Activation of specific cellular immunity toward murine leukemia in mice rejecting syngeneic somatic hybrid cells

International Nuclear Information System (INIS)

Liang, W.; Cohen, E.P.

1977-01-01

ASL-1 x LM(TK) - somatic hybrid cells form both H-2/sup a/ and H-2/sup k/ antigen complexes. After forming a localized tumor in syngeneic (A/J x C 3 H/HeJ)F 1 mice, they are rejected. Such mice are resistant to otherwise invariably lethal injections of ASL-1 cells, surviving for prolonged and, in some instances, indefinite periods. To examine the basis of immunity, the capacity of spleen cells from mice rejecting hybrid cells to stimulate the release of 51 Cr from labeled ASL-1 cells was investigated. Cells from the spleens of mice rejecting ASL-1 x LM(TK) - cells stimulated the release of 51 Cr from labeled ASL-1 cells, but not from Ehrlich ascites or P815 cells. Cells from mice injected with mitomycin-C-treated ASL-1 cells led to the release of 51 Cr from labeled ASL-1 cells as well, but the extent of 51 Cr release was approximately one-third as occurred in the presence of cells from hybrid cell-injected mice. Cells from noninjected mice or from mice injected with LM(TK) - cells failed to lead to the specific release of 51 Cr from ASL-1 cells. The presence of unlabeled ASL-1 cells, but not Ehrlich ascites cells, competitively inhibited the spleen cell-stimulated release of 51 Cr from labeled ASL-1 cells. Sera from A/J mice injected with mitomycin-C-treated ASL-1 cells contained antibodies specific for the tumor-associated antigen of ASL-1 cells

Islet-specific T cell clones transfer diabetes to nonobese diabetic (NOD) F1 mice.

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Peterson, J D; Pike, B; McDuffie, M; Haskins, K

1994-09-15

To investigate diabetes resistance to T cell-mediated disease transfer, we administered islet-specific T cell clones to the F1 progeny of nonobese diabetic (NOD) mice that were crossed with various nondiabetes-prone inbred mouse strains. We investigated four diabetogenic CD4+ T cell clones and all induced insulitis and full development of diabetes in (SWR x NOD)F1, (SJL x NOD)F1, and (C57BL/6 x NOD)F1 mice. In contrast, (BALB/c x NOD)F1 and (CBA x NOD)F1 mice were susceptible to disease transfer by some T cell clones but not others, and (C57/L x NOD)F1 mice seemed to be resistant to both insulitis and disease transfer by all of the clones tested. Disease induced by the T cell clones in susceptible F1 strains was age dependent and could only be observed in recipients younger than 13 days old. Full or partial disease resistance did not correlate with the presence or absence of I-E, different levels of Ag expression in islet cells, or differences in APC function. The results from this study suggest that there may be multiple factors contributing to susceptibility of F1 mice to T cell clone-mediated induction of diabetes, including non-MHC-related genetic background, the immunologic maturity of the recipient, and individual characteristics of the T cell clones.

The contribution of the Y chromosome to hybrid male sterility in house mice.

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Campbell, Polly; Good, Jeffrey M; Dean, Matthew D; Tucker, Priscilla K; Nachman, Michael W

2012-08-01

Hybrid sterility in the heterogametic sex is a common feature of speciation in animals. In house mice, the contribution of the Mus musculus musculus X chromosome to hybrid male sterility is large. It is not known, however, whether F1 male sterility is caused by X-Y or X-autosome incompatibilities or a combination of both. We investigated the contribution of the M. musculus domesticus Y chromosome to hybrid male sterility in a cross between wild-derived strains in which males with a M. m. musculus X chromosome and M. m. domesticus Y chromosome are partially sterile, while males from the reciprocal cross are reproductively normal. We used eight X introgression lines to combine different X chromosome genotypes with different Y chromosomes on an F1 autosomal background, and we measured a suite of male reproductive traits. Reproductive deficits were observed in most F1 males, regardless of Y chromosome genotype. Nonetheless, we found evidence for a negative interaction between the M. m. domesticus Y and an interval on the M. m. musculus X that resulted in abnormal sperm morphology. Therefore, although F1 male sterility appears to be caused mainly by X-autosome incompatibilities, X-Y incompatibilities contribute to some aspects of sterility.

Exacerbating effects of human parvovirus B19 NS1 on liver fibrosis in NZB/W F1 mice.

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Tsai-Ching Hsu

Full Text Available Systemic lupus erythematosus (SLE is an autoimmune disorder with unknown etiology that impacts various organs including liver. Recently, human parvovirus B19 (B19 is recognized to exacerbate SLE. However, the effects of B19 on liver in SLE are still unclear. Herein we aimed to investigate the effects of B19 on liver in NZB/W F1 mice by injecting subcutaneously with PBS, recombinant B19 NS1, VP1u or VP2, respectively. Our experimental results revealed that B19 NS1 protein significantly enhanced the TGF-β/Smad fibrotic signaling by increasing the expressions of TGF-β, Smad2/3, phosphorylated Smad2/3, Smad4 and Sp1. The consequent fibrosis-related proteins, PAI-1 and α-SMA, were also significantly induced in livers of NZB/W F1 mice receiving B19 NS1 protein. Accordingly, markedly increased collagen deposition was also observed in livers of NZB/W F1 mice receiving B19 NS1 protein. However, no significant difference was observed in livers of NZB/W F1 mice receiving B19 VP1u or VP2 as compared to the controls. These findings indicate that B19 NS1 plays a crucial role in exacerbating liver fibrosis in NZB/W F1 mice through enhancing the TGF-â/Smad fibrotic signaling.

Exacerbating Effects of Human Parvovirus B19 NS1 on Liver Fibrosis in NZB/W F1 Mice

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Hsu, Tsai-Ching; Tsai, Chun-Chou; Chiu, Chun-Ching; Hsu, Jeng-Dong; Tzang, Bor-Show

2013-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disorder with unknown etiology that impacts various organs including liver. Recently, human parvovirus B19 (B19) is recognized to exacerbate SLE. However, the effects of B19 on liver in SLE are still unclear. Herein we aimed to investigate the effects of B19 on liver in NZB/W F1 mice by injecting subcutaneously with PBS, recombinant B19 NS1, VP1u or VP2, respectively. Our experimental results revealed that B19 NS1 protein significantly enhanced the TGF-β/Smad fibrotic signaling by increasing the expressions of TGF-β, Smad2/3, phosphorylated Smad2/3, Smad4 and Sp1. The consequent fibrosis-related proteins, PAI-1 and α-SMA, were also significantly induced in livers of NZB/W F1 mice receiving B19 NS1 protein. Accordingly, markedly increased collagen deposition was also observed in livers of NZB/W F1 mice receiving B19 NS1 protein. However, no significant difference was observed in livers of NZB/W F1 mice receiving B19 VP1u or VP2 as compared to the controls. These findings indicate that B19 NS1 plays a crucial role in exacerbating liver fibrosis in NZB/W F1 mice through enhancing the TGF-â/Smad fibrotic signaling. PMID:23840852

Genetic identification of F1 and post-F1 serrasalmid juvenile hybrids in Brazilian aquaculture.

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Diogo Teruo Hashimoto

Full Text Available Juvenile fish trade monitoring is an important task on Brazilian fish farms. However, the identification of juvenile fish through morphological analysis is not feasible, particularly between interspecific hybrids and pure species individuals, making the monitoring of these individuals difficult. Hybrids can be erroneously identified as pure species in breeding facilities, which might reduce production on farms and negatively affect native populations due to escapes or stocking practices. In the present study, we used a multi-approach analysis (molecular and cytogenetic markers to identify juveniles of three serrasalmid species (Colossoma macropomum, Piaractus mesopotamicus and Piaractus brachypomus and their hybrids in different stocks purchased from three seed producers in Brazil. The main findings of this study were the detection of intergenus backcrossing between the hybrid ♀ patinga (P. mesopotamicus×P. brachypomus×♂ C. macropomum and the occurrence of one hybrid triploid individual. This atypical specimen might result from automixis, a mechanism that produces unreduced gametes in some organisms. Moreover, molecular identification indicated that hybrid individuals are traded as pure species or other types of interspecific hybrids, particularly post-F1 individuals. These results show that serrasalmid fish genomes exhibit high genetic heterogeneity, and multi-approach methods and regulators could improve the surveillance of the production and trade of fish species and their hybrids, thereby facilitating the sustainable development of fish farming.

BREEDING OF F1 HYBRIDS OF PUMPKIN FOR CANNING INDUSTRY

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A. M. Shantasov

2016-01-01

Full Text Available As a result of crossing with patty pan squash with male sterility, the new parent lines of Cucurbita реро L., «ANZH» and «ANZ», with the original set of morphological traits («kabakson» based on the gene of male sterility of functional type were developed. The F1 hybrids with economically valuable features were obtained. These hybrids are characterized by small fruits of pickling types, high yield and biochemical content.

Developmental trajectories and breakdown in F1 interpopulation hybrids of Tribolium castaneum

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Drury, Douglas W; Ehmke, Ross C; Jideonwo, Victoria N; Wade, Michael J

2013-01-01

When hybrid inviability is an indirect by-product of local adaptation, we expect its degree of severity between pairs of populations to vary and to be sensitive to the environment. While complete reciprocal hybrid inviability is the outcome of the gradual process of local adaptation, it is not representative of the process of accumulation of incompatibility. In the flour beetle, Tribolium castaneum, some pairs of populations exhibit complete, reciprocal F1 hybrid incompatibility while other pairs are fully or partially compatible. We characterize this naturally occurring variation in the degree and timing of expression of the hybrid incompatible phenotype to better understand the number of genes or developmental processes contributing to speciation. We assessed the morphological and developmental variation in four Tribolium castaneum populations and their 12 possible F1 hybrids at each life-history stage from egg to adult. We find that the rate of hybrid larval development is affected in all interpopulation crosses, including those eventually producing viable, fertile adults. Hybrid incompatibility manifests early in development as changes in the duration of instars and diminished success in the transition between instars are relative to the parent populations. Parent populations with similar developmental profiles may produce hybrids with disrupted development. The degree and timing of expression of hybrid inviability depends upon populations crossed, direction of the cross, and environment in which hybrids are raised. Our findings suggest that the coordinated expression of genes involved in transitional periods of development is the underlying cause of hybrid incompatibility in this species. PMID:23919145

Systematic selection for increased fruit yield in populations derived from hybridization only, F1 irradiation, and hybridization following parental irradiation in peanuts (Arachis hypogaea L.)

International Nuclear Information System (INIS)

Emery, D.A.; Wynne, J.C.

1976-01-01

Three hybrid peanut populations involving a single pair of high yielding parents were developed to determine the effects of irradiation prior to and after hybridization on the response to selection for fruit yield. The control-hybrid population was produced by making reciprocal crosses between the two parents. The pre-hybrid-irradiated population was initiated by making reciprocal crosses between the M 1 plants of the two parents irradiated as seeds. The post-hybrid-irradiated population was developed by irradiating the mature F 1 embryos of crosses between the same parents. Each of the three original populations consisted of 55 F 1 plants. Ten F 2 plants were grown from each F 1 and one F 3 plant from each F 2 was used to initiate the yield tests. Selection for increased yield was practiced systematically and uniformly in each population over the F 3 to F 5 generations until the number of lines derived from single F 1 plants was reduced to five and the number of sublines descended from particular F 2 plants to three per line for yield trials in the F 6 generation. The mean yields of the F 1 derived lines of the irradiated populations were considerably below that of the control hybrid population when selection began but they reached 99% of the control mean in the F 6 generation. Selection gains in the irradiated populations appeared to result from the removal of inferior yielding sublines since greatest progress was made by raising the lower extremities of mean F 2 derived subline ranges rather than by extending the upper extremities of the ranges. The three highest yielding lines in the F6 generation occurred in the irradiated populations while the three highest yielding sublines were found in the hybrid-control population. No incidental association between size and yield of fruit was noted and a wide range of fruit sizes was found among the high yielding lines and sublines in all populations. (author)

Megaspore competition in F1 and F2 hybrids between Oenothera hookeri and Oe. suaveolens

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Renata Śnieżko

2014-01-01

Full Text Available Megasporogenesis and development of the embryo sac were investigated in F1 and F2 hybrids from crosses of Oe. hookeri and Oe. suaveolens. All hybrids form heteropolar and homopolar magaspore tetrads; the embryo sac, however, usually develops from the micropylar megaspore. Its development may occur immediately after degeneration of three other megaspores or after a period of competition between both apical megaspores. They develop simultaneously for a relatively short time, after which the growth of the chalazal megaspore is inhibited, although the latter does not degenerate. The micropylar megaspore as a rule develops without disturbances into the embryo sac, but in some ovules it is formed from the chalazal megaspore or double ones arise from both apical megaspores of the tetrad. The frequency of the micropylar embryo sac formation seems to be dependent above all on the hybrid plant genome and not on the haploid genome of the megaspore.

Asymmetry and polymorphism of hybrid male sterility during the early stages of speciation in house mice.

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Good, Jeffrey M; Handel, Mary Ann; Nachman, Michael W

2008-01-01

House mice offer a powerful system for dissecting the genetic basis of phenotypes that isolate species in the early stages of speciation. We used a series of reciprocal crosses between wild-derived strains of Mus musculus and M. domesticus to examine F(1) hybrid male sterility, one of the primary phenotypes thought to isolate these species. We report four main results. First, we found significantly smaller testes and fewer sperm in hybrid male progeny of most crosses. Second, in some crosses hybrid male sterility was asymmetric and depended on the species origin of the X chromosome. These observations confirm and extend previous findings, underscoring the central role that the M. musculus X chromosome plays in reproductive isolation. Third, comparisons among reciprocal crosses revealed polymorphism at one or more hybrid incompatibilities within M. musculus. Fourth, the spermatogenic phenotype of this polymorphic interaction appears distinct from previously described hybrid incompatibilities between these species. These data build on previous studies of speciation in house mice and show that the genetic basis of hybrid male sterility is fairly complex, even at this early stage of divergence.

X-y interactions underlie sperm head abnormality in hybrid male house mice.

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Campbell, Polly; Nachman, Michael W

2014-04-01

The genetic basis of hybrid male sterility in house mice is complex, highly polygenic, and strongly X linked. Previous work suggested that there might be interactions between the Mus musculus musculus X and the M. m. domesticus Y with a large negative effect on sperm head morphology in hybrid males with an F1 autosomal background. To test this, we introgressed the M. m. domesticus Y onto a M. m. musculus background and measured the change in sperm morphology, testis weight, and sperm count across early backcross generations and in 11th generation backcross males in which the opportunity for X-autosome incompatibilities is effectively eliminated. We found that abnormality in sperm morphology persists in M. m. domesticus Y introgression males, and that this phenotype is rescued by M. m. domesticus introgressions on the X chromosome. In contrast, the severe reductions in testis weight and sperm count that characterize F1 males were eliminated after one generation of backcrossing. These results indicate that X-Y incompatibilities contribute specifically to sperm morphology. In contrast, X-autosome incompatibilities contribute to low testis weight, low sperm count, and sperm morphology. Restoration of normal testis weight and sperm count in first generation backcross males suggests that a small number of complex incompatibilities between loci on the M. m. musculus X and the M. m. domesticus autosomes underlie F1 male sterility. Together, these results provide insight into the genetic architecture of F1 male sterility and help to explain genome-wide patterns of introgression across the house mouse hybrid zone.

[F18]-FDG imaging of experimental animal tumours using a hybrid gamma-camera

International Nuclear Information System (INIS)

Lausson, S.; Maurel, G.; Kerrou, K.; Montravers, F.; Petegnief, Y.; Talbot, J.N.; Fredelizi, D.

2001-01-01

Positron emission tomography (PET) has been widely used in clinical studies. This technology permits detection of compounds labelled with positron emitting radionuclides and in particular, [F18]-fluorodeoxyglucose ([F18]-FDG).[F18]-FDG uptake and accumulation is generally related to malignancy; some recent works have suggested the usefulness of PET camera dedicated to small laboratory animals (micro-PET). Our study dealt with the feasibility of [F18]-FDG imaging of malignant tumours in animal models by means of an hybrid camera dedicated for human scintigraphy. We evaluated the ability of coincidence detection emission tomography (CDET) using this hybrid camera to visualize in vivo subcutaneous tumours grafted to mice or rats. P815 murine mastocytoma grafted in syngeneic DBA/2 mice resulted with foci of very high FDG uptake. Tumours with a diameter of only 3 mm were clearly visualized. Medullary thyroid cancer provoked by rMTC 6/23 and CA77 lines in syngeneic Wag/Rij rat was also detected. The differentiated CA77 tumours exhibited avidity for [F18]-FDG and a tumour, which was just palpable (diameter lower than 2 mm), was identified. In conclusion, CDET-FDG is a non-invasive imaging tool which can be used to follow grafted tumours in the small laboratory animal, even when their size is smaller than 1 cm. It has the potential to evaluate experimental anticancer treatments in small series of animals by individual follow-up. It offers the opportunity to develop experimental PET research within a nuclear medicine or biophysics department, the shift to a dedicated micro-PET device being subsequently necessary. It is indeed compulsory to strictly follow the rules for non contamination and disinfection of the hybrid camera. (authors)

Cyclophilin D Promotes Brain Mitochondrial F1FO ATP Synthase Dysfunction in Aging Mice.

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Gauba, Esha; Guo, Lan; Du, Heng

2017-01-01

Brain aging is the known strongest risk factor for Alzheimer's disease (AD). In recent years, mitochondrial deficits have been proposed to be a common mechanism linking brain aging to AD. Therefore, to elucidate the causative mechanisms of mitochondrial dysfunction in aging brains is of paramount importance for our understanding of the pathogenesis of AD, in particular its sporadic form. Cyclophilin D (CypD) is a specific mitochondrial protein. Recent studies have shown that F1FO ATP synthase oligomycin sensitivity conferring protein (OSCP) is a binding partner of CypD. The interaction of CypD with OSCP modulates F1FO ATP synthase function and mediates mitochondrial permeability transition pore (mPTP) opening. Here, we have found that increased CypD expression, enhanced CypD/OSCP interaction, and selective loss of OSCP are prominent brain mitochondrial changes in aging mice. Along with these changes, brain mitochondria from the aging mice demonstrated decreased F1FO ATP synthase activity and defective F1FO complex coupling. In contrast, CypD deficient mice exhibited substantially mitigated brain mitochondrial F1FO ATP synthase dysfunction with relatively preserved mitochondrial function during aging. Interestingly, the aging-related OSCP loss was also dramatically attenuated by CypD depletion. Therefore, the simplest interpretation of this study is that CypD promotes F1FO ATP synthase dysfunction and the resultant mitochondrial deficits in aging brains. In addition, in view of CypD and F1FO ATP synthase alterations seen in AD brains, the results further suggest that CypD-mediated F1FO ATP synthase deregulation is a shared mechanism linking mitochondrial deficits in brain aging and AD.

Synergistic tumorigenic effect of procarbazine and ionizing radiation in (BALB/c x DBA/2)F1 mice

International Nuclear Information System (INIS)

Arseneau, J.C.; Fowler, E.; Bakemeier, R.F.

1977-01-01

Female (BALB/c x DBA/2)F, (CD2F 1 ) mice were treated with procarbazine (PCB) and ionizing radiation at different times to determine whether any synergistic carcinogenic effect could be demonstrated with the combined treatment. The incidence of pulmonary adenomas in groups of mice receiving both PCB and radiation increased significantly, when compared with mice given PCB alone. The incidence of thymomas also increased significantly in groups of mice given PCB 3 days before or after radiation treatment. Two cases of adenocarcinoma apparently arising from the lacrimal gland were also observed in mice from the groups receiving the combined treatment. This tumor had not previously been associated with PCB administration in mice. The results of this experiment indicated a potentiation of the tumorigenic action of PCB by ionizing radiation in CD2F 1 mice

Chronic self-administration of alcohol results in elevated ΔFosB: comparison of hybrid mice with distinct drinking patterns

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Ozburn Angela R

2012-10-01

Full Text Available Abstract Background The inability to reduce or regulate alcohol intake is a hallmark symptom for alcohol use disorders. Research on novel behavioral and genetic models of experience-induced changes in drinking will further our knowledge on alcohol use disorders. Distinct alcohol self-administration behaviors were previously observed when comparing two F1 hybrid strains of mice: C57BL/6J x NZB/B1NJ (BxN show reduced alcohol preference after experience with high concentrations of alcohol and periods of abstinence while C57BL/6J x FVB/NJ (BxF show sustained alcohol preference. These phenotypes are interesting because these hybrids demonstrate the occurrence of genetic additivity (BxN and overdominance (BxF in ethanol intake in an experience dependent manner. Specifically, BxF exhibit sustained alcohol preference and BxN exhibit reduced alcohol preference after experience with high ethanol concentrations; however, experience with low ethanol concentrations produce sustained alcohol preference for both hybrids. In the present study, we tested the hypothesis that these phenotypes are represented by differential production of the inducible transcription factor, ΔFosB, in reward, aversion, and stress related brain regions. Results Changes in neuronal plasticity (as measured by ΔFosB levels were experience dependent, as well as brain region and genotype specific, further supporting that neuronal circuitry underlies motivational aspects of ethanol consumption. BxN mice exhibiting reduced alcohol preference had lower ΔFosB levels in the Edinger-Westphal nucleus than mice exhibiting sustained alcohol preference, and increased ΔFosB levels in central medial amygdala as compared with control mice. BxN mice showing sustained alcohol preference exhibited higher ΔFosB levels in the ventral tegmental area, Edinger-Westphal nucleus, and amygdala (central and lateral divisions. Moreover, in BxN mice ΔFosB levels in the Edinger-Westphal nucleus and ventral

Differential response of inbred and F1 hybrid embryos of Hibiscus sabdariffa L. to x-irradiation

International Nuclear Information System (INIS)

Shome, A.; Hazra, S.

1988-01-01

Radio-response of HS 4288, HS 7910 and two F 1 hybrid embryos of H. sabdariffa to X-ray doses (2-8 kR) was assessed. Reduction in shoot and root length and incidence of root injuries increased always with the increase of X-ray doses. LD 50 values of HS 4288, HS 7910, F 1 HS 4288 x HS 7910 and F 1 HS 7910 x HS 428 were in between 5 and 6 kR, 2 and 4 kR, 6 and 8 kR, and 5 and 6 kR respectively. Judging by LD 50 values and 100 per cent seedling abnormality, relatively HS 4288 and F 1 HS 4288 x HS 7910 were resistant and HS 7910 and F 1 HS 7910 x HS 4288 were susceptible. Induction of macro-mutations was different in two inbreds and also in two F 1 hybrids. Role of cytoplasmic factors for the differential response are discussed. (author). 14 refs., 5 tabs

Effects of the thymic microenvironment on autoantibody production in (NZB X NZW)F1 mice

International Nuclear Information System (INIS)

Huston, D.P.; Smathers, P.A.; Reeves, J.P.; Steinberg, A.D.

1983-01-01

The effects of the thymic microenvironment on autoantibody production in (NZB X NZW)F1 mice were studied. Neonatally thymectomized male and female F1 mice reconstituted with a parental or F1-irradiated thymic lobe were compared to nonreconstituted and sham-thymectomized controls. While maleness retarded the spontaneous production of ss- and ds-DNA antibodies, thymic grafts did not suppress antibodies to ss-DNA in either sex, but did suppress the production of antibodies to ds-DNA in female mice. A unique property of NZB thymic grafts was the inability to suppress anti-RBC antibodies in male mice. Thus, (i) the gender of the F1 recipient was the most important determinant of production of antibodies to ss-DNA, (ii) either maleness or the thymic microenvironment could retard production of anti-ds-DNA antibodies, and (iii) both gender and the thymic microenvironment were important in the regulation of anti-RBC antibody production. Since the administration of thymosin did not suppress autoantibody production, the effects of the thymic grafts was not solely via thymic hormone production. These studies suggest that sex hormones and/or the thymic microenvironment can exert a suppressive effect on autoantibody production and that autoantibodies differ in their susceptibility to such suppression

Mona F1: New pepper (Capsicum annuum L. hybrid in the Centre for Vegetable Crops

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Cvikić Dejan

2007-01-01

Full Text Available The planted area various ways of pepper consumption (fresh or processed, make pepper one of the most important cultivars in vegetable breeding. In our country, up until now, the producers have usually grown varieties and domestic populations of pepper, while in more developed countries the usage of F1 hybrids is much more popular. The first pepper hybrids have been created in the Centre for Vegetable Crops by crossing new lines with male sterility gene ms-3 and selected genotypes from pepper collection. Created hybrids have higher yield, quality fruits and early ripening. This paper is the result of comparative trial in controlled conditions. Pepper varieties Župska rana, Zlatna medalja, Palanačka kapija and Duga bela, as well as new hybrid Mona F1 were the research matherial in order to observe the most important pepper traits.

Brain energy metabolism and neuroinflammation in ageing APP/PS1-21 mice using longitudinal 18F-FDG and 18F-DPA-714 PET imaging.

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Takkinen, Jatta S; López-Picón, Francisco R; Al Majidi, Rana; Eskola, Olli; Krzyczmonik, Anna; Keller, Thomas; Löyttyniemi, Eliisa; Solin, Olof; Rinne, Juha O; Haaparanta-Solin, Merja

2017-08-01

Preclinical animal model studies of brain energy metabolism and neuroinflammation in Alzheimer's disease have produced conflicting results, hampering both the elucidation of the underlying disease mechanism and the development of effective Alzheimer's disease therapies. Here, we aimed to quantify the relationship between brain energy metabolism and neuroinflammation in the APP/PS1-21 transgenic mouse model of Alzheimer's disease using longitudinal in vivo 18 F-FDG and 18 F-DPA-714) PET imaging and ex vivo brain autoradiography. APP/PS1-21 (TG, n = 9) and wild type control mice (WT, n = 9) were studied longitudinally every third month from age 6 to 15 months with 18 F-FDG and 18 F-DPA-714 with a one-week interval between the scans. Additional TG (n = 52) and WT (n = 29) mice were used for ex vivo studies. In vivo, the 18 F-FDG SUVs were lower and the 18 F-DPA-714 binding ratios relative to the cerebellum were higher in the TG mouse cortex and hippocampus than in WT mice at age 12 to 15 months ( p < 0.05). The ex vivo cerebellum binding ratios supported the results of the in vivo 18 F-DPA-714 studies but not the 18 F-FDG studies. This longitudinal PET study demonstrated decreased energy metabolism and increased inflammation in the brains of APP/PS1-21 mice compared to WT mice.

The Pace of Hybrid Incompatibility Evolution in House Mice.

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Wang, Richard J; White, Michael A; Payseur, Bret A

2015-09-01

Hybrids between species are often sterile or inviable. This form of reproductive isolation is thought to evolve via the accumulation of mutations that interact to reduce fitness when combined in hybrids. Mathematical formulations of this "Dobzhansky-Muller model" predict an accelerating buildup of hybrid incompatibilities with divergence time (the "snowball effect"). Although the Dobzhansky-Muller model is widely accepted, the snowball effect has only been tested in two species groups. We evaluated evidence for the snowball effect in the evolution of hybrid male sterility among subspecies of house mice, a recently diverged group that shows partial reproductive isolation. We compared the history of subspecies divergence with patterns of quantitative trait loci (QTL) detected in F2 intercrosses between two pairs of subspecies (Mus musculus domesticus with M. m. musculus and M. m. domesticus with M. m. castaneus). We used a recently developed phylogenetic comparative method to statistically measure the fit of these data to the snowball prediction. To apply this method, QTL were partitioned as either shared or unshared in the two crosses. A heuristic partitioning based on the overlap of QTL confidence intervals produced unambiguous support for the snowball effect. An alternative approach combining data among crosses favored the snowball effect for the autosomes, but a linear accumulation of incompatibilities for the X chromosome. Reasoning that the X chromosome analyses are complicated by low mapping resolution, we conclude that hybrid male sterility loci have snowballed in house mice. Our study illustrates the power of comparative genetic mapping for understanding mechanisms of speciation. Copyright © 2015 by the Genetics Society of America.

PARTICULARITIES OF WHITE HEAD CABBAGE F1 HYBRID BREEDING FOR PRIDNESTROVIAN MOLDAVIAN REPUBLIC CONDITIONS

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L. I. Shpak

2016-01-01

Full Text Available A model of late maturing F1 hybrid of white head cabbage for long-term storing and suitable for national recipe “golubci” have been developed based on requirements for varieties and F1 hybrids grown in the South in the conditions of drought, high temperatures and low air humidity. Combining ability of seven self-incompatible inbred lines of white head cabbage was studied by the system of full diallel crosses in conditions of Pridnestrovian Moldavian Republic. These lines were developed on the base of heat tolerant varieties ‘Biruchekutskaya’, ‘Volna’, ‘Lada’, ‘Moldavanka’ and ‘Kharkovskaya Zimnyaya’ bred in the south. Out of 42 hybrid combinations studied 15 significantly surpassed in productivity the variety ‘Zavadovskaya’ that is traditionally grown by local farmers for pickling and recipe “golubci”. High GCA effects for productivity showed the following breeding lines: Bu1, Ml3 and Kl5. Polygenes, controlling the high yield ability, mainly were dominant and single-directed, however the correlation betweenyield ability and GCA effect was middle, r=0.63±0.35. No correlation was observed inbreeding line between GCA effect and truly heterosis effect in hybrid combinations (r=0.19. Disease resistance analysis revealed lines Bu1 and Kl5 that had shown resistance to Fusarium yellows. Two hybrid combination Kl5xBu1 and Ml3xBu1 were highly tolerant to thrips attacks according to analysis of all promising hybrid combinations, carried out in natural infection background. Weak correlation was observed between the number of damaged leaves in cabbage head and dry matter content, r=0.41±0.21, and also there is no correlation revealed with sugar contents, ascorbic acid and nitrate content. High tolerance of hybrids with participation of line Bu1 explained the partial dominance nature of the trait. Hybrid combinations Kl5xBu1 and Ml3xBu1 called ‘Batal’ and ‘Shedevr’, respectively, included in registry of Moldova and

Selection against recombinant hybrids maintains reproductive isolation in hybridizing Populus species despite F1 fertility and recurrent gene flow.

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Christe, Camille; Stölting, Kai N; Bresadola, Luisa; Fussi, Barbara; Heinze, Berthold; Wegmann, Daniel; Lexer, Christian

2016-06-01

Natural hybrid zones have proven to be precious tools for understanding the origin and maintenance of reproductive isolation (RI) and therefore species. Most available genomic studies of hybrid zones using whole- or partial-genome resequencing approaches have focused on comparisons of the parental source populations involved in genome admixture, rather than exploring fine-scale patterns of chromosomal ancestry across the full admixture gradient present between hybridizing species. We have studied three well-known European 'replicate' hybrid zones of Populus alba and P. tremula, two widespread, ecologically divergent forest trees, using up to 432 505 single-nucleotide polymorphisms (SNPs) from restriction site-associated DNA (RAD) sequencing. Estimates of fine-scale chromosomal ancestry, genomic divergence and differentiation across all 19 poplar chromosomes revealed strikingly contrasting results, including an unexpected preponderance of F1 hybrids in the centre of genomic clines on the one hand, and genomically localized, spatially variable shared variants consistent with ancient introgression between the parental species on the other. Genetic ancestry had a significant effect on survivorship of hybrid seedlings in a common garden trial, pointing to selection against early-generation recombinants. Our results indicate a role for selection against recombinant genotypes in maintaining RI in the face of apparent F1 fertility, consistent with the intragenomic 'coadaptation' model of barriers to introgression upon secondary contact. Whole-genome resequencing of hybridizing populations will clarify the roles of specific genetic pathways in RI between these model forest trees and may reveal which loci are affected most strongly by its cyclic breakdown. © 2016 John Wiley & Sons Ltd.

[Chromosomal localization of foreign genes in transgenic mice using dual-color fluorescence in situ hybridization].

Science.gov (United States)

Lin, Dan; Gong, Xiu-li; Li, Wei; Guo, Xin-bing; Zhu, Yi-wen; Huang, Ying

2008-02-01

To establish a highly sensitive and specific dual-color fluorescence in situ hybridization (D-FISH) method used for chromosomal localization of foreign genes in double transgenic mice. Two strains of double transgenic mice were used in this experiment, one was integrated with the herpes simplex virus thymidine kinase (HSV-tk) and the enhanced green fluorescence protein (eGFP), the other was with the short hairpin RNA interference(RNAi) and beta(654). Splenic cells cultured in vitro were arrested in metaphase by colchicine and hybridized with digoxigenin-labeled and biotinylated DNA probes, then detected by rhodamine-conjugated avidin and FITC-conjugated anti-digoxigenin. Dual-color fluorescence signals were detected on the same metaphase in both transgenic mice strains. In HSV-tk/eGFP double transgenic mice, strong green fluorescence for HSV-tk and red for eGFP were observed and localized at 2E5-G3 and 8A2-A4 respectively. In beta(654)/RNAi mice, beta(654) was detected as red fluorescence on chromosome 7D3-E2, and RNAi showed random integration on chromosomes. It was detected as green fluorescence on chromosome 12B1 in one mouse, while on 1E2.3-1F and 3A3 in the other. Highly sensitive and specific D-FISH method was established using the self-prepared DNA probes, and chromosomal localization of the foreign genes was also performed in combination with G-banding in double transgenic mice. This technology will facilitate the researches in transgenic animals and gene therapy models.

Characterisation of the BCM1F Analog Opto Hybrids for the CMS experiment

CERN Document Server

Srinidhi, Bheesette

2013-01-01

The BCM1F system in the CMS detector is used for measuring the beam-background and more importantly the real time luminosity and sits 1.8 m from the interaction point (IP5).There has been a proposal to upgrade the BCM1F when it would be installed for the LHC run in 2014. The BCM1F is fitted with Analog Opto-Hybrid(AOH) boards which consists of three Linear Laser Drivers (LLD) and three laser diodes. These AOH boards are affected by radiation and temperature in a long term and short term respectively. This paper studies the characteristics and behavior of these AOH boards.

Characterisation of the BCM1F Analog Opto Hybrids for the CMS experiment

CERN Document Server

Bheesette, Srinidhi

2013-01-01

The BCM1F system used in the CMS is used for measuring the beam-background and more importantly the real time luminosity and sits 1.8 m from the interaction point (IP5).There has been a proposal to upgrade the BCM1F when it would be installed for the LHC run in 2014. The BCM1F is fitted with Analog Opto-Hybrid(AOH) boards which consists of three Linear Laser Drivers (LLD) and three laser diodes. These AOH boards are affected by radiation and temperature in a long term and short term respectively. This paper studies the characteristics and behavior of these AOH boards.

Evaluation of organ-specific glucose metabolism by 18F-FDG in insulin receptor substrate-1 (IRS-1) knockout mice as a model of insulin resistance

International Nuclear Information System (INIS)

Cheng, Chao; Nakamura, Akinobu; Minamimoto, Ryogo; Shinoda, Kazuaki; Tateishi, Ukihide; Terauchi, Yasuo; Inoue, Tomio; Goto, Atsuhi; Kadowaki, Takashi

2011-01-01

Insulin resistance (IR) is a physiological condition in which the body produces insulin but does not result in a sufficient biological effect. Insulin resistance is usually asymptomatic but is associated with health problems and is a factor in the metabolic syndrome. The aim of the present study is to clarify organ-specific insulin resistance in normal daily conditions using [ 18 F]-2-fluoro-2-deoxy-D-glucose ([ 18 F]-FDG). The biodistribution of [ 18 F]-FDG was examined in insulin receptor substrate-1 (IRS-1) knockout mice, an animal model of skeletal muscle insulin resistance, and C57BL/6J (wild-type) mice with and without insulin loading. Mice received 0.5 MBq of [ 18 F]-FDG injected into the tail vein, immediately followed by nothing (control cohorts) or an intraperitoneal injection of 1.5 mU/g body weight of human insulin as an insulin loading test. Blood glucose concentrations for all of the experimental animals were assessed at 0, 20, 40, and 60 min post-injection. The mice were subsequently killed, and tissue was collected for evaluation of [ 18 F]-FDG biodistribution. The radioactivity of each organ was measured using a gamma counter. In the absence of insulin, the blood glucose concentrations of wild-type mice (132±26 mg/dl) and IRS-1 knockout mice (134±18 mg/dl) were not significantly different. Blood glucose concentrations decreased following insulin administration, with lower concentrations in wild-type mice than in knockout mice at 20, 40, and 60 min. A statistically significant difference in [ 18 F]-FDG uptake between wild-type mice and IRS-1 knockout mice was confirmed in the heart, abdominal muscle, and femoral muscle. With insulin loading, [ 18 F]-FDG uptake in the heart, back muscle, and abdominal muscle was significantly increased compared to without insulin loading in both wild-type mice and knockout mice. Our results showed that IR significantly affected [ 18 F]-FDG uptake in the heart in normal daily conditions. IR was associated with

Differences in the metabolism and disposition of inhaled [3H]benzene by F344/N rats and B6C3F1 mice

International Nuclear Information System (INIS)

Sabourin, P.J.; Bechtold, W.E.; Birnbaum, L.S.; Lucier, G.; Henderson, R.F.

1988-01-01

Benzene is a potent hematotoxin and has been shown to cause leukemia in man. Chronic toxicity studies indicate that B6C3F1 mice are more susceptible than F334/N rats to benzene toxicity. The purpose of the studies presented in this paper was to determine if there were metabolic differences between F344/N rats and B6C3F1 mice which might be responsible for this increased susceptibility. Metabolites of benzene in blood, liver, lung, and bone marrow were measured during and following a 6-hr 50 ppm exposure to benzene vapor. Hydroquinone glucuronide, hydroquinone, and muconic acid, which reflect pathways leading to potential toxic metabolites of benzene, were present in much greater concentrations in the mouse than in rat tissues. Phenylsulfate, a detoxified metabolite, and an unknown water-soluble metabolite were present in approximately equal concentrations in these two species. These results indicate that the proportion of benzene metabolized via pathways leading to the formation of potentially toxic metabolites as opposed to detoxification pathways was much higher in B6C3F1 mice than in F344 rats, which may explain the higher susceptibility of mice to benzene-induced hematotoxicity and carcinogenicity

Toxicology and carcinogenesis studies of acrylamide (CASRN 79-06-1) in F344/N rats and B6C3F1 mice (feed and drinking water studies).

Science.gov (United States)

2012-07-01

Acrylamide, a water-soluble α,β-unsaturated amide, is a contaminant in baked and fried starchy foods, including french fries, potato chips, and bread, as a result of Maillard reactions involving asparagine and reducing sugars. Additional sources of acrylamide exposure include cigarettes, laboratory procedures involving polyacrylamide gels, and various occupations (e.g, monomer production and polymerization processes). Acrylamide is carcinogenic in experimental animals. To obtain data for developing quantitative risk assessments for dietary exposures to acrylamide, the Food and Drug Administration nominated acrylamide for an in-depth toxicological evaluation by the National Toxicology Program. As part of this evaluation, male and female B6C3F1/Nctr (C57BL/6N x C3H/HeN MTV-) mice and male and female F344/N Nctr rats were exposed to acrylamide (at least 99.4% pure) in drinking water for 2 years. 2-WEEK STUDY IN RATS: Groups of four male and four female F344/N rats were administered 0, 0.14, 0.35, 0.70, 1.41, 3.52, or 7.03 mM acrylamide in the drinking water (0, 10, 25, 50, 100, 250, or 500 ppm acrylamide) or 0.0, 7.4, 18.5, 37, 74, 185, or 370 mg acrylamide per kg diet for 14 days. One male rat administered 7.03 mM acrylamide in the drinking water died on day 14. Male and female rats receiving 7.03 mM acrylamide weighed 56% and 64% of controls, respectively. Male and female rats fed 370 mg acrylamide per kg diet weighed 74% and 83% of controls, respectively. Female rats receiving 3.52 mM acrylamide in drinking water and male rats fed 185 mg acrylamide per kg diet weighed 85% and 89% of controls, respectively. Rats receiving 7.03 mM acrylamide in drinking water or 370 mg acrylamide per kg diet exhibited hind-leg paralysis on day 14. Mild to moderate dilatation of the urinary bladder was observed in all rats given 370 mg acrylamide per kg diet, and in three of four male rats and all four female rats given 7.03 mM acrylamide in drinking water, and in one of four male

Selective Somatic Elimination of NICOTIANA GLUTINOSA Chromosomes in the F(1) Hybrids of N. SUAVEOLENS and N. GLUTINOSA.

Science.gov (United States)

Gupta, S B; Gupta, P

1973-04-01

The F(1) hybrids of Nicotiana suaveolens (subgenus Petunioides, 2n = 32) and N. glutinosa (subgenus Tabacum, 2n = 24), were examined during their development, from seedlings to mature plants. It was observed that in the hybrids, there was a progressive change of dominant N. glutinosa morphological characteristics towards those of N. suaveolens, in leaf shape, stem, flower color and branching pattern. A study of mitotic chromosomes in the root-tips and in very young anthers of the mature plants indicated a significantly high average frequency of aberrant mitotic anaphases (bridges and fragments, 12% and 11% respectively). As a consequence of this phenomenon, variability in the number and size of chromosomes was observed in the PMC's and in mitotic metaphases (29-24 chromosomes). In order to establish whether the N. glutinosa chromosomes were preferentially lost, a karyological study of the parents and their F(1) hybrids was carried out and it was established that the F(1) hybrids were losing N. glutinosa chromosomes preferentially. A mechanism was suggested for the loss of these chromosomes by means of a chromatid type of breakage-fusion-bridge cycle (b-f-b cycle) and initiation of the b-f-b cycle in the hybrid due to an interaction of the regulatory mechanism of DNA replication in the haploid genomes of the parental species. However, loss of these chromosomes owing to interaction of certain genes from the two parental species cannot be ruled out.

Chronic voluntary alcohol consumption results in tolerance to sedative/hypnotic and hypothermic effects of alcohol in hybrid mice

Science.gov (United States)

Ozburn, Angela Renee; Harris, R. Adron; Blednov, Yuri A.

2013-01-01

The continuous two bottle choice test is the most common measure of alcohol consumption but there is remarkably little information about the development of tolerance or dependence with this procedure. We showed that C57BL/6JxFVB/NJ and FVB/NJxC57BL/6J F1 hybrid mice demonstrate greater preference for and consumption of alcohol than either parental strain. In order to test the ability of this genetic model of high alcohol consumption to produce neuroadaptation, we examined development of alcohol tolerance and dependence after chronic self-administration using a continuous access two-bottle choice paradigm. Ethanol-experienced mice stably consumed about 16–18 g/kg/day of ethanol. Ethanol-induced withdrawal severity was assessed (after 59 days of drinking) by scoring handling-induced convulsions; withdrawal severity was minimal and did not differ between ethanol-experienced and -naïve mice. After 71 days of drinking, the rate of ethanol clearance was similar for ethanol-experienced and -naïve mice. After 77 days of drinking, ethanol-induced loss of righting reflex (LORR) was tested daily for 5 days. Ethanol-experienced mice had a shorter duration of LORR. For both ethanol-experienced and -naïve mice, blood ethanol concentrations taken at gain of righting reflex were greater on day 5 than on day 1, indicative of tolerance. After 98 days of drinking, ethanol-induced hypothermia was assessed daily for 3 days. Both ethanol-experienced and –naïve mice developed rapid and chronic tolerance to ethanol-induced hypothermia, with significant group differences on the first day of testing. In summary, chronic, high levels of alcohol consumption in F1 hybrid mice produced rapid and chronic tolerance to both the sedative/hypnotic and hypothermic effects of ethanol; additionally, a small degree of metabolic tolerance developed. The development of tolerance supports the validity of using this model of high alcohol consumption in genetic studies of alcoholism. PMID:23313769

Influence of Background Genome on Enzymatic Characteristics of Yellow (Ay/-, Avy/-) Mice

Science.gov (United States)

Wolff, George L.; Pitot, Henry C.

1973-01-01

Identification of the fundamental polypeptide difference between yellow (Ay/-, Avy/-) and non-yellow mice is important for biomedical research because of the influence of the yellow genotype on normal and neoplastic growth and obesity. The complexity of the "yellow mouse syndrome" makes attainment of this objective dependent on the separation of those pleiotropic enzyme differences which are secondary, and depend on the background genome, from those which are primary, and depend primarily on the agouti locus genotype.—Four of nine hepatic enzyme activities assayed simultaneously differed between eight-week-old yellow (Ay/-, Avy/-) and non-yellow (A/-, a/a) male inbred and F1 hybrid mice. Among these four, only cytoplasmic malic enzyme activity was elevated in all yellow mice, as compared with the non-yellow sibs, regardless of background genome. Glucokinase, serine dehydratase, and tyrosine α-ketoglutarate transaminase activities were also changed in yellow mice, but these alterations depended on the background genome.—The ratio of malic enzyme activity to citrate-cleavage enzyme activity, possibly related to the altered fat metabolism of yellow mice, was influenced by background genome as well as by the yellow genotype.——Significant deviations of enzyme activities from mid-parent values among F1 hybrids were associated with particular background genomes; the number of such deviations was larger among yellow mice than among non-yellows and this difference was greater among C3H F1 hybrids than among C57BL/6 F1 hybrids. PMID:4405752

Inheritance of spike length in F3, F4 and F5 wheat hybrids obtained by different selection methods

Directory of Open Access Journals (Sweden)

Janković Snežana

2012-01-01

Full Text Available This study analyses the mode of inheritance of spike length in F3, F4 and F5 wheat hybrids obtained by pedigree, bulk and modified pedigree method of selection. Wheat hybrids were produced after crossing five varieties by M x N method. Three varieties were used as a female parent (Briscard, Carifen 12 and Rescler and two as a male component (Francuska and PKB-Prelivka. Descendents in F2 generation were produced from 6 F1 hybrids (3 x 2. Selection after F2 generation were undertaken from 1996 to 1999, while in 2000 the field experiments with complete breeding material were set up at the Institute 'PKB INI Agroekonomik' in Padinska Skela near Belgrade. Spike length was measured in progeny generations, from F3 to F5. It was observed that progenies had higher values for spike length than better parent (BP, with longer spikes in 5 out of 6 analyzed hybrids: Briscard x PKB-Prelivka, Carifen 12 x Francuska, Carifen 12 x PKB-Prelivka, Rescler x Francuska, and Rescler x PKB-Prelivka. From the above mentioned hybrid combinations, only Rescler x Francuska descendents in F5 generation obtained by pedigree and bulk selection inherited the spike length from the parent with lower value. High significant interaction was observed for spike length between genotype and generation of progenies in each of the applied selection methods.

Diabetes and exocrine pancreatic insufficiency in E2F1/E2F2 double-mutant mice.

Science.gov (United States)

Iglesias, Ainhoa; Murga, Matilde; Laresgoiti, Usua; Skoudy, Anouchka; Bernales, Irantzu; Fullaondo, Asier; Moreno, Bernardino; Lloreta, José; Field, Seth J; Real, Francisco X; Zubiaga, Ana M

2004-05-01

E2F transcription factors are thought to be key regulators of cell growth control. Here we use mutant mouse strains to investigate the function of E2F1 and E2F2 in vivo. E2F1/E2F2 compound-mutant mice develop nonautoimmune insulin-deficient diabetes and exocrine pancreatic dysfunction characterized by endocrine and exocrine cell dysplasia, a reduction in the number and size of acini and islets, and their replacement by ductal structures and adipose tissue. Mutant pancreatic cells exhibit increased rates of DNA replication but also of apoptosis, resulting in severe pancreatic atrophy. The expression of genes involved in DNA replication and cell cycle control was upregulated in the E2F1/E2F2 compound-mutant pancreas, suggesting that their expression is repressed by E2F1/E2F2 activities and that the inappropriate cell cycle found in the mutant pancreas is likely the result of the deregulated expression of these genes. Interestingly, the expression of ductal cell and adipocyte differentiation marker genes was also upregulated, whereas expression of pancreatic cell marker genes were downregulated. These results suggest that E2F1/E2F2 activity negatively controls growth of mature pancreatic cells and is necessary for the maintenance of differentiated pancreatic phenotypes in the adult.

Reduced sexual compatibility between cultivated and wild chicory and their F1 hybrids

DEFF Research Database (Denmark)

Hauser, T.P.; Bagger Jørgensen, Rikke; Toneatto, F.

2012-01-01

marked, and when seeds were ripe we determined whether cultivar, wild or hybrid plants had pollinated the seeds, using AFLP markers. Cultivar plants fathered much fewer seeds than expected, both on wild and hybrid plants, suggesting that some degree of incompatibility has evolved between cultivar...... (Cichorium intybus L.) has been bred as a crop at least since Roman times. To test if this has led to a loss in reproductive compatibility with wild chicory, we planted cultivar, wild, and F1 hybrid plants into two field plots, and let them pollinate freely. On 2 days, in the beginning and middle...... of the flowering season, we counted the numbers of flowering capitula and open flowers per capitulum, which in combination with counts of viable pollen per flower were used to estimate the expected proportion of seeds fathered by cultivar, wild, and hybrid plants. Open capitula on wild and hybrid plants were...

Screening of Pearl Millet F1 Hybrids for Heat Tolerance at Early Seedling Stage

Directory of Open Access Journals (Sweden)

Ashok Kumar Yadav

2014-01-01

Full Text Available Ten pearl millet genotypes selected on the basis of response to supra-optimal temperature tolerance were crossed in a half-diallel mating system. The 45 F1 hybrids produced were tested along with parents for heat tolerance and related traits at seedling stage. Field screening and laboratory screening techniques were simultaneously used for the evaluation of F1 hybrids and their parents. Heat tolerance was measured as seedling thermotolerance index (STI and seed to seedling thermotolerance index (SSTI under field conditions, but membrane thermostability (MTS in the laboratory. The hybrid H77/29-2 × CVJ-2-5-3-1-3 showed highest STI value followed by H77/833-2 × 96AC-93. The genotype H77/833-2 × 96AC-93 had the highest worth for SSTI. These three indices were highly correlated among themselves. STI values were invariably high, whereas SSTI has lower values, as it also covers the effect of under soil mortality (USM. It was seen that the heat tolerance indices STI and SSTI were not showing any perceptible pooled correlation with developmental traits except germination and emergence rate. Based on our results, it could be suggested that membrane thermostability (MTS may be used for screening large number of genotypes. Field based indices STI and SSTI may be used for evaluation of hybrids and varieties before they are released.

Dietary controlled carcinogenicity study of chloral hydrate in male B6C3F1 mice

International Nuclear Information System (INIS)

Leakey, Julian E.A.; Seng, John E.; Latendresse, John R.; Hussain, Nursreen; Allen, Laura J.; Allaben, William T.

2003-01-01

Chloral hydrate, which is used as a sedative in pediatric medicine and is a by-product of water chlorination, is hepatocarcinogenic in B6C3F 1 mice, a strain that can exhibit high rates of background liver tumor incidence, which are associated with increased body weight. In this study, dietary control was used to manipulate body growth in male B6C3F 1 mice in a 2-year bioassay of chloral hydrate. Male B6C3F 1 mice were treated with water or 25, 50, or 100 mg/kg chloral hydrate by gavage. The study compared ad libitum-fed mice with dietary controlled mice. The latter received variably restricted feed allocations to maintain their body weights on a predetermined 'idealized' weight curve predictive of a terminal background liver tumor incidence of 15-20%. These mice exhibited less individual body weight variation than did their ad libitum-fed counterparts. This was associated with a decreased variation in liver to body weight ratios, which allowed the demonstration of a statistically significant dose response to chloral hydrate in the dietary controlled, but not the ad libitum-fed, test groups. Chloral hydrate increased terminally adjusted liver tumor incidence in both dietary controlled (23.4, 23.9, 29.7, and 38.6% for the four dose groups, respectively) and ad libitum-fed mice (33.4, 52.6, 50.6, and 46.2%), but a statistically significant dose response was observed only in the dietary controlled mice. This dose response positively correlated with markers of peroxisomal proliferation in the dietary controlled mice only. The study suggests that dietary control not only improves terminal survival and decreases interassay variation, but also can increase assay sensitivity by decreasing intra-assay variation

Cadmium accumulation characteristics of low-cadmium rice (Oryza sativa L.) line and F1 hybrids grown in cadmium-contaminated soils.

