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Boron neutron capture therapy (BNCT) is a unique radiotherapy of selectively eradicating tumor cells using boron compounds (e.g., 4-borono-L-phenylalanine [BPA]) that are heterogeneously taken up at the cellular level. Such heterogenicity potentially reduces the curative efficiency. However, the effects of temporospatial heterogenicity on cell killing remain unclear. With the technical combination of radiation track detector and biophysical simulations, this study revealed the cell cycle-dependent heterogenicity of BPA uptake and subsequent biological effects of BNCT on HeLa cells expressing fluorescent ubiquitination-based cell cycle indicators, as well as the modification effects of polyvinyl alcohol (PVA). The results showed that the BPA concentration in the S/G2/M phase was higher than that in the G1/S phase and that PVA enhances the biological effects both by improving the uptake and by canceling the heterogenicity. These findings might contribute to a maximization of therapeutic efficacy when BNCT is combined with PVA and/or cell cycle-specific anticancer agents.
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Compostos de Boro , Terapia por Captura de Nêutron de Boro , Ciclo Celular , Álcool de Polivinil , Humanos , Terapia por Captura de Nêutron de Boro/métodos , Células HeLa , Álcool de Polivinil/química , Ciclo Celular/efeitos da radiação , Ciclo Celular/efeitos dos fármacos , Compostos de Boro/farmacologia , Fenilalanina/análogos & derivados , Fenilalanina/farmacologiaRESUMO
We sought to identify potential evidence-practice gaps in palliative radiotherapy using quality indicators (QIs), previously developed using a modified Delphi method. Seven QIs were used to assess the quality of radiotherapy for bone metastases (BoM) and brain metastases (BrM). Compliance rate was calculated as the percentage of patients for whom recommended medical care was conducted. Random effects models were used to estimate the pooled compliance rates. Of the 39 invited radiation oncologists, 29 (74%) from 29 centers participated in the survey; 13 (45%) were academic and 16 (55%) were non-academic hospitals. For the QIs, except for BoM-4, the pooled compliance rates were higher than 80%; however, for at least some of the centers, the compliance rate was lower than these pooled rates. For BoM-4 regarding steroid use concurrent with radiotherapy for malignant spinal cord compression, the pooled compliance rate was as low as 32%. For BoM-1 regarding the choice of radiation schedule, the compliance rate was higher in academic hospitals than in non-academic hospitals (P = 0.021). For BrM-3 regarding the initiation of radiotherapy without delay, the compliance rate was lower in academic hospitals than in non-academic hospitals (P = 0.016). In conclusion, overall, compliance rates were high; however, for many QIs, practice remains to be improved in at least some centers. Steroids are infrequently used concurrently with radiotherapy for malignant spinal cord compression.
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Cuidados Paliativos , Indicadores de Qualidade em Assistência à Saúde , Humanos , Inquéritos e Questionários , Neoplasias Encefálicas/radioterapia , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Radioterapia , Fidelidade a DiretrizesRESUMO
Most Pacific salmon species grow in the ocean, return to their native rivers to reproduce, and then die (semelparous type). However, rainbow trout survive after spawning and reproduce repeatedly until the end of their lives (iteroparous type). Little is known about how germline stem cells behave during gametogenesis in the two types of Pacific salmon. In this study, we show that all germline stem cells disappear after the first gametogenesis in Chinook and Kokanee salmon, whereas germline stem cells are maintained in rainbow trout. However, the germline stem cells of Chinook and Kokanee salmon transplanted into rainbow trout survive even after their spawning seasons and supply salmon gametes for multiple years. These results indicate that the behavior of the germline stem cells is mainly regulated by the somatic environment.
