Surrogate broodstock technology is emerging as a promising biotechnology for xenogeneic production of gametes of highly valuable fish species. In this study, we produced gametes of landlocked ...Atlantic salmon using triploid rainbow trout as recipient through germ cell transplantation technique in embryos. Spermatogonial cells were obtained from Atlantic salmon juveniles and transplantation conducted into the coelomic cavity of 150 mixed-sex triploid embryos of rainbow trout. Colonization efficiency assessed in larvae four weeks post-transplantation showed presence of PKH-26-labeled cells in 61.1% of individuals. Analysis in sexually mature adults revealed presence of donor-derived sperm in four transplanted males (10%), whereby one of them reached sexual maturity in the first year. Transplanted females became mature after the second year and donor-derived oocytes were detected in four individuals (12.1%). Milt produced by transplanted triploid males were used for artificial insemination. Genetic analysis of hatchlings revealed that progeny was composed by pure Atlantic salmon and therefore were donor-derived. In conclusion, this study shows that surrogate broodstock can be used to produce oocytes and spermatozoa using species from different genus. The production of surrogate gametes using species with a shorter life cycle represents an efficient approach to streamline the development of improved strains in aquaculture industry.
•This study demonstrated that rainbow trout can be used for the production of Atlantic salmon female and male gametes.•Using rainbow trout as recipient, it is possible to produce Atlantic salmon gametes in a shorter period of time.•Surrogate Broodstock Technology can be employed to streamline gamete production for genetic improvement programs.
Objective The therapeutic effect of pemafibrate on metabolic dysfunction-associated fatty liver disease (MAFLD) remains unknown. This retrospective, single-arm study investigated the efficacy and ...safety of pemafibrate in MAFLD patients with hypertriglyceridemia. Methods A total of 10 patients who received pemafibrate (oral, 0.1 mg, twice a day) at Gunma Saiseikai Maebashi Hospital between September 2018 and September 2019 were included. All patients underwent a liver biopsy, and the disease grade and stage were pathologically assessed based on the FLIP algorithm. Results The median age was 66.0 (53.8-74.8) years old, and 5 patients (50.0%) were men. All patients were diagnosed with non-alcoholic steatohepatitis (NASH). The fasting and non-fasting triglyceride (TG) levels were 175 (149-247) mg/dL and 228 (169-335) mg/dL, respectively. The AST and ALT values at 6 months were significantly lower than at baseline AST: 28.0 (22.0-33.8) U/L vs. 43.5 (24.0-55.0) U/L, p=0.008, ALT: 23.0 (14.8-26.5) U/L vs. 51.5 (23.0-65.3) U/L, p=0.005, respectively, especially in NASH patients with significant activity and advanced fibrosis (p=0.040 and 0.014, respectively). Fasting TG levels were significantly lower and HDL-C levels significantly higher at 6 months than at baseline (p=0.005 and 0.032, respectively). At six months, FIB-4, the aspartate aminotransferase-to-platelet ratio index, and the macrophage galactose-specific lectin-2 binding protein glycosylation isomer level were significantly improved compared with baseline (p=0.041, 0.005 and 0.005, respectively). Treatment-related adverse events were not observed. Conclusion Pemafibrate treatment may be safe and effective for MAFLD patients with hypertriglyceridemia.
A 66-year-old man, who had undergone plasma exchange 30 years previously in Egypt for the treatment of falciparum malaria, was referred to our hospital for treatment of chronic hepatitis C (HCV). An ...analysis of the 655-nucleotide 5′-untranslated region-core region sequence revealed infection with HCV subtype 1g. A phylogenetic analysis of the full-length HCV genome confirmed that the patient's HCV was subtype 1g, which was the first case identified in Japan. Although his HCV possessed several naturally occurring resistance-associated substitutions in the nonstructural (NS) 3 and NS5A regions, he was successfully treated by combination therapy with glecaprevir/pibrentasvir.