Science.gov (United States)

Li, Kun; Yu, Haiying; Li, Tingxuan; Chen, Guangdeng; Huang, Fu

2017-07-01

Cadmium (Cd) pollution has threatened severely to food safety and human health. A pot experiment and a field experiment were conducted to investigate the difference of Cd accumulation between rice (Oryza sativa L.) lines and F 1 hybrids in Cd-contaminated soils. The adverse effect on biomass of rice lines was greater than that of F 1 hybrids under Cd treatments in the pot experiment. The variations of Cd concentration among rice cultivars in different organs were smaller in stem and leaf, but larger in root and ear. Average proportion of Cd in root of F 1 hybrids was 1.39, 1.39, and 1.16 times higher than those of rice lines at the treatment of 1, 2, and 4 mg Cd kg -1 soil, respectively. Cd concentrations in ear of F 1 hybrids were significantly lower than rice lines with the reduction from 29.24 to 50.59%. Cd concentrations in brown rice of all F 1 hybrids were less than 0.2 mg kg -1 at 1 mg Cd kg -1 soil, in which Lu98A/YaHui2816, 5406A/YaHui2816, and C268A/YaHui2816 could be screened out as cadmium-safe cultivars (CSCs) for being safe even at 2 mg Cd kg -1 soil. C268A/YaHui2816 showed the lowest Cd concentration in root among F 1 hybrids, while Lu98A/YaHui2816 and 5406A/YaHui2816 showed lower capability of Cd translocation from root to shoot under Cd exposure, which eventually caused the lower Cd accumulation in brown rice. The lower level of Cd translocation contributed to reducing the accumulation of Cd in brown rice had been validated by the field experiment. Thus, Lu98A/YaHui2816, 5406A/YaHui2816, and C268A/YaHui2816 could be considered as potential CSCs to cultivate in Cd-contaminated soils (<2 mg Cd kg -1 soil).

Ectomycorrhizal colonization and growth of the hybrid larch F1 under elevated CO2 and O3

International Nuclear Information System (INIS)

Wang, Xiaona; Qu, Laiye; Mao, Qiaozhi; Watanabe, Makoto; Hoshika, Yasutomo; Koyama, Akihiro; Kawaguchi, Korin; Tamai, Yutaka; Koike, Takayoshi

2015-01-01

We studied the colonization of ectomycorrhizal fungi and species abundance of a hybrid larch (F 1 ) under elevated CO 2 and O 3. Two-year-old seedlings were planted in an Open-Top-Chamber system with treatments: Control (O 3  < 6 nmol/mol), O 3 (60 nmol/mol), CO 2 (600 μmol/mol), and CO 2  + O 3 . After two growing seasons, ectomycorrhiza (ECM) colonization and root biomass increased under elevated CO 2 . Additionally, O 3 impaired ECM colonization and species richness, and reduced stem biomass. However, there was no clear inhibition of photosynthetic capacity by O 3 . Concentrations of Al, Fe, Mo, and P in needles were reduced by O 3 , while K and Mg in the roots increased. This might explain the distinct change in ECM colonization rate and diversity. No effects of combined fumigation were observed in any parameters except the P concentration in needles. The tolerance of F 1 to O 3 might potentially be related to a shift in ECM community structure. - Highlights: • Elevated CO 2 enhanced growth of hybrid larch F 1 (F 1 ). • ECM colonization rate and species richness of ECM were reduced by O 3 . • Species abundance of ECM community differed between O 3 and control. • F 1 potentially resisted O 3 impacts via specific selection of Suillus spp. for element uptake. - Elevated CO 2 moderated the negative effects of O 3 on the growth of hybrid larch F 1 , by stimulating ectomycorrhizas and nutrient uptake

Comparisons of [18F]-1-deoxy-1-fluoro-scyllo-inositol with [18F]-FDG for PET imaging of inflammation, breast and brain cancer xenografts in athymic mice

International Nuclear Information System (INIS)

McLarty, Kristin; Moran, Matthew D.; Scollard, Deborah A.; Chan, Conrad; Sabha, Nesrin; Mukherjee, Joydeep; Guha, Abhijit; McLaurin, JoAnne; Nitz, Mark; Houle, Sylvain; Wilson, Alan A.; Reilly, Raymond M.; Vasdev, Neil

2011-01-01

Introduction: The aim of the study was to evaluate the uptake of [ 18 F]-1-deoxy-1-fluoro-scyllo-inositol ([ 18 F]-scyllo-inositol) in human breast cancer (BC) and glioma xenografts, as well as in inflammatory tissue, in immunocompromised mice. Studies of [ 18 F]-2-fluoro-2-deoxy-D-glucose ([ 18 F]-FDG) under the same conditions were also performed. Methods: Radiosynthesis of [ 18 F]-scyllo-inositol was automated using a commercial synthesis module. Tumour, inflammation and normal tissue uptakes were evaluated by biodistribution studies and positron emission tomography (PET) imaging using [ 18 F]-scyllo-inositol and [ 18 F]-FDG in mice bearing subcutaneous MDA-MB-231, MCF-7 and MDA-MB-361 human BC xenografts, intracranial U-87 MG glioma xenografts and turpentine-induced inflammation. Results: The radiosynthesis of [ 18 F]-scyllo-inositol was automated with good radiochemical yields (24.6%±3.3%, uncorrected for decay, 65±2 min, n=5) and high specific activities (≥195 GBq/μmol at end of synthesis). Uptake of [ 18 F]-scyllo-inositol was greatest in MDA-MB-231 BC tumours and was comparable to that of [ 18 F]-FDG (4.6±0.5 vs. 5.5±2.1 %ID/g, respectively; P=.40), but was marginally lower in MDA-MB-361 and MCF-7 xenografts. Uptake of [ 18 F]-scyllo-inositol in inflammation was lower than [ 18 F]-FDG. While uptake of [ 18 F]-scyllo-inositol in intracranial U-87 MG xenografts was significantly lower than [ 18 F]-FDG, the tumour-to-brain ratio was significantly higher (10.6±2.5 vs. 2.1±0.6; P=.001). Conclusions: Consistent with biodistribution studies, uptake of [ 18 F]-scyllo-inositol was successfully visualized by PET imaging in human BC and glioma xenografts, with lower accumulation in inflammatory tissue than [ 18 F]-FDG. The tumour-to-brain ratio of [ 18 F]-scyllo-inositol was also significantly higher than that of [ 18 F]-FDG for visualizing intracranial glioma xenografts in NOD SCID mice, giving a better contrast. -- Graphical Abstract: Display Omitted

Conditional E2F1 activation in transgenic mice causes testicular atrophy and dysplasia mimicking human CIS

DEFF Research Database (Denmark)

Agger, Karl; Santoni-Rugiu, Eric; Holmberg, Christian

2005-01-01

E2F1 is a crucial downstream effector of the retinoblastoma protein (pRB) pathway. To address the consequences of short-term increase in E2F1 activity in adult tissues, we generated transgenic mice expressing the human E2F1 protein fused to the oestrogen receptor (ER) ligand-binding domain...

Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice

International Nuclear Information System (INIS)

Guo, Yixian; Zhang, Lanfang; Wan, Suigui; Sun, Xuejing; Wu, Yongxia; Yu, Xue-Zhong; Xia, Chang-Qing

2014-01-01

Highlights: • Injection of UVB-irradiated iDCs induces alloantigen tolerance. • This alloantigen tolerance may be associated regulatory T cell induction. • Tolerant mice serve as bone marrow donors reduces GVHD to their F1 recipients in allo-HSCT. • Tolerance is maintained in F1 recipients for long time post HSCT. - Abstract: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the current study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice (C3H × Balb/c). The results demonstrated that this approach markedly reduced GVHD-associated death and significantly prolonged the survival of recipient mice in contrast to the groups with donors (C3H mice) that received infusion of non-UVB-irradiated DCs. Further studies showed that there were enhanced Tregs in the tolerant mice and alloantigen-specific T cell response was skewed to more IL-10-producing T cells, suggesting that these regulatory T cells might have contributed to the attenuation of GVHD. This study suggests that it is a feasible approach to preventing GVHD in Haplo-HSCT in children by pre-induction of alloantigen tolerance between the two parents. This concept may also lead to more opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT

Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice

Energy Technology Data Exchange (ETDEWEB)

Guo, Yixian; Zhang, Lanfang; Wan, Suigui; Sun, Xuejing; Wu, Yongxia [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Yu, Xue-Zhong [Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425 (United States); Xia, Chang-Qing, E-mail: cqx65@yahoo.com [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

2014-04-18

Highlights: • Injection of UVB-irradiated iDCs induces alloantigen tolerance. • This alloantigen tolerance may be associated regulatory T cell induction. • Tolerant mice serve as bone marrow donors reduces GVHD to their F1 recipients in allo-HSCT. • Tolerance is maintained in F1 recipients for long time post HSCT. - Abstract: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the current study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice (C3H × Balb/c). The results demonstrated that this approach markedly reduced GVHD-associated death and significantly prolonged the survival of recipient mice in contrast to the groups with donors (C3H mice) that received infusion of non-UVB-irradiated DCs. Further studies showed that there were enhanced Tregs in the tolerant mice and alloantigen-specific T cell response was skewed to more IL-10-producing T cells, suggesting that these regulatory T cells might have contributed to the attenuation of GVHD. This study suggests that it is a feasible approach to preventing GVHD in Haplo-HSCT in children by pre-induction of alloantigen tolerance between the two parents. This concept may also lead to more opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT.

Use of hybridization (F1 in forage sorghum (Sorghum bicolor (L. Moench breeding

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Pataki Imre

2010-01-01

Full Text Available In plants with bisexual flowers, the development of hybrids and F1 seed production is only possible by using cytoplasmatic male sterility. The discovery of such sterility and the maintainers has made it possible to utilize the phenomenon of heterosis to improve yields and yield components in forage sorghum. It has been shown that the best way to develop forage sorghum hybrids is to cross grain sorghum as the female parent and Sudan grass as the male. The objective of this study was to develop a forage sorghum hybrid for the production of green matter to be used either fresh or for silage. The sorghum hybrid developed in these efforts (Siloking is intended for multiple cutting, as the basal nodes produce buds and regrowth takes place. The performance of the new hybrid with respect to yield and quality was compared to that of the forage sorghum cultivar NS Džin. In a two-year study conducted under different growing conditions in four locations, Siloking produced an average green matter yield of 86.29 t ha-1 (two cuts, a dry matter yield of 25.34 t ha-1, and a crude protein content of 11.85 %. Siloking outperformed NS Džin in terms of yield and quality. .

Speciation and reduced hybrid female fertility in house mice.

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Suzuki, Taichi A; Nachman, Michael W

2015-09-01

In mammals, intrinsic postzygotic isolation has been well studied in males but has been less studied in females, despite the fact that female gametogenesis and pregnancy provide arenas for hybrid sterility or inviability that are absent in males. Here, we asked whether inviability or sterility is observed in female hybrids of Mus musculus domesticus and M. m. musculus, taxa which hybridize in nature and for which male sterility has been well characterized. We looked for parent-of-origin growth phenotypes by measuring adult body weights in F1 hybrids. We evaluated hybrid female fertility by crossing F1 females to a tester male and comparing multiple reproductive parameters between intrasubspecific controls and intersubspecific hybrids. Hybrid females showed no evidence of parent-of-origin overgrowth or undergrowth, providing no evidence for reduced viability. However, hybrid females had smaller litter sizes, reduced embryo survival, fewer ovulations, and fewer small follicles relative to controls. Significant variation in reproductive parameters was seen among different hybrid genotypes, suggesting that hybrid incompatibilities are polymorphic within subspecies. Differences in reproductive phenotypes in reciprocal genotypes were observed and are consistent with cyto-nuclear incompatibilities or incompatibilities involving genomic imprinting. These findings highlight the potential importance of reduced hybrid female fertility in the early stages of speciation. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

On the Hybrid F1 Characteristics of Physiology, Biochemistry, Product Quality and Resistance to Black Shank in Oriental Tobacco

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Chen X

2014-12-01

Full Text Available Experiments were conducted from 1996 to 1998 at the Hefei Institute of Economics and Technology and at the Oriental Experimental Station of the Zhejiang Province (China. Seven F1 hybrids and three parental varieties of Oriental tobaccos were evaluated for the characteristics of photosynthetic and transpiration rates, esterase isozymes, resistance to black shank, quality and product potential from the 1996-1998 growing seasons. Tobacco leaves had higher photosynthetic rates and many differences among genotypes in the early stage of plant vigorous growth compared with more mature leaves. However, transpiration rates were lower in the younger leaves and greater in the more mature leaves. All the entries had four common bands (B1, B3, B4 and B6 of the esterase isoenzymes. Differences between entries resulted from in having or not having the B2 and B5 bands and color intensity differences of all the bands. These differences could be used to identify individual entries. The F1hybrids Samsun X Toy and Samsun X Argjiro, compared with the CK Samsun control, had obvious heterotic vigor in the characteristics of product, for yield, quality and resistance to black shank. The F1 hybrid Samsun X Toy maintained higher photosynthetic and transpiration rates in the two growth stages compared to other entries. However, the F1hybrid Samsun X Argjiro had higher photosynthetic rates and lower transpiration rates in the early growth stage and the two rates were lower in the later stage, but it maintained higher photosynthetic rates for the whole growth stage. Net photosynthetic rates had a significant positive correlation with yield product, quality and resistance to black shank of the Oriental tobacco F1hybrids.

SiglecF+Gr1hi eosinophils are a distinct subpopulation within the lungs of allergen-challenged mice.

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Percopo, Caroline M; Brenner, Todd A; Ma, Michelle; Kraemer, Laura S; Hakeem, Reem M A; Lee, James J; Rosenberg, Helene F

2017-01-01

Although eosinophils as a group are readily identified by their unique morphology and staining properties, flow cytometry provides an important means for identification of subgroups based on differential expression of distinct surface Ags. Here, we characterize an eosinophil subpopulation defined by high levels of expression of the neutrophil Ag Gr1 (CD45 + CD11c - SiglecF + Gr1 hi ). SiglecF + Gr1 hi eosinophils, distinct from the canonical SiglecF + Gr1 - eosinophil population, were detected in allergen-challenged wild-type and granule protein-deficient (EPX -/- and MBP-1 -/- ) mice, but not in the eosinophil-deficient ΔdblGATA strain. In contrast to Gr1 + neutrophils, which express both cross-reacting Ags Ly6C and Ly6G, SiglecF + Gr1 hi eosinophils from allergen-challenged lung tissue are uniquely Ly6G + Although indistinguishable from the more-numerous SiglecF + Gr1 - eosinophils under light microscopy, FACS-isolated populations revealed prominent differences in cytokine contents. The lymphocyte-targeting cytokines CXCL13 and IL-27 were identified only in the SiglecF + Gr1 hi eosinophil population (at 3.9 and 4.8 pg/10 6 cells, respectively), as was the prominent proinflammatory mediator IL-13 (72 pg/10 6 cells). Interestingly, bone marrow-derived (SiglecF + ), cultured eosinophils include a more substantial Gr1 + subpopulation (∼50%); Gr1 + bmEos includes primarily a single Ly6C + and a smaller, double-positive (Ly6C + Ly6G + ) population. Taken together, our findings characterize a distinct SiglecF + Gr1 hi eosinophil subset in lungs of allergen-challenged, wild-type and granule protein-deficient mice. SiglecF + Gr1 hi eosinophils from wild-type mice maintain a distinct subset of cytokines, including those active on B and T lymphocytes. These cytokines may facilitate eosinophil-mediated immunomodulatory responses in the allergen-challenged lung as well as in other distinct microenvironments. © Society for Leukocyte Biology.

Relative radioresistance of xenogeneic and hybrid resistance to bone marrow transplantation

International Nuclear Information System (INIS)

Rauchwerger, J.M.; Gallagher, M.T.; Monie, H.J.; Trentin, J.J.

1977-01-01

Following a single exposure to 1,100 R whole-body irradiation, (C57Bl/6 x A)F 1 hybrid mice were genetically resistant to transplantation of 5 x 10 5 C57 parental bone marrow cells (hybrid resistance). Hybrid resistance was minimally broken by increasing the radiation exposure to 2,200 R, and maximally broken by increasing it to 5,000 R. Following 1,100 R, (C57Bl/6 x A)F 1 hybrid mice were genetically resistant to transplantation of 5 x 10 6 Lewis RBM cells (xenogeneic resistance). This xenogeneic resistance was not even minimally broken following 5,000 R, but was broken following 6,600 R. With different doses of parental or xenogeneic marrow cells, it was found that the amount of irradiation exposure required to break either hybrid resistance or xenogeneic resistance was inversely proportional to the dose of bone marrow cells used

The Application of Restriction Landmark Genome Scanning Method for Surveillance of Non-Mendelian Inheritance in F1 Hybrids

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Tomoko Takamiya

2009-01-01

Full Text Available We analyzed inheritance of DNA methylation in reciprocal F1 hybrids (subsp. japonica cv. Nipponbare × subsp. indica cv. Kasalath of rice (Oryza sativa L. using restriction landmark genome scanning (RLGS, and detected differing RLGS spots between the parents and reciprocal F1 hybrids. MspI/HpaII restriction sites in the DNA from these different spots were suspected to be heterozygously methylated in the Nipponbare parent. These spots segregated in F1 plants, but did not segregate in selfed progeny of Nipponbare, showing non-Mendelian inheritance of the methylation status. As a result of RT-PCR and sequencing, a specific allele of the gene nearest to the methylated sites was expressed in reciprocal F1 plants, showing evidence of biased allelic expression. These results show the applicability of RLGS for scanning of non-Mendelian inheritance of DNA methylation and biased allelic expression.

Comparative proteome analysis of drought-sensitive and drought-tolerant rapeseed roots and their hybrid F1 line under drought stress.

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Mohammadi, Payam Pour; Moieni, Ahmad; Komatsu, Setsuko

2012-11-01

Rapeseed (Brassica napus L.), which is the third leading source of vegetable oil, is sensitive to drought stress during the early vegetative growth stage. To investigate the initial response of rapeseed to drought stress, changes in the protein expression profiles of drought-sensitive (RGS-003) and drought-tolerant lines (SLM-003), and their F1 hybrid, were analyzed using a proteomics approach. Seven-day-old rapeseed seedlings were treated with drought stress by restricting water for 7 days, and proteins were extracted from roots and separated by two-dimensional polyacrylamide gel electrophoresis. In the sensitive rapeseed line, 35 protein spots were differentially expressed under drought stress, and proteins related to metabolism, energy, disease/defense, and transport were decreased. In the tolerant line, 32 protein spots were differentially expressed under drought stress, and proteins involved in metabolism, disease/defense, and transport were increased, while energy-related proteins were decreased. Six protein spots in F1 hybrid were common among expressed proteins in the drought-sensitive and -tolerant lines. Notably, tubulin beta-2 and heat shock protein 70 were decreased in the drought-sensitive line and hybrid F1 plants, while jasmonate-inducible protein and 20S proteasome subunit PAF1 were increased in the F1 hybrids and drought-tolerant line. These results indicate that (1) V-type H(+) ATPase, plasma-membrane associated cation-binding protein, HSP 90, and elongation factor EF-2 have a role in the drought tolerance of rapeseed; (2) The decreased levels of heat shock protein 70 and tubulin beta-2 in the drought-sensitive and hybrid F1 lines might explain the reduced growth of these lines in drought conditions.

Lack of carcinogenicity of tragacanth gum in B6C3F1 mice.

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Hagiwara, A; Boonyaphiphat, P; Kawabe, M; Naito, H; Shirai, T; Ito, N

1992-08-01

Tragacanth gum was administered at dietary levels of 0 (control), 1.25 and 5.0% to groups of 50 male and 50 female B6C3F1 mice for 96 wk after which all animals were maintained on a basal diet without tragacanth gum for a further 10 wk. Mean body weights of females in the 5.0% and 1.25% groups were lower than those of the controls after 11 and 16 wk, respectively. However, there were no treatment-related clinical signs or adverse effects on survival rate, urinalysis, haematology, blood biochemistry and organ weight. While detailed histopathology revealed the development of squamous cell hyperplasias, papillomas and one carcinoma in the forestomach, there was no significant treatment-related increase in the incidence of any preneoplastic or neoplastic lesion. Thus, under the experimental conditions used, tragacanth gum was not carcinogenic in B6C3F1 mice of either sex.

Performance of cotton leaf curl virus resistant intrahirsutum f/sub 1/ hybrids

International Nuclear Information System (INIS)

Baloch, M.J.

2004-01-01

The first and foremost effort to combat the devastating cotton leaf curl virus (clcv) disease would be to utilize those clcv resistant germplasm in a hybridization programme which can enhance the possibilities of selecting desirable progenies from segregating populations. In this connection, 16 clcv intrahirsutum F1 hybrids were developed and evaluated for their performance. The hybrids, on an average gave an increase of 26.02 % in seed cotton yield; 11.52 % in bolls per plant; 14.23 % in boll weight; 4.28 % in lint; 3.89 % in fibre length and 8.21 % in earliness against the average of parents. However, among the hybrids, the top three scoring for yield were, BH.121 x Cyto.9/91, Cyto.9/91 x CRIS-226 and VH-137 x CRIS-226. The number of bolls per plant was found to be a major contributing factor for increased yield because the hybrids which set higher bolls correspondingly gave higher yields. Boll weight was not regarded as an important attribute to increase yield because hybrids with moderate boll sizes were among the top three high yielders. For lint %, the hybrids CRIS-129 x LRA-5166 and FH-901 x VH-137 were first for fibre length, whereas CRIS-121 x Cyto.51 and BH-124 x CIM-448 were among the top two rankers. Regarding earliness, the hybrids CRIS-121 x Cyto. 51 gave the highest boll opening percent and next in order was the hybrid VH-137 x DNH-49. Our results thus generally suggest that although the best three hybrids were desirable for other traits, the choice of the hybrids may be made on the priority for characters to be bred. (author)

Dissociation Between Brown Adipose Tissue 18F-FDG Uptake and Thermogenesis in Uncoupling Protein 1-Deficient Mice.

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Hankir, Mohammed K; Kranz, Mathias; Keipert, Susanne; Weiner, Juliane; Andreasen, Sille G; Kern, Matthias; Patt, Marianne; Klöting, Nora; Heiker, John T; Brust, Peter; Hesse, Swen; Jastroch, Martin; Fenske, Wiebke K

2017-07-01

18 F-FDG PET imaging is routinely used to investigate brown adipose tissue (BAT) thermogenesis, which requires mitochondrial uncoupling protein 1 (UCP1). It remains uncertain, however, whether BAT 18 F-FDG uptake is a reliable surrogate measure of UCP1-mediated heat production. Methods: UCP1 knockout (KO) and wild-type (WT) mice housed at thermoneutrality were treated with the selective β3 adrenergic receptor agonist CL 316, 243 and underwent metabolic cage, infrared thermal imaging and 18 F-FDG PET/MRI experiments. Primary brown adipocytes were additionally examined for their bioenergetics by extracellular flux analysis as well as their uptake of 2-deoxy- 3 H-glucose. Results: In response to CL 316, 243 treatments, oxygen consumption, and BAT thermogenesis were diminished in UCP1 KO mice, but BAT 18 F-FDG uptake was fully retained. Isolated UCP1 KO brown adipocytes exhibited defective induction of uncoupled respiration whereas their glycolytic flux and 2-deoxy- 3 H-glucose uptake rates were largely unaffected. Conclusion: Adrenergic stimulation can increase BAT 18 F-FDG uptake independently of UCP1 thermogenic function. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Radiation dosimetry estimates of "1"8F-alfatide II based on whole-body PET imaging of mice

International Nuclear Information System (INIS)

Wang, Si-yang; Bao, Xiao; Wang, Ming-wei; Zhang, Yong-ping; Zhang, Ying-jian; Zhang, Jian-ping

2015-01-01

We estimated the dosimetry of "1"8F-alfatide II with the method established by MIRD based on biodistribution data of mice. Six mice (three females and three males) were scanned for 160 min on an Inveon MicroPET/CT scanner after injection of "1"8F-alfatide II via tail vein. Eight source organs were delineated on the CT images and their residence times calculated. The data was then converted to human using scaling factors based on organ and body weight. The absorbed doses for human and the resulting effective dose were computed by OLINDA 1.1 software. The highest absorbed doses was observed in urinary bladder wall (male 0.102 mGy/MBq, female 0.147 mGy/MBq); and the lowest one was detected in brain (male 0.0030 mGy/MBq, female 0.0036). The total effective doses were 0.0127 mSv/MBq for male and 0.0166 mSv/MBq for female, respectively. A 370-MBq injection of "1"8F-alfatide II led to an estimated effective dose of 4.70 mSv for male and 6.14 mSv for female. The potential radiation burden associated with "1"8F-alfatide II/PET imaging therefore is comparable to other PET examinations. - Highlights: • We demonstrated a proper mice model to estimate human radiation dosimetry. • This is the first paper to estimate human radiation dosimetry of "1"8F-alfatide II. • Estimated effective dose are in the range of routine nuclear medicine studies.

Comparisons of [{sup 18}F]-1-deoxy-1-fluoro-scyllo-inositol with [{sup 18}F]-FDG for PET imaging of inflammation, breast and brain cancer xenografts in athymic mice

Energy Technology Data Exchange (ETDEWEB)

McLarty, Kristin; Moran, Matthew D. [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Scollard, Deborah A.; Chan, Conrad [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Sabha, Nesrin; Mukherjee, Joydeep; Guha, Abhijit [Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, University of Toronto, ON, M5G 1X8 (Canada); McLaurin, JoAnne [Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, M5S 3H2 (Canada); Nitz, Mark [Department of Chemistry, University of Toronto, Toronto, ON, M5S 3H6 (Canada); Houle, Sylvain; Wilson, Alan A. [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Reilly, Raymond M., E-mail: raymond.reilly@utoronto.ca [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Toronto General Research Institute, University Health Network, Toronto, ON, M5G 2M9 (Canada); Department of Medical Imaging, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Vasdev, Neil, E-mail: neil.vasdev@utoronto.ca [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)

2011-10-15

Introduction: The aim of the study was to evaluate the uptake of [{sup 18}F]-1-deoxy-1-fluoro-scyllo-inositol ([{sup 18}F]-scyllo-inositol) in human breast cancer (BC) and glioma xenografts, as well as in inflammatory tissue, in immunocompromised mice. Studies of [{sup 18}F]-2-fluoro-2-deoxy-D-glucose ([{sup 18}F]-FDG) under the same conditions were also performed. Methods: Radiosynthesis of [{sup 18}F]-scyllo-inositol was automated using a commercial synthesis module. Tumour, inflammation and normal tissue uptakes were evaluated by biodistribution studies and positron emission tomography (PET) imaging using [{sup 18}F]-scyllo-inositol and [{sup 18}F]-FDG in mice bearing subcutaneous MDA-MB-231, MCF-7 and MDA-MB-361 human BC xenografts, intracranial U-87 MG glioma xenografts and turpentine-induced inflammation. Results: The radiosynthesis of [{sup 18}F]-scyllo-inositol was automated with good radiochemical yields (24.6%{+-}3.3%, uncorrected for decay, 65{+-}2 min, n=5) and high specific activities ({>=}195 GBq/{mu}mol at end of synthesis). Uptake of [{sup 18}F]-scyllo-inositol was greatest in MDA-MB-231 BC tumours and was comparable to that of [{sup 18}F]-FDG (4.6{+-}0.5 vs. 5.5{+-}2.1 %ID/g, respectively; P=.40), but was marginally lower in MDA-MB-361 and MCF-7 xenografts. Uptake of [{sup 18}F]-scyllo-inositol in inflammation was lower than [{sup 18}F]-FDG. While uptake of [{sup 18}F]-scyllo-inositol in intracranial U-87 MG xenografts was significantly lower than [{sup 18}F]-FDG, the tumour-to-brain ratio was significantly higher (10.6{+-}2.5 vs. 2.1{+-}0.6; P=.001). Conclusions: Consistent with biodistribution studies, uptake of [{sup 18}F]-scyllo-inositol was successfully visualized by PET imaging in human BC and glioma xenografts, with lower accumulation in inflammatory tissue than [{sup 18}F]-FDG. The tumour-to-brain ratio of [{sup 18}F]-scyllo-inositol was also significantly higher than that of [{sup 18}F]-FDG for visualizing intracranial glioma xenografts in

Tg.rasH2 Mice and not CByB6F1 Mice Should Be Used for 28-Day Dose Range Finding Studies Prior to 26-Week Tg.rasH2 Carcinogenicity Studies.

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Paranjpe, Madhav G; Belich, Jessica; Vidmar, Tom J; Elbekai, Reem H; McKeon, Marie; Brown, Caren

Our recent retrospective analysis of data, collected from 29 Tg.rasH2 mouse carcinogenicity studies, determined how successful the strategy of choosing the high dose for the 26-week studies was based on the estimated maximum tolerated dose (EMTD) derived from earlier 28-day dose range finding (DRF) studies conducted in CByB6F1 mice. Our analysis demonstrated that the high doses applied at EMTD in the 26-week Tg.rasH2 studies failed to detect carcinogenic effects. To investigate why the dose selection process failed in the 26-week carcinogenicity studies, the initial body weights, terminal body weights, body weight gains, food consumption, and mortality from the first 4 weeks of 26-week studies with Tg.rasH2 mice were compared with 28-day DRF studies conducted with CByB6F1 mice. Both the 26-week and the earlier respective 28-day studies were conducted with the exact same vehicle, test article, and similar dose levels. The analysis of our results further emphasizes that the EMTD and subsequent lower doses, determined on the basis of the 28-day studies in CByB6F1 mice, may not be an accurate strategy for selecting appropriate dose levels for the 26-week carcinogenicity studies in Tg.rasH2 mice. Based on the analysis presented in this article, we propose that the Tg.rasH2 mice and not the CByB6F1 mice should be used in future DRF studies. The Tg.rasH2 mice demonstrate more toxicity than the CByB6F1 mice, possibly because of their smaller size compared to CByB6F1 mice. Also, the Tg.rasH2 males appear to be more sensitive than the female Tg.rasH2 mice.

Gastrointestinal absorption of plutonium in mice, rats, and dogs: application to establishing values of f1 for soluble plutonium

International Nuclear Information System (INIS)

Bhattacharyya, M.H.; Larsen, R.P.; Oldham, R.D.; Moretti, E.S.; Spaletto, M.I.

1985-04-01

The gastrointestinal (GI) absorption of plutonium was measured in mice, rats, and dogs under conditions relevant to setting drinking water standards. The fractional GI absorption of Pu(VI) in adult mice was 2 x 10 -4 (0.02%) in fed mice and 2 x 10 -3 (0.2%) in fasted mice. The GI absorption of plutonium was independent of plutonium oxidation state, administration medium, and plutonium concentration; absorption was dependent upon animal species, state of animal fasting, state of Pu(IV) hydrolysis, and age of the animal. Fractional GI absorption values ranged from 3 x 10 -5 (0.003%) for hydrolyzed Pu(IV) administered to fed adult mice to 7 x 10 -3 (0.7%) for Pu(VI) administered to fed neonatal rats. From analysis of our data, we suggested values of f 1 (the fraction transferred from gut to blood in humans) for use in establishment of oral limits of exposure to plutonium. For an acute exposure in the occupational setting, we proposed one value of f 1 for fed (2 x 10 -4 ) and one for fasted (2 x 10 -3 ) individuals. For the environmental setting, we developed two approaches to obtaining values of f 1 ; suggested values were 6 x 10 -4 and 4 x 10 -3 , respectively. Both approaches took into account effects of animal age and fasting. We discussed uncertainties in proposed values of f 1 and made recommendations for further research. 41 refs., 8 figs., 24 tabs

Gonadal expression of aromatase and estrogen receptor alpha genes in two races of Tunisian mice and their hypofertile hybrids.

Science.gov (United States)

Saïd, Lamia; Delalande, Christelle; Britton-Davidian, Janice; Saïd, Khaled; Saad, Ali; Carreau, Serge

2007-07-01

House mice (Mus musculus domesticus) in Tunisia consists of two races, one carries the 40-acrocentric standard karyotypes and the other one is a robertsonian race (2n=22) homozygous for nine centric fusions (Rb). The F1 hybrids between the two chromosomal races showed a significant decrease in reproductive success and litter size. Such results can be related to the formation of meiotic trivalent in the hybrids leading to the production of viable aneuploid gametes and post-zygotic elimination of embryos due to chromosomal non disjunction events at meiosis. Moreover, testicular histology of F1 and backcross males showed in some cases a breakdown in spermatogenesis. In both females and males, androgens but also estrogens play an important role in gametogenesis. In this study, we have studied aromatase and estrogen receptor alpha (ERalpha) gene expression in the gonads of the two parental races and their chromosomal hybrids. The results showed that aromatase and ERalpha mRNAs are expressed in hybrid males of inter-racial crosses (female22Rb x male40Std and female40Std x male22Rb) and in hybrid females of inter-racial crosses (female22Rb x male40Std) as in the two parental races. However, in hybrid females of inter-racial crosses (female40Std x male22Rb) the amount of aromatase transcripts decreased sharply suggesting that this gene is involved in the breakdown of hybrid fertility in females, but not in males. However, in hybrid males, a putative post-translational modification of this enzyme, in terms of activity, should be verified.

Allelic interaction of F1 pollen sterility loci and abnormal chromosome behaviour caused pollen sterility in intersubspecific autotetraploid rice hybrids.

Science.gov (United States)

He, J H; Shahid, M Q; Li, Y J; Guo, H B; Cheng, X A; Liu, X D; Lu, Y G

2011-08-01

The intersubspecific hybrids of autotetraploid rice has many features that increase rice yield, but lower seed set is a major hindrance in its utilization. Pollen sterility is one of the most important factors which cause intersubspecific hybrid sterility. The hybrids with greater variation in seed set were used to study how the F(1) pollen sterile loci (S-a, S-b, and S-c) interact with each other and how abnormal chromosome behaviour and allelic interaction of F(1) sterility loci affect pollen fertility and seed set of intersubspecific autotetraploid rice hybrids. The results showed that interaction between pollen sterility loci have significant effects on the pollen fertility of autotetraploid hybrids, and pollen fertility further decreased with an increase in the allelic interaction of F(1) pollen sterility loci. Abnormal ultra-structure and microtubule distribution patterns during pollen mother cell (PMC) meiosis were found in the hybrids with low pollen fertility in interphase and leptotene, suggesting that the effect-time of pollen sterility loci interaction was very early. There were highly significant differences in the number of quadrivalents and bivalents, and in chromosome configuration among all the hybrids, and quadrivalents decreased with an increase in the seed set of autotetraploid hybrids. Many different kinds of chromosomal abnormalities, such as chromosome straggling, chromosome lagging, asynchrony of chromosome disjunction, and tri-fission were found during the various developmental stages of PMC meiosis. All these abnormalities were significantly higher in sterile hybrids than in fertile hybrids, suggesting that pollen sterility gene interactions tend to increase the chromosomal abnormalities which cause the partial abortion of male gametes and leads to the decline in the seed set of the autotetraploid rice hybrids. © 2011 The Author(s).

Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice

Energy Technology Data Exchange (ETDEWEB)

Zhou, Changqing; Gao, Liying; Flaws, Jodi A., E-mail: jflaws@illinois.edu

2017-03-01

Phthalates are used in a large variety of products, such as building materials, medical devices, and personal care products. Most previous studies on the toxicity of phthalates have focused on single phthalates, but it is also important to study the effects of phthalate mixtures because humans are exposed to phthalate mixtures. Thus, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects female reproduction in mice. To test this hypothesis, pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200 μg/kg/day, 200 and 500 mg/kg/day) daily from gestational day 10 to birth. The mixture was based on the composition of phthalates detected in urine samples from pregnant women in Illinois. The mixture included 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. Female mice born to the exposed dams were subjected to tissue collections and fertility tests at different ages. Our results indicate that prenatal exposure to the phthalate mixture significantly increased uterine weight and decreased anogenital distance on postnatal days 8 and 60, induced cystic ovaries at 13 months, disrupted estrous cyclicity, reduced fertility-related indices, and caused some breeding complications at 3, 6, and 9 months of age. Collectively, our data suggest that prenatal exposure to an environmentally relevant phthalate mixture disrupts aspects of female reproduction in mice. - Highlights: • Prenatal exposure to a phthalate mixture disrupts F1 estrous cyclicity. • Prenatal exposure to a phthalate mixture induces F1 ovarian cysts. • Prenatal exposure to a phthalate mixture decreases F1 female fertility-related indices. • Prenatal exposure to a phthalate mixture induces F1 breeding complications.

Agronomic Performance of Flue-Cured Tobacco F1 Hybrids Obtained with Different Sources of Male Sterile Cytoplasm

Directory of Open Access Journals (Sweden)

Berbec A

2014-12-01

Full Text Available Four cytoplasmic male sterile (cms F1flue-cured hybrids cv. Wiaelica × cv. Virginia Golta (VG, the male fertile analogue and the parental varieties were tested at two locations in Poland in a replicated field trial. The cms sources in the hybrids wereN. suaveolens,N. amplexicaulis,N. bigeloviiand aN. tabacumcms mutant. Under the slight to moderate pressure from black root rot present at the trial sites the hybrids showed a moderate tolerance of the disease characteristic of VG as opposed to medium strong susceptibility of Wislica. Apart from the effect of black root rot tolerance the vegetative vigor of the hybrids (plant height, leaf size, earliness was affected by cytoplasm source. The F1hybrid withN. suaveolens cytoplasm flowered approximately three days later than the remaining hybrids. Of the cms hybrids tested cmsN. bigelovii produced the tallest plants with largest mid-position leaves. Yields of cured leaves were largely influenced by black root rot and were generally higher in VG and in the hybrids than in Wislica. Leaf yields and curability were generally little affected by cms source under low pressure from black root rot. At the site with a relatively high level of black root rot infestation the yields of cmsN. suaveolens were slightly lower but the percentage of light grades slightly higher compared to those of other cms hybrids. CmsN. suaveolens was the best hybrid in terms of money returns at the low black root rot field but it was the poorest hybrid performer under high pressure from the disease. Contents of nitrogen, sugars, nicotine and ash was little affected by source of cms. There was an increased incidence of potato virus Y (PVY and white spots in cmsN. suaveolens and, to a lesser extent, in cmsN. bigelovii as compared to the remaining disease-free entries.

Growth, straightness and survival at age 32 in a Pinus strobus x P. wallichiana F1 hybrid population (Experiment 1

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Ioan Blada

2013-11-01

Full Text Available An interspecific factorial hybridization was made, where seven P. strobus female parent trees were mated to four P. wallichiana male trees, in order to transfer genes for resistance to blister-rust from the blue pine to the F1 hybrids. The hybrid seedlings and the open pollinated families of the two parents were three times consecutivelyinoculated with blister-rust. The six years old seedlings were transplanted in the field in the so called Văliug Experiment 1. The experimental design consisted in 28 hybrid full-sib families and two open pollinated families of the parent species. Plantation took place in a complete randomized block design with three blocks, with 6 to 12 seedlings per linear plot and 3 x 3 m spacing. This paper is based on the measurements made at age 32, just after the first thinning. Diameter at breast height, tree height, tree volume, stem straightness and tree survival were the five measured traits. According to ANOVA, significant (p < 0.05 and highly significant (p< 0.001 differences for diameter at breast height, tree height, volume growth rate, stem straightness and tree survival were detected between hybrid families. Highly significant (p < 0.01, p < 0.001 differences were found between eastern white pine female parents for survival, stem straightness and all growth traits, suggestingthat nuclear additive genes are controlling the respective characters. Consequently, high survival or genetic resistance to blister-rust can be found within the P. strobus species even though it is highly susceptible to this pathogen. The P. wallichiana parents exhibited significant additive effects on straightness and breast height diameter, but no significance in height, volume, and tree survival. The contribution of the additive variance to the phenotypic one was 65.7% for diameter, 58.6% for height, 50.5% for volume, 70.4% for stem straightness and 73.4% for tree survival. Hence, additive variance should be employed in a breeding program

Dissecting the genetic architecture of F-1 hybrid sterility in house mice

Czech Academy of Sciences Publication Activity Database

Dzúr-Gejdošová, Mária; Šimeček, Petr; Gregorová, Soňa; Bhattacharyya, Tanmoy; Forejt, Jiří

2012-01-01

Roč. 66, č. 11 (2012), s. 3321-3335 ISSN 0014-3820 R&D Projects: GA MŠk(CZ) LD11079 Grant - others:AV ČR(CZ) Praemium Academiae Institutional research plan: CEZ:AV0Z50520514 Keywords : hybrid sterility * reproductive isolation * recombination hotspots * chromosome X * chromosome 17 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.864, year: 2012

Prevention of pneumonic plague in mice, rats, guinea pigs and non-human primates with clinical grade rV10, rV10-2 or F1-V vaccines

Science.gov (United States)

Quenee, Lauriane E.; Ciletti, Nancy A.; Elli, Derek; Hermanas, Timothy M.; Schneewind, Olaf

2012-01-01

Yersinia pestis causes plague, a disease with high mortality in humans that can be transmitted by fleabite or aerosol. A US Food and Drug Administration (FDA)-licensed plague vaccine is currently not available. Vaccine developers have focused on two subunits of Y. pestis: LcrV, a protein at the tip of type III secretion needles, and F1, the fraction 1 pilus antigen. F1-V, a hybrid generated via translational fusion of both antigens, is being developed for licensure as a plague vaccine. The rV10 vaccine is a non-toxigenic variant of LcrV lacking residues 271–300. Here we developed Current Good Manufacturing Practice (cGMP) protocols for rV10. Comparison of clinical grade rV10 with F1-V did not reveal significant differences in plague protection in mice, guinea pigs or cynomolgus macaques. We also developed cGMP protocols for rV10-2, a variant of rV10 with an altered affinity tag. Immunization with rV10-2 adsorbed to aluminum hydroxide elicited antibodies against LcrV and conferred pneumonic plague protection in mice, rats, guinea pigs, cynomolgus macaques and African Green monkeys. The data support further development of rV10-2 for FDA Investigational New Drug (IND) authorization review and clinical testing. PMID:21763383

Protective immunity induced in mice by F8.1 and F8.2 antigens purified from Schistosoma mansoni eggs

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Claudia Campra Ferreira

1998-01-01

Full Text Available Schistosoma mansoni soluble egg antigens (SEA were fractionated by isoelectric focusing, resulting in 20 components, characterized by pH, absorbance and protein concentration. The higher absorbance fractions were submitted to electrophoresis, and fraction 8 (F8 presented a specific pattern of bands on its isoelectric point. Protein 3 was observed only on F8, and so, it was utilized to rabbit immunization, in order to evaluate its capacity of inducing protective immunity. IgG antibodies from rabbit anti-F8 serum were coupled to Sepharose, and used to obtain the specific antigen by affinity chromatography. This antigen, submitted to electrophoresis, presented two proteic bands (F8.1 and F8.2, which were transferred to nitrocellulose membrane (PVDF and sequenciated. The homology of F8.2 to known proteins was determined using the Basic Local Alignment Search Tool program (BLASTp. Significant homologies were obtained for the rabbit cytosolic Ca2+ uptake inhibitor, and for the bird a1-proteinase inhibitor. Immunization of mice with F8.1 and F8.2, in the presence of Corynebacterium parvum and Al(OH3 as adjuvant, induced a significant protection degree against challenge infection, as observed by the decrease on worm burden recovered from portal system.

Breeding of early restorer Fuhui 306 and predominant performance of F1 hybrid combinations

International Nuclear Information System (INIS)

Wu Wanyi; Liu Yongqiang; Wu Maoli; Xue Xingqiong

2004-01-01

Fuhui 306, an early rice restorer with strong restoring ability, short growth period (86 days) and no restriction of separating areas in seed production, was bred by radiation treatment. F 1 hybrid combinations with different mature period were developed when cross with different sterile lines, that combination would be widely applied to meet the requirement of different ecological environment and harvest period. (authors)

Induction of a glucocorticoid-sensitive F1-anti-parental mechanism that affects engraftment during graft-versus-host disease.

Science.gov (United States)

You-Ten, K E; Seemayer, T A; Wisse, B; Bertley, F M; Lapp, W S

1995-07-01

Studies have shown that graft-vs-host disease (GVHD) in animal models induces persistent elevated levels of circulating adrenal glucocorticoids. In this report, we investigated the effects of endogenous glucocorticoids on the outcome of GVHD by adrenalectomizing (ADX) unirradiated (C57BL/6 x A)F1 (B6AF1) mice before GVHD induction. GVHD was induced by injection of 20 x 10(6) A strain parental lymphoid cells into B6AF1 mice. Our results demonstrated that non-ADX recipient mice experienced features characteristic of GVHD on day 13, which became progressively more severe by days 18 to 21. The GVHD features included severe immunosuppression, reversal in the host splenic CD4+/CD8+ ratio, histopathologic lesions in different tissues, and high parental cell chimerism in the spleens and lymph nodes. In contrast, ADX F1 recipient mice experienced GVHD features on day 13 similar to their non-ADX counterparts; however, ADX animals recovered rapidly from GVHD by days 18 to 21. Flow cytometry showed that, although a relatively high frequency of parental cells was detected in the spleens and lymph nodes of ADX mice on day 13, nearly all of the parental cells in the peripheral lymphoid organs disappeared on days 18 to 21, the time of recovery from GVHD. The marked reduction of parental cells and recovery from GVHD were prevented by treating ADX F1 mice with either exogenous glucocorticoid, anti-asialoGM1, or anti-CD8, but not anti-NK1.1 Ab. These results suggest that a dramatic recovery from GVHD was induced by a cell-mediated, steroid-sensitive F1-anti-parental mechanism. The F1-anti-parental phenomenon described herein is different from classical hybrid resistance.

Hybrid mimics and hybrid vigor in Arabidopsis

Science.gov (United States)

Wang, Li; Greaves, Ian K.; Groszmann, Michael; Wu, Li Min; Dennis, Elizabeth S.; Peacock, W. James

2015-01-01

F1 hybrids can outperform their parents in yield and vegetative biomass, features of hybrid vigor that form the basis of the hybrid seed industry. The yield advantage of the F1 is lost in the F2 and subsequent generations. In Arabidopsis, from F2 plants that have a F1-like phenotype, we have by recurrent selection produced pure breeding F5/F6 lines, hybrid mimics, in which the characteristics of the F1 hybrid are stabilized. These hybrid mimic lines, like the F1 hybrid, have larger leaves than the parent plant, and the leaves have increased photosynthetic cell numbers, and in some lines, increased size of cells, suggesting an increased supply of photosynthate. A comparison of the differentially expressed genes in the F1 hybrid with those of eight hybrid mimic lines identified metabolic pathways altered in both; these pathways include down-regulation of defense response pathways and altered abiotic response pathways. F6 hybrid mimic lines are mostly homozygous at each locus in the genome and yet retain the large F1-like phenotype. Many alleles in the F6 plants, when they are homozygous, have expression levels different to the level in the parent. We consider this altered expression to be a consequence of transregulation of genes from one parent by genes from the other parent. Transregulation could also arise from epigenetic modifications in the F1. The pure breeding hybrid mimics have been valuable in probing the mechanisms of hybrid vigor and may also prove to be useful hybrid vigor equivalents in agriculture. PMID:26283378

Both core and F proteins of hepatitis C virus could enhance cell proliferation in transgenic mice

Energy Technology Data Exchange (ETDEWEB)

Hu, Wen-Ta [Graduate Institute of Medical Biotechnology, Tzu Chi University, Hualien, Taiwan (China); Li, Hui-Chun [Department of Biochemistry, Tzu Chi University, Hualien, Taiwan (China); Lee, Shen-Kao; Ma, Hsin-Chieh; Yang, Chee-Hing; Chen, Hung-Ling [Graduate Institute of Medical Biotechnology, Tzu Chi University, Hualien, Taiwan (China); Lo, Shih-Yen, E-mail: losylo@mail.tcu.edu.tw [Graduate Institute of Medical Biotechnology, Tzu Chi University, Hualien, Taiwan (China); Department of Laboratory Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan (China)

2013-05-24

Highlights: •HCV core and F proteins could induce hepatocyte proliferation in the transgenic mice. •β-Catenin signaling pathway was activated by core protein in the transgenic mice. •β-Catenin signaling pathway was activated by myc-F protein in the transgenic mice. •Expression of SMA protein was enhanced by core but not myc-F protein. -- Abstract: The role of the protein encoded by the alternative open reading frame (ARF/F/core+1) of the Hepatitis C virus (HCV) genome in viral pathogenesis remains unknown. The different forms of ARF/F/core+1 protein were labile in cultured cells, a myc-tag fused at the N-terminus of the F protein made it more stable. To determine the role of core and F proteins in HCV pathogenesis, transgenic mice with either protein expression under the control of Albumin promoter were generated. Expression of core protein and F protein with myc tag (myc-F) could be detected by Western blotting analysis in the livers of these mice. The ratio of liver to body weight is increased for both core and myc-F transgenic mice compared to that of wild type mice. Indeed, the proliferating cell nuclear antigen protein, a proliferation marker, was up-regulated in the transgenic mice with core or myc-F protein. Further analyses by microarray and Western blotting suggested that β-catenin signaling pathway was activated by either core or myc-F protein in the transgenic mice. These transgenic mice were further treated with either Diethynitrosamine (a tumor initiator) or Phenobarbital (a tumor promoter). Phenobarbital but not Diethynitrosamine treatment could increase the liver/body weight ratio of these mice. However, no tumor formation was observed in these mice. In conclusion, HCV core and myc-F proteins could induce hepatocyte proliferation in the transgenic mice possibly through β-catenin signaling pathway.