Assuntos
Oncorhynchus mykiss , Salmão , Animais , Células Germinativas , Reprodução , Feminino , Masculino , Gametogênese , Células-Tronco/citologia , Células-Tronco/metabolismoRESUMO
OBJECTIVE: To identify factors significantly associated with quality of life (QOL) and determine if these associations are strong enough to predict certain aspects of QOL without measuring them. METHODS: We conducted an exploratory secondary analysis of baseline data of 224 patients (enrolled between December 2020 and March 2021) from a previously published prospective observational study on radiotherapy for bone metastases at 26 centres. Using univariable linear regression, we assessed the association between patient/treatment factors and QOL scale scores as measured by the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 15-Palliative (QLQ-C15-PAL) and the EORTC QOL Questionnaire Bone Metastases module (QLQ-BM22). RESULTS: Age and sex were not significantly associated with QOL. Worse performance status, higher pain scores, and opioid and single-fraction use were significantly associated with most QOL scales; these four factors were associated with worse global QOL, worse functioning status, and more severe symptoms. The coefficients of determination for most QOL scales were less than 0.2, indicating that most of the variability in QOL scores was not explained by any of the explanatory variables. CONCLUSION: Performance status, pain intensity, and opioid and single-fraction use were significantly associated with most QOL scales. However, the associations were not strong enough to estimate QOL. ADVANCES IN KNOWLEDGE: To date, the association between treatment factors and QOL in patients with bone metastases has not been fully studied. We identified the factors that were significantly associated with QOL and found that these associations were not strong enough to predict QOL.
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Neoplasias Ósseas , Qualidade de Vida , Humanos , Estudos Transversais , Estudos Prospectivos , Analgésicos Opioides , Neoplasias Ósseas/patologia , Cuidados Paliativos , Inquéritos e QuestionáriosRESUMO
Salinity stress can greatly reduce seed production because plants are especially sensitive to salt during their reproductive stage. Here, we show that the sodium ion transporter AtHKT1;1 is specifically expressed around the phloem and xylem of the stamen in Arabidopsis thaliana to prevent a marked decrease in seed production caused by salt stress. The stamens of AtHKT1;1 mutant under salt stress overaccumulate Na+, limiting their elongation and resulting in male sterility. Specifically restricting AtHKT1;1 expression to the phloem leads to a 1.5-fold increase in the seed yield upon sodium ion stress. Expanding phloem expression of AtHKT1;1 throughout the entire plant is a promising strategy for increasing plant productivity under salinity stress.
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Proteínas de Arabidopsis , Arabidopsis , Simportadores , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Simportadores/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Sódio/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Purpose: The aim of this study was to understand the income and employment status of patients at the start of and during follow-up after palliative radiation therapy for bone metastasis. Methods and Materials: From December 2020 to March 2021, a prospective multi-institutional observational study was conducted to investigate income and employment of patients at the start of administration of radiation therapy for bone metastasis and at 2 and 6 months after treatment. Of 333 patients referred to radiation therapy for bone metastasis, 101 were not registered, mainly because of their poor general condition, and another 8 were excluded from the follow-up analysis owing to ineligibility. Results: In 224 patients analyzed, 108 had retired for reasons unrelated to cancer, 43 had retired for reasons related to cancer, 31 were taking leave, and 2 had lost their jobs at the time of registration. The number of patients who were in the working group was 40 (30 with no change in income and 10 with decreased income) at registration, 35 at 2 months, and 24 at 6 months. Younger patients (P = 0), patients with better performance status (P = 0), patients who were ambulatory (P = .008), and patients with lower scores on a numerical rating scale of pain (P = 0) were significantly more likely to be in the working group at registration. There were 9 patients who experienced improvements in their working status or income at least once in the follow-up after radiation therapy. Conclusions: The majority of patients with bone metastasis were not working at the start of or after radiation therapy, but the number of patients who were working was not negligible. Radiation oncologists should be aware of the working status of patients and provide appropriate support for each patient. The benefit of radiation therapy to support patients continuing their work and returning to work should be investigated further in prospective studies.
