. platifrons mussels, revealing the potential interaction of ocean currents and geographic barriers with adaption and reproductive isolation in shaping their migration patterns and genetic differentiation in the Northwest Pacific.
RESUMO
A 60-year-old woman, who has suffered from bilateral deafness throughout her life, visited our outpatient clinic. Computed tomography (CT) revealed inner ear malformations, which comprise cochlear aplasia with hypoplastic vestibule in the right ear and a common cavity in the left ear, and narrow internal auditory canals. We performed electronystagmography with caloric stimulation and stimulation of earth-vertical axis rotation (EVAR) or off-vertical axis rotation (OVAR), and studied vestibular evoked myogenic potentials (VEMPs) and vestibular ocular reflex (VOR). Slight horizontal nystagmus was induced by the stimulation of EVAR but not by caloric stimulation. Slight vertical nystagmus was observed during OVAR, whereas the VEMP test elicited no response. The result of horizontal or vertical VOR performed in the dark was almost normal. These findings suggest that VOR can be acquired even with severe malformation of the inner ear whose labyrinthine functions markedly reduce bilaterally until nystagmus is slightly induced by rotation stimulation.