Both core and F proteins of hepatitis C virus could enhance cell proliferation in transgenic mice

International Nuclear Information System (INIS)

Hu, Wen-Ta; Li, Hui-Chun; Lee, Shen-Kao; Ma, Hsin-Chieh; Yang, Chee-Hing; Chen, Hung-Ling; Lo, Shih-Yen

2013-01-01

Highlights: •HCV core and F proteins could induce hepatocyte proliferation in the transgenic mice. •β-Catenin signaling pathway was activated by core protein in the transgenic mice. •β-Catenin signaling pathway was activated by myc-F protein in the transgenic mice. •Expression of SMA protein was enhanced by core but not myc-F protein. -- Abstract: The role of the protein encoded by the alternative open reading frame (ARF/F/core+1) of the Hepatitis C virus (HCV) genome in viral pathogenesis remains unknown. The different forms of ARF/F/core+1 protein were labile in cultured cells, a myc-tag fused at the N-terminus of the F protein made it more stable. To determine the role of core and F proteins in HCV pathogenesis, transgenic mice with either protein expression under the control of Albumin promoter were generated. Expression of core protein and F protein with myc tag (myc-F) could be detected by Western blotting analysis in the livers of these mice. The ratio of liver to body weight is increased for both core and myc-F transgenic mice compared to that of wild type mice. Indeed, the proliferating cell nuclear antigen protein, a proliferation marker, was up-regulated in the transgenic mice with core or myc-F protein. Further analyses by microarray and Western blotting suggested that β-catenin signaling pathway was activated by either core or myc-F protein in the transgenic mice. These transgenic mice were further treated with either Diethynitrosamine (a tumor initiator) or Phenobarbital (a tumor promoter). Phenobarbital but not Diethynitrosamine treatment could increase the liver/body weight ratio of these mice. However, no tumor formation was observed in these mice. In conclusion, HCV core and myc-F proteins could induce hepatocyte proliferation in the transgenic mice possibly through β-catenin signaling pathway

Herpes simplex virus thymidine kinase imaging in mice with (1-(2'-deoxy-2'-[{sup 18}F]fluoro-1-{beta}-D-arabinofuranosyl)-5-iodouracil) and metabolite (1-(2'-deoxy-2'-[{sup 18}F]fluoro-1-{beta}-D-arabinofuranosyl)-5-uracil)

Energy Technology Data Exchange (ETDEWEB)

Nimmagadda, Sridhar; Lawhorn-Crews, Jawana M.; Shields, Anthony F. [Wayne State University, Karmanos Cancer Institute, Detroit, MI (United States); Wayne State University, Department of Medicine, Detroit, MI (United States); Mangner, Thomas J. [Wayne State University, Karmanos Cancer Institute, Detroit, MI (United States); Wayne State University, Department of Radiology, Detroit, MI (United States); Haberkorn, Uwe [University of Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany)

2009-12-15

FIAU, (1-(2{sup '}-deoxy-2{sup '}-fluoro-1-{beta}-D-arabinofuranosyl)-5-iodouracil) has been used as a substrate for herpes simplex virus thymidine kinases (HSV-TK and HSV-tk, for protein and gene expression, respectively) and other bacterial and viral thymidine kinases for noninvasive imaging applications. Previous studies have reported the formation of a de-iodinated metabolite of {sup 18}F-FIAU. This study reports the dynamic tumor uptake, biodistribution, and metabolite contribution to the activity of {sup 18}F-FIAU seen in HSV-tk gene expressing tumors and compares the distribution properties with its de-iodinated metabolite {sup 18}F-FAU. CD-1 nu/nu mice with subcutaneous MH3924A and MH3924A-stb-tk+ xenografts on opposite flanks were used for the biodistribution and imaging studies. Mice were injected IV with either {sup 18}F-FIAU or {sup 18}F-FAU. Mice underwent dynamic imaging with each tracer for 65 min followed by additional static imaging up to 150 min post-injection for some animals. Animals were sacrificed at 60 or 150 min post-injection. Samples of blood and tissue were collected for biodistribution and metabolite analysis. Regions of interest were drawn over the images obtained from both tumors to calculate the time-activity curves. Biodistribution and imaging studies showed the highest uptake of {sup 18}F-FIAU in the MH3924A-stb-tk+ tumors. Dynamic imaging studies revealed a continuous accumulation of {sup 18}F-FIAU in HSV-TK expressing tumors over 60 min. The mean biodistribution values (SUV {+-} SE) for MH3924A-stb-tk+ were 2.07 {+-} 0.40 and 6.15 {+-} 1.58 and that of MH3924A tumors were 0.19 {+-} 0.07 and 0.47 {+-} 0.06 at 60 and 150 min, respectively. In {sup 18}F-FIAU injected mice, at 60 min nearly 63% of blood activity was present as its metabolite {sup 18}F-FAU. Imaging and biodistribution studies with {sup 18}F-FAU demonstrated no specific accumulation in MH3924A-stb-tk+ tumors and SUVs for both the tumors were similar to those

Combining ability and mode of inheritance of stem thickness in forage sorghum (Sorghum bicolor L. Moench F1 hybrids

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Pataki Imre

2011-01-01

Full Text Available Aim of this research was determination of mode of inheritance, gene effects components of genetic variance, combining abilities, average contribution of lines and testers and their interactions in expression of stem thickness in forage sorghum F1 generation. Method line x tester was applied. Material comprised of eight genetically divergent A-inbred lines of grain sorghum three R lines-testers of Sudan grass and twenty-four F1 hybrids obtained by crossing lines with testers. Among tested genotypes there were significant differences in mean values of stem thickness. Analysis of variance of combining abilities showed that there were highly significant differences for general combining abilities (GCA and specific combining abilities (SCA non-additive component of genetic variance (dominance and epistasis had greater portion in total genetic variance for stem thickness. During the first research year, interaction between inbred maternal line with testers had the largest contribution in expression of stem thickness of F1 hybrid at both locations, while in the second year at location Rimski Šančevi the largest contribution belongs to lines and at location Mačvanski Prnjavor the largest contribution belongs to testers. Assessment of combining abilities showed that these inbred lines of grain sorghum can be used as mothers: SS-1 646, SS-1 688 and S-8 682 in breeding forage sorghum for thicker stem. According to SCA, promising forage sorghum hybrids are S-8 682 x ST-R lin H and P-21 656 x C-198. This research can be of importance for developing new high-yielding forage sorghum hybrids.

Genetic dissection of a key reproductive barrier between nascent species of house mice.

Science.gov (United States)

White, Michael A; Steffy, Brian; Wiltshire, Tim; Payseur, Bret A

2011-09-01

Reproductive isolation between species is often caused by deleterious interactions among loci in hybrids. Finding the genes involved in these incompatibilities provides insight into the mechanisms of speciation. With recently diverged subspecies, house mice provide a powerful system for understanding the genetics of reproductive isolation early in the speciation process. Although previous studies have yielded important clues about the genetics of hybrid male sterility in house mice, they have been restricted to F1 sterility or incompatibilities involving the X chromosome. To provide a more complete characterization of this key reproductive barrier, we conducted an F2 intercross between wild-derived inbred strains from two subspecies of house mice, Mus musculus musculus and Mus musculus domesticus. We identified a suite of autosomal and X-linked QTL that underlie measures of hybrid male sterility, including testis weight, sperm density, and sperm morphology. In many cases, the autosomal loci were unique to a specific sterility trait and exhibited an effect only when homozygous, underscoring the importance of examining reproductive barriers beyond the F1 generation. We also found novel two-locus incompatibilities between the M. m. musculus X chromosome and M. m. domesticus autosomal alleles. Our results reveal a complex genetic architecture for hybrid male sterility and suggest a prominent role for reproductive barriers in advanced generations in maintaining subspecies integrity in house mice.

Genetic Dissection of a Key Reproductive Barrier Between Nascent Species of House Mice

Science.gov (United States)

White, Michael A.; Steffy, Brian; Wiltshire, Tim; Payseur, Bret A.

2011-01-01

Reproductive isolation between species is often caused by deleterious interactions among loci in hybrids. Finding the genes involved in these incompatibilities provides insight into the mechanisms of speciation. With recently diverged subspecies, house mice provide a powerful system for understanding the genetics of reproductive isolation early in the speciation process. Although previous studies have yielded important clues about the genetics of hybrid male sterility in house mice, they have been restricted to F1 sterility or incompatibilities involving the X chromosome. To provide a more complete characterization of this key reproductive barrier, we conducted an F2 intercross between wild-derived inbred strains from two subspecies of house mice, Mus musculus musculus and Mus musculus domesticus. We identified a suite of autosomal and X-linked QTL that underlie measures of hybrid male sterility, including testis weight, sperm density, and sperm morphology. In many cases, the autosomal loci were unique to a specific sterility trait and exhibited an effect only when homozygous, underscoring the importance of examining reproductive barriers beyond the F1 generation. We also found novel two-locus incompatibilities between the M. m. musculus X chromosome and M. m. domesticus autosomal alleles. Our results reveal a complex genetic architecture for hybrid male sterility and suggest a prominent role for reproductive barriers in advanced generations in maintaining subspecies integrity in house mice. PMID:21750261

Growth, straightness and survival at age 32 in a Pinus strobus x P. wallichiana F1 hybrid population (Experiment 1

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Ioan Blada

2013-12-01

Full Text Available An interspecific factorial hybridization was made, where seven P. strobus female parent trees were mated to four P. wallichiana male trees, in order to transfer genes for resistance to blister-rust from the blue pine to the F1 hybrids. The hybrid seedlings and the open pollinated families of the two parents were three times consecutively inoculated with blister-rust. The six years old seedlings were transplanted in the fi eld in the so called Valiug Experiment 1. The experimental design consisted in 28 hybrid full-sib families and two open pollinated families of the parent species. Plantation took place in a complete randomized block design with three blocks, with 6 to 12 seedlings per linear plot and 3 x 3 m spacing. This paper is based on the measurements made at age 32, just after the fi rst thinning. Diameter at breast height, tree height, tree volume, stem straightness and tree survival were the fi ve measured traits. According to ANOVA, signifi cant (p < 0.05 and highly signifi cant (p < 0.001 differences for diameter at breast height, tree height, volume growth rate, stem straightness and tree survival were detected between hybrid families. Highly signifi cant (p< 0.01, p < 0.001 differences were found between eastern white pine female parents for survival, stem straightness and all growth traits, suggesting that nuclear additive genes are controlling the respective characters. Consequently, high survival or genetic resistance to blister-rust can be found within the P. strobus species even though it is highly susceptible to this pathogen. The P. wallichiana parents exhibited signifi cant additive effects on straightness and breast height diameter, but no signifi cance in height, volume, and tree survival. The contribution of the additive variance to the phenotypic one was 65.7% for diameter, 58.6% for height, 50.5% for volume, 70.4% for stem straightness and 73.4% for tree survival. Hence, additive variance should be employed

Radiation carcinogenesis in radiosensitive mutant Scid mice

International Nuclear Information System (INIS)

Ogiu, Toshiaki; Ishii-Ohba, Hiroko; Kobayashi, Shigeru; Nishimura, Mayumi; Shimada, Yoshiya; Tsuji, Hideo; Watanabe, Fumiaki; Suzuki, Fumio; Sado, Toshihiko

2000-01-01

The Scid mice were established as a severe combined immunodeficient mouse strain lacking both T- and B-cell functions. Scid (homozygote), its parent strain C.B-17 (wild-type) and their hybrid F1 (heterozygote) were used for analysis of the relationship between sensitivity to acute effects of ionizing radiation and radiation-tumor development. Acute effects were studied using γ-rays and LD 50(30) was found to be 4.05 Gy in Scid, 6.5 Gy in F1 and 7.2 Gy in C.B-17. When bone marrow cells were irradiated with X-rays in vitro, survival curves of C.B-17 and F1 cells showed a region of shoulder with D 0 =0.68 and 0.67 Gy, respectively, while those of Scid were of no shoulder with D 0 =0.46 Gy. Scid mice died due to tumors (most were thymic lymphoma, T/L) 20-40 weeks after irradiation with 1-3 Gy γ-rays but C.B-17 and F1 survived longer. Bone marrow transplantation was found effective to prevent the radiation T/L. FACS analysis for surface antigens of those T/L cells suggested the change of Ras oncogenes. The change of Notch 1 gene was suggested by Southern hybridization and thus a possible role of defective DNA-PK in mice alone (not in rats and humans) was suggested as well. (K.H.)

The nature of tolerance in adult recipient mice made tolerant of alloantigens with supralethal irradiation followed by syngeneic bone marrow cell transplantation plus injection of F1 spleen cells

International Nuclear Information System (INIS)

Tomita, Y.; Himeno, K.; Mayumi, H.; Tokuda, N.; Nomoto, K.

1989-01-01

The length of time after syngeneic bone marrow reconstitution when tolerance to alloantigens can be induced in adult mice during T cell differentiation from bone marrow cells was studied by exposing those T cells to (recipient x donor)F1 spleen cells. Supralethally irradiated C3H/He Slc(C3H; H-2k) mice were reconstituted with 1 x 10(7) syngeneic T cell-depleted bone marrow cells and then injected intravenously with 5 x 10(7) (C3H x C57BL/6[B6])F1 (B6C3F1; H-2bxk) or (C3H x AKR/J[AKR])F1 (AKC3F1; H-2kxk) spleen cells at various intervals. In the fully allogeneic combination of B6C3F1----C3H, EL-4 tumor originating from B6 was accepted, and survival of grafted B6 skin was significantly prolonged in the tolerant C3H mice treated with irradiation on day -1 followed by injection of syngeneic bone marrow cells on day 0 plus B6C3F1 spleen cells on days 0, 5, or 10, in a tolerogen-specific manner. In the multiminor histocompatibility antigen-disparate combination of AKC3F1----C3H, AKR skin grafts were permanently accepted in the tolerant C3H mice treated with AKC3F1 spleen cells on days 0, 5, 10, or 15. Immunological parameters, including cytotoxic T lymphocyte activity and delayed foot-pad reaction (DFR), were almost completely suppressed in C3H mice made tolerant of B6 or AKR antigens. A chimeric assay using a direct immunofluorescence method revealed that the tolerant C3H mice given B6C3F1 spleen cells on day 0 were mixed-chimeric for at least 8 weeks after syngeneic bone marrow reconstitution, but not definitely chimeric thereafter. The C3H mice given AKC3F1 spleen cells on day 0 were chimeric even 43 weeks after syngeneic bone marrow reconstitution, but the C3H mice given AKC3F1 spleen cells on day 15 showed temporal chimerism that disappeared within 43 weeks. The untolerant mice were never detectably chimeric

Tissue culture-induced genetic and epigenetic alterations in rice pure-lines, F1 hybrids and polyploids.

Science.gov (United States)

Wang, Xiaoran; Wu, Rui; Lin, Xiuyun; Bai, Yan; Song, Congdi; Yu, Xiaoming; Xu, Chunming; Zhao, Na; Dong, Yuzhu; Liu, Bao

2013-05-05

Genetic and epigenetic alterations can be invoked by plant tissue culture, which may result in heritable changes in phenotypes, a phenomenon collectively termed somaclonal variation. Although extensive studies have been conducted on the molecular nature and spectrum of tissue culture-induced genomic alterations, the issue of whether and to what extent distinct plant genotypes, e.g., pure-lines, hybrids and polyploids, may respond differentially to the tissue culture condition remains poorly understood. We investigated tissue culture-induced genetic and epigenetic alterations in a set of rice genotypes including two pure-lines (different subspecies), a pair of reciprocal F1 hybrids parented by the two pure-lines, and a pair of reciprocal tetraploids resulted from the hybrids. Using two molecular markers, amplified fragment length polymorphism (AFLP) and methylation-sensitive amplified polymorphism (MSAP), both genetic and DNA methylation alterations were detected in calli and regenerants from all six genotypes, but genetic alteration is more prominent than epigenetic alteration. While significant genotypic difference was observed in frequencies of both types of alterations, only genetic alteration showed distinctive features among the three types of genomes, with one hybrid (N/9) being exceptionally labile. Surprisingly, difference in genetic alteration frequencies between the pair of reciprocal F1 hybrids is much greater than that between the two pure-line subspecies. Difference also exists in the pair of reciprocal tetraploids, but is to a less extent than that between the hybrids. The steady-state transcript abundance of genes involved in DNA repair and DNA methylation was significantly altered in both calli and regenerants, and some of which were correlated with the genetic and/or epigenetic alterations. Our results, based on molecular marker analysis of ca. 1,000 genomic loci, document that genetic alteration is the major cause of somaclonal variation in rice

Gestational Exposure to Bisphenol A Affects the Function and Proteome Profile of F1 Spermatozoa in Adult Mice.

Science.gov (United States)

Rahman, Md Saidur; Kwon, Woo-Sung; Karmakar, Polash Chandra; Yoon, Sung-Jae; Ryu, Buom-Yong; Pang, Myung-Geol

2017-02-01

Maternal exposure to the endocrine disruptor bisphenol A (BPA) has been linked to offspring reproductive abnormalities. However, exactly how BPA affects offspring fertility remains poorly understood. The aim of the present study was to evaluate the effects of gestational BPA exposure on sperm function, fertility, and proteome profile of F1 spermatozoa in adult mice. Pregnant CD-1 mice (F0) were gavaged with BPA at three different doses (50 μg/kg bw/day, 5 mg/kg bw/day, and 50 mg/kg bw/day) on embryonic days 7 to 14. We investigated the function, fertility, and related processes of F1 spermatozoa at postnatal day 120. We also evaluated protein profiles of F1 spermatozoa to monitor their functional affiliation to disease. BPA inhibited sperm count, motility parameters, and intracellular ATP levels in a dose-dependent manner. These effects appeared to be caused by reduced numbers of stage VIII seminiferous epithelial cells in testis and decreased protein kinase A (PKA) activity and tyrosine phosphorylation in spermatozoa. We also found that BPA compromised average litter size. Proteins differentially expressed in spermatozoa from BPA treatment groups are known to play a critical role in ATP generation, oxidative stress response, fertility, and in the pathogenesis of several diseases. Our study provides mechanistic support for the hypothesis that gestational exposure to BPA alters sperm function and fertility via down-regulation of tyrosine phosphorylation through a PKA-dependent mechanism. In addition, we anticipate that the BPA-induced changes in the sperm proteome might be partly responsible for the observed effects in spermatozoa. Citation: Rahman MS, Kwon WS, Karmakar PC, Yoon SJ, Ryu BY, Pang MG. 2017. Gestational exposure to bisphenol-A affects the function and proteome profile of F1 spermatozoa in adult mice. Environ Health Perspect 125:238-245; http://dx.doi.org/10.1289/EHP378.

Reevaluation of a twenty-four-month chronic toxicity/carcinogenicity study of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in the B6C3F1 hybrid mouse.

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Parker, George A; Reddy, Gunda; Major, Michael A

2006-01-01

Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) has been widely used as an explosive in U.S. army munitions formulations since World War II. Two-year carcinogenicity studies revealed RDX to be noncarcinogenic in two strains of rats, but a 2-year carcinogenicity study in B6C3F1 mice revealed an increased incidence of hepatocellular neoplasms in females. Based on results of the study in B6C3F1 mice, RDX has been classified as a possible carcinogen. The authors reevaluated the archived histological sections from the B6C3F1 mouse study, using current histopathologic diagnostic criteria and interpretations. The earlier evaluation showed a statistically significant increase in the incidence of hepatocellular adenoma/carcinoma in female mice from the three highest dose groups (7, 35, and 175/100 mg/kg/day). The revaluation yielded a slightly lower incidence at each of the dose levels in female mice. The reduced number of hepatocellular neoplasms was largely due to reclassification of hepatocellular adenomas as foci of cytoplasmic alteration, in compliance with current diagnostic criteria. The reevaluation was reviewed by a pathology working group (PWG), which arrived at a consensus classification of each lesion. Based on the consensus diagnoses of the PWG, only one female group (35 mg/kg/day) showed a significant increase when compared to controls. The incidence of hepatocellular neoplasms for all groups, including the 35 mg/kg/day group, was within the reported incidence range for spontaneous hepatocellular neoplasms in female B6C3F1 mice. The increased incidence of hepatocellular neoplasms in female mice given RDX at 35 mg/kg/day was interpreted as equivocal evidence of a carcinogenic effect.

Evaluation of 6-([18F] fluoroacetamido)-1-hexanoic-anilide (18F-FAHA) as imaging probe in tumor xenograft mice model

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Li, Fiona; Cho, Sung Ju; Yu, Lihai; Hudson, Robert H. E.; Luyt, Leonard G.; Pin, Christopher L.; Kovacs, Michael S.; Koropatnick, James; Lee, Ting-Yim

2016-03-01

Alteration in genetic expression is as important as gene mutation in cancer development and proliferation. Epigenetic changes affect gene expression without altering the DNA sequence. Histone deacetylase (HDAC), an enzyme facilitating histone remodelling, can lead to silencing of tumor suppressor genes making HDAC inhibitors viable anticancer drugs against tumors with increased activity of the enzyme. In this study we evaluated 18F-fluroacetamido-1-hexanoicanilide (18F-FAHA), an artificial HDAC substrate, as imaging probe of HDAC activity of human tumor xenografts in immunocompromised host mice. Human breast and melanoma cell lines, MDA-MB-468 and MDA-MB-435 respectively, known to overexpress HDAC activity were xenografted into immunocompromised mice and HDAC activity was imaged using 18F-FAHA. The melanoma group was treated with saline, SAHA (suberoylanilide hydroxamic acid, an approved anticancer HDAC inhibitor) in DMSO, or DMSO as positive control. Tracer kinetic modelling and SUV were used to estimate HDAC activity from dynamic PET data. Both breast tumor and melanoma group showed great variability in binding rate constant (BRC) of 18F-FAHA suggesting highly variable inter- and intra-tumoral HDAC activity. For the SAHA treated melanoma group, HDAC activity, as monitored by BRC of 18F-FAHA, decreased more than the two (positive and negative) control groups but not tumor growth. Our preliminary study showed that noninvasive PET imaging with 18F-FAHA has the potential to identify patients for whom treatment with HDAC inhibitors are appropriate, to assess the effectiveness of that treatment as an early marker of target reduction, and also eliminate the need for invasive tissue biopsy to individualize treatment.

Heterosis and heterobeltiotic studies of F1 hybirds in brassica carinata

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Nausheen; Farhatullah; Hussain, I.; Khalil, I.; Amanullah

2015-01-01

An experiment was carried out at the University of Agriculture, Peshawar during 2012-13 using a set of F /sub 1/ hybrids of B. carinata for estimating heterosis and heterobeltiosis for important yield and quality parameters. The experimental material comprised of six B. carinata parental genotypes viz. C-88, C-89, C-90, C-93, C-95, C-97 and their 30 F /sub 1/ hybrids as direct crosses. A randomized complete block design with two replicates was used for field evaluation of 36 B. carinata genotypes (6 parental lines and 30 F /sub 1/ hybrids). Significant genetic variation was observed for primary branches plant /sup 1/, main raceme length, seed yield plant /sup 1/, oil and protein content among parents as well as F /sub 1/ hybrids. The highest heterosis and heterobeltiosis for primary branches (24.25 vs. 12.30 percentage) and main raceme length (37.31 vs. 22.93 percentage) was recorded for F /sub 1/ hybrids C-88 * C-93 and C-89 * C-97, respectively. Hybrid C-93 * C-90 had the highest positive heterosis for seed yield plant /sup 1/ (23.33 percentage). For protein content, the maximum heterosis was recorded for hybrid C-88 * C-89 (11.34 percentage). Similarly, F /sub 1/ hybrid C-88 * C-97 showed maximum heterosis for oil content (14.41 percentage). The highest heterobeltiosis was exhibited by hybrids C-90 * C-97 for seed yield (9.53 percentage) , C-89 * C-90 for oil content (7.61 percentage) and C-93 * C-97 for protein content (4.11 percentage). Based on high mean performance and heterotic values, aforemntioned hybrids and their corresponding parental lines will be exploited further for commercial hybrid production. (author)

Relationships among quantitative traits in F3, F4 and F5 wheat hybrids obtained by pedigree and bulk selection

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Janković Snežana

2010-01-01

Full Text Available Relationships among quantitative traits of wheat were analyzed in parents and their F3, F4 and F5 hybrids. Three female parents (Briscard, Carifen 12 and Rescler were crossed with two male parents (Francuska and PKB-Prelivka. Same crosses were repeated 4 years, from 1996 to 1999. Hybrids were obtained via pedigree and bulk selection. In year 2000 the field experiments were set up with all parental and hybrid material, at the Institute 'PKB INI Agroekonomik', in Padinska Skela, near Belgrade. Six traits were measured: plant height, spike length, number of spikelets per spike, number of grains per spike, 1000 grain weight and grain weight per spike. In parental genotypes, it was found grain mass per spike was in significant and positive correlation with 1000 grain mass and number of grains per spike. As in parents, correlation between grain mass per spike and 1000 grain weight was almost functional in F3, F4 and F5 hybrids. However, correlation between grain mass per spike and number of grains per spike was negative or slight positive in hybrid descendents, what is surprising because it is oppositely to the parents. Similar values of correlation coefficients were found in both applied methods of selection. This fact shows correlations change between generations. Grain mass per spike depends on a 1000 grain mass in both, parental and hybrid generations. Stable relationship between traits could be use for selection of high yielding genotypes.

Pathology of Serially Sacrificed Female B6C3F1 Mice Continuously Exposed to Very Low-Dose-Rate Gamma Rays.

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Tanaka, I B; Komura, J; Tanaka, S

2017-03-01

We have previously reported on life span shortening as well as increased incidence rates in several neoplasms in B6C3F1 mice that were continuously exposed to 21 mGy/day of gamma rays for 400 days. To clarify whether the life shortening was due to early appearance of neoplasms (shortened latency) or increased promotion/progression, 8-week-old female specific-pathogen-free B6C3F1 mice were gamma-ray irradiated at a low dose rate of 20 mGy/day for 400 days. At 100 days postirradiation, 60-90 mice were sacrificed, and thereafter every 100 days alongside the age-matched nonirradiated controls, for 700 days. Additional groups were allowed to live out their natural life span. Pathological examination was performed on all mice to identify lesions, non-neoplastic and neoplastic, as well as to determine the cause of death. Body weights were significantly increased in irradiated mice from sacrifice days 200-500. Incidence rates for spontaneously occurring non-neoplastic lesions, such as adrenal subcapsular cell hyperplasia, fatty degeneration of the liver, atrophy and tubulostromal hyperplasia of the ovaries, were significantly increased in irradiated mice. Significantly increased incidence rates with no shortening of latency periods were observed in irradiated mice for malignant lymphomas, hepatocellular adenomas/carcinomas, bronchioloalveolar adenomas, harderian gland adenoma/adenocarcinoma. Shortened latencies with significantly increased incidence rates were observed for adrenal subcapsular cell adenomas and ovarian neoplasms (tubulostromal adenoma, granulosa cell tumors) in irradiated mice. Life span shortening in mice exposed to 20 mGy/day was mostly due to malignant lymphomas. Multiple primary neoplasms were significantly increased in mice exposed to 20 mGy/day from sacrifice days 400-700 and in the life span group. Our results confirm that continuous low-dose-rate gamma-ray irradiation of female B6C3F1 mice causes both cancer induction (shortened latency) and

Toxicology and carcinogenesis studies of nitrofurantoin (CAS No. 67-20-9) in F344/n rats and B6C3F1 mice (feed studies). Technical report

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French, J.E.

1989-09-01

Two-year toxicology and carcinogenesis studies were conducted by administering diets containing 0, 600, or 1,300 ppm nitrofurantoin to groups of 50 female rats for 103 weeks. Groups of 50 male rats and 50 mice of each sex were fed diets containing 0, 1,300 or 2,500 ppm for 103 weeks. Under the conditions of these 2-year feed studies, there was some evidence of carcinogenic activity of nitrofurantoin for male F344/N rats as shown by increased incidences of uncommon kidney tubular cell neoplasms. Uncommon osteosarcomas of the bone and neoplasms of the subcutaneous tissue were observed in dosed male rats. Incidences of interstitial cell adenomas of the testis and neoplasms of the preputial gland were decreased in the 2,500-ppm group of male rats. There was no evidence of carcinogenic activity of nitrofurantoin for female F344/N rats fed diets containing 600 ppm or 1,300 ppm for 2 years. Female rats may have been able to tolerate higher doses. There was no evidence of carcinogenic activity of nitrofurantoin for male B6C3F(1) mice fed diets containing 1,300 ppm or 2,500 ppm for 2 years. There was clear evidence of carcinogenic activity of nitrofurantoin for female B6C3F(1) mice as shown by increased incidences of tubular adenomas, benign mixed tumors, and granulosa cell tumors of the ovary.

Parental resistance of irradiated mice to (CBAXM523)F/sub 1/ lymphocytes: the destiny of transplanted cells, duration of resistance and its specificity

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Kondrat' eva, T K; Fontalin, L N; Nagurskaya, E V; Novikova, T K; Blandova, Z K; Chernousov, A D [Akademiya Meditsinskikh Nauk SSSR, Moscow. Inst. Ehpidemiologii i Mikrobiologii

1979-05-01

The immunologic reactivity of mouse (CBAxM523)F/sub 1/ lymphocytes to alien antigens (ram erythrocytes) in the organisms of lethally irradiated CBA mice was studied. If the irradiation, cell transfer and antigen test-injection were performed on the same day, the activity of the transplant was suppressed as compared to the syngenic system. If the intervals between these procedures increased to three days the activity of donor cells was recovered. The retransplantation of recipient spleen cells to the irradiated CBA and F/sub 1/ mice demonstrated the viability of the transplanted cells and the absence of their transadaptation to nonsyngenic microenvironment. The resistance of the recipients could be overcome specifically by preliminary injection of F/sub 1/ mouse cells in combination with cyclophosphamide or without it. The results obtained suggest to conclude, that the genetic parental resistance of CBA mice to F/sub 1/ mouse cells is caused by the immunologically competent recipient cells that are inactivated after three days following irradiation. They do not produce a cytotoxic effect on donor cells, but limit temporarily the activity of the latter.

Competitive proliferation in the hematopoietic tissues of irradiated hybrid mice engrafted with parental bone marrow and spleen

International Nuclear Information System (INIS)

Muramatsu, S.; Monnot, P.; Duplan, J.F.

1976-01-01

e kinetics of growth and differentiation of hematopoietic stem cells differ markedly according to their origin. A study of the ability of CFU from bone marrow (BM) or spleen to repopulate hemopoietic organs has been carried out in lethally irradiated mice restored with BM cells admixed with spleen cells bearing different chromosomal markers. Hemopoietic cells originating from AKR (40 acbrocentrics) and AKR/T1ALD (36 acrocentrics + 2 metacentrics) mice were engrafted into lethally irradiated (AKR x AKR/T1ALD)F1 or (C3H x AKR/T1ALD)F1 hybrid recipients. Within 10 days, the BM-derived elements outnumbered the spleen-derived population in BM and spleen. This held even when the number of injected spleen-CFU was twice that of BM-CFU. This difference of growth rate subsided within 20 days. The first cells to reappear in the thymus bore the recipient karyotype (endoregeneration); they were later replaced by BM-derived elements but spleen-derived cecells were never present in thymus in the case of competitive engraftment. In contrast, the lymph node cells bore the BM karyotype as well as the spleen karyotype. Injecting the spleen cells 3 days prior to the BM cells partially counterbalanced the overgrowth of the BM-derived elements in the BM and spleen but did not affect the thymic repopulation which remained strictly derived from BM-CFU. When mice were injected only with BM-CFU, or only with spleen-CFU, BM-derived cells were found in the thymus as early as 10-12 days after engraftment, whereas the spleen-derived cells did not appear in the thymus until days 18-20. (author)

NTP Toxicology and Carcinogenesis Studies of Benzene (CAS No. 71-43-2) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

Science.gov (United States)

1986-04-01

Benzene ranks 16th in production volume for chemicals produced in the United States, with approximately 9.9 billion pounds being produced in 1984, 9.1 billion pounds in 1983, and 7.8 billion pounds in 1982. This simplest aromatic chemical in used in the synthesis of styrene (polystyrene plastics and synthetic rubber), phenol (phenolic resins), cyclohexane (nylon), aniline, maleic anhydride (polyester resins), alkylbenzenes (detergents), chlorobenzenes, and other products used in the production of drugs, dyes, insecticides, and plastics. Benzene, along with other light, high-octane aromatic hydrocarbons, such as toluene and xylenes, is a component of motor gasoline. Benzene is also used as a solvent, but for most applications, it has been replaced by less hazardous solvents. During the 17-week studies, groups of 10 or 15 male and female F344/N rats and B6C3F1 mice were gavaged 5 days per week with benzene in corn oil (5 ml/kg) at doses of 0 to 600 mg/kg. No benzene-related deaths occurred; in rats that received benzene, final mean body weights were 14%-22% lower compared with vehicle controls and in mice, slight dose-related reductions were observed (less than 10% differences). Doses for the 2-year studies were selected based on clinical observations (tremors in higher dosed mice), on clinical pathologic findings (lymphoid depletion in rats and leukopenia in mice), and on body weight effects. Two-year toxicology and carcinogenesis studies of benzene (greater than 99.7% pure) were conducted in groups of 50 F344/N rats and 50 B6C3F1 mice of each sex and for each dose. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil (5 ml/kg) were administered by gavage to male rats, 5 days per week, for 103 weeks. Doses of 0, 25, 50, or 100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 weeks. Ten additional animals in each of the 16 groups were killed at 12 months and necropsies were performed. Hematologic

Craniomandibular form and body size variation of first generation mouse hybrids: A model for hominin hybridization.

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Warren, Kerryn A; Ritzman, Terrence B; Humphreys, Robyn A; Percival, Christopher J; Hallgrímsson, Benedikt; Ackermann, Rebecca Rogers

2018-03-01

Hybridization occurs in a number of mammalian lineages, including among primate taxa. Analyses of ancient genomes have shown that hybridization between our lineage and other archaic hominins in Eurasia occurred numerous times in the past. However, we still have limited empirical data on what a hybrid skeleton looks like, or how to spot patterns of hybridization among fossils for which there are no genetic data. Here we use experimental mouse models to supplement previous studies of primates. We characterize size and shape variation in the cranium and mandible of three wild-derived inbred mouse strains and their first generation (F 1 ) hybrids. The three parent taxa in our analysis represent lineages that diverged over approximately the same period as the human/Neanderthal/Denisovan lineages and their hybrids are variably successful in the wild. Comparisons of body size, as quantified by long bone measurements, are also presented to determine whether the identified phenotypic effects of hybridization are localized to the cranium or represent overall body size changes. The results indicate that hybrid cranial and mandibular sizes, as well as limb length, exceed that of the parent taxa in all cases. All three F 1 hybrid crosses display similar patterns of size and form variation. These results are generally consistent with earlier studies on primates and other mammals, suggesting that the effects of hybridization may be similar across very different scenarios of hybridization, including different levels of hybrid fitness. This paper serves to supplement previous studies aimed at identifying F 1 hybrids in the fossil record and to introduce further research that will explore hybrid morphologies using mice as a proxy for better understanding hybridization in the hominin fossil record. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mode of inheritance for fruit firmness in tomato hybrids of F1 generation (Lycoperscum esculentum Mill.

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Sušić Zoran

2000-01-01

Full Text Available Present day program for tomato selection are aimed at creating the genotypes with firm fruit. The fruits with this quality surfer from minor injuries while being harvested and transported, which directly affects their better consumption purpose. By crossing seven divergent tomato genotypes that differed among themselves in fruit firmness, and by applying the method of full diallel without reciprocal crossings, we obtained 21 hybrids of F1 generation. Upon analyzing the components of the genetic variance we found out that dominant genes prevailed in inheriting this feature. Considering all the crossing combinations together, it could be concluded that super dominance was the mode of inheritance recorded in Fl generation. The hybrid combination obtained by crossing the two hybrids with the best general combining ability (V-100 x No-10 was characterized by the best specific combining ability. .

Editor's Highlight: Complete Attenuation of Mouse Lung Cell Proliferation and Tumorigenicity in CYP2F2 Knockout and CYP2F1 Humanized Mice Exposed to Inhaled Styrene for up to 2 Years Supports a Lack of Human Relevance.

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Cruzan, George; Bus, James S; Banton, Marcy I; Sarang, Satinder S; Waites, Robbie; Layko, Debra B; Raymond, James; Dodd, Darol; Andersen, Melvin E

2017-10-01

Styrene is a mouse-specific lung carcinogen, and short-term mode of action studies have demonstrated that cytotoxicity and/or cell proliferation, and genomic changes are dependent on CYP2F2 metabolism. The current study examined histopathology, cell proliferation, and genomic changes in CD-1, C57BL/6 (WT), CYP2F2(-/-) (KO), and CYP2F2(-/-) (CYP2F1, 2B6, 2A13-transgene) (TG; humanized) mice following exposure for up to 104 weeks to 0- or 120-ppm styrene vapor. Five mice per treatment group were sacrificed at 1, 26, 52, and 78 weeks. Additional 50 mice per treatment group were followed until death or 104 weeks of exposure. Cytotoxicity was present in the terminal bronchioles of some CD-1 and WT mice exposed to styrene, but not in KO or TG mice. Hyperplasia in the terminal bronchioles was present in CD-1 and WT mice exposed to styrene, but not in KO or TG mice. Increased cell proliferation, measured by KI-67 staining, occurred in CD-1 and WT mice exposed to styrene for 1 week, but not after 26, 52, or 78 weeks, nor in KO or TG mice. Styrene increased the incidence of bronchioloalveolar adenomas and carcinomas in CD-1 mice. No increase in lung tumors was found in WT despite clear evidence of lung toxicity, or, KO or TG mice. The absence of preneoplastic lesions and tumorigenicity in KO and TG mice indicates that mouse-specific CYP2F2 metabolism is responsible for both the short-term and chronic toxicity and tumorigenicity of styrene, and activation of styrene by CYP2F2 is a rodent MOA that is neither quantitatively or qualitatively relevant to humans. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Comparison of three 18F-labeled carboxylic acids with 18F-FDG of the differentiation tumor from inflammation in model mice

International Nuclear Information System (INIS)

Wang, Hongliang; Tang, Ganghua; Hu, Kongzhen; Huang, Tingting; Liang, Xiang; Wu, Zhifang; Li, Sijin

2016-01-01

The aim of this study was to compare the properties and feasibility of the glucose analog, 2- 18 F-fluoro-2-deoxy-D-glucose ( 18 F-FDG), three short 18 F-labeled carboxylic acids, 18 F-fluoroacetate ( 18 F-FAC), 2- 18 F-fluoropropionic acid ( 18 F-FPA) and 4-( 18 F)fluorobenzoic acid ( 18 F-FBA), for differentiating tumors from inflammation. Biodistributions of 18 F-FAC, 18 F-FPA and 18 F-FBA were determined on normal Kunming mice, and positron emission tomography (PET) imaging with these tracers were performed on the separate tumor-bearing mice model and inflammation mice model in comparison with 18 F-FDG. Biodistribution results showed that 18 F-FAC and 18 F-FPA had similar biodistribution profiles and the slow radioactivity clearance from most tissues excluding the in vivo defluorination of 18 F-FAC, and 18 F-FBA demonstrated a lower uptake and fast clearance in most tissues. PET imaging with 18 F-FDG, 18 F-FAC and 18 F-FPA revealed the high uptake in both tumor and inflammatory lesions. The ratios of tumor-to-inflammation were 1.63 ± 0.28 for 18 F-FDG, 1.20 ± 0.38 for 18 F-FAC, and 1.41 ± 0.33 for 18 F-FPA at 60 min postinjection, respectively. While clear tumor images with high contrast between tumor and inflammation lesion were observed in 18 F-FBA/PET with the highest ratio of tumor-to-inflammation (1.98 ± 0.15). Our data demonstrated 18 F-FBA is a promising PET probe to distinguish tumor from inflammation. But the further modification of 18 F-FBA structure is required to improve its pharmacokinetics

4f-5d hybridization in a high k dielectric

International Nuclear Information System (INIS)

Losovyj, Ya.B.; Tang, Jinke; Wang, Wendong; Hong Yuanjia; Palshin, Vadim; Tittsworth, Roland

2006-01-01

While intra-atomic f-d hybridization is expected, experimental confirmation of f-d hybridization in the photoemission final state leading to 4f band structure has been limited to 5f systems and compound systems with very shallow 4f levels. We demonstrate that core 4f states can contribute to the valence band structure in a wide band gap dielectric, in this case HfO 2 in the photoemission final state. In spite of the complications of sample charging, we find evidence of symmetry in the shallow 4f levels and wave vector dependent band dispersion, the latter consistent with the crystal structure of HfO 2

Radiosensitivity of spermatogenous epithelium stem cells of mice of different strains and age

International Nuclear Information System (INIS)

Konoplyannikova, O.A.; Konoplyannikov, A.G.

1988-01-01

In experiments on CBA and BALB/c male mices (3 months of age) and F 1 (CBAxC57BL/6) hybrides (at the age of 3, 12, and 24 months) a difference was noted in the radiosensitivity of spermatogenous epithelium stem cells displayed by the changes in their colony-forming ability to testicular tubules 42 days following local 60 Co-γ-irradiation. The older the hybrid mice the smaller was the number of spermatogenous epithelium stem cells

Meiotic sex chromosome inactivation is disrupted in sterile hybrid male house mice.

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Campbell, Polly; Good, Jeffrey M; Nachman, Michael W

2013-03-01

In male mammals, the X and Y chromosomes are transcriptionally silenced in primary spermatocytes by meiotic sex chromosome inactivation (MSCI) and remain repressed for the duration of spermatogenesis. Here, we test the longstanding hypothesis that disrupted MSCI might contribute to the preferential sterility of heterogametic hybrid males. We studied a cross between wild-derived inbred strains of Mus musculus musculus and M. m. domesticus in which sterility is asymmetric: F1 males with a M. m. musculus mother are sterile or nearly so while F1 males with a M. m. domesticus mother are normal. In previous work, we discovered widespread overexpression of X-linked genes in the testes of sterile but not fertile F1 males. Here, we ask whether this overexpression is specifically a result of disrupted MSCI. To do this, we isolated cells from different stages of spermatogenesis and measured the expression of several genes using quantitative PCR. We found that X overexpression in sterile F1 primary spermatocytes is coincident with the onset of MSCI and persists in postmeiotic spermatids. Using a series of recombinant X genotypes, we then asked whether X overexpression in hybrids is controlled by cis-acting loci across the X chromosome. We found that it is not. Instead, one large interval in the proximal portion of the M. m. musculus X chromosome is associated with both overexpression and the severity of sterility phenotypes in hybrids. These results demonstrate a strong association between X-linked hybrid male sterility and disruption of MSCI and suggest that trans-acting loci on the X are important for the transcriptional regulation of the X chromosome during spermatogenesis.

NTP toxicity studies of dimethylaminopropyl chloride, hydrochloride (CAS No. 5407-04-5) administered by Gavage to F344/N rats and B6C3F1 mice.

Science.gov (United States)

Abdo, Km

2007-07-01

Dimethylaminopropyl chloride, hydrochloride is used primarily as an industrial and research organic chemical intermediate acting as an alkylating reagent in Grignard and other types of reactions. It is also used as a pharmaceutical intermediate for the synthesis of many types of drugs, as an agricultural chemical intermediate, as a photographic chemical intermediate, and as a biochemical reagent for enzyme and other studies. Human occupational or other accidental exposure can occur by inhalation, ingestion, or skin absorption. Male and female F344/N rats and B6C3F1 mice received dimethylaminopropyl chloride, hydrochloride (greater than 99% pure) in water by gavage for 2 weeks or 3 months. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes. In the 2-week toxicity studies, groups of five male and five female F344/N rats and B6C3F1 mice were administered doses of 0, 6.25, 12.5, 25, 50, or 100 mg dimethylaminopropyl chloride, hydrochloride/kg body weight in deionized water by gavage, 5 days per week for 16 days. All dosed male and female rats and mice survived until the end of the 2-week study; one vehicle control female mouse died early. Mean body weights of all dosed groups of rats and mice were similar to those of the vehicle control groups. No gross or microscopic lesions were considered related to dimethylaminopropyl chloride, hydrochloride administration. In the 3-month toxicity studies, groups of 10 male and 10 female F344/N rats and B6C3F1 mice were administered doses of 0, 6.25, 12.5, 25, 50, or 100 mg/kg in deionized water by gavage, 5 days per week for 3 months. One male rat in the 50 mg/kg group died during week 12 of the study, and one female mouse in the 100 mg/kg group died during week 9 and another during week 13. The final mean body weights of 50 mg/kg male rats and 50 mg/kg female mice were significantly less than those of the vehicle controls. Possible chemical-related clinical findings in rats

In Vivo Interplay between p27Kip1, GATA3, ATOH1, and POU4F3 Converts Non-sensory Cells to Hair Cells in Adult Mice

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Bradley J. Walters

2017-04-01

Full Text Available Summary: Hearing loss is widespread and persistent because mature mammalian auditory hair cells (HCs are nonregenerative. In mice, the ability to regenerate HCs from surrounding supporting cells (SCs declines abruptly after postnatal maturation. We find that combining p27Kip1 deletion with ectopic ATOH1 expression surmounts this age-related decline, leading to conversion of SCs to HCs in mature mouse cochleae and after noise damage. p27Kip1 deletion, independent of canonical effects on Rb-family proteins, upregulated GATA3, a co-factor for ATOH1 that is lost from SCs with age. Co-activation of GATA3 or POU4F3 and ATOH1 promoted conversion of SCs to HCs in adult mice. Activation of POU4F3 alone also converted mature SCs to HCs in vivo. These data illuminate a genetic pathway that initiates auditory HC regeneration and suggest p27Kip1, GATA3, and POU4F3 as additional therapeutic targets for ATOH1-mediated HC regeneration. : Auditory hair cells are nonregenerative, resulting in persistent hearing loss upon damage. Walters et al. find that manipulating two genes, p27Kip1 and Atoh1, induces the conversion of nonsensory cells to hair cells in adult mice. This effect is mediated by GATA3 and POU4F3, where POU4F3 alone was found to convert nonsensory cells. Keywords: regeneration, aging, differentiation, proliferation, development, cancer, sensory, cochlea, hearing

Radiosynthesis and pharmacokinetics of [18F]fluoroethyl bufalin in hepatocellular carcinoma-bearing mice

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Yang Z

2017-01-01

Full Text Available Zhaoshuo Yang,1 Jianhua Liu,2 Qingqing Huang,3 Zhouji Zhang,1 Jiawei Zhang,1 Yanjia Pan,1 Yunke Yang,1 Dengfeng Cheng4 1Department of Chinese Traditional Medicine, Zhongshan Hospital, Fudan University, 2School of Medicine, Shanghai Jiao Tong University, 3Department of Nuclear Medicine, Shanghai 10th People’s Hospital, Tongji University School of Medicine, 4Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China Purpose: Bufalin, the main component of a Chinese traditional medicine chansu, shows convincing anticancer effects in a lot of tumor cell lines. However, its in vivo behavior is still unclear. This research aimed to evaluate how bufalin was dynamically absorbed after intravenous injection in animal models. We developed a radiosynthesis method of [18F]fluoroethyl bufalin to noninvasively evaluate the tissue biodistribution and pharmacokinetics in hepatocellular carcinoma-bearing mice. Methods: [18F]fluoroethyl bufalin was synthesized with conjugation of 18F-CH2CH2OTs and bufalin. The radiochemical purity was proved by the radio-high-performance liquid chromatography (HPLC. The pharmacokinetic studies of [18F]fluoroethyl bufalin were then performed in Institute of Cancer Research (ICR mice. Furthermore, the biodistribution and metabolism of [18F]fluoroethyl bufalin in HepG2 and SMMC-7721 tumor-bearing nude mice were studied in vivo by micro-positron emission tomography (micro-PET. Results: The radiochemical purity (RCP of [18F]fluoroethyl bufalin confirmed by radio-HPLC was 99%±0.18%, and [18F]fluoroethyl bufalin showed good in vitro and in vivo stabilities. Blood dynamics of [18F]fluoroethyl bufalin conformed to the two compartments in the ICR mice model. The pharmacokinetic parameters of [18F]fluoroethyl bufalin were calculated by DAS 2.0 software. The area under concentration–time curve (AUC0–t and the values of clearance (CL were 540.137 µg/L·min and 0.001�

Genetic variability, heritability, character association and path analysis in F/sub 1/ hybrids of tomato

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Saleem, M.Y.; Iqbal, Q.; Asghar, M.

2013-01-01

Twenty-five F/sub 1/ hybrids generated from 5*5 diallel crosses were evaluated to study the quantitative genetics of yield and some yield related traits during 2009-10. Worth of room was realized for improvement due to highly significant genetic variations among all traits studied. The highest estimates of genotypic and phenotypic coefficients of variability were recorded for number of fruits per plant while fruit width was the most heritable trait. Plant height, number of fruits per plant and fruit weight revealed significant positive genotypic and phenotypic association along with direct positive effect on fruit yield per plant. It is therefore, recommended that fruit weight, number of fruits per plant and plant height should be given due importance in selection of promising crosses to develop commercial hybrid variety in tomato. (author)

Chimaerism in lymph nodes of F1 into irradiated parental recipient chimaeras rejecting skin allografts from the other parent

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Suman, L.; Silobrcic, V.; Kastelan, A.

1978-01-01

Mice of the C57BL strain were irradiated with 800 R over the whole body. The next day they received i.v. a mixture of 50 x 10 6 spleen and bone marrow cells from (C57BL x CBA-T6T6)F 1 hybrid mice, and were challenged with CBA-T6T6 skin grafts later on. About 20% of the recipients rejected the CBA-T6T6 skin, whereas the others were completely tolerant for more than 200 days. By using the cytotoxic test, we found that both tolerant and nontolerant recipients were complete chimaeras, i.e., had only (C57BL x CBA-T6T6)F 1 cells in their lymph nodes. However, analysis of the same mice by the chromosome marker technique disclosed a proportion of host (C57BL) cells in lymph nodes of both tolerant and nontolerant chimaeras. The percentage of host metaphases in nontolerant chimaeras was significantly higher than that in tolerant chimaeras (P 1 cells reacting against skin-specific transplantation antigen(s) of the parental graft

Nitrogen-15 uptake by whole plants and root callus cultures of inbred maize lines and their F1 hybrids

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Mladenova, Y.; Karadimova, M.

1981-01-01

The uptake of nitrogen-15 by 3 maize genotypes was investigated. Comparative analysis of N15 assimilation and distribution in the organs of intact plants of two self-pollinated lines and their F1 hybrid and also in a callus tissue of roots of the same genotypes was made. From the results the conclusion is drawn that the N-use efficiency of the female line is higher than that of the male line both in intact plants and callus tissues from roots. This fact indicates that the N-use efficiency is determined not only by the functions of the cells in the shoots, suggesting the participation of the photosynthetic carboxylases but also by the functions of cells without a photosynthesizing apparatus. The N-use efficiency in the F1 hybrid manifests ''heterosis'', in spite of the intact plants or root callus tissues are being studied. (author)

The influence of blood glucose level on distribution of 18F-FDG in mice with tumor

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Fu Zhanli; Lin Jinghui; Wang Rongfu; Zhu Shaoli; Zhang Chunli; Pan Zhongyun

2003-01-01

To explore the influence of blood glucose level on 18 F-FDG uptake in tumor and normal tissues of mice, thirty five mice carrying Ehrlich ascitic cancer (EAC) are fasted 20 h and divided into four groups. The glucose loading group (n=12) and the control group (n=11) is given a solution of 50% glucose and distilled water orally just one hour before the 18 F FDG injection. Another two groups (n=5, n=7) is given a solution of 10%, 30% glucose respectively. Before 18 F-FDG intravenous injection, blood glucose levels are measured. The mice are killed one hour after the 18 F FDG injection. The tumor and normal tissues are excised, weighed, and counted by a γ well counter. The quantity of 18 F-FDG uptake is expressed as standardized uptake value (SUV). Blood glucose levels of the mice with EAC in the glucose loading group are significantly elevated than the control group (11.98 ± 3.01 mmol/L vs. 3.95 ± 1. 11 mmol/L, P 18 F-FDG uptake ratios of tumor and muscle in the glucose-loading group (1.34, 0.86, 0.48, 0.09, 1.38 respectively) are significantly lower than those in the control group (3.02, 2.62, 0.80, 0.16, 5.38 respectively) (P 18 F-FDG uptake ratios of tumor and brain, heart and blood in the glucose loading group (8.31. 1.05, 1.58, 103.00 respectively) are significantly higher than those in the control group (1.57, 0.64, 1.20, 9.73 respectively) (P 18 F-FDG distribution in mice. suggesting the blood glucose level should be controlled during clinically 18 F-FDG imaging

Upregulation of estrogen receptor expression in the uterus of ovariectomized B6C3F1 mice and Ishikawa cells treated with bromoethane

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Aoyama, Hiroaki; Couse, John F.; Hewitt, Sylvia C.; Haseman, Joseph K.; He, Hong; Zheng, Xiaolin; Majstoravich, Sonja; Korach, Kenneth S.; Dixon, D.