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The splendid alfonsino Beryx splendens is a commercially important deep-sea fish in East Asian countries. Because the wild stock of this species has been declining, there is an urgent need to develop aquaculture systems. In the present study, we investigated the long-chain polyunsaturated fatty acid (LC-PUFA) requirements of B. splendens, which are known as essential dietary components in many carnivorous marine fish species. The fatty acid profiles of the muscles, liver, and stomach contents of B. splendens suggested that it acquires substantial levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from its natural diet. The functional characterization of a fatty acid desaturase (Fads2) and three elongases (Elovl5, Elovl4a, and Elovl4b) from B. splendens confirmed their enzymatic capabilities in LC-PUFA biosynthesis. Fads2 showed Δ6 and Δ8 bifunctional desaturase activities. Elovl5 showed preferential elongase activities toward C18 and C20 PUFA substrates, whereas Elovl4a and Elovl4b showed activities toward various C18-22 substrates. Given that Fads2 showed no Δ5 desaturase activity and no other fads-like sequence was found in the B. splendens genome, EPA and arachidonic acid cannot be synthesized from C18 precursors; hence, they can be categorized as dietary essential fatty acids in B. splendens. EPA can be converted into DHA in B. splendens via the so-called Sprecher pathway. However, given that fads2 is only expressed in the brain, it is unlikely that the capacity of B. splendens to biosynthesize DHA from EPA can fulfill its physiological requirements. These results will be useful to researchers developing B. splendens aquaculture methods.
Assuntos
Proteínas de Peixes , Peixes , Animais , Elongases de Ácidos Graxos/genética , Elongases de Ácidos Graxos/metabolismo , Proteínas de Peixes/metabolismo , Peixes/metabolismo , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Essenciais , Ácido Eicosapentaenoico , Ácidos Docosa-Hexaenoicos , Dieta/veterinária , Ácidos GraxosRESUMO
Standard plastic scintillating fiber cannot detect low-energy ß-rays as the cladding prevents them from reaching the fiber core. We developed an outer-layer scintillating (OLS) fiber with a plastic scintillator on the outermost layer for low-energy ß-ray detection. The concept of fiber construction is presented. The fundamental optical properties of the OLS fiber, such as the emission spectrum, attenuation length, and scintillation decay time, were evaluated. Here, Ni-63 with a maximum energy of 67.0 keV was used as a low-energy ß-emitting nuclide. Simulation studies on the interaction between low-energy electrons emitted from Ni-63 and a single fiber were performed prior to actual measurements. The data showed that Ni-63 can be measured using silicon photomultiplier photosensors in a coincidence mode. The OLS fiber was effective for low-energy ß-ray detection.
RESUMO
In germ cell transplantation experiments, the use of sterile recipients that do not produce their own gametes is an important prerequisite. Triploidization and dnd gene knockdown (KD) methods have been widely used to produce sterile fish. However, triploidization does not produce complete sterility in some fish species, and gene KD is labor and time intensive since it requires microinjection into individual fertilized eggs. To overcome these problems, in this study, we generated homozygous mutants of the dead end (dnd) gene in rainbow trout (Oncorhynchus mykiss) using the clustered regulatory interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system, analyzed their reproductive capacity, and evaluated their suitability as recipients for germ cell transplantation. By crossing F1 heterozygous mutants produced from founders subjected to genome editing, an F2 generation consisting of approximately 1/4 homozygous knockout mutants (dnd KO) was obtained. The dnd KO hatchlings retained the same number of primordial germ cells (PGCs) as the wild-type (WT) individuals, after which the number gradually decreased. At 1 year of age, germ cells were completely absent in all analyzed individuals. To evaluate the dnd KO individuals as recipients for germ cell transplantation, germ cells prepared from donor individuals were transplanted into the abdominal cavity of dnd KO hatchlings. These cells migrated to the recipient gonads, where they initiated gametogenesis. The mature recipient individuals produced only donor-derived sperm and eggs in equivalent numbers to WT rainbow trout. These results indicate that dnd KO rainbow trout are suitable recipient candidates possessing a high capacity to nurse donor-derived germ cells.