Albinism is the most common color variation described in fish and is characterized by a white or yellow phenotype according to the species. In rainbow trout Oncorhynchus mykiss, aside from ...yellow-albino phenotypes, cobalt blue variants with autosomal, recessive inheritance have also been reported. In this study, we investigated the inheritance pattern and chromatophores distribution/abundance of cobalt blue trouts obtained from a local fish farm. Based on crosses with wild-type and dominant yellow-albino lines, we could infer that cobalt blue are dominant over wild-type and co-dominant in relation to yellow-albino phenotype, resulting in a fourth phenotype: the white-albino. Analysis of chromatophores revealed that cobalt blue trouts present melanophores, as the wild-type, and a reduced number of xanthophores. As regards to the white-albino phenotype, they were not only devoid of melanophores but also presented a reduced number of xanthophores. Cobalt blue and white-albino trouts also presented reduced body weight and a smaller pituitary gland compared to wild-type and yellow-albino phenotypes. The transcription levels of tshb and trh were up regulated in cobalt blue compared to wild type, suggesting the involvement of thyroid hormone in the expression of blue color. These phenotypes represent useful models for research on body pigmentation in salmonids and on the mechanisms behind endocrine control of color patterning.
Astyanax is an abundant fish genus in South America. Some species of this group are characterized by the presence of B chromosomes and absence of morphologically differentiated sex chromosomes. In ...this study, we used quantitative real-time polymerase chain reaction to characterize mRNA expression of dmrt1 in Astyanax scabripinnis gonads. Maturing gonads of males with the B chromosome overexpressed dmrt1. Our findings suggest that B chromosomes may have an adaptive role in A. scabripinnis sex determination and maintenance.
An 81‐year‐old man initially underwent right hepatic lobectomy for liver cancer and was pathologically diagnosed with combined hepatocellular and cholangiocarcinoma (CHC). At 13 months after ...resection, multiple lymph node metastases were observed. We started atezolizumab plus bevacizumab (Atez/Bev), achieving a 7.5‐month progression‐free survival. Atez/Bev might exhibit efficacy for CHC patients.
Although no standard systemic chemotherapy for combined hepatocellular and cholangiocarcinoma patients has yet been established, atezolizumab plus bevacizumab, which is a combination therapy of anti‐programmed death ligand‐1 and anti‐vascular endothelial growth factor, might exhibit good therapeutic outcome.
Abstract
The exposure of adult fish to warm or high temperatures is known to impair reproduction, yet the long-term reproductive impacts for treatments at early life are not well clarified. This ...study aimed to evaluate the effects of warm temperature (WT) during juvenile stage on gonad maturation, gamete quality, and offspring thermotolerance in rainbow trout. While the comparison of basic reproductive parameters in WT females did not reveal any kind of impairment, many WT males showed an atrophied, undeveloped gonad, or a smaller testis with lower milt volume; sperm quality parameters in WT males and deformity rates in the respective progeny were also highly affected. However, despite of such negative effects, many of the remaining progeny presented better rates of survival and growth when exposed to the same conditions as those of parental fish (WT), suggesting that thermal stress in
parr
stage males elicited intergenerational thermotolerance after a single generation. The present results support that prolonged warming stress during early life stages can adversely affect key reproductive aspects, but contrastingly increase offspring performance at upper thermal ranges. These findings have implications on the capacity of fish to adapt and to cope with global warming.
The species complex
is one of the most studied with respect to origin, distribution, and frequency of B chromosomes, and is considered a model organism for evolutionary studies. Research using ...population inferences about the occurrence and frequency of the B chromosome shows seasonal variation between sexes, which is associated with the presence of this supernumerary element. We hypothesized that the B chromosome could influence the sex ratio of these animals. Based on this assumption, the present work aimed to investigate if differences exist among levels of gene expression with qRT-PCR of the
(associated with testicular differentiation) and
(associated with ovarian differentiation) genes between B-carrier and non-B-carrier individuals. The results showed that for the
gene, the difference in expression between animals with B chromosomes was not accentuated compared to that in animals without this chromosome. Expression of
in B-carrier females, however, was reduced by 73.56% compared to females that lacked the B chromosome. Males had no difference in expression of the
and
genes between carriers and non-carriers of the B chromosome. Results indicate that the presence of B chromosomes is correlated with the differential expression of sex-associated genes. An analysis of these results integrated with data from other studies on the reproductive cycle in the same species reveals that this difference in expression may be expanding the reproductive cycle of the species.