2005-01-01

In a 2-year NTP bioassay, Bromoethane (BE) was found to induce endometrial neoplasms in the uterus of B6C3F1 mice [; ]. In women, hormonal influences, such as 'unopposed' estrogenic stimulus, have been implicated as important etiologic factors in uterine cancer. BE, however, does not affect the serum concentrations of sex hormones in female B6C3F1 mice [] and the mechanism of BE-induced uterine carcinogenesis still remains unclear. In the present study, we examined the estrogenic effects of BE on the uterus of ovariectomized B6C3F1 mice and on Ishikawa cells. Groups of 6 mice were given daily s.c. injections of 0, 100, 500 or 1000 mg BE/kg for 3 consecutive days. Mice treated with 17β-estradiol served as positive controls. Mice were necropsied 24 h after the final injection, and uteri were weighed and examined histologically and immunohistochemically along with the vagina. Changes observed in the estrogen-treated mice included increased uterine weights, edema and inflammation of the endometrium, increased epithelial layers of the uterine and vaginal lumens and keratinization of the vaginal epithelium. In the BE-treated mice, no such changes occurred; however, immunohistochemical staining of the uterus revealed a significant increase in immunoexpression of the estrogen receptor alpha (ERα) in the two higher dose groups. Analysis of mRNA also showed slightly increased uterine ERα expression in these groups. Upregulated expression of ERα was confirmed in BE-treated Ishikawa cells, in which Western blotting analyses identified an intense signal at approximately 66 kDa, which is consistent with ERα. These data suggest that upregulated expression of ERα may be important in the induction of endometrial neoplasms in BE-treated mice

Study of 4f hybridization in CeNiX with X=SnδGe1-δ, 0≤δ≤1

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Fuente, C. de la; Moral, A. del; Adroja, D.T.; Fraile, A.; Arnaudas, J.I.

2010-01-01

We report inelastic neutron scattering and core-level X-ray photoemission spectroscopy experiments for studying the Kondo problem in the CeNiX, X=Sn δ Ge 1-δ 0≤δ≤1 series. The neutron results confirm that they behave like a Kondo lattice for δ≥0.85, showing broad maxima at around 30 meV, typical of a crystal field magnetic scattering. So, the Ge doping could produce the suppression of the cerium magnetism observed for δ≤0.25. To open a more deep sight on this point, we have analyzed the 3d core-level XPS spectra by using the well-known Gunnarsson-Schoenhammer model. From this analysis, we have obtained the 'on-site' Coulomb bare repulsion for f states, U, and hybridization parameter, Δ, related with the hopping from the f states to the conduction ones. These U values are very similar for all compounds, about 7 eV, but the hybridization parameter slightly changes from 0.2 to 0.16 eV on increasing the Sn concentration. In Sn-rich compounds, the 4f occupation is close to spin limit fluctuation, which allows us to obtain an estimation of the Kondo temperatures, ∼1200 K, and the static 0 K susceptibility, ∼1.1x10 -3 emu/mol. Finally, we have done 'ab-initio' calculations based on the LDA+U+SO which confirm the existence of a small electronic gap opening in the DOS of Ge-rich compounds for U values lower than 7 eV.

Reproductive isolation in hybrid mice due to spermatogenesis defects at three meiotic stages.

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Oka, Ayako; Mita, Akihiko; Takada, Yuki; Koseki, Haruhiko; Shiroishi, Toshihiko

2010-09-01

Early in the process of speciation, reproductive failures occur in hybrid animals between genetically diverged populations. The sterile hybrid animals are often males in mammals and they exhibit spermatogenic disruptions, resulting in decreased number and/or malformation of mature sperms. Despite the generality of this phenomenon, comparative study of phenotypes in hybrid males from various crosses has not been done, and therefore the comprehensive genetic basis of the disruption is still elusive. In this study, we characterized the spermatogenic phenotype especially during meiosis in four different cases of reproductive isolation: B6-ChrX(MSM), PGN-ChrX(MSM), (B6 × Mus musculus musculus-NJL/Ms) F(1), and (B6 × Mus spretus) F(1). The first two are consomic strains, both bearing the X chromosome of M. m. molossinus; in B6-ChrX(MSM), the genetic background is the laboratory strain C57BL/6J (predominantly M. m. domesticus), while in PGN-ChrX(MSM) the background is the PGN2/Ms strain purely derived from wild M. m. domesticus. The last two cases are F(1) hybrids between mouse subspecies or species. Each of the hybrid males exhibited cell-cycle arrest and/or apoptosis at either one or two of three distinct meiotic stages: premeiotic stage, zygotene-to-pachytene stage of prophase I, and metaphase I. This study shows that the sterility in hybrid males is caused by spermatogenic disruptions at multiple stages, suggesting that the responsible genes function in different cellular processes. Furthermore, the stages with disruptions are not correlated with the genetic distance between the respective parental strains.

Multiple Roles of Myd88 in the Immune Response to the Plague F1-V Vaccine and in Protection against an Aerosol Challenge of Yersinia pestis CO92 in Mice

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Jennifer L. Dankmeyer

2014-01-01

Full Text Available The current candidate vaccine against Yersinia pestis infection consists of two subunit proteins: the capsule protein or F1 protein and the low calcium response V protein or V-antigen. Little is known of the recognition of the vaccine by the host’s innate immune system and how it affects the acquired immune response to the vaccine. Thus, we vaccinated Toll-like receptor (Tlr 2, 4, and 2/4-double deficient, as well as signal adaptor protein Myd88-deficient mice. We found that Tlr4 and Myd88 appeared to be required for an optimal immune response to the F1-V vaccine but not Tlr2 when compared to wild-type mice. However, there was a difference between the requirement for Tlr4 and MyD88 in vaccinated animals. When F1-V vaccinated Tlr4 mutant (lipopolysaccharide tolerant and Myd88-deficient mice were challenged by aerosol with Y. pestis CO92, all but one Tlr4 mutant mice survived the challenge, but no vaccinated Myd88-deficient mice survived the challenge. Spleens from these latter nonsurviving mice showed that Y. pestis was not cleared from the infected mice. Our results suggest that MyD88 appears to be important for both an optimal immune response to F1-V and in protection against a lethal challenge of Y. pestis CO92 in F1-V vaccinated mice.

Induction of Cyp1a1 and Cyp1b1 and formation of DNA adducts in C57BL/6, Balb/c, and F1 mice following in utero exposure to 3-methylcholanthrene

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Xu Mian; Nelson, Garret B.; Moore, Joseph E.; McCoy, Thomas P.; Dai, Jian; Manderville, Richard A.; Ross, Jeffrey A.; Miller, Mark Steven

2005-01-01

Fetal mice are more sensitive to chemical carcinogens than are adults. Previous studies from our laboratory demonstrated differences in the mutational spectrum induced in the Ki-ras gene from lung tumors isolated from [D2 x B6D2F1]F2 mice and Balb/c mice treated in utero with 3-methylcholanthrene (MC). We thus determined if differences in metabolism, adduct formation, or adduct repair influence strain-specific responses to transplacental MC exposure in C57BL/6 (B6), Balb/c (BC), and reciprocal F1 crosses between these two strains of mice. The induction of Cyp1a1 and Cyp1b1 in fetal lung and liver tissue was determined by quantitative fluorescent real-time PCR. MC treatment caused maximal induction of Cyp1a1 and Cyp1b1 RNA 2-8 h after injection in both organs. RNA levels for both genes then declined in both fetal organs, but a small biphasic, secondary increase in Cyp1a1 was observed specifically in the fetal lung 24-48 h after MC exposure in all four strains. Cyp1a1 induction by MC at 4 h was 2-5 times greater in fetal liver (7000- to 16,000-fold) than fetal lung (2000- to 6000-fold). Cyp1b1 induction in both fetal lung and liver was similar and much lower than that observed for Cyp1a1, with induction ratios of 8- to 18-fold in fetal lung and 10- to 20-fold in fetal liver. The overall kinetics and patterns of induction were thus very similar across the four strains of mice. The only significant strain-specific effect appeared to be the relatively poor induction of Cyp1b1 in the parental strain of B6 mice, especially in fetal lung tissue. We also measured the levels of MC adducts and their disappearance from lung tissue by the P 32 post-labeling assay on gestation days 18 and 19 and postnatal days 1, 4, 11, and 18. Few differences were seen between the different strains of mice; the parental strain of B6 mice had nominally higher levels of DNA adducts 2 (gestation day 19) and 4 (postnatal day 1) days after injection, although this was not statistically significant

Reactivation of Immunological Response in Lethally X-Irradiated Mice Treated with Isogeneic Bone Marrow

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Stankovic, V.; Slijepcevic, M.; Hrsak, I. [Institute Ruder Boskovic, Zagreb, Yugoslavia (Croatia)

1968-08-15

Male and female C57BL/H and CBA/H mice aged 10-12 weeks were used as recipients and donors, respectively. All recipient mice were given a lethal whole-body X-irradiation dose (850 R for C57BL and 950 R for CBA mice) followed by iv injection of 10 x 106 isogeneic eosin-negative bone-marrow cells suspended in 0.5 ml of Hank's solution. The number of eosin-positive cells was less than 10%. The state of immunological responsiveness of irradiated recipients was measured at different time intervals up to 86 days after irradiation. The immune response to bacterial antigen was measured with the titre of agglutinating antibodies in serum six days after iv antigenic stimulation with a suspension of 2 x 10{sup 7} killed Salmonella typhimurium cells. The immune response to tissue antigens was evaluated by: (a) the effectiveness of the spleen cells from isologous radiation chimeric parental mice in preventing bone marrow from F{sub 1} (C57BL x CBA) hybrid donor from therapeutically affecting lethally irradiated F j recipient mice; (b) the effectiveness of the spleen cells in inducing splenom egaly in recipient F{sub 1} hybrid mice (Simonsen test). It was found that the responsiveness to bacterial antigens reappears much earlier and increases much faster than the immunological responsiveness to tissue antigens. (author)

Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

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Guo, Tai L.; Wang, Yunbiao; Xiong, Tao; Ling, Xiao; Zheng, Jianfeng

2014-01-01

Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100 mg/kg doses (i.p.): the first dose was administered at approximately 2 weeks following the initiation of daily GE (20 mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes. - Highlights: • Diets affected streptozotocin-induced diabetes in male B6C3F1 mice. • Genistein modulation of streptozotocin diabetes can be induced by diet. �

Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

Energy Technology Data Exchange (ETDEWEB)

Guo, Tai L., E-mail: tlguo1@uga.edu [Department of Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382 (United States); Wang, Yunbiao [Department of Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7382 (United States); Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102 (China); Xiong, Tao [College of Animal Science, Yangtze University, Jingzhou City, Hubei Province 434025 (China); Ling, Xiao [Institute for Food and Drug Control of Shandong Province, Jinan City, Shandong 250012 (China); Zheng, Jianfeng [Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0613 (United States)

2014-11-01

Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100 mg/kg doses (i.p.): the first dose was administered at approximately 2 weeks following the initiation of daily GE (20 mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes. - Highlights: • Diets affected streptozotocin-induced diabetes in male B6C3F1 mice. • Genistein modulation of streptozotocin diabetes can be induced by diet. �

Adrenergic pathway activation enhances brown adipose tissue metabolism: A [18 F]FDG PET/CT study in mice

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Mirbolooki, M. Reza; Upadhyay, Sanjeev Kumar; Constantinescu, Cristian C.; Pan, Min-Liang; Mukherjee, Jogeshwar

2014-01-01

Objective: Pharmacologic approaches to study brown adipocyte activation in vivo with a potential of being translational to humans are desired. The aim of this study was to examine pre- and postsynaptic targeting of adrenergic system for enhancing brown adipose tissue (BAT) metabolism quantifiable by [ 18 F]fluoro-2-deoxyglucose ([ 18 F]FDG) positron emission tomography (PET)/computed tomography (CT) in mice. Methods: A β 3 -adrenoreceptor selective agonist (CL 316243), an adenylyl cyclase enzyme activator (forskolin) and a potent blocker of presynaptic norepinephrine transporter (atomoxetine), were injected through the tail vein of Swiss Webster mice 30 minutes before intravenous (iv) administration of [ 18 F]FDG. The mice were placed on the PET/CT bed for 30 min PET acquisition followed by 10 min CT acquisition for attenuation correction and anatomical delineation of PET images. Results: Activated interscapular (IBAT), cervical, periaortic and intercostal BAT were observed in 3-dimentional analysis of [ 18 F]FDG PET images. CL 316243 increased the total [ 18 F]FDG standard uptake value (SUV) of IBAT 5-fold greater compared to that in placebo-treated mice. It also increased the [ 18 F]FDG SUV of white adipose tissue (2.4-fold), and muscle (2.7-fold), as compared to the control. There was no significant difference in heart, brain, spleen and liver uptakes between groups. Forskolin increased [ 18 F]FDG SUV of IBAT 1.9-fold greater than that in placebo-treated mice. It also increased the [ 18 F]FDG SUV of white adipose tissue (2.2-fold) and heart (5.4-fold) compared to control. There was no significant difference in muscle, brain, spleen, and liver uptakes between groups. Atomoxetine increased [ 18 F]FDG SUV of IBAT 1.7-fold greater than that in placebo-treated mice. There were no significant differences in all other organs compared to placebo-treated mice except liver (1.6 fold increase). A positive correlation between SUV levels of IBAT and CT Hounsfield unit (HU

Promotion of hepatic preneoplastic lesions in male B6C3F1 mice by unleaded gasoline.

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Standeven, A M; Wolf, D C; Goldsworthy, T L

1995-01-01

In previous studies, unleaded gasoline (UG) vapor was found to be a liver tumor promoter and hepatocarcinogen in female mice, but UG was not a hepatocarcinogen in male mice. However, UG vapor had similar transient mitogenic effects in nonlesioned liver of both male and female mice under the conditions of the cancer bioassay. We used an initiation-promotion protocol to determine whether UG vapor acts as a liver tumor promoter in male mice and to examine proliferative effects that may be critical to tumor development. Twelve-day-old male B6C3F1 mice were injected with N-nitrosodiethylamine (DEN; 5 mg/kg, intraperitoneally) or vehicle. Starting at 5-7 weeks of age, mice were exposed by inhalation 6 hr/day, 5 days/week for 16 weeks to 0 or 2046 ppm of PS-6 blend UG. UG treatment caused a significant 2.3-fold increase in the number of macroscopic hepatic masses in DEN-initiated mice, whereas no macroscopic masses were observed in non-initiated mice. Altered hepatic foci (AHF), which were predominantly basophilic in phenotype, were found almost exclusively in DEN-initiated mice. UG treatment significantly increased both the mean volume (threefold) and the volume fraction (twofold) of the AHF without increasing the number of AHF per unit area. UG also induced hepatic pentoxyresorufin-O-dealkylase (PROD) activity, a marker of CYP2B, by more than 12-fold over control with or without DEN cotreatment. To study hepatocyte proliferative effects of UG, we treated mice with 5-bromo-2'-deoxyuridine (BrdU) via osmotic pump for 3 days before necropsy and measured hepatocyte BrdU labeling index (LI) in AHF and nonlesioned liver.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1. PMID:7588481

NTP Toxicology and Carcinogenesis Studies of Dimethyl Methylphosphonate (CAS No. 756-79-6) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

Science.gov (United States)

1987-11-01

Dimethyl methylphosphonate (98% pure) is one of four chemicals nominated by the U.S. Army for toxicology and carcinogenesis studies because it was being considered for use to simulate the physical and spectroscopic (but not the biologic) properties of anticholinesterase (nerve) agents. Dimethyl methylphosphonate is also used as a flame retardant, a preignition additive for gasoline, an antifoam agent, a plasticizer and stabilizer, a textile conditioner and antistatic agent, and an additive for solvents and low-temperature hydraulic fluids. The United States produces 0.2-2 million pounds (91,000-910,000 kg) of per year. Gavage was chosen as the route of administration for all four candidate "simulants" to mimic potential exposure. Experimental Design: Dimethyl methylphosphonate was administered in corn oil by gavage to male and female F344/N rats and B6C3F1 mice in single-administration, 15-day, and 13-week studies to obtain toxicity data, to establish dose levels for the 2-year studies, and to identify target tissues. Additional studies were also performed to determine toxicity to the reproductive system of male F344/N rats and B6C3F1 mice and to study the potential for genetic damage in bacteria, mammalian cells, and Drosophila. Single-Administration Studies: In the single-administration studies, dimethyl methylphosphonate was given to rats and mice at doses up to 6,810 mg/kg body weight. No compound-related deaths were seen in male or female rats or male mice; two high dose female mice died. Rats exhibited inactivity, unsteady gait, and prostration after dosing; mice were inactive after dosing. Fifteen-Day Studies: Rats and mice received doses of 0, 1,250, 2,500, 5,000, 10,000, or 15,000 mg/kg dimethyl methylphosphonate per day. Compound-related deaths occurred in the three highest dose groups of rats and the two highest dose groups of mice. Rats receiving doses of 2,500 mg/kg or higher were inactive and at 5,000 or 10,000 mg/kg had an unsteady gait after dosing

F-18-FDG-hybrid-camera-PET in patients with postoperative fever

International Nuclear Information System (INIS)

Meller, J.; Lehmann, K.; Siefker, U.; Meyer, I.; Altenvoerde, G.; Becker, W.; Sahlmann, C.O.; Schreiber, K.

2002-01-01

Aim: Evaluation of F-18-FDG-hybrid-camera-PET imaging in patients with undetermined postoperative fever (POF). Methods: Prospective study of 18 patients (9 women, 9 men; age 23-85 years) suffering from POF with 2-fluoro-2'-deoxyglucose (F-18-FDG) using a dual headed coincidence camera (DHCC). Surgery had been performed 5-94 days prior to our investigation. 13 of the 18 patients received antibiotic therapy during the time of evaluation. Ten (55%) had an infectious and eight (45%) a norr infectious cause of fever. Results: Increased F-18-FDG-uptake outside the surgical wound occurred in 13 regions (infection n = 11, malignancy n = 2). The sensitivity of F-18-FDG-hybrid-camera-PET in imaging infection in areas outside the surgical wound was 86% and the specificity 100%, respectively. Antibiotic therapy did not negatively influence the results of F-18-FDG-scanning. Increased F-18-FDG-uptake within the surgical wound was seen in 8 of 18 patients. The sensitivity of F-18-FDG-hybrid-camera-PET in imaging infection within the surgical wound was 100% and the specificty 56%, respectively. The interval between surgery and F-18-FDG-scanning was significantly shorter in patients with false positive results compared with patients showing true negative results (median 34 vs. 54 days; p = 0,038). Conclusion: In POF-Patients, F-18-FDG transaxial tomography performed with a F-18-FDG-hybrid-camera-PET is sensitive in the diagnosis of inflammation and malignant disease within and outside the surgical wound. Because of the accumulation of the tracer both in granulation tissue and infection, the specificity in detecting the focus of fever within the surgical wound is poor. (orig.) [de

NTP Toxicology and Carcinogenesis Studies of Molybdenum Trioxide (CAS No. 1313-27-5) in F344 Rats and B6C3F1 Mice (Inhalation Studies).

Science.gov (United States)

1997-04-01

Molybdenum is an essential element for the function of nitrogenase in plants and as a cofactor for enzymes including xanthine oxidoreductase, aldehyde oxidase, and sulfide oxidase in animals. Molybdenum trioxide is used primarily as an additive to steel and corrosion-resistant alloys. It is also used as a chemical intermediate for molybdenum products; an industrial catalyst; a pigment; a crop nutrient; components of glass, ceramics, and enamels; a flame retardant for polyester and polyvinyl chloride resins; and a reagent in chemical analyses. Molybdenum trioxide was nominated by the NCI for toxicity and carcinogenicity studies as a representative inorganic molybdenum compound. The production of molybdenum trioxide is the largest of all the molybdenum compounds examined. Male and female F344/N rats and B6C3F1 mice were exposed to molybdenum trioxide (approximately 99% pure) by inhalation for 14 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and cultured Chinese hamster ovary cells. 14-DAY STUDY IN RATS: Groups of five male and five female F344/N rats were exposed to 0, 3, 10, 30, 100, or 300 mg molybdenum trioxide/m(3). Rats were exposed for 6 hours per day, 5 days per week, for a total of 10 exposure days during a 14-day period. All rats survived to the end of the study. The final mean body weights of male rats exposed to 100 mg/m(3) and male and female rats exposed to 300 mg/m(3) were significantly lower than those of the control groups. Male rats exposed to 300 mg/m(3) lost weight during the study. There were no clinical findings related to exposure to molybdenum trioxide. No chemical-related lesions were observed. 14-DAY STUDY IN MICE: Groups of five male and five female B6C3F1 mice were exposed to 0, 3, 10, 30, 100, or 300 mg molybdenum trioxide/m(3). Mice were exposed 6 hours per day, 5 days per week, for a total of 10 exposure days during a 14-day period. All mice survived to the end of the study. Final mean

Study of 4f hybridization in CeNiX with X=Sn{sub d}eltaGe{sub 1-d}elta, 0<=delta<=1

Energy Technology Data Exchange (ETDEWEB)

Fuente, C. de la, E-mail: cesar@unizar.e [Depto. Fisica de la Materia Condensada, Laboratorio de Magnetismo, Universidad de Zaragoza and ICMA-CSIC (Spain); Moral, A. del [Depto. Fisica de la Materia Condensada, Laboratorio de Magnetismo, Universidad de Zaragoza and ICMA-CSIC (Spain); Adroja, D.T. [ISIS Facility, Rutherford Appleton Laboratory, Chilton, Didcot, Oxfordshire OX11 0QX (United Kingdom); Fraile, A. [Depto. Fisica de la Materia Condensada, Laboratorio de Magnetismo, Universidad de Zaragoza and ICMA-CSIC (Spain); Arnaudas, J.I. [Instituto de Nanociencia de Aragon, Universidad de Zaragoza (Spain)

2010-05-15

We report inelastic neutron scattering and core-level X-ray photoemission spectroscopy experiments for studying the Kondo problem in the CeNiX, X=Sn{sub d}eltaGe{sub 1-d}elta 0<=delta<=1 series. The neutron results confirm that they behave like a Kondo lattice for delta>=0.85, showing broad maxima at around 30 meV, typical of a crystal field magnetic scattering. So, the Ge doping could produce the suppression of the cerium magnetism observed for delta<=0.25. To open a more deep sight on this point, we have analyzed the 3d core-level XPS spectra by using the well-known Gunnarsson-Schoenhammer model. From this analysis, we have obtained the 'on-site' Coulomb bare repulsion for f states, U, and hybridization parameter, DELTA, related with the hopping from the f states to the conduction ones. These U values are very similar for all compounds, about 7 eV, but the hybridization parameter slightly changes from 0.2 to 0.16 eV on increasing the Sn concentration. In Sn-rich compounds, the 4f occupation is close to spin limit fluctuation, which allows us to obtain an estimation of the Kondo temperatures, approx1200 K, and the static 0 K susceptibility, approx1.1x10{sup -3} emu/mol. Finally, we have done 'ab-initio' calculations based on the LDA+U+SO which confirm the existence of a small electronic gap opening in the DOS of Ge-rich compounds for U values lower than 7 eV.

Metabolic fate of 18F-FDG in mice bearing either SCCVII squamous cell carcinoma or C3H mammary carcinoma

DEFF Research Database (Denmark)

Kaarstad, Katrin; Bender, Dirk; Bentzen, Lise

2002-01-01

in mice. METHODS: 18F-FDG was given intravenously to mice with either SCCVII squamous cell carcinoma or C3H mammary carcinoma grown on the back. 18F-Labeled metabolites were determined by radio-high-performance liquid chromatography in tumor tissue biopsies, in a time course of 180 min (12 mice of each...... tumor type), and in liver tissue biopsies 80 min after tracer injection (2 mice of each type). RESULTS: After the tracer injection, not only 18F-FDG and 18F-FDG-6-P but also 18F-FD-PG1 and 2-18F-fluoro-2-deoxy-1,6-biphosphate were detected in both tumors, relatively more in SCCVII carcinoma than in C3H...... carcinoma. Both tumors accumulated radioactivity throughout the 180-min measurement period, 4-fold more in SCCVII carcinoma than in C3H carcinoma. At 80 min, the radioactivity was approximately 6 and 1.2 times higher in the respective tumors than in liver tissue. CONCLUSION: Our results agree...

Synthesis and kinetics of [18F]4'-fluoroantipyrine in normal mice

International Nuclear Information System (INIS)

Robbins, P.J.; Fortman, D.L.; Scholz, K.L.; Fusaro, G.A.; Sodd, V.J.

1978-01-01

Antipyrine labeled with radioiodine has proven useful for studying the symmetry of human brain perfusion by gamma-camera techniques. The feasibility of preparing F-18-labeled antipyrine for eventual use with a positron camera was investigated. The preparation of [ 18 F] 4'-fluoroantipyrine and its distribution in normal mice were used to evaluate this potential. 4'-Fluoroantipyrine was prepared in 7 to 20% chemical yield by the pyrolysis of the 4'-diazonium fluoroborate salt of antipyrine. This Schiemann salt was prepared by a five-step synthesis from 1-(4'-nitrophenyl)-3-methyl-5-chloro-pyrazole. Fluorine-18 labeling of the diazonium fluoroborate salt by exchange with aqueous F-18 and pyrolysis of the dried labeled salt produced [ 18 F] 4'-fluoroantipyrine with specific activities of 0.83 to 2.7 μCi/mg. The incorporated F-18 activity ranged from 0.53 to 1.9%. The labeling procedure took about 3 hr. The labeled antipyrine was administered by tail vein to fasting female Swiss-Cox mice. Distribution of F-18 at 12, 30, 60, and 120 sec, and 10 min, after injection showed that radioactivity persisted in the brain up to 120 sec at a level greater than that of the skin and the bone. (Skin and bone samples were chosen as representative of activities in the scalp and skull surrounding the brain.) Thus, perfusion imaging of the CNS should be possible when greater quantities of high-specific-activity F-18-labeled antipyrine becomes available

Male fitness of oilseed rape (¤Brassica napus¤), weedy ¤B-rapa¤ and their F1 hybrids when pollinating ¤B-rapa¤ seeds

DEFF Research Database (Denmark)

Pertl, M.; Hauser, T.P.; Damgaard, C.

2002-01-01

The likelihood that two species hybridise and backcross may depend strongly on environmental conditions, and possibly on competitive interactions between parents and hybrids. We studied the paternity of seeds produced by weedy Brassica rapa growing in mixtures with oilseed rape (B. napus) and the...... is strongly influenced by their local frequencies, and that male fitness of F(1)hybrids, when pollinating B. rapa seeds, is low even when their female fitness (seed set) is high.......The likelihood that two species hybridise and backcross may depend strongly on environmental conditions, and possibly on competitive interactions between parents and hybrids. We studied the paternity of seeds produced by weedy Brassica rapa growing in mixtures with oilseed rape (B. napus......) and their F(1) hybrids at different frequencies and densities. Paternity was determined by the presence of a transgene, morphology, and AFLP markers. In addition, observations of flower and pollen production, and published data on pollen fertilisation success, zygote survival, and seed germination, allowed us...

Widespread over-expression of the X chromosome in sterile F₁hybrid mice.

Directory of Open Access Journals (Sweden)

Jeffrey M Good

2010-09-01

Full Text Available The X chromosome often plays a central role in hybrid male sterility between species, but it is unclear if this reflects underlying regulatory incompatibilities. Here we combine phenotypic data with genome-wide expression data to directly associate aberrant expression patterns with hybrid male sterility between two species of mice. We used a reciprocal cross in which F₁ males are sterile in one direction and fertile in the other direction, allowing us to associate expression differences with sterility rather than with other hybrid phenotypes. We found evidence of extensive over-expression of the X chromosome during spermatogenesis in sterile but not in fertile F₁ hybrid males. Over-expression was most pronounced in genes that are normally expressed after meiosis, consistent with an X chromosome-wide disruption of expression during the later stages of spermatogenesis. This pattern was not a simple consequence of faster evolutionary divergence on the X chromosome, because X-linked expression was highly conserved between the two species. Thus, transcriptional regulation of the X chromosome during spermatogenesis appears particularly sensitive to evolutionary divergence between species. Overall, these data provide evidence for an underlying regulatory basis to reproductive isolation in house mice and underscore the importance of transcriptional regulation of the X chromosome to the evolution of hybrid male sterility.

Widespread over-expression of the X chromosome in sterile F₁hybrid mice.

Science.gov (United States)

Good, Jeffrey M; Giger, Thomas; Dean, Matthew D; Nachman, Michael W

2010-09-30

The X chromosome often plays a central role in hybrid male sterility between species, but it is unclear if this reflects underlying regulatory incompatibilities. Here we combine phenotypic data with genome-wide expression data to directly associate aberrant expression patterns with hybrid male sterility between two species of mice. We used a reciprocal cross in which F₁ males are sterile in one direction and fertile in the other direction, allowing us to associate expression differences with sterility rather than with other hybrid phenotypes. We found evidence of extensive over-expression of the X chromosome during spermatogenesis in sterile but not in fertile F₁ hybrid males. Over-expression was most pronounced in genes that are normally expressed after meiosis, consistent with an X chromosome-wide disruption of expression during the later stages of spermatogenesis. This pattern was not a simple consequence of faster evolutionary divergence on the X chromosome, because X-linked expression was highly conserved between the two species. Thus, transcriptional regulation of the X chromosome during spermatogenesis appears particularly sensitive to evolutionary divergence between species. Overall, these data provide evidence for an underlying regulatory basis to reproductive isolation in house mice and underscore the importance of transcriptional regulation of the X chromosome to the evolution of hybrid male sterility.

Anatomy of $F_D$-Term Hybrid Inflation

CERN Document Server

Garbrecht, B; Pilaftsis, Apostolos; Garbrecht, Bjorn; Pallis, Constantinos; Pilaftsis, Apostolos

2006-01-01

We analyze the cosmological implications of F-term hybrid inflation with a subdominant Fayet--Iliopoulos D-term whose presence explicitly breaks a D-parity in the inflaton-waterfall sector. This scenario of inflation, which is called F_D-term hybrid model for brevity, can naturally predict lepton number violation at the electroweak scale, by tying the mu-parameter of the MSSM to an SO(3)-symmetric Majorana mass m_N, via the vacuum expectation value of the inflaton field. We show how a negative Hubble-induced mass term in a next-to-minimal extension of supergravity helps to accommodate the present CMB data and considerably weaken the strict constraints on the theoretical parameters, resulting from cosmic string effects on the power spectrum P_R. The usual gravitino overabundance constraint may be significantly relaxed in this model, once the enormous entropy release from the late decays of the ultraheavy waterfall gauge particles is properly considered. As the Universe enters a second thermalization phase invo...

Combining ability analysis in intraspecific f/sub 1/ diallel cross of upland cotton

International Nuclear Information System (INIS)

Khan, S.A.; Khan, N.U.; Mohammad, F.

2011-01-01

The research work comprised of combining ability and genetic variability in a 6 X 6 F1 diallel cross which was carried out during crop seasons 2008 and 2009 at Khyber Pakhtunkhwa Agricultural University, Peshawar, Pakistan. The parental genotypes (CIM-446, CIM-496, CIM-499, CIM-506, CIM-554 and CIM-707) were crossed in a complete diallel fashion during 2008. The 30 F1 hybrids and their parents were grown in a randomized complete block (RCB) design with three replications during 2009. Genotypes manifested significant (p less than or equal to 0.01) differences for days to first flowering, locules boll/sup -1/, seeds locule/sup -1/, lint % and seed cotton yield plant/sup -1/. The F1 hybrids showed significant increase over parents in mean values for all the traits. The correlation of seed cotton yield was significantly positive with majority of yield traits and negative with days to first flowering and lint %. Mean squares due to general (GCA) and specific combining ability (SCA) were highly significant for all the traits, except locules for GCA. Mean squares due to GCA were higher in magnitude than SCA for majority of the traits and their inheritance was mainly governed by additive type of gene action and partially by non-additive. Selection in such promising hybrids could be used in segregating generations, and also some specific cross combinations can be used for hybrid cotton production to increase the seed cotton yield. The best general combiners (CIM-446 and CIM-554) followed by CIM-496 and their utilization as one of the parents produced best specific F1 hybrids (CIM-446 X CIM-499, CIM-446 X CIM-554, CIM-496 X CIM-707 and CIM-506 X CIM-554) having valuable SCA determination and remarkable mean performance for most of the traits. Reciprocal crosses having prominent maternal effects also involved one of the general combiners for majority of the traits. The promising hybrids also exhibited earliness through which the crop can escape from pests attack and soil can

Observation of the c-f hybridization effect in valence-transition system EuPtP

Energy Technology Data Exchange (ETDEWEB)

Anzai, Hiroaki; Ichiki, Katsuya [Graduate School of Engineering, Osaka Prefecture University, Sakai (Japan); Schwier, Eike F.; Iwasawa, Hideaki; Arita, Masashi; Sato, Hitoshi; Shimada, Kenya; Namatame, Hirofumi; Taniguchi, Masaki [Hiroshima Synchrotron Radiation Center, Hiroshima University, Higashi-Hiroshima (Japan); Mitsuda, Akihiro; Wada, Hirofumi [Graduate School of Science, Kyushu University, Fukuoka (Japan); Mimura, Kojiro [Graduate School of Engineering, Osaka Prefecture University, Sakai (Japan); Hiroshima Synchrotron Radiation Center, Hiroshima University, Higashi-Hiroshima (Japan)

2017-06-15

We study the electronic structure of EuPtP, which exhibits two first-order valence transitions at T{sub 1} = 247 K and T{sub 2} = 201 K, using angle-resolved photoemission spectroscopy. Below T{sub 2}, we observe an energy gap at the crossing point of the bulk Eu 4f and conduction bands. The shape of band dispersions is described by a hybridization-band picture based on the periodic Anderson model. Our results demonstrate the c-f hybridization effect in the low-temperature phase of EuPtP. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

COMPARATIVE RESEARCHE REGARDING METABOLIC PROFILE OF THE CALIFORNIAN, NEW ZEALAND WHITE, GRAND CHINCHILLA MEAT RABIT BREEDS AND THE F1 NZCH HYBRIDS

Directory of Open Access Journals (Sweden)

DANIELA-MARCELA TOBĂ (GOINA

2008-10-01

Full Text Available Precious biological characteristics of rabbits make their breeding a very profitable occupation. The rabbit meat, organoleptically same to the white meat, is rich in proteins, but low in fats. Biological researched done in direction to elucidate the biochemical systems that are the basis for organism physiological processes, have revealed that the level in which this process are develop directly influence the rabbits productivity capacity. 60 rabbit’s heads was used as biological material, distributed in: 15 Californian, 15 New Zeeland White, 15 Grand Chinchilla and 15 F1NZCH hybrids obtained from cross-breeding the New Zeeland White as maternal form and Grand Chinchilla as paternal form. Blood was sampled from the rabbit and was biochemical analyzed. The studied indices were: total protein, albumin, urea, uric acid, creatinine, total bilirubine, cholesterol, triglyceride and glucose. The experimental lot formed from F1 NZCH hybrids registered a concentration of 2.1 mg/dl uric acid, and in the other three lots the concentration was under 2 mg/dl. In all four lots, uric acid value was in normal limits. The determined creatinine registered very low values, under 1 mg/dl, at the low limit of reference values. At hybrids from New Zeeland White as maternal form and Grand Chinchilla as paternal form, in equal environmental conditions, the serum biochemical analysis haven’t registered significant differences compared to pure breeds individuals.

Occurrence of 2n gametes in the F1 hybrids of Oriental x Asiatic lilies (Lilium): Relevance to intergenomic recombination and backcrossing

NARCIS (Netherlands)

Barba Gonzalez, R.; Lim, K.B.; Ramanna, M.S.; Visser, R.G.F.; Tuyl, van J.M.

2005-01-01

Cytological modes of the origin of 2n gametes were investigated in six different genotypes of F1 hybrids between Oriental and Asiatic (OA) lilies (Lilium, 2n = 2x = 24). Chromosome pairing between the parental genomes was very low, the average frequency range from 0.3 to 1.2 bivalents per cell among

The effect of study type on body weight and tumor incidence in B6C3F1 mice fed the NTP-2000 diet.

Science.gov (United States)

Marino, Dale J

2012-07-01

The B6C3F1 mouse is the standard mouse strain used in National Toxicology Program (NTP) carcinogenesis studies. Over time, increased liver tumorigenesis that was correlated with elevated body weights was noted in males and females. NTP therefore replaced the NIH-07 diet with the NTP-2000 diet and returned to group housing of females as lower body weights were noted in group housed mice. However, recent studies reported study-type differences in body weights at 3 months using the NTP-2000 diet with higher weights evident in drinking water and inhalation studies compared to feed studies. Therefore, body weight and tumor incidence data were collected for untreated control mice from all 2-year NTP feed (12), drinking water (8), water gavage (6) and inhalation (10) studies that used the NTP-2000 diet in order to assess the impact of study type on body weights and tumor incidences. Results show statistically significant elevated body weights and liver tumor incidences in males and females from drinking water, water gavage and inhalation studies compared to results from feed studies. Thus, the elevated body weights and liver tumorigenesis noted in mice using the NIH-07 diet were also evident using the NTP-2000 diet, which was introduced to address body weight elevations. Given the study-type dependent effects noted, these results emphasize the importance of carefully selecting historical control data for B6C3F1 mice. Moreover, because of the association between body weight and liver tumorigenesis, these results may have implications regarding dose-level selection for carcinogenicity studies involving B6C3F1 mice based on the maximum tolerated dose.

Autosomal dominant inheritance of brain cardiolipin fatty acid abnormality in VM/DK mice: association with hypoxic-induced cognitive insensitivity.

Science.gov (United States)

Ta, Nathan L; Jia, Xibei; Kiebish, Michael; Seyfried, Thomas N

2014-01-01

Cardiolipin is a complex polyglycerol phospholipid found almost exclusively in the inner mitochondrial membrane and regulates numerous enzyme activities especially those related to oxidative phosphorylation and coupled respiration. Abnormalities in cardiolipin can impair mitochondrial function and bioenergetics. We recently demonstrated that the ratio of shorter chain saturated and monounsaturated fatty acids (C16:0; C18:0; C18:1) to longer chain polyunsaturated fatty acids (C18:2; C20:4; C22:6) was significantly greater in the brains of adult VM/DK (VM) inbred mice than in the brains of C57BL/6 J (B6) mice. The cardiolipin fatty acid abnormalities in VM mice are also associated with alterations in the activity of mitochondrial respiratory complexes. In this study we found that the abnormal brain fatty acid ratio in the VM strain was inherited as an autosomal dominant trait in reciprocal B6 × VM F1 hybrids. To evaluate the potential influence of brain cardiolipin fatty acid composition on cognitive sensitivity, we placed the parental B6 and VM mice and their reciprocal male and female B6VMF1 hybrid mice (3-month-old) in a hypoxic chamber (5 % O2). Cognitive awareness (conscientiousness) under hypoxia was significantly lower in the VM parental mice and F1 hybrid mice (11.4 ± 0.4  and 11.0 ± 0.4 min, respectively) than in the parental B6 mice (15.3 ± 1.4 min), indicating an autosomal dominant inheritance like that of the brain cardiolipin abnormalities. These findings suggest that impaired cognitive awareness under hypoxia is associated with abnormalities in neural lipid composition.

IGF-1 deficiency impairs cerebral myogenic autoregulation in hypertensive mice.

Science.gov (United States)

Toth, Peter; Tucsek, Zsuzsanna; Tarantini, Stefano; Sosnowska, Danuta; Gautam, Tripti; Mitschelen, Matthew; Koller, Akos; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

2014-12-01

Aging impairs autoregulatory protection in the brain, exacerbating hypertension-induced cerebromicrovascular injury, neuroinflammation, and development of vascular cognitive impairment. Despite the importance of the age-related decline in circulating insulin-like growth factor-1 (IGF-1) levels in cerebrovascular aging, the effects of IGF-1 deficiency on functional adaptation of cerebral arteries to high blood pressure remain elusive. To determine whether IGF-1 deficiency impairs autoregulatory protection, hypertension was induced in control and IGF-1-deficient mice (Igf1(f/f)+TBG-iCre-AAV8) by chronic infusion of angiotensin-II. In hypertensive control mice, cerebral blood flow (CBF) autoregulation was extended to higher pressure values and the pressure-induced tone of middle cerebral arteries (MCAs) was increased. In hypertensive IGF-1-deficient mice, autoregulation was markedly disrupted, and MCAs did not show adaptive increases in myogenic tone. In control mice, the mechanism of adaptation to hypertension involved upregulation of TRPC channels in MCAs and this mechanism was impaired in hypertensive IGF-1-deficient mice. Likely downstream consequences of cerebrovascular autoregulatory dysfunction in hypertensive IGF-1-deficient mice included exacerbated disruption of the blood-brain barrier and neuroinflammation (microglia activation and upregulation of proinflammatory cytokines and chemokines), which were associated with impaired hippocampal cognitive function. Collectively, IGF-1 deficiency impairs autoregulatory protection in the brain of hypertensive mice, potentially exacerbating cerebromicrovascular injury and neuroinflammation mimicking the aging phenotype.

Effects of oral Lactobacillus administration on antioxidant activities and CD4+CD25+forkhead box P3 (FoxP3)+ T cells in NZB/W F1 mice.

Science.gov (United States)

Tzang, Bor-Show; Liu, Chung-Hsien; Hsu, Kuo-Ching; Chen, Yi-Hsing; Huang, Chih-Yang; Hsu, Tsai-Ching

2017-09-01

Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterised by a dysregulation of the immune system, which causes inflammation responses, excessive oxidative stress and a reduction in the number of cluster of differentiation (CD)4+CD25+forkhead box P3 (FoxP3)+ T cells. Supplementation with certain Lactobacillus strains has been suggested to be beneficial in the comprehensive treatment of SLE. However, little is known about the effect and mechanism of certain Lactobacillus strains on SLE. To investigate the effects of Lactobacillus on SLE, NZB/W F1 mice were orally gavaged with Lactobacillus paracasei GMNL-32 (GMNL-32), Lactobacillus reuteri GMNL-89 (GMNL-89) and L. reuteri GMNL-263 (GMNL-263). Supplementation with GMNL-32, GMNL-89 and GMNL-263 significantly increased antioxidant activity, reduced IL-6 and TNF-α levels and significantly decreased the toll-like receptors/myeloid differentiation primary response gene 88 signalling in NZB/W F1 mice. Notably, supplementation with GMNL-263, but not GMNL-32 and GMNL-89, in NZB/W F1 mice significantly increased the differentiation of CD4+CD25+FoxP3+ T cells. These findings reveal beneficial effects of GMNL-32, GMNL-89 and GMNL-263 on NZB/W F1 mice and suggest that these specific Lactobacillus strains can be used as part of a comprehensive treatment of SLE patients.

Sex-related differential susceptibility to doxorubicin-induced cardiotoxicity in B6C3F1 mice

International Nuclear Information System (INIS)

Jenkins, G. Ronald; Lee, Taewon; Moland, Carrie L.; Vijay, Vikrant; Herman, Eugene H.; Lewis, Sherry M.; Davis, Kelly J.; Muskhelishvili, Levan; Kerr, Susan; Fuscoe, James C.; Desai, Varsha G.

2016-01-01

Sex is a risk factor for development of cardiotoxicity, induced by the anti-cancer drug, doxorubicin (DOX), in humans. To explore potential mechanisms underlying differential susceptibility to DOX between sexes, 8-week old male and female B6C3F 1 mice were dosed with 3 mg/kg body weight DOX or an equivalent volume of saline via tail vein once a week for 6, 7, 8, and 9 consecutive weeks, resulting in 18, 21, 24, and 27 mg/kg cumulative DOX doses, respectively. At necropsy, one week after each consecutive final dose, the extent of myocardial injury was greater in male mice compared to females as indicated by higher plasma concentrations of cardiac troponin T at all cumulative DOX doses with statistically significant differences between sexes at the 21 and 24 mg/kg cumulative doses. A greater susceptibility to DOX in male mice was further confirmed by the presence of cytoplasmic vacuolization in cardiomyocytes, with left atrium being more vulnerable to DOX cardiotoxicity. The number of TUNEL-positive cardiomyocytes was mostly higher in DOX-treated male mice compared to female counterparts, showing a statistically significant sex-related difference only in left atrium at 21 mg/kg cumulative dose. DOX-treated male mice also had an increased number of γ-H2A.X-positive (measure of DNA double-strand breaks) cardiomyocytes compared to female counterparts with a significant sex effect in the ventricle at 27 mg/kg cumulative dose and right atrium at 21 and 27 mg/kg cumulative doses. This newly established mouse model provides a means to identify biomarkers and access potential mechanisms underlying sex-related differences in DOX-induced cardiotoxicity. - Highlights: • Doxorubicin caused greater heart injury in male mice than females. • Doxorubicin caused vacuolization in cardiomyocytes only in male mice. • TUNEL-positive cardiomyocytes was higher in DOX-treated male mice. • γ-H2A.X-positive cardiomyocytes was greater in DOX-treated male mice.

Effect of bone marrow-derived CD11b(+)F4/80 (+) immature dendritic cells on the balance between pro-inflammatory and anti-inflammatory cytokines in DBA/1 mice with collagen-induced arthritis.

Science.gov (United States)

Fu, Jingjing; Zhang, Lingling; Song, Shanshan; Sheng, Kangliang; Li, Ying; Li, Peipei; Song, Shasha; Wang, Qingtong; Chu, Jianhong; Wei, Wei

2014-05-01

To explore the effect of bone marrow-derived CD11b(+)F4/80(+) immature dendritic cells (BM CD11b(+)F4/80(+)iDC) on the balance between pro-inflammatory and anti-inflammatory cytokines in DBA/1 mice with collagen-induced arthritis (CIA). BM CD11b(+)F4/80(+)iDC were induced with rmGM-CSF and rmIL-4, and were identified by the expressions of toll-like receptor 2 (TLR-2), indoleamine 2,3-deoxygenase (IDO), interleukin (IL)-10, transforming growth factor (TGF)-β1 and mixed leukocyte reaction (MLR). CIA was established in DBA/1 mice by immunization with type II collagen. CIA mice were injected intravenously with BM CD11b(+)F4/80(+)iDC three times after immunization. The effect of BM CD11b(+)F4/80(+)iDC on CIA was evaluated by the arthritis index, joint histopathology, body weight, thymus index, thymocytes proliferation, IL-1β, tumor necrosis factor (TNF)-α, IL-17, IL-10 and TGF-β1 levels. BM CD11b(+)F4/80(+)iDC induced with rmGM-CSF and rmIL-4 expressed high levels of TLR-2, IDO, IL-10 and TGF-β1. Infusion of BM CD11b(+)F4/80(+)iDC in CIA mice significantly reduced the arthritis index and pathological scores of joints, recovered the weight, decreased the thymus index and inhibited thymocyte proliferation. Levels of IL-1β, TNF-α and IL-17 were decreased in BM CD11b(+)F4/80(+)iDC-treated mice. BM CD11b(+)F4/80(+)iDC can be induced successfully with rmGM-CSF and rmIL-4. BM CD11b(+)F4/80(+)iDC treatment can ameliorate the development and severity of CIA by regulating the balance between pro-inflammatory cytokines and anti-inflammatory cytokines.

Evaluation of a C57BL/6J × 129S1/SvImJ Hybrid Nestin-Thymidine Kinase Transgenic Mouse Model for Studying the Functional Significance of Exercise-Induced Adult Hippocampal Neurogenesis.

Science.gov (United States)

Hamilton, G F; Majdak, P; Miller, D S; Bucko, P J; Merritt, J R; Krebs, C P; Rhodes, J S

2015-01-01

New neurons are continuously generated in the adult hippocampus but their function remains a mystery. The nestin thymidine kinase (nestin-TK) transgenic method has been used for selective and conditional reduction of neurogenesis for the purpose of testing the functional significance of new neurons in learning, memory and motor performance. Here we explored the nestin-TK model on a hybrid genetic background (to increase heterozygosity, and "hybrid vigor"). Transgenic C57BL/6J (B6) were crossed with 129S1/SvImJ (129) producing hybrid offspring (F1) with the B6 half of the genome carrying a herpes simplex virus thymidine kinase (TK) transgene regulated by a modified nestin promoter. In the presence of exogenously administered valganciclovir, new neurons expressing TK undergo apoptosis. Female B6 nestin-TK mice ( n = 80) were evaluated for neurogenesis reduction as a positive control. Male and female F1 nestin-TK mice ( n = 223) were used to determine the impact of neurogenesis reduction on the Morris water maze (MWM) and rotarod. All mice received BrdU injections to label dividing cells and either valganciclovir or control chow, with or without a running wheel for 30 days. Both the F1 and B6 background displayed approximately 50% reduction in neurogenesis, a difference that did not impair learning and memory on the MWM or rotarod performance. Running enhanced neurogenesis and performance on the rotarod but not MWM suggesting the F1 background may not be suitable for studying pro-cognitive effects of exercise on MWM. Greater reduction of neurogenesis may be required to observe behavioral impacts. Alternatively, new neurons may not play a critical role in learning, or compensatory mechanisms in pre-existing neurons could have masked the deficits. Further work using these and other models for selectively reducing neurogenesis are needed to establish the functional significance of adult hippocampal neurogenesis in behavior.

TERMS OF CULTIVATION FOR BEE-POLLINATED CUCUMBER KARAMBOL F1 IN WINTER GLASS GREENHOUSES

Directory of Open Access Journals (Sweden)

V. G. Korol

2017-01-01

Full Text Available The group of bee-pollinated hybrids of cucumber is one of the most demanded for growing in greenhouses in winterspring period. There are ‘Atlet F1’ ‘Karambol F1’ ‘Magnit F1’ ‘Kartel  F1’  and  also  hybrids  pollinators  ‘Kazanova  F1’, ‘Begunok  F1’  ‘Bodriyachok  F1’,  which  occupy  about  800 hectares of  area in  winter  greenhouses. All  hybrids  have attractive appearance, high taste qualities, and are transportable. Buttons are in a great demand and have a high price during  all  the  time  of  cultivation,  from  February to  July. However, the bee-pollinated  cucumbers in later period are also in need, particularly for end of year celebrations. The possibility  to  grow  these  bee  pollinated  cucumbers  like ‘Karambol F1’ in these terms of cultivation is regarded in the article.

Prolonged action potential duration in cardiac ablation of PDK1 mice.

Science.gov (United States)

Han, Zhonglin; Jiang, Yu; Yang, Zhongzhou; Cao, Kejiang; Wang, Dao W

2015-01-01

The involvement of the AGC protein kinase family in regulating arrhythmia has drawn considerable attention, but the underlying mechanisms are still not clear. The aim of this study is to explore the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), one of upstream protein kinases of the AGC protein kinase family, in the pathogenesis of dysregulated electrophysiological basis. PDK1(F/F) αMHC-Cre mice and PDK1(F/F) mice were divided into experiment group and control group. Using patch clamping technology, we explored action potential duration in both groups, and investigated the functions of transient outward potassium channel and L-type Ca(2+) channel to explain the abnormal action potential duration. Significant prolongation action potential duration was found in mice with PDK1 deletion. Further, the peak current of transient outward potassium current and L-type Ca(2+) current were decreased by 84% and 49% respectively. In addition, dysregulation of channel kinetics lead to action potential duration prolongation further. In conclusion, we have demonstrated that PDK1 participates in action potential prolongation in cardiac ablation of PDK1 mice. This effect is likely to be mediated largely through downregulation of transient outward potassium current. These findings indicate the modulation of the PDK1 pathway could provide a new mechanism for abnormal electrophysiological basis.

Interallelic and intergenic incompatibilities of the Prdm9 (Hst1) gene in mouse hybrid sterility.