Assuntos
Infertilidade , Oncorhynchus mykiss , Animais , Transplante de Células/métodos , Técnicas de Inativação de Genes , Células Germinativas/transplante , Gônadas , Oncorhynchus mykiss/genéticaRESUMO
PURPOSE: A quality indicator (QI) is a valuable tool to evaluate the quality of health care systems. In palliative radiation oncology, only a few related QIs have been developed to date. In this study, we sought to develop and pilot test QIs that assess the quality of care in palliative radiation therapy. METHODS AND MATERIALS: A modified Delphi method was used to establish consensus with an expert panel. The panel consisted of 8 radiation oncologists who have expertise in palliative radiation oncology and 1 expert on Delphi methodology. Online panel meetings and e-mail surveys were conducted to develop QIs on palliative radiation therapy for bone and brain metastases. Feasibility of measurement was assessed though pilot surveys that were conducted by radiation oncologists at 5 facilities. RESULTS: After 3 online meetings and 2 e-mail surveys, we developed 4 QIs on bone metastases and 3 QIs on brain metastases. Two email surveys and 2 pilot surveys confirmed the validity of QIs and the feasibility of measurement, respectively. CONCLUSIONS: We developed valid and feasible QIs on palliative radiation therapy for bone and brain metastases. Our work may contribute to reduce the evidence-practice gaps in palliative radiation oncology.
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The aim of this study was to establish a method for the cryopreservation of spermatogonia of the yellowtail (Seriola quinqueradiata), which is the most commonly farmed fish in Japan. Testicular cells were prepared by enzymatic dissociation of testicular fragments containing an abundance of type A spermatogonia and were added to cryomedium containing dimethyl sulfoxide (DMSO), ethylene glycol, glycerol, or propylene glycol at concentrations of 0.5-2.5 M. The cells were then frozen and stored in liquid nitrogen for 3 days. After thawing, their survival and transplantability were evaluated. Testicular cells were most successfully cryopreserved in 1.0 M DMSO as indicated by survival of 34% of cells. Furthermore, in situ hybridization using the yellowtail vasa probe showed that these recovered cells contained a similar proportion of germ cells to fresh testicular cells before freezing. Transplantation of the recovered cells into the peritoneal cavities of allogeneic larvae resulted in 94% of surviving recipients having donor-derived germ cells in their gonads after 28 days. Sperm were then collected from seven randomly selected recipients once they reached 2 years of age and used to fertilize wild-type eggs, which led to an average of 26% of the first filial (F1) offspring being derived from donor fish, as confirmed through the use of microsatellite markers. Thus, we successfully cryopreserved yellowtail spermatogonia and produced functional sperm via intraperitoneal transplantation into allogeneic recipients.
Assuntos
Criopreservação , Transplante de Células-Tronco Hematopoéticas , Animais , Criopreservação/métodos , Masculino , Espermatogônias , Espermatozoides , TestículoRESUMO
In this study, the synergistic adsorption behavior of palladium [Pd(II)], molybdenum [Mo(VI)], and zirconium [Zr(IV)] in simulated high-level liquid waste was systematically investigated based on various factors, such as the contact time, concentration of nitric acid, adsorption amount, and temperature using a silica-based adsorbent impregnated with N,N'-dimethyl-N,N'-di-n-hexyl-thiodiglycolamide (Crea) and 2, 2', 2' -nitrilotris[N,N-bis(2-ethylhexyl)acetamide] (TAMIA-EH). The adsorption rates of Pd(II), Mo(VI), and Zr(IV) in this synergistic adsorption system were high; thus, equilibrium states could be obtained in only 1 h with high uptake percentages of more than 90%. The adsorption abilities of Pd(II), Mo(VI), and Zr(IV) were only slightly affected by variation in the concentration of nitric acid in the range of 0.1-5 M and solution temperature in the range of 288-313 K. Selective stripping of the adsorbed Re(VII), Pd(II), Zr(IV), and Mo(VI) was successfully achieved under elution with 5 M HNO3, 0.2 M Tu (pH 1), 50 mM DTPA (pH 2), and 50 mM DTPA dissolved in 0.5 M Na2CO3 (pH 11) solutions using the chromatography method. In addition, the adsorption performance in solid-state was studied using the particle-induced X-ray emission (PIXE) method; the obtained results were in good agreement with the results obtained via column separation.