Cancer is classified into metabolic and/or genetic disorders; notably, the tryptophan catabolism pathway is vital in different cancer types. Here, we focused on the interaction and molecular ...connection between the cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) receptor and indoleamine-2,3-dioxygenase (IDO) enzyme. To test the impact of the selected immunotherapies on breast cancer cell migration and cell survival, we used in vitro assays. Also, we test the impact of anti-CTLA-4 antibody on the IDO-positive cells. The results of cell migration and clonogenic assays showed that anti-CTLA-4 antibody reduces cancer cell migration and clonogenic abilities of murine breast cancer cells. In addition, the result of flow cytometry showed that the anti-CTLA-4 antibody did not change the percentage of IDO-positive cancer cells. Notably, administrating an IDO blocker, 1-Methyl-DL-tryptophan (1MT), reduces the efficiency of the antiCTLA-4 antibody. The enzymatic blocking of the IDO reduces the efficiency of the anti-CTLA-4 antibody on cell migration and clonogenic abilities suggesting that there is an inhibitory interaction at the molecular level between functions of CTLA-4 and IDO. It is unclear via which mechanism(s) IDO interacts with CTLA-4 signaling and also why blocking IDO makes disruption in CTLA-4 signaling in cancer cells. Indeed, evaluating the role of IDO in CTLA-4 signaling in cancer cells may assist in clarifying a poor response to CTLA-4 immunotherapies by some patients. Hence, further investigation of the molecular interaction between CTLA-4 and IDO might help to improve the efficiency of CTLA-4 immunotherapy.
Rainbow trout (Oncorhynchus mykiss) are native to the Pacific Ocean coast of North America and the Kamchatka Peninsula of Russia. Brazilian populations of rainbow trout derive from various imports ...from European countries, the United States of America (U.S.A.) and Canada, from the 1950 s onwards. A total of 347 samples from nine commercial broodstock groups sampled from five farms in Brazil were genotyped with a panel of 96 SNPs to analyze the genetic diversity and structure of commercial rainbow trout farmed in Brazil. Pairwise coefficients of relatedness of individual animals and coefficients of genetic differentiation and inbreeding of broodstock groups were obtained, in addition to tests of genetic allocation of animals to their respective group. The mean observed and expected heterozygosities were 0.405 and 0.398, respectively. The total Fst was 0.172 and the pairwise Fst estimates considering all strains ranged from 0.036 to 0.338. The UPGMA genetic distance tree shows that broodstocks declared to be originally from Canada (Kamloops region) and from Northern California (Mount Shasta) are the most genetically distant from each other and from the remaining studied groups. Genetic structure analyses suggest a best value of K= 2, separating broodstock groups originally from the U.S.A. and Canada. Structure and Principal Component Analyses (PCA) indicate that the management practices of one of the farms was efficient in properly maintaining different broodstocks separated, while in another farm unwanted admixture has been occurring. Reclassification of these animals using Structure analysis results were corroborated with PCA and GeneClass2 analyses, providing evidence that advanced analyzes with low-density SNP data can be used to improve farm management practices and even correct past errors. The present study represents the first analysis of diversity and genetic structure of commercial rainbow trout farmed in Brazil using SNP markers.
•Population structure analysis of 9 broodstocks from 5 different rainbow trout farms in different regions in Brazil.•Unknown admixture events revealed in one of the farms.•Reclassification of admixed broodstocks achieved from 88.4% to 100% success in cross-validation between methods.•Performed kinship analysis of all broodstocks.•First diversity and genetic structure study of commercial rainbow trout farmed in Brazil using SNP markers.
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