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Flachs, Petr; Mihola, Ondřej; Simeček, Petr; Gregorová, Soňa; Schimenti, John C; Matsui, Yasuhisa; Baudat, Frédéric; de Massy, Bernard; Piálek, Jaroslav; Forejt, Jiří; Trachtulec, Zdenek

2012-01-01

The Dobzhansky-Muller model of incompatibilities explains reproductive isolation between species by incorrect epistatic interactions. Although the mechanisms of speciation are of great interest, no incompatibility has been characterized at the gene level in mammals. The Hybrid sterility 1 gene (Hst1) participates in the arrest of meiosis in F(1) males of certain strains from two Mus musculus subspecies, e.g., PWD from M. m. musculus and C57BL/6J (henceforth B6) from M. m. domesticus. Hst1 has been identified as a meiotic PR-domain gene (Prdm9) encoding histone 3 methyltransferase in the male offspring of PWD females and B6 males, (PWD×B6)F(1). To characterize the incompatibilities underlying hybrid sterility, we phenotyped reproductive and meiotic markers in males with altered copy numbers of Prdm9. A partial rescue of fertility was observed upon removal of the B6 allele of Prdm9 from the azoospermic (PWD×B6)F(1) hybrids, whereas removing one of the two Prdm9 copies in PWD or B6 background had no effect on male reproduction. Incompatibility(ies) not involving Prdm9(B6) also acts in the (PWD×B6)F(1) hybrids, since the correction of hybrid sterility by Prdm9(B6) deletion was not complete. Additions and subtractions of Prdm9 copies, as well as allelic replacements, improved meiotic progression and fecundity also in the progeny-producing reciprocal (B6×PWD)F(1) males. Moreover, an increased dosage of Prdm9 and reciprocal cross enhanced fertility of other sperm-carrying male hybrids, (PWD×B6-C3H.Prdm9)F(1), harboring another Prdm9 allele of M. m. domesticus origin. The levels of Prdm9 mRNA isoforms were similar in the prepubertal testes of all types of F(1) hybrids of PWD with B6 and B6-C3H.Prdm9 despite their different prospective fertility, but decreased to 53% after removal of Prdm9(B6). Therefore, the Prdm9(B6) allele probably takes part in posttranscriptional dominant-negative hybrid interaction(s) absent in the parental strains.

Effective plague vaccination via oral delivery of plant cells expressing F1-V antigens in chloroplasts.

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Arlen, Philip A; Singleton, Michael; Adamovicz, Jeffrey J; Ding, Yi; Davoodi-Semiromi, Abdolreza; Daniell, Henry

2008-08-01

The chloroplast bioreactor is an alternative to fermentation-based systems for production of vaccine antigens and biopharmaceuticals. We report here expression of the plague F1-V fusion antigen in chloroplasts. Site-specific transgene integration and homoplasmy were confirmed by PCR and Southern blotting. Mature leaves showed the highest level of transgene expression on the third day of continuous illumination, with a maximum level of 14.8% of the total soluble protein. Swiss Webster mice were primed with adjuvant-containing subcutaneous (s.c.) doses of F1-V and then boosted with either adjuvanted s.c. doses (s.c. F1-V mice) or unadjuvanted oral doses (oral F1-V mice). Oral F1-V mice had higher prechallenge serum immunoglobulin G1 (IgG1) titers than s.c. F1-V mice. The corresponding serum levels of antigen-specific IgG2a and IgA were 2 and 3 orders of magnitude lower, respectively. After vaccination, mice were exposed to an inhaled dose of 1.02 x 10(6) CFU of aerosolized Yersinia pestis CO92 (50% lethal dose, 6.8 x 10(4) CFU). All control animals died within 3 days. F1-V given s.c. (with adjuvant) protected 33% of the immunized mice, while 88% of the oral F1-V mice survived aerosolized Y. pestis challenge. A comparison of splenic Y. pestis CFU counts showed that there was a 7- to 10-log reduction in the mean bacterial burden in survivors. Taken together, these data indicate that oral booster doses effectively elicit protective immune responses in vivo. In addition, this is the first report of a plant-derived oral vaccine that protected animals from live Y. pestis challenge, bringing the likelihood of lower-cost vaccines closer to reality.

Ablation of human colon carcinoma in nude mice by 131I-labeled monoclonal anti-carcinoembryonic antigen antibody F(ab')2 fragments

International Nuclear Information System (INIS)

Buchegger, F.; Pfister, C.; Fournier, K.; Prevel, F.; Schreyer, M.; Carrel, S.; Mach, J.P.

1989-01-01

Pooled F(ab')2 fragments of three MAbs against distinct epitopes of carcinoembryonic antigen (CEA) were used for radioimmunotherapy of nude mice bearing a subcutaneous human colon carcinoma xenograft. 9-10 d after transplantation when tumor nodules were in exponential growth, 36 mice were treated by intravenous injection of different amounts of 131 I-labeled MAb F(ab')2. All 14 mice injected with a single dose of 2,200 (n = 10) or 2,800 microCi (n = 4) showed complete tumor remission. 8 of the 10 mice treated with 2,200 microCi survived in good health for 1 yr when they were killed and shown to be tumor free. Four of nine other mice treated with four fractionated doses of 400 microCi showed no tumor relapse for more than 9 mo. In contrast, all 15 mice injected with 1,600-3,000 microCi 131 I-control IgG F(ab')2 showed tumor growth retardation of only 1-4 wk, and 15 of 16 mice injected with unlabeled anti-CEA MAb F(ab')2 showed unmodified tumor progression as compared with untreated mice. From tissue radioactivity distributions it was calculated that by an injection of 2,200 microCi 131 I-MAb F(ab')2 a mean dose of 8,335 rad was selectively delivered to the tumor, while the tissue-absorbed radiation doses for the normal organs were: peripheral blood, 2,093; stomach, 1,668; kidney, 1,289; lung, 1,185; liver, 617; spleen, 501; small intestine, 427; large intestine, 367; bone, 337; and muscle, 198. These treatments were well tolerated since out of 19 mice with complete tumor remission only 4 required bone marrow transplantation and 17 were in good health for 6-12 mo of observation

Dosage-dependent copy number gains in E2f1 and E2f3 drive hepatocellular carcinoma.

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Kent, Lindsey N; Bae, Sooin; Tsai, Shih-Yin; Tang, Xing; Srivastava, Arunima; Koivisto, Christopher; Martin, Chelsea K; Ridolfi, Elisa; Miller, Grace C; Zorko, Sarah M; Plevris, Emilia; Hadjiyannis, Yannis; Perez, Miguel; Nolan, Eric; Kladney, Raleigh; Westendorp, Bart; de Bruin, Alain; Fernandez, Soledad; Rosol, Thomas J; Pohar, Kamal S; Pipas, James M; Leone, Gustavo

2017-03-01

Disruption of the retinoblastoma (RB) tumor suppressor pathway, either through genetic mutation of upstream regulatory components or mutation of RB1 itself, is believed to be a required event in cancer. However, genetic alterations in the RB-regulated E2F family of transcription factors are infrequent, casting doubt on a direct role for E2Fs in driving cancer. In this work, a mutation analysis of human cancer revealed subtle but impactful copy number gains in E2F1 and E2F3 in hepatocellular carcinoma (HCC). Using a series of loss- and gain-of-function alleles to dial E2F transcriptional output, we have shown that copy number gains in E2f1 or E2f3b resulted in dosage-dependent spontaneous HCC in mice without the involvement of additional organs. Conversely, germ-line loss of E2f1 or E2f3b, but not E2f3a, protected mice against HCC. Combinatorial mapping of chromatin occupancy and transcriptome profiling identified an E2F1- and E2F3B-driven transcriptional program that was associated with development and progression of HCC. These findings demonstrate a direct and cell-autonomous role for E2F activators in human cancer.

Immediate Genetic and Epigenetic Changes in F1 Hybrids Parented by Species with Divergent Genomes in the Rice Genus (Oryza.

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Ying Wu

Full Text Available Inter-specific hybridization occurs frequently in higher plants, and represents a driving force of evolution and speciation. Inter-specific hybridization often induces genetic and epigenetic instabilities in the resultant homoploid hybrids or allopolyploids, a phenomenon known as genome shock. Although genetic and epigenetic consequences of hybridizations between rice subspecies (e.g., japonica and indica and closely related species sharing the same AA genome have been extensively investigated, those of inter-specific hybridizations between more remote species with different genomes in the rice genus, Oryza, remain largely unknown.We investigated the immediate chromosomal and molecular genetic/epigenetic instability of three triploid F1 hybrids produced by inter-specific crossing between species with divergent genomes of Oryza by genomic in situ hybridization (GISH and molecular marker analysis. Transcriptional and transpositional activity of several transposable elements (TEs and methylation stability of their flanking regions were also assessed. We made the following principle findings: (i all three triploid hybrids are stable in both chromosome number and gross structure; (ii stochastic changes in both DNA sequence and methylation occurred in individual plants of all three triploid hybrids, but in general methylation changes occurred at lower frequencies than genetic changes; (iii alteration in DNA methylation occurred to a greater extent in genomic loci flanking potentially active TEs than in randomly sampled loci; (iv transcriptional activation of several TEs commonly occurred in all three hybrids but transpositional events were detected in a genetic context-dependent manner.Artificially constructed inter-specific hybrids of remotely related species with divergent genomes in genus Oryza are chromosomally stable but show immediate and highly stochastic genetic and epigenetic instabilities at the molecular level. These novel hybrids might

Comparison of global brain gene expression profiles between inbred long-sleep and inbred short-sleep mice by high-density gene array hybridization.

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Xu, Y; Ehringer, M; Yang, F; Sikela, J M

2001-06-01

Inbred long-sleep (ILS) and short-sleep (ISS) mice show significant central nervous system-mediated differences in sleep time for sedative dose of ethanol and are frequently used as a rodent model for ethanol sensitivity. In this study, we have used complementary DNA (cDNA) array hybridization methodology to identify genes that are differentially expressed between the brains of ILS and ISS mice. To carry out this analysis, we used both the gene discovery array (GDA) and the Mouse GEM 1 Microarray. GDA consists of 18,378 nonredundant mouse cDNA clones on a single nylon filter. Complex probes were prepared from total brain mRNA of ILS or ISS mice by using reverse transcription and 33P labeling. The labeled probes were hybridized in parallel to the gene array filters. Data from GDA experiments were analyzed with SQL-Plus and Oracle 8. The GEM microarray includes 8,730 sequence-verified clones on a glass chip. Two fluorescently labeled probes were used to hybridize a microarray simultaneously. Data from GEM experiments were analyzed by using the GEMTools software package (Incyte). Differentially expressed genes identified from each method were confirmed by relative quantitative reverse transcription-polymerase chain reaction (RT-PCR). A total of 41 genes or expressed sequence tags (ESTs) display significant expression level differences between brains of ILS and ISS mice after GDA, GEM1 hybridization, and quantitative RT-PCR confirmation. Among them, 18 clones were expressed higher in ILS mice, and 23 clones were expressed higher in ISS mice. The individual gene or EST's function and mapping information have been analyzed. This study identified 41 genes that are differentially expressed between brains of ILS and ISS mice. Some of them may have biological relevance in mediation of phenotypic variation between ILS and ISS mice for ethanol sensitivity. This study also demonstrates that parallel gene expression comparison with high-density cDNA arrays is a rapid and

Interallelic and intergenic incompatibilities of the Prdm9 (Hst1 gene in mouse hybrid sterility.

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Petr Flachs

Full Text Available The Dobzhansky-Muller model of incompatibilities explains reproductive isolation between species by incorrect epistatic interactions. Although the mechanisms of speciation are of great interest, no incompatibility has been characterized at the gene level in mammals. The Hybrid sterility 1 gene (Hst1 participates in the arrest of meiosis in F(1 males of certain strains from two Mus musculus subspecies, e.g., PWD from M. m. musculus and C57BL/6J (henceforth B6 from M. m. domesticus. Hst1 has been identified as a meiotic PR-domain gene (Prdm9 encoding histone 3 methyltransferase in the male offspring of PWD females and B6 males, (PWD×B6F(1. To characterize the incompatibilities underlying hybrid sterility, we phenotyped reproductive and meiotic markers in males with altered copy numbers of Prdm9. A partial rescue of fertility was observed upon removal of the B6 allele of Prdm9 from the azoospermic (PWD×B6F(1 hybrids, whereas removing one of the two Prdm9 copies in PWD or B6 background had no effect on male reproduction. Incompatibility(ies not involving Prdm9(B6 also acts in the (PWD×B6F(1 hybrids, since the correction of hybrid sterility by Prdm9(B6 deletion was not complete. Additions and subtractions of Prdm9 copies, as well as allelic replacements, improved meiotic progression and fecundity also in the progeny-producing reciprocal (B6×PWDF(1 males. Moreover, an increased dosage of Prdm9 and reciprocal cross enhanced fertility of other sperm-carrying male hybrids, (PWD×B6-C3H.Prdm9F(1, harboring another Prdm9 allele of M. m. domesticus origin. The levels of Prdm9 mRNA isoforms were similar in the prepubertal testes of all types of F(1 hybrids of PWD with B6 and B6-C3H.Prdm9 despite their different prospective fertility, but decreased to 53% after removal of Prdm9(B6. Therefore, the Prdm9(B6 allele probably takes part in posttranscriptional dominant-negative hybrid interaction(s absent in the parental strains.

[Inheritance of bc1 gene in intersubspecific hybrids of rice (Oryza sativa L.)].

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Lü, Chuan-Gen; Zong, Shou-Yu; Zhao, Ling; Qi, Qing-Ming; Zou, Jiang-Shi; Ikehashi, Hiroshi

2004-10-01

Distorted segregation of the brittle culm-1 gene (bc1) on rice chromosome 3 was found with greatly increased or decreased frequency of bc1 bc1 genotype in inter-subspecific hybrids, although the gene normally transmitted to its offspring following the Mendelian Law in intra-subspecific hybrids. In a combination of Kamairazu//Ketan Nangka/Kamairazu,an increased frequency of bc1 bc1 in F1, normal segregation in F2, and increased and decreased frequency in a few F3 and F4 lines were observed. In a cross of IR36/Kamairazu, decreased frequency in F2, both normal and decreased segregations in F3 and F4, and a few lines of increased ratio in F4 were found. In F2 of Ketan Nangka/IR36//Kamairazu, increased and decreased and normal segregations were all observed. There was no significant correlation between the frequency of bc1 bc1 and pollen fertility. It implied that distorted segregation of bc1 was caused by selective fertilization of male gametes, which were governed by gametophyte genes of ga2, ga3 and ga14 on chromosome 3.

Kidney epithelium specific deletion of kelch-like ECH-associated protein 1 (Keap1) causes hydronephrosis in mice.

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Noel, Sanjeev; Arend, Lois J; Bandapalle, Samatha; Reddy, Sekhar P; Rabb, Hamid

2016-08-02

Transcription factor Nrf2 protects from experimental acute kidney injury (AKI) and is promising to limit progression in human chronic kidney disease (CKD) by upregulating multiple antioxidant genes. We recently demonstrated that deletion of Keap1, the endogenous inhibitor of Nrf2, in T lymphocytes significantly protects from AKI. In this study, we investigated the effect of Keap1 deletion on Nrf2 mediated antioxidant response in the renal tubular epithelial cells. We deleted Keap1 exon 2 and 3 in the renal tubular epithelial cells by crossing Ksp-Cre mice with Keap1 floxed (Keap1 (f/f)) mice. Deletion of Keap1 gene in the kidney epithelial cells of Ksp-Keap1 (-/-) mice and its effect on Nrf2 target gene expression was performed using PCR and real-time PCR respectively. Histological evaluation was performed on H&E stained sections. Complete blood count, serum and urine analysis were performed to assess systemic effects of defective kidney development. Student's T test was used to determine statistical difference between the groups. Ksp-Cre resulted in the deletion of Keap1 exon 2 and 3 and subsequent upregulation of Nrf2 target genes, Nqo1, Gclm and Gclc in the kidney epithelial cells of Ksp-Keap1 (-/-) mice at baseline. Renal epithelial cell specific deletion of Keap1 in Ksp-Keap1 (-/-) mice caused marked renal pelvic expansion and significant compression of medullary parenchyma consistent with hydronephrosis in both (3 month-old) males and females. Kidneys from 6 month-old Ksp-Keap1 (-/-) mice showed progressive hydronephrosis. Hematological, biochemical and urinary analysis showed significantly higher red blood cell count (p = 0.04), hemoglobin (p = 0.01), hematocrit (p = 0.02), mean cell volume (p = 0.02) and mean cell hemoglobin concentration (p = 0.003) in Ksp-Keap1 (-/-) mice in comparison to Keap1 (f/f) mice. These unexpected findings demonstrate that Keap1 deletion in renal tubular epithelial cells results in an abnormal kidney

[F-18]FDG imaging of head and neck tumors: comparison of hybrid PET, dedicated PET and CT

International Nuclear Information System (INIS)

Dresel, S.; Brinkbaeumer, K.; Schmid, R.; Poepperl, G.; Hahn, K.; Szeimies, U.

2001-01-01

Aim: Aim of the study was to evaluate [F-18]FDG imaging of head and neck tumors using a Hybrid-PET device of the 2nd or 3rd generation. Examinations were compared to dedicated PET and Spiral-CT. Methods: 54 patients suffering from head and neck tumors were examined using dedicated PET and Hybrid-PET after injection of 185-350 MBq [F-18]FDG. Examinations were carried out on the dedicated PET first followed by a scan on the Hybrid-PET. Dedicated PET was acquired in 3D mode, Hybrid-PET was performed in list mode using an axial filter. Reconstruction of data was performed iteratively on both, dedicated PET and Hybrid-PET. All patients received a CT scan in multislice technique. All finding have been verified by the goldstandard histology or in case of negative histology by follow up. Results: Using dedicated PET the primary or recurrent lesion was correctly diagnosed in 47/48 patients, using Hybrid-PET in 46/48 patients and using CT in 25/48 patients. Metastatic disease in cervical lymph nodes was diagnosed in 17/18 patients with dedicated PET, in 16/18 patients with Hybrid-PET and in 15/18 with CT. False positive results with regard to lymph node metastasis were seen with one patient for dedicated PET and Hybrid-PET, respectively, and with 18 patients for CT. In a total of 11 patients unknown metastastic lesions were seen with dedicated PET and with Hybrid-PET elsewhere in the body. Additional malignant disease other than the head and neck tumor was found in 4 patients. Conclusion: Using Hybrid-PET for [F-18]FDG imaging reveals a loss of sensitivity and specificity of about 1-5% as compared to dedicated PET in head and neck tumors. [F-18]FDG PET with both, dedicated PET and Hybrid-PET is superior to CT in the diagnosis of primary or recurrent lesions as well as in the assessment of lymph node involvement. (orig.) [de

Comparison between hybrid feedforward-feedback, feedforward, and feedback structures for active noise control of fMRI noise.

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Reddy, Rajiv M; Panahi, Issa M S

2008-01-01

The performance of FIR feedforward, IIR feedforward, FIR feedback, hybrid FIR feedforward--FIR feedback, and hybrid IIR feedforward - FIR feedback structures for active noise control (ANC) are compared for an fMRI noise application. The filtered-input normalized least squares (FxNLMS) algorithm is used to update the coefficients of the adaptive filters in all these structures. Realistic primary and secondary paths of an fMRI bore are used by estimating them on a half cylindrical acrylic bore of 0.76 m (D)x1.52 m (L). Detailed results of the performance of the ANC system are presented in the paper for each of these structures. We find that the IIR feedforward structure produces most of the performance improvement in the hybrid IIR feedforward - FIR feedback structure and adding the feedback structure becomes almost redundant in the case of fMRI noise.

Regulatory divergence of X-linked genes and hybrid male sterility in mice.

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Oka, Ayako; Shiroishi, Toshihiko

2014-01-01

Postzygotic reproductive isolation is the reduction of fertility or viability in hybrids between genetically diverged populations. One example of reproductive isolation, hybrid male sterility, may be caused by genetic incompatibility between diverged genetic factors in two distinct populations. Genetic factors involved in hybrid male sterility are disproportionately located on the X chromosome. Recent studies showing the evolutionary divergence in gene regulatory networks or epigenetic effects suggest that the genetic incompatibilities occur at much broader levels than had previously been thought (e.g., incompatibility of protein-protein interactions). The latest studies suggest that evolutionary divergence of transcriptional regulation causes genetic incompatibilities in hybrid animals, and that such incompatibilities preferentially involve X-linked genes. In this review, we focus on recent progress in understanding hybrid sterility in mice, including our studies, and we discuss the evolutionary significance of regulatory divergence for speciation.

Sex-related differential susceptibility to doxorubicin-induced cardiotoxicity in B6C3F{sub 1} mice

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Jenkins, G. Ronald [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Lee, Taewon [Department of Mathematics, Korea University, Sejong (Korea, Republic of); Moland, Carrie L.; Vijay, Vikrant [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Herman, Eugene H. [Toxicology and Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, The National Cancer Institute, Rockville, MD 20850-9734 (United States); Lewis, Sherry M. [Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Davis, Kelly J.; Muskhelishvili, Levan [Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR 72079 (United States); Kerr, Susan [Arkansas Heart Hospital, Little Rock, AR 72211 (United States); Fuscoe, James C. [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Desai, Varsha G., E-mail: varsha.desai@fda.hhs.gov [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States)

2016-11-01

Sex is a risk factor for development of cardiotoxicity, induced by the anti-cancer drug, doxorubicin (DOX), in humans. To explore potential mechanisms underlying differential susceptibility to DOX between sexes, 8-week old male and female B6C3F{sub 1} mice were dosed with 3 mg/kg body weight DOX or an equivalent volume of saline via tail vein once a week for 6, 7, 8, and 9 consecutive weeks, resulting in 18, 21, 24, and 27 mg/kg cumulative DOX doses, respectively. At necropsy, one week after each consecutive final dose, the extent of myocardial injury was greater in male mice compared to females as indicated by higher plasma concentrations of cardiac troponin T at all cumulative DOX doses with statistically significant differences between sexes at the 21 and 24 mg/kg cumulative doses. A greater susceptibility to DOX in male mice was further confirmed by the presence of cytoplasmic vacuolization in cardiomyocytes, with left atrium being more vulnerable to DOX cardiotoxicity. The number of TUNEL-positive cardiomyocytes was mostly higher in DOX-treated male mice compared to female counterparts, showing a statistically significant sex-related difference only in left atrium at 21 mg/kg cumulative dose. DOX-treated male mice also had an increased number of γ-H2A.X-positive (measure of DNA double-strand breaks) cardiomyocytes compared to female counterparts with a significant sex effect in the ventricle at 27 mg/kg cumulative dose and right atrium at 21 and 27 mg/kg cumulative doses. This newly established mouse model provides a means to identify biomarkers and access potential mechanisms underlying sex-related differences in DOX-induced cardiotoxicity. - Highlights: • Doxorubicin caused greater heart injury in male mice than females. • Doxorubicin caused vacuolization in cardiomyocytes only in male mice. • TUNEL-positive cardiomyocytes was higher in DOX-treated male mice. • γ-H2A.X-positive cardiomyocytes was greater in DOX-treated male mice.

Twenty-six-week oral carcinogenicity study of 3-monochloropropane-1,2-diol in CB6F1-rasH2 transgenic mice.

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Lee, Byoung-Seok; Park, Sang-Jin; Kim, Yong-Bum; Han, Ji-Seok; Jeong, Eun Ju; Son, Hwa-Young; Moon, Kyoung-Sik

2017-01-01

The carcinogenic potential of 3-monochloro-1,2-propanediol (3-MCPD) was evaluated in a short-term carcinogenicity testing study using CB6F1 rasH2-Tg (rasH2-Tg) mice. 3-MCPD is found in many foods and food ingredients as a result of storage or processing and is regarded as a carcinogen since it is known to induce Leydig cell and kidney tumors in rats. Male and female rasH2-Tg mice were administered 3-MCPD once daily by oral gavage at doses of 0, 10, 20, and 40 mg/kg body weight (bw) per day for 26 weeks. As a positive control, N-methyl-N-nitrosourea (MNU) was administered as a single intraperitoneal injection (75 mg/kg). In 3-MCPD-treated mice, there was no increase in the incidence of neoplastic lesions compared to the incidence in vehicle control mice. However, 3-MCPD treatment resulted in an increased incidence of tubular basophilia in the kidneys and germ cell degeneration in the testes, with degenerative germ cell debris in the epididymides of males at 20 and 40 mg/kg bw per day. In 3-MCPD-treated females, vacuolation of the brain and spinal cord was observed at 40 mg/kg bw per day; however, only one incidence of vacuolation was observed in males. Forestomach and cutaneous papilloma and/or carcinoma and lymphoma were observed in most rasH2 mice receiving MNU treatment. We concluded that 3-MCPD did not show carcinogenic potential in the present study using rasH2-Tg mice. The findings of this study suggest that the carcinogenic potential of 3-MCPD is species specific.

Conceptual design of a hybrid KrF laser system for ICF commercial applications

International Nuclear Information System (INIS)

Harris, D.B.; Lowenthal, D.D.

1986-01-01

KrF lasers appear to be the most efficient lasers operating near the optimal wavelength for laser fusion. Most high-efficiency, low-cost KrF laser designs use large electron-beam driven amplifiers and use pure angular multiplexing for the required pulse compression. A recent study carried out by Los Alamos and Spectra Technology has defined a high-efficiency hybrid KrF laser system architecture that uses both angular multiplexing and Raman beam combination. The high overall system efficiency of this hybrid design, approximately 12%, is achieved primarily through the use of e-beam sustained discharge lasers (EBSDL), and by using the efficient forward rotational Raman process in hydrogen. The new system appears attractive as a commercial-applications driver because the calculated efficiency is higher than the usual large e-beam pumped (EBP) KrF laser/pure angular multiplexing approach. In this paper, the hybrid system architecture is described, and the tradeoffs with respect to the large EBP amplifier/angular multiplexed system are discussed

Passive immunotherapy for influenza A H5N1 virus infection with equine hyperimmune globulin F(ab'2 in mice

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Li Yanbin

2006-03-01

Full Text Available Abstract Background Avian influenza virus H5N1 has demonstrated considerable pandemic potential. Currently, no effective vaccines for H5N1 infection are available, so passive immunotherapy may be an alternative strategy. To investigate the possible therapeutic effect of antibody against highly pathogenic H5N1 virus on a mammal host, we prepared specific equine anti-H5N1 IgGs from horses vaccinated with inactivated H5N1 virus, and then obtained the F(ab'2 fragments by pepsin digestion of IgGs. Methods The horses were vaccinated with inactivated H5N1 vaccine to prepare anti-H5N1 IgGs. The F(ab'2 fragments were purified from anti-H5N1 hyperimmune sera by a protocol for 'enhanced pepsin digestion'. The protective effect of the F(ab'2 fragments against H5N1 virus infection was determined in cultured MDCK cells by cytopathic effect (CPE assay and in a BALB/c mouse model by survival rate assay. Results By the protocol for 'enhanced pepsin digestion', total 16 g F(ab'2 fragments were finally obtained from one liter equine antisera with the purity of over 90%. The H5N1-specific F(ab'2 fragments had a HI titer of 1:1024, and the neutralization titre of F(ab'2 reached 1: 2048. The in vivo assay showed that 100 μg of the F(ab'2 fragments could protect BALB/c mice infected with a lethal dose of influenza H5N1 virus. Conclusion The availability of highly purified H5N1-specific F(ab'2 fragments may be promising for treatment of influenza H5N1 infection. Our work has provided experimental support for the application of the therapeutic equine immunoglobulin in future large primate or human trials.

Dimethylarsinic acid: Results of chronic toxicity/oncogenicity studies in F344 rats and in B6C3F1 mice

International Nuclear Information System (INIS)

Arnold, Lora L.; Eldan, Michal; Nyska, Abraham; Gemert, Marcia van; Cohen, Samuel M.

2006-01-01

Dimethylarsinic acid (DMA V , cacodylic acid), a foliar herbicide, was administered in the diet to B6C3F1 mice (at dose levels of 0, 8, 40, 200, and 500 ppm) and to F344 rats (at dose levels of 0, 2, 10, 40, and 100 ppm) for 2 years, according to US EPA guidelines. In mice, there were no treatment-related tumors observed at any site. Treatment-related progressive glomerulonephropathy and nephrocalcinosis were observed in the kidneys in both sexes. The incidence of vacuolation of the epithelium in the urinary bladder was increased in both sexes, but was not associated with cytotoxicity, necrosis or hyperplasia. Based on non-neoplastic lesions found in the urinary bladder, the NOEL for mice was assessed to be 40 ppm in males and 8 ppm in females. In rats, treatment-related mortality occurred early in the study in five males in the 100 ppm group and in one male in the 40 ppm group. Papillomas and carcinomas with degeneration of the urothelium, necrosis and urothelial cell hyperplasia, were found in the urinary bladders of both sexes. In male rats, one papilloma was found in each of the 10 and 40 ppm groups; one urothelial cell carcinoma was found in the 2 ppm group and two in the 100 ppm group. Four papillomas and six urothelial cell carcinomas were found in the female 100 ppm group. Non-neoplastic treatment-related kidney lesions were confined to the 40 and 100 ppm levels and included necrosis, pyelonephritis, medullary nephrocalcinosis and tubular cystic dilation, hyperplasia of the epithelial lining of the papilla, and pelvic urothelial cell hyperplasia. All of these kidney changes appear to be related to an increase in the aging nephropathy of the rat. Dose-related increases in the height of the thyroid follicular epithelium were also noted in males and females, however, such changes reflect an adaptive response of the thyroid to decreased levels of circulating thyroid hormone, rather than an adverse effect. Based on the kidney and bladder lesions, the NOEL for

Mice Lacking EGR1 Have Impaired Clock Gene (BMAL1) Oscillation, Locomotor Activity, and Body Temperature.

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Riedel, Casper Schwartz; Georg, Birgitte; Jørgensen, Henrik L; Hannibal, Jens; Fahrenkrug, Jan

2018-01-01

Early growth response transcription factor 1 (EGR1) is expressed in the suprachiasmatic nucleus (SCN) after light stimulation. We used EGR1-deficient mice to address the role of EGR1 in the clock function and light-induced resetting of the clock. The diurnal rhythms of expression of the clock genes BMAL1 and PER1 in the SCN were evaluated by semi-quantitative in situ hybridization. We found no difference in the expression of PER1 mRNA between wildtype and EGR1-deficient mice; however, the daily rhythm of BMAL1 mRNA was completely abolished in the EGR1-deficient mice. In addition, we evaluated the circadian running wheel activity, telemetric locomotor activity, and core body temperature of the mice. Loss of EGR1 neither altered light-induced phase shifts at subjective night nor affected negative masking. Overall, circadian light entrainment was found in EGR1-deficient mice but they displayed a reduced locomotor activity and an altered temperature regulation compared to wild type mice. When placed in running wheels, a subpopulation of EGR1-deficient mice displayed a more disrupted activity rhythm with no measurable endogenous period length (tau). In conclusion, the present study provides the first evidence that the circadian clock in the SCN is disturbed in mice deficient of EGR1.

Characterization of nasal potential difference in cftr knockout and F508del-CFTR mice.

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Emilie Lyne Saussereau

Full Text Available BACKGROUND: Treatments designed to correct cystic fibrosis transmembrane conductance regulator (CFTR defects must first be evaluated in preclinical experiments in the mouse model of cystic fibrosis (CF. Mice nasal mucosa mimics the bioelectric defect seen in humans. The use of nasal potential difference (V(TE to assess ionic transport is a powerful test evaluating the restoration of CFTR function. Nasal V(TE in CF mice must be well characterized for correct interpretation. METHODS: We performed V(TE measurements in large-scale studies of two mouse models of CF--B6;129 cftr knockout and FVB F508del-CFTR--and their respective wild-type (WT littermates. We assessed the repeatability of the test for cftr knockout mice and defined cutoff points distinguishing between WT and F508del-CFTR mice. RESULTS: We determined the typical V(TE values for CF and WT mice and demonstrated the existence of residual CFTR activity in F508del-CFTR mice. We characterized intra-animal variability in B6;129 mice and defined the cutoff points for F508del-CFTR chloride secretion rescue. Hyperpolarization of more than -2.15 mV after perfusion with a low-concentration Cl(- solution was considered to indicate a normal response. CONCLUSIONS: These data will make it possible to interpret changes in nasal V(TE in mouse models of CF, in future preclinical studies.

Avoidance of graft versus host reactions in cured W-anemic mice

International Nuclear Information System (INIS)

Harrison, D.E.

1976-01-01

Graft-versus-host reactions of parental cells in F 1 hybrids were studied with two unrelated inbred strains of mice that differed at the mouse major histocompatibility locus. W-anemic F 1 recipients were compared with lethally irradiated normal F 1 recipients. Both sets of recipients were populated by marrow and spleen cell grafts from parental and F 1 donors. Most W-anemic F 1 recipients were cured by parental and F 1 cell grafts (except B6 spleen). Even after 13 to 18 months, they showed little or no effect from GVH reactions. Lethally irradiated normal F 1 recipients tolerated parental marrow grafts almost as well, but gave dramatically different results with parental spleen grafts. Seventy-nine of 80 irradiated F 1 recipients of parental spleen grafts died within 1 month. Unlike lethally irradiated recipients, W-anemic recipients have substantial numbers of their own cells along with the donor cells in their lymphoid tissues. These F 1 lymphocytes may interact with parental lymphocytes in vivo to restrain reactions against F 1 allogeneic antigens

Suppression or knockout of SaF/SaM overcomes the Sa-mediated hybrid male sterility in rice

Institute of Scientific and Technical Information of China (English)

Yongyao Xie; Baixiao Niu; Yunming Long; Gousi Li; Jintao Tang; Yaling Zhang; Ding Ren; Yao-Guang Liu; Letian Chen

2017-01-01

Hybrids between the indica and japonica subspecies of rice (Oryza sativa) are usually sterile, which hinders utilization of heterosis in the inter-subspecific hybrid breeding. The complex locus Sa comprises two adjacently located genes, SaF and SaM, which interact to cause abortion of pollen grains carrying the japonica allele in japonica-indica hybrids. Here we showed that silencing of SaF or SaM by RNA interference restored male fertility in indica-japonica hybrids with heterozygous Sa. We further used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-based genome editing to knockout the SaF and SaM alleles, respectively, of an indica rice line to create hybrid-compatible lines. The resultant artificial neutral alleles did not affect pollen viability and other agricultural traits, but did break down the reproductive barrier in the hybrids. We found that some rice lines have natural neutral allele Sa-n, which was compatible with the typical japonica or indica Sa alleles in hybrids. Our results demonstrate that SaF and SaM are required for hybrid male sterility, but are not essential for pollen development. This study provides effective approaches for the generation of hybrid-compatible lines by knocking out the Sa locus or using the natural Sa-n allele to overcome hybrid male sterility in rice breeding.

Conceptual design of a hybrid KrF laser system for ICF commercial applications

International Nuclear Information System (INIS)

Harris, D.B.; Lowenthal, D.D.

1986-01-01

KrF lasers appear to be the most efficient lasers operating near the optimal wavelength for laser fusion. Most high-efficiency, low-cost KrF laser designs use large electron-beam-driven amplifiers and use pure angular multiplexing for the required pulse compression. A recent study carried out by Los Alamos National Lab. and Spectra Technology has defied a high-efficiency hybrid KrF laser system architecture that uses both angular multiplexing and Raman beam combination. The high overall system efficiency of this hybrid design, ∼ 12%, is achieved primarily through the use of electron-beam sustained discharge lasers (EBSDL), and by using the efficient forward rotational Raman process in hydrogen. The new system appears attractive as a commercial-applications driver because the calculated efficiency is higher than the usual large electron-beam-pumped (EBP) KrF laser/pure angular multiplexing approach. In this paper, the hybrid system architecture will be described, and the trade-offs with respect to the large EBP amplifier/angular multiplexed system will be discussed

Temporal stability of novelty exploration in mice exposed to different open field tests.

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Kalueff, Allan V; Keisala, Tiina; Minasyan, Anna; Kuuslahti, Marianne; Tuohimaa, Pentti

2006-03-01

We investigated behavioural activity and temporal distribution (patterning) of mouse exploration in different open field (OF) arenas. Mice of 129S1 (S1) strain were subjected in parallel to three different OF arenas (Experiment 1), two different OF arenas in two trials (Experiment 2) or two trials of the same OF test (Experiment 3). Overall, mice demonstrated a high degree of similarity in the temporal profile of novelty-induced horizontal and vertical exploration (regardless of the size, colour and shape of the OF), which remained stable in subsequent OF exposures. In Experiments 4 and 5, we tested F1 hybrid mice (BALB/c-S1; NMRI-S1), and Vitamin D receptor knockout mice (generated on S1 genetic background), again showing strikingly similar temporal patterns of their OF exploration, despite marked behavioural strain differences in anxiety and activity. These results suggest that mice are characterised by stability of temporal organization of their exploration in different OF novelty situations.

An Lck-cre transgene accelerates autoantibody production and lupus development in (NZB × NZW)F1 mice

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Nelson, Richard K.; Gould, Karen A.

2015-01-01

Lupus is an autoimmune disease characterized by the development of antinuclear autoantibodies and immune complex-mediated tissue damage. T cells in lupus patients appear to undergo apoptosis at an increased rate, and this enhanced T cell apoptosis has been postulated to contribute to lupus pathogenesis by increasing autoantigen load. However, there is no direct evidence to support this hypothesis. In this study, we show that an Lck-cre transgene, which increases T cell apoptosis as a result of T cell specific expression of cre recombinase, accelerates the development of autoantibodies and nephritis in lupus-prone (NZB×NZW)F1 mice. Although the enhanced T cell apoptosis in Lck-cre transgenic mice resulted in an overall decrease in the relative abundance of splenic CD4+ and CD8+ T cells, the proportion of activated CD4+ T cells was increased and no significant change was observed in the relative abundance of suppressive T cells. We postulate that the Lck-cre transgene promoted lupus by enhancing T cells apoptosis, which, in conjunction with the impaired clearance of apoptotic cells in lupus-prone mice, increased the nuclear antigen load and accelerated the development of anti-nuclear autoantibodies. Furthermore, our results also underscore the importance of including cre-only controls in studies using the cre-lox system. PMID:26385218

Borders and Comparative Cytoarchitecture of the Perirhinal and Postrhinal Cortices in an F1 Hybrid Mouse

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Beaudin, Stephane A.; Singh, Teghpal; Agster, Kara L.

2013-01-01

We examined the cytoarchitectonic and chemoarchitectonic organization of the cortical regions associated with the posterior rhinal fissure in the mouse brain, within the framework of what is known about these regions in the rat. Primary observations were in a first-generation hybrid mouse line, B6129PF/J1. The F1 hybrid was chosen because of the many advantages afforded in the study of the molecular and cellular bases of learning and memory. Comparisons with the parent strains, the C57BL6/J and 129P3/J are also reported. Mouse brain tissue was processed for visualization of Nissl material, myelin, acetyl cholinesterase, parvalbumin, and heavy metals. Tissue stained for heavy metals by the Timm’s method was particularly useful in the assignment of borders and in the comparative analyses because the patterns of staining were similar across species and strains. As in the rat, the areas examined were parcellated into 2 regions, the perirhinal and the postrhinal cortices. The perirhinal cortex was divided into areas 35 and 36, and the postrhinal cortex was divided into dorsal (PORd) and ventral (PORv) subregions. In addition to identifying the borders of the perirhinal cortex, we were able to identify a region in the mouse brain that shares signature features with the rat postrhinal cortex. PMID:22368084

Detrimental Effects of Helium Ion Irradiation on Cognitive Performance and Cortical Levels of MAP-2 in B6D2F1 Mice.

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Raber, Jacob; Torres, Eileen Ruth S; Akinyeke, Tunde; Lee, Joanne; Weber Boutros, Sydney J; Turker, Mitchell S; Kronenberg, Amy

2018-04-20

The space radiation environment includes helium (⁴He) ions that may impact brain function. As little is known about the effects of exposures to ⁴He ions on the brain, we assessed the behavioral and cognitive performance of C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation with ⁴He ions (250 MeV/n; linear energy transfer (LET) = 1.6 keV/μm; 0, 21, 42 or 168 cGy). Sham-irradiated mice and mice irradiated with 21 or 168 cGy showed novel object recognition, but mice irradiated with 42 cGy did not. In the passive avoidance test, mice received a slight foot shock in a dark compartment, and latency to re-enter that compartment was assessed 24 h later. Sham-irradiated mice and mice irradiated with 21 or 42 cGy showed a higher latency on Day 2 than Day 1, but the latency to enter the dark compartment in mice irradiated with 168 cGy was comparable on both days. ⁴He ion irradiation, at 42 and 168 cGy, reduced the levels of the dendritic marker microtubule-associated protein-2 (MAP-2) in the cortex. There was an effect of radiation on apolipoprotein E (apoE) levels in the hippocampus and cortex, with higher apoE levels in mice irradiated at 42 cGy than 168 cGy and a trend towards higher apoE levels in mice irradiated at 21 than 168 cGy. In addition, in the hippocampus, there was a trend towards a negative correlation between MAP-2 and apoE levels. While reduced levels of MAP-2 in the cortex might have contributed to the altered performance in the passive avoidance test, it does not seem sufficient to do so. The higher hippocampal and cortical apoE levels in mice irradiated at 42 than 168 cGy might have served as a compensatory protective response preserving their passive avoidance memory. Thus, there were no alterations in behavioral performance in the open filed or depressive-like behavior in the forced swim test, while cognitive impairments were seen in the object recognition and passive avoidance tests, but not in the contextual or cued fear

Detrimental Effects of Helium Ion Irradiation on Cognitive Performance and Cortical Levels of MAP-2 in B6D2F1 Mice

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Jacob Raber

2018-04-01

Full Text Available The space radiation environment includes helium (4He ions that may impact brain function. As little is known about the effects of exposures to 4He ions on the brain, we assessed the behavioral and cognitive performance of C57BL/6J × DBA2/J F1 (B6D2F1 mice three months following irradiation with 4He ions (250 MeV/n; linear energy transfer (LET = 1.6 keV/μm; 0, 21, 42 or 168 cGy. Sham-irradiated mice and mice irradiated with 21 or 168 cGy showed novel object recognition, but mice irradiated with 42 cGy did not. In the passive avoidance test, mice received a slight foot shock in a dark compartment, and latency to re-enter that compartment was assessed 24 h later. Sham-irradiated mice and mice irradiated with 21 or 42 cGy showed a higher latency on Day 2 than Day 1, but the latency to enter the dark compartment in mice irradiated with 168 cGy was comparable on both days. 4He ion irradiation, at 42 and 168 cGy, reduced the levels of the dendritic marker microtubule-associated protein-2 (MAP-2 in the cortex. There was an effect of radiation on apolipoprotein E (apoE levels in the hippocampus and cortex, with higher apoE levels in mice irradiated at 42 cGy than 168 cGy and a trend towards higher apoE levels in mice irradiated at 21 than 168 cGy. In addition, in the hippocampus, there was a trend towards a negative correlation between MAP-2 and apoE levels. While reduced levels of MAP-2 in the cortex might have contributed to the altered performance in the passive avoidance test, it does not seem sufficient to do so. The higher hippocampal and cortical apoE levels in mice irradiated at 42 than 168 cGy might have served as a compensatory protective response preserving their passive avoidance memory. Thus, there were no alterations in behavioral performance in the open filed or depressive-like behavior in the forced swim test, while cognitive impairments were seen in the object recognition and passive avoidance tests, but not in the contextual or cued

Immunotoxicological profile of chloramine in female B6C3F1 mice when administered in the drinking water for 28 days.

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Guo, Tai L; Germolec, Dori R; Collins, Bradley J; Luebke, Robert W; Auttachoat, Wimolnut; Smith, Matthew J; White, Kimber L

2011-01-01

Monochloramine has been used to provide a disinfecting residual in water distribution systems where it is difficult to maintain an adequate free-chlorine residual or where disinfection by-product formation is of concern. The goal of this study was to characterize the immunotoxic effects of chloramine in female B(6)C(3)F(1) mice when administered via the drinking water. Mice were exposed to chloramine-containing deionized tap water at 2, 10, 20, 100, or 200 ppm for 28 days. No statistically significant differences in drinking water consumption, body weight, body weight gain, organ weights, or hematological parameters between the exposed and control animals were noted during the experimental period. There were no changes in the percentages and numbers of total B-lymphocytes, T-lymphocytes, CD4(+) and CD8(+) T-lymphocytes, natural killer (NK) cells, and macrophages in the spleen. Exposure to chloramine did not affect the IgM antibody-forming cell response to sheep red blood cells (SRBC) or anti-SRBC IgM antibody production. Minimal effects, judged to be biologically insignificant, were observed in the mixed-leukocyte response and NK activity. In conclusion, chloramine produced no toxicological and immunotoxic effects in female B(6)C(3)F(1) mice when administered for 28 days in the drinking water at concentrations ranging from 2-200 ppm.

Cardiomyocyte specific deletion of Crif1 causes mitochondrial cardiomyopathy in mice.

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Juhee Shin

Full Text Available Mitochondria are key organelles dedicated to energy production. Crif1, which interacts with the large subunit of the mitochondrial ribosome, is indispensable for the mitochondrial translation and membrane insertion of respiratory subunits. To explore the physiological function of Crif1 in the heart, Crif1(f/f mice were crossed with Myh6-cre/Esr1 transgenic mice, which harbor cardiomyocyte-specific Cre activity in a tamoxifen-dependent manner. The tamoxifen injections were given at six weeks postnatal, and the mutant mice survived only five months due to hypertrophic heart failure. In the mutant cardiac muscles, mitochondrial mass dramatically increased, while the inner structure was altered with lack of cristae. Mutant cardiac muscles showed decreased rates of oxygen consumption and ATP production, suggesting that Crif1 plays a critical role in the maintenance of both mitochondrial structure and respiration in cardiac muscles.

Suppression or knockout of SaF/SaM overcomes the Sa-mediated hybrid male sterility in rice.

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Xie, Yongyao; Niu, Baixiao; Long, Yunming; Li, Gousi; Tang, Jintao; Zhang, Yaling; Ren, Ding; Liu, Yao-Guang; Chen, Letian

2017-09-01

Hybrids between the indica and japonica subspecies of rice (Oryza sativa) are usually sterile, which hinders utilization of heterosis in the inter-subspecific hybrid breeding. The complex locus Sa comprises two adjacently located genes, SaF and SaM, which interact to cause abortion of pollen grains carrying the japonica allele in japonica-indica hybrids. Here we showed that silencing of SaF or SaM by RNA interference restored male fertility in indica-japonica hybrids with heterozygous Sa. We further used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-based genome editing to knockout the SaF and SaM alleles, respectively, of an indica rice line to create hybrid-compatible lines. The resultant artificial neutral alleles did not affect pollen viability and other agricultural traits, but did break down the reproductive barrier in the hybrids. We found that some rice lines have natural neutral allele Sa-n, which was compatible with the typical japonica or indica Sa alleles in hybrids. Our results demonstrate that SaF and SaM are required for hybrid male sterility, but are not essential for pollen development. This study provides effective approaches for the generation of hybrid-compatible lines by knocking out the Sa locus or using the natural Sa-n allele to overcome hybrid male sterility in rice breeding. © 2017 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc. © 2017 Institute of Botany, Chinese Academy of Sciences.

Hybrid ICA-Seed-Based Methods for fMRI Functional Connectivity Assessment: A Feasibility Study

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Robert E. Kelly

2010-01-01

Full Text Available Brain functional connectivity (FC is often assessed from fMRI data using seed-based methods, such as those of detecting temporal correlation between a predefined region (seed and all other regions in the brain; or using multivariate methods, such as independent component analysis (ICA. ICA is a useful data-driven tool, but reproducibility issues complicate group inferences based on FC maps derived with ICA. These reproducibility issues can be circumvented with hybrid methods that use information from ICA-derived spatial maps as seeds to produce seed-based FC maps. We report results from five experiments to demonstrate the potential advantages of hybrid ICA-seed-based FC methods, comparing results from regressing fMRI data against task-related a priori time courses, with “back-reconstruction” from a group ICA, and with five hybrid ICA-seed-based FC methods: ROI-based with (1 single-voxel, (2 few-voxel, and (3 many-voxel seed; and dual-regression-based with (4 single ICA map and (5 multiple ICA map seed.

DEVELOPMENT OF MELON F1 SEEDS BASED ON LINES WITH GENIC MALE STERILITY

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A. S. Sokolov

2014-01-01

Full Text Available The perspective technology of development of melon of F1hybrids seeds by use maternal lines with an original form of genic mail sterility and marker trait (lobed leaves was studied. Elements of technology allow developing hybrid seeds of melon with hybridity of 90-95%.

Immunization of Mice with a Live Transconjugant Shigella Hybrid Strain Induced Th1 and Th17 Cell-Mediated Immune Responses and Confirmed Passive Protection Against Heterologous Shigellae.

Science.gov (United States)

Nag, D; Koley, H; Sinha, R; Mukherjee, P; Sarkar, C; Withey, J H; Gachhui, R

2016-02-01

An avirulent, live transconjugant Shigella hybrid (LTSHΔstx) strain was constructed in our earlier study by introducing a plasmid vector, pPR1347, into a Shiga toxin gene deleted Shigella dysenteriae 1. Three successive oral administrations of LTSHΔstx to female adult mice produced comprehensive passive heterologous protection in their offspring against challenge with wild-type shigellae. Production of NO and different cytokines such asIL-12p70, IL-1β and IL-23 in peritoneal mice macrophages indicated that LTSHΔstx induced innate and adaptive immunity in mice. Furthermore, production of IFN-γ, IL-10 and IL-17 in LTSH-primed splenic CD4+ T cell suggested that LTSHΔstx may induce Th1 and Th17 cell-mediated immune responses. Exponential increase of the serum IgG and IgA titre against whole shigellae was observed in immunized adult mice during and after the immunization with the highest peak on day 35. Antigen-specific sIgA was also determined from intestinal lavage of immunized mice. The stomach extracts of neonates from immunized mice, mainly containing mother's milk, contained significant levels of anti-LTSHΔstx immunoglobulin. These studies suggest that the LTSHΔstx could be a new live oral vaccine candidate against shigellosis in the near future. © 2015 The Foundation for the Scandinavian Journal of Immunology.

Hybrid EEG-fNIRS-Based Eight-Command Decoding for BCI: Application to Quadcopter Control.

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Khan, Muhammad Jawad; Hong, Keum-Shik

2017-01-01

In this paper, a hybrid electroencephalography-functional near-infrared spectroscopy (EEG-fNIRS) scheme to decode eight active brain commands from the frontal brain region for brain-computer interface is presented. A total of eight commands are decoded by fNIRS, as positioned on the prefrontal cortex, and by EEG, around the frontal, parietal, and visual cortices. Mental arithmetic, mental counting, mental rotation, and word formation tasks are decoded with fNIRS, in which the selected features for classification and command generation are the peak, minimum, and mean ΔHbO values within a 2-s moving window. In the case of EEG, two eyeblinks, three eyeblinks, and eye movement in the up/down and left/right directions are used for four-command generation. The features in this case are the number of peaks and the mean of the EEG signal during 1 s window. We tested the generated commands on a quadcopter in an open space. An average accuracy of 75.6% was achieved with fNIRS for four-command decoding and 86% with EEG for another four-command decoding. The testing results show the possibility of controlling a quadcopter online and in real-time using eight commands from the prefrontal and frontal cortices via the proposed hybrid EEG-fNIRS interface.

Preheating Mechanism in F-term SUSY Hybrid Inflation

International Nuclear Information System (INIS)

Mazumdar, Arindam

2012-01-01

Supersymmetric F-term hybrid inflation is one of the most popular models of inflation. Preheating process occurs in this model via two different mechanism. Firstly the standard parametric resonance and secondly, the tachyonic preheating. Generally tachyonic preheating dominates the parametric resonance for this type of models. For different values of the parameters of the theory dominance of tachyonic preheating can vary.

Experimental transmission of M. leprae into the testes of mice born from 60Co-irradiated pregnant mice

International Nuclear Information System (INIS)

Sushida, Kiyo; Tanemura, Mutsuko

1979-01-01

R 1 -mice, which were born from pregnant mice (R-P) irradiated with 60 CO 300 R were inoculated with leprosy bacilli into the testis. Recently, the author reported that the skin homograft survival duration in 60 CO-irradiated mice (R-P) was shown to be longer than the duration in the R 1 -F mice. The acid-fast bacilli, the so-called globi, were often found at the inoculated site of R-P mice, but not in the R 1 -F mice. The R 1 -F females bred with normal males and the R 2 -F females bred with normal males were both irradiated with 60 CO 300 R, and the R 2 -F male offspring from this R 1 -F and the R 3 -F male offspring from this R 2 -F showed the same increase in sensitivity to leprosy bacilli as the R-P generation. Acid-fast bacilli (globi, +G) were also found in the testes of the R 2 -F and R 3 -F males. IR-F mice which had received 131 I-Na 100 μci injections and also 60 CO 300 R irradiations during their fetus-term, showed few increase in sensitivity to infection of leprosy bacilli. (author)

Toxicology and carcinogenesis studies of p,p'-dichlorophenyl sulfone (CAS No. 80-07-9) in F344/N rats and B6C3F1 mice (feed studies).