RESUMO
In the fish germ cell transplantation system, only type A spermatogonia (ASGs) and oogonia are known to be incorporated into the recipient genital ridges, where they undergo gametogenesis. Therefore, high colonization efficiency can be achieved by enriching undifferentiated germ cells out of whole testicular cells. In this study, we used magnetic-activated cell sorting (MACS) for enriching undifferentiated germ cells of rainbow trout using a monoclonal antibody that recognizes a specific antigen located on the germ cell membrane. We screened the antibodies to be used for MACS by performing immunohistochemistry on rainbow trout gonads. Two antibodies, nos. 172 and 189, showed strong signals for ASGs and oogonia. Next, we performed MACS with antibody no. 172 using gonadal cells isolated from vasa-gfp rainbow trout showing GFP in undifferentiated germ cells. We found that GFP-positive cells are highly enriched in antibody no. 172-positive fractions. Finally, to examine the transplantability of MACS-enriched cells, we intraperitoneally transplanted sorted or unsorted cells into recipient larvae. We observed that transplantability of sorted cells, particularly ovarian cells, were significantly higher than that of unsorted cells. Therefore, MACS with antibody no. 172 could enrich ASGs and oogonia and become a powerful tool to improve transplantation efficiency in salmonids.
Assuntos
Animais Geneticamente Modificados , Anticorpos Monoclonais/química , Células Germinativas , Separação Imunomagnética , Oncorhynchus mykiss , Animais , Animais Geneticamente Modificados/genética , Animais Geneticamente Modificados/metabolismo , Feminino , Células Germinativas/citologia , Células Germinativas/transplante , Masculino , Oncorhynchus mykiss/genética , Oncorhynchus mykiss/metabolismoRESUMO
We recently established a germ cell transplantation system in salmonids. Donor germ cells transplanted into the body cavity of recipient embryos migrate toward and are incorporated into the recipient gonad, where they undergo gametogenesis. Among the various types of testicular germ cells, only type A spermatogonia (A-SG) can be incorporated into the recipient gonads. Enriching for A-SG is therefore important for improving the efficiency of germ cell transplantation. To enrich for A-SG, an antibody against a cell surface marker is a convenient and powerful approach used in mammals; however, little is known about cell surface markers for A-SG in fish. To that end, we have produced novel monoclonal antibodies (mAbs) against cell-surface molecules of rainbow trout (Oncorhynchus mykiss) A-SG. We inoculated mice with living A-SG isolated from pvasa-GFP transgenic rainbow trout using GFP-dependent flow cytometry. By fusing lymph node cells of the inoculated mice with myeloma cells, we generated 576 hybridomas. To identify hybridomas that produce mAbs capable of labeling A-SG preferentially and effectively, we screened them using cell ELISA, fluorescence microscopy, and flow cytometry. We thereby identified two mAbs that can label A-SG. By using flow cytometry with these two antibodies, we could enrich for A-SG with transplantability to recipient gonads from amongst total testicular cells. Furthermore, one of these mAbs could also label zebrafish (Danio rerio) spermatogonia. Thus, we expect these monoclonal antibodies to be powerful tools for germ cell biology and biotechnology.
Assuntos
Anticorpos Monoclonais/imunologia , Oncorhynchus mykiss/fisiologia , Espermatogônias/fisiologia , Animais , Animais Geneticamente Modificados , Cruzamento , Ensaio de Imunoadsorção Enzimática , Epitopos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Espermatogênese/genética , Espermatogênese/fisiologia , Espermatogônias/classificação , Espermatogônias/imunologiaRESUMO
During our previous work toward establishing surrogate broodstock that can produce donor-derived gametes by germ cell transplantation, we found that only type A spermatogonia (ASGs) have the potency to colonize recipient gonads. Therefore, the ability to visualize ASGs specifically would allow the sequential analysis of donor cell behavior in the recipient gonads. Here we produced monoclonal antibodies that could recognize the cell surface antigens of ASGs in Pacific bluefin tuna (Thunnus orientalis), with the aim of visualizing live ASGs. We generated monoclonal antibodies by inoculating Pacific bluefin tuna testicular cells containing ASGs into mice and then screened them using cell-based enzyme-linked immunosorbent assay (ELISA), immunocytochemistry, flow cytometry (FCM), and immunohistochemistry, which resulted in the selection of two antibodies (Nos. 152 and 180) from a pool of 1152 antibodies. We directly labeled these antibodies with fluorescent dye, which allowed ASG-like cells to be visualized in a one-step procedure using immunocytochemistry. Molecular marker analyses against the FCM-sorted fluorescent cells confirmed that ASGs were highly enriched in the antibody-positive fraction. To evaluate the migratory capability of the ASGs, we transplanted visualized cells into the peritoneal cavity of nibe croaker (Nibea mitsukurii) larvae. This resulted in incorporated fluorescent cells labeled with antibody No. 152 being detected in the recipient gonads, suggesting that the visualized ASGs possessed migratory and incorporation capabilities. Thus, the donor germ cell visualization method that was developed in this study will facilitate and simplify Pacific bluefin tuna germ cell transplantation.