Science.gov (United States)

2001-09-01

p,pN-Dichlorodiphenyl sulfone is used as a starting material in the production of polysulfones and polyethersulfones and as a component in reactive dyes in the textile industry; it is also a by-product of pesticide production. p,pN-Dichlorodiphenyl sulfone was nominated for study by the National Cancer Institute because of its history of high production and use, the prospect of increased production and use, and the absence of adequate toxicity testing. Male and female F344/N rats and B6C3F1 mice were exposed top,pN-dichlorodiphenyl sulfone (greater than 99% pure)in feed for 14 weeks or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium,cultured Chinese hamster ovary cells, and mouse bone marrow. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were fed diets containing 0, 30, 100, 300, 1,000, or 3,000 ppm p,pN-dichlorodiphenyl sulfone (equivalent to average daily doses of approximately 2, 6, 19, 65, or 200 mgp,pN-dichlorodiphenyl sulfone/kg body weight) for 14 weeks. All rats survived until the end of the study. Mean body weights of groups exposed to 300 ppm or greater were significantly less than those of the controls. Liver weights of groups exposed to 100 ppm or greater and kidney weights of 1,000 and 3,000 ppm male rats were significantly greater than those of the controls. Centrilobular hepatocyte hypertrophy of the liver was observed in most male rats exposed to 100 ppm or greater and in all female rats exposed to 300 ppm or greater, and the severities were increased in 300 ppm males and 1,000 and 3,000 ppm males and females. The incidences of nephropathy in 1,000 and 3,000 ppm female rats were significantly increased. Dose-related increases in severity of nephropathy were observed in male rats. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were fed diets containing 0, 30, 100, 300, 1,000, or 3,000 ppm p,pN-dichlorodiphenyl sulfone (equivalent to average daily doses of approximately 3.5, 15, 50

Evaluation of resistance to Neoleucinodes elegantalis Guennée and Meloidogyne incognita in an F1 hybrid of Solanum quitoense Lam.

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Manuel Francisco Polanco Puerta

2018-05-01

Full Text Available The aim of this study was to cross lulo plants of cv. La Selva to obtain a hybrid with tolerance to the fruit borer Neoleucinodes elegantalis Guenée (Lepidoptera: Crambidae and to the nematode Meloidogyne incognita (Kofoid & White (Nematoda: Heteroderidae, to obtain better-adapted plants to the conditions of the Colombian coffee-growing region and with bigger and non-dehiscent fruits. La Selva cultivar is a hybrid developed from the interspecific backcross of Solanum quitoense Lam. × Solanum hirtum Vahl with plants of lulo cv. Castilla Larga Vida. The experiment was conducted in the municipality of Dosquebradas, Risaralda, Colombia, located at 1,465 m a.s.l. F1 plants were obtained from reciprocal crossings. When inoculated with the nematode M. incognita, plants showed susceptibility in their seedling stage; however, when we carried out the evaluation six months after transplantation under field conditions, nematode infestation was less than 1%, which likely indicates the tolerance of these materials to the nematode. When assessing the resistance of the hybrid to the attack of N. elegantalis, we found that the evaluated materials were resistant to this insect. The resulting hybrids showed good agronomic characteristics, such as a good morphological structure and vigor, high productivity, good solar exposure adaptation, large fruits (5.6 cm average diameter similar to those of cv. Castilla, with yellow peel, green pulp and non-dehiscent fruits with pleasant aroma and flavor. As an undesirable characteristic plants had thorns on leaves and stems.

Dosimetric estimation of O-(3-18F-fluoropropyl)-L-tyrosine in human based on mice biodistribution data

International Nuclear Information System (INIS)

Tang Ganghua; Wang Mingfang; Luo Lei; Gan Manquan; Tang Xiaolan

2002-01-01

Objective: To estimate the radiation absorbed doses in humans due to intravenous administration of O-(3- 18 F-fluoropropyl)-L-tyrosine (FPT) based on mice biodistribution data and appraise the security of FPT in humans. Methods: FPT was injected into mice through a tail vein. At 10, 30, 60, 120 and 180 min after injection, the mice were killed by cervical fracture and biodistribution in mice were determined. Human dosimetric estimation was performed from the biodistribution of FPT in mice and the standard MIRD method using fractional radioactivity-time curves for humans. Results: The bone in human was the organ receiving highest dose of 4.29 x 10 -3 mGy/MBq, the brain received lowest dose of 1.57 x 10 -3 mGy/MBq, and other organs received doses between 1.8 x 10 -3 and 2.4 x 10 -3 mGy/MBq. The effective dose was estimated to be 9.15 x 10 -3 mSv/MBq. These results were comparable to values reported by foreign authors on the radiation dosimetry of O-(2- 18 F-fluoroethyl)-L-tyrosine. Conclusion: Human dosimetric estimation can be performed based on mice biodistribution data. The study provides an important data for clinical safety of FPT

Evaluation of methods and levels of phosphorus application in F1 hybrid capsicum (Capsicum annum L.) using 32P-labelled superphosphate

International Nuclear Information System (INIS)

Kotur, S.C.

2005-01-01

Deep placement of phosphatic fertilizer proximal to the dense distribution of roots has resulted in better absorption and utilization in many crops. The relative efficiency of various methods of fertilizer placement using 32 P-labelled superphosphate has been evaluated in wheat, oats, France bean, okra, brinjal and tomato, cabbage and onion and chilli. In this paper, studies were undertaken to evaluate different methods of superphosphate placements to F 1 hybrid capsicum applied at different levels of recommended P dose

DPP-4 inhibitor des-F-sitagliptin treatment increased insulin exocytosis from db/db mice {beta} cells

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Nagamatsu, Shinya, E-mail: shinya@ks.kyorin-u.ac.jp [Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611 (Japan); Ohara-Imaizumi, Mica; Nakamichi, Yoko; Aoyagi, Kyota; Nishiwaki, Chiyono [Department of Biochemistry, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611 (Japan)

2011-09-09

Highlights: {yields} Anti-diabetic new drug, DPP-4 inhibitor, can affect the insulin exocytosis. {yields} DPP-4 inhibitor treatment altered syntaxin 1 expression. {yields} Treatment of db/db mice with DPP-4 inhibitor increased insulin release. -- Abstract: Incretin promotes insulin secretion acutely. Recently, orally-administered DPP-4 inhibitors represent a new class of anti-hyperglycemic agents. Indeed, inhibitors of dipeptidyl peptidase-IV (DPP-4), sitagliptin, has just begun to be widely used as therapeutics for type 2 diabetes. However, the effects of sitagliptin-treatment on insulin exocytosis from single {beta}-cells are yet unknown. We therefore investigated how sitagliptin-treatment in db/db mice affects insulin exocytosis by treating db/db mice with des-F-sitagliptin for 2 weeks. Perfusion studies showed that 2 weeks-sitagliptin treatment potentiated insulin secretion. We then analyzed insulin granule motion and SNARE protein, syntaxin 1, by TIRF imaging system. TIRF imaging of insulin exocytosis showed the increased number of docked insulin granules and increased fusion events from them during first-phase release. In accord with insulin exocytosis data, des-F-sitagliptin-treatment increased the number of syntaxin 1 clusters on the plasma membrane. Thus, our data demonstrated that 2-weeks des-F-sitagliptin-treatment increased the fusion events of insulin granules, probably via increased number of docked insulin granules and that of syntaxin 1 clusters.

NTP technical report on the toxicity studies of Castor Oil (CAS No. 8001-79-4) in F344/N Rats and B6C3F1 Mice (Dosed Feed Studies).

Science.gov (United States)

Irwin, R

1992-03-01

Castor oil is a natural oil derived from the seeds of the castor bean, Ricinus communis. It is comprised largely of triglycerides with a high ricinolin content. Toxicity studies with castor oil were performed by incorporating the material at concentrations as high as 10% in diets given to F344/N rats and B6C3F1 mice of both sexes for 13 weeks. Genetic toxicity studies also were performed and were negative for mutation induction in Salmonella typhimurium, for induction of sister chromatid exchanges or chromosomal aberrations in Chinese hamster ovary cells, and for induction of micronuclei in the peripheral blood erythrocytes of mice evaluated at the end of the 13-week studies. Exposure to castor oil at dietary concentrations as high as 10% in 13-week studies did not affect survival or body weight gains of rats or mice (10 per sex and dose). There were no biologically significant effects noted in hematologic analyses in rats. Mild increases in total bile acids and in serum alkaline phosphatase were noted at various times during the studies in rats receiving the higher dietary concentrations of castor oil. Liver weights were increased in male rats receiving the 10% dietary concentration and in male and female mice receiving diets containing 5% or 10% castor oil. However, there were no histopathologic lesions associated with these liver changes, nor were there any compound-related morphologic changes in any organ in rats or mice. No significant changes were noted in a screening for male reproductive endpoints, including sperm count and motility, and no changes were observed in the length of estrous cycles of rats or mice given diets containing castor oil. Thus, no significant adverse effects of castor oil administration were noted in these studies. Synonyms: Ricinus Oil, oil of Palma Christi, tangantangan oil, phorboyl, Neoloid.

Virulent PB1-F2 residues: effects on fitness of H1N1 influenza A virus in mice and changes during evolution of human influenza A viruses.

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Alymova, Irina V; McCullers, Jonathan A; Kamal, Ram P; Vogel, Peter; Green, Amanda M; Gansebom, Shane; York, Ian A

2018-05-10

Specific residues of influenza A virus (IAV) PB1-F2 proteins may enhance inflammation or cytotoxicity. In a series of studies, we evaluated the function of these virulence-associated residues in the context of different IAV subtypes in mice. Here, we demonstrate that, as with the previously assessed pandemic 1968 (H3N2) IAV, PB1-F2 inflammatory residues increase the virulence of H1N1 IAV, suggesting that this effect might be a universal feature. Combining both inflammatory and cytotoxic residues in PB1-F2 enhanced virulence further, compared to either motif alone. Residues from these virulent motifs have been present in natural isolates from human seasonal IAV of all subtypes, but there has been a trend toward a gradual reduction in the number of virulent residues over time. However, human IAV of swine and avian origin tend to have more virulent residues than do the human-adapted seasonal strains, raising the possibility that donation of PB1 segments from these zoonotic viruses may increase the severity of some seasonal human strains. Our data suggest the value of surveillance of virulent residues in both human and animal IAV to predict the severity of influenza season.

Backcrosses in interspecific hybridization in sunflower

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Atlagić Jovanka

2003-01-01

Full Text Available When incorporating desirable traits (resistance to causal agents of various diseases from the wild relatives into the cultivated sunflower, some undesirable ones are introduced too (branching, small head diameter, low oil content, etc. To overcome this problem, backcrosses (F1 interspecific hybrids x cultivated sunflower are used, although very often desirable traits are lost in the process. Cytological analysis (meiosis and pollen viability and molecular markers (RAPD were used to estimate what portion of the parental species genome was present in (be interspecific hybrids of the F1 and BC1F1 generations. The results showed that the percentage of irregularities at meiosis increased from F1 to BC1F1 gen. They also indicated the presence of aneuploids and sterility in the cross between the hexaploid species H.rigidus and cultivated sunflower. The genetic distance between the parents was 83%, that between H.rigidus and the F1 hybrid 54 61%, and that between H.annuus and F1 hybrid 70-76%. In the BC1F1 generation, the genetic distance from Hannuus decreased to 58-66% and that from H.rigidus increased to 69-76%.

Radiolabeled F(ab')2-cetuximab for theranostic purposes in colorectal and skin tumor-bearing mice models.

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Bellaye, P-S; Moreau, M; Raguin, O; Oudot, A; Bernhard, C; Vrigneaud, J-M; Dumont, L; Vandroux, D; Denat, F; Cochet, A; Brunotte, F; Collin, B

2018-05-17

This study aimed to investigate theranostic strategies in colorectal and skin cancer based on fragments of cetuximab, an anti-EGFR mAb, labeled with radionuclide with imaging and therapeutic properties, 111 In and 177 Lu, respectively. We designed F(ab') 2 -fragments of cetuximab radiolabeled with 111 In and 177 Lu. 111 In-F(ab') 2 -cetuximab tumor targeting and biodistribution were evaluated by SPECT in BalbC nude mice bearing primary colorectal tumors. The efficacy of 111 In-F(ab') 2 -cetuximab to assess therapy efficacy was performed on BalbC nude mice bearing colorectal tumors receiving 17-DMAG, an HSP90 inhibitor. Therapeutic efficacy of the radioimmunotherapy based on 177 Lu-F(ab') 2 -cetuximab was evaluated in SWISS nude mice bearing A431 tumors. Radiolabeling procedure did not change F(ab') 2 -cetuximab and cetuximab immunoreactivity nor affinity for HER1 in vitro. 111 In-DOTAGA-F(ab') 2 -cetuximab exhibited a peak tumor uptake at 24 h post-injection and showed a high tumor specificity determined by a significant decrease in tumor uptake after the addition of an excess of unlabeled-DOTAGA-F(ab') 2 -cetuximab. SPECT imaging of 111 In-DOTAGA-F(ab') 2 -cetuximab allowed an accurate evaluation of tumor growth and successfully predicted the decrease in tumor growth induced by 17-DMAG. Finally, 177 Lu-DOTAGA-F(ab') 2 -cetuximab radioimmunotherapy showed a significant reduction of tumor growth at 4 and 8 MBq doses. 111 In-DOTAGA-F(ab') 2 -cetuximab is a reliable and stable tool for specific in vivo tumor targeting and is suitable for therapy efficacy assessment. 177 Lu-DOTAGA-F(ab') 2 -cetuximab is an interesting theranostic tool allowing therapy and imaging.

Influence of 24-Nor-Ursodeoxycholic Acid on Hepatic Disposition of [(18)F]Ciprofloxacin, a Positron Emission Tomography Study in Mice.

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Wanek, Thomas; Halilbasic, Emina; Visentin, Michele; Mairinger, Severin; Römermann, Kerstin; Stieger, Bruno; Kuntner, Claudia; Müller, Markus; Langer, Oliver; Trauner, Michael

2016-01-01

24-nor-ursodeoxycholic acid (norUDCA) is a novel therapeutic approach to cholestatic liver diseases. In mouse models of cholestasis, norUDCA induces basolateral multidrug resistance-associated proteins 4 (Mrp4) and 3 in hepatocytes, which provide alternative escape routes for bile acids accumulating during cholestasis but could also result in altered hepatic disposition of concomitantly administered substrate drugs. We used positron emission tomography imaging to study the influence of norUDCA on hepatic disposition of the model Mrp4 substrate [(18)F]ciprofloxacin in wild-type and Mdr2((-/-)) mice, a model of cholestasis. Animals underwent [(18)F]ciprofloxacin positron emission tomography at baseline and after norUDCA treatment. After norUDCA treatment, liver-to-blood area under the curve ratio of [(18)F]ciprofloxacin was significantly decreased compared to baseline, both in wild-type (-34.0 ± 2.1%) and Mdr2((-/-)) mice (-20.5 ± 6.0%). [(18)F]Ciprofloxacin uptake clearance from blood into liver was reduced by -17.1 ± 9.0% in wild-type and by -20.1 ± 7.3% in Mdr2((-/-)) mice. Real-time PCR analysis showed significant increases in hepatic Mrp4 and multidrug resistance-associated protein 3 mRNA after norUDCA. Transport experiments in organic anion transporting polypeptide (OATP)1B1-, OATP1B3-, and OATP2B1-transfected cells revealed weak transport of [(14)C]ciprofloxacin by OATP1B3 and OATP2B1 and no inhibition by norUDCA. In conclusion, our data suggest that changes in hepatic [(18)F]ciprofloxacin disposition in mice after norUDCA treatment were caused by induction of basolateral Mrp4 in hepatocytes. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Immunoprotective capability of somatic hybrid cells in comparison with parental tumor cells maintained in vitro

International Nuclear Information System (INIS)

Mizushima, Yutaka; Cohen, E.P.

1985-01-01

The immunogenicity of X-irradiated hybrid cells derived from fusion of ASL-1 leukemia (A origin) and LM (TK - ) fibroblasts (C3H origin) was compared to X-irradiated parental ASL-1 leukemia cells maintained in vivo (V-ASL-1) and to X-irradiated ASL-1 leukemia cells maintained in vitro (C-ASL-1). Immunization with hybrid cells induced transplantation resistance against tumor rechallenge with V-ASL-1 more effectively than did immunization with V-ASL-1 tumor cells. Immunization with X-irradiated C-ASL-1 cells produced the same, or slightly stronger level of transplantation resistance than that with X-irradiated hybrid cells. These findings were observed both in A/J and in (C3H/HeJxA/J) F 1 mice. These results raise a question about whether the apparent increased immunogenicity of hybrid cells is due to a result of cell fusion or a result of their growth in vitro. (author)

Hybrid EEG–fNIRS-Based Eight-Command Decoding for BCI: Application to Quadcopter Control

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Khan, Muhammad Jawad; Hong, Keum-Shik

2017-01-01

In this paper, a hybrid electroencephalography–functional near-infrared spectroscopy (EEG–fNIRS) scheme to decode eight active brain commands from the frontal brain region for brain–computer interface is presented. A total of eight commands are decoded by fNIRS, as positioned on the prefrontal cortex, and by EEG, around the frontal, parietal, and visual cortices. Mental arithmetic, mental counting, mental rotation, and word formation tasks are decoded with fNIRS, in which the selected features for classification and command generation are the peak, minimum, and mean ΔHbO values within a 2-s moving window. In the case of EEG, two eyeblinks, three eyeblinks, and eye movement in the up/down and left/right directions are used for four-command generation. The features in this case are the number of peaks and the mean of the EEG signal during 1 s window. We tested the generated commands on a quadcopter in an open space. An average accuracy of 75.6% was achieved with fNIRS for four-command decoding and 86% with EEG for another four-command decoding. The testing results show the possibility of controlling a quadcopter online and in real-time using eight commands from the prefrontal and frontal cortices via the proposed hybrid EEG–fNIRS interface. PMID:28261084

Oral toxicity study of tragacanth gum in B6C3F1 mice: development of squamous-cell hyperplasia in the forestomach and its reversibility.

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Hagiwara, A; Tanaka, H; Tiwawech, D; Shirai, T; Ito, N

1991-10-01

Tragacanth gum was administered at dietary levels of 0 (control), 0.625, 1.25, 2.5, and 5.0% to groups of 10 male and 10 female B6C3F1 mice for 13 wk. There were no treatment-associated effects regarding clinical signs, body or organ weights, and urinalysis or hematology data. Significant dose-related, but slight, elevations of plasma gamma-glutamyl transpeptidase (GGT) level were observed in all treated animals except the 0.625% females. Single or small numbers of tiny nodules were observed on the luminal surface of the forestomach in 4 males of the 5.0% group, 2 males of the 2.5% group, and 1 male each from the 1.25 and 0.625% groups. Histopathologically, they were diagnosed as squamous-cell hyperplasia. To investigate the nature of these gross lesions, tragacanth gum was fed to groups of 30 male mice at the dietary level of 5.0% for periods of up to 48 wk; 20 males served as controls. There were no treatment-related increases of plasma GGT levels at wk 24 and 48. Although squamous-cell hyperplasias were seen in 2 out of 10 mice at wk 24, none of these proliferative lesions were apparent at wk 48, after either chronic exposure or 24 wk on basal diet. Furthermore, the levels of DNA synthesis in forestomach epithelium as measured by 5-bromo-2-deoxyuridine (BrdU) immunohistochemistry were comparable to control values at wk 24 and 48. Thus, the oral toxicity of tragacanth gum to B6C3F1 mice was concluded to be negligible.

Synthesis of 2'-deoxy-2'-[{sup 18}F]-fluoro-5-iodo-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FIAU) and micro-PET imaging of suicide gene expression in tumor-bearing nude mice

Energy Technology Data Exchange (ETDEWEB)

Alauddin, M.M.; Shahinian, A.; Park, R.; Tohme, M.; Fissekis, J.D.; Conti, P.S. [Univ. of Southern California, Los Angeles, CA (United States). PET Imaging Science Center

2004-07-01

Herpes simplex virus type-1 thymidine kinase (HSV1-tk) is being used as a suicide gene for gene therapy of cancer. An in vivo method to assess the HSV1-tk enzyme activity after gene transfer is desirable to monitor gene expression as an indicator of gene delivery. Imaging of the HSV1-tk reporter gene along with various reporter probes is of current interest. We originally developed [{sup 18}F]-FHPG and [{sup 18}F]-FHBG for PET imaging of HSV1-tk gene expression and demonstrated that [{sup 18}F]-FHBG is more useful than [{sup 18}F]-FHPG for this purpose. [{sup 124}I]-FIAU has been shown to be a potential PET imaging agent for HSV1-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. We also demonstrated that radiolabeled FMAU can be used as a marker for HSV-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. Earlier we reported a synthesis for 2'-deoxy-2'-[{sup 18}F]fluoro-5-methyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FMAU) and some other 5-substituted nucleosides. We have synthesized now [{sup 18}F]-FIAU, used the tracer for micro-PET imaging of suicide gene expression in tumor-bearing nude mice, and compared the results with earlier studies using [{sup 14}C]-FMAU. (orig.)

NTP Toxicology and Carcinogenesis Studies of Xylenes (Mixed) (60% m-Xylene, 14% p-Xylene, 9% o-Xylene, and 17% Ethylbenzene) (CAS No. 1330-20-7) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

Science.gov (United States)

1986-12-01

The technical grade of xylenes (mixed) (hereafter termed xylenes) contains the three isomeric forms and ethylbenzene (percentage composition shown above). The annual production for 1985 was approximately 7.4 x 108 gallons. Xylenes is used as a solvent and a cleaning agent and as a degreaser and is a constituent of aviation and automobile fuels. Xylenes is also used in the production of benzoic acid, phthalate anhydride, and isophthalic and terephthalic acids as well as their dimethyl esters. Toxicology and carcinogenesis studies of xylenes were conducted in laboratory animals because a large number of workers are exposed and because the long- term effects of exposure to xylenes were not known. Exposure for the present studies was by gavage in corn oil. In single-administration studies, groups of five F344/N rats and B6C3F1 mice of each sex received 500, 1,000, 2,000, 4,000, or 6,000 mg/kg. Administration of xylenes caused deaths at 6,000 mg/kg in rats and mice of each sex and at 4,000 mg/kg in male rats. In rats, clinical signs observed within 24 hours of dosing at 4,000 mg/kg included prostration, muscular incoordination, and loss of hind limb movement; these effects continued through the second week of observation. Tremors, prone position, and slowed breathing were recorded for mice on day 3, but all mice appeared normal by the end of the 2- week observation period. In 14- day studies, groups of five rats of each sex were administered 0, 125, 250, 500, 1,000, or 2,000 mg/kg, and groups of five mice of each sex received 0, 250, 500, 1,000, 2,000, or 4,000 mg/kg. Chemical- related mortality occurred only at 2,000 mg/kg in rats and at 4,000 mg/kg in mice. Rats and mice exhibited shallow breathing and prostration within 48 hours following dosing at 2,000 mg/kg. These signs persisted until day 12 for rats, but no clinical signs were noted during the second week for mice. In 13- week studies, groups of 10 rats of each sex received 0, 62.5, 125, 250, 500, or 1,000 mg

Toxicokinetics of α-thujone following intravenous and gavage administration of α-thujone or α- and β-thujone mixture in male and female F344/N rats and B6C3F1 mice

International Nuclear Information System (INIS)

Waidyanatha, Suramya; Johnson, Jerry D.; Hong, S. Peter; Robinson, Veronica Godfrey; Gibbs, Seth; Graves, Steven W.; Hooth, Michelle J.; Smith, Cynthia S.

2013-01-01

Plants containing thujone have widespread use and hence have significant human exposure. α-Thujone caused seizures in rodents following gavage administration. We investigated the toxicokinetics of α-thujone in male and female F344/N rats and B6C3F1 mice following intravenous and gavage administration of α-thujone or a mixture of α- and β-thujone (which will be referred to as α,β-thujone). Absorption of α-thujone following gavage administration was rapid without any dose-, species-, sex- or test article-related effect. Absolute bioavailability of α-thujone following administration of α-thujone or α,β-thujone was generally higher in rats than in mice. In rats, females had higher bioavailability than males following administration of either test article although a sex difference was not observed in mice. C max and AUC ∞ increased greater than proportional to the dose in female rats following administration of α-thujone and in male and female mice following administration of α,β-thujone suggesting possible saturation of elimination kinetics with increasing dose. Dose-adjusted AUC ∞ for male and female rats was 5- to 15-fold and 3- to 24-fold higher than mice counterparts following administration of α-thujone and α,β-thujone, respectively (p-value < 0.0001 for all comparisons). Following both intravenous and gavage administration, α-thujone was distributed to the brains of rats and mice with females, in general, having higher brain:plasma ratios than males. These data are in support of the observed toxicity of α-thujone and α,β-thujone where females were more sensitive than males of both species to α-thujone-induced neurotoxicity. In general there was no difference in toxicokinetics between test articles when normalized to α-thujone concentration. - Highlights: • Absorption of α-thujone following gavage administration was rapid in rats and mice. • Rats undergo higher exposure to α-thujone than mice. • α-Thujone brain:plasma ratios

Toxicokinetics of α-thujone following intravenous and gavage administration of α-thujone or α- and β-thujone mixture in male and female F344/N rats and B6C3F1 mice

Energy Technology Data Exchange (ETDEWEB)

Waidyanatha, Suramya, E-mail: waidyanathas@niehs.nih.gov [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Johnson, Jerry D.; Hong, S. Peter [Battelle Memorial Institute, Columbus, OH 43201 (United States); Robinson, Veronica Godfrey [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Gibbs, Seth; Graves, Steven W. [Battelle Memorial Institute, Columbus, OH 43201 (United States); Hooth, Michelle J.; Smith, Cynthia S. [Division of National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States)

2013-09-01

Plants containing thujone have widespread use and hence have significant human exposure. α-Thujone caused seizures in rodents following gavage administration. We investigated the toxicokinetics of α-thujone in male and female F344/N rats and B6C3F1 mice following intravenous and gavage administration of α-thujone or a mixture of α- and β-thujone (which will be referred to as α,β-thujone). Absorption of α-thujone following gavage administration was rapid without any dose-, species-, sex- or test article-related effect. Absolute bioavailability of α-thujone following administration of α-thujone or α,β-thujone was generally higher in rats than in mice. In rats, females had higher bioavailability than males following administration of either test article although a sex difference was not observed in mice. C{sub max} and AUC{sub ∞} increased greater than proportional to the dose in female rats following administration of α-thujone and in male and female mice following administration of α,β-thujone suggesting possible saturation of elimination kinetics with increasing dose. Dose-adjusted AUC{sub ∞} for male and female rats was 5- to 15-fold and 3- to 24-fold higher than mice counterparts following administration of α-thujone and α,β-thujone, respectively (p-value < 0.0001 for all comparisons). Following both intravenous and gavage administration, α-thujone was distributed to the brains of rats and mice with females, in general, having higher brain:plasma ratios than males. These data are in support of the observed toxicity of α-thujone and α,β-thujone where females were more sensitive than males of both species to α-thujone-induced neurotoxicity. In general there was no difference in toxicokinetics between test articles when normalized to α-thujone concentration. - Highlights: • Absorption of α-thujone following gavage administration was rapid in rats and mice. • Rats undergo higher exposure to α-thujone than mice. • α-Thujone brain

Derivation of hybrid ES cell lines from two different strains of mice

Directory of Open Access Journals (Sweden)

Ho-Tak Lau

2016-03-01

Full Text Available Parental origin-dependent expression of the imprinted genes is essential for mammalian development. Zfp57 maintains genomic imprinting in mouse embryos and ES cells. To examine the allelic expression patterns of the imprinted genes in ES cells, we obtained multiple hybrid ES clones that were directly derived from the blastocysts generated from the cross between mice on two different genetic backgrounds. The blastocyst-derived ES clones displayed largely intact DNA methylation imprint at the tested imprinted regions. These hybrid ES clones will be useful for future studies to examine the allelic expression of the imprinted genes in ES cells and their differentiated progeny.

Intrathymic selection of NK1.1+α/β T cell antigen receptor (TCR)+ cells in transgenic mice bearing TCR specific for chicken ovalbumin and restricted to I-Ad

Science.gov (United States)

Iwabuchi, Chikako; Iwabuchi, Kazuya; Nakagawa, Ken-ichi; Takayanagi, Toshiaki; Nishihori, Hiroki; Tone, Saori; Ogasawara, Kazumasa; Good, Robert A.; Onoé, Kazunori

1998-01-01

Generation and negative selection of NK1.1+α/β T cell receptor (TCR)+ thymocytes were analyzed using TCR-transgenic (B10.D2 × DO10)F1 and (C57BL/6 × DO10)F1 mice and Rag-1−/−/DO10 mice, which had been established by breeding and backcrossing between Rag-1−/− and DO10 mice. Almost all T cells from these mice were shown to bear Vα13/Vβ8.2 that is specific for chicken ovalbumin (cOVA) and restricted to I-Ad. A normal proportion of the NK1.1+ Vα13/Vβ8.2+ thymocytes was generated in these mice. However, the actual cell number of both NK1.1+ and NK1.1− thymocytes in I-Ad/d mice (positive selecting background) was larger than that in I-Ab/d mice (negative selecting background). Markedly low but significant proportions of NK1.1+ Vα13/Vβ8.2+ cells were detected in the spleens from I-Ad/d and I-Ab/d mice. It was shown that the splenic NK1.1+ T cells of the I-Ab/d mice were anergized against stimulation through TCR. When (B10.D2 × DO10)F1 and (C57BL/6 × DO10)F1 mice were given cOVA, extensive or intermediate elimination of NK1.1+α/βTCR+ thymocytes was induced in I-Ad/d or I-Ab/d mice, respectively. However, the clonal elimination was not as complete as that seen in the major NK1.1− thymocyte population. The present findings indicate that normal generation of NK1.1+α/βTCR+ thymocytes occurs in the absence of Vα14-Jα281 and that substantial negative selection operates on the NK1.1+α/βTCR+ cells. PMID:9653164

Immunoscintigraphy of human pancreatic carcinoma in nude mice with I-131-F(ab')/sub 2/-fragments of monoclonal antibodies

International Nuclear Information System (INIS)

Senekowitsch, R.; Maul, F.D.; Wenisch, H.J.C.; Kriegel, H.; Hor, G.

1985-01-01

In the present study radioiodinated F(ab')/sub 2/-fragments of CA19-9 and antibody that reacts specifically with human gastrointestinal cancer were examined for their ability to detect human pancreatic carcinoma hosted in nude mice. Tumor-bearing mice received 80μCi of I-131-F(ab')/sub 2/ with a specific activity of 1.8μCi/μg. All mice were imaged after the injection and every 24hr up to 6 days. The retained radioactivity was also registered with a whole-body counter immediately after imaging. As a control F(ab's)/sub 2/ of a nonspecific antibody were administered in parallel to another group of animals bearing the same tumor. Three animals of each group were killed at 1,2,4 and 8 days for determination of the distribution of both labeled antibody-fragments. On scintigraphic images obtained with the CA19-9-F(ab')/sub 2/ the tumors could be visualized 24hr after injection, the best dilineation however was achieved 96hr p.i.. The biodistribution data exhibited a more rapid blood clearance for the specific fragments compared to that for the unspecific ones. Tumors showed an increase in uptake up to 48hr reaching 1.7% of the injected dose per gram, declining to values of 0.08%/g at day 6 p.i.. The highest tumor-to-blood ratios were found after 96h. They were 7 for the CA19-9-fragments compared to 1.5 for the unspecific fragments. The whole body counting revealed a more rapid excretion for the fragments of the specific monoclonal antibodies than for the unspecific ones. In summary the authors were able to show that CA19-9-F(ab')/sub 2/-fragments can be used for immunodetection of human pancreatic carcinoma hosted in nude mice

Depressed levels of prostaglandin F2α in mice lacking Akr1b7 increase basal adiposity and predispose to diet-induced obesity.

Science.gov (United States)

Volat, Fanny E; Pointud, Jean-Christophe; Pastel, Emilie; Morio, Béatrice; Sion, Benoit; Hamard, Ghislaine; Guichardant, Michel; Colas, Romain; Lefrançois-Martinez, Anne-Marie; Martinez, Antoine

2012-11-01

Negative regulators of white adipose tissue (WAT) expansion are poorly documented in vivo. Prostaglandin F(2α) (PGF(2α)) is a potent antiadipogenic factor in cultured preadipocytes, but evidence for its involvement in physiological context is lacking. We previously reported that Akr1b7, an aldo-keto reductase enriched in adipose stromal vascular fraction but absent from mature adipocytes, has antiadipogenic properties possibly supported by PGF(2α) synthase activity. To test whether lack of Akr1b7 could influence WAT homeostasis in vivo, we generated Akr1b7(-/-) mice in 129/Sv background. Akr1b7(-/-) mice displayed excessive basal adiposity resulting from adipocyte hyperplasia/hypertrophy and exhibited greater sensitivity to diet-induced obesity. Following adipose enlargement and irrespective of the diet, they developed liver steatosis and progressive insulin resistance. Akr1b7 loss was associated with decreased PGF(2α) WAT contents. Cloprostenol (PGF(2α) agonist) administration to Akr1b7(-/-) mice normalized WAT expansion by affecting both de novo adipocyte differentiation and size. Treatment of 3T3-L1 adipocytes and Akr1b7(-/-) mice with cloprostenol suggested that decreased adipocyte size resulted from inhibition of lipogenic gene expression. Hence, Akr1b7 is a major regulator of WAT development through at least two PGF(2α)-dependent mechanisms: inhibition of adipogenesis and lipogenesis. These findings provide molecular rationale to explore the status of aldo-keto reductases in dysregulations of adipose tissue homeostasis.

GENERAL AND SPECIFIC COMBINING ABILITY OF INITIAL PARENTAL FORMS IN TOMATO FOR COMPLEX OF ECONOMICALLY VALUABLE TRAITS TO DEVELOP HYBRIDS F1 OF CHERRY AND COCKTAIL TYPES

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R. K. Rechets

2017-01-01

Full Text Available Results of estimation of general and specific combining ability of male and female parental tomato forms were given for complex of traits. The estimation was carried out according to incomplete diallel crosses 15x15. Such varities   as   ‘Trapeza’,  Rosovaya  kapelka’,  ‘Seniorita’, ‘Ocharovanie’,  ‘Tigris’   ‘Vishnya  Zheltaya’  (Gavrish, ‘Denezhnoye Derevo’ (national breeding, and  lines: ‘46/06’,  ‘49/09’,  ‘295/09’,  ‘336/11’,  ‘354/11’,  ‘357/11’, ‘388/09’ (nor, ‘498’ (selection of TARI were used as intial breeding accessions, differing in bush type (determinate and indeterminate, duration of vegetative phase (ultraearly,  early, medium early, middle-ripening, fruit  shape (rounded, oval, fruit color (red, pink, black, orange, tiger and with the gene nor, fruit weight (10 g. and more, brush structure (dense, friable. As a results, ‘Trapeza’, ‘Vishnya Zheltaya’, ‘Ocharovaniye’, ‘Seniorita’, and lines: ‘295/10’, ‘49/09’,  ‘498’,  ‘357/11’,  ‘354/11’,  ‘388/09’  (nor were selected and recommended to be used in breeding program for development of heterotic hybrids with high fruit setting and generative bush type. The promising hybrids F1 with high constants of specific combining ability for a complex of economically valuable traits have been observed. Because of different lines and accessions were used in crossings, these hybrids varied in internode length of cluster type, classical or shorten; rounded or oval fruit shape; fruit  color, red (F1   combinations ‘354/11’ х ‘Seniorita’, ‘Trapeza’ х  ‘L.49/09’,  L.  ‘49/09’  х  L.354/11, pink (F1 combination ‘Rosovaya Kapelka’ х ‘L.354/11’, yellow (F1 combination ‘Ocharovaniye’ х  ‘Vishiya Zheltaya’, deep brown (F1 combination  ‘L.357/11’ х ‘L.354/11’.

Toxicology study of senna (CAS No. 8013-11-4) in C57BL/6NTAC Mice and toxicology and carcinogenesis study of senna in genetically modified C3B6.129F1/Tac-Trp53tm1Brd haploinsufficient mice (Feed Studies).

Science.gov (United States)

2012-04-01

Senna is used as a stimulant laxative in the management of constipation resulting from opioid use or when treatment with bulking or osmotic agents has failed. Increased use of senna was expected due to the removal of the stimulant laxatives danthron and phenolphthalein from the market. Senna was nominated for study by the Center for Drug Evaluation and Research, United States Food and Drug Administration (FDA) due to the wide use of laxative preparations, positive genotoxicity in vitro for some senna components or metabolites, and unknown carcinogenic potential. Because a 2-year rat study was ongoing by the manufacturer, the FDA requested that the NTP conduct a senna study in the p53(+/-) mouse. In this study, the potential for carcinogenic effects of senna was studied in the C3B6.129F1/Tac-Trp53tm1Brd N12 haploinsufficient (heterozygous F1 p53(+/-)) mouse model as an ongoing goal of the NTP to develop and test model systems for toxicology and carcinogenesis studies, especially those that can provide mechanistic information relative to understanding an agents mode of action. C57BL/6NTac mice were exposed to senna in feed for 5 weeks; heterozygous F1 p53(+/-) mice were exposed to senna in feed for 40 weeks. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes.

The E2F2 transcription factor sustains hepatic glycerophospholipid homeostasis in mice.

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Eduardo N Maldonado

Full Text Available Increasing evidence links metabolic signals to cell proliferation, but the molecular wiring that connects the two core machineries remains largely unknown. E2Fs are master regulators of cellular proliferation. We have recently shown that E2F2 activity facilitates the completion of liver regeneration after partial hepatectomy (PH by regulating the expression of genes required for S-phase entry. Our study also revealed that E2F2 determines the duration of hepatectomy-induced hepatic steatosis. A transcriptomic analysis of normal adult liver identified "lipid metabolism regulation" as a major E2F2 functional target, suggesting that E2F2 has a role in lipid homeostasis. Here we use wild-type (E2F2+/+ and E2F2 deficient (E2F2-/- mice to investigate the in vivo role of E2F2 in the composition of liver lipids and fatty acids in two metabolically different contexts: quiescence and 48-h post-PH, when cellular proliferation and anabolic demands are maximal. We show that liver regeneration is accompanied by large triglyceride and protein increases without changes in total phospholipids both in E2F2+/+ and E2F2-/- mice. Remarkably, we found that the phenotype of quiescent liver tissue from E2F2-/- mice resembles the phenotype of proliferating E2F2+/+ liver tissue, characterized by a decreased phosphatidylcholine to phosphatidylethanolamine ratio and a reprogramming of genes involved in generation of choline and ethanolamine derivatives. The diversity of fatty acids in total lipid, triglycerides and phospholipids was essentially preserved on E2F2 loss both in proliferating and non-proliferating liver tissue, although notable exceptions in inflammation-related fatty acids of defined phospholipid classes were detected. Overall, our results indicate that E2F2 activity sustains the hepatic homeostasis of major membrane glycerolipid components while it is dispensable for storage glycerolipid balance.

A Study of Selected Isozymes in Capsicum baccatum, Capsicum eximium, Capsicum cardenasii and Two Interspecific F1 Hybrids in Capsicum Species

OpenAIRE

ONUS, Ahmet Naci

2014-01-01

Selected isozymes were investigated in plants of Capsicum baccatum L. ( Solanaceae) accessions SA219 (P.G.Smith), Hawkes 6489 (P.G.Smith), Capsicum cardenasii Heiser and Smith accession SA268 (P.G.Smith), Capsicum eximium A.T.Hunz accession Hawkes 3860 (J.G.Hawkes) and two interspecific F1 hybrids, C. baccatum SA219 x C. eximium Hawkes 3860 and C. baccatum Hawkes 6489 x C. cardenasii SA 268. The standard technique of horizontal gel electrophoresis was employed. The gel was cut into severa...

NTP Toxicology and Carcinogenesis of 1,2,3-Trichloropropane (CAS No. 96-18-4) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

Science.gov (United States)

1993-08-01

1,2,3-Trichloropropane is a colorless liquid used as a paint and varnish remover, solvent, and degreasing agent, and as a crosslinking agent in the synthesis of polysulfides and hexafluoropropylene. 1,2,3-Trichloropropane may be found as an impurity in certain nematocides and soil fumigants and as a contaminant of drinking and ground water. Studies on the toxic and carcinogenic effects of 1,2,3-trichloropropane were initiated because of the close structural relationship of this chemical to other short-chain halogenated compounds that were demonstrated to be carcinogenic in experimental animals, and because of the potential for human exposure. Toxicology and carcinogenicity studies were conducted by administering 1,2,3-trichloropropane (greater than 99% pure) in corn oil by gavage to groups of F344/N rats and B6C3FI mice for 17 weeks and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium strains, mouse lymphoma cells, and Chinese hamster ovary cells. 17-Week Studies: Groups of 20 male and 20 female rats received 1,2,3-trichloropropane in corn oil by gavage at doses of 8, 16, 32, 63, 125, or 250 mg/kg body weight 5 days per week for up to 17 weeks; 30 male and 30 female rats received corn oil alone and served as controls. Animals were evaluated at 8 or 17 weeks. All rats in the 250 mg/kg groups died by week 5. One male and four female rats in the 125 mg/kg groups died during the study. The mean body weight gains and final mean body weights of males receiving 63 mg/kg and of males and females receiving 125 mg/kg were lower than those of the controls. Hematocrit values, hemoglobin concentrations, and erythrocyte counts decreased with dose in males and females. Serum alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase activities were significantly increased in some female rats receiving 125 mg/kg. Serum pseudocholinesterase activity decreased with dose in females. Increases in kidney and liver weights were related

Synthesis of 2'-deoxy-2'-[{sup 18}F]-fluoro-5-ethyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FEAU) and micro-PET imaging of HSV-tk gene expression in tumor-bearing nude mice

Energy Technology Data Exchange (ETDEWEB)

Alauddin, M.M.; Shahinian, A.; Park, R.; Tohme, M.; Fissekis, J.D.; Conti, P.S. [Univ. of Southern California, Los Angeles, CA (United States). PET Imaging Science Center

2004-07-01

Herpes simplex virus type-1 thymidine kinase (HSV1-tk) is being used as a suicide gene for gene therapy of cancer. An in vivo method to assess the HSV1-tk enzyme activity after gene transfer is desirable to monitor gene expression as an indicator of gene delivery. Imaging of the HSV1-tk reporter gene along with various reporter probes is of current interest. We originally developed [{sup 18}F]-FHPG and [{sup 18}F]-FHBG for PET imaging of HSV1-tk gene expression and demonstrated that [{sup 18}F]-FHBG is more useful than [{sup 18}F]-FHPG for this purpose. [{sup 124}I]-FIAU has been shown to be a potential PET imaging agent for HSV1-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. We also demonstrated that radiolabeled FMAU can be used as a marker for HSV-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. Earlier we reported a synthesis for 2'-deoxy-2'-[{sup 18}F]fluoro-5-methyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FMAU) and some other 5-substituted nucleosides. We have synthesized now [{sup 18}F]-FEAU, used the tracer for micro-PET imaging of suicide gene expression in tumor-bearing nude mice, and compared the results with earlier studies using [{sup 14}C]-FMAU. (orig.)

[18F]DPA 714 PET Imaging Reveals Global Neuroinflammation in Zika Virus Infected Mice

Science.gov (United States)

2017-09-12

with neurotropic viruses and the evaluation of therapeutics being developed for treatment of infectious diseases. Keywords: Zika virus , Animal...18F]DPA-714 PET Imaging Reveals Global Neuroinflammation in Zika Virus - Infected Mice Kyle Kuszpit1†, Bradley S. Hollidge2†, Xiankun Zeng3, Robert...Running Head: PET Imaging of Zika Virus -Induced Neuroinflammation Manuscript Category: Article Affiliations: 1Molecular and Translational

An Lck-cre transgene accelerates autoantibody production and lupus development in (NZB × NZW)F1 mice.

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Nelson, R K; Gould, K A

2016-02-01

Lupus is an autoimmune disease characterized by the development of antinuclear autoantibodies and immune complex-mediated tissue damage. T cells in lupus patients appear to undergo apoptosis at an increased rate, and this enhanced T cell apoptosis has been postulated to contribute to lupus pathogenesis by increasing autoantigen load. However, there is no direct evidence to support this hypothesis. In this study, we show that an Lck-cre transgene, which increases T cell apoptosis as a result of T cell-specific expression of cre recombinase, accelerates the development of autoantibodies and nephritis in lupus-prone (NZB × NZW)F1 mice. Although the enhanced T cell apoptosis in Lck-cre transgenic mice resulted in an overall decrease in the relative abundance of splenic CD4(+) and CD8(+) T cells, the proportion of activated CD4(+) T cells was increased and no significant change was observed in the relative abundance of suppressive T cells. We postulate that the Lck-cre transgene promoted lupus by enhancing T cell apoptosis, which, in conjunction with the impaired clearance of apoptotic cells in lupus-prone mice, increased the nuclear antigen load and accelerated the development of anti-nuclear autoantibodies. Furthermore, our results also underscore the importance of including cre-only controls in studies using the cre-lox system. © The Author(s) 2015.

Noninvasive Evaluation of Metabolic Tumor Volume in Lewis Lung Carcinoma Tumor-Bearing C57BL/6 Mice with Micro-PET and the Radiotracers 18F-Alfatide and 18F-FDG: A Comparative Analysis.

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Yu-Chun Wei

Full Text Available To explore the value of a new simple lyophilized kit for labeling PRGD2 peptide (18F-ALF-NOTA-PRGD2, denoted as 18F-alfatide in the determination of metabolic tumor volume (MTV with micro-PET in lewis lung carcinoma (LLC tumor-bearing C57BL/6 mice verified by pathologic examination and compared with those using 18F-fluorodeoxyglucose (FDG PET.All LLC tumor-bearing C57BL/6 mice underwent two attenuation-corrected whole-body micro-PET scans with the radiotracers 18F-alfatide and 18F-FDG within two days. 18F-alfatide metabolic tumor volume (VRGD and 18F-FDG metabolic tumor volume (VFDG were manually delineated slice by slice on PET images. Pathologic tumor volume (VPath was measured in vitro after the xenografts were removed.A total of 37 mice with NSCLC xenografts were enrolled and 33 of them underwent 18F-alfatide PET, and 35 of them underwent 18F-FDG PET and all underwent pathological examination. The mean ± standard deviation of VPath, VRGD, and VFDG were 0.59±0.32 cm3 (range,0.13~1.64 cm3, 0.61±0.37 cm3 (range,0.15~1.86 cm3, and 1.24±0.53 cm3 (range,0.17~2.20 cm3, respectively. VPath vs. VRGD, VPath vs. VFDG, and VRGD vs. VFDG comparisons were t = -0.145, P = 0.885, t = -6.239, P<0.001, and t = -5.661, P<0.001, respectively. No significant difference was found between VPath and VRGD. VFDG was much larger than VRGD and VPath. VRGD seemed more approximate to the pathologic gross tumor volume. Furthermore, VPath was more strongly correlated with VRGD (R = 0.964,P<0.001 than with VFDG (R = 0.584,P<0.001.18F-alfatide PET provided a better estimation of gross tumor volume than 18F-FDG PET in LLC tumor-bearing C57BL/6 mice.

Re-engineering the zinc fingers of PRDM9 reverses hybrid sterility in mice.

Science.gov (United States)

Davies, Benjamin; Hatton, Edouard; Altemose, Nicolas; Hussin, Julie G; Pratto, Florencia; Zhang, Gang; Hinch, Anjali Gupta; Moralli, Daniela; Biggs, Daniel; Diaz, Rebeca; Preece, Chris; Li, Ran; Bitoun, Emmanuelle; Brick, Kevin; Green, Catherine M; Camerini-Otero, R Daniel; Myers, Simon R; Donnelly, Peter

2016-02-11

The DNA-binding protein PRDM9 directs positioning of the double-strand breaks (DSBs) that initiate meiotic recombination in mice and humans. Prdm9 is the only mammalian speciation gene yet identified and is responsible for sterility phenotypes in male hybrids of certain mouse subspecies. To investigate PRDM9 binding and its role in fertility and meiotic recombination, we humanized the DNA-binding domain of PRDM9 in C57BL/6 mice. This change repositions DSB hotspots and completely restores fertility in male hybrids. Here we show that alteration of one Prdm9 allele impacts the behaviour of DSBs controlled by the other allele at chromosome-wide scales. These effects correlate strongly with the degree to which each PRDM9 variant binds both homologues at the DSB sites it controls. Furthermore, higher genome-wide levels of such 'symmetric' PRDM9 binding associate with increasing fertility measures, and comparisons of individual hotspots suggest binding symmetry plays a downstream role in the recombination process. These findings reveal that subspecies-specific degradation of PRDM9 binding sites by meiotic drive, which steadily increases asymmetric PRDM9 binding, has impacts beyond simply changing hotspot positions, and strongly support a direct involvement in hybrid infertility. Because such meiotic drive occurs across mammals, PRDM9 may play a wider, yet transient, role in the early stages of speciation.

H-2 restriction of the T cell response to chemically induced tumors: evidence from F1 → parent chimeras

International Nuclear Information System (INIS)

Lannin, D.R.; Yu, S.; McKhann, C.F.

1982-01-01

It has been well established that T cells that react to tumor antigen on virus-induced tumors must share H-2D or H-2K specificities with the tumor. It has been impossible to perform similar studies with chemically induced tumors because each chemically induced tumor expresses a unique tumor antigen that cannot be studied in association with other H-2 types. This study provies evidence that H-2 recognition is also necessary for recognition of chemically induced tumors. We have found that F 1 → parent chimeras preferentially recognize chemically induced tumors of parental H-2 type. C3H/HeJ and C57BL/6 mice were lethally irradiated and restored with (C3H x C57BL/6) F 1 hybrid bone marrow. The F 1 → C3H chimera but not the F 1 → C57BL/6 chimera was able to respond to a C3H fibrosarcoma in mixed lymphocyte-tumor cell culture and also to neutralize the tumor in an in vivo tumor neutralization assay. On the other hand, the F 1 → C57BL/6 chimera but not the F 1 → C3H chimera was able to kill the C57BL/6 lymphoma EL4 in an in vitro cytotoxicity assay. Both chimeras were tolerant to C3H and C57BL/6 alloantigens but could respond normally to Con A and to BALB/c spleen cells in mixed lymphocyte cultures and cytotoxicity assay

Fingerprinting and genetic purity assessment of F1 barley hybrids and their salt-tolerant parental lines using nSSR molecular markers.

Science.gov (United States)

Ben Romdhane, Mériam; Riahi, Leila; Jardak, Rahma; Ghorbel, Abdelwahed; Zoghlami, Nejia

2018-01-01

Hybridity and the genuineness of hybrids are prominent characteristics for quality control of seeds and thereby for varietal improvement. In the current study, the cross between two local barley genotypes (Ardhaoui: female; Testour: male) previously identified as susceptible/tolerant to salt stress in Tunisia was achieved. The hybrid genetic purity of the generated F 1 putative hybrids and the fingerprinting of the parents along with their offspring were assessed using a set of 17 nuclear SSR markers. Among the analyzed loci, 11 nSSR were shown polymorphic among the parents and their offspring. Based on the applied 11 polymorphic SSR loci, a total of 28 alleles were detected with an average of 2.54 alleles per locus. The locus HVM33 presented the highest number of alleles. The highest polymorphism information content value was detected for the locus HVM33 (0.6713) whereas the lowest PIC value (0.368) was revealed by the loci BMAC0156 , EBMAC0970 and BMAG0013 with a mean value of 0.4619. The probabilities of identical genotypes PI for the 11 microsatellite markers were 8.63 × 10 -7 . Banding patterns among parents and hybrids showed polymorphic fragments. The 11 SSR loci had produced unique fingerprints for each analyzed genotype and segregate between the two parental lines and their four hybrids. Parentage analysis confirms the hybrid purity of the four analyzed genotypes. Six Tunisian barley accessions were used as an outgroup in the multivariate analysis to confirm the efficiency of the employed 11 nSSR markers in genetic differentiation among various barley germplasms. Thus, neighbor joining and factorial analysis revealed clearly the discrimination among the parental lines, the four hybrids and the outgroup accessions. Out of the detected polymorphic 11 nuclear SSR markers, a set of five markers ( HVM33 , WMC1E8 , BMAC0154 , BMAC0040 and BMAG0007 ) were shown to be sufficient and informative enough to discriminate among the six genotypes representing the two

Intrathymic selection of NK1.1+α/β T cell antigen receptor (TCR)+ cells in transgenic mice bearing TCR specific for chicken ovalbumin and restricted to I-Ad

OpenAIRE

Iwabuchi, Chikako; Iwabuchi, Kazuya; Nakagawa, Ken-ichi; Takayanagi, Toshiaki; Nishihori, Hiroki; Tone, Saori; Ogasawara, Kazumasa; Good, Robert A.; Onoé, Kazunori

1998-01-01

Generation and negative selection of NK1.1+α/β T cell receptor (TCR)+ thymocytes were analyzed using TCR-transgenic (B10.D2 × DO10)F1 and (C57BL/6 × DO10)F1 mice and Rag-1−/−/DO10 mice, which had been established by breeding and backcrossing between Rag-1−/− and DO10 mice. Almost all T cells from these mice were shown to bear Vα13/Vβ8.2 that is specific for chicken ovalbumin (cOVA) and restricted to I-Ad. A normal proportion of the NK1.1+ Vα13/Vβ8.2+ thymocytes was generated in these mice. Ho...

Gonad morphogenesis defects drive hybrid male sterility in asymmetric hybrid breakdown of Caenorhabditis nematodes.

Science.gov (United States)

Dey, Alivia; Jin, Qi; Chen, Yen-Chu; Cutter, Asher D

2014-01-01

Determining the causes and evolution of reproductive barriers to gene flow between populations, speciation, is the key to understanding the origin of diversity in nature. Many species manifest hybrid breakdown when they intercross, characterized by increasingly exacerbated problems in later generations of hybrids. Recently, Caenorhabditis nematodes have emerged as a genetic model for studying speciation, and here we investigate the nature and causes of hybrid breakdown between Caenorhabditis remanei and C. latens. We quantify partial F1 hybrid inviability and extensive F2 hybrid inviability; the ~75% F2 embryonic arrest occurs primarily during gastrulation or embryonic elongation. Moreover, F1 hybrid males exhibit Haldane's rule asymmetrically for both sterility and inviability, being strongest when C. remanei serves as maternal parent. We show that the mechanism by which sterile hybrid males are incapable of transferring sperm or a copulatory plug involves defective gonad morphogenesis, which we hypothesize results from linker cell defects in migration and/or cell death during development. This first documented case of partial hybrid male sterility in Caenorhabditis follows expectations of Darwin's corollary to Haldane's rule for asymmetric male fitness, providing a powerful foundation for molecular dissection of intrinsic reproductive barriers and divergence of genetic pathways controlling organ morphogenesis. © 2014 Wiley Periodicals, Inc.

Immunomodulatory effects of black cohosh (Actaea racemosa) extract in female B6C3F1/N mice

International Nuclear Information System (INIS)

Smith, Matthew J.; Germolec, Dori R.; Frawley, Rachel P.; White, Kimber L.

2013-01-01

Black cohosh extracts (BCE; Actaea racemosa) are being used worldwide as an alternative to hormone replacement therapy for the management of menstrual and menopausal symptoms, yet the effects of BCE on the immune system are largely unknown. Female B 6 C 3 F 1 /N mice were treated daily with BCE (0, 62.5, 125, 250, 500, or 1000 mg/kg) for 28 days by oral gavage. Liver weights were significantly increased (26–32%) at the 1000 mg/kg dose. Dose-related increases in mean corpuscular volume and mean corpuscular hemoglobin were observed. Decreasing trends were observed in all thymic T cell populations, with the most notable dose-responsive effects on immature thymocytes. In the spleen, dose-related decreases were observed in all cell phenotypes evaluated, reaching the level of statistical significance at the 1000 mg/kg BCE dose. Splenic natural killer (NK) cell numbers were significantly decreased at all BCE doses, with the exception of absolute NK numbers at the 125 mg/kg dose. No effects were observed on T-dependent antibody responses of the humoral immune system, including the antibody-forming cell response to sheep erythrocytes (sRBC) and IgM antibody levels to both sRBC and keyhole limpet hemocyanin. Cytotoxic T cell (T CTL ) activity was increased, as was the mixed leukocyte response in one of two studies. Anti-CD3 mediated proliferation and the delayed-type hypersensitivity response were unaffected. No effects were observed on innate immunity or on bone marrow cellularity and colony-forming units. Overall, BCE exposure in B 6 C 3 F 1 /N mice for 28 days at doses up to 1000 mg/kg had minimal immune effects, with the exception of an increased T CTL response

Gamma irradiation of the interspecific hybrids Gossypium hirsutum L. x G. barbadense L. Part 1

International Nuclear Information System (INIS)

Stoilova, A.

1990-01-01

The study was aimed at combining the methods of hybridization and experimental mutagenesis and widening the possibilities of interspecific hybridization for successful breeding work. The reaction of interspecific cotton hybrids (G. hirsutum x G. barbadense) to gamma rays in the year of treatment was investigated. Four hybrid combinations resulting from reciprocal crosses between the two species were studied. Seeds of long fibre F 1 plants from each combination were divided in four equal parts (irradiated with 15, 20 and 25 krad and a control). The changes in the main biometrical indices between the control and maximum dose (25 krad) treatment showed that the F 2 hybrids were either resistant or slightly sensitive to irradiation depending on the direction of crossing in respect to growth processes, field germination and survival to the end of vegetation. 3 tabs., 2 figs., 14 refs

Gamma irradiation of the interspecific hybrids Gossypium hirsutum L. x G. barbadense L. Part 1

International Nuclear Information System (INIS)

Stoilova, A.

1990-01-01

The aim of the investigation is to combine the methods of hybridization and experimental mutagenesis and to widen the possibilities of interspecific hybridization for successful breeding work. Four hybrid combinations resulting from reciprocal crosses between the two species were studied. Seeds of long fibre F 1 plants from each combination were devided in four equal parts, three of which were irradiated with doses 15, 20 and 25 krad and one remained as control. The complex radiosensitivity evaluation of the four hybrid combinations investigated was based on the changes in the main biometrical indices comparing the control with 25 krad treatment and showed that the F 2 hybrids were either resistant or slightly sensitive to irradiation depending on the direction of crossing in respect to growth process, field germination and survival to the end of vegetation. 2 figs., 3 tabs., 14 refs

Assessment of immunotoxicity in female Fischer 344/N and Sprague Dawley rats and female B6C3F1 mice exposed to hexavalent chromium via the drinking water.

Science.gov (United States)

Shipkowski, Kelly A; Sheth, Christopher M; Smith, Matthew J; Hooth, Michelle J; White, Kimber L; Germolec, Dori R

2017-12-01

Sodium dichromate dihydrate (SDD), an inorganic compound containing hexavalent chromium (Cr(VI)), is a common environmental contaminant of groundwater sources due to widespread industrial use. There are indications in the literature that Cr(VI) may induce immunotoxic effects following dermal exposure, including acting as both an irritant and a sensitizer; however, the potential immunomodulatory effects of Cr(VI) following oral exposure are relatively unknown. Following the detection of Cr(VI) in drinking water sources, the National Toxicology Program (NTP) conducted extensive evaluations of the toxicity and carcinogenicity of SDD following drinking water exposure, including studies to assess the potential for Cr(VI) to modulate immune function. For the immunotoxicity assessments, female Fischer 344/N (F344/N) and Sprague Dawley (SD) rats and female B 6 C 3 F 1 mice were exposed to SDD in drinking water for 28 consecutive days and evaluated for alterations in cellular and humoral immune function as well as innate immunity. Rats were exposed to concentrations of 0, 14.3, 57.3, 172, or 516 ppm SDD while mice were exposed to concentrations of 0, 15.6, 31.3, 62.5, 125, or 250 ppm SDD. Final mean body weight and body weight gain were decreased relative to controls in 250 ppm B 6 C 3 F 1 mice and 516 ppm SD rats. Water consumption was significantly decreased in F344/N and SD rats exposed to 172 and 516 ppm SDD; this was attributed to poor palatability of the SDD drinking water solutions. Several red blood cell-specific parameters were significantly (5-7%) decreased in 250 ppm mice; however, these parameters were unaffected in rats. Sporadic increases in the spleen IgM antibody response to sheep red blood cells (SRBC) were observed, however, these increases were not dose-dependent and were not reproducible. No significant effects were observed in the other immunological parameters evaluated. Overall, exposure to Cr(VI) in drinking water had limited effects on

Environmental enrichment does not impact on tumor growth in mice [v1; ref status: indexed, http://f1000r.es/18c

Directory of Open Access Journals (Sweden)

Jennifer A Westwood

2013-06-01

Full Text Available The effect of environmental enrichment (EE on a variety of physiologic and disease processes has been studied in laboratory mice. During EE, a large group of mice are housed in larger cages than the standard cage and are given toys and equipment, enabling more social contact, and providing a greater surface area per mouse, and a more stimulating environment. Studies have been performed into the effect of EE on neurogenesis, brain injury, cognitive capacity, memory, learning, neuronal pathways, diseases such as Alzheimer’s, anxiety, social defeat, emotionality, depression, drug addiction, alopecia, and stereotypies. In the cancer field, three papers have reported effects on mice injected with tumors and housed in enriched environments compared with those housed in standard conditions. One paper reported a significant decrease in tumor growth in mice in EE housing. We attempted to replicate this finding in our animal facility, because the implications of repeating this finding would have profound implications for how we house all our mice in our studies on cancer. We were unable to reproduce the results in the paper in which B16F10 subcutaneous tumors of mice housed in EE conditions were smaller than those of mice housed in standard conditions. The differences in results could have been due to the different growth rate of the B16F10 cultures from the different laboratories, the microbiota of the mice housed in the two animal facilities, variations in noise and handling between the two facilities, food composition, the chemical composition of the cages or the detergents used for cleaning, or a variety of other reasons. EE alone does not appear to consistently result in decreased tumor growth, but other factors would appear to be able to counteract or inhibit the effects of EE on cancer progression.

Toxicology and Carcinogenesis Studies of Furfuryl Alcohol (CAS No. 98-00-0) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

Science.gov (United States)

1999-02-01

Furfuryl alcohol-based resins are used as binding agents in foundry sand and as corrosion inhibitors in mortar, grout, and cement. Because of their heat resistance, furan resins are used in the manufacture of fiberglass-reinforced plastic equipment. Furfuryl alcohol was selected for evaluation because of the absence of data on its carcinogenic potential and its large production volume, widespread use in manufacturing, and ubiquitous presence in consumer goods. Male and female F344/N rats and B6C3F1 mice were exposed to furfuryl alcohol (greater than 98% pure) by inhalation for 16 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse bone marrow cells. 16-DAY STUDY IN RATS: Groups of five male and five female rats were exposed to concentrations of 0, 16, 31, 63, 125, or 250 ppm furfuryl alcohol by inhalation, 6 hours per day, 5 days per week for 16 days. All male and female rats exposed to 250 ppm died by day 2 of the study, and one male rat exposed to 125 ppm died on day 5. Final mean body weights of male and female rats exposed to 125 ppm were significantly less than those of the chamber control groups. Male rats exposed to 31, 63, or 125 ppm and female rats exposed to 125 ppm gained less weight than the chamber control groups. Clinical findings included dyspnea, hypoactivity, and nasal and ocular discharge in males and females exposed to 63, 125, or 250 ppm. All exposed animals developed lesions in the nasal respiratory epithelium and olfactory epithelium, and the severities of these lesions generally increased with increasing exposure concentration. 16-DAY STUDY IN MICE: Groups of five male and five female mice were exposed to concentrations of 0, 16, 31, 63, 125, or 250 ppm furfuryl alcohol by inhalation, 6 hours per day, 5 days per week for 16 days. All male and female mice exposed to 250 ppm died by day 4 of the study, and one female mouse exposed to 125 ppm died on day

Distribution of 18F-5-fluorouracil in tumor-bearing mice and rats

International Nuclear Information System (INIS)

Shani, J.; Wolf, W.; Schlesinger, T.

1978-01-01

Extensive distribution studies of 18 F-5-fluorouracil ( 18 F-5-FU) in control and tumor-bearing mice (seven lines) and rats (eight lines) that have been shown or suspected to be responsive to 5-FU treatment were investigated with 18 F-5-FU. Studies were performed as a function of time, loading dose of 5-FU, and after a pretreatment regimen of 5-FU. Following the parenteral administration of 18 F-5-FU to tumor-bearing mice and rats there was slight preferential uptake by some of the tumor types, particularly subcutaneous leukemic tumors and breast adenocarcinomas. The degree of concentration in tumor tissue in comparison with surrounding tissues (blood, Muscle) was not such as to consider the radiopharmaceutical suitable for tumor localization. However, sufficient amounts of radioactivity localized in some tumors so that it might be possible to determine if a correlation exists between tumor uptake and anti-tumor effect of 5-fluorouracil. Another possible area of use might be in regulating the method of administration of the chemotherapeutic agent. (author)

Mutant-inducing effect of γ-ray irradiation for hybrid rice F1 derived from cross of black glutinous rice x wild rice

International Nuclear Information System (INIS)

Mao Dezhi; Tang Yilan

1998-01-01

The hybrid rice F 1 plant derived from the back crossing of glutinous rice x wild rice was irradiated with γ-ray. The result of investigation to the induced mutant showed that through the selection and backcross, a black glutinous rice strain with the short stem, cold tolerance and high yield was developed. The analysis of the ability of heredity variance showed that the selection was effective for the husk colour, black glutinous and black Indica rice, but ineffective for the white Indica rice and seed setting

Toxicity and carcinogenicity of methyl isobutyl ketone in F344N rats and B6C3F1 mice following 2-year inhalation exposure

International Nuclear Information System (INIS)

Stout, Matthew D.; Herbert, Ronald A.; Kissling, Grace E.; Suarez, Fernando; Roycroft, Joseph H.; Chhabra, Rajendra S.; Bucher, John R.

2008-01-01

Methyl isobutyl ketone (MIBK) is primarily used as a denaturant for rubbing alcohol, as a solvent and in the manufacture of methyl amyl alcohol. Inhalation of vapors is the most likely route of exposure in the work place. In order to evaluate the potential of MIBK to induce toxic and carcinogenic effects following chronic exposure, groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to MIBK at concentrations of 0, 450, 900, or 1800 ppm by inhalation, 6 h/day, 5 days per week for 2 years. Survival was decreased in male rats at 1800 ppm. Body weight gains were decreased in male rats at 900 and 1800 ppm and in female mice at 1800 ppm. The primary targets of MIBK toxicity and carcinogenicity were the kidney in rats and the liver in mice. In male rats, there was increased mineralization of the renal papilla at all exposure concentrations. The incidence of chronic progressive nephropathy (CPN) was increased at 1800 ppm and the severity was increased in all exposed groups. There were also increases in renal tubule hyperplasia at all exposure concentrations, and in adenoma and adenoma or carcinoma (combined) at 1800 ppm; these lesions are thought to represent a continuum in the progression of proliferative lesions in renal tubule epithelium. These increases may have resulted from the increased severity of CPN, either through α2μ-globulin-dependent or -independent mechanisms. An increase in mononuclear cell leukemia at 1800 ppm was an uncertain finding. Adrenal medulla hyperplasia was increased at 1800 ppm, and there was a positive trend for increases in benign or malignant pheochromocytomas (combined). In female rats, there were increases in the incidence of CPN in all exposure concentrations and in the severity at 1800 ppm, indicating that CPN was increased by mechanisms in addition to those related to α2μ-globulin. There were renal mesenchymal tumors, which have not been observed in historical control animals, in two female rats at 1800 ppm. The

Radiosynthesis, rodent biodistribution, and metabolism of 1-deoxy-1-[18F]fluoro-d-fructose

International Nuclear Information System (INIS)

Haradahira, Terushi; Tanaka, Akihiro; Maeda, Minoru; Kanazawa, Yoko; Ichiya, Yu-Ichi; Masuda, Kouji

1995-01-01

Fluorine-18 labeled analog of d-fructose, 1-deoxy-1-[ 18 F]fluoro-d-fructose (1-[ 18 F]FDFrc), was synthesized by nucleophilic substitution of [ 18 F]fluoride ion and the effect of the fluorine substitution on its in vivo metabolism was investigated. The tissue distributions of 1-[ 18 F]FDFrc in rats and tumor bearing mice showed initial high uptake and subsequent rapid washout of the radioactivity in the principal sites of d-fructose metabolism (kidneys, liver and small intestine). The uptakes in the brain and tumor (fibrosarcoma) were the lowest and moderate, respectively, but tended to increase with time. The in vivo metabolic studies of 1-[ 18 F]FDFrc and nonradiactive 1-FDFrc in mouse brain and tumor showed that the fluorinated analog remained unmetabolized in these tissues, indicating that the substitution of fluorine at the C-1 position produces a nonmetabolizable analog of d-fructose. Thus, 1-[ 18 F]FDFrc had no features of a metabolic trapping tracer without showing any appreciable organ or tumor specific localization

BROMOETHANE, CHLOROETHANE AND ETHYLENE OXIDE INDUCED UTERINE NEOPLASMS IN B6C3F1 MICE FROM 2-YEAR NTP INHALATION BIOASSAYS: PATHOLOGY AND INCIDENCE DATA REVISITED

Science.gov (United States)

SUMMARY: Chloroethane, bromoethane and etjulene oxide represent a unique set of three chemicals that induce endometrial neoplasms in the uterus of B6C3F1 mice following an inhalation route of exposure. The results of the NTP's chronic bioassays with these three compounds resu...

Genetic incompatibility dampens hybrid fertility more than hybrid viability: yeast as a case study.

Directory of Open Access Journals (Sweden)

Meibo Xu

Full Text Available Genetic incompatibility is believed to be the major cause of postzygotic reproductive isolation. Despite huge efforts seeking for speciation-related incompatibilities in the past several decades, a general understanding of how genetic incompatibility evolves in affecting hybrid fitness is not available, primarily due to the fact that the number of known incompatibilities is small. Instead of further mapping specific incompatible genes, in this paper we aimed to know the overall effects of incompatibility on fertility and viability, the two aspects of fitness, by examining 89 gametes produced by yeast S. cerevisiae-S. paradoxus F1 hybrids. Homozygous F2 hybrids formed by autodiploidization of F1 gametes were subject to tests for growth rate and sporulation efficiency. We observed much stronger defects in sporulation than in clonal growth for every single F2 hybrid strain, indicating that genetic incompatibility affects hybrid fertility more than hybrid viability in yeast. We related this finding in part to the fast-evolving nature of meiosis-related genes, and proposed that the generally low expression levels of these genes might be a cause of the observation.

Enhancement of radioprotective effectiveness of adenosine monophosphate by magnesium aspartate in mice

International Nuclear Information System (INIS)

Pospisil, M.; Netikova, J.; Kozubik, A.; Chertkov, K.S.; Ministry of Health, Moscow

1988-01-01

The enhancing effect of magnesium aspartate on the radioprotective effectiveness of adenosine monophosphate (AMP) administered to whole-body gamma-irradiated mice was studied. Male (CBA x C57BL/10)F 1 hybrid mice of a mean body weight of 32 g were used. 5 mg AMP per mouse was injected i.p. 15 min before and 15 min after irradiation; magnesium aspartate (13.3 mg per mouse) was administered s.c. 35 min before irradiation. The benefical effect of the drug combination used was manifested when investigating hematological indices at the recovery phase of sublethally irradiated animals, as well as when observing the survival of lethally irradiated mice. The synergistic radioprotective effects of AMP and magnesium aspartate are explained by the stimulatory action of both these compounds on the cell adenylate cyclase system. (author)

Basal and induced granulopoiesis in outbred, F1 hybrid and inbred mice: can inbreeding depression influence the experimental practice?

Czech Academy of Sciences Publication Activity Database

Hofer, Michal; Pospíšil, Milan; Dušek, L.; Holá, Jiřina; Hoferová, Zuzana; Weiterová, Lenka

2010-01-01

Roč. 235, č. 8 (2010), s. 928-931 ISSN 1535-3702 R&D Projects: GA ČR(CZ) GA305/08/0158 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : hematopoiesis * outbred mice * inbreeding depression Subject RIV: BO - Biophysics Impact factor: 2.954, year: 2010

Association of Increased F4/80high Macrophages With Suppression of Serum-Transfer Arthritis in Mice With Reduced FLIP in Myeloid Cells.

Science.gov (United States)

Huang, Qi-Quan; Birkett, Robert; Doyle, Renee E; Haines, G Kenneth; Perlman, Harris; Shi, Bo; Homan, Philip; Xing, Lianping; Pope, Richard M

2017-09-01

Macrophages are critical in the pathogenesis of rheumatoid arthritis (RA). We recently demonstrated that FLIP is necessary for the differentiation and/or survival of macrophages. We also showed that FLIP is highly expressed in RA synovial macrophages. This study was undertaken to determine if a reduction in FLIP in mouse macrophages reduces synovial tissue macrophages and ameliorates serum-transfer arthritis. Mice with Flip deleted in myeloid cells (Flip f/f LysM c/+ mice) and littermate controls were used. Arthritis was induced by intraperitoneal injection of K/BxN serum. Disease severity was evaluated by clinical score and change in ankle thickness, and joints were examined by histology and immunohistochemistry. Cells were isolated from the ankles and bone marrow of the mice and examined by flow cytometry, real-time quantitative reverse transcriptase-polymerase chain reaction, or Western blotting. In contrast to expectations, Flip f/f LysM c/+ mice developed more severe arthritis early in the clinical course, but peak arthritis was attenuated and the resolution phase more complete than in control mice. Prior to the induction of serum-transfer arthritis, the number of tissue-resident macrophages was reduced. On day 9 after arthritis induction, the number of F4/80 high macrophages in the joints of the Flip f/f LysM c/+ mice was not decreased, but increased. FLIP was reduced in the F4/80 high macrophages in the ankles of the Flip f/f LysM c/+ mice, while F4/80 high macrophages expressed an antiinflammatory phenotype in both the Flip f/f LysM c/+ and control mice. Our observations suggest that reducing FLIP in macrophages by increasing the number of antiinflammatory macrophages may be an effective therapeutic approach to suppress inflammation, depending on the disease stage. © 2017, American College of Rheumatology.

E2F transcription factor-1 deficiency reduces pathophysiology in the mouse model of Duchenne muscular dystrophy through increased muscle oxidative metabolism.

Science.gov (United States)

Blanchet, Emilie; Annicotte, Jean-Sébastien; Pradelli, Ludivine A; Hugon, Gérald; Matecki, Stéfan; Mornet, Dominique; Rivier, François; Fajas, Lluis

2012-09-01

E2F1 deletion leads to increased mitochondrial number and function, increased body temperature in response to cold and increased resistance to fatigue with exercise. Since E2f1-/- mice show increased muscle performance, we examined the effect of E2f1 genetic inactivation in the mdx background, a mouse model of Duchenne muscular dystrophy (DMD). E2f1-/-;mdx mice demonstrated a strong reduction of physiopathological signs of DMD, including preservation of muscle structure, decreased inflammatory profile, increased utrophin expression, resulting in better endurance and muscle contractile parameters, comparable to normal mdx mice. E2f1 deficiency in the mdx genetic background increased the oxidative metabolic gene program, mitochondrial activity and improved muscle functions. Interestingly, we observed increased E2F1 protein levels in DMD patients, suggesting that E2F1 might represent a promising target for the treatment of DMD.

The growth performance of F1 transgenic mutiara catfish

Science.gov (United States)

Iskandar; Buwono, I. D.; Agung, M. U. K.

2018-04-01

The growth of catfish (African or Sangkuriang strain) these days is tend to decreased. One of the solutions due to this problem is to improve the genetics of growth using transgenesis technology, toward more profitable. The specific objective of the research is to detect the transmission of exogenous GH (African catfish GH inserts) inside the F1 transgenic Mutiara catfish using PCR (Polymerase Chain Reaction) method and to evaluate the growth performance of transgenic Mutiara catfish made using the parameters of feed conversion (FCR = Feed Conversion Ratio). Transgenic catfish (strain mutiara) F0 and F1 carried African catfish GH (600 bp) can be produced. Superiority characters of transgenic catfish represented heritability (h2 ) and heterosis (H), indicating that the offspring of hybrid F1 transgenic mutiara catfish had phenotypes rapid growth (h2 = 17.55 % and H = 42.83 %) compared to non-transgenic catfish (h 2 = 10.07 % and H = 18.56 %). Evaluation of the efficiency of feed use parameters feed conversion ratio, shows that F1 transgenic mutiara catfish (FCR = 0.85) more efficient in converting feed into meat.

Enzyme-activity mutations detected in mice after paternal fractionated irradiation

International Nuclear Information System (INIS)

Charles, D.J.; Pretsch, W.

1986-01-01

(101/E1 X C3H/E1)F 1 -hybrid male mice were exposed in a 24-h fractionation interval to either 3.0 + 3.0-Gy or 5.1 + 5.1-Gy X-irradiation, and mated to untreated Test-stock females. The offspring were examined for mutations at 7 recessive specific loci and for activity alterations of erythrocyte enzymes controlled presumably by 12 loci. No enzyme-activity mutant was found in 3610 F 1 -offspring of the control group. In the experimental groups, no mutant was detected in 533 (3.0 + 3.0 Gy) and 173 (5.1 + 5.1 Gy) offspring from postspermatogonial germ cells treated. After treatment of spermatogonia, 1 mutant in 3388 F 1 -offspring of the 3.0 + 3.0-Gy group, and 5 mutants in 3187 F 1 offspring of the 5.1 + 5.1-Gy group were found. The mutants were all genetically confirmed. The frequency (expressed as mutants/locus/gamete) of enzyme-activity mutations is 2 (5.1 + 5.1-Gy group) to 10 (3.0 + 3.0-Gy group) times lower than the frequency of recessive specific-locus mutations. (Auth.)

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer's Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET.

Science.gov (United States)

Li, Xue-Yuan; Men, Wei-Wei; Zhu, Hua; Lei, Jian-Feng; Zuo, Fu-Xing; Wang, Zhan-Jing; Zhu, Zhao-Hui; Bao, Xin-Jie; Wang, Ren-Zhi

2016-10-18

Alzheimer's disease (AD) is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1) transgenic (Tg) mice aged 2, 3.5, 5 and 8 months using 18 F-labed fluorodeoxyglucose ( 18 F-FDG) microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr). Morris water maze (MWM) was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD). By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD). Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer's cognition after cognitive decline, at least in animals.

Environment effects for earliness and grain yield traits in F1 diallel populations of maize (Zea mays L.).

Science.gov (United States)

Ali, Sardar; Khan, Naqib Ullah; Khalil, Iftikhar Hussain; Iqbal, Muhammad; Gul, Samrin; Ahmed, Sheraz; Ali, Naushad; Sajjad, Mohammad; Afridi, Khilwat; Ali, Imtiaz; Khan, Shah Masaud

2017-10-01

Five maize inbred lines, 20 F 1 diallel hybrids and two check genotypes were evaluated through genotype × environment interaction (GEI) and GGE biplot for earliness and yield traits at four locations. Genotype, environment and GEI showed highly significant differences for all the traits. In total sum of squares, environment and genotype played a primary role, followed by GEI. Larger effects of environment and genotype to total variation influence the earliness and yield traits. However, according to the GGE biplot, the first two principal components (PC1 and PC2) explained 95% of the variation caused by GEI. GGE biplot confirmed the differential response of genotypes across environments. F 1 hybrid SWAJK-1 × FRHW-3 had better stability, with a good yield, and was considered an ideal genotype. F 1 hybrid FRHW-2 × FRHW-1 showed more earliness at CCRI and Haripur, followed by PSEV3 × FRHW-2 and its reciprocal at Swat and Mansehra, respectively. F 1 hybrids FRHW-1 × SWAJK-1, PSEV3 × SWAJK-1 and SWAJK-1 × FRHW-3 at Mansehra and Swat produced maximum grain yield, followed by SWAJK-1 × FRHW-1 and PSEV3 × FRHW-1 at Haripur and CCRI, respectively. Overall, maize genotypes showed early maturity in plain areas (CCRI and Haripur) but higher yield in hilly areas (Mansehra and Swat). © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Tackling Bet v 1 and associated food allergies with a single hybrid protein.

Science.gov (United States)

Hofer, Heidi; Asam, Claudia; Hauser, Michael; Nagl, Birgit; Laimer, Josef; Himly, Martin; Briza, Peter; Ebner, Christof; Lang, Roland; Hawranek, Thomas; Bohle, Barbara; Lackner, Peter; Ferreira, Fátima; Wallner, Michael

2017-08-01

Allergy vaccines should be easily applicable, safe, and efficacious. For Bet v 1-mediated birch pollen and associated food allergies, a single wild-type allergen does not provide a complete solution. We aimed to combine immunologically relevant epitopes of Bet v 1 and the 2 clinically most important related food allergens from apple and hazelnut to a single hybrid protein, termed MBC4. After identification of T cell epitope-containing parts on each of the 3 parental allergens, the hybrid molecule was designed to cover relevant epitopes and evaluated in silico. Thereby a mutation was introduced into the hybrid sequence, which should alter the secondary structure without compromising the immunogenic properties of the molecule. MBC4 and the parental allergens were purified to homogeneity. Analyses of secondary structure elements revealed substantial changes rendering the hybrid de facto nonreactive with patients' serum IgE. Nevertheless, the protein was monomeric in solution. MBC4 was able to activate T-cell lines from donors with birch pollen allergy and from mice immunized with the parental allergens. Moreover, on immunization of mice and rabbits, MBC4 induced cross-reactive IgG antibodies, which were able to block the binding of human serum IgE. Directed epitope rearrangements combined with a knowledge-based structural modification resulted in a protein unable to bind IgE from allergic patients. Still, properties to activate specific T cells or induce blocking antibodies were conserved. This suggests that MBC4 is a suitable vaccine candidate for the simultaneous treatment of Bet v 1 and associated food allergies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The behavior after intravenous injection in mice of multiwalled carbon nanotube / Fe3O4 hybrid MRI contrast agents.

Science.gov (United States)

Wu, Huixia; Liu, Gang; Zhuang, Yeming; Wu, Dongmei; Zhang, Haoqiang; Yang, Hong; Hu, He; Yang, Shiping

2011-07-01

Fe(3)O(4) nanoparticles were in situ loaded on the surface of multiwalled carbon nanotubes (MWCNTs) by a solvothermal method using diethylene glycol and diethanolamine as solvents and complexing agents. The as-prepared MWCNT/Fe(3)O(4) hybrids exhibited excellent hydrophilicity, superparamagnetic property at room temperature, and a high T(2) relaxivity of 175.5 mM(-1) s(-1) in aqueous solutions. In vitro experiments revealed that MWCNT/Fe(3)O(4) had an excellent magnetic resonance imaging (MRI) enhancement effect on cancer cells, and importantly, they displayed low cytotoxicity and neglectable hemolytic activity. After intravenous administration, the T(2)-weighted MRI signal in the liver and spleen of mice decreased significantly, suggesting the potential application of the hybrids as MRI contrast agents. The organ biodistribution studies, histological analyses and elimination investigations showed that the hybrids were uptaken by the liver, lung and spleen after intravenous injection, and could be excreted from the liver and kidney. Copyright © 2011 Elsevier Ltd. All rights reserved.

Development of doxorubicin-induced chronic cardiotoxicity in the B6C3F{sub 1} mouse model

Energy Technology Data Exchange (ETDEWEB)

Desai, Varsha G., E-mail: varsha.desai@fda.hhs.gov [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Herman, Eugene H. [Division of Drug Safety Research, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993 (United States); Moland, Carrie L.; Branham, William S. [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Lewis, Sherry M. [Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Davis, Kelly J. [Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR 72079 (United States); George, Nysia I. [Division Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Lee, Taewon [Department of Information and Mathematics, Korea University, Jochiwon, Chungnam 339-700 (Korea, Republic of); Kerr, Susan [Arkansas Heart Hospital, Little Rock, AR 72211 (United States); Fuscoe, James C. [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States)

2013-01-01

Serum levels of cardiac troponins serve as biomarkers of myocardial injury. However, troponins are released into the serum only after damage to cardiac tissue has occurred. Here, we report development of a mouse model of doxorubicin (DOX)-induced chronic cardiotoxicity to aid in the identification of predictive biomarkers of early events of cardiac tissue injury. Male B6C3F{sub 1} mice were administered intravenous DOX at 3 mg/kg body weight, or an equivalent volume of saline, once a week for 4, 6, 8, 10, 12, and 14 weeks, resulting in cumulative DOX doses of 12, 18, 24, 30, 36, and 42 mg/kg, respectively. Mice were sacrificed a week following the last dose. A significant reduction in body weight gain was observed in mice following exposure to a weekly DOX dose for 1 week and longer compared to saline-treated controls. DOX treatment also resulted in declines in red blood cell count, hemoglobin level, and hematocrit compared to saline-treated controls after the 2nd weekly dose until the 8th and 9th doses, followed by a modest recovery. All DOX-treated mice had significant elevations in cardiac troponin T concentrations in plasma compared to saline-treated controls, indicating cardiac tissue injury. Also, a dose-related increase in the severity of cardiac lesions was seen in mice exposed to 24 mg/kg DOX and higher cumulative doses. Mice treated with cumulative DOX doses of 30 mg/kg and higher showed a significant decline in heart rate, suggesting drug-induced cardiac dysfunction. Altogether, these findings demonstrate the development of DOX-induced chronic cardiotoxicity in B6C3F{sub 1} mice. -- Highlights: ► 24 mg/kg was a cumulative cardiotoxic dose of doxorubicin in male B6C3F{sub 1} mice. ► Doxorubicin-induced hematological toxicity was in association with splenomegaly. ► Doxorubicin induced severe testicular toxicity in B6C3F{sub 1} male mice.

Evaluation of [18F]Nifene biodistribution and dosimetry based on whole-body PET imaging of mice

International Nuclear Information System (INIS)

Constantinescu, Cristian C.; Garcia, Adriana; Mirbolooki, M. Reza; Pan, Min-Liang; Mukherjee, Jogeshwar

2013-01-01

Introduction: [ 18 F]Nifene is a novel radiotracer specific to the nicotinic acetylcholine α4β2 receptor class. In preparation for using this tracer in humans we have performed whole-body PET studies in mice to evaluate the in vivo biodistribution and dosimetry of [ 18 F]Nifene. Methods: Seven BALB/c mice (3 males, 4 females) received IV tail injections of [ 18 F]Nifene and were scanned for 2 h in an Inveon dedicated PET scanner. Each animal also received a high resolution CT scan using an Inveon CT. The CT images were used to draw volume of interest (VOI) on the following organs: brain, large intestine, small intestine, stomach, heart, kidneys, liver, lungs, pancreas, bone, spleen, testes, thymus, uterus and urinary bladder. All organ time activity curves had the decay correction reversed and were normalized to the injected activity. The area under the normalized curves was then used to compute the residence times in each organ. The absorbed doses in mouse organs were computed using the RAdiation Dose Assessment Resource (RADAR) animal models for dose assessment. The residence times in mouse organs were converted to human values using scale factors based on differences between organ and body weights. OLINDA 1.1 software was used to compute the absorbed human doses in multiple organs for both female and male phantoms. Results: The highest mouse residence times were found in urinary bladder, liver, bone, small intestine and kidneys. The largest doses in mice were found in urinary bladder and kidneys for both females and males. The elimination of radiotracer was primarily via kidney and urinary bladder with the urinary bladder being the limiting organ. The projected human effective doses were 1.51E-02 mSv/MBq for the adult male phantom and 1.65E-02 mSv/MBq for the adult female model phantom. Conclusion: This study indicates that the whole-body mouse imaging can be used as a preclinical tool for initial estimation of the absorbed doses of [ 18 F]Nifene in humans

Beta-cell lines derived from transgenic mice expressing a hybrid insulin gene-oncogene

DEFF Research Database (Denmark)

Efrat, S; Linde, S; Kofod, Hans

1988-01-01

Three pancreatic beta-cell lines have been established from insulinomas derived from transgenic mice carrying a hybrid insulin-promoted simian virus 40 tumor antigen gene. The beta tumor cell (beta TC) lines maintain the features of differentiated beta cells for about 50 passages in culture. The ...... both to immortalize a rare cell type and to provide a selection for the maintenance of its differentiated phenotype....

Short-term carcinogenicity testing of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f] quinoline (IQ) in E mu-pim-1 transgenic mice

DEFF Research Database (Denmark)

Sørensen, Ilona Kryspin; Mortensen, Alicja; Kristiansen, E.

1996-01-01

The usefulness of transgenic E mu-pim-1 mice over-expressing the pim-1 oncogene in lymphoid tissues, as sensitive test organisms was studied in a short-term carcinogenicity study. The mice were fed standard diet Altromin 1314 supplemented either with 0.03% 2-amino-1-methyl-6-phenylimidazo[4,5-b......]pyridine (PhIP) for 7 months or with 0.03% 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) for 6 months, PhIP and IQ are heterocyclic amines formed during cooking of meat and fish and are mutagenic to bacteria and cultured mammalian cells, PhIP is a potent mouse lymphomagen, while IQ is a liver carcinogen...... to non-transgenic mice. Our results suggest that the transgenic E mu-pim-1 mouse may be a useful model for short-term carcinogenicity screening of potential genotoxic carcinogens having the lymphoid system as target tissue, The carcinogen IQ which does not have the lymphoid system as a target...

Xenotropic type C virus expression in murine thymomas induced by radiation or 3-methylcholanthrene

International Nuclear Information System (INIS)

Mayer, A.; Duran-Reynals, M.L.

1981-01-01

Thymic lymphoma incidence and thymic expression of MuLV with xenotropic infectivity was monitored in AKR, RF, and reciprocal F 1 mice of the AKR X RF cross after treatment with either γ radiation or the chemical carcinogen 3-methylcholanthrene (MCA). These two inbred strains and the F 1 hybrids developed similary high incidences of thymoma, and lymphomatous cells from AKR mice and (ARK] X RF∫)F 1 mice were observed to be expressing MuLV with xenotropic host range. However, lymphoma cells from RF mice and (RF] X AKR∫)F 1 mice did not shed xenotropic MuLV. Thymic xenotropic virus expression was therefore not correlated with a high incidence of radiation or chemically induced thymoma, but rather appeared to be a phenotype genetically transmitted by AKR mice to F 1 mice of the AKR X RF cross as a dominant trait in induced thymomas. In addition, a maternal effect on thymic xenotropic virus expression in induced thymomas was observed by the comparison of reciprocal F 1 hybrids in this cross

NTP Toxicology and Carcinogenesis Studies of Barium Chloride Dihydrate (CAS No. 10326-27-9) in F344/N Rats and B6C3F1 Mice (Drinking Water Studies).

Science.gov (United States)

1994-01-01

Barium chloride dihydrate, a white crystalline granule or powder, is used in pigments, aluminum refining, leather tanning and coloring, the manufacture of magnesium metal, ceramics, glass, and paper products, as a pesticide, and in medicine as a cardiac stimulant. Toxicology and carcinogenicity studies were conducted by administering barium chloride dihydrate (99% pure) in drinking water to F344/N rats and B6C3F1 mice for 15 days, 13 weeks, and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse lymphoma cells. 15-DAY STUDY IN RATS: Groups of five males and five females received barium chloride dihydrate in the drinking water at concentrations of 0, 125, 250, 500, 1,000, or 2,000 ppm for 15 days, corresponding to average daily doses of 10, 15, 35, 60, or 110 mg barium/kg body weight to males and females. No chemical-related deaths, differences in final mean body weights, or clinical findings of toxicity were observed. Water consumption by male and female rats exposed to 2,000 ppm was slightly less (S16%) than controls during week 2. There were no significant differences in absolute or relative organ weights between exposed and control rats. No biologically significant differences in hematology, clinical chemistry, or neurobehavioral parameters occurred in rats. 15-DAY STUDY IN MICE: Groups of five males and five females received barium chloride dihydrate in the drinking water at concentrations of 0, 40, 80,173, 346, or 692 ppm for 15 days, corresponding to average daily doses of 5,10, 20, 40, or 70 mg barium/kg body weight to males and 5, 10, 15, 40, or 85 mg barium/kg body weight to females. No chemical-related deaths, differences in mean body weights or in water consumption, or clinical findings of toxicity were observed in mice. The relative liver weight of males receiving 692 ppm was significantly greater than that of the controls. The absolute and relative liver weights of females that

Effect of c-f hybridization on electric and magnetic properties of some Heavy Fermion (HF) systems

Energy Technology Data Exchange (ETDEWEB)

Sahoo, J., E-mail: jitendrasahoo2008@gmail.com [Regional Office of Vocational Education, Sambalpur, Odisha -768 004 (India); Nayak, P. [School of Physics, Sambalpur University, Sambalpur, Odisha - 768 019 (India)

2017-02-01

Representing the heavy fermion systems by the Periodic Anderson Model (PAM), we have used Zubarev technique to see the effect of c-f hybridization on the temperature dependence of resistivity and magnetic susceptibility. The calculated resistivity and magnetic susceptibility show the general features observed in these materials experimentally. Further, we have shown how the strength of hybridization as well as the position of the f-level affects both the properties and the Kondo temperature of these systems.

{sup 111}In-anti-F4/80-A3-1 antibody: a novel tracer to image macrophages

Energy Technology Data Exchange (ETDEWEB)

Terry, Samantha Y.A. [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); King' s College London, St Thomas' Hospital, Department of Imaging Chemistry and Biology, London (United Kingdom); Boerman, Otto C.; Gerrits, Danny; Franssen, Gerben M.; Oyen, Wim J.G. [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); Metselaar, Josbert M. [University of Twente, Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, Enschede (Netherlands); Lehmann, Steffi; Gerdes, Christian A. [Roche Innovation Center Zurich, Roche Pharmaceutical Research and Early Development (pRED), Zurich (Switzerland); Abiraj, Keelara [Roche Innovation Center Basel, Roche Pharmaceutical Research and Early Development (pRED), Basel (Switzerland)

2015-08-15

Here, the expression of F4/80 on the cell surface of murine macrophages was exploited to develop a novel imaging tracer that could visualize macrophages in vivo. The immunoreactive fraction and IC{sub 50} of anti-F4/80-A3-1, conjugated with diethylenetriaminepentaacetic acid (DTPA) and radiolabelled with {sup 111}In, were determined in vitro using murine bone marrow-derived macrophages. In vivo biodistribution studies were performed with {sup 111}In-anti-F4/80-A3-1 and isotype-matched control antibody {sup 111}In-rat IgG2b at 24 and 72 h post-injection (p.i.) in SCID/Beige mice bearing orthotopic MDA-MB-231 xenografts. In some studies mice were also treated with liposomal clodronate. Macrophage content in tissues was determined immunohistochemically. Micro-single photon emission computed tomography (SPECT)/CT images were also acquired. In vitro binding assays showed that {sup 111}In-anti-F4/80-A3-1 specifically binds F4/80 receptor-positive macrophages. The immunoreactivity of anti-F4/80-A3-1 was 75 % and IC{sub 50} was 0.58 nM. In vivo, injection of 10 or 100 μg {sup 111}In-anti-F4/80-A3-1 resulted in splenic uptake of 78 %ID/g and 31 %ID/g, respectively, and tumour uptake of 1.38 %ID/g and 4.08 %ID/g, respectively (72 h p.i.). Liposomal clodronate treatment reduced splenic uptake of 10 μg {sup 111}In-anti-F4/80-A3-1 from 248 %ID/g to 114 %ID/g and reduced {sup 111}In-anti-F4/80-A3-1 uptake in the liver and femur (24 h p.i.). Tracer retention in the blood and tumour uptake increased (24 h p.i.). Tumour uptake of {sup 111}In-anti-F4/80-A3-1 was visualized by microSPECT/CT. Macrophage density in the spleen and liver decreased in mice treated with liposomal clodronate. Uptake of {sup 111}In-rat IgG2b was lower in the spleen, liver and femur when compared to {sup 111}In-anti-F4/80-A3-1. Radiolabelled anti-F4/80-A3-1 antibodies specifically localize in tissues infiltrated by macrophages in mice and can be used to visualize tumours. The liver and spleen act as antigen

Hybridization experiments indicate incomplete reproductive isolating mechanism between Fasciola hepatica and Fasciola gigantica.

Science.gov (United States)

Itagaki, T; Ichinomiya, M; Fukuda, K; Fusyuku, S; Carmona, C

2011-09-01

Experiments on hybridization between Fasciola hepatica and Fasciola gigantica were carried out to clarify whether a reproductive isolating mechanism appears between the two Fasciola species. Molecular evidence for hybridization was based on the DNA sequence of the internal transcribed spacer 1 (ITS1) region in nuclear ribosomal DNA, which differs between the species. The results suggested that there were not pre-mating but post-mating isolating mechanisms between the two species. However, viable adults of the hybrids F1 and F2 were produced from both parental F. hepatica and F. gigantica. The hybrids inherited phenotypic characteristics such as ratio of body length and width and infectivity to rats from parental Fasciola hepatica and F. gigantica. These findings suggest that reproductive isolation is incomplete between Fasciola hepatica and F. gigantica. Adults of the hybrids F1 and F2 were completely different in mode of reproduction from aspermic Fasciola forms that occur in Asia and seem to be offspring originated from hybridization between F. hepatica and F. gigantica and to reproduce parthenogenetically.

1,2,3-Trichloropropane: a multisite carcinogen in rats and mice.

Science.gov (United States)

Irwin, R D; Haseman, J K; Eustis, S L

1995-05-01

1,2,3-Trichloropropane was evaluated in 2-year toxicology and carcinogenesis studies by the National Toxicology Program. The selection of this chemical for study was based on the potential for human exposure, its positive in vitro genotoxicity, and the carcinogenicity of structurally related chemicals. During the 2-year study 1,2,3-trichloropropane was administered in corn oil by gavage 5 days per week; groups of 60 F344/N rats received 0, 3, 10, or 30 mg/kg, while groups of 60 B6C3F1 mice received 0,6,20, or 60 mg/kg. Because of reduced survival associated with the development of chemical-related neoplasms, rats that received 30 mg/kg were terminated at 65 weeks (females) or 76 weeks (males). Similarly, mice that received 60 mg/kg were terminated at 73 weeks (females) or 79 weeks (males), while groups of mice that received 20 mg/kg were terminated at 88 weeks. 1,2,3-Trichloropropane induced benign and/or malignant neoplasms at multiple sites in both rats and mice; this included increased incidences of benign and malignant neoplasms of the squamous epithelium of the oral mucosa and forestomach of male and female rats, benign neoplasms of the kidney and pancreas and benign or malignant neoplasms of the preputial gland in male rats, malignant neoplasms of the mammary gland, and benign or malignant neoplasms of the clitoral gland in female rats. In mice, 1,2,3-trichloropropane induced a low incidence of malignant neoplasms of the oral mucosa in females, high incidences of benign and malignant neoplasms of the forestomach in males and females, benign neoplasms of the liver and harderian gland of males and females, and uterine neoplasms in females.

IMPROVED DERIVATION OF INPUT FUNCTION IN DYNAMIC MOUSE [18F]FDG PET USING BLADDER RADIOACTIVITY KINETICS

Science.gov (United States)

Wong, Koon-Pong; Zhang, Xiaoli; Huang, Sung-Cheng

2013-01-01

Purpose Accurate determination of the plasma input function (IF) is essential for absolute quantification of physiological parameters in positron emission tomography (PET). However, it requires an invasive and tedious procedure of arterial blood sampling that is challenging in mice because of the limited blood volume. In this study, a hybrid modeling approach is proposed to estimate the plasma IF of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in mice using accumulated radioactivity in urinary bladder together with a single late-time blood sample measurement. Methods Dynamic PET scans were performed on nine isoflurane-anesthetized male C57BL/6 mice after a bolus injection of [18F]FDG at the lateral caudal vein. During a 60- or 90-min scan, serial blood samples were taken from the femoral artery. Image data were reconstructed using filtered backprojection with CT-based attenuation correction. Total accumulated radioactivity in the urinary bladder was fitted to a renal compartmental model with the last blood sample and a 1-exponential function that described the [18F]FDG clearance in blood. Multiple late-time blood sample estimates were calculated by the blood [18F]FDG clearance equation. A sum of 4-exponentials was assumed for the plasma IF that served as a forcing function to all tissues. The estimated plasma IF was obtained by simultaneously fitting the [18F]FDG model to the time-activity curves (TACs) of liver and muscle and the forcing function to early (0–1 min) left-ventricle data (corrected for delay, dispersion, partial-volume effects and erythrocytes uptake) and the late-time blood estimates. Using only the blood sample acquired at the end of the study to estimate the IF and the use of liver TAC as an alternative IF were also investigated. Results The area under the plasma TACs calculated for all studies using the hybrid approach was not significantly different from that using all blood samples. [18F]FDG uptake constants in brain, myocardium, skeletal

Genomic networks of hybrid sterility.

Science.gov (United States)

Turner, Leslie M; White, Michael A; Tautz, Diethard; Payseur, Bret A

2014-02-01

Hybrid dysfunction, a common feature of reproductive barriers between species, is often caused by negative epistasis between loci ("Dobzhansky-Muller incompatibilities"). The nature and complexity of hybrid incompatibilities remain poorly understood because identifying interacting loci that affect complex phenotypes is difficult. With subspecies in the early stages of speciation, an array of genetic tools, and detailed knowledge of reproductive biology, house mice (Mus musculus) provide a model system for dissecting hybrid incompatibilities. Male hybrids between M. musculus subspecies often show reduced fertility. Previous studies identified loci and several X chromosome-autosome interactions that contribute to sterility. To characterize the genetic basis of hybrid sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven 'hotspots,' seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL-but not cis eQTL-were substantially lower when mapping was restricted to a 'fertile' subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility. The integrated mapping approach we employed is applicable in a broad

Engraftment Site and Effectiveness of the Pan-Caspase Inhibitor F573 to Improve Engraftment in Mouse and Human Islet Transplantation in Mice.

Science.gov (United States)

Pepper, Andrew R; Bruni, Antonio; Pawlick, Rena; Wink, John; Rafiei, Yasmin; Gala-Lopez, Boris; Bral, Mariusz; Abualhassan, Nasser; Kin, Tatsuya; Shapiro, A M James

2017-10-01

Islet transplantation is an effective therapy in type 1 diabetes and recalcitrant hypoglycemia. However, there is an ongoing need to circumvent islet loss posttransplant. We explore herein the potential of the pan-caspase inhibitor F573 to mitigate early apoptosis-mediated islet death within portal and extrahepatic portal sites in mice. Mouse or human islets were cultured in standard media ±100 μM F573 and subsequently assessed for viability and apoptosis via terminal deoxynucleotidyl transferase dUTP nick end labeling staining and caspase-3 activation. Diabetic mice were transplanted with syngeneic islets placed under the kidney capsule (KC) or into the subcutaneous deviceless (DL) site at a marginal islet dose (150 islets), or into the portal vein (PV) at a full dose (500 islets). Human islets were transplanted under the KC of diabetic immunodeficient mice at a marginal dose (500 islet equivalents). Islets were cultured in the presence of F573, and F573 was administered subcutaneously on days 0 to 5 posttransplant. Control mice were transplanted with nontreated islets and were injected with saline. Graft function was measured by nonfasting blood glucose and glucose tolerance testing. F573 markedly reduced human and mouse islet apoptosis after in vitro culture (P islet function when transplanted under the KC (P islet marginal KC transplants. Conversely, F573 significantly improved mouse islet engraftment in the PV and DL site (P islet apoptosis and improves engraftment most effectively in the portal and DL subcutaneous sites.