Assuntos
Anticorpos Monoclonais/química , Corantes Fluorescentes/química , Espermatogônias/citologia , Espermatogônias/ultraestrutura , Coloração e Rotulagem/métodos , Atum , Animais , Anticorpos Monoclonais/metabolismo , Antígenos de Superfície/imunologia , Aquicultura , Rastreamento de Células/métodos , Rastreamento de Células/veterinária , Citometria de Fluxo/métodos , Citometria de Fluxo/veterinária , Corantes Fluorescentes/metabolismo , Imuno-Histoquímica/veterinária , Masculino , Microscopia de Fluorescência/métodos , Microscopia de Fluorescência/veterinária , Especificidade de Órgãos , Perciformes , Análise do Sêmen/métodos , Análise do Sêmen/veterinária , Espermatogônias/classificação , Espermatogônias/transplante , Coloração e Rotulagem/veterináriaRESUMO
Since the late 19th century, the Amazon species Colossoma macropomum (tambaqui) has been exploited commercially and the climate change has contributed to decline in tambaqui numbers. Although germ cell cryopreservation and transplantation can help preserve the species' genetic resources semipermanently, its germ cell behavior has not been analyzed to date. In this study, we isolated the tambaqui's dead end gene (dnd) homolog (tdnd) and used it as a molecular marker for germ cells to obtain basic information essential for transplantation. The amino acid sequence showed 98% similarity and 53% identity with the zebrafish dnd. Phylogenetic analysis and the presence of consensus motifs known for dnd revealed that tdnd encodes the dnd ortholog and its transcript is detectable only in the testes and ovaries, showing a strong positive signal in oocytes and spermatogonia. The tambaqui possesses, at least, three different transcripts of tdnd which show dissimilar expression profile in undifferentiated and sexually mature animals, suggesting that they play distinct roles in germline development and they may influence the choice of donors for the cell transplantation study.
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Processamento Alternativo/genética , Células Germinativas/crescimento & desenvolvimento , Proteínas de Ligação a RNA/genética , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Animais , Biomarcadores/metabolismo , Embrião não Mamífero , Feminino , Regulação da Expressão Gênica no Desenvolvimento/genética , Células Germinativas/metabolismo , Masculino , Filogenia , Peixe-Zebra/crescimento & desenvolvimentoRESUMO
The native Amazonian fish tambaqui (Colossoma macropomum) is the second-largest scaled fish in South America and the most common native species in Brazil. To preserve genetic resources with sufficient genetic diversity through germ cell cryopreservation and transplantation techniques, a molecular marker for identifying the cells is required to trace them during the manipulation processes. The vasa gene is a promising candidate, as its specific expression in germ cell lineage has been well-conserved throughout animal evolution. In this study, the full sequence of the vasa cDNA homolog from tambaqui was isolated and characterized, showing an open reading frame of 2010â¯bp encoding 669 amino acids. The putative protein was shown to contain eight conserved motifs of the DEAD-box protein family and high similarity to vasa homologs of other species. Tambaqui vasa (tvasa) mRNA expression was specific to the gonads, and in situ hybridization showed signals only in oocytes and spermatogonia. The results suggested that tvasa could be a useful germ cell marker in this species.