Human dosimetric estimation of O-(2-18F-fluoroethyl)-L-tyrosine based on mice biodistribution data

International Nuclear Information System (INIS)

Tang Ganghua; Wang Mingfang; Luo Lei; Gan Manquan; Tang Xiaolan

2004-01-01

To estimate the human radiation absorbed doses of O-(2- 18 F-fluoroethyl)-L-tyrosine (FET), mice are considered as model. FET is injected into mice through a tail vein. At 10, 30, 60, 120 and 180 min after injection, the mice are killed by cervical fracture and the biodistribution in mice are determined. Human dosimetric estimation is performed from the biodistribution of FET in mice and the standard Medical Internal Radiation Dose (MIRD) method using time-fractional radioactivity curves for humans. The bone in human is the organ receiving highest dose of 4.78 pGy/Bq, the brain and the whole body receive the lowest dose of 1.6 pGy/Bq, and other organs receive doses between 1.6 and 3.5 pGy/Bq. The effective dose is estimated to be 9.0 pSv/Bq. The data show that a 370 MBq injection of FET leads to an estimated effective dose of 3.3 mSv, which is in the range of routine nuclear medicine investigations. The potential radiation risks associated with this study are well within accepted limits

Radiobiological properties of spermatogonial stem cells in C3H/101 hybrid mice and evaluation of the model for induction of genetic damage in spermatogonial stem cells

International Nuclear Information System (INIS)

De Rooij, V.

1993-01-01

C3H/101 (3H1) hybrid mice are studied, in order to find answers to the following questions: What are the D 0 values for killing of proliferating and quiescent stem cells by X-irradiation in 3H1 mice; How many stem cells are present per 3H1 testis and what is the density of these cells during the epithelial cycle; What are the approximate numbers of proliferating and quiescent stem cells in a 3H1 mouse testis. (R.P.) 5 figs

Pattern of leukemia induction in BC3F1 mice transplanted with irradiated lymphohemopoietic tissues

International Nuclear Information System (INIS)

Covelli, V.; Di Majo, V.; Bassani, B.; Metalli, P.; Silini, G.

1982-01-01

(C57BL/Cne X C3H/Cne)F 1 male mice spontaneously develop reticulum cell sarcoma (RCS) with an average final incidence of 56%; neither myeloid leukemia (ML) nor thymic lymphoma (TL) has been observed in intact animals. X rays (4Gy, 250 kV) induce a few cases of ML but no TL. In increasing the dose to 6 Gy, we observed a few cases of TL, no ML, and a drastic reduction (8%) of RCS. The same dose of 6 Gy fractionated into four weekly doses of 1.5 Gy induced 24% of TL. By transplanting cells into appropriately preirradiated (4 Gy) syngeneic recipients we found evidence that four weekly doses of 1.5 Gy to donor animals caused an excess of ML and drastic changes of both TL and RCS incidences and rates in recipients as a function of time postirradiation at which the lymphohemopoietic tissues are transplanted. Furthermore, the same transplanted animals showed an evident acceleration of time of appearance of RCS and an enhanced incidence of NL; the latter effect is significant 10 days after the last X-ray fraction, but not thereafter. These data are in line with the hypothesis that committed cells for these two types of systemic tumors may be present among the irradiated transplanted tissues

Differentiation of Forebrain and Hippocampal Dopamine 1-Class Receptors, D1R and D5R, in Spatial Learning and Memory

Science.gov (United States)

Sariñana, Joshua; Tonegawa, Susumu

2017-01-01

Activation of prefrontal cortical (PFC), striatal, and hippocampal dopamine 1-class receptors (D1R and D5R) is necessary for normal spatial information processing. Yet the precise role of the D1R versus the D5R in the aforementioned structures, and their specific contribution to the water-maze spatial learning task remains unknown. D1R- and D5R- specific in situ hybridization probes showed that forebrain restricted D1R and D5R KO mice (F-D1R/D5R KO) displayed D1R mRNA deletion in the medial (m)PFC, dorsal and ventral striatum, and the dentate gyrus (DG) of the hippocampus. D5R mRNA deletion was limited to the mPFC, the CA1 and DG hippocampal subregions. F-D1R/D5R KO mice were given water-maze training and displayed subtle spatial latency differences between genotypes and spatial memory deficits during both regular and reversal training. To differentiate forebrain D1R from D5R activation, forebrain restricted D1R KO (F-D1R KO) and D5R KO (F-D5R KO) mice were trained on the water-maze task. F-D1R KO animals exhibited escape latency deficits throughout regular and reversal training as well as spatial memory deficits during reversal training. F-D1R KO mice also showed perseverative behavior during the reversal spatial memory probe test. In contrast, F-D5R KO animals did not present observable deficits on the water-maze task. Because F-D1R KO mice showed water-maze deficits we tested the necessity of hippocampal D1R activation for spatial learning and memory. We trained DG restricted D1R KO (DG-D1R KO) mice on the water-maze task. DG-D1R KO mice did not present detectable spatial memory deficit, but did show subtle deficits during specific days of training. Our data provides evidence that forebrain D5R activation plays a unique role in spatial learning and memory in conjunction with D1R activation. Moreover, these data suggest that mPFC and striatal, but not DG D1R activation are essential for spatial learning and memory. PMID:26174222

HTO oral administration in mice: Pt. 1

International Nuclear Information System (INIS)

Yamamoto, O.; Yokoro, K.; Seyama, T.; Kinomura, A.; Nomura, T.

1990-01-01

Tritiated water in various concentrations was orally administered continuously to (C57BL/6N and C3H/He)F 1 female mice in a closed animal chamber. Tritium radioactivity in various organ tissues was measured periodically after initiating tritiated water intake using an automatic sample combustion system and a liquid scintillation counter. After 7 days the specific radioactivity reached a plateau. Within a range of 1.48 x 10 11 to 5.92 x 10 11 Bq/dm 3 as the concentration of tritiated water in drinking water, the time of death after initiating the administration was about 2 weeks, a typical time for haematopoietic death. A linear relationship of times of death with tritiated water concentrations in drinking water was observed, on a log-log scale, between 1.85 x 10 10 Bq/dm 3 and 1.48 x 10 11 Bq/dm 3 . At concentrations lower than 9.25 x 10 9 Bq/dm 3 , mice no longer died from haematopoietic failure. The authors conclude, therefore, that there should be a threshold dose rate for haematopoietic death. (author)

Monitoring therapy with MEK inhibitor U0126 in a novel Wilms tumor model in Wt1 knockout Igf2 transgenic mice using 18F-FDG PET with dual-contrast enhanced CT and MRI: early metabolic response without inhibition of tumor growth.

Science.gov (United States)

Flores, Leo G; Yeh, Hsin-Hsien; Soghomonyan, Suren; Young, Daniel; Bankson, James; Hu, Qianghua; Alauddin, Mian; Huff, Vicki; Gelovani, Juri G

2013-04-01

The understanding of the role of genetic alterations in Wilms tumor development could be greatly advanced using a genetically engineered mouse models that can replicate the development and progression of this disease in human patients and can be monitored using non-invasive structural and molecular imaging optimized for renal tumors. Repetitive dual-contrast computed tomography (CT; intravenous and intraperitoneal contrast), T2-weighted magnetic resonance imaging (MRI), and delayed 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) positron emission tomography (PET) were utilized for characterization of Igf2 biallelic expression/Wt1 knockout mouse model of Wilms tumor. For CT imaging, Ioversol 678 mg/ml in 200 μl was administered i.p. followed by 100 μl injected intravenously at 20 and 15 min prior to imaging, respectively. Static PET imaging studies were acquired at 1, 2, and 3 h after i.v. administration of (18)F-FDG (400 μCi). Coronal and sagittal T1-weighted images (TE/TR 8.5/620 ms) were acquired before and immediately after i.v. injection of 0.4 ml/kg gadopentetate dimeglumine followed by T2-weighted images (TE/TR 60/300 ms). Tumor tissue samples were characterized by histopathology and immunohistochemistry for Glut1, FASN, Ki67, and CD34. In addition, six Wt1-Igf2 mice were treated with a mitogen-activated protein kinase (MEK) inhibitor U0126 (50 μmol/kg i.p.) every 4 days for 6 weeks. (18)F-FDG PET/CT imaging was repeated at different days after initiation of therapy with U0126. The percent change of initial tumor volume and SUV was compared to non-treated historic control animals. Overall, the best tumor-to-adjacent kidney contrast as well as soft tissue contrast for other abdominal organs was achieved using T2-weighted MRI. Delayed (18)F-FDG PET (3-h post (18)F-FDG administration) and dual-contrast CT (intravenous and intraperitoneal contrast) provided a more accurate anatomic and metabolic characterization of Wilms tumors in Wt1-Igf2 mice

Pharmacokinetic analysis of trichloroethylene metabolism in male B6C3F1 mice: Formation and disposition of trichloroacetic acid, dichloroacetic acid, S-(1,2-dichlorovinyl)glutathione and S-(1,2-dichlorovinyl)-L-cysteine

Science.gov (United States)

Kim, Sungkyoon; Kim, David; Pollack, Gary M.; Collins, Leonard B.; Rusyn, Ivan

2009-01-01

Trichloroethylene (TCE) is a well-known carcinogen in rodents and concerns exist regarding its potential carcinogenicity in humans. Oxidative metabolites of TCE, such as dichloroacetic acid (DCA) and trichloroacetic acid (TCA), are thought to be hepatotoxic and carcinogenic in mice. The reactive products of glutathione conjugation, such as S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and S-(1,2-dichlorovinyl) glutathione (DCVG), are associated with renal toxicity in rats. Recently, we developed a new analytical method for simultaneous assessment of these TCE metabolites in small-volume biological samples. Since important gaps remain in our understanding of the pharmacokinetics of TCE and its metabolites, we studied a time-course of DCA, TCA, DCVG and DCVG formation and elimination after a single oral dose of 2100 mg/kg TCE in male B6C3F1 mice. Based on systemic concentration-time data, we constructed multi-compartment models to explore the kinetic properties of the formation and disposition of TCE metabolites, as well as the source of DCA formation. We conclude that TCE-oxide is the most likely source of DCA. According to the best-fit model, bioavailability of oral TCE was ~74%, and the half-life and clearance of each metabolite in the mouse were as follows: DCA: 0.6 hr, 0.081 ml/hr; TCA: 12 hr, 3.80 ml/hr; DCVG: 1.4 hr, 16.8 ml/hr; DCVC: 1.2 hr, 176 ml/hr. In B6C3F1 mice, oxidative metabolites are formed in much greater quantities (~3600 fold difference) than glutathione-conjugative metabolites. In addition, DCA is produced to a very limited extent relative to TCA, while most of DCVG is converted into DCVC. These pharmacokinetic studies provide insight into the kinetic properties of four key biomarkers of TCE toxicity in the mouse, representing novel information that can be used in risk assessment. PMID:19409406

Pharmacokinetic analysis of trichloroethylene metabolism in male B6C3F1 mice: Formation and disposition of trichloroacetic acid, dichloroacetic acid, S-(1,2-dichlorovinyl)glutathione and S-(1,2-dichlorovinyl)-L-cysteine

International Nuclear Information System (INIS)

Kim, Sungkyoon; Kim, David; Pollack, Gary M.; Collins, Leonard B.; Rusyn, Ivan

2009-01-01

Trichloroethylene (TCE) is a well-known carcinogen in rodents and concerns exist regarding its potential carcinogenicity in humans. Oxidative metabolites of TCE, such as dichloroacetic acid (DCA) and trichloroacetic acid (TCA), are thought to be hepatotoxic and carcinogenic in mice. The reactive products of glutathione conjugation, such as S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and S-(1,2-dichlorovinyl) glutathione (DCVG), are associated with renal toxicity in rats. Recently, we developed a new analytical method for simultaneous assessment of these TCE metabolites in small-volume biological samples. Since important gaps remain in our understanding of the pharmacokinetics of TCE and its metabolites, we studied a time-course of DCA, TCA, DCVG and DCVG formation and elimination after a single oral dose of 2100 mg/kg TCE in male B6C3F1 mice. Based on systemic concentration-time data, we constructed multi-compartment models to explore the kinetic properties of the formation and disposition of TCE metabolites, as well as the source of DCA formation. We conclude that TCE-oxide is the most likely source of DCA. According to the best-fit model, bioavailability of oral TCE was ∼ 74%, and the half-life and clearance of each metabolite in the mouse were as follows: DCA: 0.6 h, 0.081 ml/h; TCA: 12 h, 3.80 ml/h; DCVG: 1.4 h, 16.8 ml/h; DCVC: 1.2 h, 176 ml/h. In B6C3F1 mice, oxidative metabolites are formed in much greater quantities (∼ 3600 fold difference) than glutathione-conjugative metabolites. In addition, DCA is produced to a very limited extent relative to TCA, while most of DCVG is converted into DCVC. These pharmacokinetic studies provide insight into the kinetic properties of four key biomarkers of TCE toxicity in the mouse, representing novel information that can be used in risk assessment.

T cells from fully H-2 allogeneic (A replaced by B) radiation bone marrow chimeras are functionally competent and host restricted but are alloreactive against hybrid Ia determinants expressed on (A x B)F1 cells

International Nuclear Information System (INIS)

Kruisbeek, A.M.; Hathcock, K.S.; Hodes, R.J.; Singer, A.

1982-01-01

In this communication it is demonstrated that T cells from fully allogeneic A replaced by B radiation bone marrow chimeras are alloreactive against the hybrid Ia molecules expressed on the surface of heterozygous A X B cells. These results suggested that previous failures to generate cytotoxic T lymphocyte (CTL) responses from fully allogeneic chimeras by sensitizing the chimeric T cells to antigen in an (A X B)F1-priming environment might have been confounded by an ongoing alloreaction against determinants created by hybrid Ia molecules expressed on F1 cells. Consequently, the ability to generate CTL responses from fully allogeneic chimeras was re-examined by sensitizing the chimeric T cells to antigen presented by homozygous rather that F1 stimulator cells. It was found that T cells of donor bone marrow origin that mediate cytotoxic responses to trinitrophenyl-modified self determinants do differentiate into functional competence in an H-2-incompatible host environment and are restricted to the host H-2 haplotype

Intra-strain polymorphisms are detected but no genomic alteration is found in cloned mice

International Nuclear Information System (INIS)

Gotoh, Koshichi; Inoue, Kimiko; Ogura, Atsuo; Oishi, Michio

2006-01-01

In-gel competitive reassociation (IGCR) is a method for differential subtraction of polymorphic (RFLP) DNA fragments between two DNA samples of interest without probes or specific sequence information. Here, we applied the IGCR procedure to two cloned mice derived from an F1 hybrid of the C57BL/6Cr and DBA/2 strains, in order to investigate the possibility of genomic alteration in the cloned mouse genomes. Each of the five of the genomic alterations we detected between the two cloned mice corresponded to the 'intra-strain' polymorphisms in the C57BL/6Cr and DBA/2 mouse strains. Our result suggests that no severe aberration of genome sequences occurs due to somatic cell nuclear transfer

Combined SEP and anti-PD-L1 antibody produces a synergistic antitumor effect in B16-F10 melanoma-bearing mice.

Science.gov (United States)

Hu, Zhengping; Ye, Liang; Xing, Yingying; Hu, Jinhang; Xi, Tao

2018-01-09

The increased PD-L1 induces poorer prognosis in melanoma. The treatment with PD-1/PD-L1 antibodies have a low response rate. The combination immunotherapies are the encouraging drug development strategy to receive maximal therapeutic benefit. In this study, we investigated the enhanced antitumor and immunomodulatory activity of combined SEP and αPD-L1 in B16-F10 melanoma-bearing mice. The results shown that combined SEP and αPD-L1 presented significant synergistic antitumor effects, increased the frequency of CD8 + and CD4 + T cells in spleen and tumor, cytotoxic activity of CTL in spleen, and IL-2 and IFN-γ levels in splenocytes and tumor. The combination treatment also produced synergistic increase in P-ERK1/2 level in spleen. Immunohistochemistry shown that SEP induced the PD-L1 expression in melanoma tissue possibly by promoting IFN-γ excretion, which led to the synergistic anti-tumor effects of aPD-L1 and SEP. Furthermore, in the purified T lymphocyte from the naive mice, the combination of SEP and αPD-L1 had more potent than SEP or αPD-L1 in promoting T lymphocyte proliferation and cytokines secretion including IL-2 and IFN-γ, at least partially by activating MEK/ERK pathway. Our study provides the scientific basis for a clinical trial that would involve combination of anti-PD-L1 mAb and SEP for sustained melanoma control.

Evaluation of a novel Arg-Gly-Asp-conjugated α-melanocyte stimulating hormone hybrid peptide for potential melanoma therapy.

Science.gov (United States)

Yang, Jianquan; Guo, Haixun; Gallazzi, Fabio; Berwick, Marianne; Padilla, R Steven; Miao, Yubin

2009-08-19

The purpose of this study was to determine whether Arg-Gly-Asp (RGD)-conjugated α-melanocyte stimulating hormone (α-MSH) hybrid peptide could be employed to target melanocortin-1 (MC1) receptor for potential melanoma therapy. The RGD motif {cyclic(Arg-Gly-Asp-DTyr-Asp)} was coupled to [Cys(3,4,10), DPhe(7), Arg(11)]α-MSH(3-13) {(Arg(11))CCMSH} to generate RGD-Lys-(Arg(11))CCMSH hybrid peptide. The MC1 receptor binding affinity of RGD-Lys-(Arg(11))CCMSH was determined in B16/F1 melanoma cells. The internalization and efflux, melanoma targeting and pharmacokinetic properties and single photon emission computed tomography/CT (SPECT/CT) imaging of (99m)Tc-RGD-Lys-(Arg(11))CCMSH were determined in B16/F1 melanoma cells and melanoma-bearing C57 mice. Clonogenic cytotoxic effect of RGD-Lys-(Arg(11))CCMSH was examined in B16/F1 melanoma cells. RGD-Lys-(Arg(11))CCMSH displayed 2.1 nM MC1 receptor binding affinity. (99m)Tc-RGD-Lys-(Arg(11))CCMSH showed rapid internalization and extended retention in B16/F1 cells. The cellular uptake of (99m)Tc-RGD-Lys-(Arg(11))CCMSH was MC1 receptor-mediated. (99m)Tc-RGD-Lys-(Arg(11))CCMSH exhibited high tumor uptake (14.83 ± 2.94% ID/g 2 h postinjection) and prolonged tumor retention (7.59 ± 2.04% ID/g 24 h postinjection) in B16/F1 melanoma-bearing mice. Nontarget organ uptakes were generally low except for the kidneys. Whole-body clearance of (99m)Tc-RGD-Lys-(Arg(11))CCMSH was rapid, with approximately 62% of the injected radioactivity cleared through the urinary system by 2 h postinjection. Flank melanoma tumors were clearly imaged by small animal SPECT/CT using (99m)Tc-RGD-Lys-(Arg(11))CCMSH as an imaging probe 2 h postinjection. Single treatment (3 h incubation) with 100 nM of RGD-Lys-(Arg(11))CCMSH significantly (p < 0.05) decreased the clonogenic survival of B16/F1 cells by 65% compared to the untreated control cells. Favorable melanoma targeting property of (99m)Tc-RGD-Lys-(Arg(11))CCMSH and remarkable cytotoxic effect of RGD

Effect of Animal Condition and Fluvoxamine on the Result of [18F]N 3 Fluoropropyl-2β carbomethoxy-3β (4-iodophenyl) Nortropane ([18F]FP-CIT) PET Study in Mice

International Nuclear Information System (INIS)

Shin, Kwang Ho; Lee Sang Ju; Oh, Seung Jun; Kim, Jae Seung; Park, Su A; Kim, Seog Young

2012-01-01

PET (positron emission tomography) is a noninvasive imaging technique, visualizing biological aspects in vivo. In animal models, the result of PET study can be affected more prominently than in humans by the animal conditions or drug pretreatment. We assessed the effects of anesthesia, body temperature, and pretreatment with selective serotonin reuptake inhibitor on the results of [ 18F ]N 3 fluoropropyl 2β carbomethoxy 3β (4-iodophenyl) nortropane ([ 18F ]FP CIT) PET in mice. [ 18F ]FP CIT PET of C57BL/6 mice was performed in three different conditions: (1) anesthesia (isoflurane) with active warming (38.deg.C) as a reference; (2) no anesthesia or warming; (3) anesthesia without warming at room temperature. Additional groups of mine pretreated with escalating doses of fluvoxamine (5, 20, 40, 80 mg/kg) were imaged in condition (1). The time activity curve and standardized uptake value of the striatum, cerebral cortex, and bone were compared among these conditions. In all conditions, radioactivities of the striatum and cortex tended to form a plateau after rapid uptake and washout, but that of bone tended to increase gradually. When anesthetized without any warming, all the mice developed hypothermia and showed reduced bone uptake compared to the reference condition. In conditions without anesthesia, striatal and cortical uptakes compared to the reference condition. In conditions without anesthesia, striatal and cortical uptakes were reduced, whereas the bone uptake showed no change. Pretreatment with fluvoxamine increased the striatal uptake and striatal specific to cortical non specific uptake ratio, whereas the bone uptake was reduced. Anesthesia, body temperature, and fluvoxamine affect the result of [ 18F ]FP CIT PET in mice by altering striatal and bone uptakes

Syntheses and biological evaluation of {sup 18}F-labeled 3-(1-benzyl-piperidin-4-yl)-1-(1-methyl-1H-indol-3-yl)propan-1-ones for in vivo mapping of acetylcholinesterase

Energy Technology Data Exchange (ETDEWEB)

Choe, Y.-S. E-mail: yschoe@samsung.co.kr; Oh, S.-J.; Shim, Insop; Naruto, Shunji; Chi, Dae Yoon; Kim, Sang Eun; Lee, Kyung-Han; Choi, Yong; Kim, B.-T

2000-04-01

We synthesized novel {sup 18}F-labeled acetylcholinesterase (AChE) inhibitors, 3-[1-(3- and 4-[{sup 18}F]fluoromethylbenzyl)piperidin-4-yl]-1-(1-methyl-1H-indol-3-yl)propan- 1-ones ([{sup 18}F]1 and [{sup 18}F]2) and 3-[1-(4-[{sup 18}F]fluorobenzyl)piperidin-4-yl]-1-(1-methyl-1H-indol-3-yl)propan- 1-one ([{sup 18}F]3) in high yields (decay-corrected, 25%-40%) and with high effective specific activities (>37 GBq/{mu}mol). Tissue distribution studies of the [{sup 18}F]1 and the [{sup 18}F]3 in mice showed the nonspecific bindings in brain regions, with metabolic defluorination of the [{sup 18}F]1. The result suggests that these radioligands may not be suitable agents for in vivo mapping of AChE, despite their potent in vitro anti-AChE activities.

Spectroscopic monitoring of bright A-F type candidate hybrid stars discovered by the Kepler mission

Science.gov (United States)

Lampens, Patricia; Frémat, Y.; Vermeylen, Lore; De Cat, Peter; Dumortier, Louis; Sódor, Ádám; Sharka, Marek; Bognár, Zsófia

2018-04-01

We report on a study of 250 optical spectra for 50 bright A/F-type candidate hybrid pulsating stars from the Kepler field. Most of the spectra have been collected with the high-resolution spectrograph HERMES attached to the Mercator telescope, La Palma. We determined the radial velocities (RVs), projected rotational velocities, fundamental atmospheric parameters and provide a classification based on the appearance of the cross-correlation profiles and the behaviour of the RVs with time in order to find true hybrid pulsators. Additionally, we also detected new spectroscopic binary and multiple systems in our sample and determined the fraction of spectroscopic systems. In order to be able to extend this investigation to the fainter A-F type candidate hybrid stars, various high-quality spectra collected with 3-4 m sized telescopes suitably equipped with a high-resolution spectrograph and furthermore located in the Northern hemisphere would be ideal. This programme could be done using the new instruments installed at the Devasthal Observatory.

An Experimental and Theoretical Study of the Variation of 4f Hybridization Across the La1-xCexIn3 Series

Energy Technology Data Exchange (ETDEWEB)

Gout, Delphine J [ORNL; Gourdon, Olivier [ORNL; Bauer, E. D. [Los Alamos National Laboratory (LANL); Ronning, F. [Los Alamos National Laboratory (LANL); Thompson, J. D. [Los Alamos National Laboratory (LANL); Proffen, Th. [Los Alamos National Laboratory (LANL)

2008-01-01

Crystal structures of a series of La1−xCexIn3 (x = 0.02, 0.2, 0.5, or 0.8) intermetallic compounds have been investigated by both neutron and X-ray diffraction, and their physical properties have been characterized by magnetic susceptibility and specific heat measurements. Our results emphasize atypical atomic displacement parameters (ADP) for the In and the rare-earth sites. Depending on the x value, the In ADP presents either an ellipsoidal elongation (La-rich compounds) or a butterfly-like distortion (Ce-rich compounds). These deformations have been understood by theoretical techniques based on the band theory and are the result of hybridization between conduction electrons and 4f-electrons.

¹¹¹In-anti-F4/80-A3-1 antibody: a novel tracer to image macrophages.

Science.gov (United States)

Terry, Samantha Y A; Boerman, Otto C; Gerrits, Danny; Franssen, Gerben M; Metselaar, Josbert M; Lehmann, Steffi; Oyen, Wim J G; Gerdes, Christian A; Abiraj, Keelara

2015-08-01

Here, the expression of F4/80 on the cell surface of murine macrophages was exploited to develop a novel imaging tracer that could visualize macrophages in vivo. The immunoreactive fraction and IC50 of anti-F4/80-A3-1, conjugated with diethylenetriaminepentaacetic acid (DTPA) and radiolabelled with (111)In, were determined in vitro using murine bone marrow-derived macrophages. In vivo biodistribution studies were performed with (111)In-anti-F4/80-A3-1 and isotype-matched control antibody (111)In-rat IgG2b at 24 and 72 h post-injection (p.i.) in SCID/Beige mice bearing orthotopic MDA-MB-231 xenografts. In some studies mice were also treated with liposomal clodronate. Macrophage content in tissues was determined immunohistochemically. Micro-single photon emission computed tomography (SPECT)/CT images were also acquired. In vitro binding assays showed that (111)In-anti-F4/80-A3-1 specifically binds F4/80 receptor-positive macrophages. The immunoreactivity of anti-F4/80-A3-1 was 75 % and IC50 was 0.58 nM. In vivo, injection of 10 or 100 μg (111)In-anti-F4/80-A3-1 resulted in splenic uptake of 78 %ID/g and 31 %ID/g, respectively, and tumour uptake of 1.38 %ID/g and 4.08 %ID/g, respectively (72 h p.i.). Liposomal clodronate treatment reduced splenic uptake of 10 μg (111)In-anti-F4/80-A3-1 from 248 %ID/g to 114 %ID/g and reduced (111)In-anti-F4/80-A3-1 uptake in the liver and femur (24 h p.i.). Tracer retention in the blood and tumour uptake increased (24 h p.i.). Tumour uptake of (111)In-anti-F4/80-A3-1 was visualized by microSPECT/CT. Macrophage density in the spleen and liver decreased in mice treated with liposomal clodronate. Uptake of (111)In-rat IgG2b was lower in the spleen, liver and femur when compared to (111)In-anti-F4/80-A3-1. Radiolabelled anti-F4/80-A3-1 antibodies specifically localize in tissues infiltrated by macrophages in mice and can be used to visualize tumours. The liver and spleen act as antigen sink organs for macrophage-specific tracers.

Toxicology and carcinogenesis studies of tetralin (CAS No. 119-64-2) in F344/N rats and B6C3F1 mice (inhalation studies).

Science.gov (United States)

2011-04-01

Tetralin is used as an industrial solvent primarily for naphthalene, fats, resins, oils, and waxes; as a solvent and stabilizer for shoe polishes and floor waxes; as a solvent for pesticides, rubber, asphalt, and aromatic hydrocarbons (e.g., anthracene); as a dye solvent carrier in the textile industry; as a substitute for turpentine in lacquers, paints, and varnishes; in paint thinners and as a paint remover; in alkali-resistant lacquers for cleaning printing ink from rollers and type; as a constituent of motor fuels and lubricants; for the removal of naphthalene in gas distribution systems; and as an insecticide for clothes moths. Tetralin was nominated by the National Cancer Institute for carcinogenicity and disposition studies because of its structure, high production volume, and high potential for worker and consumer exposure. Male and female F344/N rats and B6C3F1 mice were exposed to tetralin (at least 97% pure) by inhalation for 2 weeks, 3 months, or 2 years; male NCI Black Reiter (NBR) rats were exposed to tetralin by inhalation for 2 weeks. Male NBR rats do not produce 2u-globulin; the NBR rats were included to study the relationship of 2u-globulin and renal lesion induction. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male (F344/N and NBR) and five female (F344/N) rats were exposed to tetralin at air concentrations of 0, 7.5, 15, 30, 60, or 120 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 12 exposures. All rats survived to the end of the studies. The final mean body weight of female rats exposed to 120 ppm and mean body weight gains of female rats exposed to 30 ppm or greater were significantly less than those of the chamber controls. Final mean body weights of exposed groups of male NBR rats and mean body weight gains of all exposed groups of male rats were significantly less than those of the chamber controls. Dark

Strategies to rescue the consequences of inducible arginase-1 deficiency in mice.

Directory of Open Access Journals (Sweden)

Laurel L Ballantyne

Full Text Available Arginase-1 catalyzes the conversion of arginine to ornithine and urea, which is the final step of the urea cycle used to remove excess ammonia from the body. Arginase-1 deficiency leads to hyperargininemia in mice and man with severe lethal consequences in the former and progressive neurological impairment to varying degrees in the latter. In a tamoxifen-induced arginase-1 deficient mouse model, mice succumb to the enzyme deficiency within 2 weeks after inducing the knockout and retain <2 % enzyme in the liver. Standard clinical care regimens for arginase-1 deficiency (low-protein diet, the nitrogen-scavenging drug sodium phenylbutyrate, ornithine supplementation either failed to extend lifespan (ornithine or only minimally prolonged lifespan (maximum 8 days with low-protein diet and drug. A conditional, tamoxifen-inducible arginase-1 transgenic mouse strain expressing the enzyme from the Rosa26 locus modestly extended lifespan of neonatal mice, but not that of 4-week old mice, when crossed to the inducible arginase-1 knockout mouse strain. Delivery of an arginase-1/enhanced green fluorescent fusion construct by adeno-associated viral delivery (rh10 serotype with a strong cytomegalovirus-chicken β-actin hybrid promoter rescued about 30% of male mice with lifespan prolongation to at least 6 months, extensive hepatic expression and restoration of significant enzyme activity in liver. In contrast, a vector of the AAV8 serotype driven by the thyroxine-binding globulin promoter led to weaker liver expression and did not rescue arginase-1 deficient mice to any great extent. Since the induced arginase-1 deficient mouse model displays a much more severe phenotype when compared to human arginase-1 deficiency, these studies reveal that it may be feasible with gene therapy strategies to correct the various manifestations of the disorder and they provide optimism for future clinical studies.

Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F.

Science.gov (United States)

Alagramam, K N; Yuan, H; Kuehn, M H; Murcia, C L; Wayne, S; Srisailpathy, C R; Lowry, R B; Knaus, R; Van Laer, L; Bernier, F P; Schwartz, S; Lee, C; Morton, C C; Mullins, R F; Ramesh, A; Van Camp, G; Hageman, G S; Woychik, R P; Smith, R J; Hagemen, G S

2001-08-01

We have determined the molecular basis for Usher syndrome type 1F (USH1F) in two families segregating for this type of syndromic deafness. By fluorescence in situ hybridization, we placed the human homolog of the mouse protocadherin Pcdh15 in the linkage interval defined by the USH1F locus. We determined the genomic structure of this novel protocadherin, and found a single-base deletion in exon 10 in one USH1F family and a nonsense mutation in exon 2 in the second. Consistent with the phenotypes observed in these families, we demonstrated expression of PCDH15 in the retina and cochlea by RT-PCR and immunohistochemistry. This report shows that protocadherins are essential for maintenance of normal retinal and cochlear function.

Mutated hybrid inflation in f(R,□R)-gravity

International Nuclear Information System (INIS)

Iihoshi, Masao

2011-01-01

A new hybrid inflationary scenario in the context of f(R,□R)-gravity is proposed. Demanding the waterfall field to 'support the potential from below' [unlike the original proposal by Stewart in Phys. Lett. B 345, 414 (1995)], we demonstrate that the scalar potential is similar to that of the large-field chaotic inflation model proposed by Linde in Phys. Lett. B 129, 177 (1983). Inflationary observables are used to constrain the parameter space of our model; in the process, an interesting limit on the number of e-folds N is found

Mutated hybrid inflation in f(R,□R)-gravity

Energy Technology Data Exchange (ETDEWEB)

Iihoshi, Masao, E-mail: iihoshi@kiso.phys.se.tmu.ac.jp [Department of Physics, Tokyo Metropolitan University, Hachioji, Tokyo 192-0397 (Japan)

2011-02-01

A new hybrid inflationary scenario in the context of f(R,□R)-gravity is proposed. Demanding the waterfall field to 'support the potential from below' [unlike the original proposal by Stewart in Phys. Lett. B 345, 414 (1995)], we demonstrate that the scalar potential is similar to that of the large-field chaotic inflation model proposed by Linde in Phys. Lett. B 129, 177 (1983). Inflationary observables are used to constrain the parameter space of our model; in the process, an interesting limit on the number of e-folds N is found.

Alteration of the spontaneous systemic autoimmune disease in (NZB x NZW)F1 mice by treatment with thimerosal (ethyl mercury)

International Nuclear Information System (INIS)

Havarinasab, S.; Hultman, P.

2006-01-01

Inorganic mercury may aggravate murine systemic autoimmune diseases which are either spontaneous (genetically determined) or induced by non-genetic mechanisms. Organic mercury species, the dominating form of mercury exposure in the human population, have not been examined in this respect. Therefore, ethyl mercury in the form of thimerosal, a preservative recently debated as a possible health hazard when present in vaccines, was administered in a dose of 0.156-5 mg/L drinking water to female (NZB x NZW)F1 (ZBWF1) mice. These mice develop an age-dependent spontaneous systemic autoimmune disease with high mortality primarily due to immune-complex (IC) glomerulonephritis. Five mg thimerosal/L drinking water (295 μg Hg/kg body weight (bw)/day) for 7 weeks induced glomerular, mesangial and systemic vessel wall IC deposits and antinuclear antibodies (ANA) which were not present in the untreated controls. After 22-25 weeks, the higher doses of thimerosal had shifted the localization of the spontaneously developing renal glomerular IC deposits from the capillary wall position seen in controls to the mesangium. The altered localization was associated with less severe histological kidney damage, less proteinuria, and reduced mortality. The effect was dose-dependent, lower doses having no effect compared with the untreated controls. A different effect of thimerosal treatment was induction of renal and splenic vessel walls IC deposits. Renal vessel wall deposits occurred at a dose of 0.313-5 mg thimerosal/L (18-295 μg Hg/kg bw/day), while splenic vessel wall deposits developed also in mice given the lowest dose of thimerosal, 0.156 mg/L (9 μg Hg/kg bw/day). The latter dose is 3- and 15-fold lower than the dose of Hg required to induce vessel wall IC deposits in genetically susceptible H-2 s mice by HgCl 2 and thimerosal, respectively. Further studies on the exact conditions needed for induction of systemic IC deposits by low-dose organic mercurials in autoimmune

Amplification of the E2F1 transcription factor gene in the HEL erythroleukemia cell line

DEFF Research Database (Denmark)

Saito, M; Helin, K; Valentine, M B

1995-01-01

, we isolated genomic clones encompassing the human E2F1 gene. We then used fluorescence in situ hybridization to localize E2F1 to human chromosome 20q11, telomeric to the p107 locus, a gene whose product is related to the retinoblastoma gene product (pRb). This finding contrasts with the 1p36 and 6q22...

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer’s Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET

Directory of Open Access Journals (Sweden)

Xue-Yuan Li

2016-10-01

Full Text Available Alzheimer’s disease (AD is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1 transgenic (Tg mice aged 2, 3.5, 5 and 8 months using 18F-labed fluorodeoxyglucose (18F-FDG microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr. Morris water maze (MWM was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD. By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD. Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer’s cognition after cognitive decline, at least in animals.

Effects of fetal exposure to gamma rays on aggressive behavior in adult male mice

International Nuclear Information System (INIS)

Minamisawa, Takeru; Hirokaga, Kouichi; Sasaki, Shunsaku; Noda, Yutaka.

1992-01-01

Aggressive behavior (AB) in first generation (F 1 ) hybrid male C57BL/6 x C3H mice irradiated on the 14th day of gestation was studied at 100-135 days of age. Gravid female mice were irradiated with 1.0 or 2.0 Gy of gamma rays to the whole body. The AB of pairs of mice were recorded with a capacitance-induction motility monitor and on videotape. Recordings were continued for 90 min, starting at 2:00 PM. Vigorous wrestling, boxing and biting were regarded as AB. Data recorded at 15-min intervals were stored on micro-computer discs. The body weight for the irradiated group was significantly lower than that for the control group. The number of instances of AB was significantly higher in the irradiated group. The AB of the 2.0 Gy group was significantly more intensive than that of the control group. No difference in the duration of AB was found for the 2 irradiated and the control groups. Results demonstrate that male mice irradiated prenatally show increased aggressiveness. (author)

Stable carbon isotope composition (δ{sup 13}C), water use efficiency, and biomass productivity of Lycopersicon esculentum, Lycopersicon pennellii, and the F{sub 1} hybrid

Energy Technology Data Exchange (ETDEWEB)

Martin, B.; Thorstenson, Y. R.

1988-09-01

Three tomatoes, Lycopersicon esculentum Mill. cv UC82B, a droughttolerant wild related species, Lycopersicon pennellii (Cor.) D'Arcy, and their F{sub 1}, hybrid, were grown in containers maintained at three levels of soil moisture. Season-long water use was obtained by summing over the season daily weight losses of each container corrected for soil evaporation. Plant biomass was determined by harvesting and weighing entire dried plants. Season-long water use efficiency (gram dry weight/kilogram H{sub 2}O) was calculated by dividing the dry biomass by the season-long water use. The season-long water use efficiency was greatest in the wild parent, poorest in the domestic parent, and intermediate (but closer to the wild parent) in the F, hybrid. Instantaneous water-use efficiency (micromole CO{sub 2}/millimole H{sub 2}O) determined by gas exchange measurements on individual leaves was poorly correlated with season-long water use efficiency. However, the relative abundance of stable carbon isotopes of leaf tissue samples was strongly correlated with the season-long water use efficiency. Also, the isotopic composition and the season-long water use efficiency of each genotype alone were strongly negatively correlated with plant dry weight when the dry weight varied as a function of soil moisture. (author)

Liver Proteome of Mice with Distinct Genetic Susceptibilities to Fluorosis Treated with Different Concentrations of F in the Drinking Water.

Science.gov (United States)

Khan, Zohaib Nisar; Sabino, Isabela Tomazini; de Souza Melo, Carina Guimarães; Martini, Tatiana; da Silva Pereira, Heloísa Aparecida Barbosa; Buzalaf, Marília Afonso Rabelo

2018-04-29

Appropriate doses of fluoride (F) have therapeutic action against dental caries, but higher levels can cause disturbances in soft and mineralized tissues. Interestingly, the susceptibility to the toxic effects of F is genetically determined. This study evaluated the effects of F on the liver proteome of mice susceptible (A/J) or resistant (129P3/J) to the effects of F. Weanling male A/J (n = 12) and 129P3/J (n = 12) mice were housed in pairs and assigned to two groups given low-F food and drinking water containing 15 or 50 ppm F for 6 weeks. Liver proteome profiles were examined using nano-LC-ESI-MS/MS. Difference in expression among the groups was determined using the PLGS software. Treatment with the lower F concentration provoked more pronounced alterations in fold change in liver proteins in comparison to the treatment with the higher F concentration. Interestingly, most of the proteins with fold change upon treatment with 15 ppm F were increased in the A/J mice compared with their 129P3/J counterparts, suggesting an attempt of the former to fight the deleterious effects of F. However, upon treatment with 50 ppm F, most proteins with fold change were decreased in the A/J mice compared with their 129P3/J counterparts, especially proteins related to oxidative stress and protein folding, which might be related to the higher susceptibility of the A/J animals to the deleterious effects of F. Our findings add light into the mechanisms underlying genetic susceptibility to fluorosis.

HyPro: A Multi-DoF Hybrid-Powered Transradial Robotic Prosthesis

Directory of Open Access Journals (Sweden)

C. L. Semasinghe

2018-01-01

Full Text Available This paper proposes a multi-DoF hybrid-powered transradial robotic prosthesis, named HyPro. The HyPro consists of two prosthetic units: hand and wrist that can achieve five grasping patterns such as power grasp, tip grasp, lateral grasp, hook grasp, and index point. It is an underactuated device with 15 degrees of freedom. A hybrid powering concept is proposed and implemented on hand unit of HyPro where the key focus is on restoration of grasp functions of biological hand. A novel underactuated mechanism is introduced to achieve the required hand preshaping for a given grasping pattern using electric power in the pregrasp stage and body power is used in grasp stage to execute the final grasping action with the selected fingers. Unlike existing hybrid prostheses where each of the joints is separately controlled by either electric or body power, the proposed prosthesis is capable of delivering grasping power in combination. The wrist unit of HyPro is designed and developed to achieve flexion-extension and supination-pronation using electric power. Experiments were carried out to evaluate the functionality and performance of the proposed hybrid-powered robotic prosthesis. The results verified the potential of HyPro to perform intended grasping patterns effectively and efficiently.

Synergistic reversal of type 1 diabetes in NOD mice with anti-CD3 and interleukin-1 blockade

DEFF Research Database (Denmark)

Ablamunits, Vitaly; Henegariu, Octavian; Hansen, Jakob Bondo

2012-01-01

(ab')(2) fragments of anti-CD3 mAb with or without IL-1 receptor antagonist (IL-1RA), or anti-IL-1ß mAb. We studied the reversal of diabetes and effects of treatment on the immune system. Mice that received a combination of anti-CD3 mAb with IL-1RA showed a more rapid rate of remission of diabetes than......Inflammatory cytokines are involved in autoimmune diabetes: among the most prominent is interleukin (IL)-1ß. We postulated that blockade of IL-1ß would modulate the effects of anti-CD3 monoclonal antibody (mAb) in treating diabetes in NOD mice. To test this, we treated hyperglycemic NOD mice with F...... arginase expression in macrophages and dendritic cells, and had delayed adoptive transfer of diabetes. After 1 month, there were increased concentrations of IgG1 isotype antibodies and reduced intrapancreatic expression of IFN-¿, IL-6, and IL-17 despite normal splenocyte cytokine secretion. These studies...

Recipient micro-environment does not dictate the Igh-V restriction specificity of T cell suppressor inducer factor (TsiF) from allogeneic bone marrow chimera in mice

International Nuclear Information System (INIS)

Noguchi, M.; Ogasawara, M.; Iwabuchi, K.; Osgasawara, K.; Ishihara, T.; Good, R.A.; Morikawa, K.; Onoe, K.

1985-01-01

The authors have ascertained previously from a study of fully allogeneic irradiation chimeras in mice that the H-2 restriction of the suppressor factor (Ly-2 T suppressor factor) is determined by the post-thymic environment protected by the donor cells, rather than by the thymic environment of the recipient. In the present study, the author analyzed differentiation influences that determine the Igh restriction specificities of the suppressor inducer T cell factor(s) (TsiF) that are produced by Ly-1+ splenic T cells in fully allogeneic bone marrow chimeras in mice. AKR mice that had been lethally irradiated and reconstituted with B10 marrow cells, [B10----AKR] chimeras, produced Ly-1 TsiF after hyper-immunization with sheep erythrocytes (SRBC) which suppressed antigen--specifically the primary antibody responses to SRBC that were generated in cells of the same Igh-Vb haplotype of donor strain and not those generated in cells of the recipient Igh-Va type. Similar results were obtained when Ly-1 TsiF from [B6----BALB/c] and [BALB/c----B6] chimeras were analyzed. Furthermore, the Ly-1 TsiF from [BALB/c----B6] chimeras suppressed the primary antibody responses of both BALB/c [H-2d, Igh-Va, Igh-Ca] and BAB-14 (H-2d, Igh-Va, Igh-Cb), but not those of CAL-20 (H-2d, Igh-Vd, Igh-Cd). These results demonstrate clearly that the Ly-1 TsiF from allogeneic bone marrow chimeras are donor Igh-V-restricted and are not influenced by the recipient micro-environment, presumably that were provided by the thymuses of the recipient mice

BMI1 loss delays photoreceptor degeneration in Rd1 mice. Bmi1 loss and neuroprotection in Rd1 mice.

Science.gov (United States)

Zencak, Dusan; Crippa, Sylvain V; Tekaya, Meriem; Tanger, Ellen; Schorderet, Daniel E; Munier, Francis L; van Lohuizen, Maarten; Arsenijevic, Yvan

2006-01-01

Retinitis pigmentosa (RP) is a heterogeneous group of genetic disorders leading to blindness, which remain untreatable at present. Rd1 mice represent a recognized model of RP, and so far only GDNF treatment provided a slight delay in the retinal degeneration in these mice. Bmi1, a transcriptional repressor, has recently been shown to be essential for neural stem cell (NSC) renewal in the brain, with an increased appearance of glial cells in vivo in Bmi1 knockout (Bmi1-/-) mice. One of the roles of glial cells is to sustain neuronal function and survival. In the view of a role of the retinal Miller glia as a source of neural protection in the retina, the increased astrocytic population in the Bmi1-/- brain led us to investigate the effect of Bmi1 loss in Rd1 mice. We observed an increase of Müller glial cells in Rd1-Bmi1-/- retinas compared to Rd1. Moreover, Rd1-Bmi1-/- mice showed 7-8 rows of photoreceptors at 30 days of age (P30), while in Rd1 littermates there was a complete disruption of the outer nuclear layer (ONL). Preliminary ERG results showed a responsiveness of Rd1-Bmi1-/- mice in scotopic vision at P35. In conclusion, Bmi1 loss prevented, or rescued, photoreceptors from degeneration to an unanticipated extent in Rd1 mice. In this chapter, we will first provide a brief review of our work on the cortical NSCs and introduce the Bmi1 oncogene, thus offering a rational to our observations on the retina.

Efficacy, pharmacokinetics, tisssue distribution, and metabolism of the Myc-Max disruptor, 10058-F4 [Z,E]-5-[4-ethylbenzylidine]-2-thioxothiazolidin-4-one, in mice.

Science.gov (United States)

Guo, Jianxia; Parise, Robert A; Joseph, Erin; Egorin, Merrill J; Lazo, John S; Prochownik, Edward V; Eiseman, Julie L

2009-03-01

c-Myc is commonly activated in many human tumors and is functionally important in cellular proliferation, differentiation, apoptosis and cell cycle progression. The activity of c-Myc requires noncovalent interaction with its client protein Max. In vitro studies indicate the thioxothiazolidinone, 10058-F4, inhibits c-Myc/Max dimerization. In this study, we report the efficacy, pharmacokinetics and metabolism of this novel protein-protein disruptor in mice. SCID mice bearing DU145 or PC-3 human prostate cancer xenografts were treated with either 20 or 30 mg/kg 10058-F4 on a qdx5 schedule for 2 weeks for efficacy studies. For pharmacokinetics and metabolism studies, mice bearing PC-3 or DU145 xenografts were treated with 20 mg/kg of 10058-F4 i.v. Plasma and tissues were collected 5-1440 min after dosing. The concentration of 10058-F4 in plasma and tissues was determined by HPLC, and metabolites were characterized by LC-MS/MS. Following a single iv dose, peak plasma 10058-F4 concentrations of approximately 300 muM were seen at 5 min and declined to below the detection limit at 360 min. Plasma concentration versus time data were best approximated by a two-compartment, open, linear model. The highest tissue concentrations of 10058-F4 were found in fat, lung, liver, and kidney. Peak tumor concentrations of 10058-F4 were at least tenfold lower than peak plasma concentrations. Eight metabolites of 10058-F4 were identified in plasma, liver, and kidney. The terminal half-life of 10058-F4 was approximately 1 h, and the volume of distribution was >200 ml/kg. No significant inhibition of tumor growth was seen after i.v. treatment of mice with either 20 or 30 mg/kg 10058-F4. The lack of significant antitumor activity of 10058-F4 in tumor-bearing mice may have resulted from its rapid metabolism and low concentration in tumors.

Identificação de híbridos de citros resistentes à mancha-marrom-de-alternária por meio de fAFLP e testes de patogenicidade Alternaria brown spot resistant citrus hybrid identification by means of fAFLP and pathogenicity tests

Directory of Open Access Journals (Sweden)

Edvan Alves Chagas

2007-07-01

Full Text Available O objetivo deste trabalho foi identificar híbridos, oriundos de hibridações controladas entre 'Folha Murcha' x 'Ponkan' e testá-los quanto à resistência a Alternaria alternata f. sp. citri. As plântulas foram obtidas via cultura in vitro de embriões. Utilizou-se o marcador molecular fAFLP para identificação dos híbridos e, em seguida, realizou-se o teste de patogenicidade nos híbridos com isolados de Alternaria alternata f. sp. citri, em condições de laboratório. Os pares de primers EcoRI AAG - MseI CAG e EcoRI ACC - MseI CAA foram os mais eficientes na identificação dos híbridos, os quais identificaram 48,5% de híbridos. Os híbridos F64, F108, F111, F113, F131 e F139 são potencialmente resistentes a Alternaria alternata f. sp. citri.The objective of this work was to identify hybrids obtained from controlled crossings between 'Folha Murcha' x 'Ponkan', and to check their resistance to Alternaria alternata f. sp. citri. The seedlings were obtained by in vitro embryo culture. The fAFLP marker technique was used to identify the hybrids, then laboratory pathogenicity test of the hybrids was accomplished with Alternaria alternata f. sp. citri isolates. The pairs of primers EcoRI AAG - Msel CAG and EcoRI ACC - Msel CAA were the most efficient for hybrids identification, and distinguished 48.5% of hybrids. Hybrids F64, F108, F111, F113, F131 and F139 showed potential resistance to the Alternaria alternata f. sp. citri.

Genetic studies on the effect of gamma-irradiation on the spermatocytes of both mice and their F1 progeny

International Nuclear Information System (INIS)

Hassan, N.H.A.; Khattab, F.I.; Roushdy, H.M.; El-Dawy, H.A.

1997-01-01

Meiotic chromosome rearrangement of spermatocytes at diakinesismetaphase I were analysed in young adult male mice irradiated by gamma-rays at 0.5, 1.5, 3 and 6 Gy and killed 3 and 6 weeks post exposure. The types of aberrations recorded were: ring four CIV, chain three plus one univalent CIII+I, chain hexavalent CVI, autosomal univalent, X-Y univalent and polyploidy. The frequencies of these aberrations showed a dose-response relationship. Chromosomal aberrations were traced in spermatocytes of F 1 generation of males irradiated at different dose levels and crossed after the 3 rd and 6th weeks of exposure with normal control females. The data showed no dose-response relationship in offsprings delivered by irradiated animals and mated after three weeks of exposure. However, in offsprings of males mated after six weeks of exposure, the number of abnormal spermatocytes increased by increasing the dose. The dose of 6.0 Gy gamma-rays caused complete sterility of the exposed males

InMotion hybrid racecar : F1 performance with LeMans endurance