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Characidae/genética , Clonagem Molecular/métodos , RNA Helicases DEAD-box/genética , Células Germinativas/metabolismo , Animais , Characidae/metabolismo , Conservação dos Recursos Naturais , Feminino , Proteínas de Peixes/genética , Masculino , Fases de Leitura Aberta , Especificidade de Órgãos , FilogeniaRESUMO
Evolutionary novelties require rewiring of transcriptional networks and/or the evolution of new gene functions. Sex determination (SD), one of the most plastic evolutionary processes, requires such novelties. Studies on the evolution of vertebrate SD revealed that new master SD genes are generally recruited from genes involved in the downstream SD regulatory genetic network. Only a single exception to this rule is currently known in vertebrates: the intriguing case of the salmonid master SD gene (sdY), which arose from duplication of an immune-related gene. This exception immediately posed the question of how a gene outside from the classical sex differentiation cascade could acquire its function as a male SD gene. Here we show that SdY became integrated in the classical vertebrate sex differentiation cascade by interacting with the Forkhead box domain of the female-determining transcription factor, Foxl2. In the presence of Foxl2, SdY is translocated to the nucleus where the SdY:Foxl2 complex prevents activation of the aromatase (cyp19a1a) promoter in cooperation with Nr5a1 (Sf1). Hence, by blocking a positive loop of regulation needed for the synthesis of estrogens in the early differentiating gonad, SdY disrupts a preset female differentiation pathway, consequently allowing testicular differentiation to proceed. These results also suggest that the evolution of unusual vertebrate master sex determination genes recruited from outside the classical pathway like sdY is strongly constrained by their ability to interact with the canonical gonadal differentiation pathway.
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Redes Reguladoras de Genes/genética , Gônadas/fisiologia , Oncorhynchus mykiss/genética , Processos de Determinação Sexual/genética , Diferenciação Sexual/genética , Animais , Aromatase/genética , Diferenciação Celular/genética , Núcleo Celular/genética , Estrogênios/genética , Feminino , Proteína Forkhead Box L2/genética , Masculino , Regiões Promotoras Genéticas/genética , Testículo/metabolismo , Translocação Genética/genéticaRESUMO
The behavior of the 1 MeV triton has been studied in order to understand the alpha particle confinement property in the deuterium operation of toroidal fusion devices. To obtain time evolution of the deuterium-tritium (D-T) neutron emission rate where the secondary DT neutron emission rate is approximately 1012 n/s, we designed two high detection efficiency scintillating fiber (Sci-Fi) detectors: a 1 mm-diameter scintillation fiber-based detector Sci-Fi1 and a 2 mm-diameter scintillation fiber-based detector Sci-Fi2. The test in an accelerator-based neutron generator was performed. The result shows that the directionality of each detector is 15° and 25°, respectively. It is found that detection efficiency for DT neutrons is around 0.23 counts/n cm2 for the Sci-Fi1 detector and is around 1.0 counts/n cm2 for the Sci-Fi2 detector.
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Objective The influence of cancer boards with respect to the treatment decisions regarding chemotherapy remains to be elucidated. In the present study, we investigated the cases that presented at our institutional cancer boards, to assess the effect of cancer boards on the treatment decisions regarding chemotherapy. Methods Data from the cancer boards at Yamagata University Hospital, Yamagata, Japan, were collected. Along with data from the clinical records, the details of the discussions and the chosen plan of treatment of the cancer boards were analyzed. Results From February 2010 to February 2014, 1,541 cases were discussed at our cancer boards. Of these, 811 cases (52.6%) involved discussions about chemotherapy. Of those 811 cases, recommendations were made to alter the treatment plans for 189 cases (23.3%). The reasons for discouraging chemotherapy varied; however, 29/45 (64.4%) cases involved discouragement for the following reasons: old age, a comorbid condition, the physical (performance) status, or insufficient evidence to administer chemotherapy. Eighty-six patients were referred to the medical oncology department through the cancer boards. Conclusion Our results showed that cancer boards have a great influence on the treatment decisions regarding chemotherapy and the prompt referral of cases to medical oncologists as necessary. In terms of future research, we will evaluate the effect of cancer boards on the prognosis and outcomes of cases using the institutional cancer registry.